sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12572 production and hosting by knowledge e editorial how to avoid plagiarism abduelbagi altayb associate editor, sudan journal of medical sciences orcid: abduelbagi altayb: https://orcid.org/0000-0002-9885-0710 this is our third short guide on academic publishing standards. at sudan journal of medical sciences (sjms), we occasionally receive manuscripts with significant levels of plagiarized content, reflecting a pervasive trend amongst junior scholars in sudan to neglect to include the proper acknowledgements for the work they cite. this is as much due to a lack of knowledge and experience as it is due to malicious intent, and this editorial will offer a short guide for junior researchers in sudan regarding the consequences of plagiarism. wilson mizner once said, “when you steal from one author, it’s plagiarism; if you steal from many, it’s research.” [1]. the simple definition of plagiarism is taking credit for someone else’s work. the world association of medical editors defines plagiarism as “the use of others’ published and unpublished ideas or words (or other intellectual property) without attribution or permission and presenting them as new and original rather than derived from an existing source.” [2]. there are many different types of plagiarism: copying and pasting, rephrasing or changing a few words of the original work, using unpublished work without credit or permission, translation from a different language without proper citation, and idea theft, as well as the emerging practice of salami publication, or publishing multiple papers from larger works. a: what not to do: 1. plagiarism is the uncited and unacknowledged reuse of another scholar’s work. this includes paraphrasing and the use of data, as well as direct quotations. if paraphrasing content, or using data from an earlier article, remember to cite the original source [3]. 2. ask for permission to use figures and tables and cite them properly. remember that the violation of authorial rights can have severe legal consequences, in addition to resulting in the retraction of the article. how to cite this article: abduelbagi altayb (2022) “how to avoid plagiarism,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 426–427. doi 10.18502/sjms.v17i4.12572 page 426 corresponding author: abduelbagi altayb; email: medc.oiu@gmail.com published 31 december 2022 production and hosting by knowledge e abduelbagi altayb. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12572&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abduelbagi altayb 3. also remember to ask for permission when making use of unpublished work and include proper attributions. b: look for guidance and support: 1. training courses helping with research methodologies and citations are available. training courses are also available for academic communication, that is, writing skills, correct paraphrasing, and understanding how to present and reference the ideas of others. 2. ask for support from the wider research community, from colleagues and senior researchers. they can give advice and review articles prior to submission, highlighting any potential issues or concerns. 3. joining experienced research groups or individual can help early career researchers to gain experience in how to properly research and cite the work of other scholars [4]. c: tools that can help: there are multiple tools and solutions available that can be used to identify potential instances of plagiarism, where work is not properly acknowledged and referenced. mark twain said “how lucky adam was. he knew when he said a good thing, nobody had said it before.” original work should always get credit [5]. references [1] johnston, a. (ed.). (1953). chapter 4. in: the legendary mizners (pp. 66). new york: farrar, straus and giroux. [2] peeran, s. w., ahmed, a. m., mugrabi, m. h., & peeran, s. a. (2013). simple steps to avoid plagiarism and improve scientific writing. libyan journal of medicine, 8(1), 21825. [3] alam, m., ratner, d., coleman, w. p. (2019). how to understand, detect, and avoid plagiarism. dermatologic surgery, 45(5), 631–637. [4] mark twain’s notebook. (1867). [5] driggers, r. (2017). ethics, plagiarism, and crosscheck: editorial. applied optics, 56(16), ed5. doi 10.18502/sjms.v17i4.12572 page 427 a: what not to do: b: look for guidance and support: c: tools that can help: references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11462 production and hosting by knowledge e short communication significance of primary fibrinogenolysis bashir abdrhman bashir associate professor of hematology, chairman of hematology department, medical laboratory sciences division, port sudan ahlia college, port sudan, sudan orcid: bashir abdrhman bashir: https://orcid.org/0000-0002-5089-9531 dear editor, primary fibrinogenolysis is a circumstance where the fibrinogen is enzymatically decomposed due to plasmin activity. this process indicates that fibrinogen is pathologically degraded by plasmin. primary fibrinogenolysis in its pure form is rare. however, it can occur if dynamic plasmin is excessively released intravenously once the clotting pathway is malfunctioning. shock, trauma, surgical interventions, acute leukemia, heatstroke, and advanced liver diseases have all been linked to primary fibrinogenolysis. it can emerge in patients experiencing breast cancer, lung cancer, prostate cancer, and renal cell carcinoma. many plasminogen activators are released into the bloodstream beyond the inhibitors’ capability. they may be produced by bodily reserves (mostly endothelial cells) [1, 2]. in this correspondence, we will explore the hemostatic alterations that have been reported and whether they are relevant to primary fibrinogenolysis. substantial bleeding is mediated by fibrinogen depletion (split by plasmin) and the release of fibrin split products from fibrinogen [1]. patients generally do not experience severe bleeding but are at substantial risk for hemorrhage resulting from hypofibrinogenemia. pronounced thrombocytopenia is expected to raise suspicions of disseminated intravascular coagulation (dic) [2]. prothrombin time and partial thromboplastin time are almost always both prolonged. platelet count is normal with an absence of microcirculatory thrombosis. one of the essential laboratory tools to discriminate between primary fibrinogenolysis and dic is platelet count, which stays normal (>150 × 109/l) in primary fibrinogenolysis while reduced in dic. secondly, antithrombin concentration is low in dic, but normal in primary fibrinogenolysis. thirdly, euglobulin clot lysis time will be markedly reduced in primary fibrinogenolysis while normal or slightly shortened in dic. finally, the absence of a high concentration of d-dimer in primary fibrinogenolysis versus its elevated concentration in dic [1]. once active bleeding develops, it is tough to distinguish between the two how to cite this article: bashir abdrhman bashir (2022) “significance of primary fibrinogenolysis,” sudan journal of medical sciences, vol. 17, no. 2, pp. 284–286. doi 10.18502/sjms.v17i2.11462 page 284 corresponding author: bashir abdrhman bashir; email: bashirbashir17@hotmail.com received 19 october 2021 accepted 29 may 2022 published 30 june 2022 production and hosting by knowledge e bashir abdrhman bashir. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bashirbashir17@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences bashir abdrhman bashir entities since fibrin is obtained as an action of thrombin activation and the lysis of fibrin produces d-dimers [3]. the best approach in patients with primary fibrinogenolysis secondary to malignant disease is often an aggressive treatment of the underlying malignant condition. a study by kulić et al. described bleeding as a presenting sign of primary fibrinogenolysis in a 64-year-old patient with prostatic cancer [4]. furthermore, a study performed by li et al. reported significant gingival bleeding as a presenting finding of primary fibrinogenolysis [2]. crissman et al. highlighted an amniotic fluid embolism due to obstetric abnormalities in a 29-year-old woman diagnosed with primary fibrinogenolysis rather than dic [5]. in contrast to dic, anti-fibrinolytic medications such as aminocaproic acid or tranexamic acid are favored remedies for primary fibrinogenolysis [3]. transfusion support with cryoprecipitate can also be provided for severe hypofibrinogenemia. if dic has developed, anti-fibrinolytic agents without systemic anticoagulation (like heparin) are contraindicated due to the potential risk of increased microvascular thrombosis [1]. caution should be exercised to balance chemotherapy-related bone marrow suppression with bleeding complications due to fibrinogenolysis. in conclusion, the significantly reduced fibrinogen and increased fibrin/fibrinogen split products (fsp) and d-dimer levels are diagnostically significant. coagulopathy should always be taken into account in diagnostic practice. with the rising frequency of cancer, primary fibrinogenolysis secondary to some malignancies may likely emerge in clinical studies. finally, precise diagnosis is critical in patients with primary fibrinogenolysis and clinical presentation for perfect management. references [1] tasneem, t. (2009). primary fibrinogenolysis. esculapio, vol. 5, no. 3, p. 1. [2] li, s. (2011). gingival bleeding as a presenting sign of primary fibrinogenolysis. oral surgery, oral medicine, oral pathology, oral radiology, and endodontology, vol. 112, no. 1, p. 3. [3] favresse, j., lippi, g., roy, p., et al. (2018). d-dimer: preanalytical, analytical, postanalytical variables, and clinical applications. critical reviews in clinical laboratory sciences, vol. 55, no. 8, pp. 548–577. [4] kulić, a., cvetković, z., and libek, v. (2016). primary hyperfibrinolysis as the presenting sign of prostate cancer: a case report. vojnosanitetski pregled, vol. 73, no. 9, pp. 877–880. doi 10.18502/sjms.v17i2.11462 page 285 sudan journal of medical sciences bashir abdrhman bashir [5] crissman, h. p., loder, c., pancaro, c., et al. (2020). case report of amniotic fluid embolism coagulopathy following abortion; use of viscoelastic point-of-care analysis. bmc pregnancy childbirth, vol. 20, p. 9. doi 10.18502/sjms.v17i2.11462 page 286 dear editor, references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12873 production and hosting by knowledge e letter covid-19 vaccine and role of community pharmacists mayyda asif bajwa1 and kanwal ashiq2* 1faculty of pharmacy, forman christine college university (fccu) lahore, pakistan 2faculty of pharmacy, superior university lahore, pakistan orcid: kanwal ashiq: https://orcid.org/0000-0001-8193-5147 dear editor, over a year and a half ago, the very first case of coronavirus sars-cov-2 was reported, causing a global pandemic, that is, covid-19. it came as a turning point, making scientists dig for maximum data on the virus and learn its management [1, 2]. in this while, some preventive measures like physical distancing and protective gears have become an essential part of daily life. one of the swift stratagems toward recovery is vaccination against covid-19. soon after discovering the genetic and phenotypic structure of the coronavirus, vaccine production was uptaken by state-of-the-art labs and pharmaceutical companies globally on an immediate basis. as per who’s announcement on july 15, 2020, around 150 countries were tied up in the covid-19 vaccine global access (covax) lead. it lent a means designed to ensure fair, speedy, and equitable covid-19 vaccines to people worldwide. such a move proved a way forward to betterment and success against disease. yet, data on safety remains essential and was derived from data available on earlier vaccine development campaigns [3]. data on previous vaccines against infectious diseases reflect saving over 23 million people from 2011 to 2020. however, the success of vaccines relies on people’s acceptance and compliance with vaccine regimens. right from the first case of the covid-19 pandemic, along with frontline workers, pharmacists testified for an active role in the delivery and supply of medications, counseling leading to the public’s understanding of the disease, testing patients, and recently in vaccine administration [4]. around the globe, we see pharmacies following business models as per regional government law. the pharmacist’s role switched from the conventional community and product-focused practice to the patient-oriented role with coverage of clinical aspects in the recent past. sophisticated setups with advanced facilities focus on providing customized therapy with a better insight into drug interaction [5–7]. how to cite this article: mayyda asif bajwa and kanwal ashiq* (2023) “covid-19 vaccine and role of community pharmacists,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 121–123. doi 10.18502/sjms.v18i1.12873 page 121 corresponding author: kanwal ashiq; email: kanwal.ashiq@superior.edu.pk received 17 february 2022 accepted 31 january 2023 published 31 march 2023 production and hosting by knowledge e bajwa and ashiq. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences bajwa and ashiq with covid-19 vaccination, the role of community pharmacists can be availed in making the immunization process controlled and more effective. the pharmacist’s position can be seen in retail setups and even vaccination centers, mimicking vaccination with tetanus and influenza viruses. the 2017 cdc data revealed that the rate of adult vaccine escalated from 23% to 28%. also, the speed of vaccines increased amongst people aged 65, with pharmacists rendering immunization. it also helps lower the rate of hospitalization and death rates, helping reduce the rate of medical care [8]. the last few years have also established the pharmacist’s role in aiding the flu shots; this has allowed patients with vaccination at the nearest point, thus saving money. this service at the end of the pharmacist can be extended over remote areas, extending the coverage. this entire model can be replicated to provide vaccine shots during the pandemic, utilize pharmacists’ expertise, and get better public health services. moreover, it builds up a cycle of trust among the public and pharmacists by being available for guidance and counseling, especially with the urgency and necessity of vaccinating people around the globe against covid-19. the proactive role of the community pharmacist will become appreciable with the involvement in eradicating the life-threatening virus, provided people give away reluctance in this matter [9, 10]. acknowledgements none. competing interests no conflict of interest was declared by the authors. references [1] ashiq, k., bajwa, m. a., & ashiq, s. (2021). covid-19 pandemic and its impact on pharmacy education. turkish journal of pharmaceutical sciences, 18(2), 122. [2] ashiq, k., naureen, b., & ashiq, s. (2021). nmetal complexes and their potential therapeutic role against covid-19: recent developments in drug designing. sudan journal of medical sciences, 16(4), 540–545. [3] su, s., du, l., & jiang, s. (2020). learning from the past: development of safe and effective covid-19 vaccines. nature reviews microbiology, 19, 211–219. doi 10.18502/sjms.v18i1.12873 page 122 sudan journal of medical sciences bajwa and ashiq [4] haynes, b. f., corey, l., fernandes, p., gilbert, p. b., hotez, p. j., rao, s., santos, m. r., schuitemaker, h., watson, m., & arvin, a. (2020). prospects for a safe covid-19 vaccine. science translational medicine, 12(568), 1–12. [5] babar, z. u. d. (2021). ten recommendations to improve pharmacy practice in low and middle-income countries (lmics). journal of pharmaceutical policy and practice, 14, 1–5. [6] khan, n., mcgarry, k., naqvi, a. a., iqbal, m. s., & haider, z. (2020). pharmacists’ viewpoint towards their professional role in healthcare system: a survey of hospital settings of pakistan. bmc health services research, 20(1), 1–15. [7] naughton, c. a. (2018). patient-centered communication. pharmacy, 6(1), 18. [8] ali, e., thulasika, p., sarah, a., tran, c. (2020). pharmacists and covid-19. journal of pharmaceutical policy and practice, 3, 36. https://doi.org/10.1186/s40545-02000241-3 [9] ashiq, k., ashiq, s., bajwa, m. a., tanveer, s., & qayyum, m. (2020). knowledge, attitude and practices among the inhabitants of lahore, pakistan towards the covid19 pandemic: an immediate online based cross-sectional survey while people are under the lockdown. bangladesh journal medical sciences, 2020, s69–s76. [10] bajwa, m. a., & ashiq, k. (2020). the covid-19 crisis and supportive role of pharmacists in cancer patients. journal of dow university health sciences, 14(2), 95–96. doi 10.18502/sjms.v18i1.12873 page 123 dear editor, acknowledgements competing interests references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10692 production and hosting by knowledge e original article the first multidisciplinary heart failure clinic in sudan: a descriptive report nasrein elgasim ahmed1, kannan o. ahmed2*, samoal abdelaziz dafalla1, huda hamid mohammed elhassan1, mohammed saeed al khalifa3, and anas bedawi babiker4 1ahmed gasim cardiac surgery and renal transplantation center, khartoum north, sudan 2clinical pharmacy and pharmacy practice department, faculty of pharmacy university of gezira, wad medani, sudan 3professor of medicine and cardiology, college of medicine, omdurman islamic university, omdurman, sudan 4royal care international hospital, khartoum, sudan abstract outcomes for patients with heart failure (hf) remain suboptimal worldwide, despite the national and international guidelines. a disease management program such as a multidisciplinary (md) team hf clinic proved to be one of the effective strategies to improve patients’ outcomes. in june 2018, the first md-hf clinic was opened at ahmed gasim cardiac surgery and renal transplantation center, khartoum, sudan. this focused report aims to share our experience and pave the way for such an approach for cardiac and other specialty services that may require md-specialized clinics. we provide a detailed report of the md team, structure, facilities, and plans of the hf clinic, which may be considered as a nucleus for an advanced hf program and heart transplant in sudan. keywords: multidisciplinary, heart failure clinic, sudan 1. introduction despite advances in medical and interventional therapy, heart failure (hf) has significant mortality and a higher rate of hospitalizations. in addition, the prognosis is poor and worse than most cancer types [1]. moreover, hf is highly prevalent, and globally, 26 million people are suffering from hf, with forecasts for 2030 estimating the prevalence to increase by 25% [2]. to date, there is no national statistic for hf in sudan in terms of prevalence, incidence, mortality, hospitalization rate, readmission, and total cost. however, limited hospitalbased studies have been done [3, 4]. despite improved survival, reduced hospitalizations, and improved quality of life (qol) of hf patients with reduced ejection fraction (hfref) in clinical trials with novel drugs and devices, in actual practice, the treatment of hfref is still suboptimal worldwide [5]. how to cite this article: nasrein elgasim ahmed, kannan o. ahmed*, samoal abdelaziz dafalla, huda hamid mohammed elhassan, mohammed saeed al khalifa, and anas bedawi babiker (2022) “the first multidisciplinary heart failure clinic in sudan: a descriptive report,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 146–151. doi 10.18502/sjms.v17i1.10692 page 146 corresponding author: kannan o. ahmed; email: omerkannan@gmail.com received 03 november 2021 accepted 03 march 2022 published 31 march 2022 production and hosting by knowledge e nasrein elgasim ahmed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:omerkannan@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nasrein elgasim ahmed et al disease management programs (dmps) such as hf clinics are effective in optimizing patients with hf compared to the usual care. therefore, dmps are now highly recommended by international guidelines to be practiced in a multidisciplinary (md) team [1]. this short communication describes the first md-hf clinic at ahmed gasim cardiac surgery and renal transplantation center, khartoum, sudan. 2. the premise the md-hf clinic was opened on june 14, 2018, at ahmed gasim cardiac surgery and renal transplant center, established in 1997 in khartoum, sudan with 230 beds. the cardiac services include busy cardiology and cardiac surgery departments that accept referrals from around the country. the clinic operates from the outpatient department of the center. the team is allocated enough room to provide privacy for patients without overlapping care provided from each specialty. although in the beginning, due to the low number of patients, the clinic operated only for one day, after a month, it started providing services for two days per week with an average of 10–15 patients per day. 3. md-hf clinic goals and structure ahmed gasim cardiac surgery and renal transplant center was established in 1997 in khartoum, sudan, and has 230 beds. the cardiac services include busy cardiology and cardiac surgery departments that accept a referral from all around the country [6]. six units form the cardiology department of the center covering invasive and noninvasive services. due to the increasing number of patients, the center adopted the policy of specialized clinics, for example, the pacemakers, arrhythmias, anticoagulants, and hf clinics for better patient care. the main goals of the center are to improve the outcome of patients with hfref, promote the concept of md team and staff competence, establish robust data for audit and research, and act as a nucleus for a more advanced hf program in sudan. 4. the md-hf clinic team the md-hf clinic team comprised of the following members: doi 10.18502/sjms.v17i1.10692 page 147 sudan journal of medical sciences nasrein elgasim ahmed et al (i) a consultant cardiologist (ii) a clinical pharmacy specialist (iii) a resident doctor trained in hf (iv) a nurse trained in hf (v) dieticians (vi) psychologists (vii) cardiac rehabilitation specialist 5. equipment and facilities registration to the clinic is made through a computerized system. the patient is admitted with specific referral criteria according to the diagnosis and cause of hfref, as shown in figure 1. the clinic is also supported with a specially designed patient file separate from the hospital file, as each discipline has a separate section to document their workup, plans, and subsequent follow-up for each patient. the clinic is supported with a booklet written in a simple local language containing information about hf, self-care, hf medications, and tables for daily weight measurement. the patient undergoes the initial basic investigations including ecg, cxr, and echocardiography plus laboratory indices (cbc, u&e, bnb [when needed]) repeated when required and at least at the optimization of medication. 6. md-hf clinic team organization the crucial point in the md-hf clinic is to nominate the individual role of each md team member without overlapping, so patients can inspire new modes of handling compared to the usual care. the cardiac nurse is the first member to welcome patients and check their eligibility for the clinic. then, the patient meets the rest of the team members, including the doctor, the clinical pharmacists, the dietitian, the cardiac rehabilitator, and the psychologist. nevertheless, some or all of the team members may need to counsel the patient together for the best possible management plan. figure 2 illustrates the role of each specialty in the hf clinic. doi 10.18502/sjms.v17i1.10692 page 148 sudan journal of medical sciences nasrein elgasim ahmed et al figure 1: referral criteria to multidisciplinary heart failure clinic. figure 2: role of each specialty in multidisciplinary heart failure clinic. 7. patient’s acceptance policy hfref patients are managed by their units, and only patients who need further optimization and maximization of medications are accepted in the clinic after a full workup and solving reversible causes of hf. figure 1 shows the patient referral criteria. doi 10.18502/sjms.v17i1.10692 page 149 sudan journal of medical sciences nasrein elgasim ahmed et al 8. what is different at the hf clinic compared to the usual care? patients will receive adequate pharmacological, nutritional, psychological, and rehabilitation support in one place in orchestral mode. in addition, educational pamphlets and booklet about hf to improve their awareness, compliance, and self-care are provided. a clear decision will be taken on whether further care is needed, for example, cardiac resynchronization therapy (crt) or left ventricular assist device (lvad). after completing the program, the patient will return to their original unit with a clear plan. 9. future plans 9.1. for patients (beneficiaries) (i) to establish service for inpatients and optimize medication during admission. (ii) homecare team for hf patients with close liaison with the primary healthcare physician and the district nurse. (iii) telemetry follow-ups for the hf clinic through telephone. (iv) online groups (facebook, twitter, whatsapp) to facilitate sharing of knowledge and experience. 9.2. for infrastructure and policies (i) to have fully automated machines and available lab tests. (ii) digitalization of the processes and records. 9.3. for growth and development (i) to liaise with the ministry of health to expand the service to other centers. (ii) to establish a certified training program for staff. (iii) to expand the program to cover the devices (crt-p, crt-d) (iv) to liaise with regional lvad and heart transplantation programs (v) advocacy and publications doi 10.18502/sjms.v17i1.10692 page 150 sudan journal of medical sciences nasrein elgasim ahmed et al acknowledgements none. competing interests none. funding nil. references [1] moertl, d., altenberger, j., bauer, n., et al. (2017). disease management programs in chronic heart failure. wiener klinische wochenschrift, vol. 129, no. 23–24, pp. 869–878. [2] hale, g. m., hassan, s. l., hummel, s. l., et al. (2017). impact of a pharmacist-managed heart failure postdischarge (bridge) clinic for veterans. annals of pharmacotherapy, vol. 51, no. 7, pp. 555–562. [3] khalil, s. i., khalil, s., albadri, h. k., et al. (eds.). (2015). emergence of ischemic cardiomyopathy as the main cause of heart failure in urban sudanese population. international cardiovascular forum journal, vol. 2. [4] suliman, a. (2011). the state of heart disease in sudan. cardiovascular journal of africa, vol. 22, no. 4, p. 191. [5] bhat, s., kansal, m., kondos, g. t., et al. (2018). outcomes of a pharmacist-managed heart failure medication titration assistance clinic. annals of pharmacotherapy, vol. 52, no. 8, pp. 724–732. [6] ahmed, k. o., eldin, i. t., yousif, m., et al. (2021). clinical pharmacist’s intervention to improve medication titration for heart failure: first experience from sudan. integrated pharmacy research & practice, vol. 10, p. 135. doi 10.18502/sjms.v17i1.10692 page 151 introduction the premise md-hf clinic goals and structure the md-hf clinic team equipment and facilities md-hf clinic team organization patient's acceptance policy what is different at the hf clinic compared to the usual care? future plans for patients (beneficiaries) for infrastructure and policies for growth and development acknowledgements competing interests funding references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12859 production and hosting by knowledge e editorial a glimpse into the future of medical education in sudan mohamed h. ahmed department of medicine and hiv metabolic clinic, milton keynes university hospital nhs foundation trust, eaglestone, milton keynes, buckinghamshire uk perhaps it’s not an exaggeration if i say that all sudanese doctors have a deep and overt love for medical education. this may be in part due to different factors related to the sudanese culture, where firstly doctors are leaders in medicine, social issues, and politics, and secondly, the majority of sudanese doctors have more inclination for teaching than research. this has created a large number of doctors with a wealth of experience of, and ideas about, medical education whose reflections unfortunately remain unpublished. a third factor relates to the strong cultural emphasis on leaving a legacy amongst sudanese doctors, which results in higher numbers opting for teaching rather than research roles. however, over the longer term, i believe this respect for medical education will prove beneficial for the country. increasingly, medical educators are understanding the value of transforming personal experience into published insights. this is, in part, driven by the rising numbers of sudanese doctors enrolling in master’s degrees in medical education, during which they are taught the importance of publishing their ideas in medical and educational journals. as a result, the number of publications by sudanese doctors on the topic of medical education has started to increase, contributing to exciting national and regional debates and discussions in this field. in particular, this trend has contributed to several developments and strategies in sudan’s medical education sector, some of which will be outlined in this editorial. 1. undergraduate medical curriculum sudanese medical graduates perform well on regional and international metrics of evaluation, gain jobs in the usa, uk, and ireland, and are successful in arab board examinations – demonstrating the strong quality of the education they receive in sudan. this strength is also highlighted by the fact that the sudan medical council (smc) was one of the first 10 medical councils globally (and first in the region) to be approved for the international accreditation of medical schools by the world federation of medical education (wfme) in 2018 [1]. the smc has implemented several noteworthy how to cite this article: mohamed h. ahmed (2023) “a glimpse into the future of medical education in sudan,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 1–5. doi 10.18502/sjms.v18i1.12859 page 1 corresponding author: mohamed h. ahmed; email: mohamed.hassan-ahmed@ mkuh.nhs.uk received 9 february 2023 accepted 14 february 2023 published 31 march 2023 production and hosting by knowledge e mohamed h. ahmed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed h. ahmed initiatives focused on medical education [2], and recent studies have demonstrated the high quality of sudanese medical students’ professional knowledge, attitude, and behavior [3]. moreover, the number of medical colleges in sudan is rising steadily, with a corresponding increase in the research into (and understanding of) new approaches and techniques for medical education (such as problem-based learning, communityoriented and hybrid curriculum). not only do these new curricula offer the opportunity to develop and test new innovative approaches but also the opportunity to evaluate their impact on different student bodies. this contributes to the broader long-term strategy of rebuilding and reforming all structures of undergraduate medical education to maintain excellent standards for all graduates of medical colleges in sudan [4]. 2. postgraduate postgraduate medical education in sudan predominantly focuses on clinical training in different specialties and lies under the responsibility of the sudan medical specialization board (smsb). the duration of training is four years, and the candidate receives mds in different clinical specialties [5]. the training is well-structured and has gained an excellent reputation. however, there is always room for improvement in any educational field. for example, abdalla et al. proposed creating a coordinating body to coordinate better diaspora contributions to the country’s healthcare [6]. establishing such a body would enhance and strengthen postgraduate medical training in different directions. this includes the effective use of new technologies and ideas; knowledge and skills transfer to facilitate staff training, staff promotion, and the retention of high-caliber healthcare workers; providing opportunities for collaboration and training in an extensive and organized fashion; and allowing for opportunities to establish a center of excellence in rare specialties [7]. this strategy would also result in a reduction in financial costs associated with training, and provide opportunities for universities and, research centers in sudan to be involved in international collaborations and clinical trials. finally, for the sudanese medical diaspora, establishing such a coordinating body would allow them to have that sense of contribution toward their mother country. doi 10.18502/sjms.v18i1.12859 page 2 sudan journal of medical sciences mohamed h. ahmed 3. research although research outputs are rising steadily, we see scope for further development in the future, especially in communicable diseases, non-communicable diseases, and medical education [8]. there is an urgent need to invest more in research, especially after the covid-19 pandemic. therefore, more incentives are needed to encourage doctors to engage in research or enroll in postgraduate md-phd programs [5, 9]. academic medicine in sudan, like academic medicine in other countries, is facing challenges in funding, dedicating time for research, and decreasing the number of doctors with research experience [10–12]. sudan is a large country located in the heart of africa with a population of different ethnic backgrounds [5]. therefore, future research based on epidemiological, population, genetic, laboratories, and cellular methods may reveal an exciting outcome. perhaps, we can echo what sir wellcome said about sudan “do the sand of this land of enigmas still hide within their depths an answer to the eternal enigma of man’s beginning and a record of his first steps upon the pathway of knowledge?” [13, 14]. from personal experience, there is significant engagement with research activities in sudan, especially after covid-19, from many doctors practicing in sudan. the medical diaspora’s input may also help boost research activities and produce more momentum for further research. it is imperative that we need to invest more in the training of future generations of young sudanese clinical scientists who will be able to contribute to research and innovations in medical education and communicable and non-communicable diseases. 4. social accountability the socially accountable medical school acts as part of the community and focuses education, research, and service activities upon the welfare of their local societies and communities [15]. ahmed et al. suggested that social accountability will improve research, teaching, and service and will also increase the chance of medical schools gaining international accreditation and excellence in medical education. they called for a social accountability alliance in sudan to increase collaboration between medical schools [16], and many medical schools are now emphasizing the importance of solving environmental and social problems, like reducing the spread of infectious diseases [17]. the faculty of medicine, university of gezira (fmug) have long-term experience with social responsibility, and many medical schools in sudan can benefit from such experience. doi 10.18502/sjms.v18i1.12859 page 3 sudan journal of medical sciences mohamed h. ahmed 5. conclusion sudan, rich in natural resources and with an increase in the number of highly qualified sudanese doctors, has the potential to develop a robust system for medical education. investment in the current and future generations by increasing funding for medical colleges, smsb, and research will allow prosperity and success not only in medical education but also in the healthcare system in sudan. i hope that this editorial will increase debate, discussion, understanding, and enthusiasm about the need to look, plan, and contemplate the future of medical education for the future generation of young sudanese doctors. references [1] world federation for medical education. (2021). accrediting agencies. available from: https://wfme.org/accreditation/accreditingagencies-status/) [2] elshazali, o. h., abdullahi, h., & karrar, z. a. (2021). progress, challenges, and partnerships of teaching medical professionalism in schools in sudan: the success story of sudan medical council. sudanese journal of paediatrics, 21(2), 110–115. [3] husain, n. e., elsheikh, n. m. a., elsheikh, m. n., mahmoud, a., sukkar, m. y., ibnouf, m. a. m., & ahmed, m. h. (2018). final year medical students and professionalism: lessons from six sudanese medical schools? journal of public health and emergency, 2, 27. [4] al mahdi, t. (2019). the path of undergraduate medical education in sudan. sudan journal of medical sciences (sjms), 14(4). https://doi.org/10.18502/sjms.v14i4.5899 [5] ahmed, m. h., husain, n. e., ahmed, m., elshiekh, m., & osman, w. n. (2022). clinician-scientist (md-phd) postgraduate programs in sudan: challenges, strategies, implementations, and future directions? journal of public health and emergency, 6, 6. [6] abdalla, f. m., omar, m. a., & badr, e. e. contribution of sudanese medical diaspora to the healthcare delivery system in sudan: exploring options and barriers. human resources for health 14(1), 28. [7] algibali, o. y., juma, b. e., algibaly, r. o., & ahmed, m. h. (2018). the role of diaspora and non-governmental organization in helping sudanese children with congenital heart diseases: 6 years’ paediatric cardiac surgery camps experience. journal of public health and emergency, 2, 26. doi 10.18502/sjms.v18i1.12859 page 4 sudan journal of medical sciences mohamed h. ahmed [8] ahmed, m. h., ahmed, m., taha, m. h., almobarak, a. o., osman, w. n., abdullah, m. e., zulfu, a., farag, e., omer, a., & husain, n. e. (2021). current and future clinical research in sudan: an opportunity for everyone to choose research in medical education, communicable and non-communicable diseases. journal of public health and emergency, 5, 28. [9] ahmed, m. h., husain, n. e., & elsheikh, m. (2021). why sudanese doctors should consider research career or phd degrees after their postgraduate medical training? journal of public health and emergency, 5, 16. [10] ahmed, m. h., husain, n. e., ibn auf, a., osman, w. n., almobarak, a. o., elshiekh, m., & ahmed, m. (2022). academic medicine in sudan: the challenges and solutions. journal of public health and emergency, 6, 5. [11] ibn auf, a., awadalla, h., ahmed, m. e., ahmed, m. h. (2019). comparing the participation of men and women in academic medicine in medical colleges in sudan: a cross-sectional survey. journal of education and health promotion, 8, 31. [12] ibn auf, a., awadalla, h., ahmed, m. e., ahmed, m. h. (2018). perception, barriers, and practice of research among teaching staff at five sudanese medical faculties. journal of public health and emergency, 2, 1–8. [13] addison, f. (1949). the wellcome excavations in the sudan (vol i, pp. 263–267). oxford university press. [14] adeel, a. a. a. (2013). henry solomon wellcome: a philanthropist and a pioneer sponsor of medical research in the sudan. sudanese journal of paediatrics, 13(2), 84–102. [15] boelen, c., & heck, j. (1995). defining and measuring the social accountability of medical schools. geneva, switzerland: division of development of human resources for health, world health organization. [16] ahmed, m. h., abdalla, m. e., & taha, m. h. (2020). why social accountability of medical schools in sudan can lead to better primary healthcare and excellence in medical education? journal of family medicine and primary care, 9, 3820–3825. [17] ahmed, m. h. (2021). why the faculty of medicine, university of gezira (fmug), sudan has the potential to lead in social accountability: reflections, opportunities and future directions. journal of public health and emergency, 5, 29. doi 10.18502/sjms.v18i1.12859 page 5 undergraduate medical curriculum postgraduate research social accountability conclusion references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12870 production and hosting by knowledge e case report a tale of 5ms: massive uterine leiomyoma mimicking ovarian malignancy along with multiple fibroids displaying multiple degenerations aakanksha koul1, archana shetty1, nidha gaffoor1*, nirupama murali1, and nagendra prasad2 11department of pathology, dr. chandramma dayananda sagar institute of medical education and research, dayananda sagar university, ramanagara, karnataka, india 2department of obstetrics and gynaecology, dr. chandramma dayananda sagar institute of medical education and research, dayananda sagar university, ramanagara, karnataka, india orcid: nidha gaffoor: https://orcid.org/0000-0003-1013-7599 abstract background: leiomyomas are by far the commonest uterine neoplasms in the female reproductive age group. giant leiomyomas are quite scarce and when longstanding tend to undergo various degenerations owing to decreased blood supply which on imaging may simulate malignancy owing to compromised blood supply and may simulate malignancy on imaging. case presentation: we present a case of a 48-year-old post-menopausal multiparous woman complaining of intermittent lower abdominal pain for a month. suspected as an ovarian tumor clinically and on ultrasound, this was seconded by raised serum ca125 levels. histopathological examination gave a definitive diagnosis of a giant uterine leiomyoma along with multiple fibroids exhibiting multiple degenerations. conclusion: degenerated leiomyomas can masquerade malignancy and hence should be one of the first differentials in women of reproductive age group presenting with complex abdominopelvic masses. keywords: hyaline, leiomyoma, malignancy, ovary, uterus 1. introduction uterine leiomyomas are benign mesenchymal tumors of smooth muscle origin usually presenting in the fifth decade of a woman’s life [1]. although monoclonal in origin, when multiple, each myoma originates from an independent myocyte [2]. they may grow into large tumors without producing any symptoms owing to a slow rate of growth, large capacity of the abdomen, and elasticity of the abdominal wall [3]. superadded secondary degenerative changes like hyaline degeneration, dystrophic calcification, and cystic degenerations are noted as they grow in size [4]. the international federation of gynaecology and obstetrics (figo) has broadly classified leiomyomas into three how to cite this article: aakanksha koul, archana shetty, nidha gaffoor*, nirupama murali, and nagendra prasad (2023) “a tale of 5ms: massive uterine leiomyoma mimicking ovarian malignancy along with multiple fibroids displaying multiple degenerations,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 104–110. doi 10.18502/sjms.v18i1.12870 page 104 corresponding author: nidha gaffoor; email: nidha.gaffoor@gmail.com received 24 february 2022 accepted 17 november 2022 published 31 march 2023 production and hosting by knowledge e aakanksha koul et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences aakanksha koul et al types according to their location – submucosal (figo type 0, 1, 2), intramural (figo type 3, 4, 5), and subserosal (figo type 6, 7). type 7 subserosal fibroids are more commonly pedunculated and may mimic ovarian tumors [5]. on ultrasound, leiomyomas are visualized as homogenous masses with hypogenic shadows. owing to various degenerations and large size, fibroids may appear heterogenous, leading to misinterpretation of malignancy [6]. we present a case of giant uterine leiomyoma which was clinically suspected to be an ovarian malignancy. in addition, multiple fibroids with four types of degenerations were reported in the same case. 2. case presentation a 48-year-old multiparous, post-menopausal woman presented to the gynecology opd with complaint of lower abdominal pain on and off for a month. there was no other relevant medical/family history. abdominal examination revealed a firm mobile mass of approximately 20×15 cm in size, the lower border of which could not be delineated. on bimanual examination, the uterus was normal in size with bilateral free fornices. the mass was non-tender and was felt separate from the uterus. ultrasound abdomen revealed a heteroechoic pelvic mass of size 19×12×17 cm with solid and cystic components and was suspected to be a malignant tumor arising from the ovary (figure 1). figure 1: ultrasound image showing a heteroechoic pelvic mass with solid and cystic areas. this was followed by a ct scan which showed a large lobulated enhancing mass lesion with necrotic areas in the pelvis, extending into the abdomen, measuring 22×15×13 cm, predominantly arising from left adnexa, suggestive of a malignant ovarian lesion. ca 125 was 210 u/ml. the patient underwent a total abdominal hysterectomy and bilateral salpingo-ophorectomy under general anesthesia. intraoperatively minimal ascites were noted. bilateral tubes and ovaries appeared normal. the mass was excised and sent in toto for histopathological examination. doi 10.18502/sjms.v18i1.12870 page 105 sudan journal of medical sciences aakanksha koul et al figure 2: (a) uterus with adnexa and leiomyoma showing bosselated surface. (b) cut section showing multiple intramural fibroids with cystic cavitation (arrow head) and calcifications (arrow). (c) cut section of giant degenerated fibroid measuring 25x20x13 cm with solid and cystic areas. figure 3: microscopic image of fibroids showing different types of degenerations (a – hyaline change [h&e,�×400], b – foci of calcifications [h&e, ×100], c – cystic change [h&e, ×400], d –myxoid change [h&e, ×100]). on gross examination, uterus with cervix measured 13.5×9.5×8 cm. the endometrium was compressed by multiple intramural and subserosal fibroids, some of which were gritty to cut. bilateral adnexa appeared unremarkable. the suspected pedunculated giant mass was seen attached to the fundus of the uterus and measured 25×20×13 cm and weighed 4.5 kg (figure 2a). on cutting open 1.5 liters of mucinous doi 10.18502/sjms.v18i1.12870 page 106 sudan journal of medical sciences aakanksha koul et al fluid was drained. the cut surface was variegated showing solid and cystic areas with septations (figures 2b & 2c). no necrotic or hemorrhagic areas were noted. sections from the ovaries and fallopian tubes were histologically unremarkable. sections from the largest mass and the smaller uterine fibroids showed features of leiomyoma with secondary degenerative changes of hyaline, myxoid, and cystic nature along with calcifications in the smaller fibroids (figures 3a–3d). the patient had an uneventful postoperative stay after which she was discharged. 3. discussion leiomyomas or fibroids are the commonest benign neoplasms and the commonest indication for hysterectomy within the reproductive age group in india [1]. its prevalence ranges from 4% in 20–30 year-olds, 11–18% in 30–40 years, and approx. 33% in 40– 60 years [7]. the patient in our case presented in her fourth decade. although the underlying pathogenesis is unclear, various associated risk factors like genetic changes, family history, race, premenopausal women, and hypertension have been described [1]. the first differential diagnosis of a large abdominopelvic mass with both solid and cystic components on imaging is an ovarian malignancy, which can be ruled out by visualizing both ovaries on ultrasound [8]. on ultrasound, fibroids normally present as heterogenous/homogeneous hypoechoic mass [6]. our case, however, presented as a heteroechoic mass with solid and cystic components. origin was also not visible as adnexa were obscured owing to the huge size of the mass. the presence of solid and cystic spaces with internal septations and calcifications are deceptive features that probably made the radiologist consider an ovarian malignancy. ovarian vascular pedicle signs in a ct scan can be used as a differentiator to confirm an ovarian mass over subserosal fibroid on a ct scan [6]. in our case, the ct scan revealed a large lobulated enhancing mass lesion with a necrotic mass arising from the left adnexa, suggestive of a malignant ovarian lesion. the pedicle sign could not be visualized. few reports suggest mri to be very useful in detecting fibroids with cystic degenerations when adnexae are not clearly visualized on ultrasound. maizlin et al. presented a case where ultrasound findings pointed toward an ovarian tumor, but mri diagnosed it to be a fibroid with cystic degenerations [6]. other differentials of leiomyomas with both solid and cystic components include endometriosis, cystic teratoma, mesothelioma, mesenteric cyst, lymphangioma, etc. [8]. biomarkers do play an important adjunct role in the diagnosis of ovarian malignancies. ca125 is a glycoprotein expressed by ovarian epithelial cells and a common biomarker doi 10.18502/sjms.v18i1.12870 page 107 sudan journal of medical sciences aakanksha koul et al used in the workup of ovarian neoplasms. it helps in diagnosis, framing treatment protocol, and prognosis. a combined panel of tk1, he4, and ca125 provide a better idea of the risk of ovarian malignancy. raised ca-125 however may also be seen in other benign and malignant gynecological disorders [9]. in our case, the raised level of ca125 supported by ultrasound findings might have added on the suspicion of malignancy. giant leiomyomas are not very common. to date, less than 100 cases of giant leiomyomas have been reported as per a literature search. in 1888, the largest leiomyoma was reported which weighed 63.3 kg [10]. as fibroids enlarge in size, they tend to outgrow their blood supply leading to ischemia and degeneration. approximately, 65% of leiomyomas undergo degeneration, the most common being hyaline degeneration (63%), followed by myxoid (19%), calcification (8%), cystic degeneration (4%), fatty change (3%), and red degeneration (3%) [6]. cystic degenerations are said to represent longstanding hyaline degenerations that have undergone liquefaction [11]. they are very rarely associated with myxoid degenerations as in our case. decreased blood supply leads to ischemia, followed by necrosis which may lead to calcification [4]. the multiple degenerations seen in our case points out to probability of long-standing fibroids, sequentially undergoing various spectrum of degenerations. long-standing fibroids may undergo a malignant sarcomatous change in 0.1% of cases [4]. genetic studies point to different pathways by which fibroids develop. reports say that around 50% of these tumors bear specific chromosomal aberrations like trisomy 12, a reciprocal translocation between chromosomes 12 and 14, and monosomy 22. such rearrangements may be responsible for the initiation, growth, as well as genetic heterogeneity observed histologically in these tumors. med 12 negative genotypes are likely to be associated with the development of larger fibroids, suggesting it to be a negative controller of tumor growth [3]. further molecular analyses would help identify putative candidate genes in uterine leiomyomata formation which may facilitate the prediction of genetic risks and patient management by appropriate therapeutic measures [12]. 4. conclusion giant uterine leiomyomas with extensive cystic degeneration can mimic ovarian malignancy clinically and radiologically, especially when the origin is unclear. it is imperative to consider degenerated leiomyoma as a differential in cases of abdominopelvic masses with raised ca125. histopathological examination is decisive and can often reveal multiple unsuspected findings on histopathology. doi 10.18502/sjms.v18i1.12870 page 108 sudan journal of medical sciences aakanksha koul et al acknowledgements nil. ethical considerations a consent form was signed by the patient. competing interests none declared. funding nil. references [1] world health organization. (2020). tumors of uterine corpus: mesenchymal tumors of uterus. in female genital tumors – who classification of tumors. 5𝑡ℎ ed. geneva: who. [2] rajshree, d. k., pushpa, c., & sonia, a. (2021). giant uterine leiomyoma (5 kg) with bunch of 45 fibroids: a challenging case during covid-19 pandemic. obstetrics & gynecology international journal, 12(4), 199–201. [3] gayathre, s. p., sivakumar, t., aashmi, c., & prashanth. (2021). giant uterine fibroid: a rare differential diagnosis for an abdominopelvic mass. international surgery journal, 8(11), 3475–3478. [4] renuka, m., & garima, a. a large cystic degenerating broad ligament leiomyoma masquerading as ovarian malignancy! journal of case reports, 5(2), 486–489. [5] christopher, w., kaitlyn, b., courtney, r., & christopher, k. (2020). laparoscopic management of a degenerating cystic leiomyoma imitating an ovarian cyst: a case report. case reports in women’s health, 27, e00205. [6] prabhu, j. k., sunita, s., shanmugapriya, c., divya, s., & shanmugapriya, r. (2021). a massive degenerative leiomyoma mimicking an ovarian tumor: a diagnostic dilemma. journal of gynecologic surgery, 37(1), 67–69. doi 10.18502/sjms.v18i1.12870 page 109 sudan journal of medical sciences aakanksha koul et al [7] mallick, d., saha, m., chakrabarti, s., & chakraborty, j. (2014). leiomyoma of broad ligament mimicking ovarian malignancy – report of a unique case. kathmandu university medical journal, 47(3), 219–221. [8] samardjiski, i., petrushevska, g., simeonova krstevska, s., paneva, i., livrinova, v., todorovska, i., ilieva, m. p., dimitrovski, s., & nikoloska, k. (2021). rare concomitant myxoid and cystic degeneration of uterine leiomyoma case report. scripta medica, 52(3), 235–238. [9] moss, e. l., hollingworth, j., & reynolds, t. m. (2005). the role of ca125 in clinical practice. journal of clinical pathology, 58, 308–312. [10] kalyan, s., & sonam, s. (2018). giant uterine leiomyoma: a case report with literature review. international journal of reproduction, contraception, obstetrics and gynecology, 7(11), 4779–4785. [11] yorita, k., tanaka, y., hirano, k., kai, y., arii, k., nakatani, k., ito, s., imai, t., fukunaga, m., & kuroda, n. (2016). a subserosal, pedunculated, multilocular uterine leiomyoma with ovarian tumor-like morphology and histological architecture of adenomatoid tumors: a case report and review of the literature. journal of medical case reports, 10(1), 352. [12] välimäki n, kuisma h, pasanen a, heikinheimo o, sjöberg j, bützow r, sarvilinna, n., heinonen, h. r., tolvanen, j., bramante, s., tanskanen, t., auvinen, j., uimari, o., alkodsi, a., lehtonen, r., kaasinen, e., palin, k., & aaltonen, l. a. (2018). genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. elife, 7, e37110. doi 10.18502/sjms.v18i1.12870 page 110 introduction case presentation discussion conclusion acknowledgements ethical considerations competing interests funding references sudan journal of medical sciences volume 12, issue no. 3, doi 10.18502/sjms.v12i3.1001 production and hosting by knowledge e research article rare suprasellar chordoid meningioma with ini1 gene mutation imad fadl-elmula1, rania giha2, sawsan a. h. deaf2, lamyaa ahmed el hassan3, ahmed m. hassan4, and mohamed a. r. arbab5 1department of histopathology, faculty of medical laboratory sciences, al neelain university, khartoum, sudan 2national centre of neurological sciences, khartoum, sudan 3department of pathology, faculty of medicine, ahfad university for women, omdurman, sudan 4institute of endemic diseases, university of khartoum, khartoum, sudan 5department of surgery, faculty of medicine, university of khartoum, khartoum, sudan abstract background: chordoid meningioma is a rare brain tumour characterized genetically by loss of genetic material from chromosome 22q at cytogenetic level resulting in mutation of nf2 gene. objectives and case report: in the present report, we described a rare case of suprasellar chordoid meningioma, which presented in a 32-year-old-woman. her only complain was throbbing headache. neurological examination showed left temporal hemianopia, decreased visual acuity (3/6), and no physical abnormalities related to castleman syndrome were noted. cranial magnetic resonance (mr) images demonstrated a 28x15 mm mass in the sellar region, which showed iso-to low intensity that enhanced vividly after gadolinium with upwards displacement of the optic chiasm. total surgical excision of the tumour was performed and subsequent histological examination of the tumour showed typical histology pattern of chordoid meningioma grade ii according to the who classification system of meningiomas. genomic dna was extracted and mutation analysis for ini1 gene using primer of exon 4, 5, 7, and 9 showed mutation involving exon 9. dna sequencing showed heterozygosity c-t mutation in exon 9 of ini1 gene leading to change of amino acid serine to phenylalanine at (codon 63). the details of this case are presented with a review of the literature. keywords: chordoid meningioma, brain tumours, ini1 gene how to cite this article: imad fadl-elmula, rania giha, sawsan ah deaf, lamyaa ahmed el hassan, ahmed m. hassan, and mohamed a. r. arbab, (2017) “rare suprasellar chordoid meningioma with ini1 gene mutation,” sudan journal of medical sciences, vol. 12 (2017), issue no. 3, 198–206. doi 10.18502/sjms.v12i3.1001 page 198 corresponding author: imad fadl-elmula; email: imad@fadl-elmula.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e imad fadl-elmula et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:imad@fadl-elmula.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e 1. introduction chordoid meningioma, accounts for 0.5% of all intracranial meningiomas. it was first described by kepes et al., in 1988, and accepted as meningiomas variants by the who classification of the central nervous system tumour in 19931,2. association of the tumour with haematologic abnormality such as microcytic anaemia and dysgammaglobulinemia and/or castleman syndrome have been repeatedly reported, especially, in paediatric patients [1], although chordoid meningioma with no hematological abnormalities have also been reported [3, 4]. microscopically chordoid meningiomas have features of meningioma similar to chordoma which is usually characterized by epitheliod cord like tumour cells. it is classified as who grade ii tumour [5]. there are eosinophilic vacuolated cells within a myxoid stroma and a lymphoplasmocytic infiltrate is often apparent and might be associated with haematological abnormalities [6]. cytogenetic analysis revealed that monosomy 22 is a common, early, and perhaps primary event in the genesis of meningioma. molecular analysis has identified several important candidate genes. of those, neurofibromatosis 2 (nf2), tumour suppressor in lung cancer-1 (tslc1), and tp53 are the most commonly reported. the ini1 (smarcb1/hsnf5) gene, maps to chromosome 22q11.2, is part of the swi/snf complex participating in transcriptional regulation by remodeling chromatin in an atp-dependent manner [7]. the swi/snf complex seems to be involved in dna replication [8]. these features characterize members of the swi/snf complex as interesting targets for genes which may be involved in tumour formation. recently, ini1 has been shown to carry mutations predominately in some central nervous system tumours such as meningiomas [9], schwannomas [10], astrocytomas11, ependymomas12 and glioblastomas11). ini1, therefore, is an interesting candidate gene for brain tumours, especially those entities that exhibit allelic loss on chromosome 22. 2. material and methods 2.1. the case a 32-year-old-female lady presented with four months history of throbbing headache and left visual field and acuity defect that worsened over the last three weeks. neurological examination showed left temporal hemianopia, decreased visual acuity (3/6), and no physical abnormalities related to castleman disease. doi 10.18502/sjms.v12i3.1001 page 199 sudan journal of medical sciences production and hosting by knowledge e routine laboratory investigations including hb, mcv, mch, total protein, albumen, and globulin were all normal. mri revealed large iso-intense sellar mass measuring 2.8?1.5 x1.5 cm that enhanced vividly after gadolinium with upwards displacement of the optic chiasm (figure f1-a). a provisional preoperative diagnosis of a pituitary macro adenoma was made. preoperative assessment of t3, t4, tsh and prolactin was normal. the patient was then operated upon through right sub frontal surgical approach. intraoperatively, a firm, circumscribed fibrous tumour with numerous vascular feeders was found. using the operating microscope, total excision of the tumour and its dural attachment was attained according to simpson classification grade i13. part of the tumour was fixed in 10% neutral formalin for histopathology examination. the other part was kept for molecular studies. 2.2. molecular analysis genomic dna was isolated using chloroform phenol extraction methods. pcr was performed under standard conditions using dntps, taq dna polymerase (promega, madison, wisconsin, usa), and a biometra uno thermoblock (biometra, gottingen, germany). primers of exon 4, 5, 7, and 9 for ini1 gene, were analyzed by sscp and direct sequencing employing a set of primers specified exon 4 forward primer, 5‘-tca ggt cct ata ctg act gg-3‘. exon 4 reverse primer, 5‘-aga act aag gcg gaa tca gc-3‘. exon 5 forward primer, 5‘-gct tcc att tca ctt tca gc-3‘. exon 5 reverse primer, 5‘-gtt ccc acg taa cac aca gg-3‘. exon 7 forward primer, 5‘-cctgggctgcaaaagctcta-3‘ exon 7 reverse primer, 5‘-ggagggagagactcatgcat-3‘ exon 9 forward primer, 5‘-tgt tcc cac ccc tac act tg-3‘. exon 9 reverse primer, 5‘-atg aat gga gac gcg cgc tct-3‘ pcr was performed in a final volume of 25 𝜇l containing 100 ng dna, 50 mm kcl, 20 mm tris-hcl ph 8.4, 200 𝜇m of each dntp, 0.1% gelatin, 10 pmol of each primer, 1.0–2.0 mm mgcl2 and 0.25 u taq polymerase. using touchdown programmed initial denaturation at 94∘c for 1 min was followed by 40 cycles on an automated thermal cycler (biometra, germany). these included denaturation at 94∘c for 35 s, annealing at temperatures ranging from 58∘c to 62∘c depending on the primer pair for 40 s, and extension at 72∘c for 40s followed by the final extension step at 72∘c for 10 min. the doi 10.18502/sjms.v12i3.1001 page 200 sudan journal of medical sciences production and hosting by knowledge e figure 1 pcr products on acrylamide gel using sscp analysis was performed on apparatus using 12% acrylamide gels. electrophoresis was run at 2–6 w and variable temperatures. doi 10.18502/sjms.v12i3.1001 page 201 sudan journal of medical sciences production and hosting by knowledge e figure 2 2.3. sequencing the same primers used for pcr analysis were used for sequencing. pcr products samples were sent for commercial sequencing at macrogen, seoul, republic of korea. the blast (basic local alignment search tool) programmer at the site of national center for biotechnology information (ncbi) was used for individual alignment of our samples. 3. results following surgery the patient had an uneventful postoperative recovery; the headache subsided and the visual acuity markedly improved to 5\6. postoperative values of t3, t4, tsh and prolactin were within normal ranges. microscopic examination of the tumour specimen revealed cluster of cohesive cells with dark regular nuclei and tapering cytoplasm arranged in a fibrous stroma showing an intense lymphocytic and plasma cells infiltration. there were scattered russell bodies in the inflammatory reaction (figure 2). the diagnosis of chordoid meningioma with doi 10.18502/sjms.v12i3.1001 page 202 sudan journal of medical sciences production and hosting by knowledge e inflammatory reaction who grade ii was made and hence the patient was submitted to conformal radiotherapy [14, 15]. the postoperative mri revealed total removal of the tumour (figure f1-b). 3.1. molecular results the sequencing indicated that the mutation was heterozygotic with heterozygosity ct mutation in exon 9 of ini1 gene, the mutation changed in the amino acid serine to phenylalanine in (codon 63) in this polymorphism data not reported in data analysis programmer. 4. discussion schmitz and co-workers have suggested an important role of ini1 gene in the pathogenesis of meningioma16. this suggestion led many to speculate that nf2 is not the only important gene in the pathogenesis of meningioma17. however, ini1 mutations were seen in only four tumours out of 126 meningiomas16. interestingly, ini1 mutations in all four cases were in the same position: nucleotide 377 (arg to his substitution). this intriguing finding prompted others to check the status of ini1 hot spots of exons 4, 5, 7 and 9 in meningioma. however, all these studies were based in europe and usa, thus no such a study was performed in african population. considering the differences in clinical, histopathological, and the natural history of meningiomas in the two populations, one may anticipate differences in the genetic profile as well. meningiomas can potentially occur at any site in the meninges. however, the most common locations known are the parasagittal and falcine tumours that account for around 24% of meningiomas, convexity tumours in 18%, olfactory groove, and tubercular sellae seen in 10% each. suprasellar chordoid meningioma is a rare tumour that may mimic pituitary adenomas. in the present case, the clinical presentation was dominated by headache and visual deterioration. the mri finding was consistent with a pituitary adenoma. association of chordoid meningioma and castleman syndrome has been reported [18, 19]. the present case did not show features of castleman syndrome. chordoid meningioma is a rare variant of meningioma; the differential diagnosis includes glioma, myxoid chondrosarcoma, chondroid chordoma, and other variants of meningiomas [4, 19–21]. usually they show trabeculae or cords of eosinophilic vacuolated cells in myxoid matrix [22]. the fact that the tumour proved to be chordoid meningioma should alert attention to this possibility in interpretation of suprasellar tumours. more-over, who grade ii doi 10.18502/sjms.v12i3.1001 page 203 sudan journal of medical sciences production and hosting by knowledge e meningiomas are considered to have an aggressive course. in the present report, there were no features of an aggressive behavior; this might be due to early detection of the tumour. the aggressive behaviour and the fibrous texture of these tumours with its close anatomical relation to the vital structures in the sellar region render tumour recurrence a potential risk. use of post-operative radio therapy lessens the chance of recurrence. close and regular follow up of these patients is mandatory to detect such recurrence. conclusion: the general belief from the clinical point of view that meningiomas are benign tumours has to be accepted with great care, since only the histological diagnosis can verify the potential aggressive behaviour of the tumour and the subsequent liability for recurrence. references [1] j. j. kepes, w. y. chen, m. h. connors, and f. s. vogel, ““chordoid” meningeal tumors in young individuals with peritumoral lymphoplasmacellular infiltrates causing systemic manifestations of the castleman syndrome. a report of seven cases,” cancer, vol. 62, no. 2, pp. 391–406, 1988. [2] p. kleihues, d. n. louis, b. w. scheithauer et al., “the who classification of tumors of the nervous system,” journal of neuropathology & experimental neurology, vol. 61, no. 3, pp. 215–225, 2002. [3] h. yano, a. hara, k. takenaka et al., “differential expression of β-catenin in human glioblastoma multiforme and normal brain tissue,” neurological research, vol. 22, no. 7, pp. 650–656, 2000. [4] m. e. couce, f. v. aker, and b. w. scheithauer, “chordoid meningioma: a clinicopathologic study of 42 cases,” american journal of surgical pathology, vol. 24, no. 7, pp. 899–905, 2000. [5] p. c. w. lui, t. k. f. chau, s. s. wong et al., “cytology of chordoid meningioma: a series of five cases with emphasis on differential diagnoses,” journal of clinical pathology, vol. 60, no. 9, pp. 1024–1028, 2007. [6] s. nagao, n. kawai, t. ohomoto, and t. oohashi, “a case of intrasellar and suprasellar meningioma with hypopituitarism,” neurological surgery, vol. 18, no. 7, pp. 637–642, 1990. [7] j. a. armstrong, j. j. bieker, and b. m. emerson, “a swi/snf-related chromatin remodeling complex, e-rc1, is required for tissue-specific transcriptional regulation by eklf in vitro,” cell, vol. 95, no. 1, pp. 93–104, 1998. doi 10.18502/sjms.v12i3.1001 page 204 sudan journal of medical sciences production and hosting by knowledge e [8] j. f. flanagan and c. l. peterson, “a role for the yeast swi/snf complex in dna replication,” nucleic acids research, vol. 27, no. 9, pp. 2022–2028, 1999. [9] j. p. dumanski, v. p. collins, m. nordenskjold, and g. a. rouleau, “molecular genetic analysis of chromosome 22 in 81 cases of meningioma,” cancer research, vol. 50, no. 18, pp. 5863–5867, 1990. [10] b. r. seizinger, r. l. martuza, and j. f. gusella, “loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma,” nature, vol. 322, no. 6080, pp. 644– 647, 1986. [11] c. d. james, e. carlbom, j. p. dumanski et al., “clonal genomic alterations in glioma malignancy stages,” cancer research, vol. 48, no. 19, pp. 5546–5551, 1988. [12] c. d. james, j. he, e. carlbom et al., “loss of genetic information in central nervous system tumors common to children and young adults,” genes, chromosomes and cancer, vol. 2, no. 2, pp. 94–102, 1990. [13] d. simpson, “the recurrence of intracranial meningiomas after surgical treatment,” journal of neurology, neurosurgery, and psychiatry, vol. 20, no. 1, pp. 22–39, 1957. [14] w. stenzel, g. röhn, h. miletic, h. radner, m. deckert, and r.-i. ernestus, “diagnostic impact of ornithine decarboxylase in meningiomas,” journal of neuro-oncology, vol. 66, no. 1-2, pp. 59–64, 2004. [15] p. kleihues and w. k. cavenee, who classification of tumours pathology and genetics of tumours of nervous system, iarc press, lyon, 2000. [16] u. schmitz, w. mueller, m. weber, n. sévenet, o. delattre, and a. v. deimling, “ini1 mutations in meningiomas at a potential hotspot in exon 9,” british journal of cancer, vol. 84, no. 2, pp. 199–201, 2001. [17] m. peyrard, i. fransson, y.-g. xie et al., “characterization of a new member of the human /-adaptin gene family from chromosome 22q12, a candidate meningioma gene,” human molecular genetics, vol. 3, no. 8, pp. 1393–1399, 1994. [18] f. c. stam, h. a. m. van alphen, and d. m. boorsma, “meningioma with conspicuous plasma cell components a histopathological and immunohistochemical study,” acta neuropathologica, vol. 49, no. 3, pp. 241–243, 1980. [19] h. kobata, a. kondo, k. iwasaki, h. kusaka, h. ito, and s. sawada, “chordoid meningioma in a child. case report,” journal of neurosurgery, vol. 88, no. 2, pp. 319– 323, 1998. [20] g. w. mierau and d. a. weeks, “chondroid chordoma,” ultrastructural pathology, vol. 11, no. 5-6, pp. 731–737, 1987. [21] d. j. brat, the elusive origin of chordoid glioma. arch pathol lab med, 130, 437-438, 2006. doi 10.18502/sjms.v12i3.1001 page 205 sudan journal of medical sciences production and hosting by knowledge e [22] m. e. couce, f. v. aker, and b. w. scheithauer, “chordoid meningioma: a clinicopathologic study of 42 cases,” american journal of surgical pathology, vol. 24, no. 7, pp. 899–905, 2000. doi 10.18502/sjms.v12i3.1001 page 206 introduction material and methods the case molecular analysis sequencing results molecular results discussion references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11457 production and hosting by knowledge e original article statistically significant difference in the first-trimester fetal heart rate between genders? olufemi adebari oloyede* and mustafa adelaja lamina fetal and maternal medicine unit, department of obstetrics and gynaecology, olabisi onabanjo university teaching hospital, ogun state, nigeria orcid: olufemi adebari oloyede: http://orcid.org/0000 0001-6332-9610 mustafa adelaja lamina: https//orchid.org/0000-0003-1819-8994 abstract background: the study aims to establish the pattern of fetal heart rates in the first and second trimesters and determine whether there is a statistically significant difference in the first-trimester fetal heart rate (fhr) of males and females. methods: this retrospective observational research is a study of fhrs measured at 11+0–13+6 wk and 18+0–23+6 wk, and ultrasound scan-diagnosed fetal sex at 18+0–23+6 wk. singleton fetuses with nonambiguous external genitalia were recruited. the fhr was measured in b or m mode with pulsed wave doppler, while ultrasound appearance of external genitalia determined the fetal sex at 18+0–23+6 weeks. student’s t-test and chi-square test were used for data analysis, and statistical significance was set at p < 0.05. results: a total of 2437 pregnancies meeting the study criteria were analyzed. the fetal sexes were 1398 (57.4%) males and 1039 (42.6%) females. there was no statistically significant difference in the first-trimester fhr between males and females (p = 0.74). however, females had higher mean fhr in both the first and second trimesters (first trimester: 165.4 ± 18.2 bpm vs 163.2 ± 17.1 bpm and second trimester: 150.9 ±22.6 bpm vs 141.9 ±23.1 bpm). the fhr reduces with the increase in gestational age. conclusion: there is no statistically significant difference in the first-trimester fhrs between sexes. keywords: statistically significant difference, fetal heart rates, fetal sexes, first trimester, ultrasound scan 1. introduction prenatal determination of fetal sex traditionally relies on ultrasound scan visualization of well-defined external genitalia anatomical features in second and third trimesters. more recently, however, other ultrasound markers such as the direction of the genital tubercle, anogenital distance, sagittal sign, and fetal heart rate (fhr) differences between sexes in the first trimester have been evaluated as reliable predictors of fetal gender [1, 2]. this rising desire for first-trimester sex determination among women is believed to be due how to cite this article: olufemi adebari oloyede* and mustafa adelaja lamina (2022) “statistically significant difference in the first-trimester fetal heart rate between genders?,” sudan journal of medical sciences, vol. 17, no. 2, pp. 236–243. doi 10.18502/sjms.v17i2.11457 page 236 corresponding author: olufemi adebari oloyede; email: oloyedeoao@gmail.com received 1 june 2021 accepted 15 january 2022 published 30 june 2022 production and hosting by knowledge e olufemi adebari oloyede and mustafa adelaja lamina. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:oloyedeoao@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences olufemi adebari oloyede and mustafa adelaja lamina to mothers’ desire for early planning of social aspects of pre-birthing activities. prenatal sex determination and reporting is illegal in some countries where it is reportedly associated with increased number of sex-biased selective termination [3, 4]. prenatal determination of sex also aids the diagnosis of suspected sex-linked genetic disease. the fhrs obtained during second and third trimesters were reported to have statistically significant difference between sexes, with the mean being higher in female fetuses [5, 6]. the outcomes of different studies that evaluated the statistically significant difference in first-trimester fhr as basis for assigning fetal sex has been mixed [7–9]. in the usa, no statistically significant difference (p = 0.62) was found between the mean first-trimester fhrs in female (167.0 ± 9.1 bpm) and male (167.3 ± 10.1 bpm) fetuses. similarly, the average female fhr of 151.7 ± 22.7 bpm and male fhr of 154.9 ± 22.8 bpm was not statistically significant (p = 0.13) [7, 9]. in addition to the above study findings, the accuracy of the strongly held maternal intuition of significant difference between fhr in male and female fetuses has not been shown to be different from that of random guessing [10]. the available studies from nigeria were not focused on the implications of fhr difference and fetal gender. the current study makes an attempt to establish the pattern of fhrs in the first and second trimesters, and to determine whether there is a statistically significant difference in the fhr between males and females. 2. materials and methods this study was a retrospective observational study of ultrasound scan procedures done between 2013, january 1 and 2018, december 31. the study data were collated from the ultrasound scan reports of pregnant patients that attended the antenatal clinics of olabisi onabanjo university teaching hospital and the ultrasound scan clinic in high rocks fetal medicine and genetic diagnosis centre, lagos. the study inclusion criteria were normal singleton pregnancies with gestational age between 11+0 and 13+6 wk based on the ultrasound crown rump length (crl) measurements and nonambiguous genitalia observed during the 18+0–23+6 wk anatomy scan. the ultrasound scans were performed by fetal medicine specialist or consultant obstetrician with expertise in obstetric ultrasound scan. transabdominal ultrasound scan was done in all patients using ge voluson p8 and sonoscape s20 on 3.5–7.5 mhz sector transducer probe. the fhrs were measured and documented at both 11+0–13+6 and 18+0–23+6wk using real-time b mode imaging of a magnified apical four-chamber view of the fetal heart. the standard protocol in the units was to activate the pulsed wavecursor, adjust and doi 10.18502/sjms.v17i2.11457 page 237 sudan journal of medical sciences olufemi adebari oloyede and mustafa adelaja lamina position 2–3 mm sample gate across the tricuspid valve, and maintain an insonation angle of <30º from the direction of the inter-ventricular septum and a sweep speed of 2–3 cm/sec for good spread of waveforms [11]. the spectral image was frozen when at least six waveforms were visible and measurement was using the electronic calipers (figure 1). the second fhr-measuring protocol used involved the activation of the m mode cursor across four chamber view of the heart and freezing of appropriate image before positioning the electronic calipers at clearly identified elevations in the m-mode tracing to measure the fhr [12] (figure 1). the fhr was recorded as beats per minute (bpm). the fetal sex was assigned based on unambiguous identification of clitoris and labia majora in female fetuses and scrotum and penile shaft in male fetuses (figure 2). the fhrs in both trimesters were reviewed and analyzed after ultrasound confirmation of nonambiguous sex at 18+0–23+6 wk. all patients that met the study criteria during the study period were recruited. descriptive statistics using percentages, means, and standard deviation were used as appropriate for continuous and categorical variables. statistical variables such as the mean fhr between male and female fetuses were compared using student’s independent samples t-tests, while variables such as proportion of male to female fetuses were compared using the chi-square test. a p < 0.05 was considered statistically significant. 3. results three thousand, three hundred and fifty-three ultrasound scans were done in the first trimester. of these, 2442 (72.8%) pregnancies participated in the second-trimester scan, 5 of which were assigned unclear fetal sex determination. the data from 2437 pregnancies were collated and analyzed. the fetal sexes were distributed as 1398 (57.4%) males and 1039 (42.6%) females, and majority (58.3%) of the ultrasound scans were done at 12+0–12+6 wk gestational age and at 20+0–20+6 wk gestational age (24.2%), respectively. in table 1, the first trimester mean fhrs in males and females were 163.2 ±18.2 and 165.5 ±17.1 bpm, respectively, with no statistically significant difference (p = 0.74), while in the second trimester, the mean fhrs were 150.9 + 22.6 and 141.9 + 23.1 bpm, respectively, with no statistically significant difference (p = 0.83). generally, fhr reduces with increasing gestational age (figure 3). the mean fhr was lower in males compared with the mean fhr in females during both 11+0–13+6 and 18+0–23+6wk gestational ages (table 1). the independent t-test comparison of the mean fhr between male and female fetuses in both trimesters showed no significant statistical difference (p = 0.74 and p = doi 10.18502/sjms.v17i2.11457 page 238 sudan journal of medical sciences olufemi adebari oloyede and mustafa adelaja lamina 0.83, respectively). the difference in the mean fhrs between sexes was higher in the second trimester compared with the first-trimester fhr difference (figure 3). a: b mode b: m mode figure 1: fetal heart rate measurement methods. a: female b: male figure 2: ultrasound scan appearance of fetal sex in second trimester. figure 3: trend in fetal heart rates in the first and second trimesters. note: x axis: fetal heart rates (bpm); y axis: gestational age (wk). doi 10.18502/sjms.v17i2.11457 page 239 sudan journal of medical sciences olufemi adebari oloyede and mustafa adelaja lamina table 1: analysis of pattern of fetal heart rates in first and second trimesters. gestational age number of fetuses fetal heart rates (male) number of fetuses fetal heart rates (female) p-value (wk) range mean sd range mean sd first trimester (2437) (1398) 0.74 11+0–11+6 183 170–192 181.0 17.9 105 164–202 180.1 17.1 12+0–12+6 1422 105–178 154.3 22.8 738 148–172 159.4 21.7 13+0–13+6 832 113–170 154.2 22.1 555 146–168 156.8 21.9 mean fhr: 163.2 + 18.2 bpm mean fhr: 165.4 + 17.1 bpm range: 105.0–195.0 bpm range: 146.0–202.0 bpm second trimester (2437) (2437) 0.83 18+0–18+6 441 130–162 154.4 21.0 247 134–158 156.4 19+0–19+6 617 141–170 152.4 23.1 396 136–152 154.4 20+0–20+6 590 140–162 148.0 23.4 314 138–154 150.8 21+0–21+6 509 105–138 138.2 18.0 241 110–148 146.0 22+0–22+6 155 110–144 126.0 20.8 97 106–150 148.2 23+0–23+6 125 114–156 132.8 21.2 103 108–152 150.0 mean fhr: 141.9 + 23.1 bpm mean fhr: 150.9 + 22.6 bpm range: 105.0–170.0 bpm range: 106–158 bpm 150 + 23.1 bpm and 152 + 22.6 bpm 4. discussion the difference in the mean fhrs in the first trimester between male and female fetuses was not statistically significant in the study population. consequently, the first-trimester fhr difference from the study is not a reliable method of assigning fetal sex. the pattern of fhr demonstrates decline in fhr with the increase in gestational age, with higher measurements in females in both trimesters. our results are consistent with research outcomes that reported the absence of statistically significant difference in the fhr between males and females in first trimester [7–9]. however, statistical difference was reported to be predictive of fetal sex by other workers [5, 6]. the trend of fhr with gestational age in the study agrees with the physiological pattern of a reduction in fhr as gestational age increases. the 11–13+6 wk of the first trimester was chosen as the period to establish the fhr difference for two reasons: (i) the functional maturation of the parasympathetic system and the morphological maturation of the heart are not well-established before 11 wk and (ii) the variations and fluctuations in the fhr is least at this gestational age period [13]. it has been reported that the morphologic maturation and parasympathetic system doi 10.18502/sjms.v17i2.11457 page 240 sudan journal of medical sciences olufemi adebari oloyede and mustafa adelaja lamina effect on the cardiac development and function in the fetuses mature with increasing gestational age and also earlier in males than females [13]. this may also explain the significant difference in fhr reported in the second and third trimesters by other researchers [5, 6]. that morphologic and autonomic effects on cardiac function are delayed and supported by the slowed reduction in fhr in females compared with males in the second trimester measurements. ultrasound scan at 11+0–13+ 6 wk gestation age provides opportunity to achieve other aims of early trimester ultrasound scan such as accurate estimation of gestational age and reliable risk prediction for aneuploidy [11, 14]. the fhr was measured in b mode or the m mode, both of which have been validated to be reliable and accurate for fhr measurement in clinical practice. the b mode is, however, the more commonly used in clinical practice. the most important strength of this study is the sample size, which is higher than the sample size in most other studies. hence, the inferences from the study are expected to have higher statistical power and be better predictive of the influence of the role of first-trimester fhr differences for assigning fetal sex. 5. conclusion the study reveals no statistically significant difference in first-trimester fhr between male and female fetuses. the fhr could therefore not be recommended for routine clinical use to avoid the consequences of misdiagnosis such as medico-legal and psycho-social issues. acknowledgements the authors acknowledges the assistance of assistant sonographers and medical records staff in the units ethical considerations ethical approval was obtained from the health research ethics committee (hrec) of olabisi onabanjo university teaching hospital, sagamu ogun state. competing interests the author received honorarium as sessional consultant in one of the study centers. doi 10.18502/sjms.v17i2.11457 page 241 sudan journal of medical sciences olufemi adebari oloyede and mustafa adelaja lamina availability of data and materials all data and materials used in the study are 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(1996). antenatal fetal heart rate and “maternal intuition” as predictors of fetal sex. journal of reproductive medicine, vol. 41, no. 6, pp. 447–449. [11] fetal medicine foundation. (n.d.). london protocols. fetal medicine foundation. retrieved from www.fmf.org [12] isuog practice guidelines. (2013). performance of first-trimester fetal ultrasound scan. ultrasound in obstetrics and gynecology, vol. 41, pp. 102–113. [13] zavala, j. h., myers, m. m., and fifer, w. p. (2020). assessment of autonomic function in the late term fetus. the effects of sex and state. developmental psychobiology, vol. 62, no. 2, pp. 224–231. [14] aibar, l., puertas, a., valverde, m., et al. (2012). fetal sex and perinatal outcomes. journal of perinatal medicine, vol. 40, pp. 271–276. doi 10.18502/sjms.v17i2.11457 page 243 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10690 production and hosting by knowledge e case report familial facial palsy: a case series of six families from the northern state, sudan mohamed osman abdelaziz and asma ahmed ziadan department of internal medicine. faculty of medicine and health sciences, university of dongola, dongola, sudan orcid: mohamed abdelaziz: https://orcid.org/0000-0003-1457-7903 abstract familial facial palsy is uncommon, accounting only for 4–14% of bell’s palsy cases. we report six families with single or recurrent episodes of familial facial palsy from northern state, sudan. the first family had two brothers with single episodes of bell’s palsy. the index case of the second family was a 19-year-old female who and nine other members of her family had a single or recurrent episodes of bell’s palsy. the third, fourth, fifth, and sixth families had eight, five, four, and five members, respectively, who developed either single or recurrent episodes of bell’s palsy. none of the index cases or other members of the six families who were examined showed evidence of facial swelling or fissured tongue suggestive of melkersson-rosenthal syndrome. literature review revealed two studies on bell’s palsy from sudan but no studies on familial facial palsy. the mode of inheritance was either autosomal dominant with variable penetrance or autosomal recessive. in the second family, there could be a possibility of autosomal recessive inheritance due to increased number of cases after consanguineous marriage. steroids remain the mainstay of treatment together with protective eye regimens. the role of physiotherapy, although widely used, is controversial. genetic analysis is recommended and family history should be considered in patients with bell’s palsy. keywords: bell’s palsy, familial facial palsy, northern state, sudan 1. introduction idiopathic facial nerve paralysis, also known as bell’s palsy (bp) remains the commonest cause of lower motor neuron (lmn) facial palsy, accounting for about 60–70% of all cases of unilateral facial palsy [1]. although there are many other causes, familial facial palsy is uncommon and accounts for about 4–14% of cases [2]. familial facial palsy or hereditary congenital facial palsy (hcfp) presents with different modes of inheritance, with two genes, hcfp1 and hcfp2 in cases with autosomal-dominant inheritance and one gene hcfp3 associated with autosomal recessive inheritance [3]. melkerssonrosenthal syndrome (mrs) is a rare disease characterized by the triad of recurrent swelling of various parts of the face such as the upper lip, lower lip, one or both cheeks, how to cite this article: mohamed osman abdelaziz and asma ahmed ziadan (2022) “familial facial palsy: a case series of six families from the northern state, sudan,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 128–137. doi 10.18502/sjms.v17i1.10690 page 128 corresponding author: mohamed abdelaziz; email: dralomda34@gmail.com; mosmanomda@uofd.edu.sd received 04 june 2021 accepted 05 march 2022 published 31 march 2022 production and hosting by knowledge e mohamed abdelaziz and asma ahmed ziadan. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dralomda34@gmail.com mailto:mosmanomda@uofd.edu.sd https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan figure 1: pedigree of the first family from the northern state, sudan with familial bell’s palsy affecting two brothers. the arrow points to the index case. eyelids, or the scalp; recurrent facial palsy; and deep fissures in the tongue. mrs may have a congenital or an acquired etiology [4, 5]. diagnosis of bp is mainly clinical but investigations, including neurological images and neurophysiological tests, can help identify the underlying cause. literature review shows two studies on bp in sudan [6, 7], however, to the best of our knowledge, no study on familial facial palsy has been conducted in sudan to date. we present six families from northern state, sudan with facial palsy and review the family history of similar conditions across different generations of the index cases. 2. case series 2.1. first case the first family, as seen in figure 1, included two brothers aged 56 and 48 years from dongola locality in the northern state, sudan who were brought as short cases for the final medical clinical examination at the faculty of medicine, university of dongola in 2016 after receiving informed consent. while the elder brother had right-side lmn facial palsy for about five years before presentation, the younger brother developed left lmn facial palsy for about two years, both had a partial recovery. the two cases showed no evidence of facial swelling or fissured tongues suggestive of mrs, nor did they have herpes zoster or parotid swelling suggestive of an underlying cause of the facial palsy. they had no past history of diabetes, hypertension, or trauma. doi 10.18502/sjms.v17i1.10690 page 129 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan figure 2: pedigree of the second family from the northern state, sudan with familial bell’s palsy with 10 (6 male and 4 female) affected individuals across three generations. the black arrow shows the index case. 2.2. second case the index case of the second family was a 19-year-old female from a rural area of dongola locality, who presented to the outpatient clinic of dongola specialized hospital on july 8, 2019 with a single-day history of acute onset deviation of the mouth to the left side associated with drooling of saliva. no headache or loss of consciousness or convulsions, or any evidence of affection of other cranial nerves or limbs weakness or numbness were reported. there was no history of trauma. clinical examination showed severe lmn right facial palsy with no other neurological deficits, no affection of taste, no hyperacusis, and no blistering eruptions over the external auditory meatus. examination of the skin and other systems was unremarkable and there was no facial swelling or fissured tongue suggestive of mrs. the patient had a past history of two episodes of left facial palsy with complete recovery, the first at the age of 8 and the second at the age of 10 years. family history revealed that her mother as well as eight other members of her family had developed either single or multiple episodes of facial palsy as illustrated in the family pedigree in figure 2. diagnosis of this patient was done on clinical grounds. the patient was started on oral prednisolone 30 mg daily for a total duration of 10 days with tapering after 5 days, together with lubricant eye drops to avoid exposure keratitis. she was also advised to perform regular facial exercise. follow-up after one week revealed partial recovery. doi 10.18502/sjms.v17i1.10690 page 130 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan figure 3: pedigree of the third family from the northern state, sudan with familial bell’s palsy with eight (five male and three female) affected individuals across three generations. the black arrow shows the index case. (note: the numbers inside the circles and rectangles indicate female and male family members in different generations and their subsequent generations who were unaffected by bell’s palsy.) 2.3. third case a 65-year-old female from wadi halfa city, halfa locality, northern state, who was known to be hypertensive for 10 years but not diabetic, presented on august 20, 2019 with a three-day history of acute onset severe right-side bp with seven other members of her family having single episodes of bp as shown in figure 3. examination of the patient revealed no features suggestive of mrs, varicella-zoster infection, or any evidence of underlying cause for the facial palsy. she was given prednisolone 40 mg/day as well as lubricant eye drops, follow-up after one week showed partial recovery. 2.4. fourth case the index case of the fourth family was a 40-year-old male patient from dalgo locality, who had two episodes of bp; right facial palsy before 17 years of age and left facial at the age of 40. examination of the patient showed no facial swelling or fissured tongue suggestive of mrs, no blistering skin eruption over the external ear or parotid swelling. there was no past history of trauma. family history revealed that four other members of doi 10.18502/sjms.v17i1.10690 page 131 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan figure 4: pedigree of the fourth family from the northern state, sudan with familial bell’s palsy with five (three male and two female) affected individuals across two generations. the black arrow shows the index case. his family, including two female children aged three and nine, had bell’s palsy as shown in figure 4. 2.5. fifth case the index case of the fifthfamily was a 16-year-old female from abri city, halfa locality who presented with right-side lmn facial palsy in 2020 with no features suggestive of mrs or any possible underlying cause. she had a past history of two episodes of similar conditions; the first in 2016 on the left side and the second in 2019 on the right side; both episodes with complete recovery. the family pedigree as seen in figure 5 shows two of her aunts and one of her uncles with single episodes of lmn facial palsy. 2.6. sixth case the index case of the sixth family was a 43-year-old male from dongola locality, who presented with left lmn facial palsy for five days in 2021. there was no swelling of the face or fissured tongue suggestive of mrs. in addition, no blistering eruption suggestive of varicella-zoster infection was seen. he had a past history of similar condition on the same side with complete recovery at the age of 13. family pedigree (figure 6) revealed that his father, sister, and his 8-year-old son had single episodes of lmn facial palsy while his elder brother had two episodes of bell’s palsy. doi 10.18502/sjms.v17i1.10690 page 132 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan figure 5: pedigree of the fifth family from the northern state, sudan with familial bell’s palsy with four affected individuals (three female and one male) across two generations. the black arrow shows the index case. (note: the numbers inside the circles and rectangles indicate female or male family members in different generations and their subsequent generations unaffected by bell’s palsy.) 3. discussion familial facial palsy is uncommon, with few case reports found in the literature [2, 8–10]. although most case reports suggested an autosomal dominant inheritance with variable penetrance [8–10], the pedigree of the second family may indicate an autosomal recessive inheritance due to the increased number of cases after consanguineous marriage. all affected members of the first and third families had single episodes of bp. the index case and two other members of the second family had recurrent facial palsy whereas the other seven had a single episode of facial palsy. the index case of the fourth family had two episodes of bp whereas the others had single episodes of bp. the index case of the fifthfamily had three episodes whereas the other affected family members had single episodes of bell’s palsy. the index case of the sixthfamily and his elder brother each had two episodes of bell’s palsy. there is no link between the affected families as they come from different parts of the northern state. regarding the gender distribution, familial facial palsy affected only males in the first family; males more than females in the second, third, fourth, and sixth families; and females more doi 10.18502/sjms.v17i1.10690 page 133 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan figure 6: pedigree of the sixth family from the northern state, sudan with familial bell’s palsy affecting five individuals (four male and one female) across three generations. the black arrow shows the index case. (note: the numbers inside the circles and rectangles indicate female and male family members in different generations and their subsequent generations who were unaffected by bell’s palsy.) than males in the fifth family. the index cases of the all six families and other family members with facial palsy who were examined revealed no clinical features suggestive of mrs. genetic testing is pertinent for these families to isolate the implicated genes. our setup and facilities are capable of taking and processing samples of blood or saliva for genetic testing. eight patients from three of the six families living in or around dongola city, the capital of the northern state, with easy access have agreed to perform genetic testing and are ready to give written informed consent for taking their blood or saliva sample for this purpose. ethical approval to perform genetic testing can be obtained from the ethics committee of the state ministry of health. interested individuals or organizations in the field of genetic studies can help us perform genetic testing for these family members. the underlying cause of familial facial palsy is postulated to be either narrow facial canal, leading to easy compression of the facial nerve, or an autoimmune process involving the nerve [10]. treatment details of most patients were not known but some of them received oral prednisolone and physiotherapy. clinical practice guidelines strongly recommend initiation of steroids within 72 hr of the onset of facial palsy as well as doi 10.18502/sjms.v17i1.10690 page 134 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan implementing eye care for those with impaired eye closure [11]. the role of physiotherapy is controversial; many methods were adopted including thermotherapy, electrotherapy, massage and facial exercise with variable outcomes and some with complications [12]. some clinical practice guidelines recommend against physiotherapy [11]. many grading systems were adopted for evaluation of facial nerve function and assessment of severity and response to treatment of facial paralysis [13]. 4. conclusion and recommendations in the six families reported here; 2, 10, 8, 5, 4, and 5 family members, respectively, were affected across different generations presenting with either a single episode or recurrent attacks of bell’s palsy. there are a few case reports in the literature with no previous reports from sudan. further genetic studies are highly recommended to determine the associated genes. we also stress upon the importance of family history in patients with facial palsy. acknowledgements the authors would like to thank all the index cases and other members of the six reported families for their consent as well for sharing the detailed history about the disease in their family members. ethical considerations informed consent was obtained from the index cases and the parents of the index case of the fifth family. any information indicating the identity of the participant such as name, mobile number, or identity documents were excluded for confidentiality purposes. competing interests none. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. doi 10.18502/sjms.v17i1.10690 page 135 sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan funding none. references [1] gilden, d. h. (2004). clinical practice. bell’s palsy. new england journal of medicine, vol. 351, no. 13, pp. 1323–1331. [2] kubik, m., robles, l., and kung, d. (2012). familial bell’s palsy: a case report and literature review. case reports in neurological medicine, vol. 2012, article 674981. [3] mehrjardi, m. y. v., maroofian, r., kalantar, s., et al. (2017). a novel loss-of-function mutation in hoxb1 associated with autosomal recessive hereditary congenital facial palsy in a large iranian family. journal of molecular syndromology, vol. 8, no. 5, pp. 261–265. [4] national organization for rare diseases. (n.d.). melkersson–rosenthal syndrome. retrieved from https://rarediseases.org/rare-diseases/melkersson-rosenthalsyndrome/#:$\sim$:text=melkersson%2drosenthal%20syndrome%20(mrs),the% 20tongue%20(fissured%20tongue) [5] cancian, m., giovannini, s., angelini, a., et al. (2019). melkersson–rosenthal syndrome: a case report of a rare disease with overlapping features. allergy, asthma & clinical immunology, vol. 15, p. 1. [6] abbas, k. e. and prabhu, s. r. (1981) bell’s palsy among sudanese children report of 7 cases and review of literature. journal of oral medicine, vol. 36, no. 4, pp. 111–113. [7] mustafa, a. h. k. and sulaiman, a. m. (2018). the epidemiology and management of bell’s palsy in sudan. open dentistry journal, vol. 12, pp. 827–836. [8] gronhoj larsen, c., gyldenlove, m., jonch, a. e., et al. (2015). a three-generation family with idiopathic facial palsy suggesting an autosomal dominant inheritance with high penetrance. case reports in otolaryngology, vol. 2015, article 683938. [9] parastatidou, s., karakaidos, d., kafalidis, g., et al. (2017). p124 familial bell’s palsy with recurrency. archives of disease in childhood, vol. 102, no. 2, p. a82. [10] quin, d., ouyang, z., and luo, w. (2009). familial recurrent bell’s palsy. neurology india, vol. 57, no. 6, pp. 783–784. [11] baugh, r. f., basura, g. j., ishii, l. e., et al. (2013). clinical practice guideline: bell’s palsy. otolaryngology–head and neck surgery, vol. 149, no. 3, pp. s1–s27. doi 10.18502/sjms.v17i1.10690 page 136 https://rarediseases.org/rare-diseases/melkersson-rosenthal-syndrome/#:$\sim $:text=melkersson%2drosenthal%20syndrome%20(mrs),the%20tongue%20(fissured%20tongue) https://rarediseases.org/rare-diseases/melkersson-rosenthal-syndrome/#:$\sim $:text=melkersson%2drosenthal%20syndrome%20(mrs),the%20tongue%20(fissured%20tongue) https://rarediseases.org/rare-diseases/melkersson-rosenthal-syndrome/#:$\sim $:text=melkersson%2drosenthal%20syndrome%20(mrs),the%20tongue%20(fissured%20tongue) sudan journal of medical sciences mohamed abdelaziz and asma ahmed ziadan [12] peitersen, e. (2002). bell’s palsy: the spontaneous course of 2,500 peripheral facial nerve palsies of different etiologies. acta oto-laryngologica. supplementum, vol. 549, pp. 4–30. [13] samsudin, w. s. w. and sundaral, k. (2013). evaluation and grading systems of facial paralysis for facial rehabilitation. journal of physical therapy science, vol. 25, pp. 515–519. doi 10.18502/sjms.v17i1.10690 page 137 introduction case series first case second case third case fourth case fifth case sixth case discussion conclusion and recommendations acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11453 production and hosting by knowledge e original article eegs findings among adults sudanese subjects presented to the national ribat university makawi a. a. osman1*, elmutaz h. taha1, eldirdiri m. elamin2, and mohammed s. elmagzoub2 1department of physiology, faculty of medicine, university of dongola, dongola, sudan 2department of physiology and neurology, faculty of medicine, the national ribat university, khartoum, sudan orcid: makawi a. a. osman: https://orcid.org/0000-0002-5866-8949 abstract background: epilepsy and seizure are one of the most common serious neurological disorders, and most patients either stop having seizures or less commonly die of them. methods: this retrospective cross-sectional study targeting adult sudanese patients was conducted in the eeg units of the department of physiology, faculty of medicine, and the national ribat university. recordings were obtained from a digital eeg machine (medtronic pl-eeg). the statistical package for social sciences (windows version 15; spss) was used for statistical analysis. the study’s main objective was to determine the percentage of abnormal eegs in adult sudanese epileptic patients who were referred to the ribat eeg unit from march 2007 to september 2010. results: nine hundred and fifty patients were included in this study, abnormal eegs was seen in 54.7%, while it was normal was in 45.3%; primary generalized seizures constituted 45.5%, while focal onset seizures were collectively observed in 43.4%, other types of epilepsy counted for 11.2%. conclusion: this study showed that males were more affected than females, abnormal eeg was maximal in the age group16–30 years. epileptiform seizure discharges decrease with age, generalized seizure discharges were dominated seizure. keywords: eeg, epilepsy, seizure 1. introduction epilepsy is a well-known chronic neurological disorder which is characterized by repeated unprovoked seizures. it is the second most common cause of mental health disability, particularly among young adults. [1,2]. these seizures are transient signs or symptoms due to abnormal, excessive, or synchronous neuronal activity in the brain. about 50 million people worldwide have epilepsy at any given time. epilepsy is usually controlled, but not cured, with medication, although surgery may be considered in difficult cases. however, it is important to note that over 30% of people with epilepsy how to cite this article: makawi a. a. osman, elmutaz h. taha, eldirdiri m. elamin, and mohammed s. elmagzoub (2022) “eegs findings among adults sudanese subjects presented to the national ribat university,” sudan journal of medical sciences, vol. 17, no. 2, pp. 183–191. doi 10.18502/sjms.v17i2.11453 page 183 corresponding author: makawi a. a. osman; email: mabairub80@gmail.com received 16 june 2020 accepted 7 may 2022 published 30 june 2022 production and hosting by knowledge e makawi a. a. osman et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mabairub80@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences makawi a. a. osman et al. do not have seizure control even with the best available medications. not all epilepsy syndromes are lifelong, some forms are confined to particular stages of childhood. epilepsy should not be understood as a single disorder, but rather as a group of syndromes with vastly divergent symptoms but all involving episodic abnormal electrical activity in the brain [1].approximately 2 million persons in the united states have epilepsy, and 3% of the general population will have epilepsy at some time in their lives [4].in recent years, important advances have been made in the diagnosis and treatment of seizure disorders [5].however, understanding of the cellular and molecular mechanisms by which epilepsy develops, or epileptogenesis, is still incomplete [6]. 1.1. electroencephalography (eeg) electroencephalography (eeg) is the measurement of electrical activity produced by brain as recorded from electrode placed on the scalp. scalp eeg measures the summed activity of post-synaptic currents. although post-synaptic potentials generate the eeg signal, it is not possible for a scalp eeg to determine the activity within a single dendrite or neuron. rather, a surface eeg reading is the summation of the synchronous activity of thousands of neurons that have similar spatial orientation, radial to the scalp. scalp eeg activity oscillates at multiple frequencies having different characteristic spatial distributions associated with different states of brain functioning such as waking and sleeping. these oscillations represent synchronized activity over a network of neurons [7]. 1.2. normal eeg waves delta waves have a frequency of up to 3 hz. they tend to be the highest in amplitude and the slowest waves. they are seen normally in adults in slow wave sleep. they are also seen normally in babies [8]. theta waves have a frequency range of 4 to 7 hz. they are seen normally in young children. they may be seen in drowsiness or arousal in older children and adults. excess theta for age represents abnormal activity [8].alpha waves have a frequency range of 8 to 12 hz. hans berger named the first rhythmic eeg activity as the “alpha wave,” seen in the 8–12 hz range in the posterior regions of the head on both sides, being higher in amplitude on the dominant side. it is brought out through relaxation and eye closure [9]. beta waves have a frequency range of 12–30 hz. they are seen usually on both sides in symmetrical distribution and are most evident doi 10.18502/sjms.v17i2.11453 page 184 sudan journal of medical sciences makawi a. a. osman et al. frontally. low amplitude beta with multiple and varying frequencies is often associated with active, busy, or anxious thinking and active concentration [9]. 2. materials and methods 2.1. subjects the study population included adult sudanese patients referred to the eeg unit of the department of physiology, faculty of medicine, national ribat university from march 2007 to september 2010. the patients (aged 16 year or older) were referred from by general practitioners and neurologists, as well as the accidents and emergency departments. 2.2. methodology all patients underwent interictal eeg examination, with both wake and sleep tracings using digital eeg machine (medtronic pl-eeg). 2.3. montages of eeg recording bipolar montage was used. each channel (i.e., waveform) represents the difference between two adjacent electrodes. the entire montage consists of a series of these channels. however, in referential montage, each channel represents the difference between a certain electrode and a designated reference electrode. 2.4. stimulating methods different stimulation methods have been used. (i) hyperventilation: patients were asked to hyperventilate for about 3–5 min, this process stimulates the brain tissues already excited by the effect of hypocapnia and alkalosis. (ii) photic stimulation: repetitive flashes of light were delivered at different rate; the routine photic stimulation started with three flashes per second and ended with thirty flashes per second for 4 min. in the sleep recording, sleep was induced in adults by diazepam in a dose of 10–20 mg i.v. chloral hydrate, which is less effective than diazepam, was used for children at a concentration of 20–40 mg/kg. the eeg recording was performed by a neurophysiologist expertise doi 10.18502/sjms.v17i2.11453 page 185 sudan journal of medical sciences makawi a. a. osman et al. technician in the neurophysiology lab of the national ribat university, and all reports were reviewed by the neurologist and neurophysiologist in the national ribat university. 2.5. exclusion criteria patients below the age of 16 years and psychotic patients were excluded from this study. 3. results 3.1. gender distribution among patients with abnormal eegs this retrospective study included a total of 950 (473 male and 477 female) adult sudanese patients referred to the eeg unit of the department of physiology, faculty of medicine, university of ribat. our study showed that 54.7% of the study population had abnormal eegs, while 45.3% had normal eegs. the effect of gender on abnormal eeg revealed a considerable difference – 63.1% (328 male) versus 36.9% (192 female) (tables 1 & 2). table 1: age distribution among patients with abnormal eegs in the total study group. age (yr) number of participants percentage 16–30 304 58.5 31–45 108 20.8 46–60 59 11.4 61–75 32 6 76–90 15 2.9 91–100 2 0.4 total 520 100 table 2: sex distribution among patients with abnormal eegs in the total study group. age (male) no. of patients percentage age (female) no. of patients percentage 16–35 230 70.2 16–35 128 66.7 36–55 55 16.7 36–55 33 17.2 56–75 35 10.7 56–75 22 11.5 76–100 8 2.4 76–100 9 4.6 total 328 100 total 192 100 doi 10.18502/sjms.v17i2.11453 page 186 sudan journal of medical sciences makawi a. a. osman et al. 3.2. abnormal eegs highly distributed between younger age patients within the total study group most abnormal eegs were maximal in patients aged 16–30 years (58.5%) in the abnormal group (table 1). this was true for both age groups. it was evident that there were no gender differences, and epileptiform discharges taper with age; still abnormal eeg tends to decrease with age in males (70.2%) as maximum percentage lie in the age group 16–35 years, compared to females (66.7%) (table 2). 3.3. distribution of presenting features in the total abnormal group patients were mainly referred by neurologists and general physicians as having or possibly having epilepsy. hence, according to history and clinical notes of referral for eeg, convulsions (focal or/and generalized) mounted to 57.69%, loss of consciousness (loc) 39.4%, headache 18.3.%, and head trauma 12.7% of the total number of study population with no significant difference between genders (figure 1). figure 1: distribution of presenting features in the total abnormal group. 3.4. the effect of sex on the presenting features in patient with abnormal eegs out of the total abnormal eegs, convulsion was distributed according to gender as follows: 60% (116) in female and 56.1% (184) in men, whereas, loc was distributed as doi 10.18502/sjms.v17i2.11453 page 187 sudan journal of medical sciences makawi a. a. osman et al. 39.6% (76) in female and 39.3% (129) in male. headache was presented as 20.8% (40) in female and 17.1% (56) in male. head trauma in females was 18.6% (28) and in males 11.6% (38). table 3: percentage of presenting features in patient with abnormal eegs. (a) male convulsion loc headache head trauma number of patients % number of patients % number of patients % number of patients % yes no 184 144 56.1 43.9 129 199 39.3 60.7 56 272 17.1 82.9 38 290 11.6 88.4 total 328 100.0 328 100.0 328 100.0 328 100.0 (b) female convulsion loc headache head trauma number of patients % number of patients % number of patients % number of patients % yes no 116 76 60.4 39.6 76 116 39.6 60.4 40 152 20.8 79.2 28 164 14.6 85.4 total 192 100.0 192 100.0 192 100.0 192 100.0 3.5. distribution of epileptiform discharges in the study population with abnormal eegs according to the types of epileptiform discharges encountered in the study group with abnormal eegs, primary generalized epileptiform discharges come at the top of the list with a percentage of(45.5%, this was followed by partial epileptiform discharge; frontally initiated (18.8%), centrally initiated (11.3%), temporally initiated (8.3%), posterior or occipitally initiated (5%), frontal intermittent rhythmic delta activity (firda) discharges (6.3%), myoclonic (2.5%), and others (2.3%) (figure 2). 4. discussion our results show that the percentage of abnormal eegs in the study population was 54.7%. these findings are similar to those reported in sudan and worldwide literature [10, 11]and were distributed as 63.1% and 36.9% in male and female, respectively, which matches with the findings of ahmed et al. [12]. the less stigma associated with epilepsy in male could be the reason for higher male cases reported in hospitals [11]. moreover, this study revealed that abnormal eeg distribution tends to decrease with age, 58.5% of abnormal eegs occurred in patients aged between 16 and 30 years, however, this percentage was only 3.3% in the age group 76–100 years. doi 10.18502/sjms.v17i2.11453 page 188 sudan journal of medical sciences makawi a. a. osman et al. figure 2: distribution of epileptiform discharges in the study population with abnormal eegs. the study also showed that the epileptiform discharge subtyping was predominated by primary generalized epileptiform discharges (45.5%) followed by frontally (18.8%), centrally (11.3%), temporally (8.3%), firda (6.3%), occipitally (5.0%) initiated epileptiform discharges, juvenile myoclonic epilepsy (jme) (2.5%), and others (2.3%). in this study, subtyping of epileptic patients was based on clinical presentation and eeg findings. primary generalized epileptiform discharges were found to be the most dominant disorder. it was 45.5% in the total study population, which is in accordance of hussein et al. [13]with minimal gender difference – 43.3% in males versus 49.4% in females. they showed that primary generalized epileptiform discharges had an incidence of 39–59% of their cases. partial epileptiform discharges were found to be 32–52%. while in this study, the partial epileptiform discharges collectively was seen in 43.4%, it was slightly less than safranski et al.’s [14]focal onset epileptiform discharges (57.3%). 5. conclusion finally, this study showed that males were more affected than females. the age group 16–30 years were more affected (58.5%). epileptiform discharges decrease with age. generalized epileptiform discharges were dominated (45%). doi 10.18502/sjms.v17i2.11453 page 189 sudan journal of medical sciences makawi a. a. osman et al. 6. recommendations since jme is misdiagnosed worldwide and as shown in this study, we recommend that full history must be taken by doctors, and a series of eeg recordings must be performed. acknowledgements the authors acknowledge the support of medical recording staff in the eeg unit of the national ribat university for their participation and great help in this work. ethical considerations the data of this work has been taken from the eeg file records. the authors took the permission from the department of physiology, faculty of medicine, national ribat university. competing interests the authors declare that there is no conflict of interest in this work. funding none received. references [1] murray, c. j., lopez, a. d., and jamison, d. t. (1994). the global burden of disease in summary results, sensitivity analysis and future directions. bulletin of the world health organization, vol. 72, pp. 495–509. [2] blume, w., lüders, h., mizrahi, e., et al. (2001). glossary of descriptive terminology for ictal semiology: report of the ilae task force on classification and terminology. epilepsia, vol. 42, no. 9, pp. 1212–1218. [3] fisher, r., van emde boas, w., blume, w., et al. (2005). epileptic seizures and epilepsy: definitions proposed by the international league against epilepsy (ilae) and the international bureau for epilepsy (ibe). epilepsia, vol. 46, no. 4, pp. 470–472. doi 10.18502/sjms.v17i2.11453 page 190 sudan journal of medical sciences makawi a. a. osman et al. [4] annegers, j. f. and wyllie, e. (2001). the epidemiology of epilepsy. in the treatment of epilepsy: principles and practice (3𝑟𝑑 ed., pp. 131–138). philadelphia: lippincott williams & wilkins. [5] schachter, s. c. (2001). epilepsy. neurologic clinics, vol. 19, pp. 57–78. [6] chang, b. s. and lowenstein, d. h. (2003). epilepsy. the new england journal of medicine, vol. 349, pp. 1257–1266. [7] epstein, c. m. and andriola, j. b. (1986). introduction to eeg and evoked potentials. j.b. lippincot co. [8] aurlien, h., gjerde, i. o., aarseth, j. h., et al. (2004). eeg background activity described by a large computerized database. clinical neurophysiology, vol. 115, pp. 665–673. [9] ruffini, g., dunne, s., fuentemilla, l., et al. (2007). first human trials of a dry electrophysiology sensor using a carbon nanotube array interface. retrieved from: https://arxiv.org/abs/physics/0701159v1 [10] blume, w. t., holloway, g. m., masako, k. g., et al. (2005). typical paroxysmal abnormalities in eeg records of epileptic patients. eplepsia, vol. 11, pp. 361–381. [11] engel, j., pedley, t. a., and aicardi, j. (1990). inerictal spike discharge in adults with epilepsy. electroencephalography and clinical neurophysiology, vol. 75, pp. 358–360. [12] ahmed, e. e. m., hussein, a., and musa, a. a. (2008). the electroencephalogram (eeg) in the diagnosis of epileptiform disorders in sudanese patients. khartoum medical journal, vol. 1, no. 1, pp. 12–14. [13] hussein, a., eltahir, a., yasin, f., et al. (2007). clinical presentation of epilepsy among adult sudanese epileptic patients. sudan journal of medical sciences, vol. 2, p. 1. [14] szaflarski, j. p., rackley, a. y., lindsell, c. j., et al. (2008). seizure control in patients with epilepsy: the physician vs. medication factors. bmc health services research, vol. 8, pp. 257–264. doi 10.18502/sjms.v17i2.11453 page 191 introduction electroencephalography (eeg) normal eeg waves materials and methods subjects methodology montages of eeg recording stimulating methods exclusion criteria results gender distribution among patients with abnormal eegs abnormal eegs highly distributed between younger agepatients within the total study group distribution of presenting features in the total abnormal group the effect of sex on the presenting features in patient with abnormal eegs distribution of epileptiform discharges in the study population with abnormal eegs discussion conclusion recommendations acknowledgements ethical considerations competing interests funding references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10686 production and hosting by knowledge e original article recent update on serum alkaline and acid phosphatases in preand postoperative breast cancer patients stalinjit singh1,2, sudershan kapoor3, mukesh chander4, and prabhjot kaur gill5* 1phd scholar, centre for interdisciplinary biomedical research, adesh university, bathinda, punjab, india 2assistant professor, department of medical lab sciences, khalsa college amritsar, punjab, india 3professor & head, department of surgery, government medical college & hospital, amritsar, punjab, india 4assistant professor, department of biotechnology, khalsa college, amritsar, punjab, india 5professor, biomedical research, sri guru ram das university of health sciences, amritsar, india orcid: prabhjot gill: https://orcid.org/0000-0003-1598-8448 abstract background: breast carcinoma in females is an ever-growing malaise with significant mortality and morbidity. in resource-poor settings, the need for a cost-effective and reliable diagnostic tool is of utmost importance. methods: in the present study, 54 histopathologically proven breast cancer patients were investigated for their preand postoperative serum alp and acp levels. results: a total of 34 cases (belonging to the age interval of 40–60 years) exhibited a significant drop in serum alp level after surgery (p = 0.002). although the serum acp also showed a postoperative decline, it was not as significant as that of serum alp. conclusion: the role of serum alp and acp in the diagnosis, prognosis, and monitoring/surveillance of breast carcinoma cannot be underestimated particularly in third-world countries lacking in medical infrastructure or resource-poor settings. keywords: alkaline phosphatase, acid phosphatase, breast cancer, malignancy 1. introduction alkaline phosphatase (alp) and acid phosphatase (acp) are hydrolase enzymes that are active under alkaline and acidic conditions, respectively. they chemically remove the phosphate group from the nucleotides and proteins [1]. growing children have a comparatively higher levels of serum alp due to active bone formation and growth. similarly, males have higher serum alp level as compared to females, while the difference is neutralized after the age of 60. in females, the serum alp is elevated during puberty, pregnancy, lactation, and menopause, which is purely physiological [2]. whereas, acp is prominently synthesized by the liver, bone marrow, prostate, and how to cite this article: stalinjit singh, sudershan kapoor, mukesh chander, and prabhjot kaur gill* (2022) “recent update on serum alkaline and acid phosphatases in preand postoperative breast cancer patients,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 70–78. doi 10.18502/sjms.v17i1.10686 page 70 corresponding author: prabhjot kaur gill; email: pjkgill@rediffmail.com received 17 january 2021 accepted 07 march 2022 published 31 march 2022 production and hosting by knowledge e stalinjit singh et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:pjkgill@rediffmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences stalinjit singh et al. spleen. however, at the same time, the pathological basis of serum alp elevation also cannot be ruled out, which can be indicative of multi-factorial etiology involving infection of the bone (osteomyelitis), autoimmune disorders (rheumatoid arthritis), ckd (chronic kidney disease), and malignancy [3]. the pathological basis of elevated serum alp and acp levels can be associated with infection, inflammation, and infiltration. serum alp is the most reliable tumor marker among others like serum acp, lactose dehydrogenase (ldh), calcium, and serum amyloid-a protein (saa) in breast carcinoma [4]. serum alp estimation is a cost-effective and reliable diagnostic tool in breast cancer, particularly in third-world countries that lack the infrastructure for the modern-day diagnosis of breast cancer [4]. the serum alp level is known to rise proportionally with the advancing stage in breast cancer [5]. breast carcinoma, like other types of malignancies, is a cumulative outcome of multiple predisposing factors which interactively initiate carcinogenesis. the prevalence of breast carcinoma increases with advancing age, particularly post-menopausal females are more prone to malignancy. cessation of a menstrual cycle is followed by altered biochemistry of female sex hormones and hence increased risk of breast carcinoma [6]. the clinical presentation of breast cancer includes multiple symptoms, which are often ignored by patients leading to the delay in medical intervention which resulted in mortality and morbidity related to the disease [7]. in the absence of metastatic spread, the surgical resection of the tumor can normalize the elevated serum alp level in breast cancer patients, thereby indicating a good prognosis [8]. there are numerous missing links in the studies regarding variation in the level of serum alp and acp in breast carcinoma. the underlying cause of elevated alp and acp levels needs to be investigated thoroughly to diagnose the malignancy in its early stage. the real-time use of serum alp and acp as a diagnostic and prognostic tool is possible only if the knowledge gaps and missing links are well understood and worked upon. therefore, the present study investigates the role of serum alp and acp pre and post operative surgery in breast cancer patients. 2. materials and methods all protocols, procedures, and instrumentation were standardized according to the setting in the department of medical laboratory sciences, khalsa college of pharmacy and technology, amritsar. doi 10.18502/sjms.v17i1.10686 page 71 sudan journal of medical sciences stalinjit singh et al. 2.1. permission the study was approved by the doctoral advisory committee, institutional research committee, and institutional ethics committee of adesh university, bathinda. permission was granted by the competent authority of government medical college and hospital (gmc&h), amritsar for the collection of blood samples of breast cancer patients from july 2017 to july 2018. the inclusion criteria for this study were: female patients with histopathologically proven malignancy breast cancer, patients with diverse demography (rural/urban) and socioeconomic status, nonpregnant female subjects, patients without autoimmune disorders (rheumatoid arthritis) and bone infections (osteomyelitis), aged >20 years, having no liver disease (cirrhosis), chronic kidney disease and hemodialysis, and mentally fit to provide informed consent and relevant information related to the disease. 2.2. sample collection fasting 2 ml of blood was drawn by venipuncture under aseptic conditions before and after the surgery (pre and postoperatively) after written informed consent was obtained from the breast cancer patients. the needles and syringes were discarded according to the protocol for biomedical waste management. 2.3. transportation blood samples were immediately transported (with 4ºc temperature maintained in a cool box) to the clinical laboratory for further processing. 2.4. enzyme assay blood samples were centrifuged at 2500 rpm for 15 min to obtain serum. p-nitrophenyl phosphate kits for serum alp and serum acp were used to measure serum alp and acp on a semi-automated analyzer (erba chem 5 plus v2). absorbance readings were taken at 405 nm wavelength with temperature maintained at 37ºc. the manufacturer’s guidelines were followed throughout the procedure. readings were reported in iu/l. doi 10.18502/sjms.v17i1.10686 page 72 sudan journal of medical sciences stalinjit singh et al. 2.5. statistical analysis all necessary analysis was done using ms-excel 2007. the means or frequencies of patient demographics were interpreted. the variation between pre and postoperative values of both serum alp and acp was analyzed by using unpaired t-test. p-value ≤ 0.05 was considered statistically significant. 3. results and discussion the present study reported 54 breast cancer patients registered at government medical college and hospital (gmc&h), amritsar. according to the age interval, the participants were divided into different age groups (table 1). among them, the most affected age group was 40–49 years (37%) followed by 50–59 years (26%). similar results were reported by the american cancer society, indian cancer society, and ncbi. whereas, anders et al [9] reported the incidence of early onset of breast cancer in females. in the current study, early onset of malignancy (12.96%) related to the age interval of 30– 39 years had been reported. data reported by ncbi and nih (2019) reveals that 11% of breast cancer cases occur in women <40 years of age. the early onset of breast carcinoma among young females is alarming and ever-increasing. predisposing risk factors are prolonged use of oral contraceptives, high animal fat intake, and low bmi in premenopausal females [10], whereas non-modifiable risk factors include familial predisposition and gene mutations [11]. in the present study, familial predisposition cases (7.4%) belonged to the age interval of 50–59 years (table 1). rural and urban distribution of patients in the current study was found to be 64.82% and 35.18%, respectively. according to the world bank collection of development indicators (2018), 65.97% of the indian population resides in the rural belt. also, it is the rural population which owing to their low socioeconomic status visits exclusively government hospitals for treatment. in total, 54 cases were confirmed for the malignancy (malignant breast lesions) as supported by fnac findings. of them, 19 subjects were confirmed with stage ii, whereas the remaining 35 had stage-iii presentation. furthermore, all of the stage-iii patients were identified with axillary lymphadenopathy (table 2). out of the 54 confirmed malignant cases, 44 had a painless lump (81.48%), while 10 had a painful lump (18.51%). a painless lump is a more common clinical feature among breast carcinoma patients [12]. further, in the current study, ulceration of skin over the lump (18.51%) was also reported. breast cancer with skin ulceration is considered a locally advanced disease [13]. the finding of skin ulceration as a symptom of locally advanced doi 10.18502/sjms.v17i1.10686 page 73 sudan journal of medical sciences stalinjit singh et al. table 1: demographics of breast carcinoma patients. age interval (yr) n = 54 percentage 30–39 07 12.96% 40–49 20 37.03% 50–59 14 25.92% 60–69 07 12.96% 70–79 06 11.11% rural 35 64.82 % urban 19 35.18% familial predisposition 04 7.40% table 2: distribution of breast cancer patients according to their symptoms. clinical symptoms no. of patients percentage stage (tnm) ii 19 35.18% iii 35 64.81% axillary lymphadenopathy 35 64.81% lump painless 44 81.48% painful 10 18.51% ulceration of skin over lump 10 18.51% skin changes (skin texture changes) of the breast involved 09 16.66% nipple discharge 08 14.81% weight loss 05 09.25% anorexia 07 12.96% malignant lesions 54 90.0% benign lesions 06 10.0% malignant + benign lesions 60 100% 0 50 100 150 200 250 300 350 400 30 35 39 39 40 43 44 44 45 45 45 47 48 49 50 50 50 51 54 55 57 62 65 66 70 72 75 s e r u m a l p i u / l age(years) pre operative post operatrive figure 1: preand postoperative serum alkaline phosphatase levels in different age groups of breast carcinoma. breast carcinoma and inflammatory breast cancer is a deciding factor for early diagnosis and the choice of treatment and its outcome. the breast skin changes were observed in 16.66% of cases whereas 14.81% of patients reported nipple discharge after skin changes in the breast. as reported earlier, nipple discharge is a characteristic feature of ductal carcinoma in situ ranging from 2% to 13% in clinical presentation [14]. the typical symptoms of breast carcinoma like a lump, ulceration, and pigmentation of skin over doi 10.18502/sjms.v17i1.10686 page 74 sudan journal of medical sciences stalinjit singh et al. table 3: comparison of pre and postoperative levels of serum alp and acp in different age groups of breast carcinoma. breast carcinoma alp iu/l acp iu/l age (yr) no. of cases mean ± sd p-value no. of cases mean ± sd pvalue 30–39 preoperative 07 202.02 ± 66.16 0.0841 07 0.70 ± 0.07 0.1064 postoperative 147.71 ± 37.97 0.62 ± 0.07 40–49 preoperative 20 207.24 ± 63.61 0.0029 20 0.72 ± 0.13 0.0812 postoperative 151.79 ± 44.98 0.65 ± 0.11 50–59 preoperative 14 201.46 ± 50.36 0.002 14 0.72 ±0.11 0.2249 postoperative 145.81 ± 34.02 0.67 ± 0.10 60–69 preoperative 07 184.32 ± 50.57 0.091 07 0.76 ± 0.32 0.620 postoperative 142.17 ± 33.61 0.69 ± 0.21 70–79 preoperative 06 174.22 ± 74.46 0.4868 06 0.66 ± 0.12 0.6577 postoperative 148.0 ± 48.72 0.62 ± 0.12 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 30 35 39 39 40 43 44 44 45 45 45 47 48 49 50 50 50 51 54 55 57 62 65 66 70 72 75 s e r u m a c p i u / l age(years) pre operative figure 2: preand postoperative serum acid phosphatase levels in different age groups of breast carcinoma. the lump, nipple discharge, and lymphadenopathy (axillary or generalized) have been reported in many studies related to breast cancer with minor variation in their distribution (ncbi, american cancer society). henceforth, weight loss in breast carcinoma can be attributed to the stage of cancer, (as the stage advances, the nutritional demand of cancer cells increases as is the cancer load) and the psychological stress related to malignancy and anorexia. therefore, the current study reported five cases with significant weight loss (>10% of body weight) accounting for 9.25% of breast cancer patients (table 2). in addition, loss of appetite (anorexia) was reported in seven patients (12.96%). both weight loss and anorexia resulted to be the outcome of psychological doi 10.18502/sjms.v17i1.10686 page 75 sudan journal of medical sciences stalinjit singh et al. stress related to cancer, altered biochemistry, the nutritional burden of caner load, and diminished taste and smell perceptions [15]. comparison of pre and postoperative levels of serum alp and acp was undertaken statistically to find any significant variation. the age group 40–49 years (n = 20) exhibited a statistically significant drop (postoperatively) in the level of serum alp from 207.24 ± 63.61 to 151.79 ± 44.98 (p = 0.002) (table 3, figure 1). however, the drop for serum acp was from 0.729 ± 0.137 to 0.657 ± 0.117 (table 3, figure 2). the age group 50–59 years (n = 14) also exhibited a statistically significant difference (p = 0.002) for the decline in postoperative serum alp level from 201.46 ± 50.36 to 145.81 ± 34.02, thus reinforcing the use of serum alp as a cost-effective tumor marker in breast carcinoma in poor resource settings [16]. serum acp levels in pre and postoperative cases in age groups 40–49 and 50–59 years showed a statistically insignificant drop from 0.72 to 0.65–0.67 iu/l with p-values 0.081 and 0.224, respectively (table 3). the maximum number of patients (20 + 14 = 34) showing a significant drop in serum alp levels postoperatively belonged to the age group 40–60 years, which had the largest number of cases. similarly, a significant drop in serum alp postoperatively in all stages has been reported earlier [8]. 4. conclusion the most common symptom of breast cancer is a lump or mass in the breast, which in most cases is painless. other findings are axillary lymphadenopathy, nipple discharge, ulceration of skin over the lump, and changes in the skin texture of the breast involved. the role of serum alp and acp as tumor markers has its advantages in resource-poor settings. furthermore, the high prevalence of breast carcinoma among females of developing countries reinforces the use of serum alp and acp as cancer markers in resource-poor settings. therefore, studies will be required to establish the value of serum alp to predict the prognosis, diagnosis, and monitoring of breast cancer. acknowledgements nil. doi 10.18502/sjms.v17i1.10686 page 76 sudan journal of medical sciences stalinjit singh et al. ethical considerations the current study was approved by the institutional ethics committee of the government medical college, amritsar (code no. gmciec00104). competing interests there are no conflicts of interest. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding there is no funding source. references [1] buchet, r., millán, j. l., and magne, d. 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(2004). studies of biochemical parameters in breast cancer with and without metastasis. indian journal of clinical biochemistry, vol. 19, no. 1, pp. 71–75. doi 10.18502/sjms.v17i1.10686 page 78 introduction materials and methods permission sample collection transportation enzyme assay statistical analysis results and discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12548 production and hosting by knowledge e research article efficacy and safety of warfarin therapy: comparison between specialized inr clinic and general medical clinic osman elsayed osman1, rabeea ibrahim haroun ismail2, rayan khalid3, and imad fadl-elmula4* 1department of medicine, faculty of medicine, al neelain university, khartoum, sudan 2department of cardiology, ahmed gasim specialized hospital, khartoum, sudan 3department of physiology, assafa college, khartoum, sudan 4department of clinical genetics, assafa college, khartoum, sudan orcid: imad fadl-elmula: https://orcid.org/0000-0003-3191-9485 abstract background: although warfarin is known as effective oral anticoagulant to prevent thromboembolic events, its’ narrow therapeutic index requires ambient and good follow-up to reduce its therapeutic complications. there is a continuous debate whether the best practice to accomplish this goal is in a specialized international normalized ratio clinic (inr-c) or in a general medical clinic (general-c). few, if any, studies have been done in sudan to compare the safety and efficacy of anticoagulant therapy in those clinics. thus, the objective of this study was to compare the efficacy and safety of anticoagulant therapy in inr-c and in general-c. methods: this is a prospective hospital-based study where 200 patients were divided into two groups (group a and b) of 100 patients. group a were in the inr-c at ahmed gasim specialized hospital and group b in the general-cat al-shaab teaching hospital. the study was conducted from september 2019 to april 2020. all patients were on warfarin treatment and regular follow-ups were conducted. demographic and clinical data were collected and analyzed statistically using spss version 20. ethical approval was obtained from the ethical committee of the sudanese medical specialization board (smsb). results: of the 200 patients, 118/59% were females and 82/41% were males. target international normalized ratio (inr) for group (a) was achieved in 56% of the patients in the first visit, increased to 63% in the second visit, and 75% in the third follow-up, compared with 24% of the patients from group (b) in the initial and second follow-up visit, to 43% in the third visit (p value=0.05). knowledge about drug and food interaction of coagulation agents was higher (91%) among patients in group (a) compared with group (b) (56%). drug interaction awareness was found in 89% of the patients in group (a) compared with only 40% in group (b) (p value=0.05). major bleeding was reported in 2% and 14% of the patients of group (a) and (b) respectively, whereas minor bleeding was seen in 4% of group (a) and 11% of group (b). conclusion: the study showed that inr-c is more efficient and safer for patients on regular warfarin therapy compared with the general-c. keywords: specialized inr clinic, anticoagulant therapy, warfarin how to cite this article: osman elsayed osman, rabeea ibrahim haroun ismail, rayan khalid, and imad fadl-elmula* (2022) “efficacy and safety of warfarin therapy: comparison between specialized inr clinic and general medical clinic,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 476–484. doi 10.18502/sjms.v17i4.12548 page 476 corresponding author: imad fadl-elmula; email: dean@assafa.edu.sd received 6 june 2021 accepted 7 february 2022 published 31 december 2022 production and hosting by knowledge e osman elsayed osman et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12548&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences osman elsayed osman et al 1. introduction warfarin is an oral anticoagulant frequently used to control and prevent thromboembolic disorders [1]. due to the diverse genetic profile of humans, the anticoagulant effect of warfarin must be monitored based on the international normalized ratio (inr) to ensure an accurate and safe dose of warfarin that is within the therapeutic range for each patient [2]. for the purposes of follow-up of patients on warfarin therapy, some authors favor specialized international normalized ratio clinics (inr-c) whereas others argue in favor of general medical clinics (general-c) that may very well achieve similar therapeutic outcomes [3,4]. the anticoagulant thrombosis center has high clinical and laboratory expertise which provides diagnosis, treatment, and follow-up of patients with thromboembolic events [5]. to achieve these goals, such clinics must provide patients with individualized anticoagulation education, management, and close followup to ensure that their inr values remain within the therapeutic goals by maintaining a therapeutic range (ttr) at or above 70% that is associated with clinical benefit in terms of efficacy and safety [6]. 2. material and methods this study is a cross-sectional prospective hospital-based study that includes 200 patients, all on warfarin therapy. of those, 100 patients were recruited from the inr-c at ahmed gasim specialized hospital (group a), and the remaining 100 patients were from general-c at al-shaab teaching hospital (group b), from september 2019 to april 2020. the demographic and clinical data including inr was collected using a predesigned questionnaire. the ethical approval was obtained from the ethical committee of the sudanese medical specialization board (smsb). the data were analyzed using spss program version 20 and the results were expressed as mean +/the standard deviation. frequency count was done on the data and the result was reported as a percentage. the results were considered statistically significant if the p value< 0.05. 3. results the results of both groups revealed that 118 (59%) of the patients were females and 82 (41%) were males of which 32% were >60 years of age, 23% were between 50–60 years, 18.5% were between 40–49 years, and 26.5% were aged less than 40 years. doi 10.18502/sjms.v17i4.12548 page 477 sudan journal of medical sciences osman elsayed osman et al the results also showed that 119 (59.5%) patients were the inhabitants of khartoum state, 40 (20%) patients were from central states, 24 (12%) patients were from western states, 13 (6.5%) patients from eastern states, and only 4 (2%) patients were from western states. of the 200 patients included in the study, 144/72% were unemployed, 28/14% worked in manual labor, 14/7% were governmental employees, and 14/7% were from the private sector. the indications for warfarin therapy of the patients of group (a) were mechanical heart valve replacement in 47%, atrial fibrillation in 28%, rheumatic heart disease in 13%, cardiomyopathy in 8%, pulmonary embolism in 3%, and deep vein thromboembolism in 1%. these indications were assigned for 17%, 29%, 31%, 17%, 3%, 4%, and 0% of the patients in group (b) respectively (p value=0.05: statistically significant difference). almost all patients (98%) from ahmed gasim specialized hospital were lifelong users of warfarin compared with (85%) of the patients at al-shaab teaching hospital. the frequency of follow-up was monthly for 89% of the patients, weekly for 9%, and yearly for 2% of the patients in group (a) compared to 86%, 14%, and 0% of the patients in group (b) respectively (p value < 0.05: statistically significant difference). patient’s knowledge about warfarin/food and warfarin/other medications interaction was reported by 91% and 89% of the patients in group (a) compared to 65% and 40% of the patients in group (b) respectively (p value < 0.05: statistically significant difference) (table 1). table 1: the level of knowledge in inr-c (group a) and general-c (group b). group a b knowledge about drug diet interaction yes 91 65 no 9 35 knowledge about medications that should not be used yes 89 40 no 11 60 p value = 0.014 < 0.05 significant major bleeding was reported in 2% of the patients attending the inr-c (group a), whereas 4% experienced minor bleeding. for those attending general-c (group b) 14% reported major bleeding and 11% experienced minor bleeding (table 2). first, second, and third inr targets were reached in 56%, 63%, and 75% of the patients attending inr-c (group a), compared with 24%, 24%, and 43% of patients attending doi 10.18502/sjms.v17i4.12548 page 478 sudan journal of medical sciences osman elsayed osman et al table 2: the complications and management percent of warfarin therapy in patients on regular follow up in inr-c (group a) and general-c (group b). complications during treatment group a b no complication seen 94 75 major bleeding (hospital attendance) 2 14 minor bleeding (no attendance) 4 11 measures required for patients no measures needed 0 14 managed at outpatient 2 6 admitted to hospital 4 5 management of complications observation 4 16 vitamin k 2 5 fresh frozen plasma 0 2 blood transfusion 0 2 possible risk factors for complications full compliance this is not a risk factor 94 75 no compliance 6 10 stopped medications 0 15 p value = 0.012 < 0.05 significant general-c (group b) respectively (p value < 0.05: statistically significant difference) (table 3). table 3: time in therapeutic range (ttr) measurements in inr-c (group a) and general-c (group b). ttr measurements group a b first visit below target 38 59 within target range 56 24 above target 6 17 second visit below target 30 56 within target range 63 24 above target 7 20 third visit below target 21 45 within target range 75 43 above target 4 12 p value = 0.025 > 0.05 significant doi 10.18502/sjms.v17i4.12548 page 479 sudan journal of medical sciences osman elsayed osman et al 4. discussion although new-generation oral anticoagulants are increasingly being introduced, warfarin remains the best choice for patients with mechanical prosthetic valves and valvular af, especially in developing countries in which the incidence of rheumatic heart disease remains high; thus, valvular af (atrial fibrillation) is a serious health problem in many developing countries including sudan [7]. the present study showed, as have many other studies, the crucial role of inr-c not only in the control of ttr but also in reducing the incidence of major and minor bleeding, increasing drug interaction knowledge among patients, and finally, better patients compliance among those attending inr-c (group a) [8]. inr monitoring can be performed in hospitals, general outpatient clinics, and specialized inr outpatient clinics. in addition to that it can be self-monitored in selective cases [9]. several studies revealed that a vast majority of thromboembolic and bleeding events happened once the inr is outside the therapeutic range that is, higher inr increases the risk of bleeding, whereas lower inr increases the risk of thromboembolism [10]. our results showed lower mean ttr in patients with major events (bleeding and ischemic events) compared with those with no major events. moreover, we have shown that the type of follow-up clinic is an independent predictor of major events. according to our knowledge, this is the first ever study in sudan that compared the warfarin patient’s follow-up in inr-c and general-c. the results suggested that patients attending inr-c had higher ttr levels and decreased bleeding and ischemia events rates. thus, by increasing the number of inr-c in sudan, we can ensure a good quality of warfarin follow-up and reduced morbidity. it was very important to assess and compare the level of the drug interaction knowledge provided by the two clinics (inr-c and the general-c clinic), especially in developing countries where most of the patients are semiliterate. for such patients, one may expect low compliance to warfarin that may lead to significant complications [11,12]. the results of the present study showed clearly that patients attending inr-c were more knowledgeable about coagulation drugs interaction with food and with other medications compared with patients attending general-c (p value<0.05: statistically significant difference). moreover, patients’ good compliance that is, attending followups was seen in the inr-c in contrast to poor compliance in the general-c [13]. doi 10.18502/sjms.v17i4.12548 page 480 sudan journal of medical sciences osman elsayed osman et al although major and minor bleeding were reported in both clinics, yet they were far less in patients attending the inr-c. similar to previous studies, it was shown that the only common side effect of warfarin is bleeding [14,15]. in this study, the measures done for patients with complications in group (a) were admission to the hospital 4(66.6%) and management as outpatients 2(33.4%), while in group (b) no measure was taken in 14 cases (56%), management at outpatient clinic 6 (24%), and admission in the hospital 5(20%). management of complications were observation for 4 (66.7%) and vitamin k for 2(33.4%) in group (a) patients. for group (b) no management was done for 14 (56%), vitamin k for 5 (20%), fresh frozen plasma for 2 (7%), observation 2(8%), and blood transfusion 2 (8%) (p value < 0.05: significant difference). the risk factors of complications were noncompliance in 6(6%) of the patients in group (a), while in group (b) the risk for complications were stopping of medications 15(15%) and no compliance 10(10%) (p value < 0.05: statistically significant difference) [16]. in this study, the inr target value was reported in (75) in group (a) compared to (43) in group (b), p value < 0.05: significant difference. these results were similar to those of li et al. in china who assessed the knowledge level regarding warfarin therapy among its users and identified the factors that significantly influence anticoagulation control [17]. alghadeeer et al. investigated the differences in anticoagulation control of warfarin using ttr between pharmacists and other health-care providers. they enrolled 62 patients, of them 33 were in a pharmacist-led clinic and 29 in a physician-led clinic. ttr levels showed significant increase among patients in the pharmacist-led clinic (82%) compared to the physician-led clinic (24%) (p<0.001). in 27 patients followed by physicians and prospectively by clinical pharmacists, ttr increased during clinical pharmacists’ care (91.70%±2.93%) versus (61.39%±5.11%,) during physician care; p<0.001) [11]. the results of the present study showed that the ttr levels of the patients followed in inr-c were significantly higher than in patients who attended general-c. moreover, it also showed lower rates of combined minor and major bleeding and ischemic events in inr-c compared with those attending the general-c. these results showed the benefits and importance of the inr-c for patients on warfarin therapy. the only negative argument may be the high cost of inr-c services, especially in countries with low-health resources such as sudan. on the other hand, the high standard of service provided by the inr-c argues in its favor since it reduces morbidity and mortality. doi 10.18502/sjms.v17i4.12548 page 481 sudan journal of medical sciences osman elsayed osman et al 5. conclusion based on the study results, one may conclude that the inr-c is more efficient and safer for follow-up of patients on warfarin therapy compared to general-c. in spite of the high cost of running inr-c in countries with low-health resources, the overall health outcome is beyond comparison with the general-c considering the expected complications and the high-concomitant cost. acknowledgements none. ethical considerations the ethical approval was obtained from the ethical committee of the sudanese medical specialization board (smsb). competing interests authors declare no conflict of interest. availability of data and material data is available with corresponding author upon request. funding none. references [1] robinson, a. a., trankle, c. r., eubanks, g., schumann, c., thompson, p., wallace, r. l., gottiparthi, s., ruth, b., kramer, c. m., salerno, m., bilchick, k. c., deen, c., kontos, m. c., & dent, j. 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(1998). comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs. archives of internal medicine, 158(15), 1641–1647. https://doi.org/10.1001/archinte.158.15.1641 [9] lafata, j. e., martin, s. a., kaatz, s., & ward, r. e. (2000). the cost-effectiveness of different management strategies for patients on chronic warfarin therapy. journal of general internal medicine, 15(1), 31–37. https://doi.org/10.1046/j.15251497.2000.01239.x [10] brown, d. g., wilkerson, e. c., & love, w. e. (2015). a review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons. journal of the american academy of dermatology, 72(3), 524–534. https://doi.org/10.1016/j.jaad.2014.10.027 [11] alghadeeer, s., alzahrani, a. a., alalayet, w. y., alkharashi, a. a., & alarifi, m. n. 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(2013). assessing bleeding risk in patients taking anticoagulants. journal of thrombosis and thrombolysis, 35(3), 312–319. https://doi.org/10.1007/s11239-013-0899-7 [15] camm, a. j., lip, g. y., de caterina, r. (2012). 2012 focused update of the esc guidelines for the management of atrial fibrillation: an update of the 2010 esc guidelines for the management of atrial fibrillation. developed with the special contribution of the european heart rhythm association. europace, 14, 1385–1413. [16] al-momany, n. h., makahleh, z. m., al-omari, n. a., al-sarayreh, h. a., & momani, r. o. (2019). analysis of factors that interrupt with inr control in the first anticoagulation clinic monitoring jordanian patients. clinical and applied thrombosis/hemostasis, 25, 1076029619870252. https://doi.org/10.1177/1076029619870252 [17] li, x., sun, s., wang, q., chen, b., zhao, z., & xu, x. (2018). assessment of patients’ warfarin knowledge and anticoagulation control at a joint physicianand pharmacist-managed clinic in china. patient preference and adherence, 12, 783– 791. https://doi.org/10.2147/ppa.s156734 doi 10.18502/sjms.v17i4.12548 page 484 introduction material and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12556 production and hosting by knowledge e research article nursing students’ satisfaction with online learning experiences during covid-19 pandemic at albaha university, saudi arabia waled a. m. ahmed nursing department, faculty of applied medical sciences, albaha university, al-baha, saudi arabia orcid: waled a. m. ahmed: https://orcid.org/0000-0002-8023-1583 abstract background: the teaching process in universities had faced several challenges during the covid-19 pandemic. as most universities have shifted to online learning, this study aimed to assess nursing students’ satisfaction with online learning during the pandemic. methods: this is a descriptive cross-sectional study; it was conducted among nursing students during the covid-19 pandemic. the authors used an adopted online questionnaire to assess students’ satisfaction. the data were analyzed by spss software. results: the study found that nursing students age was mainly between 22-24 years (78.9%), both male (46.1%) and female (53.9%) students. the nursing students’ satisfaction with online learning during covid-19 was moderate (23.68%) to high (64.47%). a significant relationship was observed between students age and sex with satisfaction levels in online learning with a p-value less than 0.05. conclusions: the study showed that the nursing students were satisfied with an online learning experience. female students and those who are between 22-24 years have significantly higher levels of satisfaction. keywords: nursing students, satisfaction, covid-19, pandemic, saudi arabia 1. introduction the effect of the covid-19 pandemic is not limited to the population’s health and economics, rather it extends to the education system of affected countries [1]. the response of the educational system in many countries was to maintain the educational process at an optimal level due to advanced technologies and development [2, 3]. however, the emergence of e-learning as a solution to ensure sustainability of teaching and learning, faced several issues during the transition from traditional learning to online learning during the pandemic [4, 5]. furthermore, nursing education faced additional challenges due to the nature of the clinical subjects which require students to be in direct contact with patients [6]. how to cite this article: waled a. m. ahmed (2022) “nursing students’ satisfaction with online learning experiences during covid-19 pandemic at albaha university, saudi arabia,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 589–598. doi 10.18502/sjms.v17i4.12556 page 589 corresponding author: waled a. m. ahmed; email: weliameen1980@hotmail.com received 11 july 2022 accepted 16 july 2022 published 31 december 2022 production and hosting by knowledge e waled a. m. ahmed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12556&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences waled a. m. ahmed the countries had applied specific protective measures to control the spread of covid-19 among students, and many colleges have shifted the classes online [710]. many universities in saudi arabia, including albaha university, have used the rafid platform (blackboard) to provide online teaching. [11-13]. nursing students have provided online learning for theoretical courses and face-to-face learning for practical and clinical courses. as stated, satisfaction of students is specifically described as their perception developed from the perceived value of education and experience gained [14]. although, it is difficult to identify factors that influence satisfaction due to its complexity [15], despite the fact, it is needed to assess satisfaction to get benefits in terms of decision-making processes [16]. the nursing students’ satisfaction levels toward different types of learning were investigated at albaha university [17-19]; however, no traced studies were conducted on the level of satisfaction toward online learning. thus, the purpose of this study is to assess nursing students’ satisfaction toward online learning during covid-19 pandemic at albaha university, saudi arabia. 2. materials and methods 2.1. study design and setting this is a descriptive cross-sectional study; it was conducted among nursing students at albaha university during covid-19 pandemic. it is one of the main governmental universities in the kingdom which is located in aqiq city, al-baha, saudi arabia. 2.2. sampling and sample size a simple random sampling technique was used among nursing students in the academic year 2020/2021. the author explained the study process and send the link of online questionnaire through whatsapp groups, the response rate was acceptable, and the sample size was 76 nursing students from both male and female sections. doi 10.18502/sjms.v17i4.12556 page 590 sudan journal of medical sciences waled a. m. ahmed 2.3. data collection tool and technique the author adopted the online questionnaire for e-learning satisfaction from one of the previous publication [20]. it was approved by three associate professors in nursing at albaha university and its reliability was approved. 2.4. scoring system the satisfaction was measured using likert scale of five, 1 for strongly disagree and 5 for strongly agree. the total score was calculated based on responses of students, where unsatisfactory for those taken 50% or less, moderate satisfaction for those scored more than 50% and less than 75%, and high satisfaction for those scored 75% or above. 2.5. data analysis the data were analyzed using spss software, version 22. the collected data were encoded into variables. the author used descriptive and inferential analysis by the program. 3. results 3.1. results summary the study findings have been presented in tables and figures. table 1 shows the nursing students age at albaha university was mainly between 22-24 years (78.9%), and they lived in al-baha region (94.7%), majority of them were unmarried (97.4%), and there were both male (46.1%) and female (53.9%) students. the nursing students’ level of satisfaction toward online learning provided during covid-19 pandemic was highly satisfactory (64.47%), moderate satisfaction level (23.68%), and those who were not satisfied represented only (11.84%), as shown in figure 1. the details of nursing students’ level of satisfaction were presented in table 2 as three main domains were included; first section was preferences and acceptance of online learning itself where students reflected strong agreement with provided statements related to the online learning. second section was about technical issues related to online learning since students also showed high satisfaction and agreement with the doi 10.18502/sjms.v17i4.12556 page 591 sudan journal of medical sciences waled a. m. ahmed related statements. lastly, the third section was about interaction and collaboration where the students reported agreement with most of the related statements. table 3 showed the relationship between demographic characteristics (age, residence marital status, and gender of nursing students) with the level of satisfaction toward online learning. the significant relationships were reported between students age with satisfaction level with a p-value less than 0.05, nursing students’ satisfaction was higher at age 22 years and above. the second significant relationship was observed between the students’ gender and satisfaction level, female students were more satisfied compared with male students toward online learning. table 1: demographic characteristics of nursing students at albaha university, n = 76. age group (yr) frequencies percentage <20 0 0.0 20–22 12 15.8 22–24 60 78.9 >24 4 5.3 residence al-baha region 72 94.7 outside al-baha region 4 5.3 marital status married 2 2.6 unmarried 74 97.4 gender male 35 46.1 female 41 53.9 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% unsa�sfactory moderate satisfaction high sa�sfac�on 11.84% 23.68% 64.47% figure 1: the level of satisfaction of nursing students toward online learning during covid-19. doi 10.18502/sjms.v17i4.12556 page 592 sudan journal of medical sciences waled a. m. ahmed table 2: level of satisfaction of nursing students towards online learning during covid-19, n = 76. satisfaction parameters strongly disagree disagree uncertain agree strongly agree 1 2 3 4 5 preferences and acceptance of online learning approach i am confident about using e-learning technology 10.5 15.8 13.2 34.2 34.2 2. the quality of lectures and videos provided, helped me in my learning 7.9 9.2 17.1 23.7 23.7 3. it was easy to download and print e-learning materials 3.9 6.6 11.8 32.9 32.9 4. i would prefer if the lectures used in the e-learning have other collaborative tools 5.3 14.5 7.9 25.0 25.0 5. i prefer using e-learning classes instead of traditional classes 1.3 5.3 18.4 22.4 22.4 technical issues of online learning 1. the response time of my e-learning system is fast 6.6 9.2 21.1 27.6 35.5 the browser speed of e-learning platform is fast 7.9 14.5 18.4 27.6 31.6 the browser is fast even during peak usage time 14.5 15.8 3.9 26.3 39.5 it was easy to navigate through the elearning platform 13.2 7.9 9.2 30.3 39.5 interaction and collaboration i was able to interact with the instructor during e-learning class 5.3 15.8 18.4 31.6 28.9 i was able to interact with my classmates during use of e-learning platform 9.2 27.6 14.5 30.3 18.4 i need collaboration and discussion with other students 15.8 7.9 11.8 30.3 34.2 it was easy to collaborate with my students’ colleagues during the class 10.5 9.2 19.7 22.4 38.2 the design of collaborative tools (chatroom and discussion board) was suitable for my needs 17.1 30.3 5.3 15.8 31.6 total satisfaction level 9.2 13.5 13.6 27.2 36.5 4. discussion the nursing students’ satisfaction level toward online learning is a fundamental part of the quality of teaching and learning, this study focused on the level of satisfaction of nursing students at albaha university. the current study findings reflected that the nursing students are satisfied with the following approach of online learning during the pandemic of covid-19. the participated nursing students were either highly satisfied doi 10.18502/sjms.v17i4.12556 page 593 sudan journal of medical sciences waled a. m. ahmed table 3: relationship between demographic characteristics of nursing students at albaha university and their level of satisfaction, n = 76. age group (yr) unsatisfactory moderate satisfaction high satisfaction p-value <20 0 0 0 0.003* 20–22 3 (25%) 5 (41.7%) 4 (33.3%) 22–24 10 (16.7%) 18 (30%) 32 (53.3%) >24 1 (25%) 1 (25%) 2 (50%) residence al-baha region 17 (23.6%) 23 (31.9%) 32 (44.4%) 0.07 outside al-baha region 1 (25%) 1 (25%) 2 (50%) marital status married 0 (0%) 1 (50%) 1 (50%) 0.4 unmarried 16 (21.6%) 25 (33.8%) 33 (44.6%) gender male 12 (34.3%) 13 (37.1%) 10 (28.6%) 0.04* female 14 (34.1%) 12 (29.3%) 15 (36.6%) or had moderate satisfaction level compared to only less than 12% who reflected their unsatisfaction. the current study findings were similar to the previous studies conducted in other countries [21] and in spain where findings showed that students had satisfaction moderate to high in both teaching methodologies [22]. furthermore, in an integrative review on nursing students’ satisfaction with e-learning during the pandemic, it was shown that they had high satisfaction levels during their learning experiences [23]. on the other hand, the current study contradicts findings with other studies, which showed students are dissatisfied with online learning [24]. another study conducted in iran showed that more than 88% of nursing students were satisfied with online learning [25]; furthermore, findings from the study conducted in iran showed that universities were not completely successful in satisfying students in online learning [26]. nursing students showed their satisfaction in online learning preferences and acceptance of online learning, technical issues related to online learning, and interaction and collaboration. similarly, in bali, indonesia, the nursing students mentioned that online learning is fairly good in terms of convenience, accessibility, and accuracy of used methods [27]. the study showed a significant correlation between students age with the level of satisfaction toward online learning where students aged between 22-24 years had higher satisfaction. likewise, another study was conducted on students readiness and doi 10.18502/sjms.v17i4.12556 page 594 sudan journal of medical sciences waled a. m. ahmed satisfaction on distance learning which showed a significant relationship between students age and value of readiness for distance learning [28]. there was also a significant relationship between students’ gender and satisfaction level, female students were more satisfied in online learning compared with male students. this, might be because the female students preferred to study from their home during the pandemic and related restrictions. however, this was the first study investigated on nursing students’ satisfaction in albaha region during the era of covid-19 pandemic. it had some limitations, such as it was conducted among a convenience sample which limited its generalizability, another limitation was that it was conducted only on nursing students; it would be more appropriate to investigate instructor’s perceptions and satisfaction. 5. conclusion the current study was conducted to assess the nursing students’ satisfaction for the online learning. the findings showed that the nursing students were satisfied in online learning in the three assesses sections preferences and acceptance of online learning, technical issues related to online learning and interaction and collaboration. female students who were between 22-24 years old expressed significantly higher levels of satisfaction compared to others. acknowledgements none. ethical considerations none. competing interests the authors declare that they have no conflict of interest. availability of data and material anonymous data are available. doi 10.18502/sjms.v17i4.12556 page 595 sudan journal of medical sciences waled a. m. ahmed funding none. 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(2022). distance education in nursing: readiness and satisfaction levels of students. journal of educational technology and online learning, 5(2), 467–480. doi 10.18502/sjms.v17i4.12556 page 598 introduction materials and methods study design and setting sampling and sample size data collection tool and technique scoring system data analysis results results summary discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10683 production and hosting by knowledge e original article the effect of neonatal training programs on nicu nurses’ knowledge and practice in the military and police hospitals of khartoum state, sudan rabab.mohamed adam1* and buthina bassyonie elssayed2 1nursing program, kamllin ahlia college, al kamlin, sudan 2faculty of nursing, albutana university, rufaa, sudan abstract background: hypothermia in neonates is a life-threatening condition. it happens due to the extrinsic thermal variations that contrast the intrauterine area. early detection methods such as increased awareness and good nursing care play an important role in the prevention of hypothermia in newborns and reduce the consequences and death resulting from it. this study aimed to evaluate the effect of training programs on nurses’ knowledge and practice with respect to caring for neonates with hypothermia. methods: this quasi-experimental study was conducted in the military and police hospitals in khartoum state, sudan. a total of 47 nurses meeting the study inclusion criteria and agreeing to participate were included. the necessary research data were collected using a structured interview and a checklist pre and three months post intervention. training program on neonatal hypothermia was offered to nurses which included the definition, causes, signs and symptoms, and treatment and prevention of neonatal hypothermia. data were analyzed using the spss v.20; descriptive and inferential statistics (t-test and chi-squared test) were used with p-values < 0.05 considered as statistically significant. results: all participants were female nurses aged 20–30 years, with a mean age of 27.7 ± 5.3 years. a majority of them (40 [85.1%]) had a bsc degree in nursing. their experiences were varied, but the most common was 1–5 years, followed by 6– 10 years (15 [32%] and 14 [29.8%], respectively). nurses’ knowledge about observing and monitoring temperature pre intervention was 73%, which increased to 94.3% post intervention with a p-value = 0.03. additionally, nurses’ practice in cases of hypothermia pre intervention was 80.01%, which increased to 82.9% post intervention. their pre intervention practice around placing the baby under radiant warmer was 72.3%, which changed to 93.6% post intervention with a p-value = 0.006. conclusion: implementation of the training program on neonatal hypothermia was very effective and significantly increased nurses’ level of knowledge and practices. we recommend similar training programs should be given to all nurses working in the neonatal intensive care units in sudan. keywords: training program, neonatal hypothermia, prevention how to cite this article: rabab.mohamed adam* and buthina bassyonie elssayed (2022) “the effect of neonatal training programs on nicu nurses’ knowledge and practice in the military and police hospitals of khartoum state, sudan,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 28–38. doi 10.18502/sjms.v17i1.10683 page 28 corresponding author: author; email: rababi145@gmail.com received 02 february 2022 accepted 09 march 2022 published 31 march 2022 production and hosting by knowledge e rabab.mohamed adam et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:rababi145@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences rabab.mohamed adam et al 1. introduction hypothermia in neonates can occur at any time and is a crucial threat for newborn survival in the neonatal period, which is the period from 0 to up to 28 days of life [1]. its incidence is higher in a period <24 hr of birth, and babies are more likely to die due to hypothermia as the neonate has at that moment to deal with the extrinsic thermal variations that contrast evidently the intrauterine area [2]. 1.1. problem statement worldwide neonatal deaths are unevenly dispensed around the world. half of the world’s newborns die at home, and >99% of all deaths occur in developing countries, where the average neonatal mortality rate is 33 per 1000, compared with 4 per 1000 in high-income countries. since neonatal deaths account for >40% of under-5 mortalities, reaching the millennium development goal (mdg) will require a substantial reduction in newborn mortality. although addressing neonatal hypothermia might promote this goal, so far little attention has been paid to it. maintaining a normal body temperature is a critical function for newborn survival [3]. 1.2. definition hypothermia is defined as a body core temperature of <35ºc (95ºf) in humans [4]. symptoms depend on the temperature. in mild hypothermia, there is shivering and mental confusion. in moderate hypothermia, shivering stops and confusion increases [5]. in severe hypothermia, there may be paradoxical undressing, in which a person removes their clothing, as well as an increased risk of the heart stopping. 1.3. causes premature birth and low birth weight. low birth weights run a higher risk of hypothermia due to lack of insulating body fat, immature nervous system, inability to efficiently conduct heat, cold birth environment, hypoglycemia, and infection. 1.4. signs and symptoms lethargy, poor feeding, cold extremities [6]. doi 10.18502/sjms.v17i1.10683 page 29 sudan journal of medical sciences rabab.mohamed adam et al 1.5. management and prevention hypothermia should be prevented through strict observance of chain of warmth including thermal control such as ensuring a warm area for delivery, keeping the baby warm and wrapping them in warm clothes, initiating early breastfeeding, delaying bathing, checking body temperature, and providing care during transport when returning back home or transferring the baby from one unit to another [7]. hypothermia prevention in neonates is a key element to prevent child mortality as most of them are vulnerable to die within the neonatal period [8]. another meaningful aspect of preventing neonatal hypothermia is keeping the baby and the mother together as the neonate body temperature depends significantly on the mother’s temperature. however, babies delivered by caesarian section (c/s) do not benefit from the usual maternal bonding, because they are usually separated from the mother and cared apart making them prone to hypothermia [9]. midwives in healthcare facilities strive to adhere to the who guidelines regarding the prevention of hypothermia in the neonates from the delivery room to the postpartum ward but the gaps are more observed when the baby is discharged from the hospital, running into the burden of the means of transport that are most of the time inadequate for the newborn baby [8]. 1.6. justification neonatal hypothermia is a life-threatening disease, widespread especially in africa, with a high mortality and morbidity rate. to reduce its incidence rate, safe care should be provided to neonates with hypothermia, and early detection methods such as increased awareness and good nursing care should be facilitated. 1.7. objectives 1.7.1. general objective to evaluate the effect of training programs on nurses’ knowledge and practice with respect to the care of neonates with hypothermia in the obstetrics and gynecology hospitals in khartoum state, sudan (2019–2021). doi 10.18502/sjms.v17i1.10683 page 30 sudan journal of medical sciences rabab.mohamed adam et al 1.7.2. specific objectives (i) to assess nurses’ knowledge regarding the various aspects of caring for neonates with hypothermia such as defining causes, signs and symptoms, and its management in the obstetrics and gynecology hospitals in khartoum state, sudan (2019– 2021). (ii) to monitor nurses’ performance when caring for neonates with hypothermia in the obstetrics and gynecology hospitals in khartoum state, sudan (2019–2021). (iii) to evaluate the effect of implemented training program on nurses’ knowledge and practice when caring for neonates with hypothermia in selected areas for >1 year (2019–2021). 2. materials and methods 2.1. study design this interventional hospital-based study aimed at assessing the effect of the training programs on nurses’ knowledge and practices regarding the nursing care of neonates with hypothermia in the obstetrics and gynecology hospitals in khartoum state, sudan. 2.2. study area this study was conducted in the neonatal units of the police and military hospitals in khartoum state, sudan. police hospitals are located in bor. the hospital was built in 1996 and receives patients from different areas of the locality. it includes a clinical reference department, a medical department, a radiolofy department, a blood bank, a kitchen, a security unit, a pediatric ward, an obstetrics and gynecology department, and two neonatal intensive care units (septic and aseptic units) that have 15 incubators and 4 radiant warmers. the per day delivery rate of the hospital is 50 babies; in a month, it admits about 35–50 babies, and 24 nurses work in different shifts. 2.3. study population the study included 47 nurses working in the neonatal intensive care units of the selected hospitals. doi 10.18502/sjms.v17i1.10683 page 31 sudan journal of medical sciences rabab.mohamed adam et al 2.4. data collection a questionnaire was designed by the researcher in english language that included nurses’ sociodemographic characteristics such as age, qualifications, years of experience, and information on nurses’ knowledge and practice before and after the training program. an observational checklist was developed by the researcher to observe the actual performance of the nurses before and after the training program. it included all nursing care and procedures needed for the care of neonates with hypothermia. 2.5. phases of the study: phases of intervention 2.5.1. pre intervention phase • permission was taken from managers and directors of the two hospitals for data collection through official letters. • a questionnaire was distributed for each available nurse to be filled under the researchers’ guidance. • each nurse was observed for her clinical skills when caring for neonates with hypothermia. 2.6. program implementation the program was designed and offered to equip nurses with essential information and practice regarding the care of neonates with hypothermia and included information about hypothermia such as its definition, causes, signs and symptoms, treatment, prevention and related procedures. 2.6.1. post intervention program a posttest was done using the same questionnaire and a checklist was used to evaluate the effect of program on nurses’ knowledge and skills. all nurses were observed by the researchers during their shift. a certificate and copies of the program was given to all participants. doi 10.18502/sjms.v17i1.10683 page 32 sudan journal of medical sciences rabab.mohamed adam et al 2.7. data analysis data were coded, entered, and analyzed using the statistical package for social science (spss) to show the results of the hypothesis of the study by using frequencies and percentages in tables and figures, and a suitable statistical method was used (descriptive and inferential). p-value, for statically significant 3. results 0 0.5 1 1.5 2 2.5 3 3.5 20-30 31-40 > 40 a x is t it le figure 1: distribution of the study sample according to their age (yr), n = 47. figure 1 shows that the majority of our study participants were in the age group 20–30 years. . 2.1 85.1 4.3 8.5 diploma bsc high diploma msc figure 2: distribution of the study sample according to education, n = 47. as seen in figure 2, a majority of our participants (85.1%) had a bachelor’s degree in nursing. doi 10.18502/sjms.v17i1.10683 page 33 sudan journal of medical sciences rabab.mohamed adam et al 19.1 32 29.8 19.1 < 1 5-jan 10-jun >1010 5 figure 3: distribution of the study sample according to the years of experience, n = 47. table 1: nurses’ knowledge about hypothermia (n = 47). pre training post training p-value f % f % nurses’ knowledge about monitoring of temperature 37 78.7 43 91.5 0.031 nurses’ knowledge about monitoring of neutral thermal environment 35 74.5 45 95.7 0.008 nurses’ knowledge about incubator care 31 66.0 45 95.7 0.001 average 73% 94.3% 0.013 furthermore, figure 3 shows that a majority of the study samples (32%) had one to five years of experience. 8.5 91.5 yes no figure 4: distribution of the study sample according to their attendance of a similar training program prior to previously. figure 4 shows that 91.5% of our study participants had not attended any training programs regarding neonatal hypothermia. doi 10.18502/sjms.v17i1.10683 page 34 sudan journal of medical sciences rabab.mohamed adam et al table 2: nurses’ practice of hypothermia management (n = 47). pre intervention post intervention p-value f % f % nurses’ practice on observing signs of hypothermia such as shivering, slow breathing, confusion, acrocyanosis 42 89.4 44 93.6 0.46 nurses’ practice on covering head, hands, legs, and avoiding undressing the infant 37 78.7 39 83 0.60 nurses’ practice on placing the baby under a radiant warmer or incubator 34 72.3 44 93.6 0.006 average 80.01% 82.97% 4. discussion the majority of our participants (74.5%) were aged 20–30 years. similar findings were reported by another sudanese study which showed that the majority of nicu nurses (60%) were in the similar age group [10]. all participants in this study were female which is similar to the findings of another study in sudan which showed that all pediatric nurses (100%) in the nicu were female. this can be attributed to hospital polices [11]. our finding is also similar to the findings of another study on ”nursing care for newborn infant with jaundice in a maternity hospital in brazil,” which reported that all nurses included in the study were aged 25–35 years [12]. the study revealed that more than two-third (85.1%) nurses had a bsc degree in nursing science. however, this finding is in contrast to the findings of another study conducted to observe the effect of a designed nursing care protocol on the clinical outcomes of neonates with hyperbilirubinemia in nicu in shebin–elkom teaching hospital which found that half of the nurses in their study were qualified by only a diploma in nursing [13]. similarly, another study conducted in yemen showed that about 83% of their study participants had a nursing diploma and no degree; this is a serious indicator for yemen which shows that the majority of their nurses are academically not qualified enough to bear their responsibilities [14]. moreover, onethird (32%) of the study participants had about one to five years of experience. this is in contrast to the results of a study conducted to verify the seriousness of nursing and find an association with respect to nursing care (age, nursing education, and experience in intensive care unit) that show the majority of samples in years of experience group to the study sample where within (under 2 years) and (2–5 years) were 50% and 40%, respectively [15]. moreover, it was found that 91.5% of the nurses had never undertaken a training course in neonatal care. this is similar to the result of another sudanese study in which 56% of the nurses had never taken a course in neonatal care [16]. moreover, in our study, nurses’ knowledge regarding neonatal hypothermia improved from 73% doi 10.18502/sjms.v17i1.10683 page 35 sudan journal of medical sciences rabab.mohamed adam et al pre intervention to 94.3% post intervention with a p-value of 0.013. however, this is in disagreement with another study that found 57.5% of their respondents had adequate knowledge about risk factors and causes of neonatal hypothermia. the study also revealed that 89.4% and 93.6% of the study sample responded with correct answers regarding the warning signs of hypothermia pre and post intervention, respectively [17]. nevertheless, the finding of the present study is better than the findings of an egyptian research that showed most of the nurses (96.7%) at pretest had inadequate knowledge about preventing hypothermia in preterm infants, while in the posttest a majority (85%) had gained adequate knowledge [18]. overall, nurses’ practice with respect to managing neonatal hypothermia had a little improvement – pre 80.01% and post 82.9%. 5. conclusion the findings of the current study proved that training programs are effective and significantly increase the knowledge and improve the practice of the nurses with respect to neonatal hypothermia. limitations the study had a few limitations such as lack of financial support to implement the intervention programs to cover all nurses in khartoum state and low sample of nurses. recommendations 1. contentious educational programs for nurses to improve their performance in icus. 2. further studies to assess nurses’ knowledge and practice in the management of neonates with hypothermia in other healthcare settings in sudan and application of their recommendations into practice. ethical considerations permission from managers, matrons, and head nurses of police and military hospitals was taken through official letters and verbal acceptance was obtained after explaining to them the purpose of the study. participants had the right to withdraw at any time. privacy and confidentiality was ensured by using coded questionnaire. doi 10.18502/sjms.v17i1.10683 page 36 sudan journal of medical sciences rabab.mohamed adam et al competing interests none. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding none. references [1] boundy, e. o., dastjerdi, r., spiegelman, d., et al. (2016). kangaroo mother care and neonatal outcomes: a meta-analysis. pediatrics, vol. 137, no. 1, p. e20152238. [2] qazi, m., saqib, n., and raina, r. (2019). knowledge regarding prevention of hypothermia in newborns among mothers in northern india. international journal of research in medical sciences, vol. 7, no. 5. [3] lunze, k. and hamer, d. (2012). thermal protection of the newborn in resource-limited environments’ perinatol. journal of perinatology, vol. 32, no. 5, pp. 317–324. [4] brown, d. j., brugger, h., boyd, j., et al. (2012). accidental hypothermia. the new england journal of medicine, vol. 367, pp. 1930–1938. [5] fears, j. w. (2011). the pocket outdoor survival guide: the ultimate guide for shortterm survival. stoeger publishing company. [6] qazi, m., saqib, n., and raina, r. (2019). knowledge regarding prevention of hypothermia in newborns among mothers in northern india. international journal of research in medical sciences, vol. 7, no. 5. [7] lunze, k., yeboah-antwi, k., marsh, d. r., et al. (2014). prevention and management of neonatal hypothermia in rural zambia. plos one, vol. 9, no. 4, p. e92006. [8] mc call, e., alderdice, f., halliday, h. l., et al. (2018). interventions to prevent hypothermia at birth in preterm and/ or low birth weight infants (review). cochrane systematic reviews, vol. 2018, no. 2, p. cd004210. doi 10.18502/sjms.v17i1.10683 page 37 sudan journal of medical sciences rabab.mohamed adam et al [9] sacks, e., moss, w. j., winch, p. j., et al. (2015). skin thermal and umbilical cord care practices for neonates in southern, rural zambia: a qualitative study. bmc pregnancy and childbirth, vol. 15, article 149. [10] altun, i. and karakoc, a. management of hypothermia impact of lecture-based interactive workshops on training of pediatric nurses. pediatric emergency care, vol. 28, no. 5, pp. 455–459. [11] babeker, z. a. (2015). assessment of nurses knowledge and practice regarding care of premature baby in neonatal intensive care unit at omdurman maternity hospital and alribat university hospital in pediatric nursing. faculty of graduate studies and scientific research, the national ribat university. [12] moula, w. i. and kambal, i. i. a. e. pediatric nurses knowledge and practices regarding nursing management of premature babies in neonatal intensive care unit at soba university hospital, khartoum state, sudan. international journal of recent research in life sciences, vol. 3, no. 4, pp. 1–9. [13] samar, d. r., anapaula, n. l., lisane, k. s., maria, a. s., francisca, w. b. (2013). nursing care for the newborn infant with jaundice in a maternity hospital. journal of nursing, vol. 7, no. 1, pp. 7017–7025. [14] ashor, g. m., khalifa, m., el-gendy, et al. (2016). effect of a designed nursing care protocol on clinical outcomes of neonates with hyperbilirubinemia (nicu) in shebin el-kom teaching hospital. international journal of novel research in health care and nursing, vol. 3, no. 3, pp. 70–76. [15] bash, n. (2016). patterns of nursing knowledge in identification of neonatal sepsis in nicu. sana’a, yemen: nursing department, sanaa university. [16] mansi, q. and aziz, a. (2017). assessment nursing care in neonatal respiratory distress. international journal of science and research, vol. 6, no. 5, pp. 550–553. [17] ashor, g. m., khalifa, m. i., el-gendy, f. m., et al. (2016). effect of a designed nursing care protocol on clinical outcomes of neonates with hyperbilirubinemia. international journal of novel research in healthcare and nursing, vol. 3, no. 3, pp. 62–76. [18] bourgault, a., ipe, l., weaver, j., et al. (2015). development of evidence-based guidelines and critical care nurses knowledge of enteral feeding. critical care nurse, vol. 27, no. 4, pp. 17–29. doi 10.18502/sjms.v17i1.10683 page 38 introduction problem statement definition causes signs and symptoms management and prevention justification objectives proxima-nova-bold-italic.otfgeneral objective proxima-nova-bold-italic.otfspecific objectives materials and methods study design study area study population data collection phases of the study: phases of intervention pre intervention phase program implementation post intervention program data analysis results discussion conclusion limitations recommendations acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12554 production and hosting by knowledge e research article women’s awareness and beliefs of breast cancer at al-baha, saudi arabia manal sa hakami nursing department, faculty of applied medical sciences, albaha university, saudi arabia orcid: manal sa hakami: https://orcid.org/0000-0003-2194-8506 abstract background: women’s awareness and beliefs about breast cancer in saudi arabia were not fully investigated. the aim of this descriptive study was to assess women’s awareness and beliefs toward breast cancer in al-baha, saudi arabia. methods: this is a descriptive cross-sectional study; it was conducted among women attending the women and child care center at alawi royal mall in alaqiq for mammogram screening of breast cancer. a convenient sampling technique was used; it included women who attended the center in the period from september 2021 to december 2021, and who agreed to participate. the data were collected using a questionnaire consisting of questions on awareness and beliefs toward breast cancer. the data were analyzed using spss software. results: the current study showed that the level of awareness in women was high toward breast cancer general information (42.9%), the meaning of malignancy (54.3%), and ways for detecting breast cancer (42.9%), it was also shown that they had fair awareness on myths related to breast cancer (45.7%), and signs and symptoms of breast cancer (51.4%). the study also showed that the women have a high level of beliefs toward breast cancer health services (48.6%), the ability of breast cancer to be prevalent in some families (45.7%), the ways of breast cancer self-detection (34.3%), and mammogram role in early detection of breast cancer (34.3%). it was found that the occupation of women and women’s level of education significantly improved the awareness in women. it was shown that the occupation of women and their level of education were significantly related to the level of beliefs toward breast cancer (21.4%) compared to 16.7% for women working in the private sectors. conclusion: women in al-baha have a high level of awareness and beliefs about breast cancer. the occupation of women and women’s level of education are associated with a high level of awareness and beliefs toward breast cancer. keywords: awareness, beliefs, breast cancer, women, screening, saudi arabia how to cite this article: manal sa hakami (2022) “women’s awareness and beliefs of breast cancer at al-baha, saudi arabia,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 565–576. doi 10.18502/sjms.v17i4.12554 page 565 corresponding author: manal sa hakami; email: hakmi@mail.net.sa received 7 may 2022 accepted 29 july 2022 published 31 december 2022 production and hosting by knowledge e manal sa hakami. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12554&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences manal sa hakami 1. introduction recently, life expectancy has been positively changed, maternal and child health has been improved, and the transmission of infectious diseases is controlled [1]. although, the countries have controlled the transmission of infectious diseases, but the spread of cancer is still uncontrolled [2, 3]. it is expected that by the year 2040, the cases of cancers will be more than 27 million annually [4]. however, due to the high rate of breast cancer (bc) morbidity and mortality, the global initiatives and activities toward this condition are low especially in the developing countries [5]. furthermore, the promotive and preventive activities remain a great challenge in providing appropriate care for communities in low-income countries [6]. bc in saudi arabia is increasing as shown in one report investigating the trend of bc in the country [7], it also showed the increase in the incidence by 17% between 2004 and 2016 [7]. although saudi arabia provides a free and high-quality breast care services, the incidence of bc and its mortality and morbidity are still increasing. husband’s knowledge and attitudes toward bc screening are not satisfactory in saudi arabia [8]. women’s awareness and beliefs of bc and its predisposing factors have been investigated in several countries such as the netherlands, america, australia, iran, arabic countries, and in saudi arabia in particular [9-16]. there is a lack of evidence of studies that assess women’s awareness and beliefs of bc in saudi arabia. the aim of this study was to assess women’s awareness and beliefs toward bc in al-baha region, saudi arabia. 2. materials and methods 2.1. design this is a descriptive cross-sectional study; it was conducted among women attending mammogram screening for bc at the women and child care center, alaqiq royal mall. 2.2. study population this study was conducted on women who attended mammogram screening for bc at the women and child care center, alaqiq royal mall, al-baha, saudi arabia. doi 10.18502/sjms.v17i4.12554 page 566 sudan journal of medical sciences manal sa hakami 2.3. inclusion criteria 1. women at age (40 years or more) according to saudi ministry of health guidelines for mammography screening. 2. attending for bc screening (mammography) to maternity and child care center. 3. agree to participate 2.4. exclusion criteria 1. age less than 40 years 2. refuse to answer the questions 2.5. sampling and sample size a convenient sampling technique was used; it included women who attended the center from september 2021 to december 2021, and agreed to participate. 2.6. data collection direct questions were asked to women concerning their awareness and beliefs toward bc. 2.7. instruments demographic questionnaire, awareness toward bc questionnaire, and beliefs toward bc questionnaire, were adopted from one questionnaire [17]. 2.8. data analysis plan data were analyzed using descriptive statistics including frequency and percentage for demographic data and for levels of women awareness and beliefs toward bc. a correlation was tested using chi-square test between the demographic variables and levels of awareness and beliefs of women. doi 10.18502/sjms.v17i4.12554 page 567 sudan journal of medical sciences manal sa hakami 3. results 3.1. summary table 1 shows that women’s age ranged between 40 and 60 years as the center allocated to conduct mammography among this age group, most of the women were at the age of 40-44 (57.1%) and 45-49 years old (28.6%). furthermore, it was found that 62.9% women came from alaqiq and 37.1% from al-baha to this center. it was also found that 80% of women were working at governmental sectors, 17.1% at private sectors, and only 2.9% do not work. the level of education was either secondary level (60%) or university education (40%). most of the women were married (80%) and only 20% were single. table 2 shows that women had high level of awareness toward bc general information (42.9%), meaning of malignancy (54.3%), and ways for detecting bc detection (42.9%), it was also shown that they had fair awareness on myths related to bc (45.7%) and signs and symptoms of bc (51.4%). it also showed that they had inadequate awareness on the bc management (54.3%) and the prevalence of bc (51.4%). furthermore, figure 1 shows that overall level of women’s awareness toward bc where 27% women had high level of awareness, 35.2% had fair level of awareness, 29.8% had inadequate awareness, and 7.9% no awareness about bc. table 3 shows that women had high level of beliefs toward bc health services (48.6%), toward ability of bc to be prevalent in some families (45.7%), ways for self-detecting bc (34.3%), and role of mammogram in early detection of bc (34.3%). it was also found that they had fair beliefs on factors related to bc (45.7%), genetic factors of bc (45.7%). it also showed that they had inadequate beliefs that bc could be treated (40%), furthermore, figure 2 shows the overall level of women’s beliefs toward bc where 31.4% women had high level of beliefs, 36.2% had fair level of beliefs, 19.7% had inadequate beliefs, and 12.7% had poor beliefs toward bc. table 4 states the relation between women characteristics (age, residence, occupation, education, and marital status) and level of their awareness toward bc were tested using chi-square test. it was showed that the occupation of women and women’s level of educations significantly improved the women’s awareness; the women working in governmental sectors had high level of awareness toward bc (36%) compared to 0% for other sectors, (p-value 0.03) and women who had university education had high level of awareness toward bc (35.7%) compared to 14.3% for secondary school (p-value 0.02). doi 10.18502/sjms.v17i4.12554 page 568 sudan journal of medical sciences manal sa hakami in table 5, the relationships between women characteristics (age, residence, occupation, education, and marital status) and level of women beliefs toward bc were tested using chi-square test. it was shown that the occupation of women and their level of education were significantly related; the women working in governmental sectors had high level of beliefs toward bc (21.4%) compared to 16.7% for women working in private sectors (p-value 0.03), and women who had university education had high level of beliefs toward bc (42.9%) compared to 23.8% for secondary school (p-value 0.01). table 1: demographic characteristics of women at al-baha region, n = 35. age (yr) frequencies percentage 40–44 20 57.1% 45–49 10 28.6% 50–54 3 8.6% 55–60 2 5.7% residence alaqiq 22 62.9% al-baha 13 37.1% occupation governmental employee 28 80.0% private employee 6 17.1% unemployed 1 2.9% education secondary school 21 60.0% university 14 40.0% marital status single 7 20.0% married 28 80.0% table 2: women’s awareness on breast cancer at al-baha region, n = 35. items not aware inadequate awareness fair awareness high awareness myths related to bc 14.3% 22.9% 45.7% 17.1% general information on bc 8.6% 20.0% 28.6% 42.9% meaning of malignancy 2.9% 11.4% 31.4% 54.3% risk factors of bc 8.6% 25.7% 37.1% 28.6% signs and symptoms of bc 5.7% 22.9% 51.4% 20.0% prevalence of bc 2.9% 51.4% 37.1% 8.6% bc could be prevented 5.7% 40.0% 34.3% 20.0% management of bc 17.1% 54.3% 20.0% 8.6% bc detection 5.7% 20.0% 31.4% 42.9% overall women’s awareness on bc 7.9% 29.8% 35.2% 27.0% doi 10.18502/sjms.v17i4.12554 page 569 sudan journal of medical sciences manal sa hakami figure 1: overall women’s awareness on breast cancer at al-baha region. table 3: women’s beliefs on breast cancer at al-baha region, n = 35. items poor beliefs inadequate beliefs fair beliefs good beliefs factors increase the risk of bc 14.3% 22.9% 45.7% 17.1% bc could be treated 5.7% 40.0% 34.3% 20.0% bc could be self-detected 2.9% 22.9% 40.0% 34.3% bc could be for genetic factors 17.1% 17.1% 45.7% 20.0% bc could be prevalent in some families 25.7% 20.0% 8.6% 45.7% mammogram is helpful in bc detection 8.6% 20.0% 37.1% 34.3% personal perception on self-examination and mammogram 17.1% 22.9% 28.6% 31.4% reasons of attending bc clinic 20.0% 5.7% 42.9% 31.4% services in bc clinic 2.9% 5.7% 42.9% 48.6% overall women’s beliefs on bc 12.7% 19.7% 36.2% 31.4% 4. discussion the current study showed that women at al-baha region had high level of awareness toward bc description, detection, and they also had fair level of awareness on myths related to bc, signs, and symptoms of bc. it was also found that they had inadequate awareness on the bc management, the prevalence. furthermore, it was reflected that 27% of women had high level of awareness toward bc, 35.2% had fair level of awareness, 29.8% had inadequate awareness, and 7.9% were not aware about bc. these findings are similar to other study which showed that women have good knowledge on bc [18]. previous reports from united arab emirates (uae) and germany have shown that women’s awareness of bc was similar to our findings; as well, most of the participants were aware on the bc description and signs and symptoms [14, 19]. doi 10.18502/sjms.v17i4.12554 page 570 sudan journal of medical sciences manal sa hakami figure 2: overall women’s beliefs on breast cancer at al-baha region. table 4: relationship between demographic variables, and the level of women’s awareness, n = 35. variables/level of awareness not aware inadequate awareness fair awareness high awareness p-value age (yr) 40–44 20% 25% 30% 25% 0.08 45–49 20% 30% 40% 10% 50–54 33% 33% 0 33% 55–60 50% 50% 0 0 residence alaqiq 18% 32% 23% 27% 0.065 al-baha 23% 31% 15% 31% occupation governmental employee 17.9% 21% 25% 36% 0.03* private employee 50% 17% 33% 0 unemployed 100% 0 0 0 education secondary school 19.0% 38.1% 28.6% 14.3% 0.02* university 21.4% 28.6% 14.3% 35.7% marital status single 14.3% 28.6% 28.6% 28.6% 0.061 married 28.6% 25.0% 25.0% 21.4% (*) significant in precent study, it was found that occupation and level of education significantly affect the awareness in women. in other words, women working in governmental sectors had high level of awareness toward bc compared to those working in other sectors, and women who had university education had high level of awareness toward bc compared doi 10.18502/sjms.v17i4.12554 page 571 sudan journal of medical sciences manal sa hakami table 5: relationship between demographic variables, and the level of women’s beliefs, n = 35. variables/level of awareness poor beliefs inadequate beliefs fair beliefs good beliefs p-value age (yr) 40–44 15.0% 20.0% 30.0% 35.0% 0.062 45–49 20.0% 40.0% 30.0% 10.0% 50–54 0.0 33.3% 0.0 66.7% 55–60 0.0 50.0% 0.0 50.0% residence alaqiq 18.2% 22.7% 31.8% 27.3% 0.07 al-baha 30.8% 23.1% 23.1% 23.1% occupation governmental employee 14.3% 25.0% 39.3% 21.4% 0.03* private employee 33.3% 33.3% 16.7% 16.7% unemployed 0.0% 100.0% 0.0% 0.0% education secondary school 14.3% 33.3% 28.6% 23.8% 0.01* university 14.3% 21.4% 21.4% 42.9% marital status single 0.0 28.6% 42.9% 28.6% 0.08 married 25.0% 21.4% 28.6% 25.0% (*) significant to those having secondary school education. the fair or low level of knowledge may contribute to decrease or delay in the uptake of medical treatment. this, especially happened for low-educated women, who had poor awareness of bc. furthermore, our findings showed a satisfactory level of women’s awareness of bc; however, one previous report in saudi arabia has shown that women lacked in punctuality of breast self-examination uptake in rural areas in the asir region [16]. the findings of this study showed that women at al-baha region had high level of beliefs toward bc. it was found that 31.4% of them had high level of beliefs, 36.2% had fair level of beliefs, 19.7% had inadequate beliefs, and 12.7% had poor beliefs toward bc. these findings are similar to other studies which showed that women have positive beliefs on bc outcomes, and poor beliefs on symptoms and risk factors [15, 18]. in precent study, it was found that the occupation and level of education significantly affect the women’s beliefs. that is to say that women working in governmental sectors had high level of beliefs toward bc compared to those working in private sectors, and women who had university education had high level of beliefs toward bc compared to those who had secondary school education. furthermore, most of our subjects consider that early detection of bc is important, and this was correlated mainly among educated doi 10.18502/sjms.v17i4.12554 page 572 sudan journal of medical sciences manal sa hakami women. their beliefs on risk factors, screening of bc was high. these findings were similar to other previous studies highlighting that they could correctly detect risk factors of bc [19]. a similar finding was also reported from studies conducted in the uae on college students and public women [14, 20]. the women’s awareness and beliefs of bc is an important contributing factor for prevention and management of bc, this will enhance bc services uptake and facilitate early detection process. however, more research is recommended to approve this, the present study highlights the current situation regarding bc in al-baha region. our study had some limitations: the findings of the current study depend on the responses of the women to the asked questions that could cause information related bias. furthermore, the sample size of our survey was small and not representative to whole al-baha region population, since it was conducted in only on bc center; however, the participated women are from different areas of al-baha region. 5. conclusion women in al-baha region have high levels of awareness and beliefs of bc. the study showed that a significant correlation between women’s occupation and level of education with levels of awareness and beliefs toward bc. acknowledgements the author would like to acknowledge al-baha health affairs, saudi arabia and would also like to thank the participant women. ethical considerations the study was approved by al-baha health affairs on september 20, 2021. competing interests i would like to confirm that there are no financial and personal relationships with other people or organizations that could inappropriately affect our work. i would also like to assure that we have no conflicts of interest related to publication of this study. doi 10.18502/sjms.v17i4.12554 page 573 sudan journal of medical sciences manal sa hakami availability of data and material data is available with corresponding author upon request. funding this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. authors’ contribution msh is the author of this research, she conducted the work related to this study. references [1] okamoto, j., & leischow, s. j. (2019). global cancer prevention. fundamentals of cancer prevention (pp. 353–375). springer. [2] nagai, h., & kim, y. h. (2017). cancer prevention from the perspective of global cancer burden patterns. journal of thoracic disease, 9(3), 448. [3] wild, c. p. (2019). the global cancer burden: necessity is the mother of prevention. nature reviews cancer, 19(3), 123–124. [4] bray, f., ferlay, j., soerjomataram, i., siegel, r. l., torre, l. a., & jemal, a. (2018). global cancer statistics 2018: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. ca: a cancer journal for clinicians, 68(6), 394–424. [5] bollyky, t. j. (2020, february 4). the growing cancer threat in africa. think global health. thinkglobalhealth.org/article/growing-cancer-threat-africa [6] uicc. (2019, november 5). cancer control in africa: paving the way to universal health coverage. https://www.uicc.org/addressing-cancer-burden-africa [7] albeshan, s. m., & alashban, y. i. (2022). incidence trends of breast cancer in saudi arabia: a joinpoint regression analysis (2004–2016). journal of king saud universityscience, 33(7), 101578. [8] sabgul, a. a., qattan, a. m., hashmi, r., & al-hanawi, m. k. (2022). husbands’ knowledge of breast cancer and their wives’ attitudes and practices related to breast cancer screening in saudi arabia: cross-sectional online survey. journal of medical internet research, 23(2), e25404. doi 10.18502/sjms.v17i4.12554 page 574 sudan journal of medical sciences manal sa hakami [9] gong, j., kampadellis, g., kong, q., & spijker, w. (2022). factors determining nonattendance in breast cancer screening among women in the netherlands: a national study. health promotion international, daac009. [10] davis, c. m. (2022). health beliefs and breast cancer screening practices among african american women in california. international quarterly of community health education, 41(3), 259–266. [11] jaffee, k., cohen, m., azaiza, f., hammad, a., hamade, h., & thompson, h. (2022). cultural barriers to breast cancer screening and medical mistrust among arab american women. journal of immigrant and minority health, 23(1), 95–102. [12] hajian-tilaki, k., & nikpour, m. (2022). accuracy of self-perceived risk perception of breast cancer development in iranian women. bmc women’s health, 21(1), 1–8. [13] macdonald, c., saunders, c. m., keogh, l. a., hunter, m., mazza, d., mclachlan, s.-a., jones, s. c., nesci, s., friedlander, m. l., hopper, j. l., emery, j. d., hickey, m., milne r. l., phillips, k.-a., kathleen cuningham consortium for research into familial breast cancer. (2022). breast cancer chemoprevention: use and views of australian women and their clinicians. cancer prevention research, 14(1), 131–144. [14] kharaba, z., buabeid, m. a., ramadan, a., ghemrawi, r., al-azayzih, a., al meslamani, a. z., alfoteih, y. (2022). knowledge, attitudes, and practices concerning breast cancer and self examination among females in uae. journal of community health, 46(5), 942–950. [15] abo al-shiekh, s. s., ibrahim, m. a., & alajerami, y. s. (2022). breast cancer knowledge and practice of breast self-examination among female university students, gaza. the scientific world journal, 2021, 6640324. [16] alqahtani, t., alqahtani, a., alshahrani, s., orayj, k., almanasef, m., alamri, a., easwaran, v., & khan, n. a. (2022). assessment of knowledge and practice of mammography and breast self-examination among the general female population in asir region of ksa. european review for medical and pharmacological sciences, 25(23), 7231–7237. [17] linsell, l., forbes, l. j., burgess, c., kapari, m., thurnham, a., & ramirez, a. j. (2010). validation of a measurement tool to assess awareness of breast cancer. european journal of cancer, 46(8), 1374–1381. [18] grunfeld, e., ramirez, a., hunter, m., & richards, m. (2002). women’s knowledge and beliefs regarding breast cancer. british journal of cancer, 86(9), 1373–1378. [19] pöhls, u. g., renner, s., fasching, p., lux, m., kreis, h., ackermann, s., bender, h.-g., & beckmann, m. w. (2004). awareness of breast cancer incidence and risk factors among healthy women. european journal of cancer prevention, 13(4), 249–256. doi 10.18502/sjms.v17i4.12554 page 575 sudan journal of medical sciences manal sa hakami [20] rahman, s. a., al–marzouki, a., otim, m., khayat, n. e. h. k., yousef, r., & rahman, p. (2019). awareness about breast cancer and breast self-examination among female students at the university of sharjah: a cross-sectional study. asian pacific journal of cancer prevention, 20(6), 1901. doi 10.18502/sjms.v17i4.12554 page 576 introduction materials and methods design study population inclusion criteria exclusion criteria sampling and sample size data collection instruments data analysis plan results summary discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding authors' contribution references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12079 production and hosting by knowledge e research article effectiveness of health awareness module on pregnant women’s perception on and experience of constipation at saad abu alela – university hospital, 2017 faiza taha department of obstetrics and gynecology, nursing faculty of nursing sciences, university of khartoum, khartoum, sudan abstract background: pregnancy predisposes women to developing constipation, and hormonal and mechanical factors, sedentary lifestyle, and alteration of diet augments the condition, leading to discomforts experienced by pregnant women. however, this can be controlled through proper education and lifestyle modification. the present study aims to check the effect of health awareness education module on the reduction of constipation among pregnant women. methods: a quasi-experimental study design was used. one hundred and twentyfive pregnant women were randomly selected from saad abu alela hospital between january and march 2017), and based on the rome ii criteria, 59 of them were found to have constipation. after obtaining consent from the women, health awareness module (information about constipation, dietary measures, increased fluid intake, and exercise) was offered to them. data were collected by structured close-ended questionnaire for the knowledge, preand post-intervention, and checklists for the practice and follow-up of the weekly outcome over two months. data were analyzed, and suitable statistical methods was used. p < 0.05 was considered as statistically significant. results: the overall prevalence of constipation was 47.2% with a prevalence of 4%, 6.4%, and 36.8% in the first, second, and third trimesters of pregnancy, respectively. pregnant women’s knowledge about constipation increased significantly from 16.9% preto 92.9 post-intervention with p = 0.000. the fiber diet intake, fluid intake, and exercise by pregnant women increased from 37.3%, 39%, and 13.6% preto 72.9%, 88.1%, and 49.1% post-intervention, respectively) with p = 0.001. moreover, 46 (78%) women were relieved of constipation post-intervention. conclusion: the health awareness module was very effective and significantly increased the level of knowledge, practice, and outcomes with respect to constipation in pregnant women. keywords: constipation, health awareness, pregnancy how to cite this article: faiza taha (2022) “effectiveness of health awareness module on pregnant women’s perception on and experience of constipation at saad abu alela – university hospital, 2017,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 292–302. doi 10.18502/sjms.v17i3.12079 page 292 corresponding author: faiza taha; email: fanasr@uofk.edu received 30 december 2021 accepted 28 may 2022 published 30 september 2022 production and hosting by knowledge e faiza taha. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences faiza taha 1. introduction constipation is a condition in which a person experiences infrequent bowel movements and sensation of incomplete evacuation resulting in passage of hard stool. it is a common complaint among pregnant women and is considered second to nausea [1]. fluctuating hormones, diet short on fluids/fiber, lack of exercise, iron pills intake, mechanical effects of the growing fetus, uterine enlargement causing compression of the rectum, paired with general anxiety can all lead to it. lack of knowledge about the safe management of constipation may complicate the condition. hormonal changes and increased progesterone in pregnancy causes decreased muscle tone and (gi) motility, leading to constipation [2]. hemorrhoids and anal fissures are two most severe complications of constipation [3]. constipation can be very troublesome and complicated by a range of disturbances that affect patients’ quality of life and physical health [4, 5]. one method for assessing constipation is the rome ii criteria, which defines constipation as the presence of at least two of the following symptoms for at least one in four defecation – straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction, manual removal to facilitate defecation, and less than three time in the week [6]. interestingly, the prevalence of constipation in pregnant women ranges from 11 to 38% [7], and those affected by it before pregnancy tend to experience more symptoms while being pregnant [8]. besides, diet short in fiber, inadequate physical activities, stress and anxiety during pregnancy can also be predisposing factors leading to constipation. however, a number of natural ways can help relieve the suffering caused by constipation. who recommends sufficient water and nutritional fiber intake to prevent constipation during pregnancy [9]. there is some evidence that suggest dietary factors such as water intake can prevent, or alleviate, bowel problems during and after pregnancy [10]. in addition, results from a cochrane review support the benefit of fiber in treating constipation during pregnancy. fiber intake increases the frequency of defecation and has no side effects. increased fluid intake as an initial measure is not only inexpensive but also easily obtainable and comes with additional benefits [11]. while constipation can cause discomfort and passive body image conception, it can also lead to psychological problems such as mood fluctuations [12]. in india, the incidence of constipation during pregnancy as one of the morbidities was reported to be lower in women from high-income than those from low-income families [13]. nutritional elements play a crucial role in preventing, or changing, bowel doi 10.18502/sjms.v17i3.12079 page 293 sudan journal of medical sciences faiza taha habit problems during and after pregnancy [14]. to manage constipation through nonpharmacological measures, mothers should be encouraged for regular bowel movement and to increase their fiber and water intake through fruits and vegetables and by drinking at least eight glasses of water daily. in addition, daily walks, good posture, good body mechanics, and daily exercise contracting the lower abdominal muscles can support venous circulation and prevent congestion in the large intestine [15]. one study reveals that many women experience constipation mainly during their second and third trimesters because of the slowed digestion. however, with increased intake of raw fruits and vegetables, whole grain cereals, fluids, mainly water, the problem can be relieved [16]. another study of chinese population shows that increasing dietary fiber intake was successful in relieving chronic constipation [17]. justification: little is known about the information pregnant women need about constipation and the extent to which they have benefited from the knowledge acquired from training modules. the current study was, therefore, conducted on pregnant women from saad abu alela hospital who reported having constipation to examine their awareness level of constipation, its management, and health outcome. patients’ nutritional history showed inadequate dietary intake of fibrous food and fluid and a general lack of physical activities and exercises. non-pharmacological means were recommended initially to manage constipation during pregnancy. 1.1. hypothesis of the study 1. h₀: training module has no significant effect on the level of knowledge, practice, and reduction of constipation in pregnant women. 2. h₁: training module has a significant effect on the level of knowledge, practice, and reduction of constipation in pregnant women. 2. materials and methods a quasi-experimental hospital-based study (pre–post intervention) was conducted at saad abu alela hospital from january to march 2017. one hundred and twenty-five pregnant women were selected randomly during regular antenatal follow-up. the sample size was calculated as follows: n = z2 (pq)/d2 p = 0.2 doi 10.18502/sjms.v17i3.12079 page 294 sudan journal of medical sciences faiza taha q = (1–p) d2 = ( 0.07) the proportion was drown from the findings of the pilot study that revealed 0.2% of pregnant women suffer from constipation. (1.96)2(0.2 × 0.8) / (0.07)2 = 3.846 × 0.16 / o.oo49 = 125 (1.96)2(0.2 × 0.8) / (0.07)2 = 3.84 × 0.16 / o.oo49 = 125 next, the women were arranged in chronological order and the sample was selected randomly from the primary healthcare center in saad abu alela hospital. a total of 59 women had reported constipation based on the rome ii criteria. after obtaining participants’ consent, the study was conducted in three phases – pre-intervention (assessment of participants’ knowledge and practices using structured close-ended questionnaire for the knowledge and a checklist for the practice); intervention (offering awareness module on constipation management, non-pharmacological measures, dietary measures, exercise, etc. to the participants); and post-intervention (data collection through a structured close-ended questionnaire for knowledge, a checklist for practice and bowel habits, a seven-day stool diary sheet used every week over two months to assess the outcome). data were analyzed using the spss and suitable descriptive and inferential statistical methods were used as paired t-test. p < 0.05 was considered the level of significance. 3. results out of 125 pregnant women visiting the antenatal clinic, 59 reporting constipation based on the rome 11 criteria were studied. majority of the participants were in the age group of 20–35 years, lived in urban areas, and were housewives. half of them were university graduates (table 1). more than two-third women were multigravida and a majority of them were in their third trimester with regular antenatal follow-up. in addition, previous experience of constipation was reported in more than one-third of them (table 2). however, the knowledge level of the women about constipation increased significantly after intervention (table 3). the ability of women in managing constipation improved significantly after intervention (table 4). a significant change was seen in women’s overall heath following the intervention (table 5). table 1 shows that 78% of the participants were aged 20–35 years, 52.5% were university graduates, and most of them were housewives 79.7% and lived in urban areas 72.9%. doi 10.18502/sjms.v17i3.12079 page 295 sudan journal of medical sciences faiza taha table 1: demographic data of the participants, n = 59. data type frequency percentage age (yr) <20 2 3.4 20–35 46 78 >35 11 18.6 residence urban 43 72.9 rural 16 27.1 occupation student 2 3.4 housewife 47 79.7 working 10 16.9 education illiterate 2 3.4 primary 6 10.2 secondary 20 33.9 university 31 52.5 economic status insufficient 23 39 sufficient 36 61 table 2: obstetrics information of the participants, n = 59. information type frequency percentage number of pregnancies primagravida 19 32.2 multigravida 40 67.8 follow-up during pregnancy irregular 15 25.4 regular 44 74.6 gestational age (wk) 1–13 5 8.5 14–26 8 13 27–40 46 78 had experienced constipation before pregnancy 23 38.9 table 2 shows that the prevalence of constipation was high in women who were multigravida (67.8%) and in their third trimester and the knowledge of the studied participants about constipation during pregnancy increased significantly post-intervention from 16.9 to 92.9%, p = 0.000. table 4 shows that the management of constipation with non-pharmacological measures post-intervention increased significantly from 30 to 70% with p = 0.001. doi 10.18502/sjms.v17i3.12079 page 296 sudan journal of medical sciences faiza taha table 3: knowledge of the study population about causes and management of constipation during pregnancy preand post-intervention, n = 59. pre-intervention post-intervention p-value frequency % frequency % hormonal changes 16 27.2 59 100 iron supplementation during pregnancy 6 9.6 54 91.5 anxiety 2 3.4 44 74.6 exercises 4 7.2 54 91.5 take high fiber diet 25– 30 gram daily 20 34.4 59 100 take large amount of fluid (10–12 cups daily) 11 19.2 59 ‘100 average 16.9 92.9 0.000 table 4: management of constipation with non-pharmacological measures during pregnancy preand post-intervention, n = 59. items pre-intervention post-intervention p-value frequency percentage (%) frequency percentage (%) take high fiber diet (25–30 gram daily) 22 37.3 43 72.9 take large amount of fluid (10–12 cups daily) 23 39 52 88.1 exercises (walking) 1.5 hr three times/wk 8 13.6 29 49.1 average 30 70 0.001 table 5: health status of the study population post-intervention (reduction of constipation), n = 59. outcome number of participants percentage (%) the condition totally improved within 3 wk 8 13.5 4 wk 20 33.9 6 wk 14 23.7 8 wk 4 6.8 total percentage of improved cases 78% the condition did not improve and constipation continued 10 17 constipation continued and led to complications 3 5.1 (hemorrhoids) total percentage of cases in which no improvement was seen 22 table 5 shows that the majority of cases improved after intervention but one-fifth of them reported no improvement, while 5% of them developed complication. doi 10.18502/sjms.v17i3.12079 page 297 sudan journal of medical sciences faiza taha 4. discussion constipation is common in pregnancy, it may be caused due to hormonal, physical, or mechanical changes, and is usually aggravated by sedentary lifestyle, improper diet, and iron supplementation. a number of natural ways can help reduce the suffering caused by constipation and health awareness and education of pregnant women plays a crucial role in it. the prevalence of constipation in our study was 47.2% and found to be more common in the third trimester of pregnancy (36.8%), which was higher than the rate found in another study, where 24% of the pregnant women developed it, and it was more common in the second trimester of pregnancy 34% [18]. in addition, a correlational study found that the prevalence of constipation was 29.6%, 19%, and 21.8% in the first, second, and third trimesters, respectively [19], while it was 24%, 26%, and 16% in the first, second, and third trimesters, respectively in another study [10]. although previous evidence shows that the prevalence of constipation is higher in the second and third trimesters, in this study, a high prevalence was seen in the third trimester of pregnancy [20]. additionally, there is a relationship between constipation and gestational age, 36.8% of the study population experience constipation in the third trimester and is generally caused by the pressure of growing uterus which interferes with bowel movement [4]. the knowledge of pregnant women regarding the causes and management of constipation increased significantly from 16.9% preto 92.9% postintervention; this increase may be related to the fact that most of them were young (78%) – 20–35 years old – and more than half (52.5%) were university-educated. the results of the present study shows the adherence of the module by the women, which = are similar to the results of previous studies that have proved that a majority of pregnant women responded to diet and fluid regulation advice [3, 6, 11] and that fiber supplementation may increase the frequency of stools [16] as the increased fibre diet and fluid intake by the participants in this study increased, respectively, from 37.3% and 39% pre-intervention to 72.9% and 88.1% post-intervention). additionally, it was found that exercise by pregnant women with constipation increased significantly from 13.6% preto 49.1% post-intervention but still more than half of them did not practice it, this may be due to their culture and wrong beliefs. overall, constipation was treated in the majority of women (46; 77.9%) post-intervention, which is consistent with the results of the study that reveal 35 (72.4%) women responded to conservative treatment [18]; study where after there was an increase in the frequency of bowel movements post-intervention [21]; and studies that supported the safe benefit of fiber in managing constipation in pregnancy [7, 8]. however, constipation persisted in 13 (22%) women doi 10.18502/sjms.v17i3.12079 page 298 sudan journal of medical sciences faiza taha who were muligravida and in third trimester with previous experience of constipation due to the lack of their muscle tone and growing uterus during the third trimester on the lower part of the (gi) tract and rectum. three women developed hemorrhoids as a result of constipation, as seen in previous studies [14, 22]. nutrition and exercise were means for prohibiting constipation and its complication in pregnancy. but the complication can develop due to several other factors [23]. management of constipation with laxatives appears to be more effective in the improvement of constipation but is accompanied by side effect as an increase in diarrhea and abdominal discomfort [16]. the strength of this study was considering the principles of intervention with weekly follow-ups of participants in order to ensure the correct use of intervention as well as answering questions and determining the outcome. in addition, fortunately, our intervention was safe with minimal side effects, so most participants accepted the type of intervention. 5. limitations a majority of the participants were in their third trimester of the pregnancy. in addition, the small sample size may not give a clear picture of the results. besides, since this study has been conducted on apparently healthy pregnant women, the results of the present study cannot be generalized on pregnant women with a complicated pregnancy 6. conclusion health awareness of pregnant women about constipation was very effective and significantly increased the level of knowledge, practice, and women’s health outcomes related to constipation during pregnancy. constipation is more common in pregnant women, mainly among multigravida women. recommendation there is an urgent need for regular antenatal classes about self-care and health promotion during pregnancy to prevent constipation. doi 10.18502/sjms.v17i3.12079 page 299 sudan journal of medical sciences faiza taha ethical considerations the study protocol was approved by the faculty of nursing sciences on january 12, 2017. participants were informed about the nature of the study and the right to withdraw at any time, without giving any reason. participants’ verbal agreement was obtained and confidentiality was maintained during the gathering, analysis, and interpretation of the participant’s data. competing interests none. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding self-funded. references [1] cullen, g., & o’donoghue, d. (2007). constipation and pregnancy. best practice & research. clinical gastroenterology, 21(5), 807– 818. https://doi.org/10.1016/j.bpg.2007.05.005 [2] pourhoseingholi, m. a., kaboli, s. a., pourhoseingholi, a., moghimi-dehkordi, b., safaee, a., mansoori, b. k., habibi, m., & zali, m. r. (2009). obesity and functional constipation; a community-based study in iran. journal of gastrointestinal and liver diseases, 18(2), 151–155. [3] vazquez, j. c. (2010, august). constipation, haemorrhoids, and heartburn in pregnancy. clinical evidence, 2010, 1–17. [4] longo, s. a., moore, r. c., canzoneri, b. j., & robichaux, a. (2010). gastrointestinal conditions during pregnancy. clinics in colon and rectal surgery, 23(2), 80– 89. https://doi.org/10.1055/s-0030-1254294 doi 10.18502/sjms.v17i3.12079 page 300 sudan journal of medical sciences faiza taha [5] thukral, c., & wolf, j. l. 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[18] bimba, k., patil, g. l., shridevi, a. s., praveena, s. n., asha, b., mandava, s., reddy, h. (2017). prevalence of constipation in pregnancy a prospective study at a tertiary care hospital. journal of gynecology, 1(2), 1–11. [19] ponce, j., martínez, b., fernández, a., ponce, m., bastida, g., plá, e., garrigues, v., & ortiz, v. (2008, january). constipation during pregnancy: a longitudinal survey based on self-reported symptoms and the rome ii criteria. european journal of gastroenterology & hepatology, 20(1), 56–61. https://doi.org/10.1097/meg.0b013e3281108058 [20] derbyshire, e., davies, j., costarelli, v., & dettmar, p. (2006, july). diet, physical inactivity and the prevalence of constipation throughout and after pregnancy. maternal and child nutrition, 2(3), 127–134. https://doi.org/10.1111/j.17408709.2006.00061.x [21] de milliano, i., tabbers, m. m., van der post, j. a., & benninga, m. a. 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(2008). constipation, haemorrhoids and heartburn in pregnancy. bmj clinical evidence, 142(3): 127–134. doi 10.18502/sjms.v17i3.12079 page 302 introduction hypothesis of the study materials and methods results discussion limitations conclusion recommendation ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13598 production and hosting by knowledge e research article knowledge and practice of glucose self-monitoring devices among patients with diabetes sami mohamed, mutasim mukhtar, khalid aseed, duaa osman, mujtaba dawelbait, ahmed saeed, nasma ahmed, nihal fadul, and rogia idriss department of internal medicine, faculty of medicine, nile university, khartoum north, sudan orcid: sami mohamed: https://orcid.org/0000-0003-0187-9056 abstract background: with blood glucose self-monitoring, patients may assess how well their glucose level is controlled, and change their treatment plan as advised by their physicians. the development and increasing availability of different devices that are readily accessible plays a significant role in glycemic control and prevention of complications through early recognition with proper practice. methods: this observational cross-sectional study includes patients with diabetes attending khartoum north diabetes and endocrinology hospital and was carried out in april–july 2021 using convenient sampling via questionnaires obtained and filled by data collectors through interviews. data analysis was done using spss software. results: out of 125 total patients, 82 had prior basic knowledge about glucose selfmonitoring devices. twenty-four patients were using it regularly, and only seven were using it daily. fifty-one patients had never used any device before. fifty-five patients owned a device, and the rest borrowed or used devices available at healthcare centers or clinics, pharmacies, relatives’ or neighbors’ devices. factors hindering the use of devices included financial difficulties and lack of education. most frequent users had a stable occupation. just below half of the patients using devices had good practice techniques with significant association with higher level of education. the rest had poor practice technique that was associated with lower level of education. conclusion: utilization of glucose self-monitoring devices is prevalent among patients with diabetes. however, many challenges require attention to facilitate ongoing selfuse with proper practice inline with education and access. keywords: diabetes, glucometer, hyperglycemia, self-monitoring, glucose control 1. introduction type 2 diabetes has become more common in several regions. it is a lifelong condition that needs continuous medical care and lifestyle changes. it is expensive to manage diabetes and its consequences, especially in developing countries [1]. numerous studies have demonstrated that controlling blood glucose levels can lower chances of developing complications [2]. although many patients with diabetes have poor glycemic control, how to cite this article: sami mohamed, mutasim mukhtar, khalid aseed, duaa osman, mujtaba dawelbait, ahmed saeed, nasma ahmed, nihal fadul, and rogia idriss (2023) “knowledge and practice of glucose self-monitoring devices among patients with diabetes,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 127–138. doi 10.18502/sjms.v18i2.13598 page 127 corresponding author: sami mohamed; email: samicm@yahoo.com received 3 january 2023 accepted 7 february 2023 published 30 june 2023 production and hosting by knowledge e sami mohamed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sami mohamed et al it is possible to improve patients’ knowledge, practice, and self-efficacy to obtain better glycemic control [3]. the effectiveness of patient education in enhancing patients’ knowledge, attitude, practice, and self-efficacy is becoming more evident. with the help of blood glucose self-measurement, patients may keep a close watch on control of their condition and, in the case of blood glucose fluctuations, modify their therapy as advised [4]. studies have shown a connection between self-monitoring frequency and positive changes in blood glucose levels [5]. patients use many devices to check their blood glucose levels [6]. unfortunately, most patients with diabetes find it unpleasant to check their blood sugar levels often. traditional measurement devices employ electrochemical techniques, which utilize a small volume of blood to be drawn by a finger prick or a thin lancet inserted under the skin. the first differs from the last in that it just gives a single reading of the glucose level [7]. large number of patients with diabetes have limited understanding of managing their condition and monitoring their blood sugar. self-checking blood glucose levels at home can give patients and doctors useful information that helps in managing their diabetes, though the price of test strips may be a factor affecting regular monitoring [8]. patients are generally interested in trying newer devices, and there is increasing acceptance of using self-monitoring devices, however, they do not necessarily use them regularly. in many populations, self-monitoring may not be associated with improved control [9]. using the device may improve physical self-awareness, thus making patients less dependent on professionals. therefore, proper techniques of self-monitoring should be taught and encouraged by healthcare providers [10]. proper practice techniques of utilizing glucose self-monitoring devices is part of many key factors determining the accuracy of test readings, and treatment errors might result from inaccurate blood glucose levels [11]. lack of education is a major contributor toward incorrect self-monitoring practice. patients must be properly educated on how to measure their own blood sugar levels in addition to how to handle and store strips. blood sugar values must be carefully interpreted as part of said education, since making wrong judgments might arise from inappropriately considering grossly atypical results [11]. many patients either own or know how to use simple self-monitoring devices. however, many do not correctly practice their utilization. and a select number learn from neighbors and family members rather than healthcare professionals [12]. diabetes treatment expenses are always rising in poor nations in which resources are scarce. however, greater financial and therapeutic benefits may come from patients’ understanding of basic concepts of self-evaluation and follow-up. thus being familiar doi 10.18502/sjms.v18i2.13598 page 128 sudan journal of medical sciences sami mohamed et al with and proficient in using self-monitoring devices help them become able to respond appropriately when encountering abnormal readings, which may indirectly reduce economic implications of disease complications. therefore, the objectives of the current study were to: identify prior knowledge about utilization of glucose self-monitoring devices; determine the prevalence of utilization of glucose self-monitoring devices; assess proper use of glucose self-monitoring devices; and assess challenges hindering use, and proper practice, of glucose self-monitoring devices. 2. materials and methods 2.1. study design this study was an observational cross-sectional study. 2.2. study population the study included patients with diabetes attending diabetes and endocrinology hospital, khartoum north, sudan, between april 2021 and july 2021. however, patients who were critically ill, lacked capacity, or refused to participate in the study were excluded. 2.3. sampling technique a convenient random sampling method was used. the sample size was 125, and was calculated using standard statistical formula with a 95% confidence level, a 50% population proportion, a 5% margin of error, and a population size of 185. 2.4. data collection data were collected via structured questionnaire filled by data collectors through direct interviews after obtaining proper consent. the questionnaire was designed by the authors using related background information, with questions concerning proper practice technique being adopted, with modification, from a previous study [10]. simple validation techniques were used including face validation in addition to qualified statistician approval, with no further validation before data collection. doi 10.18502/sjms.v18i2.13598 page 129 sudan journal of medical sciences sami mohamed et al 3. results data were analyzed using the spss statistical analysis software. categorical variables were used to present the result as frequencies and percentages. associations including cross tabulation was done using chi-square testing and assessing statistical significance where the level of significance is set to be at p-value < 0.05. total number of sample size was 125 patients. there were no incomplete responses nor lost data. moreover, 60% of the patients were males while 40% were females. most (32.8%) were in their fifth decade; 24.8% in their fourth, 22.4% were >60 years of age, 8.8% were in their third decade, and 11.2% were <30 years old. in addition, 44 (35.2%) patients were unemployed, while the rest were either students (4.8%), employees (17.6%), free workers (33.6%), or retired (8.8%). while 21.6% of patients were illiterate, 28% were at primary school level, 23.2% at secondary school level, and 27.2% at collage level. majority of patients (71, 56.8%) were diagnosed with diabetes <10 years ago (table 1). the study revealed that 82 patients (65.6%) had prior basic knowledge about glucose self-monitoring devices, while the rest (34.4%) had none. sources of information were self-learning (6, 4.8%), physician education (38, 30.4%), pharmacists (7, 5.6%), and relatives (34, 27.2%) (table 1). overall, 67 (53.6%) patients used a glucose self-monitoring device before, while 58 (46.4%) had not. most patients (32) who had used devices before were taught by their physicians, while others were taught by their relatives, neighbors, pharmacists, or had taught themselves through self-learning methods (table 2). assessment of correct and proper technique when using glucose self-monitoring devices revealed that out of the total 125 patients, 47 (37.6%) properly disinfected their hands before using the device, while 37 (24.8%) did not. in addition, 61 (48.8%) patients measured glucose level using the first drop of blood from their fingers rather than the second drop (39.2%); 50 (40%) patients discarded the needle/lancet after using it once, 16 (12.8%) did not discard it, and only 8 (6.4%) patients reused the same needle after disinfecting it. moreover, 31 (24.8%) patients punctured same finger every time rather than different fingers (44, 35.2%) and 39 (31.2%) patients measured the blood glucose both fasting and postprandial. only 5.6% of patients used devices daily and 19.2% were used it regularly (table 2). patients who provided answers corresponding to proper practice technique in two or more out of four practice technique questions (hands disinfection before use, used needle discard, different finger puncture, and first blood drop avoidance) were 44.8%, while 55.2% had answered less than two questions correctly. doi 10.18502/sjms.v18i2.13598 page 130 sudan journal of medical sciences sami mohamed et al regarding patients’ access to devices, of the 125 patients, 55 (44%) owned a device, others gained access through healthcare centers or clinics (57, 45.6%), relatives or neighbors (12, 9.6%), and one patient through pharmacies. in total, 37 (29.6%) patients considered that financial reasons constitute a major challenge preventing them from gaining access to a glucose self-monitoring device, while others (19, 15.2%) chose lack of prior knowledge and education, and significant number of patients (52, 41.6%) could not provide a specific challenge (table 2). assessing the relation of occupation to frequency of use and means of accessing devices revealed that 41.7% out of 24 regular users were independent workers, and 46.5% out of 43 non-regular users were unemployed (p-value = 0.017). out of 55 patients who owned devices, 32.7% were independent workers and 36.4% were unemployed (p-value = 0.036) (table 3). assessing the relation of proper correct technique of device use with the level of education revealed that most college or higher educated patients disinfect their hands before using the device (44.70%, p-value = 0.019) and discard first blood drop (60.00%, p-value = 0.004,). however, a significant number of higher educated patients repeat same finger puncture during device practice (51.60%, p-value = 0.007; table 4). 4. discussion most patients had prior knowledge about utilization of glucose self-monitoring devices. this might be due to the variation in sources of education either on individual level or the primary healthcare level, though relatives and neighbors played a significant role in patients’ education and support alongside physicians. significant number of patients have used a device previously whether by themselves or through assistance of relatives or healthcare centers. despite that, significant number did either implement incorrect practice techniques or had no knowledge of how to properly utilize glucose self-monitoring devices. it is important to mention that physicians and healthcare providers did not appear to be the main reference in teaching for a number of patients, with relatives and neighbors may be appearing to be closer to patients’ environment. although having access to a device and knowing how to properly practice its use do not always equate to good glycemic control in some populations [9], it still plays a significant role in determining the frequency of monitoring which, in turn, helps in prevention of unfavorable outcomes. this has been demonstrated in previous studies [5]. less than half of patients had their own self-monitoring device. this apparent low response may be due to financial difficulties and device availability, given the relatively doi 10.18502/sjms.v18i2.13598 page 131 sudan journal of medical sciences sami mohamed et al table 1: demographic data and device knowledge responses. parameter response frequency percentage gender male 75 60.00% female 50 40.00% age (yr) 31–40 11 8.80% 41–50 31 24.80% 51–60 41 32.80% >60 28 22.40% educational level illiteracy 27 21.60% primary school 35 28% secondary school 29 23.20% college 34 27.20% occupation student 6 4.80% employee 22 17.60% independent worker 42 33.60% retired 11 8.80% unemployed 44 35.20% duration of diabetes (yr) <5 31 24.80% 5–10 40 32% >10 54 43.20% device prior knowledge yes 82 65.60% no 43 34.40% source of device knowledge self-learning 6 4.80% physician 38 30.40% relatives 34 27.20% pharmacist 7 5.60% no one 40 32% high cost of devices. despite that, a significant number of patients could not provide a specific challenge preventing them from gaining access to a device. furthermore, a number of patients reuse same needles during their practice, which can be explained by test strips cost and availability. these challenges were usually found more prevalent in rural environments, whereas urban populations were relatively affected to a lesser degree [8]. just below half of the patients utilizing devices demonstrated overall proper practice of device use by providing proper responses to most questions. this is lower than expected given the level of background knowledge and source of practice education found, yet it differs from other populations that showed poor outcome to both basic knowledge and proper practice [8, 10]. however, this may be due to decreased participation of healthcare providers in the process of education and awareness of patients doi 10.18502/sjms.v18i2.13598 page 132 sudan journal of medical sciences sami mohamed et al table 2: practice technique responses and challenges hindering device utilization. parameter response frequency percentage prior use of devices yes 67 53.60% no 58 46.40% source of teaching practice techniques self-learning 9 7.20% physician 32 25.60% relatives or neighbors 28 22.40% pharmacist 4 3.20% nurses 9 7.20% no source 43 34.40% disinfecting hands before use yes 47 37.60% no 31 24.80% do not know 47 37.60% using the first drop of blood yes 61 48.80% no 15 12% do not know 49 39.20% discarding needle after single use yes 50 40% no 16 12.80% reuse after disinfecting needle 8 6.40% do not know 51 40.80% repeating same finger puncture yes 31 24.80% no 44 35.20% do not know 50 40% timing of device use fasting 15 12% after meal (postprandial) 20 16% both 39 31.20% do not know 51 40.80% frequency of device use daily 7 5.60% regular 24 19.20% non regular 43 34.40% rarely 51 40.80% means of access to devices own device 55 44% pharmacy 1 0.80% healthcare centers or clinics 57 45.60% relatives or neighbors 12 9.60% challenges hindering device utilization financial difficulties 37 29.60% no prior knowledge 19 15.20% availability of the device 11 8.80% do not think it is important 6 4.80% do not have a specific challenge 52 41.60% doi 10.18502/sjms.v18i2.13598 page 133 sudan journal of medical sciences sami mohamed et al table 3: relation between occupation vs means of access to devices and frequency of use. occupation student employee independent worker retired unemployed freq. % freq. % freq. % freq. % freq. % means of access to devices own device 3 5.50% 10 18.20% 18 32.70% 4 7.30% 20 36.40% p-value 0.036 pharmacy 1 100.00% 0 0.00% 0 0.00% 0 0.00% 0 0.00% health centers or clinics 2 3.50% 9 15.80% 21 36.80% 6 10.50% 19 33.30% relatives or neighbors 0 0.00% 3 25.00% 3 25.00% 1 8.30% 5 41.70% frequency of device use daily 1 14.30% 1 14.30% 1 14.30% 3 42.90% 1 14.30% p-value 0.017 regular 3 12.50% 5 20.80% 10 41.70% 2 8.30% 4 16.70% non regular 1 2.30% 9 20.90% 12 27.90% 1 2.30% 20 46.50% rarely 1 2.00% 7 13.70% 19 37.30% 5 9.80% 19 37.30% table 4: relation between level of education vs proper practice technique responses. level of education illiteracy primary school secondary school college freq. % freq. % freq. % freq. % disinfecting hands before use yes 7 14.90% 9 19.10% 10 21.30% 21 44.70% p-value 0.019 no 6 19.40% 9 29.00% 8 25.80% 8 25.80% do not know 14 29.80% 17 36.20% 11 23.40% 5 10.60% using the first drop of blood yes 11 18.00% 14 23.00% 16 26.20% 20 32.80% p-value 0.004 no 1 6.70% 4 26.70% 1 6.70% 9 60.00% do not know 15 30.60% 17 34.70% 12 24.50% 5 10.20% repeating same finger puncture yes 5 16.10% 3 9.70% 7 22.60% 16 51.60% p-value 0.007 no 8 18.20% 14 31.80% 10 22.70% 12 27.30% do not know 14 28.00% 18 36.00% 12 24.00% 6 12.00% who may rather reach out toward their closer environment, namely their neighbors and relatives. furthermore, different challenges may contribute indirectly toward improper practice, whether financial or environmental, through insufficient patient education. significant number of patients measured their glucose levels before and after meals which is considered a better frequency for close monitoring of blood glucose. few were regular users and more were non-regular users. the majority of those regular users doi 10.18502/sjms.v18i2.13598 page 134 sudan journal of medical sciences sami mohamed et al were independent workers, while a number of non-regular users were unemployed with statistically significant relation (p-value = 0.017). this indicates that either employment or working may help patients become more regular in self-monitoring and that may be partly due to the cost of test strips which are required for ongoing use. these findings support consistent demonstrations of occupation as a predictor of ongoing use of selfmonitoring devices [10]. when assessing the relation of correct practice to patients’ level of education, there appeared to be a statistically significant relation between proper practice techniques and higher education level. while the majority of patients with prior knowledge about self-monitoring devices had previously achieved college level of education, those with no prior knowledge were illiterate. this reflected the prominent effect of education on knowledge and awareness (p-value = 0.002). it may be explained by background knowledge that helps drive seeking expert advice in any health-related issues, which appears to be consistent in other populations [10]. 5. conclusion utilization of glucose self-monitoring devices is prevalent among patients with diabetes. however, many factors facilitating ongoing regular use require special attention, such as variation in occupation. multiple challenges, related to level of education and financial difficulties, are involved in, and significantly affect, proper practice techniques. furthermore, lack of direct involvement of healthcare services practice-related education as well as awareness may indirectly affect glycemic control in patients with diabetes. impact wide incorporation of glucose self-monitoring devices into national health insurance institutions would be beneficial in overall diabetes control and complications prevention while alleviating financial-related challenges. provision of healthcare personnel education for patients’ understanding of proper utilization alongside awareness programs encouraging promotion of self-measurement of blood glucose would impact proper practice. doi 10.18502/sjms.v18i2.13598 page 135 sudan journal of medical sciences sami mohamed et al limitations direct observation of patients live practicing glucose self-measurement using devices would further confirm proper practice and eliminate doubts or bias that might accompany data collection from plain interviews utilizing patients’ responses, which may limit accuracy of information obtained. furthermore, advanced analytical techniques including binary logistic regression assessing association between different parameters in larger populations would provide additional statistically significant information. acknowledgements expressions of appreciation and gratitude towards khartoum north diabetes and endocrinology hospital and university for providing ground and support throughout the process of this study. ethical considerations an informed verbal consent was obtained from each patient before data collection while ensuring clear confidentiality and anonymity during data collection from both patients and collectors. ethical clearance and approval was obtained from relevant authorities and study area as appropriate. competing interests authors declare no conflict of interest. availability of data and material data available within submitted article. funding neither outsourced funding nor grants were obtained from any institution or organization. doi 10.18502/sjms.v18i2.13598 page 136 sudan journal of medical sciences sami mohamed et al references [1] larejani, b., & zahedi, f. (2001). epidemiology of diabetes mellitus in iran. iranian journal of diabetes and lipid disorders, 1(1). http://ijdld.tums.ac.ir/article-1-490en.html [2] kim, h.-s., kim, n.-c., & ahn, s.-h. (2006). impact of a nurse short message service intervention for patients with diabetes. journal of nursing care quality, 21(3), 266– 271. https://doi.org/10.1097/00001786-200607000-00012 [3] mathieu-fritz et caroline guillot, a. (2017). diabetes self-monitoring devices and transformations in “patient work”. revue d’anthropologie des connaissances. https://doi.org/10.3917/rac.037.k [4] goodarzi, m., ebrahimzadeh, i., rabi, a., saedipoor, b., & jafarabadi, m. a. (2012). impact of distance education via mobile phone text messaging on knowledge, attitude, practice and self-efficacy of patients with type 2 diabetes mellitus in iran. journal of diabetes and metabolic disorders, 11(1), 10. https://doi.org/10.1186/22516581-11-10 [5] nazmi, a. s., khan, s. a., & hadithi, d. a. (2013). self-monitoring of blood glucose level among diabetic patients in muscat, oman: a pilot study. saudi journal for health sciences, 2, 54–57. https://www.saudijhealthsci.org/text.asp?2013/2/1/54/112632 [6] mol, a. (2000). what diagnostic devices do: the case of blood sugar measurement. theoretical medicine and bioethics, 21(1), 9–22. https://doi.org/10.1023/a:1009999119586 [7] villena gonzales, w., mobashsher, a. t., & abbosh, a. (2019). the progress of glucose monitoring – a review of invasive to minimally and non-invasive techniques, devices and sensors. sensors, 19(4), 800. https://doi.org/10.3390/s19040800 [8] shabnum, s., & sarwar, h. (2018). knowledge, attitude and practice of blood glucose monitoring in rural area among diabetic patients. international journal of social sciences and management, 5(3), 225–230. https://doi.org/10.3126/ijssm.v5i3.20615 [9] farhan, s. a., shaikh, a. t., zia, m., kahara, b. r., muneer, r., rehman, m., mubashir, a., sadiq, h., siddiqui, d. e., haseeb, s. m., tanveer, h., siddiq, k., mujtaba, s. b., mirza, s. a., feroz, h., & fatima, k. (2017). prevalence and predictors of home use of glucometers in diabetic patients. cureus, 9(6), e1330. https://doi.org/10.7759/cureus.1330 [10] krishnan, v., & thirunavukkarasu, j. (2016). assessment of knowledge of self blood glucose monitoring and extent of self titration of anti-diabetic drugs among diabetes mellitus patients – a cross sectional, community doi 10.18502/sjms.v18i2.13598 page 137 sudan journal of medical sciences sami mohamed et al based study. journal of clinical and diagnostic research, 10(3), fc09–fc11. https://doi.org/10.7860/jcdr/2016/18387.7396 [11] erbach, m., freckmann, g., hinzmann, r., kulzer, b., ziegler, r., heinemann, l., & schnell, o. (2016). interferences and limitations in blood glucose self-testing: an overview of the current knowledge. journal of diabetes science and technology, 10(5), 1161–1168. https://doi.org/10.1177/1932296816641433 [12] kenya, s., lebron, c., reyes arrechea, e., & li, h. (2014). glucometer use and glycemic control among hispanic patients with diabetes in southern florida. clinical therapeutics, 36(4), 485–493. https://doi.org/10.1016/j.clinthera.2013.12.009 doi 10.18502/sjms.v18i2.13598 page 138 introduction materials and methods study design study population sampling technique data collection results discussion conclusion impact limitations acknowledgements ethical considerations competing interests availability of data and material funding references microsoft word sjms.docx © this document is distributed under the creative commons attribution license (cc by). i issn: online – 1858-5051 https://knepublishing.com/index.php/sjms/index acknowledgement to reviewers 2022 the editorial team of the sudan journal of medical sciences (sjms) would like to thank the following reviewers for their time and efforts in contributing to the reviews of the submissions received in the year 2022. amal halim maria satti anwar kordofani mohammed saeed al khalifa ayman fisal ahmed foad muataz amin babikir kaballo muaz elsayed bashayer zein muhammad waqar qureshi elmuntasir salah nadia eldawi elsagad eltayb naheed memon faiza ali nasor taha nazik elmalaika obaid seid ahmed husain fatema faqueeh waled am ahmed geetu bhandoria safinaz khalil hiba awadelkareem osman fadl sittana shamseldin elshafie mohamed hyder mirghani taha umbeli wisal omer nabag sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12122 production and hosting by knowledge e research article sero-molecular epidemiology of hepatitis e virus in blood donors, gezira state, sudan: a cross-sectional study nassir abakar babiker1, adam dawoud abakar2, nawal tagelsir mohamed3, , elhadi a ahmed4, musaab ahmed5,6, mohamed h ahmed7, abdualmoniem o. musa8, nadir abuzeid9* 1central medical laboratory, wad medani teaching hospital for obstetrics & gynecology, wad medani, sudan 2department of medical parasitology, faculty of medical laboratory sciences, university of gezira, sudan 3department of parasitology, nphl research unit, khartoum, sudan 4department of medical microbiology, faculty of medical laboratory sciences, university of gezira, sudan 5college of medicine, ajman university, ajman, united arab emirates 6center of medical and bio-allied health sciences research, ajman university, ajman, united arab emirates 7department of medicine and hiv metabolic clinic, milton keynes university hospital, nhs foundation trust, milton keynes, uk 8department microbiology, faculty of medical laboratory sciences, university of kassala, kassala, sudan 9department of microbiology, faculty of medical laboratory sciences, omdurman islamic university, omdurman, sudan orcid: nadir musa khalil abuzeid: https://orcid.org/0000-0003-2074-7892 abstract background: hepatitis e virus (hev) is a hepatotropic pathogen that causes significant morbidity and mortality in humans. it is an important causative agent of viral hepatitis outbreaks. this study investigates the serological and molecular prevalence of hev in blood donors attending the central blood bank in wad medani city in gezira state, sudan. methods: the study adopted a cross-sectional descriptive design. a structured questionnaire was used to collect data concerning demographic information and risk factors associated with hev transmission. all enrolled participants (n = 300) were screened for hev igg antibodies using commercial elisa kits, then strong positive samples (n = 84) were selected and rescreened for hev igm and hev rna by rt pcr. spss version 24.0 was used for analysis. results: out of 300 male participants, 36.3% (109/300) were positive for hev igg. however, only one participant was igm positive, while the hev rna was negative. the highest prevalence rates of the virus were 42 (44.6%) among the age group of 31–40 years, 20 (48.8%) in those who consumed food from outside, 13 (50%) in three to four multiple blood donations, and 5 (62.5%) in those who consumed water from the river source. a significant association of hev igg prevalence concerning the occupation of the participants being students or farmers was detected using univariate and multivariate analysis (p-value = 0.007). how to cite this article: nassir abakar babiker, adam dawoud abakar, nawal tagelsir mohamed, , elhadi a ahmed, musaab ahmed, mohamed h ahmed, abdualmoniem o. musa, nadir abuzeid (2022) “sero-molecular epidemiology of hepatitis e virus in blood donors, gezira state, sudan: a cross-sectional study,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 376–386. doi 10.18502/sjms.v17i3.12122 page 376 corresponding author: nadir abuzeid; email: nadirabuzeid@oiu.edu.sd received 22 august 2021 accepted 5 august 2022 published 30 september 2022 production and hosting by knowledge e nassir abakar babiker et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nassir abakar babiker et al conclusion: high prevalence of hev igg was demonstrated among the healthy blood donors in this study. given the possibility of hev transmission by transfusion from donors to recipients, we recommend that routine screening for hev should be adopted by blood banks in sudan. keywords: hev igg, blood donors, hev risk factors, hev igm, hev rt pcr, sudan 1. introduction hepatitis e virus (hev) initially belonged to the family caliciviridae, but recently after the introduction of molecular techniques, the virus has been reclassified and placed in the hepeviridae family [1]. although the virus is serotypically homogenous, it has been subdivided into four genotypes: genotypes 1 and 2 are mainly found in humans, whereas genotypes 3 and 4 represent porcine hevs but can also infect humans [2]. in addition, the family of hepeviridae is phylogenetically divided into two genera, with four species in genus orthohepevirus [3]. hev prevalence rate in africa is variable. it was reported to be 45.3% in egypt [4], 5.4% and 22% in tunisia [5, 6], and 19.1% in burkina faso blood donors [7]. studies conducted among risk groups revealed the variable distribution of serological markers of hev [8–10]. transmission through pooled platelet concentrates was concluded in some studies in germany [11]. in addition, hev rna-positive blood donations from healthy blood donors were observed in japan [12]. studies from japan and europe showed that a few cases of hev were transmitted by blood transfusion, and retrospective follow-up of the transfused patients revealed elevated transaminase levels and signs of fulminant hepatitis [13–15]. a retrospective study of transfusion recipients suggested that in hev-1-endemic areas, hev could be transmitted by blood transfusion [16]. a similar conclusion was demonstrated in another study, in which some recipients exhibited hev reactivity [17] after blood transfusion. in the egyptian population, a study revealed that 80% were hev igg positive. however, only 0.26% were found to be hev rna positive [18]. a study aiming at molecular detection of hev rna revealed negative results among 239 ghanaian blood donors [19]. similar results were obtained from american plasma donations [20]. low rates of hev rt-rna were detected in studies conducted among blood donors in sweden (0.012%), germany (0.022%) [20], and egypt [18]. the hev rna seems quite difficult to detect and this may require a very large sample size with highly sensitive rt-pcr methods. in a study of blood donations in china, 30 out of 44,816 doi 10.18502/sjms.v17i3.12122 page 377 sudan journal of medical sciences nassir abakar babiker et al donations (0.07%) were hev rna-positive [21]. in addition, low hev rna production rates were concluded by fischer et al., where they could only detect 7 (0.58%) hev rna among 1203 (13.55%) positive hev igg [22]. furthermore, nassir et al. revealed a negative result concerning the hev-rna among hemodialysis patients with a positive hev seroprevalence [23]. on the other hand, the viral distribution concerning the gender and age groups revealed some variation among the studies. for example, a study conducted in iran showed a difference in hev igg by age but not gender [24]. a higher hev igg seroprevalence rate of 26.7% concluded by ahmed et al. among sudanese blood donors that are significantly associated with a young age group might raise the potential risk for hev transmission in recurrent blood transfusion by those donors. 2. materials and methods 2.1. study design and samples collection the study was a cross-sectional, hospital-based descriptive study conducted among blood donors attending the central blood bank in wad medani city, the capital of gezira state, sudan. this blood bank provides blood donation services to all localities of gezira state. therefore, donors in this study could be representatives of the population in gezira state. after testing negative during the routine screening of hbv, hcv, syphilis, and hiv for the blood transfusion, 300 blood donors were recruited for this study. before the sample collection, informed consent was taken from all participants and the demographic data, clinical data, and risk factors associated with hev transmission were documented using a structured questionnaire. about 5 ml blood was collected from each participant in an edta container using standard techniques. the plasma was separated into two aliquots, then stored at –40ºc until used for hev serological screening by elisa and hev rna by rt-pcr. 2.2. serological screening for hev the screening was performed using elisa for hev igg and hev igm. for the interpretation of the negative results for hev igg or hev igm, the positive results, and the equivocal results, the cut-off value was set as <1, >1, and 0.9–1.1, respectively, doi 10.18502/sjms.v17i3.12122 page 378 sudan journal of medical sciences nassir abakar babiker et al according to the manufacturer’s instructions. the equivocal reading was later retested for confirmation. 2.3. molecular detection for hev-rna the primer design𝑇𝑀 genesis® (uk manufacture) kits were used for the extraction and real-time pcr of hev-rna detection. the kits are specifically designed for in vitro highly purified rna extraction and quantification of hev genomes. the primers and probe sequences in the kit had 100% homology with a broad range of hev sequences based on comprehensive bioinformatics analysis. both rna extraction and real-time pcr were carried out at the national public health laboratory, khartoum, sudan, using an rt-pcr thermo cycler (rotor gene 6000, germany). the dna/rna extraction kit solution (exp date: 17/10/ 2017, batch no, 66606, g25493, 66601, 66605, p15079s, 66628, 66622, shb68127v, and 66596) and the hev-rna-specific primer and probe mix (serial number jn 160305-49345, batch number pd2879, expiry date 17.10.2017) were used according to the manufacturer’s protocol. 2.4. statistical analysis data were analyzed using the statistical package for social science (spss), version 24.0. descriptive statistics for hev prevalence and different variables are illustrated in tables 1 and 2. table 1 demonstrates the frequencies among the localities and table 2 presents the frequencies regarding the demographic and risk factors for virus transmission. the chi-square test for categorical variables was calculated. further, for the logistic regression of univariate and multivariate analysis, an odds ratio (or) with a 95% confidence interval (ci 95%) was calculated, and the statistical significance was defined as p < 0.05. 3. results 3.1. epidemiological and demographical analysis of the study groups all blood donors recruited for the current study were male, aged between 18 and 50 years and belonging from different localities of gezira state, sudan (tables 1 & 2). out of the 300 blood donors, 109 (36.3%) were hev igg-positive and 191 (63.7%) were negative (figure 1). the highest hev seroprevalence was found among participants in the age doi 10.18502/sjms.v17i3.12122 page 379 sudan journal of medical sciences nassir abakar babiker et al group of 31–40 years, with a percentage of 44.6%, and the lowest rate was predicted among the age group of 18–30 years with a prevalence of 32.5% (table 2). 3.2. hev igg seroprevalence and the associated risk factors localities the distribution of seroprevalence of hev igg among the localities were as follows: 34 (31.5%) in wad medani locality, 30 (34.1%) in south gezira locality, 16 (59.3%) in managil, 15 (37.5%) in east gezira, 10 (41.7%) in um algura, and 4 (30.7%) in hasahesa localities (p > 0.5). 3.2.1. occupations higher prevalence of the hev igg was calculated among eight (47.1%) farmers, while no prevalence of the virus was found among health workers and policemen (table 2). a significant association was calculated among students and farmers regarding the hev igg distribution and the factors of the disease in univariate and multivariate analysis (p = 0.007), table 2. 3.2.2. animal contact the hev igg seroprevalence regarding the risk of contact with the animals out of 300 blood donors resulted in 26 (46.3%) for blood donors with animal contact and 83 (34%) with no animal contact (p= 0.083), table 2. 3.2.3. food source the hev igg prevalence concerned the sites of food sources out of the 300 blood donors resulted in 74 (32.6%) at home, 20 (48.8%) outside the home, and 15 (46.9%) at home and outside the home, table 2. 3.2.4. water source out of the 300 blood donors, 100 (36.2%) hev igg-positive used wells as water sources, 5 (62.5%) used rivers, and only 4 (25%) used hafeer (a hole in the ground used to collect water during the rainy season for using it later, table 2. doi 10.18502/sjms.v17i3.12122 page 380 sudan journal of medical sciences nassir abakar babiker et al 3.2.5. the number for blood donation the hev igg prevalence concerning the numbers for the respondents who donated blood resulted in 89 (35.6%) donating blood once or twice, 13 (50%) donating three to four times, and 7 (29.2%) donating more than four times, table 2. 3.2.6. hev igm and hev rna analysis out of the 84 blood donors with hev igg strong positive samples, only 1.2% (1/84) were positive for hev igm, while no hev rna was predicted amongst any of them by using an rt-pcr assay. 0 50 100 150 200 250 a m o u n t o f d o n o rs hev igg(+) hev igg(-) 63.7% 36.3% figure 1: the distribution of hev igg among blood donors (n = 300). table 1: the hev igg distribution among blood donors according to gezira state localities (n = 300). variables hev igg univariate multivariate negative positive (%)n = 109 total or ci 95% p-value or ci 95% p-value wad medani 74 34 (31.5) 108 0.967 0.278–3.362 0.958 0.854 0.240–3.030 0.806 um alqura 14 10 (41.7) 24 0.622 0.149–2.601 0.516 0.587 0.139–2.475 0.468 south algezira 58 30 (34.1) 88 0.859 0.244–3.022 0.813 0.805 0.227–2.857 0.737 east algezira 25 15 (37.5) 40 0.741 0.194–2.830 0.661 0.664 0.171–2.58 0.555 almanagil 11 16 (59.3) 27 0.306 0.075–1.246 0.098 0.305 0.074–1.252 0.099 alhasahisa 9 4 (30.7) 13 0.306 0.075–1.246 0.098 0.305 0.074–1.252 0.099 total 191 109 (36.3) 300 or, odds ratio; c, 95% confidence interval; hev, hepatitis e virus. doi 10.18502/sjms.v17i3.12122 page 381 sudan journal of medical sciences nassir abakar babiker et al table 2: the hev igg distribution among blood donors according to demographic and risk factors. variables hev igg univariate multivariate negative positive (%)n = 109 total or ci 95% p-value or ci 95% p-value age group (yr) 18-30 135 65 (32.5%) 200 1.038 0.185–5.817 0.966 0.876 0.152–5.028 0.882 31-40 52 42 (44.6%) 94 0.619 0.108–3.546 0.59 0.544 0.093–3.178 0.499 >40 4 2 (33.3%) 6 0.619 0.108–3.546 0.59 0.544 0.093–3.178 0.499 occupation casual workers 117 87 (42.6%) 204 1.195 0.443–3.223 0.724 1.086 0.397–2.97 0.873 drivers 16 6 (27.27%) 22 0.579 0.369–5.946 0.579 1.345 0.331–5.471 0.678 policemen 8 0 8 2164 0.000–0.000 0.997 2033 0.000–0.000 0.997 engineers 7 1 (12.5%) 8 6.222 0.623–62.159 0.12 6.222 0.618–62.6 0.121 teachers 3 2 (40%) 5 1.333 0.176–10.120 0.781 1.112 0.144–8.60 0.919 health workers 2 0 2 21643 2164–216437 – 1805 1805–1805 – or, odds ratio; c, 95% confidence interval; hev, hepatitis e virus. 4. discussion studies assessing the risk of hev transmission through blood transfusion are relatively fewer than others conducted for hcv and hbv. researchers from japan and europe indicated that a few cases of hev were transmitted by blood transfusion and later developed elevation of transaminase levels and fulminant hepatitis [13–15]. another study showed that some recipients exhibited hev reactivity after a blood transfusion from an hev-infected donor [17]. according to our study, hev igg seroprevalence among healthy blood donors was 36.3%. this result was higher than that revealed by ahmed et al. [25] among sudanese blood donors (26.7%) and lower than that reported among egyptian blood donors (45.3%) [4], but higher than what was reported by other studies from other african countries [6, 7, 19]. based on the results of this study, the highest prevalence of hev igg seroprevalence was among those aged 31–40 years, 42 (44.6%). this finding could reflect a higher probability of virus exposure among this age group, which might be due to occupational hazards (e.g., farmers and animal contact as approved in the study) or other factors, for instance, this age group might be more likely to consume food outside the home which is a known risk factor for foodborne infections. however, in other studies, such as that conducted by adjei et al., hev seroprevalence was more among the elderly than in younger persons. it should be noted that statistically there was no significant association between hev prevalence and age group among blood donors in our study and this is consistent with a study conducted in the netherlands [9]. doi 10.18502/sjms.v17i3.12122 page 382 sudan journal of medical sciences nassir abakar babiker et al it was obvious, in our study, that those people who drank the river water were at a higher risk of getting infected (5; 62.5%), compared to those drinking from well sources (100; 36.2%) and hafeer (4; 25%). some evidence of significant association regarding the virus prevalence concerning the water sources revealed the highest risk of river sources compared to the well source and the lowest risk of hafeer sources, or = 5.000, p = 0.084 and or = 5.145, p = 0.081; p = 0.081, or = 5.000, ci 95% = 0.806–31.002, respectively, table 2. this might be due to a higher likelihood of contamination of the rivers by animal and human products than the wells. furthermore, our study identified those with a previous history of multiple blood donations have a higher hev igg seroprevalence 13 (50%). this is consistent with the results from other studies [13–15, 17] and as the majority of them are young, this leads to the possibility of later donations in the future which could be an additional risk for transmission. although, the hev igm seropositive in this study was the only donor; therefore, it was a limitation for our study to carry out statistical hev igm interpretation. however, the result still increases the probability to transfuse hev-contaminated blood to those patients with compromised immunity [16]. hev rna concluded in a negative result for all blood donors, and that might be for our sample size limitation to carry out the hev rt-pcr, some authors obtained a similar result for a negative hev-rna [9, 20, 24]. this study is novel in gezira state, sudan that showed relations and association of risk factors for hev and blood transfusion. the limitation of the study was the small sample size and the eclipsing period of hev, and the collection time of the viruses and ages; therefore, we could not reliably assess the true prevalence of igmand rna-positive cases. 5. conclusion the results of this study could suggest a high probability of hev transmission through blood transfusion as reflected by the high hev seroprevalence among healthy donors. the risk factors that could be identified in this study include the occupation (mainly farmers), animal contact, and river sources for drinking. acknowledgments the authors are grateful to all those who participated in this study, namely, the staff of central blood bank in wad medani city, the capital of gezira state, sudan, the doi 10.18502/sjms.v17i3.12122 page 383 sudan journal of medical sciences nassir abakar babiker et al national public health laboratory, khartoum, sudan, and the department of medical microbiology, faculty of medical laboratory of sciences, gezira university. ethical considerations not applicable. competing interests none declared. availability of data and material the dataset generated during this study is available from the corresponding author on reasonable request. funding none. references [1] emerson, s., anderson, d., arankalle, a., meng, x., purdy, m., schlauder, g., & tsarev, s. 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(2013). hepatitis e virus infection in ghanaian blood donors – the importance of immunoassay selection and confirmation. vox sanguinis, 104(1), 30–36. https://doi.org/10.1111/j.14230410.2012.01637.x [20] baylis, s. a., gärtner, t., nick, s., ovemyr, j., & blümel, j. (2012). occurrence of hepatitis e virus rna in plasma donations from sweden, germany and the united states. vox sanguinis, 103(1), 89–90. https://doi.org/10.1111/j.1423-0410.2011.01583.x [21] guo, q. s., yan, q., xiong, j. h., ge, s. x., shih, j. w., ng, m. h., zhang, j., & xia, n. s. (2010). prevalence of hepatitis e virus in chinese blood donors. journal of clinical microbiology, 48(1), 317–318. https://doi.org/10.1128/jcm.01466-09 [22] fischer, c., hofmann, m., danzer, m., hofer, k., kaar, j., & gabriel, c. (2015). seroprevalence and incidence of hepatitis e in blood donors in upper austria. plos one, 10(3), e0119576. https://doi.org/10.1371/journal.pone.0119576 [23] babiker, n. a., abakar, a. d., taha, m. a., & mohamed, n. t. (2019). sero-molecular epidemiology of hepatitis e virus among hemodialysis. jouf university medical journal, 6(3), 9–16. [24] naeimi, b., kalimani, f. m., & pourfatolah, a. a. (2015). hepatitis e virus seroprevalence among blood donors in bushehr, south of iran. hepa month, 15(11). [25] ahmed, a. b., & hamedelnil, y. f. (2015). seroprevalence of hepatitis e virus among blood donors in omdurman locality, sudan. american journal of research communication, 3(5), 252–258. doi 10.18502/sjms.v17i3.12122 page 386 introduction materials and methods study design and samples collection serological screening for hev molecular detection for hev-rna statistical analysis results epidemiological and demographical analysis ofthe study groups hev igg seroprevalence and the associated risk factors localities occupations animal contact food source water source the number for blood donation hev igm and hev rna analysis discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12867 production and hosting by knowledge e research article gunshot injuries: patterns, presentations, and outcomes of civilian hospital experiences in a developing country setting mohammed yousof bakhiet1,2, mohammedbabalrahma bashier ahmed koko1, abderahim abdelrahman kabbashi1,3, and mohamed daffalla awadalla gismalla2,4 11department of surgery, faculty of medicine, kordofan university, elobied, sudan 2department of surgery, faculty of medicine, albaha university, albaha, saudi arabia 3department of surgery, college of medicine, alrayyan colleges, madina, saudi arabia 4department of surgery, faculty of medicine, uinversity of gezira, madni, sudan orcid: mohamed gismalla: https://orcid.org/0000-0002-6081-0107 abstract background: gunshot injuries are considered a health burden as well as one of the intricate emergencies in civilian medical practice. in this study, we aim to determine the pattern of presentation and management outcome in a general hospital setting in a sub-saharan african country. methods: this is a retrospective, hospital-based study conducted between january 2015 and december 2019 in a general teaching hospital to review the clinical presentation and management outcome of gunshot injuries. all patients’ records were reviewed during the study period. results: the total number of patients involved in the study was 157 with 83% male predominant. about 50% were from the age group 20–29 years that were most affected. the commonest anatomical site affected in the study was the lower limb (41.4%) and upper limb (22.9%), and most of the patients had been diagnosed with limb fractures (49.7%) and soft tissue injuries (28.7%). wound debridement is the commonest procedure performed for 91 (58.0%) patients. the site of the pullet has a significant relation to the management outcome with a p-value of 0.002. additionally, about 45% (72 patients) have stayed more than 20 days and it was affected significantly by the types of treatment provided, which has a significant relation to a hospital stay with a p-value of 0.00. conclusion: most of the patients in this study were young males. upper and lower limb fractures were the most common presentations. wound debridement, bone fixation, and laparotomy were the most common treatments with significant success rates, despite prolonged hospital stays. keywords: epidemiology, gunshot injuries, gunshot wound, sub-saharan countries, sudan how to cite this article: mohammed yousof bakhiet, mohammedbabalrahma bashier ahmed koko, abderahim abdelrahman kabbashi, and mohamed daffalla awadalla gismalla (2023) “gunshot injuries: patterns, presentations, and outcomes of civilian hospital experiences in a developing country setting,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 71–83. doi 10.18502/sjms.v18i1.12867 page 71 corresponding author: mohamed daffalla awadalla gismalla; email: mohadaff22@gmail.com received 24 october 2022 accepted 24 november 2022 published 31 march 2023 production and hosting by knowledge e mohamed bakhiet et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed bakhiet et al 1. introduction trauma and accident injuries are a primary health problem worldwide, it affects young people and often lead to premature deaths or disabilities [1]. one of the etiological factors of trauma is gunshot injuries happening worldwide in developed and developing countries with different rates and causes [2]. in the african context, it has been reported in countries such as south africa [3], nigeria [2], tanzania [4], kenya [5], and sudan [6]. gunshot injuries and firearms are considered a major problem and health concern in africa, especially in sub-saharan countries because millions of weapons circulate outside the regular military or organized armies [5, 6]. it is now more common than in the past and contributes to significant increases in morbidity and mortality. prevalent causes of gunshot injuries in africa include communal clashes, military violence, armed robberies, and political conflicts [2]. gunshot injuries can be classified anatomically according to the site of the body affected. such common sites include the head, neck, pelvis, limbs, or multiple regions combined, which have high morbidity and mortality rates [3, 6, 7]. management outcome and treatment modalities of gunshot injuries depend mainly on the size, severity, and treatment options. in sudan, the incidence of injuries for different causes was 82.0/1000 people per year, with a low socioeconomic status population placed at an increased risk. there is a lack of reliable resources documenting injury-related deaths [8]. regarding gunshot injuries in sudan, there is no study that we know that has documents and reports the incidence, causes, or outcome. so, we look for evidence-based data to plan and promote management and prevention protocols. this study was conducted to investigate the pattern of gunshot injuries and their impact on case management, along with patient morbidity and mortality. 2. materials and methods 2.1. study design this retrospective, hospital-based study was conducted between january 2015 and december 2019 in elobeid teaching hospital to review the clinical presentation and case management outcomes of gunshot injuries. all the patients’ records were reviewed during the study period and were followed up for one year. doi 10.18502/sjms.v18i1.12867 page 72 sudan journal of medical sciences mohamed bakhiet et al 2.2. setting emergency and trauma patients were referred to the elobeid teaching hospital emergency department to receive urgent care. elobeid teaching hospital is the oldest and biggest hospital in the kordofan region and is owned and operated by the north kordofan state. it provides services for 3,140,177 people (estimated in 2016) who live in an area of 185,302 km2. patients included in this study have been referred to the hospital from the states of kordofan and darfur. the hospital is comprised of an accident and emergency department, radiological department, laboratory center with a blood bank, surgical specialty department, medical specialty department as well as an operation complex with an intensive care department. however, there is no prehospital referral system to the hospital. 2.3. inclusion and exclusion criteria all patients who presented to the hospital with gunshot injuries, resulting from civilian altercations, during the study period and received treatment in the hospital were included. patients who were dead at the time of presentation were excluded from the study population. 2.4. clinical assessment the primary assessment was done for all patients presented to the emergency department through the advanced trauma life support protocol. the emergency team checked each patient’s airways, breathing, circulation, and disability. following the primary assessment, a primary investigation was done after the patients were stabilized. the emergency department performed emergency procedures such as chest tube insertions, surgical toilets, and abdominal wound explorations under local anesthesia. lastly, the patients were categorized, according to their condition, to receive further treatment by the general surgery or orthopedic units for any additional necessary surgeries or follow-ups. 2.5. operative treatments in cases of abdominal injury or internal bleeding, operative surgeries such as laparotomy are urgently performed. orthopedic operations are typically done within three to five doi 10.18502/sjms.v18i1.12867 page 73 sudan journal of medical sciences mohamed bakhiet et al days. optimization of patients was done preoperatively (to replace the blood loss) and reviewed by an anesthetist, who then further requests relevant investigations. following the optimization, patients will be followed by the responsible units, which will assess the patients in the outpatient clinic in intervals of two weeks, one month, three months, six months, and one year depending on their condition. 2.6. data collection and analysis flowchart sheets were used to collect the baseline characteristics of the patients. age, sex, residence, education, and occupation were checked. information regarding the site of the bullet, condition at the time of presentation, diagnosis, complications, and outcomes was determined. types of operation and intervention were determined based on each case. the data collected were entered and analyzed using the spss version 21 statistical software (ibm corporation, chicago, il). results were tabulated and presented as frequencies and percentages, accordingly. for each test, p < 0.05 was considered statistically significant (95% ci). 3. results a total of 157 patients were diagnosed with gunshot injuries and included in the study. the mean age of patients was 27.7 years, ranging from 1 to 65 years. the most common age group was 20–29 years (31.8%) followed by age groups 30–39 and 10–19 with 26.1% and 22.3%, respectively. all patients’ characteristics are shown in table 1. most of the patients in this study were males 87.9% and 46.2% of them were married. in this study, 25% of the patients were residents of elobeid city while the rest were from outside the city. about two-thirds of the patients were either illiterate (36.1%) or had primary school-level education (37.3%), while some worked as farmers or laborers (36.1% and 28.5%, respectively). table 2 demonstrates the anatomical site of gunshot wounds, diagnosis, and treatment done for the patients. the anatomical site of the wounds was found mainly in the lower limbs and upper limbs in 65 patients (41.4%) and 36 patients (22.9%), respectively. additionally, the least common wound site is the perineum with only three (1.9%) patients being affected. the most common diagnosis among patients in this study were limb fractures and soft tissue injuries among 78 (49.7%) and 45 (28.7%) patients, respectively. there were three patients diagnosed with a head injury. specific treatments in this study included wound debridement which was done for 91 (58.0 %) patients. other treatments doi 10.18502/sjms.v18i1.12867 page 74 sudan journal of medical sciences mohamed bakhiet et al included bone fixation, laparotomy, and chest tube insertion which were done for the rest of the patients. there is a significant correlation (p-value < 0.05) between the final management outcome and the site of the gunshot (table 2). more than 120 (75%) patients were treated and discharged in a good condition and 27 (17.2%) were referred to specialized centers for further treatment. figure 1 presents the relation between the patient’s diagnosis and the treatment outcomes or referral to other hospitals. we found that about five (3.2%) patients were discharged against medical advice and five (3.2%) additional patients died. it was also found that about 45% (72 patients) stayed more than 20 days owing to their diagnosis and treatment options; hospital stay is demonstrated in table 3. the longest hospital stay (>20 days) was found in patients who had been diagnosed with limb fractures or soft tissue injuries with 38 and 19 cases, respectively. furthermore, the treatments provided affected the hospital stay, wound debridement, and external or/and internal fixators were found to be the commonest surgical procedures. a significant correlation (p-value < 0.05) was found between hospital stay and treatment. 0 10 20 30 40 50 60 70 limb/s fracture/s visceral perforation rib fracturehead injuryso! "ssue injury internal bleeding treated and discharged in good condi"on referred to higher care figure 1: patients who were treated or referred based on their diagnoses. 4. discussion gunshot injuries represent a major health problem worldwide, with direct burdens on health services and the economy [9, 10]. sudan is considered one of the sub-saharan countries affected by internal conflict; as a result, gunshot-related injuries and mortalities are more common [11]. doi 10.18502/sjms.v18i1.12867 page 75 sudan journal of medical sciences mohamed bakhiet et al table 1: patient characteristics (n = 157). variables frequency percentage (%) age groups (yr) 0–9 8 5.1 10–19 35 22.3 20–29 50 31.8 30–39 41 26.1 40–49 14 8.9 >50 9 5.7 gender male 138 87.9 female 19 12.1 marital status single 54 34.2 married 73 46.2 divorced 6 3.8 widow 3 1.9 residence urban 40 25.3 rural 118 74.7 level of education illiterate 57 36.1 primary school 59 37.3 intermediate school 24 15.2 secondary school 11 7.0 under school age 7 4.4 occupation labor 45 28.5 farmer 57 36.1 student 14 8.9 housewife 17 10.8 employer 4 2.5 non-employer 21 13.3 conflicts tend to arise due to different tribes and ethnic groups competing for basic resources in one place. poverty increased due to intolerance in the community and armed robberies are all considered to be important factors leading to increased gunshot violence in different parts of the country [6]. to the best of our knowledge, there are no studies that determine the extent of firearm injuries in sudan. in this study, we reviewed the data (clinical presentation, treatments, and management outcome) of 157 patients who presented to the hospital with gunshot wounds due to various causes between january 2014 and january 2019 to assess the pattern, causes, management, and outcome. the total number of patients reviewed in this study is the same or slightly higher than some available national and international [12, 13] data, but still less than the reported number from the usa and south africa [7, 14, 15]. doi 10.18502/sjms.v18i1.12867 page 76 sudan journal of medical sciences mohamed bakhiet et al table 2: management outcome in relation to the site of pullet, diagnosis, and treatment. variables management outcome total p-value treated referred dama* died site of pullet upper limb 33 0 3 0 36 0.002** lower limb 55 9 1 0 65 thorax 10 4 1 0 15 abdomen 12 7 0 5 24 back and spine 4 2 0 0 6 head and neck 4 4 0 0 8 perineum 2 1 0 0 3 diagnosis limb fracture 66 8 4 0 78 0.991 visceral perforation 8 4 0 4 16 rib fracture 8 2 0 1 11 head injury 1 2 0 0 3 soft tissue injury 35 9 1 0 45 internal bleeding 2 2 0 0 4 treatment wound debridement 70 14 5 2 91 0.823 internal fixation 6 1 0 0 7 eternal fixation 16 0 0 0 16 laparotomy 9 6 0 3 18 chest tube insertion 7 4 0 0 11 internal & external fixation 12 2 0 0 14 ∗dama, discharged against medical advice∗∗correlation is significant at the 0.05 level. gunshot injuries affect all age groups at different stages of life but are more prevalent in younger age groups [15]. the most common age group affected by gunshot injury in this study is the younger age which is in line with that reported previously by other studies [6, 15]. however, 18% of the study’s participants are comprised of the pediatric age group. interestingly, our numbers, with regard to gunshot injuries in pediatric patients, are similar to a report from south africa [14]. like other previous studies [6, 9, 13, 15–17], our data revealed that males were disproportionately affected, and this could be explained by their outdoor presence most of the time because of societal gender roles. the commonest anatomical site not affected in the body by nonfatal firearm injuries are the extremities of the upper or lower limbs, including soft tissue as well as bone tissue [7]. in this study, the lower limb followed by the upper limb is the most commonly injured (65%). conversely, the perineum was found to be the least affected site (2%). these findings are like those reported in previous literature [6, 8, 14]. however, results doi 10.18502/sjms.v18i1.12867 page 77 sudan journal of medical sciences mohamed bakhiet et al table 3: hospital stay related to diagnosis and treatment. hospital stay 0–5 days (n = 28) 6—10 days (n = 29) 11–15 days (n = 16) 16–20 days (n = 12) >20 days (n = 72) total p-value diagnosis limb fracture 11 13 8 8 38 78 0.465 visceral perforation 3 3 2 3 5 16 rib fracture 0 1 2 0 8 11 head injury 3 0 0 0 0 3 soft tissue injury 10 12 4 0 19 45 internal bleeding 1 0 0 1 2 4 treatment wound debridement 19 21 9 7 35 91 0.00∗ internal fixation 1 1 3 0 2 7 external fixation 0 2 2 0 12 16 laparotomy 4 2 1 4 7 18 chest tube insertion 2 1 1 0 7 11 internal & external fixation 2 2 0 1 9 14 ∗∗correlation is significant at the 0.05 level. from a study done in sudan, during the period of civil demonstrations, showed only one patient with a gunshot wound in the lower extremity hip bone [18]. the extent of injury and tissue damage following gunshots depends on several factors such as wound ballistics, tissue structure, and the respective anatomical relationships [19]. our data showed limbs fracture with local soft tissue injuries as the most common presenting diagnosis, followed by visceral perforations, rib fractures, and head injuries. these findings are similar to those of studies conducted previously [8, 14, 15]. furthermore, a study done by livingstone et al. in a major trauma center in the usa showed that 75% of patients admitted with gunshot wounds underwent at least one surgical intervention procedure [20]. almost all our patients underwent one or more surgical intervention(s) ranging from minor wound debridement to exploratory laparotomy. other surgical procedures included bone internal, external fixation or both, and chest tube insertion. however, some other reports showed only 53% of the patients required a surgical intervention [7]. the economic aspect of prolonged hospital stays and their burden on the healthcare system was addressed. about half of the patients in our study stayed in the hospital for more than 20 days. this is a significantly long doi 10.18502/sjms.v18i1.12867 page 78 sudan journal of medical sciences mohamed bakhiet et al hospitalization period in comparison to other studies [17, 21]. however, this long stay can be explained by the presence of open limb fractures which usually need external fixation and frequent wound debridement and dressing. the overall outcome of the patient in our data was good, where 75% of patients were treated and discharged in a good condition. about 17% of patients were referred to specialized centers for further management that is not available at our medical center. suicidal attempts are the commonest cause in developed countries [22]. however, armed robbery attacks were found to be the commonest cause of gunshot injuries based on published data from nigeria and some other african countries. [22] in this study, our findings are not in agreement with the previous studies showing personal enmity to be the more common cause of gunshot injuries. this could be explained by the presence of many interpersonal conflicts in these regions mostly due to different social reasons. according to reports from developed countries, firearm injuries have the highest case fatality rate in every age group, with a mortality rate ranging between 5.5% and 15.3% [13, 23]. furthermore, studies done in libya, tanzania, and south africa showed a gunshot mortality rate of 4.5% to 8.3% [18, 22, 24]. in our data, the mortality rate was 3.2%, which is comparable to the lower limit of these data. this could be explained by the fact that we include only the deaths that occur following the patient’s admission to the hospital and exclude any deaths occurring at the arrival or shortly after that which could tell us into survival bias. the deaths in our study population occurred within the first and second weeks of injury. according to national and international studies, all five deceased patients had gunshots to the abdomen, which are known to carry high morbidity and mortality rate [6, 25, 26]. laparotomy was done for those patients with findings of internal organ injuries. one patient underwent chest tube insertion in addition to laparotomy for an associated chest injury. 5. conclusion the patients in this study were mostly young males, with personal enmity being the common cause of injury. upper and lower limb fractures were the most common presentations. wound debridement, bone fixation, and laparotomy were the most common treatments with significant success rates, despite prolonged hospital stays. a protocol for a severity scoring system is important to be established to properly assess the patients at the time of presentation. a prospective study is needed to effectively doi 10.18502/sjms.v18i1.12867 page 79 sudan journal of medical sciences mohamed bakhiet et al evaluate the mortality rate and prehospital services or ambulance system is paramount to decreasing death occurring during patient transportation. acknowledgments the authors would like to thank the patients’ record staff and mr. ahmed bagit for the language reviewing. ethical considerations ethical approval was obtained from the elobeid teaching hospital to review patient records and use the data mentioned in the methods section of the article. competing interests the authors of this study have no financial relationships or conflicts of interest relevant to this article to disclose. availability of data and materials available upon request. funding none. references [1] gopalakrishnan, s. 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[25] al rawahi an, al hinai fa, boyd jm, doig cj, ball cg, velmahos gc, kirkpatrick aw, navsaria ph, roberts dj. outcomes of selective nonoperative management of civilian abdominal gunshot wounds: a systematic review and meta-analysis. world journal of emergency surgery. 2018 dec;13(1):p. 55-61. doi 10.18502/sjms.v18i1.12867 page 82 sudan journal of medical sciences mohamed bakhiet et al [26] philipp lichte, r. o., binnebösel, m., wildenauer, r., pape, h. c., & kobbe, p. (2010). a civilian perspective on ballistic trauma and gunshot injuries. scandinavian journal of trauma, resuscitation and emergency medicine, 18(35), 2–8. doi 10.18502/sjms.v18i1.12867 page 83 introduction materials and methods study design setting inclusion and exclusion criteria clinical assessment operative treatments data collection and analysis results discussion conclusion acknowledgments ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12110 production and hosting by knowledge e research article assessment of variation in clinical presentation of visceral leishmaniasis among patients attending the tropical diseases teaching hospital in sudan hammam abdalrhman altom mohammed ahmed, ahmed ali ahmed musa, ahmed mahmoud sayed sayedahmed*, shiraz bashir jabralseed mohammed, ehssan farouk mohamed ahmed, anas badreldeen elageb mohamed, and abdelsalam mohamed ahmed nail omdurman islamic university, khartoum, sudan orcid: ahmed ali ahmed musa: https://orcid.org/0000-0001-8603-0515 ehssan farouk mohamed ahmed: https://orcid.org/0000-0001-7862-1606 shiraz bashir jabralseed mohammed: https://orcid.org/0000-0001-9532-8743 anas badreldeen elageb mohamed: https://orcid.org/0000-0002-9150-468x ahmed mahmoud sayed sayedahmed: https://orcid.org/0000-0002-3898-8814 abstract background: visceral leishmaniasis (also known as kala-azar) is a systemic parasitic infection with many clinical presentations. the present study assesses the variation in presentations among patients who attended the tropical diseases teaching hospital (tdth) in khartoum, sudan. methods: this analytical cross-sectional, hospital-based study was conducted at the tdth between november 2019 and september 2020. medical records of patients who presented at the tdth were reviewed using a structured data extraction checklist. the chi-square test was used to determine the associations between sociodemographic and clinical presentations of patients. p-value < 0.05 was considered as statistically significant. results: out of 195 patients, 79.5% were male and 48.2% were <31 years old. fever was the main clinical presentation (90.2%) while 53.3% presented with weight loss and 72.3% and 39% presented, respectively, with splenomegaly and hepatomegaly. hiv was detected in 4.6% of the patients. rk39 was the main diagnostic test. we found a significant association between the abdominal distention and the age of the patients (p < 0.05) – age groups 11–20 and 41–50 years were more likely to present with abdominal distention than other age groups. conclusion: there is no exact clinical presentation or routine laboratory findings that are pathognomonic for visceral leishmaniasis; therefore, it should be considered in the differential diagnosis of any patient with fever, weight loss, and abdominal distention, and among patients with hiv. keywords: visceral leishmaniasis, sudan, clinical presentations how to cite this article: hammam abdalrhman altom mohammed ahmed, ahmed ali ahmed musa, ahmed mahmoud sayed sayedahmed*, shiraz bashir jabralseed mohammed, ehssan farouk mohamed ahmed, anas badreldeen elageb mohamed, and abdelsalam mohamed ahmed nail (2022) “assessment of variation in clinical presentation of visceral leishmaniasis among patients attending the tropical diseases teaching hospital in sudan,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 341–354. doi 10.18502/sjms.v17i3.12110 page 341 corresponding author: ahmed mahmoud sayed; email: ahmed1mahmoud111@ gmail.com received 21 october 2021 accepted 9 july 2022 published 30 september 2022 production and hosting by knowledge e ahmed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ahmed et al 1. introduction visceral leishmaniasis (vl; also known as kala-azar) is a systemic parasitic infection caused by leishmania donovani, l. infatum, and l. chagasi and transmitted via sand fly phlebotomus arhentipes [1]. clinical presentations include fever, malaise, anemia, weight loss, splenomegaly, hepatomegaly, bleeding tendency, among other [2], with fever often presenting first [3]. the condition may become worse as some patients may develop hepatic dysfunction or concurrent infections due to pancytopenia which is associated with vl, while some patients may develop post-kalazar dermal infection (pkdl) [4]. according to the world health organization (who), 55% of sudanese patients suffered from pkdl [5]. of note, the severity of the clinical presentations depends on the interaction between the parasite and its host, so some patients can become asymptomatic carriers or develop symptoms with varying severity due to their inability to control the multiplication of the parasite [4]. moreover, the fatality rate for untreated cases in developing countries can be as high as 100% within two years [6]. sudan is suffering from vl since the early 1900s, and several epidemics have occurred and claimed the lives of thousands of people [7]. the first epidemic in sudan was reported in 1936 in the upper nile province, wherein about 300 individuals were infected, and the death rate was nearly 80% [8]. moreover, a recent study disclosed that about 1.3 million new vl cases are reported yearly, with an estimated 20,000– 40,000 annual deaths [9]. in addition, about 94% of vl cases are from sudan, south sudan, ethiopia, india, bangladesh, and brazil [10]. furthermore, in 2015, 2902 cases of vl were reported in sudan [11]. recent reports confirm that gedaref state is a known hyper-endemic area for vl, while western upper nile, kordofan state, central sudan, and white nile state are also considered as endemic areas [12]. good understanding of the broad spectrum presentation in patients with vl and its relation to certain factors can establish a better outcome, as early diagnosis is the core stone in the management of the disease. although a number of papers have been published, there is still vagueness due to the diversity of data and classifications, and variation in people from different geographical areas. this study can provide additional information to doctors and decision-makers for improving the management of vl patients. the present study therefore assesses the variation in presentation among patients presented at the tropical diseases teaching hospital (tdth) in khartoum state, sudan. moreover, it describes the sociodemographic characteristics of patients with vl and identifies the association between the presentations of patients diagnosed with vl and the sociodemographic characteristics. doi 10.18502/sjms.v17i3.12110 page 342 sudan journal of medical sciences ahmed et al 2. materials and methods 2.1. study design and study area this is analytical, cross-sectional, hospital-based study was conducted to assess the variation in the presentations of vl among sudanese patients. it was conducted at the tdth, which is the only tropical hospital in khartoum state and the biggest in sudan, between november 2019 and september 2020. 2.2. study population medical records of all sudanese patients who presented with vl at the tdth from january 2016 to march 2020 were studied. however, patients whose files were incomplete were excluded. 2.3. study variables 1. characteristics of patients: age, gender, education, residence, occupation, income, and marital status 2. different clinical presentations, past medical history, complications, and treatment 3. laboratory results (hemoglobin, total white blood cells count, platelet count, albumin) 2.4. sampling method and sample size the total coverage method was used for all patients who visited the study center during the study period. 2.5. data collection 2.6. secondary data were collected using pretested and structured data extraction checklist from all sudanese cases reported during the study period and fulfilling the inclusion criteria. data collectors were the researchers themselves. doi 10.18502/sjms.v17i3.12110 page 343 sudan journal of medical sciences ahmed et al 2.7. data analysis data were reviewed, coded, entered, and then analyzed using the spss (statistical package social science), version 25. descriptive statistics were computed to determine frequencies and percentages. chi-square test was used to determine the associations between sociodemographic and clinical presentations of patients diagnosed with vl at the tdth. p-value < 0.05 was considered as statistically significant. 64 22 59 45 21 0 10 20 30 40 50 60 70 2016 2017 2018 2019 2020 vl cases figure 1: histogram showing the trend in vl over the 2016–2020 period. 3. results 3.1. sociodemographic characteristics table 1 presents the sociodemographic characteristics of our participants. a total of 195 patients with vl were identified during the study period. of them, 155 (79.5%) were male and 140 (71.8%) were aged <41 years. some of the patients suffered from concurrent chronic disease (table 2). 3.2. clinical presentations and hematological findings table 3 presents the clinical manifestations of our participants. out of 195 patients, 177 (90.2%) presented with fever, while 104 (53.3%) presented with weight loss. the mean hemoglobin value was 8.3 g/dl (sd = 2.2), and 177 (90.8%) participants were anemic (hemoglobin level <12 g/dl). while the mean value of the total white blood cells was 3.5 per microliter (sd = 3.4), the mean value of the platelet count was 122 per microliter (sd = 95) and a mean value of 3 g/dl (sd = 1.1) for the albumin. doi 10.18502/sjms.v17i3.12110 page 344 sudan journal of medical sciences ahmed et al table 1: sociodemographic data of vl patients who were admitted to the tdth. variables n (%) gender male 155 (79.5) female 40 (20.5) age (yr) 0–10 2 (1.1) 11–20 42 (21.5) 21–30 50 (25.6) 31–40 46 (23.6) 41–50 29 (14.9) 15–60 15 (7.7) >60 11 (5.6) marital status child 10 (6.7) single 59 (39.3) married 80(53.3) divorced 1 (0.7) residence khartoum 51 (26.2) gadarif 26 (13.3) white nile 26 (13.3) blue nile 8 (4.1) north kordofan 23 (11.8) south kordofan 15 (7.7) west kordofan 5 (2.6) north darfour 3 (1.5) south darfour 6 (3.1) west darfour 4 (2.1) central darfour 1 (0.5) nile river 1 (0.5) northern state 0 kassala state 8 (4.1) aljazeera state 4 (2.1) red sea 1 (0.5) sinnar 5 (2.6) occupation child 7 (4) unemployed 2 (1.2) farmer 37 (21.4) student 22 (12.7) shepherd 14 (18.1) housewife 25 (14.5) others 66 (38.2) income low 88 (74.6) average 29 (24.6) high 1 (0.8) doi 10.18502/sjms.v17i3.12110 page 345 sudan journal of medical sciences ahmed et al table 2: chronic diseases often observed in patients with vl admitted to the tdth. chronic diseases n (%) human immunodeficiency virus (hiv) 9 (4.6) diabetes mellitus 7 (3.6) hypertension 6 (3.1) hepatitis b virus 8 (4.1) hepatitis c virus 2 (1) table 3: clinical manifestations often observed in patients with vl admitted to the tdth. clinical picture n (%) symptoms fever 177 (90.2) weight loss 104 (53.3) fatigue 63 (32.3) weakness 3 (1.5) dyspnea 10 (5.1) abdominal pain 90 (46.2) joint pain 11 (5.6) vomiting 21 (10.8) signs hyperpigmentation 7 (3.6) yellow sclera 16 (8.2) abdominal distention 26 (13.3) lower limb edema 23 (11.8) itching 1 (0.5) lymphadenopathy 49 (25.1) splenomegaly 141 (72.3) hepatomegaly 76 (39) pallor 81 (41.5) laboratory findings (mean ± sd) hemoglobin (gr/dl) 8.2 ± 2.2 total white blood cells (per microliter) 3.5 ± 3.4 platelet count (per microliter) 122 ± 95 albumin (gr/dl) 3 ± 1.1 tested n (%) positive (n) rk39 134 (68.7) 119 rk28 3 (1.5) 2 bone marrow aspiration 70 (35.9) 62 lymph node aspiration 46 (20.5) 43 dat 43 (22) 38 skin biopsy 2 (1) 2 doi 10.18502/sjms.v17i3.12110 page 346 sudan journal of medical sciences ahmed et al table 4: concurrent infections often detected in patients with vl admitted to the tdth. concurrent infections n (%) tuberculosis 7 (3.6) gastroenteritis 26 (13.3) pneumonia 18 (9.2) malaria 11 (5.6) otitis media 0 urinary tract infection 8 (4.1) esophageal candidiasis 1 (0.5) table 5: the trend in vl admissions to the tdth from 2016 to 2020. year all hospitalizations all leishmaniasis visceral leishmaniasis cumulative # of vl cases 2016 78 66 64 2017 61 29 22 86 2018 138 81 59 145 2019 86 66 45 190 2020 54 32 21 211 total 417 274 211 211 table 6: early outcomes for vl patients who were admitted to the tdth. outcomes n (%) death (2016 to 2020) 29 (15) discharged after initial improvement 161 (83.4) referred (for nonresponse) 1 (0.5) discharged against medical advice 2 (1) 3.3. complications concurrent infections were the main complication in our participants (63, 32.3%). table 4 demonstrates the most common concurrent infections. other complications were bleeding tendency (34, 17.4%) and pkdl (8, 4.1%). 3.4. hospitalization rate out of 417 admissions to tdth during the study period, 274 were due to leishmaniasis. this includes only those patients who were admitted to the hospital as inpatient (table 5). figure 1 demonstrates the trend in vl over the 2016–2020 period. doi 10.18502/sjms.v17i3.12110 page 347 sudan journal of medical sciences ahmed et al table 7: association between clinical presentations of patients diagnosed with vl at the tdth and the corresponding age groups. clinical picture age (yr) statistics 0–10 11–20 21–30 31–40 41–50 51–60 > 60 chisquare p-value fever 2 40 46 41 26 11 11 8.046 0.235 weight loss 1 23 26 21 19 8 6 2.906 0.821 fatigue 0 18 17 15 8 4 1 6.384 0.382 weakness 0 0 1 0 0 1 1 8.676 0.193 dyspnea 0 3 2 2 2 1 0 1.501 0.959 abdominal pain 1 18 16 22 19 7 7 10.007 0.124 hyperpigmentation0 3 2 2 0 0 0 3.755 0.710 vomiting 0 2 5 6 5 2 1 3..496 0.744 joint pain 0 4 5 1 0 1 0 6.554 0.364 yellow sclera 0 3 6 3 1 3 0 5.996 0.424 abdominal distention 0 8 1 5 8 3 1 13.140 0.041∗ lower limb edema 0 1 8 6 3 4 1 8.089 0.232 itching 0 0 0 1 0 0 0 3.256 0.776 lymphadenopathy0 7 12 16 6 3 5 7.511 0.276 splenomegaly 2 33 39 31 20 7 9 8.537 0.201 hepatomegaly2 17 22 18 8 4 5 6.434 0.376 pallor 0 20 22 16 12 6 5 3.134 0.792 ∗significant association 3.5. diagnosis and treatment rk39 was the most commonly used diagnostic method, used for 134 (68.7%) of our participants. other diagnostic methods that were used were bone marrow aspiration (70, 35.9%), lymph node aspiration (46, 23.6%), dat (33, 22.1%), rk28 (3, 1.5%), and skin biopsy (2, 1%). on the other hand, sodium stibogluconate was the main drug used to treat the patients (103, 52.8%), followed by amphotericin b (93, 47.7%) and paromomycin (66, 33.8%). some patients received antibiotic therapy (36, 18.5%), 180 (92.3%) received multivitamins, while 41 (21%) required blood transfusion. early outcomes are presented in table 6. case fatality rate was calculated (tables 5 & 6) as follows: 29÷ 211 × 100 = 14.9% (from 2016 to 2020). doi 10.18502/sjms.v17i3.12110 page 348 sudan journal of medical sciences ahmed et al table 8: association between clinical presentations of patients diagnosed with vl at the tdth and their gender. clinical picture gender statistics male female chisquare p-value fever 141 36 0.036 0.850 weight loss 79 25 1.699 0.192 fatigue 51 12 0.123 0.726 weakness 2 1 0.307 0.579 dyspnea 8 2 0.002 0.967 abdominal pain 68 22 1.585 0.208 hyperpigmentation 6 1 0.173 0.678 vomiting 17 4 0.031 0.860 joint pain 10 1 0.933 0.334 yellow sclera 12 4 0.215 0.643 abdominal distention 22 4 0.484 0.487 lower limb edema 21 2 2.233 0.135 itching 1 0 0.259 0.611 lymphadenopathy 38 11 0.150 0.698 splenomegaly 116 25 2.417 0.120 hepatomegaly 65 11 2.786 0.095 pallor 65 16 0.049 0.825 3.6. association between clinical presentations and age groups table 7 presents the association between clinical presentations of vl patients at the tdth and the age groups. a significant association was seen between the abdominal distention and the age of the patients (p < 0.05). age groups 11–20 and 41–50 years were more likely to present with abdominal distention than other age groups. 3.7. association between clinical presentations and gender table 8 presents the association between clinical presentations of vl patients in tdth and gender. none of the clinical presentations was found to be associated with the gender of the patients. doi 10.18502/sjms.v17i3.12110 page 349 sudan journal of medical sciences ahmed et al table 9: association between clinical presentations of patients diagnosed with vl at the tdth and geographic areas. clinical picture geographic areas statistics khartoum state gadarif white nile blue nile north kordofan south kordofan south darfur kassala state others chisquare p-value fever 48 24 24 8 20 13 6 7 21 5.736 0.766 weight loss 23 10 16 5 8 11 4 6 16 14.186 0.116 fatigue 19 8 7 1 6 5 2 6 7 9.767 0.370 weakness 0 0 0 0 1 0 0 0 1 10.826 0.288 dyspnea 2 1 2 0 1 1 0 1 2 3.283 0.952 abdominal pain 23 15 7 1 10 7 4 4 12 15.708 0.073 hyperpigmentation 2 1 0 0 0 1 0 0 1 13.694 0.134 vomiting 3 4 4 1 1 2 1 2 3 6.478 0.691 joint pain 2 0 3 0 1 2 1 0 2 8.408 0.494 yellow sclera 2 1 5 1 0 1 0 3 3 19.348 0.022∗ abdominal distention 5 5 4 1 3 2 0 1 2 6.924 0.645 lower limb edema 6 2 2 2 4 0 2 1 4 9.177 0.421 itching 0 0 1 0 0 0 0 0 0 6.534 0.686 lymphadenopathy 15 6 5 2 7 2 3 3 4 6.027 0.737 splenomegaly 41 18 17 5 12 9 5 7 20 12.251 0.200 hepatomegaly 17 8 9 4 9 6 3 4 10 7.196 0.617 pallor 20 6 11 4 11 8 3 5 10 6.917 0.646 ∗significant association 3.8. association between clinical presentations and geographical areas table 9 presents the association between clinical presentations of vl patients in tdth and their residence. there was a significant association between the yellow sclera and patients’ place of residence (p < 0.05). patients from the white nile area were more likely to present with yellow sclera than others. 4. discussion the clinical features and laboratory findings described here are based on the data from the case files of 195 sudanese patients diagnosed with vl. we determined that vl is mainly presented by fever, weight loss, splenomegaly, anemia, hepatomegaly, and abdominal pain. in this study, 155 (95%) patients were male, and 140 (71.8%) of them were younger than 41 years. this finding is in agreement with a previous study conducted in kenya, doi 10.18502/sjms.v17i3.12110 page 350 sudan journal of medical sciences ahmed et al where 105 (77%) patients were male, and 129 (89%) were younger than 45 years [13]. moreover, a previous study conducted in india concluded that the male gender is a risk factor for vl [14]. males from a young age are more likely to sleep outside (in yards and farms), so they are more exposed to sand-fly bites [15, 16]. moreover, a majority of patients in our study presented with fever (90.2%), splenomegaly (72.3%), weight loss (53.3%), or hepatomegaly (39%). in a study conducted in brazil and mexico, the patients mainly presented with hepatomegaly (98%), splenomegaly (97.8%), or fever (97.7%) [17]. moreover, we found that 4.6% of our patients were diagnosed with hiv. this finding is in agreement with another study conducted in brazil, where 5.5% of vl patients were co-infected with hiv [18]. owing to the lack of facilities or poor reporting systems, vl/hiv co-infection is underreported in many endemic areas [19]. vl is a common opportunistic infection in hiv patients, as they are more vulnerable to vl infection, and hiv replication is accelerated in vl patients [19]. most of our patients were treated with sodium stibogluconate (52%), followed by amphotericin b (47.7%) or a combination of paromomycin and sodium stibogluconate. on the other hand, >60% of patients in brazil and bulgaria were treated with meglumine antimoniate [18, 20]. due to parasites’ drug resistance, liposomal amphotericin b is now the drug of choice for vl [21]. in our study, rk39 was the most used diagnostic test; about 61% of our patients were diagnosed by it. rk39 is a widely used test because it is a simple, sensitive, specific, and economical test [17]. in this study, bone marrow aspiration and lymph node aspiration were done for 70 and 46 patients, respectively, and no patient had undergone splenic aspiration. the splenic aspirate is more sensitive than bone marrow or lymph node aspirate; however, the splenic aspirate is a complicated procedure and associated with a risk of fatal hemorrhage [22, 23]. regarding limitations of this study, data were available in a paper-based database, this type of database is difficult to deal with, and it can be lost or damaged easily. 5. conclusion in conclusion, we found that fever was the main clinical finding, followed by splenomegaly, weight loss, and hepatomegaly. however, there is no exact clinical presentation or routine laboratory findings that are pathognomonic for vl; therefore, it should be considered in the differential diagnosis of any patient presenting with an unusual presentation from the endemic areas or with a history of recent travel. hiv is commonly associated with vl, so vl patients must be investigated for hiv infection. doi 10.18502/sjms.v17i3.12110 page 351 sudan journal of medical sciences ahmed et al acknowledgements the authors would like to thank their colleagues for the helpful guidance and extra hands, particularly shiraz bashir and abdullah mohammed. ethical considerations ethical approval was obtained from the department of community medicine at the faculty of medicine oiu and the administration of tdth. confidentiality was maintained throughout the study. competing interests authors declare no conflict of interest. availability of data and material data are available upon request. 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(2012). guidelines for diagnosis, treatment and prevention of visceral leshmaniasis in somalia. somali federal government ministry of health. doi 10.18502/sjms.v17i3.12110 page 354 introduction materials and methods study design and study area study population study variables sampling method and sample size data collection secondary data were collected using pretested and structured data extraction checklist from all sudanese cases reported during the study period and fulfilling the inclusion criteria. data collectors were the researchers themselves. data analysis results sociodemographic characteristics clinical presentations and hematological findings complications hospitalization rate diagnosis and treatment association between clinical presentations and age groups association between clinical presentations and gender association between clinical presentations and geographical areas discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11455 production and hosting by knowledge e original article knowledge, prevalence and practice of polycystic ovary syndrome among sudanese women in khartoum state, sudan: the need for health education zeinab omer alfanob1, mohamed h ahmed2, musaab ahmed3, and safaa badi4*, habab k. elkheir5 1clinical pharmacy department, faculty of pharmacy, omdurman islamic university, khartoum, sudan 2department of medicine and hiv metabolic clinic, milton keynes university hospital nhs foundation trust, eaglestone, milton keynes, buckinghamshire, united kingdom 3college of medicine, ajman university, ajman, united arab emirates 4clinical pharmacy department, faculty of pharmacy, omdurman islamic university, khartoum, sudan 5department of clinical pharmacy, oiu, department of clinical pharmacy and pharmacology, ust orcid: zeinab omer alfanob: https://orcid.org/0000-0002-2846-7871 mohamed h ahmed: https://orcid.org/0000-0001-8045-6996 musaab ahmed: https://orcid.org/0000-0002-2300-9919 safaa badi: https://orcid.org/0000-0003-3204-983x habab k.elkheir: https://orcid.org/00000001-5281-0054 abstract background: polycystic ovary syndrome (pcos) is the most common endocrine disorder and cause of infertility in women of reproductive age. knowledge of females about health problems is considered an important factor that promotes females’ health-seeking behavior. this study aimed to evaluate females’ knowledge and attitude toward pcos as well as to assess pcos prevalence among the participants. methods: a total of 240 females were included in the study between january and april 2019. a convenience sampling technique was used to select the participants. data were collected using a self-administered questionnaire and analyzed using the statistical package for social sciences (spss) version 24. the analysis included frequencies of discrete variables and descriptors and cross-tabulation of the variables using the chi-square test and logistic regression analysis. p < 0.05 was considered statistically significant. results: the results showed a low level of knowledge (scoring <9) in 41.3%, a good level (scoring between 9 and 15) in 21.3%, and also an excellent level of knowledge (scoring >15) in 37.5%. the chi-square statistical test showed significant associations between the level of knowledge and education level, urban residence, health profession, marital status, and the prevalence of pcos (p < 0.001, <0.001, <0.001, 0.045, and <0.001), respectively. logistic regression showed that the females’ knowledge about pcos was significantly associated with urban residence and being a health professional (p = 0.004 and p < 0.001, respectively). conclusion: the study highlighted that there was inadequate knowledge about the disease among participants and showed an urgent need to improve the knowledge about pcos among sudanese women. keywords: knowledge, practice, polycystic ovary syndrome (pcos), khartoum, sudan how to cite this article: zeinab omer alfanob, mohamed h ahmed, musaab ahmed, and safaa badi*, habab k. elkheir (2022) “knowledge, prevalence and practice of polycystic ovary syndrome among sudanese women in khartoum state, sudan: the need for health education ,” sudan journal of medical sciences, vol. 17, no. 2, pp. 204–217. doi 10.18502/sjms.v17i2.11455 page 204 corresponding author: safaa badi; email: safaabadi30@gmail.com received 1 september 2021 accepted 30 april 2022 published 30 june 2022 production and hosting by knowledge e zeinab omer alfanob et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:safaabadi30@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences zeinab omer alfanob et al. 1. introduction polycystic ovarian syndrome (pcos) is a condition associated with excess androgen production [1]. globally, pcos prevalence estimates range between 2.2% and 26% [2]. the high prevalence was attributed to pcos association with obesity, sedentary lifestyle, and genetic predisposing factors [3]. pcos is characterized by excessive ovarian and/or adrenal androgen secretion. ovarian factors include altered steroidogenesis as well as other factors such as hyperinsulinemia which contribute to excessive ovarian androgen production [4]. importantly, amenorrhea increases the chance of having pcos to 90%. other associated symptoms of pcos include hirsutism, acne, central obesity, and subfertility [5]. the mainstream treatment for pcos is oral contraceptives and clomiphene citrate [6, 7]. if not managed well, pcos can lead to infertility and long-term complications such as heart disease, diabetes, and metabolic syndrome [8, 9]. moreover, women with pcos have a threefold increase in the risk of developing endometrial cancer compared to women without pcos [10]. lack of knowledge in women about pcos often delays diagnosis and treatment [11]. the degree of knowledge about pcos was found to vary considerably. for instance, in saudi arabia, most women (>60%) were not aware of pcos symptoms and complications [12]. a study done among 200 female medical students of different colleges in india revealed that 28% of the medical students were unaware of pcos [13]. although pcos is a common condition, 76% of the student nurses have average knowledge about pcos and only 10.7% had good knowledge [1]. sociocultural factors can also influence knowledge and attitude about pcos. for instance, in egypt, most women had inadequate knowledge about pcos, 52.4% had poor knowledge, 45.4% do not even know the definition of pcos, 69.6% don’t know the symptoms of pcos, and 83.9% don’t know the effects of pcos [14]. while in pakistan, 10% were familiar with pcos [15]. furthermore, primary care physicians and women perceived that irregular menstrual cycles were identified as a key clinical feature of pcos [16]. a study done in the universities of quetta in 2016 to check the percentage of females’ awareness of pcos showed that 72.5% of respondents were not aware of pcos [17]. another study done in central india revealed that the lack of awareness about pcos was reported in around one-third of the participants [11]. pcos has been identified as one of the major risks for infertility and endometrial cancer. knowledge and awareness of females about pcos symptoms and its complications is essential for them to seek early medical care. accurate diagnosis at a young age may doi 10.18502/sjms.v17i2.11455 page 205 sudan journal of medical sciences zeinab omer alfanob et al. be a key to preventing further complications. also, identifying the prevalence of pcos may help the healthcare authorities in better screening and treatment options. there is no published data about knowledge of females in sudan about pcos; therefore, this study aimed at exploring the knowledge of sudanese females about pcos. 2. materials and methods 2.1. study setting this study was a descriptive cross-sectional community-based study, conducted from january to april 2019 in khartoum state, sudan. the study was conducted at public places in three different localities of khartoum state (omdurman, khartoum, and khartoum north). the population recruited were women of reproductive age (16 to 50 years; married and single) who were residents in khartoum state and agreed to participate in the study. 2.2. sample size and sampling method a convenience sampling technique was used to select the participants; 240 females were selected during the data collection period (one month). 2.3. data collection method data were collected using a close-ended questionnaire, comprehensible questions format. the questionnaire was filled out during a face-to-face interview (240 participants). the questionnaire was translated into arabic and a pretest survey was done on 30 participants, which has led to the rephrasing of several questions for better understanding. the participants included in the pilot phase were excluded from the study. 2.4. knowledge scale the knowledge was tested using 18 questions, of which 8 were about symptoms, 5 about complications, and another 5 about risk factors. for each question in the knowledge section, a score of one was given for a correct answer, whereas a zero was given for incorrect or uncertain responses. questions were rated and a total doi 10.18502/sjms.v17i2.11455 page 206 sudan journal of medical sciences zeinab omer alfanob et al. score was obtained. knowledge scores ranged between 1 and 18. a knowledge score >15 was considered excellent, between 9 and 15 as well, and <9 as low [18]. before logistic regression analysis, excellent and good levels were re-categorized as ”sufficient knowledge” (scores ≥9), and those with a low level of knowledge (scores <9) were recategorized as “insufficient knowledge” [21]. 2.5. data analysis data were analyzed using the statistical package for social sciences (spss) version 24. the analysis included frequencies of discrete variables and descriptors and crosstabulation of the variables using the chi-square test and logistic regression analysis. p < 0.05 was considered as statistically significant. then all data were expressed as text, illustrated in tables and figures. 3. results 3.1. sociodemographic characteristics of the study population the total responded participants in this study were 240 females. less than half of the participants (46%) were within the age group of 20–30 years. almost half of the participants (49%) were single, (48%) had university-level education, and (61%) weren’t healthcare professionals. the majority of participants (80%) were residents in urban areas (table 1). 3.2. knowledge while 82.1% of the participants reported that irregularity of the menstrual cycle is one of the symptoms of pcos, 88.8% reported that delayed pregnancy is one of the complications of the pcos. many females (41.3%) had a low level of knowledge, while 21.3% had a good level, and 37.5% had an excellent level of knowledge. 3.3. prevalence of and practice of pcos among the participants it was found that 32.5% of the participants had pcos; of them, 94.9% received treatment. with regards to symptoms, 78.2% of the participants who were diagnosed previously with pcos were suffering from weight gain, 79.5% from acne, 85.9% from menstrual doi 10.18502/sjms.v17i2.11455 page 207 sudan journal of medical sciences zeinab omer alfanob et al. table 1: sociodemographic characteristics among studied population (n = 240). characteristics percentage (%) age groups (yr) 16–20 9.2 20–30 45.4 30–40 25.4 40–50 20 marital status married 42 single 49 divorced 3 widow 6 educational level primary 7 secondary 14 university 48 postgraduate 31 field of study health professionals 39 non-health professionals 61 residence rural 20 urban 80 irregularity, and 70.5% from hirsutism. the vast majority of patients (91%) who were diagnosed with pcos visited a gynecologist for the treatment of cycle irregularity, while 55% visited a dermatologist for the treatment of acne (table 3). the study showed that healthcare providers were the primary source of information (mentioned by about 63.3% of the participants), followed by relatives and social media by about 52.5% and 47.9% respectively. 3.4. chi-square and logistic regression tests chi-square statistical test showed significant associations between the level of knowledge and age, education level, residence, the field of study, and marital status (p < 0.001 , <0.001, <0.001, <0.001, 0.045), respectively. furthermore, there were significant associations between knowledge and the prevalence of pcos (p < 0.001). when logistic regression was performed to determine the predictors of knowledge toward pcos, it was found that residence, study field, and being known case of pcos were significantly associated with the knowledge (p 0.004, <0.001, and <0.001), doi 10.18502/sjms.v17i2.11455 page 208 sudan journal of medical sciences zeinab omer alfanob et al. table 2: knowledge among studied participants about clinical features, complications, and risk factors of pcos (n = 240). variables percentage (%) yes no i do not know symptoms psychological disturbance 52.1 14.6 33.3 hair loss 57.9 10.8 31.3 early puberty 30.8 24.6 44.6 pelvic pain 60.4 12.5 27.1 weight gain 73.3 7.9 18.8 hirsutism 62.9 12.9 24.2 facial acne 71.7 10.4 17.9 irregularity of menstrual cycle 82.1 8.3 9.6 b. complications diabetes 41.3 13.3 45.4 cardio-vascular disease 28.3 19.2 52.5 breast and uterus cancer 44.2 14.6 41.3 premature birth 27.5 24.2 48.3 delayed pregnancy 88.8 2.1 9.2 c. risk factors obesity 75 2.9 22.1 genetic factors 59.2 8.8 32.1 diabetes 37.1 18.8 44.2 not doing exercise 58.8 8.8 32.5 not eating vegetables 50.4 15 34.6 respectively. this means that being a health professional will increase the probability of having sufficient knowledge by 10 times more than those of non-health professionals; additionally, those living in urban areas were more likely to have sufficient knowledge compared to those living in rural areas by 4.8 times. furthermore, those who were previously diagnosed with pcos were more likely to have sufficient knowledge by 10 times than those who did not (table 4). 4. discussion in this study, 46% of the participants were within the age group 20–30 years. the level of participants’ knowledge about pcos was significantly related to age (p < 0.001), educational level (p < 0.001), and being a health professional (<0.001). these results were similar to a study done in saudi arabia in which the level of awareness was significantly related to higher educational levels and health college qualifications [12]. doi 10.18502/sjms.v17i2.11455 page 209 sudan journal of medical sciences zeinab omer alfanob et al. table 3: prevalence and practice of pcos among the participants (n = 240). responses n (%) known case of pcos (n = 240) yes 78(32.5) no 162(67.5) sings of hirsutism (n = 78) yes 55(70.5) no 23(29.5) signs of mc irregularities (n = 78) yes 67(85.9) no 11(14.1) signs of acne (n = 78) yes 62(79.5) no 16(205) signs of weight gain (n = 78) yes 61(78.2) no 17(21.8) received medications (n = 78) yes 74(94.9) no 4(5.1) seek dermatologist for acne (n = 78) yes 43(55.1) no 35(44.9) seek a gynecologist for menstrual irregularity (n = 78) yes 71(91) no 7(9) table 4: predictors of knowledge about pcos by using logistic regression test: (n = 240). b p-value odd ratio age 0.766 0.506 2.150 education level 0.830 0.401 2.293 residence 1.537 0.004 4.652 marital status –0.737 0.142 0.479 field of study 2.336 <0.001 10.345 known case of pcos 2.306 <0.001 10.033 this may be explained by the fact that women with higher educational levels have better access to information, as well as good medical care. while on other hand, in this study, residence was significantly correlated with knowledge (p < 0.001), unlike the results obtained from saudi arabia, where the area of residence showed no major impact on participants’ knowledge [12]. about 80% of the females were from urban areas which showed a significant association to the knowledge score. this difference may be because females residing in urban areas had a better chance to seek medical specialists’ advice and to learn more about the condition. in this study, the main source of information was medical professionals (gynecologists), which is similar to that in saudi arabia where women did get information and guidance from medical doctors [12]. the highest percentage of participants were within the age group of 20–30 years, which made the internet and social media another doi 10.18502/sjms.v17i2.11455 page 210 sudan journal of medical sciences zeinab omer alfanob et al. source of information to raise awareness about pcos among the participants in this study. pcos is a condition that is not diagnosed using a single criterion; therefore, the presence of signs and symptoms assist in the diagnosis of pcos. in this study, the majority of females were not diagnosed with pcos, although many of them were complaining of the symptoms thereof. the highest percentage of symptoms that were experienced by females diagnosed with pcos were menstrual cycle irregularities (85.9%), acne (79.5%), weight gain (78.2%), and hirsutism (70.5%). this was higher than that found in another study conducted with medical students in india, which found that 33.5% of females had acne, 16% had cycle irregularity, and 5% had hirsutism while 2% had infertility [13]. the weight gain observed among women included in the study may be explained in part by the fact that women in khartoum are often not engaged in regular exercise. furthermore, khalil et al. showed that physical activity in sudanese women was significantly lower when compared to men [19]. the study found that the majority of females (67.5%) were not diagnosed with pcos, but complained of symptoms, while 32.5% were diagnosed with pcos. this percentage is very high; these results raise questions about the exact causes and how to minimize risk factors. however, in pakistan, only 10% were known cases of pcos [15]. while other studies conducted in different public universities of quetta obtained that only 5.5% were already diagnosed with pcos [17]. in this study, 41.3% of the females had inadequate knowledge, which is not different from other countries like egypt and pakistan where females’ knowledge was very poor [14, 15]. regarding practice, a vast majority of participants who were diagnosed with pcos reported that they seek gynecologist’s help for the treatment of delayed pregnancy and irregular menses, which is similar to the findings in indian females, which reflected that seeking pregnancy (in case of married women) and normalizing menstrual cycle (in case of single women) [20] were the main reasons to visit the gynecologist. this study revealed that 55.5% of the participants diagnosed with pcos sought a dermatologist for acne. beauty is the main concern for females in reproductive ages and makes them seek treatment against acne. the acne may be a symptom of several gynecological conditions which may delay the treatment and lead to further complications. pcos patients are mostly young and the comprehension and awareness regarding the underlying disease, to some symptoms and clinical signs they are experiencing, were generally found to be deficient among them. increasing their awareness of this issue doi 10.18502/sjms.v17i2.11455 page 211 sudan journal of medical sciences zeinab omer alfanob et al. may lead to improved quality of life and even pharmacists could play a role in the awareness and management of pcos. 5. limitations this study is not without limitations. the cross-sectional design may not allow establishing the temporal relationship with risk factors. in addition, it is difficult to suggest that the study should be considered representative for all of sudan since participant recruitments took place only in the khartoum area. however, the study is novel as it showed the level of knowledge of sudanese women about pcos and this can help in developing strategies for future policy on women’s health in sudan. 6. conclusion the study revealed that there was a high prevalence of pcos among the study participants and that the knowledge of participants about pcos symptoms and complications was not adequate. the degree of knowledge was significantly associated with educational level, being a healthcare provider, place of residence, and previous diagnosis with the disease. there is an urgent need to increase knowledge about pcos among sudanese women to increase awareness and promote health-seeking behavior for early treatment to avoid complications. acknowledgements the authors are grateful to all the participants. ethical considerations ethical approval was obtained from omdurman islamic university, faculty of pharmacy (oiu-fp-12/2017), and the participants gave consent prior to the enrolment in the study. the research purpose and objectives were explained to the participants in clear simple words. participants had the right to withdraw at any time without any deprivation. privacy and confidentiality were kept. doi 10.18502/sjms.v17i2.11455 page 212 sudan journal of medical sciences zeinab omer alfanob et al. competing interests the authors declare no competing interest. availability of data and materials data and other materials will be available upon reasonable request. funding none questionnaire evaluation of women’s knowledge about polycystic ovary syndrome (pcos) in khartoum state demographic characteristics: age (yr): 16–20 20–30 30–40 40–50 educational level: primary secondary university postgraduate place of residence: rural urban marital status: married single divorced doi 10.18502/sjms.v17i2.11455 page 213 sudan journal of medical sciences zeinab omer alfanob et al. widow field of study: medical non-medical knowledge of symptoms about pcos: irregularity of mc yes no i don’t know facial acne yes no i don’t know hirsutism yes no i don’t know weight gain yes no i don’t know pelvic pain yes no i don’t know early puberty yes no i don’t know hair loss yes no i don’t know psychological disturbance yes no i don’t know knowledge of complications about pcos: diabetes yes no i don’t know cvs disease yes no i don’t know breast and uterus cancer yes no i don’t know premature birth yes no i don’t know delayed pregnancy yes no i don’t know what is the risk factors of pcos: doi 10.18502/sjms.v17i2.11455 page 214 sudan journal of medical sciences zeinab omer alfanob et al. weight gain yes no i don’t know genetic factors yes no i don’t know diabetes yes no i don’t know not doing exercises yes no i don’t know not eating fruits and vegetables yes no i don’t know what is your source of information: health care providers yes no relatives yes no social media yes no others yes no do you have any one of these symptoms: hirsutism yes no irregularity of menses yes no facial acne yes no weight gain yes no have you been diagnosed as a pcos patient before: yes no if yes, did you receive medications yes no what is your attitude about any one of the symptoms of the disease seeking dermatologist for acne yes no seeking gynecologist for irregularity of menses yes no seeking dermatologist for delayed pregnancy yes no doi 10.18502/sjms.v17i2.11455 page 215 sudan journal of medical sciences zeinab omer alfanob et al. references [1] nayak, s. (2016). a study to assess the knowledge regarding pcos (polycystic ovarian syndrome) among nursing students at nuins. nitte university journal of health science, vol. 6, no. 3. [2] bharathi, r. v., neerajaa, j., madhavica, j. v., et al. (2017). an epidemiological survey: effect of predisposing factors for pcos in indian urban and rural population. middle east fertility society journal, vol. 22, no. 4, pp. 313–316. [3] dias, d. (2015). a descriptive study to assess the knowledge and warning signs of the polycystic ovarian syndrome among girls of selected colleges of belagavi karnataka. kle university journal, vol. 89, no. 2, pp. 142–156. [4] witchel, s. f., oberfield, s. e., and pena, a. s. (2019). polycystic ovary syndrome: pathophysiology, presentation, and treatment with emphasis on adolescent girls. journal of the endocrine society, vol. 3, no. 8, pp. 1545–1573. [5] alessa, a., dalal, a., almutairi, s., et al. (2017). awareness of polycystic ovarian syndrome among saudi females. international journal of medical science and public health, vol. 6, no. 6, pp. 1013–1020. [6] de medeiros, s. f. (2017). risks benefit size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome. reproductive biology and endocrinology, vol. 15, no. 1, p. 93. [7] lucidi, r. s. (n.d.). polycystic ovarian syndrome treatment and management. medscape. retrieved from: http://emedicine.medscape.com/article/256806-treatment. [8] palomba, s., santagni, s., falbo, a., et al. (2015). complications and challenges associated with polycystic ovary syndrome: current perspectives. international journal of women’s health, vol. 7, pp. 745–763. [9] rotterdam eshre/asrm-sponsored pcos consensus workshop group. (2004). revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. fertility and sterility, vol. 81, no. 1, pp. 19–25. [10] shafiee, m. n., chapman, c., barrett, d., et al. (2013). reviewing the molecular mechanisms which increase endometrial cancer (ec) risk in women with polycystic ovarian syndrome (pcos): time for a paradigm shift? gynecologic oncology, vol. 131, no. 2, pp. 489–492. [11] patel, j. and rai, s. (2018). polycystic ovarian syndrome (pcos) awareness among young women of central india. international journal of reproduction, contraception, obstetrics and gynecology, vol. 7, no. 10, pp. 3960–3964. doi 10.18502/sjms.v17i2.11455 page 216 sudan journal of medical sciences zeinab omer alfanob et al. [12] alsinan, a. and shaman, a. (2017). a study to measure the health awareness of polycystic ovarian syndrome in saudi arabia. global journal of health science, vol. 9, no. 8, p. 130. [13] upadhye, j. j. and shembekar, c. a. (2017). awareness of pcos (polycystic ovarian syndrome) in adolescent and young girls. international journal of reproduction, contraception, obstetrics and gynecology, vol. 6, no. 6, pp. 2297–2301. [14] ali, m. r. and mahmoud, o. m. (2019). polycystic ovarian syndrome knowledge and awareness of non-medical undergraduate students. international journal of novel research in healthcare and nursing, vol. 6, no. 3, pp 1249–1258). [15] gul, s., zahid, s., and ansari, a. (2014). pcos: symptoms and awareness in urban pakistani women. international journal of pharma research and health sciences, vol. 2, no. 5, pp. 356–360. [16] teede, h., gibson-helm, m., norman, r. j., et al. (2014). polycystic ovary syndrome: perceptions and attitudes of women and primary health care physicians on features of pcos and renaming the syndrome. the journal of clinical endocrinology and metabolism, vol. 99, no. 1, pp. e107–e111. [17] haq, n., khan, z., riaz, s., et al. (2017). prevalence and knowledge of polycystic ovary syndrome (pcos) among female science students of different public universities of quetta, pakistan. imperial journal of interdisciplinary research, vol. 35, no. 6, pp. 385–392. [18] memon, m. s., shaikh, s. a., shaikh, a. r., et al. (2015). an assessment of knowledge, attitude and practices (kap) towards diabetes and diabetic retinopathy in a suburban town of karachi. pakistan journal of medical sciences, vol. 31, no. 1, pp. 183–188. [19] khalil, s., almobarak, a. o., awadalla, h., et al. (2017). low levels of physical activity in sudanese individuals with some features of metabolic syndrome: population-based study. diabetes & metabolic syndrome, vol. 11, no. 2, pp. s551–s554. [20] sharma, s. and mishra, a. j. (2017). tabooed disease in alienated bodies: a study of women suffering from polycystic ovary syndrome (pcos). clinical epidemiology and global health, vol. 6, no. 3, pp. 130–136. [21] alirisasi, c., mulumba, p., verdonck, k., et al. (2014). knowledge, attitude and practice about cancer of the uterine cervix among women living in kinshasa, the democratic republic of congo. bmc women’s health, vol. 14, p. 30. doi 10.18502/sjms.v17i2.11455 page 217 introduction materials and methods study setting sample size and sampling method data collection method knowledge scale data analysis results sociodemographic characteristics of the study population knowledge prevalence of and practice of pcos among the participants chi-square and logistic regression tests discussion limitations conclusion acknowledgements ethical considerations competing interests availability of data and materials funding questionnaire references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10681 production and hosting by knowledge e original article association of serum leptin with prognostic factors in breast cancer amirreza hajati1, farshad talebian2, asrin babahajian1, nasrin daneshkhah3, bayazid ghaderi1* 1liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran 2student research committee, kurdistan university of medical sciences, sanandaj, iran 3faculty of nursing and midwifery, kurdistan university of medical sciences, sanandaj, iran abstract background: nowadays, cytokines such as leptin and adiponectin are introduced as prognostic factors which, according to some studies, are also associated with body mass index. this study aimed to determine serum leptin level and its relationship with prognostic factors in breast cancer patients. methods: this case–control study was conducted in the oncology department of tohid hospital, sanandaj, iran, between 2019 and 2020. hundred new cases of breast cancer patients with histological evidence were enrolled in this study. additionally, 100 ageand bmi-matched healthy individuals were recruited as the control group. the serum leptin level was measured using the elisa method. results: serum leptin levels were significantly higher in breast cancer patients compared to the control group (21.68 ± 9.16 vs 11.89 ± 4.45; p < 0.001). there was no significant relationship between plasma leptin levels with er, pr, and her2 expressions (p > 0.05). also, no significant associations were noted between leptin levels and grading and disease staging (p > 0.05). conclusion: the study found that leptin is higher in breast cancer patients than in healthy individuals, however, it did not prove that leptin is a predictive or prognostic factor. keywords: leptin, breast cancer, staging, grading 1. introduction breast cancer (bc) is the most common malignancy in women worldwide and the most common type of cancer in iran. it accounts for 30% of all cancers and 15% of all cancerrelated deaths in women. bc is a multifactorial disease, and various factors are involved in its development [1]. late-onset menopause, advanced maternal age, nulliparity, long-term use of birth control pills, hormone therapy with estrogen and progesterone for a long term, obesity and estrogen use alone, miscarriage, infertility, history of pregnancy-induced hypertension, a family history of bc, and vitamin d deficiency are associated with an increased risk of bc [2, 3]. some other factors, such as breastfeeding, oophorectomy, and multiple pregnancies, are associated with a reduced risk of bc [1]. how to cite this article: amirreza hajati, farshad talebian, asrin babahajian, nasrin daneshkhah, bayazid ghaderi* (2022) “association of serum leptin with prognostic factors in breast cancer,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 4–14. doi 10.18502/sjms.v17i1.10681 page 4 corresponding author: bayazid ghaderi; email: bayazidg@yahoo.com received 26 april 2021 accepted 12 march 2022 published 31 march 2022 production and hosting by knowledge e amirreza hajati et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bayazidg@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences amirreza hajati et al to treat this disease like other cancers, it is necessary to evaluate the survival rate and find prognostic factors. disease-free survival is defined from the onset of the disease to the time of the metastatic event or death of the patient [4]. the results of previous studies have shown that surgery and chemotherapy in younger women and hormone therapy using tamoxifen and letrozole in postmenopausal women with early bc significantly reduce the risk of cancer recurrence (43%) and improve disease-free survival. other practical factors include the degree of tumor malignancy, tumor size, number of lymph nodes involved, age, estrogen (er) and progesterone receptors (prs), metastasis, type of tumor, and lymphovascular invasion [5]. today, studies have identified cytokines such as leptin and adiponectin as prognostic factors that, according to some studies, are also associated with bmi [6]. leptin is a 167-amino acid protein mainly produced by white adipose tissue that enters the bloodstream; it can appear both in free and bounded forms in serum [7]. leptin is a neurohormone whose primary function is to regulate energy balance and food intake in the hypothalamus [8]. plasma leptin levels reflect body fat mass [9]. in addition to adipose tissue, leptin can be present in other tissues such as the placenta, gastric and colon mucosa, liver cells, and epithelial cells of the breast [10, 11]. some studies have shown an association between leptin, obesity, insulin resistance, and the risk of bc [7, 12]. however, some studies have not been able to find this association [13]. the controversy is even more remarkable, while some studies have even reported a negative relationship between leptin levels and bc [14]. studies have shown that weight gain is associated with increased mortality from cancers in various body parts [15]. multiple studies have also suggested a positive association between obesity and an increased risk of endometrial, kidney, colon, and gallbladder cancers in women and bc in postmenopausal women [16]. it has been proven that obesity can increase the risk of bc in postmenopausal women by 30– 50%. in addition, high bmi is correlated with an increased risk of inflammatory bc both before and after menopause [17]. because adipose tissue produces leptin, leptin levels are higher in obese people than in normal-weight people. in addition, there is a relatively higher level of resistance to the hormone in obese people, which indicates an increase in their serum levels [18]. leptin stimulates the proliferation of benign and malignant breast epithelial cells in the laboratory [19]. leptin is higher in women than men, which can be explained by differences in sex hormones as estrogen increases leptin expression while testosterone decreases it [20]. and given the prevalence of bc and the high number of prognostic factors, it is necessary to recognize the relationship doi 10.18502/sjms.v17i1.10681 page 5 sudan journal of medical sciences amirreza hajati et al between these factors and serum leptin levels. this study aims to determine serum leptin level and its relationship with prognostic factors for bc. 2. materials and methods 2.1. study design, setting, and patient population in this retrospective case–control study, patients with bc presenting to tohid hospital, sanandaj, iran, between 2019 and 2020 were studied. the inclusion criteria were: age >18 years, informed consent, and diagnosis of bc. census sampling method was used to select the study population. patients were excluded from the study if they were pregnant, had liver disorders, or had other types of cancer. accordingly, 100 people with bc and the same number of ageand bmi-matched healthy women were recruited as the case and control groups, respectively. 2.2. data collection data were collected using a checklist containing information regarding demographic data of all the subjects (age, sex); disease-related indicators in the group of patients such as bmi, ki67 cell proliferation factor, type of cancer histology, (histopathology), disease stage, disease grade, er, pr, lymphovascular involvement, and her2/neu. as prognostic and therapeutic indicators, the aforementioned items were collected as the mandatory items required for the assessment of patients. 2.3. paraclinical investigation fasting blood samples (5 ml) were collected from the patients and the control group to measure the leptin level. blood samples were centrifuged at 3000 rpm for 5 min to separate serum. then, it was stored at a temperature below –24ºc until the time of the tests. leptin levels were measured via the radioimmunoassay method, using a multisciences kit manufactured in iran (sensitivity 15.63–1000 pg/ml). 2.4. statistical analysis data were analyzed using the spss software, version 22. the kolmogorov–smirnov test confirmed the normality of the data. parametric statistical tests, including pearson doi 10.18502/sjms.v17i1.10681 page 6 sudan journal of medical sciences amirreza hajati et al table 1: comparison of the mean leptin level between the two groups of the bc patients and the control group. group n leptin (ng/ml) mean ± (sd) t p-value mean differences confidence interval 95% min max bc patients 100 11.89 ± (4.45) 7.99 0.000 –9.79 –13.22 –6.36 control 100 21.68 ± (9.16) table 2: association of leptin level with the status of hormone receptors in the bc patients. n leptin (ng/ml) mean ± (sd) t p-value mean differences confidence interval 95% min max er negative 23 23.21 ± (9.42) 0.91 0.36 1.98 –2.34 6.30 positive 77 21.23 ± (9.09) pr negative 28 21.46 ± (9.90) 0.15 0.88 –0.30 –4.37 3.76 positive 72 21.77 ± (8.93) her2 negative 66 21.87 ± (8.69) 0.30 0.76 0.56 –3.29 4.42 positive 34 21.31 ± (10.14) histo2ogy negative 88 21.40 ± (9.29) 0.84 0.40 –2.36 –7.96 3.24 positive 12 23.76 ± (8.19) test, independent t-test, and analysis of variance, were performed. p-value < 0.05 was considered as a significant level. 3. results the mean age of the bc patients and the control group was 47.60 ± 9.69 (range, 26–72) and 49.12 ± 8.10 (range, 28–70) years, respectively, with no significant difference (p = 0.62). the mean bmi of the patients was 29.42 ± 4.83 kg/m2. as shown in table 1, serum leptin concentration was significantly higher in the bc patients than in healthy individuals (21.68 ± 9.16 ng/ml vs 11.89 ± 4.45 ng/ml, p < 0.001). the results of this study showed that there was no significant association between serum leptin levels and the status of hormone receptors in the study patients (p > 0.05) (table 2). the mean leptin levels in bc patients with different stages and grades of the disease are presented in tables 3 and 4. based on the reported results, no significant association was observed between serum leptin levels and disease staging (p = 0.51) and grading (p = 0.50). doi 10.18502/sjms.v17i1.10681 page 7 sudan journal of medical sciences amirreza hajati et al table 3: mean values of leptin concentration in different stages of bc. stage n leptin (ng/ml) mean ± (sd) p-value 1 33 20.31 ± (9.92) 0.514 2 24 23.72 ± (7.54) 3 20 22.55 ± (8.36) 4 23 20.78 ± (10.28) table 4: mean values of leptin concentration in different grades of bc. grade n leptin (ng/ml) mean ± (sd) p-value 1 32 23.22 ± (9.25) 0.50 2 40 20.69 ± (9.38) 3 28 21.34 ± (8.81) 4. discussion the mean age of the patients in the current study was 47.60 ± 9.69 (range, 26–72) years. this is consistent with other studies, in which the mean age of patients ranged from a minimum of 47 to a maximum of 53 years [21–23]. however, there are a few studies in which the average age of patients is higher, ranging from 67 to 69 years [24, 25]. moreover, the mean bmi in our study was 29.42 ± 4.83 kg/m², ranging from a minimum of 20 to a maximum of 44 kg/m², which is consistent with most studies [26, 27]. this indicates that, in general, the mean bmi in patients with bc is higher than in healthy people. as another finding of the present study, the mean leptin level was 21.68 ng/ml in the patient group and 11.89 ng/ml in the healthy group, there was a significant difference between them (p <0.001). many studies have investigated the association of leptin with bc, and majority of them have confirmed a significant relationship between them. however, in some studies, this relationship has not been significant. for instance, the study of chen et al. [28] showed that serum leptin levels were significantly increased in patients, as compared with the control group (p = 0.025), and those with high leptin levels had larger tumors (p = 0.036). researchers concluded that elevated leptin levels were associated with a higher risk of bc and even more advanced cancers. in a study by wang et al., a significant relationship between leptin levels and bc was reported. it was concluded that serum leptin levels and the free leptin index (fli) could be considered potential indicators for assessing the prognosis of patients with bc [29]. in a meta-analysis, 43 eligible studies were reviewed. in general, serum levels of leptin in bc patients were significantly higher than in the control group (smd = 0.61, p < 0.001). even when the study of subgroups was limited to the ethnicity and status of doi 10.18502/sjms.v17i1.10681 page 8 sudan journal of medical sciences amirreza hajati et al the menstrual cycle, the serum leptin concentrations remained higher in bc patients. in addition, serum leptin levels were significantly higher in bc patients with a bmi > 25 (smd = 1.48, p = 0.034). moreover, in patients with lymph node metastasis, serum leptin concentration was significantly higher (smd = 0.53, p <0.015). this meta-analysis revealed that serum leptin level might play an essential role in the pathogenesis and invasive progression of bc. furthermore, the analysis of the ethnicity subgroup showed that the mean leptin levels were significantly higher in patients with bc among the asian population (p < 0.001) [30]. on the other hand, according to grossman et al. [31], the high adiponectin ratio to leptin indicates a favorable risk profile for bc than the low adiponectin ratio to leptin. rose et al. concluded that leptin might be a strong candidate for predicting the destructive role of fat in bc. in a study by niu et al., the results showed that higher leptin was associated with increased prevalence and growth of bc [32]. pan et al. conducted a systematic review of 35 eligible articles and concluded that there is a significant correlation between serum leptin levels and the risk of bc (smd = 0.46, 95% ci = 0.31–0.60). in the mentioned study, the analysis of the bmi subgroup showed a correlation between bc and serum leptin levels in overweight patients (p < 0.01), the results of this meta-analysis showed that leptin could be a potential biomarker for the risk of bc in women, especially overweight women [33]. other studies on the relationship between leptin and bc have confirmed a significant correlation between them [34, 35]. however, minimal studies do not approve or support this relationship [13]. laboratory studies investigating the mechanism of action of leptin in connection with bc show that leptin circulation level is the interface that informs the brain about the state of energy storage. these levels indicate the present amount of adipose tissue and are directly related to an increase in bmi. in addition, serum leptin levels are higher in women than in men even after weight correction. this can be explained by subcutaneous synthesis and regulation of estrogen and androgen [20]. one of the environmental functions of leptin is to monitor and regulate the role of energy in the interaction between energy metabolism and the immune system in a part of the body that is responsible for obesity-related inflammation [36]. it has been shown that leptin signaling, as in breast carcinogenesis, regulates the expression of cyclin d1, p53, survivin, il1, e-cadherin, vegf and its at2, and various tissue factors. in addition, it regulates molecules involved in proliferation, migration, invasion, adhesion, angiogenesis, and inflammation [37, 38]. it has been suggested that leptin at the carcinogenic level may act as a direct activator of short-term ros production in human epithelial breast cells [39]; however, other studies have previously shown that chronic leptin therapy reduces ros levels and oxidative stress in mcf-7 cells [40]. leptin has also been introduced as a mediator doi 10.18502/sjms.v17i1.10681 page 9 sudan journal of medical sciences amirreza hajati et al of tumor-stroma interaction [41], where it appears to interact between bc cells and m2 tumor-associated macrophages through stimulating il-18 production. il-8, in turn, enhances the proliferation and metastasis of tumors [42]. in addition, a recent study showed that obesity increased leptin expression at the mrna level by reducing the level of p16ink4a as a tumor suppressor protein in breast adipocytes and promoting precancerous processes [43]. based on other results of our study, comparing leptin levels in terms of the presence and absence of er, pr, her2, histo2opy, grade, and stage in the patient group, there was no statistically significant difference between the studied items (p > 0.05). this finding is consistent with all reviewed studies and indicated that there was no significant difference between bc patients with positive and negative er in terms of leptin level (p > 0.05) [27, 44]. furthermore, in studies by kim et al. [45] and wang et al. [35], there was no significant relationship between leptin and her-2, which indicates that these markers may not be associated with an increase or decrease in leptin level in patients. the results of other studies also support our findings on bc grade and stage. 5. conclusion the study proves that leptin is higher in bc patients than in healthy individuals; however, it did not prove that leptin is a predictive or prognostic factor. a larger study is needed. acknowledgements the authors would like to thank the vice-chancellor for research, kurdistan university of medical sciences, sanandaj, iran, for financial support. ethical considerations the study protocol was approved by the ethics committee of kurdistan university of medical sciences, sanandaj, iran (no. ir.muk.rec.1398.266), and informed consent was obtained from all participants prior to the study. competing interests the authors report no potential conflict of interest. doi 10.18502/sjms.v17i1.10681 page 10 sudan journal of medical sciences amirreza hajati et al availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding none. references [1] badrian, m., ahmadi, p., amani, m., et al. 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(2006). effects of the expression of leptin and leptin receptor (obr) on the prognosis of early-stage breast cancers. cancer research and treatment, vol. 38, no. 3, p. 126. doi 10.18502/sjms.v17i1.10681 page 14 introduction materials and methods study design, setting, and patient population data collection paraclinical investigation statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11460 production and hosting by knowledge e review article thyroid-stimulating hormone suppressive therapy and osteoporosis: a review and meta-analysis hyder osman mirghani1* and albaraa altowigri2 1associate professor of internal medicine and endocrine, faculty of medicine, university of tabuk, saudi arabia 2assistant professor of orthopedics, faculty of medicine, university of tabuk, saudi arabia orcid: hyder osman mirghani: https://orcid.org/0000-0002-5817-6194 abstract background: osteoporosis is a common morbid and mortal disease; thyroidstimulating hormone (tsh) suppression is the state-of-the-art for postoperative differentiated thyroid carcinoma (dtc). however, its association with osteoporosis remains controversial. the current meta-analysis assessed the relationship between tsh suppressive therapy and osteoporosis among patients with dtc. methods: we systematically searched pubmed, cochrane library, ebsco, and the first 100 articles in google scholar for relevant articles published in english during the period from 2008 to november 2020. the keywords differentiated thyroid cancer, tsh suppression, osteoporosis, low bone mineral density, osteopenia; fracture risk, disturbed bone micro-architecture, bone loss, and trabecular bone were used. one hundred and eighty-four articles were retrieved; of them, fourteen were eligible and met the inclusion and exclusion criteria. the revman system was used for data analysis. results: we included 36 cohorts from 15 studies, the studies showed higher osteoporosis and osteopenia among tsh-suppressed women, odd ratio, 2.64, 1.48– 4.68 and 2.23, 0.33–14.96, respectively. high heterogeneity was observed, i2 = 68% and 96%, respectively). the sub-analysis showed a lower bone mineral density among postmenopausal women at both femoral neck and lumbar spines, odds ratio, –0.02, –0.07 to 0.04, and –0.03, –0.06 to 0.01, i2 for heterogeneity, 69%, and 51% in contrast to men and premenopausal women who showed normal or higher bone density. conclusion: tsh suppression for dtc was associated with osteoporosis and osteopenia among postmenopausal women but not premenopausal women or men. studies focusing on trabecular bone scores are needed. keywords: tsh suppression, differentiated thyroid carcinoma, osteoporosis 1. introduction thyroid carcinoma is among the most common malignancies with an incidence of 1.7 to 4.1/100.000/yr in men and 4.5 to 8.7/100.000/yr in women [1]. dtc is on the rise worldwide due to the increasing age. patients diagnosed with thyroid carcinoma are how to cite this article: hyder osman mirghani* and albaraa altowigri (2022) “thyroid-stimulating hormone suppressive therapy and osteoporosis: a review and meta-analysis,” sudan journal of medical sciences, vol. 17, no. 2, pp. 263–278. doi 10.18502/sjms.v17i2.11460 page 263 corresponding author: hyder osman mirghani; email: s.hyder63@hotmail.com received 16 november 2020 accepted 21 may 2022 published 30 june 2022 production and hosting by knowledge e hyder osman mirghani and albaraa altowigri. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:s.hyder63@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hyder osman mirghani and albaraa altowigri usually hypothyroid or euthyroid. however, thyrotoxicosis may be observed in 3.38% of metastatic thyroid diseases [2, 3]. endogenous hyperthyroidism shortens the bone turnover cycle, accelerates bone turnover, and leads to low bone mineral density (bmd) [4]. supra-physiological doses of thyroxine are the mainstay of therapy to suppress the tsh among postoperative patients with dtc for >60 years [5]. whether tsh suppression can lead to osteoporosis is a matter of controversy. on the other hand, hypoparathyroidism observed among patients with dtc was shown to increase bmd [6]. the relationship between osteoporosis and dtc is complex and when coexist may lead to deleterious consequences. although thyrotoxicosis is well-known for its effects on bmd, the supraphysiological doses of thyroid hormone and their exact contribution to bone turnover are not well-established [7, 8]. the literature on this important health problem is scarce. given the above, we conducted this meta-analysis to assess tsh suppression effects on bmd among patients with dtc. 2. materials and methods 2.1. the selection criteria according to picos 2.1.1. the included studies we included cross-sectional, prospective and retrospective cohorts, and controlled trials. studies must assess thyroid-stimulating hormone (tsh) suppression on bmd among patients with differentiated thyroid carcinoma (dtc). 2.1.2. outcome measures to be included, the studies must investigate osteoporosis, osteopenia, bmd, or bone loss as primary or secondary outcomes. no specifications were applied for subgroups (pooled females, premenopausal, men, and postmenopausal were included). dtc is affecting all age groups, males and females. besides, osteoporosis risks are not limited to postmenopausal status. thus, including all the patients and controlling for possible risk factors might be appropriate. case reports, animal studies, and experimental studies were not included. doi 10.18502/sjms.v17i2.11460 page 264 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri records iden�fied through database searching s c r e e n in g in c lu d e d e li g ib il it y id e n ti fi c a ti o n addi�onal records iden�fied through other sources records after duplicates removed (n = 88) records screened (n = 32) records excluded (n = 17) full-text ar�cles assessed for eligibility (n =15) full-text ar�cles were excluded (n = 0) because they are not randomized trials studies included in the qualitative synthesis figure 1: the effect of long thyroid-stimulating hormone (tsh)-suppressive therapy (following surgery for differentiated thyroid carcinoma) on bone mineral density (osteoporosis). 2.1.3. patients the patients who underwent tsh suppression following thyroidectomy for dtc (males, and females, premenopausal or postmenopausal) were included. patients with other thyroid disorders that need tsh suppression including toxic goiter and thyroid cancer other than dtc were excluded. 2.2. literature search and articles selection a systematic electronic search was conducted in pub med, cochrane library, ebsco, and the first 100 articles in google scholar for relevant articles published in the english doi 10.18502/sjms.v17i2.11460 page 265 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri language. the search engine was set to include studies from the first published article up to november 2020. the terms “differentiated thyroid cancer,” “tsh suppression,” “osteoporosis,” “low bmd,” “osteopenia,” “fracture risk,” “disturbed bone microarchitecture,” “bone loss,” and “trabecular bone” were used. the protean ”and” and ”or” were applied. the two authors independently screened the titles and abstracts. one hundred and eighty-four articles were retrieved, the number stood at 88 after duplication removal. of them, 32 full-texts were screened, and only 15 were eligible after applying the inclusion and exclusion criteria (nine texts were excluded due to missing information, and another eight needed subscription). the authors resolved any discrepancy among the articles by consensus. the data were exported into an extraction sheet detailing the author’s name, year, country of publication, the study type and period, the t and z-scores of bone densitometry (dexa scan), and the number of both the interventional and control groups. the study’s risk of bias and quality was assessed using the ottawa newcastle scale (table 1). the different phases of the literature search are shown in figure 1. 2.3. statistical analysis the authors used the revman version 5.4 for data analysis, data were entered manually, the fixed effect was used unless a significant heterogeneity was observed (>50%). the funnel plot was used to test for sensitivity (lateralization). p-value < 0.05 was considered significant. 3. results out of the 184 studies included, 15 articles were included in the meta-analysis, 6 were cross-sectional, 5 were prospective cohorts, and 4 were case–control studies. most of the included studies also have a retrospective arm. seven studies were published in europe, five in asia, one in south america, one was from the usa, and one from canada. the study periods ranged from14.93 ± 2.17 months to 12.2 ± 6.6 years, and the total number of patients was 2180 versus 2707 controls. in the current meta-analysis, six studies assessed osteoporosis among women (menopausal status not uniform); of them, five studies showed a higher rate of osteoporosis in the interventional group [9–13], while one showed lower osteoporosis [14]. however, due to the significant heterogeneity observed (i2 = 68%), the random effect doi 10.18502/sjms.v17i2.11460 page 266 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri table 1: ottawa newcastle assessment for the included studies. author selection compatibility outcome score franklyn et al. (1992) [16] 3 2 4 9 kung et al. (1993) [18] 3 2 4 9 muller et al. (1995) [9] 3 2 4 9 fujiyama et al. (1995) [17] 3 2 4 9 goerres et al. (1998) [22] 3 2 4 9 eftekhari et al. (1998) [23] 3 2 4 9 reverter et al. (2005) [20] 3 2 4 9 de melo et al. (2015) [11] 3 2 4 9 wang et al. (2015) [10] 3 2 3 8 tournis et al. (2015) [21] 3 2 4 9 moon et al. (2016) [19] 3 2 3 8 de mingo dominguez et al. (2018) [15] 4 1 2 7 vera et al. (2016) [14] 3 2 3 8 mazziotti et al. (2018) [12] 4 1 3 8 zhang et al. (2018) [13] 4 2 3 9 showed a net effect favoring high osteoporosis among the tsh suppression group, odd ratio, 2.64, 1.48–4.68. the funnel plot showed significant lateralization (figure 2). regarding osteopenia, among the three studies included, two [11, 12] showed more osteopenia in the control group, and one reported a marked rate of osteopenia in the interventional group [13], the overall effect is more osteopenia among the tsh suppression, odd ratio, 2.23, 0.33–14.96 (figure 3). regarding the effects of tsh suppression among postmenopausal women, no differences in bmd was observed in lumbar spines [11, 15–21], and femoral neck [11, 16, 18–21], odd ratio, –0.02, –0.07 to 0.04, and –0.03, –0.06 to 0.01, respectively, i2 for heterogeneity, 69% and 51%, respectively, p-values, 0.52 and 0.1, respectively (figures 4 & 5). a higher value of bmd was observed among premenopausal women compared to controls in both the lumber spines [11, 16, 19, 21, and 22] and femoral neck [16, 19, 21, and 22], odd ratios, 0.05, 0.0–0.09, and 0.03, 0.0–0.06, p-values, 0.04 and 0.03, respectively (figures 6 & 7). no difference in bmd was evident between males with suppressed tsh and their counterparts, no heterogeneity was observed, odd ratio, 0.0, –0.7 to 0.06, p-value, 0.87 (figure 8). doi 10.18502/sjms.v17i2.11460 page 267 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri table 2: the effect of long thyroid-stimulating hormone (tsh) suppressive therapy (following surgery for differentiated thyroid carcinoma) on bone mineral density. author year country type patients (interventional vs controls) study period results muller et al. [9] 1995 canada prospective 25 dtc (matched for menopausal status, bmi, and age), 0/25 vs 13/25 for ext, 0/25 vs 1/25 for other sites 11 years cancer patients showed insignificant reductions of 2–5% in bmd of ls, fn, and tk and a significant 5% reduction in bmd of ext (dtc, higher t4, same tsh suppression) wang et al. [10] 2015 usa prospective comparing tsh < 0.4 mu/l and 0.4 125/537 vs 29/537 for premenopausal and postmenopausal 66 months osteoporosis increased, with no change in the recurrence rate. no increased risk of tsh level around 1 mu/l de melo et al. [11] 2015 brazil crosssectional, 21/109 for osteoporosis and 44/109 for osteopenia vs 17/109 and 49/109, postmenopausal 88 ± 70.6 months not significant vera et al. [14] 2016 italy case– control 62/74 hip, 49/74 lumbar vs 92/120, 75/120, women 36 months no relation of t4 dose, level, or duration of therapy to osteoporosis mean ± sd available mazziotti et al. [12] 2018 italy crosssectional, tsh < 0.05 and >1 35/83 vs 9/46 for osteoporosis and 35/83 vs 21/46 for osteopenia, women 5.5 years vertebral fractures were common among patients on longterm t4 and tsh levels <1 mu/l zhang et al. [13] 2018 china prospective cohort 90/152, 13/152 vs 23/68, 9/68 for osteopenia and osteoporosis, respectively, postmenopausal women 2 years osteopenia was observed, no osteoporosis. (tsh > 0.3 & tsh < 0.3 μiu/ml) 4. discussion osteoporosis is common among men and postmenopausal women in contrast to premenopausal women; therefore, much less interest is observed regarding this morbid and mortal disease in this age group [23]. tsh-suppressive therapy is on the rise due to the increasing diagnosis of dtc mirrored by improving diagnostic and screening tools [24]. we found a higher rate of osteoporosis among women (pooled and postmenopausal). doi 10.18502/sjms.v17i2.11460 page 268 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri table 3: tsh suppression for differentiated thyroid carcinoma and bone mineral density among women. author year country type premenopausal postmenopausal study period franklyn et al. [16] 1992 uk prospective 18 vs 18 controls 0.760 ± 0.140 vs 0.780 ± 0.150 lumbar spines and 1.000 ± 0.110 vs 0.970 ± 0.130 femoral neck 26 vs 26 controls 0.540 ± 0.170 vs 0.540 ± 0.220 lumbar spines and 0.810 ± 0.080 vs 0.830 ± 0.130 femoral neck 7.9 years kung et al. [18] 1993 hong kong crosssectional 34 vs 34 controls 0.749 ± 0.147 vs 0.917 ± 0.161 lumbar spines and 0.622 ± 0.123 vs 0.708 ± 0.127 femoral neck 12.2 ± 6.6 years fujiyama et al. [17] 1995 japan prospective 12 vs 12 0.849 ± 0.605 vs 0.849 ± 0.605 lumbar goerres et al. [22] 1998 switzerlandcrosssectional 7 vs 7 controls 1.006 ± 0.143 vs 0.903 ± 0.128 lumbar spines and 0.892 ± 0.141 vs 0.861 ± 0.094 femoral neck reverter et al. [20] 2005 spain crosssectional 44 vs 44 controls 1.094 ± 0.248 vs 0.978 ± 0.355 lumbar spines and 0.927 ± 0.124 vs 0.921 ± 0.148 femoral neck de melo et al. [11] 2015 brazil crosssectional 109 vs 109 1.09 ± 1.43 vs 1.11 ± 1.3, lumbar, 0.12 ± 1.1 vs 0.37 ± 1.06 femur 88 ± 70.6 months tournis et al. [21] 2015 greece case-control 40 vs 29 1.200 ± 0.100 1.100 ± 0.100 lumbar 0.940 ± 0.100 vs 0.900 ± 0.100 femoral 40 vs 60 1.100 ± 0.100 vs 1.100 ± 0.100 lumbar and 0.840 ± 0.100 vs 0.870 ± 0.100 femoral moon et al. [19] 2016 south korea case– control 25 vs 75 1.210 ± 0.110 vs 1.180 ± 0.120 lumbar, and 0.930 ± 0.100 vs 0.900 ± 0.090, femoral 74 vs 222 1.050 ± 0.150 vs 1.070 ± 0.140 lumbar, and 0.830 ± 0.110 vs 0.830 ± 0.100 femoral 36 months de mingo dominguez et al. [15] 2018 spain case– control 14 vs 84 1.00 ± 0.12 vs 0.98 ± 0.11, lumbar 14 vs 84 0.86 ± 0.12 vs 0.84 ± 0.15, lumbar 10 years bmd was higher among women with dtc who received thyroxine for tsh suppression, no difference in bmd was observed among males compared to their counterparts without tsh suppression. the current findings were similar to ku and colleagues who conducted a meta-analysis and found similar results [25]. the current findings supported the conclusion of a recent meta-analysis that included only 11 studies and focused on doi 10.18502/sjms.v17i2.11460 page 269 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri table 4: tsh suppression for differentiated thyroid carcinoma and bone mineral density among men. author year country type bmd study period franklyn et al. [16] 1992 uk prospective 5 vs 5 controls 0.710 ± 0.270 vs 0.750 ± 0.280 lumbar spines and 0.890 ± 0.110 vs 1.000 ± 0.210 femoral neck 7.9 years goerres et al. [22] 1998 switzerlandcross-sectional 17 vs 18 controls 0.965 ± 0.173 vs 1.003 ± 0.132 lumbar spines reverter et al. [20] 2005 spain cross-sectional 33 vs 33 controls 1.253 ± 0.156 vs 1.238 ± 0.171 lumbar spines and 0.948 ± 0.128 vs 0.997 ± 0.151 femoral neck eftekhari et al. [23] 2008 iran cross-sectional 11 vs 11 controls 1.110 ± 0.210 vs 1.040 ± 0.090 lumbar spines 14.93 ± 2.17 months figure 2: the effect of long thyroid-stimulating hormone (tsh)-suppressive therapy (following surgery for differentiated thyroid carcinoma) on bone mineral density (osteoporosis). the site of bmd, our study assessed additional women with osteopenia and a broad category of women without specification of menopausal status. a recent meta-analysis doi 10.18502/sjms.v17i2.11460 page 270 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri figure 3: the effect of long thyroid-stimulating hormone (tsh)-suppressive therapy (following surgery for differentiated thyroid carcinoma) on bone mineral density (osteopenia). [26] concluded the negative effects of tsh suppression on bmd (the study assessed postmenopausal women only). a broader insight for tsh suppression, which might be of minimal contribution to mortality and morbidity was suggested [27, 28]. a previous study based on american thyroid association has categorized patients into nine categories including the patient’s character, the aggressiveness of the tumor, the duration and levels of tsh suppression, and cardiovascular adverse effects [29]. besides, the time to develop osteoporosis was found to be shorter in postmenopausal women and those with a family history of the disease [30]. recent studies have suggested that trabecular bone score combined with bmd measurement might be more useful than the current practice of depending on bmd alone [31]. the contradicting findings of a higher bmd in premenopausal women might be explained by estrogen effects or lifestyles. the strength of this analysis is that we investigated both osteoporosis and osteopenia. the study limitations were: including studies with different methods of doi 10.18502/sjms.v17i2.11460 page 271 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri figure 4: tsh suppression and bone mineral density among postmenopausal women lumbar spines. outcomes assessments, the unlimited period of database search, and the heterogeneity observed in the meta-analysis. 5. conclusion tsh-suppressive therapy was associated with increased osteopenia and osteoporosis risk in postmenopausal women, no association was found between tsh suppression and osteoporosis in premenopausal women and men. further studies investigating the combined use of trabecular bone score for bone quality in addition to bmd are recommended. doi 10.18502/sjms.v17i2.11460 page 272 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri figure 5: tsh suppression and bone mineral density among postmenopausal women femoral neck. 6. the implications for research, policy, or practice: extreme caution is needed regarding the use of tsh suppression in low-risk dtc in patients at risk of/with osteoporosis. if needed, tsh suppression may need careful follow-up to keep the tsh levels at the recommended levels (<0.1 mu/l for aggressive malignancies and [<21 mu/l for low-intermediate grades) follow-up by the indicated techniques dexa-scans or qualitative computed tomography) at shorter periods may be needed. acknowledgements the authors would like to acknowledge the saudi national library for granting access to the databases. doi 10.18502/sjms.v17i2.11460 page 273 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri figure 6: tsh suppression and bone mineral density among premenopausal women lumbar spines. figure 7: tsh suppression and bone mineral density among premenopausal women lumbar spines. ethical considerations the current meta-analysis did not include any research on humans or animals published by the authors. competing interests the authors declare that they have no competing interests. doi 10.18502/sjms.v17i2.11460 page 274 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri figure 8: tsh suppression and bone mineral density among men lumbar spines. availability of data and materials the dataset used in this meta-analysis are available upon request. funding the research is self-funded and not supported financially by any institute or organization. references [1] farahati, j., mäder, u., gilman, e., et al. 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(2017). osteoporosis in premenopausal women. current opinion in rheumatology, vol. 29, no. 4, pp. 410–415. [25] ku, e. j., yoo, w. s., lee, e. k., et al. (2022). effect of tsh suppression therapy on bone mineral density in differentiated thyroid cancer: a systematic review and meta-analysis. journal of clinical endocrinology and metabolism, vol. 106, no. 12, pp. 3655–3667. doi 10.18502/sjms.v17i2.11460 page 277 sudan journal of medical sciences hyder osman mirghani and albaraa altowigri [26] kwak, d., ha, j., won, y., et al. effects of thyroid-stimulating hormone suppression after thyroidectomy for thyroid cancer on bone mineral density in postmenopausal women: a systematic review and meta-analysis. bmj open, vol. 11, no. 5, p. 043007. [27] haymart, m. r., reyes-gastelum, d., caoili, e., et al. (2020). the relationship between imaging and thyroid cancer diagnosis and survival. oncologist, vol. 25, no. 9, pp. 765–771. [28] papaleontiou, m., banerjee, m., reyes-gastelum, d., et al. (2019). risk of osteoporosis and fractures in patients with thyroid cancer: a case-control study in u.s. veterans. oncologist, vol. 24, no. 9, pp. 1166–1173. [29] biondi, b. and cooper, d. s. (2010). benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. thyroid, vol. 20, no. 2, pp. 135–146. [30] soydal, ç., özkan, e., nak, d., et al. (2019). risk factors for predicting osteoporosis in patients who receive thyrotropin suppressive levothyroxine treatment for differentiated thyroid carcinoma. molecular imaging and radionuclide therapy, vol. 28, no. 2, pp. 69–75. [31] hawkins carranza, f., guadalix iglesias, s., luisa de mingo domínguez, m., et al. (2020).trabecular bone deterioration in differentiated thyroid cancer: impact of longterm tsh suppressive therapy. cancer medicine, vol. 9, no. 16, pp. 5746–5755. doi 10.18502/sjms.v17i2.11460 page 278 introduction materials and methods the selection criteria according to picos proxima-nova-bold-italic.otfthe included studies proxima-nova-bold-italic.otfoutcome measures proxima-nova-bold-italic.otfpatients literature search and articles selection statistical analysis results discussion conclusion the implications for research, policy, or practice: acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 12, issue no. 4, doi 10.18502/sjms.v12i4.1355 production and hosting by knowledge e research article factors influencing adolescents stigmatising attitudes and perception of community reaction towards mental illness in nigeria olorunfemi akinbode1 and tolulope2 1department of community medicine, university of medical sciences, ondo city, ondo state nigeria 2department of pediatrics and child health, university of medical sciences, ondo city, ondo state, nigeria abstract background: stigma is one of the major distresses that are experienced by people with mental illness. stigmatisation results in a reduction in quality of life of those affected. objective: the objective of this study was to assess the stigmatising attitudes of adolescents towards individuals with mental illness, their perception of community reaction and factors influencing it in nigeria. method: in school adolescents (n = 402) participated in the research. they completed self-administered questionnaires regarding socio-demographic details and questions based on a vignette of a young person with a mental disorder using the standardized stigmatisation questionnaire (ssq1). the study was cross-sectional in nature and employed a multistage sampling technique. result: the mean age was 14.44years (sd=1.84).there were 265 (65.9%) males and 137(34.1%) females. approximately seventy percent of the adolescents would not be happy to sit next to a man with mental illness in a bus, 58.2% would not want him to teach their children, and an even higher percentage (72.9%) believe that most people in the community would do same. seventy percent are aware that he did not develop his problems to avoid difficult situations of life and 78.2% also know that it’s not a punishment for bad deeds. independent predictors of stigma related attitude include age p<0.002, gender p<0.010 and community perception p<0.001. conclusion: stigmatisation of mental illness is highly prevalent among adolescents. given that a significant percentage of the participants were well informed, formation of stigmatising attitude towards mental illness might be deeper than lack of knowledge. there may be a need to work on societal structure despite traditional education interventions and also encourage their contact with mentally ill persons. keywords: stigmatisation adolescents, community, mental illness, perception, societal structure how to cite this article: olorunfemi akinbode and tolulope, (2017) “factors influencing adolescents stigmatising attitudes and perception of community reaction towards mental illness in nigeria,” sudan journal of medical sciences, vol. 12 (2017), issue no. 4, 240–252. doi 10.18502/sjms.v12i4.1355 page 240 corresponding author: olorunfemi akinbode; email: isnaalah@outlook.com received 10 october 2017 accepted 18 december 2017 published 28 december 2017 production and hosting by knowledge e olorunfemi akinbode and tolulope. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:isnaalah@outlook.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences olorunfemi akinbode and tolulope 1. introduction stigma is one of the most intense distresses that are suffered by people with mental illness. they struggle with the symptoms and disabilities of the disease on one hand; on the other, they confront the consequences of stereotypes, prejudice and misconceptions often associated with mental illness. stigmatisation results in people with mental illness being deprived of the opportunities for good jobs, access to satisfactory health care service, normal everyday relationships with diverse people in society and a reduction in quality of life. stigma and associated discrimination expressed towards people with mental illness emanates from societal structures in the community and individuals’ knowledge, attitudes, and behaviors [1]. societal structures produce social knowledge within groups which are often learned [2–4]. and it represents collectively agreed notions within groups of persons [5]. adolescents also learn this social knowledge and as individuals within these societal structures they can generate impressions and reaction of the community towards people with mental illness aside their own beliefs and attitudes. behavior does not always agree with stated attitudes and when differences between clusters (by any label) in a society increases or is very marked, it promotes a pulling together within the clusters and a tendency to band against those perceived as different in order to preserve self-interest [6]. previous research has established that stigmatising attitudes develop early in childhood, persists with increasing age or grade and did not change appreciably at least eight years later [7]. attention has recently focused on the developmental expression of mental illness stigma and the subsequent design of age-appropriate stigma reduction strategies. a literature review on child and adolescent mental illness stigma reported that young children may hold negative attitudes toward individuals with mental illness and these attitudes might intensify as these children develop [8]. strategies to combat stigma and lessen discrimination associated with mental illness are necessary so as to reduce the social injustice done to those suffering from mental illness [1, 9–12]. strategies that have been designed to diminish stigma are educational, contact, and/or protest methods [12]. educational methods offset stigmatising beliefs regarding mental illness by providing accurate knowledge. contact methods offset stigmatising knowledge and attitudes via opportunities for interaction with persons with mental illness. protest methods offset stigmatizing attitudes and behaviours by suppressing their expression. exposure to people with mental disorders is known to reduce stigma in adults [13, 14] however, one study found that exposure increased stigma in adolescents [9]. among these several interventions aimed at reducing stigma educational intervention appears doi 10.18502/sjms.v12i4.1355 page 241 sudan journal of medical sciences olorunfemi akinbode and tolulope to have a small effect in young people [15, 16]. the societal structure holds the possibility of representation for stigmatizing attitudes, however, the influence of societal structure on adolescents stigmatizing attitudes has received only limited research in this environment. previous studies in the country have shown that negative views and attitudes towards mental illness are widespread in the communities [17] but no study has really looked at the influence of this view and structure on the adolescents. ongoing investigation regarding adolescent expression of stigma-related attitudes and behaviors is needed for various reasons: the extrapolation of knowledge about adultrelated stigma to adolescent-related stigma is inappropriate, design of age-appropriate stigma reduction programs to minimize transition of negative attitudes from adolescence into adulthood [9–11] is much needed and the organization of programmes targeted at the societal structure in order to have long lasting reduction in stigmatisation of mental illness is desired. even though up to 10% of children experience mental health problems, they still tend to have or hold negative attitude towards mental illness. potential for stigmatisation of mental illness by adolescents certainly exists in non-western cultures of sub-sahara africa and have been less frequently explored. the objective of this study was to assess the stigmatising attitudes of adolescent towards individuals with mental illness, their perception of community reaction and factors influencing it in nigeria. 2. materials and method study population: the study was conducted in south-western nigeria comprising majorly of yoruba speaking populace. the region has six state among which is osun state where the study was conducted. participants in the study were in-school adolescents in secondary school, both male and female students, aged between 10-19 years. they were recruited from four secondary schools located in the state. the schools were selected using a multistage sampling technique and the design was cross-sectional in nature. four hundred and ten secondary school students participated in the study and spread across the six arms of classes in each school. two of the schools were privately owned and the other two were public schools. 1. testing procedure doi 10.18502/sjms.v12i4.1355 page 242 sudan journal of medical sciences olorunfemi akinbode and tolulope the participants gave responses to questions related to socio-demographic details such as age, sex, class, type of school, religion and ethnicity. in addition to this information participants completed an attached standardized stigmatisation questionnaire based on a vignette of a young person with a mental disorder using the standardized stigmatization questionnaire (ssq1) developed by haghigat [6]. the vignette was written to satisfy dsm-iv criteria, an effort was also made not to give a diagnostic label but just a description of the man’s behavior to elicit their ability to recognize the disorder in the vignette. the vignette was: a man is twenty five years old. he is not married and lives with his parents. he has begun locking himself up in his room and also refuses to eat with the family. in the last 4 months he has stopped seeing his friends and his parents also hear him walking about in his bedroom at night while they are in bed. even though they know he is alone, they hear him shouting and sometimes arguing with himself as if someone else is there. he also refuses leaving home because he feels he is being spied upon by the neighbors. lately the doctor said he is ill. now what do you think most people would actually do or feel about this person if they knew his history. what will you also do or feel about this person if you knew the history. respondents were given questions to assess personal and perceived stigma. the first set of questions asked how they thought most people will react to the man described in the vignette in other to assess participants’ perception of community reaction while the second sets of questions assess the predisposition of respondents to enact stigmatization towards the man described in the vignette. all the interviews were completed in english. participants were instructed clearly that their names are not required and that there is no right or wrong answers. the ssq was designed to measure subjective perception of stigma. the questionnaire has been used in relatively large surveys in europe and across cultures and has contributed to valid and reliable assessment of stigmatization. the validity of the questionnaire items has also been reported. the questionnaire was pre-tested by 2 trained psychiatrists to establish its adaptability in our environment and a few descriptive words were replaced with common words meaning the same thing in our environment. the questionnaire has 13 items and is in two parts, part 1 for the assessment of perceived stigmatization and part 2 for the assessment of predisposition to enact stigma (personal stigma). the questionnaire is divided into three major domains or factors which constitute the components of stigmatization. four items in the questionnaire assess social self-interest which is a doi 10.18502/sjms.v12i4.1355 page 243 sudan journal of medical sciences olorunfemi akinbode and tolulope reflection of social distance, avoiding association with outcast or the way the society or community expects the individual in it to act. these are: would most people be happy to sit next to this man in a bus? would most people be happy to eat food which he has cooked? would most people avoid talking to him if possible? would most people think he should stay in hospital for his whole life? another 4 items dealt with evolutionary self-interest which may be genetic, economic and territorial indicating the manner in which an individual is likely to react. these are: would most people be happy if this person became the teacher of their child? would most people be happy if he married their sister? would most people be happy if he were to work together with them in their work place? would most people be frightened if this man came to live next door to them? five other items assess psychological self-interest, which perceives others as bad thus downplaying on one’s own negative attributes. these are: do most people think one of the main causes of his condition is a lack of moral strength or will power? do most people think his condition is a punishment for bad deeds? do most people think he has developed his condition to avoid the difficult problem of everyday life? do most people think he has become a failure in life? would most people think this man is a bad person? each question has an assigned score on a 4-point likert scale (having the responses definitely yes, perhaps yes, perhaps no and definitely no) with alternate response categories depending on the wording of the question so that higher scores indicate stigma. a score of 1 is for least stigma attitude and a score of 4 for highest stigma attitude. the perceived stigma question also use the same set of items but with responses based on what participants thought others would do in order to elicit participants’ perception of stigmatization by the community. the questions were of the type asking that “what would most people do” for perceived stigma and “what will you do” for personal stigma and so on. data was collected over a period of one month. 1. scale assessment and data analysis the statistical package for the social sciences version 16.0 (spss inc., chicago) program was used for statistical analysis. although the ssq questionnaire has been widely used in europe, to the best of our knowledge no evaluation has ever been undertaken to confirm its validity and reliability in our environment. for this reason the original 13 items of the instrument were assessed using an exploratory factor analysis employing doi 10.18502/sjms.v12i4.1355 page 244 sudan journal of medical sciences olorunfemi akinbode and tolulope principal component analysis with varimax rotation on items on personal stigma. all assumptions of the instrument as having three main factors were maintained, namely social, evolutionary and psychological self-interest. the questionnaire was used as a summated scale with total scores ranging from a low of 13 to a high of 52, and also as subscales; higher scores equate to greater stigma. each of the items were scored and summed resulting in stigma scales which were based on the three substructure of stigmatization and used as the dependent variables in regression analyses in trying to establish the predictors of stigma. the regression analysis examined the following as predictors of stigma; socio-demographic characteristic (age, gender, ethnicity, religion, type of school, class) and community perception (enacted). results were calculated as frequencies (%), means and standard deviations. significant variables were entered into a multiple logistic regression analysis to determine the predictors of stigma. all tests were two-tailed and significance was put at p-value less than 0.05. odds ratio (or) and 95% confidence interval was calculated for independent predictors. 3. ethical considerations ethical clearance was obtained through permission from schools review board. all participants gave assent and a general informed consent was provided by parent teachers association (pta) of each of the participating school. the purpose of the study was explained to the students but consent was sought and obtained individually. they were also assured of confidentiality. 4. results 1. socio-demographic profiles of respondents of the 410 respondents, 8 had incomplete data; hence four hundred and two participants were analyzed. the mean age of participants in years was 14.44 (sd=1.84; range = 10-19years). there were 265 (65.9%) males and 137 (34.1%) females and their age distribution is as shown in table1. all the three groups of adolescents as classified by international standard were in the study with 28.8% being early adolescents (1013 years), 60.7% middle adolescents (14-16 years) and 10.5% late adolescents (17-19 years), and the participants were mostly (95.5%) from the yoruba ethnic group which can be explained by the study location. 1. descriptive analysis of respondent stigma attitude doi 10.18502/sjms.v12i4.1355 page 245 sudan journal of medical sciences olorunfemi akinbode and tolulope variables frequency (%) variables frequency (%) age group 10-13 years 14-16 years 17-19 years 113(28.8%) 238(60.7%) 41(10.5%) ethnicity yoruba hausa ibo 384(95.5%) 12(3%) 6(1.5%) sex male female 265(65.9%) 137(34.1%) religion christianity islam others 230(57.2%) 169(42.1%) 3(0.7%) level in school junior school senior school 82(20.4%) 320(79.6%) t 1: socio-demographic profiles of respondents among respondents, (78.2%) were aware that mental illness is not a punishments for bad deeds, (72.8%) know that is not as a result of lack of moral strength or will power and 76.1%, were aware that it was not developed to avoid difficult situation of life. in spite of the level of awareness, stigmatising attitude was high among adolescents as 69.7% would not be happy to sit next to this man in a bus, 79.6% would not eat food cooked by him, and 71.9% will avoid talking to him if possible. about 58.2% would not want him to teach their children, while 72.9% believe that most people in the community would do same thing they would do. 1. exploratory factor analysis (efa) the efa was conducted using data from the 402 respondents with complete information. the 4 items which measured social self-interest (ssi) in ssq1 loaded on a factor and these had an alpha reliability coefficient of 0.91, items for evolutionary self-interest (esi) also had high loading and a reliability coefficient of 0.72 while similar items loaded as psychological self-interest (psi) and they had a reliability coefficient of 0.73. all the factors had reliability with alpha reliability coefficient of 0.82. stigma attitude scale for the adolescent was constructed by summing up the items for each of the factors that loaded. two of the subscales, esi and ssi, contain four items each with scores ranging from 4 to16. one of the 5 items on the psi scale ‘do you think this man is a bad person’ had factor loading that was less clear however since there was not enough evidence to suggest the removal of the item, from the original 13 item questionnaire, a decision was taken to retain it in the over-all scale score despite the ambiguity. we therefore drew an impression on the reliability of the questionnaire even in our environment. 1. factors associated with stigma doi 10.18502/sjms.v12i4.1355 page 246 sudan journal of medical sciences olorunfemi akinbode and tolulope variables 𝛽 se df f p community perception .140 .049 1 8.149 .001 type of school .012 .049 1 .064 .800 religion -174 .053 2 10.661 .472 tribe .101 .050 2 4.013 .772 level in school .017 .059 1 .082 .775 age .011 .045 2 .088 .002 gender .156 .453 1 .935 .010 t 2: association between stigma related attitude in the adolescents and some variables. multivariable analysis using categorical regressions indicated that socio-demographic variables such as type of school (p=0.800), religion (p=0.472), ethnicity (p=0.772), class in school (p=0.775) were not significantly associated with stigma related attitude in the adolescents in this study as shown in table 2 above and thus are not predictors of stigma tendencies in the adolescents. table 3 shows the predictors of the stigma attitude in the adolescents; these are age, gender and community perception. socio-demographic characteristic such as age which predicted stigmatisation was associated with the different components of stigma. social self-interest which implies social distance decreased with age, whereas evolutionary and psychological self-interest increased with age. mean score for overall stigma scale and the three factors were calculated and the result showed that younger adolescent (10-13years) had slightly higher overall stigma score than their older counterparts although this difference was not statistically significant. in comparing sample by gender, female respondents consistently had higher mean stigma scores across all three components than the male respondents and in all aspects of stigma had higher scores than male respondents. in these instances the scores were not statistically significant. community perception was also an important predictor of the different component of stigma, but the effects vary across the components of stigma. the effect was more marked with social self-interest than for evolutionary and psychological self-interest. all components of stigmatisation showed significant association with community perception, age differences doi 10.18502/sjms.v12i4.1355 page 247 sudan journal of medical sciences olorunfemi akinbode and tolulope variables social selfinterest (p)or, [ci] evolutionary selfinterest (p)or, [ci] psychological selfinterest (p)or, [ci] community perception &no (not enacted) (<0.001) 1.60 [1.24-4.82] (<0.001) 1.28 [1.12.3.07] (<0.012) 0.45 [0.14-0.95] age (years) &(10-13) ( <0.001 ) 0.50[ 0.20-0.86] 0.68 [0.10-0.90] (<0.002) 1.04 [1.00 2.06] 1.52 [1.10-4.50] (<0.046) 3.50 [1.95-8.53] 3.20 [1.10-9.50] gender &(female) (<0.202) 0.61 [0.24 4.82] (<0.215) 0.85 [0.331.12] (<0.144) 0.45 [0.25-5.52] &-reference category t 3: logistic regression analysis of various predictors of different components of stigma in the adolescent: or and p-values, ci. 5. discussion to the best of our knowledge, this is the first study to use the standardized stigmatisation questionnaire (ssq1) to assess adolescents’ stigmatising attitudes and their perception of community reaction towards people with mental illness in sub-saharan africa. earlier studies have either looked at stigma knowledge and attitudes among the adult population in the community or examined the perception of stigma by relatives of people with mental illness or were on a smaller scale [17]. our result revealed a strong association between community perception and all components of stigma related attitude i.e., social self-interest, evolutionary self interest and psychological self interest and strongly support the writing and presentation of stigmatisation as a unitary characteristic [18, 19]. our study found that social self-interest was highly influenced by community structure and its pursuit forms the basis of most of the stigmatisation in our environment upon which other components are built. this is comparable with findings in some previous studies in europe which argued that the seeking of self-interest is the basis of most stigma if not all human behaviour [6] although a study from australia upholds a multidirectional approach [20]. stigmatising attitudes towards mental illness was highly prevalent among this representative sample of the adolescent population despite the high level of awareness and knowledge. however, a previous study in nigeria among adult population found that poor knowledge on the cause and nature of mental illness was common in the community and also established that negative attitude to mental illness were prevalent and may hinder the social integration of those with mental illness [17]. our result. however, doi 10.18502/sjms.v12i4.1355 page 248 sudan journal of medical sciences olorunfemi akinbode and tolulope showed that although knowledge or awareness was generally a good thing, it does not reduce all aspects of stigma this is because stigmatising attitudes is not based on a lack of knowledge about mental illness alone. these findings are in keeping with previous evidence that suggests that stigmatising attitudes are not always related to knowledge [21]. it follows, therefore, that effort to reduce stigma have to do more than increasing knowledge on the stigmatised conditions. we also found that age and gender differences influenced adolescent stigmatisation of mental illness in this environment and as such, are factors which are strong enough to predict the tendency to stigmatise. social self-interest showed a complex association with age as it decreases with increase in age while evolutionary and psychological self-interest increases with age suggesting that as people grow they tend to lean towards stigmatisation because of social, economic and psychological gain [6, 18]. male adolescents were less likely to stigmatise mental illness than females in contrast to findings in earlier research in australia [20] and north america [22]. our finding supports those of earlier researchers who have suggested that societal structure to a large extent influence stigma related attitudes [1] while recognizing that there is a general human propensity to stigmatise those who are different [23]. we observed that responses on social self-interest suggesting social distance were significantly associated with community perception of stigma. according to townsend when the difference between in-group and out-group is exaggerated it tends to obscure dissension within the in-group and promote in-group cohesion [6] leading the adolescent to act in a manner expected by the community (in-group) by exhibiting stigmatising attitudes for the social self-interest of others, while the adolescent as an independent individual may not be inclined towards stigmatisation. since social and environmental forces shape the personality of the adolescent within the societal structure that he/she is a member and social distancing ensures a continuing lack of familiarity with the realities of sufferers of mental illnesses, [24] we can infer that the direction of influence is from the community to adolescents. efforts to reduce stigmatisation should, therefore, focus also on the societal structure. our finding, therefore, supports an earlier suggestion in a previous study that young people and their parents should be involved in efforts to reduce societal stigmatising attitudes [24]. our study has several limitations: causal interpretation of the findings is limited by the cross-sectional nature of the data and the fact that we cannot generalize the findings to the whole of sub-saharan africa due to the diversity in the traditional doi 10.18502/sjms.v12i4.1355 page 249 sudan journal of medical sciences olorunfemi akinbode and tolulope societal structure. the strength of this study was its use of the standardised stigmatisation questionnaire in assessment of stigmatisation from the perspective of social self-interest, evolutionary self-interest and psychological self-interest pointing at the roots of stigmatisation and where to direct efforts for intervention. in addition, the study comes from a region where adolescents stigmatising attitudes has not been previously well studied. in conclusion, the findings presented here provide a beginning for further research into societal structure and its effect on adolescents’ stigma related attitude towards mental illness. we have shown that the components of stigma all have roots in social self-interest. we also showed that age, gender differences and community perception all have an influence on stigma. stigmatisation of mental illness by adolescents is high in our environment; it is greatly influenced by the community structure, and it goes deeper than lack of knowledge. stigma reduction effort should aim not just at educational intervention for the adolescent but should also target the societal structure. references [1] a. j. gray, stigma in psychiatry, journal of the royal society of medicine, 95, no. 2, 72–76, (2002). [2] j. l. hilton and w. von hippel, stereotypes, annual review of psychology, 47, 237–271, (1996). [3] c. m. judd and b. park, definition and assessment of accuracy in social stereotypes, psychological review, 100, no. 1, 109–128, (1993). [4] j. krueger, personal beliefs and cultural stereotypes about racial characteristics, journal of personality and social psychology, 71, no. 3, 536–548, (1996). [5] p. corrigan w, waston a c, in understanding the impact of stigma on people with mental illness world psychiatry, 1, 16–20, understanding the impact of stigma on people with mental illness world psychiatry, 2002. [6] r. haghighat, the development of an instrument to measure stigmatization: factor analysis and origin of stigmatization, the european journal of psychiatry, 19, no. 3, (2005). [7] m. f. weiss, children’s attitudes toward the mentally ill: an eight-year longitudinal follow-up., psychological reports, 74, no. 1, 51–56, (1994). 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[21] p. byrne, psychiatric stigma: past, passing and to come, journal of the royal society of medicine, 90, no. 11, 618–621, (1997). [22] a. chandra and c. s. minkovitz, stigma starts early: gender differences in teen willingness to use mental health services, journal of adolescent health, 38, no. 6, 754–e8, (2006). doi 10.18502/sjms.v12i4.1355 page 251 sudan journal of medical sciences olorunfemi akinbode and tolulope [23] p. gilbert, stigmatization as a survival strategy: skeletons in the cupboard and the role of shame, in in every family in the land: tackling prejudice and discrimination against people with mental illnesses, a. h crisp, ed., and the role of shame. in every family in the land, tackling prejudice and discrimination against people with mental illnesses, 2000, www.stigma.org. [24] a. h. crisp, m. g. gelder, s. rix, h. i. meltzer, and o. j. rowlands, stigmatisation of people with mental illnesses, the british journal of psychiatry, 177, 4–7, (2000). doi 10.18502/sjms.v12i4.1355 page 252 www.stigma.org introduction materials and method ethical considerations results discussion references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12862 production and hosting by knowledge e research article estimation of atopy and allergies among sudanese children with asthma amani elgadal1,2* and omaima nail2,3 1department of pediatrics, faculty of medicine, karary university, sudan 2mohamed el-amin h. hospital, omdurman, sudan 3department of pediatrics, faculty of medicine, omdurman islamic university, sudan orcid: amani elgadal: https://orcid.org/0000-0003-0934-2755 omaima nail: https://orcid.org/0000-0002-8582-5452 abstract background: bronchial asthma is a chronic respiratory problem characterized by a reversible hyper-responsive airway obstruction that is provoked by allergens, infections, or nonspecific triggers. the study aims to assess the coexistence of atopy and allergies among children with asthma. methods: this single-center study was conducted at mohamed el-amin h. hospital, sudan. a free online sample size calculator was used. a specially designed form was used for data collection. data were analyzed using the spss version 20.0. results: a total of 300 participants were enrolled in the study, with a mean age of 7.46 ± 3.93 years. the male-to-female ratio was 1.3:1. a total of 215 (71.6%) children had a family history of asthma; atopy was allergic rhinitis in 108 (36%), eczema in 53 (17.7%), food allergy in 38 (14%), and allergic conjunctivitis in 29 (9.7%). a significant association was observed between male gender and family history of asthma, atopy, and coexisting personal history of atopy, p = 0.002, 0.004, and 0.001, respectively. all participants who had atopy had allergic rhinitis; 53 (49%) had atopic dermatitis, 29 (26.8%) had coexisting allergic conjunctivitis, and food allergies were found in 38 (35.2%) participants. common food allergies found were eggplants, fish, cow milk, and banana. atopy and allergies were common among those who were 6–10 years old, however, only allergic rhinitis was statistically significant with age (p = 0.021). conclusion: combined family history of asthma and atopy was common, few had atopy only, and fewer had neither family history nor atopy. atopy found was allergic rhinitis, conjunctivitis, eczemas, and food allergy. keywords: atopy, allergy, asthma, family history, genetic 1. introduction bronchial asthma is a common chronic respiratory problem in children, characterized by hyper-responsive airway obstruction that reverses and responds to bronchodilators, provoked by many stimuli, like allergen, infection, and/or nonspecific triggers. asthma can affect over 300 million children and adults worldwide according to the global initiative for asthma gina guidelines [1, 2]. the symptoms of asthma include recurrent how to cite this article: amani elgadal* and omaima nail (2023) “estimation of atopy and allergies among sudanese children with asthma,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 25–36. doi 10.18502/sjms.v18i1.12862 page 25 corresponding author: amani elgadal; email: amanielgaddal@gmail.com received 7 january 2022 accepted 7 october 2022 published 31 march 2023 production and hosting by knowledge e elgadal and nail. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences elgadal and nail wheezing, coughing, dyspnea, and tightness of the chest, which may be nocturnal or early in the morning. it can be manifested in early life, and nearly 33% of children have wheezing during their first three years of age, and most of them may stop wheezing by the age of six. moreover, 40% of them may continue to wheeze and develop asthma later in their lifetime [2]. at puberty, symptoms may be severe, especially in those with mild attacks. however, it may persist or revert during early adulthood [3]. the atopy is a phenotype that has an increased risk of ige-mediated diseases. its etiology probably has a genetic predisposition, which in combination with environmental factors leads to asthma risk [3]. allergy and other atopic diseases may coexist with asthma. a possible sensitization can lead to an allergic march paradigm and may occur with the early initiation of cow’s milk, as it can lead to cow’s milk allergy that vanishes in 95% of toddlers [4]. other systemic allergic manifestations such as dermatitis, rhinitis, and asthma were possible. about 60–75% of school-age children are sensitized to one or even many allergens. on the other hand, recurrent wheezing, cough, and chest tightness may develop without allergic sensitization. therefore, asthma is considered a heterogeneous disease that has many phenotypes [5]. the use of inhaled steroids since the 1980s has led to better control of asthma exacerbation and allowed children to participate in social activities and sports. increased knowledge about possible triggers is momentous alongside medication usage. however, few children with severe asthma are exceptions [5]. in practice, many other diseases have the same clinical manifestations as asthma; it is better to commence asthma treatment after excluding other conditions. approximately 60–75% of school-age children with asthma have allergies. asthma incidence and prevalence are higher in boys till the age of 14 years, this ratio reversed at puberty. boys have more asthma remissions, while females have severe attacks, which are influenced by sex hormones, as with menarche, there is a decline in lung function [6, 7]. bronchial asthma burden is higher among black than white children and is not explained by the differences in background or clinical features due to scarce data [8]. environmental and genetic factor interactions may lead to functional and structural airway changes in the form of bronchospasm, mucosal edema, and mucus plugs [8]. alveolar hypoxia causes vasoconstriction, which contributes to mismatch as an adaptive response [9]. asthma has a significant health burden and affects sleep quality, daily activities, school attendance, and academic performance. night waking can contribute to parental work absence, and family disruption [10]. doi 10.18502/sjms.v18i1.12862 page 26 sudan journal of medical sciences elgadal and nail many children are transient wheezers, who have symptoms that vanish around preschool or early primary school. they are rarely allergic, and their lung function is frequently abnormal because of their small lungs [11]. several triggers are present in most cases of asthma in children, and reactivity patterns may vary with age [12]. there have been two types of broncho-constrictor reactions to allergens in patients with asthma – early and late. within minutes of exposure, ige-induced mediator release from mast cells causes early asthmatic responses. late asthmatic responses develop 4–12 hr after antigen exposure, resulting in more severe symptoms that might linger for hours and contribute to the disease’s duration and severity. foods, household inhalants (e.g., animal allergens, molds, fungus, roach allergens, dust mites), and seasonal outdoor allergens (e.g., mold spores, polenta) are all forms of allergies [12–18]. exposure to tobacco in utero has also been linked to dna hyper-methylation in babies [19]. atopic dermatitis is a commonest chronic childhood skin problem. it is characterized by remission and recurrent pruritus, with various manifestations and severity. its diagnosis is challenging because there are no standard diagnostic criteria due to the diversity of its clinical features. many criteria were used – for example, hanifin-rajka criteria (hrc) were used commonly in hospital settings and depend on clinical experience and expert consensus. the united kingdom working party criteria (ukc) are the refined versions of hrc; both being used in hospitals as well as in community settings. also, the international study for asthma and allergy in childhood (isaac), and the reliable estimation of atopic-dermatitis in childhood (reach) are used in epidemiological surveys [20–22]. effective asthma management requires the identification of asthma triggers [23, 24]. to the best of the authors’ knowledge, there is no available published data about the magnitude of this problem among patients attending the study area. the study aims to assess the coexistence of atopy and allergy with asthma among children attending the asthma clinic. 2. materials and methods this descriptive, cross-sectional single-center study was conducted over six months, from june 1𝑠𝑡 to december 31𝑠𝑡, 2019 at the asthma clinic at mohamed el-amin hamid hospital for children, omdurman city, khartoum state, sudan. the hospital is a referral center for pediatrics in sudan and provides emergency inpatient and outpatient medical services. the asthma clinic was established in january 2012 and held once per week. a free online sample-size calculator was used (https://www.calculator.net/). there were doi 10.18502/sjms.v18i1.12862 page 27 sudan journal of medical sciences elgadal and nail 800 registered patients with asthma in the clinic. a confidence level of 95%, a margin of error of 5, and a population proportion of 50%. the minimal sample size was 260. the national institute for health and care excellence (nice) guidelines were used to diagnose asthma, allergy case definition, and the international study of asthma and allergies in children (isaac) criteria to define atopy. definition of an asthma case: recurrent attacks of reversible breathlessness, cough, and wheezing that resolved with bronchodilators or spontaneously, that is, hyperresponsiveness airway with reversible spirometry after exclusion of other causes of cough and wheezing. allergy: a child/family member with a known case of allergy, or having symptoms suggestive of allergies, like food allergy or allergic rhinitis. atopy: positive skin-prick test for common allergens, pollens, or certain types of foods. atopic dermatitis: fulfilled, which included itchy skin rash that comes and goes at least for six months, itchy skin rash during the past year that affects the elbows, popliteal fossa, ankles, buttocks, around the ears, eyes, around the neck, and/or self-reporting that they had eczema diagnosed by a physician. it also includes a history of atopy that was aggravated by environmental factors. a convenient sampling method was used for data collection; with consecutive recruitment of 300 children aged 2–17 years, known cases of asthma, and their mothers/caregivers, who voluntarily accepted to enroll in the study. children who had comorbidity were excluded. the selected participants were interviewed. the primary data were collected using a detailed questionnaire that included patients’ demographic data, habits, home environment, presence of pets, confirmed diagnosis of asthma, suggestive symptoms of atopy, and allergies such as eczema, allergic conjunctivitis, rhinitis, and sinusitis. the skin-prick test (not available in sudan) was obtained from a few patient records with confirmed allergy as secondary data. all work in this research was done in line with the declaration of helsinki. data were cleaned, coded, and entered into a microsoft excel data sheet and analyzed using spss version 20.0. categorical data were represented in the form of frequencies and proportions. the chi-square test was used as a test of significance for qualitative data. p-value (probability that the result is true) <0.05 was considered statistically significant. 3. results the study covered 300 children. of them, 134 (44.7%) were aged between 5 and 10 years, 91 (30.3%) were <5 years old, and 75 (25%) were between the ages of 11 and 17 doi 10.18502/sjms.v18i1.12862 page 28 sudan journal of medical sciences elgadal and nail years. the mean age was 7.46 ± 3.93 years, and while the minimum age was 2 years, the maximum age was 17 (table 1). the distribution of gender showed male dominance – 169 (56.3%) participants were males while 131 (43.7%) were females, giving a male-to-female ratio of 1.3:1 (table 1). furthermore, the results in figure 1 show that 215 (71.6%) children had a positive family history of asthma, and there was a coexistence of asthma and allergic rhinitis in 108 (36%), eczema in 53 (17.7%), food allergy in 38 (14%), and allergic conjunctivitis in 29 (9.7%). family history of asthma and a personal history of atopy (e.g., atopic dermatitis, drug allergy, and food allergy) were observed in 187 (62.3%) participants, and of them, 28 (9.3%) had only a family history of asthma without atopy, 60 (20%) had only atopy, 25 (8.3%) had no family history nor coexistence atopy. table 2 shows a strong association of the male gender with a family history of asthma, atopy, and coexisting personal history of atopy, with a p-value of 0.002, 0.004, and 0.001, respectively. all participants who had atopy had allergic rhinitis; 53 (49%) had associated atopic dermatitis, 29 (26.8%) had coexisting allergic conjunctivitis, and food allergy was found in 38 (35.2%) participants. the common food allergy was found in eggplant, fish, cow milk, and bananas. this means that there is an overlap of more than one allergy. atopy was found more among males but it is statistically insignificant (p-value > 0.05). table 3 shows the comparison of the family history of asthma, atopy, and personal history of atopy with age groups, it is common among 6–10 years old. personal history of atopy with age showed a significant association (p-value = 0.032) but only allergic rhinitis is statistically significant with age (p-value = 0.021). table 1: participant distribution according to their age and gender (n = 300). frequency percentage (%) age (yr) <5 91 30.3 5–10 134 44.7 11–17 75 25 total 300 100.0 (%) gender male 169 56.3 female 131 43.7 total 300 100.0 (%) 4. discussion asthma is a complex disease with several phenotypes that may occur in children. the study included 300 participants, of who 134 (44.7%) were school-aged children aged doi 10.18502/sjms.v18i1.12862 page 29 sudan journal of medical sciences elgadal and nail 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 71.60% 36% 17.70% 9.70% 14% 62.30% 9.30% 20% 8.30% figure 1: distribution of participants according to the associated atopy. table 2: association between the atopy and allergy with gender (n = 300). parameter total gender p-value female (n = 131) male (n = 169) fh of asthma 215 82 133 0.002 (38.1%) (61.9%) fh of atopy 187 70 117 0.004 (100%) (37.4%) (62.6%) personal history of atopy 108 34 74 0.001 (31.5%) (68.5%) allergic rhinitis 108 34 74 0.001 (31.5%) (68.5%) atopic dermatitis 53 17 36 (32.1%) (67.9%) 0.04 allergic conjunctivitis 29 12 17 0.477 (41.4%) (58.6%) food allergy 38 13 25 0.139 (34.2%) (65.8%) between 5 and 10 years, 91 were <5 years (30.3%), and 75 (25%) were aged between 11 and 18 years. the mean age was 7.46 ± 3.93 years, with a minimum age of two years and maximum age of seventeen years. children who get wheezing secondary to doi 10.18502/sjms.v18i1.12862 page 30 sudan journal of medical sciences elgadal and nail table 3: association between the allergens with age (n = 300). parameter age (yr) p-value ≤5 6–11 ≥12 total fh of asthma 63 (29.3%) 103 (47.9%) 49 (22.8%) 215 (100%) 0.171 fh of atopy 53 (28.3%) 91 (48.7%) 43 (23.0%) 187 (100%) 0.200 personal history of atopy 27 (25.0%) 52 (48.1%) 29 (26.9%) 108 (100%) 0.032 allergic rhinitis 27 (25.0%) 52 (48.1%) 29 (26.9%) 108 (100%) 0.021 atopic dermatitis 16 (30.2%) 24 (45.3%) 13 (24.5%) 53 (100%) 0.054 allergic conjunctivitis 10 (34.5%) 12 (41.4%) 7 (24.1%) 29 (100%) 0.87 food allergy 11 (28.9%) 16 (42.1%) 11 (28.9%) 38 (100%) 0.834 allergies at a young age are more likely to develop wheezing when they are 6–11 years old. correspondingly, children who begin wheezing after six years are more likely to have allergies, and wheezing is more likely to persist by the age of 11. proper asthma control is important for better life quality [10, 11]. overall, male predominance was noticed among the children – 56.3% males and 43.7% females. the male:female ratio was 1.3:1. pre-pubertal males had a higher asthma prevalence than females, which may be attributable to the fact that asthma in boys was identified earlier, and wheezing lasts significantly longer, making them more likely to be observed and diagnosed earlier than girls. however, among adolescents, there was female dominance. this gender reversal at puberty is explained by decreased lung function influenced by hormones [25–27]. a family history of asthma, allergies, nasal polyps, sinusitis, eczema, or rhinitis in first-degree relatives must be included in the medical history. factors that may contribute to nonadherence to asthma treatments and the use of illicit substances must be addressed in the social history [15]. the complex interaction between genetic, and nongenetic factors plays a role in the pathogenesis of asthma, as the occurrence of family history, especially among firstdegree relatives, elevates the risk of asthma development. demographic factors such as sex and obesity, and environmental factors such as smoking history and exposure to air pollution also had a role [26–33]. carlo caffarelli et al. [33] demonstrate the links between asthma and food allergy. they found that parental allergy, atopic eczemas, and allergen sensitization occur often. the severity can be worse with coexistence. however, food allergy can affect asthma control; early food sensitization can potentially begin in utero, or during the first year of life, which can predict the onset/severity of asthma. asthma symptoms may result from ingestion, and/or inhalation of the offending food; which may be severe and doi 10.18502/sjms.v18i1.12862 page 31 sudan journal of medical sciences elgadal and nail associated with fatal or near-fatal anaphylaxis. therefore, offending foods identification and risk awareness were crucial to avert exposure [34]. devika rao et al. [35] argue that early exposure to allergens like dust mites, pets, cockroaches, mice, mold, cigarette smoke, endotoxin, and air pollution has implications for allergic sensitization and asthma development. on the contrary, other studies claimed that allergen remediation had advantages in minimizing asthma morbidity. impermeable covering for dust-mite, air filtration, pest control, housing furbishing, ventilation amelioration, and pet removal can reduce allergen exposures. about three-quarters of school-age children were sensitized to one or more than one allergen. on the other hand, asthma can occur without allergic sensitization, so coughing, chest tightness, and recurrent wheezing can occur among nonallergic patients. for this reason, asthma is considered to be a heterogeneous disease that has different sub-phenotypes [5]. both family history and the atopy among participants were observed in 62.3% of cases, this is consistent with a study done by abdulrahman al-frayh1, zahid shakoor, and syed m. hasnain [30] in saudi arabia. janssens and ritz [17] argue that the gap in the knowledge about the possible potential asthma triggers may hinder the perception of these triggers; therefore, identification of the asthma triggers can prevent unnecessary avoidance of perceived triggers. abdulrahman al freyhi and zahid shakoor found in their study that 48.1% and 46.1% had positive asthma among family and close relatives. asthma was 4.2 times more likely to occur in parents or siblings than in cousins. about 18% of asthmatics had no family history of asthma, and 20.6% of respondents had asthma in their first-degree relatives. the presence of rhinitis or eczemas in the immediate family increases the risk three times. cigarette smoke exposure imparts a twofold increased risk. there were no significant predictors in both eczemas in the family or interaction with domestic pets (birds or cats) [29]. due to the relevance of perceptions about asthma triggers identification, interventions targeted toward increasing asthmatic trigger verification should focus on them. educational interventions, daily life exposure, and monitoring of asthma triggers are needed to enhance asthma control [35, 36]. 5. conclusion three hundred children were enrolled in the study with an overall male predominance of 1.3:1. the participant’s age ranged from 2 to 17 years, with a mean age of 7.46 ± 3.93 doi 10.18502/sjms.v18i1.12862 page 32 sudan journal of medical sciences elgadal and nail years. the common age was between 5 and 10 years. most participants had a positive family history of asthma. atopy found were: allergic rhinitis, conjunctivitis, eczemas, and food allergy. while most children had a combined family history of atopy with bronchial asthma, few had atopy only. fewer participants had neither family history nor coexisting atopy. future multi-center studies were needed with control groups to answer questions and overcome the limitations of this research. study limitations: this study is a single-center study and lacks a control group. the respondent’s answer is liable to subjectivity. acknowledgements the authors would like to express their sincere gratitude and thanks to the children and their families for their kind participation in the study. they are also thankful to their senior colleagues for their support. ethical considerations all work done in this research was in line with the declaration of helsinki. ethical acceptance was obtained from the administrative authorities at the hospital. written informed consent was obtained from caregivers after interviewing them and explaining the study’s purpose to guard the patient’s autonomy. data were used only for research purposes to ensure privacy and confidentiality. competing interest none declared. availability of data and material data generated and analyzed during this study are included in this article, and additional supporting files whenever possible. funding none. doi 10.18502/sjms.v18i1.12862 page 33 sudan journal of medical sciences elgadal and nail references [1] bonato, m., tiné, m., bazzan, e., biondini, d., saetta, m., & baraldo, s. 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(2012). socio-epidemiological aspects of respiratory allergic diseases in southern africa. world allergy organization journal, 5(1), 1–8. doi 10.18502/sjms.v18i1.12862 page 36 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interest availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12864 production and hosting by knowledge e research article effect of an educational program on stakeholders’ awareness about risks of cannabis use in sudan: a quasi-experimental study mohammead osman yahya mohammead1*, mohammed abdelkrim adam abdelmalik1,2, fahad alhowaymel1, and atallah alenezi1 1department of nursing, college of applied medical sciences, shaqra university, shaqra, saudi arabia 2faculty of nursing, university of elimam el mhadai, kosti city, sudan orcid: mohammead osman yahya mohammead: https://orcid.org/0000-0002-5787-2673 abstract background: this study assesses stakeholders’ awareness level of cannabis use and the effect of an educational program on their awareness in kabkabiya city of sudan. methods: this quasi-experimental research was conducted using a preand posttest design between july and november 2018. a total of 203 stakeholders were recruited in the study using a convenience sampling technique. first, using a self-reported questionnaire, the pretest data were collected before the intervention. then, the participants underwent an educational program intervention in the form of lectures and group discussions. at the end of the program, the participants were subjected to the posttest using the same questionnaire. data were analyzed using descriptive and inferential statistics. results: the results showed a poor to moderate level of awareness about cannabis use among stakeholders. a statistically significant increase in the stakeholders’ awareness levels was found after the educational program intervention with a large effect size in awareness (z = –12.299, p = 0.001, r = 0.91). the results also showed that the participants who graduated from university had a significantly higher level of awareness than others at preand posttests stages (p =< 0.001). conclusion: the educational program intervention effectively improved stakeholders’ awareness about the risks of cannabis use. this study suggests providing ongoing health education for the public and focusing on individuals with lower educational levels to increase awareness of the risks of cannabis use. keywords: educational program, awareness, cannabis use, community health, sudan how to cite this article: mohammead osman yahya mohammead*, mohammed abdelkrim adam abdelmalik, fahad alhowaymel, and atallah alenezi (2023) “effect of an educational program on stakeholders’ awareness about risks of cannabis use in sudan: a quasi-experimental study,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 48–62. doi 10.18502/sjms.v18i1.12864 page 48 corresponding author: mohammead osman yahya mohammead; email: dr.mohammead.o@gmail.com received 9 february 2022 accepted 7 october 2022 published 31 march 2023 production and hosting by knowledge e mohammead osman yahya mohammead et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammead osman yahya mohammead et al 1. introduction cannabis is one of the most commonly abused illicit drugs in a global context [1–3]. the word “marijuana” comes from the “cannabis sativa” plant [4, 5]. cannabis products come in three main forms including the herb (marijuana), resin (hashish), and oil (hash oil) [6]. hashish is the processed product of marijuana and can be smoked or ingested [7]. for centuries, marijuana has been used in many cultures to treat disorders that show moderate treatment such as chronic pain, spasticity, and chemotherapy-induced nausea and vomiting [8, 9]. however, recent evidence denotes that marijuana use has several shortand long-term adverse effects on health outcomes such as neurological problems, cognitive deterioration, respiratory symptoms, and cerebrovascular and cardiovascular disorders [10]. although evidence shows that marijuana or cannabis in general has side effects on human health, teenagers continually consume it for recreational purposes [11, 12]. cannabis is the third most frequently used substance worldwide after alcohol and tobacco. statistics show that in 2018, approximately 3.9% of the world’s individuals had used cannabis for nonmedical reasons [5, 13]. studies report that adolescents who are marijuana users have an increased risk of other substance use, injury, violent behaviors or victimization, and sexual risk behaviors compared with nonusers [14]. some research evidence claims that cannabis use is associated with low socioeconomic status, the male gender, smoking, and heavy drinking [15]. in sudan, the magnitude of substance use might be a growing problem, however, evidence about cannabis use is still lacking [16]. generally, the individual’s perceptions of the risks associated with substance use play a critical role in making their decision to engage in it [17]. furthermore, studies have shown that people who are aware of the high risk of substance use such as cannabis are generally less likely to use it, and vice versa [18]. stakeholders and stakeholder groups not only play a key role in the formulation and delivery of policy, but they are also important for knowledge and policy transfer [19]. the term stakeholders narrows the focus from the whole community to those in the community who have an interest in health concerns such as cannabis use. this allows researchers to consider the appropriate groups and individuals that should be included in this context. thus, researchers should investigate stakeholders’ knowledge about cannabis use and its associated risks. stakeholders include people, groups, communities, and organizations that can have a direct and indirect influence on the decisions and activities during a policy and project life cycle [20–23]. the incentive to include stakeholders is based on the belief that stakeholders hold different types doi 10.18502/sjms.v18i1.12864 page 49 sudan journal of medical sciences mohammead osman yahya mohammead et al of knowledge, which are complementary to science and public management [24]. therefore, their awareness and perceptions of the risks associated with cannabis use are vital in implementing awareness programs. although the prohibition on adult cannabis use has decreased the prevalence of cannabis use in young adulthood [5], there is still a paucity of data recorded in sudan about the level of stakeholders’ awareness about the risks associated with cannabis use. therefore, this study aimed to measure the impact of an educational program on stakeholders’ awareness of the dangers of cannabis use in sudan, specifically in the kabkabiya district. in addition, the study aims to find out the differences in the level of stakeholders’ knowledge based on their demographic characteristics. the study findings may help health authorities to adopt awareness campaigns and programs for adolescents and raise awareness about the side effects of cannabis use. 2. materials and methods 2.1. study design, setting, and participants the researchers utilized a quasi-experimental design on one group of participants (preand posttests). they conducted this study in the kabkabiya district which is located in the northern darfur state, sudan during the month of july 2018. after obtaining an institutional review board (irb), the researchers recruited the participants through a written invitation via administrators to participate in the study. this study included a variety of stakeholders from different educational and community-based service groups from the kabkabiya district. the stakeholders included a variety of group members from the teachers syndicate, general union of sudanese women, sudanese society for drug control, sub-football association, high school students unions, and policemen. the study included stakeholders who had not previously engaged in any program related to cannabis smoking and were willing to participate in the study. other inclusion criteria were stakeholders who were still in active positions and were aged 18 years or more. those who refused to participate or who did not show up during the datacollection phase were excluded. additionally, those who did not complete the program were also excluded from the study. doi 10.18502/sjms.v18i1.12864 page 50 sudan journal of medical sciences mohammead osman yahya mohammead et al 2.2. sample size and technique the study sample was selected using a convenience sample technique. a power analysis was conducted using g*power 3.1 to determine a sufficient sample size using an alpha (𝛼) of 0.05, a confidence level of 95%, a power of 0.80, and a medium effect size (cohen’s f2) of 0.25. based on the aforementioned parameters, the minimum desired sample size for this study was 240 participants. thus, the researchers invited 250 participants as they were aware that some invited participants may not fulfill the requirements or may drop out of the study. 2.3. measurements 2.3.1. development of the questionnaire to measure the impact of an educational program on stakeholders’ awareness of the risks of cannabis use, a self-administered questionnaire was developed in the english language based on the literature review. then, the questionnaire was translated into arabic language because it is the country’s primary language. three experts verified the questionnaire’s content. the researchers made minor changes to the original questionnaire according to the experts’ comments. then, the instrument was piloted on 30 participants to check the feasibility and the time required to complete the questionnaire for each respondent. according to the pretest findings, the researchers made necessary corrections for feasibility. the researchers excluded the participants enrolled in the pilot test from this study. in this study, the questionnaire had an adequate internal consistency of reliability with a cronbach’s alpha (𝛼) of 0.77. 2.3.2. the components of the questionnaire the questionnaire consisted of three parts. the first part consisted of four items to collect data about the demographics of the participants, such as age, gender, education, and marital status. the second part was designed to measure the level of knowledge about cannabis use among stakeholders. this part consisted of seven items on a five pointlikert scale where the points were interpreted as 5 = strongly agree, 4 = agree, 3 = neutral, 2 = disagree, and 1 = strongly disagree. the total mean scores for knowledge were calculated before and after the education program to evaluate the difference and effects of the program. doi 10.18502/sjms.v18i1.12864 page 51 sudan journal of medical sciences mohammead osman yahya mohammead et al 2.3.3. development of the educational program following an in-depth literature review and a validation of five experts in the fields of community and public health, the researchers developed an educational program. the program included a background on cannabis, the acute effects of cannabis use, the chronic effects of cannabis use, cannabis dependence, withdrawal symptoms of cannabis, somatic effects and associated health risks of cannabis, social effects of cannabis, and the prevention of cannabis use. the researchers implemented the developed educational program through various teaching methods such as lectures, group discussions, demonstrations and audio-visual materials, booklets, posters, and handbooks. 2.4. data collection the researchers distributed printed hard copies of the self-administered questionnaire to stakeholders to assess their knowledge about cannabis use (pretest). after the pretest phase was completed, the researchers began the educational program. participants were divided into three groups because of the large number and because the researchers wanted to guarantee the effective and efficient delivery of the program. each group received eight lectures over four days (two sessions per day). each lecture lasted for 90 min. the program was conducted in multiple sittings; however, the researchers provided the same lectures for all groups to ensure homogeneity. the educational materials included booklets, posters, and handbooks. the researchers then disseminated the same questionnaire to assess stakeholders’ knowledge about cannabis use (posttest). the posttest was conducted eight weeks after implementing the educational program. the researchers aimed to compare the differences between preand post-intervention and to evaluate the effectiveness of a structured educational program on the level of stakeholders’ knowledge regarding cannabis use. 2.5. data analysis data were analyzed using the statistical package for social sciences (spss) version 25. descriptive statistics were calculated for categorical data using frequencies and percentages, and for continuous data using means and standard deviations. the normal distribution of the data was analyzed using the kolmogorov–smirnova test which showed that the data was not normally distributed. thus, the researchers utilized the doi 10.18502/sjms.v18i1.12864 page 52 sudan journal of medical sciences mohammead osman yahya mohammead et al wilcoxon signed-rank test to compare median differences with the interquartile range of the preand posttests to assess the effect of the educational program on stakeholders’ knowledge about cannabis use. furthermore, cohen’s effect size was calculated and interpreted as a minor effect (d = 0.20 or r = 0.10), a medium effect (d = 0.50 or r = 0.30), or a large effect (d = 0.80 or r = 0.50) [25, 26]. finally, the kruskal–wallis h test and the mann–whitney u test were performed to determine the differences between stakeholders’ knowledge about cannabis use and demographic variables. all findings were considered statistically significant at a p-value of ≤0.05. 3. results 3.1. sample description a total of 203 participants who were enrolled in the study completed the preand posttests questionnaire. the majority of the participants were males 152 (74.9%), aged between 26–35 years 74 (36.5%), single 120 (59.1%), and nearly half of them had completed secondary school 100 (49.3%) (table 1). 3.2. stakeholders’ awareness regarding the risk of cannabis use at preand posttests the results showed that the stakeholders’ level of awareness regarding the risk of cannabis use was higher in the posttest compared to the pretest. the highest mean scores were for items “using hashish is not a problem if you are over 18 years of age” followed by “the benefits of cannabis use are less than damage and risk” and “using hashish makes a person socially isolated.” they were also similar preand post-test. however, the lowest item mean scores were different at the preand posttests. at the pretest, “the availability of hashish poses a significant risk to young people” had the lowest mean score, followed by “all drugs have the same harm to the user.” while at the posttest, “if you try hashish once, you will be unable to stop it” had the lowest mean score, followed by “the transient use of hashish is dangerous” (table 2). since the data deviated from the normal distribution, the researchers used the wilcoxon signed-rank test (nonparametric tests) to compare the differences in the median (md) scores with an interquartile range between the preand posttests to assess the effectiveness of the education intervention on stakeholder’ awareness about the risk of cannabis use. the md with the interquartile range of the stakeholder’s doi 10.18502/sjms.v18i1.12864 page 53 sudan journal of medical sciences mohammead osman yahya mohammead et al awareness score improved from the pretest (md = 2.85) to the posttest (md = 4.46). the wilcoxon signed-rank test indicated a statistically significant increase in the participants’ awareness levels after implementing the educational program with a large effect size (z = –12.299, p = 0.001, r = 0.91). these findings indicate that the educational program effectively improved stakeholders’ understanding of the risk of cannabis use (table 3). table 1: demographic variables of stakeholders (n = 203). variable frequency (%) gender male 152 (74.9%) female 51 (51%) age (yr) <25 35 (17.2) 26–35 74 (36.5%) 36–45 54 (26.6%) >46 40 (19.7%) marital status married 83 (40.9%) single 120 (59.1%) educational levels primary 37 (18.2%) secondary 100 (49.3%) university level 66 (32.5 %) 3.3. differences between stakeholders’ awareness and demographic variables the researchers performed the mann–whitney u-test and kruskal–wallis tests to determine differences between stakeholders’ awareness of demographic variables before and after implementing the educational program. the results revealed statistically significant differences between the educational level and the stakeholder’s understanding in the preand the posttests, where participants who graduated from university showed more awareness at the preand the posttests (p =< 0.001). however, there were no statistically significant differences between stakeholders’ awareness and other demographic variables (table 4). doi 10.18502/sjms.v18i1.12864 page 54 sudan journal of medical sciences mohammead osman yahya mohammead et al table 2: stakeholders’ awareness of the risk of cannabis use at the preand posttests (n = 203). items pretest awareness posttest awareness mean sd mean sd all drugs have the same harm to the user 1.93 1.171 3.95 1.271 if you try hashish once, you will be unable to stop it 2.66 1.319 3.90 1.223 the transient use of hashish is dangerous 2.18 1.399 3.93 1.299 regular use of cannabis affects all body systems 2.42 1.417 4.49 0.823 the availability of hashish poses a significant risk to young people 1.70 1.059 4.41 1.046 using hashish is not a problem if you are over 18 years of age 4.12 1.072 4.62 0.731 using hashish once a month is not dangerous 3.75 1.385 4.48 0.881 young people under the age of 18 should not use hashish 3.86 1.307 4.52 0.766 the use of hashish may lead to addiction 2.90 1.351 4.51 0.858 there is a clear link between cannabis abuse and mental problems 2.77 1.548 4.49 0.846 hashish users will use more dangerous drugs than hashish 3.31 1.498 4.58 0.932 the benefits of cannabis use are less than damage and risk 3.87 1.276 4.60 0.740 using hashish makes a person socially isolated 3.87 1.149 4.48 0.877 sd, standard deviation table 3: comparing stakeholder’ awareness at the preand posttests (n = 203). awareness n mean ± sd min max percentiles iq-r z p-value r ci 25𝑡ℎ 50𝑡ℎ (median) 75𝑡ℎ pretest 203 3.03 ± 0.95 1.38 4.69 2.46 2.85 4.00 1.54 – 12.299 0.001 0.91 1.64–2.11 posttest 203 4.40 ± 0.41 2.54 5.00 4.15 4.46 4.69 0.54 sd, standard deviation; mini, minimum; maxi, maximum; iq-r, interquartile range; r, correlation coefficient of effect size; ci, confidence interval for cohen’s d. statically significant at p-value ≤ 0.05. 4. discussion cannabis is one of the most frequently abused illicit drugs worldwide [27]. recent evidence indicates that marijuana use has several adverse effects on shortand longterm health outcomes, such as neurological problems, cognitive deterioration, respiratory symptoms, and cerebrovascular and cardiovascular disorders [10]. therefore, this study was carried out to assess the effects of a developed educational program on stakeholders’ awareness of the risks of cannabis use. in this study, most participants were males, middle age, and single. similarly, another study conducted to explore doi 10.18502/sjms.v18i1.12864 page 55 sudan journal of medical sciences mohammead osman yahya mohammead et al table 4: differences in stakeholder’ awareness with demographic variables (n = 203). variables n pretest posttest mean awareness 3.03 ± 0.95 mean rank p-value mean awareness 4.38 ± 0.41 mean rank p-value gender male 152 98.22 0.113 98.02 0.095 female 51 113.27 113.85 age (yr) <25 35 84.74 0.172 105.20 0.965 26–35 74 105.31 101.34 36–45 54 111.85 103.63 >46 40 97.68 98.23 educational level primary 37 19.08 0.001 60.19 0.001 secondary 100 87.54 77.02 university 66 170.40 163.30 marital status married 83 97.70 0.385 102.45 0.928 single 120 104.97 101.69 statically significant at p-value ≤ 0.05; mean score range (1–5) psychosocial predictors of addictive behaviors between internet use and cannabis use found that most participants were males aged over 20 [28]. evidence denotes that excessive heavy cannabis use among youth and middle-aged individuals is associated with several adverse health effects on physical and mental faculties [29]. these findings indicate that counseling programs should focus on youth and young generations. in the present study, the stakeholder’s awareness score was low at baseline before the educational program. these results agree with previous studies conducted in different countries, which reported that most participants had between poor and average knowledge scores toward cannabis use disorder [30, 31]. in this study, similar findings were reported at baseline in terms of stakeholders’ awareness; however, there was a statistically significant increase in the participants’ awareness scores at the posttest with a large effect size in awareness. this remarkable change in the level of understanding about the risk of cannabis use may be attributed to the educational program, which indicated that the program was effective. these results are consistent with a previous study conducted by gurung et al. (2020) that showed that more than half of the participants had inadequate knowledge about substance use disorders at the pretest. however, in the posttest, more than one-third of participants had adequate knowledge, doi 10.18502/sjms.v18i1.12864 page 56 sudan journal of medical sciences mohammead osman yahya mohammead et al and two-thirds of participants had moderate knowledge of substance use disorders. there was a significant improvement in awareness [32]. furthermore, this study’s findings were similar to a study conducted in india, which revealed a statistically significant increase in the mean knowledge score of cannabis use disorder among participants at the posttest compared to the pretest score in the experimental group [33, 34]. on the other hand, a previous study conducted by isralowitz et al. (2021) reported that most participants believed that medical cannabis holds significant health benefits but expressed concerns regarding potential risks associated with cannabis use [35, 36]. the researchers tested the differences between stakeholders’ awareness levels with demographic variables before and after implementing the educational program. the results showed statistically significant differences between the educational level and stakeholders’ understanding at the preand posttests. the participants who were university graduates showed a statistically significantly higher level of awareness about the risk of cannabis than other educational levels at the preand posttests. however, participants who had lower levels of education exhibited substantially less understanding of the risk of cannabis use. a possible explanation for this outcome is the lack of formal educational programs for this population to increase their awareness of the risk of cannabis use. besides, there is limited access to continuous training services in rural areas of the country. thus, future consideration should focus on providing constant health education for the individual with a low level of education to raise awareness of the risks associated with cannabis use. limitations and strengths even though this study denoted a significant improvement in the stakeholder’s awareness score at the posttest compared to the pretest, the study has some limitations. the first limitation is the lack of a control group, the study was conducted on one group at the pretest and posttest. therefore, future research may include a control group for the efficacy of the findings. the second limitation is using a convenience sampling method and implementing the program in a specific region due to difficulties in accessing other regions in the country. this limitation may affect the generalizability of the results and may not be representative of the entire population of sudan. accordingly, future research may conduct further studies in different areas of sudan to generalize the findings. doi 10.18502/sjms.v18i1.12864 page 57 sudan journal of medical sciences mohammead osman yahya mohammead et al 5. conclusion the present study assessed stakeholders’ awareness levels regarding the risk of cannabis use before and after implementing an educational program. the study concluded that the educational program effectively improved stakeholders’ awareness of the risk of cannabis use. the study results may help health authorities to adopt awareness campaigns against cannabis use among adolescents and young adults to increase awareness about the side effects of cannabis use. this study recommends ongoing health education programs for populations with specific considerations for people with low levels of education. acknowledgments the authors express their gratitude to all respondents who took part in this survey. they extend their sincere thanks to the data collectors, reviewers, constructive comments, and the data analyzer. ethical considerations before implementing the program, the researchers obtained an institutional review board (irb) approval and specific permissions to carry out this study. first, the researchers obtained an irb approval from an educational institution (the national ribat university faculty of graduate studies and scientific research) in sudan. then, permissions were obtained from local directors to facilitate study processes and get access to eligible participants. additionally, the researchers provided an extensive explanation to participants about the aim of the study, then, written informed consents were obtained before data collection and implementing the program. all included participants agreed to voluntarily participate in this study. all responses were kept strictly confidential for research purposes only. competing interests the researchers declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. doi 10.18502/sjms.v18i1.12864 page 58 sudan journal of medical sciences mohammead osman yahya mohammead et al availability of data and material the data and material of this study are available from the corresponding author upon request. funding this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. references [1] debenham, j., newton, n., birrell, l., yücel, m., lees, b., & champion, k. 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(2020). a study to assess the level of knowledge of cannabis use disorder among adolescents. indian journal of psychiatric nursing, 17(2), 79. doi 10.18502/sjms.v18i1.12864 page 61 sudan journal of medical sciences mohammead osman yahya mohammead et al [32] gurung, d., thapa, b., & paudel, a. (2020). prevalence of substance use disorders and effectiveness of educational package on knowledge regarding the disorders among adolescents in selected schools of lekhnath, nepal. international journal of innovative science and research technology, 5(7), 934–941. [33] tanushree, m., punita, b., sharma, a., & mitra, t. (2020). a study to assess the effectiveness of psycho-educative module on knowledge of cannabis use disorder among adolescents. international journal of psychiatric nursing, 6(jul–dec), 44. [34] banerjee, s. (2021). effectiveness of planned teaching programme on knowledge regarding prevention of substance abuse among students of class ix of green park sikshasadan high school, kolkata, west bengal, india. international journal of recent advances in multidisciplinary research, 2(8), 8–12. [35] isralowitz, r., reznik, a., zolotov, y., grinstein-cohen, o., wacht, o., pruginin, i., pruginin, i., yehudai, m., & edelstein, o. (2021). toward medical cannabis education in israel. complementary therapies in medicine, 58, 102709. [36] zolotov, y., grinstein cohen, o., findley, p. a., reznik, a., isralowitz, r., & willard, s. (2021). attitudes and knowledge about medical cannabis among israeli and american nursing students. nurse education today, 99, 104789. doi 10.18502/sjms.v18i1.12864 page 62 introduction materials and methods study design, setting, and participants sample size and technique measurements development of the questionnaire the components of the questionnaire development of the educational program data collection data analysis results sample description stakeholders' awareness regarding the risk of cannabis use at preand posttests differences between stakeholders' awareness anddemographic variables discussion limitations and strengths conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 12, issue no. 4, doi 10.18502/sjms.v12i4.1353 production and hosting by knowledge e research article association between exposure to beta 2 agonists and corticosteroids and acquiring benign joint hypermobility syndrome among asthmatic patients: a case-control study alsarah mutwakil abbas diab1, eman mutwakil ahmed almostafa suliman1, ayat abdallah hassan abdallah2, mohamed abdelhadi elzubair dyab3, tanzeel omer elamin awadalla2, naila mubarak kirkisawi4, and nazik elmalaika obaid seid ahmed husain5 1surgery resident, jebel aulia teaching hospital, khartoum, sudan 2general practitioner, omdurman military hospital, khartoum, sudan 3internal medicine resident, jebel aulia teaching hospital, khartoum, sudan 4department of community medicine, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 5department of pathology, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan. abstract background: beta2 (𝛽2) agonists as relievers and corticosteroids as controllers are the mainstay drugs for asthma treatment. benign joint hypermobility syndrome (bjhs) is a connective tissue disorder with musculoskeletal symptoms. we had examined the possible association between the use of 𝛽2 agonists and corticosteroids and acquiring bjhs in asthmatic patients. methods: this was a case-control, hospitalbased study including a group of asthmatics who had bjhs (cases), compared with a matched group of asthmatics without bjhs (controls) for the 𝛽2 agonists and corticosteroids past and current pattern of use. information was collected by faceto-face interview and clinical examination and from subjects’ medical records using pre-structured questionnaire. bjhs diagnosis was based on the revised brighton criteria. asthma severity was reflected by a score, which was calculated from the asthma questionnaire. comparison of exposure was done by calculation of odds ratio. results: development of bjhs was found to be significantly associated with chronicity of asthma of average duration of 13.2 years, and hence to prolonged use of 𝛽2 agonists and/or corticosteroids (or 1.019; 95% ci 0.999 1.039, p=0.006). exposure to 𝛽2 agonist and corticosteroid (87 and 79 cases and controls respectively p=0.05) high asthma score (42.9 ± 9.8 and 40.4 ± 8.3 among cases and controls respectively, p=0.011) were significantly associated with the development of bjhs. conclusion: frequent and prolonged use of 𝛽2 agonists and corticosteroids is significantly associated with acquiring bjhs. implying a possibility of changing approach and handling in asthmatics follow up. prospective and experimental studies are needed to support the evidence of association. keywords: bronchial asthma, benign joint hypermobility syndrome, beta 2 agonists, corticosteroids, brighton criteria, beighton score how to cite this article: alsarah mutwakil abbas diab, eman mutwakil ahmed almostafa suliman, ayat abdallah hassan abdallah, mohamed abdelhadi elzubair dyab, tanzeel omer elamin awadalla, naila mubarak kirkisawi, and nazik elmalaika obaid seid ahmed husain, (2017) “association between exposure to beta 2 agonists and corticosteroids and acquiring benign joint hypermobility syndrome among asthmatic patients: a case-control study,” sudan journal of medical sciences, vol. 12 (2017), issue no. 4, 215–230. doi 10.18502/sjms.v12i4.1353 page 215 corresponding author: alsarah mutwakil abbas diab; email: dr_diab7@hotmail.co.uk received 10 october 2017 accepted 18 december 2017 published 28 december 2017 production and hosting by knowledge e alsarah mutwakil abbas diab et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr_diab7@hotmail.co.uk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences alsarah mutwakil abbas diab et al 1. introduction bronchial asthma is the most common reversible cause of airflow obstruction [1]. it is increasing in prevalence worldwide [1], standardized national prevalence data are not available in sudan. available data show 12% of children in khartoum state report asthma symptoms [2, 3]. asthmatic patients are treated in a stepwise manner according to the severity of the disease [4]. the cornerstones of the treatmentare 𝛽2agonists as relievers and corticosteroids as controllers [5]. benign joint hypermobility syndrome (bjhs) is a connective tissue disorder with joint hypermobility (jhm) in which musculoskeletal symptoms are not related to systemic rheumatologic disease [6]. bjhs is diagnosed based on the revised brighton criteria [6, 7]. jhm or laxity and other extra joint manifestations in bjhs are due to qualitative or quantitative defects in collagen within the joint structure and in other tissues [6, 8, 9]. in contrast to its name, bjhs is not really benign, as it can lead to morbid complications like organ prolapse, heart valve lesions and recurrent joint dislocation [6, 10]; however, to our best of knowledge no prevalence estimations are available for it in sudan. bjhs has a genetic predisposition but the precise underlying genetic defect remains unknown [11]. an immunologic study proved that salbutamol is a potent suppressor of established collagen-induced arthritis [12]. another study found that 𝛽 2 adrenergic stimulation triggers autophagy in cardiac fibroblasts [13]. reduction of fibroblasts and hence the collagen production by asthma medications could be the underlying cause of bjhs among asthmatic patients, but this is not proved by studies. a study by morgan et al. revealed increased frequency of airway disease among patients with ehlersdanlos syndrome and bjhs and another published hypothesis had went in the track of assuming these connective tissue disorders as causes of asthma, but not the opposite [14, 15]. to the best of our knowledge, reviewing the english literature, no studies addressed the effect of asthma medications on joints or their relationship to bjhs. this study was based on our observation of asthmatic patients presented with recurrent joint dislocations and evidence of jhm. the authors’ main objective was to determine whether a significant association between exposure to medications of asthma and acquiring bjhs exists among asthmatic patients in khartoum state, with particular emphasis on the patterns of use, dose, duration of treatment and medical conditions. the hypothesis of this study had four pillars: doi 10.18502/sjms.v12i4.1353 page 216 sudan journal of medical sciences alsarah mutwakil abbas diab et al 1. use of 𝛽2 agonist is associated with acquiring the bjhs. 2. asthmatic patients using adjunct corticosteroids have more severe and rapid onset of the bjhs than asthmatic using 𝛽2 agonists only. 3. the dosage and frequency of 𝛽2 agonist use with or without corticosteroids are directly proportionate to speed of onset and severity of bjhs. 4. the duration of 𝛽2 agonist use with or without corticosteroids is directly proportionate to the speed of onset and severity of bjhs. 2. materials and methods study designthis is an analytical, hospital based case-control study, which compared a group of asthmatic patients diagnosed with bjhs (cases) to a group of asthmatic patients without bjhs (controls) and assessed their exposure, dose, and chronicity of use of 𝛽2 agonists and corticosteroids aiming to find out (if any) relationship. study setting and population: study population included all asthmatic patients visited asthma emergency rooms in three central hospitals; omdurman teaching hospital, khartoum north teaching hospital and alshaab teaching hospital, in khartoum state, sudan in the period from january 2013 through january 2014. these hospitals chosen for being central in khartoum state and serving a wide area. the reason for recruiting patients from emergency rooms was that these hospitals, as well as all hospitals in khartoum state lack specialised asthma clinics. basic procedure of the study: selection of cases: definition of “case group”: asthmatic patients diagnosed by physicians and confirmed by spirometry, and who are on treatment for at least one year, and experienced bjhs symptoms and diagnosed to have it by the investigators by the revised brighton criteria. inclusion criteria for cases: 1. male and female asthmatic patients who visited asthma emergency rooms in the chosen hospitals, during the specified study period who were found to have bjhs in terms of revised brighton criteria. 2. on asthma treatment for at least one year (as induction time for bjhs was unknown). 3. the absence of any systemic rheumatologic disease. doi 10.18502/sjms.v12i4.1353 page 217 sudan journal of medical sciences alsarah mutwakil abbas diab et al exclusion criteria for cases: 1. asthmatic patients affected by any chronic inflammatory joint conditions as these conditions are confounding factors in assessing hypermobility. 2. asthmatic patients suffering from connective tissue disorders leading to hypermobility such as marfan’s syndrome and osteogenesis imperfecta. 3. asthmatic patients on long term of corticosteroid for other disease selection of controls: definition of a “control”: known asthmatics diagnosed by physicians and confirmed by spirometry, who are comparable to cases in every way except that they do not have bjhs, and visited the same asthma emergency rooms during the specified study duration. inclusion criteria for controls: 1. male and female asthmatic patients who visited asthma emergency rooms in the chosen hospitals, during the specified study period 2. on asthma treatment for at least one year (as induction time for bjhs was unknown). 3. matched cases according to specified matching criteria. exclusion criteria for control: 1. asthmatic patients affected with any chronic inflammatory joint conditions. 2. asthmatic patients suffering from any connective tissue disorder. 3. asthmatic patients on long term of corticosteroid for other disease. matching to cases: gender, the age range of 5 years, and bmi category were used as matching criteria; one control per each case. measure of exposure: in the light of literature that hypothesises connective tissue disorder as a cause of asthma, to exclude the possibility of confounding that the connective tissue disease leads to asthma, in this study the exposure status is not the use of 𝛽2 agonists and/or corticosteroid per se, but the duration and pattern of use. it was established from historical records & ascertained from personal recall, using an interview. exposure in cases and controls was compared to estimate disease risk associated with duration and pattern of use, as follows doi 10.18502/sjms.v12i4.1353 page 218 sudan journal of medical sciences alsarah mutwakil abbas diab et al 1. data were set in a 2 by 2 fourfold tables or other. 2. results were expressed as odds ratio (exposures between cases & controls are compared by calculation of odds ratio). 3. test any differences for statistical significance by chi square tests and conditional logistic regression, to find out if the observed exposure among cases higher than the control group. sample size and sampling technique: the desired size of sample was calculated according to: formal mathematical equation that relates power of study (0.9), proportions exposed in control group and in case groups, ratio of cases vs. controls, and significance level. 𝑛 = ( 𝑟 + 1 𝑟 ) ( (𝑝) (1 − 𝑝) (𝑍𝛽 + 𝑍𝛼/2) 2 (𝑝1 − 𝑝2)2 ) n = sample size in case group r = ratio of control to cases (r = 1) z𝛽 = desired power, for 80% power, z𝛽 = 0.84 z𝛼/2 = desired level of significance (typically = 1.96) proportion exposed in control group (p𝑜) = 20% ≡ p1 proportion exposed in case group (p𝑐)≡ p2 = 𝑝𝑐 = 𝑂𝑅 𝑃𝑜 𝑃𝑜 (𝑂𝑅 − 1) + 1 𝑝𝑐 = 2(0.20) (0.20) (2 − 1) + 1 = 0.40 1.20 = 0.33 average proportion exposed = 0.33+0.22 = 0.265 𝑛 = 2(0.265)(1 − 0.265)(0.84 + 1.96) 2 (0.33 − 1.0)2 = 181 total n= 362: (181 cases and 181 controls). sampling was by complete coverage during the study period:181 cases were recruited and frequency matching was used for controls selection, matching criteria: is in terms of age group, gender and body mass index (bmi) category, (at 1:1 ratio). data collection: using personal approach with face-to-face structured interview, where questions on the survey were asked directly to the patients by the researchers. this strategy in data collection helped in reaching 100% response rate. the researchers interviewed all cases and controls on the basis of a detailed predefined performa, with doi 10.18502/sjms.v12i4.1353 page 219 sudan journal of medical sciences alsarah mutwakil abbas diab et al their medical records reviewed and all respondents were clinically examined to detect the presence of brighton diagnostic criteria for bjhs. a standard asthma questionnaire was filled to calculate asthma severity score for each participant. study variables: gender, age, chronicity of asthma in years, types of asthma medications administered by the patient including the duration and the rout of their use, any chronic disease/s, other long-term medications, patient’s recognition of jhm, family history of jhm, time of recognition of jhm in relation to being asthmatic, history of joint dislocations, asthma score and present brighton criteria were the variables of this study. asthma score: this score was structured by the investigators in order to categorise patients according to the severity of the disease, it was calculated from asthma questionnaire that covered detailed asthma history. the score was out of 90 with three categories, mild (up to 30), moderate (31-60) and severe (61-90). brighton criteria: patients were diagnosed as having bjhs based on the following revised brighton criteria published bygrahame including beighton score, which is a measure of jhm [7]. i. major criteria [7] 1. beighton scores of four (table 1). 2. arthralgia for longer than 3 months in four or more joints. ii. minor criteria 1. beighton scores of one, two, or three. 2. arthralgia (3-month duration) in one to three joints or back pain (3-month duration) or spondylosis, spondylolysis/spondylolisthesis. 3. dislocation or subluxation of more than one joint, or in one joint on more than one occasion. 4. three or more soft tissue lesions (e.g. epicondylitis, tenosynovitis, bursitis). 5. marfanoid habitus (tall, slim, span greater than the height (1.03 ratio), upper segment less than lower segment (<0.89 ratios), arachnodactyly). 6. skin striae, hyperextensibility, thin skin, or abnormal scarring. 7. ocular signs: droping eyelids, myopia, antimongoloid slant. 8. varicose veins, hernia, or uterine or rectal prolapse. doi 10.18502/sjms.v12i4.1353 page 220 sudan journal of medical sciences alsarah mutwakil abbas diab et al test points left little (fifth) finger passive dorsiflexion beyond 90∘ 1 right, little (fifth) finger passive dorsiflexion beyond 90∘ 1 left thumb passive dorsiflexion to the flexor aspect of the forearm 1 right thumb passive dorsiflexion to the flexor aspect of the forearm 1 left elbow hyperextends beyond 10∘ 1 right elbow hyperextends beyond 10∘ 1 left knee hyperextends beyond 10∘ 1 right knee hyperextends beyond 10∘ 1 forward flexion of the trunk with knees fully extended palms of hands can rest flat on the floor 1 t 1: tests for calculation of beighton score. 9. mitral valve prolapse. requirement for diagnosis any one of the following: 1. two major criteria 2. one major plus two minor criteria 3. four minor criteria 4. two minor criteria and unequivocally affected first-degree relative in family history [7]. research bias: selection bias was prevented by the clear definition of the study population, the controls were selected independently of the exposure status and a precise case definition and exposure definition were used by all investigators. measurement bias was prevented by using standard measurement instruments; questionnaires and performs to collect similar information from both cases and controls and every patient were clinically examined by two investigators to increase the accuracy of application of diagnostic criteria. recall bias prevented by using multiple sources of information for each subject such as records, follow up cards, inhaler cans to determine the dose. statistical analysis: 1. ascertain exposure rates among cases and controls: doi 10.18502/sjms.v12i4.1353 page 221 sudan journal of medical sciences alsarah mutwakil abbas diab et al 2. estimate disease risk associated with exposure: compare exposure in cases and controls (by calculation of odds ratio) 3. test any differences for statistical significance: chi-square and student t-tests were used. 95% confidence interval was used and p value ≤ 0.05 was set as statistically significant. human and animal rights: this research involved human subjects only, no experimental animals were involved. the protocol had been approved by the research department and ethical committee at ministry of health, khartoum state. results patients with bjhs (cases) were 181matched to 181 patients without bjhs (controls). females represented 68.5% of the study sample, the mean age (± sd) among both groups (34.9 ± 11.1), with 34.9 years (± 11) among cases and 34.9 (±11.2) among controls. the mean bmi (± sd) of the study sample was 24.9 (± 5.5) among cases, 25.2 (± 5.6) among controls and 25 (± 5.6) for both cases and controls. most of the patients (73.8%) were seen in omdurman teaching hospital, followed by khartoum north teaching hospital 15.7%, and10.5% from al-shaab teaching hospital. exposure to salbutamol was approximate among both cases and controls, with 98.9% and 100%, respectively, whereas more than half of cases 51.4% and controls 55.2% were using it alone. all participants were using reliever medications; the vast majority of cases via inhalational route 87.8 % (table 2). more than two-thirds (83.4%) of cases were falling within a spectrum of reliever inhaler consumption time ranging from less than a month to 3 months (table 3). there was a significant statistical correlation between exposure to asthma medications with long period ≥12.5 years (average induction time) (p = 0.006) and higher dose ≥ 4-5 inhalers consumed per year (p=0.05) and acquiring bjhs. prednisolone /hydrocortisone bursts were received by 73.5% and 81.8% of cases and controls, respectively, during emergency room visits, but was not significantly associated with developing bjhs (p=0.062). the family history of jhm was found to be positive in 16.5 % of cases and 5.5% of controls (p= 0.001), odds ratio 3.4(95% ci 1.6-7.2). only 21.5% of cases had recognized their jhm and their ability to perform moves that cannot be performed by normal individuals; out of them, 74.5% reported this after being asthmatic. the rest of cases recognized their jhm at the time of interview when examined by the investigators. doi 10.18502/sjms.v12i4.1353 page 222 sudan journal of medical sciences alsarah mutwakil abbas diab et al route of administration of reliever medication participant total case% control% inhalation by inhaler 87.8 82.3 85.1 inhalation by nebulizer 3.3 2.8 3.0 oral/ syrup 0.0 1.7 0.8 oral/ tablets 1.1 3.3 2.2 oral tablets and nebulizer 0.6 0.6 0.6 nebulizer & inhaler 5.5 7.7 6.6 oral tablets or syrup and inhaler 0.6 1.7 1.1 do not use reliever 1.1 0.0 0.6 total 100.0 100.0 100.0 t 2: route of administration of -reliever medicationsalbutamol amongstudy sample. the single inhaler consumption duration participants total % case % control % less than a month 31.5 23.2 27.3 1-3 months 51.9 51.9 51.9 4-6 months 7.2 12.2 9.7 7-9 months 1.1 1.1 1.1 10 mothsa year 1.7 3.3 2.5 more than a year 2.2 3.3 2.8 have no inhaler, using salbutamol tablets or syrup, or nebulizer 4.4 5.0 4.7 total 100 100 100 t 3: distribution of the study sample in accordance with inhaler consumption duration. the vast majority of cases (81.8 %) reported joint pain; of them71.8% had pain for more than 3 months, 8.8% had joint pain for 3 months, 1.2% for less than 3 months and 18.2% had no joint pain at all. on the other hand, joint pain was reported by 33.7% of controls (p=0.000), odds ratio 8.8 (95% ci 5.4-14.4). only 6.1% of cases and 3.3% of controls had a history of joint/s dislocation. arthralgia for more than 3 months duration in 4 or more joints was reported in 48.6% of cases and 1.7% of controls (p=0.000), odds ratio 56.143(95% ci 17.3,182.3) . doi 10.18502/sjms.v12i4.1353 page 223 sudan journal of medical sciences alsarah mutwakil abbas diab et al brighton criteria participants total % p value odd ratio ci (lower, upper) case % control% ocular signs: dropping eyelids, myopia, antimongoloid slant. 56.4 11.6 34.0 0.000 9.8 5.7,16.9 three or more soft tissue lesions 55.2 6.6 30.9 0.000 17.3 9.0,33.5 arthralgia (3-months duration) in one to three joints or back pain (3months duration) or spondylosis, spondylolysis. 34.8 23.8 29.3 0.021 1.71 1.1,2.7 arthralgia for longer than 3months in 4 or more joints 48.6 1.7 25.1 0.000 56.143 17.3,182.3 skin striae, hyperextensibility, thin skin, or abnormal scarring. 43.6 4.4 24.0 0.000 16.7 7.8,36.1 varicose veins, hernia, or uterine or rectal prolapse. 21.0 5.0 13.0 0.000 5.07 2.4,10.9 marfanoid habitus. 8.8 2.8 5.5 0.006 4.3 1.4,13.1 dislocation or subluxation of more than one joint, or in one joint on more than one occasion. 5.5 1.7 3.6 0.048 3.4 0.94,12.8 mitral valve prolapse. 0.6 0.0 0.3 0.317 t 4: brighton criteria among study sample. the mean beighton score (± sd) was 2.64 (± 1.62) among cases and 0.88 (± 1.20) among controls (p=0.000). the most common brighton criteria among cases were found to be the presence of dropping eyelid, myopia and/ or antimongoloid slant which represented 56.4% followed by the presence of 3 or more soft tissue lesions which were 55.2%.on the other hand, 11.6% of controls had a dropinge yelid, myopia and /or antimongoloid slant followed by the presence of 3 or more soft tissue lesions which were 6.6%(table 4). this table also shows thatasthmatics with most (7/9) of the brighton criteria are significantly more likely to be (𝛽) 2 agonists and corticosteroids users. diagnosis by one major and two minors criteria was the commonest among cases (40.34%) while 66.86% of controls had sub-diagnostic criteria (figure 1). development of bjhs was found to be significantly associated with chronicity of asthma of average duration of 13.2 years, and hence to prolonged use of 𝛽2 agonists doi 10.18502/sjms.v12i4.1353 page 224 sudan journal of medical sciences alsarah mutwakil abbas diab et al types of asthma medications duration of medication use in years beighton score beta 2 agonists only 1.01 ± 0.1 1.7 ± 1.6 beta 2 agonists and corticosteroid controller 2.6 ± 2.6 1.9 ± 1.8 p-value 0.000∗ 0.032∗ t 5: means of theduration of asthma medication used inyears and beighton score. and/or corticosteroids (or 1.019; 95% ci 0.999 1.039, p = 0.006), with the frequency of consuming a 200 metered dose inhaler in a mean duration of 2.2 months, and with high asthma score (42.9 ± 9.8) (p=0.011). no significant statistical correlation was found between developing bjhs and a certain type of medication per se, but it was significantly correlated with duration of salbutamol use in years (p =0.022)and the number of salbutamol inhalers consumed per month (p =0.027). acquiring bjhs correlated statistically with the duration of salbutamol alone or with corticosteroid used in years and beighton score (table 5). *statistically significant pvalue. acquiring bjhs was not found to be correlated with added chronic diseases other than asthma (p=0.083) or their medications which had been used in the previous year before the interview (p=0.91). 3. discussion to the best of our knowledge, this is the first time in english literature to demonstrate an association of bjhs among sudanese asthmatic patients compared with their matched controls. joint hypermobility(jhm ) was observed in 68.5% of females among the cases in this study, justified by the fact that bjhs has a strong genetic constituent with an autosomal dominant pattern [6], and the likelihood of developing the disease seems to be higher in a female fetus [11, 20]. compared to other populations, jhm showed lower prevalence figures in nigerians (43%) [16], followed by 38.5% in females, and 25.4% in males among iraqi students [17] and 6% in females, 2% in males among caucasians [11]. various environmental/acquired contributors, such as sex, age, sports habits, trauma, surgery, diet, and pain cognition [7, 11, 18, 19] need further exploration of their role in increasing the rate among sudanese. doi 10.18502/sjms.v12i4.1353 page 225 sudan journal of medical sciences alsarah mutwakil abbas diab et al patients with bjhs may have a family history of double-jointed relatives, recurrent dislocations or other presentations [6]. the significantly higher beighton score among cases than controls while the majority of cases (83.4%) reported a negative family history of jhm and presence of sub-diagnostic criteria among 66.8% of controls suggest this form of bjhs may be acquired. that was supported by the fact that theonset of the disease took place after being asthmatic and using the medications in 74.6% of cases who recognized their jhm. the average induction time was 1 year for regular 𝛽2 agonists only, and 2.6 years for patients using combined 𝛽2 agonists with corticosteroids as controllers, also the combination regimen increased the beighton score more than 𝛽2 agonist only (p=0.032). thus, corticosteroids were not significantly associated with bjhs, but combination with 𝛽2 agonist delayed the onset and increased the severity of the disease. the vast majority(83.4%) of cases were falling within a spectrum of a single reliever inhaler consumption period ranging from less than a month to 3 months, fragmented to 31.5% in less than a month ci 95%(24.6% 38.6%) and 51.9% during 1-3 months ci 95%(44.2%-59.2%). therefore, exposure to asthma medication with long period 12.5 years (average induction time) or more (p = .006) and higher dose ≥ 4-5 inhalers consumed/year (p=0.05) is associated with the development of bjhs. salbutamol has important effects on the immune inflammatory response and a significant therapeutic action in collagen-induced arthritis [12]. this effect was demonstrated by injection of 200 micrograms of salbutamol every day for 10 days in mice, extending the effects of salbutamol in the human situation, however, would depend on the dosage [12]. the most commonly used type of reliever medications –among study samplewas salbutamol sulphate in a pressurized metered dose inhaler with valve, each depression of the valve delivers 100 mcg of salbutamol, with a total of 200 inhalations, giving a total dose of 20mg (20000𝜇g) salbutamol per inhaler [21]. the majority of the case group in this study consumed four inhalers or more per year, therefore, they were exposed to ≥ 80mg (80000 𝜇g) at least per year. increased duration of exposure to salbutamol in years and the number of salbutamol inhalers consumed per month were significantly associated with the development of bjhs. while corticosteroids had significant synergistic effect with salbutamol by increasing the severity of jhm, the duration of its use in years was not significantly correlated with bjhs because asthmatic patients are not treated with steroids alone, hence, their effect can be evaluated only in a group of non-asthmatic patient sunder treatment of steroid only. doi 10.18502/sjms.v12i4.1353 page 226 sudan journal of medical sciences alsarah mutwakil abbas diab et al asthma per se has been excluded in this study as a cause of bjhs as well as other chronic diseases like hypertension, diabetes mellitus, and renal failure. moreover, longterm medications such as antihypertensive and oral hypoglycemic were not significantly linked to acquiring bjhs (p-value = 0.05). regarding asthma score structured by the investigators to evaluate asthma severity; it was due to patient’s ignorance and poor compliance, the questions made it easier for patients to tell as sure as possible, forced expiratory volume in the first second using a spirometer is the test for asthma attack severity, finances limited it’s use for us and our patients, all of our patients did not have an asthma diary as well the vast majority of bjhs patients presented with joint pain, which is thought to be due to excessive joint laxity that leads to wear and tear on joint surfaces and strains [6]. it is noteworthy that joint pain was not due to any arthritic disease. in this study, 81.8% of cases had a history of joint pain, 71.8% of them had pain more than 3 months, which is comparable with 33.3% of (204) studied population of hypermobile participants with arthritic disorders in nigeria [16]. this great difference is related to differences in pain threshold, attitudes to pain [22] and the effect of asthma medications. a considerable higher prevalence of dropping eyelid 56.4% and soft tissue lesion (55.2%) among cases in this study compared to patients in london where dropping eyelids was present in 41% and soft tissue lesions in 10% of the studied group [23]. this significant difference might be related to salbutamol effect on collagen, as well as corticosteroids, in addition to ethnic and environmental factors. 4. conclusion high dosage, frequency and prolonged use of (𝛽) 2 agonists and corticosteroids are significantly associated with acquiring bjhs. corticosteroid controllers decrease the patient frequency of (𝛽) 2 agonist use and lead to a more severe form of bjhs expressed in higher beighton score, however, the symptoms take place over a longer duration, this may conclude that (𝛽) 2 agonists have the primary role and corticosteroids have a synergistic role. these important side effects of asthma medications could possibly change the approach and handling of asthmatics and their follow-up. prospective and experimental studies are needed to support the evidence of association. in the future, the effect of these medications may be used in the restoration of lost joint function and movement span due to chronic inflammatory joint diseases. doi 10.18502/sjms.v12i4.1353 page 227 sudan journal of medical sciences alsarah mutwakil abbas diab et al 5. acknowledgements sincere thanks and gratitude go to mr. bakri bashir, the dedicated statistician for his devotion in work of analysis and to dr.moumin mohammed for his assistance in designing this study. 6. conflict of interest the authors declare no conflict of interest. references [1] l. yang, h. x. bai, x. huang, a. m. lee, x. tang, and p. zhang, brain biopsy in atypical dementia and primary angiitis of the central nervous system, human pathology, 51, 146–147, (2016). 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[23] m. b. mishra, p. ryan, p. atkinson, h. taylor, j. bell, d. calver, i. fogelman, a. child, g. jackson, j. b. chambers, and r. grahame, extra-articular features of benign joint hypermobility syndrome, british journal of rheumatology, 35, no. 9, 861–866, (1996). doi 10.18502/sjms.v12i4.1353 page 230 http://ca.gsk.com/media/592944/ventolin-hfa.pdf http://ca.gsk.com/media/592944/ventolin-hfa.pdf introduction materials and methods discussion conclusion acknowledgements conflict of interest references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12544 production and hosting by knowledge e research article examination of nurses’ attitudes about patient safety according to sociodemographic characteristics yasin çilhoroz* and gülnur i̇lgün department of health care management, faculty of economics and administrative sciences, hacettepe university, ankara, turkey orcid: yasin çilhoroz: https://orcid.org/0000-0002-5171-7779 gülnur i̇lgün: https://orcid.org/0000-0003-0128-4001 abstract background: patient safety is a high priority for healthcare systems worldwide. it is considered an indicator of the quality of care. establishing a patient safety attitude is the first priority in order to create a patient safety culture. nurses play a critical role in protecting and supporting patients because of the nature of their job. in this way, especially nurses’ attitudes about patient safety will be determined, and threats to patient safety that may arise in the future will be prevented. methods: in this regard, this study aimed to examine the nurses’ attitudes about patient safety according to certain sociodemographic characteristics. to accomplish this goal, the relevant data of the nurses were obtained by using the patient safety attitude scale consisting of 6 dimensions and 46 items. the research population consists of 245 nurses working in a university hospital in ankara. the sample was not calculated, and a questionnaire was distributed to all employees of which 215 nurses completed the questionnaire. data were collected between 1-30 april 2021. ethics committee approval was obtained from the hospital. the data obtained were subjected to multivariate regression analysis. results: the scale used was reliable (r=0.80). the mean of the general patient safety attitude scale is 3.22 with a standard deviation of 0.54. the majority of the participants were found to be between the age groups of 19-26 (38.1%), women (84.7%), and single (52.1%). we also found that the weekly working time of nurses and whether they got patient safety training or no had a statistically significant effect on patient safety attitudes (p<0.05). therefore, it could be said that as the working time of nurses increased, a decrease in patient safety attitudes were observed, and they exhibited more patient safety attitudes as they got patient safety training. conclusion: from this point of view, determining the weekly working hours of nurses more appropriately and making them more trained about patient safety may play a key role in creating a higher level of patient safety attitude. keywords: healthcare, nurse, patient safety, patient safety culture, patient safety attitude how to cite this article: yasin çilhoroz* and gülnur i̇lgün (2022) “examination of nurses’ attitudes about patient safety according to sociodemographic characteristics,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 444–458. doi 10.18502/sjms.v17i4.12544 page 444 corresponding author: yasin çilhoroz; email: yasincilhoroz@gmail.com received 7 may 2021 accepted 14 july 2022 published 31 december 2022 production and hosting by knowledge e yasin çilhoroz and gülnur i̇lgün. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12544&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün 1. introduction the history of patient safety, which is not a new concept in healthcare, goes back to hammurabi’s laws, and patient safety is stated in greek medicine as ”first, do no harm.” with the publication of the report titled “to err is human: building a safer health system” by the institute of medicine (iom), the issue of patient safety has attracted the attention of all stakeholders in the health sector (society, media, policy makers, etc.) [1]. in addition, in order to attract attention to the importance of patient safety, it has been revealed that 44,000-98,000 deaths per year are caused by preventable medical errors [2]. this situation has been supported by other studies. a study on patient safety found that wrong treatment in the health system was more than expected, with at least 100 patients dying every day as a result of medical errors [3]. in addition, it was also determined that those who provided these services were aware of this situation and believed that there were medical errors in 34% in the usa, 30% in canada, 27% in australia, 23% in germany, and 22% in england [4]. in another study, it was stated that more people died from medical errors relatively due to highway accidents, breast cancer, or aids within a year [5]. it is very important to ensure patient safety in the quality of healthcare service delivery. ensuring that patients receive services in a safe environment and away from all harmful situations is not only the responsibility of the hospital management but also of the healthcare professionals [6]. the concept of patient safety is defined by the world health organization (who) as the absence of irreversible harm to the patient in the process of healthcare service and minimizing the risk of unnecessary harm related to healthcare [7]. certain approaches should be adopted to ensure patient safety at the desired level. the most important of these is that employees report their mistakes without fear or hesitation, and they are encouraged in this regard [8]. in a study, it was stated that employees who experienced negativity due to an error they caused will be less willing to report an error that may occur later [9]. in addition, it is stated that the positive attitudes and behaviors of the managers and colleagues in the work environment significantly contributed to the employees reporting their mistakes [6]. nurses, who are among the most important healthcare professionals in patient care, are responsible for protecting the patients from all possible dangers, preventing or minimizing the negative consequences that may occur in the procedures and treatments applied to the patient at every stage of service provision. while nurses fulfill their responsibilities, they should be careful about the elements that harm patient safety and doi 10.18502/sjms.v17i4.12544 page 445 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün take care to protect and improve patient safety [6]. the way to achieve this is to create a good patient safety culture [10]. patient safety culture is a multidimensional concept defined as a product of individual and group behaviors, values, attitudes, perceptions, competencies, and standards that determine the commitment, style, and competence of management in managing patient safety in the context of healthcare. moreover, it is used as a management tool in the healthcare industry and is promoted by health policy makers and managers around the world [11]. however, before establishing a patient safety culture, it is necessary to determine the attitudes of healthcare professionals such as nurses toward patient safety and to decide on the necessary strategies to create a safety culture. in this respect, attitude studies are of great importance. attitude studies are carried out for the purposes of learning the attitudes of individuals in a certain time unit, predicting their future behavior, detecting negative conditions in advance and eliminating them, and preventing negative behaviors, especially by taking necessary measures in administrative matters. managers must know the attitudes of the people they work with and under their management toward the system, the rules, and themselves. thus, managers may take some precautions to predict and control the behavior of these people [6]. in this context, within the scope of this study, factors affecting the patient safety attitudes of nurses, who constitute an important professional group in terms of quantity and quality of the service they provide, will be examined. 2. materials and methods this study aimed to examine the patient safety attitudes of nurses, who have an important place in the provision of healthcare services. establishing a patient safety culture is strongly recommended by iom. establishing a patient safety culture depends on improving patient safety attitudes. in this respect, this research is important in terms of revealing the patient safety attitudes of nurses. the research population consists of 245 nurses working in a university hospital in ankara, turkey. within the scope of the study, the sample size was not calculated and a questionnaire was distributed to all employees and 215 nurses agreed to participate in the survey. therefore, the research was conducted with the participation of 215 employees (88%). data were collected between 1-30 april 2021. ethics committee approval was obtained from the hospital ethics committee. nurses participated in the study voluntarily. doi 10.18502/sjms.v17i4.12544 page 446 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün a questionnaire consisting of two parts was used in this study. the first part of this form consists of 9 questions that contain sociodemographic information (age, gender, marital status, education level, working unit, shift format, weekly working time (hours), administrative position status, and patient safety training status) of the participants. the second part of the questionnaire, the “patient safety attitude scale,” which consists of 46 questions, was developed by sexton et al. [12] and validated and reliable in turkish by baykal et al. [6]. the five-point likert-type scale is scored as “5strongly agree” and “1strongly disagree,” and some items of the scale are scored negatively. the patient safety attitude scale consists of 6 sub-dimensions (job satisfaction, teamwork, safety climate, management approach, stress identification, and working conditions). the correlation values of the scale according to the total scores are between 35 and 58. the total scale cronbach alpha value is 0.93 and the sub-dimension cronbach alpha values are 0.85, 0.86, 0.83, 0.77, 0.74, and 0.72, respectively. the data obtained within the scope of the research were subjected to multivariate regression analysis. in this way, the effect of many independent variables on patient safety attitude can be examined statistically. 3. results table 1: reliability coefficients of the scale. dimensions cronbach’s alpha (r) job satisfaction 0.71 teamwork 0.69 safety climate 0.67 management approach 0.69 stress identification 0.88 working conditions 0.73 general 0.80 it was seen that the scale used according to table 1 is reliable (r=0.80). in addition, when examined in terms of dimensions, it was found that the highest reliability coefficient was obtained in the ”stress identification (r=0.88)” dimension and the lowest reliability coefficient was obtained in the ”safety climate (r=0.67)” dimension. therefore, it was seen that both the scale and scale dimensions in general had a sufficient score for reliability [13, 14]. doi 10.18502/sjms.v17i4.12544 page 447 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün table 2: descriptive statistics of the participants. variables number percentage (%) age (yr) 19–26 82 38.1 27–34 52 24.2 35–42 46 21.4 43–51 35 16.3 gender woman 182 84.7 male 33 15.3 marital status married 103 47.9 single 112 52.1 education level high school 69 32.1 associate degree and above 146 67.9 working unit policlinic 79 36.7 clinic 136 63.3 shift format day shift + night shift 160 74.4 day shift only 32 14.9 night shift only 23 10.7 weekly working time (hr) 40–45 134 62.3 46–56 81 37.7 administrative position status yes 21 9.8 no 194 90.2 patient safety training status yes 177 82.3 no 38 17.7 descriptive statistics of the participants are presented in table 2. accordingly, the majority of the participants were found to be aged between 19-26 (38.1%), women (84.7%), single (52.1%), associate degree or higher educated (67.9%), clinical staff (63.3%), working day + night shifts (74.4%), working 40-45 hours a week (62.3%); does not have an administrative duty (90.2%); got training on patient safety (82.3%). table 3: statistics on patient safety attitude scale. dimensions mean standard deviation number job satisfaction 2.91 0.91 215 teamwork 3.48 0.62 215 safety climate 3.35 0.75 215 management approach 3.41 1.08 215 stress identification 3.01 0.85 215 working conditions 3.15 0.66 215 general 3.22 0.54 215 doi 10.18502/sjms.v17i4.12544 page 448 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün according to table 3, the mean of the general patient safety attitude scale is 3.22 with a standard deviation of 0.54. on the basis of dimensions, it was concluded that the teamwork dimension had the highest average of 3.48 and the job satisfaction dimension had the lowest average of 2.91. table 4 contains the regression analysis results. considering the general model of the study, it was found that the established model was statistically significant (p<0.05). accordingly, it was determined that the weekly working time has a negative effect on the patient safety attitude, and the patient safety training status had a positive effect on the patient safety attitude (p<0.05). that is, as the weekly working time of the nurses increased, their patient safety attitudes decreased. it was determined that those who got patient safety training had higher patient safety attitudes than those who did not. in addition, when table 4 was examined on the basis of dimensions, it was found that the models established for all dimensions were statistically significant (p<0.05). when the vif values of all models established within the scope of the research were examined, it was understood that the values are in the normal range (vif<10) and; therefore, there was no multicollinearity problem between the variables. in addition, the durbin-watson value was used to test whether the autocorrelation between variables was in the normal range (1.5-2.5); however, no autocorrelation problem was observed. 4. discussion this study aimed to examine the effect of sociodemographic characteristics on the patient safety attitudes of nurses, who have an important place in healthcare services delivery. when the general model established within the scope of the study was examined, it was seen that the weekly working time variable had an effect on the general patient safety attitudes of nurses. accordingly, it was found that as the weekly working time increases, the patient safety attitude levels of nurses decreases. with the increase in the weekly working time, factors such as stress level, workload, insomnia, or fatigue may increase, which may cause employees not to pay the necessary attention to their work, difficulty in concentrating on their work, and making mistakes. this situation is thought to explain the negative relationship between weekly working hours and patient safety attitude. similar to the results of this study, rogers et al. [15] found that the patient safety level decreased as the working time increased in a study conducted on nurses. similarly, in the study conducted by son et al. [16] on nurses, it was stated that there was a negative relationship between weekly working time and patient safety competence levels, and patient safety competence level decreased as the duration of the disease doi 10.18502/sjms.v17i4.12544 page 449 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün table 4: patient safety attitude regression analysis statistics. dimensions variables standardized beta coefficient t p-value vif f p-value r2 durbin– watson job satisfaction age –0.165 –1.666 0.097 2.367 3.862 0.001 0.16 2.202 gender (female) –0.234 –3.253 0.001 1.255 marital status (married) –0.031 –0.358 0.720 1.830 education level (high school) –0.142 –2.016 0.045 1.210 working unit (clinic) –0.118 –1.698 0.091 1.180 shift format (day shift only) 0.074 1.067 0.287 1.175 weekly working time –0.212 –2.783 0.006 1.414 administrative position status (yes) –0.112 –1.597 0.112 1.185 patient safety training status (yes) 0.135 1.863 0.064 1.266 teamwork age 0.152 1.497 0.136 2.367 2.461 0.008 0.11 2.235 gender (female) –0.035 –0.470 0.639 1.255 marital status (married) 0.279 3.122 0.002 1.830 education level (high school) –0.087 –1.198 0.232 1.210 working unit (clinic) –0.102 –1.416 0.158 1.180 shift format (day shift only) 0.204 2.850 0.005 1.175 weekly working time –0.147 –1.868 0.063 1.414 administrative position status (yes) 0.105 1.452 0.148 1.185 patient safety training status (yes) 0.171 2.295 0.023 1.266 safety climate age –0.151 –1.489 0.138 2.2370 2.581 0.004 0.12 2.214 gender (female) –0.079 –1.058 0.291 1.285 marital status (married) –0.097 –1.079 0.282 1.856 education level (high school) –0.071 –0.982 0.327 1.211 working unit (clinic) 0.001 0.011 0.992 1.187 shift format (day shift only) 0.059 0.437 0.663 4.200 doi 10.18502/sjms.v17i4.12544 page 450 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün table 4: (continued). dimensions variables standardized beta coefficient t p-value vif f p-value r2 durbin– watson weekly working time –0.236 –3.016 0.003 1.414 administrative position status (yes) 0.170 2.271 0.024 1.304 patient safety training status (yes) 0.177 2.372 0.019 1.284 management approach age –0.016 –0.167 0.868 2.370 4.975 0.001 0.21 2.281 gender (female) 0.021 –0.294 0.769 1.285 marital status (married) –0.111 –1.308 0.192 1.856 education level (high school) –0.119 –1.736 0.084 1.211 working unit (clinic) –0.014 –0.212 0.832 1.187 shift format (day shift only) 0.058 0.458 0.647 4.200 weekly working time –0.281 –3.798 <0.001 1.414 administrative position status (yes) 0.170 2.384 0.018 1.304 patient safety training status (yes) 0174 2.469 0.014 1.284 stress identification age 0.526 5.877 <0.001 2.370 4.437 0.001 0.31 1.928 gender (female) 0.250 3.792 <0.001 1.285 marital status (married) 0.099 1.248 0.213 1.856 education level (high school) 0.148 2.315 0.022 1.211 working unit (clinic) 0.031 0.496 0.621 1.187 shift format (day shift only) 0.256 2.150 0.033 4.200 weekly working time 0.118 1.705 0.090 1.414 administrative position status (yes) 0.149 2.252 0.025 1.304 patient safety training status (yes) 0.219 3.323 0.001 1.284 doi 10.18502/sjms.v17i4.12544 page 451 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün table 4: (continued). dimensions variables standardized beta coefficient t p-value vif f p-value r2 durbin– watson working conditions age –0.257 –2.545 0.012 2.370 2.616 0.004 0.12 2.427 gender (female) –0.139 –1.865 0.064 1.285 marital status (married) –0.233 –2.602 0.010 1.856 education level (high school) –0.070 –0.975 0.331 1.211 working unit (clinic) 0.042 0.585 0.559 1.187 shift format (day shift only) 0.280 2.084 0.038 4.200 weekly working time –0.211 –2.696 0.008 1.414 administrative position status (yes) 0.008 0.103 0.918 1.304 patient safety training status (yes) 0.074 0.989 0.324 1.284 general age –0.003 –0.030 0.976 2.370 2.416 0.008 0.17 2.344 gender (female) –0.099 –1.322 0.188 1.285 marital status (married) –0.007 –0.072 0.942 1.856 education level (high school) –0.114 –1.570 0.118 1.211 working unit (clinic) –0.066 –0.913 0.362 1.187 shift format (day shift only) 0.112 0.831 0.407 4.200 weekly working time –0.262 –3.332 0.001 1.414 administrative position status (yes) 0.108 1.439 0.152 1.304 patient safety training status (yes) 0.166 2.216 0.028 1.284 increased. in the study conducted by griffiths et al. [17], it was found that nurses with high working hours are more likely to exhibit a low-patient safety attitude. in the study conducted by jarrar et al. [18], it was found that there was a negative relationship between the weekly working time of nurses and their patient safety attitude levels. in the study conducted by filiz[19] on healthcare workers, it was found that long working hours reduced the patient safety attitudes of the employees. similar to the results of doi 10.18502/sjms.v17i4.12544 page 452 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün all these studies, it has been observed in the literature that there are many different studies stating that the increase in weekly working hours increases the possibility of encountering errors or adverse events that threaten patient safety [20-27]. according to the general model established in the study, another variable that had an effect on the patient safety attitudes of nurses was patient safety education. accordingly, it was found that nurses who got patient safety training had higher patient safety attitude levels than nurses who did not get training. therefore, increase in the knowledge and awareness about patient safety for nurses is vital in healthcare service delivery. this can be explained by the employees taking more care in their attitudes and behaviors that concern patient safety. similarly, in the study conducted by teleki et al. [28], it was observed that patient safety education had a positive effect on establishing a patient safety culture and reducing medical errors. in the study conducted by balç𝚤𝑚𝑎𝑡ℎk akman[29], it was found that the patient safety levels of nurses who got training on patient safety were higher. differing from the findings of these studies, in the study conducted by demirel et al. [30] it was found that there was no statistically significant difference between the patient safety attitudes of healthcare workers who received training on patient safety. regression models were also established for each subdimension of the patient safety attitude scale within the scope of the study. when these models were examined, the factors affecting the job satisfaction subdimension were gender, education level, and weekly working time; factors affecting the teamwork subdimension were marital status, working style, and patient safety education status; factors affecting the security climate and management understanding subdimensions were weekly working hours, administrative duty status, and patient safety training; factors affecting the stress definition subdimension were education level, working style, administrative duty status, and patient safety training; factors affecting working conditions subdimension were age, marital status, type of work, and weekly working time. 5. limitations this study has some limitations. first, it was done only on nurses. second, it was done in only one hospital. finally, only certain variables were used. since the research was conducted on nurses working only in one hospital, caution should be exercised in generalizing the results of this study to nurses working in other hospitals. therefore, studies involving more hospitals are recommended in the future. in this way, it will be doi 10.18502/sjms.v17i4.12544 page 453 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün possible to examine the effect of not only individual characteristics but also organizational characteristics (such as institutional ownership and number of beds) on patient safety attitudes of nurses as in this study. these factors should be considered when making the assessment. 6. conclusion according to this study, considering that the variable that has the most impact on the patient safety attitudes of nurses is the weekly working time (β=-0.262), it is recommended that hospital managers rearrange their working time and especially take care not to exceed 40 weekly working hours. in this way, the workload of nurses with very high weekly working hours can be reduced, and thus patient safety attitudes can be increased. again, according to another result of this study, nurses who received training on patient safety had higher patient safety attitudes. according to this result, hospital managers should make it compulsory to get training on patient safety for all staff, especially nurses who have not been trained on patient safety before and who have a high weekly working time, and continue to provide training at regular intervals. in addition, managers and policy makers should allocate more resources to the training of nurses on this subject for a safer healthcare service delivery process, and increase patient safety culture and awareness. acknowledgments the authors would like to thank the university health directorate and the participants who participated in this study. ethical considerations first, approval was obtained from the university hospital in order to conduct the study. then, the approval of each participant stating that they voluntarily participated in the study was obtained. finally, the questionnaire was applied to the participants. competing interests the authors declare that there is no conflict of interest. doi 10.18502/sjms.v17i4.12544 page 454 sudan journal of medical sciences yasin çilhoroz and gülnur i̇lgün availability of data and material the data that support the findings of this study are available from the corresponding author. funding none. references [1] yılmaz, a., işık, o., & akca, n. 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(2020). a the effect of patient safety attitudes and cultures on medical errors of intern students. acıbadem university health sciences journal, 11(2), 276–283. doi 10.18502/sjms.v17i4.12544 page 458 introduction materials and methods results discussion limitations conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11451 production and hosting by knowledge e original article insulin resistance and other comorbidities of obesity as independent variables on ventricular repolarization in children and adolescents zehra ilhan1, mervan bekdas1*, mehmet inanir2, and nimet kabakus1 1department of pediatrics, bolu abant izzet baysal university medical faculty, bolu, turkey 2department of cardiology, bolu abant izzet baysal university medical faculty, bolu, turkey orcid: mervan bekdas: https://orcid.org/0000-0003-2469-9509 abstract background: obesity, a rapidly increasing global health problem in all age groups, is accepted as the basis for many chronic diseases through insulin resistance mechanism. this study aimed to examine whether insulin resistance and other comorbidities of obesity have an effect on the cardiac conduction system. methods: the study included 50 obese and 47 healthy individuals aged 6–18 years. ecgs of all cases were taken; ecg waves and intervals were measured manually. results: of the obese group, 19 were boys (38%) and 31 were girls (62%), 27 were children (54%) and 23 were adolescents (46%), their ages were 11.3 ± 3.5 years. these particular characteristics were similar compared to the control group. however, in the obese group, the ecg parameters qtc (p = 0.001), qtd (p < 0.001), qtdc (p < 0.001), jtc (p < 0.001), tp-e (p < 0.001), tp-e/qt (p < 0.001), tp-e/qtc (p < 0.001), tp-e/jt (p < 0.001), and tp-e/jtc (p < 0.001) were significantly longer. twenty-five obese subjects (50%) had insulin resistance, when ecg parameters are compared to those without it, only jtc was significantly longer (332.3 ± 16.5 vs 321.7 ± 17.7 ms, p = 0.033). jtc duration mostly affected jt (p < 0.001) and qtc (p < 0.001). the 327 ms cut-off value of jtc indicated insulin resistance in the obese patients (p = 0.044) (sensitivity 60%, specificity 60%). conclusion: insulin resistance and other comorbidities of obesity may cause ventricular repolarization abnormalities at an early age. jtc, an ecg parameter, can be a guide in assessing ventricular repolarization abnormality and the risk of arrhythmia in these patients. keywords: obesity, insulin resistance, comorbidities, ventricular repolarization, child, adolescence 1. introduction the world health organization defines obesity as an excessive accumulation of body fat that may have a negative effect on health [1]. obesity is accepted as a rapidly increasing global health problem in all age groups in all developed and developing countries [2]. how to cite this article: zehra ilhan, mervan bekdas*, mehmet inanir, and nimet kabakus (2022) “insulin resistance and other comorbidities of obesity as independent variables on ventricular repolarization in children and adolescents,” sudan journal of medical sciences, vol. 17, no. 2, pp. 157–169. doi 10.18502/sjms.v17i2.11451 page 157 corresponding author: mervan bekdas; email: merbek14@yahoo.com received 19 january 2021 accepted 7 may 2022 published 30 june 2022 production and hosting by knowledge e zehra ilhan et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:merbek14@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences zehra ilhan et al. over the past 40 years, the obesity rate in children and adolescents has increased by 7 times [3]. according to the 2013 data of turkey childhood obesity research initiative study (cosi-tur) which assessed children aged 7–8 years, 8.3% of children were obese, (6.6% girls, 10% boys) [4]. in the cosi-tur 2016 study, which was repeated three years later, this rate was found to be 9.9% (8.5% in girls, 11.3% in boys), these values showed an increase of 19.3% in childhood obesity (28.8% in girls and 13% in boys), even in the short-term period. these values showed that 1 out of every 10 children in our country is obese [5]. obesity, which is one of the most common chronic manifestations of childhood, is accepted as the basis for many chronic diseases, these are complications such as hepatosteatosis, type 2 diabetes mellitus, hypertension, dyslipidemia, atherosclerosis, coronary artery disease, and cerebrovascular diseases [6, 7]. insulin resistance creates the basis for these complications. insulin resistance expresses the decreasing response to the normal level of circulating insulin [8]. prolonged qt interval, a marker of ventricular repolarization, has previously been identified as a risk factor for sudden cardiac death (scd) [9, 10], and subsequent mendelian randomization experiments have shown that this risk factor is causal [11]. on the other hand, population-based studies have shown that early repolarization is associated with an increased risk of cardiac death in western and asian general populations [12–14]. scd is seen in 6–14% patients without demonstrable structural heart disease [15]. therefore, rapid diagnosis of early repolarization has a major importance. haïssaguerre et al. [15] reported changes compatible with early repolarization in 31% of cases with fatal arrhythmias such as ventricular fibrillation, whereas nam et al. [16] reported the same results for 60% of the cases. our aim in this study is to investigate whether insulin resistance leading to different pathologies in obese causes changes in ventricular repolarization, which is an indicator of ventricular arrhythmia. 2. materials and methods in this prospective study conducted between february 2018 and september 2019, obese patients between the ages of 6 and 18 years and referred to the pediatrics clinic of our hospital were included. obesity was determined as a body mass index (bmi) above the 95-percentile and considering the age and gender of the patients. obese people did not have any other chronic disease and history of drug use. during the same period, 47 patients who did not have a chronic disease, did not use drugs, and had a bmi between 5 and 85 percentiles were also selected to form the control group. when doi 10.18502/sjms.v17i2.11451 page 158 sudan journal of medical sciences zehra ilhan et al. individuals were referred to the outpatient clinic, informed consent was obtained from them and/or parents. patients other than 6–18 years old, smokers, those with chronic diseases, type 1 diabetes, and familial hypercholesterolemia and those who did not give consent were not included in the study. a detailed history was taken from the participants, and physical examinations were performed. serum insulin, which is one of the biochemical tests, was measured by the chemiluminescence method (roche e601). insulin resistance was calculated according to the formula of homa-ir (homeostasis model assessment of insulin resistance; serum fasting blood sugar × serum insulin/405) [17]. insulin resistance was considered to be homa-ir value > 2.2 in girls and >2.6 in boys in the prepubertal period and >3.8 in girls and >5.2 in boys in the pubertal period [18]. for ecg shots, individuals were rested for 10 min, then ecg shots of 10 mm/mv amplitude and 25 mm/s velocity were performed with 12 channel ecg device (nihon kohen cardiofax ecg-1950 vet) in a supine position. ventricular repolarization was accepted as the interval (qt interval) from the beginning of the qrs complex to the end of the t wave [19]. measurements such as qt and corrected qt intervals (qtc) were used to demonstrate cardiac repolarization heterogeneity and to identify patients at risk. in addition, t wave peak and endpoint interval (tp-e) were used to show ventricular repolarization disorder in recent years [20]. tp-e/qt and tp-e/qtc ratios calculated based on this index are accepted as electrocardiographic indicators of ventricular arrhythmogenesis [21]. repolarization indicators jt and jtc are accepted as a useful marker in defining the risk of arrhythmia [22]. in our cases, all these intervals were measured manually by a cardiologist using a magnifying glass (torq 150 mm digital caliper lcd). 2.1. statistical analysis spss (statistical package for social sciences) program version 21 was used for statistical evaluation. numerical data are presented as mean ± sd and categorical data as percentile (%) numbers. student’s t-tests were used in the analysis of variables with normal distribution, and mann–whitney u-tests were used in the analysis of non-normally distributed or categorical variables. p < 0.05 was used as the level of significance. univariate linear regression analysis was used to determine the variables affecting the ecg parameters, for this, variables with p < 0.05 were used in the correlation analysis. the receiver operating characteristic (roc) curve was used to determine the threshold doi 10.18502/sjms.v17i2.11451 page 159 sudan journal of medical sciences zehra ilhan et al. ecg value, the area under the roc curve, specificity and sensitivity, and cut-off points were calculated. figure 1: roc curve analysis for jtc. 3. results fifty obese and forty-seven healthy subjects between the ages of 6 and 18 years were included in the study. there was no significant difference between the two groups in terms of age, age group, and gender. although there was a significant difference in the clinical data regarding bmi, blood pressures, fasting blood sugar, insulin, homa-ir, hba1c, and lipid profile in obese group, there was no significant difference for other variables (table 1). compared to the control group, a statistically significant difference was determined in ecg parameters such as qtc, qtd, qtdc, jtc, tp-e, tp-e/qt, tp-e/qtc, tp-e/jt, and tp-e/jtc in the obese group, while the other parameters were not different (table 2). twenty-five obese subjects (50%) had insulin resistance, while the control group had none. there was no significant difference between the two groups in terms of age, age group, bmi, and blood pressures, but there was a significant difference in the gender, fasting blood sugar, insulin, homa-ir, and triglyceride-to-hdl ratio in insulin resistance group (table 3). doi 10.18502/sjms.v17i2.11451 page 160 sudan journal of medical sciences zehra ilhan et al. table 1: comparison of demographic and clinical data of the groups. features obese (n = 50) control (n = 47) p-value age (yr) 11.3 ± 3.5 11.6 ± 2.9 0.28 age group (c/a)(n) 27/23 23/24 0.62 gender (m/f) (n) 19/31 23/24 0.67 bmi 28.7 ± 5.8 17.6 ± 3.2 <0.001 bmi percentile 97.6 ± 2.7 39.7 ± 28.5 <0.001 bmi z-score 2.1 ± 0.4 –0.3 ± 0.9 <0.001 systolic bp 115 ± 14.6 101.7 ± 13.4 <0.001 diastolic bp 75 ± 11.5 63.7 ± 9.8 <0.001 sodium (mmol/l) 137.5 ± 2.2 138.5 ± 3.1 0.068 potassium (mmol/l) 4.5 ± 0.2 4.4 ± 0.2 0.2 calcium (mg/dl) 9.9 ± 0.4 9.84 ± 0.4 0.12 magnesium (mg/dl) 1.9 ± 0.1 1.9 ± 0.1 0.3 fbs (mg/dl) 88.7 ± 10.6 84 ± 12.7 0.05 insulin (µiu/ml) 21.3 ± 28.3 7.2 ± 3.5 0.001 homa-ir 5.1 ± 8.4 1.5 ± 0.8 0.005 hba1c (%) 5.51 ± 0.29 5.3 ± 0.22 <0.001 hgb (g/dl) 13.6 ± 1 13.4 ± 0.7 0.32 cholesterol (mg/dl) 167.5 ± 28.6 160.6 ± 44.7 0.36 triglycerides (mg/dl) 122.6 ± 71.4 66 ± 30.5 <0.001 ldl (mg/dl) 89.3 ± 25.2 85.3 ± 15.8 0.36 hdl (mg/dl) 51.6 ± 11.3 68.9 ± 86.9 0.16 ldl/hdl 1.81 ± 0.64 1.53 ± 0.43 0.017 cholesterol/hdl 3.36 ± 0.81 2.84 ± 0.76 <0.001 triglycerides/hdl 2.57 ± 1.8 1.21 ± 0.66 0.002 m: male; f: female; c: child; a: adolescent; bmi: body mass index; bp: blood pressure; fbs: fasting blood sugar; homa-ir: homeostasis model assessment of insülin resistance; hba1c: hemoglobin a1c; hgb: hemoglobin; ldl: low-density lipoprotein; hdl: high-density lipoprotein. compared to those without insulin resistance, only the jtc values were statistically significantly different in the ecgs of those with insulin resistance (332.3 ± 16.5 vs 321.7 ± 17.7 ms, p = 0.033), no significant difference was observed in terms of other values (p > 0.05; table 4). compared to those without insulin resistance, gender, lipids, and blood pressure did not affect the jtc value in the insulin resistance group (p > 0.05). when we made the regression analysis, we found that jt (b = 0.31, 95% ci [0.18–0.44], p < 0.001) and qtc (b = 0.58, 95% ci [0.4–0.76], p < 0.001) affected the jtc time most (r2 = 0.72, p < 0.001). the cut-off value for jtc was determined as 327 ms in our study. accordingly, patients with jtc values higher than 327 ms have insulin resistance (auc: 0.66, 95% ci [0.51– 0.81], p = 0.044) (sensitivity 60%, specificity 60%; figure 1). doi 10.18502/sjms.v17i2.11451 page 161 sudan journal of medical sciences zehra ilhan et al. table 2: comparison of ecg parameters of obese and control groups. features obese (n = 50) control (n = 47) p-value qrs (ms) 83.0 ± 8.5 83.9 ± 10.2 0.62 qtmax (ms) 362.9 ± 25.6 361.5 ± 23.9 0.78 qtmin (ms) 339.8 ± 25.3 346.6 ± 24.2 0.11 pulse (/minute) 88.8 ± 15.1 81.7 ± 12.9 0.016 rr (second) 0.69 ± 0.11 0.75 ± 0.11 0.023 qt (ms) 351.3 ± 25.2 354.1 ± 23.9 0.58 qtc (ms) 423.7 ± 19.5 410.5 ± 17.6 0.001 qtd (ms) 23.1 ± 7.8 14.8 ± 5.6 <0.001 qtdc (ms) 27.9 ± 8.6 17.3 ± 6.6 <0.001 jt (ms) 271.4 ± 23.8 265.3 ± 21.6 0.19 jtc (ms) 327.0 ± 17.8 307.4 ± 17.5 <0.001 tp-e (ms) 85.7 ± 9.9 71.2 ± 6.8 <0.001 tp-e/qt 0.24 ± 0.2 0.20 ± 0.2 <0.001 tp-e/qtc 0.20 ± 0.02 0.17 ± 0.01 <0.001 tp-e/jt 0.31 ± 0.4 0.27 ± 0.3 <0.001 tp-e/jtc 0.26 ± 0.3 0.23 ± 0.02 <0.001 ms:milliseconds; qrs: ventricular depolarization time; qtmax: longest time showing ventricular depolarization and repolarization; qtmin: ventricular depolarization and repolarization, shortest time; rr: distance between two rs; qt: qtmax + qtmin sum; qtc: corrected qt; qtd: difference between qtmax and qtmin; qtdc: corrected qt dispersion; jt: qrs end (point j) to the end of the t wave; jtc: corrected jt; tp-e: the time between the peak point of the t wave and the end of the t wave. 4. discussion in this study, which was carried out for the first time in this age group, we found that insulin resistance and other comorbidities of obesity may cause ventricular repolarization abnormalities. obesity causes several health problems, one of which is dyslipidemia. in our study, we found that the ratio of triglycerides to hdl was significantly higher in both obese and insulin-resistant patients. it is known that this finding obtained in our study can be used to estimate insulin resistance in nonobese patients [23]. the relationship between insulin resistance and gender is controversial. insulin resistance is claimed more frequently in males [24]. on the other hand, we found that insulin resistance was higher in girls, and this result was attributed to the majority of our patients being girls in our study. our conclusion was consistent with the literature [25]. it is known that childhood obesity is a major risk factor for cardiovascular disease in adulthood [26]. over time, these patients develop hypertension, left ventricular hypertrophy, and impaired left ventricular diastolic function [27]. these are the causes that doi 10.18502/sjms.v17i2.11451 page 162 sudan journal of medical sciences zehra ilhan et al. table 3: comparison of the biochemical values of the groups according to insulin resistance. features insulin resistance (+) (n = 25) insulin resistance (–) (n = 25) p-value age (yr) 11.6 ± 3.2 11 ± 3.7 0.52 age group (c/a)(n) 13/12 14/11 0.62 gender (m/f) (n) 4/21 15/10 0.002 bmi 30 ± 6.4 27.5 ± 5 0.13 bmi percentile 98 ± 1.5 97.3 ± 3 0.32 bmi z-score 2.1 ± 0.4 2.1 ± 0.3 0.84 systolic bp 117 ± 14.7 112.9 ± 14.4 0.31 diastolic bp 77.3 ± 12.7 72.7 ± 9.8 0.16 sodium (mmol/l) 137 ± 2.5 138 ± 1.8 0.1 potassium (mmol/l) 4.5 ± 0.3 4.5 ± 0.2 0.85 calcium (mg/dl) 10 ± 0.4 9.9 ± 0.3 0.2 magnesium (mg/dl) 1.9 ± 0.18 1.9 ± 0.1 0.63 fbs (mg/dl) 92.3 ± 11.4 85.2 ± 8.6 0.016 insulin (µiu/ml) 32.4 ± 37 10.3 ± 4.2 0.005 homa-ir 8 ± 11.2 2.21 ± 0.97 0.013 hba1c (%) 5.56 ± 0.32 5.46 ± 0.25 0.21 hgb (g/dl) 13.7 ± 0.9 13.4 ± 1 0.24 cholesterol (mg/dl) 173.1 ± 24.3 161.9 ± 31.8 0.17 triglycerides (mg/dl) 159.2 ± 82.3 86.1 ± 29.6 <0.001 ldl (mg/dl) 87.1 ± 22.5 91.4 ± 27.9 0.55 hdl (mg/dl) 49.7±10.6 53.5±11.9 0.23 ldl/hdl 1.82±0.56 1.79±0.71 0.9 cholesterol/hdl 3.58±0.72 3.14±0.85 0.053 triglycerides/hdl 3.4±2 1.74±0.97 0.001 m: male; f: female; c: child; a: adolescent; bmi: body mass index; bp: blood pressure; fbs: fasting blood sugar; homa-ir: homeostasis model assessment of insülin resistance; hba1c: hemoglobin a1c; hgb: hemoglobin; ldl: low-density lipoprotein; hdl: high-density lipoprotein. increase mortality. in addition, sudden cardiac death can occur in obese children without significant structural abnormalities. in this case, attention was drawn to ventricular repolarization anomalies. abnormalities in the stage of ventricular repolarization, which is a complex electrical event, are considered as an important risk factor for ventricular arrhythmias, one of the causes of sudden cardiac death [28]. for this purpose, prolonged qt and qtc have been used in ecg, especially long qtc has been shown to cause cardiac arrhythmias such as ventricular tachycardia and fibrillation [29]. guven et al. [30] reported that obese patients had longer qtc periods than normal individuals. in our study, qtc times were longer in obese children and adolescents, however, we could doi 10.18502/sjms.v17i2.11451 page 163 sudan journal of medical sciences zehra ilhan et al. table 4: comparison of the ecg parameters of the groups according to insulin resistance. features insulin resistance (+) (n = 25) insulin resistance (-) (n = 25) p-value qrs (ms) 80.8 ± 9 85.2 ± 1.5 0.067 qtmax (ms) 357.3 ± 25.2 368.5 ± 25.3 0.12 qtmin (ms) 335.7 ± 24.4 343.9 ± 26 0.25 pulse (/min) 92.4 ± 15.7 85.2 ± 13.9 0.091 rr (second) 0.06 ± 0.1 0.72 ± 0.12 0.082 qt (ms) 346.5 ± 24.6 356.2 ± 25.4 0.11 qtc (ms) 426.5 ± 17.4 420.9 ± 21.4 0.31 qtd (ms) 21.6 ± 6.8 24.6 ± 7 0.12 qtdc (ms) 26.6 ± 8.5 29.1 ± 8.7 0.3 jt (ms) 269.9 ± 19.9 272.8 ± 27.5 0.67 jtc (ms) 332.3 ± 16.5 321.7 ± 17.7 0.033 tp-e (ms) 83.7 ± 10.1 87.7 ± 9.6 0.16 tp-e/qt 0.24 ± 0.02 0.24 ± 0.03 0.55 tp-e/qtc 0.19 ± 0.02 0.2 ± 0.02 0.1 tp-e/jt 0.31 ± 0.04 0.32 ± 0.05 0.3 tp-e/jtc 0.25 ± 0.03 0.27 ± 0.03 0.054 ms: milliseconds; qrs: ventricular depolarization time; qtmax: longest time showing ventricular depolarization and repolarization; qtmin: ventricular depolarization and repolarization, shortest time; rr: distance between two rs; qt: qtmax + qtmin sum; qtc : corrected qt; qtd: difference between qtmax and qtmin; qtdc: corrected qt dispersion; jt: qrs end (point j) to the end of the t wave; jtc: corrected jt; tp-e: the time between the peak point of the t wave and the end of the t wave. not find a relationship between insulin resistance and this parameter. this suggests that obesity prolongs qtc regardless of insulin resistance in children and adolescents. there are some who are skeptical about the relationship between prolonged qtc distance and ventricular arrhythmia [31]. therefore, it has been suggested to use different parameters in estimating the risk of arrhythmia. for this purpose, the tp-e interval, which corresponds to the time of ventricular repolarization, has begun to be used [32]. studies have shown that prolongation in the tp-e interval is associated with ventricular arrhythmia [33] and scd [34]. there are publications stating that tp-e/qt and tpe/qtc derived from these parameters can be used in the early prediction of ventricular arrhythmias that may develop [35], and there are also opponents [36]. our study has shown that these parameters are affected in obese children and adolescents, as well as in adults. unlike qt, which shows both depolarization and repolarization, the jt interval shows only the ventricular repolarization period [37]. inanir et al. [38] found that tp-e/qt and tp-e/qtc were also prolonged in addition to tp-e, which is one of the new markers showing ventricular repolarization in adult morbid obese. tp-e/jt derived from tp-e doi 10.18502/sjms.v17i2.11451 page 164 sudan journal of medical sciences zehra ilhan et al. and jt, which reflect the area of ventricular repolarization alone, is considered as a more valuable marker than tp-e/qt in reflecting repolarization anomalies [38]. the jt interval varies depending on the heart rate, it is recommended to use the jtc, the heart rate-corrected form of this parameter, to use jt more effectively [39]. qtc and jtc are alternatives for each other because elongation in both values has been associated with increased risk of ventricular arrhythmia [40], however, jtc is considered to more accurately reflect ventricular repolarization [41]. apart from tp-e, jt and jtc, it is stated that the increase in tp-e/jt and tp-e/jtc derived from these parameters can also be used in the determination of ventricular repolarization anomaly [38]. in our study involving children and adolescent obese patients, prolonged detection of tp-e/jt and tp-e/jtc suggested that these parameters could be used in predicting ventricular arrhythmia at this age. even in the absence of cardiac disease, weight-stable obese persons have a higher risk of arrhythmias and sudden death, and the risk of scd increases with increasing weight [42]. our study showed that jtc times were longer in children and adolescents with insulin resistance (332.3 ± 16.5 vs 321.7 ± 17.7, p = 0.033), this result showed that insulin resistance except obesity increased ventricular repolarization abnormality. ventricular repolarization anomalies may cause ventricular tachyarrhythmias. ventricular tachyarrhythmias leading to scd may occur even in obese individuals without heart disease [43]. it can be said that insulin resistance in obese children and adolescents is an independent risk factor that may prolong the jtc, which is an indicator of ventricular repolarization disorder. the limitation of our study is that it is a single-center study with a low number of individuals. multicenter and larger series are needed for more precise results. 5. conclusion insulin resistance and other comorbidities of obesity may cause ventricular repolarization abnormalities at an early age. jtc, an ecg parameter, can be a guide in assessing ventricular repolarization abnormality and the risk of arrhythmia in insulin-resistance patients. acknowledgements doi 10.18502/sjms.v17i2.11451 page 165 sudan journal of medical sciences zehra ilhan et al. ethical considerations the study protocol was approved by the ethics committee of abant i̇zzet baysal university (no. 2018/31). competing interests the authors declared no potential conflicts of interest. availability of data and materials funding the authors received no financial support for this research. references [1] who. 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(1988). cardiac failure and sudden death in the framingham study. american heart journal, vol. 115, no. 4, pp. 869–875. doi 10.18502/sjms.v17i2.11451 page 169 introduction materials and methods statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests funding references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12128 production and hosting by knowledge e research article diagnostic reference levels in mammography in the asian context chamudi ishara rajamuni1,2 and bimali sanjeevani weerakoon2* 1postgraduate institute of science, university of peradeniya, peradeniya, sri lanka 2department of radiography/radiotherapy, faculty of allied health sciences, university of peradeniya, peradeniya, sri lanka orcid: bimali sanjeevani weerakoon: https://orcid.org/0000-0003-0843-6389 abstract background: breast cancer is the most frequent cancer among the female population globally. therefore, early detection is helpful for effective treatments and to reduce the mortality rate. mammography is a radiological examination done with low-energy x-rays to detect abnormalities in breast tissue. this study aims to review the literature to evaluate the techniques, protocols, and conversion factors used to determine the diagnostic reference levels (drls); within the asian continent using both phantomand patient-based data. methods: related articles were systematically reviewed via pub med, google scholar, and freehand search with the aid of relevant terms. related abstracts in english were screened, and suitable articles were selected after reviewing the full-text. four hundred and thirty abstracts were screened for relevance, and 12 articles were selected. results: the study comprises four phantom-based and eight patient-based studies. the studies varied between the types of test subjects, conversion factors, breast compression thickness, and dose calculation protocols. this obstructs continuing the drls with the updates and comparisons among countries. establishments of drls in asian countries are less than the rest of the world. drls should be measured continuously, and should be updated based on other clinical parameters of the patients. conclusion: drls in mammography were measured from time to time in different geographical locations in asia by following various techniques. but when compared with the other regions of the world, there is less consideration for establishing drls in asia. there should be standard protocols and updated conversion factors according to the advancements of the technology to ensure radiation protection with optimal absorbed dose with appropriate image quality. keywords: mammography, diagnostic reference level, mean glandular dose how to cite this article: chamudi ishara rajamuni and bimali sanjeevani weerakoon* (2022) “diagnostic reference levels in mammography in the asian context,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 401–415. doi 10.18502/sjms.v17i3.12128 page 401 corresponding author: weerakoon; email: bsw888@gmail.com, bsw888@ahs.pdn.ac.lk received 23 april 2022 accepted 2 july 2022 published 30 september 2022 production and hosting by knowledge e rajamuni, weerakoon. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences rajamuni, weerakoon 1. introduction breast cancer is the most frequent cancer among the female population globally. this impacts 2.1 million women each year [1]. in 2018, it was estimated that 627,000 women died due to breast cancer; this was 15% of total cancer deaths among women worldwide [1]. at present, breast cancer cases among asian women are still lower than in their western counterparts [2]. however, there will be a gradual growth of reported cases among asian women in the near future due to the changes in lifestyle and the technical advancements in the diagnostic field [3]. currently, closer to one-quarter (24%) of breast cancer incidences were reported in the asia-pacific region (a total of 404,000 cases at a ratio of 3:100,00 women), and of them, higher percentages were reported among chinese (46%), japanese (14%), and indonesian (12%) females [4]. early detection of breast cancers is helpful for effective treatments and to reduce the mortality rate. mammography is a radiological examination done with low-energy x-rays to detect abnormalities in breast tissue. mammograms are performed on both symptomatic and asymptomatic women. according to the current guidelines of the american college of radiology (acr) and the national comprehensive cancer network (nccn), women in their 40s should begin annual mammogram screening. but those who have had breast cancer previously and who have a family history of breast or ovarian cancer should get medical advice, and must undergo mammography examinations before their 40s [5]. in the asian region, there are fewer national population-based screening programs. also, the mortality rate increases due to cultural and economic obstacles and misunderstandings about the disease [4]. breast tissue is radiosensitive; therefore, mammography examination may induce a cancer risk in healthy women. therefore, the amount of radiation to the patients during the examination should be kept as low as reasonably achievable (alara). according to the international commission of radiation protection (icrp) recommendations, there are two principles of radiation protection. they are the justification for the protection and optimization of radiation protection while considering diagnostic reference levels (drls) [6]. in mammography, mean glandular dose (mgd) is the dose quality management factor [7], and this mgd depends on surface air kerma and conversion factors [6]. according to the annals of icrp 2016, there are two methods for dose assessment in mammography. drl is a parameter used in quality control processes and radiation dose level comparison among different manufacturers. drl is a selected quantity of radiation dose defined as: an investigation level, applied as a quantitative measurement, doi 10.18502/sjms.v17i3.12128 page 402 sudan journal of medical sciences rajamuni, weerakoon on absorbed doses in the air, a simple phantom made up of tissue-equivalent material or directly on the representative patient [8]. in the early stages of medical imaging, mammography was film-screen based and with the advancement of technology the era of computed mammography (cr) and digital mammography (dm) emerged introducing the tomosynthesis techniques, which produces 3d images. this advancement had a significant influence on image quality and dose reduction. however still, most asian countries do not have any national breast screening programs. in early studies, radiation dose on the breast tissue was measured using various perspectives. different researchers define the dose as air kerma [9], entrance surface air dose [10], mid breast dose [11], total energy transmission to the breast [12], and average glandular tissue [13]. however, it was later decided that the dose to the breast could be measured as the mean glandular dose (mgd), which is the most effective method of measuring the dose because the mammary glands are highly sensitive to ionizing radiation. at present, authorities responsible for radiation protection such as the international commission of radiation protection (icrp) [14], the united states national council on radiation protection and measurements [15], the british institute of physics and engineering in medicine (ipem) [44], european protocol [17], and the international atomic energy authority (iaea) [18] recommend this standard measurement. mgd is not a direct measurement, it is calculated by considering certain assumptions and the nature of the breast tissue. moreover, it is required to consider technical factors of the machine such as kvp, hvls, tube output, and automatic exposure control (aec) mode [19]. conversion factors are established by the monte-carlo method [8]. there are both phantom-based established drls as well as patient-based drls. phantombased drls do not reflect the clinical environment well due to the variation in the composition of the patients’ breast tissue. therefore, phantom-based drls are the best measurements for quality assurance of the machine, while patient-based drls give more information for the application in a clinical setting. drls are not statistic values; therefore, it should be continuously updated according to the advancement of hardware and software. in 2014, a review was done by a group of australian researchers regarding the state of the established mammography drls in the world [20]. according to their findings, there is less contribution for drls in asian countries. most asian countries are yet to develop the drls in mammography. this study was done to review the literature to evaluate the current state of mammography drls in asian countries. doi 10.18502/sjms.v17i3.12128 page 403 sudan journal of medical sciences rajamuni, weerakoon 2. materials and methods 2.1. search strategy and study selection this study was done as a systematic review using preferred reporting items for systematic reviews and meta-analyses (prisma) [21]. literature was searched on databases like pubmed and google scholar. in addition, articles and other references not available in the databases were cross-searched using google search. following search terms were applied “mammography,” “mammography examination,” “screening,” “drls,” “diagnostic reference levels,” “mgd,” “average glandular dose,” “phantom-based drls,” “patient-based drls,” “asia,” and “asian countries.” the search was carried out with and without filters, such as the type of article (original research articles), geographical location (asian continent), and the language (english). as the first step, the articles were selected by screening the title, abstract, and keywords. the abstracts of studies discussing mgd in mammography were taken into a full-text review. after referring to the mammography quality control manual 2018 [22], selected articles were separated as phantom-based and patient-based drls. best matching articles were considered first, followed by the publication date. studies in the english language were included. 2.1.1. data extraction general details such as author names, country, and sample size were extracted in each study. mgd at 75𝑡ℎ percentile and 95𝑡ℎ percentile was extracted. two reviewers independently did the data extraction. 3. results twelve articles published between 2000 and 2020 were deemed eligible for inclusion. figure 1 presents the articles’ search strategy. new data synthesis was done by considering the variation of mgd with breast compression thickness at the 75𝑡ℎ and 95𝑡ℎ percentile values at the distribution. the selected 12 studies covered the different geographical locations of the asian continent. among them, three studies were only on phantom-based data, eight were based only on patient-based data, and one was based on both phantomand patientbased data. there are four major quality control protocols published by the american doi 10.18502/sjms.v17i3.12128 page 404 sudan journal of medical sciences rajamuni, weerakoon college of radiology (acr) [22], the european protocol (ep) [23], the iaea, ipsm [16] protocol, and two methods for conversion factors were followed to calculate mgd and determine drls. 74 articles identified through manual searching n oit a cifit n e di 356 articles identified through database searching 141 articles are duplicates s c r e e n in g e li g ib il it y 289 articles remain after removing duplicates 269 were excluded after screening title and abstract 10 full-text articles excluded due to the absence of drls, clinical data with <50 sample size. 21 full articles were evaluated for eligibility in c lu d e d 12 articles included figure 1: flow chart of preferred reporting items for systematic review and meta-analysis (prisma). 3.1. techniques of drl measurements using phantom-based data phantom is a highly specialized object made up of tissue-equivalent material used in medical imaging for dosimetry, quality control, and equipment calibration. phantombased drls are essential in assessing the performance of the machine at the installation and ongoing quality control programs. further, this technique is also crucial in evaluating the drls during the comparisons between the previous studies and at the stage of technological advancement. poly methyl methacrylate (pmma) is a commonly used doi 10.18502/sjms.v17i3.12128 page 405 sudan journal of medical sciences rajamuni, weerakoon phantom material as its radiation transmission property is similar to breast tissues. in this review, phantom-based studies done in asian countries are selected according to the type of phantom and the protocol used. in most studies, exposures were made under specified technical factors recommended by the manufacturers. selected machines were dr, cr, or screen film (sfm). phantoms used in these studies were not identical, and they were different in size and composition. the selected protocols and conversion factors also varied between the studies (table 1). three studies measured the entrance surface air kerma (esak) value, and the remaining study measured the breast entrance exposure (bee). when considering protocols and conversion factors, one study has followed the acr measurement protocol [22] with wu et al. [24] conversion factors. while the other three studies [18, 25, 29, 32]followed the acr measurement protocol [22]with dance et al. [26] conversion factors. an indian study [25]used an inexpensive in-house built phantom which consists of pmma, similar to the acr pmma phantom. it also followed acr protocol [22]with dance et al. [26] mgd conversion factors. however, in these selected studies, drl values cannot be compared directly without having a unique conversion calculation with a standard phantom. 3.2. drl measurements using phantom-based data there is a difference between the drls of the same type of phantom, which uses the same protocol and conversion factors. this may be due to the variation of technical parameters of different manufacturers. in a taiwanese study using the acr phantom, the 75𝑡ℎpercentile was obtained as 1.87mgy [27], but a turkish study [28]with the same phantom followed the iaea protocol with dance et al. [26] conversion factors produced the 75𝑡ℎ percentile as 2.0 mgy. in the indian study [25]conducted with an in-house built phantom similar to acr pmma, breast entrance exposure (bee) was measured by placing a thermoluminescence dosimeter (tld) within the engraved slot of the phantom. then the mgd was derived from bee using two different methods. the measured depth ranges in the phantom are 0.32 and 0.40 cm at 75% depth dose, 0.73 and 0.92 cm at 50% depth dose, and 1.54 and 1.78 cm at 25% depth dose. the difference in mgd values determined using two different methods was in the range of 17.5–32.6%. malaysian study [29] done with rmi156 phantom with acr protocol [22] and wu et al. [24] conversion factors produced 75𝑡ℎ percentile as 1.44 mgy. doi 10.18502/sjms.v17i3.12128 page 406 sudan journal of medical sciences rajamuni, weerakoon 3.3. techniques of drl measurements in patient-based data there is a large diversification in breast thickness and granularity within the female population around the world. this leads to a difference between the compressed breast thickness (cbt) and the amount of radiation dose received by the breast during mammography examination. therefore, establishing patient-based drls is significant for optimizing patient-specific radiation protection. a summary of the reviewed nine studies investigating patient-based drls is displayed in table 2. in almost all studies, necessary data for the calculations were obtained from the dicom images. in addition, all studies except one were conducted according to the european protocol [23]. the needed conversion factors were taken from wu et al. [24, 32] and dance et al. [26]. most studies considered the absorbed dose for craniocaudal (cc) mediolateral oblique (mlo) views in mammography examinations. all the analyses were done after performing qc procedures in the selected machines. however, it is worth highlighting that according to the results, a wide range of cbt among the female population was observed, and also mammography examinations were done with different imaging modalities of sfm, cr, and dr. therefore, the variation of the obtained mgd is unable to compare with other studies. table 1: summary of the studies related to phantom-based drls. country authors/year protocol/conversion factors method of data collection phantom type (thickness/e-cbt/ g %) average mgd mgy drl mgy 75% 95% turkey bor et al. (2008) [30] ipsm/dance et al. [26] measured esak br12 (40 mm/45 mm/50%) 1.46 2.0 taiwan hwang et al. (2019) [29] acr [22]/dance et al. [26] measured esak (using tlds) acr pmma acr sfm phantom acr dm phantom 42 mm/50% sfm 1.57 dr 1.55 1.87 india sharma et al. (2011) [25] acr [22]/dance et al. [26] ncrp-149 [31]/wu et al. [24] bee acr pmma 50 mm/50% 32–40mm – 75% depth dose 73–92 mm – 50% depth dose 154–178 mm – 25% depth dose malaysia jamal et al. (2003) [18] acr [22]/wu et al. [24] measured esak rmi156 42 mm/50% dr0 50–2.39 1.44 ipsm, institute of physical science in medicine; acr american college of radiology; ep, european protocol; iaea; international atomic energy agency; esak, entrance surface air kerma; iak, incident air kerma; bee, breast entrance exposure; pmma, poly methyl methacrylate; sfm, screen film mammography; dr, digital radiography; cr, computed tomography; ebct, equivalent breast compression thickness; g%, granularity; mgd, mean glandular dose; drls, diagnostic reference levels; tld, thermo luminescence dosimeters. 3.4. drl measurements using patient-based data the measured patient-based drls show a wide range at both the 75𝑡ℎ and 95𝑡ℎ percentiles, as shown in table 2. according to the findings, there is a higher mgd doi 10.18502/sjms.v17i3.12128 page 407 sudan journal of medical sciences rajamuni, weerakoon for the mlo view than the cc view and also drl is higher in sfm than that in cr and dr mammography machines. digital breast tomosynthesis (dbt) shows a higher value than that of 2d cr and dr systems. the range of mean drls of the reviewed studies at the 75𝑡ℎ percentile was 1.27–2.64 mgy and at the 95𝑡ℎ percentile was 1.2–2.4 mgy. two japanese studies in the cbt range of <45 mm show a 75𝑡ℎ percentile value of 1.91 [33] and 2.0 mgy [34]. although these studies were conducted in the same geographical location, the authors used two different dose calculation methods and protocols. a study conducted at qatar mgd for cc and mlo was 2.2 mgy and 2.5 mgy, respectively [35]. in this study, mgd was calculated according to the european protocol [23],and the dance et al. [26] conversion factors were used and the obtained values were higher than the mgds of other studies. this may be due to many factors such as the inclusion of symptomatic patients under the age of 40, the broad spectrum of cbt, the variation in the selection of the conversion factors, and the wide age range of the patients selected. a study done in iran [36] shows the 75𝑡ℎ percentile as 0.88 and 1.11 mgy for cc and mlo views, respectively. a study done in turkey [28]reported 1.3 and 1.8 mgy for cc and mlo views, respectively. a study done in china [37] reported that the mean mgd was about 1.6 mgy and the range of the mgd was from 0.39–5.01 mgy. furthermore, they concluded that mgd did not differ significantly between mlo and cc views and the mgd level was higher in cr than in dr and sfm. a study done in korea [38] found that the mgd per view of 2120 images was 1.81± 0.7 mgy, and they also concluded that kvp, mas, breast size, and cbt were positively associated with mgd. a worldwide survey [39] reported specific percentiles for different regions of the world. according to that, the mgd at the 75𝑡ℎ and 95𝑡ℎ percentiles was reported as 1.7 and 2.3 mgy for the asia-pacific region, respectively. for all geographic regions, the mgd per image for cc and mlo ranged from 1.4 to 1.5 mgy. a malaysian study [18] has shown that mgd differs between different ethnic groups within the asian continent; malay (3.36 mgy), chinese (3.31 mgy), and indian (3.44 mgy), and their cbt varied from 38 to 46, 33 to 39, and 40 to 48 mm, respectively. 4. discussion based on this review, two methods by dance et al. [26]and wu et al. [32] were used to calculate mgd..both methods are related to the characteristics of the x-ray spectrum and the granularity of the breast tissue. however, the selection of conversion factors depended on the manufacturer. dance et al. [26] conversion factors are the most suitable conversion factors with the technological advancement of the machine. wu doi 10.18502/sjms.v17i3.12128 page 408 sudan journal of medical sciences rajamuni, weerakoon table 2 country author number of images dose measuring method protocol and conversion factors bct mm mean glandular dose drls 75% 95% re iran bahreyni et al. [36]. (2013) 100 measured esak (tlds) ep [23] wu et al. [32] cc: 47 mlo: 53 smlo: 50–60 cc: 0.88 mlo: 1.11 cc: 0.88 mlo: 1.11 world wide geeraert et al. [39] (2012) 14,7497 estimated esak from dicom images n/a dance et al. [26] europe: 1.48 north america: 1.42 asiapacific: 1.42 europe: 1.6 north america: 1.6 asia-pacific: 1.2 europe: 2.4 north america: 2.1 asiapacific: 23 qatar naemi et al. [35] (2020) 150 measured esak (dicom images) ep [23] dance et al. [26] cc-60.3 ± 13.9 mlo67.9 ± 12.9 cc–2.2 mlo450 2.5 japan kawaguchi et al.𝑎 [34] (2014) 300 measured esak ep [23] dance et al. [26] smlo:30-40 mlo:37.6 smlo:1.88 mlo:1.84 smlo:2 turkey ayd𝚤n et al. [28] (2020) 6309 measured esak mgd esd ep [23] dance et al. [26] 40–49 50.1 cc–1.3 mlo–1.8 cc–2.3 mlo–2.7 cc–4.2 mlo–4.8 cc < 2 50–64 49.3 cc–2.2 mlo–2.6 cc–3.8 mlo–4.4 mlo < 2.5 japan asada et al. [33] (2014) na estimated esak ep [23] dance et al. [26] 42 1.58 1.91 china xiang et al. [37] (2014) 420 measured esak ep [23] dance et al. [26] 13–75 1.6 2.0 korea baek et al. [38] (2017) 560 estimated esak 47.9 1.81 malaysia jamal et al. [18] (2003) measured esak acr[22] wu et al. [24] malay: 38–46 chinese: 33–38 indian: 40–48 3.36 3.31 3.44 acr, american college of radiology; ep, european protocol; esak, entrance surface air kerma; iak, incident air kerma; sfm, screen film mammography; dr, digital radiography; cr, computed radiography; bct, breast compression thickness; g, glandularity; mgd, mean glandular dose; drls, diagnostic reference levels; tld, thermoluminescence dosimeter; cc, cranio-caudal; mlo, medio-lateral oblique; smlo, standard medio-lateral oblique. et al.[32]conversion factors are limited to a few x-ray spectra, namely mo/mo, mo/rh, and rh/rh. the phantom studies used different types of phantoms according to the selected protocol. acr and the european guidelines introduced two standard phantoms, and both consist of pmma. the composition of the phantoms and their standards vary with the advancement of technology. in-house-built phantoms, at low cost, with a similar composition to standard phantoms also had an equivalent performance on mgd measurement. doi 10.18502/sjms.v17i3.12128 page 409 sudan journal of medical sciences rajamuni, weerakoon drls are calculated at the 75𝑡ℎ and 95𝑡ℎ percentile of the dose distribution. calculations of the percentiles depend on various parameters such as age, weight, height, and bmi of the selected sample. when there is a large range of data, the 75𝑡ℎ percentile is commonly used. the application of the 75𝑡ℎpercentile mentioned the importance of dose reduction by 25%. the 95𝑡ℎ percentile is suitable for a small range of data distribution and needed only 5% of dose reduction interventions. the 75𝑡ℎand 95𝑡ℎpercentiles are essential due to the difference in dose distribution in screening mammography and diagnostic mammography. especially in the case of pathological conditions which affect breast composition. determination of the drl should satisfy with optimum image quality for better image interpretation accuracy. depending on the protocol followed, there was a wide range of cbt. phantoms that followed ep used thicker equivalent cbt (53 mm) while acr phantoms followed thinner equivalent cbt (42 mm). in patient-based studies, the mean cbt varied for the same protocol; therefore, a range of cbt was given for patient-based studies. this is due to the variation of breast composition with patient-related factors such as age, bmi, and hereditary of the females in different geographical locations of asia. no patient-based study was able to provide a standard breast compression thickness. a plot of cbt versus drls used as a good quality control measure for nonstandard breast thicknesses. table 3: summary of the protocols related to reviewed articles. protocol test subjects digital/sfm conversion factors reference levels for standard breast standard patient number nature of the phantom acr 2018 n/a pmma (4.2 cm/50%) 2d digital sfm dbt dance (2000) [26] <2.0 acr1999 n/a pmma (4.0/4.2 cm/50%) sfm wu (1991) dance (1990) [26] sobol (1990) <=3.0 eu protocol 2006 minimum 10 patients pmma (4.5/5.3 cm/50%) digital sfm dance (2000) [26] <2.5 iaea protocol 2007 10–50 patients pmma (4.0/5.0 cm/50%) digital sfm dance (2000) [26] n/a ipem 2005 minimum 10 patients pmma (4.5/5.3 cm/50%) digital sfm dance (2000) [26] <3.5 acr, american college of radiology; eu, european protocol; sfm, screen film mammography; dr, digital radiography; cr, computed radiography; bct, breast compression thickness; ipsm, institute of physical sciences in medicine; iae, international atomic energy agency. drls in mammography were measured from time to time in different geographical locations in asia by following various techniques. however, when compared with other regions of the world, there is less consideration for establishing drls in asia. most of the studies followed eu protocol and acr protocol with dance et al. [26] conversion doi 10.18502/sjms.v17i3.12128 page 410 sudan journal of medical sciences rajamuni, weerakoon factors. most countries have never continued the records on drls within the last 20 years. due to the variation in the bct, age, bmi, g%, and technological advancement, there is a range of drls. therefore, establishing internationally recognized protocols and updated conversion factors is essential for inter-study comparison and to ensure radiation protection with optimal absorbed dose with appropriate image quality. measurement of mgd of various patients regularly and calculation of drls according to the standard protocols and conversion factors will be helpful in ensuring radiation protection in mammography. acknowledgements none. competing interests none declared. availability of data and material all information pertaining to the review is available upon reasonable request to the corresponding author. funding none. references [1] world health organization. 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(2012). breast characteristics and dosimetric data in x-ray mammography – a large sample doi 10.18502/sjms.v17i3.12128 page 414 sudan journal of medical sciences rajamuni, weerakoon worldwide survey. iaea 2012 international conference on radiation protection in medicine [conference session]. bonn, germany. doi 10.18502/sjms.v17i3.12128 page 415 introduction materials and methods search strategy and study selection data extraction results techniques of drl measurements using phantom-based data drl measurements using phantom-based data techniques of drl measurements in patient-based data drl measurements using patient-based data discussion acknowledgements competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12085 production and hosting by knowledge e research article adherence to immunosuppressive medications in kidney transplant patients at three centers in khartoum state, sudan: a cross-sectional hospital study alaa abdalla abbas1, manhal eltigani ahmed1, sara mohammed el_hassan mohammed1, shahd shakir gar-alnabi1, wafa abdalla mohammed1, musaab ahmed2, mohamed hassan ahmed3, and safaa badi1* 1department of clinical pharmacy, faculty of pharmacy, omdurman islamic university, khartoum, sudan 2college of medicine, ajman university, ajman, united arab emirates. center of medical and bio-allied health sciences research, ajman university, ajman, united arab emirates 3department of medicine and hiv metabolic clinic, milton keynes university hospital nhs foundation trust, eagelstone, milton keynes, buckinghamshire, uk orcid: alaa abdalla abbas: https://orcid.org/0000-0002-6488-6934 manhal eltigani ahmed: https://orcid.org/0000-0003-0955-5873 sara mohammed el_hassan mohammed: https://orcid.org/0000-0002-3950-9344 shahd shakir gar-alnabi: https://orcid.org/0000-0001-9551-6904 wafa abdalla mohammed: https://orcid.org/0000-0001-7784-9086 musaab ahmed: https://orcid.org/0000-0002-2300-9919 mohamed hassan ahmed: https://orcid.org/0000-0001-8045-6996 safaa badi: https://orcid.org/0000-0003-3204-983x abstract background: graft survival post-kidney transplantation is of paramount importance to patients and nephrologists. nonadherence to immunosuppressive therapy can be associated with deterioration of renal function and graft rejection. this study aimed to evaluate the adherence to immunosuppressive medications in kidney transplant patients at three centers in khartoum, sudan. methods: in this descriptive cross-sectional hospital-based survey, 277 post-kidneytransplant patients were recruited. data were collected using a questionnaire and analyzed using the spss v.23. our scoring method was calculated based on morisky medication adherence scale (mmas-8) related to immunosuppressive medications and was expressed as questions in the questionnaire; every correct answer was given one mark, then the marks were gathered and their summation was expressed. results: overall, 33% ,45%, and 22% of the studied participants reported high, medium, and low adherence, respectively. the major factor for nonadherence was forgetfulness affecting 36.1% of those who did not adhere. the cost of the immunosuppressive medications did not negatively affect any of the participants’ adherence (100%). however, a significant association was seen between adherence and occupational status, duration of transplantation, shortage of immunosuppressants, recognizing the name of immunosuppressant, side effect, and forgetfulness (p-values = 0.002, 0.01, 0.006 , 0.000, 0.022, and 0.000, respectively). logistic regression analysis showed a significant association with occupational status, side effects, and forgetfulness. how to cite this article: alaa abdalla abbas, manhal eltigani ahmed, sara mohammed el_hassan mohammed, shahd shakir gar-alnabi, wafa abdalla mohammed, musaab ahmed, mohamed hassan ahmed, and safaa badi* (2022) “adherence to immunosuppressive medications in kidney transplant patients at three centers in khartoum state, sudan: a cross-sectional hospital study,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 313–329. doi 10.18502/sjms.v17i3.12085 page 313 corresponding author: safaa badi; email: safaabadi30@gmail.com received 1 september 2021 accepted 7 april 2022 published 30 september 2022 production and hosting by knowledge e alaa abdalla abbas et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences alaa abdalla abbas et al conclusion: only one-third of the participants were classed as “highly adherent” to their immunosuppressant medications. factors that can affect adherence to immunosuppressant medications were occupational status, side effects, and forgetfulness. keywords: adherence, immunosuppressive medications , kidney transplantation, khartoum, sudan 1. introduction nonadherence is defined as any “deviation from the prescribed medication regimen that is sufficient to affect adversely the intended effect of the regimen.” nonadherence to immunosuppressive therapy is associated with an increased risk of graft loss, an increased number of late acute rejections, and a significant increase in plasma level of creatinine over time. this ultimately results in higher treatment costs and poorer patient outcomes[1]. based on the previous studies, approximately one-third of solid organ transplant recipients might have nonadherence during a year, leading to about 36% of kidney allograft rejection. at three years post-transplantation, nonadherence among the recipients of kidney transplant can cost up to $33,000 per patient. nonadherence to immunosuppressants results in about 125,000 deaths per year, and 33–69% of hospital admissions [2]. in the usa, a cross-sectional study among 54 kidney transplant patients showed that 81.6% of patients were adherent to their immunosuppressant medication [3]. at the clinic of nephrology, clinical centre niš, serbia, another cross-sectional study observed that the adherence was estimated to be 71.7% and only 28.3% did not follow the prescribed therapy. this study concluded that kidney transplant patients had a high level of adherence[4]. another study showed that 67.4% of the 297 kidney-transplant patients were considered fully adherent to their immunosuppressive medication [5]. the duration of transplant can negatively influence adherence to immunosuppressant medication [1, 6]. a published study showed that at five months post-transplant, 95% of renal transplant patients remained adherent with their free immunosuppressant, however, by 12 months following the transplant, only 48% of the same cohort remained adherent[7]. in contrast, other studies stated that nonadherence is higher in early first post-transplant patients than the later one [8]. importantly, nonadherence was measured by self-report and collateral reports which showed a nonadherence of 23.7% and 3.8%, respectively, doi 10.18502/sjms.v17i3.12085 page 314 sudan journal of medical sciences alaa abdalla abbas et al while the combination of the two showed a total nonadherence of 26.4%. this study showed that forgetfulness was the greatest cause of non-adherence [9]. it is worth mentioning that education, employment, and country of origin were also significantly associated with adherence, also predictors of nonadherence included a greater period of time since transplant[10]. one study showed that 75% of nonadherent patients were found to have low calcineurin inhibitor levels. however, when this cohort of patients were provided with free medication, they became more adherent [11]. it is important to mention that the cost associated with immunosuppressant medication is an important factor in adherence in some situations, and may lead to increased risk for acute allograft loss [12–14]. different factors can be related to nonadherence such as increased serum creatinine levels – a marker of decreased kidney function; noncompliant patients had a significantly higher increase in the plasma level of creatinine over time compared with compliant patients (p < 0.001) [15]. besides, with respect to the effect of demographic status on medication adherence, some studies suggest male to be more likely to be nonadherent [16], while others show a higher risk of nonadherence in females [17]. however, many studies have found no association between medication adherence and gender[18–20]. in addition, some studies have shown younger age to be associated with nonadherence [16, 21, 22], while others have found older kidney-transplant patients to have a greater extent of nonadherence [23]. nevertheless, some studies have found no association between them[19, 24, 25]. the patients’ level of education is another factor. some studies have found no association between nonadherence and education level following renal transplantation [18, 24], while others suggest that higher level of education is associated with better adherence or vice versa [16]. moreover, some research has been conducted on the relationship between immunosuppressants adherence and ethnicity – while most studies found no association[18, 19, 24], some have found white americans to have higher adherence than african americans[26]. some research have established that higher socioeconomic status is associated with high adherence[27]; however, others found no association between them [18, 19, 24]. nonadherence consensus conference summary reported that decreased adherence to immunosuppressive medications directly contributes to allograft injury and induces chronic dysfunction [28]. nevins et al. showed that excellent post-transplant medication adherence is critical to improved outcomes and the later consequences of medication nonadherence [29]. therefore, the current study aimed to assess the adherence to immunosuppressant medication among sudanese kidney transplant patients. doi 10.18502/sjms.v17i3.12085 page 315 sudan journal of medical sciences alaa abdalla abbas et al 2. materials and methods 2.1. study setting the current study was a hospital-based descriptive cross-sectional survey carried out in the department of nephrology at ahmed gasim hospital, ibn sina hospital and dr. salma center for kidney disease between may and august 2018. 2.2. inclusion and exclusion criteria patients who had kidney transplantation and were receiving immunosuppressant post-surgery were included. patients taking immunosuppressive medication for nontransplant purposes and those who had not exceeded one month post-transplant were excluded. 2.3. sample size and sampling technique the sample size was estimated using the following equation: n = n/1 + n(e)2, where: n = sample size to be computed n = total population size e = degree of accuracy desired (or accepted margin error and it is usually set to be 0.05) using the above formula, a sample size of 281 was calculated. n = 948/(1 + 948(0.05)2) n = 281. we used stratified sampling technique and considered each center as a stratum and the number of patients in each center was calculated from their total capacity in one month according to their proportion in the centers. the number of patients collected from ahmed gasim, ibn sina, and dr. salma center for kidney was 180, 59, and 42, respectively. accordingly, ahmed gasim hospital represented 64%, ibn sina represented 21%, and dr. salma represented 15% of patients. the patients within each center were selected by simple random sampling method. doi 10.18502/sjms.v17i3.12085 page 316 sudan journal of medical sciences alaa abdalla abbas et al 2.4. data collection tool patients who came to the follow-up outpatient clinic were invited to participate in the study. twenty questionnaires were collected as a pilot study from ahmed gasim hospital and ibn sina hospital, and the questionnaires were standardized and modified until the last version was obtained. the questionnaire consisted of a set of sociodemographic characteristics, length of time post-transplant, and treatment using eight-items of morisky medication adherence scale. the questionnaires were filled during face-to-face interviews with the participants. 2.5. morisky medication adherence scale (mmas) the mmas-8 is a questionnaire with eight questions whose wording is formulated to avoid the “yes” bias seen in chronic care patients. this is important as it allows the patient to respond to questions and to fully disclose to a clinician about their nonadherence. items 1 through 7 have response choices yes or no whereas item 8 has 5-point likert response choices. each no is rated as 1 and each yes is rated as 0 except for item 5, in which each yes is rated as 1 and each no is rated as 0. for item 8, if a patient chooses response 0 the score is 1, and if they choose response 4 the score is 0. responses 1, 2, 3 are respectively rated as 0.25, 0.75, 0.75. the total mmas-8 scores can range from 0 to 8 and have been categorized into three levels of adherence: high adherence (score = 8), median adherence (score of 6 to <8), and low adherence (score <6) [30]. 2.6. data analysis data were analyzed using the statistical package for social sciences (spss) version 23 and excel 2010. we used descriptive statistics (frequency tables, means, standard deviation, median) as well as inferential statistics (chi-square test and logistic regression test). 2.7. ethical consideration approvals were obtained from omdurman islamic university, the ministry of health, ahmed gasim hospital, ibn sina hospital, and dr. salma center for kidney. verbal doi 10.18502/sjms.v17i3.12085 page 317 sudan journal of medical sciences alaa abdalla abbas et al consent was also obtained from selected participants after explaining the purpose of the study and the right to refuse or withdraw at any time during the study. 3. results a total of 281 kidney transplant patients were recruited in the study. of them, 4 declined and 277 accepted to complete the study. the median age of the participants was 42 years, and a majority of them were male (71.1%) and married (69.3%). in addition, 54.2% of the participants lived in their own homes. most patients were educated at least up to the high school level, however, more than half were unemployed. the median duration of years post-kidney transplantation was three years. out of the 277 patients in the study, 13.7% had their kidney transplants less than three months ago; 27.1% between three months and a year; 36.5% between one and six years, 11.6% between seven and ten years, and 11.2% longer than 10 years. moreover, 71.8% of the participants reported having comorbid diseases – of them, 83% had hypertension pretransplantation and 17% post-transplantation, while only 28.3% had developed diabetes pre-transplantation and 71.7% post-transplantation (table 1). 33% 45% 22% 0%0% adherence of par!cipants higly adherent medium adherence low adherence figure 1: high, medium, and low adherence among the participants. doi 10.18502/sjms.v17i3.12085 page 318 sudan journal of medical sciences alaa abdalla abbas et al table 1: demographic characteristics of the participants (n = 277). demographic data percentage gender male 71.10% female 28.90% marital status married 69.30% single 28.50% divorced 2.20% widowed 0% educational level illiterate 5.80% primary school 42.20% high school 35% bachelor degree 15.90% postgraduate 19.10% occupational status employed 37.50% retired 9.70% unemployed 52.70% accommodation status own a house 54.20% did not own a house 45.80% duration since transplantation <3 months 13.70% 3 months to 1 year 27.10% 2–6 years 36.50% 7–10 years 11.60% >10 years 11.20% co-morbid diseases hypertension (before transplantation) 54.50% hypertension (after transplantation) 10.80% diabetes (before transplantation) 5.40% diabetes (after transplantation) 13.70% 3.1. factors affecting the adherence of patients to immunosuppressive medications overall, 85% of the patients recognized the name of the immunosuppressant that they had taken. all patients had bought their medication from the centers using health insurance, so the price was not an issue. however, medications can sometimes be in short supply in sudan. about 17% of the participants reported having experienced a doi 10.18502/sjms.v17i3.12085 page 319 sudan journal of medical sciences alaa abdalla abbas et al table 2: morisky scale results for immunosuppressant’s among studied participants (n = 277). questions percentage (%) yes no do you sometimes forget to take your medications? 36.8% 63.2% people sometimes miss their medication for reason other than forgetting. thinking over the past two weeks, were there any days when you did not take your medications? 30.7% 69.3% have you ever cut back or stopped taking your medications without telling your doctor because you felt worse when you took it? 2.2% 97.8% when you travel or leave home, do you sometimes forget to bring along your medications? 13.7% 86.3% did you take all your medications yesterday? 98.2% 1.8% when you feel like your symptoms are under control, do you sometimes stop taking your medications? 0.4% 99.6% taking medications every day is a real inconvenience for some people. do you ever feel hassled about sticking to your treatment plan? 19.9% 80.1% how often do you have difficulty remembering to take all your medications? a. never / rarely 67.5% b. once in a while 14.8% c. sometimes 14.8% d. usually 2.5% e. all the time 4% shortage of immunosuppressants. of them, 42% bought their medication from another pharmacy out of health insurance, while 29% reported ordering them from outside sudan. what governs adherence in patients is adequate education and counselling. therefore, as part of the study, we also looked at the topics and tactics used by health providers in sudan regarding adherence and compliance. the most popular topic discussed by doctors (65%) were investigations and blood tests. about 48.7% of participants reported that doctors discussed the medication regimens with them. while treatment compliance and medications side effects were discussed with 36.5% and 39% of patients, respectively. with regards to the barriers that prevent patients from taking their immunosuppressants medication, 59.2% reported that nothing can prevent them from taking their medications while only 36.1% complained of forgetfulness as a barrier to adherence and only 8.3%, 4%, 3.2% reported immunosuppressant’s unavailability, cost (when there is shortage within health insurance), and side effects as barriers to adherence, respectively. doi 10.18502/sjms.v17i3.12085 page 320 sudan journal of medical sciences alaa abdalla abbas et al table 3: associations between adherence and demographic data using the chi-square test. immunosuppressant’s adherence immunosuppressant’s adherence high adherence medium adherence low adherence occupational status employed 25.00% 39.40% 35.60% retried 40.70% 44.40% 14.80% 0.002 unemployed 37.00% 48.60% 14.40% duration of transplantation <3 months 57.90% 28.90% 13.20% 3 months to 1 year 34.70% 49.30% 16.00% 2–6 years 22.80% 48.50% 28.70% 0.01 7–10 years 37.50% 34.40% 28.10% >10 years 25.80% 51.60% 22.60% shortage of immunosuppressants yes 12.80% 57.40% 29.80% no 37.00% 42.20% 20.90% 0.006 recognizing the name of immunosuppressant yes 28.00% 47.00% 25.00% no 61.00% 31.70% 7.30% 0.000 presence of side effects yes 0.00% 44.40% 55.60% no 34.00% 44.80% 21.30% 0.022 forgetfulness as a barrier yes 1.00% 45.00% 54.00% no 50.80% 44.60% 4.50% 0.00 table 4: predictors for immunosuppressant’s adherence among studied participants using logistic regression test (n = 277). variable p-value odd ratio (or) 95% c.i. for or lower upper time since transplant 0.283 0.953 0.874 1.040 shortage of your immunosuppressant? 0.926 1.045 0.409 2.670 recognizing the names of immunosuppressant 0.359 0.514 0.124 2.131 forgetfulness 0.000 30.718 12.038 78.388 occupational status 0.026 4.389 1.197 16.090 side effect 0.042 8.153 1.075 61.814 tacrolimus, mycophenolate, and prednisolone regimen was used by 45.1% of the patients, while tacrolimus, azathioprine, and prednisolone was used by 37%. doi 10.18502/sjms.v17i3.12085 page 321 sudan journal of medical sciences alaa abdalla abbas et al calcineurin inhibitors level was reported within therapeutic range among 75% of the participants. moreover, in more than three quarters of the studied participants, the lipid panels (tg, ldl, cholesterol) and renal function tests (serum creatinine, blood urea nitrogen) were reported within the normal range, while fasting blood glucose and hemoglobin levels were reported controlled in 71% and 63% of the participants, respectively. 3.2. morisky scale results more than one-third of the participants reported that they sometimes forget to take their medications, and only about 20% reported that they rarely feel hassled about sticking to their treatment plan (table 2). moreover, 33% of the study participants reported high adherence, 45% reported medium adherence, and low adherence was reported by 22%. while categorizing the participants into a binary category, we found that 78% adhered (high adherence + medium adherence) to their immunosuppressive medications while 22% did not (low adherence) (figure 1). 3.3. tests of significance we performed the kruskal–wallis test to compare the mean rank of total adherence score with occupational status and duration of transplantation and found that there was a significant difference among these groups (p-values = 0.001, 0.001). 3.4. test of associations 3.4.1. chi-square test when this test was performed to determine the associations between the adherence and other variables, we found a significant association between immunosuppressant’s adherence with occupational status, duration of transplantation, shortage of immunosuppressants, recognizing the name of immunosuppressant, side effect, and forgetfulness (table 3). doi 10.18502/sjms.v17i3.12085 page 322 sudan journal of medical sciences alaa abdalla abbas et al 3.4.2. logistic regression analysis by using logistic regression to determine the factors that predict the adherence, forgetfulness, presence of side effects, and occupational status had a statistically significant association with adherence. adhering participants were not likely to forget taking their medications by 31 times than those who did not adhere (p = 0.000, ci for or = 12.038– 78.388). moreover, those who were unemployed adhered to their medications by 4.5 times than those who were not (p = 0.026, ci for or = 11.197–16.090). furthermore, adhering participants were not likely to stop taking their medications when they experience side effects by eight times than those who did not (p = 0.042, ci for or = 1.075 – 61.814) (table 4). 4. discussion adherence to medications post-transplant is important for both graft and patient survival. the adherence was assessed using morisky scale eight-items questions. this study showed a high rate of nonadherence to immunosuppressant medication (67.1%). the duration of transplantation, knowledge of the name of immunosuppressive medications, and shortage of drugs were found to be statistically significant with the degree of adherence to immunosuppressive medications. importantly, patients with less than three months of renal transplantation were significantly adherent compared to those who had had transplantation more than three months prior. this result was similar to other studies [1, 5, 6]. in our study, unemployed patients were more adherent to medications than those who were employed. this result is similar to that of denhaerynck et al.’s [10] and contrary to kiley et al.’s [16]. zelikovsky et al. showed that better knowledge was associated with high adherence to immunosuppressive medications [31]. knowledge about immunosuppressants in our study was also significantly associated with adherence. the availability was not considered a barrier for immunosuppressive medications adherence; however, this study revealed a significant association between drug shortage and immunosuppressant’s adherence. this may be explained by the fact that medication is offered free of charge in renal transplant centers. shortage of medication is likely to occur in those who do not regularly follow-up in outpatients’ clinics. the issue of age and adherence to immunosuppressant medication showed different opinions. for instance, some studies show older patients to have good adherence, while others show younger patients to be more adherent, and some show no association between age and nonadherence[16, doi 10.18502/sjms.v17i3.12085 page 323 sudan journal of medical sciences alaa abdalla abbas et al 18, 21–23]. in this study, we found no association between age and adherence. we also found no association between gender and adherence of immunosuppressive medication, although the number of male participants was higher than the females, there was no significant difference. this was also shown in other studies [19, 20]. however, some studies suggest that male kidney transplant recipients are more likely to be nonadherent[16, 23], while others show female recipients to have a higher risk of nonadherence [17]. similar result was also observed for the role of education. for instance, education was shown to have no association with adherence, some studies have shown education to be associated with good adherence[16, 18, 23, 24, 32]. interestingly, our study showed that the number of educated patients was the largest group with no significant association with medications adherence. forgetfulness was the most common barrier that affects immunosuppressive medications adherence (p = 0.000). similar to our results, some studies found that forgetfulness has been examined qualitatively and established as the main reason for intermittent nonadherence [33–35]. since medication was offered free of charge in all the three transplant centers, it is not surprising that medication cost was not significantly associated with adherence. it is worth mentioning, studies outside sudan showed that medication cost is an important factor in patients’ adherence [13, 14, 36]. in our study, side effects was significantly associated with immunosuppressive medications adherence (p = 0.022); this can be attributed to the fact that only 36.5% of the participants stated that their doctors counseled them about the importance of medications compliance, and this may be contributed to the higher percentage of nonadherent patients which was found in this study. this study is not without limitations. first, the study is a descriptive cross-sectional survey as adherence is a dynamic process and difficult to be assessed objectively using cross-sectional study. also, the study might be associated with recall bias compared with pill count, the effective method for assessing adherence. moreover, the sample size was collected from three public centers in khartoum state by convenience random sampling; therefore, the results of this study cannot be generalized in other geographical areas in sudan. a prospective study is necessary to study the natural history of nonadherence. despite these limitations, the study is novel and provided an accurate estimate of the prevalence and risk factors associated with nonadherence to immunosuppressant medication in kidney transplant patients in sudan. doi 10.18502/sjms.v17i3.12085 page 324 sudan journal of medical sciences alaa abdalla abbas et al 5. conclusion only one-third of the participants were highly adherent to the immunosuppressants. occupational status, duration of transplantation, shortage of immunosuppressants, recognizing the name of immunosuppressant, side effects, and forgetfulness were significantly associated with adherence. 5.1. what is already known on this topic 1. graft survival post kidney transplantation is of paramount importance to patients and nephrologists. 2. nonadherence to immunosuppressive therapy can be associated with deterioration of renal function and graft rejection. 3. globally, nonadherence to immunosuppressive medication can occur in young and old patients. 5.2. what this study adds 1. only one-third of participants were classed as ”highly adherent” to their immunosuppressant medication. 2. factors that can affect adherence to immunosuppressant medication were occupational status, side effects, and forgetfulness. 3. a prospective future study is necessary to study the impact of nonadherence to immunosuppressant medication in renal transplant patients in all states of sudan. acknowledgements the authors are grateful to the staff of all the three centers. ethical considerations approvals were obtained from omdurman islamic university, the ministry of health, and ahmed gasim hospital, ibn sina hospital, and dr. salma center for kidney. verbal consent was also obtained from selected participants after explaining the purpose of the study and the right to refuse or withdraw at any time. doi 10.18502/sjms.v17i3.12085 page 325 sudan journal of medical sciences alaa abdalla abbas et al competing interests the authors declare no competing interest. references [1] couzi, l., moulin, b., morin, m., albano, l., godin, m., barrou, b., alamartine, e., morelon, e., girardot-seguin, s., mendes, l., misdrahi, d., cassuto, e., & merville, p. 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(2018). a pilot randomized controlled trial to promote immunosuppressant adherence in adult kidney transplant recipients. nephron, 135, 6–14. doi 10.18502/sjms.v17i3.12085 page 329 introduction materials and methods study setting inclusion and exclusion criteria sample size and sampling technique data collection tool morisky medication adherence scale (mmas) data analysis ethical consideration results factors affecting the adherence of patients to immunosuppressive medications morisky scale results tests of significance test of associations chi-square test logistic regression analysis discussion conclusion what is already known on this topic what this study adds acknowledgements ethical considerations competing interests references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11450 production and hosting by knowledge e editorial medical research and publication in sudan: what sudan could reasonably expect to achieve in the longer term, and how? ansam mohamed abdelaziz dafalla1 and nazik elmalaika husain2* 1student, faculty of medicine, university of science and technology, omdurman, sudan 2department of pathology, faculty of medicine and health sciences, omdurman islamic university, sudan orcid: nazik elmalaika husain: https://orcid.org/0000-0001-8333-5735 since its start in the early 19𝑡ℎ century, sudan has had a robust and hugely influential medical research community. dr andrew balfour, an englishman, proposed and equipped a tropical medicine research laboratory in 1902 [1, 2]. as a result, numerous entomology and parasitology breakthroughs were achieved, including discovering novel mosquito species that spread malaria, dengue fever, filariasis, and yellow fever [2, 3]. the sudanese pioneer, professor mansour ali haseeb, the first sudanese head of the stack in medical research laboratories 1952, made his research as impactful as possible [4, 5]. for example, when a small-pox outbreak occurred in gazira in 1938, a study involved collecting pathogenic material from patients and animals. other notable research studies included yellow fever, leishmaniasis, poliomyelitis, schistosomiasis, and onchocerciasis [5]. haseeb was one of the first editors of sudan medical publication [4] who also contributed to the alhakeem journal, the official journal of the medical students of khartoum university [6]. the above activities have resulted in a moderately healthy domestic output with regards to publishing research and developing journals, but not quite as advanced as one might expect given the current and historical strength of sudan’s research activities. according to the sudanese federal ministry of health’s research department, 31 research centers are working in health research; one specializes in endemic diseases, one in malaria, and another in mycetoma (the latest update of the department’s website was in 2015) [8]. as of march 2019, there were 19 arabic and 30 english online sudanese journals published by different higher education institutes [9]. unfortunately, none of them is scopus-indexed, and only one is pubmed-indexed. much research is published in local and other journals, but not in scopus-indexed. according to the scimago institute ranking, sudan ranks 100𝑡ℎ in the number of annual publications worldwide (240 countries) in all subject areas from 1996 to 2021. with 13,309 documents, 12,464 citable documents, 181,733 citations, 14,717 self-citations, how to cite this article: ansam mohamed abdelaziz dafalla and nazik elmalaika husain* (2022) “medical research and publication in sudan: what sudan could reasonably expect to achieve in the longer term, and how?,” sudan journal of medical sciences, vol. 17, no. 2, pp. 152–156. doi 10.18502/sjms.v17i2.11450 page 152 corresponding author: nazik elmalaika husain; email: nazikhusain@gmail.com received 10 june 2022 accepted 14 june 2022 published 30 june 2022 production and hosting by knowledge e ahmed s. a. el sayed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:nazikhusain@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ahmed s. a. el sayed 13.65 citations per document, and 119 h index. these metrics are based on scopus® data as of april 2022 [10]. furthermore, sudan ranks 15 out of 59 african countries and 13 out of 22 arab countries in all categories, as seen in figures 1 and 2. 0 1000000 2000000 3000000 4000000 5000000 6000000 7000000 documents citable documents citations figure 1: number of documents, citable documents, and citations published in 1996–2021 by the first fifteen african countries (based on scopus data as of april 2022). 0 500000 1000000 1500000 2000000 2500000 3000000 3500000 4000000 4500000 5000000 e g y p t s a u d i a ra b ia t u n is ia a lg e ri a m o ro c c o u n it e d a ra b e m ir a te s ir a q jo rd a n l e b a n o n q a ta r k u w a it o m a n s u d a n p a le s ! n e b a h ra in s y ri a n a ra b r e p u b li c l ib y a y e m e n m a u ri ta n ia s o m a li a d ji b o u ! c o m o ro s documents citable documents citations figure 2: number of documents, citable documents, and citations published in 1996–2021 by the arab countries (based on scopus data as of april 2022). figure 3 shows the research subject areas with the most publications: medicine, biochemistry, genetics and molecular biology, and agricultural and biological sciences. the medicine-categorized documents make 5115 documents and 92,361 citations, while citations per document are 18.06, and the h index is 95 (1996–2021). out of the medical papers published in 2021, 127 were on infectious diseases, 123 on public health, doi 10.18502/sjms.v17i2.11450 page 153 sudan journal of medical sciences ahmed s. a. el sayed environmental and occupational health, 43 on medical microbiology, 9 on pathology and forensic medicine, and 306 miscellaneous [10]. 213 6 252 21 90 147 91 9 56 20 83 162139 18 24 142113 69 659 68 31 17 139152 3 82 48 0 100 200 300 400 500 600 700 n u m b e r o f d o c u m e n ts subject area figure 3: number of sudanese documents published in 1996–2021 according to the different subject areas (based on scopus data as of april 2022). with a strong history and a reasonable number of research centers and journals, sudan is expected to be a leading country in research and publications. however, lack of funding [11], time [12], conflict, political instability, and brain drain [13] are significant threats to medical and health research in the country. during the 1990–2001 period, sudan’s average expenses for all scientific research institutions made 0.11% of the country’s gross domestic product. and the average value declined consistently by 9% each year [10]. considering sudan’s current situation, seeking to reduce reliance on the public budget in financing research is a step in the right direction. it can be done by encouraging the private sector contribution and internal and external collaboration. in addition, linking scientific research to development requirements may convince decision-makers that spending on scientific research is an investment form whose returns are reflected positively in reducing poverty and achieving developmental goals. furthermore, strengthening and coordinating the professional relationship between research and the statistical production centers is essential. these centers can produce a quantitative knowledge base that helps decision-makers develop and implement poverty reduction strategies and evaluate their performance scientifically. another crucial step is reducing economic and political factors of expulsion to preserve minds and attract those who emigrated. training on research methods and ethics will increase the chance of publication in scopus-indexed journals and advance citable published doi 10.18502/sjms.v17i2.11450 page 154 sudan journal of medical sciences ahmed s. a. el sayed research. fortunately, many publishers incorporate a policy that waves publication fees for researchers in low and middle-income countries. references [1] elhadd, t. a. (2015). sir henry solomon wellcome and dr andrew balfour: an enterprise on the nile and the early foundation of public health and medical research in the sudan (1899–1935). journal of the royal college of physicians of edinburgh, vol. 45, no. 2, pp. 165–172. [2] adeel, a. a. (2013). a pioneer of tropical medicine worldwide: andrew balfour, of khartoum. sudanese journal of paediatrics, vol. 13, no. 1, pp. 63–74. [3] balfour, a. (1906). mosquito work in the anglo-egyptian sudan and in the anglo-egyptian sudan generally (second report of the wellcome research laboratories at the gordon memorial college, khartoum, education department, sudan government, pp. 15–28). wellcome collection. https://wellcomecollection.org/works/mxtm3d76 [4] salih, m. a. (2013). professor mansour ali haseeb: highlights from a pioneer of biomedical research, physician and scientist. sudanese journal of paediatrics, vol. 13, no. 2, pp. 66–75. [5] haseeb, m. a. (1978). a monograph on biomedical research in the sudan. khartoum: khartoum university press. [6] haseeb, m. a. (1959). on the history of kala-azar in the sudan. al hakeem, vol. 7, p. 39. [7] national centre for research. (2022). an overview of the center [internet]. national centre for research. shorturl.at/bmovb [8] federal ministry of health, republic of sudan. (n.d.). the origins of health research. http://www.fmoh.gov.sd/research/index.php [9] bakhit, s. (2019). new list of sudanese scientific journals. preprint. https://www.researchgate.net/publication/ 332058183_new_list_of_sudanese_scientific_journals_available_online [10] sjr. scimago journal & country rank. https://www.scimagojr.com/countrysearch. php?country=sd [11] nur, e. m. (2003). an evaluation of sudan’s research capacity in the light of the international development goals. journal of development economics, vol. 5, no. 2, pp. 140–70. doi 10.18502/sjms.v17i2.11450 page 155 https://www.researchgate.net/publication/332058183_new_list_of_sudanese_scientific_journals_available_online https://www.researchgate.net/publication/332058183_new_list_of_sudanese_scientific_journals_available_online https://www.scimagojr.com/countrysearch.php?country=sd https://www.scimagojr.com/countrysearch.php?country=sd sudan journal of medical sciences ahmed s. a. el sayed [12] ibn auf, a., awadalla, h., ahmed, m. e., et al. (2019). comparing the participation of men and women in academic medicine in medical colleges in sudan: a crosssectional survey. journal of education and health promotion, vol. 8, p. 31. [13] unesco. (2015). unesco science report: towards 2030. doi 10.18502/sjms.v17i2.11450 page 156 references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12077 production and hosting by knowledge e editorial “together we build our health”: paving way forward through analyzing the context and ensuring wide participation in the first and second health forums in sudan faihaa a. a. dafalla1, heitham awadalla2, and nazik elmalaika husain3* 1health planning directorate, federal ministry of health, sudan 2department of community medicine, faculty of medicine, university of khartoum, sudan 3department of pathology, faculty of medicine and health sciences, omdurman islamic university, sudan orcid: faihaa a. a. dafalla: https://orcid.org/0000-0002-0607-7610 heitham awadalla: https://orcid.org/0000-0002-0934-6417 nazik elmalaika husain: https://orcid.org/0000-0001-8333-5735 the health forum is an innovative model for how governments can increase public participation and intersectoral collaboration that could be adapted in other contexts [1]. toward the end of 2021, the federal ministry of health (fmoh) activated the ”minister advisory council” after four years of dormancy. the council acts as an advisory group to the ministry of health and comprises 20 senior experts in health in sudan. together with 26 specialty councils, members proposed to conduct a health forum where the health sector discusses priority issues within the strategic plan. this sudan journal of health sciences (sjms) editorial explores the policy process, initial outcomes, lessons learned from these two forums, and the way forward. in march 2022, the fmoh held the first health forum in which the national health sector reform and recovery strategic plan (2022–2024) (nhsrr-sp) was presented. the first forum aimed to develop a catch-up road map for operationalizing the strategic plan to maintain at least the basic health services continuity. in addition, it aimed to ensure the engagement, contribution, and ownership of partners and health professionals. in july 2022, the second health forum was conducted. its objective was first to ensure the alignment of the forum objectives with the strategic plan, statistically, and second, to ensure that the strategies set before are still valid, if not, then readjust it, as it was preceded by a fluid unstable context. sudan’s health system is overwhelmed by poverty-associated infectious diseases, nutritional deficiencies, restrictions, economic and management issues, and political instability [2, 3]. additionally, covid-19 exhausted the already fragile health system in 2020–2021 while working to prioritize and recover healthcare policies. how to cite this article: faihaa a. a. dafalla, heitham awadalla, and nazik elmalaika husain* (2022) ““together we build our health”: paving way forward through analyzing the context and ensuring wide participation in the first and second health forums in sudan,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 287–291. doi 10.18502/sjms.v17i3.12077 page 287 corresponding author: nazik elmalaika husain; email: nazikelmalaika@oiu.edu.sd, received 5 september 2022 accepted 8 september 2022 published 30 september 2022 production and hosting by knowledge e dafalla et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dafalla et al being pivotal in emergency preparedness, disease/disaster mitigation, and recovery, the fmoh in sudan prioritized emergency care and primary healthcare to revive the health system to achieve universal health coverage during the early transitional period. gratefully, it was primarily supported by national and international partners, particularly during the covid-19 period. however, still, sudan’s current health status needs more attention. hence, this forum came to fruition in a noticeably short period under the theme that “we build our health together.” the preparation for the first health forum held on march 1–3, 2022 was extensive. two committees were formulated; logistic and scientific. the scientific committee was responsible for developing templates, suggesting topics for papers, and reviewing and approving the draft technical papers. the process took more than four months of extensive meetings and technical work. by the time of the event, 17 technical reports across the six strategic projects were documented in a booklet published on the sudan health observatory website [4]. the event concluded with 91 recommendations (figure 1) for the six strategic projects. it ranged from immediate operational to long-term interventions across the strategic period (up to the end of 2024). figure 1: grouping of the recommendations according to the thematic areas of the forum (n = 91). progress can be seen in the implementation of the 14 recommendations planned beyond the year’s first half (table 1). in addition, there are other recommendations designed to be in the other quarters. the progress in the performance has varied among the strategic projects, which was understandable given the context. however, the overall doi 10.18502/sjms.v17i3.12077 page 288 sudan journal of medical sciences dafalla et al table 1: the progress of the recommendations planned for the second quarter 2022, up to june 2022*. # theme recommendation/task task progress theme progress challenge the way forward 1 theme one: governance establish a mechanism to ensure institutionalization of the longterm vision including the recommendation of this forum. 20% 42% instability at the leadership and senior level. improvement of the institutional process through development of institutional quality management system 2 theme one: governance development of comprehensive national m&e plan. 25% limited number of staff able to work at the development process along with competing priorities. the committees started the revision and update on the existing m&e national plan in august 2022. 3 theme one: governance assignment of the global health directorate as the focal entity for all the initiated partnerships. 80% – relocate the coordination desks at the dggh, hac, and the states: a meeting with hac and the states’ representative to agree on the different roles and responsibilities regarding the partnership coordination. 4 theme one: governance activation of coordination mechanisms, especially intergovernmental bodies, and creation of joint secretariat for the various coordination mechanisms. 25% due to the lack of support to the forum secretariats from aics, frequency of meetings to be conducted was affected negatively. the uncertainty of the political context affective the national forums activation and optimization of their use. develop a concept note on the joint secretariat role, follow-up mechanism, membership, location, etc. decide on the need and feasibility on conducting an nphcc meeting and arrange as needed. 5 theme one: governance revise the mandates, relationships, and structures of the various planning and m&e units at fmoh 30% – to finalize the concept and initiate discussion on the suggested arrangements. 6 theme one: governance develop a public–private partnership framework (q4) (10%) – recruit a consultant and start the process. 7 theme one: governance finalization and adoption of the accountability framework (q3) (20%) – reactivate the technical committee and develop the assessment tool. 8 theme two: phc reactivate the existing committee for the death and birth registration. 100% 90% interruption of the supply of registers to the states. weak coordination at state level. 9 theme three: hospitals finalization of the hospital sector benefit package. 85% 68% a validation workshop for the benefit package had been conducted but package not finalized. expected to be finalized by the end of quarter three 2022. 10 theme three: hospitals expand the existing triage system in selected hospitals in selected states 50% although there are 10 selected states, aljazeera is not selected, however, it is selected by the strategic plan for the first phase on the demonstration project. theme four health security, preparedness, response, and resilience against all hazards with a focus on covid-19. nothing for the first six months – 11 theme 5: capacities take the opportunity of donors’ fund to generate the needed evidence for health. 10% 30% research priorities were not identified yet the research database establishment/upgraded through support from donors. doi 10.18502/sjms.v17i3.12077 page 289 sudan journal of medical sciences dafalla et al table 1: the progress of the recommendations planned for the second quarter 2022, up to june 2022*. # theme recommendation/task task progress theme progress challenge the way forward 12 theme five: capacities to revise and update sudan health observatory website structure and contents 50% availability of the documents from fmoh and partners. the upgrade is planned to take place by the end of the year. to be funded by the government which will enable the use of the government infrastructure. 13 theme six: pharmacy secure sufficient resources and domestic public funding to ensure the availability of essential medicines and vaccines. 0% 20% economic hardship at the country level. – 14 theme six: pharmacy ensure availability of the lifesaving medication. 80% – – 14 theme six: pharmacy activate the national pharmaceutical coordination council to ensure efficiency and effectiveness of the pharmaceutical sector. 0% technical secretariat needs to be assigned to activate the mechanism and for follow-up. – 16 theme six: pharmacy to strengthen the regulatory authority to play its roles. 0% low resources allocation. – progress is around 49%. most recommendations progress beyond their timeline (the first three months after the forum). as table 1 implies, the progress in the primary health care (phc) and hospitals themes is good. in contrast, the capacities and pharmaceutical themes need hard work due to sector complexity and the multiplicity of the stakeholders. the main observation in the healthcare system is the fragmentation of the efforts exerted for improvement, causing inefficiency and leading to stagnation in some areas and even deterioration in others. therefore, the fora call for an active collective and organized effort by all stakeholders to support all parts of the healthcare system strengthening and resilience guided by the strategic plan. in conclusion, the health forums’ theme “together we build our health” implies the need for collective efforts beyond the country’s capacities. it is reaching out to everyone and appreciates the efforts of the diaspora around the globe. the theme has extended to the second forum and is expected to last, affirming that health is a shared responsibility that starts with the individual. references [1] rasanathan, k., posayanonda, t., birmingham, m., & tangcharoensathien, v. (2012). innovation and participation for healthy public policy: the first national health assembly in thailand. health expectations, 15(1), 87–96. doi 10.18502/sjms.v17i3.12077 page 290 sudan journal of medical sciences dafalla et al [2] ebrahim, e. m. a., ghebrehiwot, l., abdalgfar, t., & juni, m. h. (2017). health care system in sudan: review and analysis of strength, weakness, opportunity, and threats (swot analysis). sudan journal of medical sciences, 12(3), 133–150. https://doi.org/10.18502/sjms.v12i3.924 [3] osman, a. k., ibrahim, m., elsheikh, m., karrar, k., & salih, h. (2021). saving the fundaments: impact of a military coup on the sudan health system. sudan journal of medical sciences, 16(4), 567–574. https://doi.org/10.18502/sjms.v16i4.9959),. [4] the sudan health observatory. (n.d.). knowledge hub. 4. the sudan health observatory. http://sho.gov.sd/controller/knowledge_hub.php?sm_id=133&mid=110&lid=1 doi 10.18502/sjms.v17i3.12077 page 291 references sudan journal of medical sciences volume 12, issue no. 4, doi 10.18502/sjms.v12i4.1352 production and hosting by knowledge e research article graduates perception towards instructional methods of emergency medicine: affecting their self-confidence in emergency departments mohamed daffalla awadalla, ahmed abd elrahman abdalla, and sami mahjoub taha department of surgery, faculty of medicine, gezira university, sudan abstract background: teaching emergencies has the ability to provide medical students with animportant knowledge and skills. in this study, we assessed the perception of faculty of medicine, university of gezira graduates regarding instructional methods of emergencies and their performance in emergency departments. materials and methods: this is a cross-sectional survey, which was conducted among newly graduated doctors, during their internship rotation. we assessed the graduateperception about instructional methods of teaching em during medical school and how they deal with emergencies. likert’s scale of five points was used for assessment of the graduate response. this data was used for a correlation analysis. result: ninety three graduates were enrolled. male doctors’ numbers was 41(44%). most of the graduated doctors agreed that clinical round and practical session in teaching emergency are useful among 80(86%) and 74(79.6%) of them respectively. less number of graduated students 45 (48.4%) and 43 (36.6%) agreed that problem-based learning and seminar are useful in teaching emergency. numbers of graduates who feel competence to assess and diagnose patients, request a relevant investigation, and can put a treatment plan and start the managements are 60(68.8%), 76(81.8%) and 61 (65.6%) respectively. conclusion: there are some strength and weakness in emergency teaching during medical school which affects their self-confidence when dealing with emergencies. keywords: emergency medicine, instructional methods, perception, self-confidence, graduates how to cite this article: mohamed daffalla awadalla, ahmed abd elrahman abdalla, and sami mahjoub taha, (2017) “graduates perception towards instructional methods of emergency medicine: affecting their self-confidence in emergency departments,” sudan journal of medical sciences, vol. 12 (2017), issue no. 4, 207–214. doi 10.18502/sjms.v12i4.1352 page 207 corresponding author: mohamed daffalla awadalla; email: mohadaff22@gmail.com received 10 october 2017 accepted 18 december 2017 published 28 december 2017 production and hosting by knowledge e mohamed d. awadalla et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mohadaff22@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed d. awadalla et al 1. introduction emergency medicine specialty has the ability to enrich medical school curricula by providing students with diverse learning opportunities at all levels of education [1]. there are opportunities to integrate em contents in a wide range of pre-clinical courses such as pathophysiology, physical diagnosis, and medical ethics [1]. during the clinical years, em is often integrated into the curriculum either as part of a broader course heading or as a dedicated em clerkship. advantages of clinical education in em include reinforcement of basic life support skills, learning differentiation and treatment of common acute problems, and assessment of the undifferentiated patient [2]. teaching of em among undergraduates has gaps and problems. it needs motivations and challenges to reach educational targets [3]. still, teaching em done primarily through traditional methods such as lectures, tutorials, and bed side teaching in many medical schools [4]. at emergency departments, medical students, specialty trainee and nurses all of them get benefits from bed side training sessions [5]. other teaching techniques as case or problem based learning also used. but, there is difficulty in getting patients with acute condition suitable for teaching all the time. this motivates undergraduate’s educators to use simulation based learning [6]. simulation based training (sbt) by using skills lab facilities allow educators to structure training of undergraduate medical students for the acquisition of clinical skills in a simulated and sheltered learning environment. since such skills labs train students using manikins, part-task trainers or simulators, patient injuries arising from the inexperience of medical trainees can be prevented, thus fulfilling an ethical imperative [7]. the current survey was conducted to assess the perception of graduates regarding instructional methods during medical school. the study questions are the instructional methods of teaching em is useful or not, from graduates’ points of view. is there is any relation between teaching methods and doctors’ competence. 2. material and methods this is a cross sectional survey, conducted during march 2016. self-administered questionnaire was distributed to all interns (house-officers). we include all doctors working in medani teaching hospital (medical, surgical, pediatrics and obstetric departments). all participantsgraduated from faculty of medicine, university of gezira, within 1year. fmug is established in 1975 and the first patch was taken in 1978. at the time of the survey the participants completed four houseman ship rotations. doi 10.18502/sjms.v12i4.1352 page 208 sudan journal of medical sciences mohamed d. awadalla et al emergency contents in fmug are divided within the curriculum in the systems courses (pre-clerkship) e.g. cardio-pulmonary course and gastro-intestinal course integrated with basic science. there is no separate emergency course. also, emergency topics were taught within clerk-ship courses with more concentration in clinical and treatment concern. the instructional methods in this medical school are lectures, pbl, seminars, clinical rounds, attending ed duties. at the time of the study they did their intern-ship rotation (house-man). the intern spends 3 months in each one of the four main departments (department of medicine, surgery, pediatric, and obstetrics & gynecology). during this period, they follow the consultant, who is the direct supervise of them. they had activity of covering the emergency departments as a part of their consultant team. they will be also supervised by the registrars (residents) or medical officers (senior house-officer). this survey focused on evaluating the perception of the graduates regard the instructional methods of teaching emergency medicine. it gives information regarding their feeling andperception about the usefulness of instructional methods of emergency medicine. the datasheet addressed the following instructional methods; lectures, problem base learning,seminar, clinical round, practical session attendance, night duties attendance. the perception of the graduates upon their own selfcompetence when dealing with emergency inemergency department also included in the data. we look for any relation em teaching methods in medical school and graduate’s self-confidence in ed. likert scale was used to assess perception of the graduates regarding instructionalmethods. if the graduates are strongly agreed about the idea or the statement regarding the teaching method, this will score 5 out of 5 in the scale, and if he is strongly disagreeing, willscore 1. the data was collected using a self-administered questionnaire which were distributed to the participant and recollected in the same day. all collected data were tabulated for analysis. statistical analyses were performed using ibm spss statistics for windows, version 20.0 (ibm corp., armonk, ny). correlation analysis was performed and pearson’s correlation coefficient was calculated to assess the strength of correlation between em teaching methods and perception of graduates’ regard selfconfidence. a “p” value of less than 0.05 was considered statistically significant. ethical approval was obtained. 3. result total number of participants was 93 doctors all of them newly graduated; they just finished their internship training, male. male doctors’ numbers was 41(44%). their doi 10.18502/sjms.v12i4.1352 page 209 sudan journal of medical sciences mohamed d. awadalla et al figure 1: perception of graduates regarding em instructional methods. figure 2: likert scale regards teaching methods. perceptions toward instructional methods of teaching emergency medicine throughout the medical school curriculum were shown in (fig.1 &2). most of the participants agreed that clinical rounds (bed side teaching) and practical sessions (basic skills lab) were useful in teaching emergency medical problems, with 80(86%) and 74 (79.6%) respectively. average number of participants 55(58.1%) agreed that lectures were useful in teaching emergency medicine. less number of participants 45 (48.4%) and 43 (36.6%) were agreed that pbl and seminar were useful in teaching emergency. sixty five (67.9%) of participants agreed that night doi 10.18502/sjms.v12i4.1352 page 210 sudan journal of medical sciences mohamed d. awadalla et al strongly agree agree neutral disagree strongly disagree mean likert assessment and classify 35.5% 33.3% 23.7% 7.5% 3.9 request relevant investigation 32.3% 49.5% 14% 4.3% 4,09 plan and start managements 25.8% 39.8% 24.7% 8.6% 1.1% 3,8 t 1: perception of graduates’ regard confidence in emergency departments the graduates can do in ed instructional methods which related to competence p value assessment and diagnosis pbl 0.006 observe the emergency team 0.003 request relevant investigation pbl 0.008 observe the emergency team 0.022 practical teaching 0.020 plan and start managements participate in managements of patients 0.046 night duties 0.027 ed; emergency departments, pbl; problem based learning. t 2: relation between perception of graduates’ regard self-confidence in ed and em. duties attendance in the emergency department with emergency team was useful. in ed, 53(57%) of participants agreed that they observedthe ed team while working, while 54(58.1%) of them agreed that they participated with theed team while working. the mean average of likert scale is shown in (fig.1&2). the responses of graduates regard their self-competence on ed shown in (table 1.) sixty four (68.8%) participants were self-confident that they can assess and diagnose critically ill patients, 76(81.8%) of them were confidently can request relevant investigation, and 61 (65.6%) can put a treatment plan and start the managements with confidence. in this study, statistical relation between graduates’ self-confidence in ed and some instructional methods of teaching emergency shown is in (table 2). perceptions of graduates regarding assessment and diagnosis of critically ill patients in ed are significantly related to pbl (p value 0.006) and observe the emergency team (p value doi 10.18502/sjms.v12i4.1352 page 211 sudan journal of medical sciences mohamed d. awadalla et al 0.003). perceptions of graduates regarding request relevant investigation are significantly related to pbl (p value 0.008), practical teaching (p value 0.020) observe the emergency team (p value 0.022). perceptions of graduates regarding plan and start managements of critically ill patients in ed are significantly related to participate in managements of patients (p value 0.046) and night duties (p value 0.027). 4. discussion the instructional methods of teaching em in faculty of medicine university of gezira which re-evaluated are lectures, pbl, seminar, bedside teaching rounds, practical and simulated session and night duties attendance at emergency department. those methods are similar for teaching emergencies in malaysia [4] and united state [6] medical schools. in this study, perception of graduated doctors regard instructional methods is variable. clinical bed sides teaching and practical session (simulated lab session) get the highest points in this study. bedside teaching for emergencies has a great valuable role in teaching undergraduates students. they will expose to real life situations and scenarios in emergency departments. at emergency department, the tutor or instructor give them a lot of knowledge, skills, attitude and experiences that will not get by another modality. bed sides teaching should be used effectively to get the maximum benefit [9, 10]. in this study graduate’s perception regarding practical teaching (simulated lab session) is highly positive. this is matching the recent concept towards simulated based learning as effective tools in emergency medicine education and procedure skills training. in this study, lecture as a teaching modality for emergency get less point in comparison to bedside and practical teaching. in contrast, it gets higher points in comparison with pbl sessions and seminar. this contradiction is going with literature. a lot of papers highlight the strength of lecture [11-13]. some educators talk about lecture weakness in medical education. they critique the mode of instruction and its transfer of information as a one-way communication with little cognitive gain [14, 15]. in this study, the lowest points get by seminar and problem based learning. these low points reflect some dissatisfaction from graduate’s regard pbl and seminar. these types of instructional methods need more training to the tutor and teacher. we need to check the how it is conduct. also, some students prefer lecture because it is easy to get knowledge. in this study the graduates’ views regard their competence in the ed is variable more than two third of them can dell with emergency patients. they can assess and diagnose emergencies. also, they can request relevant investigation and doi 10.18502/sjms.v12i4.1352 page 212 sudan journal of medical sciences mohamed d. awadalla et al put plan of managements. we found significant relation between some instructional methods and competence in ed. these instructional methods are pbl, night duties attendance, observing emergency team and participate with the emergency team in the ed. 5. conclusion we can conclude that, the perception of graduates’ doctor’s regards teaching methods isabove average. more than two third of them have self-confidence regard dealing withemergency. lastly there is strong relation between pbl, night duties attendance, and observing emergency team and graduates’ self-confidence. one of the limitations is small sample size. participants cannot give conclusive comment regard the teaching methods. references [1] c. j. pitre, the unique educational value of emergency medicine student interest groups, the journal of emergency medicine, 22, no. 4, 427–428, (2002). [2] w. p. burdick, n. j. jouriles, g. d’onofrio, l. e. kass, j. f. mahoney, and k. m. restifo, emergency medicine in undergraduate education, academic emergency medicine, 5, no. 11, 1105–1110, (1998). [3] m. d. gismalla and a. a. alawad, undergraduate emergency medicine education: problems and challenges, austin emerg med, 3, no. 1, p. 1049, (2017). [4] i. m. saiboon, m. j. jaafar, n. s. ahmad, z. ahmad, f. a. hamzah, and s. m. jamal, simulation based education in delivering emergency medicine module, 388–393 [5] ws. thayer, osler the teacher. bull johns hopkins hosp, in osler the teacher. bull johns hopkins hosp 1919, 30, 198–200, 1230-1233, 303, 1919. [6] r. h. steadman, w. c. coates, m. h. yue, r. matevosian, b. r. larmon, l. mccullough, and d. ariel, simulation-based training is superior to problem-based learning for the acquisition of critical assessment and management skills, critical care medicine, 34, no. 1, 151–157, (2006). [7] a. ziv, p. root wolpe, s. d. small, and s. glick, simulation-based medical education: an ethical imperative, academic medicine: journal of the association of american medical colleges, 78, no. 8, 783–788, (2003). [8] d. c. kern, t. a. parrino, and d. r. korst, the lasting value of clinical skills, journal of the american medical association, 254, no. 1, 70–76, (1985). doi 10.18502/sjms.v12i4.1352 page 213 sudan journal of medical sciences mohamed d. awadalla et al [9] g. bandiera, s. lee, and r. tiberius, creating effective learning in today’s emergency departments: how accomplished teachers get it done, annals of emergency medicine, 45, no. 3, 253–261, (2005). [10] c. heidenreich, p. lye, d. simpson, and m. lourich, the search for effective and efficient ambulatory teaching methods through the literature, pediatrics, 105, no. 1, 231–237, (2000). [11] b. g. charlton, lectures are such an effective teaching method because they exploit evolved human psychology to improve learning, medical hypotheses, 67, no. 6, 1261– 1265, (2006). [12] b. graffam, active learning in medical education: strategies for beginning implementation, medical teacher, 29, no. 1, 38–42, (2007). [13] b. g. charlton, science school and culture school: improving the efficiency of high school science teaching in a system of mass science education, medical hypotheses, 67, no. 1, 1–5, (2006). [14] za. sebai, medical education: which way forward? j family community med, 8, no. 3, 17–18, (2001). [15] smith b edward h, lecturing: case studies, experience and practice. london: kogan; 2001. doi 10.18502/sjms.v12i4.1352 page 214 introduction material and methods result discussion conclusion references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10680 production and hosting by knowledge e editorial digital transformation in higher education institutions in a limited-resource setting: a luxury or a must despite challenges? nazik elmalaika husain department of pathology, faculty of medicine and health sciences, omdurman islamic university, omdurman, khartoum, sudan. orcid: nazik elmalaika husain: https://orcid.org/0000-0001-8333-5735 although digital transformation (dt) increases productivity, value creation, and social welfare [1] some still view it as a luxury that cannot be achieved in limited-resource settings. this editorial considers how the value of dt is increased when geopolitics, economic, and pandemic crises are combined with digitalization, particularly in a resource-limited setting. although dt is a hot topic right now, the benefits of digital products, services, and channels for academic ecosystems have been widely recognized since the 1990s. however, there is currently no commonly accepted definition for the term dt [2]. digital transformation is broadly used in business models. it is defined as “a process in which digital technologies cause disruptions, prompting strategic reactions from firms seeking to shift their value creation paths while managing structural changes and organizational constraints that influence the positive and negative results of this process” [2]. higher education institutions can be considered a business model; hence the exact definition is applied. in light of the recent innovation in products, processes, and business models, coupled with the unprecedented impact of covid-19, higher educational approaches to entrepreneurship are being reshaped in a way that emphasizes the social and local dimensions of innovation. in addition, over the last decade, digital technologies have enabled people to access big and open data, the internet of things, and crowdsourcing platforms. as a result, higher education institutions are encouraged to collaborate, create, and share knowledge and resources with the outside world using the new information and communication technology (ict) tools. more efficient, sustainable, and fair uses of the new or existing ict tools will ultimately lead to innovation [3]. there are two global trends that seem particularly relevant at the moment: the un’s sustainable development goals (sdgs) initiative, launched in 2015, and the education how to cite this article: nazik elmalaika husain (2022) “digital transformation in higher education institutions in a limited-resource setting: a luxury or a must despite challenges?,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 1–3. doi 10.18502/sjms.v17i1.10680 page 1 corresponding author: nazik elmalaika husain; email: nazikelmalaika@oiu.edu.sd published 31 march 2022 production and hosting by knowledge e nazik elmalaika husain. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:nazikelmalaika@oiu.edu.sd https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nazik elmalaika husain for sustainable development as a critical enabler of all sdgs. in addition, sdg 4 on quality education, which calls for inclusive and equitable quality education and lifelong learning for everyone, combines both approaches [3]. higher education institutions must adapt their existing teaching and learning strategies to survive and maintain their competitive position in the long run. higher education leaders have highlighted four principal aims. these objectives include improving the learning environment for students, increasing operational efficiency, increasing computer capacity for cutting-edge research, and stimulating educational innovation [4]. higher education institutions are primarily tasked with strengthening students’ employability skills for a specific vocation to prepare them to survive in the labor market for the next 30 or 40 years. as a result, higher education institutions must prioritize the development of students’ self-efficacy and adaptive skills [5]; digital transformation can assist with learning contextualization. courses and modules, as well as all learning environments, must focus on such competencies. if we can accomplish this, we will begin to revolutionize education by building concrete visualizations of “critical thinking in a field” and enhancing the ongoing learning there [4]. in response to covid-19, new methods have emerged for conducting education and business. these include hybrid or pure e-learning and e-work, which require an active digital transformation in the workplace [6]. moreover, when a firm has dt, it has lower cost, better operating efficiency, and better innovation success leading to better performance [7]. higher education institutions in lowand middle-income countries (lmics) need to reduce their costs, operate efficiently, and innovate to reach a better performance. these objectives can be fulfilled through efficient dt. moreover, learning or working from home through dt can save time and effort and reduce transportation costs, especially in areas with a wide geographical distribution of employees, students, or clients. furthermore, unstable political situations or lack of safety can be overcome by dt. nevertheless, dt is not just about technology. recent research has increased our understanding of specific aspects of the dt phenomenon. in line with previous findings on it-enabled transformation, research has shown that technology is only one piece of the intricate puzzle that must be addressed for businesses to remain competitive in the digital age [2]. companies invest millions into “digital transformation” initiatives, but the results are often not worth it. that is because they focus on technology rather than driving change. they should not just align technology investments with professional goals, but also lean on internal knowledge rather than outside consultants, acknowledging job losses doi 10.18502/sjms.v17i1.10680 page 2 sudan journal of medical sciences nazik elmalaika husain that may be felt, and using insider knowledge before outside consultants. moreover, they should understand how changes will affect customer experience and use process methods borrowed from the tech world to facilitate change (8). still, many challenges may face the implication of dt in higher education, particularly in lmics, including prioritization, decentralized decision-making, human resistance to change, gaps in digital tech talent, and a narrow view of return on investment (roi) [4]. despite all challenges, dt remains a must. higher education institutes with limited resources have to make intelligent collaborations and successful innovations to forge their path to the future. references [1] ebert, c. and duarte, c. (2018). digital transformation. ieee software, vol. 35, no. 4, pp. 16–21. [2] schallmo, d., williams, c., and boardman, l. (2017). digital transformation of business models — best practice, enablers, and roadmap. international journal of innovation management, vol. 21, p. 08. [3] kaputa, v., loučanová, e., and tejerina-gaite, f. a. (2022). digital transformation in higher education institutions as a driver of social oriented innovations. in c. păunescu, k.-l. lepik, and n. spencer (eds.), social innovation in higher education: landscape, practices, and opportunities (p. 61). springer international publishing: 61. [4] alenezi, m. (2021). deep dive into digital transformation in higher education institutions. education sciences, vol. 11, no. 12, p. 770. [5] chappell, c., gonczi, a., and hager, p. (ed.). (2020). competencybased education. in understanding adult education and training. routledge. https://www.taylorfrancis.com/chapters/edit/10.4324/978100311829918/competency-based-education-clive-chappell-andrew-gonczi-paul-hager [6] cho, h. y. and lee, h. j. (2022). digital transformation for efficient communication in the workplace: analyzing the flow coworking tool. business communication research and practice, vol. 5, no. 1, pp. 20–28. https://www.kci.go.kr/kciportal/ci/ serearticlesearch/cisereartiview.kci?serearticlesearchbean.artiid=art002811037 [7] zhai, h., yang, m., and cha, k. (2022). does digital transformation enhance a firm’s performance? evidence from china. technology in society, vol. 68, p. [8] tabrizi, b., lam, e., girard, k., et al. (2019). digital transformation is not about technology. harvard business review. https://hbr.org/2019/03/digital-transformation-is-notabout-technology doi 10.18502/sjms.v17i1.10680 page 3 https://www.kci.go.kr/kciportal/ci/serearticlesearch/cisereartiview.kci?serearticlesearchbean.artiid=art002811037 https://www.kci.go.kr/kciportal/ci/serearticlesearch/cisereartiview.kci?serearticlesearchbean.artiid=art002811037 references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12872 production and hosting by knowledge e commentary bay 11-7082: an anti-inflammatory drug for covid-19 mohadeseh nemati1, fahima danesh pouya1, elmira roshani asl1, yousef rasmi1,2* 1department of biochemistry, faculty of medicine, urmia university of medical sciences, urmia, iran 2cellular and molecular research center, cellular and molecular research medicine institute, urmia university of medical sciences, urmia, iran orcid: yousef rasmi: https://orcid.org/0000-0003-1506-1909 abstract the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is a new coronavirus named by the international committee on taxonomy of viruses. covid-19 patients have high mortality due to respiratory failure from acute respiratory distress syndrome (ards) induced by sars-cov-2. the abnormal activation of p21-activated kinase (pak1, rac/cdc42-activated kinase 1) is reported in covid-19. the pak1 induces nuclear factor kappa b (nf-κb) activation as well as inflammatory pathways through its stimulation. bay 11-7082 {(e) 3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile is one of the therapies that inhibit inflammation via mentioned signaling pathway, therefore, we suggest that this drug can potentially be effective in treating covid-19. keywords: bay 11-7082, covid-19, pak1 in late december 2019, a case of unknown pneumonia was described in wuhan, people’s republic of china (prc) [1]. the “covid-19” and “severe acute respiratory syndrome coronavirus 2” (sars-cov-2) are the names of the disease induced by novel coronavirus and the virus that suggested by the world health organization (who) and the international committee on taxonomy of viruses, respectively [2] respiratory failure from acute respiratory distress syndrome (ards) initiated by sars-cov-2 is the leading cause of mortality [3]. p21-activated kinase (pak1, rac/cdc42-activated kinase 1) is the key “pathogenic” kinase. the unusual stimulation of pak1 induces several disorders/diseases including viral infections such as covid-19 and influenza, and inflammation [4, 5]. in the pak1 signaling pathway, first, epidermal growth factor (egf) stimulates the epidermal growth factor receptor (egfr) and then activates the downstream factor, ras (guanosine-nucleotide-binding protein). this factor is upstream of pak1. in the end, pak1 may activate inflammatory pathways by nuclear factor kappa b (nf-κb) activation [6]. the nf-κb in most cells’ cytoplasm is bound to an inhibitory protein, ikb (inhibitory protein of nf-κb complex). it has been revealed that cytokines and how to cite this article: mohadeseh nemati, fahima danesh pouya, elmira roshani asl, yousef rasmi* (2023) “bay 11-7082: an anti-inflammatory drug for covid-19,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 117–120. doi 10.18502/sjms.v18i1.12872 page 117 corresponding author: yousef rasmi; email: rasmiy@umsu.ac.ir received 26 october 2020 accepted 19 december 2022 published 31 march 2023 production and hosting by knowledge e mohadeseh nemati et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohadeseh nemati et al egf, epidermal growth factor; egfr, epidermal growth factor receptor; ras, guanosine-nucleotide-binding protein; pak1, p21 activated kinase 1; nf-κb, nuclear factor kappa b; no, nitric oxide; pge2, prostaglandin e2; tnf-α, tumor necrosis factor-alpha; il-1β, interleukin-1β; il-18, interleukin-18; tlr, toll-like receptor; ros, reactive oxygen species; ikk, iκb kinase; ikb, inhibitory protein of nf-κb complex; nlrp3, nlr family pyrin domain containing 3. figure 1: anti-inflammatory effect of bay 11-7082 on covid-19. oxidative stress stimulation lead to the activation of nf-κb. in this stimulation process, iκb kinase (ikk) phosphorylates iκb, and then it undergoes proteolytic degradation by the proteasome-dependent pathway [7]. nuclear translocation of nf-κb elevates the transcription of several inflammatory factors including chemokines, adhesion molecules, and cytokines [7, 8]. so, we suggest the treatment of hyperinflammation using existing, approved therapies to decrease the rising mortality. one of the therapies that suppress inflammation is bay 11-7082 (e) 3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile that inhibits ikk and phosphorylation of ikb [9], so nf-κb remains in an inactive form. as a result, bay 11-7082 blocks the expression of tumor necrosis factor-𝛼 (tnf-𝛼), prostaglandin e2 (pge2), and nitric oxide (no), famous inflammatory responses created by activated nf-𝜅b [10]. the inhibitory effect of bay-11-7082 is frequently shown as an investigation test to determine the involvement of ikk, and nf-κb, in a biological process, for instance, lung adenocarcinoma in mouse models [11]. strickson et al showed that bay-11-7082 suppresses the activation of ikk indirectly in response to interleukin-1 or lipopolysaccharide (lps) in several cells such as t-cell leukemia and b-cell lymphoma [12]. also, it is shown that bay-11-7082 inhibits the nlr family pyrin domain containing 3 (nlrp3) inflammasome [13]. the inflammasome refers to doi 10.18502/sjms.v18i1.12872 page 118 sudan journal of medical sciences mohadeseh nemati et al assemblies that activate caspase-1 [14], which changes inactive pro-interleukin-1β (proil-1β) and pro-interleukin-18 (pro-il-18) into active pro-inflammatory cytokines il-1β and il-18 [15, 16]. these processes are designed in the innate immune cells’ cytoplasm due to threat signals [14]. the nlrp3 inflammasome is important as it is stimulated by danger signals, such as viruses, small molecule immune activators, bacteria, purified microbial products, crystalline or aggregated materials, and components of dying cells [14]. nlrp3 is expressed in the cytosol of dendritic cells, monocytes, lymphocytes, neutrophils, osteoblasts, and epithelial cells [17]. so, bay-11-7082 by inhibition of the nlrp3 inflammasome prevents the expression of the pro-inflammatory cytokines, il18, and il-1β in an nfkb-independent mechanism [13]. the investigations reported that serum il-1β increased in covid-19 patients [1]. according to this signaling pathway that is active in covid-19 and the inhibitory influence of bay-11-7082 on this pathway, we suggest that this drug can potentially be effective in treating covid-19 (figure 1). competing interests none declared. references [1] huang, c., wang, y., li, x., ren, l., zhao, j., hu, y., zhang, l., fan, g., xu, j., gu, x., cheng, z., yu, t., xia, j., wei, y., wu, w., xie, x., yin, w., li, h., liu, m.,…cao, b. (2020) clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet, 395(10223), 497–506. [2] world health organization. (2020). naming the coronavirus disease (covid-19) and the virus that causes it. brazilian journal of implantology and health sciences, 2(3). [3] ruan, q., yang, k., wang, w., jiang, l., & song, j. (2020). clinical predictors of mortality due to covid-19 based on an analysis of data of 150 patients from wuhan, china. intensive care medicine, 46(5), 846–848. [4] maruta, h. (2014). herbal therapeutics that block the oncogenic kinase pak1: a practical approach towards pak1�dependent diseases and longevity. phytotherapy research, 28(5), 656–672. [5] maruta, h., & he, h. (2020). pak1-blockers: potential therapeutics against covid-19. medicine in drug discovery, 6, 100039. [6] dammann, k., khare, v., & gasche, c. (2014). tracing paks from gi inflammation to cancer. gut, 63(7), 1173–1184. doi 10.18502/sjms.v18i1.12872 page 119 sudan journal of medical sciences mohadeseh nemati et al [7] bowie, a., & o’neill, l. a. (2000). oxidative stress and nuclear factor-κb activation: a reassessment of the evidence in the light of recent discoveries. biochemical pharmacology, 59(1), 13–23. [8] tedgui, a., & mallat, z. (2001). anti-inflammatory mechanisms in the vascular wall. circulation research, 88(9), 877–887. [9] pierce, j. w., schoenleber, r., jesmok, g., best, j., moore, s. a., collins, t., & gerritsen, m. e. (1997). novel inhibitors of cytokine-induced iκbα phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. journal of biological chemistry, 272(34), 21096–21103. [10] hussein, s. z., mohd yusoff, k., makpol, s., & mohd yusof, y. a. (2013). gelam honey attenuates carrageenan-induced rat paw inflammation via nf-κb pathway. plos one, 8(8), e72365. [11] xue, w., meylan, e., oliver, t. g., feldser, d. m., winslow, m. m., bronson, r., & jacks, t. (2011). response and resistance to nf-κb inhibitors in mouse models of lung adenocarcinoma. cancer discovery, 1(3), 236–247. [12] strickson, s., campbell, d. g., emmerich, c. h., knebel, a., plater, l., ritorto, m. s., shpiro, n., & cohen, p. (2013). the anti-inflammatory drug bay 11-7082 suppresses the myd88-dependent signalling network by targeting the ubiquitin system. biochemical journal, 451(3), 427–437. [13] juliana, c., fernandes-alnemri, t., wu, j., datta, p., solorzano, l., yu, j.-w., meng, r., quong, a. a., latz, e., scott, c. p., & alnemri, e. s. (2010). anti-inflammatory compounds parthenolide and bay 11-7082 are direct inhibitors of the inflammasome. journal of biological chemistry, 285(13), 9792–9802. [14] martinon, f., mayor, a., & tschopp, j. (2009). the inflammasomes: guardians of the body. annual review of immunology, 27, 229–265. [15] dinarello, c. a. (1998). interleukin�1β, interleukin�18, and the interleukin�1β converting enzyme. annals of the new york academy of sciences, 856(1), 1–11. [16] dinarello, c. a. (2009). immunological and inflammatory functions of the interleukin-1 family. annual review of immunology, 27, 519–550. [17] kummer, j. a., broekhuizen, r., everett, h., agostini, l., kuijk, l., martinon, f., bruggen, r. v., & tschopp, j. (2007). inflammasome components nalp 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. journal of histochemistry & cytochemistry, 55(5), 443–452. doi 10.18502/sjms.v18i1.12872 page 120 competing interests references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12552 production and hosting by knowledge e research article anxiety and depression among sudanese nurses during the covid-19 pandemic: a cross-sectional study hammad a. fadlalmola1, mohammed a. abdelmalik2,3*, huda kh. masaad4, abdalbasit a. mariod5,6, abdalla ma. osman7, eyas g. osman8, kalthoum i.yousif9, aisha m. adam10, sahar a. ebrahim11, amal m. elhusein12 1taibah university, almadenah, saudi arabia 2department of nursing, college of applied medical sciences at shaqra, shaqra university, saudi arabia 3faculty of medicine and health sciences, university of el imam el mahdi nursing, kosti, white nile, sudan 4applied medical science college, hafr albatin university, saudi arabia 5university of jeddah, saudi arabia 6indigenous knowledge and heritage center, ghibaish college of science and technology, ghibaish, sudan 7department of community and mental health, college of nursing, najran university, najran, saudi arabia 8college of community, shaqra university, saudi arabia 9faculty of nursing sciences, almughtaribeen university, jabra, khartoum, sudan 10faculty of nursing sciences, al neelain university, sudan 11medical nursing department,faculty of nursing sciences, university of khartoum, sudan 12college of applied medical science, nursing department, bisha university bisha, saudi arabia orcid: mohammed a. abdelmalik: https://orcid.org/0000-0002-3161-8351 amal m. elhusein: https://orcid.org/0000-0003-1619-0235 abstract background: while treating patients during a pandemic, nurses are at risk of mental health issues caused by the stress they face. this study aimed to examine the degree of anxiety and depression among sudanese nurses throughout the coronavirus disease 2019 (covid-19) pandemic and demographic features and their association with depression and anxiety. methods: an online-based cross-sectional study was conducted on sudanese nurses. data were collected from eligible nurses using a three-part questionnaire: demographic questions, the generalized anxiety disorder-7 (gad-7), and the major depression index (mdi). we used the chi-square test and spearman or point biserial correlation to assess the association between demographics, anxiety, and depression. results: two hundred and forty-six nurses from sudan participated in this study. around 69.5% of participants experienced mild to severe anxiety, while 26.4% revealed mild to severe depression. we found a significant association between depression and anxiety (p < 0.001). however, we did not find a significant association between depression or anxiety categories and the baseline characteristics of participants. conclusion: our study demonstrates high rates of anxiety and depression among sudanese nurses throughout the covid-19 pandemic. as we found no association between anxiety and depression with personal characteristics, psychological support should be given to all nurses’ categories as all of them nearly have the same risk for anxiety and depression. keywords: anxiety, depression, sudanese nurses, covid-19 pandemic how to cite this article: hammad a. fadlalmola, mohammed a. abdelmalik*, huda kh. masaad, abdalbasit a. mariod, abdalla ma. osman, eyas g. osman, kalthoum i.yousif, aisha m. adam, sahar a. ebrahim, amal m. elhusein (2022) “anxiety and depression among sudanese nurses during the covid-19 pandemic: a cross-sectional study,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 539–555. doi 10.18502/sjms.v17i4.12552 page 539 corresponding author: mohammed a. abdelmalik; email: mohammedabdelkrim9@gmail.com received 24 april 2022 accepted 4 june 2022 published 31 december 2022 production and hosting by knowledge e hammad a. fadlalmola et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12552&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hammad a. fadlalmola et al 1. introduction coronaviruses are rna viruses that trigger respiratory, gastrointestinal, hepatic, and neurological disorders in humans and other mammals. six distinct coronavirus species can cause human illness. it is typical for four viruses to induce common cold symptoms in immunocompetent people: 229e (oc43), nl63 (hku1), and nl63 (oc43) [1]click or tap here to enter text.. the two other viruses, sars-cov and mers-cov, have been linked to deadly illnesses in humans [2]click or tap here to enter text.. there were two epidemics of severe acute respiratory syndrome in guangdong province, china, caused by sars-cov. the mers-cov was the cause of the middle eastern epidemics of severe respiratory illness in 2012 [3]click or tap here to enter text.. new coronaviruses are expected to evolve regularly because of their high prevalence, widespread dispersion, and tremendous genetic shifting. many regional health facilities in wuhan, hubei province, have reported groups of pneumonia patients with an unknown etiology in late december 2019 [4]click or tap here to enter text.. the chinese center for disease control and prevention (china cdc), hubei province, and wuhan municipal health officials conducted an epidemiologic and etiologic investigation on december 31, 2019 [4]. the newly discovered coronavirus was declared a pandemic under the international health regulation by the world health organization (who) on january 30, 2020. the pandemic death rates have been enormous, with psychological and emotional implications for the rest of the world. on may 30, 2020, 5,819,962 cases were diagnosed as covid-19 with 362,786 deaths worldwide [5]. on february 15, 2022, sudan recorded a total of 59,631 covid-19 cases, of which 3,831 were deaths [6]. moreover, number of laboratories were increased in order to cope with covid-19 testing. in addition, sudan’s infection prevention and control program ensured that all patients seeking treatment for acute respiratory ailments were thoroughly tested [6, 7]click or tap here to enter text.. people of many ages and backgrounds have been affected by the pandemic, from healthy people to those at risk. in hospitals and isolation units, nurses can suffer from mass panic, depression, and anxiety because of the widespread quarantine [8]click or tap here to enter text.. they have direct contact with coronavirus patients confirmed or suspected, apart from these the increase in workload, infection risk, and mental health difficulties are all challenges they must deal with [9]. the covid-19 pandemic has exacerbated nurses’ worry, terror, panic attacks, posttraumatic stress, and psychological disturbances, as well as their contact avoidance, depressive tendencies, sleep difficulties, and anxieties about infecting their loved ones. doi 10.18502/sjms.v17i4.12552 page 540 sudan journal of medical sciences hammad a. fadlalmola et al although mental and psychosocial illnesses are common in nurses, many do not get regular mental health support [10]click or tap here to enter text.. this may lead to increased medical errors and accidents that put patients at risk due to nurses’ mental health difficulties that would affect their cognitive functions, attention, and clinical decision-making [11]click or tap here to enter text.. the sars outbreak in 2003 had a severe psychological impact on nurses [12]. these nurses were afraid of catching the disease and spreading it to their families and coworkers, with many having the desire to leave their jobs. there was also a greater prevalence of feelings of anxiety, stress, and depression, all of which have the potential to have long-term effects on mental health [13, 14]. psychological services have been widely deployed in response to the covid-19 pandemic, including phone, internet, and application-based intervention. on february 2, 2020, china’s state council announced the establishment of national hotlines for psychological assistance during the outbreak. on the other hand, nurses had very few options for their mental health treatment [15]. nonetheless, it is essential to address healthcare workers’ mental health problems to combat the pandemic better [16]click or tap here to enter text.. therefore, we aimed to assess depression and anxiety among sudanese nurses during the covid-19 pandemic by quantifying the severity of depression and anxiety, their relationship to demographic variables, and their relationship to each other. 2. materials and methods 2.1. study design an online-based cross-sectional study to evaluate depression and anxiety and their factors among nurses fronting the covid-19 pandemic in sudan. 2.2. sampling we used the convenience sampling method to collect data from eligible nurses. with a confidence interval level of 95% and a margin of error of 5%, epi info v.7 was used to calculate the sample size based on the prevalence of anxiety (20.2, 90.5) and depression (12.7%, 94.1) [17, 18]click or tap here to enter text.. according to health officials, the total number of nurses is nearly 6000. therefore, the sample size was calculated to be 238, 166, 130, or 86 participants. doi 10.18502/sjms.v17i4.12552 page 541 sudan journal of medical sciences hammad a. fadlalmola et al 2.3. measurements three parts self-administered questionnaire was used to collect the data: a demographic part, the generalized anxiety disorder (gad-7) part, and the major depression index (mdi) part. demographic questions asked about the respondent’s age, gender, marital status, place of employment (department), degree of education, and years of experience. anxiety in the study individuals was measured using the gad-7 questionnaire. the early version of the gad questionnaire included 13-items was first used in the years 2004 and 2005; 2740 adult patients in 15 clinics across the united states completed the initial 13-item version of the gad questionnaire. seven of these items were recommended for inclusion in the final edition. the initial investigation results show that this tool is reliable and valid. each question was answered by one of these answers: not at all (0), several days (1), more than half the days (2), or nearly every day (3). a score of 5-9 indicates mild anxiety, 10-14 of moderate anxiety, and more than 15 indicates severe anxiety [19-20]click or tap here to enter text.. mdi is a self-rating depression scale that has been clinically verified and is used in epidemiological studies [21, 22]click or tap here to enter text. with 10 items taken directly from the 10𝑡ℎ version of the international classification of diseases (icd) list of depressive symptoms. each question was answered by one of the following answers: at no time (0), some of the time (1), slightly less than half the time (2), slightly more than half the time (3), most of the time (4), or all the time (5). according to the participants’ answers, we categorized them into four categories: no depression (<20), mild depression (20-24), moderate depression (25-29), or severe depression (≥30) [23]click or tap here to enter text.. 2.4. statistical analysis the continuous variables were checked using the kolmogorov-smirnov test to test their normality. continuous variables were described as median and range, whereas categorical data were expressed as frequency and percentage. the association between different baseline categories, anxiety, and depression were tested using the chi-square test, spearman correlation, and point biserial correlation; p-value >0.05 was statistically significant, and data were analyzed with spss version 25 [24]click or tap here to enter text.. doi 10.18502/sjms.v17i4.12552 page 542 sudan journal of medical sciences hammad a. fadlalmola et al 3. results 3.1. demographic characteristics two hundred and forty-six nurses participated in this study, of which 86 (35%) aged between 24 and 29 years old, and 74 (30.1%) were between 30 and 35 years old. most nurses were females, 164 (66.7 %), of which 149 had bachelor’s degrees 149 (60.6 %). fifty-six nurses (22.6 %) had 10 or more years of experience, and 82 (33.3 %) nurses had only three years of experience. detailed characteristics of the participants are presented in table 1. 3.2. anxiety levels among participants regarding anxiety assessed by gad 7 questionnaire, 75 nurses (30.5 %) had no anxiety, 83 nurses (33.7 %) had mild anxiety, 64 nurses (26 %) had moderate anxiety, and 24 nurses (9.8 %) had severe anxiety. the median anxiety score was seven, and the range was (0-21). the full detailed answer to the seven questions is shown in table 2. 3.3. depression levels among participants depression among nurses was assessed using mdi. it showed that 181 nurses (73.6%) had no depression, 20 (8.1%) had mild depression, 14 (5.7 %) had moderate depression, and 31(12.6%) had severe depression. the median depression score was 12, and the range was (0-55). the full detailed answer to the questions is shown in table 3. 3.4. association and correlation between anxiety and demographics we found no significant association or correlation between anxiety score or categories and the following baseline characteristics: age, sex, marital status, education level, department, and years of experience with p values of 0.069, 0.19, 0.52, 0.4, 0.97, and 0.15 respectively (table 4, supplementary table 1). 3.5. association between depression and demographics we also analyzed the association between depression categories and baseline characteristics. no significant association or correlation was observed between depression doi 10.18502/sjms.v17i4.12552 page 543 sudan journal of medical sciences hammad a. fadlalmola et al table 1: general demographics. characteristics n (%)∗𝑎 age, yr 18–23 32 (13) 24–29 86 (35) 30–35 74 (30.1) 36–41 39 (15.9) 41 and above 15 (6.1) sex male 82 (33.3) female 164 (66.7) marital status married 118 (48) divorced 7 (2.8) single 119 (48.4) widowed 2 (0.8) education level bachelor 149 (60.6) diploma 20 (8.1) master 63 (25.6) phd 14 (5.7) department blood bank 1 (0.4) cardiac department 14 (5.7) critical care unit (ccu) 12 (4.9) diabetic specialist center 1 (0.4) dialysis unit 15 (6.1) educator 1 (0.4) emergency unit 28 (11.4) endoscopy 1 (0.4) field clinic 1 (0.4) general ward 42 (17.1) head nurse 1 (0.4) intensive care unit (icu) 62 (25.2) maternity and childbirth ward 8 (3.3) mental health department 7 (2.8) neonatal intensive care unit (nicu) 1 (0.4) newborn unit 17 (6.9) nursing administration 2 (0.8) obstetric department 1 (0.4) score or categories and the following baseline characteristics: age, sex, marital status, doi 10.18502/sjms.v17i4.12552 page 544 sudan journal of medical sciences hammad a. fadlalmola et al table 1: general demographics. characteristics n (%)∗𝑎 oncology and cancer unit 2 (0.8) opd 1 (0.4) operations department 17 (6.9) orthopedic ward 5 (2) pediatric intensive care unit (picu) 1 (0.4) professor 4 (1.6) respiratory department 1 (0.4) years of experience, yr 3 82 (33.3) 4–6 79 (32.1) 4–9 29 (11.8) 10 or more 56 (22.8) ∗𝑎valid percent was used if there were any missing data. education level, department, and years of experience with p values of 0.42, 0.52, 0.95, 0.99, 0.61, and 0.43 3.6. association between anxiety and depression our study found a significantly moderate correlation between anxiety and depression scores in the case of depression or anxiety, defined as an outcome variable. the r-value was 0.576, and the p-value was> 0.0001 (tables 4 and 5). 4. discussion anxiety and depression among sudanese nurses during the covid-19 pandemic were the key point of our study, which aimed to determine their prevalence and correlate it with various demographic variables. according to the gad-7 questionnaire, the median anxiety score among nurses in our study was 7, and around 69.5% of participants experienced mild to severe anxiety levels. according to margaretha et al., 33.3% of healthcare practitioners reported experiencing anxiety during the covid-19 crisis [25]click or tap here to enter text.. according to a comprehensive study conducted during the covid-19 pandemic, 23.2% of healthcare providers (hcps) exhibited anxiety symptoms [26]click or tap here to enter doi 10.18502/sjms.v17i4.12552 page 545 sudan journal of medical sciences hammad a. fadlalmola et al table 2: gad-7 questions for anxiety. characteristics n (%)∗𝑎 feeling nervous, anxious, or on edge? not at all 67 (27.2) several days 81 (32.9) more than half the days 61 (24.8) nearly every day 37 (15) not being able to stop or control worrying? not at all 85 (34.6) several days 88 (35.8) more than half the days 43 (17.5) nearly every day 30 (12.2) worrying too much about different things? not at all 77 (31.3) several days 84 (34.1) more than half the days 48 (19.5) nearly every day 37 (15) trouble relaxing? not at all 82 (33.3) several days 88 (35.8) more than half the days 52 (20.3) nearly every day 26 (10.6) being so restless that it is hard to sit still? not at all 98 (39.8) several days 76 (30.9) more than half the days 42 (17.1) nearly every day 30 (12.2) becoming easily annoyed or irritable? not at all 99 (40.2) several days 82 (33.3) more than half the days 34 (13.8) nearly every day 31 (12.6) feeling afraid as if something awful might happen? not at all 71 (28.9) several days 96 (39) more than half the days 43 (17.5) nearly every day 36 (14.6) anxiety severity no anxiety 75 (30.5) mild anxiety 83 (33.7) moderate anxiety 64 (26) severe anxiety 24 (9.8) anxiety score 7 (0-21)∗𝑏 ∗𝑎valid percent was used if there were any missing data. ∗𝑏data is presented as median (range). doi 10.18502/sjms.v17i4.12552 page 546 sudan journal of medical sciences hammad a. fadlalmola et al table 3: mdi questions for depression. characteristics n (%)∗𝑎 1. felt low in spirits or sad? at no time 58 (23.6) some of the time 99 (40.2) slightly less than half the time 33 (13.4) slightly more than half the time 28 (11.4) most of the time 12 (4.9) all the time 16 (6.5) 2. lost interest in daily activities? at no time 48 (19.5) some of the time 99 (40.2) slightly less than half the time 37 (15) slightly more than half the time 27 (11) most of the time 15 (6.1) all the time 20 (8.1) 3. feeling lack in energy and strength? at no time 93 (37.8) some of the time 73 (29.7) slightly less than half the time 36 (14.6) slightly more than half the time 15 (6.1) most of the time 15 (6.1) all the time 14 (5.7) 4. felt less confident? at no time 98 (39.8) some of the time 64 (26) slightly less than half the time 45 (18.3) slightly more than half the time 17 (6.9) most of the time 12 (4.9) all the time 10 (4.1) 5. had a bad conscience or feelings of guilt? at no time 98 (39.8) some of the time 64 (26) slightly less than half the time 45 (18.3) slightly more than half the time 17 (6.9) most of the time 12 (4.9) all the time 10 (4.1) text.. according to an online study, 90.5% of egyptian hcps exposed to the covid19 pandemic displayed varying levels of anxiety [18].click or tap here to enter text. the inconsistencies could be explained by variations in anxiety levels in samples and working conditions between the two studies. as many as 70% of those who participated doi 10.18502/sjms.v17i4.12552 page 547 sudan journal of medical sciences hammad a. fadlalmola et al table 3: mdi questions for depression. characteristics n (%)∗𝑎 6. felt that life was not worth living? at no time 105 (42.7) some of the time 71 (28.9) slightly less than half the time 29 (11.8) slightly more than half the time 23 (9.3) most of the time 10 (4.1) all the time 8 (3.3) 7. had difficulty in concentrating, e.g. when reading the newspaper or watching television? at no time 80 (32.5) some of the time 83 (33.7) slightly less than half the time 39 (15.9) slightly more than half the time 20 (8.1) most of the time 16 (6.5) all the time 8 (3.3) 8a. felt very restless? at no time 68 (27.6) some of the time 85 (34.6) slightly less than half the time 45 (18.3) slightly more than half the time 24 (9.8) most of the time 15 (6.1) all the time 9 (3.7) 8b. felt subdued or slowed down? at no time 81 (32.9) some of the time 82 (3.3) slightly less than half the time 44 (17.9) slightly more than half the time 22 (8.9) most of the time 10 (4.1) all the time 7 (2.8) 9. had trouble sleeping at night? at no time 70 (28.5) some of the time 82 (33.3) slightly less than half the time 38 (15.4) slightly more than half the time 27 (11) most of the time 14 (5.7) all the time 15 (6.1) in the egyptian study were doctors and nurses. egypt has a shortage of doctors of 0.5 per 1000 people, as reported by the world bank [18]click or tap here to enter text., and a shortage of nurses of 1.9 per 1000 people. a high workload was observed, during the covid-19 epidemic, due to a lack of staff, which eventually increased the anxiety doi 10.18502/sjms.v17i4.12552 page 548 sudan journal of medical sciences hammad a. fadlalmola et al table 3: mdi questions for depression. characteristics n (%)∗𝑎 10a. suffered from reduced appetite at no time 75 (30.5) some of the time 84 (34.1) slightly less than half the time 42 (17.1) slightly more than half the time 18 (7.3) most of the time 17 (6.9) all the time 10 (4.1) 10b. suffered from increased appetite? at no time 105 (42.7) some of the time 71 (28.9) slightly less than half the time 27 (11) slightly more than half the time 19 (7.7) most of the time 12 (4.9) all the time 12 (4.9) depression severity no depression 181 (73.6) mild depression 20 (8.1) moderate depression 14 (5.7) severe depression 31 (12.6) depression score 12 (0-55)∗𝑏 ∗𝑎valid percent was used if there were any missing data. ∗𝑏 data were presented as median (range) table 4: correlation between anxiety score and baseline characteristics. age sex marital status education level department years of experience depression score r –0.116 0.083 –0.041 –0.051 0.002 –0.092 0.576 p-value 0.069 0.193 0.521 0.427 0.974 0.152 >0.0001 number 246 246 246 246 246 246 246 table 5: correlation between depression score and baseline characteristics. age sex marital status education level department years of experience anxiety score r –0.052 0.041 0.004 0.001 –0.032 –0.050 0.576 p-value 0.417 0.524 0.946 0.989 0.613 0.435 >0.0001 number 246 246 246 246 246 246 246 respectively (table 5, supplementary table 2). symptoms [27, 28]. lack of personal protective measures and other essential equipment during the initial phases of covid-19 pandemicmight have led to hcp concerns. hcps doi 10.18502/sjms.v17i4.12552 page 549 sudan journal of medical sciences hammad a. fadlalmola et al can be protected from the psychological effects of the covid-19 pandemic if they have sufficient staff and personal protective equipment. in our study, 26.4% of nurses showed signs of depression. while in motahedi et al.’s study, 57% of the participants reported being depressed at some point [29]. about 40-45% of the frontline nurses surveyed in wuhan reported experiencing anxiety or depression, with about 11-14% of those experiencing moderate to severe anxiety or sadness. bannai et al. found that 22.8% of hcps reported depression symptoms during covid-19. more than 94% of hcps reported mild to severe depression throughout the pandemic of covid-19 [18]; according to aly et al., anxiety and depression have been linked to long work hours [30]. it can be concluded that longer working hours cause an increased prevalence of anxiety and depression [18]. in our study, anxiety and depression were revealed to be directly linked. the similar pathophysiology of anxiety and depression shows that the two illnesses may co-occur, even though they are clinically separate [31]. in addition, prior studies have indicated that depression and anxiety are linked. a correlation between sadness and anxiety has been found among italian healthcare workers. hcps were also more likely to be affected by anxiety and depression during the outbreaks of diseases such as sars or ebola [32]click or tap here to enter text.. anxiety and depression were not significantly associated with any of the demographic factors that we looked for in our research. this was also found in egypt in an online cross-sectional study. the difference was not statistically significant when the study participants were compared by age and gender to the frequency of their reported stress, anxiety, and depression. on the other hand, a prior study indicated that female hcps had higher anxiety levels than their male counterparts [29]. female healthcare workers were more anxious during the covid-19 epidemic in other iranian studies [28, 33]. these studies suggest this association could be explained by the vulnerability of females to a variety of stresses, including difficulty in managing work and personal life as well as the lack of proper support; as a result, it was predicted that their psychological distress would rise during the covid-19 pandemic [34]click or tap here to enter text.. also, gender disparity in depression and anxiety may be attributable to women’s historically more candid responses to anxiety-related questions [35]click or tap here to enter text.. memory, understanding, and reporting of experiences varied between men and women [36]click or tap here to enter text.. a pandemic significantly strains a country’s political, economic, and healthcare systems. according to the who study, 93% of nations around the globe , had restrictions on access to mental health care during the covid-19 era. however, owing to doi 10.18502/sjms.v17i4.12552 page 550 sudan journal of medical sciences hammad a. fadlalmola et al the catastrophic consequences of this condition on mental health, immediate access to psychological treatments is required [37]click or tap here to enter text.. limited resources during the pandemic, necessitates careful planning, also there are other ways to provide prompt psychological help, including informal networks of support and telemedicine [38]click or tap here to enter text.. our study has some limitations as it was conducted online, and some nurses who were unavailable or not interested in social media throughout the study period may have missed it, which may increase the risk of selection bias due to the web-based survey. in addition, baseline anxiety and depression scores could not be assessed and adjusted as a confounder for participants because of the abrupt beginning of the pandemic. also, cross-sectional studies could not establish causality. 5. conclusion our study demonstrates high rates of anxiety and depression among sudanese nurses throughout the covid-19 pandemic. as we found no association between anxiety and depression with personal characteristics, psychological support should be given to all nurses’ categories as all of them nearly have the same risk for anxiety and depression. acknowledgments the authors in this study expressed gratitude to sudanese nurses who managed their time and participated voluntarily. ethical consideration ethics concerns included the following: 1) the first sentence in the online survey was a check box representing the participant’s agreement to continue the survey with acceptance of the survey’s ethical consideration. 2) the data was saved strictly confidential for research purposes. 3) the participants were made aware that their participation was completely voluntary and could choose not to participate for any reason. 4) there was no disruption in workflow due to this study’s objectives. competing interests in this study, all authors have no conflicts of financial or personal interest to declare. doi 10.18502/sjms.v17i4.12552 page 551 sudan journal of medical sciences hammad a. fadlalmola et al availability of data and material all data for this study that were generated and/or analyzed during the study are available upon request from the corresponding author. funding all the authors in this study confirm that this work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. author contributions 1. study concept and design or acquisition, analysis, or interpretation of data by hammad a. fadlalmola and eyas gaffar abdelraheem osman. 2. drafting the article or revising it critically for important intellectual content by mohammed a. abdelmalik, huda k. masaad, huda kh. masaad, abdalbasit a. mariod. 3. final approval of the version to be 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[14] mulfinger, n., sander, a., stuber, f., brinster, r., junne, f., limprecht, r., jarczok, m. n., seifried-dübon, t., rieger, m. a., zipfel, s., peters, m., stiawa, m., maatouk, i., helaß, m., nikendei, c., rothermund, e., hander, n., ziegenhain, u., gulde, m., … gündel, h. (2019). cluster-randomised trial evaluating a complex intervention to improve mental health and well-being of employees working in hospital a protocol for the seegen trial. bmc public health, 19(1), 1694. [15] qiu, d., li, y., li, l., he, j., ouyang, f., & xiao, s. (2020). policies to improve the mental health of people influenced by covid-19 in china: a scoping review. frontiers in psychiatry, 11, 588137. [16] banerjee, d. (2020). the covid-19 outbreak: crucial role the psychiatrists can play. asian journal of psychiatry, 50, 102014. doi 10.18502/sjms.v17i4.12552 page 553 sudan journal of medical sciences hammad a. fadlalmola et al [17] dua, j., dong, l., wang, t., yuan, c., fu, r., zhang, l., liu, b., zhang, m., yin, y., qin, j., bouey, j., zhao, m., & li, x. (2020). psychological symptoms among frontline healthcare workers during covid-19 outbreak in wuhan. general hospital psychiatry, 67, 144–145. [18] aly, h. m., nemr, n. a., kishk, r. m., & abu bakr elsaid, n. m. (2022). stress, anxiety and depression among healthcare workers facing covid-19 pandemic in egypt: a cross-sectional online-based study. bmj open, 11, 45281. [19] sanford, j., agrawal, a., & miotto, k. (2022). psychological distress among women healthcare workers: a health system’s experience developing emotional support services during the covid-19 pandemic. frontiers in global women’s health, 2, 614723. [20] rutter, l. a., & brown, t. a. 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(2020). determinants psychological distress of indonesian health care providers during covid-19 pandemic. systematic reviews in pharmacy, 11(6), 1052–1059. [26] pappa, s., ntella, v., giannakas, t., giannakoulis, v. g., papoutsi, e., & katsaounou, p. (2020). prevalence of depression, anxiety, and insomnia among healthcare workers during the covid-19 pandemic: a systematic review and meta-analysis. brain, behavior, and immunity, 88, 901–907. [27] moghadam, k. n., chehrzad, m. m., masouleh, s. r., mardani, a., maleki, m., akhlaghi, e., & harding, c. (2022). nursing workload in intensive care units and the influence of patient and nurse characteristics. nursing in critical care, 26(6), 425–431. [28] moghanibashi-mansourieh, a. 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(2010). gender differences in depression and ptsd symptoms following combat exposure. research article depression and anxiety, 27, 1027–1033. [36] lu, s., hu, s., guan, y., xiao, j., cai, d., gao, z., sang, z., wei, j., zhang, x., & margraf, j. (2018). measurement invariance of the depression anxiety stress scales-21 across gender in a sample of chinese university students. frontiers in psychology, 9, 2064. [37] lauer, s. a., grantz, k. h., bi, q., jones, f. k., zheng, q., meredith, h., azman, a. s., & reich, n. g. (2020). the incubation period of coronavirus disease 2019 (covid19) from publicly reported confirmed cases: estimation and application. annals of internal medicine, 172(9), 577–582. [38] maleki, m., mardani, a., & vaismoradi, m. (2022). insecure employment contracts during the covid-19 pandemic and the need for participation in policy making. public health, 18(23), 12548. doi 10.18502/sjms.v17i4.12552 page 555 introduction materials and methods study design sampling measurements statistical analysis results demographic characteristics anxiety levels among participants depression levels among participants association and correlation between anxiety and demographics association between depression and demographics association between anxiety and depression discussion conclusion acknowledgments ethical consideration competing interests availability of data and material funding author contributions references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11458 production and hosting by knowledge e case report short spinous process of cervical vertebrae in a sudanese subject: a case report assad rezigalla1* and abdelrahman ali2,3 1department of basic medical sciences, faculty of medicine, university of bisha, saudi arabia 2department of surgery, military hospital (omdurman), omdurman, sudan 3neurosurgical department, king khalid hospital (tabuk), saudi arabia orcid: assad rezigalla: https://orcid.org/0000-0002-9693-9586 abdelrahman ali: https://orcid.org/0000-0002-1835-9957 abstract introduction: the spinous process is part of the vertebrae and provides muscle attachment for some muscles and ligaments. they are important landmarks and play a role in screw placement during surgical intervention. this report describes a case of a sudanese with a short cervical spinous process and draws attention to the possibility of anatomical variations in general and the shortage of cervical spinous processes specifically. case report: a 70-year-old sudanese male presented to the emergency department following a road traffic accident. after standard management and patient stabilization, the x-ray showed that the spinous processes of c 3, 4, and 5 cervical vertebrae were short, and those of c 6 and 7 have abnormal anatomy. the inter-spinous distances were well-maintained. the joints and articulations processes of cervical vertebrae were normal without cortication. the patient was stable and admitted for 24 hr for observation and then discharged on analgesics. conclusion: this is the first case report of the short spinous process among sudanese. some of the cervical spinous processes were short, and others had abnormal anatomy. no obvious manifestations were linked to the case. discussion of anatomical variations should be carried out and implemented with care and in line with the normal and latest developments in biological, anthropology, forensic, and related sciences. such anatomical abnormality should be considered during radiographing, preparation, and surgical intervention planning. the normal adaption resulting from congenital abnormality or variation can be used as a method for reconstruction surgeries and provides alternatives to clinical management. keywords: short spinous process, cervical, sudanese, anatomical variation 1. introduction the cervical part of the vertebral column (c) performs specific tasks. mainly, it forms stable support while maintaining a significant range of mobility. moreover, it protects the cervical segment of the spinal cord [1, 2]. any morphological variation or disorder affecting the cervical vertebrae can significantly lower the quality of life [1]. how to cite this article: assad rezigalla* and abdelrahman ali (2022) “short spinous process of cervical vertebrae in a sudanese subject: a case report,” sudan journal of medical sciences, vol. 17, no. 2, pp. 244–251. doi 10.18502/sjms.v17i2.11458 page 244 corresponding author: assad rezigalla; email: assadkafe@yahoo.com received 16 may 2020 accepted 7 may 2022 published 30 june 2022 production and hosting by knowledge e assad rezigalla et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:assadkafe@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences assad rezigalla et al. the cervical spinous process is part of the vertebrae that provides muscle attachment for some muscles in the neck, back, and upper limb. they are important surface landmarks and play a role in screw placement or implants in the cervical spine [3– 5]. the cervical spine, apart from the axis and atlas, is developed from cells of the sclerotome of cervical somites [6, 7]. the development of the cervical neural arch begins during the third to sixth week of intrauterine life. the neural arch develops from chondral ossification centers extending from the vertebral body (centrum) and a secondary ossification center on the tip of the spinous process [8]. the development spinous process is completed by the second decade, following the fusion of the secondary ossification centers [8, 9]. typically, the spinous processes of cervical vertebrae are short and increase in length and possess a bifid end. bifurcation (bifid) of the cervical spinous processes was described as a characteristic feature [2]. the cervical spinous processes are subjected to variations in regards to the length, types, and mode of bifurcations and deviation from the median plane [10]. these abnormalities can be asymptomatic or detected incidentally, or mimic traumatic lesions and may cause recurrent episodes of pain affecting the quality of life [11]. congenital variations of the cervical spine can be associated with other abnormalities such as vacterl (vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, limb abnormalities) association or clinical syndromes such as klippel-feil and morquio or dystrophic dwarfism, spondyloepiphyseal dysplasia, and osteogenesis imperfect [11, 12]. a few studies researched the anatomy of the cervical vertebra [1, 5, 13–17]. out of these studies, only two reported the length of the spinous process [13, 14]. the length of the spinous process is measured from the lower posterior tip of the process to the vertebral body centroid [13, 14]. usually, the length of the spinous process decreased slightly from c 2 to c 3; it remained constant through c 5 and significantly increased at c 7 [13, 14]. reporting this case report is important because it is the first case describing a short spinous process among sudanese. it provides a reference value for the cervical spinous process and provides anatomical knowledge about the region to help radiographing and surgical intervention. this report describes a case of a sudanese with a short cervical spinous process and draws attention to the possibility of anatomical variations in general and the shortage of cervical spinous processes specifically. doi 10.18502/sjms.v17i2.11458 page 245 sudan journal of medical sciences assad rezigalla et al. 2. case report a 70-year-old sudanese male was presented to the emergency department in omdurman military hospital (omdurman, khartoum), following a road traffic accident (pedestrian road hit). after standard management and patient stabilization, a radiograph of the chest and cervical spine and computed tomography (ct) of the head was requested. apart from the normal findings in the imaging workup, the cervical x-ray showed that the spinous processes of c 3, 4, and 5 were short, and those of c 6 and 7 had abnormal anatomy. on reassessment, the patient denied any history of trauma or surgical intervention in the cervical region. the neck examination revealed that there was no surgical scar, palpable spinous process of c 6 and 7, normal range of neck motion, the power of upper limbs was grade five, and the sensation was normal. further radiological investigations through ct (figure 1) and 3d construct ct scan of the cervical spine (figure 2) confirmed the shortage of c 2, 3, 4, and 5, and none of the spinous processes had bifid end. the inter-spinous distances were well-maintained. the joints and articulations processes of cervical vertebrae were normal without cortication. the lengths of the cervical spinous process were measured from the anterior end to the posterior tip of the spinous process. the length was considered the main out of the three measurements done by the same observer (figure 1). figure 1: ct scan of the patient’s neck. the spinous process of cervical vertebrae appears short. doi 10.18502/sjms.v17i2.11458 page 246 sudan journal of medical sciences assad rezigalla et al. figure 2: the 3d construct ct scan of the cervical spine. (2a) right lateral view; (2b) left lateral view; (2c) posterior view. the spinous processes are short and have no bifid end. table 1: the comparison of the length of the cervical vertebrae. spinous process current study panjabi et al. [13] bazaldúa et al. [21] mean sd mean sd c 2 20.58 33.7 1.39 – – c 3 8.59 29.6 0.78 15.3 3.11 c 4 10.52 30.3 1.07 15.38 2.61 c 5 16.16 28.5 0.98 16.63 3.04 c 6 32.38 34.2 1.88 21.81 5.00 c 7 33.93 45.7 0.84 28.12 5.86 the patient was stable and admitted for 24 hr for observation and then discharged without complaints on analgesics. the patient was referred to a neurology and orthopedic outpatient clinic for further assessment. 3. discussion shortage of the cervical spinous process can be due to failure of complete fusion of chondrification centers extending from the centrum to the neural arches or arrest of the secondary ossification center in the tip of the spinous process [18]. also, it can be due to genetic or sporadically in an isolated manner or associated with other organs [19]. the presence of a non-bifid spinous process with normal inter-spinous distances and articulations supports the possibility of arrest of the secondary ossification center on the tip of the spinous process rather than incomplete fusion of the vertebral arch. the shortage of cervical spinous processes is part of neural arch anomalies [20]. in the current case, apart from c 7, 6, and 2, which were the longest, respectively, c3 was the shortest, preceded by c 4 and 5. despite the difference in length between panjabi et al., bazaldúa et al., and the current findings, the pattern of spinous length was doi 10.18502/sjms.v17i2.11458 page 247 sudan journal of medical sciences assad rezigalla et al. maintained. these findings are in accordance with the standard anatomy literature [21]. the shortage of the spinous process can affect muscle attachment to it and the supporting functions of ligaments. such affection can limit cervical movements and present some complaints or symptoms. in the present case, the physical examination revealed normal findings. normal findings in the clinical examination support the possibility of adaptation in regard to muscles and ligament attachments that maintained the normal functions. such a mode of adaptation can be beneficial for planning reconstruction surgeries on the back of the cervical spine. also, the size of the screws and surgical implants should be considered in advance because using f regular size can lead to other complications. although the cervical spinous process abnormalities are rare, the most commonly reported are non-bifid spine, duplicated spinous process (of the c7), unilateral hyperplasia, deviation of the spinous processes, and non-united secondary ossification centers of the spinous processes [20, 22, 23]. 4. conclusion this study describes a case report of a sudanese with short cervical spinous processes and draws attention to the possibility of anatomical variations in general and the specific shortage of cervical spinous processes. discussion of anatomical variations should be carried out and implemented with care and in line with the normal and latest developments in biological, anthropology, forensic, and related sciences. the presence of anatomical variation or abnormality can affect clinical evaluation and subsequent surgical intervention or mimic other clinical conditions. the normal adaption resulting from congenital abnormality or variation can be used as a method for reconstruction surgeries and provides alternatives to clinical management. in such spine cases, the implant of screws and relevant manipulation should be adapted according to the variation. acknowledgments the authors acknowledge our colleagues for their help and support. special thanks and appreciation to the participant. special thanks to the college dean and administration of college of medicine, university of bisha (bisha, saudi arabia), and the head of the department of neurological surgery, sudan armed forces hospital, omdurman, sudan for help and allowing the use of facilities. doi 10.18502/sjms.v17i2.11458 page 248 sudan journal of medical sciences assad rezigalla et al. ethical considerations written consent and acceptance to participate were obtained from the participant. competing interests the authors declare no conflict of interest. availability of data and material the study data will be available upon reasonable request to the corresponding author. funding none received. references [1] swartz, e. e., floyd, r., and cendoma, m. 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(2018). malformed vertebrae: a clinical and imaging review. insights into imaging, vol. 9, no. 3, pp. 343–355. doi 10.18502/sjms.v17i2.11458 page 250 sudan journal of medical sciences assad rezigalla et al. [20] ravikanth, r. and pottangadi, r. (2018). nonunited secondary ossification centers of the spinous processes of vertebrae at multiple levels presenting as aberrant articulations in an adult. journal of craniovertebral junction & spine, vol. 9, no. 3, pp. 216–217. [21] bazaldúa, c., gonzález, l., gómez, s., et al. (2011). morphometric study of cervical vertebrae c3-c7 in a population from northeastern mexico. international journal of morphology, vol. 29, no. 2, pp. 325–330. [22] cho, w., maeda, t., park, y., et al. (2012). the incidence of bifid c7 spinous processes. global spine journal, vol. 2, no. 2, pp. 99–103. [23] tubbs, r. s., shoja, m. m., and loukas, m. (2016). bergman’s comprehensive encyclopedia of human anatomic variation. hoboken, nj: john wiley & sons. doi 10.18502/sjms.v17i2.11458 page 251 introduction case report discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12115 production and hosting by knowledge e letter shaping healthcare system under industry 5.0: trends and barriers zeeshan asim institute of business and management, karachi, pakistan orcid: zeeshan asim: https://orcid.org/0000-0002-2156-5006 some significant discoveries over the history of human society have led to radical social transformation. the birth of the wheel, the incandescent light bulb, electricity, and the development of the internet have all reshaped human history [1]. the emergence of the coronavirus 2 (sars-cov-2) pandemic in early 2020 was one such event. even though the pandemic cannot be acclaimed for such an abrupt transformation in the healthcare sector over the last two years, smart healthcare has expedited across the globe [2, 3]. a frequent transition in digital technologies, from conventional healthcare practices to intelligent healthcare practices, is set to reshape healthcare practices across the globe. healthcare systems fused with intelligent technologies to pave healthcare data conveniently and connect resources for efficiently managing uncertain healthcare demands intelligently. the evolution of the smart healthcare system under industry 4.0 is going through the reshaping of health 5.0. the paramount urgency came from the management of the electronic health records (ehr) system that helps clinical professionals upload, screen, share and access the healthcare data hosted from cloud databases at any time. however, hosted information at cloud servers was susceptible to vigorous security outbreaks by maleficent entities to access patient clinical data, which undoubtedly was sold for illegal purposes. to dilute such obstacles, emerging technologies such as ai (artificial intelligence), machine learning (ml), deep learning (dl), augmented reality (ar), virtual reality (vr), big data analytics, block chair, cloud computing, 5g, digital mobile technologies, advance robotics, internet of thing, (iot) and web 3.0 were integrated to previous healthcare generations [4]. this evolution is known as healthcare 4.0. the main goal is to administer the patient-centric clinical service through smart learning. most healthcare-related industries have comprehensively reshaped existing clinical practices into industry 4.0. such evolution consistently reshapes how these smart high-tech firms upgrade their business practices and enhance operational consistency across the value chain. compared to the manufacturing sector, the responsive healthcare delivery how to cite this article: zeeshan asim (2022) “shaping healthcare system under industry 5.0: trends and barriers,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 423–425. doi 10.18502/sjms.v17i3.12115 page 423 corresponding author: zeeshan asim; email: zeeshanasimump@gmail.com received 18 may 2022 accepted 6 june 2022 published 30 september 2022 production and hosting by knowledge e zeeshan asim. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences zeeshan asim mechanism is considered a paradigm shift to leap forward to the new digital era of healthcare 5.0. however, a few barriers are involved as most clinical practice moves toward industry 5.0. among many technologists, this new digital era of healthcare 5.0 is considered complex and challenging in many aspects, including even intelligently monitoring disease control, delivering virtual healthcare, and clinical decision-making. however, there are some potential barriers to adopting healthcare 5.0 across healthcare industries, such as heterogeneity of the clinical data, irregularity, and interactiveness during the formulation of clinical information, limited computational capabilities, inadequate utilization of energy, lack of validity among sensor’s data, and lack of robustness among intelligent models. in addition, there is a potential absence in recognizing psychological and emotional data, which is layered with deficiencies in customized, innovative applications [5]. this allows the scholarly world to spotlight intelligent sensors coupled with these hyper customized abilities to support responsive healthcare. innovative healthcare technologies, consistently dynamic, constitute anomalous opportunities in caregiver systems across the globe to cultivate high response in traditional and virtual healthcare practices. over time, compelling progress has been made in the healthcare sector over the last century. however, the potential absence of understanding psychological and emotional data, layered with deficiencies of customized smart applications, always calls for digital integration among intelligent sensors across the healthcare system through emerging digital technologies. the integration of these technologies plays a pivotal role in developing a new concept known as healthcare 5.0. the emergence of healthcare 5.0 enables a paradigm shift in traditional healthcare systems allowing smart diagnostic and disease control mechanisms, virtual caregiver assistance, cloud assistance for healthcare information, augmented assistant healthcare decision-making and precision medicine. such evolution consistently reshapes high-tech firms to enhance their clinical operations diagonally among various healthcare venues to deliver patient-centric responses through smart care. still, structuring resilient and robust healthcare 5.0 faces multiple limitations. the limitations include organizational barriers, regularity and privacy barriers, technological and structural barriers, religious and cultural barriers, and intelligent healthcare policy barriers to the successful execution of healthcare 5.0. therefore, despite focusing on developing smart healthcare technologies, scholars also need to include domestic and international stakeholders from multi-disciplines such as legal, it, medical, pharmaceutical, nursing and business to promote a highly reliable healthcare operational model. doi 10.18502/sjms.v17i3.12115 page 424 sudan journal of medical sciences zeeshan asim acknowledgements none. competing interests none. funding none. references [1] wolchover, n., & leggett, j. (2021, december 22). top 10 inventions that changed the world. live science. https://www.livescience.com/33749-top-10-inventions-changedworld.html [2] kumar, a., & sharma, k. (2021). digital transformation and emerging technologies for covid-19 pandemic: social, global, and industry perspectives. in: f. al-turjman (ed.). artificial intelligence and machine learning for covid-19. springer. [3] kapoor, a., guha, s., kanti das, m., goswami, k. c., & yadav, r. (2020). digital healthcare: the only solution for better healthcare during covid-19 pandemic? indian heart journal, 72(2), 61–64. https://doi.org/10.1016/j.ihj.2020.04.001 [4] li, j., & carayon, p. (2021). health care 4.0: a vision for smart and connected health care. iise transactions on healthcare systems engineering, 11(3), 171–180. https://doi.org/10.1080/24725579.2021.1884627 [5] mbunge, e., muchemwa, b., jiyane, s., & batani, j. (2021). sensors and healthcare 5.0: transformative shift in virtual care through emerging digital health technologies. global health journal, 5(4), 169–177. https://doi.org/10.1016/j.glohj.2021.11.008 doi 10.18502/sjms.v17i3.12115 page 425 acknowledgements competing interests funding references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10691 production and hosting by knowledge e original article covid-19 in combination with hlh in a child with severe aplastic anemia alireza jenabzadeh1, mohammad naghibi2, and farzan safi dahaj3* 1assistant professor, hematology and oncology research center, shahid sadoughi university of medical sciences, yazd, iran 2pediatric resident, school of medicine, shahid sadoughi university of medical sciences, yazd, iran 3student research committee, shahid sadoughi university of medical sciences, yazd, iran orcid: alireza jenabzadeh: https://orcid.org/0000-0001-8831-9611 mohammad naghibi: https://orcid.org/0000-0002-8534-7438 abstract since december 2019, the coronavirus (covid-19) has spread all over the world. this disease may present differently in immune-compromised persons. some of the virus’s impacts have yet to be identified. in this case report, we report a three-year-and-threemonth-old child with aplastic anemia who was concurrently infected with covid-19 and hlh (hemophagocytic lymphohistiocytosis). she was referred to our center for further investigation of aplastic anemia with concurrent fever. through examination due to splenomegaly, more evaluations were done. during admission, the pcr test for covid-19 became positive, however, because of the fulfillment of the hlh criteria, she was diagnosed with this disease development. she was treated for hlh with ivig and dexamethasone while getting covid-19 treatment. following medicines and followup, her wbc and hb count started to rise, aside from the plt count. she continues to receive plts because of her thrombocytopenia till a suitable donor for bmt (bone marrow transplant) is found. this case scenario highlights the covid-19 concurrent complications for paying attention to underlying disease for better diagnosis and management. keywords: covid-19, pediatrics, pancytopenia, aplastic anemia 1. introduction the coronavirus disease 2019 (covid-19), caused by coronavirus-2 (sars-cov-2), has been spreading around the world since december 2019. it was declared a pandemic by the who in march 2020 [1]. covid-19 affects every patient in different ways. children are less likely to be associated with an increased risk of serious disease than adults. of note, the mortality rate for this population is estimated to be <1% [2]. in addition, infected individuals with covid-19 appear to have a reduced risk of immune deficiency than those with other underlying diseases. it also had better outcomes compared to other comorbidities [1, 3, 4]. how to cite this article: alireza jenabzadeh, mohammad naghibi, and farzan safi dahaj* (2022) “covid-19 in combination with hlh in a child with severe aplastic anemia,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 138–145. doi 10.18502/sjms.v17i1.10691 page 138 corresponding author: farzan safi dahaj; email: safi.farzan@yahoo.com received 16 november 2021 accepted 28 february 2022 published 31 march 2022 production and hosting by knowledge e alireza jenabzadeh et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:safi.farzan@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences alireza jenabzadeh et al studies have reported fulfillment of secondary hemophagocytic lymphohistiocytosis (shlh) diagnostic criteria in some individuals with covid-19. as a result, covid-19 might cause shlh [1, 4]. patients with this condition have a sudden onset of fever, cytopenia, coagulopathy, increased transaminase levels, hyperferritinemia, and multiorgan dysfunction. the mainstays of treatment include chemotherapy, glucocorticoids, and intravenous immunoglobulin (ivig) [1, 2, 4, 5]. except for the studies by adel and magdy [1] and mostafavi et al. [4], there has been no case of hlh coexisting with severe aplastic anemia in a child infected with covid19. in this case report, we report a three-year-and-three-month-old child with aplastic anemia who was concurrently infected with covid-19 and hlh. 2. case report 2.1. history and examination a three-year-and-three-month-old girl presented to the hospital with a fever. her medical records from a month earlier at a different facility showed signs of weakness and lethargy. it should be noted that once the doctors discovered pancytopenia, they did an aspiration and a bone marrow biopsy. the pathological findings of a bone marrow test done a month earlier revealed that the child had aplastic anemia. the child had a fever when she came to our center, and the spleen was touched below the ribs during the examination. the child had pancytopenia (wbcs: 700 cells/µl, 5% neutrophils, and 95% lymphocytes [anc: 35, alc: 665 cells/µl], hb: 10.2 gr/dl, and plts: 39,000 cells/µl). a consultation with endocrinology, infectious disease, and immunology services was done to examine the possible causes of aplastic anemia. among the infectious causes tested for, viral agents such as ebv, cmv, hbv, hcv, hiv, hav, vzv, parvovirus b19, mumps, rubella, and influenza were requested; however, only parvovirus b19 igm and igg were positive, which were also excluded when the pcr results were provided. this indicates that parvovirus b19 was not detected. furthermore, blood culture was sent using the bactec method, which was reported to be negative, and the chromosomal fragility test with suspicion of fanconi anemia (fa) was also sent, which was also reported to be negative (fragility test was not increased). the patient developed a fever on the first day of admission and tested positive for covid-19. we found no signs of lung disease throughout the examinations, and she did not have tachypnea, asthma, or respiratory distress. chest x-ray revealed a normal lung field and a normal mediastinum (figure 1). given that spleen enlargement should not doi 10.18502/sjms.v17i1.10691 page 139 sudan journal of medical sciences alireza jenabzadeh et al occur in aplastic anemia, if such enlargement is found, the reasons for splenomegaly should be explored. we further investigated the reasons for the spleen enlargement, and eventually, based on the hlh criteria, we arrived at the following diagnosis: the kid had a fever, bicytopenia, splenomegaly, ferritin >500 (6382 ng/ml), fasting triglyceride >265 mg/dl, and malignancy signs in a chest x-ray, abdomen ultrasound, and bone marrow aspiration and biopsy. it should be noted, however, that fibrinogen was found to be normal (586 mg/dl). because the child was also diagnosed with aplastic anemia, injecting etoposide was deemed inappropriate for her. dexamethasone (10 mg/m2; two weeks) and ivig (0.5 gr/kg/day; four doses) were also used to treat hlh. of course, the doctors requested interleukin-6 for the patient, so that if the child’s condition is suitable and there is a justification for the use of tocilizumab based on the il-6 level, this medicine can be used to treat both hlh and covid-19. however, because its level was 1.0 pg/ml and the il-6 level was normal (normal range: 7 pg/ml), we did not utilize this medication. at the same time, a consultation with the pediatric infectious disease service was done for the treatment of covid-19, and based on the results, the interferon β-1a and lopinavir/ritonavir were continued for five days. after the covid-19 treatment time elapsed and given the child’s overall good health, she was discharged, but she remained under medical care for bone marrow condition and the requirement to get packed cells and platelets. the child’s wbc began to increase approximately three months after the diagnosis of aplastic anemia (two months after the first visit to this facility), and the wbc returned to normal after three and a half months (trends of laboratory findings in this patient is shown in table 1). almost simultaneously with the increase in wbc, the child’s hb increased, so that the last time she received packed cells was about three-and-a-half months after the onset of aplastic anemia (or, to put it another way, two-and-a-half months after her first visit to this center), but the number of platelets continued to decrease. platelets were given to the child two or three times each week. the child’s chance to receive platelets was limited by a platelet count of fewer than 10,000 or uncontrolled hemorrhage. infectious, endocrine, rheumatology, and immunology consultations were done immediately after diagnosis to determine the underlying causes of hlh, but no diagnosis was made. given that the child had received platelets for about six months, hla typing was performed for the child and her family to undergo bone marrow transplantation. there was, however, no full-match donor. on the other hand, because chronic aplastic anemia necessitates bone marrow transplantation, genetic hlh tests were expensive for the family and didn’t make a significant difference in therapy, therefore we didn’t examine doi 10.18502/sjms.v17i1.10691 page 140 sudan journal of medical sciences alireza jenabzadeh et al table 1: laboratory findings related to the patient. index/day 14 days before admission admission day 0 day 1 day 2 day 3 day 4 day 6 day 9 discharge 34 days after discharge 50 days after discharge 147 days after discharge wbc (reference 3700– 10000_103 cells/_l) 3300 700 1100 1600 – – 1200 600 1200 2100 7600 neutrophil, % 35 5 – – – – – – – 28.7 72.2 lymphocyte, % 65 95 – – – – 88.6 – – 52.8 22.7 hemoglobin (reference 10.5–13.5 g/dl) 9.9 10.2 9.4 8 – – 9.1 9 9.8 7 10.9 platelet count (reference 150.0– 450.0_103 cells/_l) 13000 39000 5000 16000 – – 14000 40000 19000 17000 63000 retic, % – – – 0.2 – – – – – – – fibrinogen (reference 200–400 mg/dl) – – – – 586 412 – – 429 – – triglycerides (normal fasting < 265 mg/dl) – – – – – 353 443 – 285 – – ferritin (reference 7–140 ng/ml) – – – – 6382 >1500 – – – – – c-reactive protein – – 2+ 1+ – – – – 2+ 2+ 2+ esr 1st h (reference <15/1st h) – – – 98 – – – – – 104 – urea, mg/dla – – 35 – – – – – – – 26 creatinin, mg/dla – – 0.5 – – – – – – – 0.4 rt-pcr for sars-cov-2 – – pos – – – – neg – – – sars-cov-2: severe acute respiratory syndrome coronavirus 2. the underlying hlh genes (if the hlh had a genetic basis, we would recommend bone marrow transplantation). at the time of writing this paper, the child was under medical care for the need to receive platelets, and our next step was to find a suitable donor for bone marrow transplantation; if no suitable donor was found, we will consider medicinal therapies. 3. discussion children of any age can become infected with covid-19. according to the centers for disease control and prevention (cdc), around 12–14% of confirmed coronavirus infections are children under the age of 18. it is also worth noting that the mortality rate for this group is believed to be <1%. moreover, children are less prone than adults to be impacted by the major disease [2]. in egypt, adel and magdy reported confirmed doi 10.18502/sjms.v17i1.10691 page 141 sudan journal of medical sciences alireza jenabzadeh et al figure 1: chest radiograph of the three-year-and-three-month-old child with aplastic anemia (day 1 of hospitalization). covid-19 with shlh in a 71-day-old infant whose symptoms worsened in about a week and who died because of vasoplegic shock development [1].mostafavi et al. reported an 18-month-old boy who developed covid-19-induced shlh and successfully recovered from shlh and covid-19 in isfahan, iran [4].this report also explains the case of a three-year-and-three-month-old child who had covid-19 and hlh simultaneously, and recovered from the disease, except for thrombocytopenia. the reason for the reduced severity of covid-19 in children is unknown. one possible explanation for this condition is that children have a poorer immune response to coronavirus [6–8]. among other factors, we may note the various expressions of angiotensin-converting enzyme receptor, which is one of the coronavirus’s potentially harmful mechanisms in children’s respiratory systems [9]. furthermore, lowering the likelihood of children’s exposure or limiting the frequency of their tests are reasons for this problem. other explanations include viral involvement in the respiratory system, which has lowered covid-19 virus accumulation in their respiratory system [10]. similar to the egyptian child with covid-19 and hlh, in this study, the reported case had no symptoms of respiratory tract involvement or hypoxemia while there was mild respiratory tract involvement and hypoxemia reported by mostafavi et al. however, symptoms in the egyptian case got worse and led to patient’s death, while the case from isfahan recovered from hypoxemia and invasive ventilation [1, 4]. our case also developed nonrespiratory-involved covid-19 with disturbances in hematologic indexes. doi 10.18502/sjms.v17i1.10691 page 142 sudan journal of medical sciences alireza jenabzadeh et al although immune system insufficiency has been considered as an underlying cause of covid-19 in some of these reports, the link between immune-deficiency patients and severe covid-19 cases has yet to be reported [11]. it appears that the probability of immunological insufficiency in patients infected with covid-19 is lower than in those with other underlying illnesses. it also had better outcomes compared to other comorbidities [2, 6–9]. in limited research on children with covid-19, the severity of the disease was observed to be low when immunosuppressive medications were administered to kidney transplant and inflammatory bowel disease patients [12, 13]. in a study of 187 children aged two to four years with cancer in new york, only 20 tests were found to be positive, and 1 of them required hospitalization. the study also revealed that as compared to the general population, this group is less prone to covid-19 infection and its adverse effects [11]. in filocamo et al.’s study on children suffering from covid-19 and receiving immunosuppressive medications for rheumatology illness, it was discovered that this group is not at a greater risk of severe covid-19 respiratory complications or lifethreatening consequences [14]. in this case report, a child referred to the health facility with aplastic anemia was diagnosed with hlh and covid-19. among the reasons (drug, shlh, infection with viruses [ebv, cmv, hbv, hcv, hiv, hav, vzv, parvovirus b19, mumps, rubella, and influenza], and malignancy) for aplastic anemia, because of the splenomegaly and the increase in liver transaminases, triglycerides, and ferritin, we suspected the hlh. while the treatment for hlh is chemotherapy with etoposide and glucocorticoids and ivig, in this case, due to the aplastic anemia, dexamethasone and ivig were used, besides interferon β-1a and lopinavir/ritonavir as the national protocol for covid-19 treatment. except for the hydroxychloroquine, the same treatment regimens were used for covid19 and hlh treatment in our and mostafavi et al.’s patients. neither ours nor mostafavi et al.’s study used tocilizumab because of the normal level of il-6 [4]. 4. conclusion the symptoms of covid-19 in our patient were very mild due to the low number of wbcs and, as a result, released cytokines. children may experience nonspecific covid-19 symptoms, so keeping an open mind is important. we suggest that further extensive research in the field of covid-19 and hlh be performed in light of the literature. doi 10.18502/sjms.v17i1.10691 page 143 sudan journal of medical sciences alireza jenabzadeh et al acknowledgements nil. ethical considerations this study was approved by yazd shahid sadoughi medical science university ethics commission (code: ir.ssu.medicine.rec.1400.180). also, written informed consent to publish the information was obtained from the patient’s legal guardians. competing interests nil. availability of data and material the authors confirm that all relevant data are included in the article and/or its supplementary information files. funding none. references [1] adel, m. and magdy, a. (2021). sars-cov-2 infection in an infant with non-respiratory manifestations: a case report. egyptian pediatric association gazette, vol. 69, no. 1, p. 3. [2] deville, j. g., song, e., and ouellette, c. p. (2021). covid-19: clinical manifestations and diagnosis in children. uptodate. [3] akçabelen, y., yozgat, a. k., ozkaya-parlakay, a., et al. (2020). covid-19 in a child with severe aplastic anemia. authorea preprints. [4] mostafavi, s. n., sadeghizadeh, a., babaei, s., et al. (2020). successful recovery of a child with covid-19-induced secondary hemophagocytic lymphohistiocytosis. archives of pediatric infectious diseases, vol. 10, no. 1, p. e111434. doi 10.18502/sjms.v17i1.10691 page 144 sudan journal of medical sciences alireza jenabzadeh et al [5] arceci, r. j. (2016). histiocytosis syndromes. lanzkowsky’s manual of pediatric hematology and oncology (pp. 407–428). elsevier. [6] brodin, p. (2020). why is covid-19 so mild in children? acta paediatrica, vol. 109, no. 6, pp. 1082–1083. [7] cyranoski, d. (2020). why children avoid the worst coronavirus complications might lie in their arteries. nature, vol. 582, no. 7812, pp. 324–325. [8] zimmermann, p. and curtis, n. (2021). why is covid-19 less severe in children? a review of the proposed mechanisms underlying the age-related difference in severity of sars-cov-2 infections. archives of disease in childhood, vol. 106, no. 5, pp. 429–439. [9] bunyavanich, s., do, a., and vicencio, a. (2020). nasal gene expression of angiotensin-converting enzyme 2 in children and adults. jama, vol. 323, no. 23, pp. 2427–2429. [10] hyde, z. (2021). difference in sars-cov-2 attack rate between children and adults may reflect bias. clinical infectious diseases, vol. 74, no. 1, pp. 152–155. [11] boulad, f., kamboj, m., bouvier, n., et al. (2020). covid-19 in children with cancer in new york city. jama oncology, vol. 6, no. 9, pp. 1459–1460. [12] marlais, m., wlodkowski, t., vivarelli, m., et al. (2020). the severity of covid-19 in children on immunosuppressive medication. the lancet child & adolescent health, vol. 4, no. 7, pp. e17–e18. [13] turner, d., huang, y., martín-de-carpi, j., et al. (2020). corona virus disease 2019 and paediatric inflammatory bowel diseases: global experience and provisional guidance (march 2020) from the paediatric ibd porto group of european society of paediatric gastroenterology, hepatology, and nutrition. journal of pediatric gastroenterology and nutrition, vol. 70, no. 6, pp. 727–733. [14] filocamo, g., minoia, f., carbogno, s., et al. (2021). absence of severe complications from sars-cov-2 infection in children with rheumatic diseases treated with biologic drugs. journal of rheumatology, vol. 48, no. 8, pp. 1343–1344. doi 10.18502/sjms.v17i1.10691 page 145 introduction case report history and examination discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11461 production and hosting by knowledge e short communication the menace of predatory journals prerna agarwal* and bharti bhandari government institute of medical sciences, greater noida, gautam buddha nagar, uttar pradesh, india orcid: prerna agarwal: https://orcid.org/0000-0001-9466-1253 bharti bhandari: https://orcid.org/0000-0002-0030-9601 1. what is a predatory journal? authors often receive emails with “call for papers” or “rapid publication in indexed international journal” subject lines. the links provided in such emails lead to obscure journal homepp. which leave a naive author amazed at the opportunity to get their work published so easily or an experienced author completely wary. these are “predatory journals.” the term was first used in the year 2008, when jeffrey beall, a librarian with the university of colorado, usa listed poor-quality open-access publishing houses and their journals in his “beall’s list” and used the term to identify them [1]. these journals bypass the rigorous peer-review process of articles, making it a mere eye-wash and offer quick open-access publication to the authors at a bearable cost [2]. 2. what are the perils of publishing with predatory journals? (figure 1) while a new researcher/author may be unaware of their existence and be lured by the ease of publication with these journals, some authors with weak ethical principles purposefully publish with these journals to enhance their curriculum vitae and advance their career [3]. the practice, in any case, has become a money minting business for such publishers at the cost of credibility of both the research and the researcher. it jeopardizes the sanctity of research process, makes a waste of the resources of funding agencies and other stake holders, and puts the career of researchers at risk. moreover, such poorly reviewed works dilute the contribution of genuine work to advancement of science and discovery. the nuisance of plagiarism, table research, conflicts of interest, etc. all thrive under the umbrella of predatory journals. how to cite this article: prerna agarwal* and bharti bhandari (2022) “the menace of predatory journals,” sudan journal of medical sciences, vol. 17, no. 2, pp. 279–283. doi 10.18502/sjms.v17i2.11461 page 279 corresponding author: prerna agarwal; email: dr.prernanaagarwal@gmail. com received 17 december 2021 accepted 31 march 2022 published 30 june 2022 production and hosting by knowledge e prerna agarwal and bharti bhandari. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr.prernanaagarwal@gmail.com mailto:dr.prernanaagarwal@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences prerna agarwal and bharti bhandari figure 1: predatory publication practices. 3. how does one identify a predatory journal? (figure 2) figure 2 it is important that researchers be vigilant and not fall prey to the honey trap laid down by these illegitimate journals. “call for papers” from the editors of these journals often flood inboxes. their websites may appear very attractive. but careful inspection reveals doi 10.18502/sjms.v17i2.11461 page 280 sudan journal of medical sciences prerna agarwal and bharti bhandari obscure indexing databases, unimpressive editorial boards, absent online manuscript submission system, rapid review and publication promise, and of course, unclear article processing method, including publishing charges. once the manuscript is submitted, it may be accepted and published in no time, many a times without a review, in sharp contrast to the desk rejection often met with legitimate journals. the themes of papers published by these journals may often be irrelevant to the scope of the journal cited on their websites. examination of these papers reveals their paucity of scientific and language critique [2–5]. 4. what pushes authors toward predatory journals? (figure 1) predatory journals thrive mainly because of paucity of opportunities available to a new researcher, and paucity of quality in the work. budding researchers often face desk rejection because of their affiliation to the lesser-known universities and lesser-known nations. they end up spending more time in finding appropriate journal, redoing work according to journals’ requirements and in the submissionresubmission process, etc. than they actually spent in doing the work and writing the manuscript. while facing the pressure of time to deliver their research output (publications) in their profession, paper publication becomes an arduous task. and “predatory journals” ease it! the other aspect pertains to the quality of work presented in the paper. good indexed journals subject manuscripts to stringent scrutiny and only few manuscripts meet those standards. and then there is “fabricated” research data as well that gets exposed during the process. however, every researcher would like their work to see the light of day and that the work be counted. again, “predatory journals” are here to help! of course, there are also those researchers who fall into the trap of predatory journals because of sheer ignorance [3]. 5. what can be done to do away with the predatory publishing practices? conveniently, if the predatory journals do not get their business, they will die their own death! while it is easier said than done, continuous efforts to create awareness about predatory publishing practices among researchers, funding agencies, and readers are required. researchers must always uphold their integrity and commitment to doi 10.18502/sjms.v17i2.11461 page 281 sudan journal of medical sciences prerna agarwal and bharti bhandari advancement of science in its truest sense. editors and publishers must vow to abide by committee on publication ethics (cope) guidelines. legal action against the publishers as well as the authors may also be resorted to if such need arises. researchers should be discouraged from including their predatory journal publications in their cvs, as such publications may be identified and discredited in career advancement, funding of such researchers may be restricted, etc. [2, 5]. it is in the best interest of science, researchers, and beneficiaries of research that the encroachment by these shady journals be curbed to preserve the sanctity and meaningfulness of research. it calls for our collective efforts to enforce the same. acknowledgements none. competing interests no potential conflict of interest relevant to this article was reported. funding none. references [1] butler, d. (2013). investigating journals: the dark side of publishing. nature, vol. 495, pp. 433–435. https://doi.org/10.1038/495433a [2] linacre, s., bisaccio, m., and earle, l. (2019). publishing in an environment of predation: the many things you really wanted to know, but did not know how to ask. journal of business-to-business marketing, vol. 26, no. 2, pp. 217–228. https://doi.org/10.1080/1051712x.2019.1603423 [3] cortegiani, a., manca, a., and giarratano, a. (2020). predatory journals and conferences: why fake counts. current opinion in anaesthesiology, vol. 33, no. 2, pp. 192–197. https://doi.org/10.1097/aco.0000000000000829 [4] cobey, k. d., lalu, m. m., skidmore, b., et al. (2018). what is a predatory journal? a scoping review. f1000research, vol. 7, p. 1001. https://doi.org/10.12688/f1000research.15256.2 doi 10.18502/sjms.v17i2.11461 page 282 sudan journal of medical sciences prerna agarwal and bharti bhandari [5] angadi, p. v. and kaur, h. (2020). research integrity at risk: predatory journals are a growing threat. archives of iranian medicine, vol. 23, no. 2, pp. 113–116. http://www.aimjournal.ir/article/aim-8215 doi 10.18502/sjms.v17i2.11461 page 283 what is a predatory journal? what are the perils of publishing with predatory journals? (figure 1) how does one identify a predatory journal? (figure 2) what pushes authors toward predatory journals? (figure 1) what can be done to do away with the predatory publishing practices? acknowledgements competing interests funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13597 production and hosting by knowledge e editorial the importance of peer review and guidelines for becoming a reviewer dr emily choynowski head of research development and dissemination, knowledge e, dubai, uae orcid: emily choynowski: https://orcid.org/0000-0002-6681-1709 peer review is a vitally important part of the academic ecosystem and is integral to the credibility and sustainability of all scholarly communications. the process by which independent and unbiased experts evaluate scholarly manuscripts to help determine whether they are suitable for publication, peer review not only ensures that only the best possible version of a manuscript is published but also helps to prevent the dissemination of bad science by identifying inadequate or faulty research. this editorial will offer a brief overview of peer review – what it is, why it matters, and how to be a reviewer. however, as the pressure on researchers to publish their work increases and the number of academic journals grows, so too do the pressures on editorial boards to find suitable peer reviewers. as competent reviewers with the requisite expertise, the available time, and the willingness to make a voluntary (without renumeration) contribution to the academic community are growing increasingly scarce, this integral cornerstone of the whole research edifice is now at risk. we, therefore, urge all our readers to consider becoming peer reviewers. serving as a peer reviewer will not only help to advance global scholarly research but also help with individual career development. there is an increasing drive toward public recognition of reviewers and their work, and peer review activities can now contribute to professional development and employment key performance indicators (kpis). in addition, reviewing can give advanced access to groundbreaking new research and offer valuable networking opportunities with leading journals in the field. how to become a reviewer there are typically three reasons why people feel they are not suitable to review an article. first, they might lack the relevant expertise in the subject field. second, they might not have time. third, they might not feel equipped and confident in their ability how to cite this article: dr emily choynowski (2023) “the importance of peer review and guidelines for becoming a reviewer,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 124–126. doi 10.18502/sjms.v18i2.13597 page 124 corresponding author: dr emily choynowski; email: e.choynowski@knowledgee.com received 5 june 2023 accepted 7 june 2023 published 30 june 2023 production and hosting by knowledge e dr emily choynowski. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dr emily choynowski to conduct a review. we cannot help with the first consideration; however, we hope to address the second two issues and encourage all our readers to consider becoming peer reviewers for journals within their field. so, let us start with the question of timing. as researchers and medical professionals, we have countless demands upon our time, and it can often feel like there is nothing left for additional tasks. however, a peer review need not take up that much time (the average review is only 400–500 words and requires around 3–4 hr to produce). moreover, reviewing activities can be scheduled to fit around existing commitments, and many editorial boards will give quite long lead times, of two months or more. if a researcher wishes to become a reviewer, the first step is to identify suitable journals to review for (typically, these will be the journals the researcher already engages with, either as a reader or as a contributing author). researchers should contact the editorial board, offering to be a reviewer and outline their areas of expertise and academic qualifications – to demonstrate their suitability for the role. in particular, we advise researchers to take a few minutes to consider what the editorial boards will look for, and shape their approach accordingly. in our view, editorial boards usually look for reviewers who are (1) experts in the field and have ideally published in this area; (2) unbiased with no conflicts of interest; (3) available and capable of delivering the review in a timely manner; and finally, (4) capable of being constructive rather than destructive, providing helpful feedback rather than negative criticism. conducting a review when a reviewer receives an invitation to review, there are a few key questions to help determine whether or not they should accept the invitation. first, do they have the necessary subject knowledge? second, do they have time to conduct the review and return the report within the requested timeframe? third, do they understand the journal’s scope and the editor’s well enough to be able to evaluate a manuscript’s suitability for that publication? the answer to all three of these questions should be “yes.” finally, are there any conflicts of interest which might influence the review – if so, the reviewer should inform the editor, who will decide whether to proceed. after accepting a review invitation, the reviewer will need to read the manuscript, evaluate its suitability for the journal, and write up a report. we usually suggest the reviewer reads the manuscript at least twice – first skimming it to look for significant issues and then conducting an in-depth examination. doi 10.18502/sjms.v18i2.13597 page 125 sudan journal of medical sciences dr emily choynowski editors will have individual criteria and checklists, and reporting guidelines can vary by subject field and type of study. however, four essential questions should form the basis of any peer review: does the manuscript make a clear and quantifiable contribution to the field?; is the research properly conducted?; are the findings correctly reported and analyzed; and is the manuscript suitable for the journal? common issues which reviewers need to identify and address to prevent the publication of unsuitable manuscripts include studies similar or identical to something published already, poorly written or poorly structured manuscripts, missing content or content that does not conform to the journal’s author guidelines, a lack of relevant and recent references for the topic of study, and a general lack of academic rigor. when writing the review, the reviewer needs to provide constructive and unbiased criticism, avoid personal or offensive comments, and aim for concision. the review report should identify what contributions the manuscript makes to the field, confirm that the manuscript displays academic rigor (with evidence of efficient and effective research, appropriate citations, and proper analysis), and evaluate whether the study lies within the journal scope and is it appropriate for the target readership. where applicable, the review report should highlight potential strengths and weaknesses and make relevant suggestions for improvement. finally, the review report should offer a straightforward decision for the editor regarding whether to accept, return for revision, or reject. we hope you have found this brief overview helpful and informative, and we hope you will all consider contributing to the progress of scholarly research within your subject fields in the future. doi 10.18502/sjms.v18i2.13597 page 126 how to become a reviewer conducting a review sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12557 production and hosting by knowledge e research article knowledge and practice regarding hemodialysis procedure among nurses working at the dialysis centers, in khartoum, sudan: a cross-sectional study elwaleed idris sagiron1 and ahmed abdalla jarelnape2* 1al-ghad international colleges for applied medical, saudi arabia 2al baha university, faculty of applied medical sciences, nursing department, saudi arabia orcid: elwaleed idris sagiron: https://orcid.org/0000-0001-6077-4727 ahmed abdalla jarelnape: https://orcid.org/0000-0001-5327-9250 abstract background: hemodialysis procedures is considered as a supportive management for kidney failure. nurses play a major role in hemodialysis procedures, because most of the complications facing patients during dialysis as hypotension, cramped muscles, and weak pulse, need nurses with knowledge and practical experience. the current study aimed to assess nurses’ knowledge and practice about hemodialysis procedures. methods: this is a cross-sectional study, which included 103 nurses who worked in dialysis centers in khartoum state in sudan, from february to may 2022. a selfadministered questionnaire and observational checklists were used to collect the data and was analyzed using the statistical program for social science (spss) version 23, the knowledge and practice score was calculated, and the mean was obtained. results: the results of our study showed the mean scores of the participant knowledge 11.3, and practice 13.6, and also showed statistical significance regarding the relationship between the level of education and knowledge of nurses regarding hemodialysis procedure; p-value = 0.01. conclusion: the study concluded that there is sufficient knowledge and practice of nurses in dialysis centers, and there is also a relationship between educational level and knowledge, so the study recommends conducting continuous training for nurses in dialysis centers. keywords: nurses’ knowledge, practice, hemodialysis procedure 1. introduction hemodialysis procedure is a must for patients with kidney failure, nurses in dialysis centers play a critical role in enhancing patient care, and reducing potential complications [1]. hemodialysis, peritoneal dialysis, and kidney transplantation are the three methods of renal replacement therapy that are now available for end-stage renal failure [2-4]. how to cite this article: elwaleed idris sagiron and ahmed abdalla jarelnape* (2022) “knowledge and practice regarding hemodialysis procedure among nurses working at the dialysis centers, in khartoum, sudan: a cross-sectional study,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 599–609. doi 10.18502/sjms.v17i4.12557 page 599 corresponding author: ahmed abdalla jarelnape; email: ahmed5074@gmail.com received 27 august 2022 accepted 22 september 2022 published 31 december 2022 production and hosting by knowledge e elwaleed idris sagiron and ahmed abdalla jarelnape. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12557&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape renal replacement therapy, hemodialysis is the most routinely utilized [5]. the number of people with end-stage renal disease is rising all around the world, and the number of people who need hemodialysis is rising as well [6]. end-stage renal disease is led to the accumulation of toxins and waste in the body and may lead to reduced appetite, weight loss, puffy eyes, difficulty sleeping, decrease in urination, dry skin, itching, fatigue, swelling of the ankles, feet, and an increase in electrolytes, the most dangerous of which is an increase in potassium, the consequences of hyperkalemia are also influenced by other factors, such as the presence of heart disease or another blood electrolyte (calcium and magnesium) disorders that can increase the risk of arrhythmias [7, 8]. new treatments, such as high-flux dialysis and hemodiafiltration, have been used in clinical practice to improve the removal of moderate to large-sized molecular poisons, and small to medium-sized molecules can be eliminated with high-flux hemodialysis [9]. the glomerular filtration rate per 1.8 m2 of end-stage renal illness is less than 20 ml/min. kidney replacement therapy, such as dialysis or renal transplantation, is required because the renal function has gotten so bad that it can no longer sustain life over the long term. renal dialysis is needed; nevertheless if the glomerular filtration rate is less than 8% and the amount of uremia is high [10]. kidney illness raises your risk of having a heart attack or stroke because the kidneys are damaged and unable to properly filter blood. additionally, waste builds up in the body due to kidney illness. important risk factors for kidney disease include hypertension, diabetes, and a family history of renal impairment, around 662,000 americans have kidney disease, with 470,000 receiving dialysis and 190,000 receiving a functioning kidney transplant [11, 12]. hemodialysis procedure requires trained nursing staff as they have special training of the procedure to achieve satisfactory results without complication [13]. the period of stay for kidney failure patients to receive dialysis is the worst experience during their stay in the hospital [14]. there is a limitation of data on dialysis unit nurses experiences with hemodialysis procedures with adults and the errors that can occur during the procedure, their experiences will be essential in developing future linked interventions with specific instructional activities aimed at reducing possible complications. 2. materials and methods 2.1. study design, setting, population and period this was a cross-sectional analytical study among nurses working in dialysis centers in khartoum state in sudan, from february to may 2022. these dialysis centers were: doi 10.18502/sjms.v17i4.12557 page 600 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape hemodialysis center at omdurman hospital, hemodialysis center at ahmed qasem hospital, and dialysis center ibn sina hospital. 2.2. inclusion and exclusion criteria the inclusion criteria were as follows, registered nurses working in hemodialysis units and collaborators nurses in hemodialysis units who have spent more than six months, and those who agreed to participate in the study. exclusion criteria are students in the training period and collaborators with less than six months experience. 2.3. study sample a total coverage sampling composed of 103 nurses was included in the study from dialysis centers in khartoum state in sudan, mentioned above in the population section. 2.4. data collection instrument the data were collected by using a questionnaire and observational checklists, the questionnaire contains two main parts, the first is demographic data of the participants (age, gender, level of education, years of experience, and previous training courses, and the second part of the questionnaire to assess participants’ knowledge about hemodialysis procedure, contains 15 questions regarding the protocols used in dialysis and the care of patients during it. a reliability test for the questionnaire was made, and the reliability of the questionnaire was 0.88 for the cronbach alpha of the program, the questionnaire questions were designed from previous studies [15]. to suit the environment and place of study. 2.5. study score knowledge and practice score, a score of one was awarded for a correct response, and zero degrees was a score for an incorrect response in the scoring system for overall knowledge of hemodialysis. for producing the mean score, a percent score was calculated from these scores, if the nurse obtains a score of knowledge 75% or more then it was considered satisfactory, and less than 75% was considered unsatisfactory. participants’ observation checklists, to assess participants’ practice with hemodialysis procedure, contains the steps involved in the dialysis, a score of one was provided for totally completing (competent) certain nursing practice stages, while a score of zero was given for not completing them (incompetent). the grades were converted into a doi 10.18502/sjms.v17i4.12557 page 601 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape percentage, giving a mean score for the part and those who got 75% or more were considered competent whereas less than 75% were considered incompetent. 2.6. statistical analysis the study data were analyzed by statistical program for social science (spss) version 23. the variables that were entered for analysis are demographic data, level of knowledge, and practice toward hemodialysis procedure, a set score of one was awarded for a correct response and zero degrees was a score for an incorrect response, pvalue of <0.05 was considered statistically significant for chi-square test to assess the relationship between variables. 3. results 3.1. demographic characteristics table 1 showed the demographic variables that the study participants had (68%) of the participants were female, (83%) of the participants had a bachelor’s degree, and only (2%) had a phd, most of the subjects (71%) were between 28–33 years old, (46%) of the participants had experience ranging from (1-4 years), and (87%) of the participants had attended a special training course about hemodialysis. table 1: demographic characteristics of the study participants (n = 103). variable frequency (no.) percentage (%) sex male 33 32% female 70 68% educational qualification diploma 11 10.7% bachelor 85 82.5% master’s 5 4.9% phd 2 1.9% age (yr) 22–27 21 20.4% 28–33 71 68.9% >34 11 10.7% experience (yr) 1–4 67 67.3 % 4–7 24 21% >8 12 11.7% special training course about hemodialysis yes 87 84.5% no 16 15.5% doi 10.18502/sjms.v17i4.12557 page 602 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape 3.2. knowledge regarding hemodialysis among study participants table 2 shows the responses of the study participants where all aspects of the hemodialysis procedure were satisfactory, the result of the mean value of the participants correct knowledge regarding hemodialysis was (73%) while the incorrect knowledge of the participants was (27%), a significant difference was observed at (p-value < 0.05). table 2: knowledge regarding hemodialysis among study participants (n = 103). knowledge about hemodialysis procedure correct no. (%) incorrect no. (%) p-value definition of hemodialysis? 89 (86) 14 (14) 0.01 indication of hemodialysis? 71 (69) 32 (31) 0.02 when is dialysis needed? 75 (73) 28 (27) 0.02 what are the benefits of hemodialysis? 91 (88) 12 (12) 0.01 what are the types of dialysis? 66 (64) 37 (36) 0.03 how many dialysis in a week? 86 (83) 17 (17) 0.00 how long is a dialysis session? 81 (79) 22 (21) 0.01 hemodialysis benefits for patients with kidney failure? 80 (78) 23 (22) 0.01 what are the side effects of hemodialysis? 61 (59) 42 (41) 0.03 complications of hemodialysis? 71 (69) 32 (31) 0.02 why does blood pressure drop during diagnosis? 59 (57) 44 (43) 0.03 overall knowledge score about hemodialysis 75 (73) 28 (27) 0.01 3.3. practice regarding hemodialysis among study participants table 3 shows the responses of the study participants regarding the practical aspect of performing hemodialysis, the results of the study showed the efficiency of nurses in most of the procedures, and the overall practical score for hemodialysis was (78%). table 4 shows statistical significance at a p-value < 0.05 of nurses, regarding the relationship between the level of education and knowledge of hemodialysis procedures. table 5 shows there is statistical significance at a p-value < 0.05 regarding the relationship between age and knowledge of the participants about hemodialysis procedures. table 6 shows there was no statistical significance at a p-value < 0.05 about the relationship between sex and knowledge of the participants about hemodialysis. table 7 shows the students’ sources of information regarding hemodialysis, (50%) of the participants got information through workshops and seminars, (30%) by searching online, and about (13%) obtained information through the exchange of experiences with colleagues. doi 10.18502/sjms.v17i4.12557 page 603 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape table 3: practice regarding hemodialysis among study participants (n = 103). practice about hemodialysis procedure competent no. (%) incompetent no. (%) p-value setup l initiate dialysis machine 103 (100) 0 (0) 0.00 take steps to infection control 95 (92) 8 (8) 0.01 general assessment of the patient (vital signs) 77 (75) 26 (25) 0.02 checks for machine (alarm settings) 89 (86) 14 (14) 0.01 assess and monitor patient and equipment during dialysis 71 (69) 32 (31) 0.02 checks access to hemodialysis. 91 (88) 12 (12) 0.01 checks equipment of hemodialysis (water system, dialysate, dialyzer) 87 (84) 16 (16) 0.01 checks if medications are given during diagnosis? 67 (65) 36 (35) 0.02 size of a dialysis catheter? 61 (59) 42 (41) 0.03 type of catheter used for hemodialysis? 59 (57) 44 (43) 0.04 overall practice score about hemodialysis 80 (78) 23 (22) 0.02 table 4: relationship between the knowledge of the participants about hemodialysis procedure and educational qualification (n = 103). knowledge p-value educational qualification educational qualification satisfactory no. % unsatisfactory no. % 0.01 diploma 7 (6.8) 4 (3.9) bachelor 73 (70.9) 12 (11.6) master’s 5 (4.8) 0 (0) phd 2 (1.9 0 (0) *there is a significant difference at the 0.05 level. table 5: relationship between the knowledge of the participants about hemodialysis procedure and age (n = 103). knowledge p-value age category age category (yr) satisfactory no. % unsatisfactory no. % 0.01 22–27 15 (14.6) 6 (5.8) 28–33 58 (56.3) 13 (12.6) >34 11 (10.7) 0 (0) *there is a significant difference at the 0.05 level. table 6: relationship between the knowledge of the participants about hemodialysis and sex (n = 103). knowledge p-value sex sex satisfactory no. % unsatisfactory no. % 0.06 male 28 (27.2) 5 (4.8) female 46 (44.7) 24 (23.3) *there was no significant difference at the 0.05 level. doi 10.18502/sjms.v17i4.12557 page 604 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape table 7: sources of information about hemodialysis (n = 103). sources of information about hemodialysis frequency (no.) percentage (%) through workshops and seminars 51 49.5% through the period of study and training 10 9.7% by searching on the internet 29 28.2% through the experiences of colleagues 13 12.6% total 103 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% participants knowledge correct incorrect figure 1: the percentage of participants in the study knowledge (n = 103). 0% 10% 20% 30% 40% 50% 60% 70% 80% participants practical competent incompetent figure 2: the percentage of participants in the study practical experience (n = 103). doi 10.18502/sjms.v17i4.12557 page 605 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape 4. discussion the objective of this study was to describe the nurses’ knowledge and practice regarding hemodialysis procedures, which is a significant challenge for nurses working in dialysis centers. the complications that occur during hemodialysis sessions, such as hypotension are one of the biggest problems when facing patients, this consequence was supported by a study that found that hypotension, or low blood pressure, is one of the most prevalent complications during the patients first session of hemodialysis [16]. table 5 states the significant association between the age of participants and their mean knowledge and practice score (p-value=0.01). this result was supported by a study conducted about the experience of nurses in hemodialysis care, naturally, we found that nurses with higher degrees and practical experiences were more knowledgeable [22]. regarding the demographic characteristics of the participants in the study table 1. (68%) of them were females, this result is consistent with a study conducted in sudan, the results of which were also (70%), the highest percentage of participants were females [17]. the study also showed that (82%) of them hold a bachelor’s degree also in agreement with the previous study [17], in the percentage of educational qualifications for the study group. it was found that 69% of the participants were aged between (28-33 years), and this result is similar to a study conducted in assiut egypt on the knowledge and practice of nurses about dialysis [18]. this study shows that 67% of the participants in the study had experiences between 1-4 years a similar study was held in porur, chennai [19]. it was found that 74% had less than five years of experience in dialysis units, the reason that most nurses working in dialysis units are recent graduates with a desire to work in specialized units. regarding special training courses about hemodialysis, the results of the study showed that (85%) of the nurses had attended training courses and workshops on hemodialysis. this result differs from a study conducted to measure the knowledge of nurses in hemodialysis units, where it was found that (61%) of them did not receive any training courses [20]. but recently, the dialysis units went to hold training courses for the medical staff constantly, which had a positive impact on the outputs of the work of the hemodialysis units and reduced the complications arising from it. regarding the total knowledge level of the participants in the study, we found that most of them (73%) had sufficient knowledge about hemodialysis in all its aspects. this result was in agreement with many other studies on dialysis, including studies [20, 21] about nurses’ knowledge of hemodialysis, and the results were good (72%, 74%). this is due to the aforementioned reason that the dialysis units have continuous courses and workshops, and also because the results showed that most of the medical staff are recent graduates and therefore, they have recent information. doi 10.18502/sjms.v17i4.12557 page 606 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape regarding the total practice level of the participants in the study, we found that majority of nurses (78%) had competent practice about hemodialysis in all its aspects, this result is in agreement with a study on the practice of nurses about hemodialysis, which found that (60%) of them had satisfactory practical experience [20]. 5. conclusion since the study was conducted in the kidney centers in the state of khartoum; therefore, the results of the study cannot be generalized to every kidney center in sudan, it is good that in the future more studies will be conducted on this matter, we also recommend that there should be continuous training courses for nurses in dialysis centers, most of the participants had adequate knowledge toward hemodialysis procedure. acknowledgements none. ethical considerations none. competing interests the authors declare that they have no conflict of interest. availability of data and material anonymous data are available. funding none. references [1] emran, s. (2022). nephrology nurses’ views in giving a dietary recommendation for dialysis patients: an interview study. belitung nursing journal, 7(7), 425–430. doi 10.18502/sjms.v17i4.12557 page 607 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape [2] han, d., bock, m., glover, j., & vemulakonda, v. m. (2022). outcomes of dialysis in neonates with anuric end-stage renal disease at birth: ethical considerations. journal of perinatology, 13(5), 159 [3] khan, s., & rosner, m. (2017). peritoneal dialysis for patients with end-stage renal disease and liver cirrhosis. journal of the international society for peritoneal dialysis, 38(2), 397–401. [4] manzi, e., posada, j. g., mesa, l., echeverri, g. j., duran, c., caicedo, l. a., villegas, j. i., & tobón, g. j. (2017). kidney transplantation for end-stage renal disease in lupus nephritis, a very safe procedure: a single latin american transplant center experience. lupus, 26(11), 456–512. [5] jin, d. c., yun, s. r., lee, s. w., han, s. w., kim, w., park, j., & kim, y. k. (2015). lessons from 30 years’ data of korean end-stage renal disease registry. kidney research and clinical practice, 43(4), 132–139. [6] kirsch, a. h., lyko, r., nilsson, l. g., beck, w., amdahl, m., lechner, p., schneider, a., wanner, c., rosenkranz, a. r., & krieter, d. h. (2017). performance of hemodialysis with novel medium cut-off dialyzers. nephrology dialysis transplantation, 32(3), 165–172. [7] vanholder, r., pletinck, a., schepers, e., glorieux, g. (2018). biochemical and clinical impact of organic uremic retention solutes: a comprehensive update. toxins, 10(5), 133–159. [8] mustafa, s., & baris, h. n. (2020). comparison of circulating levels of uremic toxins in hemodialysis patients treated with medium cut-off membranes and high-flux membranes. blood purification, 94(1), 733–742. [9] yeter, h .h., korucu, b., akcay, o. f., derici, k., derici, u., & arinsoy, t. (2020). effects of medium cut-off dialysis membranes on inflammation and oxidative stress in patients on maintenance hemodialysis. international urology and nephrology, 52(5), 1779– 1789. [10] al-abbas, a., peter, s., helen, n., et al. (2019). detection and evaluation of chronic kidney disease. american journal of kidney diseases, 59(4), 523–530. [11] watnick, s. (2018). the kidney accelerator: innovation wanted, nephrologists needed. clinical journal of the american society of nephrology, 13(2), 1750–1761. [12] saha, m., & allon, m. (2017). diagnosis, treatment, and prevention of hemodialysis emergencies. clinical journal of the american society of nephrology, 12(1), 357– 369. [13] barbose, g. s., & valdares, g. v. (2014). becoming proficient knowledge and practice of hemodialysis nurses. escola anna nery, 18(1), 163–166. doi 10.18502/sjms.v17i4.12557 page 608 sudan journal of medical sciences elwaleed idris sagiron and ahmed abdalla jarelnape [14] brady, b. m., zhao, b., niu, j., winkelmayer, w. c., milstein, a., chertow, g. m., & erickson, k. f. (2018). patient-reported experiences of dialysis care within a national pay-for-performance system. jama internal medicine, 11(1), 1358–1367. [15] hadi, q., & alreda, d. j. (2022). assessment of nurses’ knowledge and practices concerning hemodialysis adequacy guideline in baghdad teaching hospitals. kufa journal for nursing sciences, 11(1), 1–9. [16] mahmood, a., aziz, k., ahmed, s., baig, z. f., muhammad, w., rahman, m. (2018). frequency of acute complications of hemodialysis in adult age group at a tertiary care center. pafmj-pakistan armed forces medical journal, 9(2), 1219–1224. [17] jarelnape, a. a. a. (2022). nurses’ knowledge about the discharge plan for patients after cardiac surgery at the sudan heart institute. majmaah journal of health sciences, 9(2), 71–79. [18] hassona, f. m. (2011). evaluation of an educational program: a report from the hemodialysis unit in zagazig univer-sity hospitals, egypt. nephrology nursing journal, 7(3), 39–53. [19] kanagarajah, s., velraja, s., & arambakkam, h. j. (2022). knowledge, attitude, and practices of renal diets among hemodialysis patients. biomedical and biotechnology research journal, 6(1), 86–92. [20] al-mawsheki, e., ibrahim, m. h., & taha, n. m. (2016). nurses’ knowledge and practice regarding care for the patients during hemodialysis. the medical journal of cairo university, 4(1), 1135–1141. [21] yousef, y. e., elashir, u. m., mahmoud, s. r., & maghraby, n. (2019). the effect of nursing educational program on knowledge and practice of nurses regarding infection control measures for children under hemodialysis. egyptian nursing journal, 7(3), 113–133. [22] shahdadi, h., & rahnama, m. (2018). experience of nurses in hemodialysis care: a phenomenological study. journal of clinical medicine, 7(2), 30–45. doi 10.18502/sjms.v17i4.12557 page 609 introduction materials and methods study design, setting, population and period inclusion and exclusion criteria study sample data collection instrument study score statistical analysis results demographic characteristics knowledge regarding hemodialysis among study participants practice regarding hemodialysis among study participants discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10689 production and hosting by knowledge e original article isolation, extraction, and characterization of verotoxin-producing escherichia coli o157:h7 from diarrheal stool samples muhammad musthafa poyil1, ponmurugan karuppiah2,3*, suresh s. s. raja4, p. sasikumar5 1department of basic medical sciences, college of medicine, prince sattam bin abdulaziz university, al-kharj, saudi arabia 2department of botany and microbiology, college of science, king saud university, riyadh, saudi arabia 3department of microbiology, k.s. rangasamy college of arts and science, tiruchengode, namakkal, tamil nadu, india 4department of microbiology, government arts and science college, perambalur, tamil nadu, india 5department of microbiology, the madura college, madurai, tamil nadu, india abstract background: escherichia coli o157:h7 infection causes hemorrhagic colitis and is diagnosed based on symptoms such as cramps, stomach pain, and watery diarrhea. shiga-like toxins (verotoxin) produced by escherichia coli o157:h7 damages endothelial cells of both kidney and brain, causing renal dysfunction and neurological problems. methods: the present study focuses on identifying the prevalence of verotoxinproducing escherichia coli o157:h7 among diarrheal inpatients at erode government hospital, india, and its antibiogram. further, the verotoxins were characterized by using sds-page analysis. a total of 123 diarrheal stool samples were collected, and 37 of them (30.08% of the total samples) were found to have the presence of e. coli. the organisms were identified based on their colony morphology on various media, cell morphology, and biochemical tests. the shiga-like toxin production was identified by non-fermentation of sorbitol on smac agar plates. confirmation of shiga-like toxin was performed using agglutination assay. results: in total, 12 isolates showed agglutination and these isolates were confirmed to be e. coli o157:h7. the molecular weight of the verotoxin was found to be between 20 and 29 kd. the antibiogram profile of the four isolated strains against 10 standard antibiotics was determined. conclusion: the results of this study show the occurrence of drug resistance on hemorrhagic colitis causing e. coli o157:h7. keywords: e. coli, verotoxin, diarrhea, hemorrhagic colitis how to cite this article: muhammad musthafa poyil, ponmurugan karuppiah*, suresh s. s. raja, p. sasikumar (2022) “isolation, extraction, and characterization of verotoxin-producing escherichia coli o157:h7 from diarrheal stool samples,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 116–127. doi 10.18502/sjms.v17i1.10689 page 116 corresponding author: muhammad poyil; email: pmusthu@gmail.com received 15 september 2021 accepted 19 february 2022 published 31 march 2022 production and hosting by knowledge e muhammad musthafa poyil et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:pmusthu@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences muhammad musthafa poyil et al 1. introduction escherichia coli is a predominant pathogenic microorganism that causes various conditions such as urinary tract infections, diarrhea, pneumonia, meningitis, and bacteremia. escherichia coli-synthesizing toxins with a cytolytic effect on vero cells were primarily termed as verotoxin-producing e. coli (vtec) [1]. verotoxin and shiga toxin were observed to be slightly similar in structures and the shiga toxin-producing e. coli were termed as shiga toxin-producing e. coli (setc). among the strains of setc, the clinically isolated hemorrhagic colitis (hc)-causing serotypes were designated as enterohemorrhagic e. coli (ehec) [2]. the virulent nature of ehec is due to the bacteriophage-induced shiga toxin. this toxin regulates diarrhea and hc to hemolytic uremic syndrome (hus) as well. stx 1 and stx 2 are the two types of immunologically varied shiga toxins synthesized in ehec. stx 1 was similar to the shiga toxin synthesized by shigella dysenteriae. another virulent factor includes an external membrane protein known as intimin, which was found to be vital for colonizing the intestine. enterohemolysin is encoded by a 60mda plasmid called p o157. enterohemolysin functions by lysis of rbc and providing an iron source to the pathogen [3]. the toxin produced by s. dysenteriae type 1 that is active on vero cells is named shiga toxin; two related toxins produced by e. coli o157:h7 are named shiga-like toxins 1 and 2 (slt-1 and slt-2) or verotoxins 1 and 2 (vt-1 and vt-2). shiga toxin and shigalike toxin (slt–1) are immunologically, biologically, and structurally closely related or identical. slt–2 is also biologically (activity on vero cells) and structurally (a and b subunit structures) related to but differs immunologically from shiga toxin and slt-1. the assay on vero cells seems to be a useful method for their detection [4, 5]. the fecal–oral route was the common method of transmission. oftentimes, humans are infected through carriers such as animals and fomites. birds are identified to be evident vectors for transmission. pathogen outbreaks are mostly related to the consumption of poorly cooked or packaged animal products; in particular ground beef, however, unpasteurized milk and dried meats, alfalfa sprouts, and other infected vegetable products have often triggered epidemics [6]. escherichia coli o157:h7 infection causes hc; this infection is generally diagnosed based on symptoms such as cramp, stomachache, and watery diarrhea accompanied by bloody diarrhea which may be absent in the primary stages and dehydration may be probable. the infection is observed to be self-limiting and lasts about a week in healthy doi 10.18502/sjms.v17i1.10689 page 117 sudan journal of medical sciences muhammad musthafa poyil et al adults [7]. severe complications may occur in a small percentage of cases. shiga-like toxins (verotoxin) produced by e. coli o157:h7 damages endothelial cells of both kidney and brain, causing renal dysfunction and neurological problems. hus can occur in 5– 10% of infected patients – generally, the week after the onset of diarrhea and is evaluated by renal dysfunction, which can lead to enduring injury and hemolytic anemia. severe complications like seizures colonic perforation, hypertension, strokes, pancreatitis, and coma may also be observed. few patients exhibit lifelong insulin-dependent diabetes mellitus. although hus can impact all age groups, children <10 years old are highly prone to this disease [8]. therefore, the main objectives of the present study were to find out the occurrence of verotoxin-producing strains of e. coli o157:h7 among diarrheal patients, to perform the antibiogram analysis of the isolated strains, and to characterize them using sds-page analysis. 2. materials and methods 2.1. sample collection and processing a total of 123 human diarrheal stool samples were collected in a sterile wide-mouth container and processed for microbial isolation. stool samples were collected from inpatients at the erode government hospital, india. the fecal samples were homogenized (10 gm of feces in 100 ml of trypticase soy broth) immediately after collection from both the infected person and animal [9]. it was incubated for 14 hr in shaker at 37ºc and then a loop full of culture was plated on macconkey agar incubated at 37ºc for 24 hr. 2.2. identification of e. coli presumptive e. coli colonies were biochemically confirmed. the biochemical tests performed were oxidase test, indole production test, methyl red test, voges–proskauer test, citrate utilization test, triple sugar iron agar test, gram’s staining and motility analysis. the lactose-fermenting colonies were examined for hemolysis in blood agar, fermentation of lactose in macconkey agar, and in eosin methylene blue agar. doi 10.18502/sjms.v17i1.10689 page 118 sudan journal of medical sciences muhammad musthafa poyil et al 2.3. antibiotic susceptibility test the culture was tested against 13 antibiotics. the antibiotics were ampicillin, amoxicillin, ciprofloxacin, chloramphenicol, gentamicin, kanamycin, neomycin, nalidixic acid, penicillin-g, polymyxin-b, rifampicin, streptomycin, and tetracycline 2.4. preliminary confirmation of shiga-like toxin-producing e. coli the confirmed e. coli colonies were plated on sorbitol macconkey agar (smac) by using the streak plate technique to confirm the shiga-like toxin-producing e. coli. after plating, the plates were incubated at 37ºc for 24 hr [10]. 2.5. serotyping for conformation of shiga-like toxin-producing e. coli escherichia coli o and h antigens were investigated based on standard protocols. agglutination assay was performed on glass slides by adding a drop (20 𝜇l) of antiserum in pbs with a loop full of bacteria. agglutination reactions were examined within a few seconds. bacterial culture in 1 drop of pbs was used as control. agglutination reactions were evaluated by live bacterial cultures, and confirmation tests were repeatedly performed by heating the bacterial cultures for 1 hr at 100ºc. 2.6. production of verotoxin/shiga-like toxin by e. coli cultures were oxygenated to the maximum by aeration and vigorous agitation at 300 rpm on a rotatory shaker for higher toxin production. after this, 1 ml of culture was transported to modified syncase broth (msb) [11] for the detection and purification of the toxin. to 50 ml of the stock solution, 5 ml of 2% (w/v) glucose and 0.04% of tryptophan were added. 2.7. extraction of shiga-like toxins the supernatant from overnight cultures was taken. seventy percent ammonium sulfate solution was added and incubated overnight for precipitation. the pellet was suspended in 250 ml of 10 mm tris hcl (ph – 7.4) and centrifuged at 11,950 rpm at 4ºc. the final cell pellet was resuspended in 10 ml of 10 mm tris hcl (ph – 7.4) and dialyzed doi 10.18502/sjms.v17i1.10689 page 119 sudan journal of medical sciences muhammad musthafa poyil et al figure 1: identification of verotoxin-producing e. coli o157:h7 in sorbiltol macconkey agar (smac) plates. extensively against 10 mm tris (ph – 7.4) for at least 24 hr. the dialyzed ammonium sulfate precipitate was characterized using sds – page to determine the molecular weight of the extracted toxin. 3. results 3.1. isolation and identification of e. coli a total of 123 samples were collected both from the diarrheal stool. bacteria that produce verotoxin were isolated by using enrichment culture method followed by streak plate method by using trypticase soy agar medium. in the present study, over 37 serotypes (30.08%) of e. coli were isolated and the colonies on agar medium were analyzed based on their colony morphology, cell morphology, and biochemical tests. in biochemical tests, the isolates were observed to be gram-negative rods, motile. tryptophan was breaking down by the production of indole. methyl red was produced. citrate was not utilized and the result of voges–proskauer test was negative. oxidase was produced. and almost all the sugars were fermented by this organism such as glucose, lactose, mannitol, and mannose, and it produced negative results in the urease test. the results are presented in table 1. on comparing the results with bergey’s manual of determinative bacteriology, the isolate was identified as e. coli. most strains ferment lactose and thus grow as smooth, glossy, pink colonies on macconkey agar and produce a clear zone of hemolysis on the blood agar medium. they produce greenish metallic sheen on eosin methylene blue agar. doi 10.18502/sjms.v17i1.10689 page 120 sudan journal of medical sciences muhammad musthafa poyil et al table 1: biochemical characterization. biochemical test results gram staining g (–)ve motility test + indole production test + methyl red test + voges–proskauer test – citrate utilization test – oxidase test – tsi test a/a h2s production test – glucose fermentation test – lactose fermentation test + mannitol fermentation test + maltose fermentation test + urease test – sorbitol fermentation test s+ = v–; s– = v+ +: positive; –: negative; v–: verotoxin negative; v+: verotoxin positive. table 2: antibiotic susceptibility. bacterial isolates antibiotics$/zone of inhibition a ac cf c g k n na p pb r s t a1 17.00 (s) 18.00 (s) 21.00 (s) 11.00 (r) 18.00 (s) 18.00 (s) 13.00 (i) 0.00 (r) 0.00 (r) 0.00 (r) 10.00 (s) 13.00 (i) 17.00 (i) a2 15.00 (i) 10.00 (r) 16.00 (i) 15.00 (i) 17.00 (s) 13.00 (r) 17.00 (s) 9.00 (r) 0.00 (r) 0.00 (r) 9.00 (s) 13.00 (i) 10.00 (r) a3 17.00 (s) 19.00 (r) 19.00 (i) 21.00 (s) 17.00 (s) 14.00 (i) 15.00 (i) 0.00 (r) 0.00 (r) 0.00 (r) 11.00 (s) 17.00 (s) 10.00 (r) a4 17.00 (s) 19.00 (s) 20.00 (s) 12.00 (r) 19.00 (s) 17.00(s) 14.00 (i) 0.00 (r) 0.00 (r) 0.00 (r) 10.00 (s) 18.00 (s) 12.00 (r) $a: ampicillin; ac: amoxicillin; cf: ciprofloxacin; c: chloramphenicol; g: gentamicin; k: kanamycin; n: neomycin; na: nalidixic acid; p: penicillin-g; pb: polymyxin-b; r: rifampicin; s: streptomycin; t: tetracycline. total=37 e. coli e.coli o157: h7 32.43% 67.57% figure 2: occurrence of e. coli o157:h7 in human diarrheal samples. doi 10.18502/sjms.v17i1.10689 page 121 sudan journal of medical sciences muhammad musthafa poyil et al lane 1 : protein molecular size marker lane 2: verotoxin in lb broth lane 3: verotoxin in msb figure 3: sds-page analysis of verotoxin. 3.2. preliminary confirmation of shiga-like toxin-producing e. coli after incubation for 24 hr, the small, pale yellow colored (negative), round colonies appeared on the sorbitol macconkey agar medium. while the non-verotoxin-producing e. coli ferment sorbitol and produce pink-colored colonies, verotoxin-producing e. coli fail to ferment sorbitol and produce white-colored colonies. in this study, all 37 isolates were verotoxin-positive and failed to ferment sorbitol. the colonies of this isolated strain on smac medium were colorless which permits presumptive identification of this organism (figure 1). all e. coli o157:h7 strains identified to date have been observed to produce verotoxin and do not ferment sorbitol [10]. 3.3. confirmation of shiga-like toxin-producing e. coli thirty-seven isolates were further tested according to the standard procedures of serotyping; of them, twelve isolates were confirmed as o157 and h7 (figure 2). agglutination results show that antibody typing reagent supports the required sensitivity and specificity for identifying the e. coli serotype o 157:h7. doi 10.18502/sjms.v17i1.10689 page 122 sudan journal of medical sciences muhammad musthafa poyil et al 3.4. characterization of shiga-like toxin the shiga-like toxin was produced with the use of msb and it was extracted by ammonium sulfate precipitation method. the protein was extracted from e. coli which are isolated from animal and human fecal samples. the molecular weight of the protein was between 20,000 and 29,000 da (figure 3). on comparing to lb broth, the band which was observed in msb gave a better result [12]. 3.5. antibiotic susceptibility test the four isolated strains were subjected to antibiogram analysis against 10 antibiotics. after incubation, the results were noted. the size of the zone was compared with the zone size-interpretative chart (table 2). 4. discussion a cross-sectional study observed that the major pathogenic organism causing the disease was e. coli o157:h7, a species that was not previously reported as a human pathogen. since then, e. coli o157:h7 has caused large food-borne outbreak infections worldwide. the center for disease control and prevention (cdc) has recently identified that e. coli o157:h7 is the fourth most predominant diarrhea-causing bacteria next to campylobacter sp., salmonella sp., and shigella sp. this pathogen is a gram-negative motile rods belonging to the family of enterobacteriaceae and was the primary reason for the hc in humans. escherichia coli o157:h7 infection occurs globally and e. coli o157:h7 remains to be viable for more than three months in feces and soil, and infections can occur from weeks to months in widely used acidic foods such as mayonnaise, sausage, apple cider, and cheddar even at refrigeration temperature [13]. thus, the present study concentrates on the identification of e. coli o157:h7 from diarrheal stool samples. of the 123 samples, strains from 37 samples were found to have e. coli. escherichia coli was confirmed by colony morphology on various media and produced green metallic sheen on emb agar plates. further, it was confirmed by several biochemical tests. the shiga-like toxin production was identified by non-fermentation of sorbitol on smac agar plates. confirmation of shiga-like toxin was performed using agglutination assay. twelve isolates showed agglutination and these isolates were confirmed to be e. coli o157:h7. doi 10.18502/sjms.v17i1.10689 page 123 sudan journal of medical sciences muhammad musthafa poyil et al escherichia coli o157:h7 has been reported in domestic animals like cattle, sheep, goats, pigs, dogs, and poultry. cattle are the major reservoir for the pathogen and young animals shed e. coli in the fecal. pathogens in feces can remain for weeks to months and can also be intermittent. many types of stec other than o157:h7 have been observed more commonly in cattle and most predominantly in fecal samples [14]. similar results were observed for sheep and goats which carry other strains of stec [15]. these observations denote that few stec strains are mutated for colonizing the intestinal layer of their animal hosts and remain permanently for several years [16]. the effect of shiga toxin and shiga-like toxin 2 has been observed to differ from cell type due to the gb3 receptors, which is present in certain tissues like sensory neuron and renal cell. in such cells, the concentration of receptor and interaction was regulated by factors like tumor necrosis factor (tnf), interleukins, and fatty acid content of the membranes. shiga-like toxin and shiga-like toxin 2 differ in their effects on different tissues. moreover, both two types have been shown to induce cell death. shiga-like toxins were characterized by sds-page analysis [17]. the strains were cultivated in msb and supernatants were subjected to ammonium sulfate precipitation and dialysis. the purified proteins were characterized using sds-page analysis. the molecular weight of the toxins was found to be between 20 and 29 kda. such toxins have several interesting effects at the cellular level. once the shiga-like toxins have been enclosed, it is invariably transported through the golgi apparatus to the rough endoplasmic reticulum where ribosomes are their major targets. the shiga-like toxin also inhibits protein synthesis and regulates cytokines such as il-1, il-6, and il-8. the shiga-like toxin is also observed to express tnf-7, inducing f-acting de-polymerization and activating α kinase. recent studies have shown that shiga-like toxin is cytotoxic for primary cultures of human colonic cells. shiga toxin can induce vascular cellular damage, as capillary lesions observed in hemolytic-uremic syndrome resemble those found in cerebral vessels of animals administered with these toxins [17, 18]. further from the antibiogram analysis, the strains were found to be resistant to most of the commonly used antibiotics. this indicates the occurrence of drug resistance in verotoxin-producing e. coli o157:h7. 5. conclusion a total of 123 samples were collected both from diarrheal stools and strains from 37 samples (43.02%) were found to be e. coli. the organisms were identified based on doi 10.18502/sjms.v17i1.10689 page 124 sudan journal of medical sciences muhammad musthafa poyil et al their colony morphology on various media, cell morphology, and biochemical tests. the shiga-like toxin production was identified by non-fermentation of sorbitol on smac agar plates. confirmation of shiga-like toxin was performed using agglutination assay. twelve isolates showed agglutination and these isolates were confirmed to be e. coli o157:h7. the molecular weight of the verotoxin was found to be between 20 and 29 kda. the antibiogram profile of the four isolated strains against 10 standard antibiotics was determined. acknowledgements the authors are grateful to the deanship of scientific research, prince sattam bin abdulaziz university, al-kharj, saudi arabia for its support and encouragement in conducting the research and publishing this report. ethical considerations competing interests the authors declare no conflict of interest. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding none. references [1] bryan, a., youngster, i., and mcadam, a. j. 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(2018). isolation, genotyping and antimicrobial resistance of shiga toxin-producing escherichia coli. journal of microbiology, immunology and infection, vol. 51, no. 4, pp. 425–434. [19] wieczorek, k. and osek, j. (2020). identification and molecular characteristics of verotoxin-producing escherichia coli (vtec) from bovine and pig carcasses isolated in poland during 2014–2018. food microbiology, vol. 92, p. 103587. doi 10.18502/sjms.v17i1.10689 page 127 introduction materials and methods sample collection and processing identification of e. coli antibiotic susceptibility test preliminary confirmation of shiga-like toxin-producing e. coli serotyping for conformation of shiga-like toxin-producing e. coli production of verotoxin/shiga-like toxin by e. coli extraction of shiga-like toxins results isolation and identification of e. coli preliminary confirmation of shiga-like toxin-producing e. coli confirmation of shiga-like toxin-producing e. coli characterization of shiga-like toxin antibiotic susceptibility test discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12083 production and hosting by knowledge e research article familial medullary thyroid cancer: five-year review of the most frequent mutations in the ret gene: an update blanca estela díaz castañeda1, mariela eulogio vences1, brian emmanuel díaz gordillo1, miriam deyanira rodríguez piña1, and hugo mendieta zerón1,2* 1faculty of medicine, autonomous university of the state of mexico, mexico 2ciprés grupo médico cgm sc orcid: blanca estela díaz castañeda: https://orcid.org/0000-0001-7330-1427 mariela eulogio vences: https://orcid.org/0000-0003-2788-6174 brian emmanuel díaz gordillo: https://orcid.org/0000-0002-0367-6343 miriam deyanira rodríguez piña: https://orcid.org/0000-0003-1882-2814 hugo mendieta zerón: https://orcid.org/0000-0003-3492-8950 abstract background: familial medullary thyroid cancer (fmtc) is hereditary in 25% of cases. patients with an inherited form of fmtc usually have a germline mutation in the ret proto-oncogene (10q11.2); these mutations generally occur in exons 10 (codons 618 and 620) and 11 (codons 630, 631, and 634). methods: a narrative review of articles focused on the pathology of familial medullary thyroid cancer was carried out using the next databases pubmed, sciencedirect, bmc, springer, frontiers, pmc, wiley online library, cold spring harbor and elsevier. this search was carried out between august and september 2021. results: 19 studies were selected in which the following mutations were found: five studies (26.31%) reported mutation in exon 10; three studies (15.78%) in exon 11; three studies in exon 13 (one of them associated with a rare mutation in exon 7) (10.52% plus 5.26%); three studies (15.78%) in exon 14; two studies (10.52%) in exon 15; two (10.52%) in exon 16; and one (5.26%) rare fmtc no ret. the two most frequent mutations were in codons 620 of exon 10 and 804 of exon 14. conclusion: the findings of this review are consistent with the medical literature, finding the most common ret mutations in exon 10 and codon 620. it is essential that in patients with a presumptive diagnosis, genetic studies (identification of germline mutations in the ret proto-oncogene, located on chromosome 10q11.2) be performed. keywords: familial medullary thyroid cancer, ret proto-oncogene, thyroidectomy two points why this article is of interest: 1. it is an update on the most frequent ret mutations, associated with medullary thyroid cancer. 2. from a clinical point of view, knowing the ret two main mutations are in codons 620 and 804 of exons 10 and 14, respectively, would allow to request a specific molecular biology study to confirm the mutations when there is a case with criteria for familial medullary thyroid cancer. how to cite this article: blanca estela díaz castañeda, mariela eulogio vences, brian emmanuel díaz gordillo, miriam deyanira rodríguez piña, and hugo mendieta zerón* (2022) “familial medullary thyroid cancer: five-year review of the most frequent mutations in the ret gene: an update,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 303–312. doi 10.18502/sjms.v17i3.12083 page 303 corresponding author: hugo mendieta zerón; email: drmendietaz@yahoo.com received 21 january 2022 accepted 16 may 2022 published 30 september 2022 production and hosting by knowledge e castañeda et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences castañeda et al 1. introduction medullary thyroid cancer (mtc) is a neuroendocrine tumor of parafollicular or c cells of the thyroid gland, responsible for calcitonin production [1]. it accounts for 5% of all thyroid cancers and frequently occurs sporadically (75% of mtcs are sporadic and unilateral) or hereditarily (bilateral multifocal). since the latter is associated with genetic conditions that depend on clinical data or other extra-thyroid manifestations, they have been classified into multiple endocrine neoplasia type 2 (men2) or familial medullary thyroid cancer (fmtc), with 25% of understudied patients corresponding to the familial type or men2 [2, 3]. approximately 25% of mtc cases associated with pathogenic variants at the germline level are based on ret proto-oncogenes (10q11.2 locus), representing etiologic factors for fmtc or men2 development, including genetic conditions associated with autosomal dominant inheritance patterns [3]. usually, ligand binding activates the ret receptor, promoting the signal transduction pathway that results in cell proliferation. however, the ret protein could become a nonphosphorylated tyrosine kinase receptor when no ligand is bound. contrastively, mutations in the ret proto-oncogene of cancer cells could lead to autophosphorylation of tyrosine residues, causing the ret receptor to be activated. hence, there is a relationship between the site of ret mutations and the phenotype. in addition, these mutations present diverse transformations, which could depend on their location in the ret molecule [4]. the ret protein comprises two regions: (i) an extracellular region with a ligandbinding domain that consists of a cadherin-like domain and a highly conserved cysteinerich domain and (ii) an intracellular region comprising two tyrosine kinase domains. ligand binding causes the cysteine-rich domain to facilitate receptor dimerization and autophosphorylation, activating the tyrosine kinase and signaling pathways, including jak/stat, pi3k/akt, and ras/raf/mapk. subsequently, ret produces neoplasms in two main ways: ret mutations or ret fusions [5]. furthermore, typical fmtc mutations occur in exons 10 (codons 618 and 620) and 11 (codons 630, 631, and 634) of the ret gene, they mainly affect cysteine-rich extracellular domains and are less associated with the tyrosine kinase domain. finally, mtc accounts for 13% of all thyroid cancerrelated deaths, with an overall survival rate and prognosis that is intermediate to those of patients with differentiated thyroid and anaplastic thyroid cancers [3]. doi 10.18502/sjms.v17i3.12083 page 304 sudan journal of medical sciences castañeda et al 2. materials and methods a narrative review of articles that focused on fmtc pathology was conducted using the following databases: pubmed, sciencedirect, bmc, springer, frontiers, pmc, wiley online library, cold spring harbor, and elsevier. this search was performed between august 2, 2021 and september 10, 2021. three independent authors conducted the search and selection of articles. the final choices of the included articles were based first on the title and abstract and then on the specified inclusion and exclusion criteria. finally, once all necessary information had been collected, full texts were read and the main ideas extracted. the inclusion criteria were studies that focused on fmtc, which was related to genetic mutations and in association with the ret proto-oncogene, its presenting pathology, and/or related family lines. furthermore, studies considered included case reports, case series, retrospective studies, letters to the editor, cohort studies, and peer reviews. however, the exclusion criteria were as follows: studies with publication dates older than five years, those related to sporadic mtc and familial non-mtcs, clinical trials, systematic reviews, narrative reviews, meta-analyses, and multicenter/cross-sectional studies. 3. results following the systematic search, 118 related articles were obtained, 19 of which were of interest and importance to this study. of the 19 included studies, 5 reported mutations in exon 10 (26.31%); 3 studies each reported mutations in exons 11 (15.78%), 13 (one of them associated with a rare mutation in exon 7) (10.52% plus 5.26%), and 14 (15.78%); 2 studies each reported mutations in exons 15 (10.52%) and 16 (10.52%); and then 1 rare fmtc no ret (5.26%) was reported. the two most frequent mutations were in codons 620 and 804 of exons 10 and 14, respectively. interestingly, of the 17 clinical cases reported, 12 (70.58%) were female and 5 (29.42%) were male. the mean age within the clinical cases was 38 years and the median was 44 years (age range, 2–70 years). table 1 shows the most critical findings of the mtc investigation identified in this review. doi 10.18502/sjms.v17i3.12083 page 305 sudan journal of medical sciences castañeda et al table 1: mtc clinical cases. country patient’s age (yr) sex family history exon(s) codon(s)/ variant(s) peru [3] 24 female fourth generation with fmtc 11 cys630ser spain [6] 2 female the patient is the index case 10 cys620ser china [7] 57 male deceased sister 10 c620y china [7] 61 male deceased sister 10 c620y israel [8] 45 male consanguinity history 7 y 13 a432a & l769l india [9] 44 female four sisters and two members of the next generation 15 ser891ala turquía [10] 44 female big brother 11 634 lebanon [11] 14 female mother 13 l790f (c.2370g> t) denmark [11] 70 female mother and aunt 13 l790f (c.2370g> t) usa [12] 62 female sister, maternal aunt, and son 14 p.v804m italy [13] 66 male older sister 16 p.met918thr italy [13] 68 female younger brother 16 p.met918thr usa [14] 3 female father and three siblings 14 v804m japan [15] 5 female mother 11 634/cys634gly china [16] 48 female patient is the index case 10 p.c611y germany [17] 17 male eight family members 15 p.s891a united kingdom [18] 22 female patient is index case familial nonret mtc familial non-ret mtc hungary [19] na six members of the second generation several generations 14 v804m and the variant s836s china [20] na six ret mutationpositive members three-generation family 10 y606c 4. discussion functions of ret proto-oncogene germline mutations in the pathogenesis of fmtc cause presenting clinical manifestations to depend on the organs, specific mutation, and age of follow-up. therefore, diagnosis in patients with fmtc requires a procedure involving a biopsy of the thyroid nodule or thyroidectomy to detect the final pathology. doi 10.18502/sjms.v17i3.12083 page 306 sudan journal of medical sciences castañeda et al likewise, its evaluation requires imaging methods, such as ultrasound with lymph-node mapping, calcitonin and carcinoembryonic antigen-level measurements, and genetic testing (to rule out ret proto-oncogene germline mutations). these assessments also evaluate the presence of hyperparathyroidism and rule out the possibility of pheochromocytoma (pheo) [5]. although symptomatic thyroid nodule is a frequent reason for consultation, it is estimated that 35% of the population will have a nodule during their lifetime. however, only 10% of these will be associated with some thyroid cancer types. based on the above hypothesis, there are different ways to determine whether the nodule is neoplastic. for this purpose, ultrasonographic characteristics of the nodule can be estimated with a biopsy, obtained using a fine needle guided by ultrasound. this procedure reduces false negatives and the fact that, more frequently, a nodule of fixed and complex characteristics is mostly associated with a neoplastic etiology, including the existence of ipsilateral cervical lymphadenopathies, which should also be considered a warning sign. in clinical history, it is also prevalent to find data of altered thyroid functions, such as hypothyroidism or hyperthyroidism, leading to hormone measurements, such as triiodothyronine (t3/t3l), thyroxine (t4l), and thyroid-stimulating hormone (tsh). however, it has been estimated that more than half of the thyroid cancer cases are clinically asymptomatic. therefore, it is important to inquire about voice alterations (dysphonia), cervical, digestive, and airway compression, dysphagia, and/or foreign body sensations during interrogations. furthermore, since thyroid hyperfunction is closely related to cancer, serum tsh levels are useful to rule out nodule hyperfunction. nevertheless, elevated thyroglobulin levels are often considered a warning sign (particularly useful in following up patients undergoing total thyroidectomy and radioactive iodine ablation), including hormone estimation. ultrasound is considered important for evaluating nodule characteristics. therefore, this procedure should be performed in the thyroid gland and lateral necks. if the findings of this last study are a hypogenic nodule, microcalcifications, intranodular vascular flow, disproportionate measures, infiltrating margins, or the presence of cervical nodes with loss of the fatty hilum, then, a fine needle biopsy guided by ultrasound should be conducted. although a thyroid scan should not be a routine, it is essential when there is evidence of hyperthyroidism or a functioning nodule (decrease in tsh, with or without elevation of thyroid hormones in the blood). in addition, supposing there is a need to assess metastasis or neoplastic extensions in the mediastinum, deep cervical fascia, doi 10.18502/sjms.v17i3.12083 page 307 sudan journal of medical sciences castañeda et al or upper airway, computerized tomography or magnetic resonance imaging studies are recommended [21]. during diagnosis, parathyroid hyperplasia (pph) and/or pheo should be ruled out during the preoperative stage in any patient with suspected mtc. if the study confirms ret mutations, pheo should be ruled out by measuring 24-hr urinary metanephrines and evaluating the presence of pph through the parathyroid hormone, calcium, and phosphorus in the blood, ruling out an association with men2. however, if performing an ret proto-oncogene study before surgery is impossible, the presence of pheo and pph should always be ruled out [21]. diagnosis in patients with mtc can be preoperative during the study of a thyroid nodule that is active in ret proto-oncogene mutation carrier relatives. it can even be postoperative. nevertheless, the high penetrance of ret mutation pathogenesis implies the need for early diagnosis. since mtc is aggressive and produces calcitonin, therapeutic surgery is essential, with an objective prognosis according to the tumor stage and adequate initial surgical treatment being crucial. furthermore, based on the dominant condition of inheritance and the close relationship between genotype and phenotype that is associated with the disease aggressiveness, it is important to perform a genetic study on these patient groups. according to the american thyroid association guidelines, three risk groups have been established when identifying an ret mutation: 1. ata-hst→ very high risk 2. ata-h → high risk 3. ata-m → moderate risk the first group, ata-hst, presents a very high risk of mutations in codon m918t of exon 16 and an invasive mtc phenotype in children under one year. as a result, prophylactic thyroidectomy is recommended before that corresponding age. however, the second group, ata-h, is characterized by a high risk of mutations in codons c634f/g/r/s/w/y and a883f of exons 11 and 13. its phenotype corresponds to men2a with a high incidence of oef at 20 years and men2b. therefore, its management comprises prophylactic thyroidectomy at five years of age. finally, the third group, corresponding to ata-m or ata-mod, is a moderate risk. mutations here were distributed in exons 5, 8, 10, 11, 13–15, and 16, and its phenotype was that of later onset of mtc. hence, less aggressive evolution (nem2a and mtc) studies for which a prophylactic doi 10.18502/sjms.v17i3.12083 page 308 sudan journal of medical sciences castañeda et al thyroidectomy, including pheo and pph, is advisable. the above classification guides the time and extent of thyroid surgery. emphasis has also been placed on exons 10, 11, 13–15, and 16 (90% of the mutations), including exons 5 and 8. subsequently, ret gene studies were conducted through sanger sequencing of the exons previously amplified by pcr [22]. surgical treatment is not only the therapeutic alternative for cases of sporadic or hereditary mtc but also the best prophylactic measure to reduce thyroid cancer, including neoplasms associated with men2a and 2b. therefore, for postsurgical management, levothyroxine supplementation (initial dose 1.6–1.8 mcg/kg/day) is recommended. in addition, while tsh should be maintained in the normal range based on age, it should not be suppressed. besides, radioiodine (radioactive iodine) should not be used in mtc since it has no use [21]. 5. conclusion based on the data collected and the understudied literature, fmtc was identified as an essential dominant genetic entity in patients with a presumptive diagnosis. from the genetic studies (identification of germline mutations in the ret proto-oncogene, located on chromosome 10q11.2), the characteristic mutations of fmtc notably occurred in exons 10 (codons 618 and 620) and 11 (codons 630, 631, and 634) of the ret protooncogene, consistent with the findings of this review. however, exon 10 and codon 620 were the sites where mutations occurred most frequently. as for treatments, evidence in favor of radical thyroidectomy was postulated not only as the surgical procedure of choice but also as a prophylactic measure. this procedure was also considered the best alternative to prevent its progression when combined with adequate postsurgical hormone replacement therapy like levothyroxine. acknowledgements the authors would like to thank the students’ team of the latin american scientific association (ascila) for the suggesting ideas to improve the manuscript. ethical considerations not applicable. doi 10.18502/sjms.v17i3.12083 page 309 sudan journal of medical sciences castañeda et al competing interests the authors declare no competing interests. availability of data and material all data used are available in 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(2017). cirugía profiláctica en cáncer medular de tiroides hereditario. revista chilena de cirugía, 69(3), 268–272. https://doi.org/10.1016/j.rchic.2016.11.002 doi 10.18502/sjms.v17i3.12083 page 312 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12866 production and hosting by knowledge e research article is prolonged sitting a risk factor in developing hemorrhoids and anal fissures? gamal e.h.a. shallaly1*, el fatih m. malik2, mohamed abdelmonem ali3, maysa h. m. hamza4, babikir a. b. ibrahim5, hassan e.h.m. ahmed5, mohamed m. i. elhajahmed6, and modather m.e. salih6 1department of surgery, faculty of medicine, alzaiem alazhari university 2faculty of medicine, university of khartoum, sudan 3faculty of medicine, omdurman islamic university, sudan 4department of surgery, faculty of medicine, karary university, sudan 5department of anatomy, faculty of medicine, omdurman islamic university, sudan 6department of surgery, faculty of medicine, omdurman islamic university, sudan orcid: gamal e.h.a. shallaly: https://orcid.org/0000-0002-8941-0721 abstract background: anal fissures and hemorrhoids are common anal conditions. they cause significant morbidity, social embarrassment, and work absenteeism. in addition, they form a significant workload on the healthcare system. nevertheless, the etiology of these conditions is still contentious. it has been observed that hemorrhoids and anal fissures are associated with prolonged sitting. this study aims to investigate this observation. methods: this is a case–control study. we compared 81 patients with symptomatic and endoscopically proven hemorrhoids and/or anal fissures with 162 controls with no symptoms or endoscopic evidence of perianal disease. the study was conducted at khartoum north teaching hospital (knth) endoscopy unit between january and december 2019. demographic data, sitting hours per day, and endoscopic findings of patients and controls were recorded in a proforma. the cases and controls were matched for age, sex, and bowel habits. data were analyzed and compared using the spss version 23. results: the mean sitting hours for cases was 5.99 (sd 3.4) whereas that for controls was 4.0 (sd 3.0) with a highly significant difference (p < 0.001). sitting for 5 hr or more per day (exposure) was associated with an increased risk of developing hemorrhoids and/or anal fissures [odds ratio 3.68, 95% ci: 2.1–6.47]. conclusion: the study showed that sitting down for 5 hr or more per day might increase the risk of developing hemorrhoids and/or anal fissures. this finding could help in the prevention and treatment of these diseases and the reduction of recurrences. keywords: hemorrhoids, anal fissure, endoscopy, prolonged sitting hours how to cite this article: gamal e.h.a. shallaly*, el fatih m. malik, mohamed abdelmonem ali, maysa h. m. hamza, babikir a. b. ibrahim, hassan e.h.m. ahmed, mohamed m. i. elhajahmed, and modather m.e. salih (2023) “is prolonged sitting a risk factor in developing hemorrhoids and anal fissures?,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 63–70. doi 10.18502/sjms.v18i1.12866 page 63 corresponding author: gamal e.h.a. shallaly; email: gamalshallaly@hotmail.com received 1 august 2022 accepted 12 august 2022 published 31 march 2023 production and hosting by knowledge e gamal e.h.a. shallaly et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences gamal e.h.a. shallaly et al 1. introduction hemorrhoids and anal fissures are common anal conditions. they (and their treatment) cause a lot of pain and morbidity to the patient. they form a large workload on health services and entail high financial expenses for patients and health providers [1]. nevertheless, their true incidence and prevalence are difficult to know for certain [1–3]. this is due to many reasons, such as embarrassment, fear, availability of over-thecounter medications, and nonmedical healers [2–4]. in addition, social and economic difficulties are just other reasons to mention [1]. hemorrhoids are defined as distal displacement and venous distension of anal cushions [2, 3]. some epidemiological studies estimate that hemorrhoids affect 39– 52% of adults in the western world [2]. although a common condition, the etiology of hemorrhoids is still contentious. while some authorities reported a low-fiber diet and constipation as risk factors [4], others did not find an association [5]. middle age (45–65 years old), obesity, and pregnancy are, so far, supported by good evidence [2, 6]. an anal fissure (af) is defined as “a linear or oval shaped tear or wound in the mucosa of the anal canal starting below the dentate line extending to the anal verge” [7]. af is also a common perianal condition [3]. the etiology is still uncertain, but most authorities believe it starts as trauma to the anoderm. risk factors include constipation, obesity, and hypothyroidism [8]. the importance of knowing the risk factors of any disease is that this knowledge helps in the primary prevention of that disease and the prevention of its recurrence. prolonged sitting with straining on the lavatory has been identified as a risk factor, but not sitting down at work or leisure [2, 3]. interestingly and historically, the only perianal condition that proved to be associated with sitting down at work was pilonidal sinus, which affected jeep drivers in world-war ii [9, 10]. many patients with hemorrhoids and anal fissures give a history of prolonged sitting down at work and/or for other reasons. a review of the english literature does not show any study to verify or nullify this observation [6]. recent literature on the subject is also lacking. this study was done to investigate this observation. doi 10.18502/sjms.v18i1.12866 page 64 sudan journal of medical sciences gamal e.h.a. shallaly et al 2. materials and methods 2.1. study design this case–control study was conducted at khartoum north teaching hospital (knth), sudan, between january and december 2019. 2.2. sample size the sample size for the patients and controls was calculated using kelsey and fleiss methods (https://www.openepi.com/samplesize/sscc.htm). the confidence level was chosen to be 95%, the power 80%, the hypothetical proportion of patients with exposure (0.66), and the hypothetical proportion of controls with exposure (0.35). the minimum sample size was calculated to be 31 for cases and 61 for controls (kelsey) and 30 vs 59, respectively (fleiss). it was decided to include larger numbers to strengthen the study. 2.3. patients and controls we included 81 patients and 162 controls. the cases were patients who presented to the endoscopy unit with clear symptoms of hemorrhoids and/or fissures in-ano and were diagnosed to have these conditions endoscopically. patients with anal fissures and/or hemorrhoids who had other (or secondary) causes, such as tumors and/or inflammatory bowel disease, were excluded. females who had a history of amenorrhea were also excluded. the controls were selected from patients who had an endoscopy (sigmoidoscopy and/or colonoscopy) for gastrointestinal disorders who did not have anal fissures or hemorrhoids. 2.4. data collection and analysis a proforma was designed to collect information on the patients and record the findings at endoscopy. the information collected included demographic data on patients such as age, sex, occupation, and average sitting hours per day. the same data were collected from controls. data were analyzed using the spss version 23. the mean (sd) of age and hours of sitting down was calculated together with the frequency of each sex among cases doi 10.18502/sjms.v18i1.12866 page 65 sudan journal of medical sciences gamal e.h.a. shallaly et al and control. a bivariate analysis was conducted and the odds ratio (or) with a 95% confidence interval (ci) was estimated. 3. results both cases and controls were matched by age (t-value = 0.686, p = 0.493) (https://mathcracker.com/t-test-for-two-means#results). the ages of both patients and controls displayed normal curves. the mean age of patients was 43.5 years (16.5), whereas the mean age of controls was 42.1 years (14.2). over 90% of both the cases and controls were aged between 20 and 69 years with almost 50% between 30 and 49 years (table 1). males were slightly more than females in both the controls and patients. the male-to-female ratios for controls and patients were 1.7:1 and 1.8:1, respectively. regarding the symptom of a change in bowel habits, there was no significant difference between patients and controls. table 1: the age distribution of cases and controls. age group (yr) patients no. % control no. % 10–19 3 1.9 4 4.9 20–29 27 16.7 12 14.8 30–39 50 30.9 18 22.2 40–49 37 22.8 19 23.5 50–59 20 12.3 12 14.8 60–69 17 10.5 9 11.1 70+ 8 4.9 7 8.6 total 162 100% 81 100% the two main presenting symptoms were rectal bleeding and anal pain in 53 patients (65.4%). thirty-three patients (40.7%) complained of constipation and seven (8.6%) had perianal discharge; however, some patients had more than one symptom. the endoscopic diagnosis was as follows: 46 patients (56.8%) had hemorrhoids, 23 (28.4%) had anal fissures, and 12 (14.8%) had a combination. those who had other conditions such as rectal carcinoma or polyps were excluded. the distribution of sitting hours for both cases and controls formed normal distribution curves. the mean sitting hours for the controls was 4.0 hr (sd 3.0), median 4.0, whereas that of the cases was 5.99 hr (sd 3.4) median (5.5). comparing the two means using a t-test for independent samples, the t-value was 3.987. the p-value was 0.000105. the difference was thus highly significant (p < 0.00). doi 10.18502/sjms.v18i1.12866 page 66 sudan journal of medical sciences gamal e.h.a. shallaly et al when cases and controls were grouped according to sitting hours categories (0–2 hr/3–4 hr/5–6 hr/7–8/ hr, and 9+ hr), it was observed that the number of cases with sitting hours equal to or more than 5 hr was twice the number whose sitting time was <5 hr a day (table 2). table 2: distribution of cases and controls according to sitting hour categories. sitting hours no. of patients % no. of controls % 0–2 13 16 47 29 3–4 14 17.3 58 35.8 5–6 25 30.9 23 14.2 7–8 15 18.5 18 11.1 9+ 14 17.3 16 9.9 total 81 100% 162 100% it was also observed that 5 hr is the mean of the two means of cases and controls (6 and 4 hr, respectively. we, therefore, proposed the use of 5 hr as the exposure time to calculate the odds ratio. the odds ratio was 3.68. it was calculated by 2×2 table (table 3). the 95% confidence interval for this odds ratio lies between 2.1 and 6.47, and the 99% confidence interval between 1.76 and 7.72 (t-statistics.co.uk). table 3: calculation of the odds ratio. exposure to ≥5 hr of sitting cases (%) controls (%) exposed 54 (66.67%) 57 (35.18%) unexposed 27 (33.33%) 105 (64.82%) total 81 (100%) 162 (100%) odds ratio 3.7 95% confidence interval 2.1–6.47 4. discussion according to this study, sitting down for more than 5 hr per day may be a risk factor for developing hemorrhoids and/or anal fissures. the risk of prolonged sitting is attached to the mere sitting down whether at work, (e.g., drivers), studying, or at leisure. several studies have shown that the posterior commissure of the anal canal receives less blood supply than the other part of the anal canal [11–13]. this may explain why 75% of fissures occur in the posterior midline [2]. prolonged sitting may also exaggerate this ischemia. doi 10.18502/sjms.v18i1.12866 page 67 sudan journal of medical sciences gamal e.h.a. shallaly et al about hemorrhoid pathophysiology, the pathogenesis is still controversial. our findings; however, agree with the possibilities proposed by corman and thompson [14, 15]. prolonged sitting may hamper venous drainage causing distension and dilatation of the veins of the internal venous plexus of the hemorrhoids and consequently abnormal distension of the arteriovenous anastomosis within the hemorrhoidal cushions. this will eventually lead to the downward displacement and prolapse of the hemorrhoidal tissue. the absence of hemorrhoids in animals and its high prevalence in men may be attributed to their upright posture and sitting-down habits. there is now some evidence that prolonged sitting, a unique habit of men, may be a risk factor in developing both hemorrhoids and fissures. the importance of identifying prolonged sitting hours as a risk factor for anal fissures and symptomatic hemorrhoids comes from the ease and the socioeconomic impact of its prevention. most of our patients (65%) are young, aged between 10 and 50 years. anal fissure pain and hemorrhoids symptoms and complications, such as rectal bleeding, can cause a lot of disruption to their studies, work, and productivity. the treatment, which may require surgery, also adds to the prolonged morbidity and financial burden on both the patients and the health services. this risk factor (of prolonged sitting) must be discussed with the patients, and advice or counseling should be given to them regarding their occupation or way of living. limitations there are limitations to our study. we tried as far as we could to eliminate confounders so that the differences between cases and controls were thus focused on the sitting hours. some confounding factors such as pregnancy and hypothyroidism were not verified by tests but by excluding those who gave a positive history. nevertheless, this study opens the door to further investigate the association between prolonged sitting down and perianal conditions such as anal fissures and hemorrhoids. 5. conclusion this study sheds light on prolonged sitting down, at work or otherwise, as a possible risk factor in the etiology of anal fissures and hemorrhoids. sitting continuously for five or more hours a day seems to increase the risk of developing hemorrhoids and/or anal fissures. it is hoped that this information helps in the primary prevention of these common anal conditions and prevents recurrence after treatment. doi 10.18502/sjms.v18i1.12866 page 68 sudan journal of medical sciences gamal e.h.a. shallaly et al acknowledgments the authors acknowledge the cooperation and dedication of the medical and nursing staff of the gastroenterology endoscopy unit at khartoum north teaching hospital (knth), sudan. ethical considerations the study was approved by the ethical committees at khartoum north teaching hospital (knth) and the alzaiem alazhari university (aau). informed consent was obtained from all individual participants included in the study (cases and controls). informed consent was obtained from all participants of the study at endoscopy. in addition, the study does not contain identifying information about participants. competing interests the authors declare that they have no competing interests. availability of data and material anonymous data are available. funding this study was self-funded. references [1] sandler, r. s., & peery, a. f. (2019). rethinking what we know about hemorrhoids. clinical gastroenterology and hepatology, 17(1), 8–15. [2] ganz, r. a. (2013). the evaluation and treatment of haemorrhoids: a guide for the gastroenterologist. clinical gastroenterology and hepatology, 11, 593–603. [3] peery, a. f., sandler, r. s., galanko, j. a., bresalier, r. s., figueiredo, j. c., ahnen, d. j., barry, e. l., & baron, j. a. (2015). risk factors for haemorrhoids on screening colonoscopy. plos one, 10(9), e0139100. doi 10.18502/sjms.v18i1.12866 page 69 sudan journal of medical sciences gamal e.h.a. shallaly et al [4] kaidar-person, o., person, b., & wexner, s. d. (2007). haemorrhoidal disease: a comprehensive review. american college of surgeons, 204(1), 102–117. [5] johanson, j. f., & sonnenberg, a. (1994). constipation is not a risk factor for haemorrhoids: a case–control study of potential etiological agents. american journal of gastroenterology, 89(11), 1981–1986. [6] gardner, i. h., siddharthan, r. v., & tsikitis, v. l. (2020). benign anorectal disease: hemorrhoids, fissures, and fistulas. annals of gastroenterology, 33, 9–18. [7] beaty, j. s., & shashidharan, m. (2016). anal fissure. clinics in colon and rectal surgery, 29, 30–37. [8] mapel, d. w., schum, m., & worley, a. v. (2014). the epidemiology and treatment of anal fissures in a population-based cohort. bmc gastroenterology, 14, 129. [9] casberg, m. a. (1949). infected pilonidal cysts and sinuses. bulletin of the us army medical department, 9, 493–496. [10] clothier, p. r., & haywood, i. r. (1984). the natural history of the post anal (pilonidal) sinus. annals of the royal college of surgeons of england, 6, 201–203. [11] gordon, p. h., & nivatvongs, s. (1999). principles and practice of surgery for the colon, rectum and anus (p. 218). 2nd ed. st. louis, mo: quality medical publishing, inc. [12] klosterhalfen, b., vogel, p., rixen, h., & mittermayer, c. (1989). topography of the inferior rectal artery: a possible cause of chronic, primary anal fissure. diseases of the colon & rectum, 32(1), 43–52. [13] schouten, w. r., briel, j. w., & auwerda, j. j. (1994). relationship between anal pressure and anodermal blood flow. the vascular pathogenesis of anal fissures. diseases of the colon & rectum, 37(7), 664–669. [14] corman, m. l. (1998). haemorrhoids. in m. l. corman (ed.) colon and rectal surgery (pp. 147–205). 4th ed. philadelphia, pa: lippincott-raven. [15] thomson, w. h. (1975). the nature of haemorrhoids. british journal of surgery, 62, 542–552. doi 10.18502/sjms.v18i1.12866 page 70 introduction materials and methods study design sample size patients and controls data collection and analysis results discussion limitations conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12549 production and hosting by knowledge e research article association between hemoglobin a1c and the severity of acute ischemic stroke in sudanese patients in omdurman military hospital omer abdalla elamin abdelgadir1*, amal mahmoud saeed2, abubaker shadoul mohamed farah2, mohanad elsebty mohammed alhassan ahmed2, mogahid ahmed osman farah2, abdelhadi ahmed abdelhadi elsayed2, awab abdalhafiz altahir ahmedelbasheir2, mahmoud saeed saad mahgoub2, ahmed khalafalla mohamed ahmed2 1msc physiology-alneelain university 2university of khartoum, sudan orcid: omer abdalla elamin abdelgadir: https://orcid.org/0000-0003-2662-9627 abubaker shadoul mohamed farah: https://orcid.org/0000-0003-0201-3916 mohanad elsebty mohammed alhassan ahmed: https://orcid.org/0000-0002-7994-4826 mogahid ahmed osman farah: https://orcid.org/0000-0002-2659-878x abdelhadi ahmed abdelhadi elsayed: https://orcid.org/0000-0002-5674-2201 awab abdalhafiz altahir ahmedelbasheir: https://orcid.org/0000-0001-8884-47901-8884-4790 mahmoud saeed saad mahgoub: https://orcid.org/0000-0003-1695-2121 ahmed khalafalla mohamed ahmed: https://orcid.org/0000-0003-2886-3046 abstract background: hemoglobin a1c (hba1c) levels are known to be linked to a higher risk of stroke. however, no research data is available on the impact of hba1c on the severity of acute ischemic stroke in sudan. methods: this study is a descriptive, cross-sectional hospital-based study of 40 cases of acute ischemic stroke. ischemic stroke was confirmed using computed tomography (ct) scan at admission; all subjects’ blood hba1c levels were also measured. participants were divided into two subgroups based on hba1c at admission, good glycemic control (ggc) (<7 hba1c) and poor glycemic control (pgc) (>7 hba1c), and neurological impairment was assessed using the national institutes of health stroke scale (nihss). results: the age distribution of the participants was 45-85 years, with an average age of 63.5±9.2 years with the highest frequency (67.5%) in the age group of 55-75 years. pgc had a statistically significant high hba1c value of 8.9±1.3 (p=0.000), when compared to ggc subgroups 5.1±0. the association between stroke severity and hba1c levels on admission in this study was statistically significant (p value=0.005), on admission (78.6%) pgc had moderate to severe stroke (> 18.8 nihss) versus (33.3%) that of the ggc (>10.4nihss). the frequency of elevated hba1c levels in patients with acute ischemic stroke was 70% in this study. conclusion: pgc was shown to be linked to the occurrence of stroke and to its severity. keywords: ischemic stroke, hba1c, nihss how to cite this article: omer abdalla elamin abdelgadir*, amal mahmoud saeed, abubaker shadoul mohamed farah, mohanad elsebty mohammed alhassan ahmed, mogahid ahmed osman farah, abdelhadi ahmed abdelhadi elsayed, awab abdalhafiz altahir ahmedelbasheir, mahmoud saeed saad mahgoub, ahmed khalafalla mohamed ahmed (2022) “association between hemoglobin a1c and the severity of acute ischemic stroke in sudanese patients in omdurman military hospital,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 485–497. doi 10.18502/sjms.v17i4.12549 page 485 corresponding author: omer abdalla elamin abdelgadir; email: omer.abdelgadir91@ gmail.com received 1 october 2021 accepted 13 september 2022 published 31 december 2022 production and hosting by knowledge e omer abdalla elamin abdelgadir et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12549&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences omer abdalla elamin abdelgadir et al 1. introduction a total of 17 million people worldwide had a stroke in 2010. between 1990 and 2010, the number of strokes in developed countries declined roughly by 10%, while it grew by 10% in developing countries [1]. stroke is a major health problem in the middle east, causing severe disability and death, with a fatality rate that is anticipated to double by 2030 [2]. according to the most recent world health organization (who) data, stroke fatalities in sudan were 27,222, or 10.17% of all deaths, placing sudan at number 27 in the world. although the risk factors for stroke in sudan are similar to those in developed nations, the peak age group for mortality in sudan is a decade earlier than in the developed countries [3]. as in many other lowand middle-income nations, the prevalence of diabetes mellitus (dm) began to rise in sudan. it is expected to affect 8% of the population but has reached 19% in some northern states [4, 5, 6]. although it has been linked to inheritance in some cases, obesity is responsible for 40% of cases [7]. because most patients cannot afford the medicine, pgc has resulted in chronic diabetes problems (treatment is not readily available and poor quality of life [8, 9, 10]. the sudanese community’s sedentary lifestyles and bad dietary habits make it difficult to implement preventive measures, but patients with diabetes require lifetime treatment, which is difficult to maintain in a state where insolvency is the norm [11]. nihss is a widely used clinical assessment tool to assess the severity of stroke patients, determine appropriate treatment, and predict patient outcomes. “the nihss is a 15neurologic examination stroke scale item that evaluates the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual field impairment, extraocular movement, motor strength, ataxia, dysarthria, and sensory impairment level. each item is assigned a score from 0 to 4, with 0 as normal, and there is an allowance for items that cannot be tested [12]. hba1c levels have been linked to stroke in the past. however, no research has been done in sudan on the impact of hba1c on the severity of stroke in acute cases. in sudan, strategies to prevent stroke and improve outcomes remain insensitive and ambiguous due to a lack of documented evidence and the impacts of their implementation. these strategies include increasing public awareness and understanding of stroke, preventing and managing recognized risk factors for stroke, and treating stroke patients in the stroke ward. doi 10.18502/sjms.v17i4.12549 page 486 sudan journal of medical sciences omer abdalla elamin abdelgadir et al 2. materials and methods this was a descriptive hospital-based cross-sectional study from january 2019 to september 2020. it was held at one of the main military hospitals in omdurman—a general hospital with a neurology section that caters primarily to military personnel and their families. the sampling technique was total coverage of all patients with acute ischemic stroke presenting to omdurman military hospital and who fulfilled the required criteria. among 69 patients admitted with stroke in the period between february and may, 16 were excluded due to hemorrhagic stroke, 7 patients had intravenous glucose before or during the study period, 3 patients had a chronic ischemic stroke (more than three months), 2 patients had a recent blood transfusion, and 1 had hemoglobinopathy (documented on history and medical records). the remaining 40 patients were included in the study. they were given information about the study in order to obtain their informed consent. 2.1. data collection patient demographics, clinical results, laboratory, and radiographic findings were all covered in a questionnaire interview after patients assent. in the emergency room, each patient underwent a clinical evaluation that included blood pressure measurements and a neurological examination to determine the severity of their stroke using nihss. a venous blood sample was obtained and sent to the laboratory for hba1c testing after an ischemic stroke was identified. (hba1c levels in healthy adult males and females in sudan range from 1.2% to 6.5%) [13]. most current guidelines circulated by professional associations for diabetes, including the american diabetes association [14], recommend hba1c <7% as the optimal target for glycemic control. as a result, the patients were divided into four groups: 1. patients with good glycemic control (ggc): hba1c less than 7, 2. patients with poor glycemic control (pgc): hba1c greater than 7. 3. newly diagnosed diabetes: random blood sugar (rbg) levels greater than 200 mg/dl/l, no history of diabetes, and hba1c level greater than 7. 4. stress hyperglycemic: rbg greater than 200 mg/dl /l, no history of diabetes, and hba1c less than 7%. doi 10.18502/sjms.v17i4.12549 page 487 sudan journal of medical sciences omer abdalla elamin abdelgadir et al following the completion of the questionnaire, 5 ml of venous blood was obtained from each participant under sterile conditions. the blood was collected and deposited in ethylenediaminetetraacetic acid (edta) container for hba1c testing (samples that were icteric, lipemic, hemolyzed, or bacterially contaminated were not used.), hba1c was determined using a commercial reagent kit from roche company and a modified enzyme-linked immunosorbent assay (elisa) reader known as cobas integra 800. the study measured several dependent and independent variables, including the severity of ischemic stroke, hba1c, demographic data, and other risk factors. 2.2. data management and analysis the accuracy of the data received at the end of each participant’s contact was verified. all of the data was kept secure by utilizing a laptop with a password that only (the researcher) knew, as well as storing it in locked closets. statistical package for social science (spss) statistics version 16.0 was used for the statistical analysis. absolute and relative frequencies were used to summarize categorical data (counts and percentages). the mean and 95% confidence interval, as well as the mean and standard deviation (sd) were used to portray quantitative data. for demographic and clinical data, parametric procedures (chi-square test for categorical data, student-t test for continuous data) were utilized because the data were normally distributed. spearman’s correlation coefficient was used to perform correlation analysis (r). statistical significance was defined as a p-value of less than 0.05. also, multiple linear regressions were used to determine the involvement of cofactors in acute ischemic stroke severity. tables, graphs, and charts were used to examine the relationship between the dependent and independent variables. 3. results 3.1. demographic information the study group’s ages ranged from 45 to 85 years, with a mean age of 63.5±9.2 years, and with the highest frequency (67.5%) in the 55 to 75 age group. males were 28 (mean age: 64.6±8.2 years) and females were 12 (mean age: 61±11.11years) with a male to female ratio of 2:1. a bulk of patients came from khartoum, algazira, northern, and kurdufan states, accounting for 30%, 22.5%, 10%, and 10%, respectively. however, 70% of the patients resided in their own homes, whereas 30% lived in retirement facilities, 77.5% doi 10.18502/sjms.v17i4.12549 page 488 sudan journal of medical sciences omer abdalla elamin abdelgadir et al of the patients were married, 15% of those who took part have a university diploma, and 50% were unemployed. all patients had a simple ct scan, with 75% of ct scans taking place within 24 hours of the onset of symptoms; one patient also had to undergo magnetic resonance imaging (mri). in 47.5% of instances, an electrocardiogram (ecg) was conducted, and in 22.5% an echocardiogram (echo) was performed. in 10% of the patients, carotid ultrasonography and doppler were performed. according to the trial of org 10172 in acute stroke treatment (toast) classification of stroke subtypes, 25% of cases were caused by cardiac embolism, while the remaining 75% were unknown. 3.2. patient’s risk factors hypertension (htn) is the leading cause (47.5%) of risk factors for ischemic stroke (47.5%), and dm is the second most common cause with 35%. it was found that 30% of the male patients smoked cigarettes, while 7.5% drank alcohol. in this study, 25% of the participants had heart illnesses, including atrial fibrillation (a.fib) and carotid stenosis in one case. a history of peptic ulcer was found in 20% of the cases. three of the patients who took part in the study had chronic renal disease. a family history of stroke at ages less than 55 was observed in 15% of the cases. three patients had a history of past strokes. 3.3. patient’s investigations total cholesterol, triglycerides, high-density lipoprotein cholesterol (hdl), and lowdensity lipoprotein (ldl) measurements were taken for 4,5,3,3 patients respectively; this small number of samples could be related to the high cost of the tests. as a result, we did not look at their role in stroke severity. 3.4. regression a multivariate linear regression model was used to predict the severity of a stroke. this was based on an eight-predictor system, (stroke severity=-0.722+ (0.527) dm +0.008 age +0.125 a.fib + (-0.258-) htn +0.988 hba1c level+0.208 smoking +0.724 alcohol consumption +0.000 rbg on admission) with f test (3.16) =2.626 and p-value =0.025, the model proved statistically viable for predicting stroke severity. to predict the severity of a stroke, the combination of the eight predictors accounted for r=0.636. although all doi 10.18502/sjms.v17i4.12549 page 489 sudan journal of medical sciences omer abdalla elamin abdelgadir et al eight predictors played an effect on stroke severity, only the hba1c level (p=0.001) had a statistically significant impact of 0.988. age, dm, a.fib, htn, smoking, alcohol, and rbg each contributed (0.008, 0.527, 0.125, -0.258-, 0.208, 0.724, 0.000) but were not significant (p=0.613, 0.720, 0.308, 0.492, 0.229, 0.712 respectively). table 1: the mean and standard deviation of age between participant genders. gender number mean of age std. deviation male 28 64.6071 8.22525 female 12 61.0833 11.17187 both 40 63.5500 9.20410 table 2: the characteristic and variation of categorical values in the study groups. no. variable ggc (%) pgg (%) total n (%) chi-square test p-value 1-gender male 9(75) 19(67.8) 28(70%) female 3(25) 9(32.2) 12(30%) 0.204 0.651 2-a.fib yes 5(41.6) 5(17.9) 10(25%) no 7(58.4) 23(82.1) 30(75) 2.540 0.111 3-htn yes 8(66.6) 11(39.2) 19(47.5) no 4(33.4) 17(60.8) 21(52.5) 2.521 0.112 4-dm yes 3(25) 11(39.3) 14(35) no 9(75) 17(60.7) 26(65) 0.754 0.385 5-smoking yes 5(41.6) 7(25) 12(30) no 7(58.4) 21(75) 28(70) 1.111 0.292 6-alcohol yes 1(8.3) 2(7.1) 3(7.5) no 11(91.7) 26(92.9) 37(92.5) .017 0.896 7-toast cardio embolism 5(41.7) 5(17.8) 10(25) undetermined causes 7(58.3) 23(82.2) 30(75) 2.540 0.111 table 3: the characteristic and variation of continuous values in the study groups. no. ggc pgc total levene test p-value 1-age l 65.3+/–11.6 62.8+/–8.1 63.5+/–9.2 0.053 0.430 rbg on admission l 167.25+/–79.5 220.50+/–127.4 202.75+/–115.3 0.050 0.196 hba1c 5.1+/–0.5 8.9+/–1.3 7.75+/–2.05 0.003 0.000 nihss 10.4+/–5.0 18.8+/–4.6 16.3+/–6.1 0.392 0.000 4. discussion this study has shown that the peak age group for stroke is 10 years less than in industrialized nations, yet sudan has the same stroke risk factors as other countries; doi 10.18502/sjms.v17i4.12549 page 490 sudan journal of medical sciences omer abdalla elamin abdelgadir et al table 4: the association between stroke severity and hba1c categories on admission. no. nihss ggc n (%) pgc n (%) total n (%) chi-square p-value 1moderate stroke 8 (66.7) 6 (21.4) 14 (35) moderate to severe stroke 4 (33.3) 9 (32.1) 13 (32.5) 10.48 0.005 l severe stroke 0 (0) 13 (46.5) 13 (32.5) table 5: the correlation between nihss and hba1c. national institutes of health stroke scale hba1c categories national institutes of health stroke scale pearson correlation 1 0.512∗∗ sig. (2-tailed) 0.001 n 40 40 category pearson correlation 0.512∗∗ 1 sig. (2-tailed) 0.001 n 40 40 **correlation is significant at the 0.01 level (2-tailed). figure 1: the percentage of age distribution among participant. the most common is hypertension, which is followed by diabetes mellitus. however, the number of patients in this study is small and a bigger study is needed to determine the risk factors influencing this population. doi 10.18502/sjms.v17i4.12549 page 491 sudan journal of medical sciences omer abdalla elamin abdelgadir et al figure 2: the glycemic status based on hba1c. figure 3: the stroke severity classification based on nihss. the sex distribution was dominated by men and this conclusion is in line with the findings of other epidemiological studies [2, 15,16]. only 36 individuals were subjected to an rbg test when they were admitted. of those diagnosed with diabetes, 38.5% had hyperglycemia while 61.5% were euglycemic. doi 10.18502/sjms.v17i4.12549 page 492 sudan journal of medical sciences omer abdalla elamin abdelgadir et al hyperglycemia was seen in 34.8% of nondiabetic patients; however, 17 patients were diagnosed with dm at the time of admission. perttu j. lindsberg and risto o roine [17] found that two-thirds (66%) of all patients with ischemic stroke had hyperglycemia, whereas hyperglycemia was found in 36.1% of patients in our study. they also said that known diabetes and newly diagnosed diabetes patients made up to one-third of the cases (33%) and those same groups made up to 32.5 % of the study participants. in comparison to the study by naveed et al., the pgc group constituted 24.7 %, while in this study pgc group comprised 70% of the study participants [18]. pgc had a statistically significant association with hba1c value 8.9+/-1.3 (p value 0.000) when compared to ggc 5.1+/-0.5; another study found a similar result (8.510+/1.260) in pgc and (5.921 +/_0.501) in ggc [19]. on admission, pgc group had an rbg of 220.50+/127.4 and ggc group had an rbg of 167.25+/-79.5. men in pgc accounted for 67.8% of the participants, whereas women accounted for 32.2 %. in pgc, the average age was 62.8+/-8.1 while in ggc it was 65.3+/-11.6. people aged between 55 and 75 years accounted for 52.5% of all pgc, which could explain why the age of beginning of stroke in sudan is 10 years earlier than in industrialized nations [3], despite the fact that this number is insignificant (p value=0.249). it is possible that this is due to the small number of participants. on admission, 78.6% of pgc patients had a moderate to severe stroke (nihss > 18.8) compared to 33.3% of ggc patients (nihss > 10.4), which was statistically significant (p value=0.005), another study [19] found that (90%) of pgc patients had moderate to severe stroke (> 7nihss) at the time of admission, compared to (46.63%) of ggc patients. hba1c and stroke severity had a statistically significant relationship, with coefficients of determination (r 2=26.2) of r=0.512, p=0.001, assuming a non-normal distribution of either of the variables, spearman rank correlation r=0.511, p=0.001, (r2=26.1), in both tests hba1c levels and the severity of the stroke were statistically significant. this result was in line with findings from other investigations [19,20,21] with an r square of .512, the regression equation is nihss= (2.417+917*hba1c) was statistically significant (f (1, 18) = 13.467, p=.001). according to the findings of this study, higher hba1c levels account for 70% of individuals with acute ischemic stroke. stroke severity has been linked to pgc. hba1c levels are a predictor of the degree of neurological impairment in individuals with acute ischemic stroke when measured on admission. we recommend that based on the above-mentioned findings: doi 10.18502/sjms.v17i4.12549 page 493 sudan journal of medical sciences omer abdalla elamin abdelgadir et al 1patients who have had an ischemic stroke should be tested for hyperglycemia or an increased hba1c level to avoid permanent hyperglycemia and other complications. 2due to the high-mortality rate from stroke conditions in sudan, a well-equipped stroke clinic and epidemiologic research center are urgently needed to fulfill the following goals: i. a program for prevention and control should be implemented and made feasible (especially at the level of primary health care, the general public should be aware of the symptoms of stroke, and the importance of early access to medical services). ii. determine the prevalence and incidence of stroke. iii. carry out more research to see if improved glycemic management before a stroke might improve the clinical course and outcome of those who have had an acute ischemic stroke. acknowledgments the authors would like to thank al-neelain university –graduate college for allowing me to conduct my research and providing any assistance requested. special thanks to the staff and members of the master of physiology for their continued support. ethical considerations ethical approval was obtained from al-neelain institutional review board, omdurman military hospital, and informed consent were obtained from all patients with confidential information. patients were informed that they could refuse to take part in the study. competing interests none declared. availability of data and material all data and materials associated with this paper were available through the corresponding author upon reasonable request. doi 10.18502/sjms.v17i4.12549 page 494 sudan journal of medical sciences omer abdalla elamin abdelgadir et al funding none. references [1] feigin, v. l., forouzanfar, m. h., krishnamurthi, r., mensah, g. a., connor, m., bennett, d. a., moran, a. e., sacco, r. l., anderson, l., truelsen, t., o’donnell, m., venketasubramanian, n., barker-collo, s., lawes, c. m., wang, w., shinohara, y., witt, e., ezzati, m., naghavi, m., …global burden of diseases, injuries, and risk factors study 2010 (gbd 2010) and the gbd stroke experts group. 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(2019). “clinical outcome in ischemic stroke patients with hyperglycemia.” iosr journal of dental and medical sciences (iosr-jdms), 18(2), 30-39. [21] mi, d., wang, p., yang, b., pu, y., yang, z., & liu, l. (2017). correlation of hyperglycemia with mortality after acute ischemic stroke. therapeutic advances in neurological disorders, 11, 175628561773168. doi 10.18502/sjms.v17i4.12549 page 497 introduction materials and methods data collection data management and analysis results demographic information patient's risk factors patient's investigations regression discussion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12555 production and hosting by knowledge e research article histopathologic pattern of thyroid disease in 1351 thyroidectomy patients gamal eldin hussein a. el shallaly1*, babiker a. b. ibrahim2, modather m. e. salih2, mohamed m. i. elhajahmed2, mohammed f. e. mohammed3, reem o. m. daffalla4, ruaa e. h. yassin4, and rayan m. m. ahmed4 1department of surgery, karary university, sudan 2department of surgery, faculty of medicine, omdurman islamic university, sudan 3department of orthopedic surgery and traumatology, faculty of medicine, omdurman islamic university, sudan 4faculty of medicine, omdurman islamic university, sudan orcid: gamal eldin hussein a. el shallaly: https://orcid.org/0000-0002-8941-0721 abstract background thyroid disease poses a major clinical problem. knowledge of the pattern and distribution of thyroid disease is important to establish prevention and treatment protocols. this is hampered by lack of data. methods this is a retrospective descriptive study of histopathology reports on thyroid tissue surgically excised from patients over a 10-year-period (from 2009-2020) at a major teaching hospital. demographic data on patients included the age, gender, geographical location and ethnic origin. results a total of 1351 histopathological reports on thyroid patients were studied. twenty one patients (1.6%) had thyroglossal cysts and 1330 patients (98.4%) had goiters. the mean age was 40.6 years (sd±13.25), (range 11-85years). the majority (88%) were females most of our patients come from khartoum (76.3%), followed by white nile (6.4%), and el gazira states (4.5%). the commonest ethnic groups affected were the nuba (11.6%) and jaalin (8%). the majority of patients (85%) had benign thyroid diseases, and only (15%) had neoplastic disease. simple multinodular goiter (smng) accounted for (78.6%) of benign thyroid disease. follicular adenoma was the commonest benign neoplasm (98%), whereas papillary carcinoma was the commonest malignant tumour (44.9%), followed by follicular carcinoma and hurthle cell tumours (43.9%). medullary and anaplastic carcinomas each accounted for (4.1%) of patients. conclusions the study identified the histopathological pattern of thyroid disease. smng was the commonest benign disease. follicular and hurtle cell carcinoma combined were almost as frequent as papillary carcinoma. prevention of smng by iodinization, early detection of thyroid neoplasms, and studies on goitrogens should be activated. keywords: thyroid disease, histopathology, thyroglossal cyst, goiter, thyroid cancer, thyroidectomy, sudan, multinodular colloid goiter, thyroid adenoma. how to cite this article: gamal eldin hussein a. el shallaly*, babiker a. b. ibrahim, modather m. e. salih, mohamed m. i. elhajahmed, mohammed f. e. mohammed, reem o. m. daffalla, ruaa e. h. yassin, and rayan m. m. ahmed (2022) “histopathologic pattern of thyroid disease in 1351 thyroidectomy patients ,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 577–588. doi 10.18502/sjms.v17i4.12555 page 577 corresponding author: gamal eldin hussein a. el shallaly; email: gamalshallaly@hotmail.com received 3 june 2022 accepted 15 july 2022 published 31 december 2022 production and hosting by knowledge e gamal eldin hussein a. el shallaly et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12555&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences gamal eldin hussein a. el shallaly et al 1. introduction thyroid disease poses a major clinical problem in our country. the overall prevalence of endemic goiter has increased from 22% (range 13-87%) to 38.8% (12.2-77.7%) despite all programs for the control of iodine deficiency disorders [1, 2]. currently, thyroid surgery is performed in almost every surgical operative list in major hospitals across the country. in addition, goiter is a standard case in clinical examinations in surgery and medicine, both at the undergraduate osce and postgraduate md levels. areas far from the sea, particularly the western parts (darfur state), have been endemic to iodine deficiency [2-4]. this is so much so that local folklore poetry glorifies a large neck as a sign of charm and beauty of women. kosti city (white nile state), though nearer to the sea than darfur, has been found to have the highest prevalence of the disease [2]. historically, goiter was thought to be introduced into africa in the 19𝑡ℎ or even 20𝑡ℎ century and got prevalent in sennar by 1825 [5]. omdurman city forms one of the three major cities of the capital khartoum. it is a cosmopolitan city inhabited by millions of people coming from all regions of sudan. omdurman teaching hospital (oth) is thus visited by a great variety of patients of variable ethnicity. establishing a data base as well as identifying the pattern of thyroid disease and its distribution in the country helps policymakers to plan preventive and early detection measures as well as protocols of management. the objective of this study was to identify the pattern of the histopathology of thyroid disease in thyroid tissue samples removed surgically at oth. to our knowledge, this is the largest collection of samples being studied and analyzed. 2. materials and methods this is a retrospective descriptive study of histopathology reports on thyroid tissue surgically excised from patients over a 10-year period (from 2009 to 2020). demographic data on patients included the age, gender, geographical location, and ethnic origin. statistical analysis of the data was done using ibm spss statistics for windows, version 25 (ibm corp., armonk, n.y., usa). 3. results a total of 1351 histopathological results were included. twenty-one patients (1.6%) had thyroglossal cysts and 1329 patients (98.4%) had goiter. the mean age of all the patients doi 10.18502/sjms.v17i4.12555 page 578 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al was 40.6 years (sd±13.25), range (11-85 years). the majority (88%) were females giving a ratio of female to male ratio of 7.3:1. the mean age for patients undergoing an operation for thyroglossal cysts was 35.9 (16.6), range (14-75 years) with almost equal female (f) to male (m) ratio; 1.1f:1m. the mean age of patients with benign (non-neoplastic) goiters was 40.5 (12.7), range (12-85) years. the mean age of patients with neoplastic goiters was 41.6 (15.4), range (11-80) years. the differences were not statistically significant between the ages of simple (non-neoplastic) and neoplastic goiters (p=0.278), as well as between simple and thyroglossal cyst patients (p=0.102). most of our patients come from khartoum state (76.3%). this was followed by the states of white nile (6.4%), and el gazira states (4.5%). the commonest ethnic groups affected were nuba (11.6%) followed by the jaalin tribes (8%). the distribution of patients in sudan is shown in the map (figure 1). the general pattern of thyroid disease is shown (table 1). the majority of patients (85%) had simple benign thyroid diseases, while neoplastic thyroid disease (both malignant and benign) accounted for 15% of the patients (figure 2). figure 1: distribution of thyroid diseases in sudan. generally, smng and colloid goiters predominate 75.5%. all thyroid cancers accounted for 7.3% of the specimens, whereas follicular adenomas were 7.1%. inflammatory thyroid disease accounted for 3.2%. toxic thyroid disease accounted for 1.8%, of doi 10.18502/sjms.v17i4.12555 page 579 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al table 1: pattern of thyroid disease. histopathology frequency percentage multinodular goiter 837 62.9 simple colloid goiter 182 13.7 simple physiological goiter 45 3.4 toxic nodule 3 .2 toxic multinodular goiter 20 1.5 toxic diffuse goiter 2 .2 inflammatory goiter (thyroiditis) 43 3.2 follicular adenoma 97 7.3 metastatic carcinoma 2 .2 medullary carcinoma 4 .3 anaplastic carcinoma 4 .3 hurthle type carcinoma 15 1.1 papillary carcinoma 44 3.3 follicular carcinoma 28 2.1 mixed carcinoma 1 .1 hylined trabecular adenoma 2 .2 non conclusive sample 1 .1 total 1330 100.0 thyroid diseases n=1350 goiter n=1329 (98.5%) non-neoplastic n=1132 (85%) simple n=1064 (94%) mng 836 (78.6%) colloid 182 (17.1%) physiological 45 (2.3%) inflammatory n=43 (3.8%) toxic n=25 (2.2%) nodular 20 (80%) solitary nodule 3 (12%) diffuse 2 (8%) neoplastic n=197 (15%) thyroglossal cyst n=21 (1.5%) figure 2: thyroid disease: general pattern. which nodular thyroid disease being the most common 1.5%, and diffuse goiters being the least common (0.1%). in the category of benign thyroid disease, simple multinodular goiter (smng) accounted for 78.6% of benign thyroid diseases. thyroid neoplasms (benign and doi 10.18502/sjms.v17i4.12555 page 580 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al neoplas�c n = 197 benign n = 99 (50.3%) follicular adenoma n = 97 (98%) hyalined trabecular adenoms (2%) malignant n = 98 (49.7%) primary (10 ) n = 96 (98%) metastatic (20 ) n = 2 (2%) figure 3: neoplastic thyroid disease. primary malignant neoplasm n = 98 follicular n = 28 (28.6%) hurthle cell n = 15 (15.3%) papillary n = 44 (44.9%) mixed n = 1 (1%) medullary n = 4 (4.1%) anaplas!c n = 4 (4.1%) figure 4: primary malignant thyroid disease. malignant) accounted for nearly equal proportions (50.3 percent and 49.7 percent, respectively) thyroid neoplasms (benign and malignant) accounted for nearly equal doi 10.18502/sjms.v17i4.12555 page 581 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al table 2: mean age, gender and non-neoplastic vs neoplastic ratios. study mean age (sd) f:m ratio non-neoplastic % neoplastic % el shallaly (sudan) (2009– 2020) n = 1330 40.5 (13.25) 7.3:1 85 15 koyuncuire (turkey) (2006– 2014) n = 1149 41.41 (12.29) 7.9:1 86.9 13.1 tsegaye (ethiopia) 1994– 1998 n = 780 nr 4.5:1 79 21 al-wageeh (yemen) 2014– 2015 n = 260 40.06 (13.18) 9:1 68.5 31.5 chayla et al. (tanzania) (2008–2010) n = 152 38.4 (12.5) 11.7:1 85.5 14.5 table 3: comparison pattern of thyroid disease. nodular colloid goitre adenoma carcinoma thyroiditis toxic el shallaly (sudan) (2009–2020) n = 1330 76.6% 7.5% 7.4% 3.2 1.9 tsegaye (ethiopia) (1994–1998) n = 780 76.9 12.8 8.2 2.1 nr chayla et al. (tanzania) (2008–2010) n = 152 76.3 6.6 7.9 1.3 7.9 koyuncuire (turkey) (2006–2014) n = 1149 81.7 4.8 (follicular) 8.4 4.2 0.4 (grave’s) al-wageeh (yemen) 2014–2015 n = 260 63.1 4.6 26.9 5.4 nr nr: not reported. table 4: comparison of mean age (sd) of patients with thyroid cancer. study mean age (sd) range makki 2014–2017 n = 166 51 (17) 15–85 el shallaly et al. 2009–2020 n = 98 44 (17) 11–80 p-value 0.0014 highly significant proportions 50.3% and 49.7%, respectively. follicular adenoma was the most common benign tumor (98%) (figure 3). thyroid carcinoma was reported in 98 samples. the mean age of patients with thyroid cancer was 44 (sd±17) years. papillary carcinoma was the commonest malignant tumor (44.9%), followed by follicular carcinoma (28.6%). however, if we consider hurthle cell tumor (15.3%) as a type of follicular carcinoma, the percentage increases to 43.9%, making follicular tumor almost as common as papillary tumors. medullary and anaplastic carcinomas both accounted for 4.1% of patients (figure 4). doi 10.18502/sjms.v17i4.12555 page 582 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al table 5: thyroid cancer types. study follicular % hurthle cell ca% papillary % anaplastic % medullary% metastatic and others % makki(sudan) (2007–2014) n = 166 43% nr 27% 10% 2% 6% metastatic 5% sarcoma/lymphoma our study (sudan) (2009–2020) n = 98 28.6 % 15.3% 44.9% 4.1% 4.1% 3% metastatic koyuncuire (turkey) (2006–2014) n = 95 4 (4.2% ) 16 (16.8%) 70 (73.7%) nr 1 ( 1% ) 3 (wdt-ump) +1 (settle) american thyroid association (usa) 10–15% 3–5% 70–80% 2% 2% tsegaye (ethiopia) 1994–1998 n = 64 15.6 nr 76.6 6.3 1.5 nr: not reported; wdt-ump: well-differentiated tumors of uncertain malignant potential; settle: spindle epithelial tumor with thymus like element. the mean age of patients with cancer was, with increasing order: papillary 39.5 years (sd±17); range (11-80), follicular 46.1 (±15.2); range (23-75), hurthle cell 49.2 (±16.1); range (18-70), medullary 54 (±11.8); range 37-63, and anaplastic 57.3 (±11.9); range (50-75). 4. discussion several studies confirmed that iodine deficiency is the major cause of endemic goiter in sudan [1-4]. historically, goiter was observed in sennar since the 19𝑡ℎ century [5]. sudanese studies have shown an increase in the prevalence of goiters in darfur (western sudan) from 57% to 85% over a period of 20 years [1, 2]. classically goiter is known to be common in areas of western sudan due to its far distance from the sea. however, a more recent study by medani et al. showed that the prevalence of goiter is very high in central sudan and that iodine deficiency is still prevalent despite longstanding programs for the control of iodine deficiency disorders [2]. our study showed that goiter has become common in tribes living along the nile in northern sudan and nearer to the sea than previously reported. the mean age of patients with simple benign disease was (40.5) years. there was an obvious female preponderance. benign (nonneoplastic) thyroid diseases constituted the majority of patients ranging from 69-87% of patients (table 2). these findings as doi 10.18502/sjms.v17i4.12555 page 583 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al well as thyroid disease patterns were generally in concordance with that reported in countries where iodine deficiency is endemic [6-9] (table 3). our study confirmed that, of all benign thyroid diseases, simple nodular colloid goiter was the commonest pathology (76.6%) dealt with in the surgery. all efforts should; therefore, be made to put in place an integrated national program including health education, primary prevention by adding iodide to diet, early detection, and management. the latter should include providing proper preoperative management including provision of appropriate investigations, proper operative theatre setup, proper training of surgeons, nurses, anesthetists, and quality postoperative care, in order to make surgery safe. regarding thyroid neoplasms, the mean age of patients with malignant thyroid disease was 44 years (sd±17). there was no statistically significant difference between the ages of those with simple benign thyroid disease and those with malignant disorders. of real concern, our study showed that thyroid malignancies are significantly (p=0014) occurring in younger patients than reported previously by makki [10] (table 3). this finding has also been observed in another sudanese study by osman et al. [11]. thyroid cancers in patients younger than 45 years had better prognosis if they were detected early [12]. the cutoff age of 45 years as a prognostic factor has been included in thyroid tnm staging since 1983 [13, 14]. recently, the american joint committee on cancer (ajcc) has increased the cutoff age to 55 years [15-17]. the finding that papillary carcinoma was the major thyroid malignancy is comparable to global findings. however, the finding that the combination of follicular and hurthle cell carcinomas are almost as frequent as papillary carcinoma needs some reflection. hurthle cell carcinoma is considered a variant or subtype of follicular carcinoma. hurthle cell carcinoma originates from follicular cells and is diagnosed when hurthle cells constitute more than 75% of cells in follicular cancer [18, 19]. there is an accumulation of strong evidences that iodine deficiency and endemic goiter are predisposing factors in follicular carcinoma [2022]. in addition, treatment with iodides in salt has resulted in decreased incidence of follicular cancer in certain parts of the world [23, 24]. there is even a piece of recent molecular evidence that follicular adenoma can develop into follicular carcinoma [25]. this appears to be mimicking the adenomacarcinoma sequence in large bowel malignancies. it is not surprising; therefore, to find in an area with iodine deficiency endemic goiter, that follicular (and hurthle cell) carcinomas are almost of equal proportions to papillary carcinoma. a study from western sudan even showed that follicular carcinoma is more frequent than papillary carcinoma, with proportions of 50% and 35.7%, respectively [26]. doi 10.18502/sjms.v17i4.12555 page 584 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al this finding is in contradistinction to findings in other regions of the globe, such as the usa, turkey, and ethiopia where papillary thyroid cancer significantly predominates [27, 6, 7] (table 5). in our study, simple nodular (endemic) goiter accounts for 76.6% of all cases and the combination of follicular adenoma and carcinoma accounted for 15%. as these diseases seem to be connected, one could argue that over 90% of thyroid disease could be eliminated by a simple but proper introduction of iodide to the diet of the target population. 5. conclusions the study identified the histopathological pattern and geographical distribution of thyroid disease. smng was the commonest benign disease. follicular and hurtle cell carcinomas combined were almost as frequent as papillary carcinoma, in contradistinction with that reported and globally. policy makers should make plans for prevention of smng and early detection of thyroid neoplasms. health education of public and protocols of management of thyroid diseases acknowledgements the authors are greatly indebted to the laboratory staff and administration at omdurman teaching hospital. ethical considerations ethical approval was obtained from omdurman islamic university and omdurman hospital research and ethics committees. informed consent was obtained from all participants of the study. in addition, the study does not contain identifying information about participants. competing interests the authors declare that they have no conflict of interest. doi 10.18502/sjms.v17i4.12555 page 585 sudan journal of medical sciences gamal eldin hussein a. el shallaly et al availability of data and material anonymous data are available. funding this study was self-funded. authors’ contribution gamal eldin hussein a. el shallaly: writing-original draft, methodology, supervision, and validation. babiker a. b. ibrahim: conceptualization, visualization, and reviewing. modather m. e. salih: data collection, investigation, software, and analysis. mohamed m. i. elhajahmed: data collection, investigation, software, and analysis. mohammed f. e. mohammed: data collection, investigation, software, and analysis. reem o. m. daffalla: data curation, investigation, software, and analysis. ruaa e. h. yassin: data curation, investigation, software, and analysis. rayan m. m. ahmed: data curation, investigation, software, and analysis. all: review and final approval. references [1] ministry of health. 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(n.d.). cancer of the thyroid. https://www.thyroid.org/cancer-of-the-thyroid/ doi 10.18502/sjms.v17i4.12555 page 588 introduction materials and methods results discussion conclusions acknowledgements ethical considerations competing interests availability of data and material funding authors' contribution references sudan journal of medical sciences volume 12, issue no. 4, doi 10.18502/sjms.v12i4.1354 production and hosting by knowledge e research article the level of ischemic modified albumin (ima) as risk marker for cardio vascular disease (cvd) among some diabetic patients (type ii) in khartoum state-sudan sadik i.1, yagoub z.2, sayed n.3, el nour a.1, abide el hameed m.1, and satee b. abid1 1faculty of medical laboratory science, omdurman islamic university 2faculty of medical laboratory science, sharq al nile college 3pediatric department, turkey hospital khartoum abstract background: recent literature reports show large interest in ischemic modified albumin (ima) biochemical marker for detection of myocardial injury. special attention is focused in estimation of ima test for the diagnosis and evaluation of myocardial ischemia as well as others acute coronary syndrome in emergency patients. objective: evaluation of ischemia-modified albumin (ima) in well controlled and uncontrolled patients with type 2 diabetes mellitus and estimation of its connection with cardiovascular disease.measurement the levelof ima as risk marker for cardio vascular disease (cvd) in diabetic patients that arrived to emergency department with signs and symptoms of cvd. methodology: 140 subjects enrolled in this study ,70 diabetes mellitus patients with signs and symptoms of cvd, and other 70 apparently non diabetic healthy subjects’ as controls, , the levels of biomarker ima was measured as the risk marker of cvdin controlled and uncontrolled diabeticpatients with type2,the diagnostic potential was evaluated by receiver operating characteristic analysis and their relationships were analyzed. this study was done in shab hospital, khartoum. period from 1st of february 2015 to october 2015. results: the results showed that cvd were predominant among diabetic female 57 % and peaked at age 75.5 years among 40-75 year old. the ima was significantly increase in diabetic patients when compare with normal healthy group with cut off value ( 0.97 iu/l ), and there is also significantly increase in ima level in uncontrolled diabetic patients (mean ± sd; 14.70 + 10.66) that presented with acute chest pain and havea signs and symptoms of cardiac ischemia when compared with the wellcontrolled diabetic patients(mean ± sd; 3.74 ± 3.68). controlled and uncontrolled diabetic patients were determined by the level of their hba1c and comparison with the means of ima level in their serum. conclusions: increase ima level in poor control and long stand diabetic patients could help to identify the higher risk for develop to cvd, and the most common complication such as suffering from local or systemic hypoxic conditions, as acute ischemic stroke, peripheral vascular disease. keywords: ischemia, type 2 diabetes mellitus, cardiovascular disease, ischemic modified albumin how to cite this article: sadik i., yagoub z., sayed n., el nour a., abide el hameed m., and satee b. abid, (2017) “the level of ischemic modified albumin (ima) as risk marker for cardio vascular disease (cvd) among some diabetic patients (type ii) in khartoum state-sudan,” sudan journal of medical sciences, vol. 12 (2017), issue no. 4, 231–239. doi 10.18502/sjms.v12i4.1354 page 231 corresponding author: isam sadik; email: isnaalah@outlook.com received 10 october 2017 accepted 18 december 2017 published 28 december 2017 production and hosting by knowledge e isam sadik et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:isnaalah@outlook.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences isam sadik et al 1. introduction recent literature reports show large interest in new biochemical markerischemic modified albumin (ima) for detection of myocardial injury. special attention is focused in estimation of ima test for the diagnosis and evaluation of myocardial ischemia as well as others acute coronary syndrome in emergency patients [1]. because ischemia, and the resulting biochemical changes, can occur in any vessel, the specificity of ima for cardiac ischemia is unclear [1]. myocardial ischemia and accompanying hypoxia induced the structural modification of human serum albumin (has)[2]. has performs many essential functions in organism, among the others direct protective oxidative stress. this molecule represents one of the circulating antioxidant in plasma and plays a vital role in the efficient antioxidant defense of the organism [2, 3]. there are several data on ima in patients with different states with ischemia of non-cardiac origin such as systemic sclerosis [4, 5] peripheral vascular disease, skeletal muscle ischemia during arthroscopic knee surgery and exercise induce, but no one concerns diabetes [6]. hyperglycemia and oxidative stress can induce chronic ischemia in diabetic patients. it could lead to necrosis of different tissues [7, 8]. diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion and insulin action or both. the chronic hyperglycemia is associated with long-term damage, dysfunction, and failure of normal functioning of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels [9]. the prevalence of diabetes mellitus is rising all over the world and have been increasing rapidly recently in sudan reach 1.4 million cases in 2015 [10]. uncontrolled state of hyperglycemia leads to a variety of complications including peripheral vascular diseases, nephropathy, neuropathy, retinopathy, morbidity, and/or mortality. type 2 diabetes and their related complications of hypertension, hyperlipidemia and atherosclerotic vascular disease and also demonstrated an association of metabolic syndrome with the development of cardiovascular disease (cvd), and more confirmation related to mortality rate increment was given by type 2 diabetes and their related complications cardiovascular disease remains the leading cause of death, and myocardial infraction (mi) tend to be more extensive and have poorly survival rate than in age, weight and sex matched in individuals without diabetes [11]. doi 10.18502/sjms.v12i4.1354 page 232 sudan journal of medical sciences isam sadik et al 2. material and methods study design this quantitively exploratory descriptive research study was done al shab’s hospital for cardiology and chest in khartoum during 1st of february 2015 to october 2015. inclusion criteria: test group: standardized clinical data were collected for each patient, which included time of presentation at the emergency department, approximate duration of symptoms of the acute chest pain. exclusion criteria: patients with liver disorders, autoimmune disorders, pregnant women, patients with symptoms and signs suggestive of acute mesenteric ischemia, acute renal failure, peripheral vascular disease, or brain ischemia were not enrolled in the study. study population patient selection seventy patients with type 2 diabetes mellitus, arriving to emergency unit in hospital. suffering from acute chest pain with manifestations suggestive of acute myocardial ischemia, including those such as chest pain, shortness of breath, lower jaw pain, left arm pain, epigastric pain, new or increasing lower extremity edema, palpitations, and other symptoms suggestive of an anginal equivalent. the ecg measured in the ed as part of the standard of care at the al shab hospital. ‘ control group selection seventy healthy volunteers’ individuals’ age and sex matched whom didn’t have any evidence of diabetes and coronary artery disease were taken as the control group. samples processing demographic dates(sex, age), an ecg and biochemical dates were collected .blood for ima and hba1c levels were collected within two hours of arrival, ima riskmarker testing were performed before any heparin/thrombolytic treatment was started. blood samples collected in tubes containing lithium heparin at the time of the patient’s presentation to the emergency department, centrifuge for 5 minutes and preserve at -70 c. technique of use: ischemic modified albumin (ima): that assayed in intervals at 2 4 hours and 6 8 hours. the microtiter plate provided in this kit has been pre-coated with an antibody specific to ima. standards or samples are then added to the appropriate microtiter doi 10.18502/sjms.v12i4.1354 page 233 sudan journal of medical sciences isam sadik et al plate wells with a biotin-conjugated antibody preparation specific for ima and avidin conjugated to horseradish peroxidase (hrp) is added to each microplate well and incubated.then a tmb (3,3’,5,5’ tetramethyl-benzidine) substrate solution is added to each well. only those wells that contain ima, biotin-conjugated antibody and enzymeconjugated avidin will exhibit a change in color. the enzyme-substrate reaction is terminated by the addition of a sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450 nm ± 2 nm. the 3 concentration of ima in the samples is then determined by comparing the o.d. of the samples to the standard: reference values reported by the manufacturer (0.21+ 0.65)by eisa themicro titer plate provided kit has been pre-coated with an antibody specific to ima. hba1c assay: was done by method based on boronate affinity chromatography using nycocard reader ii. ethical consideration the study protocol was approved by ethical committee for medical and health research at omdurman islamic university and local ethics committee of medical director of al shab hospitalkhartoum. data analysis was done using statistical package spss version parametric values were analyzed using one-way analysis of variance (anova), followed by t. test and pearson’s correlation analysis, used for statistical analysis of the data; p < 0.05 was considered to be statistically significant‘ 3. results this study was conducted on 70 known diabetic patients (type 2) arrived to the emergency department of alshab hospital, khartoum state, with acute chest pain, as case group, and 70 apparently non diabetic healthy subjects’ volunteers whom didn’t have any evidence of coronary artery disease. age and sex for both groups were matched. table 1 shows that demographics dates 30 male (43%) and 40 female (57%) and the 70 healthy control group 30 male (43%) and 40 female (43%). and age means in 2 groups was (57.5 ±17.6) versus (59.4±18.5) years (p =0.992). there was no significant difference table:2 shows that means level of ima in both diabetic patients ( case group) and in the normal healthy non diabetic control group. means ± sd (10.78±10.25), (3.21±10.73) respectively , (p.value 0.003), there was significant difference figure 1 shows that the diagnostic performance of ima obtained from receiver operating characteristic, area under curve (roc , auc=0.84.) have a sensitivity (81.4% )and specificity (80%) at cut off value =0.97 doi 10.18502/sjms.v12i4.1354 page 234 sudan journal of medical sciences isam sadik et al group frequency percent meanof age ±sd p.value case female 40 57.0% 57.5 ±17.6 0.992 male 30 43.0% total 70 100.0% control female 40 57.0% 59.4±18.5 male 30 43.0% total 70 100.0% t 1: baseline demographic (sex & age) characterizations in case and the control group. group number mean std. deviation p.value ami case 70 10.78 10.25 0.03 control 70 3.21 10.73 t 2: comparison means of plasma (ima) in case group and control group. hba1c % level in dm n mean std. deviation p.value ami iu\ml ≤ 7% hba1c 25 3.74 3.68 0.0001 >7% hba1c 45 14.70 8.66 t 3: ima means level within diabetic groups (controlled group = ≤ 7% hba1c with hba1c level, uncontrolled > 7% hba1c) table 3. shows that serum levels of ima were high significant different when compare the poor controlled diabetic group (45 patients , hba1c > 7%) with signs and symptoms of ischemic heart disease ,and good controlled diabetic group (25 patients hba1c < 7%) , mean± sd; (14.70±8.66), (3.74± 3.68), respectively p. value 0.0001. figure 2 shows that uncontrolled diabetic patients (hba1c > 7 % ) with long during have high frequency level of ima ,whereas controlled patients(hba1c < 7 % ) have a lower frequency , figure 2 shows that the female have high frequency to d.m than male. 4. discussion the ima measurement as a marker of myocardial ischemia without myocardial necrosis and/or preceding myocardial necrosis has introduced the hope for improved diagnosis in patients with ihd without or with non-specific ecg changes [12]. ima has been proven to be an early biochemical marker to detect ischemia in patients of myocardial doi 10.18502/sjms.v12i4.1354 page 235 sudan journal of medical sciences isam sadik et al figure 1: diagnostic performance of ima as risk marker in diabetic patients, auc=0.84. sensitivity=81.4% and specificity=80% at cut off value =0.97. infarction. the lack of oxygen modifies albumin at n-terminus residues, thus decreasing its affinity to co (ii) [13]. increased ima levels have been found in a number of conditions with an ischemic element in their pathophysiology. only one preliminary study has been reported so far in diabetes mellitus with vascular complications, which showed increased levels of ima and its positive correlation with glycated haemoglobin (hba1c), therefore this study was planned to analyze ima levels in type 2 diabetes mellitus patients devoid of renal and cardiovascular complications [14, 15]. the levels of ima were expressed as iu/ml units, in study population use it as risk marker for cardiovascular disease. we found that the serum levels of ima were significantly higher in diabetic patients when compared with normal healthy non diabetic (p value = 0.003)this agree with previous study show that the ima is a novel marker of tissue ischemia and accepted as a marker of oxidative stress in type 2 diabetes patients [15] and others study report that definite and precise mechanisms for ima production in vivo, it appears to be related to the generation of reactive oxygen species (ros) due to ischemia-reperfusion that modifies metal binding domains of albumin molecule [16]. diabetic complications are due to various micro and macroangio-pathic events producing increased oxidative stress and decreased levels of antioxidants, which can lead to modification of albumin molecule of ima than patients with less than 5 years doi 10.18502/sjms.v12i4.1354 page 236 sudan journal of medical sciences isam sadik et al figure 2: histogram shows long–stand diabetes patients ami levels frequency accordance to gender. (1 represent female, 2 represent males). duration of diabetes(long-stand diabetes) have a lower than the other one [18, 17]. in this current study there was significantly difference increase in ima level among poor controlled (hba1c > 7%) diabetic patients ( mean; 14.70 ± 8.66)when compared with the good controlled(hba1c < 7%), diabetic (mean; 3.74 ± 3.68), the patients(longstand diabetes) duration more than 5 years have high frequency level of ima than patients with less than 5 years duration .by referring to the gender (figure 2) show that the female have high frequency of ima ul/ml level rather than male. 5. conclusion ischemic modified albumin level was elevated significantly within long duration and uncontrolled diabetic patient whom have sign of early myocardial ischemia, as cardiac biomarkers ima show as highly sensitive for early diagnostic of acute chest pain. doi 10.18502/sjms.v12i4.1354 page 237 sudan journal of medical sciences isam sadik et al references [1] a. piwowara, k. knapik-kordecka, and m. warwasa, hypertension and diabetology of, in hypertension and diabetology of, 2, p. 4, wroclaw medical university, disease markers, 2008. 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[17] r. a. defronzo, pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes, diabetes reviews, 5, no. 3, 177–269, (1997). doi 10.18502/sjms.v12i4.1354 page 239 introduction material and methods results discussion conclusion references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10685 production and hosting by knowledge e original article the antibiotic resistance and multidrug resistance pattern of uropathogenic escherichia coli at soba university hospital: a descriptive retrospective survey hagir mohamed eezzeldin1, safaa badi2, and bashir alsiddig yousef3* 1department of clinical pharmacy, faculty of pharmacy, university of khartoum, al-qasr ave, khartoum, sudan 2department of clinical pharmacy, faculty of pharmacy, omdurman islamic university, aboseid street, khartoum, sudan 3department of pharmacology, faculty of pharmacy, university of khartoum, al-qasr ave, khartoum, sudan orcid: bashir alsiddig yousef: https://orcid.org/0000-0001-7832-4556 abstract background: the irrational use of antibiotics for the treatment of urinary tract infections (utis) may lead to increased antimicrobial resistance among uropathogenic escherichia coli (e. coli), as well as multidrug resistance worldwide, which will limit available treatment options for utis caused by these organisms. this study aimed to determine the resistance pattern of e. coli causing utis in out-patients and in-patients of soba university hospital. methods: data were collected from the laboratory records in the department of microbiology in soba teaching hospital by using a predesigned checklist and then analyzed using the statistical package for social sciences. bivariate analysis (chisquare test) was used to compare between variables. results: out of the 231 e. coli urine cultures, 160 (69.3%) were collected from females. the results showed high resistance to ampicillin (92.4%), amoxicillin-clavulanic acid (83.3%), cephalexin (90.6%), cefuroxime (72%), ceftazidime (71%), ceftriaxone (72%), ciprofloxacin (68%), and co-trimoxazole (75.3%). collectively, around 188 (81.4%) were multidrug-resistant. on the other hand, the sensitivities of e. coli isolates were 68.8%, 93.1%, 89.4%, and 100% to gentamicin, amikacin, nitrofurantoin, and carbapenems, respectively. conclusion: the rate of e. coli resistance was observed to be high to the commonly prescribed drugs for utis, including ampicillin, amoxicillin/clavulanic acid, different cephalosporins, fluoroquinolones, and co-trimoxazole. however, e. coli showed lower resistance rates to nitrofurantoin, amikacin, and carbapenems. thus, these drugs can be reserved for the empirical treatment of utis caused by e. coli. keywords: escherichia coli, urinary tract infection, multidrug resistance, soba university hospital how to cite this article: hagir mohamed eezzeldin, safaa badi, and bashir alsiddig yousef* (2022) “the antibiotic resistance and multidrug resistance pattern of uropathogenic escherichia coli at soba university hospital: a descriptive retrospective survey,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 56–69. doi 10.18502/sjms.v17i1.10685 page 56 corresponding author: bashir alsiddig yousef; email: bashiralsiddiq@gmail.com received 07 may 2021 accepted 02 march 2022 published 31 march 2022 production and hosting by knowledge e hagir mohamed eezzeldin et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bashiralsiddiq@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hagir mohamed eezzeldin et al 1. introduction urinary tract infections (utis) are one of the most frequent infectious diseases that affect humans and is considered a critical public health problem [1, 2]. in united states, utis are responsible for around 7 million clinic visits per year and cost $2 billion annually [1]. the main etiology of utis is the microbial invasion to different tissues of the urinary tract system [3]. among bacteria causing utis, escherichia coli (e. coli) is considered as the most predominant cause of both community and nosocomial utis. other uticausing bacteria include proteus spp, staphylococcus saprophyticus, klebsiella spp, and other enterobacteriaceae [2, 4]. clinically, e. coli can cause uncomplicated and complicated utis. in uncomplicated utis, individuals develop infection without any structural or neurological abnormalities in the urinary tract; it can either be upper utis (pyelonephritis) or lower utis (cystitis) [5]. many risk factors are associated with utis, including a previous uti, female gender, vaginal infection, obesity, diabetes, and genetic susceptibility [6]. in complicated utis, other factors such as compromised immune system, urinary obstruction, neurological disease, renal failure, and foreign bodies can predispose to uti [7, 8]. treatment of utis requires assessment of the patient by evaluating the symptoms or signs, determining the type of uti, and knowing the previous antimicrobial therapy in case of recurrent infection [9]. many antibiotics commonly prescribed for the treatment of utis include ciprofloxacin, nitrofurantoin, co-trimoxazole, and ampicillin [10]. according to clinical practice guidelines, fluoroquinolones have been recommended for lower utis, whereas intravenous cephalosporins are commonly administered for upper utis. moreover, the recommended first-line antimicrobial for acute uncomplicated bacterial infection is nitrofurantoin or fosfomycin or co-trimoxazole; the second-line options include fluoroquinolones and β-lactams antibiotics, while for β-lactamase-producing organisms, it recommends using fosfomycin or fluoroquinolones or piperacillin-tazobactam or carbapenems. whereas, for multi-drug resistance (mdr), the recommended antibiotics are fluoroquinolones, ceftazidime, piperacillin-tazobactam, carbapenems, aminoglycosides, and colistin [11]. however, extensive use of antibiotics in treating utis is highly correlated to antimicrobial resistance [1, 12] and the emergence of mdr that is defined as organisms being resistant to at least three classes of antimicrobial agents [13]. moreover, antibiotic resistance is a public health problem, which may result in treatment failure and poor clinical outcomes such as development of complications, prolonged hospitalization, and need for intravenous therapy [14, 15]. doi 10.18502/sjms.v17i1.10685 page 57 sudan journal of medical sciences hagir mohamed eezzeldin et al knowledge of the causative organisms and their sensitivity pattern is crucial for empirical therapy for various infections. since e. coli is the most predominant causative agent for utis, regular antibiogram of e. coli strains at different hospitals is crucial for better adaptation of empirical antibiotic therapy. hence, our study aimed to explore the pattern of antibiotic resistance by uropathogenic e.coli isolate from urine samples at soba university hospital in khartoum state. 2. materials and methods 2.1. study setting this retrospective cross-sectional hospital-based survey used medical records of the patients visiting soba hospital in khartoum, sudan between january and december 2017, who underwent the antibiotic sensitivity test (disc-diffusion method) for the e. coli isolates. 2.2. inclusion and exclusion criteria all medical records of patients for whom e. coli antibiogram was done were included, while patient records with incomplete information were excluded. 2.3. sample size and sampling method a total of 231 patients met the inclusion criteria and were included in the study. 2.4. data collection tool data were collected retrospectively from patient records using a data collection sheet, which consisted of the sociodemographic data of the patient, and the list of used medications with the sensitivity findings (sensitive or resistant). doi 10.18502/sjms.v17i1.10685 page 58 sudan journal of medical sciences hagir mohamed eezzeldin et al 2.5. data analysis data were analyzed by the international business machines (ibm) statistical package for social sciences [spss] for windows, v.22.0 software [armonk, ny: ibm corp]. descriptive statistics (frequency tables) and bivariate analysis (chi-square) was done. p-value ≤ 0.05 was considered significant in comparative data. 3. results of the 231 urine culture samples, 160 (69.3%) were of females and 71 (30.7%) of males. additionally, while 159 (68.8%) samples were of adults, 72 (31.6%) were of pediatric patients. regarding patient age, 20.8% of the participants were aged 1–6 years, and 28.6% were >60 years (table 1) regarding the antibiotics sensitivity pattern for different antibiotics, as shown in table 2, the pattern to β-lactams antibiotics were varied, e. coli was resistant to ampicillin in 91.5% of the participants, and it was resistant to amoxicillin-clavulanic acid in 84.6%. furthermore, the resistance rates for e. coli strains against cephalexin, cefuroxime, ceftazidime, and ceftriaxone were 69%, 73.1%, 71.7%, and 71.8%, respectively. moreover, e. coli bacteria were resistant to ciprofloxacin in around two-thirds (65.9%) of the participants, and to gentamicin in about one-third (32.2%) of them. however, it was resistant to nitrofurantoin in only 10.6% of the samples. interestingly, 99.6% of e. coli samples were sensitive to carbapenems (table 2). on the other hand, the frequency of e. coli stains with mdr (with resistance to at least three classes of the antimicrobial agents) were 188 (81.4%) (figure 1). furthermore, e. coli samples from pediatric or adult patients showed different resistance and sensitivity patterns toward various antibacterial agents (tables 3 and 4). when chi-square was performed to determine the association of the antibiotic resistance and sociodemographic characteristics of the participants, the study showed no significant association between the sensitivity to antibacterial drugs and the gender or the age groups. however, the admission status (inor outpatient) was significantly associated with the sensitivity to cephalexin, cefuroxime, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, and nitrofurantoin (0.041, 0.009, 0.003, 0.006, 0.000, 0.042, 0.012), respectively. doi 10.18502/sjms.v17i1.10685 page 59 sudan journal of medical sciences hagir mohamed eezzeldin et al figure 1: distribution of study sample according to multiple antibiotics resistance. table 1: demographic characteristics of the participants (n = 231). variable number (frequency %) gender male 71 (30.7%) female 160 (69.3%) age category adult 159 (68.8%) pediatric 72 (31.2%) age group (yr) 1–6 48 (20.8%) 7–12 20 (8.6%) 13–18 4 (1.7%) 19–30 13 (5.6) 31–40 19 (8.4) 41–50 29 (12.5) 51–60 32 (13.8) >60 66 (28.6) admission unit inpatient 160 (69.3%) outpatient 71 (30.7%) 4. discussion the emergence of antibiotic resistance in e. coli and other microorganisms that cause utis is increasing day by day, making it a critical health problem. thus, in order to provide proper treatment for utis, it is crucial to measure the antibiotic resistance patterns in e. coli isolates [16]. in the present study, the total e.coli samples isolated within the study period were 231. we found that the occurrence of uropathogenic e. coli frequency was higher in females than in males; this may occur due to the difference in the anatomy of the urinary tract of the females, and the hormonal effects, pregnancy, certain type of birth control, and behavioral patterns [17–20]. regarding the resistant pattern, 91.5% doi 10.18502/sjms.v17i1.10685 page 60 sudan journal of medical sciences hagir mohamed eezzeldin et al table 2: distribution of study sample according to sensitivity pattern (n = 231). antibiotic class antibiotic sensitivity test n (%) β-lactams ampicillin nrst† (n = 43) rst∗ (n = 188) resistance 172 (91.5%) sensitive 16 (8.5%) amoxicillin + clavulanic acid nrst (n = 10) rst (n = 221) resistance 187 (84.6%) sensitive 34 (15.4%) cephalosporin cephalexin nrst (n = 173) rst (n = 58) resistance 40 (69%) sensitive 18 (31%) cefuroxime nrst (n = 8) rst (n = 223) resistance 163 (73.1%) sensitive 60 (26.9%) ceftazidime nrst (n = 8) rst (n = 223) resistance 160 (71.7%) sensitive 63 (28.3%) ceftriaxone nrst (n = 4) rst (n = 227) resistance 163 (71.8%) sensitive 64 (28.2%) flouroquinolones ciprofloxacin nrst (n = 8) rst (n = 223) resistance 147 (65.9%) sensitive 77 (34.1%) aminoglycosides gentamycin nrst (n = 60) rst (n = 171) resistance 55 (32.2%) sensitive 116 (67.8%) amikacin nrst (n = 4) rst (n = 227) resistance 20 (8.8%) sensitive 208 (91.2%) carbapenems meropenem and imipenem nrst (n = 2) rst (n = 229) resistance 1 (0.4%) sensitive 228 (99.6%) sulphonamides co-trimoxazole nrst (n = 4) rst (n = 227) resistance 169 (73.2%) sensitive 58 (26.8%) others nitrofurantoin nrst (n = 5) rst (n = 226) resistance 24 (10.6%) sensitive 202 (89.4%) ∗rst: requested sensitivity test; †nrst: not requested sensitivity test. doi 10.18502/sjms.v17i1.10685 page 61 sudan journal of medical sciences hagir mohamed eezzeldin et al table 3: distribution of pediatric patients’ sample according to sensitivity pattern (n = 72). antibiotic class antibiotic sensitivity test n (%) β-lactams ampicillin nrst† (n = 14) rst* (n =58) resistance 55 (94.8%) sensitive 3 (5.2%) amoxicillin + clavulanic acid nrst (n = 2) rst (n = 70) resistance 59 (84.3%) sensitive 11 (15.7%) cephalosporin cefuroxime nrst (n = 4) rst (n = 68) resistance 51 (75%) sensitive 17 (25%) ceftazidime nrst (n = 4) rst (n = 68) resistance 48 (70.6%) sensitive 20 (29.4%) ceftriaxone nrst (n = 0) rst (n = 72) resistance 51 (70.8%) sensitive 21 (29.2%) flouroquinolones ciprofloxacin nrst (n = 1) rst (n = 71) resistance 46 (64.8%) sensitive 25 (35.2%) aminoglycosides gentamycin nrst (n = 16) rst (n = 56) resistance 19 (33.9%) sensitive 37 (66.1%) amikacin nrst (n = 0) rst (n = 72) resistance 7 (9.9%) sensitive 65 (90.1%) carbapenems meropenem and imipenem nrst (n = 2) rst (n = 70) resistance 1 (1.4%) sensitive 69 (98.6%) sulphonamides co-trimoxazole nrst (n = 1) rst (n = 71) resistance 56 (78.9%) sensitive 15 (21.1%) others nitrofurantoin nrst (n = 2) rst (n = 70) resistance 11 (15.7%) sensitive 59 (84.3%) *rst: requested sensitivity test; † nrst: not requested sensitivity test. and 84.6% of e.coli samples were resistant to ampicillin and co-amoxiclav, respectively, which indicated a cautious use of these antibiotics for the treatment of utis. similar findings were seen in india and pakistan [21–23]. the resistance rates were also high for cephalosporin antibiotics, including cephalexin (90.6%), ceftazidime (71%), cefuroxime doi 10.18502/sjms.v17i1.10685 page 62 sudan journal of medical sciences hagir mohamed eezzeldin et al table 4: distribution of adult patients’ sample according to sensitivity pattern (n = 159). antibiotic class antibiotic sensitivity test n (%) β-lactams ampicillin nrst† (n = 29) rst* (n = 130) resistance 117 (90%) sensitive 13 (10%) amoxicillin + clavulanic acid nrst (n = 8) rst (n = 151) resistance 128 (84.7%) sensitive 23 (15.3%) cephalosporin cephalexin nrst (n = 113) rst (n = 46) resistance 32 (69.6%) sensitive 14 (30.4%) cefuroxime nrst (n = 4) rst (n = 155) resistance 112 (72.3%) sensitive 43 (27.7%) ceftazidime nrst (n = 4) rst (n = 155) resistance 112 (72.3%) sensitive 43 (27.7%) ceftriaxone nrst (n = 4) rst (n = 155) resistance 112 (72.3%) sensitive 43 (27.7%) flouroquinolones ciprofloxacin nrst (n = 7) rst (n = 152) resistance 101 (66.4%) sensitive 52 (33.6%) aminoglycosides gentamycin nrst (n = 44) rst (n = 115) resistance 36 (31.3%) sensitive 79 (68.7%) amikacin nrst (n = 3) rst (n = 156) resistance 13 (8.3%) sensitive 143 (91.7%) carbapenems meropenem and imipenem nrst (n= 0) rst (n = 159) resistance 0 (0%) sensitive 159 (100%) sulphonamides co-trimoxazole nrst (n = 3) rst (n = 156) resistance 113 (72.4%) sensitive 43 (27.6%) others nitrofurantoin nrst (n = 3) rst (n = 156) resistance 13 (8.3%) sensitive 143 (91.7%) *rst: requested sensitivity test; †nrst: not requested sensitivity test doi 10.18502/sjms.v17i1.10685 page 63 sudan journal of medical sciences hagir mohamed eezzeldin et al (72%), and ceftriaxone (72%), which renders them inefficient as empirical therapy against utis. the main reason for that is the irrational prescribing of these classes of drugs in different hospitals in sudan [24–26]. however, in united states, due to the rational prescribing of antibiotics, the resistance rates to penicillin and cephalosporins were comparatively low [27]. trimethoprim-sulfamethoxazole (co-trimoxazole) has been widely used for the treatment of utis, but our results showed high resistance (74.4%), this result is inconsistent with other studies [21, 27]. among aminoglycosides, the observed resistance rate for gentamicin and amikacin were 32.2% and 8.8%, respectively, with a significant association with the kind of admission (p < 0.05). similar results were observed in a hospital in tamil nadu, india, where gentamicin and amikacin resistance rates were 30.4% and 10.5%, respectively [19]. however, even with high sensitivities for these antibiotics, the utilization of aminoglycosides is low, due to their nephrotoxicity and ototoxicity [28]. on the other hand, fluoroquinolones, especially ciprofloxacin, have been the most frequently used antibiotic for utis in the recent past [29]. in the present study, e. coli strains were highly resistant (65.9%) to ciprofloxacin, this finding is concerning, as fluoroquinolones are frequently used empirically to treat utis, especially complicated infections. interestingly, the resistance to nitrofurantoin was very low (10.6%) in comparison to other antibiotics, which suggest using this drug as the first-line option in the empirical treatment of uncomplicated cystitis and other lower utis. this low rate of resistance may be due to the limited use of nitrofurantoin in the last years. these findings were also observed worldwide [21, 30]. among the carbapenems class of antibiotics, this study demonstrated there was only one resistant case for all tested isolates, as these drugs are restricted for severe infections. in contrast to another study done in a tertiary care hospital in india that showed relatively high resistance (43.3%) to carbapenems, these may have resulted due to misuse and overuse of this class in the hospital [31]. in addition, the current study showed a high rate (81.4%) of mdr of e. coli in comparison to another study done in the united states that showed only 7.1% of mdr [32]. a high occurrence of mdr could result from many factors including hospitalization, diabetes, chronic renal disease, and catheterization [33, 34]. limitations the limitations of the current study are: firstly, the cross-sectional design in one hospital may not allow generalization of the findings to all hospitals in sudan. secondly, doi 10.18502/sjms.v17i1.10685 page 64 sudan journal of medical sciences hagir mohamed eezzeldin et al many incomplete and missed data were also reported. despite these limitations, this surveillance is essential, as it demonstrates the situation of the e. coli resistance to antibiotics which will help a lot in the proper selection of empirical therapy to treat utis. however, prospective studies are urgently needed in other sudanese hospitals in order to determine the resistance and sensitivity patterns for e. coli and microorganisms. 5. conclusion the uropathogenic e.coli are highly resistant to the majority of antibiotics commonly used in the clinical practice in inpatients and outpatients. the e. coli resistance rate was observed to be high for ampicillin, combination b-lactamase inhibitor (amoxicillin/clavulanic acid), and cephalosporin (cefuroxime, ceftazidime, and ceftriaxone), fluoroquinolones, and co-trimoxazole. however, e. coli showed lower resistance to nitrofurantoin, amikacin, and carbapenems; this can be reserved for empirical treatment of utis. according to our findings, we recommend using nitrofurantoin as an empirical therapy for the treatment of lower utis. acknowledgements the authors would like to thank all members of the department of microbiology at soba university hospital for their help and collaboration. ethical considerations the ethical clearance was obtained from the ethical committee of the faculty of pharmacy, university of khartoum. additional approval was taken from the administration of soba university hospital and the department of microbiology in the hospital before starting data collection. all collected data were coded while ensuring confidentiality throughout the study. competing interests there are no conflicts of interest. doi 10.18502/sjms.v17i1.10685 page 65 sudan journal of medical sciences hagir mohamed eezzeldin et al availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding none. references [1] mazzariol, a., bazaj, a., and cornaglia, g. 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(2014). nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary escherichia coli from us outpatients. journal of antimicrobial chemotherapy, vol. 69, no. 12, pp. 3259–3262. [31] hasan, a. s., nair, d., kaur, j., et al. (2007). resistance patterns of urinary isolates in a tertiary indian hospital. journal of ayub medical college abbottabad, vol. 19, no. 1, pp. 39–41. doi 10.18502/sjms.v17i1.10685 page 68 sudan journal of medical sciences hagir mohamed eezzeldin et al [32] sahm, d. f., thornsberry, c., mayfield, d. c., et al. (2001). multidrug-resistant urinary tract isolates of escherichia coli: prevalence and patient demographics in the united states in 2000. antimicrobial agents and chemotherapy, vol. 45, no. 5, pp. 1402– 1406. [33] khawcharoenporn, t., vasoo, s., and singh, k. (2013). urinary tract infections due to multidrug-resistant enterobacteriaceae: prevalence and risk factors in a chicago emergency department. emergency medicine international, vol. 2013, article 258517. [34] tenney, j., hudson, n., alnifaidy, h., et al. (2018). risk factors for aquiring multidrugresistant organisms in urinary tract infections: a systematic doi 10.18502/sjms.v17i1.10685 page 69 introduction materials and methods study setting inclusion and exclusion criteria sample size and sampling method data collection tool data analysis results discussion limitations conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11454 production and hosting by knowledge e original article seroprevalence of west nile virus in regular blood donors referred to the blood bank of kurdistan province, iran asrin babahajian,1 pezhman sharifi,1* woria babahajiani,2 seyvan vafaii,2 vahid yousefinejad,1 serveh babahajiani,2 behzad mohsenpour,1 rasoul nasiri kalmarzi,3 mohammad aziz rasouli,4 masoomeh souri2 1liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran 2blood transfusion organization, kurdistan, sanandaj, iran 3lung diseases and allergy research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran 4clinical research development center, kowsar hospital, kurdistan university of medical sciences, sanandaj, iran orcid: asrin babahajian: https://orcid.org/0000-0003-0278-1560 pezhman sharifi: https://orcid.org/0000-0001-7953-9487 woria babahajiani: https://orcid.org/0000-0002-7295-0246 seyvan vafaii: https://orcid.org/0000-0003-2483-036x vahid yousefinejad: https://orcid.org/0000-0002-9928-938x serveh babahajiani: https://orcid.org/0000-0003-2691-7995 behzad mohsenpour: https://orcid.org/0000-0001-8675-4492 rasoul nasiri kalmarzi: https://orcid.org/0000-0001-6351-2909 mohammad azizi rasouli: https://orcid.org/0000-0003-3359-774x masoomeh souri: https://orcid.org/0000-0002-1731-8264 abstract background: west nile virus is an infection that is most commonly caused by infected mosquito bites, however, blood transfusions, organ transplants, breast feeding, pregnant mother-to-the fetus transmission, and occupational transmission among laboratory and medical staff are also the less common routes of infection. given the endemic nature of this virus in the middle east, the aim of this study was to investigate the presence of this virus in regular blood donors, as the reliable source of blood supply needed for patients in hospitals. methods: in this descriptive analytical study, venous blood samples were collected from 259 regular blood donors referred to the blood transfusion organization of kurdistan. after separating blood serum, the amount of igm and igg antibodies against west nile virus was measured via elisa test. results: concerning antibodies, igg and igm against west nile virus were positive in 14 patients (5.4%) and 3 patients (1.2%), respectively. seropositive igg levels were observed in 11 patients over the age of 40 (12.5%) but only in 3 patients under 40 years of age (1.8%). the difference was statistically significant (or = 7.95; 95% ci: 2.16–29.32; p < 0.01). conclusion: given the value of blood and blood products obtained from regular blood donors for therapeutic purposes and the significant prevalence of the virus and considering the presence of cases with positive igm, it seems necessary to screen blood donors in blood transfusion centers in the western parts of iran. keywords: seroprevalence, west nile virus, regular blood donors, blood bank, kurdistan, iran how to cite this article: asrin babahajian, pezhman sharifi,* woria babahajiani, seyvan vafaii, vahid yousefinejad, serveh babahajiani, behzad mohsenpour, rasoul nasiri kalmarzi, mohammad aziz rasouli, masoomeh souri (2022) “seroprevalence of west nile virus in regular blood donors referred to the blood bank of kurdistan province, iran,” sudan journal of medical sciences, vol. 17, no. 2, pp. 192–203. doi 10.18502/sjms.v17i2.11454 page 192 corresponding author: pezhman sharifi; email: pezhman.sh7@gmail.com received 10 may 2021 accepted 3 may 2022 published 30 june 2022 production and hosting by knowledge e asrin babahajian et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:pezhman.sh7@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences asrin babahajian et al. 1. introduction west nile virus (wnv) is a member of flaviviridae family and of the genus of flavivirus that has a small, spherical, coated shape as well as a single-stranded rna genome with positive polarity (+ssrna) [1, 2]. the virus proliferates in the tissues of arthropods carrier (culex species mosquitoes) without causing disease or injury [2]. birds are also considered to be its reservoir hosts. this virus is a virus conserved in nature and its transmission cycle is mosquito–bird–mosquito and its first cycle includes mosquitoes [3, 4]. most cases are infected via mosquito bites, and other ways of infecting humans are through blood transfusions, organ transplants, breast feeding, pregnant mothers-tofetus transmission, and occupational transmissions in laboratories and medical centers, which are less common [5]. horses, like humans, are considered dead-end hosts, that is, their infection does not spread the virus [6]. migratory birds appear to be the main cause of the spread of the virus, including re-spread of wnv from endemic areas to areas with scattered (single-catch) cases [7]. the virus is historically an endemic infection in africa, west asia, and the middle east, and is the most widespread flavivirus in africa, eurasia, australia, and north america [8, 9]. the virus is not limited to international borders and is observed in all continents with different ecological regions, which indicates the flexibility of the virus [10]. surveillance data from the us center for disease control and prevention (cdc) in 2014 showed that the wnv is the most common cause of arboviral neurological diseases in the united states [1, 11]. people infected with the virus (about 80%) do not have any signs or symptoms, but about 20% of people experience signs and symptoms. the virus causes influenzalike symptoms such as muscle aches, fever, headache, weakness, lymphadenopathy, abdominal pain, fatigue, vomiting, and sometimes bloody diarrhea, and severe symptoms such as encephalitis and meningitis or sudden paralysis (polio-like syndrome) and even death (which occurs in about 1 out of 150 people infected with wnv virus in the elderly patients or patients with weakened immune systems or patients with chronic diseases) [6, 12, 13]. hepatitis, pancreatitis, and myocarditis are also the rare outcomes of the infection with the virus [3, 14]. there is currently no definitive cure for wnv infection, and treatment for this infection is largely focused on supportive acts and controlling the symptoms of the disease, which is a time-consuming process [1]. although inactivated and recombinant vaccines are available for use in animals, no approved vaccine or antiviral treatment is currently available for humans [15]. considering the mentioned cases and the spread and endemicity of this virus in the middle east region and the doi 10.18502/sjms.v17i2.11454 page 193 sudan journal of medical sciences asrin babahajian et al. proximity of western provinces of iran with the endemic areas, the aim of this study was to investigate the presence of this virus in regular blood donors as the most important and reliable sources of blood supply for patients. it is hoped that the results of the study would be used to highlight the need for screening this virus in the blood banks in the western provinces of iran. 2. materials and methods 2.1. study design and setting in this descriptive analytical cross-sectional study, individuals who were referred to the blood transfusion organization of kurdistan for blood donation over a period of one year (2018–2019) were investigated. 2.2. participants the subjects of this study included regular blood donors referred to the blood transfusion organization (individuals who donated blood at least twice a year) who were 18 to 65 years old; they were selected through census method. those who did not consent to participate were excluded from the study. the sampling was performed via convenience sampling method; accordingly, one out of three blood donors was randomly examined to reach the required sample size. 2.3. sampling after collecting the sociodemographic information of the participants by one of the researchers using a questionnaire, 5 cc of venous blood was collected from the median cubital vein of the participants to measure the level of igm and igg antibodies against wnv. blood samples were kept at room temperature for 15 to 30 min and after centrifugation (3000 rpm) for 15 min, their serum was isolated. serum samples were stored in a freezer at a temperature of –20ºc until testing. the amount of igm and igg antibodies against wnv was measured via elisa method using euroimmun kits made in germany with lot numbers of ei2662-9601g and ei2662-9601m following the manufacturer’s instructions. when performing the wnv igg test, a level <16 ru/ml was considered as negative, a level of 16 to 22 was considered as borderline, and a level >22 was considered as positive. when performing the wnv igm test, a ratio of <0.8 doi 10.18502/sjms.v17i2.11454 page 194 sudan journal of medical sciences asrin babahajian et al. was considered as negative, a ratio from 0.8 to 1.1 was considered as borderline, and a ratio of >1.1 was considered as positive. in cases reported as borderline, antibody titer was checked again after one week. 2.4. sample size based on a previous study [16] and considering p = 0.20, a first-type error of 5%, and a test power of 80%, the sample size was calculated to be 245 people and finally 259 people were examined to increase the accuracy of the results. 2.5. statistical analysis the results of the study were analyzed using spss v.20 software. qualitative data were reported as frequency and percentage and quantitative data, in case of normal distribution, data were reported as mean ± standard deviation and, in case of the lack of normal distribution, as median (iqr). chi-square test was used to compare quantitative variables between seropositive and seronegative individuals. the significance level in this study was set at p < 0.05. 3. results a total of 246 men (95%) and 13 women (5%) with a mean age of 35 years (within the age range of 20 to 60 years) participated in the study. the sociodemographic characteristics of the participants are presented in table 1. of the 259 serum samples collected from regular blood donors, positive igg and igm antibodies against wnv were observed in 14 (5.4%) and 3 cases (1.2%), respectively. seropositive igg levels were observed in 11 samples over the age of 40 (12.5%) but only in 3 samples under 40 years of age (1.8%), and the difference was statistically significant (or = 7.95; 95% ci: 2.16 to 29.32; p < 0.01). concerning the other variables, gender (p = 0.50), marital status (p = 0.20), place of residence (p = 0.62), history of underlying diseases (p = 0.61), and contact with animals (p = 0.06) did not have a significant relationship with positive igg against the virus. among the cases with seropositive igg, except for a 37-year-old woman, the rest were male with a mean age ± standard deviation of 45.5 ± 7.6 years. all the participants were living in the city, and except for one, all were married. of all, seven were self-employed, five were employees, one was housewife, and one was farmer. four reported contact doi 10.18502/sjms.v17i2.11454 page 195 sudan journal of medical sciences asrin babahajian et al. with animals, and half of them (n = 7) reported traveling to other countries, of whom six traveled to the middle east and one to southeast asia. none of the participants had a history of underlying disease or neurological disorders. the participants’ igg titers ranged from 49.60 to 424.94. concerning blood type, it was a in seven cases, o in five cases, and b in two cases. rh was negative in only two cases, and it was positive in the rest (table 2). as shown in table 3, no history of contact with animals and traveling abroad were reported in three individuals with seropositive igm. all the cases were male and less than 40 years old. one was living in rural areas and one was employed while two were self-employed. table 1: characteristics of the study population. n (%) variables 13 (5.0%) female gender 246 (95.0%) male 63 (24.3%) 20–29 age (yr) 108 (41.7%) 30–39 59 (22.8%) 40–49 29 (11.2%) 50–60 198 (76.4%) married marital status 61 (23.6%) single 237 (91.5%) urban place of residence 22 (8.5%) rural 90 (34.7%) employee professions 7 (2.7%) farmer 31 (12.0%) housewife/unemployed 11 (4.3%) army 120 (46.3%) self-employed 90 (34.7%) a blood type 53 (20.5%) b 101 (39.0%) o 15 (5.8%) ab 233 (90.0%) + rh 26 (10.0%) – doi 10.18502/sjms.v17i2.11454 page 196 sudan journal of medical sciences asrin babahajian et al. table 2: the status of studied variables in blood donors with a positive igg west nile virus laboratory test. no gender age (yr) professions location marital status animal contact traveling abroad bgrh igg level (ru/ml) 1 m 41 selfemployment urban married no yes o+ 295.56 2 m 46 selfemployment urban married no no o−− 424.94 3 m 54 selfemployment urban married no no o+ 324.31 4 f 37 housewife urban single yes no a+ 252.12 5 m 40 employee urban married no no a+ 149.85 6 m 37 employee urban married yes no a+ 276.69 7 m 43 selfemployment urban married no no b+ 321.01 8 m 37 farmer urban married no no a+ 168.24 9 m 44 selfemployment urban married no yes o+ 120.57 10 m 53 selfemployment urban married yes yes o−− 276.87 11 m 60 employee urban married no yes b+ 293.42 12 m 41 selfemployment urban married yes yes a+ 265.07 13 m 40 employee urban married no yes a+ 49.60 14 m 56 employee urban married no yes a+ 243.31 table 3: the status of studied variables in blood donors with a positive igm west nile virus laboratory test. no gender age (yr) professions location marital status animal contact traveling abroad bgrh igmratio 1 m 38 selfemployed urban married no no b+ 1.44 2 m 30 employee urban married no no a+ 1.47 3 m 24 selfemployed rural single no no o+ 1.12 4. discussion based on the results of this study, the prevalence of positive wnv igg and wnv igm antibodies in regular blood donors was 5.4% (n = 14) and 1.2% (n = 3), respectively. in addition, the prevalence of cases with positive igg was higher in people over 40 years old than in people under 40 years old and the difference was statistically significant. other variables such as gender, marital status, place of residence, history of underlying diseases, and contact with animals were not significantly associated with positive igg antibody against the virus. doi 10.18502/sjms.v17i2.11454 page 197 sudan journal of medical sciences asrin babahajian et al. concerning the prevalence of wnv igg antibody, the results of the present study are in line with many studies conducted in other countries, especially in the middle east and other parts of the world such as libya, algeria, northern cyprus, bolivia, hungary, greece and jordan, as well as in studies carried out in iran, in which the prevalence of the aforementioned antibody ranged from 2.34% to 8.61% [5, 17–25]. in particular, studies in northern cyprus and hungary had been conducted on blood donors. nevertheless, contrasting results had also been observed in studies conducted on blood donors in sudan (44.4%) and egypt (55%) [26, 27], which are inconsistent with the findings of this study. in a study conducted in israel on samples collected in serum bank of israel, 11.1% of cases had positive antibody [28]. in the african country of zambia, the prevalence of this antibody was 10.3% in a population of native farmers [29]. as observed, the prevalence of this antibody is completely different in various populations and regions of the world; it seems that the proximity to endemic centers of this disease (countries and regions around the nile river), health status in different developing and developed communities, as well as the implementation of health programs such as carrier control programs in different parts of the world are the important and effective factors influencing the prevalence of this infection. concerning the wnv igm antibody, the prevalence of positive cases was 1.2% (n = 3) which despite its small amount is consistent with the results of a study by yousof et al. that was conducted in 2018 in sudan (2.2%) [26]; nevertheless, it is not consistent with the prevalence observed in a study in hungary (0.14%) [20]. despite the small prevalence of this antibody, it is an important issue because positive wnv igm indicates the active presence of the virus in the body and the virus can be transmitted through blood transfusions. it is a more important issue in this study because the population under our study included regular blood donors who donate blood at least twice a year, and each time they are examined fully for clinical symptoms and undergo medical examinations and microbial and viral tests such as hepatitis. b, c, hiv, and rpr. because of these examinations and controls that are performed at every case of blood donation, they are completely healthy people whose blood is important for the blood transfusion organization as well as hospitals and medical centers and is considered to be reliable and safe. furthermore, in this study, it was observed that the prevalence of seropositive igg in people over 40 years of age was higher than that in people under 40 years of age and the difference was statistically significant (p < 0.01) which could be due to the higher level of exposure of people to infectious agents with increasing age. this finding is consistent with the results of hadjichristodoulou et al.’s study in greece [21] doi 10.18502/sjms.v17i2.11454 page 198 sudan journal of medical sciences asrin babahajian et al. and obaidat et al.’s in jordan [22], but it was not consistent with the results of nagy et al.’s study in hungary [20]. the controversy in the results might be attributed to differences in geographical and health conditions of the two regions as well as the differences between the statistical population and the sample size in the two studies. other studied variables such as gender, marital status, place of residence, history of underlying diseases, and contact with animals were not significantly associated with positive igg against the virus in the participants; it is not in line with the results of studies by hadjichristodoulou et al. and bassal et al. [28] which showed that place of residence was associated with positive antibody, and a study by obaidat et al. which reported that positive igg antibody was significantly associated with gender. the controversy in the results could be due to differences in environmental, geographical, and health conditions in these studies, as well as differences between the statistical populations investigated in the present study and other studies. as presented in table 2, all the cases with positive igg were living in urban areas and all but one were married. of all, seven were self-employed, five were employees, one was a housewife, and one was a farmer. in addition, four had a history of contact with animals and half (seven persons) had a history of traveling to other countries, of whom six traveled to the middle east and one to the southeast asia. it is worth noting that none of the participants had a history of underlying disease or neurological disorders. moreover, the igg antibody titer of seropositive individuals varied between 49.60 and 424.94. moreover, the blood type was a in seven cases, o in five cases, and b in two cases. rh was negative in only two cases, and it was positive in the rest. as shown in table 3, all the people who were seropositive for igm antibodies were male and aged less than 40 years old. one of them was living in rural areas and one was employee and two were self-employed. finally, none of them reported contact with animals or traveling abroad. as strength of the present study was that it was conducted on regular blood donors, that is, those who donate blood at least twice a year, who are the most important and reliable blood donors and the main sources of blood supply to hospitals and medical centers. they undergo full clinical and medical examinations and viral and microbial tests, and because of clinical and laboratory control of these people and their donated blood, they are considered as the most important and reliable source of blood for therapeutic uses. this study also had some limitations; it was conducted only on regular donors referred to the blood transfusion organization of kurdistan province. hence, in order to conduct more comprehensive studies, it is recommended to investigate regular blood donors from other western and border provinces such as kermanshah, ilam, etc. doi 10.18502/sjms.v17i2.11454 page 199 sudan journal of medical sciences asrin babahajian et al. according to the results of this study and given the value of blood products obtained from regular blood donors for therapeutic purposes, since a significant prevalence of this virus and positive cases of igm were observed among the studied population, it is suggested to take measures to screen blood donors along with virus and microbial tests routinely performed by the blood transfusion organization. it can be performed in a similar way as the testing of blood donors for htlv in blood transfusion centers in khorasan province, which is being performed due to the spread of the virus in the province. the decisions and plans for the western part of the country regarding this issue must be made by the blood transfusion organization and officials and decision makers in the ministry of health (this suggestion is especially important for blood donors over the age of 40, and it seems essential to be performed because of the significant association of seropositive cases with the virus antibody in people over the age of 40). it is also worth mentioning that due to the high prevalence of positive cases of igm in the subjects and the proximity of these areas to the endemic regions of the virus, it seems necessary to take measures for more control and monitoring at the borders. in addition, to control and eliminate carriers, officials and those involved in health and administration fields must make plans for the development and implementation of more strict and serious health programs. furthermore, given the ignorance and lack of public awareness regarding the virus and its complications, as well as ignorance about ways to control and prevent the infection, people must be informed through the mass media and training workshops. 5. conclusion based on the results of this study, the prevalence of positive wnv igg antibody and wnv igm antibody in regular blood donors in kurdistan province was 5.4% and 1.2%, respectively. moreover, the prevalence of cases with positive igg was higher in people over the age of 40 than in those younger than that. acknowledgements the present article was extracted from the research project. the authors would also like to thank the esteemed staff and the employees of the blood transfusion organization of kurdistan province for their admirable cooperation in the implementation of this project. doi 10.18502/sjms.v17i2.11454 page 200 sudan journal of medical sciences asrin babahajian et al. ethical considerations this study was approved by the ethics committee of kurdistan university of medical sciences (ir.muk.rec.1396/355). written informed consent was obtained from all the participants, and the principles of data confidentiality, as recommended by helsinki convention, were observed by researchers. competing interests the authors declare no conflict of interests. availability of data and material all relevant data and methodological details pertaining to this study are available to anyinterested researchers upon reasonable request to corresponding author. funding this sudy was financially supported by kurdistan university of medical sciences. references [1] david, s. and abraham, a. m. 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(2015). seroprevalence of west nile virus specific igg and igm antibodies in north-western and western provinces of zambia. african health sciences, vol. 15, no. 3, pp. 803–809. doi 10.18502/sjms.v17i2.11454 page 203 introduction materials and methods study design and setting participants sampling sample size statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12863 production and hosting by knowledge e research article awareness of final-year medical students of omdurman islamic university on their career choices omer e. a. elbashier1*, maab o. a. ibrahim2, hatoon m. a. abdalla2, hefa a. i. elseed2, hiba h. i. rahama2, yusra a. a. abbas2 1department of surgery, faculty of medicine, omdurman islamic university (oiu), khartoum, sudan 2faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan orcid: omer e. a. elbashier: https://orcid.org/0000-0002-6814-6757 abstract background: medical students undergo a complex process as a student to make a career decision and pursue further specialization. this study explores the factors that influence the career choices of the two genders studying in the final year of medicine at omdurman islamic university. methods: this institution-based cross-sectional study was conducted on 194 male and female fifth-year medical students studying at omdurman islamic university. the questionnaire contains 15 multiple-choice questions to determine the factors affecting students’ career choices – lifestyle, income, family impact,…etc. – and the association between gender and the specialties they choose to pursue. results: the specialties were preferred in the following order: surgery by 22.9%, internal medicine by 18.3%, obstetric gynecology by 13.8%, and pediatric by 10% (limited to the four major specialties). the least chosen specialties were histopathology, emergency medicine, psychiatry, and anesthesia (all were 0.9%). family medicine and forensics were not chosen by any participant. females significantly preferred dermatology, obstetrics and gynecology, otolaryngology, and pediatrics compared to their male counterparts. whereas, males compared to females significantly preferred orthopedics and surgery. the factors influencing change in students’ specialties based on their gender were family views and family obligations. nearly 80% of students choose a career based on personal interest; lifestyle and financial reward were also seen to play an important role in choosing a specialty. about 91% of participants agreed that there is a need for guidance. a great proportion of final-year students (62%) preferred to specialize abroad and related it to a good lifestyle and financial stability. conclusion: this study showed that the students’ awareness about specialty choices was limited to certain specialties as seen in the literature. the most preferred specialties were surgery (22.9%), internal medicine (18.3%), obstetrics and gynecology (13.8%), and pediatric (10%). there are many factors influencing the selection of specialties, however, the most common one is personal interest followed by lifestyle issues and financial reward. additionally, there is a significant gender difference in career-choice decisions. keywords: career choice, preferred medical specialty, awareness toward specialty how to cite this article: omer e. a. elbashier*, maab o. a. ibrahim, hatoon m. a. abdalla, hefa a. i. elseed, hiba h. i. rahama, yusra a. a. abbas (2023) “awareness of final-year medical students of omdurman islamic university on their career choices,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 37–47. doi 10.18502/sjms.v18i1.12863 page 37 corresponding author: omer e. a. elbashier; email: omarg2002@hotmail.com received 28 january 2022 accepted 18 december 2022 published 31 march 2023 production and hosting by knowledge e omer e. a. elbashier et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences omer e. a. elbashier et al 1. introduction during the 2020 coronavirus outbreak, a global shortage of healthcare workers was witnessed in some specialties and the service focused on controlling the pandemic [1], this led to many facilities putting non-covid cases on halt [2]. this has pointed to the need for certain specialties to prepare themselves to face such disasters. developing countries, including sudan, were affected more due to their limited facilities and resources. therefore, it is not surprising that the career choices of medical students along with the factors involved in making those choices are of great significance for a balanced distribution of doctors in different specialties, as well as planning the workforce of healthcare services [3]. studies have shown that many factors influence medical student’s choices toward certain specialties [4–8]; for instance, intellectual ability, technical abilities, long-term expertise, engagement, or the ability to function in unique situations, which may be ideally matched to specific characteristics, skills, and physical structures [9].knowledge about medicine and specialties has become widely available recently [6], and while some students may choose their specialization even before registering for college, others may do it after college and during internships [8]. new studies in other nations have identified several variables linked to selection and desire, such as gender, job prospects, reputation, employment, and role modeling by department staff [10, 11]. dale and martha stated that the controllable lifestyle and income of medical students have become more crucial in their career decisions, and the relative impact of these considerations differs significantly between the specialties [12].many students do prefer surgery for its high income, although it is considered the lowest in lifestyle [13].a self-reported survey done by surgical residents in the united states revealed that surgery residents work more hours than their peers in other specialties [14] with high work stress [15].females have become a growing part of medical schools in japan, the united states, and europe. however, globally, the roles of females appear to have been undervalued. gender determines not only the preferred specialization but also the reasons for that selection [10, 16, 17].prior knowledge about a specialty, which is now readily available, and clinical experience in the study period together with the mentoring effect might give the students a critical view of specialties [18–21]. therefore, studying career interests can serve to provide essential information to assist in the preparation of educational programs, set goals, and prepare for the availability of appropriate healthcare [7]. this study focuses on final-year medical students doi 10.18502/sjms.v18i1.12863 page 38 sudan journal of medical sciences omer e. a. elbashier et al because a higher percentage of medical students settle on their fields of specialty in the final year of their undergraduate medical training [22]. 2. methods this study is a descriptive prospective cross-sectional, institution-based study. it was conducted from november 3𝑟𝑑to 22𝑛𝑑, 2020 at the faculty of medicine and health sciences of omdurman islamic university, khartoum, sudan. a self-administered, semistructured questionnaire was designed by researchers based on relevant literature reviews to collect demographic information and future specialties preferences as well as factors that influence those decisions [1, 9, 15, 16]. a medical education expert validated the questionnaire, which was then pretested on a random sample of students to ensure that the questions were understandable. it was distributed to 194 male and female fifthyear students recruited for the study. the sample was computed using epi info version 7 with a total population of 391, an expected frequency of 50%, a margin of error of 5%, a design effect of 1, and a confidence level of 95% resulting in a sample size of 194. sampling was done using a nonprobability convenience technique. the questionnaires were administered using google form to a telegram group of 384 final-year medical students; the responses stopped when the desired sample had been collected, thus, the first responders were included in the study. the questionnaire contained 15 multiplechoice questions. the variables included awareness toward career choosing, factors influencing the choices, gender, age, and socioeconomic status. data were analyzed using the statistical package for social science spss v22, and the p-value was considered significant if <0.05. the descriptive frequency analysis was done for all variables. the chi-square test was used to assess the association between gender and specialty preference. 3. results a total of 194 students were included in this study – 112 females (58%) and 82 males (42%). the mean age of the participants was 24 ± 2 years. 3.1. stage of career decision about 53% of students had determined what specialty they wanted to pursue after graduation – of them, 73% had decided their specialty before medical school, 15% doi 10.18502/sjms.v18i1.12863 page 39 sudan journal of medical sciences omer e. a. elbashier et al preclinical, and 12% during clinical rotation. however, 47% had not decided yet because of the lack of knowledge (19%), the lack of interest (12%), and the lack of workshops (10%) and role models (6%). 3.2. the preferred specialties for both genders, the most preferred specialties were limited to the four major specialties of surgery (22.9%), internal medicine (18.3%), obstetrics and gynecology (13.8%), and pediatrics (10.0%). the least chosen specialties were emergency medicine, histopathology, and radiology (all 00.9%; table 1). 3.3. gender and career choices a significant association was seen between the students’ gender and their career choices (p-value < 0.05). females preferred dermatology, obstetrics and gynecology, otolaryngology, and pediatrics, while males preferred orthopedics and surgery (table 2). the most influential factor was the family view (59%) and responsibility toward families (41%). 3.4. rating of the motivational factors for specialty preference nearly 80% of students decided to choose a career based on personal interest. they also indicated that lifestyle (63%) and financial rewards (52%) play an important role in choosing a specialty. other factors that were considered significant by at least half of the respondents related to future job opportunities (42%), social factors (30%), and role modeling (10%). 3.5. guidance preference among final students about 91% of participants agreed that there is a need for guidance during medical school. the most preferred form of guidance was workshops (67%), followed by lectures from the college curriculum (61%), and conferences (60%). doi 10.18502/sjms.v18i1.12863 page 40 sudan journal of medical sciences omer e. a. elbashier et al table 1: the preferred specialties among students (male vs female). ratio specialty total (%) females males 22.9% 08.2% 14.7% surgery 18.3% 11.9% 06.4% internal medicine 13.8% 11.9% 01.9% obstetrics and gynecology 10.0% 08.2% 01.8% pediatric 09.1% 08.2% 00.9% dermatology 07.3% 04.5% 02.7% ophthalmology 07.3% 00.9% 06.4% orthopedic 05.5% 04.5% 01.0% otolaryngology 01.8% 00.0% 01.8% anesthesia 01.8% 00.0% 01.8% neurosurgery 00.9% 00.9% 00.0% emergency medicine 00.9% 00.9% 00.0% histopathology 00.9% 00.9% 00.0% radiology 00.9% 00.9% 00.0% psychiatry 00.9% 00.9% 00.0% cardiac surgery 4. discussion this survey showed that for both the male and female students, the most preferred specialties were limited to the four major ones. this is similar to another study where general practitioners/family medicine was the most preferred specialty (18.8%), followed by surgery (9.5%), pediatrics (7.6%), internal medicine (7.1%), emergency medicine (4.6%), orthopedics (3.8%), and urology (3.3%) [8].these findings could be mainly because of the lack of knowledge about certain specialties, the substantial representation of the faculty curriculum in our medical schools, as well as the role modeling by a large number of consultants in these major specialties. moreover, the lack of clear guidance during medical rotation made most of the students decide on their specialty before medical school; while the other half (47%) had no choice because of the lack of knowledge and the lack of interest. in addition, other surveys concluded that 10% of the students did not decide due to a lack of knowledge, while the majority of students who choose their specialties decided during clinical rotation [3, 22]. doi 10.18502/sjms.v18i1.12863 page 41 sudan journal of medical sciences omer e. a. elbashier et al table 2: gender preferences for each specialty. specialty chosen gender chi-square tests p-value males females surgery n 16 9 0.001 % 64% 36% pediatric n 2 9 % 18% 82% dermatology n 1 9 % 10% 90% orthopedic n 7 1 % 88% 13% otolaryngology n 1 5 % 17% 83% internal medicine n 7 13 % 35% 65% obstetrics and gynecology n 2 13 % 13% 87% ophthalmology n 3 5 % 38% 63% emergency medicine n 0 1 % 0% 100% histopathology n 0 1 % 0% 100% anesthesia n 2 0 % 100% 0% radiology n 0 1 % 0% 100% neurosurgery n 2 0 % 100% 0% psychiatry n 0 1 % 0% 100% cardiac surgery n 0 1 % 0% 100% n, number of students. 4.1. the gender and career choices the results showed a significant association between gender and choice of specialty among medical students. female students were interested more in dermatology (90%), obstetrics and gynecology (87%), otolaryngology (83%), and pediatrics (82%), while males significantly preferred orthopedics (88%) and surgery (64%); table 2. doi 10.18502/sjms.v18i1.12863 page 42 sudan journal of medical sciences omer e. a. elbashier et al this is similar to another study which demonstrated that while males preferred surgery (14.7%), orthopedics (6.4%), and internal medicine (6.4%), females preferred internal medicine (11.9%) and obstetrics and gynecology (11.9%) equally, followed by pediatrics and dermatology (8.2% for both). this is also comparable to another study which has stated that the most chosen specialty by female students were pediatrics (15.6%), obstetrics and gynecology (12%), and psychiatry (5.7%). for males, the most chosen specialty was surgery (46.4%) and medicine (25.3%) [3]. furthermore, in a nigerian study, it was found that male students tended to specialize in obstetrics and gynecology more than female students (18.5% vs 11.9%) [22] compared to 1.9% vs 11.9% in this study. 4.2. factors affecting career choice in this study, personal interest (80%) was the most influential factor that contributed to the students’ career decisions. this result is consistent with other studies, where the majority of participants chose a career based on personal interest [11, 17, 23]. this similarity could be because of the expanded knowledge about medicine and specialties, mainly from the media. lifestyle is another important factor found in 63% of the cases, which is comparable to the 62% found in an indian study [9].similarly, another studyshowed that the quality of life was an important factor determining students; preference: psychiatry was chosen by 64.5%, social medicine and public health by 46.7%, and surgical specialties by 39.9% [24].financial reward was also a considerable factor (52%), as found in other studies [11, 17]. students from low-income countries aspired to a good lifestyle and high income while choosing their specialty. that is also why many young sudanese doctors think about working abroad early in their careers [25]. other factors such as future job opportunities, social factors, and a few years of specialty were: 42%, 30%, and 16% compared to 27.9%, 24.6%, and 27.5% observed in a similar study, respectively [11].the role model was one of the least rated factors (10% compared to 34.8% and 68.5% in other studies [11, 17].this could be because of the large number of students in clinical rounds in comparison to the number of consultants and the short duration of clinical courses at omdurman islamic university. doi 10.18502/sjms.v18i1.12863 page 43 sudan journal of medical sciences omer e. a. elbashier et al 5. conclusion this study showed that the students’ awareness about specialty choices was limited to certain specialties as seen in the literature. the most preferred specialties were surgery, internal medicine, obstetrics and gynecology, and pediatrics for both sexes. females preferred internal medicine, obstetrics and gynecology, pediatrics, and dermatology. while males preferred surgery, orthopedics, and internal medicine. family medicine was not selected by any participant, which was unrelated to the literature. the least chosen specialties were emergency medicine, histopathology, and radiology which were exclusively chosen by females. lack of knowledge was the principal cause of not choosing a future specialty. of the many factors influencing students’ selection of specialties, the most common one was personal interest followed by lifestyle issues and financial reward, and the last one was role modeling. this study and further comprehensive studies might open the doors for filling the gaps in the curricula of medical schools and help achieve the needs of the community. limitations this study is a single-center study and only included the final-year medical students, hence, some of the findings might not represent the career preference of all medical students in the country. acknowledgements none. ethical considerations ethical clearance was obtained from the research ethical committee (rec), faculty of medicine, omdurman islamic university. competing interests none declared. doi 10.18502/sjms.v18i1.12863 page 44 sudan journal of medical sciences omer e. a. elbashier et al availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. references [1] khan, i., bashar, m. a., tiwari, h. k., & reddy, m. m. (2022). perception of medical professionals from tertiary care teaching institutes towards the specialty of community medicine and its specialists amid the covid-19 pandemic. international journal of medicine and public health, 12(2), 71–75. [2] looi, m. k. (2020). covid-19: is a second wave hitting europe? bmj, m4113. [3] mohamed, a. a., khan, w. s., abdelrazig, y. m., elzain, y. i., khalil, h. o., elsayed, o. b., & ibrahim, o. a. (2015). factors considered by undergraduate medical students when selecting specialty of their future careers. pan african medical journal, 20, 102. [4] arshad, s., mccombe, g., carberry, c., harrold, a., & cullen, w. (2020). what factors influence medical students to enter a career in general practice? a scoping review. irish journal of medical science, 190(2), 657–665. [5] goel, s., angeli, f., dhirar, n., singla, n., & ruwaard, d. (2018). what motivates medical students to select medical studies: a systematic literature review. bmc medical education, 18(1), 16. [6] peel, j. k., schlachta, c. m., & alkhamesi, n. a. (2018). a systematic review of the factors affecting choice of surgery as a career. canadian journal of surgery, 61(1), 58–67. [7] yang, y., li, j., wu, x., wang, j., li, w., zhu, y., chen, c., & lin, h. (2019). factors influencing subspecialty choice among medical students: a systematic review and meta-analysis. bmj open, 9(3), e022097. [8] weissman, c., zisk-rony, r. y., schroeder, j. e., weiss, y. g., avidan, a., elchalal, u., & tandeter, h. (2012). medical specialty considerations by medical students early in their clinical experience. israel journal of health policy research, 1(1), 13. [9] petrides, k., & mcmanus, i. (2004). mapping medical careers: questionnaire assessment of career preferences in medical school applicants and final-year students. bmc medical education, 4(1), 18. doi 10.18502/sjms.v18i1.12863 page 45 sudan journal of medical sciences omer e. a. elbashier et al [10] kawamoto, r., ninomiya, d., kasai, y., kusunoki, t., ohtsuka, n., kumagi, t., & abe, m. (2016). gender difference in preference of specialty as a career choice among japanese medical students. bmc medical education, 16(1), 288. [11] kumar, r., & dhaliwal, u. (2011). career choices of undergraduate medical students. the national medical journal of india, 24(3), 166–169. [12] newton, d. a., grayson, m. s., & thompson, l. f. (2005). the variable influence of lifestyle and income on medical students’ career specialty choices: data from two u.s. medical schools, 1998–2004. academic medicine, 80(9), 809–814. [13] dorsey, e. r., jarjoura, d., & rutecki, g. w. (2003). influence of controllable lifestyle on recent trends in specialty choice by us medical students. jama, 290(9), 1173. [14] baldwin, d. c., daugherty, s. r., tsai, r., & scotti, m. j. (2003). a national survey of residents’ self-reported work hours: thinking beyond specialty. academic medicine, 78(11), 1154–1163. [15] shanafelt, t. d., balch, c. m., bechamps, g. j., russell, t., dyrbye, l., satele, d., collicott, p., novotny, p. j., sloan, j., & freischlag, j. a. (2009). burnout and career satisfaction among american surgeons. annals of surgery, 250(3), 463–471. [16] chung, y. c., lin, c. y., huang, c. n., & yang, j. h. (2013). perceptions on gender awareness and considerations in career choices of medical students in a medical school in taiwan. the kaohsiung journal of medical sciences, 29(11), 629–635. [17] huda, n., & yousuf, s. (2006). career preference of final year medical students of ziauddin medical university. education for health: change in learning & practice, 19(3), 345–353. [18] kaderli, r., buser, c., stefenelli, u., & businger, a. (2011). students’ interest in becoming a general surgeon before and after a surgical clerkship in germanspeaking switzerland. swiss medical weekly, 141(3334). [19] o’herrin, j. k., lewis, b. j., rikkers, l. f., & chen, h. (2004). why do students choose careers in surgery? journal of surgical research, 119(2), 124–129. [20] jaffer, u., pennell, a., & musonda, p. (2010). general surgical trainee experiences of mentoring: a uk regional audit. journal of surgical education, 67(1), 19–24. [21] cochran, a., paukert, j. l., scales, e. m., & neumayer, l. a. (2004). how medical students define surgical mentors. the american journal of surgery, 187(6), 698– 701. [22] ossai, e. n., uwakwe, k. a., anyanwagu, u. c., ibiok, n. c., azuogu, b. n., & ekeke, n. (2016). specialty preferences among final year medical students in medical schools of southeast nigeria: need for career guidance. bmc medical education, 16(1), 259. doi 10.18502/sjms.v18i1.12863 page 46 sudan journal of medical sciences omer e. a. elbashier et al [23] azu, o. o., naidu, e., & naidu, j. (2013). choice of speciality amongst first-year medical students in the nelson r. mandela school of medicine, university of kwazulu-natal. african journal of primary health care & family medicine, 5(1), a513. [24] lefevre, j. h., roupret, m., kerneis, s., & karila, l. (2010). career choices of medical students: a national survey of 1780 students. medical education, 44(6), 603–612. [25] abdalla, f. m., omar, m. a., & badr, e. e. (2016). contribution of sudanese medical diaspora to the healthcare delivery system in sudan: exploring options and barriers. human resources for health, 14(s1), 28. doi 10.18502/sjms.v18i1.12863 page 47 introduction methods results stage of career decision the preferred specialties gender and career choices rating of the motivational factors for specialty preference guidance preference among final students discussion the gender and career choices factors affecting career choice conclusion limitations acknowledgements ethical considerations competing interests availability of data and material references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12868 production and hosting by knowledge e review article review of plastic and reconstructive surgery in a general hospital setting: experience from a developing country mohammed yousof bakhiet1,2*, elbadwai hassan-mohamed habiballa3, sami mahmoud assil4, and mohamed daffalla awadalla gismalla2,5 1department of surgery, faculty of medicine, kordofan university, elobeid, sudan 2albaha university, faculty of medicine, saudi arabia 3department of plastic, reconstruction, hand and microsurgery, prince motaib ibn abdelaziz hospital, aljouf, saudi arabia 4department of preventive medicine, tabuk health affairs, saudi arabia 5department of surgery, faculty of medicine, university of gezira, medani, sudan orcid: mohammed bakhiet: https://orcid.org/0000-0001-8128-4583 abstract background: plastic and reconstructive surgery in developing countries and underserved areas are significantly limited and face changes to start a proper service. this study presents a review of plastic surgery services and experiences in a district hospital located in an underserved area. methods: this descriptive, retrospective, hospital-based study was conducted to review patients who presented to the plastic and reconstruction departments from january 2014 to january 2015. all patients seen in the outpatient clinic or emergency departments for plastic surgical consultation or management were included in the study. results: the total of 403 cases fulfilled the inclusion criteria. the emergency surgical operation performed in our unit were distributed in the following descending order; fingertip injury (32%), cut wrist (12.7%), cut extensor tendon (9.9%), gunshot injuries (9.4%), fracture of a small bone of the hand (8.3%), and lower limb trauma. surgery for congenital deformities constituted the most elective operation done in our unit (31.6 %), followed by tumor surgery (18.7%), burn surgery (17.3%), aesthetic surgery procedure (12.2%), and other miscellaneous cases (12.2%). conclusion: this report demonstrates the efficacy of secondary hospital setting to accommodate a large volume of patients during the first year of establishment, and further predicting development needs, staff training, and governmental support. keywords: plastic surgery, reconstruction, underserve area, sub-saharan, developing countries how to cite this article: mohammed yousof bakhiet*, elbadwai hassan-mohamed habiballa, sami mahmoud assil, and mohamed daffalla awadalla gismalla (2023) “review of plastic and reconstructive surgery in a general hospital setting: experience from a developing country,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 84–96. doi 10.18502/sjms.v18i1.12868 page 84 corresponding author: mohammed yousof bakhiet; email: bakhietmoh@yahoo.com received 28 november 2022 accepted 23 december 2022 published 31 march 2023 production and hosting by knowledge e mohammed bakhiet et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammed bakhiet et al 1. introduction plastic surgery is considered a type of surgical specialty that needs variable principles and skills and operates on resolving the congenital or acquired ailments presented in each patient’s organ(s) or system. the reconstructive part of plastic surgery encompasses a variety of procedures that play an important role in managing many patients’ problems and reducing hospital costs by decreasing the length of hospital stay [1, 2]. plastic surgery also involves various specialties including burn, trauma, tumor surgery, aesthetic surgery, cleft surgery, and hand surgery [3]. generally, the common causes of surgical conditions are injuries, malignancies, and congenital anomalies; however, plastic and reconstructive surgeons perform nearly one-half of these emergencies and important procedures [4, 5]. in the united states, there is an increased tendency to establish plastic surgery departments independently, rather than including them with other surgical specialties [6]. in contrast, some developing countries consider plastic surgery as an unnecessary field, and the establishment of a department in publicly funded hospitals was not considered [7]. for instance, there is a significant lack of data from sub-saharan africa regarding plastic surgery practice [8]. however, plastic surgery cases represent about 20% of the surgical workload in rural hospitals [9]. in zambia, for example, there are no plastic surgery units outside of the capital. instead, a mobile service delivers the necessary services to rural areas. this model of mobile service delivery operates based on two to three visits annually [5]. up until the past decade, plastic surgery services in sudan used to be exclusively conducted in khartoum at two centers – the omdurman hospital [10] and the soba hospital [11]. however, after a training specialty was established in sudan’s medical specialization board in 2010, more than five units were established inside khartoum state and the other five units in other states [12]. this study reviews and demonstrates plastic surgery services and experiences in a district hospital and underserved areas. additionally, challenges and obstacles of the hospital setup as well as the development plans have been discussed. 2. materials and methods 2.1. study type this descriptive, retrospective, hospital-based study was conducted to review patients who presented to the plastic and reconstruction departments from january 2014 to january 2015. doi 10.18502/sjms.v18i1.12868 page 85 sudan journal of medical sciences mohammed bakhiet et al 2.2. inclusion and exclusion criteria all patients seen in the outpatient clinic or emergency departments for the purposes of surgical consultation and management were included in the study. 2.3. study area the elobeid teaching hospital is a referral governmental hospital in north kordofan state. the hospital has 600 beds. there are eight internal medicine units, five surgical units, three orthopedic units, and an ent unit, forming the medical and surgical departments. furthermore, the hospital has emergency departments, radiological departments, central laboratories, and operating rooms. 2.4. plastic and reconstruction units this is the first functioning plastic surgery unit in the hospital, headed by a plastic surgeon specialist and two residents. 2.5. perioperative assessments preoperative assessments vary between elective cases and emergency patients. every patient was evaluated by the plastic surgery team and the final decision was taken following that evaluation. additionally, the relevant investigations were requested, and definitive surgery was done urgently. elective cases were also evaluated and enrolled in the treatment program. the type of anesthesia usually depends on the patient’s diagnosis and the type of surgery. it can include block, spinal, or general anesthesia according to the site and the age of the patient. moreover, the surgical technique depends on the type of operation which for a wide range of pathology needs plastic and reconstructive surgery. a tourniquet was used in cases that needed a bloodless field to allow generous dissection and clean anatomy. the principles of the reconstructive ladder were followed to cover the defects according to our setting. these include primary closure, healing by secondary intension skin, graft, local, regional, and distant flap. in cases of cleft lip repair, millard repair was utilized for the procedure, whereas bipedicle mucoperiosteal flaps were used for cleft palate repair. in tumor surgery, we employed a wide local excision with a safety margin followed by immediate reconstruction according to the site and the size of the defect. in the rest of the procedures, the same principles were applied. postoperatively, the doi 10.18502/sjms.v18i1.12868 page 86 sudan journal of medical sciences mohammed bakhiet et al patients were seen in the outpatient clinic every two weeks, one month, two months, and six months. all patients’ dressings and plaster of paris abdications were done in the clinic. in some cases, the patients required further rehabilitation or chemotherapy to achieve satisfactory results. 2.6. data collection a flowchart form was used to collect the data. classification of work, diagnosis, and operations were collected, tabulated, and analyzed. data were analyzed using the statistical package for the social services (spss) version 21.0. 3. results a total of 403 cases were included in the study. patients were aged from 3 months to 85 years with most of the cases being males (83.4%). three hundred and twenty patients required surgical intervention (79.4%), whereas seventy-four (18.4%) patients were treated conservatively. nine patients (2.2%) were referred for further management. out of the 320 surgical operations done, 181 had emergency surgical intervention, whereas 139 had elective operations. the conservative management provided for patients in our series include different procedures such as wound dressings for a burn patient, local wound debridement, and steroid injections for keloid. nine (2.2%) patients were referred for further management. the emergency surgical operation performed in our unit are distributed as follows – fingertip injury (32%), cut wrist (12.7%), cut extensor tendon (9.9%), gunshot injuries (9.4%), fracture in the small bone of the hand (8.3%), lower limb trauma (figure 1) (6.6%), a cut wound in the face (6.6%), peripheral nerve injuries (5%) (figure 2), eyelid injury, and crush hand injuries (each 2.2%). ring avulsion injuries, thumb amputation, and human bites constitute the least common conditions (each 1.7%) (figure 3). all emergency surgical procedures are shown in table 1. table 2 demonstrates the elective surgical procedures. surgery for congenital deformities constituted most elective operations done in our unit (31.6 %), followed by tumor surgery (18.7%), burn surgery cases (17.3) (figure 4), aesthetic surgery procedure (12.2%), and other miscellaneous cases (12.2%). elective hand surgery procedures represent the rest of the elective operations (8%). forty-four patients were operated on for congenital deformities. these anomalies include a cleft lip (25), cleft (6), polydactyly (5), hypospadias (4) hemangioma (3), and spina bifida (figure 5). the oncological surgical procedures were done for 26 patients, doi 10.18502/sjms.v18i1.12868 page 87 sudan journal of medical sciences mohammed bakhiet et al and these were categorized according to the nature of the tumor. the categories were squamous cell carcinoma (8), basal cell carcinoma (6), malignant melanoma (3), and soft tissue sarcoma (4). resection with a safety margin was performed and the reconstruction was done according to the reconstructive ladder based on available options. the site of the squamous cell carcinoma was the scalp in six cases and the lower limb in the rest. the site of the basal cell carcinoma was mainly in the face and resection with local flap reconstruction was done (e.g., midline forehead flap) (figure 6). moreover, we had three cases of advanced breast carcinoma operated on for defect covering using a tram flap in two cases and a split-thickness skin graft for one patient (figure 7). post-burn contracture releases were done in five patients, and they were reconstructed using a skin graft or flap depending on the site. one patient developed a severe form of contracture following a third-degree burn and his family refused to be grafted, they were therefore discharged against medical advice. eleven patients required operative intervention for elective hand surgery conditions, three underwent tendon transfer for low radial nerve injury, two underwent tendon graft for neglected tendon injury, and two underwent mallet finger treatment. four patients underwent surgery for hand mycetoma. aesthetic surgery was performed in 17 cases. the most common operations performed on patients were an abdominoplasty (seven cases), followed by scar revision (five cases) and reduction mammoplasty (four cases). surgery for gynecomastia was done for one patient in table 3. most of the plastic surgical procedures were successful with a reasonable hospital stay time of three to five days after surgery. the overall success rate for the operation was 96%. two flaps failed – one tram flap for breast reconstruction for carcinoma of the breast and another local fasciocutaneous flap for distal leg defect following trauma. five cases of skin grafts had taken graft less than 30% due to infection. moreover, we encountered two cases of wound dehiscence in cleft lip and cleft palate congenital deformity. one patient died following a full-thickness flame burn on the third day. 4. discussion plastic surgery as a specialty started following the first world war when patients with complex wounds presented a problem for management [7]. plastic surgery treated injuries, malignancy, and congenital anomalies, which constitute 66% of measured surgical diseases worldwide in disability-adjusted life years (dalys) [2]. in sudan, plastic surgery services were historically provided only in the capital, and this was due to the lack of plastic surgeons to run them [12]. however, this fact began to doi 10.18502/sjms.v18i1.12868 page 88 sudan journal of medical sciences mohammed bakhiet et al figure 1: hand trauma: a, b, and c show the finger tip degolving injury. d, e, and f prsent the neglected hand burn. figure 2: nerve injury and repair. change after a local program for training plastic surgeons started in 2010. in this study, we reviewed the data of 403 patients who presented to the plastic surgery unit in the elobeid teaching hospital from january 2014 to january 2015 who needed surgical intervention. the goal of documenting this work is to raise awareness on the future doi 10.18502/sjms.v18i1.12868 page 89 sudan journal of medical sciences mohammed bakhiet et al figure 3: skin graft. figure 4: burn management. direction of this surgery, as the concept of plastic surgery in this region is still largely considered a cosmetic luxury. the total number of patients reviewed in this study is the same as that available in international data [1, 7, 8]. a study done by kieran et al. showed the ratio of elective to emergency procedures to be 2:1 [13], whereas in our series the emergency operations were almost equal to elective ones. our data showed a great volume of hand injuries in plastic surgery emergency operations, which is inconsistent with other data from sub-saharan africa [8, 14] .the most common elective operation performed in our unit was surgery for congenital anomalies, with cleft lip and palate representing the majority, followed by burn surgery. however, a study conducted by guzman et al. showed that burn surgery was the most common operation, followed by congenital anomalies [8]. this could be explained by raising awareness in the community about these anomalies and encouraging their early presentation for treatment. nevertheless, we operated on two adult patients for cleft lip. regarding the doi 10.18502/sjms.v18i1.12868 page 90 sudan journal of medical sciences mohammed bakhiet et al figure 5: clif lip repair. figure 6: a, b, and c show squamous cell carcinoma. e, f, g, and h show basal cell carcinoma. reconstructive ladder, we followed in our series, a skin graft was found to be the most common procedure, whereas the v-y advancement flap was the most common flap done for fingertip injuries. we did not use free tissue transfer in our setting due to a lack of facilities. these include a lack of microsurgery-trained personnel and equipment, which makes the management of some cases challenging, so we referred some cases to more well-equipped centers. recently, plastic and reconstructive surgeries have become cost-effective and have had a positive impact on the economy [2]. the total number of plastic surgery cases treated in the first year of establishing the units indicates the need for developing this service in parts of the country where the catchment area is large, the access to the doi 10.18502/sjms.v18i1.12868 page 91 sudan journal of medical sciences mohammed bakhiet et al figure 7: breast canser reconstruction. table 1: types of emergency reconstructive work. classification diagnosis operation/proceduren = 181 percentage (%) hand injuries fingertip injury skin graft + local flap 58 32 cut wrist exploration and repair 23 12.7 cut extensor exploration and repair 18 9.9 nerve injury primary repair 9 5 crush hand skin graft + local flap 4 2.2 ring avulsion injury distant flap 3 1.7 thumb amputation skin graft + local flap 3 1.7 fracture hand bones orif + closed reduction 15 8.3 gunshot gunshot injury skin graft + local flap 17 9.4 lower limb lower limb trauma skin graft + local flap 12 6.6 face cuts over the face direct skin closure 12 6.6 eye lid injury direct skin closure 4 2.2 human bite lip + nose direct closure repair + composite flap 3 1.7 service in the capital is demanding financially, and difficult in terms of traveling. we tried to provide the best service according to the locally available resources. we are reporting this work now to provide information about the services available to patients. however, plastic surgery has been on a downward trend recently in our country and we need to raise the attention of the stallholders in providing health services to this problem. this is particularly true because, in the last five years, five units of plastic surgery service were established and started to provide great work for patients in five cities – medani, nyala, doi 10.18502/sjms.v18i1.12868 page 92 sudan journal of medical sciences mohammed bakhiet et al table 2: types of elective reconstructive work. elective surgery diagnosis procedure operation total n = 139 % burn surgery burn contracture skin graft 19 24 17.3 release 5 congenital anomalies cleft lip and/or palate repair 31 44 31.6 polydactyl excision & primary closure 5 spina bifida excision & direct skin closure 1 hypospadias preputial skin flap 4 hemangioma excision & primary closure 3 tumor surgery scc* skin graft + local flap 8 27 18.7 bcc** skin graft + local flap 6 malignant melanoma excision + graft 5 ca breast mastectomy + myocutaneous flap 4 soft tissue sarcoma excision + graft 4 aesthetic surgery procedure sagging abdomen abdominoplasty 7 17 12.2 scar revision revision 5 macromastia reduction mammoplasty 4 gynecomastia subcutaneous mastectomy 1 neglected hand injury two stage tendon graft 2 11 8 elective hand surgery mallet finger k-wire fixation 2 drop wrist tendon transfer 3 mycetoma hand excision with secondary intension and/or graft 4 miscellaneous mycetoma foot excision and skin graft 2 17 12.2 keloid surgery excision and steroid injection 12 cut achilles tend primary repair 3 ∗scc, squamous cell carcinoma; **bcc, basal cell carcinoma. eldamazin, elobeid, and elgadarif. within two years of this, only two centers were still providing the service. the main reasons for this decline, in our opinion, are inadequate funding, lack of awareness of plastic surgery as an important subspecialty, and lack of strategic planning for medical personnel training in the field. all these factors affect the long-term sustainability of these units to provide the service. future research is needed to address the issue confronting the plastic surgery specialty, particularly the increase in the number of trained plastic surgeons over the last five years. doi 10.18502/sjms.v18i1.12868 page 93 sudan journal of medical sciences mohammed bakhiet et al table 3: types of flap and graft procedure. myocuteneous flap gastrocnemius 2 ld 1 tram 2 fasciocutaneous flap v-y advancement 26 thenar 5 cross finger 6 radial forearm 1 groin 4 first dorsal metacarpal artery 2 medial and lateral malleolar 4 random pattern fasciocutaneous 6 composite 1 scalp 5 median forehead 4 preputial skin flap 4 skin graft stsg 50 ftsg 15 5. conclusion this study reports the experience of a plastic surgeon working in a hospital with no specialized setting for plastic surgery with reasonable success in terms of the immediate outcome. a large volume of patients’ need help in those areas, so upgrading the hospital and establishment with well-equipped units to support plastic surgeons in the peripheries and enhancing their training is crucial to develop the service outside the capital. what is already known in this topic? 1. the way of treating and managing patients 2. difficulties in establishing the new services in developing countries and subsaharan countries what this study adds? 1. this is the first report documenting the work done by a plastic surgeon working in a district hospital in sudan. doi 10.18502/sjms.v18i1.12868 page 94 sudan journal of medical sciences mohammed bakhiet et al 2. it reflects the obstacle facing plastic surgery service in our setting and suggestions for solutions. acknowledgements none. ethical considerations ethical approval was obtained from the elobeid teaching hospital to review patient records and use the data mentioned in the study. additionally, patient consent was obtained for the use of their photographs for publication and educational purposes. competing interests the authors of this study have no financial relationships or conflicts of interest relevant to this article to disclose. availability of data and material data is available with corresponding author upon request. funding none. references [1] al-moghrabi, a., abu shaban, n., ghaith, j. s., & elsous, a. (2019). development of reconstructive surgery services in the gaza strip, palestine. annals of burns and fire disasters, xxxii(1), 17–21. [2] borrelli, m. r. (2018). what is the role of plastic surgery in global health? a review. world journal of plastic surgery, 7(3), 275–282. [3] rogers, a. d., dos passos, g., & hudson, d. a. (2013). the scope of plastic surgery. south african journal of surgery, 51(3), 106–109. doi 10.18502/sjms.v18i1.12868 page 95 sudan journal of medical sciences mohammed bakhiet et al [4] ibrahim, a. (2014). sub-specialization in plastic surgery in sub-saharan africa: capacities, gaps and opportunities. pan african medical journal, 19, 13. [5] jovic, g., corlew, d. s., & bowman, k. g. (2012). plastic and reconstructive surgery in zambia: epidemiology of 16 years of practice. world journal of surgery, 36(2), 241–246. [6] loewenstein, s. n., duquette, s., valsangkar, n., avula, u., lad, n., socas, j., flores r. l., sood, r., & koniaris, l. g. (2017). does the organization of plastic surgery units into independent departments affect academic productivity? plastic and reconstructive surgery, 104(5), 1059–1064. [7] mishra, b., koirala, r., tripathi, n., shrestha, k. r., adhikary, b., & shah, s. (2011). plastic surgery-myths and realities in developing countries: experience from eastern nepal. plastic surgery international, 2011, 870902. [8] guzman, k. j., gemo, n., martins, d. b., santos, p., deugarte, d. a., ademo, f., kulber, d., & issufo, c. (2018). current challenges of plastic surgical care in sub-saharan africa (maputo, mozambique). plastic and reconstructive surgery – global open, 6(8), e1893. [9] hodges, s., wilson, j., & hodges, a. (2009). plastic and reconstructive surgery in uganda–10 years experience. paediatric anaesthesia, 19(1), 12–18. [10] hamza, a. a., abdalrahim, h. m., idris, s. a., & ahmed, o. m. (2013). evaluating the operative notes of patients undergoing surgery at omdurman teaching hospital, sudan. journal of applied medical sciences, 1(6), 668–672. [11] abdulhadi yagoub edries mahamoud, s. m. m. (2014). indications and outcomes of abdominoplasty in sudanese patients. global journal of human-social science, 14(2). [12] mahmoud, s. m. (2014). the sudanese society of plastic and reconstructive surgeons 6th annual conference summary 28–30th of march 2014. sudan medical journal, 50(1), 53–54. [13] kieran, i., fitzgerald, e., murphy, s., & o’shaughnessy, m. (2013). changes in the workload composition in a plastic surgery unit over a 12 year period. irish journal of medical science, 182(4), 657–662. [14] abebe, m. w. (2019). common causes and types of hand injuries and their pattern of occurrence in yekatit 12 hospital, addis ababa, ethiopia. the pan african medical journal, 33, 142. doi 10.18502/sjms.v18i1.12868 page 96 introduction materials and methods study type inclusion and exclusion criteria study area plastic and reconstruction units perioperative assessments data collection results discussion conclusion what is already known in this topic? what this study adds? acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13600 production and hosting by knowledge e research article attitudes of patients attending omdurman teaching hospital vct center, sudan toward hiv/aids voluntary counseling and testing services maha hamed mohamed ali1, osman babiker osman2, adam dawria1, amna hamid imam babeker1, yahya hussein ahmed abdalla3, mohammed a. shanawaz2, nahid elfaki4, salma mohammed gomaa doalbet5, and waled am ahmed6,7 1public health department, faculty of applied medical sciences, king khalid university, saudi arabia 2public health department, faculty of applied medical sciences, al-baha university, saudi arabia 3nursing college, najran university, najran, saudi arabia 4community health and psychiatric nursing department, college of nursing, najran university, saudi arabia 5nursing department, faculty of applied medical sciences, hafr albaten university, hafr abaten, saudi arabia 6nursing department, faculty of applied medical sciences, al-baha university, saudi arabia 7community medicine department, faculty of medicine, postgraduate studies, al-saeeda university, sana’a, yemen orcid: maha hamed mohamed ali: https://orcid.org/0000-0001-9902-4747 osman babiker osman: https://orcid.org/0000-0002-1762-0981 adam dawria: https://orcid.org/0000-0003-1597-1160 amna hamid imam babeker: https://orcid.org/0000-0002-6631-4593 yahya hussein ahmed abdalla: https://orcid.org/0000-0002-9805-4669 mohammed a. shanawaz: https://orcid.org/0000-0001-5253-5910 nahid elfaki: https://orcid.org/0000-0002-5624-4675 salma mohammed gomaa doalbet: https://orcid.org/0009-0007-9522-921x waled am ahmed: https://orcid.org/0000-0002-8023-1583 abstract background: despite the availability of hiv/aids voluntary counselling and testing services in omdurman teaching hospital, the level of uptake remains low, and the prevalence of hiv/aids in sudan is still high. this situation suggests that there may be some underlying factors, such as patients’ attitudes toward the services provided, that are affecting their willingness to access them. therefore, this study aimed to assess the attitude of patients attending hiv/aids voluntary counselling and testing services in omdurman teaching hospital, sudan. methods: a descriptive hospital-based study was conducted at omdurman teaching hospital, sudan. all patients attending hiv/aids counseling and voluntary services center were invited to participate in this study, and of the 200 invited, 150 patients participated with a response rate of 75%. data were collected using a structured interview questionnaire and then analyzed by spss (version 23). how to cite this article: maha hamed mohamed ali, osman babiker osman, adam dawria, amna hamid imam babeker, yahya hussein ahmed abdalla, mohammed a. shanawaz, nahid elfaki, salma mohammed gomaa doalbet, and waled am ahmed (2023) “attitudes of patients attending omdurman teaching hospital vct center, sudan toward hiv/aids voluntary counseling and testing services,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 153–164. doi 10.18502/sjms.v18i2.13600 page 153 corresponding author: waled am ahmed; email: weliameen1980@hotmail.com received 22 september 2022 accepted 24 february 2023 published 30 june 2023 production and hosting by knowledge e maha hamed mohamed ali et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences maha hamed mohamed ali et al abstract results: the findings revealed that many patients (92%) have a positive attitude toward hiv voluntary counselling and testing and believed that the shared information is informative and influential. it was also observed that 80% of the patients who received counselling had lower levels of social and psychological stress and stigma. conclusion: the study highlighted the positive attitude of patients to utilize hiv/aids voluntary counselling and testing services which reduces the social and psychological stresses and stigma among hiv patients. females and muslim patients had a positive attitude. keywords: hiv, voluntary counselling and testing, stigma, psychological stresses, sudan 1. introduction hiv/aids is considered one of the major health problems globally, mainly affecting the population of poor developing countries such as african societies. the global hiv/aids epidemic report, hiv/aids is one of the world’s most serious public health problems. the 2020 data shows that about 37.6 million people were infected with hiv worldwide. among them, 35.9 million were adults and 1.7 million children [1]. the highest endemic regions with hiv were reported in lowand middle-income countries; there were 20.6 million (55%) in eastern and southern africa, 4.7 million (13%) in western and central africa, 5.7 million (15%) in asia and the pacific, and 2.2 million (6%) in western and central europe and north america in 2020 [1]. according to the literature, voluntary counselling and testing as a process of enabling individuals to make informed decisions, voluntary hiv testing, in combination with preand posttest counselling, has become increasingly important in regional and international preventive efforts [2]. the vct counselling process consists of pretest, posttest, and follow-up counselling. it is suitable for individuals, couples, families, and children and can be adapted to the needs and capacities of the settings in which it is to be delivered [3, 4]. voluntary counseling and testing (vct) services is one of the most effective strategies for the prevention and control of hiv/aids, which was first established in sudan in 2004 by snap [5]. previous studies on patients’ knowledge and attitude toward vct in sudan reported that the studies conducted on women at reproductive age which showed that they were knowledgeable on the transmission and willing to uptake the test [6, 7]. the content and approach of the vct counselling process may vary considerably for and with various groups, such as counselling for young people, drug users, or sex doi 10.18502/sjms.v18i2.13600 page 154 sudan journal of medical sciences maha hamed mohamed ali et al workers or even the education level of targeted groups [8]. while it usually involves at least two sessions (pretest and posttest counselling), more sessions can be offered before or after the test, or during the time the client is waiting for test results [9, 10]. pretest hiv counselling should be offered before taking an hiv test; and the counsellor should prepare the client for the test by explaining what an hiv test is, as well as by correcting misinformation about hiv/aids. some of the information about hiv and vct can be provided to groups [11, 12]. it is important that everyone requesting vct has access to individual counselling before being tested. informed consent from the person being tested is usually a minimum ethical requirement before an hiv test [13]. posttest vct counselling should be offered to all patients with the main goal of the session being to help clients understand their test results and initiate adaptation to their seropositive or negative status [14, 15]. the determinants reported among sudanese communities were varied toward the obstacle to uptake vct services; among university students, however, they were willing to uptake the test, the influencing factors were not considering themselves a vulnerable group or not knowing the vct or having no knowledge about the test or being afraid of being positive [16]. despite the availability of vct services in omdurman teaching hospital, the level of its uptake is still low, and the prevalence of hiv/aids in sudan is high. this situation suggests that there may be some underlying factors, such as patients’ attitudes toward the services provided that are affecting their willingness to access them. to identify these factors, there is a need to assess the attitudes of patients attending hiv/aids voluntary counselling and testing services in omdurman teaching hospital. this information could be used to improve the quality and accessibility of the services, increase patient uptake, and reduce the burden of hiv/aids in sudan. 2. materials and methods a descriptive hospital-based study was conducted at omdurman teaching hospital and included patients attending hiv/aids counseling and voluntary services center at the omdurman teaching hospital. a non-probability convenient sample was used to collect data from the patients. all patients attending hiv/aids counseling and voluntary services center during the data collection period (january to april 2022) were invited to participate in the study. a total of 150 patients responded and agreed to participate, with a response rate of doi 10.18502/sjms.v18i2.13600 page 155 sudan journal of medical sciences maha hamed mohamed ali et al 75%. all included patients were adult, males and females, resided in khartoum, and had agreed to participate. the dependent variable was the attitude of patients toward hiv/aids vct services at the center, while the independent variables include patients’ demographic characteristics such as age, sex, education, marital status, and occupation. data were collected from patients using an interview questionnaire including a series of questions prepared by the researchers. vct for hiv involved two counselling sessions: one prior to taking the test known as ”pretest counselling” among 88% of the patients and one following the hiv test when the results were given, often referred to as ”posttest counselling” among 96% of the patients. the questionnaire was well designed to include all needed variables, and it was pretested on a small scale of targets before being implemented on a larger scale; such techniques were adopted to ensure that the questionnaire is valid and reliable. validity is the degree to which an instrument measures what it is intended to measure, and reliability refers to the degree of consistency or accuracy with which an instrument measures the attribute it is designed to measure [17, 18]. for this questionnaire, 15 patients from another vct center were included and its findings showed that an adequate internal consistency of reliability was obtained; the cronbach’s alpha was at the acceptable level of 0.84. the patients received questionnaire and explanation about the aim and process of the study, and were assured that their data will be kept confidential. data was analyzed using the spss program version 23. the tables were used to represent the findings as frequency and percentage and then an association between patients’ characteristics and the attitudes toward vct services for hiv. p-value less than or equal to 0.05 was taken as a cut-off value for significance. odds ratio and 95% confidence interval was also constructed along with the corresponding p-value. 3. results the demographic information obtained from the hiv-infected patients showed that 46% of them were male while 54% were female, and that they were aged between 15 and 34 years (56%). moreover, 16% of them were illiterate, 62% were in school, and 22% were studying in universities. additionally, 56% of them were married and only 14% were employed (table 1). table 2 shows that the counseling sessions were attended by all patients, with 36% attending before the tests and 64% attending after the tests. additionally, 70% of patients doi 10.18502/sjms.v18i2.13600 page 156 sudan journal of medical sciences maha hamed mohamed ali et al received their results directly from physicians, while 76% were tested at the vct center and 24% were tested at hospitals and then referred for counseling. table 3 reflects the attitude of hiv-infected patients toward vct’s services: 92% of the patients considered vcts services as secure and confidential, 70% got the required information from the vct center, 82% reported that counselors were supportive, and 88% felt stigma free post counseling. however, 74% of the patients reported that they felt troubled after being informed of the results. the majority of patients (72.67%) decided to attend subsequent vct sessions. table 3 also shows that the overall positive attitude of hiv patients was 73.7%. table 4 presents the relationship between patients’ characteristics and the attitudes toward vct for hiv. it shows the significant associations between education (literate patients), marital status (married), occupation (employed), and religion (muslim) and patients’ attitude. table 1: demographic variables of patients attending preand post-vct services at omdurman teaching hospital, sudan. variables frequency percentage sex males 69 46% females 81 54% age (yr) 15–24 24 16% 25–34 60 40% 35–44 36 24% >45 30 20% education illiterate 24 16% primary 51 34% secondary 42 28% university 33 22% marital status married 84 56% single 33 22% widowed 18 12% divorced 15 10% occupation housewife 57 38% free business 42 28% student 24 16% skilled labor 6 4% employee 21 14% religion muslim 112 74.67% non-muslim 38 25.33% doi 10.18502/sjms.v18i2.13600 page 157 sudan journal of medical sciences maha hamed mohamed ali et al table 2: diagnosis site distribution by healthcare in khartoum, sudan. diagnosis site health cadre vct center hospital* total freq. % freq. % freq. % physician 90 60 15 30 105 70.0 councilor 24 16 21 42 45 30.0 total 114 76.0 36 24.0 150 100.0 ∗in the omdurman teaching hospital and not in the vct center table 3: patients’ response toward vct services at omdurman teaching hospital, sudan. response items positive response freq % confidentiality and privacy were secured 138 92% counselling sessions were informative and sufficient 105 70% counselors were supportive 123 82% counselling sessions help families to support and accept the patient 132 88% patient attended the post testing counselling sessions 96 64% patient was worried, scared, and in doubt when informed of having hiv 111 74% keen to continue attending the counselling sessions 109 72.67% overall positive attitude of infected patients toward vcts mean = 73.7% ± 3.4 table 4: patients’ characteristics associated with the attitude toward vct center at omdurman teaching hospital, sudan. variables univariate multivariate or 95%ci p-value or 95%ci p-value gender females 1.1 0.8–1.4 0.53 0.4 0.2–1.1 0.07 age (yr) 15–24 0.9 0.7–1.5 0.32 0.7 0.5–1.2 0.08 education literate 2.3 1.3–3.6 0.03 1.4 1.1–1.8 0.01 marital status married 1.6 0.9–2.2 0.06 1.3 0.9–1.9 0.02 occupation employee 1.9 1.5–2.6 0.02 2.5 1.9–2.9 0.01 religion muslim 2.5 1.8–3.7 0.01 3.1 2.7–4.2 0.01 *significant; or, odds ratio; ci, confidence interval 4. discussion the study showed that patients infected with hiv were aged between 15 and 44 years, more than half were females of child-bearing age, and most of them were literate. similar findings were reported from malawi in 2000 where the age of 76% participants were between 15 and 29 years and females were infected more than males [19]. in this study, 36% of the patients attending vct centers received pre-counseling services, higher than the rate from malawian study [19] where only 9.4% of patients doi 10.18502/sjms.v18i2.13600 page 158 sudan journal of medical sciences maha hamed mohamed ali et al coming before the test for counseling, this wide contrast could be attributed to variations of reasons described in the literature for getting tested for hiv as response to signs of illness, when individuals feel at risk or vulnerable to hiv infection [20]. these reasons are of course to a large extent governed by the seroprevalence that entirely differ in the two countries, where the seroprevalence in sudan was estimated as 1.6% in 2003, compared to 14–16% in the same years in malawi, that fear and stigma from the test increases with increased risk of contracting the virus [21, 22]. the vct for hiv usually involves two counselling sessions: one prior to taking the test known as ”pretest counselling” and one following the hiv test when the results are given, often referred to as ”posttest counselling” [23]. in our study, the results showed that 88% of patients feel stigma-free post-counseling and enhanced the social relations with their families and community members. several reports and published articles about vct in neighbor countries (kenya, tanzania, uganda, and zambia) showed wide variations in responses of patients toward these services [23–25]; similar findings were reported in a study carried out in zambia [26]. patients infected with hiv/aids are socially neglected as they suffer from stigma and psychological stresses, as shown in one study conducted in china since about 90% had negative attitude toward hiv-infected patients [27]. according to the study, 73.7% of hiv patients displayed a positive attitude, which suggests a possible decrease in the prevalence of hiv/aids in sudan in the near future. these results are consistent with a previous study conducted in sudan in 2007, where 72.8% of pregnant women believed that vct was important [7], and also similar to another study conducted at one urban neighborhood of lusaka, where counselling and the test results and exhibited positive attitudes toward the role of the post-counseling received in reducing the negative expected responses beside encourage them to take medical care [28]. similar findings were also reported by a study in nigeria which showed the acceptance of vct services among pregnant women [29]. despite the positive attitude toward vct services for hiv, the utilization rate for those services in africa is still low as reported form zambia since 37% are ready to utilize such services and only 3.6% actually utilized such services [30, 31]. the univariate and multivariate associations between the patients’ characteristics and attitude level were statistically significant between education (literate patients); marital status (married patients); occupation (employed patients); and the religion (muslim patients) and the patients’ attitude toward vct services. these findings are similar to the finding of one study conducted in sudan by mahmoud et al. [7], which showed doi 10.18502/sjms.v18i2.13600 page 159 sudan journal of medical sciences maha hamed mohamed ali et al that there were significant associations between age, religion, and patients’ knowledge and attitude toward hiv/aids and their willingness to uptake vct services [7]. although, the study is unique for sudanese people to express their attitude toward testing for culturally sensitive topic, it has several limitations: (1) the study was conducted in omdurman teaching hospital vct center, which may not be an appropriate representative of the entire population of patients in sudan. this could limit the generalizability of the study findings to other settings or populations. (2) it was conducted in a country where secondary data are incomplete or may not always be available. (3) the questionnaire used in the study may not have captured all relevant factors that influence attitudes toward vct services, such as cultural beliefs, religious practices, or social norms. this could limit the ability to fully understand the complexity of attitudes toward vct services in sudan. (4) finally, a social desirability bias is suspected as participants may have provided socially desirable responses to the questionnaire rather than their true attitudes toward hiv/aids vct services. this could be due to fear of being stigmatized or judged by others, or a desire to please the researchers. 5. conclusion the study concludes that the positive attitude of hiv patients to utilize hiv voluntary counselling and testing services reduces the social and psychological stresses and stigma among hiv patients. females and muslims significantly reflected more positive attitudes. the provision of vct services using innovative approaches to enhance utilization is essential in order to overcome the hiv/aids stigma and psychological stresses in sudan. acknowledgements the authors are grateful to the study participants who voluntarily took part in the study. we wish to acknowledge the vct center at the omdurman teaching hospital for allowing conducting this study. ethical considerations a verbal consent and agreement was obtained from participants prior to the beginning of the study, which was obtained before collecting the data by explaining the purpose of the study and confidentiality of collected data to the participants. then they were given doi 10.18502/sjms.v18i2.13600 page 160 sudan journal of medical sciences maha hamed mohamed ali et al the right to decide whether to participate or not and asked to provide verbal agreement, this is because some participants are illiterate and could not provide written consent. the participation and answering the interview questionnaire was considered a verbal agreement to participate in the study. so, all participants provided verbal agreement before completing the interview questionnaire. the study was approved from the ethical committee of the nursing college, international university of africa, sudan. the committee approved the using of verbal process as described in the submitted proposal. competing interests the authors declare that the manuscript is the product of a dissertation for an academic degree program. the authors also declare that there are no any conflict of interest related to this manuscript. availability of data and materials the data are available upon request, please contact the corresponding author for data. funding no funding was received to conduct this study form any agency nor institution. references [1] hiv.gov global statistics. 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(2008). voluntary hiv counselling and testing among men in rural western uganda: implications for hiv prevention. bmc public health, 8(1), 263. https://doi.org/10.1186/1471-2458-8-263 doi 10.18502/sjms.v18i2.13600 page 164 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13599 production and hosting by knowledge e research article climate change as a significant factor to the aggravation of coronary artery disease among elderly: a basis for emphasizing community-based self-care measures eladio martin s. gumabay, karen mae s. alcantara, jaylord g. ugaddan, and dexter c. centeno university of saint louis tuguegarao, philippines orcid: eladio martin s. gumabay: https://orcid.org/0000-0002-2440-2130 karen mae s. alcantara: https://orcid.org/0000-0002-5746-555x jaylord g. ugaddan: https://orcid.org/0000-0002-9907-1567 dexter c. centeno: https://orcid.org/0009-0009-3600-463x abstract background: this research study explored the lived experience of the elderly with coronary artery disease (cad) relevant to the effects of climate change as a basis for enhanced and strengthened community-based self-care measures. methods: a descriptive phenomenological design was employed in the study. consented face-to-face interview sessions with audio recordings were conducted to gather rich information. the data collected from 28 participants were analyzed using the modified stevick-colaizzi-keen method. results: three themes emerged upon a thorough analysis of the results: (1) elucidating the elderly’s perception of climate change; (2) unveiling the effects of climate change on cad; and (3) managing health-related behaviors in a changing environment. evidence has revealed that climate change causes and aggravates this disease. cad manifestations worsen when an elderly person is exposed to sudden changes in weather conditions, where various signs and symptoms are evident. conclusion: in conclusion, elderly clients have an awareness of the concept of climate change and its physiologic effects on cad; hence, employment of practical self-care measures and practices in managing manifestations, significantly helps them adapt and cope with the adverse effects climate change brings. keywords: climate change, coronary artery disease, elderly, phenomenology, adaptation, coping, geriatric nursing, self-care, community-based interventions 1. introduction communities live in an aggressive competitive relationship with nature. the persistent quest for advancement, relief, and refuge has intensified the stress on the environment. as a result, the life-supporting environment has been forced to change more swiftly than ever. the consequences of this have brought problematic issues arising around how to cite this article: eladio martin s. gumabay, karen mae s. alcantara, jaylord g. ugaddan, and dexter c. centeno (2023) “climate change as a significant factor to the aggravation of coronary artery disease among elderly: a basis for emphasizing community-based self-care measures,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 139–152. doi 10.18502/sjms.v18i2.13599 page 139 corresponding author: eladio martin s. gumabay; email: em_gumabay@yahoo.com received 8 january 2023 accepted 13 january 2023 published 30 june 2023 production and hosting by knowledge e eladio martin s. gumabay et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences eladio martin s. gumabay et al. the globe; eventually resulting in an environmental crisis and ultimately affecting the human population and life-sustaining schemes. climate change steers the wheel toward disease migration, exacerbating present and developing health concerns; thus, putting the health status of the people at risk. literature contends that a change in environmental temperature aggravates cardiovascular diseases, such as coronary artery disease (cad) [1, 2]. climate change plays a crucial role in how the general population scrutinizes nature as well as the changes happening in it [3]. this change persists as time evolves and is deemed to be a major catastrophe of the new millennium [4, 5]. it was further asserted that climate change covers a multitude of climatic variations as a product of extensive emission of greenhouse gases [6]. this resultant alteration is primarily relevant to human activities [1, 6, 7]. cad is a complex disorder that involves a significant interaction of inherent and environmental factors. even though there are advanced and modernized ways of treatment to manage this disease, it is still recognized as the world’s leading cause of mortality among adults and the elderly [2, 8]. the effects of alternating weather conditions and extremely high or low temperatures on health are well known, and cardiac effects are a major component [1]. managing the health effects of temperature in response to climate change is a global public challenge [9]. elderly clients both with and without cardiovascular conditions are vulnerable due to immune system deterioration. furthermore, the researchers posit that people, especially the elderly are not often aware of the negative impacts of climate change on their health and certain existing diseases, while they frequently go unmindful that the latter is a significant factor in the development or aggravation of cad. there is little evidence of elderly awareness and perception of climate change; hence, they and the public remain ambivalent regarding this environmental issue and its effects on human health [4, 5]. the authors also added that this can be a result of individual differences (e.g., political orientation, science, educational attainment, and social media). increasing public awareness of the risks posed by climate change is an important predictor and catalyzes to attain adaptation. once the common manifestations are identified through the implementation of community-based strategies, it will safeguard the health of the public, more especially, the elderly by mitigating the negative effects of climate change. on that note, the theory of sister callista roy’s extended adaptation model in the community is employed by the elderly [10]. the framework explicates that human is biopsychosocial and is enforced to adapt stimuli from the external environment as a compensatory process to preserve the physiologic function of the human system. in order to achieve this, healthcare providers doi 10.18502/sjms.v18i2.13599 page 140 sudan journal of medical sciences eladio martin s. gumabay et al. should utilize measures to empower adaptive and coping mechanisms through health promotion and disease prevention to enhance individual functioning. with the foregoing explications, the researchers explored the lived experiences of the elderly on climate change, which is considered as a significant risk factor in the aggravation of coronary artery disease. through this study, the elderly and the community would gain awareness and improve practices to manage and cope with the aggravated signs and symptoms of cad during climate change; thus, also advancing geriatric nursing knowledge. 2. methods 2.1. research design the research study is limited to exploring and describing the perceptions of elderly clients on the effects of extreme temperature changes in the environment as a significant factor in the aggravation of cad. hence, the researchers employed a descriptive phenomenological design to elicit information on the lived experiences of the elderly. 2.2. locale of the study this research study was conducted in the province of cagayan situated in northern philippines. 2.3. study participants the number of samples needed in qualitative research depends on data saturation. the researchers used purposive sampling to elicit information [11, 12]. eligibility of the participants were based on the following criteria: (1) elderly diagnosed with cad for at least 6 months since the time data gathering was conducted; (2) elderly aging from 60-85 years old; (3) elderly who could comprehend and articulate easily in their local dialect as well as filipino and/or english; and, (4) who manifest interest in partaking in the study. the researchers reached data saturation with the 16𝑡ℎ respondent; however, they continued gathering data up to the 28𝑡ℎ participant to draw out more information to enrich the co-creation of data. doi 10.18502/sjms.v18i2.13599 page 141 sudan journal of medical sciences eladio martin s. gumabay et al. 2.4. data collection procedure before gathering the data, the researchers sought necessary permits and consent and each participant was given an informed consent form after explaining the purpose of the study. the researchers explored the lived experiences of the participants through faceto-face in-depth interviews along with consented audio recordings. semi-structured open-ended guide questions were asked to obtain the necessary information. field notes were jotted down during each interview session, the latter lasted an average of 34 min. likewise, all of them were notified about the confidentiality of the data and their right to any time withdraw it. 2.5. data analysis data were analyzed utilizing the stevick-colaizzi-keen method [13, 14]. the authors emphasized the importance of spending sufficient time with the participants to obtain a complete understanding of the situation being studied. completeness of data will be attained by using different perspectives of data gathering. in this study, the researchers conducted interview sessions along with jotting down significant cues. member checking was performed in order to validate the accuracy and completeness of data. constant communication with participants was done to ensure that they are updated on the analysis phase of the research process. it is worth noting that the informants’ verbalizations were carefully translated into the english language with the help of two english professors. original transcripts were a combination of either filipino and/or the participants’ local dialect. 3. results twenty-eight participants participated. upon in-depth analysis, the researchers yielded the following themes: (1) elucidating the individual’s perception on climate change; (2) unveiling the cardiovascular effects of climate change; and (3) managing health-related behaviors in a changing environment. theme 1: elucidating the elderly’s perception of climate change. 27 of the participants stated that they have previously encountered the term climate change and global warming. in addition to that some also mentioned and included the perceived causes and factors that contribute to climate change. doi 10.18502/sjms.v18i2.13599 page 142 sudan journal of medical sciences eladio martin s. gumabay et al. 1001: [of course. that is characterized by sudden changes in weather conditions from warm to cold temperatures. it’s somehow unpredictable.] 1003: [yes. i’ve heard it before. that it is characterized by a sudden shifting of climate from warm to cold. one presumed cause of climate change is burning of plastic material.] 1006: [yes. this is characterized by the sudden shifting of warm to cold climate. the latter causes cough and colds.] 1007: [yes, i’ve heard that already. it’s the change in our weather conditions due to pollution.] 1009: [okay. yes. climate change or global warming is the alteration of weather conditions and environmental temperature. it greatly affects our body.] 1011: [yes. that is characterized by the sudden change in climate that may bring certain diseases.] 1016: [yes. climate change has a very broad meaning. it means, there are a lot of factors that contribute to climate change such as destruction of ozone layers due to nuclear bomb testing. it gets hot when it is hot and chilly during the cold season. it gets warmer and warmer during the summer season, to extremes.] theme 2: unveiling the effects of climate change on cad. when asked if changes in the weather condition impose negative effects on human health, 26 participants commonly shared various physiologic manifestations like difficulty of breathing, easy fatigability, palpitations, fainting, dizziness, headache, and chest pain. 1002: [before i was hospitalized, i experience worse difficulty of breathing because of hot and cold weather conditions.] 1003: [warm and cold temperatures have a significant effect on the condition of my heart. during the warm season, there is an unexplainable feeling of intense warmth. i also experience palpitation and i get tired easily.] 1006: [warm and cold seasons influence my cardiac status. say for an instance, during extremely hot weather you will get tired easily, whereas during the cold season you will suffer from cough and colds.] 1007: [of course! during the warm season, i experience easy fatigability, headache, and palpitation. when the weather is too cold my body freezes. i think the cold and warm season has the same effect.] 1008: [both warm and cold climates affect the condition of the heart. i experience more difficulty of breathing, palpitation, easy fatigability, and sweating of both hands. during cold weather, i usually shiver more and sometimes have difficulty in breathing.] doi 10.18502/sjms.v18i2.13599 page 143 sudan journal of medical sciences eladio martin s. gumabay et al. 1022: [there is an effect on my cardiac status. when the weather is cold, i experience palpitations. during the warm season, i also suffer from severe palpitations, headache, dizziness, easy fatigability, and nape pain. for me it is more favorable to have cold rather than warm weather because the latter imposes a worse effect like persistent hypertension, more nape pain, palpitations, and increased frequency of headache.] theme 3: managing health-related behaviors in a changing environment. the participants gave numerous answers on how they should manage climate change. twentythree mentioned that the following self-care measures combat the effects of warm weather conditions: (1) taking a bath two or more times per day, especially during the warm season to release body heat; (2) staying indoors to avoid prolonged exposure to sunlight; (3) drinking plenty of water as long as the body can tolerate and if there is no underlying contraindication; (4) staying under the shade of trees; (5) use of an electric fan in rotating mode; (6) using light clothing during warm weather while using sweater and socks during cold weather; and, (7) alternating activities of daily living and rest periods. on the other hand, practices involved in managing the effects of cold weather conditions according to all participants include: (1) staying indoors to avoid prolonged exposure to the cold wind breeze; (2) drinking warm water; (3) regular exercise; (4) use jackets, pants, and socks; and (5) oil application on the body. 1002: [every morning upon waking up, refrain from going outside so that you do not get sick because of the fog. during warm weather conditions, you should also avoid going out to prevent too much heat exposure whereas during cold season they are advised to exercise such as jogging or walking.] 1003: [during hot days, i make sure i get enough ventilation and take a bath maybe once or twice. when the weather is extremely cold, if possible, you need to take a warm bath, drink warm water and avoid alcoholic beverages.] 1005: [i usually drink water coming from earthenware if the weather is hot.] 1006: [if it is cold, refrain from going out. just like me, i put on socks, jacket, pants or even a hood during this kind of weather. you could also apply oil. on the other hand, if it is warm, you may take a bath a couple of times daily. they should also wear light clothing. we also avoid going out beyond 11 o’clock. if you are a farmer, just like us, we often go to the field early in the morning most probably at 3:30-4:00 a.m., and then we will go home at 9:30 in the evening.] 1009: [we need to have a regular bath and rest during the hot season. regular consultations and check-ups with the doctor are also very important. elderly people are recommended to stay inside their houses or under the trees to get fresh air. they may doi 10.18502/sjms.v18i2.13599 page 144 sudan journal of medical sciences eladio martin s. gumabay et al. also use electric fans if they wish to. during the cold season, we need to wear thick sweaters, hoods, and socks, and may also use heaters to make the body warm. they should also refrain from going outside their houses during this time.] 1016: [during the hot season, they must avoid going outside. they must stay in places having good ventilation or they can stay under the trees. they should also avoid overworking and staying in the field during this time. when the cold season strikes, they must employ remedies to make their body warm such as wearing layers of clothing, hoods, socks, and making a bonfire.] 1028: [i would suggest people with cardiovascular malfunctioning to carefully take good care of themselves by eating fresh fruits during warm weather in which they can be getting vitamins and drinking lots of water. likewise, it is not advisable for them to be tired, so rest is very important. during cold weather, it is safe to keep the body warm and also to take supplementary vitamins to keep the body going. hot milk or hot chocolate will do so the body will be healthy and strong.] climate change is a multi-faceted environmental issue. this dilemma brings catastrophic events and implications, especially to human health and well-being. as such, it poses a great risk to the vulnerable population, particularly the elderly. awareness, therefore, is essential in order to address this issue by employing adaptive self-care measures. awareness of the complexities of climate change results in recognition of its potential effects. to manage this, people tend to implement and formulate effective measures to adapt to it. in return, these interventions will prevent the worsening of pre-existing medical conditions and future occurrences of disease such as in the case of coronary artery disease (cad). on the latter note, creating awareness will greatly aid elderly clients to be cognizant with the impacts of climate change on health, specifically the cardiovascular system. hence, conscientious planning, organization, and application of adaptive measures will be employed as a turning point to improve and strengthen the prevention of cad aggravation. 4. discussion climate change is undeniably the biggest environmental problem that the world faces today. it is believed to be the root cause of various catastrophic phenomena that were documented. it affects the public and posits negative impressions on health in numerous ways. it is presumed to worsen and beget devastating, enormous, and dreadful consequences in the future unless efforts are made to control its effects [1618]. doi 10.18502/sjms.v18i2.13599 page 145 sudan journal of medical sciences eladio martin s. gumabay et al. salience is vital in addressing the adverse effects of climate change [19]. the result of this research study shows that most of the participants positively claimed that they have previous knowledge on climate change. this evidence is consistent with previous research that there is an increasing level of public awareness when it comes to observing and perceiving either vast or little changes in the weather condition [1, 6, 20]. this is predominantly due to the widespread use of electronic media such as television, radio, the internet, and other telecommunication devices. in this research study, participants identified several contributory factors of climate change like burning of plastic material and pollution [5, 18, 21]. climate change has a strong correlation with the declining state of wellness among individuals. it imposes significant threats and aggravates predefined health issues [1, 18]. the incidence of cardiovascular diseases such as cad has largely escalated due to varying weather conditions. the rising number of environmental-related issues affects every individual. similar to the result of this research study, the most vulnerable population includes the elderly with or without pre-existing cardiovascular medical conditions [4, 22]. literature illustrated several reasons for this: (1) weakened physiologic ability to maintain thermoregulation; and (2) decreased capacity to adapt to the situation and the environment [6, 9, 20]. anent this, the study has considered the age of the participants as a significant variable that greatly affects their vulnerability. also, participants who were exposed to heavy workloads often experience more pronounced effects compared to those with minimal activity. increased activity imposes greater demand on the heart; thus, limiting its capability to function normally or cope with demands [1]. lastly, all the participants were living in the urban area, thereby predisposing them to acquire climate changerelated problems such as cad [1, 4, 23]. generally, the results show that the participants have been experiencing a series of manifestations associated with the cardiovascular system, specifically those who were diagnosed with cad experienced worst conditions when exposed to alternating weather conditions. it was recorded that higher incidence of cad occurs during extreme environmental temperature conditions [23, 24]. participants claimed that during warm weather conditions, they often experience fainting, shortness of breath, severe palpitation, headache, dizziness, and fatigue. literature contends that these manifestations are primarily due to impaired thermoregulation, elevated cholesterol level, increased blood viscosity and pressure, and change in the body’s sweating threshold [1, 6]. on the other hand, participants claimed that signs and symptoms were also experienced during cold weather conditions like palpitations, shortness of breath, fatigue, and dizziness. this is a result of increased blood pressure, heart rate, elevated cholesterol doi 10.18502/sjms.v18i2.13599 page 146 sudan journal of medical sciences eladio martin s. gumabay et al. level, and marked peripheral vasoconstriction [6]. this is also supported by a study [25] that the signs and symptoms are triggered during extreme low temperatures. however, results also revealed that few of them did not recognize any significant effect during cold climates. the necessity is to address the impacts of climate change on the health of the elderly to prevent a more complex adverse effect in the future. understanding the complexities of climate change would make the public more resilient [21]. the participants enumerated several practical self-care measures to adapt to or mitigate the consequences of the changing climate. during the upsurge of temperature, they mentioned the following: (i) accomplish tasks before the temperature gets too high; (ii) stay indoors; (iii) alternate rest and activity period; (iv) drink plenty of water as tolerated; (v) wearing light and loose clothes, (vi) taking cold shower or bath two or more times per day; (vii) avoid too much alcohol; (viii) recognize effects to cad; and, (ix) staying in a cool environment. all these are consistent with existing knowledge on people and not only on elderly who have cad [2, 18, 21].whereas, during cold exposure, the participants suggested the following adaptive strategies as they find them efficient and effective: (i) drink plenty of water; (ii) refrain from going outside the house when the breeze is cold; (iii) take a warm shower; iv) oil application; and (v) wear thick clothes. effective management on the effects of climate change through the utilization of adaptive coping strategies greatly helps the public to be resilient, especially those at risk and/or with existing cardiovascular medical conditions. dealing with the vast and complex health effects of climate change is incredibly challenging. this study is an eye-opener not only for the nursing profession but more especially for the elderly and those living with elderly people. the results of this research study significantly add to the existing body of knowledge that climate change is a phenomenon that everyone must deal with, regardless of age, educational attainment, culture, or place of residence. specifically, the elderly, even though they do not have formal awareness of the theory or framework, are already selfguided on roy’s extended adaptation model. this research study demonstrated that they implement practical self-care strategies as they compensate for the physiological effects of climate change on their cad; henceforth, explicitly presenting or showing that simple community-based interventions in day-to-day living and as needed are vital to be emphasized to help the elderly cope with their condition. furthermore, this study proves and emphasizes to the elderly diagnosed with cad that they can prevent occurrences or manage their manifestations well during extreme environmental temperature conditions. doi 10.18502/sjms.v18i2.13599 page 147 sudan journal of medical sciences eladio martin s. gumabay et al. the results of the study are important in the field of research, elderly nursing, and community health nursing. it serves as a basis to influence healthcare workers like nurses, the elderly, and their respective families to be more aware of climate change consequences. relevantly, nurses and the community health workers must enhance their capabilities and potential to educate for the benefit of community people through health promotion and health restoration. this research study demonstrated approaches that may be helpful in developing effective interventions, which aid in establishing nursing care strategies and substantial guidance in nursing education, elderly care, geriatric nursing, and community health nursing. study limitations within the lens of phenomenological research design and utilizing roy’s extended adaptation model, this research study is focused on describing the lived experiences of the elderly diagnosed with cad, specifically, on the effects of climate change on their condition. this was only conducted in one northern province of the philippines; hence, the context and perception on the effects of climate change on their existing cad might be culturally or medically different from other provinces and countries. 5. conclusion this research study concludes that elderly clients have an awareness of climate change brought about by global warming and that it aggravates physiologic manifestations of cad. this further concludes that elderly people residing in urban areas who are exposed to sudden changes involving extreme environmental temperatures are at risk of an aggravated cad condition. significantly, employment of simple community-based and practical self-care measures and practices as an adaptation to climate change helps the elderly prevent and control the manifestations of cad. climate change because of environmental and atmospheric changes possess a great impact on the health of every individual; hence, it is recommended that the community, together with the nursing profession and other health sectors to continuously collaborate and strengthen their commitment toward educating and raising awareness, especially of and for the elderly. public health organizations should implement adaptation strategies to minimize the health effects of prolonged hot and cold environmental exposure. the following community-based recommendations manage manifestations of cad: doi 10.18502/sjms.v18i2.13599 page 148 sudan journal of medical sciences eladio martin s. gumabay et al. 1. during warm weather conditions, self-care measures must be employed such as the following: 2. accomplishing tasks before the temperature gets too high 3. staying indoors 4. alternating rest and activity period 5. drinking plenty of water as tolerated 6. wearing loose fitting clothes 7. taking cold shower or bath two or more times per day 8. avoiding liquor beverages 9. recognizing effects of health-related diseases, and 10. staying in a cool environment 11. during cold weather conditions, adaptive strategies are to be more emphasized, such as: 12. drinking warm water as tolerated and without medical contraindication. 13. refraining from going outside the house, especially when the breeze is cold 14. taking warm showers 15. applying oil on the body, and 16. wearing protective clothing such as sweater, jacket, and socks acknowledgments none. ethical considerations ethical clearance #6052, for this research study, was granted by the university research ethics board (ureb) of the university of saint louis tuguegarao, philippines. the researchers guaranteed that the rights of the participants were guarded through informed consent. the latter served as evidence that the participants fully understood doi 10.18502/sjms.v18i2.13599 page 149 sudan journal of medical sciences eladio martin s. gumabay et al. and agreed with the content of the study [15]. the participants were informed that the interview sessions were recorded. the researchers ensured that confidentiality was maintained for all the data and anonymity of participants identities. a designated code for each respondent was used to avoid disclosure of their identity. the materials used during the study were destroyed upon the 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(2015). human adaptation strategies to abrupt climate change in puerto rico ca. 3.5 ka. the holocene, 25(4), 627-640. [24] davídkovová, h., plavcová, e., kynčl, j., & kyselý, j. (2014). impacts of hot and cold spells differ for acute and chronic ischaemic heart diseases. bmc public health, 14(1), 1-11. [25] gumabay, e. m. s., ramirez, r. c., dimaya, j. m. m., & beltran, m. m. (2018). adversity of prolonged extreme cold exposure among adult clients diagnosed with coronary artery diseases: a primer for recommending community health nursing intervention. nursing open, 5(1), 62-69. doi 10.18502/sjms.v18i2.13599 page 152 introduction methods research design locale of the study study participants data collection procedure data analysis results discussion study limitations conclusion acknowledgments ethical considerations competing interests funding references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12103 production and hosting by knowledge e research article evaluation of fine-needle aspiration cytology (fnac) sensitivity compared to pcr for diagnosing tuberculosis lymphadenitis omar mustafa1, ebtehal mohamed2, ahmed omer2, abdelmonem mohamed2, sheima abdemagid3, alaa ali4, nafisa hassan5, mayada khalil6, and nagia suliman6 1department of histopathology and cytology, college of medical laboratories science, university of medical science and technology (umst) 2department of clinical chemistry, college of medical laboratory science, al-neelain university 3department of microbiology, college of medical laboratory science, university of alzaiem al azhari 4department of hematology and immunohematology, college of medical laboratory science, sudan university of science and technology 5department of clinical chemistry, college of medical laboratory science, university of el imam el mahdi 6department of medical microbiology, college of medical laboratory science, university of gezira orcid: abdelmonem mohammed: https://orcid.org/0000-0002-3925-5268 ahmed omer: https://orcid.org/0000-0001-9035-5558 mayada khalil: https://orcid.org/0000-0001-7619-097x shiema abdelmagid: https://orcid.org/0000-0003-0090-1514 alaa ali: https://orcid.org/0000-0002-7482-7065 nagia suliman: https://orcid.org/0000-0002-0072-9315 ebtehal mohamed: https://orcid.org/0000-0003-2690-1248 nafisa hassan: https://orcid.org/0000-0002-2923-0198 omer mustafa: https://orcid.org/0000-0002-2540-1877 abstract background: tuberculosis (tb) is a major healthcare burden in sudan and other developing countries, it is considered the second most common cause of death from infectious diseases after those due to aids. in sudan, tb lymphadenitis (tbla) remains one of the major health problems. this descriptive cross-sectional study was conducted at the university of medical sciences and technology (umst) and total labcare diagnostic center (tdc). the study aims to compare the sensitivity of fine needle aspiration cytology (fnac) smears with that of the polymerase chain reaction (pcr) for the diagnosis of tbla. methods: fifty-five dry smears were obtained using fine-needle aspiration (fna) from an enlarged lymph node. pcr was applied to detect the target gene (is6110). maygrunwald-giemsa (mgg) or diff quick stains were used. results: two (4%) patients with tbla were non-necrotic, while fifty-three of them (96%) were necrotic. moreover, 17 (30%) fine-needle lymph node aspiration specimens were confirmed by pcr to be positive for mycobacterium tuberculosis complex (mtb complex) while 38 (70%) of them were negative. conclusion: there was no significant difference between the sensitivity of pcr and that of fnac (p-value = 0.33). how to cite this article: omar mustafa, ebtehal mohamed, ahmed omer, abdelmonem mohamed, sheima abdemagid, alaa ali, nafisa hassan, mayada khalil, and nagia suliman (2022) “evaluation of fine-needle aspiration cytology (fnac) sensitivity compared to pcr for diagnosing tuberculosis lymphadenitis,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 330–340. doi 10.18502/sjms.v17i3.12103 page 330 corresponding author: nagia suliman; email: nagisuliman@hotmail.com received 20 december 2021 accepted 21 may 2022 published 30 september 2022 production and hosting by knowledge e omar mustafa et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences omar mustafa et al keywords: tuberculosis, lymphadenitis, lymph node, fnac, pcr 1. introduction tuberculosis (tb) is a common infectious agent associated with prominent levels of morbidity and mortality, especially in developing countries [1, 2]. globally, in 2018, about 10 million tb cases and 1.5 million tb deaths were estimated [3]. in africa, the prevalence of tb remains as one of the major health problems due to malnutrition, poverty, and poor diagnosis. based on a previously published report, about 30–40% of hiv patients die from tb in african countries [4]. sudan is considered one of the endemic areas of tb. according to the who, in 2013, 20,181 tb cases were detected, of which 980 (30%) were new sputum smear-positive cases. however, there are many unreported cases due to the low-quality system of data reporting [5, 6]. one of the who tb strategies after 2015 is global reduction in tb epidemic death and incidence rate of up to 90% and 95%, respectively [7]. tb is caused by a bacterium called mycobacterium tuberculosis, which is a member of m. tuberculosis complex (m. tuberculosis, m. bovis, m. microti, and m. africanum). there are two forms of clinical tb – pulmonary tb (ptb) which usually attacks the lungs and extrapulmonary tb (eptb) that attacks other organs such as the kidneys, spine, and brain [8]. however, the major eptb is tbla. it causes an enlargement of lymph nodes caused by infection or inflammation [9]. both the diagnosis and therapy for tbla represent a challenge because it has physical and laboratory findings feature similar to other pathologic processes [10]. it is difficult to diagnose tbla by routine methods such as the microscopic ziehl-neelsen (zn) stain and microbiology culture in the lowenstein-jensen medium. among the most practical applications for cytological analysis of lymph node aspirates is fine needle aspiration cytology (fnac) [11, 12]. fine needle aspiration (fna) is accepted by most patients as a noninvasive method and is considered by pathologists for evaluating lymphadenopathy and preserving lymph node structure [13]. enlarged lymph nodes are a prime target for fna. although, as mentioned in the previously published studies, cytology can provide a definitive morphological prognosis of lymphadenopathy, but combination with confirmatory techniques is recommended. in the current study, the molecular technique used is polymerase chain reaction (pcr) to detect the m. tuberculosis complex. pcr is the molecular tool that permits the exponential amplification of target dna [14]. the use of pcr to diagnose mycobacterial infection is not a novel procedure, however, pcr still represents a gold standard for molecular techniques and adds diagnostic value doi 10.18502/sjms.v17i3.12103 page 331 sudan journal of medical sciences omar mustafa et al for suspicious results. the goal of this study was to assess the sensitivity of fnac technique compared to pcr in confirming tbla. 2. materials and methods a descriptive cross-sectional laboratory-based research was carried out at the university of medical sciences and technology and total labcare diagnostic center. fifty-five patients were included from both genders of different age groups. fine needle lymph node aspiration specimens were collected under all aseptic precautions, using standard disposable 27-gauge needles (figure 1). high-quality smears were prepared and stained with diff-quick (romanowski stain). in the staining procedure of figure 1: collection of a sample trapped in the hub of the biopsy needle, the sample was aspirated with another needle mounted on a syringe. diff-quick, air-dried smears are fixed in diff-quick fixative (or methanol) for 30 sec followed by stain with diff-quick solution i for 30 sec, and then stain with diff-quick solution ii for 30 sec. then, they are rinsed in tap water to remove excess stain and rapidly dehydrated in absolute alcohol. after that the slides are cleared and mounted. 2.1. dna extraction dna was extracted by scraping lymph node smears material. cinnagen, iran kit was used, the kit contains lysis buffer to rupture and release the cells’ constituents, the precipitation solution was used to precipitate proteins with other substances, but the dna flooded in the mixture. this method used column tube which contains silica particles plate, positive charge of the silica attached to dna and passed other substances. the doi 10.18502/sjms.v17i3.12103 page 332 sudan journal of medical sciences omar mustafa et al elution buffer of this kit was warmed at 64ºc, which eluded the dna and the dna was obtained at the bottom of new 1.5 ml eppendorf tubes. 2.2. pcr reagents dna template; pcr master mix contains taqtmdna polymerase (5u/μl), dntps 2.5 mm each, reaction buffer (10×); stock primers (forward and reverse primers were 5′-gcctacgtggcctttgtcac-3′ and 5′-c3-gtccagatggcttgctcgat-3′ respectively [15]; dna mtb-positive; ddh2o (double distilled water); and gel loading dye (1×). 2.3. pcr protocol extracted dna was brought at –20ºc, thawed, and kept on ice cryo-rack for processing. at the same time, stock primers, dntps, and reaction buffer were brought at room temperature (rt) and kept on ice cryo-rack for thawing. sterile pcr water was brought out from refrigerator and aliquoted on 1.5-ml tubes. 2.3.1. pcr optimization small fraction of positive control (brought from tuberculosis unit in the national health laboratory) was first subjected to pcr amplification. after successful amplification, the rest of the samples were analyzed. in the events of the negative results, samples were diluted from the outer product up to one in hundred and the original dna was diluted up to tenfold to minimize the inhibitors. 2.3.2. pcr procedure in pcr room at the biological safety cabinet class ii, the maxim pcr premix tubes (20 µl) and the dna sample both stored at –20ºc were taken out and, respectively, placed on ice and bench for thawing. next, 2-µl tb primer mix (forward and reverse) was added to each maxim tube and 13-µl ddh2o was added to the sample tube and positive control while 18-µl ddh2o was added to the negative control. moreover, 5-μl dna was added to each tube (filter tips were used), vortex for 5 sec and all samples were run in pcr machine. doi 10.18502/sjms.v17i3.12103 page 333 sudan journal of medical sciences omar mustafa et al 2.3.3. pcr amplification of mtb gene the amplification was carried out using 10× pcr buffer (10 mmtris-hcl, ph 8.3, 50 mm kcl, 1.5 mmmgcl2); 2.5mm of each dntps, dna template and i-taqtmdna polymerase (5u/μl) in a final volume 20 μl. reactions were performed in a thermal cycler tc-412 with the following thermal profile: primary denaturing at 94ºc for 5 min, denaturing at 94ºc for 30 sec, annealing temperature at 62ºc for 30 sec, extension at 72ºc for 1 min, and a final extension at 72ºc for 30 sec for 40 cycles for the outer pcr. then the pcr products were examined in the agarose gel. 2.4. electrophoresis protocol 2.4.1. 10x tbe tris-borate-edta (tbe) buffer preparation the working solution of 1x tbe was prepared from the stock solution (1 l) which contained the following: 89 mmtris base, 89 mm boric acid, and 2 mm edta. it was used for agarose gel preparation and as a running buffer for electrophoresis. 2.4.2. preparation of dna loading dye solution, (bromophenol blue) the dye was prepared as follows: 0.25 gm of bromophenol blue (sigma), 50% pure glycerol (10 ml) and 0.4 m edta. it was then mixed and stored in a brown bottle at 4ºc. 2.4.3. preparation of 100 base pairs ladder dna ladder was prepared for electrophoresis as follows: 5 μl dna ladder (sigma), 5 μl water, and 2 μl gel loading dye, the mixture was stored at –20ºc. 2.4.4. preparation of agarose gel for pcr product (2%) in clean dry bottle, 50 ml of 1x tbe buffer was added, 1 gram of agarose powder was then added to the bottle. the powder was dissolved by heating the solution in a microwave, and then cooled at room temperature (until 50ºc). next, the solution was poured in a gel tray with two combs row (well-maker) until completely solidified. in the running tank, 500 ml of 1x tbe buffer was added with 1 µl of dna-safe stain. agarose gel plate was placed in the running direction and the first well was loaded with dna marker (100 pb) and the second with negative control. samples were loaded in the next doi 10.18502/sjms.v17i3.12103 page 334 sudan journal of medical sciences omar mustafa et al wells, and the last well was loaded with positive control. the power supply was adjusted to 100ma for 30 min. finally, the gel plate was transferred to the gel documentation system to visualize the dna and photograph the bands. 3. results the study involved 55 patients, 24 male and 31 female, with an average age of 37.5 years. all cases showed enlarged cervical lymph nodes. fine needle aspiration for cytological examination showed that 53 (96%) cases had tbla with necrosis and granulomatous inflammation with or without detection of epithelioid cells, while 2 cases showed non-necrotizing granulomatous lymphadenitis with only epithelioid and inflammatory cells detected (figures 1 & 2). products of pcr on gel electrophoresis are shown in figure 4. the correlation between cytological findings and pcr results are set out in table 1, showing a chi-square with p-value > 0.05 which was considered statistically insignificant (<0.05 was considered significant). figure 2: tuberculosis lymphadenitis with necrotizing shows granulomas variable in size with a mixture of epithelioid macrophages and lymphocytes. ‘ chi-square p-value was obtained = 0.335∗. doi 10.18502/sjms.v17i3.12103 page 335 sudan journal of medical sciences omar mustafa et al figure 3: tuberculosis lymphadenitis with necrotixing material and a few degenerating nuclei (romanowsky stain). figure 4: pcr products on gel electrophoresis under uv light. upper row right of gel (m): dna marker; l1: positive control; l7: negative control; l4–l6: positive samples for mtb complex; l2 and l3: negative for mtb complex. 4. discussion pcr is considered as one of the confirmatory methods for tb. there are other molecular techniques such as nucleic acid amplification test (naat) and genexpert (gxp) both doi 10.18502/sjms.v17i3.12103 page 336 sudan journal of medical sciences omar mustafa et al table 1: comparison of overall sensitivity of cytology and pcr. cross-tabulation pcr total positive negative cytology necrotizing 17 36 53 (30%) (66%) (96%) non-necrotizing 0 2 2 0 (4%) (4%) total 17 38 55 (30%) (70%) (100%) of which depend on the principle of nucleic acid detection of tb. but in the current setting, the pcr technique was used as a confirmatory method for fnac results. in the present study, 55 patients were enrolled with a suspicion of cervical tbla. fine needle lymph node aspirate was collected and examined cytologically. fifty-three smears showed necrotic material while two were non-necrotic. all these smears were diagnosed as cervical tbla. pcr was done and 17 (30%) specimens were positive and 38 (70%) were negative for mtb complex. our specimens have shown lower pcrpositivity numbers which may be attributed to many factors, including the small amount of specimen and subsequently fewer organisms (especially, after splitting the specimen for cytological assays), internal variations in the dna extraction and concentration. the storage temperature of the specimen could also affect the sensitivity, especially in tropical areas where the temperatures are high [16]. while our cytological findings have shown higher positivity of 53 (96%) smears with necrosis this may be due to their larger size and well-stained smears on the slide. statistically, there was an insignificant difference between the pcr sensitivity compared to the fnac with a p-value of 0.33. pcr-positive specimens also were positive for cytological smears diagnosed as tbla. thus, our results agree with chantranuwat et al. (2006), tansuphasiri et al. (2004) [17, 18]. 5. conclusion there was no significant difference between the fnac and pcr sensitivities in the diagnosis of tbla. all pcr-positive cases also showed cytological positivity for tbla. pcr could be used as a confirmatory test for mgg or diff-quick-stained cytological smears. pcr could be used as a practical and valuable method when no smear specimen is available. however, a molecular technique like pcr is costly and unavailable in a limited resource setting. so, fnac could be an effective diagnostic technique for doi 10.18502/sjms.v17i3.12103 page 337 sudan journal of medical sciences omar mustafa et al tbla, because it is easy to perform, cost-effective, and convenient, especially in high prevalence areas in poor economies with limited resources. acknowledgements the authors are thankful to dr. alfatih aboalbasher yousif and dr. maha mahgoub for their logistic support. ethical considerations informed consent was obtained from all patients. competing interests none declared. availability of data and material data is available with corresponding author upon request. funding none. references [1] mittal, p., handa, u., mohan, h., & gupta, v. (2011). comparative evaluation of fine needle aspiration cytology, culture, and pcr in diagnosis of tuberculous lymphadenitis. diagnostic cytopathology, 39, 822–826. https://doi.org/10.1002/dc.21472 [2] zammarchi, l., bartalesi, f., & bartoloni, a. (2014). tuberculosis in tropical areas and immigrants. mediterranean journal of hematology and infectious diseases, 6(1), e2014043. https://doi.org/10.4084/mjhid.2014.043 [3] cdc. (2020). tuberculosis. cdc. https://www.cdc.gov/globalhealth/newsroom/topics/tb/index.html [4] chatterjee, d., & pramanik, a. k. (2015). tuberculosis in the african continent: a comprehensive review. pathophysiology, 22(1), 73–83. doi 10.18502/sjms.v17i3.12103 page 338 sudan journal of medical sciences omar mustafa et al https://doi.org/10.1016/j.pathophys.2014.12.005 [5] abdallah, t. m., & ali, a. a. (2012). epidemiology of tuberculosis in eastern sudan. asian pacific journal of tropical biomedicine, 2(12), 999–1001. https://doi.org/10.1016/s2221-1691(13)60013-1 [6] who. (2015). sudan / tuberculosis. who. http://www.emro.who.int/sdn/ programmes/stop-tb-sudan.html [7] hwang, s. h., kim, d. e., sung, h., park, b. m., cho, m. j., yoon, o. j., & lee, d. h. (2015). simple detection of the is6110 sequence of mycobacterium tuberculosis complex in sputum, based on pcr with graphene oxide. plos one, 10(8), e0136954. https://doi.org/10.1371/journal.pone.0136954 [8] narayana reddy, r. a., narayana, s. m., & shariff, s. (2013). role of fine-needle aspiration cytology and fluid cytology in extra-pulmonary tuberculosis. diagnostic cytopathology, 41, 392-398. https://doi.org/10.1002/dc.22827 [9] lazarus, a. a., & thilagar, b. (2007). tuberculous lymphadenitis. disease-a-month, 53(1), 10–15. https://doi.org/10.1016/j.disamonth.2006.10.001 [10] mohapatra, p. r., & janmeja, a. k. (2009). tuberculous lymphadenitis. the journal of the association of physicians of india, 57, 585–590. [11] patwardhan, s. a., bhargava, p., bhide, v. m., & kelkar, d. s. (2011). a study of tubercular lymphadenitis: a comparison of various laboratory diagnostic modalities with a special reference to tubercular polymerase chain reaction. indian journal of medical microbiology, 29(4), 389–394. https://doi.org/10.4103/0255-0857.90173 [12] rathod, g. b., & parmar, p. (2012). fine needle aspiration cytology of swellings of head and neck region. indian journal of medical sciences, 66(3–4), 49–54. https://doi.org/10.4103/0019-5359.110896 [13] wakely, p. e., jr., & cibas, e. s. (2009). chapter 11 lymph nodes. in: e. s. cibas & b. s. ducatman (eds.). cytology (3rd ed.). (319–357). science direct. https://doi.org/10.1016/b978-1-4160-5329-3.00011-6 [14] caetano-anolles, d. (2013). polymerase chain reaction. in: s. maloy & k. hughes (eds.). brenner’s encyclopedia of genetics brenner’s encyclopedia of genetics (2𝑛𝑑 ed.). (392–395). academic press. https://doi.org/10.1016/b978-0-12-374984-0.01186-4 [15] hwang, s. h., kim, d. e., sung, h., park, b. m., cho, m. j., yoon, o. j., & lee, d. h. (2015). simple detection of the is6110 sequence of mycobacterium tuberculosis complex in sputum, based on pcr with graphene oxide. plos one, 10(8), e0136954. https://doi.org/10.1371/journal.pone.0136954 doi 10.18502/sjms.v17i3.12103 page 339 http://www.emro.who.int/sdn/programmes/stop-tb-sudan.html http://www.emro.who.int/sdn/programmes/stop-tb-sudan.html sudan journal of medical sciences omar mustafa et al [16] lorenz, t. c. (2012). polymerase chain reaction: basic protocol plus troubleshooting and optimization strategies. journal of visualized experiments, e3998(63), e3998. https://doi.org/10.3791/3998 [17] chantranuwat, c., assanasen, t., shuangshoti, s., & sampatanukul, p. (2006). polymerase chain reaction for detection of mycobacterium tuberculosis in papanicolaou-stained fine needle aspirated smears for diagnosis of cervical tuberculous lymphadenitis. the southeast asian journal of tropical medicine and public health, 37(5), 940–947. [18] tansuphasiri, u., boonrat, p., & rienthong, s. (2004). direct identification of mycobacterium tuberculosis from sputum on ziehl-neelsen acid fast stained slides by use of silica-based filter combined with polymerase chain reaction assay. journal of the medical association of thailand, 87(2), 180–189. doi 10.18502/sjms.v17i3.12103 page 340 introduction materials and methods dna extraction pcr reagents pcr protocol pcr optimization pcr procedure pcr amplification of mtb gene electrophoresis protocol 10x tbe tris-borate-edta (tbe) buffer preparation preparation of dna loading dye solution, (bromophenol blue) preparation of 100 base pairs ladder preparation of agarose gel for pcr product (2%) results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12553 production and hosting by knowledge e research article scleroderma associated with monoclonal gammopathy of undetermined significance dalya m. m. abdelmaged1, carol a. avila2, michelle a. rivera3, and abubaker a. mohamedsharif4* 1md, faculty of medicine, al neelain university, khartoum, sudan 2universidad de carabobo, valencia, venezuela 3weill cornell medicine, usa weill cornell medicine, usa 4faculty of medicine, university of khartoum, khartoum, sudan orcid: abubaker a. mohamedsharif: https://orcid.org/0000-0002-2600-9666 abstract a 53-year-old female presented with itchiness in her back. she has a 5 years history of tightness of the skin on her face, neck, and torso bilaterally. she did not have other symptoms suggestive of systemic sclerosis (scleroderma), and her rheumatologic workup was negative. skin biopsy showed increased dermal mucin confirming a diagnosis of scleredema. further workup with serum protein electrophoresis (spep) showed an m-spike, confirming the diagnosis of monoclonal gammopathy of undetermined significance mgus as the underlying pathology. keywords: serum protein electrophoresis (spep), monoclonal gammopathy of undetermined significance (mgus), double-stranded dna (dsdna), antinuclear antibodies immunoglobulin g (ana igg), anti-sjogren’s syndrome (ssb), antitopoisomerase antibody-type (scl), ribonucleic acid (rna), cyclic citrullinated peptide (ccp), u1 small nuclear ribonucleoprotein particle (u1 rnp), multiple myeloma (mm), immunomodulatory drugs (imids), proteasome inhibitors (pis), intravenous immunoglobulins (ivig) 1. introduction this is a case of a rare connective tissue disorder characterized by the accumulation of collagen and aminoglycans in the dermis (1). the skin manifestations mimic scleroderma (systemic sclerosis); however, scleredema spares hands and feet (2). scleredema can be associated with paraproteinemia and diabetes (3–5) and requires specialist investigation and management. gammopathies can be an underlying cause of scleredema; therefore, early diagnosis can aid in prompt treatment. in this case report, we present an example of the importance of a multidisciplinary approach to diagnose patients with rare connective tissue diseases. rheumatologists should involve dermatologists and other specialists in diagnosing cases that present with subtle symptoms like skin tightness/itchiness even in the setting of seronegativity. how to cite this article: dalya m. m. abdelmaged, carol a. avila, michelle a. rivera, and abubaker a. mohamedsharif* (2022) “scleroderma associated with monoclonal gammopathy of undetermined significance,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 556–564. doi 10.18502/sjms.v17i4.12553 page 556 corresponding author: abubaker a. mohamedsharif; email: abubakerabdalgafar@gmail.com received 6 may 2022 accepted 9 september 2022 published 31 december 2022 production and hosting by knowledge e abubaker a. mohamedsharif et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12553&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abubaker a. mohamedsharif et al for instance, this patient’s condition was initially confused with scleroderma (systemic sclerosis). in addition, this case report presents a successful diagnosis of mgus as a result of a meticulous search for an underlying cause of scleredema. it is worth mentioning that this patient has a family history of mgus and multiple myeloma (mm) in her father and mother, which might point to a familial link to her condition. 2. case presentation a 53-year-old female presented to a dermatologist with itching in the left back area. she was nondiabetic and did not have any chronic conditions. relevant to this history, the patient stated that her skin had been changing for the past 5 years. she noticed progressive tightness of the skin of her face, neck, and arms. for a while, she thought it was “tight muscles or fascia.” it worsened over the years and she also noticed involvement of her torso and legs. three years prior to her presentation she went to the emergency room for a separate issue (choked on a fishbone), where physician suspected that she had scleroderma. therefore, she was referred to a rheumatologist for further workup. initially, based on her skin examination, the rheumatologist suspected scleroderma. however, she tested negative for dsdna, smith, ana igg, ssb, scl, centromere, rna polymerase iii, jo 1, ccp, ana by hep 2, u1 rnp, rnp 70, ro 52, ro 60, ssb, rheumatoid factor, anticardiolipin igm/igg, beta-2 glycoprotein igm/igg, antithyroglobulin igg, and thyroid peroxidase igg. therefore, the rheumatologist informed the patient that her blood tests are negative for scleroderma. eventually, she visited the dermatologist for skin screening and itchiness on her back. she reported night sweats due to menopause but denied any weight changes, fever, or chills. she also denied dry eyes, dry mouth, joint pain, muscle aches, migraine headaches, changes in vision, and any history of blood clots or miscarriages. she described a history of intermittent acid reflux aggravated by certain foods and relieved by calcium carbonate (antacid). on examination, she was a well-appearing caucasian female, with infiltrative thickening of the skin on the torso, neck, and arms (figure 1). her hands, fingers, and feet are spared. upon inquiry, she denied skin infection before these skin changes. the examination was negative for malar rash, parotid enlargement, raynaud’s phenomenon, sclerodactyly, telangiectasia, calcinosis, nasal and digital ulcerations, alopecia, nail changes, genital ulcers, or joint swelling. the oropharynx was clear, without ulcerations, and the mucous membranes were moist without oral telangiectasias. there was no palpable lymphadenopathy. no tenderness doi 10.18502/sjms.v17i4.12553 page 557 sudan journal of medical sciences abubaker a. mohamedsharif et al or synovitis was noted on the examination of the metacarpophalangeal, proximalinterphalangeal, distal-interphalangeal, metatarsal-phalangeal joints, ankles, and wrists bilaterally. she was able to make tight fists bilaterally. she had preserved range of motion in both shoulders, wrists, and elbows. based on the distribution of skin involvement, the dermatologist suspected scleredema rather than scleroderma. a 4mm punch biopsy on the left mid-forearm was performed to establish the diagnosis (figure 2). the biopsy results showed increased dermal mucin, and a sparse perivascular chronic inflammatory infiltrate. the overlying epidermis appeared uninvolved with orthokeratosis. colloidal iron stain highlighted the dermal mucin. periodic acid schiff with diastase (pas-d) stain was negative for fungal hyphae. cd34 immunostaining showed retained expression within the dermis. these distinctive histological features were consistent with scleredema. figure 1: left-arm skin thickness. figure 2: left-arm punch biopsy site. doi 10.18502/sjms.v17i4.12553 page 558 sudan journal of medical sciences abubaker a. mohamedsharif et al this diagnosis prompted further workup by the primary care physician for possible underlying and associated conditions. her investigations were negative for diabetes, thyroid disease, other collagen storage diseases, and liver disease. however, the workup revealed an m-spike of 0.6 on spep, which led to the diagnosis of mgus. therefore, a diagnosis of scleredema secondary to monoclonal gammopathy of undetermined significance was made. interestingly, the patient has a strong family history of mgus and mm with both her mother and father diagnosed with mm. therefore, this patient also represents a case of inherited susceptibility to mm. the patient underwent further workup with a hematologist which confirmed igg kappa mgus. the studies showed a free kappa light chain of 36.6, free lambda chain of 11.1 with a ratio of 3.3. her immunoglobulin levels were iga 41, igg 1268, and igm 81. these results confirmed that she had a low risk (igg subtype, serum m protein <1.5g/dl with flc ratio <8) with no myeloma-defining events at this time. her mgus was classified as low-risk according to the mayo clinic criteria (6). she was also evaluated for mm and was found to have a low-risk igg-subtype mgus with only a 5-7% chance of evolving to malignant plasma cell dyscrasia at 20 years. differential diagnosis: scleroderma was the most important differential diagnosis for this patient. initially, she was suspected of having scleroderma rather than scleredema. contrary to scleroderma, scleredema spares the distal extremities including hands, fingers, and feet (7–9). scleromyxedema, a mimicking condition, displays a sclerodermiform papular eruption and histopathologic mucin deposition in the upper and mid dermis (2,10,11,12). unlike scleredema, it causes fibroblast proliferation and fibrosis (2). similar to scleredema, scleromyxedema is associated with systemic disorders like paraproteinemia (usually ig�) (2,8,11) but not thyroid disease (2,8,10,12). treatment: scleredema has been linked to monoclonal paraproteinemia (mgus) and mm (5,8,13,14). about 25% of patients with scleredema are found to have paraproteinemias such as mgus (most common), myeloma, and amyloidosis (5,8,13). the appropriate management for mgus-related cases remain questionable with inconsistent outcomes. treatments include immunomodulatory drugs (imids), proteasome inhibitors (pis), intravenous immunoglobulins (ivig), and dermatologic treatments such as phototherapy and corticosteroids (4,15,16). it is unclear as to what is the appropriate treatment option for patients of scleredema secondary to mgus, who would otherwise not require treatment given low-risk disease with no myeloma defining events (primary treatment for scleredema versus myeloma treatment). there are toxicities associated with myeloma doi 10.18502/sjms.v17i4.12553 page 559 sudan journal of medical sciences abubaker a. mohamedsharif et al monotherapies, making this option less appealing, especially in this patient’s case because she has a low risk of evolving to mm. the patient in this case report had a normal range of motion of her joints and no significant limitations from her skin disease. therefore, methotrexate and phototherapy were not recommended. however, they can be considered in the future if required as per references (17). outcome and follow-up: the patient in this case report had low-risk mgus with a slight chance of ever evolving to mm. as such, given this unique case, she will undergo regular monitoring for paraproteinemia. the patient follow-up plan comprises a multidisciplinary approach with a dermatologist, hematologist, and rheumatologist. she will be monitored for the evolution of mm. like other patients with low-risk mgus, this patient will be followed up with a periodic serum protein electrophoresis (6,9). it is performed at six months and subsequently every 2-3 years if the results remain steady and no symptoms point toward plasma cell malignancy (6). although the patient’s skin involvement is quite extensive, it has not led to significant disability. she has good mobility in her shoulders. however, physical therapy was recommended to prevent future disability. 3. discussion cutaneous mucinosis, a group of connective tissue disorders, is characterized by increased proliferation and deposition of acid glycosaminoglycan (mainly hyaluronic acid) in the upper and mid reticular dermis (2,18). it does not involve the epidermis, deep dermis, or subcutis (1,3). primary mucinosis, also known as degenerative or inflammatory mucinosis, is characterized by increased deposition of mucin as the main histologic feature (8,18). it is divided into two groups, dermal and follicular types (8,18). the dermal type comprises, among others, scleredema, dysthyroid mucinosis, papular-nodular mucinosis associated with lupus erythematosus, and cutaneous mucinosis of infancy (8,18). the follicular type can be found in follicular mucinosis (pinkus) and urticaria-like follicular mucinosis (8,18). in secondary mucinosis, mucin deposition is not the main finding (18). it involves conditions like mycosis fungoides, spongiotic dermatitis, basal cell carcinoma, squamous cell carcinoma, warts, scleroderma, lupus erythematosus, dermatomyositis, granuloma doi 10.18502/sjms.v17i4.12553 page 560 sudan journal of medical sciences abubaker a. mohamedsharif et al annulare, acanthosis nigricans, lymphoma, lupus erythematosus, hypertrophic lichen planus, lichen striatus and sarcoidosis (18). scleredema presents with thickening and tightening of the skin (19). the initial course is characterized by the involvement of the skin in the neck and then it extends over the torso and arms symmetrically (19). contrary to scleroderma, scleredema spares the distal extremities, including hands and feet, and causes non-pitting edema which can be associated with erythema and peau d’orange (2). initially, the skin looks doughy and progresses over time into a woody induration (5,8). scleredema is classified into three groups. type i accounts for the majority of the cases (55%). it is acute, develops after a febrile infection, is usually caused by streptococcus pyogenes or viral infection and self-resolves in weeks to months (3,4). type ii is a slowly progressive disorder associated with paraproteinemia (25% of cases) (2). finally, type iii is called scleredema adultorum of buschke or diabeticorum and it occurs in patients with diabetes (2,3,17,19,20, 21). the pathophysiology of scleredema is not well understood. however, it is known that serum factors like immunoglobulins and cytokines increase the synthesis of glycosaminoglycans (2,5,8,13,18,22). it is thought that the persistent stimulation of the collagen by antigens from scleredema produces monoclonal immunoglobulins (5). however, no immunoglobulins are found in negative direct immunofluorescence of the involved skin (5,21). a negative ana result will support the differentiation of diagnoses such as scleredema, scleromyxedema, and systemic sclerosis (1,3,8). the onset of scleredema might not be noticed by patients and it will be identified by treating physicians (17). the confirmation of the diagnosis of scleredema should be done by performing a tissue biopsy (4,5,20,23). histopathologic findings include mucin deposits between collagen bundles in the dermis. monoclonal gammopathy of undetermined significance is an asymptomatic premalignant condition that can precede mm. the risk progression to mm is approximately 1% per year. (6,15). some of the risk factors to develop mgus include age, race, and hereditary factors (6,15). individuals whose parents had mgus are at a high risk of developing mgus, especially, first-degree children (6,15). acknowledgments the authors express their sincere thanks to all medical staff who participated in thisstudy for their valuable support and to the patient for her participation. doi 10.18502/sjms.v17i4.12553 page 561 sudan journal of medical sciences abubaker a. mohamedsharif et al ethical considerations ethical clearance was obtained from the research ethical committee (rec), faculty ofmedicine, alneelain university. written consent was taken from the patient. competing interests the authors declare that they have no competing interests. availability of data and materials the datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. funding this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors to design the study and collection, analysis, and interpretation of data and write the manuscript. references [1] ioannidou, d. i., krasagakis, k., stefanidou, m. p., karampekios, s., panayiotidis, j., & tosca, a. d. (2005). scleredema adultorum of buschke presenting as periorbital edema: a diagnostic challenge. journal of the american academy of dermatology, 52(2 suppl 1), 41–44. [2] jablonska, s., & blaszczyk, m. (1998). scleroderma-like disorders [internet]. seminars in cutaneous medicine and surgery, 17, 65–76. [3] beers, w. h., ince, a., & moore, t. l. (2006). scleredema adultorum of buschke: a case report and review of the literature. seminars in arthritis and rheumatism, 35(6), 355–359. [4] alp, h., orbak, z., & aktas, a. (2003). scleredema adultorum due to streptococcal infection. pediatrics international, 45(1), 101–103. [5] angeli-besson, c., koeppel, m. c., jacquet, p., andrac, l., sayag, j. (1994). electron-beam therapy in scleredema adultorum with associated monoclonal hypergammaglobulinaemia. british journal of dermatology, 130(3), 394–397. doi 10.18502/sjms.v17i4.12553 page 562 sudan journal of medical sciences abubaker a. mohamedsharif et al [6] kyle, r. a., durie, b. g. m., rajkumar, s. v., landgren, o., blade, j., merlini, g., kröger, n., einsele, h., vesole, d. h., dimopoulos, m., san miguel, j., avet-loiseau, h., hajek, r., chen, w. m., anderson, k. c., ludwig, h., sonneveld, p., pavlovsky, s., palumbo, a., … boccadoro, m. (2010). monoclonal gammopathy of undetermined significance (mgus) and smoldering (asymptomatic) multiple myeloma: imwg consensus perspectives risk factors for progression and guidelines for monitoring and management. leukemia, 24(6), 1121–1127. [7] mitchell, d. c., agnihothri, r., scott, g. a., korman, b., & richardson, c. t. (2019). a case of concurrent systemic sclerosis and scleredema. jaad case reports, 5(11), 940–942. [8] orteu, c. h., ong, v. h., & denton, c. p. (2020). scleroderma mimics clinical features and management. best practice & research: clinical rheumatology, 34(1), 101489. [9] mcfadden, n., ree, k., søyland, e., & larsen, t. e. (1987). scleredema adultorum associated with a monoclonal gammopathy and generalized hyperpigmentation. archives of dermatology, 123(5), 629–632. [10] sala, a. c. b., cunha, p. r., pinto, c. a. l., alves, de moraes alves, c. a. x., paiva, i. b., & araujo, a. p. v. (2016). scleromyxedema: clinical diagnosis and autopsy findings. anais brasileiros de dermatologia, 91(5 suppl 1), 48–50. [11] popović, d., paravina, m., jovanović, d., karanikolić, v., & ljubisavljević, d. (2016). scleromyxedema (arndt-gottron syndrome): a case report. serbian journal of dermatology and venereology, 8, 28–38. [12] rongioletti, f., & rebora, a. (2001). updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema. journal of the american academy of dermatology, 44(2), 273–281. [13] basarab, t., burrows, n. p., munn, s. e., & russell jones, r. (1997). systemic involvement in scleredema of buschke associated with igg-kappa paraproteinaemia. british journal of dermatology, 136(6), 939–942. [14] chang, h. k., kim, y. c., & kwon, b. s. (2004). widespread scleredema accompanied with a monoclonal gammopathy in a patient with advanced ankylosing spondylitis. journal of korean medical science, 19, 481. [15] ho, m., patel, a., goh, c. y., moscvin, m., zhang, l., & bianchi, g. (2020). changing paradigms in diagnosis and treatment of monoclonal gammopathy of undetermined significance (mgus) and smoldering multiple myeloma (smm). leukemia, 34(12), 3111–3125. [16] barnes, m., kumar, v., le, t.-h., nabeel, s., singh, j., rana, v., kaell, a., & barnes, h. (2020). a case of paraproteinemia-associated scleredema successfully treated with doi 10.18502/sjms.v17i4.12553 page 563 sudan journal of medical sciences abubaker a. mohamedsharif et al thalidomide. jaad case reports, 6(10), 1039–1041. [17] rongioletti, f., kaiser, f., cinotti, e., metze, d., battistella, m., calzavara-pinton, p. g., damevska, k., girolomoni, g., andré, j, perrot, j.-l., kempf, w., cavelier-balloy, b. (2015). scleredema. a multicentre study of characteristics, comorbidities, course and therapy in 44 patients. journal of the european academy of dermatology and venereology, 29(12), 2399–2404. [18] rongioletti, f., & rebora, a. (2001). cutaneous mucinoses: microscopic criteria for diagnosis. american journal of dermatopathology, 23(3), 257–267. [19] könemann, s., hesselmann, s., bölling, t., grabbe, s., schuck, a., moustakis, c., de simoni, d., willich, n., & micke, o. (2004). radiotherapy of benign diseasesscleredema adultorum buschke. strahlentherapie und onkologie, 180(12), 811–814. [20] cole, g. w., headley, j., & skowsky, r. (1983). scleredema diabeticorum: a common and distinct cutaneous manifestation of diabetes mellitus. diabetes care, 6(2), 189– 192. [21] venencie, p. y., powell, f. c., su, w. p., & perry, h. o. (1984). scleredema: a review of thirty-three cases. journal of the american academy of dermatology, 11(1), 128–134. [22] keragala, b. s. d. p., herath, h. m. m. t. b., janappriya, g. h. d. c., dissanayaka, b. s., shyamini, s. c., liyanagama, d. p., balendran, t., constantine, s. r., & gunasekera, c. n. (2019). scleredema associated with immunoglobulin a-κ smoldering myeloma: a case report and review of the literature. journal of medical case reports, 13(1), 145. [23] tran, k., boyd, k. p., robinson, m. r., & whitlow, m. (2013). scleredema diabeticorum. dermatology online journal, 19(12), 20718. doi 10.18502/sjms.v17i4.12553 page 564 introduction case presentation discussion acknowledgments ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11452 production and hosting by knowledge e original article a comparative questionnaire-based study on learning styles and studying resources among undergraduate medical students in public and private universities khadija mahamadou1 and khalid a. awad2 1university of medical sciences and technology, khartoum, sudan 2department of anatomy, faculty of medicine, university of khartoum, khartoum, sudan orcid: khalid a. awad: https://orcid.org/0000-0002-2751-5050 abstract background: learning styles are circumstances beneath which learners most expeditiously and successfully understand, process, store, and recall what they are attempting to learn. the main goal of the current study was to compare different methods of study and learning style predilections amongst undergraduate mbbs students who attend public and private universities. methods: the current study was a descriptive cross-sectional research. data collected were obtained through a questionnaire filled by secondand third-year students in omdurman islamic university oiu (public) and university of medical sciences and technology – umst (private) using systematic random sampling. using the spss version 23 software, the data were analyzed and chi-square test was used to test the significance considering the α (alpha) level of significance as 0.05. results: the application of the chi-square test showed that there is no relation between the a method of study used and the students’ grades (p = 0.333). the most preferred learning style in oiu was found to be aural (60.0%), while in umst it was read/write (57.9%). the most preferred source of studying used in oiu was found to be extracourses (private courses given outside the university), whereas in umst it was found to be the teachers’ slides. conclusion: the most preferred learning style for public university was found to be aural while for private university it was found to read/write. this factor must be taken into consideration while teaching sessions are being conducted. interestingly, there was no statistical association between the study methodology and students’ grades. keywords: learning predilections, learning styles, studying methods, instructing techniques, teaching and learning 1. introduction learning can be defined as the relatively permanent change in an individual’s behavior which comprises their knowledge, skills, and attitude. this can involve studying, reading, memorization of facts or attending school, so as to find out about a subject [1]. learning how to cite this article: khadija mahamadou and khalid a. awad (2022) “a comparative questionnaire-based study on learning styles and studying resources among undergraduate medical students in public and private universities,” sudan journal of medical sciences, vol. 17, no. 2, pp. 170–182. doi 10.18502/sjms.v17i2.11452 page 170 corresponding author: khadija mahamadou; email: khalid-alamin@uofk.edu received 5 july 2020 accepted 21 may 2022 published 30 june 2022 production and hosting by knowledge e khadija mahamadou; khalid a. awad. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:khalid-alamin@uofk.edu https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences khadija mahamadou; khalid a. awad styles are circumstances beneath which learners most expeditiously and successfully understand, process, store, and recall what they are attempting to learn [2]. medical school is a unique learning environment as by the time of graduation, students are expected to attain many new skills ranging from taking blood to breaking bad news. in addition, they should be able to integrate skills with knowledge in order to diagnose patients. in the end, they are expected to find out what they need to study and master that material [3]. the learner’s preferred mode of learning characterizes their learning style. four modes of learning styles have been defined by neil – visual, auditory, read/write and kinesthetic (vark) learners [4]. the reason behind choosing this specific data collection tool is that the variables used here are derived from simple and actual events that happen in our daily life. viewed in this way, a study performed by fleming on the vark website showed that nearly 60% of the respondents tested the accuracy of its results, while 5% disagreed with its outcomes and the remainder said that they have no idea about their learning predilections [5]. it is essential that every medical teacher meets the educational needs of the students by assessing their learning preferences and developing an appropriate approach [6].the learning system in universities differs from the one found in schools where students are passive learners. with the constant emergence of new information, medical education requires lifelong learning in order to stay up-to-date. some of the undergraduate students suffer from a language barrier in the beginning in order to attain the best medical knowledge [3]. medical students often complain of studying hard but with no expected results, hence attention should be drawn to different methods of learning and studying to achieve the expected results [3]. the past decade has witnessed a change in medical education from being teachercentered to student-centered. different instruction techniques are being used at the preclinical level to target undergraduates with different learning styles. these range from teacher-centered instruction technique to providing real-life events in which students can learn and demonstration through videos as well as problem-based learning (pbl). the question of whether or not these methods are appealing and useful to students needs to be answered [6]. a number of studies have been done to address these issues. in sudan, kamil et al. conducted a study which showed that adopting an interactive method of lecturing enables the vital role of students in the learning process. they also found that adopting a bilingual type of instruction enhances the knowledge and encourages students’ contribution [7]. doi 10.18502/sjms.v17i2.11452 page 171 sudan journal of medical sciences khadija mahamadou; khalid a. awad the idea of learning styles has undergone indepth analysis in empirical literature in a trial to grasp the dynamic processes of learning [8]. keefe described a learning style as “the complex of intellectual, perceptible, and physiological characteristics that serve as relatively stable indicators of how a learner perceives, interacts, and responds to learning surroundings.” [8]. understanding undergraduates learning styles is crucial for lecturers, as every learning style needs different instructional materials. alignment of undergraduates’ learning styles and instructors’ instructing techniques increases the undergraduates’ understanding of the course content. numerous studies have been done to deal with this issue; one of which is a study among preclinical undergraduate medical students of the international medical university (imu) in kuala lumpur. this study showed that majority of students had unimodal (kinesthetic) learning style [9]. another study by ojeh et al., among preclinical medical students in barbados (2014) using the validated vark questionnaire, showed that most preclinical medicals students are multimodal learners [10]. furthermore, similar conclusions on learning styles have been reported by other studies [11–15]. in this study, we shed light on the different study methodologies and tools that students utilize. as it is already known, undergraduates have different learning predilections and these learning predilections should be addressed in order to attain the maximum knowledge during their medical course. some students attain results below their expectations despite their considerable efforts throughout the academic year. furthermore, with the shifting of medical education to be student-centered, their opinion should be taken into consideration. therefore, the main goal of the current study is to compare between public and private universities in terms of their learning predilections and studying methods. 2. materials and methods the current study is a descriptive, cross-sectional, comparative, questionnaire-based study conducted among students studying in omdurman islamic university (oiu) and the university of medical sciences and technology (umst). students studying in the second and third years at the faculty of medicine in oiu and umst were enrolled in the study. oiu is a government university located in the omdurman locality, khartoum state, sudan, while umst is a private university located in the khartoum locality, khartoum state, sudan. doi 10.18502/sjms.v17i2.11452 page 172 sudan journal of medical sciences khadija mahamadou; khalid a. awad 2.1. study sample sample size was calculated using the formula for known population, and the estimated sample size for oiu and umst were found to be 207 and 146, respectively. using the stratified sampling technique, the number of second-year students who participated in this study was 92 from umst and 102 from oiu, while those in the third year were 54 (umst) and 105 (oiu). 2.2. data collection data were collected using two questionnaires. 1. vark which symbolizes visual, aural, read/write, and kinesthetic sensory modalities that are applied to profile learning predilections. the version applied was the vark version 7.8 developed by fleming (http://vark-learn.com) [5] comprising 16 questions. the completed vark questionnaire was then evaluated online. 2. a written questionnaire was used to obtain the demographical characteristics such as location, age, gender, year in which they are studying and their study methodology. after gaining informed consent, hard copies of two questionnaires were distributed. the participants were then invited to respond to the questionnaires anonymously or to write their names if they wished to get their vark results. a) data analysis data were analyzed through the spss version 23 software, and chi-square test was used to test the significance, taking α (alpha) level of significance as 0.05 per statistical convention. the results were generated in the form of charts, tables, and graphs. 3. results out of the 353 questionnaires that were given, 336 were completely filled and returned (95.2% response rate). students from umst were 146 (43.5%) and 190 (56.5%) students were from oiu. the age of the participants ranged between 16 and 24 years, while the mean age was 18.95 ± 1.186 years. among the participants, 60 (18%) were male and 273 (82%) were female. regarding the academic year, 183 (55.1%) were in second year while 149 (44.9%) were third-year participants (table 1; figure 1). doi 10.18502/sjms.v17i2.11452 page 173 sudan journal of medical sciences khadija mahamadou; khalid a. awad regarding students’ perception on whether their grades are affected by the way they study, figure 2 shows that 86.8% of students agreed that their method of study does affect their grades while 13.2% disagreed. most students agreed that the best method to study was by both understanding and memorizing (85.4%), and stated that they revise what they studied twice (42.8%). most students preferred teaching to be in english language (58.1%). moreover, 53.5% of the students agreed that case-based learning (cbl) and problem-based learning (pbl) should be increased. of the total students, 64.7% agreed that tutorials should be improved and suggested that they should be done in smaller groups, include past exams with more interaction between students and teachers in addition to the outlines of the tutorial being given beforehand (a day before). regarding seminars, 78.1% of students believed that they are useful while 21.8% did not (table 2). most of the students, regardless of their grades (distinction, very good, good, pass, and fail) agreed that their grades are affected by their method of study. however, no statistical association was found between the study methodology and students’ grades (p-value = 0.333) (table 3). the vark questionnaire results showed that the most preferred learning modality for oiu was found to be unimodal (aural), while the preferred learning modality for umst was found to be read/write (table 4). while comparing the study methodologies between umst and oiu, a co-variable (the best way student obtain information, that is, study resource) was used to determine the method of study. table 5 shows that the most preferred study methodology in the oiu was extra-courses (81.5%) followed by peers (66.2%). however, contrastingly, the umst students chose teachers’ slides (46.5%) followed by videos (44.8%). 4. discussion in this study, while determining students’ study methodology, it was found that the english language was the most preferred instructional language which contradicts kamil et al.’s study [7] conducted in sudan that suggested that bilingual instruction attracts students attention. this contrast may be justified by the fact that most students in the current study had studied in english medium throughout their higher secondary school education. concerning the tutorials, a majority of participants agreed that they need improvement in many ways. this contradicts kamil et al.’s [7] study in which most students agreed that tutorials were useful. this difference could be explained by the fact that the doi 10.18502/sjms.v17i2.11452 page 174 sudan journal of medical sciences khadija mahamadou; khalid a. awad table 1: the demographic characteristics of the study participants. demographics (n = 336) n frequency percentage gender 333 (3 missing) male 60 18 female 273 82 location 336 umst 146 43.5 oiu 190 56.5 academic year 332 (4 missing) year 2 183 55.1 year 3 149 44.9 figure 1: the age distribution of the study participants (n = 333). tutorial sessions in the studied universities were not very interactive. somehow tutorials turned into a lecture on the same topic that was explained in the original lecture, and students therefore lost interest and felt as though it was a repetition of the same topic. in addition, this study showed that students were pleased with seminars while in the study of khane and joshi [6], it was least preferred. perhaps, environment or ethnic background play a role in this distinction, and further research is needed in this area. doi 10.18502/sjms.v17i2.11452 page 175 sudan journal of medical sciences khadija mahamadou; khalid a. awad figure 2: students’ perception on whether their method of study affects their grades. students can use a variety of modes for learning; however, one mode can be dominant and preferred or there can be equal preference for one or more modes. the majority of university lecturers assume that the reason behind students’ educational poor performance is the lack of hard work and study; however, this poor performance could occur due to a discrepancy between students’ learning styles and instructors’ instructing method. in view of this, one of the important factors for applicable education is to look at students’ learning styles at the start of every academic year and apply pertinent instructing technique accordingly [11]. in light of this, while comparing a public (oiu) university with a private one (umst), the preferred learning modality for oiu students was found to be aural which is not the same as preferred learning method (kinesthetic) found in a public university by jmanai et al. [14]. with regards to umst, the results were also not in line with that of joshi et al. in their study, which was done in a private university, it was found that the preferred learning style was multimodal [15], which contradicts the results obtained in this study, in which the dominant style was unimodal (read/write). however, shahrakipour et al.’s study [11] showed the same results. interestingly, learning styles show variations among different schools, and educators need to assess their students’ learning styles in teaching and learning and in discussing examination results. nowadays, students have access to various study resources [16]. in the present study, students, depending on whether they were from a government or a private school, described different study resources. extra-courses and peers were the most used resources in the oiu, which may reflect the effect of increase emigration of expert doi 10.18502/sjms.v17i2.11452 page 176 sudan journal of medical sciences khadija mahamadou; khalid a. awad table 2: students’ reflections on study methodology and some instructional methods. the best method to study (n = 335) (1 missing) frequency percentage by understanding 40 11.9 by memorization 9 2.7 both 286 85.4 number of times they revise what they have studied (n = 334) (2 missing) once 103 30.8 twice 143 42.8 three 49 14.7 others 39 11.7 preferred instructional language (n = 334) (2 missing) / english 194 58.1 arabic 7 2.1 both 133 39.8 problem-based learning/case-based learning in the curriculum (n = 327) (9 missing) satisfactory 122 37.3 should be increased 175 53.5 should be decreased 30 9.2 tutorials in the curriculum (n = 334) (2 missing) satisfactory 118 35.3 need improvements 216 64.7 interactive sessions between students and teachers 66 include assignment and past exams 43 omit tutorials 30 outline about the topic prior to tutorial 27 increase tutorials 33 taken seriously by students 17 seminars in the curriculum (n = 331) (5 missing) yes 259 78.2 no 72 21.8 academic staff in sudanese public schools [17]. at umst, students relied mainly on teachers‘ slides and videos indicating the different study resources seen in medical schools. in line with the results of umst students, a survey-based study done in australia showed dependence on traditional resources such as lecture notes and textbooks in addition to e-learning resources such as videos [18]. medical school administrators, teachers, and students should keep in mind the increasing use of e-learning resources [19]. doi 10.18502/sjms.v17i2.11452 page 177 sudan journal of medical sciences khadija mahamadou; khalid a. awad table 3: students’ perception on whether their method of study affects their grades. students’ perception on whether their method of studying affects their grades total yes no overall grades in last exam excellent 11.3% count 35 3 38 % within over all grades in last exam 92.1% 7.9% 100.0% good 41.2% count 120 18 138 % within over all grades in last exam 87.0% 13.0% 100.0% pass 36.4% count 104 15 119 % within over all grades in last exam 87.4% 12.6% 100.0% fail 10.1% count 26 8 34 % within over all grades in last exam 76.5% 23.5% 100.0% very good 0.9% count 3 0 3 % within over all grades in last exam 100.0% 0.0% 100.0% total count 288 44 332 % within over all grades in last exam 86.7% 13.3% 100.0% p-value = 0.333. 4.1. strengths and limitations the strength of this study is that in contrast to most previous studies, we compared the learning styles and study methodologies between the students of public and private medical universities. the limitation of this study is that it did not include males from the oiu. the faculty of medicine is divided into two sections, males and females, respectively. the permission was sought from female section only. 5. conclusion the most preferred learning style for a public university was found to be aural while for a private university it was read/write. this factor must be taken into consideration doi 10.18502/sjms.v17i2.11452 page 178 sudan journal of medical sciences khadija mahamadou; khalid a. awad table 4: vark results among students of oiu and umst. location total umst oiu vark results vark count 28 41 69 % within vark results 40.6% 59.4% 100.0% vak count 8 11 19 % within vark results 42.1% 57.9% 100.0% var count 2 2 4 % within vark results 50.0% 50.0% 100.0% vrk count 4 4 8 % within vark results 50.0% 50.0% 100.0% ark count 4 3 7 % within vark results 57.1% 42.9% 100.0% vk count 6 5 11 % within vark results 54.5% 45.5% 100.0% ar count 3 8 11 % within vark results 27.3% 72.7% 100.0% rk count 2 2 4 % within vark results 50.0% 50.0% 100.0% ak count 5 13 18 % within vark results 27.8% 72.2% 100.0% vr count 2 3 5 % within vark results 40.0% 60.0% 100.0% va count 1 5 6 % within vark results 16.7% 83.3% 100.0% a count 28 42 70 % within vark results 40.0% 60.0% 100.0% k count 32 31 63 % within vark results 50.8% 49.2% 100.0% r count 11 8 19 % within vark results 57.9% 42.1% 100.0% v count 10 12 22 % within vark results 45.5% 54.5% 100.0% total count 146 190 336 % within vark results 43.5% 56.5% 100.0% while teaching sessions are being conducted. with regards to study resources, publicuniversity students relied on courses whereas the private-university students preferred teachers’ slides. interestingly, there was no association between the method of study and students’ grade. doi 10.18502/sjms.v17i2.11452 page 179 sudan journal of medical sciences khadija mahamadou; khalid a. awad table 5: comparison between study methodologies of umst and oiu students. location total umst oiu study resource teachers slides count 92 106 198 % within study resource 46.5% 53.5% references count 87 132 219 % within study resource 39.7% 60.3% videos count 108 133 241 % within study resource 44.8% 55.2% courses count 10 44 54 % within study resource 18.5% 81.5% peers count 26 51 77 % within study resource 33.8% 66.2% total count 323 466 789 acknowledgments the authors would like to thank the university administration of oiu and umst for their help in completing this research. they would also like to thank dr. mohammed hamza for raising a number of interesting points of discussion and possible future research directions. also, thanks are extended to mrs. sally baraka for proofreading this article. furthermore, authors would like to thank all students who participated in this study. ethical considerations the study protocol was approved by the research technical and ethical committee at the faculty of medicine, umst. it was also sought from the administration of faculty of medicine, oiu. in addition, the participants were assured confidentiality and given the option to participate in the study. students’ privacy and confidentiality were maintained. competing interests none. doi 10.18502/sjms.v17i2.11452 page 180 sudan journal of medical sciences khadija mahamadou; khalid a. awad availability of data and materials all data and materials associated with this study are available through the corresponding author upon reasonable request. funding none. references [1] aba english. (2019). what is the difference between learn and study? [web log post]. retrieved from: https://blog.abaenglish.com/what-is-the-difference-betweenlearn-and-study [2] salah, a. t., alameen, m. g., elsheikh, n., et al. (2015). type of high secondary school (governmental vs. private) and type of high secondary school certificate (sudanese vs. arabian): do they affect learning style? sudan journal of medical sciences, vol. 10, no. 3. [3] ] evans, d and brown, j. (2009). how to succeed at medical school (2𝑛𝑑 ed.). wileyblackwell. [4] almigbal, t. h. (2015). relationship between the learning style preferences of medical students and academic achievement. saudi medical journal, vol. 36, no. 3, p. 349. [5] vark. (n.d.). the vark questionnaire. retrieved from: http://vark-learn.com/the-varkquestionnaire/ [6] khane, r. s. and joshi, a. a. (2014). a questionnaire based survey from first year mbbs students about teaching learning methods of physiology in private medical college. medical science, vol. 3, no. 2. [7] kamil, a. i. and kheder, s. i. (2015). methods of instruction in the national university: preferences, opinions, and students’ perception (2014–2015). sudan medical monitor, vol. 10, no. 4, p. 117. [8] keefe, j. w. (ed.). (1987). learning style: theory and practice. reston, usa: national association of secondary school principals. [9] liew, s. c., sidhu, j., and barua, a. (2015). the relationship between learning preferences (styles and approaches) and learning outcomes among pre-clinical undergraduate medical students. bmc medical education, vol. 15, no. 1, p. 44. doi 10.18502/sjms.v17i2.11452 page 181 sudan journal of medical sciences khadija mahamadou; khalid a. awad [10] ojen, n., sobers-grannumna, n., gauru, u., et al. (2017). learning style preferences: a study of pre-clinical medical students in barbados. journal of advances in medical education & professionalism, vol. 5, no. 4, p. 185. [11] shahrakipour, m., arbabisarjou, a., zare, s., et al. (2017). learning styles in students of medical sciences. global journal of health science, vol. 9, no. 2, pp. 192–200. [12] rahman, s. m., alam, t., alam, n. n., et al. (2017). medical undergraduates preference in learning style: a single-institute experience from bangladesh. kuwait medical journal, vol. 49, no. 1, pp. 12–16. [13] soundariya, k., deepika, v., and kalaiselvan, g. (2017). a study on the learning styles and learning approaches among medical students. national journal of physiology, pharmacy and pharmacology, vol. 7, no. 10, p. 1020. [14] jamani, n. a., abdaziz, k. h., ab karim, h. s., et al. (2018). learning style preferences among pre-clinical medical students in a public university in pahang. age, vol. 21, pp. 0–84. [15] joshi, a., prabhakaran, a., ganjiwale, j., et al. (2018). identification of learning styles in 1st year undergraduate mbbs students of a private medical school in western india. national journal of physiology, pharmacy and pharmacology, vol. 8, no. 1, pp. 102–6. [16] baudains, c., metters, e., easton, g., et al. (2013). what educational resources are medical students using for personal study during primary care attachments? education for primary care. , vol. 24, no. 5, pp. 340–345. [17] abdall, s. z. (2016). quality assurance in sudanese higher education: current status and challenges ahead. journal of total quality management, vol. 17, no. 1, pp. 1–18. [18] wynter, l., burgess, a., kalman, e., et al. (2019). medical students: what educational resources are they using? bmc medical education, vol. 19, no. 1, p. 36. [19] romanov, k. and aarnio, m. (2006). a survey of the use of electronic scientific information resources among medical and dental students. bmc medical education, vol. 6, no. 1, p. 28. doi 10.18502/sjms.v17i2.11452 page 182 introduction materials and methods study sample data collection results discussion strengths and limitations conclusion acknowledgments ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 13, issue no. 1, doi 10.18502/sjms.v13i1.1684 production and hosting by knowledge e research article an 8-year retrospective review of gastrointestinal medical emergency conditions at a tertiary health facility in nigeria oguntoye oluwatosin oluwagbenga and yusuf musah mbbs, fwacp(gastroenterol), consultant gastroenterologist, department of internal medicine, afe babalola university ado-ekiti/federal teaching hospital, ido-ekiti, ekiti state, nigeria mbbs, fmcp (nigeria), consultant gastroenterologist, department of internal medicine, afe babalola university ando-ekiti/federal teaching hospital, ido-ekiti, ekiti state, nigeria abstract background: globally, gastrointestinal emergency conditions constitute a considerable proportion of the medical emergency cases seen in the emergency room. objective: this study investigated the spectrum of gastrointestinal medical emergency conditions seen in the emergency room of federal teaching hospital ido-ekiti, nigeria. materials and methods: the emergency room admission register was used to obtain the following information: age, sex, diagnosis, year of admission and the outcome. the period under review was 1st january 2009 to 31st december 2016. the data was analyzed using the spss version 21.0 software package. results: a total number of 5,912 patients with medical emergency conditions were admitted into the emergency room during the period under review, out of which 813(13.7%) were gastrointestinal medical emergency conditions. the age range of the patients was 15 to 100years with a mean(±sd) of 47.32±18.938. acute exacerbation of acid peptic disorders(29.3%) was the most common indication for emergency room admission followed by acute gastroenteritis(26.8%) and decompensated chronic liver disease(14.3%). decompensated chronic liver disease and upper gastrointestinal bleeding were the conditions with the highest mortality being 31.8% and 29.5% respectively. conclusion: gastrointestinal medical conditions are common indications for emergency admission. measures should be taken to avoid these preventable conditions in a bid to reduce their morbidity and mortality. keywords: gastrointestinal, medical, emergency room how to cite this article: oguntoye oluwatosin oluwagbenga and yusuf musah, (2018) “an 8-year retrospective review of gastrointestinal medical emergency conditions at a tertiary health facility in nigeria,” sudan journal of medical sciences, vol. 13 (2018), issue no. 1, 1–11. doi 10.18502/sjms.v13i1.1684 page 1 corresponding author: oguntoye oluwatosin oluwagbenga; email: proflast@yahoo.com received 15 december 2017 accepted 25 february 2018 published 14 march 2018 production and hosting by knowledge e oguntoye oluwatosin oluwagbenga and yusuf musah. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:proflast@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah 1. introduction globally, gastrointestinal emergency conditions constitute a considerable proportion of the medical emergency cases seen in the emergency room of health institutions [1–5]. the gastrointestinal system can be affected by various disease pathological processes which could be infectious, non-infectious or neoplastic in nature and these disease conditions can present as medical or surgical emergencies [6]. awareness and knowledge of the spectrum of gastrointestinal medical emergency conditions in our environment will help in proper healthcare planning, policy making and provision of the required essential health services in the emergency room to reduce the morbidity and mortality associated with them. there is paucity of data in the literature as regards the spectrum and incidence of the gastrointestinal medical emergency conditions seen in nigerian health institutions. this study is aimed at determining the spectrum of the various gastrointestinal medical emergency conditions seen in the emergency room of federal teaching hospital, idoekiti, nigeria. it is an eight-year retrospective study of cases seen from 1st january 2009 to 31st december 2016. 2. materials and methods 2.1. study location and data collection this is a retrospective study that was carried out at the emergency room of federal teaching hospital, ido-ekiti, ekiti state, nigeria. the hospital is situated in ido-osi local government area (lga) of ekiti state. ekiti state is one of the 36 states of the federal republic of nigeria located in the southwest sub-region with an estimated population of 2,384,212 people, while ido-osi lga, a rural setting, has an estimated population of 159,114 people. the hospital was established in 1998 as a federal medical centre that provides secondary care services and was later upgraded to the status of a teaching hospital in 2015 after being affiliated with afe babalola university ado-ekiti, ekiti state for the training of medical and nursing students. the hospital has 179 beds with 18 clinical departments and 73 consultants (specialists). it provides residency training in internal medicine, sugery, obstetrics and gyanaecology and paediatrics departments. it provides tertiary care services for people in ekiti state and adjourning parts of kwara, osun, ondo and kogi states. doi 10.18502/sjms.v13i1.1684 page 2 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah the emergency room admission register was reviewed for the data from 1st january 2009 to 31st december 2016. age, sex, diagnosis, year of admission and the outcomes were collected. the inclusion criteria: patients who were admitted into the emergency room of the hospital within the period under review with any gastrointestinal medical emergency condition. exclusion criteria: those who were admitted outside the period under review, those with other medical and surgical conditions and those who were brought in dead on arrival. the data of 813 study subjects was used for the study. ethical approval was obtained from the ethics and research committee of the institution. 2.2. data analysis the data obtained was analyzed using the statistical package for the social sciences (spss) version 21.0 (spss chicago inc. il u.s.a). descriptive statistics used included frequency tables, means and standard deviations. 3. results a total number of 5,912 patients with medical emergency conditions were admitted into the emergency room during the period under review, out of which 813(13.7%) were gastrointestinal medical emergency conditions. they were 442(54.4%) males and 371(45.6%) females with a male to female ratio of 1.2 to 1. the age range of the patients was 15 to 100 years with a mean (±sd) of 47.32 (±18.938). the patients aged 65years and above had the highest number of admissions [189 (23.2%)] while patients aged 15 to 24 years constituted the lowest number of admissions [85 patients(10.5%)] as shown in figure 1. figure 2 depicts the number of gastrointestinal medical emergency conditions admitted annually from 2009 to 2016. the highest number of admissions was in 2012 [160 patients (19.7%)] while the lowest was in 2015 [45 patients (5.5%)] with a mean (±sd) of 101.62 (±42.775) admissions per year. majority of the patients [423 (52.0%)] were subsequently admitted to the medical wards for further care after receiving initial emergency care in the emergency room over a variable period of time usually lasting from a few hours to 48hours. 303 (37.3%) patients whose conditions resolved after the initial emergency care were discharged doi 10.18502/sjms.v13i1.1684 page 3 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah figure 1: age group distribution of the study population. from the emergency room to the gastroenterology and hepatology specialist clinic for further follow-up. the five possible outcomes for every patient admitted into our emergency room were ward admission, discharged home, referred to another hospital, discharged against medical advice or death. the outcome from this study is as shown in table 1. sixteen (2.0%) patients were referred for various reasons from the emergency room to other tertiary hospitals usually located in an urban community while 27(3.3%) patients discharged themselves against medical advice. the mortality rate in the emergency room from gastrointestinal medical emergency conditions was 5.4%. acute exacerbation of acid peptic disorders (29.3%) were the most common indications for emergency room admission. these conditions include acute gastritis from non-steroidal anti-inflammatory drugs (nsaids) use or consumption of herbs or toxic substances; peptic ulcer disease (pud) and gastroesophageal reflux disease (gerd) among others. majority (52.1%) of these patients were subsequently admitted to the adult medical wards for further care. doi 10.18502/sjms.v13i1.1684 page 4 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah figure 2: annual number of admitted cases from 2009 – 2016. acute gastroenteritis was the second most common indication for emergency room admission followed by decompensated chronic liver disease being 26.8% and 14.3% respectively. hepatic abscess was the least commonly seen condition in this study. decompensated chronic liver disease and upper gastrointestinal bleeding were the conditions that carried the highest mortality being 31.8% and 29.5% respectively. 4. discussion globally, gastrointestinal emergency conditions constitute a considerable proportion of the medical emergency cases seen in the emergency room of health institutions [1–5]. in this study, elderly patients aged 65years and above were the most common age population seen; this is reflective of the fact that the hospital is located in a rural environment which is predominantly made up of the elderly. the community is a retirement home for indigenes after many years of service in an urban community. the total number of gastrointestinal medical emergency admissions in this study was quite low when compared with similar studies [1–3]. this could be due to a number doi 10.18502/sjms.v13i1.1684 page 5 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah outcome diagnosis ward admission discharged referred dama died total % exacerbation of apd 124 94 4 11 5 238 29.3 ugib 65 15 2 1 13 96 11.8 acute gastroenteritis 72 133 2 8 3 218 26.8 food poisoning 2 4 0 1 0 7 0.9 acute diarrhoea 8 11 0 1 1 21 2.6 chronic diarrhoea 10 3 0 0 0 13 1.6 dysentery 1 3 0 0 2 6 0.7 typhoid fever 14 22 1 1 1 39 4.8 acute abdominal pain 14 6 0 0 0 20 2.5 abdominal tuberculosis 4 1 0 0 1 6 0.7 acute viral hepatitis 6 2 0 0 2 10 1.2 acute cholecystitis 4 0 0 0 0 4 0.5 decompensated cld 85 7 6 4 14 116 14.3 hepatocellular carcinoma 13 2 1 0 2 18 2.2 liver abscess 1 0 0 0 0 1 0.1 total 423 303 16 27 44 813 100.0 key: dama: discharge against medical advice, apd: acid peptic disorders, ugib: upper gastrointestinal bleeding, cld: chronic liver disease. t 1: diagnosis and outcome of the patients admitted to the emergency room. of factors which include the fact that the hospital is located in a rural environment which has a small population compared to an urban community. also, the low educational status of the populace and preference of traditional remedies to orthodox treatment are contributory. the poor socio-economic status of the residents also prevents them from patronizing the hospital considering the cost of services and treatment which they cannot afford. majority of the residents are self-employed; artisans, farmers and traders and they are not registered under the national health insurance scheme which would have considerably reduced the cost of accessing care in the hospital. the other factors that discourage high patronage include frequent industrial actions by various professional groups among the health care workers which were quite significant in the year 2015; thus the least number of admissions was recorded in that doi 10.18502/sjms.v13i1.1684 page 6 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah year. also, non-availability of facilities for optimal care of these patients necessitating referral to other tertiary hospitals. in this study, acute exacerbation of acid peptic disorders was the most common indication for emergency admission (29.3%) but the specific type was not yet ascertained since an upper gastrointestinal endoscopy was not done. the prevalence of helicobacter pylori infection is high in nigeria [7]. jemilohun et al reported a prevalence of 64% among patients with dyspepsia in ibadan, nigeria [8]. its prevalence has been documented in the literature to be high in developing countries, and associated with low levels of education, dwelling in a rural environment, low social economic status, and poor sanitation [7]. these risk factors were present in our study population and may explain their high admission rate for acid peptic disorders considering that majority of our patients could be harboring helicobacter pylori. various factors could have been responsible for precipitating the acute exacerbations our patients had and these include consumption of herbs which is common practice among rural dwellers, use of non-steroidal anti-inflammatory drugs for relief of musculoskeletal pain which could arise from farming activities and/or rheumatologic conditions such as osteoarthritis which is very common among the elderly. also many of the elderly patients may have various cardiovascular risk factors necessitating long term aspirin (75mg) use which is also a risk factor for acute exacerbation among other factors [9]. the mortality from acute exacerbation of acid peptic disorders in this study (11.4%) could have been from complications such as peritonitis as a result of perforated viscus and from upper gastrointestinal haemorrhage. ogah et al in a 2-year retrospective review of medical admissions at the emergency unit of federal medical centre, abeokuta, nigeria in which a total of 2,377 patients were admitted; 159(6.7%) of them had gastrointestinal medical emergencies out of which 123(77.4%) had acid peptic disorders making it the commonest indication for admission followed by chronic liver disease[21 patients(13.2%)]. these findings were similar to what was found in our study. decompensated chronic liver disease was the third most common indication for emergency admission in our study; the primary aetiology is likely due to chronic hepatitis b virus infection. chronic hepatitis b virus infection is highly prevalent in sub-saharan africa and south-east asia with an average prevalence rate of 13.7% in nigeria (about 23 million nigerians are hbsag positive).10,11 the other common causes of chronic liver disease in nigeria are alcoholic liver disease, chronic hepatitis c virus infection, alpha-1-antitrypsin deficiency and non-alcoholic fatty liver disease. the other causes are less common [12]. doi 10.18502/sjms.v13i1.1684 page 7 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah features of decompensation include ascites, jaundice, hypoalbuminaemia, coagulopathy, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, portopulmonary hypertension, hepatic hydrothorax, upper gastrointestinal bleeding which could be variceal or non-variceal and malignant transformation to hepatocellular carcinoma among others [12]. these features are poor prognostic indices for the patients and liver transplantation is the only hope of long term survival for them; therefore it is not surprising that decompensated chronic liver disease was the commonest cause of mortality (31.8%) in this study. upper gastrointestinal bleeding was the second commonest cause of mortality in this study (29.5%). upper gastrointestinal bleeding is traditionally defined as bleeding from the gastrointestinal tract that is proximal to the ligament of treitz [13]. risk factors include use of nsaids, aspirin, alcohol consumption, cigarette smoking, acid peptic disorders and chronic liver disease among others [13–15]. upper gastrointestinal bleeding is a potentially fatal condition with a mortality rate of 6%-13% in the literature despite advances in critical care monitoring and support [16]. rukewe et al at the university college hospital ibadan, nigeria reported a mortality rate of 13.6% among patients with upper gastrointestinal bleeding over a 2-year period [13]. the mortality rate from our study was higher. discharge against medical advice (dama) was a relatively common practice among our study population. this is usually as a result of poverty, illiteracy, low socioeconomic class, preference for traditional remedies. occasionally it could also be due to lack of the expected clinical improvement or dissatisfaction with the hospital environment. the referral rate of 2.0% from our study could have been as a result of various reasons ranging from non-availability of the required investigative equipment or hospital consumables to lack of space for admission, on-going industrial action by health care workers and patients request for referral among others. the emergency room mortality rate from gastrointestinal diseases in this study was 5.4% and this could have been due to various factors including late presentation of the patient to the emergency room and inadequate emergency resuscitative facilities including medications. a significant number of patients in this study were managed and discharged from the emergency room (37.3%) without requiring further admission to the wards. this could suggest that such cases were not major and/or that gastrointestinal medical conditions responds well when early and appropriate treatment measures are instituted. doi 10.18502/sjms.v13i1.1684 page 8 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah 5. limitation this study was conducted using the emergency room admission register which usually contain limited amount of information unlike the case notes of the individual patients which would have provided more detailed clinical information particularly if the patients’ medical records are available in an electronic format for easy assessment and would also allow for retrospective review of cases of over a much longer period. 6. conclusion acute exacerbation of acid peptic disorders, acute gastroenteritis and decompensated chronic liver disease in that order were the commonest indications for emergency admission. decompensated chronic liver disease was the commonest cause of mortality. there is therefore a need to enhance public enlightenment about avoidance of the risk factors for these preventable gastrointestinal conditions in a bid to reduce the morbidity and mortality associated with them. 7. acknowledgement special thanks to the house officers and residents of internal medicine department, federal teaching hospital, ido-ekiti, nigeria for their support towards making this research a success. 8. funding the authors bore the entire cost of the research and did not receive any financial support from any organization. 9. conflict of interest disclosure the authors declared no conflicts of interest. references [1] ogah os, akinyemi ro, adesemowo a and ogbodo ei. a two-year review of medical admissions at the emergency unit of a nigerian tertiary health facility. doi 10.18502/sjms.v13i1.1684 page 9 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah afr. j. biomed. res. 2012; 15: 59 – 63. [2] odenigbo cu and oguejiofor oc. pattern of medical admissions at the federal medical centre, asaba a two year review. niger j clin pract. 2009; 12: 395-397. [3] ogun sa, adelowo oo, familoni ob, jaiyesimi ae and fakoya ea. pattern and outcome of medical admissions at the ogun state university teaching hospital, sagamu a three year review. west afr j med. 2000; 19: 304-308. [4] lewis j, bilker w and brensinger c. hospitalization and mortality rates from peptic ulcer disease and gi bleeding in the 1990s: relationship to sales of nonsteroidal anti-inflammatory drugs and acid suppression medications. am j gastroenterol. 2002; 97: 2540-2549. [5] rockhall ta, logan rf, devlin hb and northfield tc. incidence of and mortality from acute upper gastrointestinal haemorrhage in the united kingdom. steering committee and members of the national audit of acute upper gastrointestinal haemorrhage. bmj. 1995; 311:222-226. [6] bloom s, webster g and marks d ed. emergencies. in oxford handbook of gastroenterology and hepatology. 2nd edition. oxford univeristy press 2012; section 5: 563-597. [7] hameed l, onyekwere ac, otegbayo ja and abdulkareem fb. a clinicopathological study of dyspeptic subjects in lagos, nigeria. gastroenterol insights 2012;4:e11. [8] jemilohun ac, otegbayo ja, ola so, oluwasola oa and akere a. prevalence of helicobacter pylori among nigerian patients with dyspepsia in ibadan. pan african medical journal 2011; 6:18-25. [9] nwokediuku s, omuemu c and akere a. guidelines for the management of dyspepsia and gastroesophageal reflux disease. nigerian journal of gastroenterology and hepatology 2015; 7(2):93-108. [10] malu ao, borodo mm, ndububa da, ojo os, anomneze ee, lesi oa et al. hepatitis b and c treatment guidelines for nigeria 2015. nigerian journal of gastroenterology and hepatology 2015;7(2):63-75. [11] musa bm, bussell s, borodo mm, samaila aa and femi ol. prevalence of hepatitis b virus infection in nigeria, 2000-2013: a systematic review and meta-analysis. niger j clin pract. 2015;18:163-172. [12] ndububa d, ojo o, lesi o, samaila a and ngim o. management of hepatocellular carcinoma. nigerian journal of gastroenterology and hepatology 2015;7(2):77-92. [13] rukewe a, otegbayo ja and fatiregun a. clinical characteristics and outcome of patients with upper gastrointestinal bleeding at the emergency department of a doi 10.18502/sjms.v13i1.1684 page 10 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga and yusuf musah tertiary hospital in nigeria. annals of ibadan postgraduate medicine 2015; 13(2): 24-28. [14] ajayi ao, adegun pt, ajayi ea, solomon oa, adeoti ao and akolawole ma. aetiology and management outcome of upper gastrointestinal bleeding in adult patients presenting at ekiti state university teaching hospital, ado-ekiti, nigeria. greener journal of medical sciences 2013; 3(3):93-97. [15] mellemkjaer l, blot wj and sørensen ht. upper gastrointestinal bleeding among users of nsaids: a population-based cohort study in denmark. br j clin pharmacol. 2002; 53:173-181. [16] holster il and kuipers ej. management of acute nonvariceal upper gastrointestinal bleeding: current policies. world j gastroenterol. 2012;18(11): 1202-1207. doi 10.18502/sjms.v13i1.1684 page 11 introduction materials and methods study location and data collection data analysis results discussion limitation conclusion acknowledgement funding conflict of interest disclosure references sudan journal of medical sciences volume 17, issue no. 3, doi 10.18502/sjms.v17i3.12125 production and hosting by knowledge e research article computational screening of repurposed drugs targeting sars-cov-2 main protease by molecular docking yow hui yin1,2 and tang yin-quan2,3* 1school of pharmacy, faculty of health and medical sciences taylor’s university, subang jaya, malaysia 2centre for drug discovery and molecular pharmacology (cddmp), faculty of health and medical sciences, taylor’s university, subang jaya, malaysia 3school of biosciences, faculty of health and medical sciences taylor’s university, subang jaya, malaysia orcid: tang yin-quan: https://orcid.org/0000-0001-7327-2830 yow hui yin: https://orcid.org/0000-0002-9455-0817 abstract background: covid-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome coronavirus type 2 (sars-cov-2), which poses significant global health and economic crisis that urges effective treatment. methods: a total of 11 molecules (baricitinib, danoprevir, dexamethasone, hydroxychloroquine, ivermectin, lopinavir, methylprednisolone, remdesivir, ritonavir and saridegib, ascorbic acid, and cepharanthine) were selected for molecular docking studies using autodock vina to study their antiviral activities via targeting sars-cov’s main protease (mpro), a cysteine protease that mediates the maturation cleavage of polyproteins during virus replication. results: three drugs showed stronger binding affinity toward mpro than n3 (active mpro inhibitor as control): danoprevir (–7.7 kcal/mol), remdesivir (–8.1 kcal/mol), and saridegib (–7.8 kcal/mol). two primary conventional hydrogen bonds were identified in the danoprevir-mpro complex at glya:143 and glna:189, whereas the residue glua:166 formed a carbon–hydrogen bond. seven main conventional hydrogen bonds were identified in the remdesivir at asna:142, sera:144, cysa:145, hisa:163, glua:166, and glna:189, whereas two carbon–hydrogen bonds were formed by the residues hisa:41 and meta:165. cepharanthine showed a better binding affinity toward mpro (–7.9 kcal/mol) than ascorbic acid (–5.4 kcal/mol). four carbon–hydrogen bonds were formed in the cepharanthine-mpro complex at hisa:164, proa;168, glna;189, and thra:190. conclusion: the findings of this study propose that these drugs are potentially inhibiting the sar-cov-2 virus by targeting the mpro protein. keywords: repurposed drug, covid-19, mpro, docking how to cite this article: yow hui yin and tang yin-quan (2022) “computational screening of repurposed drugs targeting sars-cov-2 main protease by molecular docking,” sudan journal of medical sciences, vol. 17, issue no. 3, pages 387–400. doi 10.18502/sjms.v17i3.12125 page 387 corresponding author: tang yin-quan; email: yinquan.tang@taylors.edu.my received 22 february 2022 accepted 29 july 2022 published 30 september 2022 production and hosting by knowledge e yow hui yin, tang yin-quan. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences yow hui yin, tang yin-quan 1. introduction the outbreak of novel coronavirus disease (covid-19) back in december 2019 confronts a global health crisis due to its fast transmission and mutation nature, and the lack of definitive treatment. to date, over 328 million cases have been reported with more than 5.55 million deaths [1]. this disease is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the symptoms extend from mild to severe illness, including acute respiratory distress syndrome and severe pneumonia that requires intensive care admission [2]. the vaccination program has been driven and accelerated globally in the past one year to control this devastating covid-19 pandemic, approximately 60% of the world population received at least one dose of the vaccine [3]. a full vaccination has been reported to reduce disease transmission, hospitalization, and mortality [4]. however, this is complicated with the abilities of sar-cov-2 to mutate and diminish the effectiveness of vaccines, particularly the recent emergence of the fast-spreading omicron variant [5]. hence, an effective and potent treatment is still needed in combating this disease. drug repurposing is a promising area in drug discovery to identify novel therapeutic indications for previously studied drugs. it offers a great opportunity for drug discovery by reducing the drug development timeline and cost, as well as overcoming the high attrition rate from the de novo drug discovery process [6]. repurposed drugs like remdesivir, baricitinib, hydroxychloroquine, dexamethasone, danoprevir, ritonavir, and lopinavir were selected for treating covid-19 due to their therapeutic effect against human coronaviruses, such as sars-cov-1 and the middle east respiratory syndrome coronavirus (mers-cov) [7]. some large-scale randomized clinical trials have been completed and others are underway to further evaluate the effectiveness of these repurposed drugs in managing covid-19 patients. however, controversial findings were reported in terms of the effectiveness of these drugs. computer-aided drug discovery and development is a recent approach used to enhance the efficiency and productivity in the drug discovery and development pipeline. through the computational structure-based virtual screening using molecular docking strategies, the interactions between the tested compound and binding site can be predicted and its binding affinity can be calculated from the software [8]. leveraging chemical and biological information between tested compounds and binding sites is crucial in identifying and optimizing new potential drugs. structurally, the sar-cov-2 comprises four (4) structural proteins: spike proteins (s), membrane protein (m), nucleocapsid (n), and envelope proteins (e). n protein forms the doi 10.18502/sjms.v17i3.12125 page 388 sudan journal of medical sciences yow hui yin, tang yin-quan capsid outside the genome (i.e., a single-stranded positive-sense rna) and is further packed by an envelope that associates with m, s, and e proteins [9]. these proteins (specifically proteases and spike proteins) are the targeted protein for molecular docking to understand the protein–ligand interactions at the active binding site in this virus [10]. main protease (mpro), also known as 3-chymotrypsin-like protease (3clpro), is one of the vital targets that is potentially targeted by an antiviral agent to suppress viral replication. the mpro plays an important role in posttranslational modifications of replicase polyproteins that further catalyzes the processing of the viral protein [11]. hence, this study aims to investigate the potential inhibitory action of several selected repurposed drugs targeting mpro through molecular docking. in addition, this study also highlights the possible inhibitory action of potential natural compounds (ascorbic acid and cepharanthine) against mpro. 2. methods 2.1. protein retrieval and preparation sars-cov-2 mpro was used as the main target for this study. the crystal structure of the covid-19 mpro in complex with an inhibitor n3 (pdb id: 6lu7, chain a, 2.16 å) [12] was downloaded from the protein data bank (www.rcsb.org) and chosen as the model of mpro. the ligand n3 (n-[(5-methylisoxazol-3yl)carbonyl]alanyl-l-valyl-n∼1∼-((1r,2z)4-(benzyloxy)-4-oxo-1-{[(3r)-2-xopyrrolidin-3-yl]methyl}but-2-enyl)-l-leucinamide) was used as a control. the retrieved crystal structure was prepared using biovia discovery studio visualizer (biovia, dassault systèmes, biovia discovery studio visualizer, version 20.1.0.192, san diego: dassault systèmes, 2021) to remove water and n3 ligand molecules. the binding site residues of the n3 ligand were identified and their binding pocket is shown as a red balloon in mpro (figure 1), whereby their key residues are presented in table 1. the prepared .pdb file was then saved and reviewed for its ramachandran plot to evaluate its readiness for docking analysis using the rampage server (http://mordred.bioc.cam.ac.uk/∼rapper/rampage.php) [13]. table 1: grid selection and targeted key residue. pdb id key residues center 6lu7 thr:24, thr:25, thr:26, leu:27, his:41, thr:45, ser:46, met:49, phe:139, leu:140, asn:141, gly:142, ser:143, cyc:144, his:163, met:165, glu:166, his:172 x: -10.7292 y: 12.4176 z: 68.8161 doi 10.18502/sjms.v17i3.12125 page 389 sudan journal of medical sciences yow hui yin, tang yin-quan figure 1: binding pocket (red color balloon) of sars-cov-2’s main protease. 2.2. ligand retrieval and preparation a total of 12 ligands were retrieved in sdf formats from the pubchem database (ncbi) (http://pubchem.ncbi.nlm.nih.gov) (table 2). optimization was performed in each downloaded ligand for their molecular geometry, torsional barriers, and intermolecularinteraction geometry by using mmff94 partial forcefield in autodock vina in pyrx (https://pyrx.sourceforge.io/home). before the molecular docking study, all ligands were saved in autodock-specific coordinate file .pdbqt format where ‘pdbqt’ stands for protein data bank (pdb) format file along with charges (q) and autodock atom types (t). 2.3. docking visualization, validation, and analysis all the prepared proteins and ligands were submitted for docking analysis in the built-in autodock vina in the pyrx program (https://pyrx.sourceforge.io/home) [14]. site-specific molecular docking was conducted according to the grid selection parameter (table 1). the binding result table and the best model for each protein–ligand interaction were saved. the discovery studio 2021 (biovia) was used for conducting docking visualization to construct 3d and 2d binding conformation diagrams [15]. docking visualization and analysis were accomplished in microsoft windows pc with intel® core𝑇𝑀 i5-8265u cpu @1.60 ghz, 8 gb ram. doi 10.18502/sjms.v17i3.12125 page 390 sudan journal of medical sciences yow hui yin, tang yin-quan table 2: ligands to target mpro (6lu7). no. ligand name pubchem cid list of repurposed drug 1 baricitinib 44205240 2 danoprevir 9460579 3 dexamethasone 5743 4 hydroxychloroquine 3652 5 ivermectin 6321424 6 lopinavir 92727 7 methylprednisolone 6741 8 remdesivir 121304016 9 ritonavir 392622 10 saridegib 25027363 list of potential natural compounds 11 ascorbic acid 54670067 12 cepharanthine 10206 3. results and discussion we evaluated a total of 12 ligands (mixtures of repurposed drugs and natural bioactive compounds), where most of them are currently in clinical trials for the covid-19 disease. the antiviral mechanisms of these promising drugs are still poorly understood. the viral mpro, (also called 3clpro) controlling the coronavirus replication activities has become an attractive target for therapy. therefore, in this study, the potential inhibitory action of several ligands targeting mpro was investigated. here, n3 was used in the docking studies as a control. the binding affinity of n3 was reported at –7.1 kcal/mol [16], while other reports showed the binding energy at –7.85 kcal/mol [17]. further, the average binding affinity of n3 at –7.48 kcal/mol was calculated and used for subsequent comparative analysis. the binding affinity of each ligand (repurposed drugs and natural compounds) toward the protein target is shown in table 3. among the 10 tested drugs, only three drugs indicated stronger binding affinity toward mpro than n3 (control): danoprevir (–7.7 kcal/mol), remdesivir (–8.1 kcal/mol), and saridegib (–7.8 kcal/mol). figure 2b shows the 2d and 3d molecular interaction of danoprevir targeting mpro. there were two main conventional hydrogen bonds identified in this danoprevir–mpro complex at glya:143 and glna:189, whereby the residue glua:166 formed a carbon– hydrogen bond. the formation of hydrogen bonds is crucial as it gives a stabilization effect in ligand–protein interaction [18]. besides hydrogen bonds, other key residues doi 10.18502/sjms.v17i3.12125 page 391 sudan journal of medical sciences yow hui yin, tang yin-quan interact through hydrophobic bonds (alkyl [proa:168] and π-sigma [alaa:191]) and electrostatic bonds (van der waals). the presence of hydrophobic bonds could be attributed to the interaction between hydrophobic amino acids with a polar solvent [19]. table 3: the binding affinity energy of ligands and their interactions targeting sars-cov-2 main protease (mpro). no. ligand name binding affinity energy (kcal/mol) interactions with mpro residues# total number of interactions hydrogen bond hydrophobic interaction hydrogen bond hydrophobic interaction 1 baricitinib –7.4 gly143, thr190 cyc145, his163 2 2 2 danoprevir –7.7 gly143, gln189, glu166 pro168, ala191 4 2 3 dexamethasone –7.1 glu166 – 2 0 4 hydroxychloroquine –6.0 leu141, asn142 his41, met165 2 3 5 ivermectin –7.9 – – 1 0 6 lopinavir –7.4 asn142, met165, glu166, gln189 leu27, his41, met49, cys145, pro168 6 6 7 methylprednisolone –7.1 glu166 – 1 0 8 remdesivir –8.1 asn142, ser144, cys145, his163, glu166, gln189 his41, met165 9 2 9 ritonavir –7.4 asn142, his163, his164, glu166 leu141, cys145, met165, leu167, pro168 8 7 10 saridegib –7.8 asn142, gly143, gln189 cys145 3 1 11 ascorbic acid –5.4 leu141, asn142, gly143, ser144, cys145 – 7 0 12 cepharanthine –7.9 his164, pro168, gln189, thr190 met165, pro168 4 3 #residues in bold are binding sites of n3 on mpro. two types of hydrogen bonds are detected: conventional hydrogen bond and carbon–hydrogen bond. in comparison, the carbon–hydrogen bond (ch⋯o) is known to be weaker than the conventional hydrogen bond and this is due to cho’s average distance, which is longer than the conventional hydrogen bonds (nh···o, oh···o, oh···n, and nh···n). several reports have stated that the carbon-hydrogen (ch⋯o) bond plays an essential role in the molecular recognition process [20-22]. danoprevir is a new ns3/4a protease inhibitor with potent and broad-spectrum antiviral activity against the hepatitis c virus [23]. it was proposed that sars-cov-2 mpro has a similar structure to other rna viruses, including the hepatitis c virus [24]. from our molecular docking simulation, danoprevir demonstrated strong interactions with mpro. this finding is congruent with the findings reported by da costa et al. [25]. this strong binding affinity may explain its promising effect in a clinical trial. treatment of danoprevir boosted with ritonavir improved the clinical condition of patients with doi 10.18502/sjms.v17i3.12125 page 392 sudan journal of medical sciences yow hui yin, tang yin-quan figure 2: molecular interaction of (a) baricitinib, (b) danoprevir, (c) dexamethasone, (d) hydroxychloroquine, (e) ivermectin, (f) lopinavir, (g) methylprednisolone, (h) remdesivir, (i) ritonavir, and (j) saridegib against sars-cov-2 main protease (mpro). figure 3: molecular interaction between (a) ascorbic acid and (b) cepharanthine against sars-cov-2 main protease (mpro). moderate covid-19 and increased the discharge rate without adverse outcomes [26]. this further confirms the potential of danoprevir in treating covid-19 infection. among all the tested ligands, remdesivir showed the strongest inhibitory action against mpro with the strongest binding affinity energy at –8.1 kcal/mol. this could be due to a high number of hydrogen bonds formed in the remdesivir–mpro complex (figure 2h). there are seven primary conventional hydrogen bonds identified in the remdesivir at asna:142, sera:144, cysa:145, hisa:163, glua:166, and glna:189, whereas two carbon–hydrogen bonds were formed by the residues hisa:41 and meta:165. the lower binding affinity of remdesivir is more likely associated with the double bonding of key residues, such as glua:166 interacts in hydrogen and π-anion binding. while other doi 10.18502/sjms.v17i3.12125 page 393 sudan journal of medical sciences yow hui yin, tang yin-quan key residues interact via hydrophobic bonds through the πalkyl (hisa:41) and alkyl (meta:165) interactions. the π-interaction is believed to give an important impact on the ligands’ binding energy to their receptors [20]. remdesivir drug is one of the agents authorized by the food and drug administration (fda) to treat covid-19 patients since october 2020 and remains active against various sars-cov-2 variants, including alpha, beta, gamma, delta, and omicron [27]. it is a wide-spectrum antiviral agent effective against various viruses, including the ebola virus, measles and mumps virus, and coronaviruses [28]. our study findings are consistent with other studies, which also suggested that remdesivir strongly binds to the mpro of sars-cov-2 [29, 30]. these interactions may explain its significant positive outcomes in randomized clinical trials by reducing the recovery time, mortality, and preventing the progression into serious respiratory diseases and oxygen requirement among those patients who received supplementary oxygen [31]. the hedgehog signaling pathway plays an important role in embryogenesis, tissue homeostasis, and remodeling [32]. in addition, there is emerging evidence that hedgehog signaling is a target for some pathogens, including influenza a virus, human immunodeficiency virus, and hepatitis [32]. a recent study reported that the sonic hedgehog signaling pathway plays some role in patients with covid-19-associated pneumomediastinum [33]. therefore, saridegib is included as a tested compound in this study. saridegib, also known as ipi-926, is a cyclopamine-derived hedgehog pathway inhibitor that has been clinically investigated for various types of cancer [34]. figure 2j shows the 2d and 3d molecular interactions between saridegib against mpro. like danoprevir, two main conventional hydrogen bonds were formed in the saridegib– mpro complex at asn a:142 and gly a:143, and glna:189, whereby the residue glna:189 formed a carbon–hydrogen bond. while other key residues interact through hydrophobic bonds via alkyl interaction at cysa:145. to date, saridegib is not investigated preclinically or clinically as a treatment for covid-19 patients. interestingly, this study demonstrated that saridegib has strong inhibitory action against mpro, which elucidates that it may have some degree of antiviral activity and further investigation is needed to confirm this finding. cepharanthine showed better binding affinity toward mpro (–7.9 kcal/mol) than ascorbic acid (–5.4 kcal/mol. as shown in figure 3b, four carbon–hydrogen bonds were formed in the cepharanthine–mpro complex at hisa:164, proa;168, glna;189, and thra:190. other key residues interact through three hydrophobic bonds (alkyl, πalkyl, and π-π t shaped sigma) and one electrostatic bond (πanion). the π-anion interaction is characterized as the favorable non-covalent electrostatic interaction between anions doi 10.18502/sjms.v17i3.12125 page 394 sudan journal of medical sciences yow hui yin, tang yin-quan located on top of the aromatic ring where the binding energy is controlled by the electrostatic anion-induced polarity contribution [35, 36]. cepharanthine is an alkaloid isolated from stephania cepharantha hayata. it has been widely used in japan since 1951 for various indications, including leukopenia, alopecia, and viper bite. it is also reported with antiviral activities against coronavirus, influenza virus, and hepatitis b and c viruses [37, 38]. its antiviral activity against sars-cov-2 is postulated to be associated with its ability to hinder the sar-cov-2 entry phase in viral infection [39] and interactions with nonstructural proteins [40]. this study also provides an insight on interactions of cepharanthine to mpro, which might be attributed to its potential antiviral effect against sar-cov-2. ascorbic acid (vitamin c) is a known potent antioxidant that acts by scavenging reactive oxygen species. several studies suggested that vitamin c supplementation is effective in preventing and treating virus infection by decreasing the susceptibility to viral respiratory infections and pneumonia [41]. however, the role of ascorbic acid in treating covid-19 patients remains unclear, and ongoing clinical trials are conducted to investigate this [41]. based on the finding from molecular docking, ascorbic acid poorly interacts with mpro. the study focused on the potential of several selected repurposed drugs and some natural compounds to be used in the treatment of covid-19 infection, based on the virtual screening of their interactions on mpro. it provides preliminary insight into understanding the potential mechanism of these agents toward the sar-cov-2 virus. further, molecular docking on other sar-cov-2 proteins and proteases, such as s protein, n protein, e protein, m protein, nsps, and papain-like protease to have a better illustration in terms of interactions between the drugs with the viral proteins is recommended. this could provide valuable information in drug discovery and development. 4. conclusion all 12 molecules (baricitinib, danoprevir, dexamethasone, hydroxychloroquine, ivermectin, lopinavir, methylprednisolone, remdesivir, ritonavir and saridegib, ascorbic acid, and cepharanthine) showed antiviral activity against covid-19 infection through their inhibitory action targeting mpro. our findings indicate the potential mechanism of these molecules by inhibiting mpro protein in the sar-cov-2 virus. nevertheless, further molecular docking on other viral proteins is warranted to understand the interactions of these molecules with other viral proteins, which is vital in discovering and developing novel treatments for the covid-19. doi 10.18502/sjms.v17i3.12125 page 395 sudan journal of medical sciences yow hui yin, tang yin-quan acknowledgments none ethical considerations not applicable. competing interests none declared. availability of data and material the dataset generated during this study is available from the corresponding author on reasonable request. funding this research was mainly funded by the ministry of higher education (mohe) malaysia through fundamental research grant scheme (frgs/1/2020/skk0/taylor/02/2). the funding for niche area research was supported by the mohe-frgs (frgs/1/2019/skk09/taylor/03/1), national cancer council malaysia (makna) cancer research award (cra) 2021 and malaysia toray 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(2020). what is the role of supplementation with ascorbic acid, zinc, vitamin d, or n-acetylcysteine for prevention or treatment of covid-19? cleveland clinic journal of medicine. https://doi.org/10.3949/ccjm.87a.ccc046 doi 10.18502/sjms.v17i3.12125 page 400 introduction methods protein retrieval and preparation ligand retrieval and preparation docking visualization, validation, and analysis results and discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13608 production and hosting by knowledge e commentary recurring outbreaks of lassa fever in nigeria: understanding the root causes and strategies for the future bashar haruna gulumbe1, uzairu aminu1, usman umar liman2, abdulrakib abdulrahim1, and zaharaddin muhammad kalgo1 1department of microbiology, faculty of science, federal university birnin-kebbi, kebbi state, nigeria 2department of biochemistry, faculty of science, federal university birnin-kebbi, kebbi state, nigeria orcid: bashar haruna gulumbe: https://orcid.org/0000-0003-0642-6902 uzairu aminu: https://orcid.org/0009-0008-5040-6726 usman umar liman: https://orcid.org/0000-0003-4945-5228 abdulrakib abdulrahim: https://orcid.org/0000-0002-2939-7086 zaharaddin muhammad kalgo: https://orcid.org/0000-0002-4754-7041 abstract lassa fever is a severe public health problem in nigeria with far-reaching political, social, cultural, and religious ramifications. thus, a further understanding of the disease is critical. despite attempts to end the viral epidemic, the illness has persisted, leading to several major outbreaks in decades. additionally, the country’s epidemic in 2019– 2020 set a new global record for the number of lassa fever cases. this year, 244 cases and 37 deaths had been reported as of january 2023. to identify gaps and provide recommendations for the complete eradication of lassa fever in the country. this paper investigates the underlying causes of the continuous outbreaks of the illness in nigeria and the measures to prevent it. the frequent outbreaks of lassa fever in nigeria have been linked to several factors, including inadequate waste management, poor sanitation, restricted access to healthcare, and abject poverty. the reoccurring outbreaks are also attributed to a lack of political will, funding, poor coordination and communication, and low public awareness of the illness and its prevention. to effectively stop outbreaks of lassa fever in nigeria, the government and partners must continuously put into practice tried-and-true prevention measures such as improved surveillance to detect outbreaks earlier, increased funding and resources to support effective control measures, better primary healthcare facilities and training for healthcare professionals, heightened community engagement and education to raise awareness, and more effective vector control methods to reduce rodent populations, while looking for innovative approaches and dealing with the underlying social and economic problems contributing to the viral persistence. keywords: lassa fever, hemorrhagic fever, lhf, nigeria, viral infection how to cite this article: bashar haruna gulumbe, uzairu aminu, usman umar liman, abdulrakib abdulrahim, and zaharaddin muhammad kalgo (2023) “recurring outbreaks of lassa fever in nigeria: understanding the root causes and strategies for the future,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 257–264. doi 10.18502/sjms.v18i2.13608 page 257 corresponding author: bashar haruna gulumbe; email: bashar.haruna@fubk.edu.ng received 12 february 2023 accepted 24 february 2023 published 30 june 2023 production and hosting by knowledge e bashar haruna gulumbe et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences bashar haruna gulumbe et al. 1. introduction lassa fever is a viral hemorrhagic illness that is caused by the lassa fever virus, an enveloped, single-stranded rna virus that was named after the city of lassa in borno state, nigeria. the virus’s coding mechanism is in the form of ambisense, and its rna genome is bi-segmented. the envelope glycoprotein complex (gp), which appears as trimeric spikes on the surface of the virus, is a key target for the development of antibody-based vaccinations and treatments [1]. it was initially identified in 1969 during an outbreak in the city of jos in plateau state, nigeria. certain west african nations, particularly nigeria, liberia, sierra leone, and guinea, have endemic zoonotic diseases [2, 3]. humans are vulnerable to lassa fever through contact with the urine or feces of infected rodents, which are common in parts of west africa. the virus is shed in their bodily fluids and can be transmitted to humans through direct contact with rodents or their excreta. people can also become infected with lassa fever through contact with objects contaminated with the virus, such as household items or food [4]. based on the disease’s generalized symptoms and clinical presentation, which include fever, vomiting, exhaustion, abdominal discomfort, sore throat, chest pain, and myalgia, identifying the disease’s onset is frequently challenging. it could develop into major side effects including encephalitis, breathing issues, hemorrhage, neurological issues, hearing loss, and death can occur often due to multiple organ failure, shock, and bleeding. it is estimated that between 300,000 and 500,000 cases of lassa fever occur each year in west africa, with 5,000 to 10,000 deaths reported annually [5]. in nigeria, there is a persistent outbreak of lassa fever that usually lasts from december to june each year. for example, with more than 1189 confirmed cases and 244 fatalities, the year 2020 saw one of the deadliest epidemics in recent memory [6]. the actual numbers are likely to be much higher, as many cases go unreported or are misdiagnosed [6]. in recent years, lassa fever-related high mortality and has been reported in edo, ondo, ebonyi, plateau, bauchi, and taraba states [6]. however, the outbreak can occur in any state and has indeed been documented in all the states in the past [7]. nigeria is now experiencing a crisis due to the highly contagious and fatal viral hemorrhagic sickness. according to the status report from january 22, 2023, there were 244 confirmed cases and 37 fatalities overall [8]. public health authorities and members of the general public are both deeply concerned about the current outbreak in nigeria, with the nigeria center for disease control and prevention (ncdc) activating the emergency operations center for lassa fever recently to strengthen the response to increasing cases. doi 10.18502/sjms.v18i2.13608 page 258 sudan journal of medical sciences bashar haruna gulumbe et al. despite these efforts, lassa fever is still a significant issue in nigeria, demonstrating the need for more research and funding for managing and preventing the illness. in this analysis, we delve into the recurrent outbreaks of lassa fever in nigeria, the ongoing spread of the virus, the containment efforts that have been put in place, and the challenges that are hindering progress. the aim is to gather the information that will assist in developing targeted infection-control and prevention strategies to combat this persistent public health threat. 1.1. recurring lassa fever outbreaks in nigeria lassa fever has regularly afflicted nigeria since it was first discovered there in 1969 [9]. nigeria has had epidemics of the disease in several of its states, most frequently between december and june [6, 10]. concerns regarding how lassa fever could impact the country’s public health have been raised due to the rising number of cases reported over time [8]. in nigeria in 2000, there was a big outbreak of lassa fever with several hundred documented cases and several dozen fatalities [7]. over the years, several outbreaks were reported, with some years reporting more cases than others. for instance, 2012 was a year that also witnessed a marked increase in reported cases, with a total of 1723 and 219 suspected and confirmed cases, respectively [11]. epidemiological outbreaks of lassa fever remained in nigeria during the following years, with varying degrees of severity. the sickness developed a large pandemic in 2016, with over 918 suspected and 209 confirmed cases. even though there were fewer cases in 2017, the sickness nevertheless posed a major danger to the country’s general health [11]. in the year 2018, there was a significant increase in reported cases, with over 600 confirmed cases and over 191 fatalities [6]. more than 800 confirmed cases and 170 fatalities occurred in 2019, marking the start of yet another major outbreak [6, 7]. over 1189 confirmed cases and 244 fatalities were reported in the nation in 2020, a considerable rise from the previous year, with fewer cases recorded in 2021 [6]. however, nigeria saw another significant lassa outbreak in the first quarter of 2022, with over 900 confirmed cases and nearly 200 fatalities [12]. health officials reported high infections and fatalities in several places where the epidemic was particularly severe [8]. in response, the nigerian government and international health organizations intensified their efforts to stop the virus’s spread. these efforts included raising public awareness, enhancing infection control in healthcare institutions, and implementing better surveillance systems. currently, lassa fever outbreaks are still a problem in nigeria [8]. public health experts continue to be concerned about the situation, and doi 10.18502/sjms.v18i2.13608 page 259 sudan journal of medical sciences bashar haruna gulumbe et al. there is a constant need for efficient solutions to stop the virus’s spread and safeguard communities from its effects. 1.2. factors feeling recurring lassa outbreaks in nigeria as shown in figure 1, numerous variables are thought to be responsible for the recurrence of lassa fever epidemics in nigeria, including poor sanitation, poor waste management, and a lack of access to efficient primary care, among others [8, 9]. people who come into contact with infected food, household items, or rodent urine or excrement may get the virus. the danger of contracting the virus is increased by lax hygiene and sanitation standards. the frequent outbreaks of lassa fever are also due to overcrowding; more the number of people in a smaller area, the higher the chances of contact with the diseased mice or contaminated surfaces [8]. inadequate waste management techniques can also foster the reproduction and spread of rats, which are the main hosts for pests. nigeria is a country with a high population of people living in rural areas in close association with animals, including rodents, providing a breeding ground for lassa to spread. figure 1: factors fuelling recurring lassa fever outbreaks in nigeria. limited access to healthcare services, particularly in rural areas, also contributes to the recurring outbreaks of lassa fever. this makes it difficult for patients to receive prompt and effective treatment, which can result in more severe outcomes and higher mortality rates [13]. furthermore, the healthcare infrastructure in nigeria is often ill-equipped to respond to outbreaks of infectious diseases like lassa fever [14]. there are often shortages of personal protective equipment, diagnostic tests, and antiviral treatments, which limit the ability of healthcare workers to respond to outbreaks effectively. doi 10.18502/sjms.v18i2.13608 page 260 sudan journal of medical sciences bashar haruna gulumbe et al. other factors include a lack of political will and insufficient finance. ineffective communication and coordination between many groups and people involved in disease management activities, which together can lead to inefficiencies and gaps in the response. for example, if the government and other decision-makers lack the political will to handle lassa fever, response efforts can only receive limited resources and attention [9, 14]. thus, the disease may continue to spread if organizations cannot conduct efficient monitoring, research, and control operations due to a lack of financing. the frequent outbreaks of lassa fever in nigeria can also be linked to a lack of public awareness of the illness and its methods of prevention. without a thorough grasp of the risks posed by the virus and the steps to be taken to prevent its transmission, people may engage in actions that increase their vulnerability to infection. 1.3. efforts by governments and partners to contain the ongoing outbreak to address the ongoing outbreak of lassa fever in nigeria, the nigeria center for disease control (ncdc) has adopted several actions. to better coordinate the response, the national emergency operations center’s alert level 2 has been activated, along with the state public health operation centers in the impacted states [8]. rapid reaction teams have been sent to several states, and case management and infection prevention and control (ipc) protocols have been made available to the general public and healthcare professionals. the distribution of medical response supplies to treatment facilities is underway, as are enhanced surveillance measures and the clinical management of confirmed patients. the seven national lassa fever laboratories operate efficiently to process samples promptly. the federal ministry of environment is also implementing an environmental response campaign to control the spread of the virus through vector and environmental control [8]. the ncdc is also increasing its community engagement efforts through various communication channels. international organizations such as the world health organization (who) and the center for disease control and prevention (cdc) have also been involved in efforts to address the outbreak. these organizations have provided technical assistance, medical supplies, and funding to help strengthen nigeria’s health system and respond to the crisis. however, these interventions have also been deployed in the past and have not succeeded in eliminating recurring outbreaks of lassa in the country. therefore, more strict measures are necessary. doi 10.18502/sjms.v18i2.13608 page 261 sudan journal of medical sciences bashar haruna gulumbe et al. 1.4. recommendations recurrent outbreaks of lassa fever in nigeria persist despite ongoing efforts to control its spread. a comprehensive approach, including enhanced surveillance, improved funding and resources, better healthcare facilities and skills, increased community engagement and education, and efficient vector control measures, are necessary to eradicate the disease. the government must continuously implement proven strategies, while seeking new solutions and addressing underlying social and economic issues such as poverty and poor sanitation. the control of vector-borne diseases requires a multipronged approach, including the establishment of a community-based surveillance system, the use of technology for rapid illness detection, and the development of a coordinated response strategy. enhancing disease control efforts also involves the investigation and creation of novel medications and vaccines, collaboration with international organizations, and the implementation of strategies such as an early warning system, door-to-door education campaigns, community involvement in disease surveillance, and telemedicine systems. the government needs to collaborate with all stakeholders to address poverty and improve living conditions, as these factors are closely linked to human exposure to disease vectors. the government must keep implanting these tried-and-true strategies for preventing the spread of contagious illnesses like lassa fever in a sustained manner while simultaneously looking for solutions. importantly, addressing the underlying social and economic problems, such as poverty and inadequate sanitation, that contribute to the spread of the disease should be prioritized. 2. conclusion the lassa virus issue in nigeria has severe ramifications for regional and national economic growth and public health. aside from endangering human health, illness has a detrimental effect on commerce, tourism, and agriculture, which fuels the rise of social inequality and poverty. all parties, including the government, foreign organizations, and the corporate sector, must collaborate to develop a thorough and coordinated response to nigeria’s complicated and ongoing lassa fever problem. this includes improving surveillance to detect outbreaks earlier, allocating more funds and resources to support control measures, enhancing primary healthcare facilities and providing training to healthcare professionals, increasing community engagement and education to raise doi 10.18502/sjms.v18i2.13608 page 262 sudan journal of medical sciences bashar haruna gulumbe et al. awareness about the disease, and implementing more effective vector control methods to reduce rodent populations. additionally, innovative approaches should be explored to address the underlying social and economic issues that contribute to the persistence of the virus. the success of these initiatives would depend on everyone’s capacity to cooperate in order to safeguard nigeria’s population’s health and well-being. acknowledgements none. competing interests none. funding none. references [1] aloke, c., obasi, n. a., aja, p. m., emelike, c. u., egwu, c. o., jeje, o., edeogu, c. 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(2020, may). lassa fever outbreak continues across nigeria. the lancet. infectious diseases, 20(5), 543. doi 10.18502/sjms.v18i2.13608 page 264 https://ncdc.gov.ng/news/438/ncdc-activates-lassa-fever-emergency-operations-centre-to-strengthen-the-response-to-rising-cases-of-lassa-fever-in-nigeria https://ncdc.gov.ng/news/438/ncdc-activates-lassa-fever-emergency-operations-centre-to-strengthen-the-response-to-rising-cases-of-lassa-fever-in-nigeria https://ncdc.gov.ng/diseases/sitreps/?cat=5&name=an%20update%20of%20lassa%20fever%20outbreak%20in%20nigeria https://ncdc.gov.ng/diseases/sitreps/?cat=5&name=an%20update%20of%20lassa%20fever%20outbreak%20in%20nigeria https://ncdc.gov.ng/diseases/sitreps/?cat=5&name=an%20update%20of%20lassa%20fever%20outbreak%20in%20nigeria https://www.who.int/news-room/spotlight/one-year-into-the-ebola-epidemic/factors-that-contributed-to-undetected-spread-of-the-ebola-virus-and-impeded-rapid-containment https://www.who.int/news-room/spotlight/one-year-into-the-ebola-epidemic/factors-that-contributed-to-undetected-spread-of-the-ebola-virus-and-impeded-rapid-containment https://www.who.int/news-room/spotlight/one-year-into-the-ebola-epidemic/factors-that-contributed-to-undetected-spread-of-the-ebola-virus-and-impeded-rapid-containment introduction recurring lassa fever outbreaks in nigeria factors feeling recurring lassa outbreaks in nigeria efforts by governments and partners to contain the ongoing outbreak recommendations conclusion acknowledgements competing interests funding references sudan journal of medical sciences volume 17, issue no. 1, doi 10.18502/sjms.v17i1.10682 production and hosting by knowledge e original article patient satisfaction and its predictors in the general hospitals of southwest saudi arabia: a cross-sectional survey anas elias1*, suhaila abdalkarim1, walaa mohammed m2, ghaliya yahya ali2, manal mohammed ahmed2, meaad youns khan2, hind mousa faqeeh2, arwa ali ahmed alhazmi2, ola hamad ahmad2, reem ali jubran2, mohamed salih mahfouz1 1department of family and community medicine, faculty of medicine, jazan university, jazan, kingdom of saudi arabia 2faculty of medicine, jazan university, jazan, kingdom of saudi arabia orcid: anas elias: https://orcid.org/0000-0001-8281-1373 mohamed salih mahfouz : https://orcid.org/0000-0002-3155-6381 abstract background: patient satisfaction occupies a central position in measuring the quality of care as it provides information on the provider’s success, meeting the patient’s values and expectations. hence, it is an essential tool for assessing health services outcomes. this study aimed to assess patients’ satisfaction level and factors influencing healthcare quality of general hospitals in the jazan region, saudi arabia (sa). methods: this observational cross-sectional study was conducted on a sample of 423 patients selected through stratified random sampling from general hospitals of the jazan region. results: the overall satisfaction rate among the study participants was 80.9%. satisfaction with food services was the highest (91.15%) followed by doctor services (81.0%), reception and entry procedures (80%), and nursing services (78.15%). the various aspects of satisfaction with doctors and nurses included the treatment prescribed by physicians, clarity in communication with patients, compassion and providing clear explanation of what they were doing. however, about 27.3% of the patients were dissatisfied with the length of waiting period before seeing a doctor. binary logistic regression analysis suggested that uneducated patients and patients with secondary school education were more likely to have higher satisfaction level than university-educated patients (or = 3.40, 95% c.i. [1.56–7.45], p = 0.002), (or = 2.66, 95% c.i. [1.28–5.55], p = 0.009), and (or = 2.29, 95% c.i. [1.40–3.73], p = 0.001), respectively. conclusion: the health services satisfaction level was high in the jazan population. however, some aspects of dissatisfaction were reported, such as the long waiting period before seeing a doctor. these aspects are recommended to be improved to ensure that the services provided by general hospitals are of high quality. keywords: satisfaction, health services, general hospitals, jazan how to cite this article: anas elias*, suhaila abdalkarim, walaa mohammed m, ghaliya yahya ali, manal mohammed ahmed, meaad youns khan, hind mousa faqeeh, arwa ali ahmed alhazmi, ola hamad ahmad, reem ali jubran, mohamed salih mahfouz (2022) “patient satisfaction and its predictors in the general hospitals of southwest saudi arabia: a cross-sectional survey,” sudan journal of medical sciences, vol. 17, issue no. 1, pages 15–27. doi 10.18502/sjms.v17i1.10682 page 15 corresponding author: anas elias; email: anas2005me@gmail.com received 12 january 2022 accepted 02 march 2022 published 31 march 2022 production and hosting by knowledge e anas elias et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:anas2005me@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences anas elias et al 1. introduction patient satisfaction occupies a central position in measuring the quality of care and provides information on the provider’s success in meeting patients’ values and expectations. hence, it is an important tool for assessing healthcare services outcomes [1–3]. patients’ experience and viewpoints are an essential index for improving the quality of healthcare services [4]. caring for patient satisfaction leads to compliance improvement, continuity of care, and eventually, better health outcome [5, 6]. healthcare sector planning reforms increasingly highlight the need to improve patient satisfaction with healthcare services; therefore, identifying patients’ needs and evaluating the provided healthcare services is the starting step for delivering patient-centered care [6]. research on patient satisfaction in the kingdom saudi arabia (ksa) suggested various degrees of satisfaction among healthcare visitors [7–11]. a study conducted in riyadh, ksa (2006) to assess the satisfaction derived from the healthcare services showed that 56.3% of the participants were unsatisfied with the services [7]. in 2013, based on the evaluation of nurses’ services and their impact on patient satisfaction, investigators at al-noor specialist hospital in makkah recommended the need for raising awareness of the nurses [9]. furthermore, in makkah, ksa, a study investigating services provided for the patients revealed that the majority of the patients agreed on the cleanness of food equipment (96.8%), while the aspect with least satisfaction was that there was no place to warm up or freeze food as reported by 92.0% and 90.8%, respectively [10]. moreover, a large study was conducted in 2011 in six regions of ksa. it included 15 hospitals to evaluate patient satisfaction with hospital healthcare services affiliated to the ksa ministry of health. the overall rate of satisfaction with hospital services of the ministry of health was 70.6% [11]. numerous researchers analyzed the effects of personal features, processes, and outcomes of care on patient satisfaction. in a meta-analysis study, tucker and adams, (2001) recognized care, empathy, reliability, and responsiveness as predictors of patient satisfaction [12]. cleary and mcneil (1988) grouped patient satisfaction determinants into three care features: structure, process, and outcomes [13]. age, gender, employment, health status, and educational level were found to be significantly associated with patient satisfaction[14–16]. meeting patient expectations have been demonstrated to affect their satisfaction [17]. studies cited were conducted in different regions of ksa. however, to the best of our knowledge, no study has been conducted in the jazan region, southwest ksa, which doi 10.18502/sjms.v17i1.10682 page 16 sudan journal of medical sciences anas elias et al has about 17 general hospitals. hence, the main objective of this study was to assess the level of patient satisfaction with the service provided in the general hospitals of the jazan region and investigate the factors influencing patient satisfaction with the healthcare services in the jazan region. 2. materials and methods 2.1. study design, setting, and population an observational cross-sectional survey was conducted on patients admitted to general hospitals in the jazan region. the region is located in the southwestern corner of ksa and is subdivided into 17 governorates that has a population of 1.365 million, according to a 2010 census. the 17 general hospitals in the jazan region are spread across the region’s five healthcare sectors. the study population comprised adult people admitted to general hospitals during the study period. 2.2. sampling procedures the study sample size was estimated to be 440 patients depending on the standardized formula for cross-sectional surveys [18]. the sample size was calculated based on the assumption of 50% satisfaction level, with an estimated error ≤5%, and within a 95% confidence. the final sample size was increased to 440 participants after accounting for a 10% nonresponse rate. stratified random sampling was used for selecting hospitals from the healthcare sectors of the region. in the final stage, the sample from each hospital was selected using simple random sampling. 2.3. data collection and study instrument data were collected using a self-administered questionnaire. the questionnaire represents a modified version of a standard survey instrument hospital consumer assessment of health care providers and system (hcahps) modified to suit the saudi community setting and culture [19]. the final version of the questionnaire included patients’ background characteristics and the satisfaction items, which had a total of 24 items distributed into five domains, namely, patient satisfaction with the services at the hospital entrance; physician services; nursing services; cleanness in the hospital; food services doi 10.18502/sjms.v17i1.10682 page 17 sudan journal of medical sciences anas elias et al and general patient satisfaction with healthcare services. a five-point scale likerttype questions (strongly agree [5], agree [4], uncertain [3], disagree [2], and strongly disagree [1]) was used. for data analysis, the lowest score was valued as (1) for strongly dissatisfied and the highest as (5) for strongly satisfied. a pilot study with 30 patients admitted to different wards was conducted to assess the questionnaire’s reliability, validity, and clarity and to ensure the appropriateness of wording, formatting, length, and order of the questions. analysis of reliability based on cronbach’s alpha revealed an overall value of 0.93, while for the different domains, it ranged from 0.83 to 0.88. 2.4. data analysis the completed questionnaires were revised to avoid mistakes. descriptive statistics, including simple tabulation, frequencies, proportion, and cross-tabulations, were used for data analysis. the logistic regression model was also used to evaluate factors associated with the level of patient satisfaction and the corresponding ors with their 95% cis were also estimated. a p-value < 0.05 was used to indicate statistical significance. data entry and analysis were performed using the statistical package for social sciences (spss) v.20. 3. results a total of 423 patients responded to the study, with a 96.1% response rate (423 out of 440). table 1 shows the sociodemographic features of the participants. of those 423, 177 (41.8%) were male and 246 (58.2%) female. while most patients (233 [55.1%]) were aged between 20 and 35 years, 59 (13.9%) were <20 years. in addition, 205 participants (48.5%) were non-working, 82 (19.4%) were students, and 136 (32.2%) were employed. table 2 shows patient satisfaction based on the different services provided. as seen in the table, 376 (88.9%), patients were satisfied with the receptionist and entry procedures. however, 108 (25.5%) patients were dissatisfied with the length of the waiting period before seeing a doctor. in comparison, 361 (84.3%) patients confirmed that the examination rooms had a suitable temperature, and 343 (81.1%) were satisfied its privacy. satisfaction with food hygiene; its temperature; taste and healthiness; and the time of meal servicing was 92.5% (271), 86.7% (254), 94.2% (275), and 94.4% (278), respectively. table 3 presents patient satisfaction according to different service categories (domains). while the overall satisfaction rate was 80.9% (293), the dissatisfaction rate doi 10.18502/sjms.v17i1.10682 page 18 sudan journal of medical sciences anas elias et al table 1: sociodemographic features of the study participants (n = 423). demographic characteristics number percentage (%) gender male 177 41.8 female 246 58.2 age (yr) <20 59 13.9 20–35 233 55.1 36–50 84 19.9 >50 47 11.1 education level illiterate 54 12.8 primary 54 12.8 intermediate or secondary 157 37.1 university 158 37.4 nationality saudi 383 90.5 non-saudi 40 9.5 occupation student 82 19.4 employed 136 32.2 not working 205 48.5 income high 18 4.3 moderate 304 71.9 low 101 23.9 was 19.1% (72). satisfaction with food services scored the highest (240 [91.2%]), followed by doctor services (320 [80.0%]) and reception and entry procedures (308 [80.0%]). the highest rate of dissatisfaction was reported for hospital cleanness (101 [25.8%]). binary logistic regression analysis suggested that uneducated patients, patients with primary and secondary school education were more likely to have higher satisfaction level than university-educated patients (or = 3.40, 95% c.i. [1.56–7.45], p = 0.002), (or = 2.66, 95% c.i. [1.28–5.55], p = 0.009), and (or = 2.29, 95% c.i. [1.40–3.73], p = 0.001), respectively (table 4). 4. discussion the current study aimed to determine the satisfaction levels of patients admitted to the general hospitals in the jazan region, ksa and find out the related factors associated with the level of satisfaction. there is an increasing need to investigate in more depth the different components of patient satisfaction and their predictors. this study revealed that the overall client satisfaction level with the hospital services was 80.9%. this is similar to what was reported by the ministry of health, ksa, where the doi 10.18502/sjms.v17i1.10682 page 19 sudan journal of medical sciences anas elias et al table 2: patient satisfaction with different satisfaction items (n = 423). domains items strongly agree n (%) agree n (%) uncertain n (%) disagree n (%) strongly disagree n (%) reception and entry procedures receptionist was helpful and concerned about patient complaint. 200 (47.3) 136 (32.2) 40 (9.5) 34 (8) 13 (3.1) the waiting period before admission to the doctor was appropriate. 156 (36.9) 132 (31.2) 27 (6.4) 67 (15.8) 41 (9.7) the examination room temperature was moderate and calm. 178 (42.1) 157 (37.1) 26 (6.1) 42 (9.9) 20 (4.7) the examination rooms were private. 174 (41.1) 132 (31.2) 37 (8.7) 45 (10.6) 35 (8.3) the admission procedure was easy. 156 (36.9) 119 (28.1) 60 (14.2) 45 (10.6) 43 (10.2) doctor services the doctor receives the patient with cheerfully and treats kindly and respectfully. 219 (51.8) 120 (28.4) 19 (4.5) 45 (10.6) 20 (4.7) the doctor introduce himself and gets to know the patient to facilitate communication between them. 150 (35.5) 107 (25.3) 43 (10.2) 78 (18.4) 45 (10.6) the doctor gives the patient sufficient time to listen to his complaints and answer all his questions. 207 (48.9) 121 (28.6) 30 (7.1) 40 (9.5) 25 (5.9) the doctor would explain the case to the patient. 199 (47) 128 (30.3) 27 (6.4) 45 (10.6) 24(5.7) the doctor speaks to the patient in words that fit the patient’s language and understanding. 207 (48.9) 143 (33.8) 23 (5.4) 34 (8) 16 (3.8) nurse services the nurse introduce herself and gets to know the patient to facilitate communication between them. 148 (35) 94 (22.2) 43 (10.2) 90 (21.3) 48 (11.3) the nurse treats patients in a humane and respectful way. 200 (47.3) 150 (35.5) 22 (5.2) 34(8) 17(4) the nurse administered medicines, conducted tests at appropriate times and explained everything she did to the patient. 200 (47.3) 132 (31.2) 26 (6.1) 47 (11.1) 18(4.3) the nurse responded quickly when needed. 180 (42.6) 129 (30.5) 27 (6.4) 47 (11.1) 40 (9.5) doi 10.18502/sjms.v17i1.10682 page 20 sudan journal of medical sciences anas elias et al table 2: (continued). domains items strongly agree n (%) agree n (%) uncertain n (%) disagree n (%) strongly disagree n (%) hospital cleanness the hospital entrances and corridors were clean and tidy. 196 (46.3) 110 (26) 35 (8.3) 50 (11.8) 45(10.6) the examination and waiting rooms were clean. 182 (43) 124 (29.3) 22 (5.2) 50 (11.8) 45 (10.6) bathroom was clean. 155 (36.6) 102 (24.1) 41 (9.7) 60 (14.2) 65 (15.4) food services the food was served clean and tidy. 170 (58.0) 79 (27.0) 22 (7.5) 19 (6.5) 3 (1.0) the food served was hot and delicious. 148 (50.5) 75 (25.6) 31 (10.6) 27 (9.2) 12 (4.1) the food served was healthy and suitable for consumption. 164 (56.2) 70 (24) 41 (14) 12 (4.1) 5 (1.7) the mealtimes were adequate. 172 (58.7) 82 (28) 24 (8.2) 12 (2.8) 3 (7) table 3: patient satisfaction according to different domains (n = 423). components satisfied n (%) dissatisfied n (%) patient satisfaction with reception and entry procedures 308 (80.0) 75 (20.0) patient satisfaction with doctor services 320 (81.0) 74 (19.0) patient satisfaction with nurse services 308 (78.2) 85 (21.8) patient satisfaction with hospital cleanness 290 (74.2) 101 (25.8) patient satisfaction with food services 240 (91.2) 23 (8.8) overall level of satisfaction 293 (80.9) 72 (19.1) patient satisfaction report for the first part of 2020 showed that 81.81% of the admitted patients in jazan hospitals were satisfied with the services. the same survey revealed that the overall level of satisfaction in all ksa was 82.57% [20]. our study indicated that 81% of the study participants were satisfied with the services provided by doctors, 85% were satisfied with the way doctors welcomed them, and 83% were satisfied with the doctor’s explanation of the patient’s condition. similar results were reported by owaidh et al. in southern saudi arabia; in their study, doctor services received a high patient satisfaction score of 90.1% [21], while in our study, it scored the second highest (81%). generally, the literature suggested that doctor–patient interaction is usually associated with patient satisfaction [22–24]. moreover, 78.1% of our study participants were satisfied with the nurse services in the general hospitals. this is similar to the results of al-doghaither’s study (2000) in which 77% of their participants were satisfied with the nursing care provided at king khaled university hospital, riyadh [25]. the study revealed that our results were higher for doi 10.18502/sjms.v17i1.10682 page 21 sudan journal of medical sciences anas elias et al table 4: predictors of patient satisfaction among the study participants. factors satisfied cor ( 95% c.l.) p-value yes n (%) no n (%) gender male 130 (73.4) 47 (26.6) 1.17 (0.76–1.80) 0.483 female 173 (70.3) 73 (29.7) 1 age (yr) <20 42 (71.2) 17 (28.8) 0.51 (0.20–1.31) 0.159 20–35 163 (70.0) 70 (30.0) 0.48 (0.21–1.07) 0.074 36–50 59 (70.2) 25 (29.8) 0.48 (0.2–1.18) 0.111 >50 39 (83.0) 8 (17.0) 1 level of education illiterate 45 (83.3) 9 (16.7) 3.40 (1.56–7.45) 0.020 primary school 43 (79.6) 11 (20.4) 2.66 (1.28–5.55) 0.009 secondary school 121 (77.1) 36 (22.9) 2.29(1.40–3.73) 0.001 university and above 94 (59.5) 64 (40.5) 1 occupation student 55 (67.1) 27 (32.9) 0.61 (0.34–1.07) 0.082 employee 90 (66.2) 46 (33.8) 0.58 (0.36–0.94) 0.028 not working 158 (77.1) 47 (22.9) 1 income high 10 (55.6) 8 (44.4) 0.35 (0.12–0.99) 0.047 moderate 214 (70.4) 90 (29.6) 0.66 (0.39–1.13) 0.129 low 79 (78.2) 22 (21.8) 1 or: crude odds ratio; c.i.: confidence intervals nurse introducing herself to the patient (57.2%), nurse being respectful (82.8%), nurses’ response to the patient appeal (73.1%), and nurses’ explanation of the medication she provided 78.5%. many researchers documented a high satisfaction with nursing services in different settings [27, 62]. the possible explanation for that is the kindness of nurses and good communication with patients [28–30]. the findings of this study confirmed that food services recorded the highest satisfaction (91.1%) among the study participants. this pattern is similar to many studies conducted in ksa. the ministry of health patient satisfaction report produced a satisfaction of 81.22% with food. a study conducted in makkah showed that 78.8% of patients were satisfied with hospitals’ quality of food services [10]. the satisfaction with the hospital rooms’ cleanliness was 72.3% and 79.2% for the maintenance of appropriate room temperature. additionally, a study conducted in riyadh ended with a 79.6% satisfaction rate for the cleanness of treating rooms and 78.1% for the maintenance of room temperature [31]. these findings are also consistent with the ministry of health patient satisfaction report [20]. our findings showed an increase in patient satisfaction with the increase in patient’s age while the satisfaction level was about 70% for patients aged <50, it was doi 10.18502/sjms.v17i1.10682 page 22 sudan journal of medical sciences anas elias et al 83% for those aged >50. this finding is supported by the literature that showed that older patients tend to have a higher satisfaction level [32–34]. binary logistic regression analysis suggested that uneducated patients and patients with secondary school education were more likely to have lower satisfaction levels than the university-educated patients. this is also consistent with previous research indicating the negative association between education level and level of satisfaction [33–36]. limitations our research has some limitations that should be mentioned; first, the research was conducted only in jazan region, which decreases the potentiality of generalizing the study results to the other areas in ksa. second, data were collected using a selfreported questionnaire, a method which is a source of potential error. finally, patient satisfaction is a patient’s expectations for their care encounter. hence, it is a subjective healthcare measure [37, 38], as two patients receiving the same services may have different opinions. despite these limitations, our study for the first time provided an estimate for the level of satisfaction with the healthcare services provided in the general hospitals of jazan region. 5. conclusion the satisfaction level of jazan population with healthcare services was high. however, there were some aspects of dissatisfaction, including the waiting period before seeing the doctor, admission management, and hygiene in public places. these aspects are recommended to be improved to ensure high-quality services are provided by the general hospitals in jazan. acknowledgements the authors extend their appreciation to the jazan health directorate and the general hospitals of the jazan region selected for the study. they would also like to thank the participants who participated in this study. doi 10.18502/sjms.v17i1.10682 page 23 sudan journal of medical sciences anas elias et al ethical considerations the current study was conducted following the ksa ethical regulations guidelines. the ethical approval for the current study was obtained from the ethical committee of jazan hospital (#1806) and the ethical committee of jazan university. competing interests none. availability of data and materials all data and materials used in the study are available from the corresponding author upon reasonable request. 6. funding none. references [1] westaway, m. s., rheeder, p., van zyl, d. g., et al. 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(1998). debating survey approaches. health affairs, vol. 17, no. 1, pp. 265–268. doi 10.18502/sjms.v17i1.10682 page 27 introduction materials and methods study design, setting, and population sampling procedures data collection and study instrument data analysis results discussion limitations conclusion acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 18, issue no. 1, doi 10.18502/sjms.v18i1.12861 production and hosting by knowledge e research article epidemiological aspects and antibiotics susceptibility patterns of streptococcus pyogenes isolated from subjects with tonsillitis, sudan elnaim bushra ahmed1,2, elsir ali abu groun3, babiker saad almugadam4, yousif musa alobaid ahmed4, aymen mudawe nurain mudawe5, nassir abakar babiker6, and nadir abuzeid1* 1department of microbiology, faculty of medical laboratory sciences, omdurman islamic university, omdurman, sudan 2department of medical laboratory investigations, kosti police hospital, kosti, sudan 3department of microbiology, faculty of medical laboratory sciences, university of khartoum, khartoum, sudan 4department of microbiology, faculty of medical laboratory sciences, university of el imam el mahdi, sudan, sudan 5delta college of science and technology, omdurman , sudan 6central medical laboratory, wad medani teaching hospital for obstetrics & gynecology, wad medani, sudan orcid: elnaim bushra ahmed: https://orcid.org/0000-0003-1066-9245 babiker saad almugadam: https://orcid.org/0000-0003-3014-8359 yousif musa alobaid ahmed: https://orcid.org/0000-0002-0863-3262 nadir abuzeid: https://orcid.org/0000-0003-2074-7892 abstract background: globally, streptococcus pharyngitis is a major public health challenge. the current study investigates the prevalence of streptococcal pyogenes among children under 17 years old in ent kosti teaching hospital and examines the susceptibility of isolated s. pyogenes strains to commonly used antibiotics. methods: a total of 384 throat swabs were obtained from children under the age of 17 who attended the kosti teaching hospital between 2019 and 2021. streptococcus pyogenes was isolated by conventional microbiology procedures. each s. pyogenes strain was subjected to antibiotic susceptibility testing according to the clsi guidelines. results: most participants of this study were females 219 (57%) and aged between 5 and 10 years 259 (67.4%). out of the 384 participants, 134 (34.9%) and 255 (66.4%) suffered from lymphadenopathy and tonsil hyperplasia, respectively. interestingly, lymphadenopathy and tonsil hyperplasia were more (p � 0.05) in the 5–10 age group than those aged 11–16 years. moreover, 41.4% of the participants were infected by a gas sore throat. gas sore throat is significantly associated with lymphadenopathy (aor: 2.375, 95% ci: 1.479–3.815, p � 0.000) and tonsil hyperplasia (aor: 3.374, 95% ci: 1.939–5.874, p � 0.000). notably, males (aor: 0.853, 95% ci: 0.549–1.325, p 0.479) and individuals aged 5–10 years (aor: 0.867, 95% ci: 0.464–1.618, p 0.654) were less likely to have a gas sore throat. in our study, all isolated strains were sensitive to penicillin. clindamycin, azithromycin, and erythromycin resistance were observed in 7 (4.4%), 44 (27.7%), and 47 (29.6%) isolates, respectively. conclusion: the study displayed the current situation of gas sore throat in the white nile state. penicillin was found to be the effective drug to cure s. tonsillitis but a high rate of resistance to macrolides was noticed which is an alarming sign. how to cite this article: elnaim bushra ahmed, elsir ali abu groun, babiker saad almugadam, yousif musa alobaid ahmed, aymen mudawe nurain mudawe, nassir abakar babiker, and nadir abuzeid* (2023) “epidemiological aspects and antibiotics susceptibility patterns of streptococcus pyogenes isolated from subjects with tonsillitis, sudan,” sudan journal of medical sciences, vol. 18, issue no. 1, pages 6–24. doi 10.18502/sjms.v18i1.12861 page 6 corresponding author: nadir abuzeid; email: nadirabuzeid@oiu.edu.sd received 2 december 2021 accepted 17 november 2022 published 31 march 2023 production and hosting by knowledge e elnaim bushra ahmed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences elnaim bushra ahmed et al keywords: azithromycin, clindamycin, erythromycin, gas, streptococcus pyogenes 1. introduction pharyngitis or tonsillitis (sore throat) is defined as an inflammatory process involving the mucous membranes of the oropharynx and tonsils [1]. tonsillitis is a major problem that threatens the health and socioeconomic lives of many people [1, 2]. viruses are a common cause of pharyngitis; however, >15–30% of this condition is associated with group a streptococcus (gas) infection [3, 4]. streptococcal pharyngitis is a highly important disease, and its ultimate frequency arises among children aged 5–15 years [5]. the common signs of illness are usually abrupt and include painful throat, rapid onset fever, discomfort swallowing, enlarged tonsils, and tender cervical lymph nodes [6]. transmission of s. pyogene mainly occurs with direct contact, contaminated objects, or nasal secretions from infected persons or carriers [7]. the occurrence of the disease is varied according to seasonal and environmental conditions [8]. streptococcus pyogenes (s. pyogene), also identified as lancefield gas, is a significant pathogenic bacteria associated with a wide range of human diseases. much data collection and assessment of the global burden of gas infection indicated that about 616 million suffer from pharyngitis, with a minimum of 111 million cases of skin diseases (pyoderma). more seriously, 18.1 million people complained of invasive diseases and not less than 517,000 deaths occurred due to serious invasive diseases and disease sequelae [9–13]. this data reflects the important rank of gas among pathogenic bacteria and express the effect of gas on worldwide mortality and morbidity [10, 12, 14]. gas is an exceptional causative agent of diseases that require an etiologic identification and specific treatment [12]. the diagnosis of pharyngitis based on the history of disease with clinical remakes is useful, however, accurate diagnosis requires laboratory analysis [15, 16]. in children, the mcisaac scoring system is the most common clinical prediction procedure used for the identification of streptococcal pharyngitis. culturing throat swab on sheep blood remains the perfect technique for the identification of gas infections [5]. rapid antigen detection tests and serodiagnosis, including anti-deoxyribonuclease b (adnase b) and antistreptolysin o (aso), are additional diagnostic tools for gas diseases [17]. penicillin and its products are still the drugs of choice, however, in patients who are allergic to it, macrolide is the alternative drug prescribed to treat s. pyogenes infections [18]. growing macrolide resistance has been stated. furthermore, the fastest developing problem of antibiotic resistance of s. pyogenes is raised. evidence about increasing minimum doi 10.18502/sjms.v18i1.12861 page 7 sudan journal of medical sciences elnaim bushra ahmed et al inhibitory concentration or reduced susceptibility to penicillin has been documented [19]. various resistance rates have been reported according to geographical location and researcher [20, 21]. unfortunately, little data on gas pharyngitis were available regarding low-income countries [22]. sudan is a poor country with poor health resources, researches concerning s. pharyngitis among children remains an ignored problem with few data available on the topic [23–27]. moreover, trial treatment of microbial infections including tonsillitis without culture to recognize the causative pathogens is current practice in our study area and all over sudan. furthermore, data on prevalence, antibiotic susceptibility testing, and features related to s. pharyngitis among children in our state were least studied. thus, this study intended to investigate the prevalence of gas, antibiotics susceptibility patterns, and related aspects of s. pyogenes among children with pharyngitis in white nile state, sudan. 2. materials and methods 2.1. study design and period this cross-sectional study was conducted at the kosti teaching hospital between 2019 and 2021. 2.2. study area situated in southern sudan and located between latitudes 12 to 13.30º north and longitude 31 to 33.30º east, white nile state shares its border with khartoum state in the north, north kordofan state in the west, south kordofan and upper nile states in the south-west, the state of southern sudan in the south, and the states of al-gazira and sennar in the east. the state has a total area of 16,000 km2. it has a population of 1.7 million according to the 2008 population census. of this number, 85% live in rural areas and around 15% in urban areas. agriculture is the main source of livelihood in the state, and 65% of the state population work either as farmers or as seasonal laborers. white nile remains one of the least developed areas in the country. there are 3 teaching and 19 rural hospitals. the most important towns are al-dweim, algabaleen, al-kawwa, rabak the capital of the state, and kosti which is the largest town housing the kosti teaching hospital (the largest hospital in the state in which the current study was carried out). doi 10.18502/sjms.v18i1.12861 page 8 sudan journal of medical sciences elnaim bushra ahmed et al 2.3. ethical considerations the study approval was taken from omdurman islamic university (khartoum). authorities of kosti teaching hospital granted permission to collect the specimens. written consent was obtained from the investigated children’s parents or guardians. a verbal agreement was obtained from all children. 2.4. study participants, data, and sample size the study participants were children with tonsillitis between the ages of 5 and 15 years who attended the kosti teaching hospital ent unit. each participant underwent a general physical examination by an ent consultant before being selected for the study. patients with a history of respiratory surgery, autoimmune disease, radiotherapy, body abnormality, or chemotherapy were excluded. children who were under antimicrobial use or those who had a history of antibiotic use at least seven days before the presentation were excluded. data collection was done by using a pre-test questionnaire that covered the patients’ demographical data (age, gender, and residence) and clinical information (sore throat, fever, tonsils hyperemia, and cervical lymphadenopathy). figure 1 shows the study flow diagram. the sample size was estimated using the following formula: n = z2 × p (p–1)/d2, where n is the sample size, z is the standard normal variable (corresponding to the 95% level of significance = 1.96), p is the expected prevalence = 0.5% as determined by a preliminary study, and d is the precision corresponding to the effect size = 0.05. based on the above data, n = (1.96)2 × p (p–1)/(0.05)2 = 384. 2.5. samples collection and processing of specimens under good light and using the tongue depressor, the inside of the mouth was examined for signs of inflammation and the presence of pus and exudates. using a sterile cotton swab, the two infected tonsils were swabbed and care was taken to avoid contamination of swabs with saliva or touching any part of the mouse. all swabs collected were labeled and immediately transferred to the laboratory. doi 10.18502/sjms.v18i1.12861 page 9 sudan journal of medical sciences elnaim bushra ahmed et al p a r t i c i p a n t ’ s s e l e c t i o n and data collection study flowchart statistical analysis and data presentation sample collection and laboratory analysis p a rt i c i p a n t ’ s s e l e c ti o n b a s e d o n s tu d y exclusion and inclusion criteria and the main targeted criteria was age ≤ 16 years all data were analyzed using ibm spss statistics for windows (version 21) and presented in figures and tables. the results were expressed as numbers and percentages throat swab was collected from everyone.subsequently, all the samples were cultivated and the isolated streptococcus pyogenes were tested for their susceptibility to antibiotics figure 1: study flow chart. 2.6. inoculation of collected sample on culture media 5% sheep blood agar (hi media, india) was the growing medium used to isolate the organisms. throat specimens were rolled firmly over one-sixth of the plate to deposit the specimen, the wire loop was used to streak the inoculum over the surface of the plate, and plates were incubated at 35ºc overnight. a candle jar was used to provide an atmosphere of co2. after 24 hr of incubation, each plate was checked for colonies with 𝛽-hemolytic characteristics. culture plates negative for β-hemolytic colonies were incubated for an additional 24 hr to allow for the recovery and detection of slow growers. selected 𝛽-hemolytic colonies were subjected to another sub-culture using blood agar plates to obtain pure growth. after overnight incubation, the pure colonies were tested for their gram reaction, catalase. all 𝛽-hemolytic and catalase-negative colonies were tested for bacitracin susceptibility bacteria. the bacterial suspension was evenly spread onto a blood agar plate using a swab, and 0.05 u bacitracin disc (hi media, india) was placed on the inoculated surface and incubated in a candle jar for 18–24 hr at 35ºc. any zone of inhibition surrounding the disc was indicative of a presumptive gas. 2.7. bacterial isolates three hundred eighty-four throat swabs were collected from subjects with tonsils infection (tonsillitis) from 2019 to 2021 in kosti, sudan. the specimens were collected from the main hospital of the state ent unit. only 159 s. pyogenes out of inoculated bacteria were reported as s. pyogenes based on colony morphology, beta-hemolysis on sheep blood agar, and sensitivity to bacitracin disc (0.05 u, himedia, india). doi 10.18502/sjms.v18i1.12861 page 10 sudan journal of medical sciences elnaim bushra ahmed et al 2.8. antibiotics susceptibility testing the sensitivity testing was done after sub-culturing the bacteria onto a 5% blood agar medium (hi-media, india) overnight incubation at 37ºc to yield a new growth of s. pyogenes. the test was performed according to the clinical laboratory standards institute (clsi) [28]. about three to five well-defined colonies were picked using a sterile wire loop and emulsified into 3–5 ml sterile physiological saline to prepare a turbidity suspension equivalent to the 0.5 mcfarland standards. using a sterile cotton swab, the suspension of the test organism was inoculated into mueller–hinton sensitivity mediumbased blood agar (hi-media, india). next, sterile forceps were used to transfer the antimicrobial discs (erythromycin 15 mg, azithromycin15 mg, penicillin 10 mg, clindamycin 2 mg) onto the inoculated plate (all antibiotics were from hi-media, india). the inoculated plates were incubated overnight at 37ºc and in the presence of 5% co2 provided by using a candle jar. following the incubation, the zones of inhibition were measured by using a ruler and reported in mm. compared with the manufacturer’s reference chart results, the generated results were provided (hi-media, india). the susceptibility of isolates to each antibiotic was recorded as sensitive, resistant, or intermediated. streptococcus pyogenes atcc1916 was used as a control. 2.9. statistical analysis all data were analyzed using ibm spss statistics for windows (version 21). the results were expressed as numbers and percentages. the statistical differences were evaluated using the chi-squared and fisher’s exact tests. multinomials and binary were involved in investigating the associations of dependent variables with the independent factors. a p-value � 0.05 was considered significant. 3. results 3.1. sociodemographic and clinical features of the study participants three hundred and eighty-four participants were enrolled in this research – 219 (57%) females and 165 (43%) males. the age of the studied participants ranged from 5 to 15 years with a mean age of 9.0 and a standard deviation (sd) of 3.0. the vast majority of study participants 259 (67.4%) were between the ages of 5 and 10 years. moreover, about 296 (77.1%) participants were from urban and 88 (22.9%) were from rural areas. doi 10.18502/sjms.v18i1.12861 page 11 sudan journal of medical sciences elnaim bushra ahmed et al furthermore, 268 (69.8%) participants were in primary school, 59 (15.4%) in secondary school, and <57 (14.8) in kindergarten (table 1). out of the 384 participants, only 34.9% had lymphadenopathy and 66.4% suffered from tonsil hyperplasia. fever and sore throat were found in all patients. interestingly, there was a significant dissimilarity (p � 0.05) in the occurrence of lymphadenopathy and tonsil hyperplasia, which were more in the 5–10 years age group compared to individuals of 11–16 years (table 2). table 1: characteristics of the study participants. variable frequency: n (%) gender male 165 (43) female 219 (57) age (yr) 5–10 259 (67.4) 11–16 125 (33.6) residence urban 296 (77.1) rural 88 (22.9) education level kindergarten 57 (14.8) primary school 268 (69.8) secondary school 59 (15.4) n, number. 3.2. prevalence of gas sore throat the overall prevalence of gas associated with tonsillitis (sore throat) in this research was 159 (41.4%) and 225 (58.6%) due to non-gas sore throat (figure 2). there was no significant variation in the frequency of gas sore throat among gender, age groups, education levels, and residence, p � 0.05. regarding the link of gas sore throat with the clinical features, we found that the frequency of gas sore throat was significantly higher in individuals with lymphadenopathy or tonsil hyperplasia, p � 0.05. the findings of logistic regression analysis also revealed that gas sore throat is significantly associated with lymphadenopathy (aor: 2.375, 95% ci: 1.479–3.815, p � 0.000) and tonsil hyperplasia (or: 3.374, 95% ci: 1.939–5.874, p � 0.000). notably, males (or: 0.853, 95% ci: 0.549–1.325, p 0.479) and individuals aged 5–10 years (or: 0.867, 95% ci: 0.464–1.618, p 0.654) were less likely to be infected by a gas sore throat, but it is not significant. consequently, lymphadenopathy and tonsil hyperplasia (p < 0.05) were independent predictors of s. pyogenes pharyngitis in children (table 3). doi 10.18502/sjms.v18i1.12861 page 12 sudan journal of medical sciences elnaim bushra ahmed et al table 2: clinical features of the study subjects. variable frequency: n (%) fever sore throat lymphadenopathy tonsil hyperemia yes no yes no yes no yes no overall 384 (100) 0 (0) 384 (100) 0 (0) 134 (34.9) 250 (65.1) 255 (66.4) 129 (33.6) gender male 165 (100) 0 (0) 165 (100) 0 (0) 62 (37.6) 103 (62.4) 106 (64.2) 59 (35.8) female 219 (100) 0 (0) 219 (100) 0 (0) 72 (32.9) 147 (67.1) 149 (68) 70 (32) x2 – 0.915 0.607 p-value – 0.339 0.436 age (yr) 5–10 259 (100) 0 (0) 259 (100) 0 (0) 110 (42.5) 149 (57.5) 206 (79.5) 53 (20.5) 11–16 125 (100) 0 (0) 125 (100) 0 (0) 24 (19.2) 101 (80.8) 49 (39.2) 76 (60.8) x2 – – 20.097 61.491 p-value – – �0.000 �0.000 residence urban 296 (100) 0 (0) 296 (100) 0 (0) 94 (31.8) 202 (68.2) 193 (65.2) 103 (34.8) rural 88 (100) 0 (0) 88 (100) 0 (0) 40 (45.5) 48 (54.5) 62 (70.5) 26 (29.5) x2 – – 5.602 0.839 p-value – – 0.018 0.36 education level kindergarten57 (100) 0 (0) 57 (100) 0 (0) 29 (50.9) 28 (49.1) 48 (84.2) 9 (15.8) primary school 268 (100) 0 (0) 268 (100) 0 (0) 95 (35.4) 173(64.6) 185 (69) 83 (31) secondary school 59 (100) 0 (0) 59 (100) 0 (0) 10 (16.9) 49 (83.1) 22 (37.3) 37 (62.7) x2 – – 14.808 31.35 p-value – – 0.001 �0.000 data assessed by pearson chi-square.n, number; x2, chi-square. 3.3. antibiotics susceptibility findings 159 gas isolates were tested for their susceptibility to erythromycin (15 μg), clindamycin (2 μg), penicillin (10 u), and azithromycin (15 μg). we found that all the isolated strains were sensitive to penicillin. however, the frequency of antibiotic resistance to clindamycin, azithromycin, and erythromycin resistance was observed in 7 (4.4%), 44 (27.7%), and 47 (29.6%) of isolates, respectively (figure 3). additionally, the rate of clindamycin, erythromycin, and azithromycin resistance was more in individuals suffering from lymphadenopathy (p � 0.05) or tonsil hyperplasia (p � 0.05). furthermore, the rate of clindamycin and azithromycin resistance was also more in males than females but it was not significant (table 4). doi 10.18502/sjms.v18i1.12861 page 13 sudan journal of medical sciences elnaim bushra ahmed et al prevalence: n (%) gas non-gas 159 (41.4) 225 (58.6) figure 2: overall prevalence of streptococcal sore throat. gas, group a streptococci; non-gas, non-group a streptococci; n, number. 159 (100%) clindamycin 152 (95.6) 7 (4.4) erythromycin 112 (70.4) 47 (29.6) azithromycin sensitive resistant 115 (72.3) 44 (27.7) pencillin frequency expressed as n (%) figure 3: susceptibility of the isolated gas to antibiotics. gas, group a streptococci; n, number. 4. discussion human infections caused by s. pyogenes are a common reason for morbidity and mortality globally [29]. the prevalence of acute pharyngotonsillitis caused by s. pyogenes is approximately 15 to 30%. this percentage varies from region to region [30]. in the doi 10.18502/sjms.v18i1.12861 page 14 sudan journal of medical sciences elnaim bushra ahmed et al table 3: association of streptococcal sore throat with gender, age groups, residence, and clinical features of participants. variable prevalence association unadjusted adjusted n (%) x2 p-value or (95%ci) p-value aor (95% ci) p-value gender female 95 (43.4) 1 1 male 64 (38.8) 0.818 0.366 0.853 (0.549– 1.325) 0.479 0.853 (0.549– 1.325) 0.479 age (yr) 11–16 49 (39.2) 1 1 5–10 110 (42.5) 0.372 0.542 0.867 (0.464– 1.618) 0.654 0.867 (0.464– 1.618) 0.654 residence rural 35 (39.8) 1 1 urban 124 (41.9) 0.126 0.723 1.317 (0.783– 2.217) 0.300 1.317 (0.783– 0.217) 0.300 education level secondary school 29 (49.2) 1 1 primary school 104 (38.8) 2.622 0.27 1.016 (0.547– 1.889) 0.959 0.398 (0.151– 1.048) 0.062 kindergarten 26 (45.6) 0.398 (0.151– 1.048) 0.062 0.391 (0.183– 0.837) 0.016 clinical features lymphadenopathy no 83 (33.2) 1 1 yes 76 (56.7) 19.886 0.000 2.375 (1.479– 3.815) 0.000 2.375 (1.479– 3.815) 0.000 tonsil hyperplasia no 31(24) 1 1 yes 128 (50.2) 24.173 0.000 3.374 (1.939– 5.874) 0.000 3.374 (1.939– 5.874) 0.000 statistical analysis performed using pearson chi-square and binary and multinomial logistic regression. n, number; x2 , chi-square; or, odd ratio; aor, adjusted odd ratio; ci, confidence interval. present study, we present the prevalence of s. pyogenes associated with tonsillitis among sudanese children who attended the kosti teaching hospital. a total of 384 study participants were involved in this study, of which 165 (43%) were males and 219 (57%) were females. our findings reveal that of the 384 patients, only 159 (41.4%) were infected by a gas sore throat and 58.6% by a non-gas sore throat. this was lower when compared with a previous study carried out in the study area [26]. it is also lesser than that found in mohammed et al.’ study (2016) (86%), which was conducted in khartoum city, sudan [25]. in contrast, it is higher than the results of al fadhil et al. (35.5%) and abdelwahab et al.’s (2014) (6%) studies, which were also conducted in khartoum city, sudan [23, 24]. the prevalence of s. pyogenes associated with pharyngitis among children in african studies compared to the current study was higher (66.7%) in a nigerian study by uzodimma et al. and lower in an egyptian study by sultan et al. (28%), a kenyan study by osowicki et al. (23% ), and an ethiopian study by tesfaw et al. (11.3%) [30–33]. doi 10.18502/sjms.v18i1.12861 page 15 sudan journal of medical sciences elnaim bushra ahmed et al table 4: relationship of antibiotics susceptibility patterns of the gas isolates (n = 159) with gender, age groups, residence, and clinical features of study subjects. variable number clindamycin: n (%) erythromycin: n (%) azithromycin: n (%) s r s r s r gender male 64 61 (95.3) 3 (4.7) 47 (72.3) 18 (27.7) 46 (70.8) 19 (29.2) female 95 91 (95.8) 4 (4.2) 65 (68.4) 30 (31.6) 69 (72.6) 26 (27.4) x2 0.000 0.278 0.066 p-value 1.000𝐶 0.598 0.797 age (yr) 5–10 110 104 (94.5) 6 (5.5) 77 (70) 33 (30) 78 (70.9) 32 (29.1) 11–16 49 48 (98) 1 (2) 35 (70) 15 (30) 37 (74) 13 (26) x2 0.303 0.000 0.162 p-value 0.582𝐶 1.000 0.687 residence urban 124 118 (95.2) 6 (4.8) 85 (68.5) 39 (31.5) 88 (71) 36 (29) rural 335 34 (97.1) 1 (2.9) 27 (77.1) 8 (22.9) 27 (77.1) 8 (22.9) x2 – – – p-value 1.000𝐹 0.404𝐹 0.528𝐹 education level kindergarten 26 24 (92.3) 2 (7.7) 17 (65.4) 9 (34.6) 17 (65.4) 9 (34.6) primary school 104 99 (99.2) 5 (4.8) 75 (72.1) 29 (27.9) 77 (74) 27 (26) secondary school 29 29 (100) 0 (0) 20 (69) 9 (31) 21 (72.4) 8 (27.6) x2 1.864 0.603 0.881 p-value 0.367𝐹 0.766𝐹 0.704𝐹 clinical features lymphadenopathy yes 76 72 (94.7) 4 (5.3) 50 (65.8) 26 (34.2) 51 (67.1) 25 (32.9) no 83 80 (96.4) 3 (3.6) 62 (74.7) 21 (25.3) 64 (77.1) 19 (22.9) x2 – 1.512 1.983 p-value 0.710𝐹 0.219 0.159 tonsil hyperplasia yes 128 121 (94.5) 7 (5.5) 84 (65.6) 44 (34.4) 87 (68) 41 (32) no 31 31 (96.4) 0 (0) 28 (90.3) 3 (9.7) 28 (90.3) 3 (9.7) x2 – – – p-value 0.347𝐹 0.008𝐹 0.013𝐹 data analysis performed using pearson’s chi-square and fisher’s exact test𝐹 . n, number; x2 , chi-square; s, sensitive; r, resistant; gas, group a streptococci. moreover, the occurrence of tonsils infection was predominant observed among urbanized patients 124 (41.9%), while the disease was found only in 35 (39.8) patients from rural areas. this could be due to the living conditions and personnel behavior or more likely due to the consumption of cold drinks and fast food, which are easily available in the urbanized area compared to rural areas. the result of this research revealed that gas tonsillitis predominately occurred in children aged 5–10 years (68%) and the incidence among those aged 11–16 years is relatively low (32%). similar observations were reported for the age group of 6–12 years (61%) [34]. however, contrary to the doi 10.18502/sjms.v18i1.12861 page 16 sudan journal of medical sciences elnaim bushra ahmed et al results of the current study, a previous study performed on this subject area showed a higher rate of streptococcal pharyngitis among those aged 16–20 (85.7%) than those who were 11–15 (70%) and 5–10 (56.2%) years old. the distribution of streptococcal pharyngitis was more in female patients (95 [43.4%]) than in male patients (64 [38.8%]). similarly, mohammed et al. and ahmed et al.’s studies reported that the majority of those who complained of tonsillitis were females. this is probably because the number of female patients admitted was more than male patients. on the other hand, singh et al. reported that the frequency of streptococcal pharyngitis was more in boys than girls [35]. furthermore, it was noted that 64% of primary school students, 19% of secondary school students, and 17% from kindergarten were infected by gas pharyngitis. our finding was proportionally 19%, which is similar to the results of sharma et al. who found a gas frequency of 17.5% in children aged 11–15 years (secondary-school level) [59]. however, the current research showed a higher frequency of gas in the age group 5–10 years. this may be due to cross-infection because of overloaded classrooms and poor air circulation in them, low immunity, and the nature of children’s activity. probably, the variation between studies could be due to the difference in sample size, study subjects, climates, seasons, and diagnostic procedures. according to the ast results, all isolates were sensitive to penicillin, which is similar to the findings of other previous studies [36–39]. in contrast to these results, a previous study carried out in egypt found that four strains of s. pyogene were resistant to penicillin [40], which is different from our findings and the available literature. the efficiency of this drug could be due to the incapability of gas to generate β-lactam enzymes. however, penicillin can be ineffective in treating s. pyogenes infections, as its action is evaded through the introduction into the epithelial cells, which is difficult for penicillin to reach inside cells [41]. moreover, the development of the biofilm phenomenon [42] and the presence of other β-lactamaseproducing bacteria act as protective tools for s. pyogenes [43, 44]. many previous studies showed comparable findings. indeed, the rate of resistance to erythromycin was 21.3%, egypt [40], lebanon 23%, [45], and greece 22.8 % [46], which is lower than our result. sayyahfar et al.’s study reported that 33.9% of gas isolates were resistant to erythromycin [47]. the findings of these studies are considered more relevant to our study in which the resistance rate to erythromycin was 29.6%. compared to this, several studies showed a low rate of resistance to erythromycin as reported in norway (2.7%) [ 48], the united states (5.2%) [49], france (6.5%) [50], italy (7.4%) [29], spain (2.8%) [51], tunis (5.2%) [52], and taiwan (10.7%) [53]. additionally, the clindamycin resistance rate of gas in our study was 4.4%, however, many studies have shown higher results doi 10.18502/sjms.v18i1.12861 page 17 sudan journal of medical sciences elnaim bushra ahmed et al – for instance, iran (13.5%) and korea (32.5%) [54, 55]. on the other hand, a low rate of clindamycin was reported in italy (1.4%) and the usa (0.5%) [56, 57]. our study showed an azithromycin resistance of 27.7% which is similar to the results of sharma et al. (28.6%) and rijal et al. (24%) [58, 59]. in contrast to these results, recently khademi et al. reported that the resistance of azithromycin was 12%. the variation of reports outcomes may be due to the diversity of genotypic and phenotypic characters of circulating strains, or guidelines of antibiotic utilization rules between the different sites of the earth. 5. conclusion the high proportion of gas was isolated from the throats of children suffering from tonsillitis in white nile state. regardless of the resistance of isolates to some antibiotics, penicillin still is the drug of choice for streptococcal tonsillitis with 100% sensitivity. gas tonsillitis with lymphadenopathy or tonsil hyperplasia showed a significant frequency of macrolides resistance. the development of macrolides resistance among isolates of gas reflects the need for alternative choices for the management of gas tonsillitis in subjects with a penicillin allergy. acknowledgments the authors are grateful to all those who participated in this study, namely, the staff of the department of medical laboratory investigations, ent unit hospital, kosti, sudan, national public health laboratory, khartoum, sudan, and the department of medical microbiology, faculty of medical laboratory of sciences, omdurman islamic university, omdurman, sudan. competing interests none declared. availability of data and material the dataset generated during this study are available from the corresponding author on reasonable request. doi 10.18502/sjms.v18i1.12861 page 18 sudan journal of medical sciences elnaim bushra ahmed et al funding none. references [1] hurst, j. r., kasper, k. j., sule, a. n., & mccormick, j. k. 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(2014). prevalance of streptococcus pyogenes infection in children aged between 5 to 15 years with acute tonsillopharyngitis and its antibiogram. iosr journal of dental and medical sciences (iosr-jdms), 1(13), .55–50 [59] rijal, k. r., dhakal, n., shah, r. c., timilsina, s., mahato, p., & thapa, s. (2009). antibiotic susceptibility of group a streptococcus isolated from throat swab culture of school children in pokhara, nepal. nepal medical college journal, 11(4), 238–240. doi 10.18502/sjms.v18i1.12861 page 24 introduction materials and methods study design and period study area ethical considerations study participants, data, and sample size samples collection and processing of specimens inoculation of collected sample on culture media bacterial isolates antibiotics susceptibility testing statistical analysis results sociodemographic and clinical features of the study participants prevalence of gas sore throat antibiotics susceptibility findings discussion conclusion acknowledgments competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13606 production and hosting by knowledge e review article a review of medical microbiology curriculum integration in the integrated modular system of education at medical schools in saudi arabia mohammed sarosh khan1 and muhammad musthafa poyil2 1department of basic medical science, college of medicine, prince sattam bin abdulaziz university, al-kharj, ksa 2department of basic medical science, college of medicine, prince sattam bin abdulaziz university, al-kharj, ksa orcid: mohammed sarosh khan khan: https://orcid.org/0000-0002-2416-4304 abstract medical or clinical microbiology has its importance in the curriculum of undergraduate degree programs of all medical colleges of the kingdom of saudi arabia. this review describes the preclinical medical microbiology teaching at prince sattam bin abdulaziz university as a hybrid module, it is integrated into blocks or system-based courses. various teaching and practical approaches were discussed and elaborated. several challenges and potential suggestions were also emphasized for innovation in an integrated system of teaching. keywords: curriculum medical microbiology, integration, teaching 1. introduction medical or clinical microbiology is one of the essential parts of the medical curriculum in the kingdom of saudi arabia like other nations [1, 2]. undergraduate medical students require an understanding of bacteriology, virology, mycology, and parasitology during basic pre-clinical medical years. it often includes basic concepts such as the use of aseptic techniques, the study of the structure and physiological and molecular characteristics of a major group of medically important microorganisms (e.g., bacteria, virus, fungi, and parasites), pathogenicity and mechanisms of infection, life cycle, the mode of action of antimicrobial agents, the epidemiology and principles of laboratory diagnostic testing, and infection control and preventions. modern-day medical practitioners need a robust grassroot-level understanding of medical microbiology. the most commonly observed medical diagnoses in the inpatient and outpatient settings in hospitals are infections [3–5]. medical practitioners require how to cite this article: mohammed sarosh khan and muhammad musthafa poyil (2023) “a review of medical microbiology curriculum integration in the integrated modular system of education at medical schools in saudi arabia,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 231–241. doi 10.18502/sjms.v18i2.13606 page 231 corresponding author: mohammed sarosh khan; email: mo.khan@psau.edu.sa received 10 may 2022 accepted 30 december 2022 published 30 june 2023 production and hosting by knowledge e mohammed khan et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammed khan et al general knowledge and practical skills to control the infections caused by pathogens that are multidrug-resistant against potential new antimicrobial agents [6]. rapid globalization is resulting in local epidemics or pandemics such as ebola and chikungunya, sars, covid, etc., which necessitates the grooming of medical graduates on the emerging infectious causative organisms such as viruses and others responsible for the pandemics [7–9]. conventionally, medical students have studied microbes mainly as disease-causing hazardous infectious agents, and very old traditional techniques were used for identifying them. however, the latest molecular diagnostic methods are rapidly becoming a dominant means for organism identification and confirmation [10]. the medical education unit of the medical college has also explored innovative education methodology that focuses on the proactive, self-reliant, or autonomous mode of instruction to teach this rapidly developing region [11–13]. medical microbiology has gained more importance in medical education due to the emerging widespread infectious diseases growing universally and resulting in considerable human morbidity and fatality. furthermore, the medical microbiology-oriented questions comprise a significant section for competitive medical licensing examinations for national medical boards such as saudi commission for health practitioner’s exams as well as the us medical licensing examination (usmle). this review is the primary initial review to comprehensively describe preclinical medical student microbiology and parasitology teaching at prince sattam bin abdulaziz university (psau), al-kharj, saudi arabia. 2. medical degree program/syllabus format the medical degree curriculum in the medical school of prince sattam bin abdulaziz university has been organized into three different phases or blocks and each phase includes different modular courses. formal medical microbiology teaching is included in the second and third years of medical school (phases i & ii). in both these phases, medical students learn different modules that include basic integrated foundation modules on musculoskeletal and gastrointestinal tract, urinary system, reproductive system, cardiovascular system, endocrine, neuro and special senses, and blood immune system. the traditional system of medical colleges teaches microbiology and parasitology as separate subjects, however, the new systems have integrated microbiology and parasitology longitudinally or horizontally [14] in the preclinical curriculum. the integration doi 10.18502/sjms.v18i2.13606 page 232 sudan journal of medical sciences mohammed khan et al of microbiology and parasitology is the most noteworthy or fundamental challenge for the majority of medical schools. although many coordinators notified a productive and successful merger, others stated a broad or common concern that integration or unification has led to a significant reduction in total teaching hours. many different schools of thought reported the theoretical merits of curriculum integration [14], however, its benefit for enhancing or supporting medical student learning has been comprehensive [15, 16]. nevertheless, there is a small scientific data or investigation about the unification of microbiology and parasitology and the basic fundamental sciences into a block or system-based curriculum, which needs further research. the enhanced cooperation between microbiologists and clinician practitioners could be meant to accomplish an equilibrium between the two disciplines of basic science and clinics. this collaboration has effectively integrated the contents to emend medical student education in such a unified curriculum. it is potentially supported by a discipline coordinator with professionals in microbiology and parasitology along with efficient clinical infectious disease specialists to supervise the relevant subject matter inducted in all blocks. the medical school has successfully integrated all subject disciplines in each module. the integration of microbiology and pharmacology disciplines has a specific correlation concerning its application. depending upon the basic subject skeletal of the module, both the subjects were integrated in a manner to have a better understanding for the medical students. the subject experts covered topics like bacterial growth and modes of action of antimicrobials as interdisciplinary lectures (idl) together. similarly, fungal diseases or viral diseases and antifungals or antivirals were covered together and the idl viz. tuberculosis and antimicrobials or leprosy and its treatment to name a few. the usage of hybrid-integrated learning as a key or central scheme applied by the medical school in psau throughout the curriculum for the integration is a well-thought approach for the benefit of medical students [17]. finally, to decide which curriculum plan layout is the most efficacious for microbiology and parasitology and other similar science domains, further study of the fieldis needed. doi 10.18502/sjms.v18i2.13606 page 233 sudan journal of medical sciences mohammed khan et al 3. the objective of the course study content the curriculum’s objectives include knowledge, cognitive skills, interpersonal skills and responsibilities, psychomotor and clinical skills, and communication and information techniques. every system-based module is organized in a manner to provide the medical students with the basic and applied knowledge, and the laboratory and clinical skills relevant to different subjects at the level of basic science years. each module has credit hours of microbiology and parasitology education and contextualizes medical microbiology and parasitology within a clinical case scenario. each phase has been designed so that the students demonstrate professional behavior and strictly adhere to the principles of biomedical ethics in medical career; respect the principles of group dynamics and function effectively in teams; and communicate effectively with colleagues, patients, and the community using different communication methods. 4. varied modes of teaching the interactive subject lectures, idl, small groups for problem-based learning tutorials facilitated by faculty members (pbl), as well as integrated clinical case discussions (iccd) and team-based seminar learning were used for teaching at the medical school of psau. this new learning educational scheme was integrated to increase progressive education through expert support group learning, “flipped classroom,” small group schooling, peer-group teaching, clinical case-based processing, and alive or simulated patient case examples. the explanation for the enhanced active study or learning program was to increase the merger or combination of the curriculum, favor more student adaptability, and conform to standard guidelines. the subject experts delivered the lectures. the concept of an interdisciplinary lecture was designed to merge important topics like the mode of action of antibiotics on the bacterial cell wall, together and to be presented by the experts of subjects of microbiology and pharmacology. in the problem, the faculty member facilitated learning among students in small groups (8–10) and a case scenario was presented to them. the group selected its group leader and scribed to discuss the clinical case during the first session and extract the main objectives of the case. after approximately a week, the same group would sit again doi 10.18502/sjms.v18i2.13606 page 234 sudan journal of medical sciences mohammed khan et al with the facilitator to debrief the second session and discuss the case. the facilitator observes the team performance evaluation and maintains the discipline of the group. the iccd is also conducted in a way similar to pbl, but the only difference is that the clinical case is provided to the group a week before and then discussed in one session only. the facilitator evaluates the group by having a small quiz related to the same scenario and then clarifying their doubts related to the case. the study guide of every module provides the outline of the topics to be covered in each lecture. the recommended course resource was textbooks and online material. laboratory-based methods of instruction are one of the very useful tools used at medical school to assess psychomotor skills. the practicals in the laboratory were designed as per the module requirement, viz. in the foundation module, the exercises related to sterilization and types of culture medium used in microbiology and various tools application. the laboratory practicals were modular based, and similar to the digestive module, more emphasis was given on the organism causing enteric diseases and the life cycle of the different parasites causing the diseases and their identification. the teaching society would practically conclude that a medico acquires more from a practical or experiment push approach or “hands-on” to relearning rather than from simply hearing lectures [18]. a varied form of diverse approaches or online activities were specially presented to compensate for the practical hands-on during the pandemic. these activities ranged from “demonstration of a technique” by the tutor to small student groups to experiment. the whole class of the teaching fraternity would agree and reflect that they faced at least some hindrance to presenting practical microbiology or parasitology in the classroom. 5. evaluation system methodology the medical student’s knowledge is commonly evaluated through multiple-choice exams. they are also evaluated based on their involvement and performance in small group discussions and team-based learning exercises. other methods of assessment include assignments and small projects and quizzes. doi 10.18502/sjms.v18i2.13606 page 235 sudan journal of medical sciences mohammed khan et al 6. acceptance toward collaboration integration of microbiology and parasitology into organ system modules or blocks was also a big task for the medical education unit of the medical college. the reported reasons for the change in the curriculum planning include enhancing clinical relevance, reducing preclinical timing, and meeting accreditation standards. the theme enclosing the integrated curriculum improvements includes new latest technological education modalities to exploit the maximum clinical applicability or curriculum relevance. although it has reduced the total allotted teaching time in microbiology and parasitology, for medicos, the special concentration is the pathogenic aspect of medical microbiology, diagnostics, and prevention. medical colleges have been dragged toward a more centrally structured or unified curriculum in which microbiology and parasitology are not the particular focus of separate coursework. burton [19] pointed out that these improved changes have lessened the content of information on pathogenic aspects required by medicos. 7. recent innovation suggestions (new inventions) the use of videos and animated pictures and digital demonstrations as an important portion of a flipped lecture room and current online modules are the most frequently described technological innovations. the smart, interactive electronic white board [20] is one of the more advanced technological inventions that can help medical students. these boards find their first usage in corporate boardroom services and are staged for teacher training [21]. the electronic whiteboards can function independently as a projector to exhibit visual images or as a touchscreen computer. however, it is common in present modern-day lecture rooms and experimental laboratories at some universities [22] and their usage in academic settings will undoubtedly expand. for medical microbiology education, mccarthy et al. [23] described the usage of smart interactive technology to develop “virtual patients.” they pointed out the emergent indication that the integration of this kind of computer technology into microbiology education may improve a lot of education strategies as compared to conventional lecture formulations. doi 10.18502/sjms.v18i2.13606 page 236 sudan journal of medical sciences mohammed khan et al 8. realized achieved outcomes the effective integration of all disciplines in module-based teaching is important. these disciplines include anatomy, histology, physiology, pharmacology, biochemistry immunology, pathology, and microbiology and parasitology. medical students perceive the course integration success as a tool that helps them to prepare for saudi commission for health practitioner exams as well as the us medical licensing examination (usmle). 9. objections or dissent the main struggle referred to by the correspondent was to successfully incorporate microbiology and parasitology into modules in the preclinical curriculum to keep an equilibrium between basic fundamental sciences and clinical information. the second concern by the correspondent was the time allocation for teaching microbiology and parasitology during the preclinical curriculum has been considerably reduced. the medical student also overwhelmingly reported that there is a shortage of time to effectively learn the course material. 10. conclusion it has been identified that microbiology is a predominant course and microbiologists have leadership and teaching roles. the relevant medical microbiology basic science content in the preclinical curriculum helps to develop a foundation for the post-clinical years. this can facilitate the improvement of the medicos understanding of the practice of infectious communicable diseases while concentrating on specific fields or regions such as the mechanism of antimicrobial resistance, sepsis, and immune deficiency that make them susceptible to infection. an understanding of these topics will support the academician’s possibilities to demonstrate the linkage between basic fundamental science, insurance, and clinical medicine especially applicable in the present-day modern age. the lack of medical microbiology exposure during the undergraduate degree program may probably present a challenge to medico foreign with this integrated theme and perhaps impart to the stressful academic workload for their postgraduate program. the author also believes that antimicrobial stewardship must be stressed strongly concurrently with the basic fundamental learning of microorganisms and agents rather than waiting till the practitioner’s career stages later, taking into consideration the doi 10.18502/sjms.v18i2.13606 page 237 sudan journal of medical sciences mohammed khan et al increase in resistance to antimicrobials and frequency of prescribing antibiotics in almost all medical fields [24]. this knowledge at the preliminary stage will establish stewardship into medico’s core understanding of diagnosis and treatment of infections. these incorporated principles will help them in future prescribing medical practices [25]. the majority of the academicians supported communication and enhanced collaboration with other course coordinators to meet these needs. the elaboration of a multidisciplinary organization of preclinical microbiology professionals could enable sharing of teaching materials and group participation in necessary scientific research work [26, 27]. a similar issue of reduced teaching hours of the subject has been elucidated from the study of medical schools from albaha university, al-azhar and cairo university by ihab shafek atta et al. 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(2020). drawbacks in the implementation of an integrated medical curriculum at medical schools and their potential solutions. education in medicine journal, 12(1), 29– 42. https://doi.org/10.21315/eimj2020.12.1.4 doi 10.18502/sjms.v18i2.13606 page 241 introduction medical degree program/syllabus format the objective of the course study content varied modes of teaching evaluation system methodology acceptance toward collaboration recent innovation suggestions (new inventions) realized achieved outcomes objections or dissent conclusion acknowledgements competing interests availability of data and material funding references sudan journal of medical sciences volume 13, issue no. 2, doi 10.18502/sjms.v13i2.2640 production and hosting by knowledge e case report investigation of diffuse hair fall case due to vitamin d deficiency: a case report and literature review h. h. suad1 and gad allah modawe2 1omdurman islamic university, faculty of medicine and health sciences, department of dermatology 2omdurman islamic university, faculty of medicine and health sciences, department of biochemistry abstract a 45-year-old female from northern sudan presented a complaint of diffuse hair loss from her scalp for 4 years. the condition started when she was in saudi arabia, where she resided for five years with her husband and children. the condition is associated with fatigability and easily falling asleep. the condition is static with no known relieving or aggravating factors. she looks well, not pale, jaundiced or cyanosed, regular pulse, no lymph node enlargement; thyroid is central with normal size and no lower limb edema. scalp: looks normal, no scales or erosions. hair: hair is dry with normal texture; loss is diffuse, no apparent patch of alopecia. axillary and pubic hair is normal. all investigations were within normal values except serum vitamin d that was found to be very low: 9 (average value 30–300). management plans to correct the deficiency for three months, and then a daily maintenance dose is to be prescribed. the monitoring of vitamin d serum level is to be assessed to avoid hyper vitaminosis. vitamin d supplement was prescribed as oral tabs of 50,000 iu weekly for three months. daily maintenance dose of 1000 iu was prescribed. improvement was noticed starting from the first month, and excellent result was achieved after three months of daily supplementation; daily maintenance dose was then prescribed with an advice of being outdoors to enhance endogenous synthesis. conclusion: serum vitamin d level should be assessed in patients with hair loss, especially those at a risk because of being indoors. keywords: vitamin d, diffuse hair loss, scalps how to cite this article: h. h. suad and gad allah modawe (2018) “investigation of diffuse hair fall case due to vitamin d deficiency: a case report and literature review,” sudan journal of medical sciences, vol. 13, issue no. 2, pages 91–97. doi 10.18502/sjms.v13i2.2640 page 91 corresponding author: h. h. suad; email: dr.suadhassan4@gmail.com received 10 february 2018 accepted 15 june 2018 published 28 june 2018 production and hosting by knowledge e h. h. suad and gad allah modawe. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr.suadhassan4@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences h. h. suad and gad allah modawe 1. introduction vitamin d refers to a group of fat-soluble secosteroids that are very important to the body because they increase intestinal absorption of calcium magnesium and phosphate, they also have other biologic effects. vitamind3 and vitamin d2 are considered the most important compounds in this group [1]. they can be taken in diet [2]. vitamin d is synthesized in the skin from cholesterol through a chemical reaction that is dependent on sun exposure (specially uvb). it undergoes enzymatic conversion by hydroxylation in the liver and kidney to change to the active form. they are considered as hormones rather than vitamins [3]. cholecalciferol is converted in the liver to 25hydroxycholecalciferol, ergocalciferol is hydroxylated in position 25 to form the active metabolite 25 hydroxyergocalciferol, serum level of these two metabolites are measured to assess vitamin d status of the individual [4, 5]. calcifediol is further hydroxylated by the kidneys to form 1,25-dihydroxycholecalciferol, the biologically active form of vitamin d [6]. it circulates as a hormone in the blood, having a major role in regulating the level of calcium and phosphate, they also act in enhancing the promotion of healthy growth and bone remodeling. calcitriol also acts as immune modulator and anti-inflammatory [7]. diffuse hair loss in women can be caused by many factors, the most common cause is female pattern hair loss (fphl) [8]. diffuse hair loss occurs due to changes in hair follicle cycling [9].an androgen-dependent nature has not been proven in fphl. most women with fphl do not have biochemical hyperandrogenism [1]. women without circulating androgens may also develop fphl [10], suggesting a possible role for nonandrogen-dependent mechanisms. this could explain why some women with fphl do not respond to androgen inhibition therapy [11]. the found normal serum level of vitamin d is needed to delay cellular-aging process in the body including hair, this fact explains hair loss when there is vitamin d deficiency [12], and serum vitamin d level should be assessed in women suffering from hair loss [13]. rasheed et al. found that low serum vitamin d and serum ferritin are lower in patients with fphl and also diffuse hair loss in patients aging 18–45 years; they suggested that serum levels of vitamin d and ferritin should be assessed, concluding that their correction may be beneficial when they are low [14]. cerman et al. screened 86 patients with a specific type of hair loss, alopecia areata, in a cross-sectional study and found that vitamin d is significantly lower in patients with alopecia areata than the control. they suggested screening all patients with alopecia doi 10.18502/sjms.v13i2.2640 page 92 sudan journal of medical sciences h. h. suad and gad allah modawe areata for vitamin d deficiency and thought that supplementation of such patients with vitamin d can be of value [15]. an endocrine society for clinical practice stated that vitamin d deficiency is common among all age groups, and that few foods contain vitamin d, and the main source for vitamin d is the synthesis in the skin by the ultraviolet light; so people at risk should be screened for its deficiency because it is associated with many health problems. the society had established guidelines for the prevention and treatment of the deficiency of vitamin d and also recommended the supplementation with vitamin d for prevention and treatment of the deficiency [16]. 2. case report a 45-year-old female from northern sudan presented a complaint of diffuse hair loss from her scalp for 4 years. the condition began when she was in saudi arabia, where she resided with her husband and children for five years. the condition is associated with fatigability and easily falling asleep. the condition is static with no known relieving or aggravating factors. systemic review revealed no abnormality, no palpitation, hyperor hypohidrosis, but she feels depressed, is a newly discovered diabetic, and hypertensiveness is unknown. she has a past history of hospital admission as a child for tonsillectomy and adenoidectomy, but no history of blood transfusion. she’s has no regular medications apart from metformin 500 mg, which was prescribed by her doctor for the control of mild diabetes mellitus. she has a family history of diabetes mellitus and asthma, but no history of diffuses hair loss. the patient is a house wife married for 20 years, has two daughters and two sons: the eldest is 19 years old and the youngest is 7 years old. they live in their own house—a two-floor building with a big courtyard in khartoum north—but very rarely stay outside. being a house wife she has been staying indoors and rarely goes outdoors during the day, but when she does, she puts on a sunscreen with spf 50+. she has regular period, with average loss. on examination, she looks well, not pale, jaundiced or cyanosed, regular pulse, no lymph node enlargement, thyroid is central with normal size and no lower limb edema. scalp: looks normal. hair: hair is dry with normal texture, loss is diffuse, no apparent patch of alopecia. no scales or erosions. axillary and pubic hair are normal. doi 10.18502/sjms.v13i2.2640 page 93 sudan journal of medical sciences h. h. suad and gad allah modawe 3. investigations urine analysis: normal findings; stool analysis: normal findings; cbc: normal findings. thyroid function tests: normal levels of t4, t3 and tsh. total iron load normal. fasting blood glucose is 121 mg/dl. hba1c is 6. serum vitamin d low: 9 (average value 30–300). 4. treatment management plans to correct the deficiency for three months and then a daily maintenance dose is to be prescribed. the monitoring of vitamin d serum level is to be assessed to avoid hyper vitaminosis. vitamin d supplement was prescribed as oral tabs of 50,000 iu weekly for three months. daily maintenance dose of 1000 iu was prescribed. outcome excellent result was achieved starting from the first month in the form of decrease in loss, and by the end of three months, the hair was normally regrowing. the symptoms of fatigability and good mood were also improved. 5. discussion vitamin d is an essential vitamin for our body serving many functions that are necessary for our well-being and health. it is synthesized from a precursor in the skin through the aid of uvb, but the body can also obtain it from diet [2]. its role in calcium and phosphate homeostasis is well known [7], but its relation to diffuse hair loss is still not very clear, so it is suggested by some authors to assess the serum levels of vitamin d in females with hair loss [13]. some studies showed an association of vitamin d deficiency with alopecia areata, but clear studies to diffuse hair loss are still lacking. diffuse hair fall is one of the common complains encountered in dermatology clinics, which can be due to many factors including diseases of the scalp, for example, seborreic dermatitis, pityriasis capitis, etc. some systemic and endocrine diseases and drugs may also be involved in the etiology; in some patients, it can be due to mineral depletion, for example, iron. stress is also mentioned as a cause of diffuse hair loss. doi 10.18502/sjms.v13i2.2640 page 94 sudan journal of medical sciences h. h. suad and gad allah modawe in this case, all the known causes of diffuse hair loss had been excluded by history, examination and investigations. an optimal concentration of vitamin d is needed to delay the aging process and loss of cells including hair [12]. serum vitamin d in this case was measured and severe deficiency was found. serum vitamin d deficiency in areas like sudan is not usually suspected because of the continuous exposure to the sun since the synthesis of vitamin d in the skin requires ultraviolet rays [3]. the deficiency in this case can be justified by the fact that the patient was mostly living indoors in saudi arabia for five years. also, the style of life in sudan is also changing, where there is a tendency of living in flats and houses with low sun exposure. the improvement in hair loss was obtained with correction of vitamin d using oral supplements, which of course points to a close relationship between vitamin d deficiency and hair loss. so, vitamin d deficiency was found to be linked to the different modalities and types of hair losses [14–16]; in this article, vitamin d deficiency was also found to be linked to diffuse hair loss, but moreover correction of this deficiency and follow-up were also done. 6. conclusion and recommendations vitamin d deficiency is to be considered in patients with diffuse hair loss. further studies in this respect are to be conducted. health education for being outdoors is necessary to avoid the deficiency of vitamin d. the use of sun screens should be minimized since they hinder absorption of ultraviolet light, and so reducing the synthesis of vitamin d in the skin leads to its deficiency with all the consequences. references [1] holick, m. f. (march 2006). high prevalence of vitamin d inadequacy and implication for health. mayo clinic proceedings, vol. 81, no. 3, pp. 353-373. [2] calvo, m. s., whiting, s. j., barton, c. n. (february 2005). vitamin d intake: a global perspective of current status. the journal of nutrition, vol. 135, no. 2, pp. 310-316. doi 10.18502/sjms.v13i2.2640 page 95 sudan journal of medical sciences h. h. suad and gad allah modawe [3] norman, a. w. (august 2008). from vitamin d to hormone d: fundamentals of the vitamin d endocrine system essential for good health. the american journal of good nutrition, vol. 88, no. 2, pp. 491s-499s, pmid 18689389. [4] lab tests online (usa). vitamin d tests. american association for clinical chemistry. retrieved june 23, 2013. [5] hollis, b. w. (january 1996). assessment of vitamin d nutritional and hormonal status: what to measure and how to do it. calcified tissue international, vol. 58, no. 1, pp. 4-5. [6] holick, m. f., schnoes, h. k., deluca, h. f., et al. (july 1971). isolation and identification of 1,25-dihydroxycholecalciferol. a metabolite of vitamin d active in intestine. biochemistry, vol. 10, no. 14, pp. 2799-2804. [7] nih office of dietary supplements. (february 11, 2016). vitamin d. retrieved june 6, 2017. [8] olsen, e. a. (2001). female pattern hair loss. journal of the american academy of dermatology, vol. 45, pp. s70-s80. [9] tobin, d. j., guinn, a., magerl, m., et al. (2003). plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications for hair growth control. journal of investigative dermatology, vol. 120, pp. 895-904. [10] orme, s., cullen, d., and messenger, a. (1999). diffuse female hair loss: are androgens necessary? british journal of dermatology, vol. 141, pp. 521-523. [11] olsen, e. (2003). female pattern hair loss, in e. olsen (ed.) disorders of hair growth: diagnosis and treatment (2nd edition), pp. 338-339. new york, ny: mcgraw-hill professional. [12] bolland, m. j., ames, r. w., grey, a. b., et al. (2008). does degree of baldness influence vitamin d status? the medical journal of australia, vol. 189, nos. 11-12, pp. 674-675. [13] amor, k., rashid, r., and mirmirani, p. (2010). does d matter? the role of vitamin d in hair disorders and hair follicle cycling. dermatology online journal, vol. 16, no. 2, p. 3. [14] rasheed, h., mahjoob, d., hegazy, r., et al. (2013). serum ferritin and vitamin d in female hair loss: do they play a role [abstract]? skin pharmacology and physiology, vol. 26, no. 2, pp. 101-107. [15] cerman, a. a., solak, s. s., and altunay, l. k. (march 2014). vitamin d deficiency in alopecia areata. british journal of dermatology, vol. 170, no. 6, pp. 1299-1304. doi 10.18502/sjms.v13i2.2640 page 96 sudan journal of medical sciences h. h. suad and gad allah modawe [16] holick, m. f., binkley, n. c., bischoff-ferrari, h. a., et al. (july 1, 2011). evaluation, treatment, and prevention of vitamin d deficiency: an endocrine society clinical practice guideline. the journal of clinical endocrinology & metabolism, vol. 96, no. 7, pp. 1911-1930. doi 10.18502/sjms.v13i2.2640 page 97 introduction case report investigations treatment discussion conclusion and recommendations references sudan journal of medical sciences volume 13, issue no. 2, doi 10.18502/sjms.v13i2.2643 production and hosting by knowledge e case report presentation of invasive fungal rhinosinusitis in sudanese children: a report of four cases sharfi ahmed and khalid awad elseed faculty of medicine, omdurman islamic university, sudan abstract fungal rhinosinusitis (fs) is considered as a disease spectrum that ranges from allergic fungal sinusitis (afs) and chronic fungal rhinosinusitis (cfs) to invasive fungal rhinosinusitis (ifs) invading the orbit, dura, and intra-cranium. fungal rhinosinusitis is a common disease in sudan. objective: to present four rare cases of invasive fungal rhinosinusitis in sudanese children presented with orbital extension. patients and method: the authors have reported four cases of children in the age range of 9–11 years, two girls and two boys; they were presented with invasive fungal rhinosinusitis in africa ent hospital (sudan) during the period from september 2015 to august 2017. patients’ diagnosis was made by endoscopic examination, ct, and mri, and it was confirmed by tissue biopsy.results: patients’ age range was 9–11 years, two girls and two boys. the unilateral disease was the commonest type. an orbital extension was detected in all cases on ct and mri. no intracranial extension was detected. aspergillus flavus was the most responsible agent detected in all the four cases.conclusion: fungal rhinosinusitis (fs) is a common disease in adult sudanese patients but rarely affects children. it is mainly caused by aspergillus species. the disease is extensive and can be associated with orbital and intracranial complications. keywords: fungal rhinosinusitis, children, sudan 1. introduction the etiology of chronic rhinosinusitis (crs) is unclear. it has been recently suggested that a fungus-mediated process is the primary cause of crs with and without polyps [1]. fungal infections of the nose and sinuses appear to be increasingly common and invade eye structures [2, 3]. as it can be difficult to confirm the presence of fungi, both histologically and by culture, the radiological features may be of paramount importance in initiating a careful search for fungal elements [3]. how to cite this article: sharfi ahmed and khalid awad elseed (2018) “presentation of invasive fungal rhinosinusitis in sudanese children: a report of four cases,” sudan journal of medical sciences, vol. 13, issue no. 2, pages 125–131. doi 10.18502/sjms.v13i2.2643 page 125 corresponding author: sharfi ahmed; email: doctorsharfi@gmail.com received 25 april 2018 accepted 15 june 2018 published 28 june 2018 production and hosting by knowledge e sharfi ahmed and khalid awad elseed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:doctorsharfi@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sharfi ahmed and khalid awad elseed classification of fungal rhinosinusitis (fs) into invasive and non-invasive depends mainly on the presence or absence of fungal hyphae within the mucosa, and not on the presence of bone erosion, which can be found in non-invasive forms [4, 5]. in sudan, the condition was first noticed by sanderson et al. when they reported a granuloma resembling aspergillosis granuloma in biopsy material from three patients with proptosis [6]. bella et al. in 1973 reported 46 cases of primary paranasal aspergillosis granuloma seen in sudan [7, 8]. this disease mainly affects age groups between 11 and 50 years, and it comes from different localities in sudan. the symptoms were mainly nasal obstruction, headache, rhinorrhea, external ethmoid swelling or cheek swelling and proptosis [6, 9]. recently, a chronic destructive form of paranasal sinus mycoses characterized by sinus expansion and bony erosion was described [9]. paranasal aspergillosis seems to be a rare disease in the world in general, but is relatively common in sudan [9, 10]. mahgoub declared that mycetoma mycoses in sudan are significant health problems and pointed out the importance of paranasal aspergillus granuloma [11, 12]. 2. patients and methods during the period from september 2015 to august 2017, a total of four patients with suspected invasive fungal rhinosinusitis (ifs)—two girls and two boys—were selected. the prospective analysis was done in africa ent hospital in khartoum sudan, where functional endoscopic sinus surgery (fess) was performed on all kids. fungal cultures, serology, and microscopy to detect fungal elements in the nasal cavity were carried out for all patients. patients were considered fungus-positive if at least one of these methods could demonstrate fungal elements. specimens for histopathology and cultures were taken postoperatively, and serology was performed for all patients. 3. results all four patients were diagnosed as fs, and were presented with sinonasal polyposis and neuro-orbital complications. ct and mri were done for all the four patients. doi 10.18502/sjms.v13i2.2643 page 126 sudan journal of medical sciences sharfi ahmed and khalid awad elseed case 1 female, from port-sudan, 9 years old, weight 23 kg, had no history of asthma. investigations include: cbc, urine analysis was normal; serology for aspergillosis was strongly positive with aspergillus flavus and in; culture/sensitivity direct = fungal hyphae seen, culture = aspergillus flavus; rt eye proptosis/rt nasal polyps/lt nasal septal deviation. ct, mri findings: metallic sign in the sinuses. fess was done. the patient started itraconazole caps 100mg for one year with regular follow-up with blood investigation and nasal endoscopy. case 2 female, aged 10 years, weight 24 kg, from port-sudan and had no history of asthma. the patient was presented with nasal obstruction for one year and lt eye proptosis, endoscopy showed; extensive nasal polyposis. ct, mri findings: sinuses were full of fungi. fess findings: lt polyposis, muddy fungal material from maxillary, ethmoidal sinuses and sphenoid were cleaned. pulsatile, exposed posterior skull base dura, was preserved, and the orbital cavity was cleaned from the fungal muddy material lt eye was decompressed. cases 3 and 4 both were male, aged 8 and 9 years, respectively, weighing 20 and 24 kg, respectively, having no history of asthma. investigations include: cbc, urine analysis, and cxr were normal; serology for aspergillosis was positive with aspergillus flavus and in; culture media, fungal hyphae were seen. ct, mri findings: sinonasal masses and the metallic sign were seen in the sinuses. fess was done for both kids, and they started itraconazole caps 100mg for 1 year with regular follow-up. doi 10.18502/sjms.v13i2.2643 page 127 sudan journal of medical sciences sharfi ahmed and khalid awad elseed no. sex age c/s histopathologys/s diagnosis drugs 1 male 8 a. flavus mucosal invasion –nasal obstruction – proptosis –headache ct mri itraconazole caps + isotonic solution spray 2 female 9 a. flavus septate fungal hyphae was seen –nasal obstruction – proptosis –headache ct mri itraconazole caps + nasal spray 3 female 10 a. flavus mucosal invasion –nasal obstruction – proptosis –headache mri ct itraconazole caps + rhinocort spray 4 male 9 a. flavus mucosal invasion –nasal obstruction – proptosis –headache mri ct serology itraconazole caps + flixonase spray table 1: the result of age, sex, culture/sensitivity (c/s), histopathology, symptoms /signs (s/s), images and drugs options. symptoms/signs no. % nasal obstruction 4 100 nasal mass 4 100 anosmia 3 75 postnasal drip 3 75 cacosmia 3 75 proptosis 4 100 headache 4 100 nasal discharge (greenish secretions) 4 100 table 2: clinical presentation. 4. discussion the diagnostic criteria for afrs vary among authors, but the most widely accepted are the five criteria described by bent and kuhn. to diagnose afrs, the presence of allergic mucin in histopathology specimens is important in addition to the demonstration of fungal elements [13]. doi 10.18502/sjms.v13i2.2643 page 128 sudan journal of medical sciences sharfi ahmed and khalid awad elseed aspergillus species were found to be the common species of fungi causing rhinosinusitis in sudan, and this is in agreement with previously published sudanese series [9, 12, 14]. no gender was predominant in childhood, but in the adult, female was found to be predominate; this is in a harmony with the majority of the national and international studies [1, 2, 6–10, 15]. complications included orbital, and intracranial extensions were found in two patients (50%), which agrees with a group of authors [3, 5, 6, 9, 16]. in this study, two kids started their disease as a non-invasive type and changed to an invasive type during the study period; this also goes with thacker et al. who recommended that fungal sinusitis should be considered a potentially progressive continuum, where the non-invasive disease may coexist with an invasive form [17]. aspergillus fumigatus was considered the primary etiologic agent of afrs cases and was found as a predominant etiologic agent in western literature [18, 19]. however, in contrast, a. flavus is the predominant etiologic agent causing chronic fungal rhinosinusitis (cfs) in sudan. in the international literature, mucormycosis is the most implicated fungus for invasive fungal sinusitis (ifs) [9, 12, 14–16]. 5. conclusion fungal rhinosinusitis (fs, cfs, afs, and ifs) is a common disease in sudan that mostly affects females of young age groups and is rare among kids. the usual presentation is a nasal mass or polyp and can be associated with orbital and intracranial invasion. the main causative agents are aspergillus species with a. flavus being the most commonly encountered. recommendation fungal rhinosinusitis (fs, cfs, afs, and ifs) is a common disease in sudan but rarely affects kids. more studies and efforts must be done to look for best methods of management. conflict of interests the authors declare no conflict of interests. doi 10.18502/sjms.v13i2.2643 page 129 sudan journal of medical sciences sharfi ahmed and khalid awad elseed acknowledgment the authors would like to thank professor karimeldin mohamed ali, mr. abdelaziz w. abdalla and miss azaz m. bashier for their great help. references [1] ponikau ju, sherris da, kern eb, homburger ha, frigas e, gaffeyta, et al. the diagnosis and incidence of allergic fungal sinusitis. mayo clinproc 1999;74: 877-84 [2] hora je. primary aspergillosis of the paranasal sinuses and associated areas. laryng oscope 1965;75:768-73. [3] wright re. two cases of granuloma invading the orbit due to aspergillosis.br j ophthal 1972;12:545-59. [4] deshazoetal.classification of funal sinusitis. rhinology 1997;39:283-4. [5] deshazoetal .a new classification and diagnostic criteria for invasive fungal sinusitis. arch otolaryngol head neck surg 1997.123:1181-1188. [6] rudwan ma, sheikh ha,. aspergilloma of the paranasal sinuses is a common cause of unilateral proptosis in sudan. clin radiol 1976;27: 497-02. [7] sandison at,gentles jc, davidson cm,banko m. aspergilloma of the paranasal sinuses and orbit in nothern sudan. sabourndia 1969;6:57-69. [8] bella v, malik oa , . mahgoub el, el hassanma,etal. further observation on the primary paranasal sinuses aspergillus granuloma in sudan. trop med hyg1973;22:765-772. [9] yagi hi, gumma sa etal.nasosinuses aspergillosis in sudanese patients. clinical features, pathology, diagnosis and treatment. the j of oto and lary. 1999;28.2:90:94. [10] stammberger h, etal. aspergillosis of the paranasalsinuses. annoto rhino laryngo 1985 .94(119):1-11. doi 10.18502/sjms.v13i2.2643 page 130 sudan journal of medical sciences sharfi ahmed and khalid awad elseed [11] milosev b, mahgoub el s,etal. primary aspergilloma of the paranasal sinuses in sudan.br j surgery 1969;56:132-7. [12] mahgoub el s. mycological and serological studies on aspergillousflavus isolated from the paranasal sinuses aspergilloma.trop med hyg 1971; 74:168-75. [13] bent j, kuhn fa. diagnosis of allergic fungal sinusitis.otolaryngol head neck surg . 1994; 111:580-588. [14] mahgoub el s. el hassan ma. pulmonary aspergilloma caused by aspergillousflavus 1975. thoraxj ;27 233-37. [15] dawalatly ee, amin jt, elhassan ay etal. primary paranasal sinuses aspergillosis in soudiaarabia . trop med j . i988 jul .40(3): 247-50. [16] thakar a, sarkar c, dhiwakar m, bahadur s, dahiya s. allergic fungal sinusitis:expanding the clinicopathologic spectrum. otolaryngol head neck surg . 2004;130:209-216. [17] katzenstein al, sale sr, greenberger pa. allergic aspergillus sinusitis: a newly recognized form of sinusitis. j allergy clinimmunol . 1983;72:89-93. [18] schubert ms. allergic fungal sinusitis. otolaryngolclin north am . 2004;37:301-326. [19] sharfi ao, elmustafa. clinical features of fungal rhinosinusitis in sudan. pajr , vol. 3, no. 1, march, 2013. doi 10.18502/sjms.v13i2.2643 page 131 introduction patients and methods results case 1 case 2 cases 3 and 4 discussion conclusion recommendation conflict of interests acknowledgment references sudan journal of medical sciences volume 13, issue no. 1, doi 10.18502/sjms.v13i1.1686 production and hosting by knowledge e research article knowledge, attitude and practice of hepatitis (b) among healthcare workers in relation to their vaccination status in khartoum, sudan, 2015: a cross-sectional study almustafa siddig mohammed mustafa1, almegdad sharafaldin mohamed ahmed1,tariq ahmed abdelbaset alamin1, mutaz tarig hassanahmed shaheen1, awab mohamed mohamed ahmed hilali1, moneeb hassan mohammed alamin fadul1, ahmed abdelaziz abugrain abdelsalam1, mohamed ahmed sidahmed abdelrahim1 , and mohamed nasr mohamed ahmed elsheikh 1,2 1faculty of medicine, university of khartoum, khartoum, 11111, sudan 2education development center, nahda college, khartoum, 11111, sudan abstract background: hepatitis b is a serious chronic infection of the liver and caused by hepatitis b virus. it is an endemic disease in sudan. healthcare workers are occupationally more prone to acquire the disease. evaluation of their knowledge, attitude and practice and their vaccination status, are very important in the control of the disease. the aim of this study was to assess the knowledge, attitude, and practice of healthcare workers towards hepatitis b and their vaccination status. materials and methods: in total, 372 healthcare workers were enrolled in the study, which was conducted at 10 public hospitals in khartoum state during july-august 2015. after taking written informed consent from the khartoum state research department, self-administrated questionnaires were distributed to the healthcare workers. the kap score was the sum of the three categories, which is 32 points, and the mean was then obtained. results: the study revealed that the respondents’ mean scores of knowledge, attitude, and practice (kap) were 18.4, 2.14 and 2.49, respectively. the study also showed that doctors have the highest kap score in comparison with other occupations. doctors are the least occupational category that uses gloves when dealing with patient’s blood. the kap score was found higher among vaccinated healthcare workers 27.4% in comparison to unvaccinated ones, that yield to a significant the association between kap score and vac-cination status (p-value 0.007). conclusions: this study concluded that, there is a positive association between the level of vaccination among health care workers and their knowledge, attitude and practice of hepatitis b virus. further studies would be recommended on larger population. how to cite this article: almustafa siddig mohammed mustafa, almegdad sharafaldin mohamed ahmed,tariq ahmed abdelbaset alamin, mutaz tarig hassanahmed shaheen, awab mohamed mohamed ahmed hilali, moneeb hassan mohammed alamin fadul, ahmed abdelaziz abugrain abdelsalam, mohamed ahmed sidahmed abdelrahim, and mohamed nasr mohamed ahmed elsheikh, (2018) “knowledge, attitude and practice of hepatitis (b) among healthcare workers in relation to their vaccination status in khartoum, sudan, 2015: a cross-sectional study,” sudan journal of medical sciences, vol. 13 (2018), issue no. 1, 22–214. doi 10.18502/sjms.v13i1.1686 page 22 corresponding author: mohamed nasr elsheikh; email: almohamed1991@gmail.com received 4 december 2017 accepted 25 march 2018 published 14 march 2018 production and hosting by knowledge e almustafa siddig mohammed mustafa et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0002-0987-4172 https://orcid.org/0000-0001-9474-4219 mailto:almohamed1991@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences almustafa siddig mohammed mustafa et al keywords: kap study, hepatitis b, health care workers, vaccination, kartoum, sudan, general hospitals 1. introduction hepatitis b (hb) is a serious chronic infection of the liver and caused by hb virus (hbv). during the acute phase, the majority of hb patients are asymptomatic. however, the symptoms may last for several weeks in those who are symptomatic [1]. hbv can be transmitted through different mechanisms, including contact with blood and blood products, sexual intercourse, contaminated needles and haemodialysis [2]. healthcare workers (hcws) are defined as “all paid and unpaid persons working in health-care settings who have the potential for exposure to infectious materials (e.g. blood, tissue and specific body fluids, and medical supplies, equipment, or environmental surfaces contaminated with these substances)” [3]. the world health organization estimated that about 240 million patients are currently infected with hbv [1]. worldwide, sub-saharan africa and east asia are considered to have the highest prevalence of hb (5-10% chronically infected adult patients) [1]. the prevalence of hb surface antigen (hbsag) in sudan is more than 8% [5]. the prevalence of hbv among hcws in not exactly known, but it was estimated to be similar to that of nonhcw [6]. annually, more than 60,000 cases of hbv infection among hcws are due to contaminated sharp injuries alone [7]. there was a significant reduction in the incidence of hb infection after the introduction of the hbv vaccines [8]. worldwide, many studies have been conducted to assess the level of the knowledge, attitude, and practice of hcws toward hbv, and others have evaluated the vaccination status of hcws [9–11, 14]. previous studies conducted in sudan have addressed these two issues; some were conducted in public hospitals outside the capital (khartoum) and those conducted inside the capital were limited to few hospitals [9–11]. the purpose of this study was to assess the level of knowledge, attitude, and practice of the sudanese hcws toward hbv and their vaccination status in multiple public hospitals in khartoum state. this can help in exploring barriers for not getting hbv vaccination and creating effective strategies to limit the hbv infection in hcws. doi 10.18502/sjms.v13i1.1686 page 23 sudan journal of medical sciences almustafa siddig mohammed mustafa et al 2. methods 2.1. study setting and participants it was a cross-sectional analytical study among hcws in 10 chosen public hospitals in khartoum in the sudan, from july to august 2015. these hospitals were: soba university hospital, khartoum teaching hospital, khartoum north teaching hospital, omdurman teaching hospital, military hospital helipad, khartoum dental teaching hospital, radiation and isotopes center-khartoum, alshaab specialized teaching hospital, ibrahim malik teaching hospital, e.n.t specialized hospital. the inclusion criteria were as follows: hcws who were working in the medical service across different departments and specialties during the time of the study (doctors, nurses, lab technicians, midwives and dentists); and those who agreed to participate in the study. 2.2. sampling technique we obtain the total number of hcws and distribution in different specialties in khartoum state from the ministry of health annual report. [12]. we could not employ random sampling because of the lack of an accurate list of names of all hcws in the city’s hospitals. we included 372 hcws in our study out of a total population of 10331 hcws [12, 13]. 2.3. sample size calculation the sample size was obtained using the following formula: sample size = n/(1+n(d)2 where: n= population size = 10331 d = level of precision = 0.05. 2.4. study questionnaire a self-administered was used, 39 items questionnaire composed of five sections. in addition to the socio-demographic and work-related characteristics, 25 questions evaluated knowledge towards hb, four questions assessed attitude, three questions doi 10.18502/sjms.v13i1.1686 page 24 sudan journal of medical sciences almustafa siddig mohammed mustafa et al explored practices towards hb, and five assessed the respondent’s vaccination status. the questions were designed after performing a wide range literature review [14–20]. 2.5. statistical analysis we used spss v20.0 for data entry and analysis. the study predictor variables were the socio-demographic data and the levels of knowledge, attitude and practice towards hb, while the outcome variable is the vaccination status of the respondents. we assigned one point for each correct answer and zero points for each incorrect one. the total number of points was 25, 4, and 3 points for knowledge, attitude and practice, respectively. the kap score was the sum of the three categories, which is 32 points. a p-value of <0.05 was considered statistically significant for chi-square test to assess the relationship between variables. 3. results the mean age of study participants was 30.01 years and the male to female ratio was 1:2. most of the participants were doctors: 119 (32.0%). the socio-demographics of the 372 respondents are shown in table 1. 3.1. assessment of knowledge knowledge was assessed by questions focusing on hb causes, transmission, sign and symptoms, and management. the average respondents’ knowledge score was 18.4 points. regarding occupational distribution, all dentists scored above the average and 117 (98.3%) of doctors scored above the average. on the other hand, 20.0% of respondents thought that hb could be transmitted through contaminated food. in addition, only 9.9% of respondents scored high points on the knowledge assessment questions. more than 70.0% of the study respondents have a good level of knowledge, as assessed by the mode of transmission questions. also, 213 (96.0%) of respondents knew the correct method of diagnosing hb. 3.2. assessment of attitude attitude towards hb was assessed by four questions. this study showed that 81.5% of respondents did not know the guidelines that should be followed after a needle injury. doi 10.18502/sjms.v13i1.1686 page 25 sudan journal of medical sciences almustafa siddig mohammed mustafa et al characteristics n percentage gender male 128 34.4 female 242 65.1 missing 2 0.5 occupation doctor 119 32.0 lab technician 35 9.4 nurse 187 50.3 midwife 12 3.2 dentist 19 5.1 age groups, years 20-30 254 68.3 31-40 66 17.7 41-50 33 8.9 51-60 9 2.4 missing 10 2.7 vaccination status: vaccinated 270 72.6 not vaccinated 102 27.4 total 372 100 t 1: descriptive statistics of the study respondents. in addition, 46% of respondents stated that hb patients should be quarantined, and 41.7%said that they will not share household items with a hb patient because it is not safe. overall, the average respondents’ attitude score was 2.14 points “of 4 points”. 3.3. assessment of practice the results showed that 17.5% of respondents avoid dealing with hb patients, and 12.6% of doctors do not wear gloves when they deal with the patients. 3.4. vaccination status this study revealed that 27.4% of respondents were not vaccinated against hb. in total, 71.3% did not obtain the post-vaccination test to ensure the efficiency of the vaccination. hospitals were found to be the most frequent place where respondents had obtained their vaccination 61.0% of the vaccinated respondents received their vaccination there. in total, 7.4% of the respondents were not vaccinated due to the financial deficit, while 37.2% did not know where they could find the vaccine. doi 10.18502/sjms.v13i1.1686 page 26 sudan journal of medical sciences almustafa siddig mohammed mustafa et al knowledge (pvalue)∗ attitude (p-value)∗ practice association(pvalue)∗ age 0.00 0.01 0.21 gender 0.85 0.47 0.86 occupation 0.03 0.01 0.00 vaccination status 0.02 0.51 0.00 *(p-value is significant when less than 0.05) t 2: associations between kap scores and respondent characteristics. 3.5. mean kap score the mean overall kap score was found to be moderate (20-25 points, out of 32 points), with doctors scoring the highest kap score compared with other occupations. association of descriptive characteristics and mean kap scores the study revealed that there is a positive significant association between the age of participants and their mean kap score (p-value=0.014), but this association was weak (cramer’s v score= 0.148). the association between the gender of respondents and their mean kap score was insignificant (p-value =0.422). in addition, the study found a moderate association between the occupation of the respondents and their mean kap score (p-value=0.001; cramer’s v score=0.193). a good kap score was associated with doctors, 57 (47.8%) of them scored high scores in this study. other descriptive statistical associations are listed in table 2. 3.5.1. correlation between knowledge and practice the study found that there is a strong association between the respondents’ level of knowledge and their good practice towards hb (p-value< 0.001, cramer’s v score =0.381). in addition, the study showed that there is a significant association between the level of respondents’ knowledge and their vaccination status (p-value=0.029), and this association was strong (cramer’s v score =0.306). doi 10.18502/sjms.v13i1.1686 page 27 sudan journal of medical sciences almustafa siddig mohammed mustafa et al figure 1: association between the average kap score of the respondents and their vaccination status. 3.5.2. correlation between the mean kap score and the vaccination status this study found out that there is a moderate association between the mean kap score of the respondents and their vaccination status (p-value= 0.007; cramer’s v score =0.164; figure 1), and this was the primary result of this study. 4. discussion the aim of the current study was to assess kap scores towards hb among hcws in public hospitals in khartoum state. hcws are crucial in controlling hb. the study found that there is a significant association between the age of participants and their mean kap score (p-value=0.014), (cramer’s v score=0.148). this may be due to increased experience by age and being in contact with patients for a long time. the study found a moderate association between the occupation of the participants and their mean kap score (p-value=0.001; cramer’s v score=0.193), where doctors were associated with the highest kap scores (47.8% of doctors scored ‘good’ in this study). doi 10.18502/sjms.v13i1.1686 page 28 sudan journal of medical sciences almustafa siddig mohammed mustafa et al this study shows that 58.3% of the respondents scored a moderate level of knowledge towards hb.a similar study was held in tikrit cityiraq [14], in which a good level of knowledge was found amongst the medical staff. the deference between our study and iraqi study may come from the different approaches in fighting the disease in both countries. regarding the symptoms, only 9.9% of respondents showed a good level of knowledge; low knowledge about hb symptoms leads to a delay in the early diagnosis of the disease and may increase the rate of transmission of the disease among the population. in addition, the study found that 20% of respondents thought that contaminated food can transmit hbv, while10% didn’t know if food can transmit hb or not. this finding reveals a huge misconception about hb and among hcws. this study showed that 46% of respondents said that hb patients should be quarantined, and this negative attitude may increase the stigma towards hb patients in society. surprisingly, our study shows that 81.5% of respondents didn’t know the guidelines that should be followed after a needle injury, and this is a dangerous indicator as these guidelines should be known by every hcw in order to decrease the chance of acquiring the disease. our study showed that the majority of respondents who do not wear gloves when they are dealing with patients were doctors (representing 12.6% out of the total number of doctors), which is similar to a study carried out in wad madani-sudan [11]. that study showed that 10.4% of doctors did not wear gloves when they deal with patients, and this is a dangerous indicator of careless practice towards this disease. this study revealed that 27.4% of respondents were not vaccinated against hb. however, compared to a previous study published in 2011 [11], there was a significant improvement in the vaccination status among hcws; 26.19% in the previous study compared with 72.6% in the present study. moreover, this study revealed that doctors, in comparison with other occupations, have the highest kap scores, and vaccinated respondents have a higher mean kap score than non-vaccinated respondents. there was a moderate association between the mean kap score of the respondents and their vaccination status (p-value=0.007; cramer’s v=0.164). 5. conclusions although the study was performed in the capital city of sudan, the research findings cannot be generalized to the whole population of hcws in sudan. therefore, we recommend conducting more research in this area. also, we had difficulties in finding doi 10.18502/sjms.v13i1.1686 page 29 sudan journal of medical sciences almustafa siddig mohammed mustafa et al a validated internationally standardized hb kap questionnaire with a proper scoring system for hcws, especially in the arabic language. we recommend that higher authorities continually assess the knowledge of hcws about infectious organisms and hb, especially in developing countries. we believe that by increasing the level of knowledge of hcws, it is possible to decrease the prevalence of hbv among the general population; therefore, we recommend that health education of hcws should be increased by conducting workshops, symposiums and training about hb and post-exposure prophylaxis guidelines, and guidelines should be available at all health facilities. we also compel that the ministry of health and hospitals establish guidelines for accepting only vaccinated new hcws and to organize vaccination campaigns for already employed, non-vaccinated hcws. 6. acknowledgements many thanks to dr. sarah eltahir (mbbs, university of khartoum) for her help in revising the manuscript. 7. ethics consideration we obtained ethical clearance from the khartoum state ministry of health research department. 8. competing interests the author declares that they have no competing interests. availability of data and materialdata are available upon request. 9. author contributions asmm, asma, taaa, mths, ammh, mhmf, and aaaa contributed to the study design, data collection and analysis, and preparation of the manuscript. masa contributed to interpretation of data and revision of the manuscript. mnme contributed to preparation and revision of the manuscript and supervised the whole process. all authors were involved in the revision of the manuscript and have agreed to the final content. doi 10.18502/sjms.v13i1.1686 page 30 sudan journal of medical sciences almustafa siddig mohammed mustafa et al references [1] world health organization (who). hepatitis b [internet]. 2016 [cited 2016 dec 1]. 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[20] hwang e, cheung r. global epidemiology of hepatitis b virus (hbv) infection. n a j med sci. 2012;4:7. doi 10.18502/sjms.v13i1.1686 page 32 introduction methods study setting and participants sampling technique sample size calculation study questionnaire statistical analysis results assessment of knowledge assessment of attitude assessment of practice vaccination status mean kap score correlation between knowledge and practice correlation between the mean kap score and the vaccination status discussion conclusions acknowledgements ethics consideration competing interests author contributions references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13602 production and hosting by knowledge e research article expression of programmed death ligand-1 and correlation with clinicopathological features and cd8 infiltration in breast cancer shahenaz s salih1, mohammed s abdelaziz1, altaf s mosad1, ibtihal m abdelhag2, elmassry re3, and nadia a eldawi4 1department of histopathology and cytology, college of medical laboratory sciences, sudan university of science and technology, khartoum, khartoum, sudan 2department of histopathology & cytology, omdurman islamic university, khartoum, khartoum, sudan 3alrayan colleges, college of health sciences and nursing, almadina, saudi arabia 4histopathology, royal care hospital, khartoum, sudan orcid: shahenaz s salih: https://orcid.org/0000-0001-9420-8619 abstract background: breast cancer (bc) is considered one of the most diversified types of tumors, characterized by a high mutational burden in the tumor milieu and a lack of immune cell makeup. the programmed death receptor-1 (pd -1)/programmed death ligand-1 (pd -l1) axis has been identified as a new target in the field of immunotherapy because, when activated, they worsen the future scenarios of the disease by helping tumor cells (tc) to escape immune surveillance. this study aims to investigate the expression of pd-l1 in bc tissues from sudanese ladies and correlate its expression with clinicopathological features and the infiltration of cd8+t lymphocytes by immunohistochemistry (ihc). methods: one hundred and fifty archived bc blocks were collected from national public health laboratory from january 2019 to august 2020. data regarding age, tnm staging, grade, and hormonal status were considered. tissue sections were examined using ihc to determine the expression of pd-l1 and cd8. results: among one hundred and fifty bc samples, 73 (48.7%) were tnbcs, and 77 (51.3%) were hormone-positive bcs. pd-l1 was significantly associated with bc subtypes, especially tnbcs (p = 0.001), a similar significant association was shown with cd8 infiltration (p = 0.006). none of the clinicopathological features were associated with pd-l1 expression. conclusion: pd-l1 expression is strongly associated with tnbc’s and linked to cd8+ cells infiltration to the tumor milieu. moreover, no correlation has been observed between the expression of pd-l1 and clinicopathological features in this study. keywords: immune therapy, pd-1, pd-l1, tils infiltration, tnbcs, immune-check points blockers how to cite this article: shahenaz s salih, mohammed s abdelaziz, altaf s mosad, ibtihal m abdelhag, elmassry re, and nadia a eldawi (2023) “expression of programmed death ligand-1 and correlation with clinicopathological features and cd8 infiltration in breast cancer,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 177–189. doi 10.18502/sjms.v18i2.13602 page 177 corresponding author: shahenaz s salih; email: shahinaznour86@gmail.com received 14 january 2023 accepted 1 march 2023 published 30 june 2023 production and hosting by knowledge e shahenaz s salih et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences shahenaz s salih et al 1. introduction breast cancer (bc) treatment has significantly advanced in recent years, allowing for the creation of tailored and targeted therapies that delay the spread of the illness and prolong patient lives. for the triple-negative population lacking focused therapy choices, there is still a demand for novel therapeutic options for dispersed or invasive diseases [1]. cancer immunotherapy has lately been a key source of research, notably for immune checkpoint targeted therapy, such as cytotoxic lymphocyte-associated antigen-4 (ctla4) and the programmed death receptor-1 (pd-1)/programmed death ligand-1 (pd-l1) axis, as well as breast cancer susceptibility gene 1 (brca1) [2]. the pd-1’s primary ligand, pdl1, can cause tumor-related immune cells to commit apoptosis; hence, it is considered to take part in cancer immune evasion in the tumor milieu [2]. as bc is considered to be one of the most heterogeneous types of cancer that may result in variations within the tumor-immune milieu composition and the impact of immune checkpoint inhibitors, five intrinsic subtypes of bc have been identified as a result of gene expression profiling: luminal a and b, her2-rich, claudin-deficient, and basal-like (which is frequently used synonymously with tnbc in the literature) [2, 3]. the incidences of these subgroups have been reported to differ along with outcomes, and responses to chemotherapy, and this makes them a potential target for studies of immune-check points therapies, the immune therapies [3]. programmed death-1 is abundantly expressed on activated monocytes, dendritic cells, b cells, natural killer cells, and cytotoxic effector t-cells (cd4 and cd8); whereas its ligands (the pd-l1 and pd-l2) can be expressed by normal and tcs as well as other cells in the tumor microenvironment such as tumor-infiltrating lymphocytes (tils), macrophages, and fibroblasts [4]. physiologically, t-lymphocytes become less active and competent to react to invading antigens when pd-1 binds to its ligands, and this contributes to the prevention of immune cell attacks on normal cells; hence, the description “immune-check points” comes to the surface. in the context of cancer, this physiological protective mechanism causes tcs to evade the immune system’s recognition and subsequent elimination [2]. according to theories, either oncogenic processes [4] or activated tumor antigenspecific t cells that release interferons like cd8+ [5] can cause tcs to express pd-l1 constitutively. interferon stimulates and tightly modulates the pd-l1 gene, and it has been seen that interferon and other inflammatory genes are linearly correlated with pd-l1 transcript expression in bc [6]. doi 10.18502/sjms.v18i2.13602 page 178 sudan journal of medical sciences shahenaz s salih et al according to the data, the responses to the pd-1/pd-l1 pathway inhibition may depend largely on inducible pd-l1 expression, in this situation, responses to anticancer necessitate the pre-existence of pd-1-positive t-cells with tumor antigen specificity [4]. moreover, various studies have correlated increased pd-l1 protein/mrna expression and number of tils on the tumor side [7-10]. hence, tils and tumor pd-l1 overexpression may be functionally related [10]. on the other hand, pd-l1 expression has been strongly correlated with unfavorable clinicopathologic characteristics of bc [11]. in the summary of the meta-analysis study by huang et al., it was observed that pdl1 positive expression was significantly related to ductal carcinoma, size of the tumor, grade 3 tumors, er negative, pr negative, tnbcs along with tils, but not with patient age or lymph node metastases [12]; and there were many different conclusions on the prognostic and/or predictive relevance of pd-l1’s expression in bc [13]. this diversity may be justified by the heterogeneity of pd-l1’s expression along different antibody clones, spatial expression (cytoplasmic or membranous), cell type expressing this marker (tils versus tcs), and tissue type used whether it is tma or whole tissue [12, 13]. in this study, we are correlating pd-l1 expression to molecular types of bc and assessing the relevance and significance of the co-expression of pd-l1 and cd8+ tils. 2. methods this retrospective case study aims to study the expression of pd-l1 and cd8+t lymphocyte infiltration by immunohistochemistry (ihc) in bc tissues and to correlate pd-l1 expression with clinicopathological characteristics. one hundred and fifty archived bc blocks have been collected from stak, the national public health laboratory, from january 2019 to august 2020. the formalin fixed paraffin embedded bc blocks were sectioned in 3 consecutive paraffin sections each of 3 µm thickness, one of the sections was stained with hematoxylin and eosin to reaffirm diagnosis, and the rest of the sections were picked onto a charged slide for subsequent ihc demonstration with anti-cd8 and anti-pd-l1. data considering age, histological diagnosis, histological grading, lymph node involvement, tumor size and metastasis, the clinicopathological features along with data describing hormonal status (estrogen (er), progesterone receptors (pr), and human epidermal growth factor receptor-2 (her2)) were also considered and gathered. anti-cd8 mouse monoclonal antibody (32-m4dako), and anti-pd-l1 mouse monoclonal antibody (73-10, abcam, uk) were used to raise immune-staining. positive pd-l1 doi 10.18502/sjms.v18i2.13602 page 179 sudan journal of medical sciences shahenaz s salih et al expression in the cytoplasm and/or cellular membrane was considered, this positivity has been counted and scored based on a system that counts the percentage and intensity of positivity utilizing the histo-scoring system (h-score), the system which classifies cells down to staining intensity and cellular density. a cut-off point of 100 was used to divide the expression into two groups: (0-99 as negative; 100-300 as positive expression) [14]. data analysis was done using spss-version 20 and graph-pad prism 8 was used for graphing. statistical tests such as frequencies, crosstabulation, chi-square, mannwhitney, and kruskal-wallis were used. in all the analyses done, a two-tailed p value of .05 was deemed statistically significant. 3. results among one hundred and fifty bc samples, 73 (48.7%) were tnbcs, and 77 (51.3%) were hormonally positive bcs. the median age was 50 years (range: 23-80 years). females aged 40-59 years were predominantly affected by bc, constituting 51.3% of the total population, while younger women (less than 40 years) and older women (more than 60 years) were the least affected, constituting 23.3% and 25.4% respectively. invasive ductal carcinoma of the breast was the most prevalent histologic type (81.3%), with stage i tumors being the most prevalent (46.0%), and grade iii tumors being the next most frequent (47.3%). regarding types of bc, luminal a was the most prevalent molecular subtype (84.8%). table 1 presents frequencies and significance levels of association with pd-l1 expression. the immuno-histochemical labeling describing the positive rates of pd-l1 in tc was 30% (45/150); this expression was anticipated to be caused by flooding of the tumor microenvironment with tils, particularly cd8 positive cells, the crucial component in induced expression of pd-l1. consequently, cd8 was one of the most intriguing targets for ihc analysis to ascertain whether there is a connection between cd8 and pd-l1 expressions. table 2 demonstrates a statistically significant correlation between pd-l1 expression and cd8 infiltration at the tumor location p value (< .05). regarding the mode of distribution of pd-l1’s scores among different categories of bc, we performed the kruskal-wallis test to explore the allocation of pd-l1 scores among bc molecular subtypes highlighted by hormonal expression patterns in luminal a, luminal b, her2 enriched, and triple-negative bc. table 3 elaborates on diverse pd-l1 distribution among molecular subsets of bc, given that the cut-off point of 100 is taken as a point to govern pd-l1 negativity or doi 10.18502/sjms.v18i2.13602 page 180 sudan journal of medical sciences shahenaz s salih et al positivity through the h-score ranges (0-300). the test found a significant diversity in distribution between molecular subtypes of bc in (p = 0.011). similarly, this score distribution dissimilarity was double highlighted in bc samples when simply classified as tnbcs and non-tnbcs regardless of detailed luminal status. mann-whitney test was applied to evaluate the variation of pd-l1 score distribution among the two groups of bc, the triple negative, and their hormonal positive counterparts. in figure 1, there was an obvious variable distribution of pd-l1 scores across tnbcs and non-tnbcs. in addition, closely related result finding was addressed to bc types from a histological point of classification, we found that there was a significant dissimilar distribution of pd-l1’s scores across idc, ilc, and other tumor types like papillary carcinoma, and intraductal hypersecretory breast carcinoma (p = 0.028), this is well illustrated in table 4. table 1: characterizes the distribution of clinicopathological features of bc and its association with pd-l1 expression. clinicopathological data frequency percentage (%) p-value pd-l1: positive negative 45 105 30 70 – age group (yr): ≤39 40–59 ≥60 35 77 38 23.3 51.3 25.3 0.36 stage: i ii iii iv 69 27 53 1 46.0 18.0 35.3 0.7 0.34 grade: i ii iii 15 64 71 10.0 42.7 47.3 0.58 tumor type: idc ilc others 122 6 22 81.3 4.0 14.7 0.028 total 150 100% table 2: the correlation between pd-l1 and cd8. pd-l1 negative positive negative 49 (83.1%) 10 (16.9%) cd8 positive 56 (61.5%) 35 (38.5%) total 105 45 p-value = 0.006 doi 10.18502/sjms.v18i2.13602 page 181 sudan journal of medical sciences shahenaz s salih et al table 3: distribution of pd-l1 across molecular subtypes of breast cancer. pd-l1 negative positive bc subtypes (score is less than or equal 99) (score is more than or equal to 100) luminal a 39 (84.8%) 7(15.2%) total = 46 p-value = 0.011 luminal b 16 (76.2%) 5(23.8%) total = 21 her2 enriched 9 (90.0%) 1(10.0%) total = 77 total = 10 triple negative bc 41 (56.2%) 32 (43.8%) total = 73 total 105 45 t n b c s n -n -t n b c s 0 20 40 60 80 f re q u e n c y negative positive 41 32 64 13 figure 1: the difference in pd-l1 distribution between tnbcs and non-tnbcs. table 4: expression of pd-l1 across histological types of breast cancer using kruskal–wallis test. pd-l1 negative positive bc subtypes (score is less than or equal 99) (score is more than or equal to 100) idc 45 (62.5%) 27 (37.5%) p-value = 0.028 ilc 33 (86.8%) 5 (13.2%) others 27 (67.5%) 13 (32.5%) total 105 45 doi 10.18502/sjms.v18i2.13602 page 182 sudan journal of medical sciences shahenaz s salih et al a b figure 2: (a) expression of pd-l1 in tumors cells. (b) tumor cells expressing pd-l1 and immune cells. 4. discussion of all cancers affecting women globally, bc has the greatest incidence and fatality rates, it has been anticipated by globocan that by the year 2040, the incidences in africa may virtually be doubled from the meantime [15]. little is known about incidences in sudan but according to data from the khartoum state cancer registry for the years 2009 to 2010, bc was the most prevalent type of cancer among sudanese women [16]. this dictates rapid and intensive searches in different treatment regimens that eradicates cancer safely with few side effects, hence immune-therapeutic options have dragged attention and rapid attempts to examine different populations from different ethnicities. pd-l1 as predicting marker for subsequent immune-check blockers, was subjected to association tests with the age group of bc’s patients along with the clinicopathological characteristics stage, grade, and molecular subtypes. in this study, pd-l1 was expressed in rates of 30% which seems to be in a reasonable range among studies held on whole tissue section [11, 17, 18]. in general terms, there is a considerable discrepancy between rates of pd-l1 expression as there is no standardized method for scoring beside variable cut-off points for pd-l1 positivity [12]. in the current study, we found that there is an insignificant link between the age of patients and pd-l1’s expression, this comes in concordance with a conclusion by ayoub et al. and lou et al. while when it comes to the term of bc’s grade and stage, we found no link between any and pd-l1 expression unlike what was concluded by researchers in the same studies [11, 19]; moreover, data from cbioportal-tcga, pancancer atlas that retrieved from 1082 patients’ samples diagnosed with invasive breast carcinoma, presented that the correlation between age and pd-l1 expression at the level of mrna (cd274 gene mrna expression) was insignificant indicating that expression of pd-l1 is not linked to how young or old is the subject, in other words, age is not a factor that doi 10.18502/sjms.v18i2.13602 page 183 sudan journal of medical sciences shahenaz s salih et al underlines the level of expression, and this supports the same conclusion we made around the variable [20, 21]. in addition, we utilized data pooled in the oncodb database (https://oncodb.org) to compare our clinical findings of age and stage with correlation analysis based oncodb between cd274 gene expression, age, and pathological stage. oncodb is a web-based tool for investigating aberrant patterns in gene expression as well as viral infection that are linked to clinical parameters in cancers [22]. the database analysis spotted neither age nor stage having any significant link to pd-l1 expression (p-values 8.3e-01 and 8.6e-02 respectively) [22], our findings also go in concordance with this web-based analysis. regarding differences in pd-l1 expression/distribution between histological types of bc, we found significant and variable distribution between idc, ilc, and other tumors with predominance in idc, this result is supported by reports from kassardjian et al. who found the only positive pd-l1 expression was in 4.1% idc versus negative/absent expression in the remaining tumors [23], likewise, data from cbioportal-tcga, pancancer atlas graphicly reveals that cd274 gene/pd-l1 expressions are more accumulated in idcs than other types of breast tumors [20, 21]. additionally, pd-l1 expression was significantly obvious in tnbcs versus non-tnbc tumors, a finding that is supported by qin and his colleagues [24, 25]. on the same level, the minute differences in the distribution of pd-l1 positivity among the molecular subtypes of bc, tnbcs, luminal types, and her2 enriched type were found to be significant in concordance with data from the cancer genome atlas and conclusions from many other studies [24, 26-28]. a strong positive association between cd8-positive tumors and pd-l1 expression points to the pivotal role of tils infiltration in the tumor microenvironment and expression of pd-l1, our finding is consistent with what has been reported in many studies [29]. and according to shenasa et al. who concluded that tils has no unusual predictability for gaining substantial benefits from chemotherapy but still can tell that the primary molecular subgroups, the non-luminal, and basal bc subtypes are frequently willing to immunotherapy [30]. in general terms, tils like cd8, cd4, b cells, and macrophages were found to be associated with favorable outcomes of the disease [28] (27). on the other hand, mrna gene expression correlations of cd274 gene (pd-l1 protein) and cd8+lymphocytes gene cd8a are the mrnas that are hugely considered as the role players controlling subsequent protein expression steps and lead the translation in the tumor microenvironment. moreover, we once more looked at the data provided in the cbioportal-tcga, pancancer atlas from the aspect of mrna expressions of cd274 doi 10.18502/sjms.v18i2.13602 page 184 sudan journal of medical sciences shahenaz s salih et al and cd8a genes, and found significant links at the level of protein expression and til infiltration. we also highlighted in our study that tcga data conclusions state strong positive correlation between two genes at the mrna level (their p-value = 9.26e-88) [20, 21]. 5. conclusion to the best of our knowledge, this study is the first to illustrate pd-l1 expression in sudanese women with bc. as shown in this study, the distribution of pd-l1 expression in tcs varied between molecular subtypes of bc with an obvious predominance in tnbcs, the most aggressive type of bc, and this predicts a promising response to the newly invented treatment regimen. hence, to determine whether patients may gain from pd-1/pd-l1 checkpoint blockade therapy, it is necessary to deep dive into the tumor microenvironment to study the pattern of pd-l1’s expression amongst the broad subtypes of bc. on the other hand, the absence of a significant correlation between pdl-1 expression and clinicopathological features seen in this study necessitates further studies attempting to elaborate this association considering the demographic data from sudanese bc to make concrete for further advanced studies exploring mutational levels in the tumor milieu. acknowledgments the author would like to acknowledge the ministry of high education, the national public health laboratory, military hospital helipad-histopathology and cytology, dr. mohamed el-hadi, dr. fatima magzoub, dr. aliaa, dr. wafaa abdallah, and dr. mariam abbas ibrahim for their support and cooperation. ethical considerations the sudan university of science and technology’s institutional ethics committee gave its approval to this work (reference number for the ethical committee is dsr-iec-05-08). since most patients passed while survivors had no contact information, it was difficult to obtain their consent. hence to protect patients’ privacy, all samples and medical data utilized in this study have been securely anonymized. doi 10.18502/sjms.v18i2.13602 page 185 sudan journal of medical sciences shahenaz s salih et al competing interests no competing interests were disclosed. availability of data and material the dataset generated during this study are available from the corresponding author on reasonable request. funding this project has been funded by the ministry of high education in 2019. references [1] stovgaard, e. s., dyhl-polk, a., roslind, a., balslev, e., & nielsen, d. 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(2022). neither tumor-infiltrating lymphocytes nor cytotoxic t cells predict enhanced benefit from chemotherapy in the dbcg77b phase iii clinical trial. cancers (basel), 14(15), 3808. doi 10.18502/sjms.v18i2.13602 page 189 introduction methods results discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 2, doi 10.18502/sjms.v17i2.11456 production and hosting by knowledge e original article association of tsh levels in the therapeutically neglected range of 6.5–8 miu/l with significant changes in liver and kidney function: a retrospective study of the kashmiri population tousief irshad ahmed*1 and ruqaya aziz2 1tutor demonstrator, department of biochemistry, skims medical college and hospital, srinagar, j&k, india 2professor and head, department of biochemistry, skims medical college and hospital, srinagar, j&k, india orcid: tousief irshad ahmed: https://orcid.org/0000-0003-3037-6204 abstract background: the thyroid gland secretes hormones crucial for growth, differentiation, regulation of metabolic processes, and homeostasis. in response to underactivity of this gland, the pituitary secretes thyrotropin, also known as the thyroid-stimulating hormone (tsh). medication for thyroid hypofunction is usually started when tsh levels exceed 10 miu/l. however, we hypothesize that tsh levels much below this therapeutic threshold level may herald significant renal and hepatic dysfunction. the present study was thus conducted to assess liver and kidney function parameters in cases having tsh in the subclinical range with particular focus on the therapeutically neglected (6.5–8 miu/l) range. methods: hospital laboratory archives of 297 adults with laboratory evidence of hypothyroidism, that is, tsh > 6.5 miu/l, were retrieved and compared with data obtained from 430 euthyroid hospital controls, that is, tsh < 2.5 miu/l, also from the same period. the thyroid profile and clinical chemistry analyses were performed on beckman coulter’s unicel dxi 800 and au 5800, respectively. spss version 20 was used to analyze the results. results: significant differences in triiodothyronine (t3), thyroxine (t4), tsh, urea, creatinine, total bilirubin, total protein (tp), and liver enzymes were observed between cases with tsh > 6.5 miu/l and controls (p < 0.05). there was also a significant difference in t4, tsh, urea, creatinine, total bilirubin, albumin and aspartate aminotransferase (ast) among cases with tsh in the range of 6.5–8 miu/l when compared with controls (p < 0.05). a correlation of t3 with tsh, urea, and creatinine was seen (p < 0.05). no correlations between tsh and other clinical chemistry parameters could be observed. however, in the 6.5–8 miu/l subgroup, correlation of tsh was seen with tp and albumin only. how to cite this article: tousief irshad ahmed* and ruqaya aziz (2022) “association of tsh levels in the therapeutically neglected range of 6.5–8 miu/l with significant changes in liver and kidney function: a retrospective study of the kashmiri population,” sudan journal of medical sciences, vol. 17, no. 2, pp. 218–235. doi 10.18502/sjms.v17i2.11456 page 218 corresponding author: tousief irshad ahmed; email: khagankhan@gmail.com received 16 october 2021 accepted 7 may 2022 published 30 june 2022 production and hosting by knowledge e tousief irshad ahmed and ruqaya aziz. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:khagankhan@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz conclusion: authors found that, as a rule, subtle renal and hepatic dysfunction were established in cases with tsh levels <8 miu/l, which was below the typical “therapeutic cut-off” of 10 miu/l. accordingly, we advocate against incautiousness and suggest regular monitoring, especially in the 6.5–8 miu/l range. keywords: subclinical hypothyroidism, liver function test, kidney function test, thyroidstimulating hormone 1. introduction thyroid hormones (ths), namely thyroxine (t4) and 3, 5,3i l-tri-iodothyronine (t3), secreted by the thyroid gland following synthesis from the amino acid tyrosine in the thyroid follicles act as the “master regulators,” exerting a profound influence on almost every cell of the body by “canonical” and “non-canonical” mechanisms [1]. ths are crucial for regulating protein, carbohydrate, and fat metabolism. they are essential for the general processes of metabolism, development and growth, which they accomplish through various genomic as well as non-genomic routes. of particular importance is the action of ths on the liver, where they actively modulate glucose, cholesterol, and fatty acid metabolism and stimulate de-novo lipogenesis. these hepatic actions have a bearing on basal energy expenditure, thermogenesis, and metabolic homeostasis [2]. ths act on kidneys where they regulate the renal hemodynamics by direct mechanisms and by modulating ion transport in the glomerular and tubular cells. ths also affect the organs above by influencing the cardiac output. hypothyroidism adversely affects cardiac contractility, myocardial oxygen consumption, vascular resistance, blood pressure, and electrophysiological conduction. as ths have genomic effects, any reduction in their concentrations result in decline of translational products involved in myocardial contractility, endothelial vasodilation, and renin synthesis. response to β-adrenergic stimulus is also downgraded. this has a profound impact on the renal milieu [3]. certain studies have hinted at histological changes in hypothyroidism. several observational studies have shown that elevated thyroid-stimulating hormone (tsh) levels are significantly associated with the development of non-alcoholic fatty liver disease (nafld). this can be partly explained by the steatogenic changes induced by an underactive thyroid. modulation of signal transduction pathways, impairment in lipid metabolism, increased de-novo lipogenesis, and upregulation of reactive oxygen doi 10.18502/sjms.v17i2.11456 page 219 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz species (ros) and inflammatory cytokines can all be triggered by disturbances in thyroid function [4]. hypothyroidism and hyperthyroidism indicate underactivity and overactivity of the thyroid gland, respectively [5]. subclinical hypothyroidism (sch) is a laboratory diagnosis wherein tsh levels are higher than normal, while levels of t3 and t4 remain in the normal range. hypothyroidism is the most prevalent among thyroid disorders in south asia and especially so in the northern himalayan states of india, where iodine deficiency has been a historical concern. coastal indian cities have a lower prevalence of hypothyroidism (both sch and overt) than northern inland territories. in fact, a north indian study suggested that the prevalence of sch could be as high as 19.3% [6]. of late, questions on thyroid gland underactivity have been arising, primarily whether cases of th values falling marginally outside of normal limits should be pharmacologically addressed, or is overprescription of t4 for the treatment of these “laboratory derangements” a genuine concern in that, are we treating the lab reports or the patient themselves?[7]. sch is usually characterized by laboratory evidence of increased tsh (5–10 miu/l or more) along with average t4 values. older studies did not provide sufficient evidence for the benefits of treatment at tsh values of 4.5–10 miu/l [8]. in fact, treatment was only recommended for tsh values higher than the threshold value of 10 miu/l [9]. a comprehensive perusal of recent studies shows that levothyroxine is generally prescribed only in manifest hypothyroidism. therapy for sch is usually discouraged unless tsh values exceed 10 miu/l [10]. however, there is a possibility that undue focus on the 10 miu/l threshold may potentially leave out many who are otherwise worthy of the medication. specific ailments, such as psychiatric disorders [11], unexplained infertility [12], and metabolic syndrome may have a thyroid basis. pathological alterations in crucial analytes as seen in hyperinsulinemia, insulin resistance, dyslipidemia, hypercoagulability, cardiovascular status (as gauged by elevated hscrp), and hyperuricemia are often closely related to thyroid function. these alterations may manifest themselves even at tsh levels <10 miu/l [13]. in many such cases, despite midto high-normal tsh values, subtle thyroid dysfunction is evident beyond doubt. evidently, there is a possibility of the setting in of indiscreet biochemical changes which may benefit from early therapy. all these questions lend more weight to the concept of individualized assessment of thyroid function status [5]. some persons may not have any (obvious) symptoms, and clues obtained from measuring biochemical parameters despite borderline th measurements may herald a less than assuring prognosis. in doi 10.18502/sjms.v17i2.11456 page 220 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz such persons, therapy initiation at high-normal to moderately raised tsh levels may provide both tangible and intangible benefits. 1.1. renal effects of thyroid hypofunction the thyroid influences both the kidney and liver (figure 2). bulur et al. observed that t4 therapy in previously hypothyroid patients caused renal function to improve significantly as the raised creatinine and tsh levels normalized. they also attributed the raised creatinine levels in hypothyroidism to a reduction in gfr and renal plasma flow. this was in turn due to a “hypodynamic state” of the circulatory system in addition to the lack of th-induced inotropic and chronotropic stimulus. creatinine was thus not cleared from the circulation in such individuals with the same vigor as seen in euthyroid individuals [14]. either that or actual effects on glomerular physiology or both may be the reason for creatinine elevation. animal studies on hypothyroid rats showed histological evidence of a reduction in glomerular capillary density, which indicated a pro-angiogenic role for ths [15]. these hormones may also be instrumental in increasing vascularity. in addition, they exert an activatory effect on the renin–angiotensin system (ras), both with and without the involvement of the sympathetic nervous system. in a study by ichihara et al., t3 was found to increase renin secretion and renin mrna in juxtaglomerular cell cultures by calcium-dependent and independent mechanisms [16]. certain indirect (endocrine/paracrine) effects mediated via signal proteins like vascular endothelial growth factor (vegf) and insulin-like growth factor type 1 (igf-1) are also contributory to the renal effects seen in sch [17]. 1.2. hepatic effects of thyroid hypofunction historically, the liver has always been an indispensable organ for medical research. it is probably the most influenced by the thyroid. preliminary studies on rat liver and kidneys during the early second world war period revealed that the administration of t4 and tsh had definitive effects on tissue respiration and organ weight, with the former hormone consistently elevating the oxygen consumption rates (qo2) as compared to the latter [18]. the effect of th perturbations on liver function was demonstrated in another study during the cold war period, utilizing electrophoresis. the said study showed alterations in serum protein patterns in thyroid disorders, with hypothyroid patients exhibiting lower albumin levels and elevated β globulin fractions. treatment with t4, however, tended to reduce levels of both these fractions [19]. a seminal work doi 10.18502/sjms.v17i2.11456 page 221 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz on biochemical changes underlying cellular differentiation during t3-induced metamorphosis in tadpoles observed a significant increase in specific activities of liver nucleic acids and proteins when administered the th. the liver rna: dna ratio also increased indicating active transcription triggered by t3 [20]. the same year, while studying the effect of t3 on the growth of the liver in thyroidectomized rats, an indian researcher, jamshed tata, observed accelerated incorporation of amino acids into nuclear protein. he also reported an increased turnover of basic nuclear proteins [21]. an early animal experiment to assess the role of ths on hepatic metabolism revealed an increased efficiency in lactate utilization in hypothyroid rats administered t3. the sensitivity to glucagon improved and gluconeogenesis was also found to be markedly enhanced. the gluconeogenic enzyme pyruvate carboxylase appeared to be highly responsive to t3. the latter hormonewas also effective in reducing urea formation. redox equilibrium of the perfused hypothyroid liver, which showed a more reduced state, possibly due to underutilization of nadh in gluconeogenesis, was normalized by the administration of t3[22]. in the early 1970s, the pioneer of th action, j.h. oppenheimer, identified high-affinity receptors for t3 in nuclei of rat liver and kidney [23]. in one of the earliest reviews on th action, he mentioned that the interaction of t3 (and to a much lesser extent t4) with the receptors resulted in significant modulation of gene activity. enzymes vital to carbohydrate and lipid metabolism, such as α-glycerophosphate dehydrogenase and malic enzyme, were particularly affected by t3(by that time, they were already being used as resourceful indices for studying the hormone’s effects in rat liver). the rat liver tissue had a high binding capacity and a larger number of binding sites per nucleus compared to several other organs [24]. the liver affects circulating th concentrations as well. carrier proteins that bind t4 and transport it to different targets in the body are synthesized and degraded by the liver. only 0.04% of t4 circulates freely. most of it is complexed with th carrier proteins like thyroxine-binding globulin (tbg), thyroxinebinding pre-albumin (tbpa), albumin, and other plasma proteins. the hepatocyte thus represents a central control point. peripheral deiodination is also accomplished by deiodinases which synthesized in the liver. the liver–thyroid relationship is thus a twoway interaction [25]. the purpose of this study was to assess derangements in routine liver and kidney biochemical parameters in subclinical and overt hypothyroidism with respect to controls. special attention was paid to the analysis of such derangements in the therapeutically neglected tsh range of 6.5–8 miu/l. we also attempted to determine the correlation between t3, t4, tsh levels and these parameters. doi 10.18502/sjms.v17i2.11456 page 222 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz 2. materials and methods 2.1. study population hospital laboratory archives of adult opd patients visiting skims (sher-i-kashmir institute of medical sciences) medical college and hospital, srinagar, jammu & kashmir, india between january 2017 and march 2021 were accessed and scanned for all records with laboratory evidence of hypothyroidism, that is, tsh > 6.5 miu/l (including mild/significant sch and oh). after several rounds of exclusion, records of 297 adults (78 males [26.26%] and 219 females [73.74%]) were retrieved and compared with data obtained from 430 euthyroid hospital controls, that is, tsh < 2.5 miu/l (57 males [13.26%] and 373 females [86.74%]), also from the same period. 2.2. inclusion and exclusion criteria adults of either sex were included. those with a history of thyroid surgery or use of t4, amiodarone, or lithium were excluded. we also excluded all records with tsh levels between 2.51 and 6.49 miu/l or <0.5 miu/l for both cases and controls. the scheme of enrollment of data is given in figure 1. 2.3. data collection methodology the authors’ laboratory currently uses a reference range for tsh of 0.45 to 6.0 miu/l. thus, 4997 lab archives with adequate quality control (qc) results were retrospectively scanned, and data of all individuals with tsh levels > 6.5 miu/l were considered. after exclusion, it was narrowed down to 297 records. these included routine lft (n = 281) and kft (n = 297) records. cases were divided into two groups for statistical analysis. the first group had tsh in the “therapeutically neglected” range of 6.5–8 miu/l (n = 44 for lft and n = 48 for kft), while the second group had tsh in the “therapeutically important” range of >8 miu/l (n = 237 for lft and n = 249 for kft). hospital controls were used, also from the lab archive database, wherein data having tsh in the range of 0.5–2.5 miu/l (n = 430) were selected. 2.4. protocol and procedure all retrospective records we obtained were of patients who, as per routine protocol, were advised to report for sampling after an overnight fast. a single blood draw was used to doi 10.18502/sjms.v17i2.11456 page 223 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz obtain a 4–6 ml venous blood sample and divided into two aliquots immediately post phlebotomy. one aliquot was sent to the biochemistry laboratory, and another aliquot was sent to the immunology section, which performs the thyroid panel. immediately after receipt of the aliquots, centrifugation for 5 min at 3000 g was performed. serum was subsequently separated. while the biochemistry aliquots were immediately processed and analyzed after a brief (15–30 min) delay to allow for data entry, the thyroid panel aliquot was subject to a moderate (30–60 min) delay for sufficient batch size to form and then processed. generally, the average turnaround time (tat; from sample registration to report authentication) of biochemistry samples is in the 60–120 min range, while thyroid panel tat averages around 120–180 min. different technical staff performed the analyses of each aliquot and results were automatically uploaded on the hospital lan (local area network). 2.5. measurement of t3, t4, and tsh t3, t4, and tsh (3𝑟𝑑 gen) levels were estimated on beckman coulter’s unicel dxi 800 access immunoassay system. this analyzer utilizes chemiluminescent detection and magnetic particle-separation technology. reference intervals provided by the manufacturer were tsh 0.45–5.33 miu/l for tsh, 0.87–1.78 ng/ml for t3, and 6.09–12.23 μg/dl for t4. the sensitivities of tsh, t3, and t4 were 0.01 miu/l, 0.1 ng/ml, and 0.50 μg/dl, respectively. 2.6. measurement of biochemical parameters the biochemical parameters, namely urea, creatinine, total bilirubin, total protein, albumin, aspartate aminotransferase (ast), alanine aminotransferase (alt), and alkaline phosphatase (alp) were examined on beckman coulter’s au5800 clinical chemistry system. this analyzer is based on the principles of spectrophotometry and potentiometry. 2.7. quality control apart from stringent daily maintenance and calibration protocols, internal controls for clinical chemistry and immunoassay parameters provided by bio-rad® laboratories were run at least twice daily. any nonconformity or errors reported were investigated and root cause analysis performed. outliers or results exceeding linearity were subject to repeat doi 10.18502/sjms.v17i2.11456 page 224 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz testing with suitable dilution. the intraassay coefficients of variation (cv) for t3, t4, and tsh were <10%. the clinical chemistry parameters also had acceptable cvs (table 1). 2.8. statistical analysis the recorded data were compiled and entered in a spreadsheet (microsoft excel) and then exported to data editor of spss version 20.0 (spss inc., chicago, illinois, usa). continuous variables were expressed as mean ± sd, and categorical variables were summarized as frequencies and percentages. the student’s independent t-test was employed for comparing continuous variables. karl pearson’s correlation coefficient was applied to determine the correlation of tsh, t3 and t4 with various parameters among study cases. a p-value of < 0.05 was considered statistically significant. all p-values were two-tailed. 3. results in the present study, on comparison of liver and kidney function parameters, it was found that the total bilirubin, total protein, globulin, liver enzymes aspartate aminotransferase (ast), alanine aminotransferase (alt) and alkaline phosphatase (alp), urea and creatinine were significantly elevated in the cases which had tsh > 6.5 miu/l when compared to the controls (table 2). the same effect was seen when comparing the group with tsh > 8 miu/l to controls (table 3). albumin levels were not statistically different in the cases vis-à-vis controls. globulin levels were higher nonetheless, and this resulted in lower a/g ratios in the cases. however, on comparing cases with tsh levels in the 6.5–8 miu/l range to controls, we found that the total protein, alt and alp ceased to show a statistically significant difference. at the same time, albumin and the other lft and kft parameters remained significantly elevated (table 4). thus, the rise in urea, creatinine, total bilirubin, albumin, globulin, and ast appears to have established itself in this “therapeutically neglected” range, even though t3 and t4 levels, despite being significantly lower, were still mainly in the normal to low normal range. no significant correlations were found between tsh/t4 and any biochemical parameter. nonetheless, we did find a significant correlation between serum t3 and urea, creatinine (p =< 0.001), and a moderately significant correlation between serum t3 and alp (p = 0.059). interestingly, when we limited the analysis to tsh in the range of 6.5–10, we found a significant correlation between tsh on the one hand and total protein (p = 0.004), albumin (p = 0.013) on the other. urea levels also showed a doi 10.18502/sjms.v17i2.11456 page 225 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz moderate correlation in this tsh range (p = 0.086) (table 5). thus, the fluctuations in tsh levels observed in individuals within this range may be accompanied by corresponding changes in the above parameters. figure 1: scheme of data enrollment. table 1: assay specifications of hepatic and renal parameters. analyte method reference range sensitivity intra-assay cv urea adaptation of the enzymatic method utilizing glutamate-dehydrogenase (gldh) 17–43 mg/dl 5 mg/dl ≤5% creatinine kinetic modification of the jaffe procedure 0.6–1.3 mg/dl 0.2 mg/dl ≤3% total bilirubin 3,5-dichlorophenyldiazonium tetrafluoroborate (dpd) modification of diazo method 0.3–1.0 mg/dl 0.01 mg/dl ≤3% total protein weichselbaum modification of biuret 6.4–8.9 g/dl 3 g/dl ≤3% albumin modification of doumas and rodkey bromocresol green method 3.5–5.7 g/dl 1.5 g/dl ≤3% ast modification of the international federation of clinical chemistry (ifcc) method 13–39 u/l 3 u/l ≤10% alt wroblewski and ladue modification of the international federation of clinical chemistry (ifcc) method 7–52 u/l 3 u/l ≤10% alp bowers and mccomb method 30–120 u/l 5 u/l ≤10% 4. discussion we found substantial derangements in almost all of the recorded kidney and liver function parameters in those with tsh > 6.5 miu/l. most of these derangements doi 10.18502/sjms.v17i2.11456 page 226 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz figure 2: underlying mechanisms for the effects of thyroid hypofunction on the liver and kidney. were evident even at tsh levels <8 miu/l. we could also establish a significant negative correlation between tri-iodothyronine levels and the renal function markers. liver function indicators such as total bilirubin, albumin, globulin, some of the liver enzymes, as well as kidney function parameters were affected even in the narrow tsh range of 6.5–8 miu/l. in the 6.5–10 miu/l range, the presence of significant correlations between tsh levels and total protein, albumin, and urea were evident. thus, tsh levels far below the conventional “therapeutic boundary” of 10 miu/l were often associated with laboratory evidence of incipient organ impairment. our findings compare with the indian study by arora et al., who reported significantly higher levels of creatinine (albeit not exceeding the reference range) in hypothyroid subjects compared to euthyroid controls (p < 0.001) and also with another indian study by yadav et al. which observed significantly raised serum alt, alp, and total protein levels in sch subjects (tsh 6–9.9 miu/l) [26, 27]. a third indian study by saini et al. demonstrated higher urea and creatinine levels in sch and oh patients than controls doi 10.18502/sjms.v17i2.11456 page 227 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz table 2: comparison of lft parameters in cases and controls. parameter cases (tsh > 6.5) (n = 281) controls (tsh < 2.5) (n = 425) p-value mean sd mean sd t3 1.20 0.53 1.41 0.35 <0.001* t4 8.41 2.31 10.09 1.95 <0.001* tsh 16.73 39.58 1.70 0.51 <0.001* total bilirubin 0.74 0.43 0.59 0.28 <0.001* tp 7.65 0.72 7.44 0.52 <0.001* albumin 4.09 0.59 4.08 0.50 0.822 globulin 3.57 0.56 3.371 0.39 <0.001* a/g ratio 1.17 0.26 1.23 0.21 0.002* ast 37.22 25.90 30.95 15.78 <0.001* alt 37.03 36.53 31.57 24.17 0.017* alp 124.62 55.52 115.25 65.73 0.035* comparison of kft parameters in cases and controls parameter cases (tsh > 6.5) (n = 297) controls (tsh < 2.5) (n = 430) p-value mean sd mean sd urea 26.45 11.04 19.71 8.55 <0.001* creatinine 0.74 0.39 0.51 0.19 <0.001* table 3: comparison of lft parameters in cases with tsh > 8 and controls. parameter cases (n = 237) controls (tsh < 2.5) (n = 425) p-value mean sd mean sd t3 1.18 0.51 1.41 0.35 <0.001* t4 8.37 2.41 10.09 1.95 <0.001* tsh 18.39 42.69 1.70 0.51 <0.001* total bilirubin 0.72 0.42 0.59 0.28 <0.001* tp 7.68 0.72 7.44 0.52 <0.001* albumin 4.13 0.60 4.08 0.50 0.311 globulin 3.57 0.583 3.371 0.39 < .001* a/g ratio 1.11 0.2 1.23 0.21 0.02* ast 37.21 23.49 30.95 15.78 <0.001* alt 38.16 38.34 31.57 24.17 0.007* alp 126.89 58.24 115.25 65.73 0.023* comparison of kft parameters in cases with >8 miu/l and controls parameter cases (tsh > 8) (n = 249) controls (tsh < 2.5) (n = 430) p-value mean sd mean sd urea 27.16 11.35 19.71 8.55 <0.001* creatinine 0.75 0.41 0.51 0.19 <0.001* [17]. arora et al., however, reported no significant differences in urea levels of cases and controls. they reported a positive correlation between serum tsh on the one doi 10.18502/sjms.v17i2.11456 page 228 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz table 4: comparison of lft parameters in cases with tsh 6.5–8 miu/l and controls. parameter cases (n = 44) controls (tsh < 2.5 miu/l) (n = 425) p-value mean sd mean sd t3 1.32 0.60 1.41 0.35 0.211 t4 8.63 1.64 10.09 1.95 <0.001* tsh 7.25 0.48 1.70 0.51 <0.001* total bilirubin 0.85 0.49 0.59 0.28 <0.001* tp 7.46 0.71 7.44 0.52 0.803 albumin 3.90 0.49 4.08 0.50 0.022* globulin 3.55 0.46 3.371 0.39 .00588* a/g ratio 1.11 0.2 1.23 0.21 0.00416* ast 37.28 36.84 30.95 15.78 0.035* alt 30.83 23.67 31.57 24.17 0.847 alp 111.76 34.26 115.25 65.73 0.735 comparison of kft parameters in cases with tsh 6.5–8 miu/l and controls parameter cases (n = 49) controls (tsh < 2.5 miu/l) (n = 430) p-value mean sd mean sd urea 22.72 8.38 19.71 8.55 0.022* creatinine 0.70 0.27 0.51 0.19 <0.001* table 5: correlation of tsh with various parameters among study cases for tsh values 6.5–10 miu/l. parameter pearson correlation p-value t3 0.352 <0.001* t4 –0.382 <0.001* urea 0.142 0.084 creatinine 0.041 0.619 total bilirubin –0.095 0.295 total protein 0.242 0.004* albumin 0.212 0.013* globulin 0.017 0.842 ast –0.003 0.972 alt 0.107 0.213 alp 0.128 0.137 hand and serum alt, ast, total protein, and albumin on the other, and a negative correlation between serum t4 and the latter four parameters. yadav et al. found a positive correlation between tsh and the liver enzymes, ast and alp. saini et al. also reported a negative correlation between tsh with urea. however, as seen in the results, our study could not replicate the correlation results of the three indian studies in cases with tsh > 6.5 miu/l. one scholar confirmed our findings of higher bilirubin levels doi 10.18502/sjms.v17i2.11456 page 229 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz in sch subjects. he additionally reported lower albumin levels, a finding which we observed in subjects with tsh in the 6.5–8 miu/l range [28]. our observation is that kidney function is affected in sch and oh, as typified in direct measurements such as creatinine and indirect measurements such as estimated glomerular filtration rate (egfr). we found support for our findings in a study by schairer et al., who studied a cohort of chronic kidney disease (ckd) patients posttransplantation, concluding that positive changes in tsh (δtsh) were associated with decrease in (egfr) (to the tune of 1.34 ml/min for every 1 µiu/ml increase in tsh) [29]. another study by shin et al. focusing on ckd patients with sch found that tsh reduction secondary to th replacement therapy was helpful in preventing the deterioration of renal function [30]. tsuda et al. reported drastic glomerular hemodynamic effects of hypothyroidism, even in the high-normal tsh range. tsh was found to have a significant positive correlation with afferent arteriole vascular resistance and a significant negative correlation with renal plasma flow (rpf), renal blood flow (rbf), and gfr. this may have arisen due to the direct action of tsh on its specific receptors in the kidneys. thus, the effects of compromised thyroid function would lead to suppressed renal function [31]. recent studies such as that of kim et al. found that lower thyroid function was associated with higher prevalence and risk of nonalcoholic steatohepatitis (nash) and fibrosis. they found histological evidence of extensive hepatic steatosis showing significant hepatocyte “balloon degeneration” and fibrosis. highand high-normal tsh levels were closely related to nash and nash-related advanced fibrosis. this could be explained by the increasing propensity for development of insulin resistance and other metabolic disturbances brought about by dyslipidemia and obesity in hypothyroid individuals. insulin resistance has been shown to improve with th therapy. other mechanisms of thyroid hypofunction-induced hepatic damage are oxidative stress, mitochondrial dysfunction, and altered th signaling in hepatocyte fibrogenesis [32]. tsh on binding to receptors on hepatocytes has been found to upregulate sterol regulatory element-binding protein-1c (srebp-1c) activity. this may induce steatogenic changes [4]. our findings of higher bilirubin and liver enzymes in subjects with tsh > 8 miu/l would be secondary to the above changes. the findings of elevated bilirubin, low albumin, high globulin, and high ast in the tsh range of 6.5–8 miu/l suggest that thyroid dysfunction in this range of tsh profoundly induces impairment in lipid metabolism. this in turn results in steatogenic changes by the various mechanisms discussed previously, thus precipitating and/or potentiating hepatic injury [28]. in some cases, cholestatic jaundice coincident with hypothyroidism has been ascribed to the impairment in bilirubin and doi 10.18502/sjms.v17i2.11456 page 230 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz bile excretion, which is secondary to the hepatic injury. the enzyme activity of udpglucuronyl transferase may also be reduced, thus hampering bilirubin excretion. diminution in bile flow also results from an increased membrane cholesterol–phospholipid ratio and the consequent reduction in fluidity. membrane transporters may thus be affected [25]. consequently bilirubin levels rise in hypothyroidism. ast may rise due to a combination of myopathies and hepatic injury. hypothyroidism is an inflammatory state, possibly elevating liver enzyme levels and increasing total proteins, mostly the inflammatory globulins, which could partially explain our findings of raised globulin levels in all the cases with tsh > 6.5 miu/l [26]. a significant positive correlation between tsh and total proteins, albumin in the 6.5–8 miu/l range suggests that hepatic damage may have already started in this range. putative mechanisms of this damage are hepatic congestion secondary to hypothyroidism-induced cardiac compromise and augmented state of vascular endothelial permeability, in addition to the changes mentioned above [33]. 5. conclusion we suggest physicians exercise caution in cases having tsh in the range of 6.5–8 miu/l without apparent signs and symptoms. the results of our study strongly emphasize that alterations possibly involving steatogenic changes in the liver, and insidious decrements in kidney function, among myriad other processes discussed above, establish themselves in this range, and a treatment initiation threshold of 8 or 10 miu/l tsh may be incautious. a new diagnostic scoring system, which takes into account tsh levels for evaluating steatogenic liver changes must be envisaged [4]. thyroid hypofunction may precipitate/worsen kidney disease, especially in hospitalized patients [17]. in cases of established liver injury, hypothyroidism should not be ruled out as a significant causative factor [33]. it is thus imperative to perform regular liver and kidney function tests for all patients, even for tsh levels <8 miu/l. also, the possibility of th analogues in reversing hypothyroidism-induced fatty change (as well as other indiscreet biochemical changes) at this range of 6.5–8 miu/l may be considered and further researched [34]. the direct positive correlation of tsh with total protein and albumin in this range suggests that efforts to reduce tsh levels even in this therapeutically neglected range may have tangible benefits. doi 10.18502/sjms.v17i2.11456 page 231 sudan journal of medical sciences tousief irshad ahmed and ruqaya aziz acknowledgements the authors would like to thank the technical staff at the central biochemistry laboratory of skims medical college for their support. ethical consideration ethical clearance for the study was obtained from the institutional ethical committee of skims medical college, bemina, srinagar, j&k, india. competing interests none declared. availability of data and material all data and materials associated with this study are available through the corresponding author upon reasonable request. funding none. references [1] brix, k., szumska, j., weber, j., et al. 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(2011). setpoints and susceptibility: do small differences in thyroid function really matter? clinical endocrinology, vol. 75, no. 2, pp. 158–159. doi 10.18502/sjms.v17i2.11456 page 235 introduction renal effects of thyroid hypofunction hepatic effects of thyroid hypofunction materials and methods study population inclusion and exclusion criteria data collection methodology protocol and procedure measurement of t3, t4, and tsh measurement of biochemical parameters quality control statistical analysis results discussion conclusion acknowledgements ethical consideration competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12543 production and hosting by knowledge e research article the sudanese medical education in the light of flexner report ayman fisal ahmed foad department of pathology, national university, sudan orcid: ayman fisal ahmed foad: https://orcid.org/0000-0003-2618-7785 abstract medical education as a profession is a legitimate offspring of flexner’s report in 1910. it strived to excel in preparing future doctors and increasing the competency of medical practitioners. we provide a scientific critique of flexner’s report, displaying its merits and shortcomings and shedding a spotlight on sudan’s medical education milestones and its current strive for excellence and innovation in curricula designing, accreditation, graduate competencies, staff professional development, and quality improvement. since the publication of this inspiring study, a global effort has been launched to improve the quality of health system policies and health professions’ competency through education. all stakeholders now seek fundamental reform in medical education in sudan to improve its quality and trustworthiness. based on this study, our impost does not necessarily propose following its footsteps but instead evaluates its stimulating role in planning and intervention. keywords: flexner report, carnegie report, sudan medical education revolution, competency, accreditation, racism, female education, longitudinal integrated clerkship, professional development 1. introduction this article tries to shed light on the history and current status of medical education in sudan, using flexner’s report as a model. it might be a redundant idea and published frequently; nonetheless, different opinions and point of view are additive to the subject. the first recognized established hospital dates to the 6𝑡ℎ century in persia [1]. this consideration entrenched the concept of the medical corporation. doctors used to visit the patients in their homes, as there was no dedicated place for treatment or isolation of sick people. at the dawn of the 8𝑡ℎ century, the first islamic bimarstan was established in damascus [1]. as a result, hospitals were recognized as centers for treating patients and training doctors. formal medical training in america dated 200 years before flexner’s report through apprenticeship, which lacked uniformity or standardization. the first traditional medical teaching was recorded in 1750 [2]. john morgan started a formal medical training how to cite this article: ayman fisal ahmed foad (2022) “the sudanese medical education in the light of flexner report,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 428–443. doi 10.18502/sjms.v17i4.12543 page 428 corresponding author: ayman fisal ahmed foad; email: aymanfisal@yahoo.com received 11 january 2022 accepted 6 july 2022 published 31 december 2022 production and hosting by knowledge e ayman fisal ahmed foad. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12543&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ayman fisal ahmed foad practice back in 1765 in a philadelphia hospital. thomas bond (1841-1901) defended the notion that didactic teaching is not enough to prepare doctors for clinical practice, and that they should have supervised bedside training [2]. the first recognized medical school in sub-saharan africa dated 1896, in madagascar (universite d’antanarivo). the sum of recognized medical schools in sub-saharan africa before 1950 reached 13; in the 1980s, the number increased to 51 [3]. the university of khartoum, the first sudanese school of medicine, was established in 1924 before the declaration of independence from british colonization. in the middle east, the first medical school was found in beirut in 1868 [4]. the first established medical school in egypt was kasr al-ainy in 1872, followed by alexandria a century later [5]. flexner was a latin and greek graduate from john hopkins after attaining a master’s degree in education. based on his brother’s background in medical training, flexner was influenced by the dutch style of medical education, and he tried to mirror john hopkins’s practice in the american and canadian medical schools. john hopkins still reserves a pioneering status as a private research-oriented educational facility. flexner’s observations aimed to repair deficient formal training and introduce evidence-based practice on the conscious decisions of graduates. a track-centered practice was encouraged by some institutes [2]. j. newman pioneered a leadership concept for universities complemented by the community [2], which became an integral part of medical curricula. the carnegie report was a milestone in the development of medical education in the usa and canada. however, this has been pursued as a continuous endeavor for amendment and correction [6]. the impact of this report resonated globally, creating a motion to generate invigilating organizations to maintain quality and excellence in medical schools [7]. the global result of the report is rooted in its sweeping outcomes on american and canadian medical education and the political role of north american countries at the inception of the last century. 2. materials and methods the carnegie (flexner report), which was released in 1910, is carefully analyzed, with emphasis on its most contentious points and contemporary subjects. the critique reflects the authors’ observation, striving to maintain a scientific, non-biased approach by supplementing information collected from public press and scientific journals published in the last three decades. doi 10.18502/sjms.v17i4.12543 page 429 sudan journal of medical sciences ayman fisal ahmed foad 3. discussion 3.1. the impact of flexner report 3.1.1. dual phases in medical schools (preclinical and clinical) flexner’s background as an educator and school principal amended his visits to 155 medical schools around america and canada to critique the curriculum, infrastructure, students, and teaching methods. he recommended separating teaching in medical schools into two phases; the preclinical phase, where basic medical sciences essential as a foundation should be taught, and the clinical phase where bedside training will be covered. due to his academic background, he encouraged adding laboratory training to study medicine. his approach has been challenged by new educational theories that advocate for an integrated medical system in which clinical sciences are taught alongside basic medical sciences and clinical correlations. in terms of delivering knowledge to students and capturing their attention with intriguing relevant clinical problems, integration proved superior to traditional teaching. this approach helped a lot with the expanse of knowledge beyond the capacity of the four-year proposed program to cover. it is advised that basic sciences relevant to clinical practice be thoroughly covered while skimming over irrelevant facts. medical education is now concerned with all facets of learning processes, postgraduate specialty training, professional development, continuous training, and competency exams for registration and license renewal. the scope of medical education has been broadened to include all aspects of the healthcare system. many medical schools are now abandoning the classical ologies system in order to favor the integrating-based curriculum. the level of integration and its efficiency varied widely based on variants of educational theories [8]. the integrated module system needs to be supplemented by an adequate staff, an apparent inadequacy deterring its proper application. the integrated approach proved to be superior in information delivery and retention. affiliation and partnership of medical colleges with well-established local and regional institutes with the conjoint utilization of resources and consultation services are advisable solutions. this was reflected in the partnership between well-established institutes and newly emerged ones in sudan, which helped develop and sustain these institutes. doi 10.18502/sjms.v17i4.12543 page 430 sudan journal of medical sciences ayman fisal ahmed foad the longitudinal integrated clerkship (lic), a clinical education model based on the ideas of social cognitive theory and contextual learning [9], this model’s framework intentionally creates ongoing ties between faculty, students, and patients, improving student discipline, moral conduct, and professionalism [10]. many pioneering medical institutes in sudan have the capabilities to pursue this with an arsenal of teaching hospitals and available staff. designing integrated courses is approached differently by many institutes; some are clinically integrated from the get-go, and some integrate only in phase two; some institutes integrate conceptually by providing didactic knowledge with simulation in the pre-clerkship phase and introducing clinical rounds with actual patients later, now the trend is to integrate clinical practice in lic schemata; as we used to say to our students “we are treating patients, not diseases.” unfortunately, we all recall patients’ frustration when they wander between departments seeking multidisciplinary inputs to their ailment; students undergoing lic can follow patients through their weekly rotational activities in multiple clinical specialties.lic is regarded as a motivator in engaging students in the learning process, and vividly educates the mind to use rationally allocated basic science information, abilities, and attitudes to serve the primary objective of safe and efficient clinical practice [11]. during the covid-19 epidemic, the lic, according to desai, was an unexpected godsend since academic calendars were barely disturbed compared to traditional clerkship curricula [12]. in sudan, the lic concept is proposed and contemplated by many institutes but not yet approved by the curriculum committees, as it requires a tremendous organizational effort to allocate training posts and assign clinical supervisors. according to one of the lic students, his pediatric rotation of one-year duration consisted of working in the same clinic. “i completed newborn checkups as well as child visits for the same patient at 2, 4, 6, and even 9 months of age.” [12]. this constitutes only a glimpse of a herd of benefits potentially attained in lic. 3.1.2. a scientific approach to study medicine flexner commends the german style of medical education, reflected in the john hopkins school of medicine. this approach entertains extensive laboratory training for the students. medicine mainly stood over the centuries as a profession-only practice, and doi 10.18502/sjms.v17i4.12543 page 431 sudan journal of medical sciences ayman fisal ahmed foad the scientific part was mostly ignored. flexner validated evidence-based medical training and practice and encouraged research in esteemed medical schools for emerging social health issues as a part of accreditation requirements. 3.1.3. competency of the graduates assuring that all minimum sets of resources are made available in medical schools can help in validating and testing the competence of the graduates. flexner was not a doctor, albeit his brother was; his background endorsed the report even more because this is an insight of an observer who does not have a biased judgment, and his realizations and conclusions had been based solely on careful surveillance of the system layout, not the content. readers of the reports will realize that flexner did not use either a written questionnaire or a checklist in his report. he based his data mainly on adaptive scrutiny, which may strip his reported data from some creditability. harden proposed his spice [13] model of medical education that is student-centered, problem-based, integrated, community-based, elective, and systematic in contrast to the old-fashioned traditional medical education that is teacher-centered, rote learningbased, discipline-based (ologies), hospital-based, standard, and apprenticeship based. medical education in sudan is currently undergoing transformational trends toward competency-based curricula; in his proposal for competencyor outcome-based curricula in sudanese medical education, ”sudan meds,” dr. abdullah attempted to replicate canadian and ksa experiences [14]. 3.1.4. learning resources flexner surveillance visits focused on the capabilities of medical schools to provide proper training for students. he critiqued profitable medical schools and advised governmental schools to allocate an ample budget for establishing good training and progress. he recommended the allocation of some poorly installed institutes for the training of black or female doctors, reflecting america’s prevailing segregation politics in the last century. now we have many learning resources, including simulation and electronic libraries. laboratory-based training in developing countries suffers significantly from the lack of resources; mohammed et al. strengthened the utility of laboratory training in medical schools [15]. doi 10.18502/sjms.v17i4.12543 page 432 sudan journal of medical sciences ayman fisal ahmed foad simulation is now widely introduced as an indispensable resource in medical education for training undergraduates and postgraduates. mannequins currently use sophisticated software and sensors to deliver a realistic experience for students. more it companies need encouragement to invest and invent in this realm to increase diversity and lower costs [16]. the simulation problem includes depersonalization of the teaching experience and its steep cost and required maintenance. no doubt, their capabilities of mimicking symptoms and signs with rebound fidelity are cherished. sudan indeed lagged in many of these essential learning resources, but students’ accessibility to hospitals and patients compensated for these inadequacies. an alternative solution in sudan is to provide collaborative simulation centers, which are utilized by many medical colleges to circumvent budget constraints. online educational platforms and virtual classrooms have been around for about two decades; the covid-19 pandemic forced us to utilize these platforms intensely. online learning platforms need reliable infrastructural elements [17–19]. its advantage can be transferred by providing an experienced educator for large numbers of learners beyond the boundaries of place and time. these platforms lack active engagement, but are ever-evolving, and programmers solve many problems. this method of education proved to have paramount importance during the covid-19 pandemic for continuous professional development and post-graduate programs. the instability and insufficiency of well-established e-learning tools and infrastructure in many medical institutes in sudan drastically hindered medical education during the unsettled political status and covid-19 pandemic [20]. during the late 90s, the faculties of medicine at khartoum and gezira supervised an educational network providing plenary lectures to outreached and newly established institutes. for the lack of continuous support and development, these activities seized to exist despite the tremendous technological advancement in sudan. 3.1.5. accreditation of medical schools flexner focused on the selection criteria of students, schools’ resources and financial plan, and affiliated training hospitals in his nationwide visits. following his study, a government initiative was launched, and almost half of the institutes were ruled incapable of teaching medical students. some of these institutes have been dissolved, some have been combined, and some have been excused from being in sectarian zones or scattered for training black physicians or women. this was the first considerable doi 10.18502/sjms.v17i4.12543 page 433 sudan journal of medical sciences ayman fisal ahmed foad countrywide accrediting procedure for medical schools. this ground-breaking approach was quickly implemented globally to ensure the aptitude and skill of medical schools and practitioners. akpa gbary et al. stated that accreditation of african medical schools is not frequent or thorough. many institutes proved to have poor curricula and ancient laboratory settings [21]. without international (world federation of medical education) and regional (african conference of deans of french-speaking medical schools (cadmef)) exchange of experiences and collaboration, with the provision of at least one accreditation procedure per decade, many inadequacies may pass unnoticed with significant catastrophic deterioration of the health system. galina et al. displayed in the who-wfme report that there are around 442 schools in europe and that only western european medical schools comply with european union standards. an italian initiative for eu medical schools started in bologna in 1999 and culminated in the ”tuning educational structures in europe” pilot in 2000 for medical school accreditation. ghanim et al. quantified about 214 medical schools in 22 eastern mediterranean countries in 2004, and the majority are now recognized by the who’s world directory of medical schools. in sudan, the educational revolution in the 90s was followed by a massive expansion of the number of medical schools and was recently shadowed by the expansion of private medical schools. the sudan medical council faces a significant burden in ensuring the competency of both medical schools and graduates. this summoned a common thought nowadays by medical educationists “a time for evolution”! dr. tahra identified three significant milestones in sudanese medical education: the founding of kitchener medical school before independence in 1924, the formation of district medical colleges (gezira and juba) in 1975, and the education revolution phase in 1991 [22]; undoubtedly, these pioneering colleges are leading the way in regional medical education. the fourth stage, which is marked by the establishment of dozens of private medical schools, is worth mentioning; according to the 2021 guide for university application, the number of medical colleges has reached 51 [23], which reflects a global trend occurring in india [24], the united kingdom and the usa [25, 26]. continuous professional development and workshops centered on relevant medical educational issues are frequently carried out at institutional and national levels in partnership with khartoum and gezira educational development centers (edc) [27]. the sudan medical council (smc) was established in 1955, and it was granted “recognition status” as per the regulation of the world federation for medical education (wfme) in 2018 [28]. doi 10.18502/sjms.v17i4.12543 page 434 sudan journal of medical sciences ayman fisal ahmed foad the sudan medical council’s key responsibilities as part of the accreditation process are to ”defend, promote, and preserve” quality and safety for graduates and the community. it focuses on nine parameters that must be met [29,30]. the national commission for academic accreditation and assessment (ncaaa) in saudi arabia provides a comparable checklist [31]. 3.1.6. private school and profitable organization flexner advised for the closure of private and profitable medical schools, which might be a justifiable necessity in the pre-world war-i era. now the number of private medical schools is on the rise, and capitalism forces even governmental schools to economize their spending and pursue a profit-based administration style. there is no conflict between maintaining the quality of medical education and profitability. unjustifiable expenditure on healthcare facilities and medical education necessitated interventional measures to be applied, as demonstrated by the ksa experience [32]. now in sudan, there are almost 51 private and public medical schools; this trend followed the void in the middle east employment posts, mainly in gulf countries, as the fraction number of graduates who succeed in granting a job in sudan is only marginal. under the control of the sudan medical council accreditation process, many of these schools attained decent standards, notwithstanding many are lagging. with the emergence of many private medical schools’ admission policies became less stringent [33]. some claim private schools are more concerned about students’ affordability than integrity. the provision of continuous funding in medical institutes is a prime function of the government in governmental institutes. private institutes need to tackle their resources and wisely spend on their requirements with their prospect focused on the return of the revenue. the international economic crises forced many institutes to shrink their staff members or put the load in students’ behalf by either increasing the intuition fees or the number of recruits. an advised solution is to create other funding resources and profitable revenues [34]. 3.1.7. racism the report implicitly suggested promoting the medical practice in america and canada to decrease the number of colored candidates! [35]. in chapter xiv (pages 180-181), flexner brightly exposed the racist behavior of the american community back then. doi 10.18502/sjms.v17i4.12543 page 435 sudan journal of medical sciences ayman fisal ahmed foad black doctors should only treat the black community was his prevailed suggestion in his report [2]. even accepted black candidates, in his opinion, should endure nonsurgicalfocused training. another foul statement implies even worst intentions: black candidates’ numbers should be kept to the minimum, trained differently, and treated differently, compared to their fellow white graduates [2, 36]. the uk premier football league logo is “no room for racism” and is promoted worldwide via their broadcast [37]. many international teaching and employing organizations declare this statement during recruitment processes. in sudan, since the independence, reserved seats in medical schools have been assigned to candidates from under-resourced remote areas to distribute opportunities to foster development in these locales fairly. racism and favoritism no doubt deterred the development of medical education and practice in sudan and africa. for many reasons, no factual data or investigation briefs regarding racial and gender bias are disclosed in sudanese scientific literature or public press. 3.1.8. female education sudan pioneered medical teaching for women in the region; dr. khalida zahir (1927– 2015) [38] and dr. zarouhi sarkissian [39] (thuraya mohamed saadafter conversion to islam 1960) (1926-1982) were the first female graduates from kitchener medical school (university of khartoum) in 1952. both were social activists who participated in community development and fought for female rights. the law in sudan gives women the right to equal pay and a 25% seat share in the parliament. the share of accepted female candidates in medical schools in sudan reached 69.5% in 2012 [40]. this implies that the majority of medical professionals in the upcoming years will be female! furthermore, a sudanese school of medicine for women was established in 1990, after the inauguration of ahfad public university in omdurman by badri in 1966, and has graduated many eminent female physicians [41]. 3.1.9. educator vs. practitioner one of the recommendations of flexner is that medical educators should exclusively devote themselves to teaching. this is refutable in modern practice, as it has been attested that a good practitioner is a good teacher. this statement is valid in other doi 10.18502/sjms.v17i4.12543 page 436 sudan journal of medical sciences ayman fisal ahmed foad disciplines; nevertheless, medicine is a scientific profession, and both sides of the coin should be considered. no one would like to be taught by someone who has never been exposed to patients or rarely does. this issue may further exacerbate the impact of an overwhelming number of non-medical scientists who teach fundamental medical sciences due to medical graduates’ lack of passion for these basic medical scientist careers. ashraf overtly expressed the adverse effect of the participation of non-medical staff in medical education in pakistan [42]. the same motion happened in sudan during the 90s, with the vast expansion of the number of medical schools. omdurman islamic university took the initiative and launched a program for graduating nonmedical basic medical scientists. many graduates found themselves straying and unwelcomed in many medical schools, which forced them to enroll as students in mbbs programs, and often concomitantly teach at the same institutes. another good experience from sudan was encouraging clinical specialties staff to have another degree in basic medical sciences. some advocated giving incentives to basic medical science specialists to foster the poor offered salaries, as has been followed at the university of khartoum, faculty of medicine. medical institutes should provide a hospitable working environment with space for professional development, continuous medical education, and research opportunities [43]. an educational facility that does not promote the carrier of its staff members often loses them for seeking better opportunities to satisfy their ambitions. staff should be encouraged to publish in a rebuttable peer-reviewed medical journal as a professional requirement and actively participate in mentoring and guiding student research [44]. 3.1.10. osteopathy, psychiatry, and complementary medicine unfortunately, in africa, social and religious beliefs encourage people to mainly utilize advice and recipes prepared by herbalists as the primary therapeutic option in 80% of the population [45]. flexner recommended dismantling nonscientific approaches of medicine at that time: psychiatry, osteopathy, chiropractic, and complementary medicine. some considered his observations to be a paradigm shift in these practices and caused an astounding adverse effect; on the contrary, others assert that his recommendations forced them to initiate evidence-based practices. complementary medical practices have become a sound, evidence-based profession in eastern and western countries. acupuncture, osteopathy, and reflexology are now recognized and organized by accreditation organizations with the practice’s required degree and license. doi 10.18502/sjms.v17i4.12543 page 437 sudan journal of medical sciences ayman fisal ahmed foad the trend now in arabic and african countries is to formulate accreditation organizations for complementary health practices and offer training and reinforcement to practitioners and researchers to develop these realms. dr. altigani almahi launched the first psychiatric treatment clinic in sudan in khartoum in 1949 [18], a long time after the establishment of the khartoum teaching hospital in 1904, which may reflect the delay of the emergence of modern psychiatry, mirroring what has happened in the usa and canada. undoubtedly, the vast majority of the population in sudan relies on traditional healers and shiek roqia. in sudan, traditional healers and herbalists are not under the supervision of the ministry of health, and often quacks invade the profession and do profound harm to the community. nongovernmental organizations in sudan endorse continuous public awareness activities to increase awareness of these practices. 3.1.11. the carnegie report stated, “fewer and better doctors” [2] this approach is currently contradicted due to the insisting need of the communities for health promotion, especially in africa and the middle east. according to the world bank, the number of physicians per 1000 in sudan is 0.2618 compared to 4.6 in germany. for the proper delivery of professional medical practice, the number of graduates should increase; adverse outcomes have been recorded with the association of low staffing. zurn et al. explained in a who report two types of human resources shortages “dynamic versus static imbalance” [46]. sudan now suffers from the massive migration of brilliant, trained medical professionals seeking better working accommodation; consequently, despite the considerable number of graduates, our population is still underserved. no compromise should be accepted regarding the quality of the education process and its graduates; with persistent exertion of inspection, we can grasp these far-fetched goals. 4. conclusion sudanese medical education faced comparable milestones to the flexner era. new challenges have emerged and addressed in sudan, including distance learning, accreditation, and competency-based curricula reforming. the pioneering impact of the flexner report crossed the borders and resonated globally. the report is a milestone in medical education. it reflected the prevailing ideas in the last century regarding racism, and gender bias, which affected the social rights doi 10.18502/sjms.v17i4.12543 page 438 sudan journal of medical sciences ayman fisal ahmed foad of women and colored citizens. in sudan, the relevance of these concerns should be addressed by providing a plausible solution. a continuous endeavor has been set in motion globally since the emergence of this inspiring report to increase the quality of health system stringent policies and health professions competency through education. a significant revision in medical education status by all the stakeholders in sudan to foster its quality and reliability is currently sought. our reflection based on this report does not necessarily recommend following in its footsteps but instead considers its stirring role in planning and intervention. acknowledgements none. ethical considerations none. competing interests authors declare no conflict of interest. availability of data and material data is available with corresponding author upon request. funding none. references [1] history of hospitals wikipedia [internet]. 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(2002). imbalances in the health workforce. briefing paper acknowledgements. doi 10.18502/sjms.v17i4.12543 page 443 introduction materials and methods discussion the impact of flexner report dual phases in medical schools (preclinical and clinical) a scientific approach to study medicine competency of the graduates learning resources accreditation of medical schools private school and profitable organization racism female education educator vs. practitioner osteopathy, psychiatry, and complementary medicine the carnegie report stated, ``fewer and better doctors'' 2 conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 17, issue no. 4, doi 10.18502/sjms.v17i4.12547 production and hosting by knowledge e research article efficacy and safety of gum arabic on renal failure patients: systematic review and meta-analysis selma abdelrahman hussein1, hammad ali fadlalmola2, suzy munir salama3*, eyas gaffar osman4, abdalbasit adam mariod5 1industrial and system engineering, engineering college, princess nourah bint abdulrahman 2nursing college, taibah university, saudi arabia 3indigenous knowledge and heritage center, ghibaish college of science and technology, ghibaish, sudan 4college of science and humanities-shaqra university, saudi arabia 5college of sciences and arts-alkamil, university of jeddah, alkamil, saudi arabia orcid: suzy munir salama: https://orcid.org/0000-0003-0430-1436 abstract background: chronic renal failure (crf) is a long-term disease caused by progressive kidney dysfunction due to many reasons leading to a significant rise in serum levels of creatinine and urea reaching the advanced stage where the patient goes for frequent hemodialysis. this study aims to discuss the evaluation of the efficacy of gum arabic (ga) supplementation on the serum level of creatinine, urea, sodium, and potassium in crf patients. methods: four databases pubmed, web of science, scopus, and the cochrane library were searched for clinical trials assessment of gum arabic intervention in crf patients. animal trials and experimental protocols were excluded. screening of data and data extraction were done by two reviewers independently of each other. meta-analysis was conducted on the selected studies using revman and the resulting description was summarized through the forest plot tool on the efficacy of ga on 4 variables, creatinine, urea, sodium, and potassium in crf patients. results: from 574 studies searched, only 4 studies were included in this systemic review and meta-analysis. although one of the studies had proved the objectives of the review but it was removed from the meta-analysis due to the heterogeneity caused by its inclusion. conclusion: the few studies included in the current review revealed significant efficacy of ga treatment on the serum level of creatinine, urea, and sodium, but not potassium. keywords: gum arabic, kidney, clinical how to cite this article: selma abdelrahman hussein, hammad ali fadlalmola, suzy munir salama*, eyas gaffar osman, abdalbasit adam mariod (2022) “efficacy and safety of gum arabic on renal failure patients: systematic review and meta-analysis,” sudan journal of medical sciences, vol. 17, issue no. 4, pages 459–475. doi 10.18502/sjms.v17i4.12547 page 459 corresponding author: suzy munir salama; email: s.salama999@hotmail.com received 5 june 2021 accepted 9 september 2022 published 31 december 2022 production and hosting by knowledge e selma abdelrahman hussein et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v17i4.12547&domain=pdf&date_stamp=2022-12-12 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences selma abdelrahman hussein et al. 1. introduction gum arabic (ga) is a natural dietary fiber; it is considered as the best of all soluble fibers and a direct additive to liquid foods [1]]. in addition to its high-soluble dietary fiber content (85-90%, w/w), ga is safe, odorless, tasteless, lowest in viscosity, and stable in acid solutions [2]]. ga has a high-molecular weight and is composed majorly of macromolecules (carbohydrates and protein), minerals, and amino acids; the major carbohydrates in ga are rhamnose, arabinose, galactose, and glucuronic acid [3]. it is rich in amino acids such as hydroxyproline, serine, threonine, proline, leucine, and histidine [4], ga is a valuable source of four antioxidant minerals like copper, iron, manganese, and zinc [5]. studies demonstrated ga to be a successful prebiotic [6]. ga belongs to the class of nondigestible fibers, as it ferments with bacteria to convert into short-chain fatty acids in the digestive system [7]. the natural characteristics of ga associated with qualitative and quantitative indicators include moisture, ash content, volatile compounds, and inner energy, which exactly represents the world standards [8]. recent studies have shown the therapeutic action of ga [9]. ga is used to treat many diseases as it improves the performance of the digestive system and improves the appetite [10]. as for patients with kidney failure, it helps them obtain sufficient energy from their food [11]. chronic kidney failure is often associated with a lack of dietary fiber consumption, excessive utilization of antibiotics, edema of the intestinal wall, and iron intake [12]. patients with renal disorders suffer from a state of inflammation originating from the gastrointestinal tract; and uremia is associated with a steady increase in the bacteria count in the large intestine and the jejunum, which results in the presence of bacteria in the stool [13]. many studies have been conducted on the importance of ga for treating kidney diseases and kidney failure, adding ga to drinking water contributes significantly to alleviating kidney problems regardless of its effect on the metabolism of intestinal bacterial ammonia [14-16]. the daily addition of 10-40 g of ga to the diet of ongoing kidney failure patients, substantially decreased the amount of c-reactive protein (crp) level which could positively affect death of these patients [17]. in addition, 90 g ga/day was able to decrease the hyperglycemia in chronic renal disease [18]. ali et al. hypothesized that addition of ga to patients with hemodialysis would decrease oxidative stress and thus decrease the state of hemodialysis-related chronic inflammatory activation [19]. almosawi announced that implementation with ga might be an option in contrast to renal substitution treatment to enhance the personal satisfaction and lessen the requirement doi 10.18502/sjms.v17i4.12547 page 460 sudan journal of medical sciences selma abdelrahman hussein et al. for dialysis in kids in some countries [20]. the customary admission of ga notwithstanding a low-protein/high-calorie diet candelay the requirement for hemodialysis or peritoneal dialysis in kids’. further, the impact of ga oral therapy on the metabolic profile of renal failure (rf) patients was evaluated, they found that oral intake of ga could possibly reduce antagonistic impacts of crf [21]. rf which is the outcome of broadly contrasting illnesses of the kidney is an overwhelming clinical, social, and economic issue for patients and their families. most patients with rf will in the long run arrive at the state of esrd, become suggestive, and require replacement of their renal capacity [22]. the initial search for literature reviews on the effectiveness of ga on the metabolic profile of chronic kidney patients did not show any previous reviews. this systematic review was carried out to show the utilization of ga in healing and mitigating the side effects of chronic kidney disease and preserving the lives of kidney patients. 2. materials and methods 2.1. study selection based on the methodology of search and data extraction conducted previously [23], we searched pubmed, web of science, scopus and the cochrane library for data from 1980 to 2020. all the studies before 1980 were omitted from the search, using the keywords ”gum arabic” or ”sudani gum” or ”acacia gum” or ”gum acacia” or ”acacia” or ”senegal gum” or ”indian gum” and ”chronic kidney disease” or ”ckd” or ”chronic renal failure” or ”crf” or ”renal insufficiency” or ”hemodialysis” or ”peritoneal dialysis” or ”dialysis”. we made some restrictions on rcts, human, and english language only studies. to ascertain the efficacy and safety of the ga for the treatment of patients with renal failure, we included controlled randomized trials examining the impact of ga on patients with renal failure. we excluded trials that used ga in the therapy of patients with renal failure for other purposes such as uric acid, fiber diet duration, controlled feeding, and non-english language publications. 2.2. data extraction each article was independently reviewed and had relevant data extracted by two independent reviewers (ss and eg). extracted data included information on study doi 10.18502/sjms.v17i4.12547 page 461 sudan journal of medical sciences selma abdelrahman hussein et al. setting, design, randomization, blinding, sample size, and participant characteristics; dose of the ga and comparator, follow-up, and funding. mean and standard deviation data on serum urea and serum creatinine for end of treatment were extracted as priori end points. the preferred reporting items of systematic review and meta-analysis (prisma) flow diagram of the studies screened and selected for the present systematic review is mapped on figure 1. 574 reports identified pubmed 174 (1980 to sept 1, 2020) scopus 105 (1980 to sept 1, 2020) web of science 277 (1980 to sept 1, 2020) cochrane library 18 (1980 to sept 1, 2020) s c r e e n in g in c lu d e d e li g ib il it y id e n ti fi c a ti o n additional records identified through other sources (n = 16) records after duplicates removed (n = 476) records screened (n = 476) records excluded (n = 453) full-text articles assessed for eligibility (n = 23) full-text articles excluded, with reasons (n = 19) studies included in qualitative synthesis (n = 4) studies included in quantitative synthesis (meta-analysis) (n = 4) figure 1: the prisma flow diagram of the studies’ screened and selected. doi 10.18502/sjms.v17i4.12547 page 462 sudan journal of medical sciences selma abdelrahman hussein et al. 2.3. statistical analysis data were analyzed using review manager (revman) version 5.4.1. data were pooled using the generic inverse variance method with random-effects models and data were expressed as mean differences (mds) with 95% confidence intervals (cis). inter-study heterogeneity was assessed by the cochran q statistic (χ2), with the significance at p value = 0.10 and quantified by the i2 statistic, where a value of ⩾ 50% indicates substantial heterogeneity. potential sources of methodological heterogeneity were investigated by sensitivity analysis in which each individual trial was removed systematically and the pooled effect estimates were recalculated. we assessed and interpreted heterogeneity according to the recommendations in the cochrane handbook of systematic reviews and meta-analysis [24]. 2.4. creatinine for creatinine analysis, four studies were used in figure 3-a, b, c, and d. the four studies showed high-heterogeneity test, as evidenced by the p value > 0.1 of i2 = 99%, and the total effect of the pooled effect estimated a probability value of 0.08. this effect was significant at a confidence interval of 90% but not effective at the level of 95%. to reduce the effect of the heterogeneity, we conducted a sensitivity analysis and used the leave-one-out method. the study of farman et al., 2020, deviated the most from the rest of the studies based on the forest funnel plot, so it was removed and the pooled effect estimates were recalculated; the new results are shown in figures 3-c and d. the decrease in the level of heterogeneity (i2) was recorded as 21% in the three studies, ali et al., 2008, bliss et al., 1996, and elamin et al., 2017, and the hypothesis of homogeneity of the studies with a p value = 0.28 was accepted. the analysis of the pooled effect of ga on the decrease in creatinine despite the presence of the diamond shape left of the null line showed obvious, non-significant results (p value = 0.58). the funnel plot estimated that the three studies 1996, 2008, and 2017 were all within the confidence level, while the study of elamin et al., 2017 recorded 41% higher weighted value compared to the other two studies. 2.5. urea the forest plot of the studies included in the analysis of the efficacy of ga intervention on the serum level of urea is displayed in figures 4-e, f, g, h, i, and j. because the p doi 10.18502/sjms.v17i4.12547 page 463 sudan journal of medical sciences selma abdelrahman hussein et al. value was 0.05 and the level of heterogeneity was high (i2 = 97%), the four studies ali et al., 2008; bliss et al., 1996; elamin et al., 2017; and farman et al., 2020 revealed a significant effect on the decrease of urea by ga intervention. by using the leave-one-out method and omitting the study of farman et al., 2020, the heterogeneity decreased to i2 = 72%, but the heterogeneity remained present (p value = 0.03). results illustrated in figure 4-g showed that the diamond shape is located on the left side of the null line, but without significant effect on the decrease of urea due to the doses of ga used during intervention periods. additionally, when the study of ali et al., 2008 was removed, the homogeneity occurred leading to the disappearance of variance, where the p value recorded was 0.14 and the overall effect of ga on the high level of urea was not significant (p value = 0.23). 2.6. sodium analysis of sodium was done based on three studies, elkarib et al., 2016, elamin et al., 2017, and farman et al., 2020 using forest plot (figures 5-k, l, m, and n). analysis suggested that no overall significant decrease was recorded in serum level of sodium during ga intervention. also, there was a high heterogeneity in the three studies analyzed. therefore, the study of farman et al., 2020 was removed resulting in reduction in the heterogeneity produced (p value = 0.16) despite the appearance of significant decrease in the blood sodium level during ga supplementation (p value = 0.001). the studies analyzed revealed clinically significant reduction rate of 2.21 m/mol in 95% confidence intervals of mean difference uci = 3.54 and lci = 0.87 m/mol as illustrated in figure 5-m. 2.7. potassium analysis for potassium was based on three studies, as shown in figures 6-o, p, q, and r. all the studies included gave high heterogeneity and not significant increase in the serum level of potassium in the treated patients (figure 5-q), even after the removal of the study of farman et al., 2020 that recorded decrease in potassium during intervention period. it is true that the studies of elkarib et al., 2016 and elamin et al., 2017 showed increase in the potassium level as the diamond shape moved to the right side of the null line, but this increase was still not significant (p value = 0.23). doi 10.18502/sjms.v17i4.12547 page 464 sudan journal of medical sciences selma abdelrahman hussein et al. a creatinine b study or subgroup ali et al., 2008 bliss et al., 1996 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 13.55; chi² = 423.32, df = 3 (p < 0.00001); i² = 99% test for overall effect: z = 1.75 (p = 0.08) mean 4.44 4.5 2.57 0.93 sd 0.72 0.8 0.94 0.53 total 12 16 30 50 108 mean 4.93 4.4 2.54 13.7 sd 0.73 0.8 0.87 4.2 total 12 16 30 50 108 weight 25.1% 25.1% 25.2% 24.6% 100.0% iv, random, 95% ci -0.49 [-1.07, 0.09] 0.10 [-0.45, 0.65] 0.03 [-0.43, 0.49] -12.77 [-13.94, -11.60] -3.23 [-6.86, 0.39] intervention group control group mean difference mean difference iv, random, 95% ci -10 -5 0 5 10 intervention group control group -10 -5 0 5 10 0 0.2 0.4 0.6 0.8 1 md se(md) ali et al., 2008bliss et al., 1996 elamin et al., 2017 farman et al., 2020 c d study or subgroup ali et al., 2008 bliss et al., 1996 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 0.02; chi² = 2.54, df = 2 (p = 0.28); i² = 21% test for overall effect: z = 0.55 (p = 0.58) mean 4.44 4.5 2.57 0.93 sd 0.72 0.8 0.94 0.53 total 12 16 30 50 58 mean 4.93 4.4 2.54 13.7 sd 0.73 0.8 0.87 4.2 total 12 16 30 50 58 weight 28.4% 30.6% 41.0% 0.0% 100.0% iv, random, 95% ci -0.49 [-1.07, 0.09] 0.10 [-0.45, 0.65] 0.03 [-0.43, 0.49] -12.77 [-13.94, -11.60] -0.10 [-0.44, 0.25] intervention group control group mean difference mean difference iv, random, 95% ci -2 -1 0 1 2 intervention group control group -2 -1 0 1 2 0 0.1 0.2 0.3 0.4 0.5 md se(md) ali et al., 2008 bliss et al., 1996 elamin et al., 2017 figure 2: forest plot in the meta-analysis of the studies included in the efficacy of ga intervention on serum level of creatinine. 3. discussion chronic renal disease (crf) is a long-term disease that appears as gradual decrease in the renal function progressing to end-stage renal failure. the leading reasons of the disease can be referred to many factors including glomerular and tubular diseases, renal stones, and nephrotic disorders [4]. one of the important demands that has been doi 10.18502/sjms.v17i4.12547 page 465 sudan journal of medical sciences selma abdelrahman hussein et al. e urea f study or subgroup ali et al., 2008 bliss et al., 1996 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 642.02; chi² = 88.10, df = 3 (p < 0.00001); i² = 97% test for overall effect: z = 1.96 (p = 0.05) mean 125.67 94.16 81.52 18.5 sd 62.12 10.7 31.77 2.7 total 12 16 30 50 108 mean 182.67 107 80.92 65.4 sd 36.03 12.84 29.97 10.4 total 12 16 30 50 108 weight 17.2% 28.0% 26.2% 28.6% 100.0% iv, random, 95% ci -57.00 [-97.63, -16.37] -12.84 [-21.03, -4.65] 0.60 [-15.03, 16.23] -46.90 [-49.88, -43.92] -26.68 [-53.31, -0.06] intervention group control group mean difference mean difference iv, random, 95% ci -50 -25 0 25 50 intervention group control group -50 -25 0 25 50 0 10 20 30 40 50 md se(md) ali et al., 2008 bliss et al., 1996 elamin et al., 2017 farman et al., 2020 g h i study or subgroup ali et al., 2008 bliss et al., 1996 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 183.71; chi² = 7.22, df = 2 (p = 0.03); i² = 72% test for overall effect: z = 1.50 (p = 0.13) mean 125.67 94.16 81.52 18.5 sd 62.12 10.7 31.77 2.7 total 12 16 30 50 58 mean 182.67 107 80.92 65.4 sd 36.03 12.84 29.97 10.4 total 12 16 30 50 58 weight 15.3% 46.7% 38.0% 0.0% 100.0% iv, random, 95% ci -57.00 [-97.63, -16.37] -12.84 [-21.03, -4.65] 0.60 [-15.03, 16.23] -46.90 [-49.88, -43.92] -14.50 [-33.49, 4.50] intervention group control group mean difference mean difference iv, random, 95% ci -50 -25 0 25 50 intervention group control group study or subgroup ali et al., 2008 bliss et al., 1996 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 49.79; chi² = 2.23, df = 1 (p = 0.14); i² = 55% test for overall effect: z = 1.21 (p = 0.23) mean 125.67 94.16 81.52 18.5 sd 62.12 10.7 31.77 2.7 total 12 16 30 50 46 mean 182.67 107 80.92 65.4 sd 36.03 12.84 29.97 10.4 total 12 16 30 50 46 weight 0.0% 62.8% 37.2% 0.0% 100.0% iv, random, 95% ci -57.00 [-97.63, -16.37] -12.84 [-21.03, -4.65] 0.60 [-15.03, 16.23] -46.90 [-49.88, -43.92] -7.84 [-20.57, 4.90] intervention group control group mean difference mean difference iv, random, 95% ci -50 -25 0 25 50 intervention group control group j -50 -25 0 25 50 0 2 4 6 8 10 md se(md) bliss et al., 1996 elamin et al., 2017 figure 3: forest plot in the meta-analysis of the studies included in the efficacy of ga intervention on serum level of urea in crf disease. focused by healthcare organizations in both developed and developing countries is chronic renal failure (crf) disease due to the high incidence of the disease, especially in doi 10.18502/sjms.v17i4.12547 page 466 sudan journal of medical sciences selma abdelrahman hussein et al. k sodium l m study or subgroup alkarib et al., 2016 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 56.85; chi² = 286.12, df = 2 (p < 0.00001); i² = 99% test for overall effect: z = 0.42 (p = 0.67) mean 135 136.3 142 sd 2.04 3.1 2.1 total 24 30 50 104 mean 137.86 137.8 132.1 sd 2.54 2.4 3.1 total 24 30 50 104 weight 33.3% 33.3% 33.4% 100.0% iv, random, 95% ci -2.86 [-4.16, -1.56] -1.50 [-2.90, -0.10] 9.90 [8.86, 10.94] 1.86 [-6.71, 10.42] intervention group control group mean difference mean difference iv, random, 95% ci -10 -5 0 5 10 intervention group control group -10 -5 0 5 10 0 0.2 0.4 0.6 0.8 1 md se(md) alkarib et al., 2016 elamin et al., 2017 farman et al., 2020 study or subgroup alkarib et al., 2016 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 0.45; chi² = 1.94, df = 1 (p = 0.16); i² = 48% test for overall effect: z = 3.25 (p = 0.001) mean 135 136.3 142 sd 2.04 3.1 2.1 total 24 30 50 54 mean 137.86 137.8 132.1 sd 2.54 2.4 3.1 total 24 30 50 54 weight 51.9% 48.1% 0.0% 100.0% iv, random, 95% ci -2.86 [-4.16, -1.56] -1.50 [-2.90, -0.10] 9.90 [8.86, 10.94] -2.21 [-3.54, -0.87] intervention group control group mean difference mean difference iv, random, 95% ci -10 -5 0 5 10 intervention group control group n -10 -5 0 5 10 0 0.2 0.4 0.6 0.8 1 md se(md) alkarib et al., 2016 elamin et al., 2017 figure 4: forest plot in the meta-analysis of the studies included in the efficacy of ga intervention on serum level of sodium in crf disease. some developing countries. earlier studies on the incidence of crf prevalence in sudan had recorded a yearly average increase in crf patients of about 100 cases per million population, most of them were below the age of 40 [25]. studies attributed the reasons of incident crf cases in sudan to stone diseases, hypertension, and diabetes mellitus [26]. lameire et al., 2005 reported that new patients treated with renal replacement therapy in 25 countries of the european union due to end-stage renal failure was estimated to be 36,000 per year according to the report issued by the european renal association/european dialysis and transplant association registry 2001 [27]. 3.1. effect of ga on serum creatinine and urea recent studies exposed the positive effects of low-protein diet (lpd) and prebiotic activity of nutrients in managing the renal function of crf patients [28]. in chronic renal doi 10.18502/sjms.v17i4.12547 page 467 sudan journal of medical sciences selma abdelrahman hussein et al. o potassium p q study or subgroup alkarib et al., 2016 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 8.33; chi² = 865.94, df = 2 (p < 0.00001); i² = 100% test for overall effect: z = 0.56 (p = 0.58) mean 5.25 4.6 4.11 sd 0.4 0.6 0.32 total 24 30 50 104 mean 4.157 4.5 8.1 sd 0.74 0.5 0.7 total 24 30 50 104 weight 33.3% 33.3% 33.4% 100.0% iv, random, 95% ci 1.09 [0.76, 1.43] 0.10 [-0.18, 0.38] -3.99 [-4.20, -3.78] -0.93 [-4.20, 2.34] intervention group control group mean difference mean difference iv, random, 95% ci -4 -2 0 2 4 control group intervention group -4 -2 0 2 4 0 0.05 0.1 0.15 0.2 md se(md) alkarib et al., 2016 elamin et al., 2017 farman et al., 2020 study or subgroup alkarib et al., 2016 elamin et al., 2017 farman et al., 2020 total (95% ci) heterogeneity: tau² = 0.47; chi² = 19.79, df = 1 (p < 0.00001); i² = 95% test for overall effect: z = 1.19 (p = 0.23) mean 5.25 4.6 4.11 sd 0.4 0.6 0.32 total 24 30 50 54 mean 4.157 4.5 8.1 sd 0.74 0.5 0.7 total 24 30 50 54 weight 49.5% 50.5% 0.0% 100.0% iv, random, 95% ci 1.09 [0.76, 1.43] 0.10 [-0.18, 0.38] -3.99 [-4.20, -3.78] 0.59 [-0.38, 1.56] intervention group control group mean difference mean difference iv, random, 95% ci -4 -2 0 2 4 control group intervention group r -4 -2 0 2 4 0 0.05 0.1 0.15 0.2 md se(md) alkarib et al., 2016 elamin et al., 2017 figure 5: forest plot in the meta-analysis of the studies included in the efficacy of ga intervention on serum level of potassium in crf disease. disease patients, the advantageous intestinal bacteria, that produces the important short-chain fatty acids, are damaged leading to increase in the toxic bacteria that generate uremic toxic substances [29]. additionally, studies showed that the prebiotic ingredients in food supplements play crucial role in removing uremic toxins from blood via growth and stimulation of beneficial intestinal bacteria [30]. world health organization and food and drug administration have approved the prebiotic activity of ga (obaid, 2020). in the current systematic review and meta-analysis, the study of bliss et al., 1996 suggested insignificant effect in the serum level of creatinine together with significant reduction in the serum level of urea in the crf patients examined during the one-month intervention period of 50 g ga. the study attributed the decrease of blood urea in the intervention period to the low-protein diet and high-fiber content of ga that enhanced nitrogen excretion in the stool. additionally, the fermentation of colon bacteria to the dietary fibers of ga and their increased utilization of the resulting nitrogen with growth had decreased urea during intervention compared to baseline. doi 10.18502/sjms.v17i4.12547 page 468 sudan journal of medical sciences selma abdelrahman hussein et al. on the other hand, the non-significant effect of ga intervention to creatinine level was due to the short period of intervention [31]. ali and his colleagues, 2008 reported that supplementation of crf patients with 50 g ga for 3 months intervention had significantly decreased the serum levels of creatinine and urea. the study explained the decrease of intervention creatinine due to the high activity of colonic bacteria that utilized nitrogen from the nitrogenous human wastes. in addition, the decrease of blood urea was referred to the fiber content of ga that enhanced nitrogen excretion in the stool and decreased nitrogen content of blood urea [21]. elamin et al., 2017 reported the non-significant effect of the dose tested (10 g) for ga on the serum creatinine and urea of all crf patients in the trial study due to the short period of intervention (1 month), lack of low-protein diet (lpd) taken, and the advanced stage of renal insufficiency/dialysis dependency of patients subjected to the study [17]. the study of farman et al., 2020 showed significant decline in the serum levels of creatinine and urea due to the long period of intervention dose (30 g of ga/6 months) as well as the prebiotic activity of ga [5]. although the study of farman et al., 2020 suggested clear evidence for the efficacy of long-term intervention (6 months) of ga on the high-blood level of creatinine and urea in crf patients, but the study was removed from the meta-analysis of creatinine because of the heterogeneity caused with the inclusion of the study (i2 = 99%, p value = 0.08). additionally, studies of ali et al., 2008 and farman et al., 2020 were removed to reverse the heterogeneity caused with their inclusion on the meta-analysis of urea (i2 = 97%, p value = 0.05) reaching homogeneity (i2 = 55%, p value = 0.14). the factors affecting the efficacy of ga supplementation on serum creatinine and urea in crf patients are illustrated in figure 6. factors affecting the efficacy of decreasing serum creatinine and urea in crf patients period of treatment the stage of crf patients the prebiotic activity of gum arabic longer period is more effective efficacy in earlier stage of crf than advanced stage enhancing the bacteria with lpd figure 6: factors affecting the role of ga supplementation on patients with chronic renal failure (crf). doi 10.18502/sjms.v17i4.12547 page 469 sudan journal of medical sciences selma abdelrahman hussein et al. 3.2. effect of ga on serum sodium and potassium researches on the effect of ga supplementation has reported that the addition of ga to the diet decreased the serum level of sodium and potassium in experimentally-induced chronic renal failure [32]. another study published that treatment experimental animals with ga did not show significant effect on the plasma level of sodium and potassium in gentamycin-induced renal damage [33]. alkarib et al., 2016 showed that gradual increase of intervention dose of ga (10 g – 25 g) for 4 months had significantly lowered the serum level of sodium and elevated the level of potassium in the crf patients subjected to the trial study [34]. elamin et al., 2017 reported that supplementation of crf patients with 10 g of ga for one month showed a significant decrease in the blood level of sodium without affecting the blood level of potassium [17]. farman et al., 2020 exposed that the intake of 30 g of ga on daily basis for 6 months caused significant increase in sodium and decrease in potassium level of blood in crf patients. the study referred these reversed effects of ga on the blood level of sodium and potassium due to the high-calcium content of ga that stimulated the calcium receptor leading to inhibition of the sodium and potassium co-transport in the thick ascending limb [5, 35]. accordingly, the meta-analysis study excluded the study of farman et al., to reduce the heterogeneity caused from i2 = 99% to 48%, p value = 0.16. regarding the high heterogeneity appeared (100%) in the meta-analysis of potassium with the inclusion of the three studies, the exclusion of the study of farman et al., 2020, did not reduce the heterogeneity that remained very high (99%) indicating overall non-significant efficacy of gum arabic intervention on the serum level of potassium in crf patients. 4. limitations the present systematic review and meta-analysis showed significant heterogeneity in the analysis performed due to the few clinical studies conducted on the efficacy of ga in chronic renal failure. more clinical case studies are required to be conducted on this topic to resolve the heterogeneity of the study and confirm the results analyzed. also, complicated scientific terms were avoided in english language writing of the current study to be easy for all readers to understand the analysis performed. doi 10.18502/sjms.v17i4.12547 page 470 sudan journal of medical sciences selma abdelrahman hussein et al. 5. conclusion the efficacy of ga supplementation on the serum creatinine, urea, sodium, and potassium of chronic renal failure (crf) patients depends on the period of treatment where a longer period of treatment is applied, the more significant reduction was obtained on serum urea and creatinine but not on sodium and potassium. in addition, the crf stage of the patient plays a role in the efficacy of intervention where the efficacy of ga treatment in early stage is more significant than the advanced stage. moreover, the intake of lpd shows obvious enhancement to the prebiotic activity of colon bacteria and subsequently significant reduction in the blood level of creatinine and urea. however, based on the studies collected and used in the present systematic review and metaanalysis, it can be confirmed that ga is effective in the early stages of renal failure more than late stages. more clinical trials are required to confirm the factors mentioned. acknowledgements none. ethical considerations none. competing interests authors declare no conflict of interest. availability of data and material data is available with corresponding author upon request. funding none. doi 10.18502/sjms.v17i4.12547 page 471 sudan journal of medical sciences selma abdelrahman hussein et al. references [1] satti, n. m. e., afa, m., bawadekji, a., & 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[34] alkarib, s. y., saeed, a. m., khalid, s. a., groun, e. a., & ghalib, m. b. (2016). gum arabic role in high blood pressure among patients with stage iii chronic kidney disease. journal of pharmacological and clinical research, 1(4), 1–6. https://doi.org/10.19080/jpcr.2016.01.555569 [35] jung, j., foroud, t. m., eckert, g. j., flury-wetherill, l., edenberg, h. j., xuei, x., zaidi, s. a., & pratt, j. h. (2009). association of the calcium-sensing receptor gene with blood pressure and urinary calcium in african-americans. the journal of clinical endocrinology and metabolism, 94(3), 1042–1048. https://doi.org/10.1210/jc.20081861 doi 10.18502/sjms.v17i4.12547 page 475 introduction materials and methods study selection data extraction statistical analysis creatinine urea sodium potassium discussion effect of ga on serum creatinine and urea effect of ga on serum sodium and potassium limitations conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13604 production and hosting by knowledge e research article exploring work-related anxiety among newly graduated nurses in the riyadh region kholoud r. alrashedi1 and amira boshra2 1aliman general hospital, riyadh, saudi arabia 2department of nursing, college of applied medical sciences, majmaah university, al-majmaah, saudi arabia orcid: kholoud r. alrashedi: https://orcid.org/0000-0003-0833-0146 kholoud r. alrashedi: https://orcid.org/0000-0003-0833-0146 amira boshra: https://orcid.org/0000-0003-4498-370x abstract background: work-related anxiety among nurses has been linked to various issues, including a heavy workload, work-related conflict, a lack of resources, and stress. this research aims to explore work-related anxiety among recently graduated nurses in saudi arabia’s riyadh region. methods: a descriptive, cross-sectional, and relational research design examined work-related anxiety among newly graduated nurses. a sample of 400 nurses was recruited from five saudi hospitals in the riyadh region. this study used the job anxiety scale (jas) as a study tool. the tool is a self-rating scale of 70 items for assessing job anxiety but only 25 items were applied to this research. a self-administered questionnaire was used to gather demographic information. results: this study revealed that there was, overall, low work-related anxiety among the nurse participants. on the one hand, age, gender, educational qualification, job experience, workplace, and work scheduling (hours per week) were found to impact work-related anxiety substantially. on the other hand, work position, nationality, unit of care, and marital status were found to play no significant role in work-related anxiety. conclusion: the study’s findings indicate the importance of paying more attention to workplace anxiety. as anxiety may affect nurses’ ability to attend to the needs of patients in their care units, addressing it can reduce burnout and the desire to quit. changes in work processes, care models, and leadership may be effective in creating a supportive environment that decreases stress and anxiety, promote learning, and provides patients with optimal and safe nursing care. health policymakers and nurse managers in saudi arabia should develop particular intervention programs to reduce work-related anxiety among newly graduated nurses. managers must seek techniques that help to adapt the present environment to the needs of nurses, as well as approaches that offer newly graduating nurses essential assistance, such as clinical supervision. keywords: work-related anxiety, workplace anxiety, newly graduated nurses, quality healthcare services, riyadh region how to cite this article: kholoud r. alrashedi and amira boshra (2023) “exploring work-related anxiety among newly graduated nurses in the riyadh region,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 203–220. doi 10.18502/sjms.v18i2.13604 page 203 corresponding author: amira boshra; email: a.yahia@mu.edu.sa received 18 february 2023 accepted 4 march 2023 published 30 june 2023 production and hosting by knowledge e alrashedi and boshra. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences alrashedi and boshra 1. introduction work-related anxiety, inexperience, emotional and physical stress, nursing shortages, bullying, and lack of support have been implicated in these difficulties and the subsequent abandonment of jobs [1, 2]. the kingdom of saudi arabia’s healthcare system is charged with the sole responsibility of meeting the basic healthcare needs of the saudi people with high-quality services [1]. the profession is highly stressful and has a high prevalence of work-related emotional and physical burnout and anxiety [3]. this stress has necessitated rotational day and night shifts of 8 to 12 hours [4, 5]. however, the shift duration is sometimes unpredictable and is determined by inpatient needs and other staff issues. this leads to unplanned overtime, resulting in mental and physical distress and fatigue [6,7]. several other studies have shown that newly graduated nurses face difficulties in adapting to their new jobs, which require them to practice in stressful, laborious, and complex work systems [8]. work-related anxiety has been known to have several adverse effects on nurses. these include absenteeism, medical errors, impaired job performance, reduced mental acuity, musculoskeletal disorders, physical pain, social problems, mood changes, and mental issues [6, 9]. in the study conducted in saudi arabia by waled, a descriptive cross-sectional result showed that the anxiety levels of the nurses in this study ranged from 0.60 to 1.52. the results of this study showed an inverse association between anxiety levels and critical care nurses’ ages that were statistically significant. the critical care nurses in the hospitals in albaha were only mildly anxious. anxious mood, tension, insomnia, physical sensations, and terror are among the most frequently reported signs and symptoms of anxiety [10]. a descriptive cross-sectional study was conducted in saudi arabia the result revealed that the research cohort’s nursing students experienced moderate stress from a variety of stressors. they frequently avoided the situation and in response, adopted a problemsolving strategy. to lessen stress among nursing students, institutions need to follow a set routine [11]. the present study aims to explore work-related anxiety among newly graduated nurses in the riyadh region of saudi arabia and to measure its impact on delivering quality healthcare services. exploring work-related anxiety amongst newly graduated doi 10.18502/sjms.v18i2.13604 page 204 sudan journal of medical sciences alrashedi and boshra nurses will furnish hospital administrators, nurse managers, and other relevant authorities with the information needed to address this situation, improve the delivery of quality healthcare services, and help achieve vision 2030. this study aims to explore work-related anxiety among newly graduated nurses in the riyadh region of saudi arabia. 2. methods 2.1. research design the present study employed a descriptive, cross-sectional, relational research design to assess work-related anxiety in newly graduated nurses in the riyadh region of saudi arabia. 2.2. study setting this study was carried out at five hospitals in riyadh, saudi arabia: king saud medical city, al-iman hospital, diriyah hospital, king khalid hospital, and shaqra hospital. in addition to serving as the nation’s capital, riyadh has a population of over 7.6 million, making it the city with the most residents in both saudi arabia and the arabian peninsula. 2.3. study sample 2.3.1. sampling design the present study employed the convenience sampling method to recruit newly graduated nurses who had given their consent and met the study’s inclusion criteria. convenience sampling is a technique adopted in many disciplines to collect research data from an available pool of participants. it has several advantages, including quick data collection, cost-effectiveness, ease of use, and readily available samples [13]. 2.3.2. sample size the total population of newly graduates was 1076 in the selected hospital. the sample size (n) was determined using the following formula: doi 10.18502/sjms.v18i2.13604 page 205 sudan journal of medical sciences alrashedi and boshra n = z2x p x (1-p)/e2 where z is equal to 1.96 for a confidence level (α) of 95%, p is the proportion (expressed as a decimal) and e represents the margin of error. however, to an estimated sample size of 385, we added 5% for the attrition rate so the total should be 385 + 19 = 404, but during data collection, we found that only 400 newly graduated nurses were recruited for this study for harmonization. 2.3.3. inclusion and exclusion criteria the inclusion criteria for this study are newly graduated nurses in their first year of employment who have freely given their consent to participate in the study. nurses who do not meet these selection criteria, other healthcare professionals, and nurses with more than three years of experience were excluded. 2.4. research instruments the present study employed the job anxiety scale (jas) designed by linden et al. [13]. the tool is a 70-item self-rating scale for assessing job anxiety including thoughts, feelings, and behavior, but only 25 items related to thoughts were applied to this study. it was divided into 14 subscales that were created with factor analysis. each item is assessed on a five-point likert scale, with 0 indicating no agreement and 4 indicating complete agreement. the overall intensity of work anxiety is computed as the mean score of the 70 questions. the tool’s retest reliability has been tested and confirmed to be r(tt) = 0.82 after 7–10 days interval of questionnaires on clinical samples in previous studies (n = 611; [13, 14]. a structured interview on workplace-related anxiety (work anxiety interview, wai) was also used to provide convergent validity criteria for the scale validity [13]. 2.5. validity and reliability of the instrument the degree of consistency with which an instrument measures an attribute determines how reliable it is as a target attribute. for this study, a principal component analysis was carried out, and the summary result showed no component variable less than 0.4 (<0.4). bartlett’s test of sphericity analysis for each sub-domain of the questionnaire was significant (>0.05). moreover, cronbach’s alpha value was excellent, beating satisfactory (0.94). doi 10.18502/sjms.v18i2.13604 page 206 sudan journal of medical sciences alrashedi and boshra 2.6. data collection data were gathered using a self-administered questionnaire tailored to collect the demographic characteristics of the study subjects as well as a scale to assess their work-related anxiety. questionnaires were used to collect data in this study because they provide a quick, efficient, and relatively cheap way of procuring large amounts of data from a large sample of participants. ethical approval, institutional permissions, and the consent of study subjects were obtained, and data confidentiality was assured. 2.7. data analysis the statistical package for the social sciences (spss) version 22.0 was used to analyze the study’s data. the qualitative data on the essential variables were provided in the form of frequencies and percentages, and descriptive statistics were used to describe the data. meanwhile, the mean and standard deviation were used to characterize the quantitative data. the results were determined using a confidence range of 95%, and a p-value of 0.05 was chosen as the level of statistical significance. finally, multiple linear (stepwise) regression was used to test more of the two items to assess the influence (if any) of gender, age, marital status, educational qualification, work experience, and other demographic variables on work-related anxiety, and whether recently graduated nurses in the riyadh region of saudi arabia experience work-related anxiety and whether this worry affects their job performance. 3. results the findings of this study are presented in three main parts. 1) the demographic characteristics of the respondents used in this study; 2) statements related to the perceived extent of work-related anxiety among the participants; and 3) the relationship between work-related anxiety and the selected demographic variables. anxiety is one of the major factors responsible for newly graduated nurse turnover in saudi arabia’s healthcare system. therefore, there is a significant need to address workrelated anxiety for the adequate sustenance of the healthcare sector and to ensure the availability of nurses. exploring work-related anxiety amongst newly graduated nurses will furnish hospital administrators, nurse managers, and other relevant authorities with the information needed to address this situation, improve the delivery of quality healthcare services and help to achieve vision 2030. doi 10.18502/sjms.v18i2.13604 page 207 sudan journal of medical sciences alrashedi and boshra 3.1. demographic characteristics of the respondents this section includes data about the respondents’ gender, age, marital status, educational qualification, work experience, and other demographic variables. in this study, 92.5% of the participants were saudi nurses, and the mean age of the sample was 27.30 ± 5.28 years. more than half the participants (75.5%) were between 20 and 29 years old, while only 3.8% were 40 years old or above. about half the participants (51.2%) were single, while only 41% were married. concerning the respondents’ educational level, 49.2% of the participants had a diploma, while 38% had completed a bachelor’s degree. the vast majority of the participants (80%) had worked for less than 1 year. more than half the respondents (86.5%) worked less than 50 hours and 37% worked in critical care units in the hospital. approximately 87% of participants had a work schedule of fewer than 50 hours per week, and the workplace with the most participants in this study was king saud medical city (39%). the second deals with statements related to the perceived extent of work-related anxiety among the participants. overall, the participants summary of the likert score showed that the anxiety level per questionnaire of all respondents was 2.10, demonstrating that the respondents exhibit low overall anxiety. the third shows the relationship between work-related anxiety and the selected demographic variables. the results also showed that age, gender, educational qualification, work experience, workplace, and work scheduling (hours per week) significantly influenced work-related anxiety. however, work position, nationality, unit of care, and marital status did not significantly affect work-related anxiety. 4. discussion work-related anxiety among nurses has been linked to a variety of causes, including overburdening workloads [15], conflicts with other healthcare providers [16], a dearth of resources [17, 18], exposure to death and dying, demographics, and workplace stress [19, 20]. studies have shown that these factors (among others) contribute to increased anxiety levels among newly graduated nurses [21, 22]. the time between nursing school and becoming a registered nurse is fraught with anxiety, tension, and even dread [23, 24]. in a study conducted among recently hired nurses in taiwan, the first year of a two-year residency course was associated with moderate anxiety and work stress [25]. doi 10.18502/sjms.v18i2.13604 page 208 sudan journal of medical sciences alrashedi and boshra table 1: socio-demographic characteristics of respondents n = 400. s/n category sub-category frequency distribution n % gender male female 84 316 21 79 age 20–29 30–39 40 and above 302 83 15 75.5 20.7 3.8 mean ± sd 27.30 ± 5.28 marital status single married divorce widower 205 164 24 7 51.2 41 6.0 1.8 educational qualification diploma bachelor postgraduate studies 197 152 51 49.2 38 12.8 nationality saudi non-saudi 369 31 92.5 7.5 work experience less than 1 year 1–2 years 320 80 80 20 unit of care critical areas general ward opd and others nursing office 148 143 60 49 37.0 35.7 15.0 12.3 work position staff nurse head nurse 393 7 98.3 1.7 work place king saud medical city al-iman hospital diriyah hospital king khalid hospital shaqra hospital 155 89 78 45 33 38.8 22.3 19.5 11.3 8.2 hours of work per week less than 50 h more than 50 h 346 54 86.5 13.5 how long have you worked at the hospital less than 1 year 1–4 years 328 72 82.0 18.0 answers in the following questionnaire relate to current workstation last job 324 76 81.0 19.0 about a fifth of the participants in a sample of similar greek critical care nurses reported experiencing moderate to severe anxiety [26]. meanwhile, a chinese study found that nearly 44% of chinese nurses dealt with some form of anxiety (19). finally, a study of iranian nurses echoed the same findings [27]. however, following the study’s null hypothesis and contrary to the literature mentioned above about similar study designs, individuals in the current study generally indicated no prevalent work-related anxiety. even though most participants had a year or lesser work experience, this finding can be explained by the fact that most had passed the probationary evaluation phase. this fits with the results of an observational study with a different sampling technique used in purposive sampling by alhroub et al. [28] on the anxiety levels of newly hired nurses at a jordanian cancer hospital. the authors found that the anxiety levels of newly employed nurses consistently increased from the start to finish of the general nursing orientation program (gno) and that these levels began to fall after three months [28]. doi 10.18502/sjms.v18i2.13604 page 209 sudan journal of medical sciences alrashedi and boshra table 2: work-related anxiety frequency distribution n = 400. item strongly disagree disagree neutral agree strongly agree total “the circumstances at my workplace makes me sick.” number 254 44 60 24 18 400 percent (%) 63.5 11.0 15.0 6.0 4.5 100 % “when thinking about my workplace, everything in my body is tense.” number 200 88 68 32 12 400 percent (%) 50.0 22.0 17.0 8.0 3.0 100% “even in my free time, i continue thinking about work.” number 185 107 66 33 9 400 percent (%) 46.3 26.8 16.5 8.3 2.3 100 % “when imagining having to pass a complete working day at this workplace, i get feelings of panic.” number 130 154 72 28 16 400 percent (%) 32.6 38.6 18.0 7.0 4.0 100 % “i have experienced symptoms like trembling, blushing, sweating, or racing heart in some situations in my workplace.” number 129 151 70 43 7 400 percent (%) 32.3 37.8 17.5 10.8 1.8 100% “i have miserable feelings at my workplace that restrict my capacities for achievement.” number 141 136 73 38 12 400 percent (%) 35.3 34.0 18.3 9.5 3.0 100% “i suffer because i cannot be sure that everything will not change at work.” number 129 140 78 44 9 400 percent (%) 32.3 35.0 19.5 11.0 2.3 100% “colleagues or family have told me that i should not always worry so much about work.” number 139 128 81 39 13 400 percent (%) 34.8 32.0 20.3 9.8 3.3 100% “i do not know how to react when i am confronted with new tasks at work.” number 156 124 68 42 10 400 percent (%) 39 31 17.0 10.5 2.5 100% “the conditions under which i work make me nervous.” number 140 128 79 36 17 400 doi 10.18502/sjms.v18i2.13604 page 210 sudan journal of medical sciences alrashedi and boshra table 2: (continued). percent (%) 35 32 19.8 9.0 4.3 100% “my sleep is worse before working days in contrast to non-working days.” number 150 119 80 40 11 400 percent (%) 37.5 29.8 20.0 10.0 2.8 100% “my work ruins my state of health.” number 147 136 69 37 11 400 percent (%) 36.8 34.0 17.3 9.3 2.8 100% “whenever possible, i avoid coming near the site of my workplace.” number 148 135 64 42 11 400 percent (%) 37 33.8 16.0 10.5 2.8 100% “in my work, one does not get the proper salary for the achievements that one has to do.” number 151 122 72 42 13 400 percent (%) 37.8 30.5 18.0 10.5 3.3 100% “when i see colleagues or superiors from a distance outside my workplace, i try not to meet them directly.” number 136 138 77 35 14 400 percent (%) 34.0 34.5 19.3 8.8 3.5 100% “i had to go on sick leave once or several times because i could not stand the problems at my workplace any longer.” number 128 146 76 36 14 400 percent (%) 32.0 36.5 19.0 9.0 3.5 100% “on my way to my workplace, i would rather turn and walk back.” number 127 146 76 37 14 400 percent (%) 31.8 36.5 19.0 9.3 3.5 100% “i make many mistakes at work, or i am too slow.” number 129 135 82 40 14 400 percent (%) 32.3 33.8 20.5 10.0 3.5 100% “i have experienced a terrible event at the workplace that is still present in my mind and makes me feel frightened at work.” number 151 125 70 41 13 400 percent (%) 37.8 31.3 17.5 10.3 3.3 100% “i feel unsure when somebody observes me.” number 144 132 66 39 19 400 doi 10.18502/sjms.v18i2.13604 page 211 sudan journal of medical sciences alrashedi and boshra table 2: (continued). percent (%) 36.0 33.0 16.5 9.8 4.8 100% “my thoughts about work problems hinder me from carrying out other everyday activities.” number 139 135 65 42 18 400 percent (%) 34.8 33.8 16.3 10.8 4.5 100% “i have health-related impairments that reduce my capacities in working achievement.” number 138 134 77 38 13 400 percent (%) 34.5 33.5 19.3 9.5 3.3 100% “i fear that colleagues could judge me negatively because of my health impairments.” number 132 140 85 31 12 400 percent (%) 33.0 35.0 21.3 7.8 3.0 100% “i am suffering from worries that i cannot put aside or stop.” number 118 157 77 34 14 400 percent (%) 29.5 39.3 19.3 8.5 3.5 100% “the loss of my workplace is/would be existentially threatening.” number 133 144 69 35 19 400 percent (%) 33.3 36.0 17.3 8.8 4.8 100% table 3: shows the relationship between work-related anxiety and the selected demographic variables n = 400. s/n demographic factor chi-square p-value 1 gender 57.62 0.0001 2 age 23.43 0.0001 3 marital status 9.55 0.21 4 educational qualification 32.09 0.0001 5 work experience 38.61 0.001 6 workplace 18.57 0.004 7 hours of work per week 17.79 0.002 8 nationality 4.26 0.22 9 unit of care 10.27 0.18 10 work position 13.44 0.08 11 hospital tenure 31.01 0.0008 in comparison to a study conducted in saudi arabia by waled with a similar design a descriptive cross-sectional result showed that the anxiety levels of the nurses in this study range from 0.60 to 1.52 was considered a very low level of anxiety [10]. doi 10.18502/sjms.v18i2.13604 page 212 sudan journal of medical sciences alrashedi and boshra the present study also found that the level of education a nurse possessed substantially influenced their level of work-related anxiety. according to rambur et al. [29], who used a different study design, “the rn job analysis and retention study” (jars nurses with a bachelor’s degree (bsn)” were better able to handle occupational stress–a potential cause of anxiety–than their associate degree-holding counterparts. to better equip freshly graduated nurses and help them cope with the stress and anxiety of the nursing profession, it may be necessary to establish a structure that promotes the gradual advancement of all levels of nursing education to a minimum of bsn. this is comparable to the advice given in a 2019 study on stress and coping mechanisms for student nurses in clinical training in saudi arabia, which suggests employing regular avoidance of circumstances and the use of problem-solving techniques in response. institutions must adhere to a predetermined schedule to reduce stress among nursing students [11]. according to the present study’s findings, work hours per week also contribute significantly to work-related anxiety. this is consistent with several studies that have found a correlation between shift work and increased stress on the job. according to a cross-sectional epidemiological study in eastern saudi arabia, nurses who experienced work-related stress and anxiety were more likely to have worked in shifts [30]. moreover, a similar cross-sectional study design showed that longer shifts or work hours led to more work, such as the manual handling of equipment or patients, which was strongly linked to work-related stress [31]. the present study also indicated that demographic parameters such as work experience and age influenced the perception of work-related anxiety. this result is consistent with abu-feddeh and darawad [32], a quantitative descriptive cross-sectional design with a similar sampling technique that found a strong correlation between age and workplace stress. the workloads of newly licensed nurses may increase as they age and take on more responsibility in the field. moreover, registered nurses in hospitals report that excessive workload is a significant source of stress in their profession [33]. ang et al. [34] a mixed-method sequential explanatory study corroborated these findings, reporting that nursing became more emotionally draining for respondents as they got older. indeed, the emotional and physical demands of providing complex patient care can prove taxing for nurses (such as lifting and moving patients, rearranging duty schedules, and working longer hours [35]. in comparison to descriptive crosssectional designs, patients’ illnesses and deaths raise nurses’ awareness of their aging and mortality, which may lead to higher emotional stress and anxiety [36]. in comparison with different designs of qualitative research, the fact that most of the participants in doi 10.18502/sjms.v18i2.13604 page 213 sudan journal of medical sciences alrashedi and boshra this study (75.5%) were still relatively young (20–29 years) may also help explain the lack of a noticeable trend toward work-related anxiety. based on the findings of this study, neither a work position nor a unit of care played a significant role in predicting work-related stress. however, this observation is at odds with the results of alhroub et al. [28], who found that newly hired nurses in a general hospital unit reported much higher work stress than those in an emergency or operating room. keskin et al. [37] showed a similar effect of work stress and anxiety: increased workload and the number of patients in general care units contributed to feelings of anxiety and depression amongst nurses. these variations in occupational stress and anxiety are attributed to the larger number of patients in the general ward, the higher complexity of their treatment, the greater likelihood that the nurses will work overtime [38, 39]. a possible explanation for the present study’s contrary finding may be that most participants (37%) worked in critical units. nevertheless, the results of this study are consistent with those of blomberg et al. [40], a cross-sectional design that found that recent nursing graduates had similar stress levels regardless of their placement. 4.1. limitations when interpreting the findings, it is essential to keep the study’s limitations in mind. first, the current study relied on convenience sampling, which could reduce the results’ generalizability. second, the use of self-reported questionnaires is another limitation, as it depends on the study participants’ honesty and may thus lead to under-reporting of anxiety. third, the researcher’s capacity to collect sensitive data on work-related anxiety among the study participants may have been limited by the use of quantitative methods. fourth, 20% of the nursing participants had experience of more than a year. this may have led to lower anxiety and work stress levels than if all participants had less than a year of experience. 5. conclusion the current study explored the significant factors contributing to work-related anxiety among newly graduated nurses in saudi arabia. overall, there was low perceived anxiety at work among the participants. however, some demographic characteristics, including gender, education level, work experience, and scheduling, were linked to anxiety; these characteristics were found to play a significant role in the perception of work-related anxiety. the study’s findings suggest that it is necessary to pay more doi 10.18502/sjms.v18i2.13604 page 214 sudan journal of medical sciences alrashedi and boshra attention to workplace anxiety, which may affect nurses’ capacity to attend to the requirements of patients in their care units. to provide safe patient care, nursing administrators must be involved in efforts to adjust nursing programs and implement the necessary techniques to lower anxiety and stress levels among newly graduated nurses, helping them settle into their new responsibilities without difficulty. the study implies that saudi arabian health policymakers and nurse managers should create specific intervention programs to lessen work-related anxiety in recently graduated nurses. managers must look for methods that assist in adapting the current environment to the demands of nurses as well as strategies that provide recently graduated nurses with crucial support, such as clinical supervision. the researcher suggests that additional research on anxiety be done using a different sampling strategy. 6. recommendations more attention must be paid to work-related anxiety and stress among newly graduated nurses in order to reduce burnout and the intent to quit. during their orientation phase, newly graduated nurses should attend training classes on how to react effectively to challenging work situations, which may help reduce the detrimental effects of stress. in addition, mindfulness-based stress reduction (mbsr) programs and online peer support [41] can help new nurses transition better into their nursing careers. such programs could be included as part of nursing residencies. nurse managers should put in more effort to guarantee that newly hired nurses will have more suitable job responsibilities and nurse-to-patient ratios. managers must look for methods to adapt the current environment to nurses’ needs and strategies that provide newly graduating nurses with essential assistance, such as clinical supervision. nurse supervisors must consider that these nurses are new and inexperienced and work in an environment that places significant expectations on them. a change in workflows, care models, and leadership may help create a supportive environment that reduces stress and anxiety, promote learning, and offers the best and safest nursing care for patients. it is challenging to change the nature of hospital practices and patient care to make the environment less stressful. doi 10.18502/sjms.v18i2.13604 page 215 sudan journal of medical sciences alrashedi and boshra acknowledgments the authors would like to thank the deanship of scientific research at majmaah university, al-majmaah city, kingdom of saudi arabia, for supporting this work under project no. r-2023-189. ethical considerations ethical considerations were taken into account to ensure the confidentiality and privacy of the collected data, which were analyzed anonymously and only used for research purposes. a national bioethics certificate was obtained from the ethical research committee at king saud medical city hospitals. rb registration number with kacst, ksa: h-01-r-053 irb registration number u.s. department of hhs iorg #: iorg0010374), and the study was approved by the directorate of health affairs in riyadh, saudi arabia. before the commencement of the study, ethical approval was also obtained from the ethics department of majmmah university, and hospital officials were informed about the study’s aim and scope. all participants were granted informed consent after receiving clear information about this research; also, they were reminded that they might drown at any time. competing interests the author declares no conflicts of interest in this paper. availability of data and material data is available with the corresponding author upon request. funding deanship of scientific research at majmaah university, al-majmaah city, kingdom of saudi arabia. doi 10.18502/sjms.v18i2.13604 page 216 sudan journal of medical sciences alrashedi and boshra references [1] al-dossary, r. n. 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(2019). experiences of peer support for newly qualified nurses in a dedicated online group: study protocol. journal of advanced nursing, 75(7), 1585–1591. doi 10.18502/sjms.v18i2.13604 page 220 introduction methods research design study setting study sample sampling design sample size inclusion and exclusion criteria research instruments validity and reliability of the instrument data collection data analysis results demographic characteristics of the respondents discussion limitations conclusion recommendations acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 13, issue no. 1, doi 10.18502/sjms.v13i1.1689 production and hosting by knowledge e research article prevalence of topical corticosteroids related adverse drug events and associated factors in selected community pharmacies and cosmetic shops of addis ababa, ethiopia mahlet tsegaye2, tariku shimels2 , and arebu i. bilal1 1department of pharmaceutics and social pharmacy, school of pharmacy, college of health sciences, addis ababa university, addis ababa, ethiopia 2ethiopian federal police commission health service directorate, medical logistics and pharmacy services coordination, ethiopia abstract introduction: inappropriate use of topical corticosteroids was found to cause different dermatological complications. despite its complex adverse effects, misuse of topical corticosteroids has been a common practice throughout the world. the objective of this study was to assess the prevalence of misuse of topical corticosteroids and its associated factors in selected community pharmacies and cosmetics shops of addis ababa. methods: a cross-sectional study design was conducted from february to april in twelve community pharmacies and six cosmetics shops in addis ababa. a convenience sampling method using semi-structured interviews was used to collect topical corticosteroids use pattern and related adverse events. descriptive statistics were used to summarize the nature and frequency of cosmetic use while binary and multinomial logistic regression was employed to test associated factors. statistical significance was set at p<0.05. result: from a total of 286 participants, more than two third obtained the topical corticosteroids as over the counter. among these, majority (59.8%) used for beautification purpose. more than half of the users faced adverse drug events and the most common affected site was face. educational status was found to be associated with otc use of corticosteroids. age, reading of label, frequency of application, recommendation by friends and, mixing with other cosmetics and water have shown statistically significant association with occurrence of adverse drug events. conclusion: majority of the topical corticosteroids were obtained without prescription for the purpose of beautification rather than treatment. a higher proportion of cosmetic users reported to have experienced at least one adverse event. there needs to consider safety concerns related to topical corticosteroids use in the city. keywords: addis ababa, adverse drug events, cosmetics, ethiopia, topical corticosteroids how to cite this article: mahlet tsegaye, tariku shimels, and arebu i. bilal, (2018) “prevalence of topical corticosteroids related adverse drug events and associated factors in selected community pharmacies and cosmetic shops of addis ababa, ethiopia,” sudan journal of medical sciences, vol. 13 (2018), issue no. 1, 62–77. doi 10.18502/sjms.v13i1.1689 page 62 corresponding author: tariku shimels; email: tarphar2008@gmail.com received 26 december 2017 accepted 2 march 2018 published 14 march 2018 production and hosting by knowledge e mahlet tsegaye et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0001-5212-7597 http://orcid.org/0000-0001-8079-9550 mailto:tarphar2008@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mahlet tsegaye et al 1. introduction topical corticosteroids (tcs) are group of drugs which has anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictive effects [1]. corticosteroids work by binding to a specific receptor in the cellular cytoplasm and modulating the transcription of multiple genes that lead to the suppression of the production of inflammatory substances such as; prostaglandins and leukotrienes as well as by inhibiting the recruitment of inflammatory cells into the skin [1, 2]. since their introduction in the early 1950’s, tcs have become the cornerstone of treatment mainly; for non-infective dermatologic disorders associated with inflammation [3–5]. these disorders include a wide variety of dermatoses, such as atopic dermatitis, eczema, contact dermatitis, psoriasis, seborrheic dermatitis, vitiligo, lichen scleroses and intertrigo [6, 7]. topical corticosteroids are the first-line therapy for the treatment of atopic dermatitis according to various independently published international guidelines from both dermatology and allergy groups worldwide [8, 10, 11]. other studies have also documented that these agents have a positive impact on the quality of life of patients [12, 13]. topical corticosteroids have been shown to be a safe treatment options both in short-term daily use and long-term intermittent application [14].they are, specifically, recommended when patients have failed to respond to consistent eczema skin care regimen, including the regular use of moisturizers (emollients), appropriate antibacterial measures, and trying to eliminate any possible allergens that may be contributing to the underlying conditions [8]. the potency of tcs has been assessed by measuring their vasoconstrictive effect on the skin. based on their potency, british national formulary (bnf) divides the topical corticosteroids into four groups, whereas american system divides them into seven classes, where class i represents super potent or ultra-potent drugs and class vii the least potent. previous studies indicated significantly increased proportion of dermatological visits related to a number of local and systemic adverse effects from misuse of tc over the face, ranging from dermatitis and skin rashes to the development of diabetes mellitus, hypertension and renal problems [15, 16]. the quick amelioration of signs and symptoms of many facial dermatoses, the easy access of tc by the people and their use as a cosmetics agent are the most important reasons for irrational use of these groups of drugs [17, 18]. doi 10.18502/sjms.v13i1.1689 page 63 sudan journal of medical sciences mahlet tsegaye et al despite the occurrence of complex adverse effects, misuse of tcs has become a common practice in the community. this study was conducted to assess the pattern of misuse on tcs and factors associated to this practice in selected community pharmacies and cosmetic shops of addis ababa. 2. methods 2.1. description of the study area and settings addis ababa is the capital city of ethiopia with a total population of 3,384,569 with annual growth rate of 3.8% as reported on the 2007 census conducted by the central statistical agency of ethiopia [19]. according to the 2008 ethiopian health and health related indicators report, there were 378 pharmacies, 273 drug stores and 1 rural drug vender in the city [20]. 2.2. study deign a cross-sectional study design was conducted from february to april 2017 in selected community pharmacies and cosmetics shops of addis ababa. 2.3. source and study population the source population included all tc users who visited community pharmacies and cosmetics shops in addis ababa city administration whereas; the study population included all customers who came to purchase tc with or without prescription during the study period. 2.4. sampling procedure and sample size calculations because tcs were out of stock in the market during the stated period, convenience sampling method was used to select pharmacies and cosmetics shops. all customers who came to buy tcs with or without prescription in the selected community pharmacies were asked for consent and were made to fill out the questionnaires. those sent by other tc users were not asked since true information could not be obtained from them. and in cosmetic shops, customers who came to purchase tcs which are doi 10.18502/sjms.v13i1.1689 page 64 sudan journal of medical sciences mahlet tsegaye et al not allowed (intermittent to super potent tcs) to be sold in cosmetic shops were asked to fill out the questionnaire. the minimum number of sample required for this study was determined by using single population proportion formula considering the following assumptions: 𝑛 = (𝑍𝛼/2) 2𝑃 (1 − 𝑃) (𝐸)2 where, n= the required sample size p=the prevalence of misuse of topical corticosteroids (p=0.79) z= z score at 95% confidence interval=1.96 e = the margin of error=0.05 accordingly, the sample size will be: 𝑛 = (1.96) 2 × 0.79(1 − 0.79) (0.05)2 = 255 assuming 10% non-response rate, the total sample size was 286. 2.5. inclusion and exclusion criteria topical corticosteroid users in selected community pharmacy and cosmetics shop aged 18 or above were included in the study whilst, consumers of other cosmetics products, those aged below 18 and, those sent by other tc users were excluded from the study. 2.6. data collection methods and quality assurance quantitative data collection method was employed and, a structured questionnaire was used to determine the prevalence of tc misuse. the data collection questionnaire was designed in english and transcribed to amharic (the national working language of the country). training was given to data collectors and supervisors. pre-test was done two days before the start of actual data collection at one of the study areas. based on the findings from the pretest, the questionnaire was revised and adopted. 2.7. data entry and analysis descriptive statistics were used to summarize the nature and frequency of cosmetic use. bivariate logistic regression analyses were applied to investigate the determinants doi 10.18502/sjms.v13i1.1689 page 65 sudan journal of medical sciences mahlet tsegaye et al of cosmetic use associated with adverse events. all explanatory variables associated with the outcome variable in the bivariate analysis with p<0.20 were included in the multivariate logistic regression model. spss version 20 for windows was used for the data entry and analysis. statistical significance was set at p<0.05. 2.8. operational definitions misuse: the use of tcs out of the intended purpose (treatment). topical corticosteroids: any preparation that contains one or a combination of tcs in the form of cream, ointment or lotion to be applied on the skin. cosmetic shops: shops in which all kinds of cosmetics products are sold. cosmetics: tcs used for beautification purpose. community pharmacies: drug retail outlets including drug stores and pharmacies not owned by health facilities. otc use: use of tcs without appropriate prescription paper. 2.9. ethical consideration the institutional ethical review board of the school of pharmacy, addis ababa university, gave permission to conduct the study. an official letter of cooperation was also written from the department of pharmaceutics and social pharmacy and, the study was conducted after securing permission from the selected community pharmacies and cosmetics shops. moreover, verbal consent was sought from every participant after explaining about the nature of the study, objective, and expected duration of the interview. every subject was informed that participation in the study was fully voluntary. to assure anonymity, the name and address of the study participants were not recorded on the questionnaires and all the information gathered was kept confidential. 3. results findings from selected cosmetic shops and community pharmacies among the 286 study participants approached in the study sites, 211(73.8%) were female. one hundred thirty three (46.5%) of the participants were in the age group 18-28. more than half of tc users were single (54.5%). majority of the participants had a higher educational background (56.6%) (table 1). doi 10.18502/sjms.v13i1.1689 page 66 sudan journal of medical sciences mahlet tsegaye et al variables frequency percent gender male 75 26.2 female 211 73.8 age (yrs.) 18-28 133 46.5 29-39 104 36.4 >40 49 17.1 marital status single 156 54.5 married 130 45.5 educational status 1-12 grade 124 43.4 higher education 162 56.6 occupation student 31 10.8 government employee 40 14.0 unemployed 17 5.9 non-governmental employee 58 20.3 private work 140 49.0 t 1: socio-demographic characteristics of topical corticosteroid users in selected community pharmacies and cosmetics shops of addis ababa, ethiopia. 3.1. extent of over the counter use of topical corticosteroids more than two third (68.5%) of the participants utilized tcs as over the counter (otc) and majority (60%) used the tcs for beautification purpose. most of the participants (44.1%) in the study area selected the tcs by consulting a health professional while about one third of the participants selected tcs by asking a friend. many of the participants (73.4%) claimed to read information that is written on the container and 138 (48.3%) have reported that they read this information always when purchasing cosmetics. expiry date is the most commonly read information reported by 131 (45.8%) subjects (table 2). doi 10.18502/sjms.v13i1.1689 page 67 sudan journal of medical sciences mahlet tsegaye et al characteristics number percent type of prescription otc 196 68.5 prescribed 90 31.5 purpose of use treatment 107 37.4 beautification 171 59.8 duration of application less than1 month 94 32.9 1-6 month 81 28.3 greater than 6 month 111 38.8 frequency of application once 194 67.8 twice 74 25.9 three and greater than three times 18 6.3 do you read information’s on the container yes 210 73.4 no 76 26.6 how do you use different cosmetics use each alone 210 73.4 use different types by mixing 40 14.0 use by mixing with water 36 12.6 t 2: pattern of topical corticosteroids utilization in selected community pharmacies and cosmetics shops in addis ababa, february 2017. 3.2. adverse effects and actions taken one hundred fifty (52.4%) of the participants faced any sort of adverse drug event (ade) and, the most commonly affected site was face (45%) followed by arm pit and hair (17.1%). twenty nine (19.3%) of those who faced the ades stopped using tcs for some time and started back again when symptoms disappeared. only 39 (13.6%) of the study participants consulted health professionals. allergic reactions were the most common problems faced by the users, followed by development of hair on face, sore on skin and face, acne, discoloration on face and skin, hair brittleness and breakage (figure 1). doi 10.18502/sjms.v13i1.1689 page 68 sudan journal of medical sciences mahlet tsegaye et al figure 1: common adr seen in tc users in selected pharmacies and cosmetic shops of addis ababa, february 2017. a-allergic reaction, b-development of hair on the face, c-sore on skin and face, d -acne, ediscoloration on face and skin, f-hair brittleness and breakage, g-photosensitization, hfeasibility of blood vessels, i-hyperpigmentation, j-skin thinning, k-stinging and darkening of the arm pit, l-contact dermatitis, m-hypopigmentation 3.3. factors associated with otc use of tc a logistic regression analysis was used to determine association between patients’ socio-demographic variables and otc utilization of tcs. significant association was detected between otc use and education. participants who were in grades 1-12 (lower level education) had two times used tcs as otc than those who were in higher education with aor=2.67, 95%ci (1.49-4.79). however other socio-demographic variables like age, gender, marital status, and occupation did not show a statistically significant association (table 3). 3.4. factors associated with adverse effects of tc a statically significant association was detected between adverse events and age. those participants in the age group 29-39 reported more adverse events than those in the age group 18-28 and greater than 40. with aor=2.45, 95% ci (1.11-5.39). a significant association was also observed between frequency of application and adverse events. participants who applied a tc once and twice per day have a lesser probability of reporting ades as compared to those who applied more than twice with doi 10.18502/sjms.v13i1.1689 page 69 sudan journal of medical sciences mahlet tsegaye et al otc use variables yes no cor aor age 18-28 92 41 1.19[0.59-2.38] 1.35[0.622.94] 29-39 72 32 1.18[0.58-2.45] 1.31[0.62-2.77] greater than 40 32 17 1.00 1.00 gender female 145 66 1.03[0.58-1.82] 0.97[0.531.75] male 51 24 1.00 1.00 educational status 1-12 98 267 2.46[1.44-4.20]* 2.67[1.494.79]* higher education 98 64 1.00 1.00 marital status single 100 56 0.63[0.38-1.05] 0.69[0.391.24] married 96 34 1.00 1.00 occupation student 23 8 1.27[0.52-3.07] 0.96[0.362.54] governmental employee 25 15 0.73[0.355-1.53] 0.79[0.371.68] unemployed 11 6 0.81[0.28-2.34] 0.54[0.171.65] non-governmental work 40 18 0.98[0.50-1.91] 1.07[0.53-2.16] private 97 43 1.00 1.00 t 3: factors affecting otc utilization of tcs in selected pharmacies and cosmetic shops of addis ababa, february 2017. aor=0.16, 95% ci(0.44-0.69) and aor= 0.15, 95%ci(0.39-0.63) respectively. the probability of ade were three and five times higher for those who selected their tc by asking their friends and who looks appearance and aroma respectively as compared to those who used cost and affordability as a selection criteria (aor= 3.32, 95% ci (1.646.75)); (aor=5.21, 95%ci (1.48-14.33)) respectively. occurrence of ades was three times higher for those who used their tc by mixing with other agents (aor= 3.58, doi 10.18502/sjms.v13i1.1689 page 70 sudan journal of medical sciences mahlet tsegaye et al 95% ci (2.2-7.83)). in addition, the occurance of ade were also two times higher for those tcs users who mixed their cosmetics with water (aor=2.56, 95%ci (1.55-4.32)). 4. discussion the number of participants who reported to have experienced adverse cosmetic events was higher as compared to figures documented in other parts of ethiopia [21, 22] and in other countries such as the netherlands [23], uk [24], nepal [25], and rio de janeiro [26]. however, a higher figure had also been reported in a study by bilal et al. among residents of jigjiga town in the same country [27]. this can be explained, partly, by the little priority given to cosmetic use safety evaluations and laboratory assessments in ethiopia [28, 29]. in addition, most cosmetics outlets lack proper channels of supply where most of these products are smuggled by nonprofessional and uneducated sellers. this, in turn, may result in poor storage of the products, product exposure to sunlight and inappropriate handling of products as compared to cosmetics obtained from drug retail outlets [22]. this study also has shown that more number of female was found to use tcs than male. similar findings were obtained inside the country [30, 31]. this practice is again reported in the rest of the world such as; south africa, india, pakistan and iraq [3234]. higher prevalence of tcs use among the females might be attributed to their considerable interest to feel clean and attractive, increasing sexual stamina, feeling good and sexually active as well as countering sexual risks as reported in some studies [35, 36]. other studies have also documented that females reported skin diseases, emotional distress and associated contact dermatitis more often compared to males [37–39]. even though an earlier study indicated that there were otc uses of tcs [31], the higher figure in this study may indicate the degree to how much the professionals were not following the ethics and rules that govern the pharmaceutical sector. this problem had been reflected in the significant number of tc users reporting an ade. the fact that those in grades 1-12 (lower level education) had a two times higher probability of using tc as otc indicates that there needs to do an educational campaign on this group of users. the frequency of use had also shown a statistically significant association with the occurrence of ade. similar findings were reported inside the country where higher frequency of use increased the occurrence of the ade [27]. this study has clearly doi 10.18502/sjms.v13i1.1689 page 71 sudan journal of medical sciences mahlet tsegaye et al adverse effects variables yes no cor aor age (yrs.) 18-28 66 67 1.21[0.62-2.33] 1.46[0.65-3.27] 29-39 62 42 1.81[0.91-3.59] 2.45[1.11-5.39]* >40 22 27 1.00 1.00 sex male 43 32 1.00 1.00 female 107 104 0.76[0.45-1.30] 0.71[0.38-1.32] educational status grades 1-12 24 39 1.40[0.879-2.25] 0.93[0.50-1.72] higher education 32 29 1.00 1.00 marital status single 76 80 0.71[0.45-1.14] 0.66[0.37-1.18] married 74 56 1.00 1.00 occupation student 15 16 0.96[0.44-2.10] 0.59[0.22-1.54] governmental employee 26 14 1.91[0.92-3.96] 1.99[0.84-4.70] unemployed 12 5 2.47[0.826-7.37] 1.76[0.45-6.78] non-governmental work 28 30 0.96[0.521-1.77] 0.75[0.36-1.56] private 69 71 1.00 1.00 duration of application less than a month 50 44 1.28[0.74-2.23] 1.02[0.52-1.98] 1-6 months 48 33 1.65[0.92-2.945] 1.29[0.66-2.53] greater than 6 months 52 59 1.00 1.00 frequency of application once 97 97 0.28[0.91-0.89]* 0.16[0.44-0.69]* twice 39 35 0.31[0.09-1.05] 0.15[0.39-0.63]* 3 or more times 14 4 1.00 1.00 selection of tcs recommended by friends 51 27 3.10 [1.36-6.98.]* 3.32[1.64-6.75]* looking appearance and aroma 15 5 4.92 [1.46-16.53]* 5.21[1.48-14.33]* recommended by health professionals 59 60 1.61 [0.75-3.43] 1.34[0.82-3.11] recommended by shop owners 11 21 0.861 [0.32-2.30] 1.12[0.45-2.2] low cost 14 23 1.00 1.00 use of different cosmetics using tcs without mixing with other cosmetics 99 116 1.00 1.00 using tcs by mixing with other cosmetics 30 9 3.90[1.77-8.61]* 3.58[2.2-7.83] using tcs by mixing with water 21 11 2.23 [1.02-4.866] 2.56 [1.55-4.32] *statistically significant association at 95% ci t 4: factors affecting adverse effects of tc in selected pharmacies and cosmetic shops of addis ababa, february 2017. doi 10.18502/sjms.v13i1.1689 page 72 sudan journal of medical sciences mahlet tsegaye et al shown that the participants who selected their tcs by friends as well as by looking appearance and aroma were at a higher risk to develop an ade. this underscores the importance of consulting health professionals while selecting the tcs for use. likewise, a three and two times increase in ade was reported by tc users who applied through mixing it with other cosmetics and water. this could be explained by presence of interaction between cosmetic products or a synergistic effect of the products to each other. similar studies also reported that mixing of cosmetics with other substances like water and saliva increase the ade [21, 27]. this study has tried to catch those users who visited both community pharmacies and cosmetics shops for obtaining their tc. however, some of the adverse events reported by the study participants might have not, necessarily, been caused by the cosmetic product they used. there needs further investigation for causality assessment which was beyond the scope of this study. 5. conclusion the result of this study has revealed that most tcs were being utilized without a prescription. besides, many participants have reported to purchase tcs for beautification purpose rather than treatment. significant number of users had experienced adverse events in which frequency of application, the way of selection and mixing the tc with other cosmetics and substances were important predictors for such events. there needs a due consideration on cosmetic use-related safety concerns through awareness creation programs and promoting the concept of cosmetovigilance among cosmetic sellers, users, and other stakeholders. 6. list of abbreviations adr: adverse drug reaction aor: adjusted odds ratio bnf: british national formulary cor: crudes odds ratio csa: central statistical agency of ethiopia fmhaca: food medicine and healthcare administration and control authority otc: over the counter spss: statistical package for the social science program tc: topical corticosteroids doi 10.18502/sjms.v13i1.1689 page 73 sudan journal of medical sciences mahlet tsegaye et al 7. acknowledgment we would like to thank all the selected pharmacies and cosmetic shops for accepting our requests and helping us collect the data. we also forward our gratitude to the clients who gave the informed consent and participated in this study. references [1] carlos g, uribe p. & fernández-peñas p. rational use of topical corticosteroids. aust prescr. 2013; 36:5-6. doi: 10.18773/austprescr.2013.063. 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[7] woodson jm. the role of low-potency topical steroids in day-to-day practice. skin and aging supplement of december. 2009; 1-8. available at: http://www.the-dermatologist.com/sites/default/files/supplements/ ferndale1_supp.pdf. accessed on 18 august 2017. [8] atherton dj. topical corticosteroids in atopic dermatitis. bmj. 2003; 327(7421): 942– 943. doi: 10.1136/bmj.327.7421.942. [9] eichenfield lf, tom wl, berger tg, krol a, paller as, schwarzenberger k, et al. guidelines of care for the management of atopic dermatitis: section 2. management and treatment of atopic dermatitis with topical therapies. j am acad dermatol. 2014; 71(1):116-32. 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[13] msika p, de belilovsky c, piccardi n, chebassier n, baudouin c, chadoutaud b. new emollient with topical corticosteroid-sparing effect in treatment of childhood atopic dermatitis: scorad and quality of life improvement. pediatric dermatology. 2008;25: 606–612. doi:10.1111/j.1525-1470.2008.00783. [14] samarasekera ej, sawyer l, wonderling d, tucker r and smith ch. topical therapies for the treatment of plaque psoriasis: systematic review and network metaanalyses. br j dermatol. 2013; 168: 954–967. doi:10.1111/bjd.12276 [15] bhat yj, manzoor s, qayoom s. steroid-induced rosacea: a clinical study of 200 patients. indian journal of dermatology.2011; 56(1): 30-32. [16] noruka e, okoye o. topical steroid abuse: its use as a depigmenting agent. j natl med assoc. 2006 jun;98(6):934-9. [17] rathi sk, d’souza p. rational and ethical use of topical corticosteroids based on safety and efficacy. indian j dermatol. 2012 jul-aug; 57(4): 251–259. 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[22] meharie bg, ambaye as, haimanot ym. a cross-sectional study on assessment of cosmetics utlization and self reported adverse reactions among wollo university, dessie campus female students. dessie, north east ethiopia. eur j phar med res.2014; 2:49-63. doi 10.18502/sjms.v13i1.1689 page 75 sudan journal of medical sciences mahlet tsegaye et al [23] degroot ac, nater jp, van der lendes r, et al. adverse effects of cosmetics and toiletries: a retrospective study in the general population. int j cosmet sci. 1987;9:255–259. doi: 10.1111/j.1467-2494.1987.tb00481.x. [24] consumer’s association. reactions of the skin to cosmetic and toiletry products. consumer’s association survey. london: pharmaceutical press; 1979. [25] giovanni cd, arcoracid v, gambardella l. cosmetovigilance survey: are cosmetics considered safe by consumers. pharmacol res. 2006;53:16–21. doi: 10.1016/j.phrs.2005.08.003. 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[30] negussie h. assessment of utilization pattern of topical steroids in alert hospital. masters thesis). department of pharmaceutics and social pharmacy, school of pharmacy, addis ababa university. 2014. available at; etd.aau.edu.et/bitstream/123456789/6101/1/hanna. [31] bantayehu n. assessment of over the counter utilization of topical corticoteroids in addis ababa. aau liberaries home. 2015. available at: http://hdl.handle.net/123456789/8629 [32] noiesen e, munk md, larsen k, hoyen m, agner t. gender differences in topical treatments of allergic contact dermatitis. acta derm venereol. 2009; 89: 79–110. [33] chohan sn, suhail m, salman s, bajwa um, saeed m, kausar s, suhail t. facial abuse of topical steroids and fairness creams: a clinical study of 200 patients. journal of pakistan association of dermatology.2016; 24: 204-211. [34] al dhalimi m, al jawahiry n. misuse of topical corticosteroids: a clinical study in an iraqi hospital.2006; 12(6):847-52. [35] korichi r, pelle-de-queral d, gazano g, aubert a. why women use makeup: implication of psychological traits in makeup functions. j. cosmet. sci. 2008; 59, doi 10.18502/sjms.v13i1.1689 page 76 sudan journal of medical sciences mahlet tsegaye et al 127-137. doi: 10.11622/smedj.2014100 [36] jallian f, ahmadpanah m, karimi m, vahidinia a, emdadi sh. prevalence and reasons for cosmetics products use among female students in hamedan universities. dermatology and cosmetics. 2013, 3(1); 9-15. [37] meding b. differences between the sexes with regard to work related skin disease. contact dermatitis.2000;43;65-71. [38] cvetkovski rs, zachariae r, jensen h,olsen j, johansen jd, agner t. quality of life and depression in a population of occupational hand eczema patients.contact dermatitis. 2006;54:106-111. [39] kadyk d, hall s, belsito d. quality of life of patients with allergic contact dermatitis: an exploratory analysis by gender, ethenicity, age and occupation. dermatitis. 2004;15:117-124. doi 10.18502/sjms.v13i1.1689 page 77 introduction methods description of the study area and settings study deign source and study population sampling procedure and sample size calculations inclusion and exclusion criteria data collection methods and quality assurance data entry and analysis operational definitions ethical consideration results extent of over the counter use of topical corticosteroids adverse effects and actions taken factors associated with otc use of tc factors associated with adverse effects of tc discussion conclusion list of abbreviations acknowledgment references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5208 production and hosting by knowledge e research article evaluation of ll 37 lipoprotein as innate immunity marker among sudanese patients cutaneous leishmania ayat h. bakr1, abugroun e. a.2, abdelkarim a. abdrabo3, omeyma a. mohamed4, mokhtar m. a.5, and gadallah modawe6 1department of microbiology, university of science and technology, khartoum, sudan 2university of science and technology, khartoum, sudan 3department of clinical chemistry, faculty of medical laboratories science, al-neelain university, khartoum, sudan 4department of clinical chemistry, faculty of medical laboratories science, sudan international university, khartoum, sudan 5the institute of endemic diseases, university of khartoum, sudan 6omdurman islamic university, faculty of medicine, department of biochemistry, omdurman, sudan abstract background: the leishmaniasis is a group of diseases with a broad range of clinical manifestations caused by several species of parasites belonging to the genus leishmania. ll-37/hcap18, the only cathelicidin in human, is expressed as an 18kda preproprotein. the most prominent function of cathelicidin is their ability to inhibit propagation of a diverse range of microorganisms, which occurs at a micromolar range. objective: the study was aimed to evaluate the ll37 plasma level in leishmania sudanese patients. methods: in a case-control study, 300 subjects were enrolled (200 as case and 100 controls); 5 ml venous blood was collected in edta container, then plasma was obtained and stored frozen at –80°c. ll 37 was estimated using competitive elisa. the data were analyzed using spss version 21. results: the results revealed that 115 (57%) of leishimania patients were male and 85 (43%) were female. plasma ll 37 level was significantly increased in leishmania patients (1.30 ± 0.71) compared to the control (0.21 ± 0.20) with (p-value 0.000). conclusion: leishmania patients had higher levels of plasma ll37, suggesting effective antimicrobial immunity process enhancing healing of cutaneous leishmaniasis. keywords: cathelicidin, ll37, innate immunity, leishmania, sudan 1. introduction the leishmaniases are a group of diseases with a broad range of clinical manifestations caused by several species of parasites belonging to the genus leishmania (family: trypanosomatidae). the leishmania parasite, a haemo-flagellate protozoan organism, how to cite this article: ayat h. bakr, abugroun e. a., abdelkarim a. abdrabo, omeyma a. mohamed, mokhtar m. a., and gadallah modawe (2019) “evaluation of ll 37 lipoprotein as innate immunity marker among sudanese patients cutaneous leishmania,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 91–96. doi 10.18502/sjms.v14i3.5208 page 91 corresponding author: abdelkarim a. abdrabo; email: abdrabokarim@gmail.com received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e ayat h. bakr et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abdrabokarim@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ayat h. bakr et al is exclusively transmitted by the bite of a female sandfly of the genera phlebotomus or lutzomyia. there are three clinical forms of leishmaniasis: visceral leishmaniasis (vl) including post-kala-azar dermal leishmaniasis (pkdl), cutaneous leishmaniasis (cl), and cl with the involvement of the mucous membranes, also called mucocutaneous leishmaniasis (mcl) [1]. cl in sudan is similar to the disease in other endemic areas. there are three types: nodular or nodular-ulcerative, ulcerative, and diffuse infiltrative [2]. most patients have multiple lesions of the modular or ulcerative type[3]. typically, lesions start to heal spontaneously after approximately three months [4]. unlike american mucocutaneous leishmaniasis, sudanese mucosal leishmaniasis (sml) is not preceded or accompanied by cutaneous lesions. three clinical presentations of sml have been reported: nasal, which is characterized by nasal obstruction, mucoid discharge, and slight bleeding; oral, where the patient complains of a sensation of fullness of the mouth, spontaneous loss of teeth and bleeding from the gum; and oro-nasal, where the hard palate may perforate. the disease is almost exclusively found in adult males (20– 70 yr) [5]. cathelicidins are a family of evolutionarily conserved antimicrobial peptides described in mammals, birds, fish, and reptiles. this class of pleiotropic peptides is an important mediator of innate immunity against microbial pathogens and provides first-line defense against infection by promoting rapid elimination of pathogens. ll37/hcap18 is the only cathelicidin in human [6]. the most prominent function of cathelicidins is their ability to inhibit propagation of a diverse range of microorganisms, which occurs at micromolar range [7]. besides their direct antimicrobial action, recent studies have revealed multiple functions of cathelicidins in many other activities relating to tissue repair and innate immunity. the human and porcine cathelicidins, ll-37/hcap18 and pr-39, respectively, for examples, have been reported to modulate the activity of immune and 7, 8, 9 inflammatory cells [8, 9]. cathelicidins have also been shown to promote re-epithelialization of human skin wounds [10] and rat gastric ulcer [11]. the study was aimed to evaluate the ll37 plasma level in leishmania sudanese patients. 2. methods in this case-control study, 300 subjects were enrolled, 200 diagnosed with cl infection and 100 as control (free of cl infection). blood samples were drawn after obtaining written informed consent from the patients; 5 ml of venous blood was collected from each subject in edta container, then plasma was obtained and stored frozen at –80°c. ll 37 was estimated using competitive elisa. data were expressed as percentage and doi 10.18502/sjms.v14i3.5208 page 92 sudan journal of medical sciences ayat h. bakr et al differences in variables mean levels between the two groups were tested by student’s 𝑡-test. 3. results and discussion figure 1: distribution of patients according to the gender. figure 2: distribution of patients according to age. the results showed that 115 (57.0%) of leishmania patients were males and 85 (43.0%) were females (figure 1). regarding the age group, the higher proportion (47%) of leishmania patients was found among the 12–29 yr old, followed by 30–47 yr, and then 48–65 yr (figure 2). the mean values of ll-37 (plasma level ng/ml) for the cases was doi 10.18502/sjms.v14i3.5208 page 93 sudan journal of medical sciences ayat h. bakr et al l l 3 7 l e v e l c a s e c o n tr o l 0.0 0.5 1.0 1.5 2.0 2.5 p -value 0.000 1.30 0.21 figure 3: mean of ll-37 across study groups. l l 3 7 l e v e l m a le f e m a le 0.0 0.5 1.0 1.5 2.0 p -value 0.000 0.17 0.98 figure 4: mean of ll-37 across gender. 1.30 ± 0.71 and for the control group was 0.21 ± 0.25, significant differences increase was found between cases and control groups with a p-value of 0.000. (figure 3). the mean ll-37 level was significantly increased in female leishmania patients compared to male leishmania patients p-value 0.000 (figure 4). ll-37 is one of the most studied antimicrobial peptides that play important roles in the innate immune system. in addition to its anti-infective activities, ll-37 stimulates local angiogenesis, acts synergistically with the epidermal growth factor receptor to promote epithelial growth, and attracts monocytes and neutrophils through formyl peptide receptors on these cells. in this way, the peptide helps orchestrate the inflammatory process [12–14]. unlike the present study, which studied the plasma level of ll-37, kulkarni mm et al. studied the role of this host peptide in control of the dissemination of cutaneous infection by the parasitic protozoan leishmania, using a mouse knock-out model in cathelicidin-type antimicrobial peptides (camp) [15]. they found that the presence of pronounced host inflammatory infiltration in lesions and lymph nodes of infected animals was camp-dependent. to our knowledge, this is the first study of plasma ll37 in cutaneous leishmania patients. doi 10.18502/sjms.v14i3.5208 page 94 sudan journal of medical sciences ayat h. bakr et al the present study data revealed an increase in plasma ll 37 levels among cutaneous leishmania patients suggesting increased expression of ll 37 is moreover able to limit dissemination of cl. these results support the kulkarni mm et al.’s suggestion that camp is crucial for the local control of cutaneous lesion development and parasite growth and metastasis [15]. 4. conclusion leishmania patients have higher levels of plasma ll37, suggesting effective antimicrobial immunity process enhancing healing of cl. references [1] osman, o. f., kager, p. a., and oskam, l. (2000). leishmaniasis in sudan: a literature review with emphasis on clinical aspects. tropical medicine and international health, vol. 5, no. 8, pp. 553–562. [2] abdalla, r. e., ali, m., wasfi, a. i., et al. (1973). cutaneous leishmaniasis in sudan. transactions of the royal society of tropical medicine and hygiene, vol. 67, no. 4, pp. 549–559. [3] el-safi, s. h., peters, w., el-toam, b., et al. (1991). studies on the leishmaniases in sudan. 2. clinical and parasitological studies on cutaneous leishmaniasis. transactions of the royal society of tropical medicine and hygiene, vol. 85, no. 4, pp. 457–464. [4] abdalla, r. e. and sherif, h. (1978). epidemic of cutaneous leishmaniasis in northern sudan. annals of tropical medicine & parasitology, vol. 72, no. 4, pp. 349–352. [5] abdalla, r. e., el hadi, a., ahmed, m. a., et al. (1975). sudan mucosal leishmaniasis. transactions of the royal society of tropical medicine and hygiene, vol. 69, no. 5–6, pp. 443–449. [6] wu. w. k., wang, g., coffelt, s. b., et al. (2010). emerging roles of the host defense peptide ll-37 in human cancer and its potential therapeutic applications. international journal of cancer, vol. 127, no. 8, pp. 1741–1747. [7] gallo, r. l. and nizet, v. (2003). endogenous production of antimicrobial peptides in innate immunity and human disease. current allergy and asthma reports, vol. 3, pp. 402–409. [8] huang, h. j., ross, c. r., and blecha, f. (1997). chemoattractant properties of pr-39, a neutrophil antibacterial peptide. journal of leukocyte biology, vol. 61, pp. 624–629. doi 10.18502/sjms.v14i3.5208 page 95 sudan journal of medical sciences ayat h. bakr et al [9] de, y., chen, q., schmidt, a. p., et al. (2000). ll-37, the neutrophil granuleand epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (fprl1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and t cells. journal of experimental medicine, vol. 192, pp. 1069–1074. [10] heilborn, j. d., nilsson, m. f., kratz, g., et al. (2003). the cathelicidin anti-microbial peptide ll-37 is involved in reepithelialization of human skin wounds and is lacking in chronic ulcer epithelium. journal of investigative dermatology, vol. 120, pp. 379– 389. [11] yang, y. h., wu, w. k., tai, e. k., et al. (2006). the cationic host defense peptide rcramp promotes gastric ulcer healing in rats. journal of pharmacology and experimental therapeutics, vol. 318, pp. 547–554. [12] zasloff, m. (2002). antimicrobial peptides of multicellular organisms. nature, vol. 415, no. 6870, p. 389. [13] vandamme, d., landuyt, b., luyten, w., et al. (2012). a comprehensive summary of ll-37, the factotum human cathelicidin peptide. cellular immunology, vol. 280, no. 1, pp. 22–35. [14] bucki, r., leszczyńska, k., namiot, a., et al. (2010). cathelicidin ll-37: a multitask antimicrobial peptide. archivum immunologiae et therapiae experimentalis, vol. 58, no. 1, pp. 15–25. [15] kulkarni, m. m., barbi, j., mcmaster, w. r., et al. (2011). mammalian antimicrobial peptide influences control of cutaneous leishmania infection. cell microbiology, vol. 13, pp. 913–923. doi 10.18502/sjms.v14i3.5208 page 96 introduction methods results and discussion conclusion references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4375 production and hosting by knowledge e research article treatment of extensive plaque psoriasis and psoriatic arthropathy using methotrexate in a patient with high serum alkaline phosphatase suad hh1, muna mohammed el amin2, gad allah modawe3, and osman elbasheer4 1department of dermatology, omdurman islamic university, omdurman, sudan 2department of community medicine, omdurman islamic university, omdurman, sudan 3department of biochemistry, omdurman islamic university, omdurman, sudan 4khartoum dermatology teaching hospital, khartoum state, sudan abstract background: psoriasis is an autoimmune inflammatory, chronic, and relapsing disease of the skin, which can also present with severe joint inflammation and deformity. there are many treatment options, but the severe forms of psoriasis are treated successfully with cytotoxic and biologic therapies. methotrexate being cheap and available in sudan is considered a good option for patients with severe and extensive forms of psoriasis. one of the main drawbacks is hepatotoxicity. the aim of this report is to share an experience of treating the patient with oral methotrexate in the presence of a relative contraindication to this therapy. method: we present a 60-year-old female with extensive skin psoriasis and psoriatic arthropathy. investigations showed high serum alkaline phosphatase and low serum albumen. other liver enzymes, cbc, ultrasound abdomen were all unremarkable. patient was admitted and a weekly dose of methotrexate was given in addition to topical preparation and supportive treatment; three months later, patient improved and was moved to topical therapy. a check of serum alkaline phosphatase and albumen every week was done. results: the patient was successfully and safely treated with methotrexate. serum alkaline phosphatase was normal within the second month treatment, and serum albumen was normal after only one month of treatment. conclusion: high serum alkaline phosphatase is considered a relative contraindication to the use of methotrexate, high level can be found in bone diseases. serum albumen can be low in dermatologic diseases with excessive shedding of scales and can be corrected with protein formulas and high protein diets. recommendations: methotrexate is recommended for the treatment of severe morbid forms of psoriasis. the biologic therapy for severe forms of psoriasis is now available and can be a good alternative for the treatment of severe forms of psoriasis in good centers and for patients who can afford and in patients with absolute contraindications to methotrexate therapy. keywords: psoriasis, psoriatic arthropathy, alkaline phosphatase, methotrexate how to cite this article: suad hh, muna mohammed el amin, gad allah modawe, and osman elbasheer (2019) “treatment of extensive plaque psoriasis and psoriatic arthropathy using methotrexate in a patient with high serum alkaline phosphatase,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 1–8. doi 10.18502/sjms.v14i1.4375 page 1 received 21 january 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e suad hh et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4375&domain=pdf&date_stamp=2019-03-31 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences suad hh et al 1. introduction psoriasis is a particular autoimmune systemic inflammatory disease of great interest. it has a chronic, relapsing, and remitting course that has devastating impact on a person’s health-related quality of life (hrql) [1]. psoriasis is a common health problem with an estimated worldwide prevalence of 2–3%, with great regional and ethnic variations. caucasians predominate [2]. few studies have reported on the incidence of psoriasis in the middle east, including two small single-center studies conducted in 2004 that found the incidence of psoriasis to be 3.4%, in the south-western and eastern saudi arabia (3). similar to all autoimmune diseases, the pathophysiology of psoriasis is so complicated, not yet fully understood, and expresses a mixture of genetic, environmental and behavioral influences. while, clinically, the signs and symptoms appear to be caused by hyper proliferation and inflammation of epidermal cells. in psoriasis, an immunologic response involving t-lymphocytes and cytokines alters the epidermal skin cell cycle to result in the formation of the psoriatic plaques, the whole mark of the disease [4]. since the mid-1950s, methotrexate has become the gold standard by which other systemic psoriasis medications are measured (5). in 1972, the food and drug administration (fda) approved methotrexate for the treatment of psoriasis and provided a formal basis for its use. guidelines are published since this approval to standardize the use of methotrexate. these guidelines addressed indications, contraindications, pretreatment evaluation, monitoring of therapy, dosages, adverse reactions, and overdose. the original guidelines endorsed liver biopsy as the gold standard for detecting liver damage and introduced a histological classification standard for grading liver biopsy specimens. since their original publication in 1972, the guidelines have continued to evolve over the years and have undergone four revisions [6, 7]. the latest set was published in 1998 where liver biopsies were replaced by blood tests for liver fibrosis, serum aminoterminal propeptide of type iii procollagen (piiipn), based on results of small studies [8]. methotrexate is a relatively safe medication as a serious damage to the liver undisputedly occurs in less than 1% or even less than 0.1% of the patients. the burden for patients might not outweigh the potential damage [9]. efforts to treat severe psoriasis continues to increase; in 1974, a survey revealed that 52% of dermatologists used methotrexate to treat psoriasis, this increased in 1987 when another survey showed that the number of dermatologists who used methotrexate had doi 10.18502/sjms.v14i1.4375 page 2 sudan journal of medical sciences suad hh et al increased slightly to 58%. in 2001, millions of prescriptions were written for methotrexate, of which approximately 11% were for psoriasis (9). administered either as monotherapy or in combination with the other schemes, methotrexate exerts its effects by acting as both immunomodulatory and anti-metabolite agent due to the downregulation of t-cell-mediated pro-inflammatory markers and inhibition growth of keratinocytes and decrease in the endothelial expression of icam-1 and e-selectin (10). clinical data from trials suggest that 24% and 100% of psoriasis patients achieved pasi-75 at week 12 at mtx dosage of 7.5 and 15 mg, respectively. however, we found that 73% and 40% of patients reached pasi-75 at week 12 in group b and a, respectively (11). during 1985, lanes et al. had followed 30 patients with psoriasis and other nonmalignant diseases with liver biopsies done before treatment with low-dose methotrexate, 15 mg/week, and then at oneto two-year intervals as long as they continued the methotrexate. all patients were symptomatically improved on this regimen. the 15 patients who had normal liver biopsies at the start of the study had normal biopsies after methotrexate, 15 others had minor hepatic histological abnormalities before treatment, 11 had fatty infiltration, 10 showed no significant change after treatment, while 1 had increased fat and portal fibrosis on a fourth liver biopsy done seven years after mtx was begun. this last patient, a former alcohol abuser, continued methotrexate and showed no further worsening at 8 years. the remaining four had portal fibrosis before treatment. one patient had less fibrosis after methotrexate, two patients slightly more fibrosis, and one a marked increase in portal fibrosis. no patient developed cirrhosis or clinical liver disease. these results suggest that in the absence of alcohol consumption, low-dose weekly methotrexate treatment rarely causes clinically significant liver damage. similar results for hepatotoxicity associated with low-dose, long-term methotrexate treatment of rheumatoid arthritis was shown by szanto et al. in 1987. relative contraindication for methotrexate therapy include kidney failure, gastric ulcer, hypoalbuminemia, elevated liver enzymes, active infectious diseases, treatment with immunosuppressant, interactions with other drugs, hyperlipidemia, folic-acid deficiency, alcohol abuse, obesity, diabetes, active or past history of hepatitis, lack of patient compliance, and old age. while there are some other conditions that are considered absolute contraindications for treatment with methotrexate (12). case report: a 60-year old female, married and residing in gezeira state has a known case of chronic plaque psoriasis since 20 years, with remissions and relapses, emollients and some preparations being used according to dermatologist prescription. doi 10.18502/sjms.v14i1.4375 page 3 sudan journal of medical sciences suad hh et al in the last presentation, the patient had an extensive involvement of her skin affecting the extensors of limbs, face, trunk more marked over the lower parts and scalp. the condition was associated with severe bilateral hip joint pain and finger deformities, so severe that the patient had to use a wheel chair. pt was otherwise normal, no complains related to other systems, no abdominal pain, no chest pain, no palpitations or headache. no past history of schistosomiasis, hematuria, malèna, jaundice, or liver disease. no previous hospital admission. pt not known diabetic or hypertensive. no family history of psoriasis or other skin disease. no history of alcohol consumption. not on chronic medication, apart from the preparations for psoriasis. patient is a house wife; her husband is an employee in a company with a low income, she is postmenopausal, with two daughters and two sons. o l e: patient was uncomfortable, pushed on a wheel chair. not pale or jaundiced. normal pulse and bp. no palpable lymph nodes. lower limbs: pitting edema present bilaterally. examination of the chest and heart revealed no abnormality. abdomen showed no tenderness, no organomegaly. liver was of normal size. skin: lesions were located over the extensors of both upper and lower limbs, face and trunk involvement was more extensive on the lower half with no specific pattern of distribution in the form of well-demarcated papules and plaques covered with easily detached white silvery scales. the skin between the lesions is erythematous and tender. scalp: all covered with easily detached scales with well-demarcated psoriatic corona. palms and soles show hyperkeratosis. mucous membranes were normal. joints: painful interphalangeal joints with finger deformities. bilateral painful tender hips. investigations: urine and stool analysis showed no abnormality. cbc showed slightly raised wbc. rbcs, hb, and platelets were all normal. liver function tests: slight increase of alkaline phosphatase and low serum albumen, other liver enzymes were all normal. renal function tests and electrolytes were normal. rheumatoid factor –ve. us abdomen: no organomegaly, liver is of normal size and texture, and no evidence of chronic liver disease. x-ray hips and x-ray hands: inflammatory changes consistent with psoriatic arthritis. doi 10.18502/sjms.v14i1.4375 page 4 sudan journal of medical sciences suad hh et al cxr: clear. ecg: normal. 2. plan of management admission, treatment with general measures included emollients, protein formulas, high protein diet, tonics, and systemic antibiotics. specific measures included methotrexate tabs 15 mg/week divided in three doses 12 hours apart with 5 mg folic acid tabs, skin preparation included 5% salicylic acid and 4% coal tar in 100 g vaseline once a day. coal tar shampoo for the scalp every other day. follow-up included daily assessment of the clinical state, mainly for the regression of psoriatic plaques, erythema, scales, and lower limb edema. eye examination for jaundice is important, hip and finger examination for normal non-restricted joint movement should all be performed. follow-up by investigations included weekly measurement of liver function tests with enzymes and cbc. 3. outcome after the second week, the condition improved in terms of edema, joint pain, and skin condition. in the third and fourth weeks, much improvement was seen and the patient could stand with support. the second month, the patient could walk with support, and so static improvement was noticed. at the end of the third month, the patient was discharged in good condition and could walk unsupported with marked clinical improvement of the skin condition on topical treatment with coal tar in vaseline and divobet (divonex + betamethasone) cream. follow-up by investigations showed weekly reduction of alkaline phosphatase level and was normal by the fifth week. hemoglobin level was low in the third month for which ferrous sulphate was prescribed. serum albumin was corrected by diet and protein formula, and it was normal after one month. on discharge, liver function test was normal including alkaline phosphatase. patient was discharged in good condition with respect to the clinical and laboratory status. 4. discussion psoriasis is an autoimmune chronic inflammatory skin disease with remissions and relapses; it can affect joints causing psoriatic arthritis and can be so severe leading to erythroderma. doi 10.18502/sjms.v14i1.4375 page 5 sudan journal of medical sciences suad hh et al the treatment of the localized forms can usually improve with topical agents, but severe forms like extensive plaque psoriasis, pustular psoriasis, psoriatic arthritis, and erythrodermic psoriasis need systemic treatment as well. psoriatic arthritis occurs in 30% of patients. it can result in permanent joint damage, methotrexate is the most commonly prescribed medication together with nsaids. methotrexate is a relatively safe cytotoxic antimetabolite drug that has been approved by the fda for the treatment of severe variants of psoriasis since 1972 [6, 7]. serious damage due to methotrexate occurs in less than 1% or even less than 0.1% of patients [9]. it is effective in the treatment of severe forms of psoriasis, it acts as immunomodulatory and antimetabolite due to the down regulation of t-cell-mediated pro-inflammatory markers (10). studies done showed that in the absence of alcohol consumption, a weekly low dose of methotrexate rarely causes clinically significant liver damage. guidelines for the use of methotrexate had been studied and clearly stated [6, 7]. the treatment of the reported case was considered challenging because of the need to a systemic medication, the options are methotrexate, cyclosporine and biologic therapy; the last two are very expensive in sudan and the patient couldn’t afford it; the former is cheap but the patient has an elevated alkaline phosphatase and low serum albumin which are considered relative contraindications for its use (12). in one study, portal fibrosis was encountered after seven years of use of methotrexate in a patient with psoriasis. follow-up of liver damage was done through biopsies which were then replaced by the blood tests in 1998 by fda (8). alkaline phosphatase is found in various tissues in the body, highest concentrations being found in the liver and bones; elevated levels can indicate tissue damage mainly bone or liver. hypo albuminemia can be found in patients with scaly skin diseases where excessive shedding of scales takes place. the american academy of dermatology suggests the following investigations before starting treatment with methotrexate: cbc, s. creatinine, blood urea nitrogen, and liver function tests with enzymes. depending on all of the aforementioned facts, a decision for managing the patient with methotrexate was made. the plan was: admission, base line investigations, weekly oral methotrexate, topical antipsoriasis treatment, systemic antibiotics for uti, supportive therapy and tonics, clinical follow-up, and through investigations such as liver function tests and cbc. doi 10.18502/sjms.v14i1.4375 page 6 sudan journal of medical sciences suad hh et al baseline investigations done were normal apart from minor uti, elevated serum alkaline phosphatase, low serum albumin, inflammatory changes of hand and hip joints indicating psoriatic arthritis. the patient was well managed with systemic therapy using weekly doses of methotrexate in addition to topical therapy using salicylic acid and coal tar preparations. the treatment of this patient was really challenging. methotrexate is a cheap medication but it is hepatotoxic. this patient has high serum alkaline phosphatase and low serum albumen, on the other hand, the biologic therapy is highly expensive and unaffordable by the patient. 5. conclusion in the absence of liver disease and alcohol consumption excluded by history, examination and investigations, high serum alkaline phosphatase is considered a relative contraindication to methotrexate therapy that can be given successfully and safely to patients with severe forms of psoriasis under close supervision in the ward. 6. recommendation methotrexate is recommended for the treatment of severe morbid forms of psoriasis. for those who can afford or in good centers the other option is the biologic therapy or cyclosporine mainly in patients with absolute contraindications to methotrexate. references [1] rapp, s. r., feldman, s. r., exum, m. l., et al. (1999). psoriasis causes as much disability as other major medical diseases. journal of the american academy of dermatology, vol. 41, p. 401e7 [2] national institute for health and clinical excellence. (2008). infliximab for the treatment of psoriasis. retrieved from: http://www.nice.org.uk/ta134> (last accessed july 25, 2008). [3] alakloby, o. m. (2005). pattern of skin disease in eastern saudi arabia. saudi medical journal, vol. 26, p. 1610. [4] national institute for health and clinical excellence. (2008). adalimumab for the treatment of psoriasis. retrieved from: http://www.nice.org.uk/ta146 (last accessed doi 10.18502/sjms.v14i1.4375 page 7 http://www.nice.org.uk/ta134 http://www.nice.org.uk/ta146 sudan journal of medical sciences suad hh et al august 30, 2008). [5] roenigk, h. h., auerbach, r., maibach, h. i., et al. (1998). methotrexate in psoriasis: consensus conference. journal of the american academy of dermatology, vol. 38, pp. 478–485. [6] roenigk, h. h., maibach, h. i., and weinstein, g. p. (1973). methotrexate therapy for psoriasis, guideline revisions. archives of dermatology, vol. 108, p. 35. [7] roenigk, h. h., auerbach, r., maibach, h. i., et al. (1982). methotrexate guidelines– revised. journal of the american academy of dermatology, vol. 6, pp. 145–155. [8] martyn-simmons, c. l., rosenberg, w. m. c., cross, r., et al. (2014). validity of noninvasive markers of methotrexate-induced hepatotoxicity: a retrospective cohort. dermatology, vol. 171, no. 2, pp. 267–273. retrieved from: https://doi.org/10.1111/bjd. 12782 [9] peckham, p. e., weinstein, g. d., and mccullough, j. l. (1987). the treatment of severe psoriasis, a national survey. archives of dermatology, vol. 123, pp. 1303–1307. [10] dahlman-ghozlan, k., ortonne jp, heilborn j, et al. altered tissue expression pattern of cell adhesion molecules, icam-1, e-selectin and vcam-1, in bullous pemphigoid during methotrexate therapy. exp dermatol 2004;13:65e9. [11] montaudi,_e. h., sbidian, e., paul, c., et al. (2011). methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity. journal of the european academy of dermatology and venereology, vol. 25, p. 12. [12] retrieved from: https://www.researchgate.net. doi 10.18502/sjms.v14i1.4375 page 8 https://doi.org/10.1111/bjd.12782 https://doi.org/10.1111/bjd.12782 https://www.researchgate.net introduction plan of management outcome discussion conclusion recommendation references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4377 production and hosting by knowledge e research article epidemiology of antibiotic resistance in culture-positive hospitalized patients in selected hospitals in khartoum, sudan nagwa m. el amin1, einas a. osman2, leena al-hassan3, and ihab b abdalrahman4 1qassim college of medicine, qassim university, ksa 2africa university, sudan 3brighton and sussex centre for global health research, brighton, uk 4department of internal medicine, university of khartoum, sudan abstract objective: to study the prevelence of antibiotic resistance and the prevalent bacterial isolates in hospitalized patients in khartoum hospitals. materials & methods: a cross-sectional prevalence study was carried out during the period of april–november 2015 in khartoum; 226 bacterial cultures were included. identification of isolates using standard biochemical tests and antibiotic susceptibilities were determined using disc diffusion method. results were interpreted according to the standards of the british society of antimicrobial chemotherapy. results: eight bacterial species were isolated: staphylococcus aureus, enterococcus faecalis, streptococcus spp., klebsiella pneumoniae, pseudomonas spp., escherichia coli, proteus spp., and acinetobacter spp. s. aureus was the most prevalent, the majority of which were resistant to methicillin/oxacillin (mrsa). cultures in our study were mainly from urine (36.7%), blood samples (37.2%), and wound cultures (19%). more than 90% of the tested isolates were resistant to cefuroxime; 54% and 73.8% of gram-positive and gram-negative isolates, respectively, were resistant to ceftazidime. furthermore, there was a high meropenem resistance among gram-negative isolates tested. multi-resistant acinetobacter spp. as well as vancomycin-resistant s. aureus was isolated. gram-negative isolates showed good susceptibilities to aminoglycosides as well as ciprofloxacin. however, the high resistance rate to these antibiotics was observed in gram-positive isolates in these hospitals. conclusion: methicillin-resistant s. aureus was the most prevalent organism. gramnegative isolates showed good susceptibilities to aminoglycosides and ciprofloxacin. there were high resistance rates to cefuroxime, ceftazidime, and meropenem. five vancomycin-resistant s. aureus were identified. keywords: antibiotic resistance, khartoum hospitals how to cite this article: nagwa m. el amin, einas a. osman, leena al-hassan, and ihab b abdalrahman (2019) “epidemiology of antibiotic resistance in culture-positive hospitalized patients in selected hospitals in khartoum, sudan,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 15–23. doi 10.18502/sjms.v14i1.4377 page 15 corresponding author: nagwa m. el amin; email: nagwaelamin@qumed.edu.sa received 15 january 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e nagwa m. el amin et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4377&domain=pdf&date_stamp=2019-03-31 mailto:nagwaelamin@qumed.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nagwa m. el amin et al 1. introduction the worldwide spread of bacterial resistance to antimicrobial agents may limit the future progress of medicine. a huge environmental antibiotic pressure, resulting from industrial production and marketing of these drugs, has simultaneously contributed to the increase in the diversity of resistant phenotypes, to the selection of the fittest among them, and to the spreading of resistance genes. the antimicrobial resistance is recognized as global crises, and in 2012, who patient safety launched a book, the evolving threat of antimicrobial resistance options for action. in sudan, few studies were performed to assess the problem of antibiotic resistance which we expect to be a major one as antibiotics use is not under control, and infection control measures are not regularly practiced in hospitals [1]. the aim of this study was to study the frequency of antibiotic-resistant bacteria and to identify the most prevalent organisms causing hospital infections in four hospitals in khartoum state. we also studied the prevalence of multi-resistant bacteria in the hospitals included in the study. 2. materials and methods ethical approval was obtained from the ministry of health khartoum, sudan. a crosssectional study was conducted. 2.1. sampling procedure the samples included bacteria grown on media. the sample frame composed of all positive cultures during the study period. systematic random sampling was used to select the sample. 2.2. patients and samples the study was carried out in four tertiary hospitals in khartoum, sudan. samples (blood in case of sepsis or from other sites of infection) were collected by the hospital staff upon the development of infection. when bacterial growth was confirmed by the microbiology laboratories at the hospital, the species were identified and stored at –80ºc until further use. the isolates were identified using basic biochemical identification tests according to the clinical and laboratory standards institute [2, 3]. antibiotic doi 10.18502/sjms.v14i1.4377 page 16 sudan journal of medical sciences nagwa m. el amin et al susceptibility testing was performed using the disc diffusion method according to the british society for antimicrobial chemotherapy (bsac) [4, 5]. a database was set up to record the data associated with the bacterial sample. 3. results during the period between april and november 2015, 622 positive cultures were grown in the four different hospitals under study (soba university hospital, omdurman pediatric hospital, reibat hospital, and bahri teaching hospital). two hundred and twenty-eight isolates were selected by a systematic random stratified method from hospitals’ microbiology laboratories. isolates were recovered from different clinical samples, collected from hospitalized patients with clinical symptoms and signs of infection. the phenotypic identification revealed mainly eight bacterial species (spp.) including staphylococcus aureus, enterococcus faecalis, streptococcus spp. (figure 1), klebsiella pneumoniae, pseudomonas spp., escherichia coli, proteus spp., and acinetobacter spp (figure 2). soba university hospital and reibat hospital laboratories are the only hospitals in our study that performed blood cultures. all four microbiology laboratories processed different clinical samples such as urine, wound swabs, sputum, body fluids, and swabs from the upper respiratory tract. gram-positive bacteria mainly s. aureus and s. faecalis were the most frequent isolates from all sites of infection. gram-negative bacilli were mainly isolated from blood and urine cultures. analysis of the antibiotic susceptibility pattern among the isolates in the study had shown a high resistance rate to many 𝛽-lactam antibiotics. the highest resistance rate was found to be to amoxicillin, followed by cefoxitin, cefuroxime, and ampicillin, respectively (tables 1 and 2). staphylococcus aureus was the most prevalent organism causing infections in all the hospitals studied (figure 1). the majority of s. aureus isolates were resistant to methicillin/oxacillin (mrsa), which indicates their multi-resistant phenotype. infection with mrsa was highest among omdurman hospital patients where 80% of the s. aureus isolates were mrsa. alarmingly, vancomycin-resistant s. aureus (vrsa) isolates were found in two of the hospitals under study and multi-resistant acinetobacter spp. as well as carbapenem (meropenem)-resistant gram-negative bacteria were isolated doi 10.18502/sjms.v14i1.4377 page 17 sudan journal of medical sciences nagwa m. el amin et al in one hospital. twenty percent of the gram-negative isolates tested for meropenem susceptibility was resistant to this antibiotic. gram-negative isolates from all four hospitals showed good susceptibilities to aminoglycosides such gentamycin and amikacin as well as the fluoroquinolone, ciprofloxacin (table 2). however, a high resistance rate was observed in gram-positive isolates in these hospitals (table 1). table 1: antibiotic susceptibility pattern among gram-positive isolates. antibiotic % susceptible isolates % resistant isolates vancomycin 92.8 7.2 gentamycin 79.3 20.7 ceftriaxone 73.9 26.1 amikacin 67.7 32.3 cefotaxime 54.2 45.8 ciprofloxacin 59.3 40.7 ceftazidime 45.9 54.1 erythromycin 38.2 61.8 oxacillin/methicillin 38.1 61.9 trimethoprim-sulfamethoxazole 36.7 63.3 amoxicillin-clavulanate 35.7 64.3 ampicillin 25 75 table 2: antibiotic susceptibility pattern among gram-negative isolates. antibiotic % susceptible isolates % resistant isolates colistin 100 0 amikacin 92.5 7.5 meropenem 79.8 20.2 gentamycin 77.6 22.4 ceftriaxone 63.2 36.8 ciprofloxacin 62.2 37.8 trimethoprimsulfamethoxazole 33.7 66.3 ceftazidime 26.2 73.8 piperacillin-tazobactam 14.7 85.3 cefuroxime 5.3 94.7 cefoxitin 5.1 ampicillin/amoxicillin 1 99 doi 10.18502/sjms.v14i1.4377 page 18 sudan journal of medical sciences nagwa m. el amin et al figure 1: gram-positive bacteria cultured from hospitalized infected patients over an eight-months period with s. aureus being the most common in all four hospitals. figure 2: klebsiella pneumoniae was the most prevalent gram-negative isolate during the study period and acinetobacter spp. was the least prevalent. 4. discussion the majority of positive cultures in this study were isolated from patients with urinary tract infections (uti) (36.7%) and blood samples from patients with bloodstream infections. uti, particularly catheter-associated urinary tract infections (cautis) were shown to account for approximately 40% of all healthcare-associated infections [7]. despite studies showing the benefit of interventions for the prevention of cauti, the adoption of these practices has not occurred in many hospitals in sudan. the most frequent pathogens causing healthcare-associated uti include e. coli, p. aeruginosa, enterococci, and candida albicans; in our study, uti was mainly caused doi 10.18502/sjms.v14i1.4377 page 19 sudan journal of medical sciences nagwa m. el amin et al by k. pneumoniae, s. aureus, e. coli, e. faecalis, pseudomonas spp., and proteus spp. studies have shown that both the species distribution and rates of resistance vary considerably among the institutions and regions [7, 8]. the second highest culture-positive rate in this study was observed in blood cultures that have very serious implications as shown in former studies. it is well recognized that hospital-acquired severe sepsis was associated with both higher mortality and resource utilization than community-acquired severe sepsis [9]. cultures from wounds, including surgical site infections (ssis), were the third frequent positive cultures in this study (19%). ssis are a major contributor to the morbidity and mortality in postsurgical care. the risk for ssis is multifactorial and includes a host of microbial, patient-related, and procedure-related factors [10]. the incidence of ssi was shown to be as high as 20%, depending on the surgical procedure, the surveillance criteria used, and the quality of data collection. in many ssis, the responsible pathogens originate from the patient’s endogenous flora. the causative pathogens depend on the type of surgery; the most commonly isolated organisms are s. aureus, coagulase-negative staphylococci, enterococcus spp., and e. coli [11]. in the current study, wound infections, including ssis, were frequently caused by s. aureus, the majority of which were mrsa. high prevalence of mrsa is a major problem identified in this study and needs to be addressed urgently. methods such as screening for colonization with mrsa is needed as it has been shown to increase the risk of infection [12–14]. vrsa was identified in two hospitals. the emergence of vrsa emphasizes the high need for programs to prevent the spread of antimicrobial-resistant microorganisms and control the use of antimicrobial drugs in healthcare settings. multi-resistant acinetobacter spp. was isolated in the intensive care unit-hospitalized patients in one of the hospitals studied. acinetobacter spp. was grown from different infection sites. since the 1970s, the spread of multidrug-resistant (mdr) acinetobacter strains among critically ill, hospitalized patients, and subsequent epidemics, have become an increasing cause of concern. before the 1970s, acinetobacter infections were mostly post-surgical uti in patients hospitalized in surgical units. the significant improvement in resuscitation techniques during the last 30 years has changed the types of infection caused by acinetobacter spp. and since the 1980s, it has spread rapidly among patients in intensive care units [15, 16]. the isolates in the present study exhibited high resistance rates to many antibiotics including cephalosporin and carbapenem antibiotics. resistance to ceftazidime ranged doi 10.18502/sjms.v14i1.4377 page 20 sudan journal of medical sciences nagwa m. el amin et al from 54.1% to as high as 73.8% in some hospitals. the presence of the extended 𝛽lactamase ctx-m is likely in these isolates [17, 18]. the very high rate of resistance to amoxicillin (99%) amongst the isolates in the current study is very alarming. the probability of spread of a resistant clone should be investigated. high resistance to meropenem was found in gram-negative isolates under study that must be handled seriously as carbapenem resistance spreads rapidly and causes challenges in treatment, resulting in high mortality and morbidity rates. it is necessary to observe the use of these antibiotics and to take essential infection control precautions to avoid the spread of this resistance [19–22]. 5. conclusions • staphylococcus aureus was the most prevalent organism all the hospitals studied. the majority of s. aureus isolates were mrsa. • gram-negative isolates from all four hospitals showed good susceptibilities to gentamycin and amikacin as well as ciprofloxacin. however, a high resistance rate was observed in gram-positive isolates in these hospitals. • there are high resistance rates to cefuroxime and ceftazidime. high carbapenem resistance was found amongst gram-negative isolates. • five vrsa were identified. references [1] ibrahim, m. e., bilal, n. e., and hamid, m. e. 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(2014). the evolving threat of antimicrobial resistance: options for action. indian journal of medical research, vol. 139, no. 1, pp. 182–183. retrieved from: http://www.ijmr.org.in/article.asp?issn=0971-5916;year= 2014;volume=139;issue=1;spage=182;epage=183;aulast=kapi. doi 10.18502/sjms.v14i1.4377 page 23 http://download.springer.com/static/pdf/228/art%3a10.1186%2f2047-2994-3-17.pdf?originurl=http://aricjournal.biomedcentral.com/article/10.1186/2047-2994-3-17&token2=exp=1473179291~acl=/static/pdf/228/art%253a10.1186%25 http://download.springer.com/static/pdf/228/art%3a10.1186%2f2047-2994-3-17.pdf?originurl=http://aricjournal.biomedcentral.com/article/10.1186/2047-2994-3-17&token2=exp=1473179291~acl=/static/pdf/228/art%253a10.1186%25 http://download.springer.com/static/pdf/228/art%3a10.1186%2f2047-2994-3-17.pdf?originurl=http://aricjournal.biomedcentral.com/article/10.1186/2047-2994-3-17&token2=exp=1473179291~acl=/static/pdf/228/art%253a10.1186%25 http://ovidsp.ovid.com/ovidweb.cgi?t=js&page=reference&d=emed11&news=n&an=2013695730 http://ovidsp.ovid.com/ovidweb.cgi?t=js&page=reference&d=emed11&news=n&an=2013695730 http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2014;volume=139;issue=1;spage=182;epage=183;aulast=kapi http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2014;volume=139;issue=1;spage=182;epage=183;aulast=kapi introduction materials and methods sampling procedure patients and samples results discussion conclusions references sudan journal of medical sciences volume 13, issue no. 4, doi 10.18502/sjms.v13i4.3593 production and hosting by knowledge e research article zap-70 expression in b-chronic lymphocytic leukemia in sudanese patients enaam abdel-rhman abdel-gader1,2, nada hassan eltayeb3, tasniem ahmed eltahir2, osama ali altayeb4, eman abbass fadul4, eldirdiri m. abdel rahman2, and tarig h. merghani5 1department of pathology, faculty of medicine, alneelain university, khartoum, sudan 2khartoum radioisotope center, khartoum, sudan 3department of physiology, faculty of medicine, alneelain university, khartoum, sudan 4flow cytometry laboratory for leukemia & lymphoma diagnosis, khartoum, sudan 5department of physiology, faculty of medicine, university of khartoum, khartoum, sudan abstract background: chronic lymphocytic leukemia is the most common form of leukemia in adults. the prognostic impact of zap-70 in cll has been reported in several studies. the aim of conducting this study was to investigate the prevalence of zap-70 in sudanese patients with chronic lymphocytic leukemia attending khartoum oncology hospital. materials and methods: a total of 93 newly diagnosed patients with chronic lymphocytic leukemia were enrolled in this study. lymphadenopathy and organomegaly were assessed in all participants using clinical examination, chest radiography, and abdominal ultrasound. full blood count was carried out by an automated hematology analyzer. zap-70 was evaluated using flowcytometry on peripheral blood samples. zap-70 was defined as positive expression at a cutoff level of 20%. results: there were 63 (67.7%) males and 30 (32.3%) females and the median age of the group was 63 years; 68 patients (73.1%) were presented with anemia and 66 (70.9%) had lymphadenopath;y. majority of our patients 35 (37.6%) were in rai stage iv. zap-70 positivity was detected in 21 patients (22.6%). there was no statistically significant association of zap-70 with age, sex, lymphadenopathy, organomegaly, hemoglobin concentration, total white blood cell count, platelet count and rai staging system (p-value > 0.05). conclusion: only 21 patients (22.6%) were zap-70 positive. there was no association between zap-70 and the study variables. further studies to evaluate prognostic role of zap-70 in sudanese patients with chronic lymphocytic leukemia are recommended. keywords: zap-70, chronic lymphocytic leukemia, flowcytometry how to cite this article: enaam abdel-rhman abdel-gader, nada hassan eltayeb, tasniem ahmed eltahir, osama ali altayeb, eman abbass fadul, eldirdiri m. abdel rahman, and tarig h. merghani (2018) “zap-70 expression in b-chronic lymphocytic leukemia in sudanese patients,” sudan journal of medical sciences, vol. 13, issue no. 4, pages 230–239. doi 10.18502/sjms.v13i4.3593 page 230 corresponding author: enaam abdel-rhman abdel-gader; email: enaamresearch@gmail.com received 10 october 2018 accepted 12 december 2018 published 26 december 2018 production and hosting by knowledge e enaam abdel-rhman abdel-gader et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v13i4.3593&domain=pdf&date_stamp=2018-12-26 mailto:enaamresearch@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences enaam abdel-rhman abdel-gader et al 1. introduction chronic lymphocytic leukemia (cll) is characterized by a heterogeneous clinical course [1] with survival times ranging from months to decades; this heterogeneity reflects the biological diversity of cll [2]. neoplastic cells express certain markers that can help to predict the prognosis of patients with cll [3, 4]. the detection of these markers provides a vital tool that can stratify patients into groups with good or poor prognosis [5]. the traditional prognostic parameters (clinical stage, pattern of bone marrow infiltration, lymphocyte doubling time, beta-2 microglobulin levels, and lactate dehydrogenase level) are valuable but less accurate in prediction of disease progression [6, 7]. last years, research in prognostic factors in cll has focused on biological factors such as the variable region of the immunoglobulin heavy chain gene (igvh) mutational status, cd38 and zap-70 expression. the strongest independent prognostic factor in cll is the presence of igvh somatic mutations [8]. however, igvh mutation studies are not cost effective, technically demanding and are not available at most centers. therefore, there is a need for surrogate marker that is reliable, easily standardized and more suitable for application in clinical laboratories [9]. the zeta-chain-associated protein kinase-70 (zap-70) was first described in 2003 [5] and is present in normal t-cells, nk-cells, and not present in normal b-cells. published reports demonstrated a strong association between overexpression of zap-70 and unmutated ighv genes in cll. also, low expression of zap-70 is associated to mutated ighv genes [5, 10, 11] and time to disease progression and overall survival (os) [5, 10– 13]. although there has a consensus on the prognostic significance of zap-70, the detection method of zap-70 at various laboratories has been a source of discussion [14]. several methods are used to study zap-70 expression in cll but flowcytometry remains the most suitable, reliable and applicable method into routine use [10]. crespo et al. [15] and rassenti et al. [11] demonstrated that patients with more than 20% zap-70 positive cells have higher risk of disease progression and lower survival rates compared with those with less than 20% zap-70-positive cells, suggesting that zap-70 might be more indicative of worse prognosis compared with the mutational status of the ighv. in this study, the authors aimed to determine the frequency of zap-70 among sudanese patients with chronic lymphocytic leukaemia and to associate zap-70 doi 10.18502/sjms.v13i4.3593 page 231 sudan journal of medical sciences enaam abdel-rhman abdel-gader et al expression to age, sex, lymphadenopathy, organomegaly, haemoglobin concentration, twbcs count, platelet count, and modified rai clinical staging system. 2. materials and methods 2.1. patients a total of 93(69.7% males and 30.3% females) newly diagnosed (based on cbc and immunophenotyping), untreated b-cll patients, attending the khartoum oncology hospital during the period from september 2016 to february 2017, were enrolled in this cross-sectional study. patients were diagnosed as cll, in accordance with the international cll workshop criteria [16] and the guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [17]. also, all the patients were staged according to the rai staging system [18]; 3 ml of peripheral blood (pb) was collected in edta tubes from each patient according to the standard protocol. the pb samples were processed within 6–24 h of collection, preserved at room temperature (22–24ºc). clinical and demographic data were collected in a predesigned questionnaire. this study was approved by the ethical committee of the sudan medical specialty board (smsb) and an informed consent was obtained from all patients before sampling in accordance to the guidelines and requirements of the ethical committee. 3. methods 3.1. clinical examination each patient was subjected to a history taking and physical examination that was performed to determine the diameters of lymph nodes. chest x-ray and abdominal ultrasound were used to evaluate the size of the liver and spleen. 3.2. complete blood count (cbc) cbc was carried out using automated cell counter (sysmex xe-2100𝑇𝑀). 3.3. immunophenotyping (ipt) ipt was carried out to confirm the diagnosis of cll using the following monoclonal antibodies (mo ab) (beckman coulter); cd45, cd5, cd19, cd20, cd22, cd23, kappa and doi 10.18502/sjms.v13i4.3593 page 232 sudan journal of medical sciences enaam abdel-rhman abdel-gader et al lambda light chains, fmc7, cd79b. a marker was considered positive at a cutoff level of 20%. 3.4. flowcytometric analysis of intracellular zap-70 expression four color flowcytometer (coulter epics xl-mcltm flowcytometer – miami, florida – usa) with system ii software was used to detect and measure the intracellular zap70 expression in pb samples according to the following protocol; first perfix-nc a fixation and permeabilization kit was used as follows: pipette 50 μl of blood sample into the bottom of each appropriately labeled tube. add 5 μl of the fixativereagent to each tube. vortex immediately and incubate for 15 min at room temperature (18–25∘c). vortex the fixed specimen again and add 300 μl of the permeabilizing reagent to each tube; vortex immediately. then, immediately add to each tube 20 μl zap-70 isoclonic control. vortex immediately and incubate for 10 min at room temperature (18–25∘c). add to each tube 20 μl zap-70-pe (pn b57658). vortex immediately and incubate for 45 min at room temperature protected from light. add 3 ml of the final 1 x reagent (prepared from the 10 x concentrated final solution) to each tube; vortex immediately. pellet the cells at 500 x g for 5 minutes, and completely discard the supernatant by aspiration. re-suspend the cell pellet in 0.5 ml of the same final 1x reagent; the sample is now ready for acquisition on a flowcytometer. the zap-70 expression was considered positive at a cutoff level of 20%. 3.5. data analysis the collected data were analyzed using the software program of the statistical package for social science for windows (spss), version 19. quantitative variables were summarized as mean and median and qualitative variables as percentage. categorical variables were analyzed using chi-square test. p value less than 0.05 was defined as significant. 3.6. results a total of 93 cll patients (63 (67.7%) males and 30 (32.3%) females) were involved in this study with a mean (± sd) age 62.29 ± 11.68, median 63 years (range: 36–95). according to rai staging system, 35 (37.6%) patients were in stage iv, 28 (30.1%) patients were in stage iii, 17 (18.3%) patients were stage ii, 9 (9.7%) patients were doi 10.18502/sjms.v13i4.3593 page 233 sudan journal of medical sciences enaam abdel-rhman abdel-gader et al in stage i, 4 (4.3%) patients were stage 0; 66 (71.0%) patients presented with lymphadenopathy, 50 (53.8%) with splenomegaly, 23 (24.7%) with hepatomegaly. anemia was detected in 68 (73.1%) patients and thrombocytopenia in 42 (45.2%) patients (table 1). immunophenotyping results revealed characteristic cll immunophenotype. we found that the mean (±sd) expression of zap70 was 17.06 ± 21.89, with a median of 8.3 (range: 0.03–85.5%). out of 93 patients, only 21 (22.6%) patients were positive for zap70 expressions at cutoff levels of 20%, whereas 72 (77.4%) patients were negative. no significant association was observed between zap70 expressions at cutoff levels of 20% and the study variables (age, sex, lymphadenopathy, organomegaly, hb concentration, twbcs count, platelets count, and rai staging system) (p-value > 0.05) (table 2). t 1: demographic, clinical and laboratory characteristics of patients. parameter frequency no. (%) parameter frequency no. (%) age hemoglobin (g/dl) mean ± sd 62.29 ± 11.68 low 68 (73.1%) median (range) 63 (36–95) normal 25 (26.9%) ≥ 60 61 (65.6%) leukocyte count (×109/l) < 60 32 (34.4%) < 50 27 (29.0%) sex ≥ 50 66 (71.0%) male: female ratio 1:0.48 platelets count (×109/l) male 63 (67.7%) < 150 42 (45.2%) female 30 (32.3%) ≥ 150 51 (54.8%) lymphadenopathy rai staging system present 66 (71.0%) stage 0 4 (4.3%) absent 27 (29.0%) stage i 9 (9.7%) splenomegaly stage ii 17 (18.3%) present 50 (53.8%) stage iii 28 (30.1%) absent 43 (46.2%) stage iv 35(37.6%) hepatomegaly zap-70 expression present 23 (24.7%) positive 21 (22.6%) absent 70 (75.3%) negative 72 (77.4%) 4. discussion zap-70 has a great future as a prognostic marker as it has been found that zap-70 is highly predictive of time to treatment in a large cohort of early-stage (rai 0-1) and untreated cll [11, 19]. the optimal cutoff for zap-70 positivity was defined by many authors as 20% [10, 12, 20, 21]. we found that 21 (22.6%) patients were positive for doi 10.18502/sjms.v13i4.3593 page 234 sudan journal of medical sciences enaam abdel-rhman abdel-gader et al t 2: association of zap-70 expression with the study variables. variables zap-70 frequency no. (%) p-value zap-70 positive zap-70 negative age ≥ 60 11 (52.4%) 50 (69.4%) 0.15 < 60 10 (47.6%) 22 (30.6%) sex male 14 (15.1%) 49 (52.7%) 0.91 female 7 (7.5%) 23 (24.7%) lymphadenopathy present 15 (16.1%) 51 (54.8%) 0.96 absent 6 (6.5%) 21 (22.6%) splenomegaly present 12 (12.9%) 38 (40.9%) 0.83 absent 9 (9.7%) 34 (36.5%) hepatomegaly present 5 (5.4%) 18 (19.4%) 0.85 absent 16 (17.2%) 54 (58.0%) hemoglobin concentration (g/dl) low 15 (16.1%) 53 (57.0%) 0.84 normal 6 (6.5%) 19 (20.4%) twbcs count ×109 < 50 5 (5.4%) 22 (23.7%) 0.55 ≥ 50 16 (17.2%) 50 (53.7%) platelet count ×109 < 150 9 (9.7%) 33 (35.5%) 0.81 ≥ 150 12 (12.9%) 39 (41.9%) rai staging system stage 0 1 (1.1%) 3 (3.2%) 0.88 stage i 1 (1.1%) 8 (8.6%) stage ii 3 (3.2%) 14 (15.1%) stage iii 7 (7.5%) 21 (22.6%) stage iv 9 (9.6%) 26 (28.0%) zap70 expressions at cutoff levels of 20% and 72 (77.4%) patients were negative. many published reports indicated zap-70 positivity in cll ranging from 25% to 57% as presented in table 3; our result is slightly lower. our results revealed that there was no significant association of zap-70 with age, sex, lymphadenopathy, organomegaly, hemoglobin concentration, twbcs count, platelets count, and rai staging system (p > 0.05). our findings go in line with a study done by gogia et al. from india who reported no association of zap-70 positivity with doi 10.18502/sjms.v13i4.3593 page 235 sudan journal of medical sciences enaam abdel-rhman abdel-gader et al age, sex, lymphadenopathy, organomegaly, and rai staging system [9]. a study by del poeta et al. and hus et al. indicated a significant correlation between high zap-70 levels and advanced rai stage and splenomegaly [20 22]. this is in disagreement with our results. on the other hand, el-kinawy et al. reported that zap-70 expression was significantly associated with advanced rai stages 3 and 4, while it was negatively correlated to hb levels and platelet counts [23]. crespo et al. [10] found that at a cutoff of 20%, zap70 positivity clearly separated cll patients into two groups; those with < 20% zap70 had increased survival time and decreased chance of disease progression. in most laboratories, zap70 is considered positive when at least 20% of the cll-cells have a signal that is greater than the background control signal. subjectivity in these methods can lead to variable results among research laboratories. to overcome this subjectivity, it has been suggested that mean fluorescence intensity (mfi) values from cll-cells and background t lymphocytes should be measured rather than calculating the percentage of positive cells [24]. rossi et al [24] reported that when using mfi values and calculating the ratio of t-cells to b-cells, those patients with a ratio lower than 3 had a shorter time-to-treatment than zap70-negative cll patients and those estimated to be zap70-positive by the t-cell percentage method only [25]. unfortunately, prognostic impact of zap70 could not be investigated in our study due to lack of follow-up. contrast of our results with other workers may be contributed to by many factors such as biology of disease in the sudanese population, sample sizes, and sensitivity of method. t 3: comparison of zap 70 with literature. study year no. of patients zap 70% crespo et al. [10] 2003 56 57 schoroer et al. [26] 2005 252 46 hus et al. [24] 2006 156 36 d’arena et al. [21] 2007 157 36 gogia et al. [9] 2013 80 25 present study 2017 93 22.6 5. conclusion the present study was aimed to study the prevalence of zap-70 in cll patients and to relate them to the study variables (age, sex, lymphadenopathy, organomegaly, doi 10.18502/sjms.v13i4.3593 page 236 sudan journal of medical sciences enaam abdel-rhman abdel-gader et al hemoglobin concentration, twbcs count, platelets count, and rai staging system). zap-70 positivity was detected in 21 patients (22.6%). there was higher frequency of high-risk group among study population. there was no significant association of zap-70 positivity with the study variables. the prognostic value of zap-70 should be tested in the setting of a controlled prospective trial. further studies are strongly recommended to develop a standardized flowcytometry protocol using mfi and t/b ratio method to verify the prognostic impact of zap70. acknowledgment the authors are grateful to those who have contributed so much to this work; khartoum oncology hospital staff and the flowcytometry laboratory for leukemia & lymphoma diagnosis. conflict of interests the authors declare that they have no competing interests. references [1] rozman, c. and montserrat, e. 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(2005). combined analysis of zap 70 and cd 38 expression as a predictor of disease progression in b cell chronic lymphocytic leukemia. leukemia, vol. 19, pp. 750–758. doi 10.18502/sjms.v13i4.3593 page 239 introduction materials and methods patients methods clinical examination complete blood count (cbc) immunophenotyping (ipt) flowcytometric analysis of intracellular zap-70 expression data analysis results discussion conclusion acknowledgment conflict of interests references sudan journal of medical sciences volume 13, issue no. 4, doi 10.18502/sjms.v13i4.3606 production and hosting by knowledge e research article the knowledge of palliative care and the attitude toward it among the nurses at sabia general hospital 2018 manal bilal omdurman islamic university, omdurman, sudan abstract background: the aim of this study is to assess the knowledge of palliative care and the attitude toward it among the nurses working in sabia general hospitals and to find out the association between the nursing staff, knowledge, attitude, and selected demographic variables. material and methods: the author performed a cross-sectional descriptive survey using a self-administered questionnaire. the total number of completed and returned questionnaires was 53, giving a 100% response rate. the study was conducted between december 2017 and january 2018 and a simple random sampling was performed among 53 nurses working in the sabia general hospital. methodology: for data collection, a self-administrative questionnaire was developed and used for assessment by the researcher. nurses’ socio-demographic characteristics such as their age, gender, nursing qualification, department of work, work experience, training in caring terminally ill clients, and their knowledge of and attitude toward palliative care were assessed; the relation between socio demographic data and knowledge and attitude was also assessed. results showed that respondents had fair knowledge of palliative care 27 (50.9%) and fair attitude 30 (56.6%). it was proved that there is a significant relation between knowledge and demographic data; p-value is 0.004. conclusion: nurses showed poor knowledge toward palliative care and half of them showed a fair attitude. keywords: nurses, knowledge, attitude, palliative care 1. introduction life-threatening diseases cause a decrease in the quality of life and they bring about various problems including physical, psychosocial, and spiritual, and especially pain. in patients with diseases that cannot be treated despite the advances in medicine, approaches aiming at reducing the patient’s distress and improving the quality of life should be applied. in accordance with this view, the approach of palliative care has been developed in order to meet the needs of patients and their relatives [1]. how to cite this article: manal bilal (2018) “the knowledge of palliative care and the attitude toward it among the nurses at sabia general hospital 2018,” sudan journal of medical sciences, vol. 13, issue no. 4, pages 301–310. doi 10.18502/sjms.v13i4.3606 page 301 corresponding author: manal bilal; email: manalbelal52@gmail.com received 5 november 2018 accepted 12 december 2018 published 26 december 2018 production and hosting by knowledge e manal bilal. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v13i4.3606&domain=pdf&date_stamp=2018-12-26 mailto:manalbelal52@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences manal bilal palliative care refers to the comfort care that is given to terminally ill person so as to promote comfort and relieve pain. the goal of this care is to provide comfort and highest-quality life; and to not only cure patients, but also address their mental and spiritual needs along with the physical ones [2]. the term ‘palliative’ is derived from the latin word ‘pallium’, meaning a piece of cloth or a curtain [3]. one essential characteristics of palliative care is the necessity of the team approach. the nurse who spends a long time with patients and aims to give them the best-quality care has a prominent place in this team. this is because a nurse is the one member of the health discipline who deals with the life-threatening diseases most closely and directly provides care to patients whose death is imminent [4]. nurses are highest in number when it comes to the healthcare providers in almost every country; they are often the primary caregivers. nurses have been historically involved in the provision of palliative care. they have played various roles in the development of palliative care, offering leadership, support, and focus for the movement [5]. it is necessary for the palliative patients to be admitted to hospital because the problems cannot be handled at home due to the insufficient family care. more than half of the home patients move in their last months only to die because of acute medical problems, lack of professional homecare, or an overload of the informal care [6]. a very important value for palliative care is to enable people to make decision regarding the selection of their end-of-life care and the place of death. data also suggest that most people with advanced illnesses prefer to be cared for and die at home or close to it [7]. nurses as well as other healthcare workers often feel unprepared for their tasks in palliative care and are in much need of more expertise in the field of pain and symptom management, communication, and dealing with ethical dilemmas [8]. aim of the study: to assess the knowledge of palliative care and attitude toward it among the nurses working in sabia general hospital and to find the association between the nursing staff, knowledge, attitude, and selected demographic variables. 2. methodology 2.1. study design descriptive cross-sectional study was used for conducting the study. doi 10.18502/sjms.v13i4.3606 page 302 sudan journal of medical sciences manal bilal 2.1.1. study setting the data were collected from icu, er, medical wards, and surgical wards at sabia general hospital. 2.1.2. study period the study was conducted between december 2017 and january 2018. 2.1.3. study sample simple random sampling consisted of 53 nurses working in the sabia general hospital. 2.1.4. methodology for data collection, a self-administrative questionnaire was developed and used for assessment by the researcher. a. nurses’ socio-demographic characteristic such as their age, gender, nursing qualification, department of work, work experience, training in caring terminally ill clients b. the participants’ knowledge was assessed as follows: each question had true and false choices: 1 point awarded for each correct answer, 0 for incorrect. correct responses were summed up to get a total knowledge score for each participant. total score for all questions reached 19 grades. the knowledge scores were classified into poor knowledge (≤ 50%), fair knowledge(65–50%), and (≥ 65%) good knowledge. c. the attitude was assessed using a 5-item likert scale (ranging from strongly agree (5) to strongly disagree (1)). it had 12-item rating scale with the highest score of 5 for each option and total possible score was 60. the attitude scores were categorized into good (≥ 65%), fair(65–50%), and poor (≤ 50%). data were analyzed using spss package, version 20. the data was analyzed using descriptive (frequency and percentage) and inferential statistics based on the objectives. doi 10.18502/sjms.v13i4.3606 page 303 sudan journal of medical sciences manal bilal 3. results the majority of respondents, 26 (49.1%) were 20 to 30 years old, followed by 18 (34.0%) who were 31–40 years old, and 9 (17.0%) 41–50 years old. out of the total, 27 (50.9%) were female and 26 (49.1%) male. the level of education of the majority of participants, that is, 25 (47.2%) of them were either a diploma or less, which is near to half of respondents. other educational qualifications recorded included 22 (41.5%) nursing bachelor and nursing master6 (11.3%). around 18 (34.0%) were from surgical ward, 14 (26.4%) from medical ward, 13 (24.5%) from icu, and 8 (15.1%) from the emergency department. the majority of nurses, that is 32 (60.4%) of them, had less than 5 years of experience and only 18 (34.0%) indicated more than 5 years of nursing experience and only 3 (5.7%) had between 11 and 15 years of experience. respondents were asked to record if they had received training toward pc, and the findings revealed that only 21(39.6%) nurses had received the training, while 32 (60.4%) of them did not, as shown in table (1). table 2, 3 show that 27(49.1%) nurses had poor mean score knowledge, while 26 (50.9%) had fair mean knowledge level of palliative care. as seen in table 4, more than half of the nurses were more likely to disagree of palliative care being given only to dying patient, 25(47.2%), as well as they also disagree if the nurse should withdraw his/her involvement with the patient 26(49.1). also, 22(41.5%) of them disagreed with the benefits for the chronically sick person to verbalize his/her feelings. on the attitude that the length of time required to give nursing care to a dying person would frustrate the nurse, 31(58.5%) of them disagree, while 12(22.6%) agree. on the attitude of the family to maintain as normal an environment as possible for the dying member, 21(39.6) disagreed, while only 11(20.8%) agreed. the attitude that the family should be involved in the physical care of the dying person were varied from agreeing to disagreeing, 18(34.0%) and 16(30.2%). most nurses disagreed on the question about difficulties to establish close relationship with the family of dying member, 31(58.5%). approximately, more than half of nurses, 31(58.5), agreed with the fact that nursing care for the patient’s family should continue throughout the period of grief and bereavement. it is interesting to note that nursing care should be extended to the family of the dying person (approximately 27(50.9%). about 26.0% agreed that when a patient asks, “nurse am i dying?,” they think it is doi 10.18502/sjms.v13i4.3606 page 304 sudan journal of medical sciences manal bilal t 1: socio demographic data. variable frequency % age 20–30 years 26 49.1 31–40 years 18 34 41–50 years 9 17 gender male 26 49.1 female 27 50.9 nursing qualification diploma or less 25 47.2 bachelor 22 41.5 master 6 11.3 department of work medical ward 14 26.4 surgical ward 18 34 intensive care unit 13 24.5 emergency department 8 15.1 working experience less than 5 years 32 60.4 5–10 years 18 34 11–15 years 3 5.7 training toward pc yes 21 39.6 no 32 60.4 best to change the subject to something cheerful. and they would be uncomfortable if upon entering the room of a terminally ill person, they found him/her crying 21(39.6%) while their attitudes were slightly different regarding the fear to become friends with chronically sick and dying patients. half of them disagree to becoming friends with the patients 27(50.9%). table 5 reveals that there is a high statistically significant relation between nurses’ demographic data and the total mean knowledge (0.004,) and no statistical relation between the total mean of knowledge of palliative care and the hospitals and departments of work (0.201). doi 10.18502/sjms.v13i4.3606 page 305 sudan journal of medical sciences manal bilal t 2: knowledge of nurses about palliative care. statement true(%) false(%) palliative care should be applied as early as possible in patients with chronic and life-threatening diseases 41(77.4) 12(22.6) palliative care is one of the most important components of cancer prevention 12(22.6) 41(77.4) palliative care is a service that starts as soon as diagnosis is made in patients with cancer 21(39.6) 32(60.4) palliative care is a service only for patients with cancer 32(60.4) 21(39.6) palliative care is essentially the care for terminally ill patients 32(60.4) 21(39.6) palliative care helps patients to relieve pain and to improve the quality of care 15(28.3) 38(71.7) palliative care is a therapeutic care 30(56.6) 23(43.4) palliative care seeks to maximize the functional capacity of the individual by being sensitive to religious values, beliefs, culture, and individuality 26(49.1) 27(50.9) palliative care should be started when medical and surgical methods of treatment are ineffective 21(39.6) 32(60.4) palliative care helps patients to relieve pain and suffering during the terminal period and provides a good death without losing one’s dignity 31(58.5) 22(41.5) 4. discussion in this study, the respondents’ age ranges between 21 and25, which represents 50% with a diploma or less, also, most of them are female; half of them did not receive any training program for palliative care, and their experience is less than 5 years. it is necessary for nurses to have good knowledge and attitude toward palliative care, and assessing nursing knowledge and attitude is also important because knowledge and good attitude play an important role in delegating care to the dying member. regarding their knowledge about palliative care, their mean knowledge was between fair and poor. in this study, the description of knowledge scores have shown that 50.9% had fair knowledge and 49.1% had poor knowledge about palliative care. to the contrary, the same study was conducted in addis ababa, and the findings showed that 30.5% of nurses had a good knowledge about the palliative care [9]. the poor or fair knowledge in this study may be due to the lack of updating information regarding palliative care, and this might be due to the fact that pc education program was not carried out regularly in the hospital, or the nurses have to overwork in bedside care due to the shortage in the nursing staff. due to which they have limited time to enhance and update their knowledge on palliative care. doi 10.18502/sjms.v13i4.3606 page 306 sudan journal of medical sciences manal bilal t 3: knowledge of nurses about palliative care. statement yes(%) no(%) palliative care is applied regardless of whether the individual receives treatment 30(56.6) 23(43.4) in the palliative care approach, family members are supported during disease process and during grief period after the death 31(58.5) 22(41.5) palliative care only consists of pain control 31(58.5) 22(41.5) palliative care neither slows down nor accelerates death 38(71.7) 15(28.3) in palliative care the continuity of care is maintained by being together with the patient everywhere including hospital, home, mobile clinic, day care center, and nursing home 43(81.1) 10(18.9) persons who benefit from palliative care should contact with health professionals at any time 25(47.2) 28(52.8) chronic diseases such as chronic obstructive pulmonary disease are also included in the context of palliative care 35(66.0) 18(34) palliative care and hospice care serve the same purpose 28(52.8) 25(47.2 palliative care team includes physicians, nurses, social workers, psychologists physiotherapists, dieticians, pharmacists, chaplains, patients’ relatives, and volunteers 38(71.7) 15(28.3) mean knowledge no % good (> 65%) 0 0 fair (50–65%) 27 50.9 poor (< 50%) 26 49.1 in similar a study conducted in the northern districts, palestine, the mean knowledge of participants turned out to be poor (45.8 %), which in a way supports our study [10]. the description of attitude shows that the mean scores of respondents, 30 (56.6%) of them had fair attitude and 23 (43.4%) had poor attitude toward palliative care. this finding is in contrary with the findings of the study conducted in addis ababa, where 259 (76%) had favorable attitude toward pc [9]. additionally, another study conducted in india indicated that 92.8% of nursing students had favorable attitude (56.7 ± 8.5) toward palliative care which is in contrary to this study [11]. with respect to correlation between knowledge, attitude, and socio demographic data (age, gender, qualification, and work experience), there is a significant relation between knowledge and socio demographic data like age, period of experience, and qualification, p-value 0.004. it means when the nurses’ experience and qualification doi 10.18502/sjms.v13i4.3606 page 307 sudan journal of medical sciences manal bilal t 4: attitude of nurses toward palliative care. statement strongly disagree disagree uncertain agree strongly agree palliative care is given only to the dying patient 25(47.2) 9(17.0) 6(11.3) 0 13(24.5) as a patient nears death; the nurse should withdraw from his/her involvement with the patient 26(49.1) 17(32.1) 1(1.9) 1(1.9) 8(15.1) it is beneficial for the chronically sick person to verbalize his/her feelings 22(41.5) 4(7.5) 3(5.7) 5(9.4) 19(35.8) the length of time required to give nursing care to a dying person would frustrate me 31(58.5) 6(11.3) 1(1.9) 3(5.7) 12(22.6) family should maintain as normal an environment as possible for their dying member 21(39.6) 17(32.1) 3(5.7) 1(1.9) 11(20.8) the family should be involved in the physical care of the dying person 16(30.2) 2(3.8) 2(3.8) 15(28.3) 18(34.0) it is difficult to form a close relationship with the family of a dying member 31(58.5) 3(5.7) 1(1.9) 13(24.5) 5(9.4) nursing care for the patient’s family should continue throughout the period of grief and bereavement 5(9.4) 3(5.7) 1(1.9) 13(24.5) 31(58.5) nursing care should extend to the family of the dying person 0 13(24.5) 1(1.9) 27(50.9) 22.6)) 12 when a patient asks, “nurse am i dying?,” i think it is best to change the subject to something cheerful 27(50.9) 13(24.5) 1(1.9) 0 12(22.6) i am afraid to become friends with chronically sick and dying patients 27(50.9) 13(24.5) 1(1.9) 0 12(22.6) i would be uncomfortable if i entered the room of a terminally ill person and found him/her crying 9(17.0) 5(9.4) 3(5.7) 15(28.3) 21(39.6) mean attitude frequency % good (> 65%) 0 0 fair (50–65%) 30 56.6 poor (< 50%) 23 43.4 increase, their favorable knowledge also improves, which is similar to the study conducted in india, where they found a significant relation between knowledge and demographic data(age), p-value 0.01 [1], while the correlation between attitude and demographic data is insignificant p-value 0.201. doi 10.18502/sjms.v13i4.3606 page 308 sudan journal of medical sciences manal bilal t 5: association between mean scores of knowledge of and attitude toward the palliative care with selected variables. item mean sd p-value knowledge age 1.6792 0.7538 gender 1.5094 0.50469 nursing qualification 1.6981 0.74897 work experience 1.4528 0.60657 0.004 attitudes age 1.6792 0.7538 0.201 gender 1.5094 0.50469 nursing qualification 1.6981 0.74897 work experience 1.4528 0.60657 5. conclusions and recommendations at the end of this study, it was found that nursing students’ knowledge about the concepts of palliative care was poor and attitude was fair; it was affected by sociodemographic characteristics such as age, gender, and qualification, and work experience significantly more than the knowledge. references [1] elçigil, a. (2012). palliative care nursing. gülhane t𝚤p derg, vol. 54, pp. 329–334. [2] retrieved from http://www.growthhouse.org/palliat.html [cited in 2010]. [3] pastrana, t., jünger, s., ostgathe, c., et al. (2008). a matter of definition key elements identified in a discourse analysis of definitions of palliative care. palliative medicine, vol. 22, no. 3, pp. 222–232. [4] prem, v., karvannan, h., kumar, s. p., et al. (2012). study of nurses’ knowledge about palliative care: a quantitative cross-sectional survey. indian journal of palliative care, vol. 18, no. 2, pp. 122–127. [5] allen, d. and marshall, e. s. (2008). children with hiv/aids: a vulnerable population with unique needs for palliative care. journal of hospice & palliative nursing„ pp. 10359–10367. [6] visser, g. (2006). mantelzorg in de palliatief terminale fase. den haag: nizw zorg/lemma. [7] tang, s. t. (2003). when death is imminent: where terminally ill patients with cancer prefer to die and why. cancer nursing, vol. 26, pp. 245–251. doi 10.18502/sjms.v13i4.3606 page 309 http://www.growthhouse.org/palliat.html sudan journal of medical sciences manal bilal [8] armes, p. j. and addington-hall, j. m. (2003). perspectives on symptom control in patients receiving community palliative care. palliative medicine, vol. 17, no. 7, pp. 608–615. [9] kassa, h., murugan, r., zewdu, f., et al. (2014). assessment of knowledge, attitude and practice and associated factors towards palliative care among nurses working in selected hospitals, addis ababa, ethiopia. bmc palliative care, vol. 13, no. 6. [10] ayed, a., sayej, s., harazneh, l., et al. (2015). the nurses’ knowledge and attitudes towards the palliative care. journal of education and practice, vol. 6, no. 4, pp. 91–99. [11] karkada, s., nayak, b., and malathi. (2011). awareness of palliative care among diploma nursing students. indian journal of palliative care, vol. 17, no. 1, pp. 20–23. doi 10.18502/sjms.v13i4.3606 page 310 introduction methodology study design study setting study period study sample methodology results discussion conclusions and recommendations references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2957 production and hosting by knowledge e research article tutors: the valuable resource to enhance medical students’ motivation mohamed nasr elsheikh1, reem khalil1, alsarah diab2, rayyan abdalnabi1, mohamed muneer1, ahmed elhassan1, fadwa mohammed1, shimaa mahalah1, amna khairy1, shahd abdalnabi1, salma shammet3, islam ahmed munier1, ragda abdallah1, mohamed abdelrahim1, najla basheer ahmed mohammed1, nazik elmalaika husain2, siham ahmed balla1, and magda elhadi4 1faculty of medicine, university of khartoum, sudan 2faculty of medicine, omdurman islamic university, sudan 3faculty of oral and dental medicine, university of karary, sudan 4faculty of medicine, university of gezira, sudan abstract background: students’ academic performance is largely affected by their motivation. moreover, health professions’ education needs motivated students who are keen to tolerate the burden of clinical work along with the academic excellence to graduate competently. this study assessed the effect of tutors on students’ motivation. method: a cross-sectional, institution-based study of the first-year medical students at university of khartoum, sudan was conducted. a self-administered questionnaire was used comprising a modified motivated strategies for learning questionnaire (mslq) with students’ evaluation of their tutors after semester one community medicine course. a total of 237 out of 324 students responded. pearson productmoment correlation coefficient was used to test the relationship between motivation and evaluation. hierarchical multiple regression model tested the ability of evaluation factors to predict motivation score. results: there was a significant association between tutor’s characteristics regarding creativity in conducting the sessions, igniting discussion, and adequacy of knowledge about the course contents and the motivation score (p-value = 0.001). there was a strong, positive correlation between the perceived evaluation score and perceived motivation score (r = 0.505, n = 206, p < 0.0005). after controlling age, gender, paternal educational levels, and scores of sudanese certificate upon entry, r squared change = 0.28, f change (9.181) = 8.416, p < 0.001. in the final model, the content of the course was statistically significant, standardized beta = 0.285, indicating that content uniquely explains 5.7% of the variance in total perceived motivation score. conclusion: the evaluation score explained 28% of the variance in student motivation. students’ motivation is significantly associated with tutor’s teaching skills concerning knowledge, creativity, students’ involvement, and attractiveness in conducting the tutorials. improving course content can enhance students’ motivation toward community medicine. keywords: motivation, medical students, tutor, community medicine, sudan how to cite this article: mohamed nasr elsheikh, reem khalil, alsarah diab, rayyan abdalnabi, mohamed muneer, ahmed elhassan, fadwa mohammed, shimaa mahalah, amna khairy, shahd abdalnabi, salma shammet, islam ahmed munier, ragda abdallah, mohamed abdelrahim, najla basheer ahmed mohammed, nazik elmalaika husain, siham ahmed balla, and magda elhadi (2018) “tutors: the valuable resource to enhance medical students’ motivation,” sudan journal of medical sciences, vol. 13, issue no. 3, pages 196–206. doi 10.18502/sjms.v13i3.2957 page 196 corresponding author: mohamed nasr elsheikh; email: almohamed1991@gmail.com received 14 august 2018 accepted 20 september 2018 published 24 september 2018 production and hosting by knowledge e mohamed nasr elsheikh et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:almohamed1991@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed nasr elsheikh et al 1. introduction tutors vary essentially from teachers who lead lecture-based teaching session, as they teach students how to learn and hence prepare them for life-long learning [1]. the effectiveness of tutors in terms of their inherent interest in teaching, subject-matter expertise, and clear communication with student is well-known to enhance a medical student’s achievements [2]. there has been trends of research on tutors, which has included their effect on students’ achievement, process variables, and the relationship between tutors’ characteristics and differential contextual circumstances [3]. nevertheless, none of the studies have addressed their role in students’ motivation. motivation has several theoretical perspectives that focus on the basis of the level of motivation, except for the self-determination theory (sdt) that focuses on the quality of motivation [4]. the sdt emphasizes on the fact that different attributes of motivation in a spectrum has different educational outcomes, which are bounded at one end by intrinsic motivation and by extrinsic motivation at the other, regardless of the motivation level [5, 6]. in recent years, there has been an increase in interest and research into student motivation in medical education, after the light has been shed to the enhancing effect of intrinsic motivation on student learning [7, 8]. the academic performance of medical students is seriously affected by their motivation [9], motivated students can achieve mastery of their field and be academically accomplished [10]. motivation plays a crucial role among medical students, given the different learning settings; from didactic lecture halls to bedside sessions, and the great demand of study and practice on students [9]. motivation is also affected by several factors, some studies have highlighted the effect of parent support, teacher support, problem-based learning curriculum, and types of assessment [11–13]. this study addressed motivation as a dependent variable. it aimed at identifying the effect of tutors on student motivation during the community medicine course among the first-year medical students. 2. methods 2.1. study area this was a descriptive cross-sectional, institution-based study among the first-year medical students at the faculty of medicine, university of khartoum, sudan. doi 10.18502/sjms.v13i3.2957 page 197 sudan journal of medical sciences mohamed nasr elsheikh et al this faculty is located in khartoum city (the capital of the country, sudan). it is the oldest, and number one-ranked medical school in the country. the school admits almost a class of more than 300 students each year. it offers the student upon graduation the bachelor of medicine and bachelor of surgery (mbbs). it has its tertiary hospital, man clinics, and health facilities.the school’s curriculum was updated in the last five years. community medicine became a longitudinal course after this update, which is now spread throughout different study years. 2.2. study population first-year medical students at the faculty of medicine, university of khartoum, were targeted in this study. data were collected immediately after the students finished their first semester. the class size was 324, and the authors covered them completely. informed consent was taken before enrollment in the study. both male and female students were included. the students’ community is highly diverse, with many of them coming from different parts of the country with different backgrounds. the common thing between them is that they are all the top students in the country in their high school certification exam. 2.3. data management and statistical analysis data were collected through a self-administrated semi-structured questionnaire that consisted of three sections; the first contained the demographic data, parents’ educational levels, reading hours per week and the secondary school certificate score. the second section was a pretested modified version of motivated strategies for learning questionnaire (mslq) that was used to measure students’ motivation [14], with internal consistency (cronbach alpha = 0.699), it was constructed with nine questions for both intrinsic and extrinsic motivation, in a form of 7-point likert’s scale (1 = not at all true of me, 7 = very true of me). the motivation likert’s scale points were cumulatively summed to generate the motivation score out of maximum 63 points and then converted into percentages. the motivation score has been furthermore categorized as follows: less than 25% (no motivation), 25–75% (moderate motivation), and more than 75% (high motivation). the questionnaire assessed motivational beliefs including self-efficacy, an individual’s belief in his/her ability for success, and intrinsic value, the degree to which one studies material for the purpose of mastery [15, 16], it also measures the evaluation doi 10.18502/sjms.v13i3.2957 page 198 sudan journal of medical sciences mohamed nasr elsheikh et al score. the evaluation score was the sum of students’ ratings for their tutor’s knowledge, caring about discussion, and creativity and attractiveness in tutorials in addition to the content of the course and venue (on the 7-point likert’s scale), adopted from the department of community medicine students’ feedback questionnaire. data were managed through social package of social sciences (spss), version 25, the associations between variable were tested using one-way analysis of variants test (anova), the relationship between perceived evaluation score, perceived motivation was investigated using pearson product-moment correlation coefficient, and hierarchical multiple regression was used to assess the ability of nine evaluation factors to predict levels of motivation. 3. results out of 237 students, females represented 73.2% of it. the mean age of the respondents ± sd was 19 ± 0.75 years. their mean score of the secondary school certificate was 93.1% (n = 213). regarding the educational level of parents, 61.1% of students’ mothers were educated to university level and more, 31.2% educated to the secondary school level, 3.8% to primary schools, and only 1.3% were illiterate. regarding fathers, 74.3% of students’ fathers were educated to university level and more, 19.8% educated to secondary school level, and only one student’s father (0.4%) was illiterate (table 1). there is a significant association between the fathers’ educational level and motivation score 0.006, but not of the mothers’ educational level (p = 0.50). t 1: educational level of first-year medical students’ parents at the university of khartoum (n = 237). educational level mother father illiterate 1.3% 0.4% khalwa 2.1% 1.3% primary 3.8% 4.2% secondary 31.4% 19.8% university and above 61.4% 74.3% only 6% of students were highly motivated, 56.7% of students were moderately motivated with more internal motivation, 34.6% were moderately motivated with more external motivation, and 2.7% were amotivated (figure 1). the mean score of students’ satisfaction with their tutors’ ability to conduct a creative and attractive tutorial ± sd was 4.28 ± 2.38 out of 7, for their satisfaction with tutors’ care for discussions in tutorial sessions, the mean score ± sd was 4.86 ± 2.20 doi 10.18502/sjms.v13i3.2957 page 199 sudan journal of medical sciences mohamed nasr elsheikh et al figure 1: quality of motivation in first-year medical students of the university of khartoum toward community medicine course. out of 7, and for their satisfaction with the adequacy of tutor’s knowledge about the content of community health course in semester one that helped in understanding difficulties, the mean score ± sd was 5.09 ± 2.06 out of 7. there was a significant association between the motivation score and the tutors’ characteristics in terms of creativity in conducting the sessions, igniting discussion, and adequacy of knowledge about the course contents (p-value = 0.001). the relationship between perceived evaluation score and perceived motivation was investigated using pearson product-moment correlation coefficient. preliminary analyses were performed to ensure no violation of the assumptions of normality, linearity, and homoscedasticity (figure 2). there was a strong, positive correlation between the two variables, r = 0.505, n = 206, p < 0.0005, with high levels of perceived evaluation score associated with higher levels of perceived motivation score (figure 3). hierarchical multiple regression was used to assess the ability of nine evaluation factors to predict levels of motivation after controlling the influence of age, gender, paternal education level, and scores of sudanese certificate upon entry. preliminary analyses were performed to ensure no violation of the assumptions of normality, linearity, multicollinearity, and homoscedasticity. age, gender, paternal education level, and scores of sudanese certificate upon entry were entered at step 1, explaining 4% of the variance in perceived motivation. after the entry of the evaluation factors at step doi 10.18502/sjms.v13i3.2957 page 200 sudan journal of medical sciences mohamed nasr elsheikh et al figure 2: normal probability plot (p-p) of the regression standardized residuals (left) and the scatter plot (right). figure 3: scatter plot showing the effect of evaluation score (independent variable) on motivational score (dependent variable), r2 = 0.255. 2, the total variance explained by the model as a whole was 32.6%, f (14,181) = 6.25, p < 0.001. the nine evaluation factors explained an additional 28% of the variance in motivation, after controlling for age, gender, paternal education level, and scores of sudanese certificate upon entry, r squared change = 0.28, f change (9,181) = 8.416, p < 0.001. in the final model, only one evaluating factor regarding the content was statistically significant, standardized beta = 0.285. doi 10.18502/sjms.v13i3.2957 page 201 sudan journal of medical sciences mohamed nasr elsheikh et al the content in the evaluation score has a part correlation coefficient of 0.239, indicating that content alone uniquely explains 5.7% of the variance in total perceived motivation score. 4. discussion most of the students were below 20-year entrants; the motivation quality did not significantly vary in accordance with age (p = 0.08). relevant literature found only a difference in the motivation between mature-ageand normal-age entrants [17]. domination of females among the study sample reflects the current situation of the dramatic expansion of female students enrolled in medical schools in sudan [18]. in this study, the quality of motivation showed no difference with regard to gender (p = 0.058) that is comparable to findings of studies that investigated motivational elements such as scientific nature of medicine and intellectual challenge, where males and females were similar [19–21]. in contrast to other studies that showed significant variation between females and males in terms of motivation [22], females tend to show more intrinsic motivation, like their desire to help people [19]. males are found to have more extrinsic motivation, such as looking for financial security, social status, and prestige [23]. among tutorial groups, the motivation of female students was also found to be significantly higher than the male students [22]. respondents in this study were descendants of academic families (61.1% and 74.3 of students’ mothers and fathers were educated to university level or more, respectively), and the educational level of fathers had significant association with the students’ motivation (p-value = 0.006), this implies that the role of father’s education is greater in motivating their children. mcharg highlighted the role of parents in motivating their children in his study conducted in the united kingdom among the first and second years’ medical students [11]. a large proportion of semester-one students was intrinsically motivated toward the course (66%), this might be attributed to the interestingness of the course material, aim of excellence, and their curiosity. on the other hand, very few of them were extrinsically motivated (29.5%), and this may be linked to seeking good results in exams, attractiveness of teaching methods, and the ease and understandability of the materials. in this study, tutors have highly significant influence in the summative scores of motivations of their students (p 0.001), by possessing certain characteristics, such as creativity, elaborating discussion of concepts during the session, and having a firm doi 10.18502/sjms.v13i3.2957 page 202 sudan journal of medical sciences mohamed nasr elsheikh et al grasp of course contents. a study by hommes investigated the motivational influences by the tutor on the tutorial group function, where students considered lack of motivation as an important inhibitor of the learning process, and they expected the tutor to do something about it [24]. the beta value obtained in this analysis can also be used for other more practical purposes than the theoretical model testing shown here. if we could increase the content by one standard deviation (which is 1.87), the perceived motivation score would be likely to increase by 0.285 standard deviation units. this figure should be taken into account when designing a specific intervention to increase the overall perceived motivation score among the students. modifying the content of the course to make it more interesting, understandable, linked it to other courses in medicine, and clarifying that it’s useful in practicing medicine and for population health can significantly change the motivation score. 5. conclusion semester-one medical students of the university of khartoum are internally motivated toward the course of community medicine. their ages and gender had no significant influence on their motivation score. the impact of fathers’ educational level is more profound than the mothers’ on their children’s motivation. the perception of the firstyear medical students of the university of khartoum of their tutor’s performance in terms of teaching skills and knowledge had a strong association with the summative motivation score. further studies with larger sample size and the original version of mslq are recommended. intervention to increase the motivation toward community medicine can be designed with specific consideration drawn to the content of the course with the predicted outcome. this will further facilitate the monitoring and evaluation process of these interventions used in a specified duration by comparing the change to the motivation score, to what is predicted beforehand using this model. conflict of interests the authors declare that they have no conflict of interest. doi 10.18502/sjms.v13i3.2957 page 203 sudan journal of medical sciences mohamed nasr elsheikh et al ethical clearance ethical approval was obtained from the department of community medicine, university of khartoum. the rights and purpose and the study were explained to firstyear medical students. assurance of voluntary participation and confidentiality was affirmed before the researcher distributed the questionnaire among them. informed written consent was obtained from those who agreed to participate. availability of data and materials the datasets generated and/or analyzed during the current study are not publicly available at this time as they are in use for answering further research questions. the data will be available afterward through the first author of the manuscript on reasonable request. acknowledgement the authors would like to thank all the student who participated in this study and also to acknowledge dr. derek jones (university of edinburgh, msc. in clinical education faculty) for his patient and careful revision of the manuscript. author contributions all authors had significant contribution to the study concept, designing, and/or data collection and entry. mne, mm, and nm performed the statistical analyses. all authors contributed in drafting the manuscript and all of them read and approved the final manuscript. references [1] williams, s. m. 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(april 15, 2014). medical students perceive better group learning processes when large classes are made to seem small. m. j. costa (ed.). plos one, vol. 9, no. 4, p. e93328. doi 10.18502/sjms.v13i3.2957 page 206 introduction methods study area study population data management and statistical analysis results discussion conclusion conflict of interests ethical clearance availability of data and materials acknowledgement author contributions references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13609 production and hosting by knowledge e letter inappropriate prescribing of cefixime 400 mg every 12 hours dose durr-e-shahwar siddiqui department of pharmacology, faculty of pharmacy and pharmaceutical sciences, university of karachi, pakistan orcid: durr-e-shahwar siddiqui: https://orcid.org/0000-0003-1448-9970 dear editor, cefixime is a third-generation cephalosporin that treats otitis media, bronchitis, pharyngitis, urinary tract infection, uncomplicated gonorrhea, typhoid fever, and other infectious diseases. cefixime falls in pregnancy category b as per food & drug administration. the day-by-day increasing use of cefixime by humans for mild infections and its inappropriate prescribing is giving rise to the development of microbial resistance against this beneficial antibiotic. every four out of five discharge summaries of postoperative lower segment caesarean section patients contained cefixime 400 milligrams (mg) every 12 hr dose (twice a day) for 7 to 10 days as prophylactic therapy at a secondary care hospital of pakistan. moreover in adults, prescribing of cefixime 400 mg every 12 hr dose for mild infections by clinicians is becoming a common practice without any authentic clinical guideline. prescribers generally confuse 200 mg every 12 hr dose with 400 mg every 12 hr dose of cefixime. the reported adverse effects of cefixime are mostly related to gastrointestinal tract, and amongst them diarrhea is the most frequent [1]. certain prescribers consider that 200 mg every 12 hr dose of cefixime carries less chance of diarrhea and other gastrointestinal adverse effects than 400 mg every 24 hr dose (once a day). in reality, although 200 mg every 12 hr dose of cefixime takes slightly less time to reach maximum plasma concentration (c𝑚𝑎𝑥) than 400 mg every 24 hr dose, however, it is not highly significant and has no added clinical advantage. it only increases the cost of therapy and such inappropriate or irrational dosing of cefixime leads to microbial resistance. additionally, cefixime does not accumulate in serum or urine, and irrespective of the dosage – 200 mg twice a day or 400 mg once a day – its concentration in urine while clearance from the body also does not vary significantly. moreover, 4.74 mg/l is the maximum serum concentration of cefixime antibiotic that is achieved at 3.9 hr through a single dose of 400 mg, while half-life of cefixime is 3.5 hr. the usual recommended how to cite this article: durr-e-shahwar siddiqui (2023) “inappropriate prescribing of cefixime 400 mg every 12 hours dose,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 265–267. doi 10.18502/sjms.v18i2.13609 page 265 corresponding author: durr-e-shahwar siddiqui; email: silver_shine27@hotmail.com received 31 october 2022 accepted 30 january 2023 published 30 june 2023 production and hosting by knowledge e durr-e-shahwar siddiqui. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences durr-e-shahwar siddiqui dose of cefixime in pediatric population is 4 mg/kg every 12 hr or 8 mg/kg every 24 hr apart. for adults, the usual recommended dose in most of the infectious diseases is 400 mg every 24 hr or 200 mg every 12 hr. the duration of therapy depends upon the severity and type of infection. usually, the therapy of cefixime lasts up to 5, 7, 10, or maximum 14 days. in the treatment of uncomplicated gonorrhea, single dose of 800 mg cefixime appears effective [2]. the international academy of philippines (iap) recommended a cefixime dose of 400 mg every 12 hr for adults and 10 mg/kg every 12 hr for pediatric populations for 7 to 14 days in uncomplicated typhoid fever and as empiric therapy for suspected enteric fever after baseline investigations are sent [3]. it was also reported that 400 mg every 12 hours dose of cefixime for 10 days for early syphilis carried safety as a major benefit and 87% of patients were treated successfully [4]. none of the established data till date supports the use of 400 mg every 12 hr dose of cefixime for mild infections or in postsurgical prophylaxis of infections. clinical interventions by pharmacists for cefixime in postoperative surgical prophylaxis reduced the surgical site infection from 21% to 15% [5]. the prescribing of cefixime in correct doses must be promoted as per diagnosis and culture sensitivity of micro-organisms. authentic clinical guidelines must be considered for antibiotic prescribing in all healthcare set-ups worldwide. inappropriate prescribing of 400 mg every 12 hr dose of cefixime for mild infections or for prophylaxis of postoperative infections such as in lower segment caesarean sections must be highly discouraged. pharmacists must play active role in prescriptions review and determine the correct dose for patients keeping in view the diagnosis and available culture sensitivity results. prescribers must also be convinced to prescribe appropriate dose of cefixime as per authentic clinical guidelines. acknowledgements none. competing interests the author declares that there is no conflict of interest to disclose. doi 10.18502/sjms.v18i2.13609 page 266 sudan journal of medical sciences durr-e-shahwar siddiqui funding this research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. references [1] british national formulary. (2022). bacterial infection. bnf, 82, 487. [2] hazra, a., collison, m. w., & davis, a. m. (2022). cdc sexually transmitted infections treatment guidelines, 2021. journal of the american medical association, 327(9), 870–871. https://doi.org/10.1001/jama.2022.1246 [3] medical microbiology and infectious diseases society of pakistan. (2019). typhoid management guidelines. mmidsp. https://www.mmidsp.com/typhoid-managementguidelines-2019/ [4] stafylis, c., keith, k., mehta, s., tellalian, d., burian, p., millner, c., & klausner, j. d. (2021). clinical efficacy of cefixime for the treatment of early syphilis. clinical infectious diseases, 73(5), 907–910. https://doi.org/10.1093/cid/ciab187 [5] butt, s. z., ahmad, m., saeed, h., saleem, z., & javaid, z. (2019). postsurgical antibiotic prophylaxis: impact of pharmacist’s educational intervention on appropriate use of antibiotics. journal of infection and public health, 12(6), 854– 860. https://doi.org/10.1016/j.jiph.2019.05.015 doi 10.18502/sjms.v18i2.13609 page 267 dear editor, acknowledgements competing interests funding references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2955 production and hosting by knowledge e research article identification of proteus mirabilis on banknotes using 16s rrna gene in khartoum state alaa abdalla mukhtar1, noha ahmed abd alfadil2, malik suliman mohamed3, hisham n altayb4, salaheldein g elzaki5, and mohamed salih hassan6 1department of pharmaceutical chemistry, faculty of pharmacy, omdurman islamic university, khartoum, sudan 2department of pharmaceutics, faculty of pharmacy, university of alneileen, khartoum, sudan 3department of pharmaceutics, faculty of pharmacy, university of khartoum, khartoum, sudan 4department of microbiology, faculty of medical laboratories, sudan university of science and technology, khartoum, sudan 5department of epidemiology, tropical medicine research institute, national centre for research, khartoum, sudan 6applied bioinformatics center, africa city of technology, khartoum, sudan abstract background: the presence of pathogenic bacteria in circulated currency was recorded as a public health hazard. in this study, all examined sudanese banknotes (100%) were found to be contaminated by gram-negative bacteria. proteus mirabilis were recovered from 10 examined notes (22.2%, f = 10), e. coli (13.3%, f = 6) and klebsiella spp. (8.9%, f = 4) were also identified. only the most resistant p. mirabilis isolate was identified using culture-based and 16s rrna gene sequencing techniques. methods: proteus isolates were identified phenotypically and tested for their susceptibility to 16 of commonly used antibiotics, then most resistant isolate was confirmed genotypically via 16s rrna gene amplification and sequencing. bioinformatics analysis using blast for sequence similarity search, clustal w program for multiple sequence alignment, mega7 software for phylogenetic analysis. tree was constructed to show the evolutionary relationships of the obtained sequence with similar sequences in the databases using. results: the obtained sequence was found to be 100% identical to p. mirabilis 16s rrna gene using blast. the phylogenetic tree was constructed to show the evolutionary relationships of the obtained sequence with similar sequences in the databases using mega7 software, and the closest strain was found to be p. mirabilis strain from india (eu411047). conclusion: this study has shown that some currency notes circulated at khartoum transportation are carriers of antimicrobial-resistant p. mirabilis that could be potential source for their transmission in public. keywords: proteus mirabilis, banknotes, 16s rrna, khartoum state how to cite this article: alaa abdalla mukhtar, noha ahmed abd alfadil, malik suliman mohamed, hisham n altayb, salaheldein g elzaki, and mohamed salih hassan (2018) “identification of proteus mirabilis on banknotes using 16s rrna gene in khartoum state,” sudan journal of medical sciences, vol. 13, issue no. 3, pages 175–186. doi 10.18502/sjms.v13i3.2955 page 175 corresponding author: alaa abdalla mukhtar; email: pharma199322@gmail.com received 2 august 2018 accepted 15 september 2018 published 24 september 2018 production and hosting by knowledge e alaa abdalla mukhtar et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:pharma199322@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences alaa abdalla mukhtar et al 1. introduction proteus mirabilis causes 90% of proteus infections [1]. it has been implicated in meningitis, empyema, osteomyelitis, and gastroenteritis. also, it frequently causes health care-associated infections of the urinary tract, surgical wounds and lower respiratory tract [2]. identification of bacteria is frequently performed by isolation of the organisms and study of their phenotypic characteristics, including gram staining, morphology, culture requirements, and biochemical reactions [3]. however, these traditional techniques have some disadvantages. firstly, they are time-consuming and laborious. secondly, a variability of culture due to different environmental conditions may lead to ambiguous results. thirdly, a pure culture is required to undertake identification making the identification of fastidious and unculturable bacteria difficult and sometimes impossible [4]. moreover, phenotypic systems cannot account for the variable characteristics observed among members of the same species, resulting in poor precision upon repeated testing [5]. construction of phylogeny tree based on phenotypic methods may be more difficult because it needs a comparison of a large set of independent co-varying characters, and it is difficult to perform cladistic analyses based on it [6]. in addition to the fact that phenotype represents a very small part of each organism’s genome [7]. 16s rrna gene is highly conserved within species and among species of the same genus, and hence, can be used as an alternative technique for identification of bacteria to the species level [8, 9]. specific properties of the 16s rrna gene include its ubiquitous distribution, mosaic structure [10], and relative stability that qualify it to be used in the taxonomic assignment and phylogenetic relationship determination [11]. the genotypic bacterial identification begins with nucleotide sequence analysis of the pcr product of specific gene/s followed by a comparison of these sequences with known sequences stored in a database [12, 13]. the 16s rrna gene is suitable for identification since its size (1500 bp) is large enough for bioinformatics purposes [14]. direct sequencing of 16s rrna genes from environmental samples has become a standard and convenient method of assessing microbial population abundance [15], structure, and function in microbial communities [16, 17]. this study aimed to identify the bacterial isolates recovered from sudanese banknotes using culture-based and 16s rrna gene sequencing techniques. doi 10.18502/sjms.v13i3.2955 page 176 sudan journal of medical sciences alaa abdalla mukhtar et al 2. materials and methods 2.1. sources of banknotes prospective study was conducted in march 2016 in which a total of 45 sudanese banknotes were randomly collected from different sources; hospitals (f = 15), food sellers (f = 15), transporters (f = 15). five ‘mint’ brand new notes were collected from the bank before being touched with bankers to be used as controls. these new banknotes were included in the study to ensure whether the banknotes are contaminated from their source or during handling in the circulation. the banknotes studied were two, five, ten, twenty and fifty sudanese pounds. all banknotes were in good shape and not damaged and transported into sterile plastic petri dishes to the microbiological laboratory for bacterial isolation, identification and antibiotic sensitivity testing. 2.2. phenotypic analysis of bacteria from sudanese banknotes 2.2.1. bacterial extraction and biochemical tests the banknotes were moistened with sterile distilled water, swabbed both sides by cotton-tipped swab and directly inoculated on 5% blood agar and macconkey agar plates. for bacterial growth observation, the inoculated plates were incubated aerobically at 37ºc for 24 hrs. the cultural characteristic of the recovered contaminants of each banknote were examined and the suspected colonies were stained by gramstaining method. the gram-negative, rod-shaped bacilli and swarm colonies on media were sub-cultured in nutrient agar plates for further identification tests. biochemical tests (catalase test, oxidase test, motility, indole test, urease, glucose fermentation test and lactose fermentation test) were carried out [17]. 2.2.2. susceptibility tests samples were tested for their susceptibility to these antibiotics: amoxicillin (amx) 25 µg, amoxyclav (amc) 30 µg, cephalexin (cn) 30 µg, cefuroxime (cxm) 30 µg, ceftriaxone (ctr) 30 µg, ceftazidime (caz) 30 µg, gentamicin (gen) 10 µg, kanamycin (k) 30 µg, co-trimoxazole (cot) 25 µg, erythromycin (e) 5 µg, azithromycin (azm) 15 µg, ciprofloxacin (cip) 30 µg, levofloxacin (le) 5 µg, nitrofurantoin (nit) 200 µg, chloramphenicol (c) 30 µg, and meropenem (mem) 10 µg using kirby–bauer disc diffusion method [18]. doi 10.18502/sjms.v13i3.2955 page 177 sudan journal of medical sciences alaa abdalla mukhtar et al 2.3. genotypic analysis of bacteria from sudanese banknotes 2.3.1. dna extraction more resistant isolate recovered from examined sudanese banknotes was subjected to genotypic analysis. three colonies from pure sub-cultured isolate was suspended in 200µl 1x phosphate buffer saline (pbs). genomic dna was extracted using chelex extraction protocol [19] and quantified using (genequant, amersham) according to manufacturer’s protocol. 2.3.2. 16s rrna gene amplification forward primer 27f (5′-agagtttgatcctggctcag-3′) and reverse primer 1495r (5′ctacggctaccttgttacga-3′) [20] were used to amplify 16s rrna gene. the pcr reaction mixture (itron, korea) were as follows: 2.5 unit taq dna polymerase, 2.5 mmmm dntp, 1x reaction buffer (10x), 1x gel loading buffer, 5µl of template dna, 1µl of primer (27f:10pmol/µ), 1µl of primer (1495r10 pmol/µl) and 15µl of distilled water mixed in a final volume of 25µl. the pcr conditions were; 94ºc for 5 minute, 37 cycles of 94ºc for 1 minute, 58ºc for 1 minute, 72ºc for 1 minute, and final extension at 72ºc for 10 minutes. amplification was done using thermocycler system (bio-rad, usa). 2.3.3. detection of amplified product by agarose gel electrophoresis the pcr products were assessed by gel electrophoresis. one percent agarose gel with 0.5% ethidium bromide were mixed and 5μl of pcr product and ladder (itron, korea) were transferred into separated wells in the gel. the electric current was allowed at 100 volts for 30 minute, while uv trans-illuminator (uvp, usa) was used for the observation of dna bands [21]. the obtained fragment was sent to be sequenced in microgen company (seoul, south korea). 2.4. bioinformatics analysis the 16s rrna gene sequence was analyzed using blast [22] with non-redundant (nr) ncbi genbank database to find closely related bacterial 16s rrna gene sequences. the 16s rrna gene sequence of proteus isolate was submitted to ncbi database with accession number (ky 039269). nineteen sequences of high-quality 16s rrna gene were selected from silva database [23] and subjected for multiple sequence alignment doi 10.18502/sjms.v13i3.2955 page 178 sudan journal of medical sciences alaa abdalla mukhtar et al using clustal w program [24] within bioedit software [25], with total alignment score 1661794. the phylogenetic tree was constructed according to maximum likelihood method using mega 7 software [26]. 3. results 3.1. results of susceptibility tests all p. mirabilis isolates were completely sensitive to meropenem (mem), levofloxacin (lev), ciprofloxacin (cip), gentamicin (gen), ceftazidime (caz), ceftriaxone (ctr), cephalexin (cn), and amoxyclav (amc), as well as they were completely resistant to azithromycin (azm) and erythromycin (e). however, resistant strains of p. mirabilis isolates to kanamycin (k), chloramphenicol (c), nitrofurantoin (nit), co-trimoxazole (cot), cefuroxime (cxm) and amoxicillin (amx) 25µg were also detected, as shown in table 1. t 1: susceptibility test of p. mirabilis isolates using disc diffusion assay. antibiotics mem c lev cip k gen nit cot azm e caz ctr cxm cn amc amx sensitive isolates 100% 86% 100% 100% 57% 100% 0% 43% 0% 100% 0% 100% 57% 100% 100% 57% resistant isolates 0% 14% 0% 0% 14% 0% 57% 57% 100% 100% 0% 0% 43% 0% 0% 43% intermedia te isolates 0% 0% 0% 0% 29% 0% 43% 0% 0% 0% 0% 0% 0% 0% 0% 0% table 1 shows the results of susceptibility test of p. mirabilis isolates toward commonly used antibiotics using disc diffusion assay. 3.2. dna quantification results t 2: dna concentrations in µg/l using genequant. sample no. protein µg/l ratio ssdna µg/l purity % sample 1 0.4 1.2 39.0 69 sample 2 0.3 1.4 39.5 75 sample 3 0.4 1.3 48.0 72 sample 4 0.3 1.3 38.8 74 sample 5 0.3 1.5 52.0 82 table 2 illustrates the dna concentrations of five samples using genequant machine. only sample 5 was adopted for further processes. doi 10.18502/sjms.v13i3.2955 page 179 sudan journal of medical sciences alaa abdalla mukhtar et al 3.3. fragments separation using gel electrophoresis figure 1: amplified fragment detection, l: ladder (500 bp), s: sample 5. figure 1 represents separated band of sample 5 compared with bands of ladder using gel electrophoresis. 3.4. multiple sequence alignment figure 2: multiple sequence alignment of 19 databases 16s rrna genes with 16s rrna gene of p. mirabilis isolate (ky 039269) from sudan. figure 2 shows the result of multiple sequence alignment of 19 databases 16s rrna genes with 16s rrna gene of p. mirabilis isolate (ky 039269) from sudan. 3.5. phylogenetic analysis evolutionary history was inferred using maximum likelihood method based on tamuranei model. the tree was constructed by mega7 software [26]. 16s rrna gene of p. mirabilis isolate from sudanese notes (ky 039269) is closely related to16s rrna gene of p. mirabilis isolate from india (eu411047) as shown in figure 3. doi 10.18502/sjms.v13i3.2955 page 180 sudan journal of medical sciences alaa abdalla mukhtar et al figure 3: phylogenetic tree of 16s rrna gene of p. mirabilis isolate from sudanese notes (ky 039269). 4. discussion the result of this study represents that 22.2% of tested sudanese banknotes were contaminated by p. mirabilis that is agreed with results from india and nigeria where it was found in banknotes at low frequency [27, 28]. banknotes contamination rate is incredibly high at khartoum transport circulation that may be due to more frequent exchange, poor hygiene and environmental conditions such as temperature and humidity [29]. the risk of transmission of pathogenic microorganisms and diseases by banknotes was reported worldwide, but most of these studies were performed in the tropical or sub-tropical regions of the world [30, 31]. banknotes and coins were reported as carriers of potentially pathogenic microorganism since the beginning of the seventies [32, 33]. the 16s rrna gene that is commonly used for identification and classification of microbes from environmental samples [34, 35] was used in this study for identification of banknotes isolates after biochemical tests. banknotes-associated microorganisms detected previously using 16s rrna gene [36, 37]. it can be used for identification for bacterial strains more accurately than it is possible with phenotypic analysis, allowing identification of strains that are poorly culturable or do not exhibit distinguishable phenotypic traits [12]. in this study, the most resistant isolate toward examined antibiotics was chosen for dna extraction and sequencing for identification and also to detect changes in 16s rrna sequence that may explain their resistance to these antibiotics [38]. after quantification of extracted dna, gel electrophoresis and dna sequencing, doi 10.18502/sjms.v13i3.2955 page 181 sudan journal of medical sciences alaa abdalla mukhtar et al the obtained 756 pb sequence with the aid of blast and multiple sequence alignment confirmed that the isolate was p. mirabilis with 100% identity to the database sequence. it is known that the full-length or near-full-length 16s rrna gene sequences is crucial for making confident genus and species-level taxonomic placements [39]. the 16s rrna gene could be used as phylogenetic marker because of its functional constancy and the presence of conserved and variable sequence regions evolving at very different rates. it is also critical for the concurrent universal amplification and measurement of both close and distant phylogenetic relationships. so, it can be used in the assignment of close relationships at the genus level [12], and in several cases at the species level [39, 40]. phylogenetic analysis using maximum likelihood method based on tamura-nei model [26] showed that the closest strain to our isolate is p. mirabilis identified in india (eu411047). sequencing independent techniques such as pulsedfield gel electrophoresis (pfge) [41, 42], random amplified polymorphism deoxyribonucleic acid (rapd) [43], and restriction fragment length polymorphism (rflp) [44] have broad availability and cost lower than other typing methods; however, 16s rrna sequencing has high discriminatory power, 100% typeability and good reproducibility [45]. p. mirabilis isolates were found to be resistant to some antibiotics. a lot of studies detected p. mirabilis as extended-spectrum beta-lactamases esbls producer [46]. a number of studies had focused on antibiotic resistance among bacteria recovered from banknotes [47]. isolates that are resistant to commonly used antibiotics represents risks and public-health hazards to the community and individuals handling banknotes [48]. 5. conclusion our study has shown that some currency notes circulated at khartoum transportation are carriers of antimicrobial-resistant p. mirabilis that could be potential source for their transmission in public. awareness about the health risk of contaminated currency and proper hand hygiene might be necessary. notes sterilization and electronic credit cards use are recommended. conflict of interests the authors declare that there is no conflict of interest regarding the publication of this article. doi 10.18502/sjms.v13i3.2955 page 182 sudan journal of medical sciences alaa abdalla mukhtar et al acknowledgments the authors would like to thank the africa city of technology for their support. references [1] coker, c., bakare, o. o., and mobley, h. l. 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(2014). microbial contamination of currency notes and coins in circulation: a potential public health hazard. biomedicine and biotechnology, vol. 2, no. 3, pp. 46–53. doi 10.18502/sjms.v13i3.2955 page 186 introduction materials and methods sources of banknotes phenotypic analysis of bacteria from sudanese banknotes bacterial extraction and biochemical tests susceptibility tests genotypic analysis of bacteria from sudanese banknotes dna extraction 16s rrna gene amplification detection of amplified product by agarose gel electrophoresis bioinformatics analysis results results of susceptibility tests dna quantification results fragments separation using gel electrophoresis multiple sequence alignment phylogenetic analysis discussion conclusion conflict of interests acknowledgments references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2953 production and hosting by knowledge e research article frequency of erectile dysfunction following pelvic fracture among patients admitted to two wits teaching hospitals, south africa daou gdeh, mohamed haffejee, and marietha nel division of urology, department of surgery, school of clinical medicine, faculty of health sciences, university of the witwatersrand, 7 york road, parktown, johannesburg, south africa abstract background: erectile dysfunction that can range from weak to severe is one of the most important sequelae of pelvic fractures and may be transient or permanent. importantly, erectile dysfunction is more prevalent when the pelvic fracture is associated with urethral injury. this study aimed to evaluate the frequency of erectile dysfunction post pelvic fracture and determine the frequency of spontaneous recovery of erectile function within the first six months from the time of injury in a south african sample population. materials and methods: this study was a cross-sectional study of records of patients who were admitted to the orthopedic department at helen joseph academic hospital and the male sexual dysfunction clinic at charlotte maxeke johannesburg academic hospital, in johannesburg, south africa, with a pelvic fracture between july 1, 2011 and april 30, 2015. results: a total of 53 patients aged between 18 and 80 years (mean: 7.57 ± sd3.45) meeting the study-inclusion criteria participated in the study, of which 50.9% had a b2 type pelvic fracture and 20% had a c type fracture. of the 53 patients, 43.4% reported erectile dysfunction. the majority (88%) of patients indicated a recovery of erectile function between 2 and 8 months after the injury. however, 86% of those patients were still suffering from other forms of sexual impairment like orgasmic dysfunction and lack of sexual satisfaction. interestingly, sexual desire seemed to be preserved. patients with sexual dysfunction were more likely to have had a urethral injury as well as a more severe fracture. conclusions: in our sample of 53 patients, almost half (43.4%) reported sexual dysfunction after a pelvic fracture. importantly, patients with a severe pelvic fracture and urethral damage should be followed-up after surgery, as the risk of long-term sexual dysfunction is increased in these particular patients. keywords: pelvic fracture, erectile dysfunction, tile classification, iief score how to cite this article: daou gdeh, mohamed haffejee, and marietha nel (2018) “frequency of erectile dysfunction following pelvic fracture among patients admitted to two wits teaching hospitals, south africa,” sudan journal of medical sciences, vol. 13, issue no. 3, pages 144–167. doi 10.18502/sjms.v13i3.2953 page 144 corresponding author: daou gdeh; email: daougdeh@gmail.com received 19 june 2018 accepted 11 september 2018 published 24 september 2018 production and hosting by knowledge e daou gdeh et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:daougdeh@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences daou gdeh et al 1. introduction pelvic fractures usually occur in older people with osteoporosis, due to falls and minor injuries. these types of pelvic fractures are usually not associated with urological complications including erectile dysfunction (ed) [1]. in contrast, pelvic fractures in healthy young people usually occur as a result of high-energy trauma, for example, pedestrian vehicle accidents, motor vehicle accidents, crushing injuries, or fall from heights [2]. there are several classifications of pelvic fractures, the most common classification systems are: 1. tile pelvic classification 2. young and burgess classification the tile pelvic classification was used in this study. it has three 3 major groups (a, b, and c) with each of these three groups subdivided into three subtypes as follows: astable pelvic fractures a1: the fracture is not involving the pelvic ring (avulsion innominate bone, crest fracture or iliac wing fracture) a2: stable or minimally displaced fracture of the pelvic ring a3: transverse sacral fracture (denis zone iii sacral fracture) brotationally unstable, vertically stable b1: open book injury (external rotation) b2: lateral compression injury (internal rotation) b3: bilateral compression injury crotationally and vertically unstable c1: unilateral c2: bilateral c3: bilateral and associated with acetabular fracture [1] the other classification of pelvic fracture that could be used is the young and burgess classification of pelvic fractures [3], as shown in table 1. pelvic fractures can result in long-term urological complications, including urethral stricture (as a result of urethral injury), urinary incontinence and ed [4, 5]. indeed, doi 10.18502/sjms.v13i3.2953 page 145 sudan journal of medical sciences daou gdeh et al t 1: young and burgess classification of pelvic fractures [adapted from 3]. type description (1) anteroposterior compression (apc) apc i diastasis of symphysis < 2.5cm apc ii diastasis of symphysis > 2.5cm, diastasis in the anterior part of the si joint, while posterior si ligaments are intact apc iii diastasis of symphysis > 2.5cm, disruption of both anterior and posterior si ligaments with dislocation in the si joint (2) lateral compression (lc) lc i oblique fracture of pubic rami and anterior compression fracture of sacral ala on ipsilateral side lc ii fracture of pubic rami and posterior fracture of ipsilateral iliac bone with dislocation lc iii ipsilateral lateral compression (lc) and contralateral anteroposterior compression (apc) (3) vertical shear (vs) fracture by superior and posterior force urethral injury is seen in 4–25% of pelvic fracture cases. there is a strong relationship between pelvic fracture and subsequent sexual dysfunction, especially if the patient had a urethral injury too, compared to the other causes of ed, such as pelvic (or perineal) trauma that accounts for 3–5% of all ed cases [6]. it was believed that the early urethral repair can help to avoid ed [7– 12]. however, subasi et al. (2004) studied 55 male patients who had severe pelvic fractures. eleven (20%) of them had urethral injuries, and six (14.6%) of the 11 patients developed ed regardless of timing of urethroplasty (early or late) [4]. furthermore, barrett et al. (2013) compiled a systemic review and a meta-analysis, reviewing 161 articles on pelvic fractures accompanied by urethral injuries. they compared outcomes of those who had early urethral realignment to those who had late repair. both groups showed ed [13]. the prostatic urethra is the most fixed portion of the human male urethra. it is fixed to the symphysis pubis and ischiopubic rami by puboprostatic ligaments and the urogenital diaphragm, making the prostatic urethra vulnerable to rupture by any shearing forces accompanying pelvic fracture [14–16]. furthermore, any superior or posterior displacement of the symphysis pubis will also result in disruption of the prostatic urethra [6]. patients will present with urethral bleeding, urinary retention and a high riding prostate on clinical examination. urethral injury following a pelvic fracture most commonly occurs in the bulbomembranous part of the urethra [17]. few studies have reported on the overall incidence of sexual dysfunction following pelvic trauma. in 2001, machtens et al. reported in their study that 11.6% of men with doi 10.18502/sjms.v13i3.2953 page 146 sudan journal of medical sciences daou gdeh et al pelvic fractures developed ed [18]. malavaud et al. (2000) indicated that all men who sustained pelvic fractures reported low sexual satisfaction with 23.9% having significant sexual dysfunction and 42% who suffered urethral injuries reporting impotence [17]. king et al. (1975) reported that 42% of men who had urethral injuries developed sexual dysfunction, while sexual impairment was seen in 5.5% [19]. in addition, malavaud et al. (2000) who also studied men with pelvic injuries using the international index of erectile function (iief) score, showed that 80.4% of these patients reported recovery of their sexual activity within four weeks, while the rest reported different degrees of sexual impairment [17]. importantly, the etiology of ed following pelvic fracture may be due to vascular, neurological, corporal and/or psychological factors [19–21]. vascular damage in the pelvis may be in the form of vessel-wall tear or intimal damage, which may lead to vascular thrombosis and blockage [6, 22]. indeed, sharlip et al. (1981) reviewed the pelvic angiography of patients who had obliteration of the internal pudendal artery at the level of the urogenital diaphragm. they remained sexually impaired despite good collateral vascular formation and good retrograde filling of the dorsal and deep penile vessels [23]. the formation of an arterio-venous fistula between the iliac vessels may also cause ed but can be surgically corrected [6]. severe pelvic neurological damage may also result in ed, especially if the damage involves the lumbosacral plexus. neurological damage may occur at the time of injury or when the patient undergoes pelvic surgery. some of these patients show partial neurological recovery within 3–24 months [6]. corporal injury in those who suffered pelvic trauma can also contribute to cause ed. the proximal part of the corpora is fixed to the surrounding structures and to the pubic rami, making it susceptible to shearing forces and hematoma formation. healing of the hematoma by fibrosis around the corpora may occur, making it non-dilatable during sexual excitement [24]. furthermore, due to the trauma of the injury and the long hospital stay, patients are susceptible to depression, which in turn affects sexual activity [6]. approximately up to 10% of people who survived a major traumatic injury may develop post-traumatic stress disorders [25], of which 80% will develop sexual dysfunction caused by the post-traumatic stress-disorder medications [26]. however, sexual performance can be improved by the withdrawal of such medications [27]. importantly, any patient who has sexual impairment will develop a psychological response, which can ultimately worsen any underlying anatomical pathology [6]. doi 10.18502/sjms.v13i3.2953 page 147 sudan journal of medical sciences daou gdeh et al all these factors contribute to the patient’s sexual health after the trauma of a pelvic fracture, and should thus be taken into consideration by clinicians. 2. materials and methods this was a retrospective cross-sectional study of pelvic fracture patient records. the study included patients aged between 18 and 80 years who never suffered from sexual dysfunction before sustaining a major pelvic trauma. the tile pelvic classification system was used to determine the severity of the pelvic fracture, finding that 50.9% of the patients had a b2-type fracture and 20% had a type c facture. the study has excluded those patients who suffer from chronic medical illnesses such as diabetes mellitus with hypertension, those suffering from psychological illnesses, those who sustained head or spinal injuries and those were taking medication to treat sexual dysfunctions. 2.1. inclusion criteria a. patients who sustained type b or type c pelvic fractures (tile pelvic classification) b. patients aged between 18 and 80 years 2.2. exclusion criteria a. patients who had ed prior to the pelvic fracture injury b. patients suffering from other major medicalor psychological illnesses c. patients on medication that can affect erectile function d. patients who sustained heador spinal injury e. patients who sustained major trauma and were admitted for three or more weeks in the intensive care unit (icu) f. patients who used medications to treat ed within four weeks before answering the questionnaire g. patients with diabetes mellitus accompanied by hypertension doi 10.18502/sjms.v13i3.2953 page 148 sudan journal of medical sciences daou gdeh et al 2.3. time of the study the data collection took place between november 1, 2015 and november 20, 2015. 2.4. study location the study was performed at the helen joseph academic hospital (hjah) and the male sexual dysfunction clinic (msdc) at the charlotte maxeke johannesburg academic hospital (cmjah). 2.5. sample size all telephonically contactable patients who met the study inclusion criteria and consented to participate were included in the study. 2.6. data collection the database of the orthopedics departments at hjah and the msdc at cmjah was accessed to obtain the details about the patient. we accessed the electronic databases of these two hospitals using the name and hospital number to obtain contact details for each patient. each patient was contacted telephonically with an open speaker in the presence of a witness/translator. the information sheet was read to the patient before telephonic consent was obtained. patients were asked to verbally complete the iief score as per appendix a, reporting on frequency of erection, successful penetration, confidence and maintenance of erection, satisfaction of intercourse and sex life, reaching climax and sexual desire. the orthopedic database was also accessed to obtain patients’ demographic details and to classify them according to the severity of the pelvic fracture, using the tile pelvic fracture classification. 3. data analysis descriptive statistics using mean and standard deviation or median and range, as appropriate, were used for analysis of numerical data. categorical data were described using percentages. for the comparison of patients with sexual dysfunction to those doi 10.18502/sjms.v13i3.2953 page 149 sudan journal of medical sciences daou gdeh et al without, a combination of unpaired t-tests and fishers exact tests were used for numerical and categorical data, respectively. 4. results a total of 53 participants answered the iief score questionnaire. the orthopedic database was accessed to obtain contact details and to classify the patients according to the severity of the pelvic fracture, using the tile pelvic fracture classification. half (50.9%) of the patients had a b2 type of fracture and 20% had a type c facture. figure 1: distribution of the participants according to the tile pelvic classification. there were no significant differences in age and time since injury or sexual drive between the two groups (type b versus type c) analyzed. patients with sexual dysfunction were significantly more likely to have urethral injury and type c pelvic fractures. patients with sexual dysfunction had significantly lower scores (when they answered iief score) indicating greater severity of injury) on all sub-sections of the sexual dysfunction questionnaire (except for sexual drive), and had a lower overall score. doi 10.18502/sjms.v13i3.2953 page 150 sudan journal of medical sciences daou gdeh et al figure 2: frequency of ed after pelvic fracture among the studied patients. figure 3: spontaneous recovery period of ed following pelvic fractures. 5. discussion the paucity in the literature on studies assessing the frequency of ed after pelvic fractures and the spontaneous recovery of erectile function in south africa necessitated this study. doi 10.18502/sjms.v13i3.2953 page 151 sudan journal of medical sciences daou gdeh et al figure 4: severity of sexual dysfunction among the studied group (according to iief score). figure 5: the severity of orgasmic dysfunction among the studied patents. a number of pelvic classification systems exist. the most commonly used systems are the tile pelvic classification and the young and burgess classification [1]. in the present study, the tile pelvic classification was used to classify the pelvic fractures of participating patients. the majority (n = 27 or 50.9%) of the participating patients had doi 10.18502/sjms.v13i3.2953 page 152 sudan journal of medical sciences daou gdeh et al figure 6: the severity of sexual desire impairment among the studied group. figure 7: the prevalence of intercourse dissatisfaction. tile b2 fractures. of the other 26 patients, 8 had b1 (15%), 9 had b3 (16.9%), 6 had c1 (11.3%), and 3 had c2 (5.6%) type pelvic fractures. of the 53 patients included in our study, 23 (43.3%) developed ed secondary to their pelvic fractures. although, 4 out of 53 (7.5%) participants had hypertension (well-controlled) and 8 patients (16%) were smokers; all 12 of these patients had normal erectile function. doi 10.18502/sjms.v13i3.2953 page 153 sudan journal of medical sciences daou gdeh et al figure 8: the overall sexual dissatisfaction among the studied group [based on the international index of erectile function (iief-5)]. t 2: statistical analysis of patients with and without sexual dysfunction. number of patients no dysfunction dysfunction p-value test 53 30 23 age (years) 34.8 (14.3) 38.6 (13.2) 0.3317 unpaired t-test time since injury (months) 28.9 (14.4) 24.9 (10.8) 0.2963 unpaired t-test urethral injury (no/yes) 28/2 9/12 0.0001 fishers exact type b versus c* 29/1 15/6 0.0151 fishers exact erectile dysfunction (median-range) 10.5(8–19) 14(6–27) 0.0001 fishers exact orgasmic dysfunction 2(2–8) 2(2–9) 0.0368 fishers exact sexual drive 4(3–7) 5(2–8) 0.2558 fishers exact intercourse satisfaction 6(4–10) 8(5–11) 0.0002 fishers exact overall 2(2–7) 5(2–8) 0.001 fishers exact note: *type b or c pelvic fracture as per tile pelvic classification. the overall rate of ed after pelvic fracture studies reported in the literature is 11– 42%. king et al. (1975) performed a study on 90 patients and found that 42% developed ed [19], whereas malavaud et al. (2000) reviewed 46 patients who sustained pelvic fractures and found that 23.9% had ed [17]. furthermore, king et al. (1975) found in their study that out of the 42% of patients who developed ed, only 4 (5.5%) had permanent sexual dysfunction [19]; but unfortunately they did not specify which aspects of sexual function was affected. in contrast to king et al. (1975), malavaud et al. doi 10.18502/sjms.v13i3.2953 page 154 sudan journal of medical sciences daou gdeh et al (2000) reported that 29.7% of the pelvic fracture patients in his study developed a permanent sexual dysfunction [17]. however, machtens et al. (2001) reported in a much larger study that out of 1 722 participants, only 200 (11.6%) suffered ed [18]. although the majority (86%) of patients in this study reported recovery of erectile function within 2 to 8 months, the other domains of the iief (orgasmic function, libido, sexual satisfaction and overall satisfaction) except for sexual desire, according to patients’ answers, were lower than in those patients who had no sexual dysfunction after the fracture. indeed, out of the 86% of patients who reported recovery of erectile function, 72% still had severe orgasmic dysfunction, 80% had mild to moderate sexual desire (libido) impairment, 92% had mild to moderate intercourse dissatisfaction, and 70% suffered moderate to severe overall dissatisfaction. malavaud et al., (2000), reported that a percentage as high as 80.4% of the patients in their study, showed spontaneous sexual function recovery within 4 weeks [17]. this is in agreement with our study in which 86% of pelvic fracture patients reported recovery of their sexual functions and reported being able to perform sexual intercourse to some extent. in contrast, most of the participating patients in our study reported that erections were only recovered within 3 months to 8 months post injury. however, most of these patients were not completely sexually satisfied, and therefore, we reviewed the other domains of sexual function. we noticed that such patients indeed had impairment in one or more domains, compared to patients who had not developed ed after pelvic fracture. the possible reasons for the sexual dissatisfaction may be chronic skeletal pain, painful ejaculation or urethral stricture as a result of the pelvic fracture. some of the patients with urethral strictures may still have a stricture as sequelae to the pelvic fracture and some may have had a failed urethroplasty and are awaiting repeat procedures. although spontaneous ed recovery may be explained by recovery of neuropraxia, the absorption of a pelvic hematoma compressing the neurovascular bundle, other as yet unknown reasons may also contribute to spontaneous recovery and this warrants further studies. 6. study limitations the lack of a functioning electronic database in the department of orthopedics at the chbah and the cmjah limited the patient study numbers, as badly hand-written and incomplete patient records had to be resorted to instead. since it was a retrospective study, contact details of patients had changed over time, making telephonic patient doi 10.18502/sjms.v13i3.2953 page 155 sudan journal of medical sciences daou gdeh et al contact difficult and thus limiting the patient numbers. unavailability of literature about this condition in south africa added to the limitations of this study. 7. conclusion this study found the frequency of ed post pelvic fractures in a south african sample population to be 43.3%, which concurs with the finding by king et al. (1975) of 42%. in addition, this study determined the frequency of spontaneous recovery of erectile function within the first 3–8 months from the time of injury to be 86%, which agrees with the 80.4% reported in the study of malavaud et al. (2000). although spontaneous ed recovery may be explained by the recovery of neuropraxia, other as yet unknown reasons do exist and warrant further investigation. however, most of the ed-recovered patients in this study were not completely sexually satisfied due to chronic skeletal pain, painful ejaculation, or urethral stricture as a result of the pelvic fracture, which is the ground for future studies. ethical clearance the project was approved by the human research ethics committee of the university of the witwatersrand (medical). the ethics certificate was obtained on august 28, 2015 with the clearance number: m150502 as per appendix b. all the patients’ personal details were only made available to the researcher for the purpose of this research study. patient confidentiality was respected by collecting the data anonymously and by using a numbering system on the data collection sheet without any personal identifiers such as names, surnames, or birth dates. acknowledgements the main author would like to thank the following people for their assistance and guidance in preparation of this research: professor mohamed haffejee, the head of the urology division, department of surgery, at the university of the witwatersrand. dr marietha nel, department of surgery, university of the witwatersrand for the advice, support, proofreading, and editing this article. doi 10.18502/sjms.v13i3.2953 page 156 sudan journal of medical sciences daou gdeh et al colleagues who helped the author with the telephonic interviews, witnessed the consents, and helped to translate the telephonic conversations; dr ramesh nadimpalli, dr charles mathys and dr ck sello. in addition to the head of the department of orthopedics at helen joseph academic hospital, the author is thankful to professor a. aden, who gave permission to access the departmental database. references [1] rommens, p. m., wagner, d., and hofmann, a. (2012). surgical management of osteoporotic pelvic fractures: a new challenge. european journal of trauma and emergency surgery, vol. 38, no. 5, pp. 152–156, pubmed (accessed on december 2015). [2] holstein, j. h., culemann, u., pohlemann, t. (2012). what are predictors of mortality in patients with pelvic fractures? clinical orthopaedics and related research, vol. 470, pp. 2090–2097, pubmed (accessed on december 2015). [3] manson, t. i., o’toole, r. v., whitney, a., et al. (2010). young-burgess classification of pelvic ring fractures: does it predict mortality, transfusion requirements, and nonorthopaedic injuries. journal of orthopaedic trauma, vol. 24, no. 10, pp. 603–609, pubmed (accessed on december 2015). [4] . subasia, m., arslana, h., necmioglua, s., et al. (2004). long term outcomes of conservatively treated paediatric pelvic fractures injury. international journal of the care of the injured, vol. 35, no. 10, pp. 771–781, pubmed (accessed on december 2015). 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(2011). lower urinary tract injuries following blunt trauma: a review of contemporary management. reviews in urology, vol. 13, no. 3, pp. 119–130, pubmed (accessed on december 2015). [17] malavaud, b., mouzin, m., tricoire, j. l., et al. (2000). evaluation of male sexual function after pelvic trauma by the international index of erectile function. gold journal of urology, vol. 55, no. 6, pp. 842–846, pubmed (accessed on december 2015). [18] machtens, s., gansslen, a., pohlemann, t., et al. (2001). erectile dysfunction in relation to traumatic pelvic injuries or pelvic fractures. british journal of urology international, vol. 78, no. 1, pp. 441–448. retrieved from http://onlinelibrary.wiley. com/doi/10.1046/j.1464-410x.2001.02147.x/pdf (accessed on december 2015) [19] king, j. (1975). impotence after fractures of the pelvis. journal of bone and joint surgery, american volume, vol. 57, no. 8, pp. 110–1109, pubmed (accessed on december 2015). doi 10.18502/sjms.v13i3.2953 page 158 http://onlinelibrary.wiley.com/doi/10.1046/j.1464-410x.2001.02147.x/pdf http://onlinelibrary.wiley.com/doi/10.1046/j.1464-410x.2001.02147.x/pdf sudan journal of medical sciences daou gdeh et al [20] mark, s. d., keane, t. e., vandemark, r. m., et al. (1995). impotence following pelvic fracture urethral injury: incidence, aetiology and management. british journal of urology, vol. 75, no. 1, pp. 62–64, pubmed (accessed on december 2015). [21] robinson, l. q., woodcock, j. p., and stephenson, t. p. (1987). results of investigation of impotence in patients with overt or probable neuropathy. british journal of urology, vol. 60, no. 6, pp. 583–587, pubmed (accessed on december 2015). [22] matthews, l. a., herbener, t. e., and seftel, a. d. (1995). impotence associated with blunt pelvic and perineal trauma: penile revascularization as a treatment option. seminars in urology, vol. 13, no. 1, pp. 66–72, pubmed (accessed on december 2015). [23] sharlip, i. d. (1981). penile arteriography in impotence after pelvic trauma. the journal of urology, vol. 126, no. 4, pp. 477–481, pubmed (accessed on december 2015). [24] munarriz, r. m., yan, q. r., znehra, a., et al. (1995). blunt trauma: the pathophysiology of hemodynamic injury leading to erectile dysfunction. the journal of urology, vol. 153, no. 6, pp. 1831–1840, pubmed (accessed on december 2015). [25] brom, d., kleber, r. j., and hofman, m. c. (1993). victims of traffic accidents: incidence and prevention of post-traumatic stress disorder. journal of clinical psychology, vol. 49, no. 2, pp. 131–140, pubmed (accessed on december 2015). [26] reznik, i., zemishlany, z., kotler, m., et al. (2002). sildenafil citrate for the sexual dysfunction in antidepressant-treated male patients with posttraumatic stress disorder. a preliminary pilot open-label study. psychotherapy and psychosomatics journal, vol. 71, no. 3, pp. 173–176, pubmed (accessed on december 2015). [27] fossey, m. d. and hamner, m. b. (1994–1995). clonazepam-related sexual dysfunction in male veterans with ptsd. journal of anxiety disorders, vol. 1, no. 5, pp. 233– 236, pubmed (accessed on december 2015). doi 10.18502/sjms.v13i3.2953 page 159 sudan journal of medical sciences daou gdeh et al appendices appendix a charlotte maxeke johannesburg academic hospital, university of the witwatersrand, johannesburg, department of urology study title: erectile dysfunction following pelvic fracture data collection sheet (1) participant information participant study number: age: race: african white asian colored other date of injury associated urethral injury: yes/no type of pelvic fracture: chronic medical illnesses: yes/no (if yes please specify) smoking: yes/no (2) iief questionnaire assessment if you are sexually active and/or desire evaluation, please continue with the questions below (circle one answer for each question) 1. over the past 4 weeks, how often were you able to get an erection during sexual activity? doi 10.18502/sjms.v13i3.2953 page 160 sudan journal of medical sciences daou gdeh et al 0. no sexual activity 1. almost always or always 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never 2. over the past 4 weeks, when you had erections with sexual stimulation, how often were your erections hard enough for penetration? 0. no sexual stimulation 1. almost always or always 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never the next question is only applicable to patients who show normal score: have you had sexual difficulties in the first six months after your injury? yes/no if yes, for how long? please circle. 1 month; 2 months; 3 months; 4 months; 5 months; 6 months questions 3, 4, and 5 will ask about erections you may have had during sexual intercourse. 3. over the past 4 weeks, when you attempted sexual intercourse, how often were you able to penetrate (enter) your partner? 0. did not attempt intercourse 1. almost always or always 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never 4. over the past 4 weeks, during sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? 0. did not attempt intercourse 1. almost always or always doi 10.18502/sjms.v13i3.2953 page 161 sudan journal of medical sciences daou gdeh et al 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never 5. over the past 4 weeks, during sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? 0. a few times (much less than half the time) 1. did not attempt intercourse 2. almost always or always 3. most times (much more than half the time) 4. sometimes (about half the time) 5. almost never or never 6. over the past 4 weeks, how many times have you attempted sexual intercourse? 0. no attempts 1. 1–2 attempts 2. 3–4 attempts 3. 5–6 attempts 4. 7–10 attempts 5. 11 or more attempts 7. over the past 4 weeks, when you attempted sexual intercourse how often was it satisfactory for you? 0. did not attempt intercourse 1. almost always or always 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never 8. over the past 4 weeks, how much have you enjoyed sexual intercourse? 0. no intercourse 1. very highly enjoyable 2. highly enjoyable doi 10.18502/sjms.v13i3.2953 page 162 sudan journal of medical sciences daou gdeh et al 3. fairly enjoyable 4. not very enjoyable 5. not enjoyable 9. over the past 4 weeks, when you had sexual stimulation or intercourse how often did you ejaculate? 0. did not attempt intercourse 1. almost always or always 2. most times (more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never 10. over the past 4 weeks, when you had sexual stimulation or intercourse how often did you have the feeling of orgasm or climax (with or without ejaculation)? 0. no sexual stimulation or intercourse 1. almost always or always 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never questions 11 and 12 ask about sexual desire. let’s define sexual desire as a feeling that may include wanting to have a sexual experience (for example, masturbation or intercourse), thinking about having sex or feeling frustrated due to a lack of sex. 11. over the past 4 weeks, how often have you felt sexual desire? 1. almost always or always 2. most times (much more than half the time) 3. sometimes (about half the time) 4. a few times (much less than half the time) 5. almost never or never 12. over the past 4 weeks, how would you rate your level of sexual desire? 1. very high 2. high doi 10.18502/sjms.v13i3.2953 page 163 sudan journal of medical sciences daou gdeh et al 3. moderate 4. low 5. very low or none at all 13. over the past 4 weeks, how satisfied have you been with you overall sex life? 1. very satisfied 2. moderately satisfied 3. about equally satisfied and dissatisfied 4. moderately dissatisfied 5. very dissatisfied 14. over the past 4 weeks, how satisfied have you been with your sexual relationship with your partner? 1. very satisfied 2. moderately satisfied 3. about equally satisfied and dissatisfied 4. moderately dissatisfied 5. very dissatisfied 15. over the past 4 weeks, how do you rate your confidence that you can get and keep your erection? 1. very high 2. high 3. moderate 4. low 5. very low domain questions # total score erectile function 1, 2, 3, 4, 5, 15 _________ orgasmic function 9, 10 _________ sexual desire 11, 12 _________ intercourse satisfaction 6, 7, 8 _________ overall satisfaction 13, 14 _________ clinical interpretation i. erectile function total scores can be interpreted as follows: score interpretation doi 10.18502/sjms.v13i3.2953 page 164 sudan journal of medical sciences daou gdeh et al 0–6 severe dysfunction 7–12 moderate dysfunction 13–18 mild to moderate dysfunction 19–24 mild dysfunction 25–30 no dysfunction ii. orgasmic function total scores can be interpreted as follows: score interpretation 0–2 severe dysfunction 3–4 moderate dysfunction 5–6 mild to moderate dysfunction 7–8 mild dysfunction 9–10 no dysfunction iii. sexual desire total scores can be interpreted as follows: score interpretation 0–2 severe dysfunction 3–4 moderate dysfunction 5–6 mild to moderate dysfunction 7–8 mild dysfunction 9–10 no dysfunction iv. intercourse satisfaction total scores can be interpreted as follows: score interpretation 0–3 severe dysfunction 4–6 moderate dysfunction 7–9 mild to moderate dysfunction 10–12 mild dysfunction 13–15 no dysfunction v. overall satisfaction total scores can be interpreted as follows: score interpretation 0–2 severe dysfunction 3–4 moderate dysfunction 5–6 mild to moderate dysfunction 7–8 mild dysfunction 9–10 no dysfunction doi 10.18502/sjms.v13i3.2953 page 165 sudan journal of medical sciences daou gdeh et al the next question is only applicable to patients who show normal score: have you had sexual difficulties in the first six months after your injury? yes/no if yes, for how long? please circle. 1 month; 2 months; 3 months; 4 months; 5 months; 6 months doi 10.18502/sjms.v13i3.2953 page 166 sudan journal of medical sciences daou gdeh et al appendix b doi 10.18502/sjms.v13i3.2953 page 167 introduction materials and methods inclusion criteria exclusion criteria time of the study study location sample size data collection data analysis results discussion study limitations conclusion ethical clearance acknowledgements references appendices appendix a appendix b sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5212 production and hosting by knowledge e research article medical education in sudan: a recommendation to adopt competency-based medical education curricula for improving practices (sudanimeds) mohamed hassan taha sudan is a leading country in health professions education (hpe), a sector which started 100 years ago. the history of hpe in sudan dates back to 1918 with the training of medical assistants, with a school for modern midwifery opening in 1921 [1]. the first college of medicine in sudan—kitchener school of medicine (ksm)—was established in 1924 and is currently a part of the university of khartoum [2]. about half-a-century later, two more medical schools—juba university school in 1977 and gezira university school in 1978— were established. in the 1990s, there was an enormous expansion in higher education, particularly in colleges of medicine, with more than 30 being inaugurated [3]. currently, sudan has more than 60 colleges of medicine. several problems facing newly established medical schools in sudan have been identified in recent years: challenges in designing an appropriate curriculum, lack of essential educational resources crucial to run a school consistent with quality standards, extreme shortage of qualified medical faculty due to migration, and lack of appropriate clinical training facilities and teaching hospitals [2, 3]. furthermore, there are concerns that the significant expansion of higher education in sudan, along with unparalleled strategic planning for establishing these medical schools to ensure proper training of medical students and a clear national policy for ensuring the competency of graduates, might affect the quality of the services provided to patients [3, 4]. several studies have suggested that the provision of high-quality and safe patient care can only be guaranteed if medical students receive proper clinical teaching [5– 7]. therefore, several medical schools worldwide are increasingly focused on improving clinical teaching, implementing competency-based medical education (cbme) [8]. cbme is an educational approach to guarantee that medical graduates develop the competencies required to fulfil patients’ needs in society [9]. this means that teaching, how to cite this article: mohamed hassan taha (2019) “medical education in sudan: a recommendation to adopt competency-based medical education curricula for improving practices (sudanimeds),” sudan journal of medical sciences, vol. 14, issue no. 3, pages 126–131. doi 10.18502/sjms.v14i3.5212 page 126 corresponding author: mohamed hassan taha; email: mtaha@sharjah.ac.ae received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e mohamed hassan taha. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mtaha@sharjah.ac.ae https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed hassan taha learning, and assessment focus on the development of competencies and continues till the desired competency is achieved [10]. most countries that have adopted cbme have used a national competency framework developed by local higher authorities. these frameworks do not necessarily aim at unifying the curricula of the medical schools in these countries, but instead ensure the minimal competencies required at the level of graduation for the safe provision of medical care. several competency frameworks have been developed and implemented worldwide: the canmeds initiative in canada; the accreditation council of graduate medical education of the united states of america; tomorrow’s doctors: recommendations on undergraduate medical education in the united kingdom; the scottish doctor competency framework; good medical practice; the australian curriculum framework for junior doctors; the 2009 framework for undergraduate medical education in the netherlands; swedish medical education standards; the brown university nine abilities, medical school objectives project by aamc; global minimal essential requirements; the european medical tuning project; dundee 12 outcomes; and the international medical college outcomes malaysia [11–16]. figures 1 and 2 show examples of these competency frameworks, focusing on the main themes around which the core competencies have been developed. figure 1: example of national competency framework in the region (saudimeds) [18]. doi 10.18502/sjms.v14i3.5212 page 127 sudan journal of medical sciences mohamed hassan taha figure 2: example of national competency framework in canada (canmeds) [19]. 1. roadmap for the development of the national competency framework (sudanese medical education directives sudanimeds) similar to most international frameworks, the following approach is suggested: 1. review of previous work. 2. running of many workshops and virtual meetings to develop the first draft of the framework. 3. agreement of the major domains, sub-domains, and competencies/learning outcomes following these consultative workshops. 4. involvement of the stakeholders, which could be achieved by the use of the delphi technique [17]. 5. involvement of all sudanese medical schools and national medical education experts. 6. review of the finalized framework by international experts of medical education who participated in developing national and international cbme frameworks and are involved in accreditation of medical schools worldwide. these steps are important, but the most important points that need to be considered in experts’ views and recommendation should have been taken into consideration in doi 10.18502/sjms.v14i3.5212 page 128 sudan journal of medical sciences mohamed hassan taha the final draft of the sudanese national competency framework; sudanese medical education directives (sudanimeds). 2. elements of the suggested framework this framework might be developed at different levels, including (a) core competencies for undergraduate medical curricula for sudanese doctors, (b) enabling competencies that should be useful as guidance for learning outcomes in the medical curriculum, (c) clinical presentations that clinical training needs to emphasize, and (d) clinical skills and procedures needed to be mastered before graduation. 3. the importance of sudanimeds (suggested framework) this framework should be used as a guiding principle for curriculum design and development for all medical schools. the core competencies of the graduates and their characteristics could be shaped from the core competencies for this framework. the course learning outcomes could also be extracted from this framework. moreover, all clinical presentations and skills that should be covered in undergraduate medical schools in sudan could be extracted from this framework. 4. who should collaborate to develop this framework? several higher authorities and governing bodies could participate in the development of this national framework and transformation into cbme, such as the association of deans of medical schools, the sudanese association of medical education, medical education development centers in medical schools, the sudan medical council, the sudan medical specialization board, and national and international experts in medical education. references [1] haseeb, m. a. (1967). medical education in the sudan. academic medicine, vol. 42, no. 7, pp. 666–672. [2] fahal, a. h. (2007). medical education in the sudan: its strengths and weaknesses. medical teacher, vol. 29, no. 9, pp. 910–914. doi 10.18502/sjms.v14i3.5212 page 129 sudan journal of medical sciences mohamed hassan taha [3] ahmed, a. a. (2012). medical education in sudan: emerging issues and acute needs. sudanese journal of public health, vol. 7, no. 2, pp. 56–64. [4] ahmed, y., taha, m. h., alneel, s., et al. (2018). evaluation of the learning environment and the perceived weakness of the curriculum: student perspective. international journal of research in medical sciences, vol. 7, no. 1, p. 165. [5] tolsgaard, m. g. (2013). clinical skills training in undergraduate medical education using a student-centered approach. danish medical journal, vol. 60, no. 8, p. 14. [6] leach, d. c. and philibert, i. (2006). high-quality learning for high-quality health care: getting it right. jama, vol. 296, no. 9, pp. 1132–1134. [7] taha, m. h., ahmed, y., abdalla, m.e., et al. (2019). exploring factors affecting the quality of postgraduate medical education in sudan: residents perspective. international journal of research in medical sciences, vol. 6, no. 2, pp. 1–9. [8] harden, r. m. (2006). trends and the future of postgraduate medical education. emergency medicine journal, vol. 23, no. 10, pp. 798–802. retrieved from: http: //emj.bmj.com/cgi/doi/10.1136/emj.2005.033738 [9] frank, j. r., snell, l. s., ten, c. o., et al. (2010). competency-based medical education: theory to practice. medical teacher, vol. 32, no. 8, pp. 638–645. [10] iobst, w. f., sherbino, j., cate, o. t., et al. (2010). competency-based medical education in postgraduate medical education. medical teacher, vol. 34, no. 8, pp. 651–656. [11] rose, s. h. and long, t. r. (2010). accreditation council for graduate medical education (acgme) annual anesthesiology residency and fellowship program review: a ”report card” model for continuous improvement. bmc medical education, vol. 10, no. 1, p. 13. [12] bandiera, g., sherbino, j., and frank, j. r. (2006). the canmeds assessment tools handbook: an introductory guide to assessment methods for the canmeds competencies. royal college of physicians and surgeons of canada. [13] committee gmce. (1993). tomorrow’s doctors: recommendations on undergraduate medical education. general medical council london. [14] ross, m. t., macrae, c., scott, j., et al. (2014). core competencies in teaching and training for doctors in scotland: a review of the literature and stakeholder survey. medical teacher, vol. 36, no. 6, pp. 527–538. [15] laan, r. f. j. m., leunissen, r. r. m., and van herwaarden, c. l. a. (2010). the 2009 framework for undergraduate medical education in the netherlands. tijdschr voor med onderwijs, vol. 29, no. 1, pp. 10–15. doi 10.18502/sjms.v14i3.5212 page 130 http://emj.bmj.com/cgi/doi/10.1136/emj.2005.033738 http://emj.bmj.com/cgi/doi/10.1136/emj.2005.033738 sudan journal of medical sciences mohamed hassan taha [16] ahmed, y., taha, m. h., al-neel, s., et al. (2018). students’ perception of the learning environment and its relation to their study year and performance in sudan. international journal of medical education, vol. 9, pp. 145–150. [17] hsu, c.-c. and sandford, b. a. (2007). the delphi technique: making sense of consensus. practical assessment, research and evaluation, vol. 12, no. 10, pp. 1–8. [18] zaini, r. g., bin abdulrahman, k. a., al-khotani, a. a., et al. (2011). saudi meds: a competence specification for saudi medical graduates. medical teacher, vol. 33, no. 7, pp. 582–584. [19] frank, j. r., snell, l., and sherbino, j. (2014). the draft canmeds 2015 physician competency framework–series iv. ottawa r coll physicians surg canada. doi 10.18502/sjms.v14i3.5212 page 131 roadmap for the development of the national competency framework (sudanese medical education directives sudanimeds) elements of the suggested framework the importance of sudanimeds (suggested framework) who should collaborate to develop this framework? references sudan journal of medical sciences volume 13, issue no. 4, doi 10.18502/sjms.v13i4.3597 production and hosting by knowledge e research article assessment of plasma fibrinogen level and lipid profile in sudanese smokers h. zaki, r. mustafa, h. mahgoub, and b. abdalla department of biochemistry and nutrition, faculty of medicine, university of gezira, sudan abstract background: cigarette smoking is a leading preventable risk factor for the development and progression of cardiovascular diseases (cvds). epidemiologic studies in smokers confirm the association between the alteration in lipid profile levels and cvds risk. fibrinogen, an acute phase reactant with active involvement in endothelial function, thrombosis and inflammation. it is signified as a systemic marker of carotid atherosclerosis. the purpose of this study was to assess the level of fibrinogen and lipid parameters in sudanese tobacco smokers. methods: this case-control study included 55 adult male of a current smoking status; their ages ranged between 18 and 54 years, and 100 non-smokers considered as controls. we evaluated the effect of cigarette smoking on plasma fibrinogen and serum lipid profile. the american heart association guidelines and reference ranges were used to identify the smokers with increased risk of coronary heart disease. results: our study revealed an increase in the levels of fibrinogen, total cholesterol, and low-density lipoprotein cholesterol (ldl-c) among smokers than controls, whereas the mean level of and triglycerides did not differ. the levels of highdensity lipoprotein cholesterol hdl-c demonstrated decrement. further, smokers were classified according to the atherogenic risk index ldl-c/hdl-c ratio, the studied parameters fibrinogen, total cholesterol, and triglycerides were significantly increased in those who have ratio 4.5 and more (p = 0.001, p = 0.018, p = 0.007, respectively). smokers with atherogenic index ≥ 4.5 were more likely to have ≥ 300 mg/dl fibrinogen level (odds ratio (or) 3.96, 95% confidence interval (95%ci) 1.14– 13.73, p = 0.026). moreover, the level of the fibrinogen can be predicted by linear regression equation: fibrinogen level = 19.49 + 79.08 (the ratio of ldl-c ⁄hdl-c), r = 0.37, p = 0.008, 95%ci 21.20–136.95. conclusion: increased fibrinogen, ldl-c, and ldlc/hdl-c ratio may potentiate the development of cardiovascular disease in smokers. keywords: fibrinogen, lipid profile, smokers how to cite this article: h. zaki, r. mustafa, h. mahgoub, and b. abdalla (2018) “assessment of plasma fibrinogen level and lipid profile in sudanese smokers,” sudan journal of medical sciences, vol. 13, issue no. 4, pages 251–263. doi 10.18502/sjms.v13i4.3597 page 251 corresponding author: h. zaki; email: hanizaki@uofg.edu.sd received 9 september 2018 accepted 5 december 2018 published 26 december 2018 production and hosting by knowledge e h. zaki et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v13i4.3597&domain=pdf&date_stamp=2018-12-26 mailto:hanizaki@uofg.edu.sd https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences h. zaki et al 1. introduction the tobacco epidemic is one of the biggest public health threats the world affronted, killing around 6 million people a year. more than 5 millions of those deaths are the result of direct tobacco use. nearly 80% of the more than 1 billion smokers worldwide live in lowand middle-income countries with increased risk to cardiovascular diseases (cvds) [1, 2]. smoking is estimated to cause nearly 10% of cvds. the risk of cvds mortality for persons who smoke cigarettes is about double that of lifetime non-smokers [3]. disease risk due to smoking is not limited to smokers only, passive smoking, exposure to environmental tobacco smoke, is associated with adverse health effects, and it increases the risk of several diseases [4]. the smokers and passive smokers have a different lifestyle than non-smokers, as these people consume more calories, fat, and alcohol, and less fibre, fruit, vegetables, vitamin supplements, and useful oilseeds, which increase the incidence of atherosclerosis and coronary artery diseases in smokers [5]. several studies confirm that smoking increases the level of inflammatory markers in blood as white blood cell count, fibrinogen, and c-reactive protein [6, 7]. smokers have high-level total cholesterol (tc) and ldl cholesterol (ldl-c) levels and lower hdl cholesterol (hdl-c) levels exacerbating the risk of myocardial infarction, sudden cardiac death, stroke, peripheral vascular disease [8]. most of the proposed proatherogenic actions of smoking, such as interference with blood coagulation, induction of endothelial dysfunction, and promotion of lipid per oxidation, reverse themselves shortly after cessation of smoking [9]. fibrinogen is a plasma glycoprotein produced by hepatocytes in response to interlukin-1, interleukin-6, and tumour necrosis-α during acute severe infections [10, 11]. there is growing evidence from prospective studies that a higher plasma fibrinogen concentration is associated with increased risk, incidence, and severity of coronary heart disease [12–14]. various studies suggested association between smoking status and elevated fibrinogen levels [15–18]. the purpose of this study was to assess the level of fibrinogen and lipid profile parameters in sudanese tobacco smokers. 2. materials and methods doi 10.18502/sjms.v13i4.3597 page 252 sudan journal of medical sciences h. zaki et al 2.1. study design and study subjects the present study has been approved by the faculty of medicine, university of gezira ethics committee. furthermore, all smokers signed the formal consent before data and sample collection. this case-control recruited 55 male cigarettes smokers and 100 age– sex-matched non-smokers. all of them were from the gezira state – wad-medani city, sudan. a questionnaire was designed to collect personal information, clinical data, and smoking history from each participant. the study participants were clinically evaluated for their health, none of the participant reported to have diseases/disorders or medications that affect fibrinogen level or lipid parameters. blood samples were collected from participants in sodium citrate to measure plasma fibrinogen, and plain container for serum lipid profile estimation. all the blood samples were centrifuged at 3000rpm for 5 min at the room temperature and plasma lipid profile with fibrinogen were measured immediately. automated analyzer accent-200 was used to estimate plasma fibrinogen by immuno-turbidimetric assay; and lipid profile by enzymatic spectrophotometric method. 2.2. statistical analysis statistical analysis was carried out using statistical package for sciences (spss, version 20). data were expressed as mean ± standard error of mean (sem) and compared firstly with controls and secondly with the provided reference values of the reagents and the data published in the literature. the smokers were stratified according to the atherogenic index (ldl-c/hdl-c) into two groups, group i (less than 4.5) and group ii (4.5 and more), means of continuous variables were compared between the two groups using t-test. then, the logistic regression analysis was performed to measure the risk estimate by odds ratio, 95% confidence intervals (95%ci), and p-value of having high concentrations of fibrinogen level in the two atherogenic groups. besides, the linear regression test was applied to predict the level of fibrinogen in smokers using the atherogenic index. 3. results doi 10.18502/sjms.v13i4.3597 page 253 sudan journal of medical sciences h. zaki et al 3.1. the general characteristics of the study group and the comparison of the measured parameters smokers’ ages ranged between 18 and 54 years with the mean age of 27.60 ± 0.95. the mean smoking duration was 6.6 ± 0.66 years and the average number of cigarettes per smoker per day was 9.8 ± 1.56. table 1 shows the measured lipid profile parameters and fibrinogen level in the two groups, levels of cholesterol, ldl-c, and fibrinogen were significantly increased in smokers than non-smokers (p < 0.0001). the hdl-c was markedly decreased in the smokers group, while the triglycerides level did not differ. t 1: lipid parameters and fibrinogen level in smokers and non-smokers groups. parameters smokers (n = 55) non-smokers (n = 100) p-value cholesterol (mg/dl) 185.11 ± 4.72 133.31 ± 1.81 < 0.0001 hdl-c (mg/dl) 29.91 ± 0.85 55.14 ± 2.03 < 0.0001 ldl-c (mg/dl) 145.76 ± 3.10 86.28 ± 1.37 < 0.0001 triglycerides (mg/dl) 126.07 ± 3.81 120.90 ± 5.13 0.4904 fibrinogen (mg/dl) 423.44 ± 33.91 284.98 ± 4.15 < 0.0001 3.2. the risk of developing cardiovascular disease among smokers based on the reference range of lipid parameters and fibrinogen the mean levels of lipid profile and fibrinogen in smokers were compared to the reference ranges of the american heart association [19] displaying the percentage of smoker who are at risk of cardiovascular diseases. according to the published guidelines, table 2 shows that 12.73% of the smokers were at high risk of developing cvds. the hdl-c showed a marked decrease, 92.73% of the whole group with increased risk. the ldl-c level was increased as compared with the reference range, 32.73% of the smokers were highly susceptible to cvds risk. for the atherogenic index ldl-c⁄hdl-c, the mean was 5.05 ± 0.17, indicating that the studied smokers were at high risk. of the 55 smokers, only 16.36% had borderline high triglycerides. the fibrinogen level 423.44 mg/dl was high when compared with the reference range (365 mg/dl) of the american heart association. normal plasma fibrinogen levels range were defined as 200–400 mg/dl, and hyperfibrinogenemia was defined as plasma fibrinogen concentrations greater than 400 doi 10.18502/sjms.v13i4.3597 page 254 sudan journal of medical sciences h. zaki et al t 2: mean levels of the lipid parameters and fibrinogen, and risk participants according to the reference ranges. lipid parameters mean ± se (n = 55) smokers at the border line of cvds risk smokers at high cvds risk cholesterol (mg/dl) 185.11 ± 4.72 3.64% 12.73% hdl-c (mg/dl) 29.91 ± 0.85 7.27% 92.73% ldl-c (mg/dl) 145.76 ± 3.10 45.45% 32.73% ldl-c⁄hdl-c 5.05 ± 0.17 18.18% 72.73% triglycerides (mg/dl) 126.07 ± 3.81 16.36% – fibrinogen level fibrinogen (mg/dl) 423.44 ± 33.91 27.27%|| 36.36%† notes: the american heart association guidelines: the total cholesterol optimal range < 200mg/dl, range from 200–239 mg/dl, demonstrates borderline of risk, ≥ 240 mg/dl indicates high risk to cvds; optimal ldl-c in the range < 100 mg/dl, while 100–129 mg/dl considered as near optimal, 130–150 mg/dl defines the borderline risk and ≥ 160mg/dl the high cvds risk; hdl-c < 60 mg/dl specifies the group of adult men at the borderline risk, while the high cvds risk men are classified at < 40 mg/dl; the hypertriglycerideamia denotes borderline risk at 150–190 mg/dl, and ≥ 200 mg/dl represents the high-risk group; the ldl-c⁄hdl-c ≥ 4.5 indicates high atherogenic risk. mg/dl [20]. || specifies smokers with fibrinogen level ≤ 400mg/dl, † indicates smokers with fibrinogen level > 400mg/dl. 3.3. comparing levels of cholesterol, triglycerides, and fibrinogen between atherogenic groups the study group was stratified according to the ldl-c ⁄hdl-c ratio into low-risk group of less than 4.5 (group i) and high-risk group that had 4.5 and more (group ii). the level of cholesterol was higher in group ii compared to group i, the difference between the two group was statistically significant (p = 0.018). the mean serum triglycerides was significantly higher in group ii than in group1(p = 0.007). group ii, the high atherogenic risk group, showed conspicuous increase in fibrinogen level compared to group i (p = 0.001). all these data are demonstrated in table 3 and figure 1. t 3: the mean levels of cholesterol, triglycerides, and fibrinogen in smokers atherogenic groups. variables atherogenic < 4.5 group i (n = 15) atherogenic ≥ 4.5 group ii (n = 40) p-value cholesterol 168.73 ± 7.06 191.25 ± 5.67 0.018 triglycerides 111.47 ± 5.32 131.55 ± 4.58 0.007 fibrinogen 293.00 ± 27.21 472.35 ± 43.18 0.001 note: ldl-c and hdl-c levels were not represented in the variables because they were expressed as ldl-c/hdl-c ratio (atherogenic index). doi 10.18502/sjms.v13i4.3597 page 255 sudan journal of medical sciences h. zaki et al 3.4. risk estimate for cardiovascualar diseases using ldl-c⁄hdl-c ratio and fibrinogen level the risk estimate of having high fibrinogen as a risk factor for cardiovascular events was assessed in smokers using logistic regression analysis (table 4). no significant association was observed between the level of total cholesterol, ldl-c, or triglycerides. considerably, the smokers with atherogenic index ≥ 4.5 are 3.96% more likely to have high fibrinogen ≥ 300 mg/dl and hence more vulnerable to cardiovascular diseases (p = 0.026). t 4: frequency of smokers and risk estimate of having high fibrinogen according to the normal and high ranges of total cholesterol, ldl-c, triglycerides levels, and ldl-c⁄hdl-c ratio. ldl-c⁄hdl-c ratio fibrinogen level p-value (or, 95%ci) ≥ 300 mg/dl < 300 mg/dl cholesterol ≥ 200 26 14 0.73 (0.81, 0.24–2.74) cholesterol < 200 9 6 ldl-c ≥ 130 31 15 0.20 (2.58, 0.61–11.04) ldl-c < 130 4 5 tg ≥ 150 7 2 0.34 (2.25, 0.42–12.06) tg < 150 28 18 atherogenic ≥ 4.5 29 11 0.026 (3.96, 1.14–13.73) atherogenic < 4.5 6 9 note: hdl-c was removed from the logistic regression model because all smokers were having hdl-c < 60mg/dl. figure 1: the correlate of fibrinogen level to the ldl-c/hdl-c ratio. doi 10.18502/sjms.v13i4.3597 page 256 sudan journal of medical sciences h. zaki et al 4. discussion smoking has been recognized as an important risk factor for the cvds, attributed to the alterations of the plasma fibrinogen and lipoprotein pattern [21, 22]. our study was conducted to evaluate the level of fibrinogen and lipid profile in sudanese smokers. according to the reference range of the fibrinogen level, the study showed increased mean level of fibrinogen among sudanese smokers. this result was supported by several global studies, which confirmed an increased level of fibrinogen among smokers [22–24]. in sudan, a comparative study was done that revealed the increase of fibrinogen level among healthy smokers, whereas the level was decreased among non-smokers and ceased smokers, plasma fibrinogen may remain elevated for several years after cessation [25, 26]. in that scenario, it was proved that a primary role for increased synthesis in producing the hyperfibrinogenaemia associated with smoking: an influential study for smokers showed that cessation from smoking for a period of only two weeks induces a significant decrease in the rate of fibrinogen synthesis by the liver, with a concomitant reduction in the plasma fibrinogen concentration [27]. the association between fibrinogen and carotid atherosclerosis was investigated; high incidence of carotid atherosclerosis was reported among smokers, whilst this trend was not manifested for non-smokers or former smokers [17]. in this study, 92.73% of the smokers showed low hdl-c level < 40mg/dl, and 72.73% of the smokers have ≥ 4.5 ldl-c ⁄hdl-c ratio. highest fibrinogen levels were observed in smokers with high atherogenic risk. clinical studies have documented that fibrinogen is not only a blood coagulation factor but also an inflammatory marker, influencing leukocyte recruitment, and particularly modulating the adhesive behaviour of the neutrophils [28]. a number of studies reported that a high plasma fibrinogen level is an independent and major risk marker of cardiovascular diseases [29–31]. in a population sample of adults without clinically obvious atherosclerotic disease, elevated fibrinogen levels ascertained to be associated to carotid intima-media thickness, representing a systemic marker of carotid atherosclerosis [32]. in the same consensus, cigarette smoking linked with elevated serum levels of cholesterol, ldl-c, triglycerides, and lower plasma concentrations of hdl-c than non-smoker [33, 34]. our study does not indicate extreme deviation from normal reference ranges. similar results were obtained from controlled clinical trial in polish smokers; higher lipid values with elevated lipid peroxidation products were found when compared with the nonsmokers’ group, annotating the cigarette-smoking risk in the onset of atherosclerosis and coronary heart disease [35]. nicotine and carbon monoxide seem to play a major doi 10.18502/sjms.v13i4.3597 page 257 sudan journal of medical sciences h. zaki et al role in the effect of smoking on vessels. in addition to its acute haemodynamic effects, tobacco not only has an atherogenic effect (endothelial toxicity and changes in lipid profile), but it also facilitates thrombosis (by alteration of platelet functions and elevation of fibrinogen level, haematocrit level and blood viscosity) and vascular contraction (through modification of prostaglandin metabolism and action on catecholamines or decrease of nitric oxide production) [36]. smoking in adolescence and young adulthood might increase the risk of cardiovascular events [34]. in this study, it is worth pointing out that 60% of the study smokers with age less than 35 years, younger smokers give prediction to longer smoking duration and hence aggravating the risk of dyslipidaemia. confirmation to this suggestion, the smokers with high atherogenic index are more likely to have higher fibrinogen level increasing their vulnerability to develop cardiovascular events. our data showed that this linear correlation between fibrinogen and atherogenic index was substantiated by the following equation: fibrinogen level = 19.49 + 79.08 (the ratio of ldl-c⁄hdl-c), r = 0.37, p = 0.008. hence, smokers with ldl-c ⁄hdl-c ratio = 4.5 might have fibrinogen level 375.35 mg/dl. 5. conclusion significant elevation of fibrinogen, ldl-c levels, and ldl-c ⁄hdl-c ratio concomitant with significant decrease in serum hdl-c concentration were remarked among sudanese smokers. smokers with high atherogenic index are more liklely to have increased level of fibrinogen. it was suggested that the increase of fibrinogen level in addition to alterations of lipid profile increase the risk of cardiovascular disease among sudanese smokers. 6. limitations of the study overall, the study included a small number of smokers, and little attention was paid to post-study follow-up. acknowledgements the authors acknowledge all the study participants. doi 10.18502/sjms.v13i4.3597 page 258 sudan journal of medical sciences h. zaki et al funding this research received no specific grant from any funding agency. conflict of interest the authors declare no conflict of interest. authors’ contribution hani yousif zaki and reem sideeg mustafa participated in designing the study, collection of data, and the practical work. hani yousif zaki and hiba mahgoub ali interpreted the data. badreldin elsoni abdalla made amendments on the manuscript draft. all authors meticulously revised and approved the final manuscript. references [1] moran, a. e., roth, g. a., narula, j., et al. 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(2004). validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease. haematologica, vol. 89, no. 10, pp. 1226–1231. [33] bazzano, l. a., he, j., muntner, p., et al. (2003). relationship between cigarette smoking and novel risk factors for cardiovascular disease in the united states. annals of internal medicine, vol. 138, no. 11, pp. 891–897. [34] mammas, i. n., bertsias, g. k., linardakis, m., et al. (2003). cigarette smoking, alcohol consumption, and serum lipid profile among medical students in greece. european journal of public health, vol. 13, no. 3, pp. 278–282. [35] sliwinska-mosson, m., mihulka, e., and milnerowicz, h. (2014). [assessment of lipid profile in non-smoking and smoking young health persons]. przeglad lekarski, vol. 71, no. 11, pp. 585–587. doi 10.18502/sjms.v13i4.3597 page 262 sudan journal of medical sciences h. zaki et al [36] messner, b. and bernhard, d. (2014). smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. arteriosclerosis, thrombosis, and vascular biology, vol. 34, no. 3, pp. 509–515. doi: 10.1161/atvbaha.113.300156. doi 10.18502/sjms.v13i4.3597 page 263 introduction materials and methods study design and study subjects statistical analysis results the general characteristics of the study group andthe comparison of the measured parameters the risk of developing cardiovascular disease amongsmokers based on the reference range of lipid parameters and fibrinogen comparing levels of cholesterol, triglycerides, and fibrinogen between atherogenic groups risk estimate for cardiovascualar diseases using ldl-c⁄hdl-c ratio and fibrinogen level discussion conclusion limitations of the study acknowledgements funding conflict of interest authors' contribution references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4381 production and hosting by knowledge e research article clinical and biochemical manifestations of severe sickle cell anemia in adult patients in steady state in ile-ife, nigeria oguntoye oluwatosin oluwagbenga1, ndububa dennis a.2, yusuf musah.1, bolarinwa rahman a.3, and ayoola oluwagbemiga o.4 1department of internal medicine, afe babalola university ado-ekiti/federal teaching hospital, ido-ekiti, ekiti state, nigeria 2department of medicine, obafemi awolowo university, ile-ife/obafemi awolowo university teaching hospitals complex, ile-ife, osun state, nigeria 3department of hematology, obafemi awolowo university, ile-ife/obafemi awolowo university teaching hospitals complex, ile-ife, osun state, nigeria 4department of radiology, obafemi awolowo university, ile-ife/obafemi awolowo university teaching hospitals complex, ile-ife, osun state, nigeria abstract background: there are documented established markers (indices) of disease severity in patients with sickle cell anemia (sca) and they determine the course of the disease. this study investigated the pattern and prevalence of some of these markers of disease severity in adult patients with sca in steady state attending the hematology clinic of a federal tertiary teaching hospital in ile-ife, nigeria. materials and methods: this was a descriptive study. basic demographic data and relevant clinical information was obtained using a well-structured questionnaire and the case files (hospital records) of 50 consecutive sca (hbss) patients. results: the study group comprised of 21(42%) males and 29(58%) females. the age range was 18–45years with a mean(±sd) of 27.6±7.607. hepatomegaly(64%), frequent episodes of vaso-occlusive crisis, that is, ≥ 3 episodes per year(30%) and dactylitis in infanthood(26%) were the most common clinical parameters identified in these patients while a high serum total bilirubin of > 51µmol/l(26%) was the most common laboratory parameter seen in these patients. conclusion: markers of disease severity were identified in the patients with sca in this study. the presence of these markers in an sca patient connotes severe disease and they determine the course of the disease. therefore, there is a need to pay more attention to these patients by following them up more closely. keywords: disease severity, markers, sickle cell anemia, steady state, adults, patients how to cite this article: oguntoye oluwatosin oluwagbenga, ndububa dennis a., yusuf musah., bolarinwa rahman a., and ayoola oluwagbemiga o. (2019) “clinical and biochemical manifestations of severe sickle cell anemia in adult patients in steady state in ile-ife, nigeria,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 52–63. doi 10.18502/sjms.v14i1.4381 page 52 corresponding author: oguntoye oluwatosin oluwagbenga; email: proflast@yahoo.com received 9 february 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e oguntoye oluwatosin oluwagbenga et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4381&domain=pdf&date_stamp=2019-03-31 mailto:proflast@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al 1. introduction sickle cell anemia (sca) is an autosomal recessive genetic disorder caused by a defect in the hbb gene which codes for hemoglobin ß chain [1, 2]. this leads to the production of abnormal hemoglobin chains within the red blood cell, which causes rigidity and sickling of the cell, leading to vascular occlusion and ischemia in multiple organs [3, 4]. the normal human hemoglobin molecule is a heterotetramer composed of four hemoglobin chains (two α and two β) and the normal adult hemoglobin is hemoglobin aa [3]. the abnormal genes occur as a result of glutamic acid-to-valine substitution at the sixth base position in the β hemoglobin gene on chromosome 11 [3]. sickle cell anemia results from the inheritance of two sickle β hemoglobin genes as hbss [4]. sickle cell anemia is particularly common among people whose ancestors come from sub-saharan africa, india, saudi arabia, and mediterranean countries. each year about 300,000 infants are born with major hemoglobin disorders – including more than 200,000 cases of sickle-cell anemia in africa [5, 6]. in nigeria, by far the most populous country in the sub-region, 24% of the population are the carriers of the mutant gene (hbas) and the prevalence of sickle-cell anemia (hbss) is about 2% [5, 7–9]. the resultant changes in the red blood cells causes chronic intermittent vasoocclusive events resulting in tissue ischemia; chronic hemolytic anemia resulting in varying degrees of anemia; and multiple organ damage from microinfarcts that can affect any organ in the body, including the bones, lungs, liver, kidneys, brain, eyes, heart, skin, and joints [2]. episodes of crisis also occur and these include hemolytic crisis, aplastic crisis, acute sequestration crisis, and vaso-occlusive crisis [4]. there are documented established markers (indices) of disease severity in patients with sca in the literature (item 1) and they determine the course of the disease. these markers include both clinical and laboratory parameters [10, 11]. identification of these markers of disease severity among adult sca patients in steady state affords us the opportunity to know the course of the disease in these patients over the past years as well as to predict the likely course of the disease in the years to come. this would enable physicians to tailor management plans for the patients and also aid prompt intervention as the need arises, thereby preventing or reducing the complications that otherwise would have resulted. this would reduce the overall morbidity and mortality associated with sca. presently, there is paucity of data in nigeria on this topic. this study determined the pattern and the prevalence of the markers of disease severity in adult sca patients in steady state in ile-ife, nigeria, which now provides the much needed information for doi 10.18502/sjms.v14i1.4381 page 53 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al holistic management of these patients as well as scientific data for further research on this topic. 2. materials and methods 2.1. selection of study subjects this was a descriptive study that was carried out at the hematology clinic of a federal tertiary teaching hospital in ile-ife, osun state in the south western geopolitical zone of nigeria between june 2014 and april 2015. the inclusion criteria for this study consisted of patients ≥18 years of age with sca [hemoglobin ss (hbss) genotype], who must be in steady state and have given written informed consent to be recruited. the following categories of patients were excluded from the study; patients less than 18 years of age, patients with other hemoglobinopathies such as hbsc, hbcc, hbs b thalassemia etc., patients in sickle cell crisis and patients who were pregnant. a total of 50 study subjects (patients) were recruited for the study. selection of patients for the study was done by consecutive selection of 50 consenting sca patients. ethical approval was obtained from the ethics and research committee of the institution. 2.2. evaluation of study subjects the patients were interviewed to elicit important relevant history and to ensure that they fulfill the set inclusion criteria for the study. a structured questionnaire was designed for the study which was used to collect demographic and relevant clinical information. the following information was obtained from the patients’ case files (hospital records): frequency of crisis, last episode of crisis, nature of crisis, complications, previous hospitalizations, total units of blood transfusion ever received, steady state hemoglobin level, co-morbidities, drug history, family history of hemoglobinopathies and relevant social history. the objective of the patient evaluation performed in this study was to identify the presence of the well-documented and established markers of disease severity in sca patients. it was impossible to assess for all these markers in this study, thus some were selected. a physical examination was conducted on the study subjects including the measurement of anthropometric parameters (height and weight to calculate body mass index). blood samples were collected to ascertain the hemoglobin genotype of the study subjects as well as for full blood count and serum bilirubin. doi 10.18502/sjms.v14i1.4381 page 54 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al hepatic ultrasonographic evaluation was also performed for all the study subjects in order to assess for hepatomegaly which is one of the markers of disease severity and this was done in the ultrasound room of the radiology department of the institution. the hepatic ultrasound scan was done by the same consultant radiologist in order to avoid inter-observer variations and differences. a mindray real-time ultrasound machine model dc-7 was used. the liver span was taken as the liver length measured at the level of the mid-clavicular line along the long axis of the right lobe of the liver. in adults, hepatomegaly is defined as the long axis of the liver, longer than 155 mm and this cut-off was used in this study. 2.3. data analysis the data obtained was analyzed using the statistical package for the social sciences (spss) version 17.0 computer software package (spss chicago inc. il u.s.a). descriptive statistics used included frequency tables, percentages, means, and standard deviations. 2.4. study definitions sickle cell anemia: persons with hemoglobin genotype ss (hbss). normal individuals: persons with hemoglobin genotype aa (hbaa). steady state: a patient with sca is said to be in steady state when there is no recent drop in the hemoglobin level and there is absence of infection, pain, acute complicating factors or acute clinical symptoms or crisis for at least three months established by a careful history and complete physical examination [12]. sickle cell crisis: crisis in patients with sca refers to the episodes of acute illness attributable to the sickling phenomenon in which there is a sudden exacerbation of symptoms and signs of patients who had hitherto been in stable condition. this could be in the form of pain or vaso-occlusive crisis, aplastic crisis, acute sequestration crisis, or hemolytic crisis [12]. 3. results the study group (hbss patients) comprised of 21 (42%) males and 29 (58%) females. the ages ranged from 18 to 45 years with a mean(±sd) of 27.6±7.607. the bmi of the patients ranged from 15.10 to 26.50 kg/m² with a mean(±sd) of 19.36±2.185. the mean bmi for the patients was within the normal range. twenty-four doi 10.18502/sjms.v14i1.4381 page 55 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al (48%) of the patients were underweight, one (2 %) was overweight, and none was obese. amongst the underweight patients, none fulfilled the criteria for failure to thrive (table 1). table 1: the established markers (indices) of disease severity in sickle cell anemia [10, 11]. clinical parameters history of frequent vaso-occlusive/pain crisis (≥ 3 pain episodes per year) history of stroke history of priapism evidence of avascular osteonecrosis presence of pulmonary hypertension history of acute chest syndrome hepatomegaly evidence of renal insufficiency frequent blood transfusions (≥ 3 transfusions per year to treat the complications of sickle cell anemia) dactylitis in early childhood (occurring before the age of one year) frequent hospitalizations related to sickle cell crisis— sequestration, aplastic (≥ 3 hospital admissions per year) chronic leg ulceration failure to thrive (weight or body mass index for age less than the 5𝑡ℎ percentile) use of hydroxyurea (to treat the complications of sickle cell anemia) laboratory parameters leukocytosis in the absence of infection (> 15,000/mm3) chronic severe anemia (hemoglobin concentration < 6.6g/dl) high packed cell volume (pcv > 30%)/high hemoglobin concentration (>10g/dl) low fetal hemoglobin level (hbf < 3%) high serum total bilirubin level (> 51µmol/l) high lactate dehydrogenase level (ldh > 700 iu/l) high serum ferritin level (>2500mg/l) the mean(±sd) age at first diagnosis of sca in the patients was 6.46±4.827 with a range of 3 months – 19 years. all of them had had one form of sickle cell crisis or the other in the past as shown in table 2. all the patients had had vaso-occlusive crisis (voc) in the past. nineteen (38%) patients experienced one episode of voc per year while 15 (30%) and 13 (26%) experienced two and three episodes per year, respectively. only 25 (50%) of the patients had had hemolytic crisis in the past. out of these 25 patients, 20 (80%) and 3 (12%) had one and two episodes per year, respectively. only one patient (2%) had hepatic sequestration crises in the past and only two (4%) had ever had a splenic sequestration crisis in the past. none had aplastic crisis. forty (80 %) of the patients had had blood transfusion in the past. the units of blood received by the patients ranged from 1 to 30 units with a mean(±sd) of 4.69±5.445. one patient had doi 10.18502/sjms.v14i1.4381 page 56 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al had exchange blood transfusions done four times on account of complications of sca; mainly repeated episodes of priapism. six (12%) patients had had ≥ 3 units of blood transfused per year to treat the complications of sca. thirteen (26%) of the patients had dactylitis within the first year life. a 19-year old male patient (2%) had two past episodes of left ischemic stroke. two (4%) patients had history of acute chest syndrome while four (8%) had had priapism in the past. four (8%) patients had a past history of avascular necrosis of the femur, six (12%) had chronic leg ulcer, two (4%) had septic arthritis, and six (12 %) had a past history of chronic osteomyelitis (table 2). table 2: history of sickle cell crisis and complications. sickle cell crisis crisis present absent number/(%) number/(%) vaso-occlusive 50 (100) 0 (0) hemolytic 25 (50) 25 (50) aplastic 0 (0) 50 (100) sequestration hepatic 1 (2) 49 (98) splenic 2 (4) 48 (96) complications complication present absent number/(%) number/(%) dactylitis 13 (26) 37 (74) stroke 1 (2) 49 (98) acs 2 (4) 48 (96) priapism 4 (8) 46 (92) avn 4 (8) 46 (92) septic arthritis 2 (4) 48 (96) chronic leg ulcer 6 (12) 44 (88) chronic osteomyelitis 6 (12) 44 (88) note: acs = acute chest syndrome; avn = avascular necrosis. the full blood count and serum bilirubin results of the patients were as shown in table 3. the range of the steady state hemoglobin concentration (g/dl) of the patients from their hospital records was 6.3–11.3g/dl with a mean(±sd) of 8.52±1.114. the range of the newly analyzed hemoglobin concentration of the patients was 5–12g/dl with a mean(±sd) of 8.52±1.329. thirteen (26%) of the patients had a serum total bilirubin value greater than 51 µmol/l. doi 10.18502/sjms.v14i1.4381 page 57 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al the ultrasonographic liver span measurement of the patients ranged from 12.30 to 25.57 cm with a mean(±sd) of 16.56±2.357. the patients had a significantly long liver span (see figure 1). thirty-two (64%) of the patients had a liver span longer than 15.5 cm. table 3: hematologic and biochemical investigation results. parameters reference values range mean±sd ss hb. conc. (g/dl) 5–9 6.3–11.3 8.52±1.114 ss pcv (%) 15–27 19–34 25.54±3.406 hb. conc. (g/dl) 11.5–17.5 5–12 8.52±1.329 pcv (%) 36–52 17–36 25.85±3.924 wbc (/mm³) 3000–9000 3300–17500 10236.00±3448.277 plt (x10³/mm³) 100–300 71–568 293.920±139.342 b1 (µmol/l) < 20 8.6–93.0 40.51±20.871 b2 (µmol/l) < 5 0.5–44.0 7.81±8.382 note: ss hb. conc. = steady state hemoglobin concentration; ss pcv = steady state packed cell volume; wbc = white cell count; plt = platelet count; b1=total bilirubin; b2 = conjugated bilirubin; and na = not applicable. figure 1: sonogram showing massive hepatomegaly in a patient with sickle cell anemia (sca). the lower lobe of the liver extends well below the lower pole of right kidney and the liver measures 22.3 cm in span exceeding the normal limit of 15.5 cm. table 4 shows the markers of disease severity identified in the patients with sca. hepatomegaly (64%), frequent episodes of vaso-occlusive crisis, that is, ≥ 3 episodes per year (30%), and dactylitis in infanthood (26%) were the most common clinical parameters identified in these patients in that order, while a high serum total bilirubin of > 51µmol/l (26%) was the most common laboratory parameter seen in these patients. doi 10.18502/sjms.v14i1.4381 page 58 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al table 5 shows the total number of markers of sca disease severity identified in the patients. four (8%) of the patients had no identified marker of disease severity while 43 (86%) patients had between 1 and 4 identified markers of disease severity. two (4%) patients had five identified markers of disease severity and only one patient (2%) had up to seven identified markers of disease severity. as shown in table 6, more patients had clinical parameters than laboratory parameters; 43 (86%) patients versus 23 (46%) patients. table 4: frequency of the indices of disease severity identified in the sickle cell anemia patients. clinical parameters number of patients (%) history of frequent vaso-occlusive/pain crisis (≥ 3 pain episodes per year) 15 (30) history of stroke 1 (2) history of priapism 4 (8) evidence of avascular osteonecrosis 4 (8) history of acute chest syndrome 2 (4) hepatomegaly 32 (64) evidence of renal insufficiency 1 (2) dactylitis in early childhood (occurring before the age of one year) 13 (26) chronic leg ulceration 6 (12) use of hydroxyurea (to treat the complications of sickle cell anemia) 1 (2) frequent blood transfusions (≥ 3 transfusions per year to treat the complications of sickle cell anemia) 6 (12) laboratory parameters number of patients (%) leukocytosis in the absence of infection (> 15,000/mm³) 5 (10) chronic severe anemia (hemoglobin concentration < 6.6g/dl) 2 (4) high serum total bilirubin level (> 51µmol/l) 13 (26) high packed cell volume (pcv > 30%)/high hemoglobin concentration (>10g/dl) 5 (10) 4. discussion xandra et al. [13] defined the concept of severity as “the rate and extent of reversible and irreversible damage to organs brought on by the sickle cell disease process, resulting in impairment requiring medical intervention.” several attempts have been made till date by researchers to develop a universally accepted system for assessing disease severity in sca patients and these include the cooperative study of sickle cell disease (csscd) and the bayesian network modeling (developed by boston medical centre) [10]. presently, there is no consensus scoring system for assessing the severity of disease in patients with sca but a large number of indices have been used by researchers as doi 10.18502/sjms.v14i1.4381 page 59 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al table 5: total number of the indices of disease severity identified in the sickle cell anemia patients. clinical parameters laboratory parameters total number of parameters number number of patients (%) number number of patients (%) number number of patients (%) 0 7 (14) 0 27 (54) 0 4 (8) 1 18 (36) 1 21 (42) 1 13 (26) 2 13 (26) 2 2 (4) 2 16 (32) 3 8 (16) total 50 (100) 3 8 (16) 4 3 (6) 4 6 (12) 5 0 (0) 5 2 (4) 6 1 (2) 6 0 (0) total 50 (100) 7 1 (2) total 50 (100) markers of disease severity in sca, and these markers include clinical and laboratory parameters (table 1) [10, 11]. the presence of any of these markers in a patient with sca connotes severe disease, and the severity of the disease increases with an increasing number of these markers present in an individual patient. a high serum total bilirubin (>51µmol/l) was the most common laboratory parameter observed in this study with a prevalence of 26%. elevated serum bilirubin levels, predominantly the unconjugated fraction, are universal in sickle cell patients even in steady state due to chronic hemolysis but a persistently high total bilirubin suggests chronic significant hemolysis in these patients signifying a severe disease course and there is a need to follow them up very closely. hepatomegaly (64%) was the most common clinical parameter identified in this study. frequent episodes of vaso-occlusive crisis (≥3 episodes per year) and dactylitis (occurring before the age of one year) were the other common clinical parameters identified in this study. hepatomegaly is a common finding in sca, and it is largely due to the extramedullary hematopoiesis in response to the chronic anemia in this condition [3, 4]. hepatomegaly can also be due to transfusional hemosiderosis and chronic viral hepatitis [14, 15]. however, in nigeria, which is a malaria endemic area, frequent episodes of malaria is also a major cause of the hepatomegaly seen in these patients [15]. in this study, the most common indication for hospital admission in the sca patients apart from a sickle cell crisis was malaria; this could have contributed to the development of the hepatomegaly seen in these patients. olaniyi et al. found a prevalence of hepatomegaly of 62.2% among sca patients in ibadan, nigeria [15]. balci et al. found a prevalence of 72.6% among sca patients in turkey [16], and papadaki et al. found a prevalence of 70.5% among sickle cell disease doi 10.18502/sjms.v14i1.4381 page 60 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al patients in greece [17]. in this study, hepatic ultrasonographic evaluation of the patients revealed hepatomegaly with a prevalence of 64% (32 patients). persistent hepatomegaly is one of the established markers of disease severity in sca patients [10, 11]. olatunji et al. in ilorin, nigeria, also established that persistent hepatomegaly is an index of disease severity in patients with sca [18]. persistent hepatomegaly in patients with sca implies that such patients have the tendency to run a more severe clinical course than those without and there is a need to pay more attention to them [18]. 4.1. limitations of the study the findings from this study should be considered in line with some limitations that include absence of long-term patient follow-up in order to reassess these markers of disease severity for the long-term effect on the course of the disease. also, this study selectively investigated some of the established markers of disease severity due to limited resources, thus the pattern of the other markers in these patients is not known. future research should be geared towards developing a consensus scoring system for assessing disease severity in patients with sca. 5. conclusion hepatomegaly, frequent episodes of vaso-occlusive crisis, dactylitis in infanthood, and a high total bilirubin were the most common markers of disease severity identified in this study. a significantly larger number of patients had the clinical parameters compared to the laboratory parameters. previous research had shown that the presence of any of these markers in an sca patient connotes severe disease and the severity of the disease increases with increasing number of these markers present in an individual patient. patients with more markers of disease severity have the tendency to run a more severe clinical course than those without or less markers and there is a need to pay more attention to these patients by following them up more closely. therefore, efforts should be stepped-up to maintain sca patients in steady state as much as possible as this would prevent or limit complications or additional severity markers from arising, which could occur as a result of frequent crisis. such efforts would reduce the overall morbidity and mortality associated with sca. doi 10.18502/sjms.v14i1.4381 page 61 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al acknowledgement the authors would like to thank the members of the staff of hematology and radiology departments of obafemi awolowo university teaching hospitals complex, ile-ife, nigeria, for their support towards making this research a success. funding the authors bore the entire cost of the research and did not receive any financial support from any organization. conflict of interest the authors declared no conflicts of interest. references [1] bender, m. a. and hobbs, w. (2012). sickle cell disease. genereviews𝑇𝑀. ncbi bookshelf. retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/20301551 (accessed on may 17, 2012). [2] maakaron, j. e. and besa, e. c. (2013). sickle cell anemia. medscape reference. retrieved from: http://www.emedicine.medscape.com/article/205926 (accessed on january 28, 2013). [3] beutler, e., lichtman, m. a., and coller, b. s. (eds.). (2001). sickle cell disease, in william hematology (sixth edition), pp. 581–589. mcgraw-hill. [4] hoffbrand, a. v., catovsky, d., and tuddenham, e. g. (eds.). (2005). sickle cell disease, in postgraduate hematology (fifth edition), pp. 104–118. blackwell. [5] world health organization. (april 24, 2006). 59𝑡ℎ world health assembly, provisional agenda item 11.4, pp. 1-5. geneva: who. [6] anie, k. a., egunjobi, f. e., and akinyanju, o. o. (2010). psychosocial impact of sickle cell disorder: perspectives from a nigerian setting. globalization and health, vol. 6, pp. 1–6. [7] durosinmi, m. a., odebiyi, a. i., akinola, n. o., et al. (1997). acceptability of prenatal diagnosis of sickle cell anemia by a sample of the nigerian population. african journal of medicine and medical sciences, vol. 26, pp. 55–58. doi 10.18502/sjms.v14i1.4381 page 62 http://www.ncbi.nlm.nih.gov/pubmed/20301551 http://www.emedicine.medscape.com/article/205926 sudan journal of medical sciences oguntoye oluwatosin oluwagbenga et al [8] halim, n. k., famodu, a. a., and wemambu, s. n. (eds.). (2001). sickle cell disease, in textbook of clinical hematology and immunology (second edition), pp. 24–28. ambik. [9] animasahun, b. a. and temiye, e. o. (2011). the influence of socio-economic status on the hemoglobin level and anthropometry of sickle cell anemia patients in steady state at the lagos university teaching hospital. nigerian journal of clinical practice, vol. 14, pp. 422–427. [10] sebastiani, p., nolan, v. g., baldwin, c. t., et al. (2007). a network model to predict the risk of death in sickle cell disease. blood, vol. 110, pp. 2727–2735. [11] steinberg, m. h. (2005). predicting clinical severity in sickle cell anemia. british journal of hematology, vol. 129, pp. 465–481. [12] bookchin, r. m. and lew, v. l. (1996). pathophysiology of sickle cell anemia. hematology/oncology clinics of north america, vol. 10, pp. 124–1253. [13] xandra, w., johanna, h., harriet, h., et al. (2010). development and validation of a pediatric severity index for sickle cell patients. american journal of hematology, vol. 85, pp. 746–751. [14] banerjee, s., owen, c., and chopra, s. (2001). sickle cell hepatopathy. hepatology, vol. 33, pp. 1021–1028. [15] olaniyi, j. a. and abjah, u. m. (2007). frequency of hepatomegaly and splenomegaly in nigerian patients with sickle cell disease. wajm, vol. 26, pp. 274–277. [16] balci, a., karazincir, s., sangun, o., et al. (2008). prevalence of abdominal ultrasonographic abnormalities in patients with sickle cell disease. diagnostic and interventional radiology, vol. 14, pp. 133–137. [17] papadaki, m. g., kattamis, a. c., and papadaki, i. g. (2003). abdominal ultrasonographic findings in patients with sickle-cell anemia and thalassaemia intermedia. pediatric radiology, vol. 33, pp. 515–521. [18] olatunji, p. o. and falusi, a. g. (1994). persistent hepatomegaly: an index of severity in sickle cell anemia. east african medical journal, vol. 71, pp. 742–744. doi 10.18502/sjms.v14i1.4381 page 63 introduction materials and methods selection of study subjects evaluation of study subjects data analysis study definitions results discussion limitations of the study conclusion acknowledgement funding conflict of interest references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4379 production and hosting by knowledge e research article knowledge of and attitude towards epilepsy among women in ile-ife, nigeria funmito o. fehintola, samuel a. olowookere, caleb a. adegbenro, temitope o. afolabi, victor oladapo, akinyele o. oladimeji, opeyemi e. oladipo, olayinka r. olagunju, and ademola a. olajide department of community health, obafemi awolowo university, ile-ife, nigeria abstract background: epilepsy is a non-contagious chronic disease with sufferers experiencing embarrassments amidst other challenges. family caregivers are mainly women with some of them suffering from the disease. this study assessed the knowledge and attitude of women residents in an urban community towards epilepsy. materials and methods: this descriptive cross-sectional study recruited 400 randomly selected women in ile-ife. the data was collected with the use of a pre-tested interviewer-administered questionnaire on knowledge of and attitude to epilepsy. data was analysed using descriptive and inferential statistics. results: most respondents (99.3%) were aware of the disease with their main sources of information from their parents, friends, and neighbours. only 15.3% of respondents had good knowledge of epilepsy, while 35% had positive attitude to epilepsy. factors associated with good knowledge of epilepsy among respondents include having higher education (or = 3.154, 95%ci = 1.574–6.323, p = 0.001) and higher income (or = 3.055, 95%ci = 1.404–6.651, p = 0.005), while factors associated with positive attitude towards epilepsy include older age group (or = 1.943, 95%ci = 1.281–2.945, p = 0.002) and higher income (or = 2.932, 95%ci = 1.345–6.386, p = 0.007). conclusions: although the level of awareness is high, respondents’ knowledge and attitude were inadequate. there is a need for a community education about epilepsy, targeting women who are major stakeholders with the aim of improving their knowledge and attitude towards the disease. keywords: knowledge, attitude, women, urban community, epilepsy 1. introduction epilepsy is a clinical phenomenon resulting from a neurological disorder characterised by recurrent seizures or periods of unusual behaviour, sensations, feelings, and sometimes loss of consciousness [1, 2]. according to the international league against epilepsy, it is a brain disorder characterized by abnormal synchronous neuronal how to cite this article: funmito o. fehintola, samuel a. olowookere, caleb a. adegbenro, temitope o. afolabi, victor oladapo, akinyele o. oladimeji, opeyemi e. oladipo, olayinka r. olagunju, and ademola a. olajide (2019) “knowledge of and attitude towards epilepsy among women in ile-ife, nigeria,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 31–44. doi 10.18502/sjms.v14i1.4379 page 31 corresponding author: samuel anu olowookere; email: sanuolowookere@yahoo.com received 12 february 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e funmito o. fehintola et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4379&domain=pdf&date_stamp=2019-03-31 mailto:sanuolowookere@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences funmito o. fehintola et al discharges leading to symptoms and/or signs and the neurobiological, physical, social, and psychological consequences. the disease has existed for thousands of years, but it was only in the last hundred years that a better understanding of the disease condition began to evolve. the major symptom of epilepsy is the epileptic seizure that could be frightening and strange to laymen. although the disease can begin at any age, majority of the cases occur in childhood with care being provided by women [2, 3]. these women are mostly the mothers of the children with epilepsy with majority reporting that their children experience high level of stigma due to inappropriate beliefs and misconceptions about the disease in the community [4–6]. also, anxiety and low quality of life have been reported among these women especially those having lower knowledge about epilepsy [2]. even though sex ratios in the epidemiology of epilepsy are not fully established, a previous study stated that boys are slightly more likely to develop epilepsy than girls [2]. however, a study by savic et al. (2014) stated that the prevalence of idiopathic generalized epilepsy, childhood absence epilepsy, and juvenile myoclonic epilepsy are more in girls than boys [3]. approximately 25–30% of people with epilepsy will continue to experience seizures even with best available therapies [4]. epilepsy affects over 50 million people world-wide [5]; hence, a relatively common condition, with higher prevalence rates in developing countries. the prevalence of active convulsive epilepsy in sub-saharan africa ranges from 2.2 to 58 per 1000 with approximately 4.4 million people affected [5]. it is estimated that about 3% of people receive a diagnosis of epilepsy at some point in their lifetime, with 70% achieving remission [6]. about 70% of cases of seizures are idiopathic [7]. factors that have the potential to cause epilepsy include brain epileptic syndromes, congenital infections, tumours, brain injury, degenerative brain diseases, cerebral hypoxia, stroke, and toxins [7–9]. most seizures last for 1 to 2 minutes, however, when a seizure stops, people with epilepsy may have post-ictal symptoms like headache, numbness or tingling, confusion, sore muscles, unusual sensations, extreme tiredness, faecal or urinary incontinence [8]. though, epilepsy is a common disease, it is reported to be associated with a significant social discrimination and stigmatization as a result of misconceptions, limited knowledge, and poor public awareness [9]. most of the negative attitudes documented in people with epilepsy are in relation to marriage, job employment, education, and social acceptance; hence, the person with epilepsy is most likely to drop out of school, lose his or her job, and find it difficult to make friends [10]. women are notable caregiver in the community, hence assessing awareness and knowledge about epilepsy among them will provide needed information and improve doi 10.18502/sjms.v14i1.4379 page 32 sudan journal of medical sciences funmito o. fehintola et al the ability to cope successfully with the disease by minimizing the potentially harmful management practices, emotional impact of seizures, and diminish the perceived stigmatization or feelings of social isolation among people suffering from the condition. study carried out in kaduna, nigeria on mothers’ perspectives on childhood epilepsy reported that the mothers demonstrated appreciable deficiencies in the knowledge of epilepsy, particularly with regards to its aetiology and outcome, and exhibit a negative attitudinal disposition towards children with epilepsy [11]. studies with similar poor epilepsy perspectives among adults have been reported from nigeria and several lowand middle-income countries [8, 12, 13]. reports about perspectives of adults on epilepsy from nigeria have consistently demonstrated misconceptions about the aetiology and outcome of epilepsy; some studies suggesting an infectious mode of transmission, spiritual or traditional mode of therapy, varying degrees of abuse, stigma and discrimination against those with the disease [11–13]. globally, having poor epilepsy perspectives has been associated with rural populations in these countries, poor socioeconomic status, strong cultural beliefs about the aetiology of epilepsy and health systems that are weak in the provision of epilepsy-related health services. these studies also reported that negative attitudes continue to prevail over people with epilepsy in most part of the world especially in resource limited setting such as nigeria [12–14]. although, several studies have reported high level of awareness in various population, the reported misconceptions, religious and cultural beliefs about the cause and management of epilepsy and stigma experience of people with epilepsy have made the life of these people miserable indicating urgent need to address these research findings [15–17]. community-based education is reportedly very useful in correcting these ignorance, misconceptions, negative religious and cultural beliefs about the disease [18, 19]. health workers with targeted training about such disease will be able to carry out this community health education among community members that include opinion leaders (traditional rulers, religious leaders), the youth or the elderly [20, 21]. this could lead to positive change in the health-seeking behaviour of community members with subsequent improvement in quality of life of people with epilepsy [21, 22]. this study assessed the knowledge of women about epilepsy and their attitude towards people with epilepsy in ile-ife, osun state, nigeria. 2. methods the study employed a descriptive cross-sectional design and the target population were women resident in ife central local government area, ile-ife, nigeria. ile-ife is the doi 10.18502/sjms.v14i1.4379 page 33 sudan journal of medical sciences funmito o. fehintola et al origin of the yoruba and an urban town with estimated population of 167,000, consisting mainly the yoruba and other ethnic groups including igbo and hausa. the study was carried out over a period of three months. those included in the study were consenting women aged 18 years and above, residing in ile-ife, nigeria. a total of 400 subjects were enrolled in the study after determining the sample size using formula for descriptive studies: n = z2p(1–p)/d2 [23]. a pre-tested semi-structured interviewer-administered questionnaire was used to collect data after the consent was obtained from the participants. the questionnaire has various sections focusing on the socio-demographic characteristics, knowledge about epilepsy with questions on awareness, source of information about epilepsy, signs and symptoms of epilepsy, previous experience of observing somebody convulsed, characteristics of the seizure, relationship with the person, what was done to the person to abort the seizure, family history of epilepsy, its causes, and health-seeking behaviour of people with epilepsy. the questionnaire also assessed attitudes towards epilepsy and people with epilepsy that include disclosure issues, stigma, and discrimination. face validity of the questionnaire was done by the authors with necessary adjustment made to the questions. the survey instrument was available in english language but translated into yoruba to accommodate non-english speaking respondents and then back-translated into english language. respondents were interviewed in the afternoon and evenings by the final-year medical students who were trained in administering the instrument. multi-stage sampling was used as the sampling technique to select the participants. in the first stage, one ward was selected by balloting from the electoral wards in ife central local government area. in the second stage, one enumeration area was selected by balloting from all the enumeration areas in the selected ward. in the third stage, all households in the selected enumeration area were recruited into the study. in the fourth stage, all eligible women in the selected household were approached to participate in the study till the sample size was achieved. data collected were analysed using the statistical package for social science (spss) version 20. univariate analysis was carried out to determine the socio-demographic distribution of study participants through the use of frequency tables and percentages. the appropriate bivariate analysis was carried out to determine the relevant association. knowledge and attitude score was computed with ‘+1’ assigned for correct response, while ‘0’ was assigned for incorrect response. the mean score was used as cut-off with score graded as good or poor knowledge, positive and negative attitude. bivariate chi-square test and multivariate regression analyses were performed on participant doi 10.18502/sjms.v14i1.4379 page 34 sudan journal of medical sciences funmito o. fehintola et al variables and knowledge and attitude to epilepsy. variables in the bivariate test with pvalue < 0.2 were included in the multivariate model. the level of statistical significance was taken to be < 0.05. ethical clearance was obtained from the research and ethics committee of obafemi awolowo university teaching hospitals complex, ile-ife, nigeria prior to the commencement of the study. participation in the study was completely voluntary and the respondents were assured of confidentiality. data collected were kept in a passwordprotected computer. 3. results a total of 400 respondents completed the study and were analysed. the mean age (sd) was 40.5 (14.3) years with a range of 16–80 years. majority (96.8%) were yoruba. about 54% of respondents were 35 years and above. majority of respondents were married, had secondary education, and earned above the minimum wage (table 1). table 2 shows that 99.3% of the respondents are aware of epilepsy, 95.3% were aware through parents, while 0.7% have never heard about it. about 53% of respondents believed it was contagious with only 27% aware of medical treatment for epilepsy while majority (75.8%) of the respondents believed it was caused by spiritual attack. loss of consciousness was the most common symptoms of epilepsy mentioned by the respondents (84.5%). about 49% of respondents mentioned distancing oneself from epileptic patient as the action to take while an epileptic patient is convulsing. overall, 84.7% of respondents have poor knowledge of epilepsy while only 15.3% have good knowledge. according to table 3, 35% had a positive attitude to epilepsy. about 70% of respondents agreed that persons with epilepsy can get married while 21.3% disagreed; 44% of respondents agreed that employing someone with epilepsy is wrong while 48.8% disagreed; 81% of respondents agreed that person with epilepsy should not drive and 82% of respondents agreed that known epileptic patient should not be a factory worker. table 4 reports that about 26% of respondents who attended tertiary institution have good knowledge compared to 14.1% and 10.1% who attended secondary and primary schools, respectively, and the association is significant; 18% of respondents who were christians have a good knowledge of epilepsy compared to 7.3% of their muslim counterparts. about 19% of those with high income have good knowledge compared to 7.0% of those with low income (p = 0.003). doi 10.18502/sjms.v14i1.4379 page 35 sudan journal of medical sciences funmito o. fehintola et al table 1: socio-demographic characteristics of respondents. variables frequency (n = 400) percentage (%) age in years < 35 183 45.8 35 and above 217 54.2 level of education none 57 14.2 primary 102 25.5 secondary 149 37.3 tertiary 92 23 marital status single 75 18.8 married 276 69 divorced 6 1.5 widowed 43 10.7 religion christianity 304 76 islamic 96 24 ethnicity yoruba 387 96.8 igbo 10 2.5 hausa 3 0.7 income per month (naira) <18000 (≈50 us dollars) 112 28 ≥18000 (≈50 us dollars) 288 72 table 5 reports that 43.2% of respondents who were less than 35 years had a positive attitude to epilepsy compared to 28.1% of those who were 35 years and above and the association was significant. over 31% of respondents who were muslims had positive attitude compared to 36.4% of the christians, but the statistical association was not significant. about 18% of those with high income had positive attitude compared with 7.1% of those with low income (p = 0.005). factors associated with good knowledge of epilepsy among respondents include having higher education (or = 3.154, 95%ci = 1.574–6.323, p = 0.001) and higher income (or = 3.055, 95%ci = 1.404–6.651, p = 0.005), while factors associated with positive attitude towards epilepsy include older age group (or = 1.943, 95%ci = 1.281–2.945, p = 0.002) and higher income (or = 2.932, 95%ci = 1.345–6.386, p = 0.007) (table 6). doi 10.18502/sjms.v14i1.4379 page 36 sudan journal of medical sciences funmito o. fehintola et al table 2: respondents’ knowledge about epilepsy. variables frequency (n = 400) % ever heard of epilepsy yes 397 99.3 no 3 0.7 *source of information parents 381 95.3 media 116 29 health worker 57 14.3 is epilepsy contagious yes 211 52.7 no 189 47.3 medical treatment for epilepsy yes no 107 26.7 293 73.3 *causes of epilepsy spiritual attack 303 75.8 lizard 196 49 brain injury/birth trauma 162 40.5 inherited 170 42.6 *symptoms of epilepsy loss of consciousness 338 84.5 foaming from the month 329 82.3 falling to the ground 312 78 *actions taken to help convulsing individual distance yourself 194 48.5 putting legs on fire 187 46.8 pour water 154 38.5 take off dangerous object 136 34 take to hospital 78 19.5 knowledge score good 61 15.3 poor 339 84.7 note: *multiple response. 4. discussion this study reported high awareness about epilepsy among the respondents. this report was similar to findings of a community-based study in turkey in which awareness was 81% [14]. this also corroborated findings of local studies that reported high awareness doi 10.18502/sjms.v14i1.4379 page 37 sudan journal of medical sciences funmito o. fehintola et al table 3: respondents’ attitude towards epilepsy. variables frequency (n = 400) % attitude score positive 140 35 negative 260 65 person suffering from epilepsy should freely disclose it agree 172 43 disagree 204 51 indifferent 24 6 persons with epilepsy can get married agree 278 69.5 disagree 85 21.3 indifferent 37 9.2 marriage to a known epileptic should lead to divorce agree 107 26.8 disagree 226 56.5 indifferent 67 16.7 employing someone with epilepsy is wrong agree 176 44 disagree 195 48.8 indifferent 29 7.2 children with epilepsy should be allowed to play with other children agree 204 51 disagree 171 42.8 indifferent 25 6.2 someone with epilepsy should attend social gathering agree 143 35.8 disagree 230 57.5 indifferent 27 6.7 person with epilepsy should not drive agree 325 81.3 disagree 57 14.3 indifferent 18 4.4 persons with epilepsy should not be factory workers agree 326 81.5 disagree 55 13.7 indifferent 19 4.8 of the disease [12, 16]. however, the major source of information about epilepsy in this doi 10.18502/sjms.v14i1.4379 page 38 sudan journal of medical sciences funmito o. fehintola et al table 4: association between selected socio-demographic characteristics of respondents and their knowledge about epilepsy. variable knowledge total statistical indices poor (n = 339) good (n = 61) age group (years) 𝜒2 = 0.745 < 35 152 (83.1) 31(16.9) 183(100) p = 0.388 ≥ 35 187(86.2) 30(13.8) 217(100) df =1 level of education none/primary 143(89.9) 16(10.1) 159(100) 𝜒2 = 11.82 secondary 128(85.9) 21(14.1) 149(100) p = 0.003 tertiary 68(73.9) 24(26.1) 92(100) df = 2 marital status 𝜒2 = 0.863 *not married 102(82.3) 22(17.7) 124(100) p = 0.353 married 237(85.9) 39(14.1) 276(100) df = 1 religion 𝜒2 = 0.781 christianity 250(82.2) 54(17.8) 304(100) p = 0.377 islam 89(92.7) 7(7.3) 96(100) df = 1 income per month 𝜒2 = 8.590 < 18000 (≈50 us dollars) 107(93.0) 8(7.0) 112(100) p = 0.003 ≥ 18000 (≈50 us dollars) 232(81.4) 53(18.6) 288(100) df = 1 note: *single, divorced, widow. table 5: association between selected socio-demographic characteristics of respondents and their attitude to epilepsy. variable attitude total statistical indices negative (n = 260) positive (n = 140) age group 𝜒2 = 9.896 < 35 years 104(56.8) 79(43.2) 183(100) p = 0.002 ≥ 35 156(71.9) 61(28.1) 217(100) df = 1 religion 𝜒2 = 0.781 christianity 194(63.6) 110(36.4) 304(100) p = 0.377 islam 66(68.8) 30(31.2) 96(100) df = 1 knowledge 𝜒2 = 0.036 poor 221(65.2) 118(34.8) 339(100) p = 0.850 good 39(63.9) 22(36.1) 61(100) df = 1 income per month (naira) 𝜒2 = 7.911 < 18000 (≈50 us dollars) 104 (92.9) 8(7.1) 112(100) p = 0.005 ≥ 18000 (≈50 us dollars) 235(81.6) 53(18.4) 288(100) df = 1 study included friends, parents, and neighbours, while few respondents heard about doi 10.18502/sjms.v14i1.4379 page 39 sudan journal of medical sciences funmito o. fehintola et al table 6: logistic regression analysis of factors associated with knowledge and attitude to epilepsy. factors or 95%ci p-value knowledge about epilepsy education level none/primary (ref.) secondary 1.466 0.733–2.931 0.279 tertiary 3.154 1.574–6.323 0.001 income (naira) < 18,000 (ref.) ≥ 18,000 3.055 1.404–6.651 0.005 attitude towards epilepsy age group (years) < 35 (ref.) ≥ 35 1.943 1.281–2.945 0.002 income (naira) < 18000 (ref.) ≥ 18000 2.932 1.345–6.386 0.007 the disease from health workers. previous studies have reported similar findings [1, 14]. these sources of information about epilepsy are largely inaccurate and misleading as reported in studies in this environment [11–13]. despite a high awareness about the disease, the knowledge of causes and clinical features were poor with believes such as spiritual cause, eating lizard, and contagious aetiology prevalent among the respondents. ezeala-adikaibe et al. in 2013 reported similar findings with about half of their respondents believing that epilepsy was contagious while more than one-third believed that it was due to spiritual attack [16]. these findings on spiritual and infectious cause of epilepsy however support the inclination of populations in sub-saharan africa towards the cultural or religious belief on the origin of epilepsy [11–13]. this belief shows the poor knowledge and misconceptions about epilepsy among this population [11]. also, most respondents in our study do not know that epilepsy is medically treatable, hence they are likely to seek help elsewhere instead of the hospitals, like traditional healers or herbal medicine practitioners. the findings of this study are similar to the findings of other previous studies in this locality [18–20]. for instance, frank-briggs et al. in 2011 reported that 83% of their respondents having various misconceptions about the disease with majority seeking care for their children with epilepsy from spiritual and herbal medicine practitioners [17]. doi 10.18502/sjms.v14i1.4379 page 40 sudan journal of medical sciences funmito o. fehintola et al the findings of this study showed that the general attitude towards epilepsy as a disease and people with epilepsy was poor. the fact that over four-fifth of our respondents would choose to distance themselves from somebody with an epileptic attack further indicates the effect of poor knowledge among our respondents. the findings of this study are similar to the previous reports from kabir et al. in 2005 [13] and mustapha et al. in 2013 [19]. majority of our respondents believed that epilepsy is not a disease that should be freely disclosed. this negative non-supporting attitude is traceable to their unreliable source of information about the disease and is welldocumented in previous studies [13, 19, 20]. also, the socio-demographic variables were found to have a significant association with the knowledge and attitude including the higher educational status, higher income, and younger age group. these findings are similar to that of lim et al [21] and neni et al. [22]. the poor knowledge and negative attitude seen in older age group may be as a result of age-long and deep-seated socio-cultural beliefs and value systems. this study also found that knowledge did not significantly influence respondents’ attitude towards epilepsy. this was contrary to the findings of neni et al. [22]. this finding may be as a result of high level of stigmatization associated with this disease condition in our environment. the findings of this study should be interpreted in the light of some limitations. firstly, this is a cross-sectional study that makes it difficult to establish causality. also it is based on self-reporting which is subject to bias. nevertheless, our findings have significant implication for epilepsy and its management in resource-poor countries like nigeria. 5. conclusions in conclusion, although the level of awareness is high, respondents’ had poor knowledge of and negative attitude towards epilepsy. there is a need for continuous community education about epilepsy with the aim of improving the knowledge and attitude of members of the community towards the disease. this will ensure early presentation of sufferers to the health facility. also, healthcare workers need to be trained so that they can anchor the education of community members on epilepsy. this will correct the misconceptions about this disease and reduce significantly the stigma and discrimination suffered by people with epilepsy. doi 10.18502/sjms.v14i1.4379 page 41 sudan journal of medical sciences funmito o. fehintola et al conflict of interest the authors declare no conflict of interest. acknowledgements the authors wish to thank all the women who participated in this study. references [1] almutairi, a. m., ansari, t., sami, w., et al. (2016). public knowledge and attitude towards epilepsy in majmaah. journal of neurosciences in rural practice, vol. 7, no. 4, pp. 499–503. [2] osuntokun, b. (1972). epilepsy in the developing countries in the nigerian profile. epilepsia, vol. 13, no. 1, pp. 107–111. [3] savic, i. (2014). sex differences in human epilepsy. experimental neurology, vol. 259, pp. 38–43. [4] macleod, s. and appleton, r. e. (2007). the new antiepileptic drugs. archives of disease in childhood-education & practice, vol. 92, no. 6, pp. 182–188. [5] paul, a., adeloye, d., george-carey, r., et al. (2012). an estimate of the prevalence of epilepsy in sub-saharan africa: a systematic analysis. journal of global health, vol. 2, no. 2, pp. 1–13. [6] rugg-gunn, f. j. and sander, j. w. (2012). management of chronic epilepsy. bmj, vol. 345, e4576. [7] lepping, l. and zaagman, p. (2009). midazolam and epilepsy in people with learning disabilities: laura klepping and peter zaagman look at the evidence on midazolam, and whether it is a safe, effective and appropriate epilepsy rescue medication for people with learning disabilities. learning disability practice, vol. 12, no. 2, pp. 30– 35. [8] world health organization. (2011). global perspectives on epilepsy: improving access to epilepsy care. [9] lee, s., yoo, h., lee, b., et al. (2005). factors contributing to the stigma of epilepsy. seizure, vol. 14, pp. 157–163. [10] bandstra, n. f., camfield, c. s., and camfield, p. r. (2008). stigma of epilepsy. the canadian journal of neurological sciences, vol. 35, no. 04, pp. 436–440. doi 10.18502/sjms.v14i1.4379 page 42 sudan journal of medical sciences funmito o. fehintola et al [11] eseigbe, e. e., enogela, j., adama, s. j., et al. 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(2018). the impact of an enlightment program on community perception towards children with epilepsy. international journal of research in medical sciences, vol. 6, no. 3, pp. 729–733. [16] ezeala-adikaibe, b., achor, j., onwukwe, j., et al. (2013). knowledge, attitude and practice towards epilepsy among secondary school students in enugu, south east nigeria. seizure, vol. 22, no. 4, pp. 299–302. [17] frank-briggs, a. i. and alikor, e. (2011). knowledge and attitudes of parents toward children with epilepsy. annals of african medicine, vol. 10, no. 3, pp. 238–242. [18] owolabi, l. f., shehu, n. m., and owolabi, s. d. (2014). epilepsy and education in developing countries: a survey of school teachers’ knowledge about epilepsy and their attitude towards students with epilepsy in northwestern nigeria. pan african medical journal, vol. 18, no. 255, pp. 1–10. [19] mustapha, a., odu, o., and akande, o. (2013). knowledge, attitudes and perceptions of epilepsy among secondary school teachers in osogbo south-west nigeria: a community based study. nigerian journal of clinical practice, vol. 16, no. 1, pp. 12–18. [20] komolafe, m. a., sunmonu, t. a., afolabi, o. t., et al. (2012). the social and economic impacts of epilepsy on women in nigeria. epilepsy & behavior, vol. 24, no. 1, pp. 97–101. [21] lim, k. s., lim, c. h., and tan, c. t. (2011). attitudes toward epilepsy, a systematic review. neurol asia, vol. 16, no. 4, pp. 269–280. [22] neni, s. w., latif, a. z. a., wong, s. y., et al. (2010). awareness, knowledge and attitudes towards epilepsy among rural populations in east coast peninsular malaysia: a preliminary exploration. seizure, vol. 19, no. 5, pp. 280–290. doi 10.18502/sjms.v14i1.4379 page 43 sudan journal of medical sciences funmito o. fehintola et al [23] araoye, m. o. (2003). research methodology with statistics for health and social sciences, pp. 115–120. ilorin: nathadex publisher. doi 10.18502/sjms.v14i1.4379 page 44 introduction methods results discussion conclusions conflict of interest acknowledgements references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5205 production and hosting by knowledge e research article perception of faculty members of regional medical school toward faculty development program karimeldin mohamed ali salih1,2,3, abdullah m. al-shahrani4, ibrahim awad eljac5, and mohammed abbas1,6 1pediatric department, college of medicine, university of bisha, ksa 2medical education department, college of medicine, university of bisha, ksa 3pediatric department, college of medicine, university of bahri, sudan 4family medicine, college of medicine, university of bisha, ksa 5community medicine department, college of medicine, university of bisha, ksa 6pediatric department, faculty of medicine, kassala university, sudan abstract introduction: any types or process of activities that are performed by a group or an individual to enhance, promote, and improve the performance, competencies or skills of a health professional at an institute level are defined as faculty development which has many other names like staff development, academic development, and educational development. the importance of faculty development stressed by harden is equivalent to curriculum development, which is a very difficult assignment. objectives: to determine the pattern of faculty members’ perception toward their weekly faculty development program. methodology: enrolling the faculty members of the college of medicine, university of bisha, kingdom of saudi arabia (com/ub,ksa). com/ub adopting the innovative curriculum (problem-based learning, team-based learning, interactive lectures, and case-based learning and seminars. each tuesday, faculty members gather in the faculty development academic program (fdap) room to discuss issues related to medical education and quality. usually, there is a presentation on the selected topic over 25 min, followed by a discussion and workshop, and finally, a recommendation is drawn. the inclusion criterion is those staying in the college for a period of more than one year. new joiners and those staying for a period of less than one year were excluded. faculty members were enrolled optionally and requested to fill a validated questionnaire. results: the response rate was 92% of total staff. more than 89%, 87%, 86% and 74% thought that the fdap is useful to them, helps them in addressing academic issues in the faculty, is an enriching experience, and thought that it helps them in constructing high-quality multiple choice questions (mcqs). finally, 84% were interested in presenting topics in fdp. conclusion: fdap was positively perceived by the faculty members of the university bisha/college of medicine, since it enriches their experience and satisfies their academic job. keywords: faculty, development, academic, program, mcqs how to cite this article: karimeldin mohamed ali salih, abdullah m. al-shahrani, ibrahim awad eljac, and mohammed abbas (2019) “perception of faculty members of regional medical school toward faculty development program,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 128–140. doi 10.18502/sjms.v14i3.5205 page 128 corresponding author: karimeldin mohamed ali salih received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e karimeldin mohamed ali salih et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences karimeldin mohamed ali salih et al 1. introduction any types or process of activities that are performed by a group or an individual to enhance, promote, improve the performance, competencies, or skills of the health professional at the institutional level is defined as faculty development, which has many other synonymous names such as staff development, academic development, educational development [1, 2]. faculty development refers to a range of activities that are perceived to help academicians in improving their professional skills that are vital for carrying out their teaching, research, or administrative activities in medical education [3]. in medical education conventions, faculty development has been considered to play a decisive role in sustaining academic vitality [4]. faculty development program (fdap) has been considered as a stand-alone educational pedagogy in fostering knowledge and professional skills of faculty [5]. however, few studies have provided objective reports about the impact of such programs in a healthcare system. many education specialists consider faculty development as the process of improving instructor’s skills and conducting any other rules that can promote the entire institution [2–4]. the strategies for improving the learning environment include: effective use of available resources with the emphasis on integrating technology in teaching, providing easy and comfortable access to various information communication technology tools, and establishing learning centers equipped with all required technology. similar to these strategies, guze [6] emphasized the importance of using technology as an infrastructure to enhance learning environment and as a basis to address many of the challenges facing medical education. most specialists consider faculty development as an essential component of medical education that helps teachers to act precisely, accurately, and confidently from undergraduate to continuing learning [7–9]. the explosion of medical technology, patient care, medical education reform, and innovations became a continuous process without end. since the world federation of medical education (wfme) suggested that the integration of courses should continue from undergradutes up to the phase of continuous education, the need for a sort of program has been created to update medical staff in general and faculty in particular [10]. in order for the faculty members to provide skillful instruction, valid assessment, fulfilling the mission of the institute, and to be accountable, a continuous education on competencies that are missed during their own training can be enhanced by the faculty development activities in their institute on a regular basis [11]. in order to integrate community needs for medical schools, health professionals in general and faculty members in particular should adhere to innovative instruction and assessment within an innovative curriculum [12, 13]. this era doi 10.18502/sjms.v14i3.5205 page 129 sudan journal of medical sciences karimeldin mohamed ali salih et al of quality makes many international bodies like the wfme, the association for medical education in europe (amee) and others in north america and canada to persuade educational quality, and hence the development and continuous training of faculty members cannot be over-emphasized [14]. if the institute is fighting for accountability, accreditation, and implementation of the mission to achieve success, productivity, and satisfaction, much resources and time should be directed toward faculty development (15). the importance of faculty development was stressed by harden (2009) as being equivalent to curriculum development, which is a very difficult assignment [16, 17]. the question that needs an urgent answer is how do the faculty members of the college of medicine, university of bishah (com/ub) perceived their faculty development program that is conducted weekly [18–20]. the curriculum of com/bu is an innovative one, which needs continuous faculty development academic program (fdap) to familiarize the instructor with its science, as most of them have not practiced it before [21]. the objective of this study is to determine the pattern of faculty members’ perception toward a faculty development program. 2. methods this study was conducted in the college of medicine/university of bishah (ksa), which was founded four years ago. the learning process included problem-based learning (pbl), team-based learning (tbl), seminars, and case-based learning (cbl) either in skill labs, hospital, or classroom. assessment was done through multiple choice questions (mcqs), structured short answers (ssa), objective structured practical exam (ospe), and objective structured clinical exam (osce). 2.1. setting up the fdap the fdap is conducted every tuesday between 10 am and 12 pm to improve the staff’s teaching skills. the topics in medical education, quality and researches are selected, and then a staff who is senior or well-trained in any one of the selected topic delivers a presentation for 25 min, this is followed by a workshop and a discussion, and finally some recommendation is made for the work quality improvement based on the international guidelines for medical education and quality [22, 23]. doi 10.18502/sjms.v14i3.5205 page 130 sudan journal of medical sciences karimeldin mohamed ali salih et al 2.2. data collection and analysis a well-structured validated questionnaire which reflect the real needs from the faculty in order to conduct their work and execute their curriculum effectively has been designed by an expert in medical education and quality assurance. although the total population of our staff is small, the enrolment was optional. the population targeted for the research was the entire staff in the college who are about 40 faculty members, of which 37 answered the question with a response rate of 92%. the inclusion criterion included the staff working in the college for at least more than one academic year and the exclusion criterion was those who had just joined the college recently (less than one year) as they were yet not in a position to perceive the faculty development program (i.e., less exposure). the questionnaires distributed to the included staff manually as hard copy requested them to fill it personally, voluntarily, individually, and anonymously. the filled questionnaire was received by the author for analysis. an acceptance to be enrolled was considered as consent [24, 25]. 2.2.1. statistical analysis spss version 21, descriptive statistics was used, p-value was used with 0.05 confidence level to reject the null hypothesis for analysis, and the permission was taken from the com research committee. an agreement of the staff to be enrolled was considered as informed consent. 3. results 3.1. teaching background of the faculty members the response rate was 92%, and 71.875%, 9.375%, and 18.75% received their undergraduate by classical, innovative, and hybrid curriculum, respectively. 3.2. faculty member’s teaching experience before joining the university almost 56.25% of the faculty members practiced teaching through innovative curriculum before. doi 10.18502/sjms.v14i3.5205 page 131 sudan journal of medical sciences karimeldin mohamed ali salih et al figure 1: mode of receiving undergraduate studies. figure 2: staff practicing innovative methods of instruction before joining ub/com. 3.3. faculty member’s participation in fdap staff member participated actively < 10, 10–15, and > 15 times in participation in fdap by 12.5%, 25.0%, and 62.5%, respectively. doi 10.18502/sjms.v14i3.5205 page 132 sudan journal of medical sciences karimeldin mohamed ali salih et al figure 3: staff presentations in fdm ub/com. 3.4. characteristic of participation in fdap more than 83%, 9%, and 6% of the staff regularly participate, rarely participate, and do not participate, respectively. figure 4: characterization of staff’s participation in the fpd in ub/com. 3.5. fdp direct/indirect outcomes more than 89% feel fdap is useful to them, more than 87% mentioned that it helps them in addressing academic issues among the faculty members; 86% consider it as enriching, 84% are interested in presenting topics in fdp rather than their experiences, doi 10.18502/sjms.v14i3.5205 page 133 sudan journal of medical sciences karimeldin mohamed ali salih et al and finally, 74% thought that fdap helps them in constructing high-quality mcqs. with an obvious significant impact (p < 0.05) of the faculty member’s perception toward their fdap, the faculty staff skills in innovative curriculum was improved. indirect outcome: develop the university ranking and accreditation. 4. discussion from this study, it is very obvious that most staff members came from the non-innovative curriculum with significant response 0.05, yet they make use of attending and participating in fdap, which indicates its usefulness in providing chances for learning new skills, as proved by other studies [26–28]. the study observed that 84% of the faculty members are interested in the presentation, which is in agreement with other studies [29, 30], while 86% consider it as enriching their experience as teaching staff, which add a lot of skills to them, in finding that it is confirmed by other authorities (31). despite the heavy work and follow-up on our presentation, the rate of positive perception of the staff to the topics is covers all medical domains, the outcomes as in any other studies might be explained by having innovative curriculum and perhaps the staff experience of assessing the presentations is well developed since the college started functioning fdap three years ago. faculty members who participated in this study also valued the need for curriculum reform with the emphasis on: learners’ need to demonstrate competencies, the shift from content basedto outcomes-based curricula, making the medical education curriculum more student-centered than teachercentered and more integrated both horizontally and vertically and problem-based. the strategy measures for change implementation in medical education in saudi arabia, according to the results of current study, include: curriculum reform, faculty development and improving the learning environment. these strategies should be combined with organizational measures that facilitate the change process and overcome obstacles against change [32, 33]. the interest on fdap and the positive attitude toward fdap definitely will build a feeling of strong belonging to the institute as pointed out by some authorities [34], however, this feeling will create strong challenges for motivation to the administration [20, 21]; 74% thought that fdp helps them in constructing highquality mcqs. although, teachers who adopt their job might do it more accurately if they respond adequately [35]. at the beginning of the learning methods of fdap, lecturer should explain the purpose of learning, build a positive attitude toward the subject, and describe something that is expected by the students [36]. lecturers must first explain the processes and procedures in detail in order to better understand doi 10.18502/sjms.v14i3.5205 page 134 sudan journal of medical sciences karimeldin mohamed ali salih et al this method and [37]. the tutors must teach the students that the main objective of students to search and learn a large amount of information is to investigate critical issues related to the case. during the phase of the investigative lesson, the students are encouraged to critically evaluate the articles being investigated [38]. hamza et al. (2015) who wrote a scientific report in ksa found that fdap really improves mcqs writing, which supports our findings, since it is within the same context [39], together with other findings in usa items writing for usmle [40]. positive perceptions found include: being an active learner; being a systematic learner; developing friendly relationships; adjusting personal characteristics when learning; and having freedom while learning. these are consistent with the findings from this study. it is warranted to measure these perceived benefits with reliable and valid tools over time in future research [41]. area for improvement: this results reflect small size population, absence of randomization. all positive perception of the staffs need validation and evaluation through the verification of students’ performance, behavior, and professionalism that should be carried out when evaluating the usefulness of fadp [42]. the professional development and academic stature of an institution’s faculty members are connected to its educational vivacity [43]. this can be materialized by a dynamic and energetic fdp that has been shown to lead to the enhancement of faculty’s skills in all the five desired domains, that is, teaching, assessment, curriculum support, organizational leadership, and mentoring [43]. faculty development endorses the educational improvements and strategies that are dignitary and are executed in a professional manner. professional organizations and experts have recommended fdps for greater awareness and attainment of knowledge in teaching and learning [44]. strength: this current work draws the attention of policymakers in high educational institutes to the importance of changing opinions and experience between faculty members from different educational backgrounds, and moreover addresses the teamwork interaction, collaboration, and continuous medical education [45]. 5. conclusion in an era of technology and information, a single person experience is not enough for coping with innovation in high education. therefore, faculty development adds experience to faculty members, regardless of their previous education, experience, and practice. doi 10.18502/sjms.v14i3.5205 page 135 sudan journal of medical sciences karimeldin mohamed ali salih et al recommendation it is highly recommended for every medical institute to develop fdap to improve performance and to evaluate the fdap. conflict of interest the authors declare that there is no conflict of interest. authors’ contribution karimeldin mohamed ali salih is the principle investigator and contributed in final layout, discussion, and methodology; abdullah m. al-shahrani helped in the layout and revision of the article and samples; ibrahim awad eljac contributed in the analysis of data; and mohammed abbas contributed in the introduction, discussion. references [1] cui, g., yuan, a., zhu, l., et al. 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[44] maguire, s., li, a., cunich, m., et al. (2019). evaluating the effectiveness of an evidence-based online training program for health professionals in eating disorders. journal of eating disorders, vol. 7, p. 14. [45] alkhaldi, m., abed, y., pfeiffer, c., et al. (2018). assessing policy-makers’, academics’ and experts’ satisfaction with the performance of the palestinian health research system: a qualitative study. health research policy and systems, vol. 16, no. 1, p. 66. doi 10.18502/sjms.v14i3.5205 page 140 introduction methods setting up the fdap data collection and analysis statistical analysis results teaching background of the faculty members faculty member's teaching experience before joining the university faculty member's participation in fdap characteristic of participation in fdap fdp direct/indirect outcomes discussion conclusion recommendation conflict of interest authors' contribution references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13601 production and hosting by knowledge e research article chronotype, daytime sleepiness, and related factors effects on skipping classroom among medical students in tabuk turki aqahtani, abdulaziz albalawi, jalawi alotaibi, atheer alshareef, tariq alrasheed, hyder mirghani, iman mirza, amerah alatawi, hani albalawi, and mohammed sheik faculty of medicine, university of tabuk, tabuk, saudi arabia orcid: hyder mirghani: http://orcid.org/0000-0002-5817-6194 abstract background: lecture attendance is very critical in medical practice. good sleep hygiene is crucial for academic performance. therefore, this research aimed to assess the relationship between daytime sleepiness and the chronotype, and skipping the classroom. methods: a cross-sectional study was conducted among medical students in tabuk from april 2022 to july 2022. three hundred and thirty-four medical students were randomly selected. a standardized questionnaire based on the daytime sleepiness scale, morningness–eveningness questionnaire, and risk for skipping classrooms was used. the students detailed their sleeping habits for two weeks and then responded to the questionnaire distributed directly by the researchers who attended to solve any difficulties. results: out of the 334 students,74.7% skipped the classroom last month. the most common reason for absence was the lecturer directly reading from the slide show (72.8%), followed by late lectures (67.8%), lecturers’ presentation skills (65.6%), and lack of interest (57.9%). daytime sleepiness was evident in 40.1% of the students and was associated with skipping lectures (wald, 3.86, p-value, 0.049, and 95% ci, 0.19–0.91). the majority were intermediate chronotypes (66.4%), followed by evening chronotypes (24.2%) with no association with skipping classrooms. conclusion: skipping lectures is common among medical students in tabuk city, saudi arabia; the causes were lecture timing, daytime sleepiness, and lecturers’ presentation skills. most students were an intermediate chronotype that was not associated with classroom absence. further larger multi-center studies are needed. keywords: skipping classrooms, medical students, daytime sleepiness, chronotype, saudi arabia how to cite this article: turki aqahtani, abdulaziz albalawi, jalawi alotaibi, atheer alshareef, tariq alrasheed, hyder mirghani, iman mirza, amerah alatawi, hani albalawi, and mohammed sheik (2023) “chronotype, daytime sleepiness, and related factors effects on skipping classroom among medical students in tabuk ,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 165–176. doi 10.18502/sjms.v18i2.13601 page 165 corresponding author: hyder mirghani; email: s.hyder63@hotmail.com received 28 october 2022 accepted 13 january 2023 published 30 june 2023 production and hosting by knowledge e turki aqahtani et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences turki aqahtani et al 1. introduction despite significant educational advances, traditional lectures are still practiced in medical education together with hospital-based clinical training and simulation labs [1]. lecture attendance, although very critical in medical practice, is widely neglected. the risk factors for absence from the classroom are primarily individual (sleepiness, illness, and inefficiency of lectures in crowded classrooms) [1]. previous literature showed that interventions at improving the student’s attitude about classroom attendance are beneficial [2]. in addition, absence’s effects on college students’ academic achievement have been previously documented [3, 4]. acknowledging that it is not possible to memorize everything in medicine, and the presence of other attractable learning resources (the united states medical licensing examination [usmle]) might be plausible to absenteeism. however, usmle’s recent pass/fail adoption may positively influence traditional lecture attendance [5]. the time of activity during the day determines the chronotype of an individual (early chronotype who prefers morning activity, also known as pearls, intermediate and late chronotype, also known as night owls) [6]. early school timing was associated with poor daytime dysfunction in both morning and evening chronotypes [7]. in addition, the evening chronotype during the day (circadian misalignment) achieves less than when working in the evening [8]. excessive daytime sleepiness, a public health issue, is prevalent among most populations. although commonly attributed to lifestyle or laziness, it has been linked to cardiovascular diseases, depression, work errors, and car accidents. daytime sleepiness is the inability to maintain alertness and wakefulness during major waking day episodes, with unintentional and inappropriate sleep occurring almost every day for at least three months [9, 10]. excessive daytime sleepiness could lead to fatigue and substantially impair attention and academic achievement. in addition, the kingdom of saudi arabia is a vast country with ethnic, cultural, and environmental diversity. furthermore, different medical schools use different curricula and timetables, so the studies conducted in the western world and other regions of saudi arabia may not apply to tabuk, saudi arabia. rique et al. [10] conducted a study among medical students in brazil and found that daytime sleepiness is not associated with chronotype. on the other hand, a european study found a relationship between evening chronotype and daytime sleepiness [11]. the research hypothesis is that late chronotype might skip lectures due to circadian misalignment and excessive daytime sleepiness. doi 10.18502/sjms.v18i2.13601 page 166 sudan journal of medical sciences turki aqahtani et al to the best of my knowledge, no researchers have assessed the relationship between chronotype and daytime sleepiness with skipping class lectures. thus, this study aims to investigate the same among medical students in tabuk, saudi arabia. 2. materials and methods a cross-sectional study was conducted among medical students in tabuk university, kingdom saudi arabia between april and july 2022. three hundred and thirty-four medical students (second through sixth class) were randomly selected from the faculty of medicine by simple random sampling technique. first-year medical students and those on sedative medications were excluded. first-class students were excluded because of the different curriculum. all students who agreed were approached. a standardized questionnaire based on the daytime sleepiness scale, morningness– eveningness questionnaire, and risk for skipping classrooms was used. participants were invited to sign a written informed consent and then respond to the questionnaire. the students detailed their sleeping habits for two weeks and then responded to the questionnaire distributed directly by the researchers who attended to solve any difficulties. 2.1. sample size calculation a list of 772 students was obtained from the deanship of academic affairs. a simple random sampling method was used to get the final sample. the sample size was determined using a single population proportion formula with the following assumptions; the magnitude of skipping classroom (p = 50%; no previous study in the study area), 95% ui, and the margin of error (d) = 5%. the minimum sample size was 334 students. 2.2. classroom skipping assessment 1. skipping classroom was calculated by the number of skipped lectures or clinical sessions/month or if the student froze the year or was forbidden from the examination due to absence. finally, a meeting was held with the participants, and all information regarding the research objectives and how to fill out the questionnaire was conveyed to them. 2. this study intended to establish the relationship among the following variables: doi 10.18502/sjms.v18i2.13601 page 167 sudan journal of medical sciences turki aqahtani et al 3. daytime sleepiness 4. morningness–eveningness 5. skipping classroom 2.3. daytime sleepiness measurement the epworth sleepiness scale (ess), a well-validated [11] self-reported questionnaire, was used to assess excessive daytime sleepiness. the scale is an eight components choice question. the questionnaire asks the subjects to rate their probability of falling asleep or dose in eight different situations. sitting and reading, watching tv, sitting inactive in public places, as a passenger in a car for 1 hr without a break, lying down to rest in the afternoon when circumstances permit, sitting talking to someone, sitting quietly after lunch without alcohol, and in a car, while stopped for a few minutes in traffic. each question had four choices (no = zero, 1 = mild, 2 = moderate, and 3 = severe) with an aggregate of 0–24. students who scored ≥10 were considered excessive daytime sleepers [12]. 2.4. morningness–eveningness measurement to determine the morningness–eveningness, a standardized tool, the morningness– eveningness questionnaire (meq), a self-administered validated questionnaire developed by the researchers james a home and olov ostebrg (1976), was used. its primary purpose is to measure whether a person’s circadian rhythm (biological clock) produces alertness in the morning, evening, or in between [13–15]. the morningness–eveningness questionnaire includes 19 questions, each with five or four components detailing sleep habits with the following scoring: a score of 16– 30 indicating a definite evening, 31–41 moderate evening, 24–58 intermediate, 59–69 moderate morning, and 70–86 definite morning. 2.5. reasons for skipping lectures reasons behind skipping lectures included early or late timings and the availability of lectures to students through other sources. in addition, other reasons provided were: below-expectation quality of lectures (e.g., reading directly from the slides or organization of the show), students being uninterested in the topic, the lecturer being doi 10.18502/sjms.v18i2.13601 page 168 sudan journal of medical sciences turki aqahtani et al relaxed about attendance, the transportation factor, and student’s perception that the lecture did not benefit them or prepare them for the examination. open-ended questions were included for other reasons for absence. 2.6. data analysis microsoft excel was used for data gathering, and the statistical package for social sciences and the chi-square test were used to compare categorical data. in addition, the binary logistic regression analysis was used for the relationship between various variables. data were presented as percentages or mean ± sd unless otherwise indicated. a p-value of <0.05 was considered significant. 3. results the study included 334 medical students, aged 19–28 years with a mean age of 24.49 ± 1.92 years. their cumulative grade average was 4.03 ± 0.76 out of 5, their time to reach the college was 20.15 ± 9.78 min, the daytime sleepiness and chronotype scores were 8.65 ± 4.22 and 47.47 ± 9.11, respectively, and skipping classroom was 2.99 ± 3.46 times (table 1). moreover, 67.6% of the participants were women, 80% of the students believed that the lectures positively influence their performance, 77.9% were on the side of optional classrooms, and only 45% will attend classrooms if the video is provided. the most common reason for absence was that the lecturer was directly reading from the slide show (72.8%), followed by late lectures (67.8%), and lecturers’ presentation skills (65.6%). in addition, the open questions mentioned fatigue, menstrual periods, lack of concentration, and long lectures without breaks. notably, 57.9% of the students were not interested in the lectures, and 74.7% skipped classrooms last month. daytime sleepiness was evident in 40.1% of the students, and the majority were intermediate chronotypes (66.4%), followed by evening chronotypes (24.2%), while the minority were morning larks (table 2).in the current study, women were younger than men (22.19 ± 1.97 vs. 23.11 ± 2.02, p-value < 0.001, 95% ci, 0.47–1.35) and took more time to reach college (21.57 ± 11.28 vs. 18.59 ± 7.57, p-value, 0.035, 95% ci, –5.73–0.002), table 3 shows a comparison between male and female students. in this study, skipping classrooms was associated with age (wald, 4.36, p-value, 0.037, and 95% ci, 0.52–0.98) and daytime sleepiness (wald, 3.86, p-value, 0.049, and 95% ci, 0.19-0.91). however, no association was found between skipping classrooms doi 10.18502/sjms.v18i2.13601 page 169 sudan journal of medical sciences turki aqahtani et al and cumulative grade average (wald, 0.010, p-value, 0.920, and 95% ci, 0.45–2.41, transportation (wald, 0.092, p-value, 0.762, and 95% ci, 0.95–1.03), and chronotype (wald, 2.38, p-value, 0.122, and 95% ci, 0.16–0.99) (table 4). table 1: basic characteristics of medical students, university of tabuk, saudi arabia. character mean ± sd age (19–28 yr) 24.49 ± 1.92 cumulative grade average (1.2–5.0) 4.03 ± 0.76 time to reach the college (min) 20.15 ± 9.78 skipping classrooms 2.99 ± 3.46 epworth sleepiness scale 8.65 ± 4.22 morningness–eveningness score 47.47 ± 9.11 table 2: sleep pattern, reasons for skipping classroom, and the importance of attendance among medical students at the university of tabuk, saudi arabia. character no (%) sex women men 226 (67.6%) 108 (32.3%) lectures positively influence performance 260 (80%) optional classrooms 258 (77.9%) attending if video was provided 149 (45%) reason of absence early lectures late lectures lecturers’ presentation skills the lecturer is not strict in taking attendance the lecturer reads directly from the slideshows lack of interest 165 (49.8%) 225 (67.8%) 217 (65.6%) 79 (23.8%) 241 (72.8%) 191 (57.9%) daytime sleepiness excessive daytime sleepiness 129 (40.1%) 30 (9.3%) chronotype morning intermediate evening 31 (9.5%) 217 (66.4%) 79 (24.2%) skipping classroom 216 (74.7%) table 3: comparison between males and females at the university of tabuk, saudi arabia regarding skipping classroom. character males females p-value 95% ci age (19–28 yr) 23.11 ± 2.02 22.19 ± 1.97 <0.001 0.47–1.35 cumulative grade average (1.2–5.0) 3.92 ± 0.73 4.14 ± 0.79 0.052 –0.0.43–0.002 time to the college (min) 18.59 ± 7.57 21.57 ± 11.28 0.035 –5.73–0.002 skipping classrooms 2.92 ± 3.33 3.01 ± 3.54 0.806 —9.43–0.73 epworth sleepiness scale 8.21 ± 4.07 8.85 ± 4.28 0.203 –1.62–0.34 morningness– eveningness score 47.11 ± 9.81 47.64 ± 8.78 0.625 –2.65–1.59 ∗t-test doi 10.18502/sjms.v18i2.13601 page 170 sudan journal of medical sciences turki aqahtani et al table 4: relationship between skipping classes and daytime sleepiness, chronotype, transportation, cumulative grade average, age, and gender among the medical students of the university of tabuk. character wald difference p-value 95% ci age (yr) 4.36 1 0.037 0.52–0.98 sex 0.003 1 0.956 0.40–2.63 cumulative grade average 0.010 1 0.920 0.45–2.41 time to the college (min) 0.092 1 0.762 0.95–1.03 daytime sleepiness 3.86 1 0.049 0.19–0.91 morningness– eveningness score 2.38 1 0.122 0.16–0.99 constant 0.85 0.356 ∗binary logistic regression analysis 4. discussion in the present study, 80% of the students believed that the lectures positively influenced their performance, 77.9% were on the side of optional classrooms, and only 45% will attend classrooms if videos are provided. a study conducted among medical students in five public and private sector colleges [16] reported that lectures are helpful in line with the present findings. in the present study, 74.7% of the students skipped at least one lecture in the past month. the main reasons behind skipping classrooms were the lecturer’s presentation skills, the time of lectures, and the lack of interest. policies for rescheduling the lectures and improving the lecturers’ presentation skills are needed. notably, a lack of interest in lectures is a warning because it might be that the students joined medicine against their choice. lack of interest and absence after graduation will substantially affect patient’s care. the lecturers’ presentation skill was the most common reason for absence in a study conducted among medical students in the usa [17]. further studies observed that lecture timings and the lecturers’ presentation skill as the main factors for absence in agreement with our findings [15]. the current study found daytime sleepiness in 40.1% of the students, in agreement with el hangouche et al. [18], who conducted a survey among medical students in morocco and found daytime sleepiness in 36.6%. previous studies from saudi arabia have reported a prevalence of 37.8% [19]. in the present data, no differences between males and females regarding daytime sleepiness support the findings of a previous meta-analysis [20]. no association was evident between daytime sleepiness and cumulative grade average, similar to a prior study in jordon[21]. authors from jordon reported no difference in daytime sleepiness among females and males similar to the current doi 10.18502/sjms.v18i2.13601 page 171 sudan journal of medical sciences turki aqahtani et al findings in which the daytime sleepiness was not different across gender. our results contradict abdulghani and colleagues’ [22], who published a study in malaysia and found more daytime sleepiness among women. similarly, our results also contradict the findings of a recent study that reported a high excessive daytime sleepiness (54.4%), especially among women [23]. excessive daytime sleepiness might be due to poor sleep quality or duration. investigating the causes of daytime sleepiness, including meal timing, caffeinated drinks, and display viewing, is needed [24]. the present study showed a positive correlation between daytime sleepiness and skipping classrooms. similarly, bati et al. reported that sleepiness is among the most cited reasons for skipping lectures in turkey [1]. in this study, 9.5%, 66.4%, and 24.2% were morning, intermediate, and evening chronotypes (with no difference between women and men), similar to previous studies [25, 26]. there is no association between skipping lectures and chronotype; similar results were reported by an earlier study [10]. a plausible explanation might be the dominance of the intermediate chronotype. evening chronotype, social jetlag, and short sleep duration are significant determinants of daytime sleepiness [27]. the association between skipping lectures and age found in this study might be due to peer influence and familiarity with the program. interventions targeting specific age groups might improve attendance rates. desalegn et al. [28] found no association between skipping classrooms and cumulative grade average (gpa) in agreement with our findings. our findings also support previous observations [29, 30]. on the other hand, alamoudi et al. [15] found better academic performance among non-skippers. the gpa is a cumulative grade over the years and might not reflect the student’s performance during the survey. limitations the study was limited by the cross-sectional methodology and being a single-center study. thus, generalization cannot be ensured. 5. conclusion most students had skipped at least one lecture in the past month; the causes were lecture timing and lecturers’ presentation skills. daytime sleepiness was prevalent among medical students in tabuk university, saudi arabia, and was associated with skipping doi 10.18502/sjms.v18i2.13601 page 172 sudan journal of medical sciences turki aqahtani et al classrooms. most students were intermediate chronotype that was not associated with classroom absence. further larger multi-center studies are needed. acknowledgments the authors would like to extend their sincere gratitude to the deanship of higher education and scientific research, university of tabuk, saudi arabia, for the financial support of this research under grant number (s-1443-0003). ethical considerations all participants signed written informed consent and their privacy was secured according to the declaration of helsinki. furthermore, ethical clearance was obtained from the ethical committee of the university of tabuk (ref, ut-164-27-2021. dated 13/12/2021). competing interests none to declare. availability of data and material the data and material of this study are available from the corresponding author upon request. funding none. references [1] bati, a. h., mandiracioglu, a., orgun, f., & govsa, f. 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(2018). comprehensive assessment of the impact of life habits on sleep disturbance, chronotype, and daytime sleepiness among high-school students. sleep medicine, 44, 12–18. https://doi.org/10.1016/j.sleep.2017.10.011 [25] tan, m. n., mevsim, v., pozlu cifci, m., sayan, h., ercan, a. e., ergin, o. f., oksuz, u., & ensari, s. (2020). who is happier among preclinical medical students: the impact of chronotype preference. chronobiology international, 37(8), 1163– 1172. https://doi.org/10.1080/07420528.2020.1761373 [26] li, t., xie, y., tao, s., yang, y., xu, h., zou, l., tao, f., & wu, x. (2020). chronotype, sleep, and depressive symptoms among chinese college students: a cross-sectional study. frontiers in neurology, 11, 592825. https://doi.org/10.3389/fneur.2020.592825 [27] kolomeichuk, s. n., randler, c., morozov, a. v., gubin, d. g., & drake, c. l. (2021). social jetlag and excessive daytime sleepiness from a sample of russian children and adolescents. nature and science of sleep, 13, 729– 737. https://doi.org/10.2147/nss.s290895 [28] desalegn, a. a., berhan, a., & berhan, y. (2014). absenteeism among medical and health science undergraduate students at hawassa university, ethiopia. bmc medical education, 14, 81. [29] azab, e., saksena, y., alghanem, t., midle, j. b., molgaard, k., albright, s., & karimbux, n. (2016). relationship among dental students’ class lecture attendance, use of online resources, and performance. journal of dental education, 80(4), 452– 458. https://doi.org/10.1002/j.0022-0337.2016.80.4.tb06103.x [30] alghamdi, a. y. k., albarkati, b., alrehili, o., & salih, m (2016). prevalence causes and impacts of absenteeism among medical students at uqu. education 6(1):9–12. doi 10.18502/sjms.v18i2.13601 page 176 introduction materials and methods sample size calculation classroom skipping assessment daytime sleepiness measurement morningness–eveningness measurement reasons for skipping lectures data analysis results discussion limitations conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5216 production and hosting by knowledge e research article assessment of the necessity of routine lumber puncture among children with fever and convulsions nader mutwakel osman1 and james peter garkuoth gai2 1department of paediatric and child health, fuculty of medicine 2mohamed al amin hamid paediatric hospital omderuman abstract background: the routine investigation of doing lumbar puncture in patient with febrile convulsion is increasing practiced in many hospital. objectives: the aim of this study was to assess the necessity of routine lumbar puncture (lp) to diagnose meningitis in children who present with fever and convulsions. methods: this is an observational, cross-sectional, hospital-based study, carried out in mohammed al-amin hamid pediatrics hospital-omdurman sudan, during the period from the first of january through 31 july 2018. it involved all (146) children aged 5 months to 6years, who presented with fever and convulsions, undergone lumbar puncture, and parents signed written informed consents. children with known neurological diseases were excluded from this study. data collected included, age, gender, convulsions type and duration, post-ictal state, routine vaccination status, general condition, recent antibiotics use, past history of fever and convulsions, temperature degree, signs of meningeal irritation, and conscious level. data were analyzed by statistical package for social sciences (spss) version 23. results: the result revealed that total number of 146 children, male were 62% (n=91), female were 38% (n=55). 5-11 months 35.6% (n=52) 1-3years 43.8% (n=64), and 4-6 years 20.6% (n=30). about 80% of the patients were younger than 4 years of age. convulsion was generalized in 97.9%, lasted less than 15 minutes in 99.3%, spontaneously aborted in 94.5%, post-ictal state was brief in 88.4%, first attack in 98.6%, and there was no family history in 97.3%,p=0.000. there was no neck stiffness and photophobia in 92.5% and 98.6% respectively, p=0.000. patients general condition were well in 76.7% and toxic in 23.3%. cerebrospinal fluids (csf) color was clear in 97% and turbid in 3% of patients. csf white cells was less than 5 in 93.8%, and csf sugar and protein were normal in 97.3% and 96.6% respectively, p=0.000. csf culture was negative for all patients, and almost all (97%, n=141) of the patients were diagnosed as febrile convulsions and sent home, compared to 3% (n=5) who were diagnosed clinically as meningitis. conclusion: this study revealed that, csf culture was negative for all patients, and almost all were diagnosed as febrile convulsions. however, 5 patients were diagnosed clinically as meningitis. hence, this findings, challenge the routine lumbar puncture in children who present with fever and convulsion. how to cite this article: nader mutwakel osman and james peter garkuoth gai (2019) “assessment of the necessity of routine lumber puncture among children with fever and convulsions,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 162–171. doi 10.18502/sjms.v14i3.5216 page 162 corresponding author: nader mutwakel osman; email: nadermosman@gmail.com received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e nader mutwakel osman and james peter garkuoth gai. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:nadermosman@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai 1. introduction since the introduction of lumbar puncture (lp) in the 19𝑡ℎ century (1891) by . quincke [1], it remains the most commonly used invasive diagnostic procedure. it involves insertion of a specialized needle in the lumbar spine interspaces (l3-l4 or l4-l5) in order to withdraw cerebrospinal fluids (csf). beside the diagnosis of meningitis and other central nervous system (cns) infections, lp is also used to diagnose subarachnoid hemorrhage and to relief increased intracranial pressure (icp). [1–3] it is contraindicated in critically ill patients, impaired conscious level, cardiopulmonary compromise, bleeding disorder or coagulopathy, raised intracranial pressure, and infection at the puncture site. its complications include introduction of traumatic (bloody) and dry tap, post-puncture headache, cerebral herniation, and hemorrhage (external and /or intracranial; epidural, subdural, and subarachnoid) [2, 3]. seizure is a frightening event to the family, and imposes challenge to the health professionals so lumbar puncture still an important diagnostic procedure to exclude meningitis and it is curried out routinely in some settings, although the current evidence suggests selective rather than routine use. bacterial meningitis is rare in patients with complex febrile seizures who otherwise appear well and have no other signs and symptoms on physical examination [4, 5]. there are two types of febrile convulsion, typical (simple) occurs in children 6 month to 5 years, generalized, lasting less than 15 minutes, does not recur within the 24 hours, and normal neurological examination, and the atypical (complex) which is localized, prolonged-lasting 15 minutes or more, recurs within the 24hours,and abnormal neurological examination [2]. according to the american academy of pediatrics (aap), the febrile seizure is defined as convulsions accompanied with fever (temperature 38 degree or more) without central nervous system (cns) infection that occurs in children 6-60 months. it is the most common convulsion occurs in 2% to 5% of all children [3]. it has been found that, sudden and prolonged rise in body temperature and upper respiratory infection predispose to febrile seizure. [6, 7] and according to the updated aap guidelines (2011) lumbar puncture should be performed in any child who presents with fever and seizure and has history, signs and symptoms suggesting meningeal irritation or intracranial infection.but any infant aged 6 to 12months who presents with seizure and fever, a lumbar puncture is an option when the child is considered not immunized or the status of immunization is not known. also lumbar puncture is an option in the child who presents with fever and seizure and is pretreated with antibiotics [7]. doi 10.18502/sjms.v14i3.5216 page 163 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai according to sudanese guidelines, lp should be considered in all children aged < 18 month with their first febrile convulsions,any child with suspected meningitis and any infant and child who received recent antibiotics [8]. 2. materials and methods this was a cross-sectional, observational, hospital-based study that was conducted in mohammed al-amin hamid teaching hospital (omdurman) one of the largest pediatrics teaching hospital in sudan, established during the period from 1𝑠𝑡january through 31𝑠𝑡 july 2018. total coverage of all children who fulfilled the inclusion criteria for all children (5 months to 6years of age) who are admitted to the emergency department with fever and convulsions and undergone lumber puncture during the study period whom parents signed written informed consents, were included in the study, with exclusion criteria of the children less than 5 months and above 6 years, and those who have known neurological disorders were excluded from the study. data were directly collected from the parents and patients assessment through check list questionnaire and meningitis record (a register book provided by the ministry of health in order to keep record and surveillance of the suspected cases of meningitis). ethical approval was obtained from sudan medical specialization board (smsb) ethical committee and informed consent was signed by the parent care givers. the study variable include age, gender, convulsions type and duration, post-ictal state, routine vaccination status, patient general condition, recent antibiotics use, previous history of fever associated seizures, temperature degree, signs of meningeal irritation, and conscious level. data were processed by computer and analyzed using spss version 23. 3. results of total 146 children, male were 62% (n=91), female were 38% (n=55)-male: female (1.6:1). 5-11months 35.6% (n=52), 1-3 years 43.8% (n=64), and 4-6 years 20.6% (n=30). about 80% of the patients were younger than 4years of age. see table 1 according to history for those who received antibiotic before getting convulsion were 70 (47.9%) and those who did not receive antibiotic were 76 (52.1%.). most of the patients were vaccinated (n 114) 78% and those not vaccinated were (n 29) 19.9% and only 3 patients their vaccination status were unknown 2.1%. see table 2. doi 10.18502/sjms.v14i3.5216 page 164 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai the convulsion was generalized in 97.9%, lasted less than 15 minutes in 99.3%, spontaneously aborted in 94.5%, first attack in 98.6%, and there was no family history in 97.3%, p=0.000. post-ictal state was brief in 88.4%. see table 3 there was no neck stiffness or photophobia in 92.5% and 98.6% respectively. patients general condition were well in 76.7% and toxic in 23.3% see table 4 according to investigation characteristic blood film for malaria was positive for only one patient (0.7%) negative for 142 patients (97.2%) and not done for 3 patients (2.1%) see table 5. cerebrospinal fluids (csf) color was clear in 97% and turbid in 3% of patients, p=0.000. csf white cells were less than 5 cells in 93.8%, csf sugar and protein were normal in 97.3% and 96.6% respectively, p=0.000. csf culture was negative for all patients, see table 6. and almost all 97%, (n=141) of them were diagnosed as febrile convulsion, and the remaining 3% (n=5) were diagnosed and treated clinically as meningitis interestingly, those diagnosed clinically as meningitis, were pretreated with antibiotics, not vaccinated, toxic look and have significant csf findings (turbid color, low sugar, and high protein and white cells). (*statistical significance is set as p < 0.05). table 1: demographic distribution of the study population (n =146). demographical characteristics frequency % age 5 -11 month 1-3years 4-6 years 52 64 30 35.6 43.8 20.6 gender male 91 62 female 55 38 table 2: distribution of the study population according to history characteristics (n = 146). history characteristics frequency % recent antibiotics use yes no 70 76 47.9 52.1 routine vaccination status vaccinated not vaccinated status unknown 114 29 3 78 19.9 2.1 patient previous history of fever and convulsion yes no 2 144 1.4 98.6 family history of febrile convulsion yes no 4 142 2.7 97.3 doi 10.18502/sjms.v14i3.5216 page 165 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai table 3: distribution of the study population according to convulsions characteristics (n= 146). convulsions characteristics frequency % convulsion type generalized focal 143 3 97.9 2.1 convulsion duration < 5 minutes 5-15 minutes >15 minutes 120 25 1 82.2 17.1 0.7 post-ictal state brief (<30 minutes) prolonged (>30 minutes) 129 17 88.4 11.6 convulsions onset < 24 hours after fever >24 hours after fever 132 14 90.4 9.6 convulsion abortion spontaneous by diazepam by phenytoin 138 8 0 94.5 5.5 0 table 4: distribution of the study population according to clinical characteristics (n=146). clinical characteristics frequency % bulging anterior fontanel yes no 19 127 13 87 kerning’s and or brudzinski’s sign positive negative not done not applicable 2 46 30 68 1.4 31.5 20.5 46.6 neck stiffness positive negative 11 135 7.5 92.5 photophobia yes no not checked 1 144 1 0.7 98.6 0.7 patient general condition well toxic 112 34 76.7 23.3 fever high grade low grade 141 5 96.6 3.4 4. discussion this cross-sectional, observational study attempts to investigate the necessity of routine lumbar puncture in children who present with fever and convulsions, because there is no well-established data or studies in our community regarding this matter. as bacterial meningitis is a life threatening infectious disease affecting the meninges, doi 10.18502/sjms.v14i3.5216 page 166 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai table 5: distribution of the study population according to investigation characteristics (n =146). investigations frequency % gram stain positive negative 0 146 0.0 100 blood film for malaria positive negative not done 1 142 3 0.7 97.2 2.1 c-reactive protein (crp) positive negative not done 1 2 143 0.7 1.4 97.9 blood culture done not done 0 146 0.0 100 latex agglutination test done not done 0 146 0.0 100 fundal examination before lp done not done 0 146 0.0 100 ct brain before lp done not done 0 146 0.0 100 table 6: distribution of the study population according to csf results (n =146). csf results frequency % csf white cells < 5 5-100 100-500 > 500 137 6 2 1 93.8 4.1 1.4 0.7 csf protein normal elevated markedly elevated 141 4 1 96.6 2.7 0.7 csf sugar normal low markedly low 142 3 1 97.3 2 0.7 csf culture positive negative 0 146 0 100 csf color clear turbid red 139 5 2 95.2 3.4 1.4 and the commonest organism are haemophilus influenza type b (hib), streptococcal pneumonae, neissaria meningitides, and group b streptococci (gbs) [9]. doi 10.18502/sjms.v14i3.5216 page 167 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai in africa, bacterial meningitis occurs mainly within the meningitis belt, and sudanwhich falls within this belt, accounts for about 2 in every 100 cases of meningitis. but, the prevalence and incidence of meningitis in sudan significantly reduced since the introduction of hib, pneumococcal, and meningococcal type a vaccines into sudan immunization schedule in 2008, 2013, and 2016 respectively [10, 11]. generally, with the increasing coverage of vaccination, the morbidity and mortality from the commonest causes of bacterial meningitis is dramatically reduced [12, 13]. antibiotic pretreatment (recent antibiotics use) is said to affect the clinical features of meningitis, that is why it is stated that lp should be carried out in children with fever and seizures who received antibiotic [8–15]. as it has been found in a recent study that, csf will become sterile for meningococcal and pneumococcal bacteria in 2 and 4 hours of third generation cephalosporin antibiotics respectively [16]. several studies had been done in the world for the need to do lumbar puncture for patients with febrile convulsion or not.as for the retrospective cohort review for children aged 6 to 18 months by kimia in 2009 found the risk of bacterial meningitis presenting as first simple febrile seizure is very low. and they recommend that, the current aap guidelines should be reconsidered [17]. also a retrospective cross sectional observational study done by auvin in 2017 and oluwabusi. curr opin investigating infants aged 6-11 months with conclusion that, the risk of bacterial meningitis is extremely low in children with simple febrile convulsions [18]. a systemic review and meta-analysis done by najaf-zadeh revealed that, the utility of routine lumbar puncture for the diagnosis of central nervous system (cns) infection, is very low. similar results were obtained by hom j. in a systemic review which concluded that, the risk of bacterial meningitis in children presenting with simple febrile convulsions is very low [19, 20]. majority of our study population in this study, have features suggestive of first simple febrile convulsions (generalized, brief, spontaneously aborted, normal neurological and csf examination), and about 80% of them received routine vaccination according to the national immunization schedule, and almost all (97%) were sent home with the final diagnosis of febrile convulsions, once the csf biochemistry was normal and csf culture showed negative results on the third day of sample collection, compared to 3% whom were diagnosed clinically as meningitis, figure [7]. interestingly, those diagnosed clinically as meningitis, were pretreated with antibiotics, not vaccinated, toxic at presentation, and have significant csf findings (turbid color, low sugar, and high protein and white cells). doi 10.18502/sjms.v14i3.5216 page 168 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai the findings of our study are supported by the updated american academy of paediatric (aap) guideline [7], and prospective studies by ghotbi et al. [14], and laman et al. [21], another similar results were obtained from retrospective studies by kimia aa et al. [7], casasoprana a et al. [22] and azita t et al. [23]. many studies attempt to identify the risks and predictors of meningitis in children who present with fever and convulsions. prolonged seizures (lasting more than 30 minutes), first attack, post-ictal drowsiness, fever and complex convulsions, impaired conscious level, body temperature 38 or more, age younger than 18 months, and neurological deficits were found to be predictive of meningitis in children presented with fever and convulsions [24, 25, 26]. in contrast to these findings, few studies as for joshi batajoo et al. [27] have done a prospective study which stated that, lp is necessary to rule out meningitis in infants 6-12 months who present with fever and convulsions even in the absence of meningeal signs. another retrospective study which investigated children younger than 12 month, concluded that, lp should be considered in all infants with simple febrile seizure even if fully vaccinated [28]. supported by the above mentioned studies, our study provides another evidence that, routine lumbar puncture in children who present with fever and simple generalized convulsion, clinical assessment supports the diagnosis of simple febrile convulsions, fully vaccinated and not received antibiotic is not necessary. our study sustained some limitations, being a single center study and a rather small sample size, renders the results not generalizable. a wider multi-center research is needed. 5. conclusion investigating the need for routine lumbar puncture in children who present with fever and convulsions was the aim of this study. this research revealed that, csf culture was negative for all patients, and almost all were diagnosed as febrile convulsions. however, 5 patients were diagnosed clinically as meningitis and treated accordingly. our study revealed that, the utility of routine lumbar puncture for the diagnosis of central nervous system (cns) infection, is very low hence, these findings challenge the necessity of routine lp to diagnose meningitis in the absence of positive physical signs and symptoms suggestive of central nervous system infection. doi 10.18502/sjms.v14i3.5216 page 169 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai acknowledgement the authors express their sincere appreciation to the administration of mohammed al-amin hamid pediatrics hospital-omdurman sudan for giving the approval and assistance in conducting the research and we are grateful to parent and doctor who participate in the study references [1] pearce jm. walter essex wynter, quincke, and lumbar puncture. j neurol neurosurgery psychiatry. 1994; 57(2):179. [2] medscape/meningitis [3] nelson’s textbook of pediatric 19th edition. 2090/2610 [4] kimia aa, et al. yield of lumbar puncture among children who present with their first complex febrile. pediatrics.2010;126(1): 62-69 [5] erin m. fletcher and ghazalasharieff. west j emerg med. may 2013; 14(3): 206-211. [6] gontko-romanowska k et al.: the assessment of risk factors for febrile seizures in children. neurolneurochir pol. 2017 nov dec; 51(6):454-458. doi: 10.1016/j.pjnns.2017.07.011. epub 2017 jul 31 [7] subcommittee on, american a. neurodiagnostic evaluation of the child with a simple febrile seizure.pediatrics.2011; 127 (2): 389-384. [8] sudanese management protocol for pediatric emergencies, 3rd edition, 2015.28 /176 [9] mohammad m attarpour et al. iran j microbiol. 2014 aug; 6(4): 211-218. [10] ipums-dhs (demographic and health surveys [11] whosudan first to introduce life-saving meningococcal type a vaccine into routine immunization. [12] wahl b, et al. lancet global health.2018) [13] guidelines for the management of suspected and confirmed bacterial meningitis in canadian children. updated dec. 2018 [14] ghotbi f, et al. an assessment of the necessity of lumbar puncture in children with seizure and fever j pak med assoc. 2009 [15] reet s, et al. pediatrics in review. august 2013, vol.34/issue 8. [16] reet s, et al. pediatrics in review. august 2013, vol.34/issue 8. doi 10.18502/sjms.v14i3.5216 page 170 sudan journal of medical sciences nader mutwakel osman and james peter garkuoth gai [17] kimia aa, et al. utility of lumbar puncture for first simple febrile seizure among children 6 to 18month of age. pediatrics.2009 [18] guedj r, et al. acad emerg med. 2015 [19] hom j, et at. acad emerg med. 2011 [20] najaf-zadeh et al. risk of bacterial meningitis in young children with a first seizure in the context of fever: a systemic review and meta-analysis [21] laman m, et al. cli infect dis. 2010 [22] casasoprana a, et al. value of lumbar puncture after a first febrile seizure in children aged less than 18months. arch pediatr 2013 involving 157 children [23] azita tavasoli et al. frequency of meningitis in children presenting with febrile seizures. iran j child neurol. 2014 autumn;8(4): 51-56 [24] who recommendations 2015. doi 10.18502/sjms.v14i3.5216 page 171 introduction materials and methods results discussion conclusion acknowledgement references sudan journal of medical sciences volume 13, issue no. 1, doi 10.18502/sjms.v13i1.1685 production and hosting by knowledge e research article abo, rhesus blood groups and transfusion-transmitted infections among blood donors in gabon christ-dominique ngassaki-yoka1,2, jophrette mireille ntsame ndong2, and cyrille bisseye1 1laboratory of molecular and cellular biology, university of sciences and techniques of masuku (ustm), p.o. box 943, franceville, gabon 2national blood transfusion center, p.o. box 13895, libreville, gabon abstract background: few studies focused on the study of blood groups in gabon. this study aimed to determine the phenotypic frequency of abo and rhesus antigens in blood donors of libreville and to assess the association between abo blood groups and transfusion-transmitted infections. materials and methods: the study of abo and rhesus blood groups concerned 4,744 blood donors. abo and rhesus phenotyping were obtained using monoclonal monospecific antisera: anti-a, anti-b, anti-ab, anti-d, anti-e, anti-c, anti-c, and anti-e with an automate (qwalys® 3, diagast, france) or a card gel (id card, bio-rad) according to manufacturer’s instructions. results: the phenotypic frequency of blood group antigens a, b, ab and o were respectively 21.0%; 17.6%; 2.6% and 58.9%. those of rhesus antigens d, d, c, c, e and e were 97.7%; 2.3%; 15.9%; 99.9%; 17.6%; 99.3%, respectively. the prevalence of abo and rh antigens in gabonese donors reported here are significantly different from those of neighboring countries. no association was found between the prevalence of hiv, hcv and syphilis and abo blood groups. instead, hbv seroprevalence was twice as high among non-o blood groups donors compared with blood group o donors [or = 2 (ci 1.26 to 3.2), p = 0.003]. conclusions: this study provides new data on phenotypic frequency of abo and rh blood groups in a representative sample of the gabonese blood donor population. it suggests a significant association between abo blood group and hbv infection. keywords: abo, rhesus, blood donors, hbv, gabon 1. introduction blood transfusion remains a therapy carrying specific risks not only because of the possible blood incompatibility between the donor and the recipient; but also because how to cite this article: christ-dominique ngassaki-yoka, jophrette mireille ntsame ndong, cyrille bisseye, (2018) “abo, rhesus blood groups and transfusion-transmitted infections among blood donors in gabon,” sudan journal of medical sciences, vol. 13 (2018), issue no. 1, 12–21. doi 10.18502/sjms.v13i1.1685 page 12 corresponding author: cyrille bisseye; email: cbisseye@gmail.com received 19 december 2017 accepted 28 february 2018 published 14 march 2018 production and hosting by knowledge e christ-dominique ngassaki-yoka et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0002-6888-6317 mailto:cbisseye@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences christ-dominique ngassaki-yoka et al of the potential transmission of blood borne pathogens. one of the ways to limit the post-transfusion adverse events is to phenotype blood donors for the main red cell blood group systems and to simultaneously detect the transfusion-transmitted infections (ttis). according to the who, in 39 countries blood donations are still not routinely tested for ttis including hiv, hbv, hcv and syphilis; 47% of blood bags in low-income countries are examined in laboratories without quality assurance [1]. it is estimated that 1.6 million blood units/year are deferred and destroyed due to the presence of tti’s markers [1]. the understanding of blood group systems has evolved to include not only blood transfusion compatibility but also the relationship between some infectious diseases and the antigens in erythrocytes [2]. several studies have shown an association between specific blood group antigens and the risk of pancreatic cancer [3–5]. associations between the abo system and various diseases including malaria infection, cerebral thrombosis and ovarian cancer have also been found [6–8]. in gabon, few studies have been devoted to blood groups. this relative lack of information has led to undertaking this study. this investigation aimed to determine the phenotypic frequencies of the abo and rhesus d, c, c, e, e antigens in the gabonese population and to study the association between transfusion-transmitted infections and the abo blood groups. 2. materials and methods 2.1. blood donors a retrospective analysis of blood donors’ data from january to may 2015 in the national blood transfusion center (cnts) in libreville, gabon was conducted. volunteer and family/replacement donors were all apparently healthy subjects, selected after responding to a questionnaire including a medical history. they were aged 17–65 years weighing over 50 kg and eligible for blood donation. socio-demographic characteristics were recorded, and venous blood was collected in blood collection bags following standard procedures. 2.2. determination of abo and rh phenotyping abo and rhesus phenotyping were obtained using monoclonal monospecific antisera: anti-a, anti-b, anti-ab, anti-d, anti-e, anti-c, anti-c, and anti-e with an automate doi 10.18502/sjms.v13i1.1685 page 13 sudan journal of medical sciences christ-dominique ngassaki-yoka et al (qwalys® 3, diagast, france) or a card gel (id card, bio-rad) according to manufacturer’s instructions. positive and negative control red cells were used and the bethvincent and simonin-michon’s tests were performed as controls. 2.3. serological analysis antibodies to hcv and hiv types 1 and 2 were detected using monolisa hcv agab ultra version 2 and genscreen hiv-1/2 version 2 (bio-rad, marnes-la-coquette, france). hepatitis b surface antigen (hbsag) and antibodies to treponema pallidum were screened with monolisa hbsag ultra and treponema pallidum haemagglutination test (bio-rad, marnes-la-coquette, france) following the manufacturer’s instructions. 2.4. statistical analysis data analysis was done by using the statistical package for the social sciences (spss version 20.0) and epi-info version 6.04dfr (cdc, atlanta, usa). the results were considered significant for p < 0.05. 3. results 3.1. abo and rh phenotypic frequencies from a total of 4,744 blood donors, 59.7% were in the age group of 21-30 years with a mean age of 29.9 ± 7.0 (range 17-61 years). of these, 83.1% donors were male and 16.9% donors were female. among blood donors the overall prevalence of blood groups o, a, b and ab were 58.9%; 21.0%; 17.6% and 2.6%, respectively (table 1). the majority of blood donors from o blood group were male (48.8%). ab blood group was the least represented among blood donors (2.2% of male and 0.4% of female) (table 1). in the rhesus blood group, 5 antigens were tested: d (rh1), c (rh2), e (rh3), c (rh4) and e (rh5). the absence of the d antigen was denoted d (rhesus negative). the frequencies of rhesus antigens d, d, c, e, c and e were respectively 97.7%; 2.3%; 15.9%; 17.6%; 99.9% and 99.3% (table 2). the majority of rhesus negative individuals was male (2.0%) and from o blood group (1.4%). only 0.3% of female was rhesus negative and 0.1% of blood donors were both ab blood group and rhesus negative (table 2). doi 10.18502/sjms.v13i1.1685 page 14 sudan journal of medical sciences christ-dominique ngassaki-yoka et al blood groups o a b ab n (%) n (%) n (%) n (%) sex male 2,314 (48.8) 832 (17.5) 692 (14.6) 105 (2.2) female 478 (10.1) 162 (3.4) 144 (3.0) 17 (0.4) age groups (years) ≤ 20 88 (1.9) 29 (0.6) 29 (0.6) 5 (0.1) 21-30 1,658 (35.0) 597 (12.6) 507 (10.7) 71 (1.5) 31-40 775 (16.3) 276 (5.8) 221 (4.7) 38 (0.8) > 40 271 (5.7) 92 (1.9) 79 (1.7) 8 (0.2) total 2,792 (58.9) 994 (21.0) 836 (17.6) 122 (2.6) t 1: frequency of abo blood groups in blood donors according to sex and age groups. the major rh phenotypes observed among blood donors were respectively dccee (66.5%), dccee (15.3%) and dccee (13.5%). the minor phenotypes obtained were dccee (1.5%), ddccee (1.5%), dccee (0.8%), dccee (0.7%), dccee (0.1%) and dccee (0.02%). 3.2. association between blood groups and transfusion-transmitted infections among blood donors 233/4,744 (4.9%) were infected with at least one pathogen. the overall seroprevalence of antibodies to hiv, hcv and syphilis was 1.1%; 0.5% and 1.6%; hbsag prevalence was 1.7%. the seroprevalence of hiv, hbv, hcv and syphilis markers was compared between blood donors of blood group o and non-o as shown in table 3. hiv, hcv and syphilis markers seroprevalence was similar in blood donors of group o compared to non-o blood groups (table 3). however, the prevalence of hbsag was twice higher among non-o blood groups donors compared to donors of o blood group [or= 2; 95%ci: 1.3, 3.2; p = 0.003]. doi 10.18502/sjms.v13i1.1685 page 15 sudan journal of medical sciences christ-dominique ngassaki-yoka et al sex blood groups male female o a b ab rh antigens n (%) n (%) n (%) n (%) n (%) n (%) d 3,846 (81.1%) 787 (16.6%) 2726 (57.5%) 972 (20.5%) 818 (17.2%) 117 (2.5%) d 97 (2.0%) 14 (0.3%) 66 (1.4%) 22 (0.5%) 18 (0.4%) 5 (0.1%) c 617 (13.0%) 138 (2.9%) 442 (9.3%) 165 (3.5%) 126 (2.7%) 22 (0.5%) c 3,938 (83.0%) 800 (16.9%) 2787 (58.8%) 994 (21.0%) 835 (17.6%) 122 (2.6%) e 694 (14.6%) 143 (3.0%) 491 (10.4%) 175 (3.7%) 142 (3.0%) 29 (0.6%) e 3,915 (82.5%) 795 (16.8%) 2770 (58.4%) 991 (20. 9%) 828 (17.5%) 121 (2.6%) t 2: distribution of rhesus antigens according to sex and blood groups. blood groups n hiv positive n (%) or (ic 95%) p-values o 2,792 29 (1.0) 0.635 non o 1,952 24 (1.2) 1.2 (0. 7-2.1) hbv positive n (%) o 2,792 34 (1.2) 0.003 non o 1,952 47 (2.4) 2 (1.3-3.2) hcv positive n (%) o 2,792 10 (0.4) 0.288 non o 1,952 12 (0.6) 1.7 (0.7-4.3) syphilis positive n (%) o 2,792 44 (1.6) 0.848 non o 1,952 33 (1.7%) 1.1 (0.7-1.7) or= odds ratio ; ci = confidence interval. in bold significant p-value t 3: prevalence of hiv, hbv, hcv and syphilis according to abo blood groups. 4. discussion this study aimed to determine the prevalence of abo and rhesus blood groups among blood donors and their association with ttis. this study shows the distribution of abo and rhesus phenotypes in a relatively large population of gabonese blood donors. the phenotypic frequency of blood groups a, b, ab, o and d were respectively 21.0%, doi 10.18502/sjms.v13i1.1685 page 16 sudan journal of medical sciences christ-dominique ngassaki-yoka et al continents/countries frequencies of abo and rhd (%) references o a b ab d present study (n= 4,744) 58.9 21.0 17.6 2.6 97.7 africa congo (n= 5,400) 52.3 23.1 21.1 3.5 ref. [13] cameroon (n= 14,546) 48.6 25.1 21.9 4.5 96.3 ref. [14] burkina faso (n= 37,210) 43.4 22.7 28.2 5.8 86.2 ref. [15] morocco (n= 344,954) 46.1 33.9 15.7 4.3 ref. [16] europe france 43.0 45.0 9.0 3.0 85.0 ref. [17] asia india (n = 12,701) 28.7 28.7 32.1 10.5 94.5 ref. [8] japon 29.9 39.8 19.9 9.9 ref. [19] usa 46.6 37.1 12.2 4.1 85.4 ref. [20] t 4: comparison of abo frequency in gabonese blood donors and in previous studies. 17.6%, 2.6%, 58.9 and 97.7% (tables 1 and 2). group o and rh positive blood groups were predominant in contrast with ab and rh negative groups. the ab blood group was relatively rare, (0.4% in women and 2.2% in men). there were very few rh negative women (0.3%) limiting the risk of maternal-fetal incompatibility and its prevention during pregnancy. the major rhesus phenotypes observed were dccee (66.5%), dccee (15.3%), dccee (13.5%). indeed, dccee rhesus phenotype has been previously described as more prevalent in black populations9. the frequency of dccee phenotype found in our study is comparable to that reported in mali10. however, it is lower than the 73.6% reported in southern nigeria [11]. the prevalence of the abo blood groups were compared with those obtained in a previous study in gabon, which reported the following phenotypic frequencies: 20% for a, 17.3% for b, 4.1% for ab and 58.6% for group o [12]. these results are similar to ours presented here. however, ab blood group prevalence was higher in the study by languillat et al [12], although the difference observed was not statistically significant (x2 = 2.4, p = 0.122). frequencies of the abo and rh blood groups obtained from blood donors were compared to neighboring donor populations of central africa (congo and cameroon), west africa (burkina faso), north africa (morocco) and the world (table 4). the prevalence of abo phenotypes in gabon was significantly different from those observed in other african countries such as congo, cameroon, burkina faso, and morocco [13–16]. in fact, the frequency of the o blood group was higher than that observed in these african countries while the prevalence of blood groups a and b was lower. unsurprisingly, the abo phenotypic prevalences in this study were very different from those observed in doi 10.18502/sjms.v13i1.1685 page 17 sudan journal of medical sciences christ-dominique ngassaki-yoka et al asia, including india and japan; in europe and the usa [17–20]. this could be explained by the genetic distance between the predominantly gabonese black population and population of caucasian and asian descent. the high prevalence of group o in subsaharan africa has been in part attributed to selection related to malaria being less severe clinically in carriers of o blood group [21–23]. this study also evaluated the association between abo blood groups and bloodborne infections such as hiv, hbv, hcv and syphilis. the prevalence of seroreactive hiv, hbv, hcv and syphilis markers was 1.1%, 1.7%, 0.5% and 1.6%, respectively. these seroprevalences were lower than seroreactivities reported in a previous study [24]. no confirmation was performed so that the prevalence of antibodies to hiv, hcv and syphilis was likely considerably overestimated. the difference between the two sample sizes, the selection of gabonese donors only in the present study and the evolution of these infections’ epidemiology could partly explain these differences. no significant association between hiv, hcv, syphilis and abo blood groups was found among blood donors. however, the risk of hbv infection appeared twice higher among nono donors compared to o blood group donors. this result would need to be supported by detection of hbv dna with a sensitive assay. it is however in agreement with previous studies [25, 26]. a recent study showed a higher risk of hepatocellular carcinoma associated with hepatitis b in non-o blood group compared to o blood group patients [27]. 5. conclusion this study reports the prevalence of the abo and rhd blood groups in a representative sample of the gabonese blood donor population. it also suggests the association between the abo blood group and chronic hbv infection. 6. declarations acknowledgments: we thank all the participants of this study, the cnts’ staff colette holmann yeno, ripaire mboumba, rita alembe mayindo, anicet mouity matoumba and jpa for critically reading the manuscript. ethics approval: this study was approved by the cnts ethics committee. competing interests: the authors declare no conflict of interest. availability of data and material: data and material could be available on demand. doi 10.18502/sjms.v13i1.1685 page 18 sudan journal of medical sciences christ-dominique ngassaki-yoka et al funding: we are grateful to the national blood transfusion center its financial support through le programme de support à la recherche. references [1] world health organization. “global database on blood safety”. 2011 [2] anstee dj, “the relationship between blood groups and disease”, blood, vol. 115, no. 23, pp. 4635-4643, 2010. [3] b. m. wolpin, a. t. chan, p. hartge et al.,“abo blood group and the risk of pancreatic cancer”, journal of the national cancer institute, vol. 101, no. 6, pp. 424-31, 2009. [4] b. m. wolpin, p. kraft, m. gross et al.,“pancreatic cancer risk and abo blood group alleles: results from the pancreatic cancer cohort consortium”, cancer research, vol. 70, no. 3, pp. 1015-23, 2010 [5] b. m. wolpin, p. kraft, m. xu et al.,“variant abo blood group alleles, secretor status, and risk of pancreatic cancer: results from the pancreatic cancer cohort consortium”, cancer epidemiology, biomarkers & prevention, vol. 19, no. 12, dec, pp. 3140-9, 2010 [6] g. bedu-addo, p. p. gai, s. meese, t. a. eggelte, k. thangaraj and f. p. mockenhaupt. reduced prevalence of placental malaria in primiparae with blood group o. malaria journal, vol. 13, pp. 289, 2014. [7] k. l. wiggins, n. l. smith, n. l. glazer et al.,“abo genotype and risk of thrombotic events and hemorrhagic stroke”, journal of thrombosis and haemostasis, vol. 7, no. 2, pp. 263-9, 2009. [8] m. a. gates, b. m. wolpin, d. w. cramer, s. e. hankinson and s. s. tworoger. “abo blood group and incidence of epithelial ovarian cancer”, international journal of cancer, vol. 128, no. 2, pp. 482-6, 2011. [9] s. mazières and j. chiaroni. “approche anthropologique des groupes sanguins érythrocytaires ”, in: j. l. eurotext (editions), 2015. [10] s. guindo, “phénotype érythrocytaire dans les systèmes de groupes sanguins immunogènes chez les donneurs de sang à bamako”. thèse de pharmarcie, université de bamako, 2005. [11] z. a. jeremiah and c. odumody. “rh antigens and phenotype frequencies of the ibibio, efik, and ibo ethnic nationalities in calabar, nigeria”, immunohematology, vol. 21, no.1, pp. 21-4, 2005. [12] g. languillat, j. cartron, r. gerbal and c. salmon. “erythrocyte phenotypes in gabon. i. hemotypologic data”, revue française de transfusion et immuno-hématologie, vol. 23, no.6, pp. 675-82, 1980 doi 10.18502/sjms.v13i1.1685 page 19 sudan journal of medical sciences christ-dominique ngassaki-yoka et al [13] a. empana and a. jouvenceaux. “erythrocyte phenotypes and gene frequency of the abo system in the congo population. evaluation based on 5,400 subjects”, revue française de transfusion et immuno-hématologie, vol. 25, no.1, pp. 19-24, 1982. [14] s. t. ndoula, j. j. noubiap, j. r. nansseu and a. wonkam. “phenotypic and allelic distribution of the abo and rhesus (d) blood groups in the cameroonian population”, international journal of immunogenetics, vol. 41, no. 3, pp. 206-10, 2014. [15] c. bisseye, m. sanou, b. m. nagalo et al., “epidemiology of syphilis in regional blood transfusion centres in burkina faso, west africa”, pan african medical journal, vol. 16, pp. 69, 2013. [16] n. habti, n. nourichafi and n. benchemsi. “abo polymorphism in blood donors in morocco”, transfusion clinique et biologique, vol. 11, no. 2, pp. 95-7, 2004. [17] https://www.ints.fr/sangtransfgrsanguin.aspx [18] p. garg, s. upadhyay, s. s. chufal, y. hasan and i. tayal. “prevalance of abo and rhesus blood groups in blood donors: a study from a tertiary care teaching hospital of kumaon region of uttarakhand”, journal of clinical and diagnostic research, vol. 8, no.12, pp. fc16-9, 2014. [19] e. hosoi, “biological and clinical aspects of abo blood group system”, journal of medical investigation, vol. 55, no. 3-4, pp. 174-82, 2008 [20] g. garratty, s. a. glynn, r. mcentire and s. retrovirus epidemiology donor. “abo and rh(d) phenotype frequencies of different racial/ethnic groups in the united states”, transfusion, vol. 44, no. 5, pp. 703-6, 2004. 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[24] l. k. rerambiah, l. e. rerambiah, c. bengone and j. f. djoba siawaya. “the risk of transfusion-transmitted viral infections at the gabonese national blood transfusion centre”, blood transfusion, vol. 12, no. 3, jul, pp. 330-3, 2014. doi 10.18502/sjms.v13i1.1685 page 20 https://www.ints.fr/sangtransfgrsanguin.aspx sudan journal of medical sciences christ-dominique ngassaki-yoka et al [25] d. s. wang, d. l. chen, c. ren et al., “abo blood group, hepatitis b viral infection and risk of pancreatic cancer”, international journal of cancer, vol. 131, no. 2, pp. 461-8, 2012. [26] f. mohammadali and a. pourfathollah. “association of abo and rh blood groups to blood-borne infections among blood donors in tehran–iran”, iranian journal of public health, vol. 43, no.7, pp. 981-989, 2014. [27] m. iavarone, c. della corte, c. pelucchi et al., “risk of hepatocellular carcinoma in relation to abo blood type”, digestive and liver disease, vol. 48, no. 1, pp. 94-6, 2015. doi 10.18502/sjms.v13i1.1685 page 21 introduction materials and methods blood donors determination of abo and rh phenotyping serological analysis statistical analysis results abo and rh phenotypic frequencies association between blood groups and transfusion-transmitted infections discussion conclusion declarations references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5904 production and hosting by knowledge e research article causes for the delay of ileostomy closure in rectal cancer surgery octavian andronic1,2, georgiana radu1, adriana elena nica1,2, marius coţofană1,2, and sorin mircea oprescu1,2 1the university of medicine and pharmacy carol davila, bucharest, romania 2university emergency hospital of bucharest, romania abstract rectal cancer represents a challenge for the general surgeon as patients’ quality of life after the management of the neoplasm is starting to become more and more important. our review is focused on loop ileostomies and the reasons why their closure might be delayed. we have tried to gather these reasons all together from our experience and from the literature in order to understand whether there are any aspects that can be improved. after a thorough search through different scientific databases we managed to include a total of 29 articles in our research and the information gathered has led to the conclusions of this narrative review. there are many reasons why the closure of an ileostomy might be delayed. while some of them are related to the patient and cannot be controlled or prevented (age, comorbidities), most of the factors that can interfere are preventable (adjuvant therapy, postoperative complications, patient’s wish). keywords: ileostomy; rectal cancer; low anterior resection 1. introduction a need for balance between oncological safety and quality of life have been more and more brought to practitioner’s attention, so, preserving nervous elements while dissecting the mesorectum [1] as well as identifying essential techniques in order to preserve digestive and urogenital functions became a strong desideratum today [2, 3]. the implementation of stomas in order to temporary divert the natural flow of intestinal contents is a relatively new technique in the history of rectal surgery. the first attempts of creating a stoma have taken place before the 1700s [4], but had poor results and high mortality and morbidity rates due to the absence of any asepsis and antisepsis measures. the total lack of anesthesia was also an impediment in developing safer techniques. the first ileostomies were performed at the end of the19th century mostly for patients with obstructing lesions in the colon. unfortunately, the attempts were again not very successful and had high morbidity and mortality rates. the early procedure consisted of bringing several centimeters of intestine through the incision and securing them outside the abdominal cavity using a metal clamp in the hope of orchestrating how to cite this article: octavian andronic, georgiana radu, adriana elena nica, marius coțofană, and sorin mircea oprescu (2019) “causes for the delay of ileostomy closure in rectal cancer surgery,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 257–265. doi 10.18502/sjms.v14i4.5904 page 257 corresponding author: octavian andronic phone no. 0040724024019 e-mail: andronicoctavian@gmail.com received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e octavian andronic et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences octavian andronic et al a “self-maturation” process [5]. there are two main types of ileostomies depending on whether reattachment of the loop to the remaining portion of the intestine is intended or not: the loop ileostomy and the end ileostomy.. a loop ileostomy is used to protect a distal anastomosis in order to reduce the risk of an anastomotic leakage due to stool pressing on the two stumps of the bowel. this type of ileostomy is a temporary one as it can and will be reversed at a later date, usually after a period of 3 to 6 months. a meta-analysis showed a big variability of the number of days since the moment of admission until the moment of the ileostomy’s closure, with an interval between 10 and 1830 days [6]. for various reasons, in 4 out of 5 patients the ileostomy is closed after a longer period of time than first intended [7], and in approximately 1 out of 5 patients to whom the stoma was planned as temporary it becomes permanent in the end [6–8]. the importance of this problem of closure moment of an ileostomy is currently addressed in the multicenter study close-it, which intends to identify the optimal moment as well as the causes that might delay it [10]. suggestions that a delay in the closure of an ileostomy can increase the incidence of lars (low anterior resection syndrome) have also been made in the last years. this idea came up as more and more patients who underwent a low anterior resection for rectal cancer have reported suffering a poor bowel function after the surgical closure of a loop ileostomy. lars is a well-known factor that can reduce the quality of life. a recent study reported that a delay of more than 6 months in the closure of an ileostomy was associated with a 3.7x increased risk of major bowel dysfunction afterwards [10]. our review is focused on loop ileostomies and the reasons why their closure might be delayed. we have tried to gather these reasons all together from the literature in order to understand whether there are any aspects which can be improved. identifying, understanding and successfully solving any problems that can cause a delay in the restoration of bowel continuity will lead to a better outcome and, consequently, a better quality of life for patients. 2. methods a thorough search through different scientific databases – scopus, pubmed, web of science, using the following keywords formula: ((”ileostomy” or ”temporary stoma”) and (”rectal cancer” or ”low anterior resection”)) was performed. after careful consideration, articles that were most relevant to the subject of our review – reasons for a delayed closure of an ileostomy were included. in the end we managed to include a total of 29 articles in our research and the information gathered has led to the doi 10.18502/sjms.v14i4.5904 page 258 sudan journal of medical sciences octavian andronic et al conclusions of this narrative review. we considered a delay in closure of the ileostomy, postponing this procedure relative to the time initial proposed. the limitation of the study is that there is little data available regarding the factors that could lead to a delay of ileostomy closure. those few studies that have underlined their existence have been criticized for analyzing heterogeneous patient populations, benign as well as malignant diseases, elective or emergent procedures, including different types of stomas in the same study, as well as other reasons [11]. 3. results by analyzing the identified articles, we could systematize some of the most common causes that could represent grounds for further research and a better understanding of the management of loop ileostomies: 3.1. patients’ age the analysis by taylor et. al. [12] indicates a delay in the closure of the ileostomy for patients older than 70, as well as a high rate of becoming permanent for patients in the same age group. most results show a slight increase of the period for ileostomy closure and a bigger percent of permanent stomas in elderly patients, without statistical significance [9], [12]–[14] but kye et. al. conclude in their study that the closure of diverting stoma may be shortened even in elderly patients [15]. 3.2. adjuvant chemotherapy diverting loop ileostomies are hard to manage for both the patient and the medical system as they can increase the complication rates of adjuvant chemotherapy. for this reason, most centers choose to restore the continuity of the gastrointestinal tract after more than one month following the end of the adjuvant chemotherapy, thus increasing the time until the closure. adjusting both chemotherapy timings and dosages, as well as the adequate moments for surgical interventions because of the ileostomy is burdensome for both the patient (increasing mortality and morbidity and decreasing the quality of life) and the health system (the longer the patient is hospitalized, the costlier it will be for the health system) [16]. in their study, waterland p. et al. had 22 out of 63 (35%) patients to whom they needed to postpone the closure of their ileostomy (by more than 6 months) due to adjuvant chemotherapy [17]. in a study by brown s. r. doi 10.18502/sjms.v14i4.5904 page 259 sudan journal of medical sciences octavian andronic et al et al., the authors compared the outcomes after closing the ileostomy either before or after adjuvant chemotherapy. their results showed that the overall survival was slightly lower in group of patients with ileostomy closure after chemotherapy versus the group with closure before chemotherapy, but, without statistical significance. [18]. flooden et al. show that for 10% of patients in whom the ileostomy was closed later than initially planned, it was because of reasons related to post-operative chemotherapy [7]. also, david et al. have identified chemotherapy as the factor with the highest correlation with a delay in the restorations of digestive continuation, having an almost double growth rate of this interval[19]. in the research of vallribera et. al., the closure of the ileostomy was also delayed due to the need for adjuvant treatment [20]. 3.3. postoperative complications linked to the ileostomy complication rates specific to loop ileostomies vary between 5.7% to 41% and some of them lead to a need of reoperation, thus delaying the final closure of the stoma. in his article from 2008, brian rk has described early postoperative complications that can occur and influence not only the morbidity and mortality of the patient, but also the time between the implementation and closure of a stoma. he analyzed both colostomies and ileostomies stating that the data regarding individual complication rates is conflicting. the factors described in his article are: improper stoma site selection, vascular compromise, retraction, peristomal skin irritation, peristomal infection, abscess and fistula formation, acute parastomal hernia/bowel obstruction and technical errors (such as maturation of the wrong limb of intestine or improper maturation techniques) [21]. vijayraj et al. report complications such as peristomal skin irritations, necrosis, retraction and wound infections in patients with loop ileostomies [22]. 3.4. postsurgical complications in other places than the ileostomy site the early (early closure of a temporary ileostomy in patients with rectal cancer) study compared morbidity and mortality associated with early closure (8-13 days) versus standard procedure of closing the stoma after more than 12 weeks since its implementation. only patients who did not have any postoperative complications (such as infections or anastomotic leakage) were included in the study. out of 418 patients assessed for eligibility, 37 (8.85%) patients were excluded due to a suspected anastomotic leakage, thus cancelling the chance for them to have an early closure of their ileostomy [23]. doi 10.18502/sjms.v14i4.5904 page 260 sudan journal of medical sciences octavian andronic et al waterlandet al reported that for 21 out of 63 patients (21%) they needed to postpone the closure of their ileostomy due to an anastomotic leak following the initial operation [17]. another study by haksal m. et al. stated that an anastomotic leak was the most common reason for the failure of stoma takedown in their series. other relevant postoperative complications in their study were surgical site infection and evisceration [11]. matthiessen et al. reported that for 10.3% of all patients who had a lower anterior resection and a protective ileostomy, the presence of an anastomotic fistula has delayed the reestablishment of the intestinal continuation with up to 50 months [24]. the fear of anastomotic complications, especially for patients with a low anterior resection, is still an important factor taken into account when the decision to postpone the closure of the ileostomy is taken, even in the absence of any clinical and radiological signs[25]. 3.5. other medical/surgical interventions the same study by haksal m. et al. stated that three of their patients had additional urinary problems (fistula, nephrostomy and/or urinary incontinence) that needed to be addressed before the closure of the ileostomy due to advanced (clinical t4) initial disease. the closure of their ileostomies was postponed due to a potential need of further medical or surgical treatments [11]. 3.6. comorbidities david et al. show a statistically significant difference between patients with multiple comorbidities (evaluated using charlson’s comorbidity index) and patients without any other associated problems related to the moment of the ileostomy’s closure as well as the percentage of ileostomies that remained definitive. thus, for patients suffering from other comorbidities the percentage of permanenced ileostomies was bigger by 10%, while the average interval before the ileostomy closure grew by 50 days [19]. 3.7. patients’ wishes sometimes patients (mostly older ones) refuse to return to the hospital for the closure of their ileostomies or postpone the intervention. this is actually mentioned in some studies with a frequency that ranges between 5 and 42% of cases [6, 8]. doi 10.18502/sjms.v14i4.5904 page 261 sudan journal of medical sciences octavian andronic et al 4. discussions a standard period for the closure of an ileostomy of 3 to 6 months is agreed upon by most surgeons who perform ileostomies on a regularly basis. there are no clear indications towards an optimal time of reversal, but recent evidence suggests that an early reversal (as early as two weeks) may be more beneficial for the patient [26]. despite this, there are cases where it is impossible to rapidly reverse the ileostomy because of different factors that can intervene. the closure of the ileostomy itself, usually considered an easy procedure, is sometimes problematic as it may be accompanied by high morbidity and mortality rates in an important number of cases. different closure techniques, manual/mechanical, with or without resection have been utilized without a statistically significant difference identified related to the complication rate for each one [20]. the only less frequent complication in the case of a closure by resection followed by a mechanical laterolateral anastomosis, compared to manual anastomosis, was ileus [27]. a prospective study published in 2016 showed that patient associated comorbidities – anemia and obesity – represent risk factors for serious complications that need reoperation, while technique related factors do not have a decisive role [28]. in what concerns the quality of life, a study by zhen et al. did not find any statistically significant differences between the group of patients who had an early ileostomy closure versus the one that had a delayed one [14]. regarding the risk of having post-operative complications: gastrointestinal (ileus, wound infections, rectal bleeding, pseudomembranous colitis, intestinal obstructions, anastomotic leaks, intestinal necrosis), renal (urinary tract infections, acute renal failure), respiratory (pneumonia) and general (thromboembolisms, sepsis, evisceration, abscesses), some studies show a higher incidence in patients that had a late closure of their ileostomies [16,28–30], while others show a lower incidence in the same situation [29]. 5. conclusions there are many reasons why the closure of an ileostomy might be delayed. while some of them are related to the patient and cannot be controlled or prevented (age, comorbidities), most of the factors than can interfere are preventable (adjuvant therapy, postoperative complications, patient’s wish). one of the easiest ways to prevent complications is making sure that the conditions for creating an ileostomy are fulfilled doi 10.18502/sjms.v14i4.5904 page 262 sudan journal of medical sciences octavian andronic et al as much as possible: asepsis to reduce the rate of contamination, a good technique and choosing the best spot for the stoma on the patient’s abdomen. reestablishing bowel continuity as soon as after two weeks since the implementation of the stoma is feasible and has been proven advantageous for the patient. further research is needed and encouraged as ileostomies are used on a large scale worldwide in order to offer patients optimal management with best oncological and functional outcomes. references [1] ion, d., stoian, r. v., pãduraru, d. n., et al. 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(2017). risk factors for complications after diverting ileostomy closure in patients who have undergone rectal cancer surgery. surgery today, vol. 47, no. 10, pp. 1238–1242. doi 10.18502/sjms.v14i4.5904 page 265 introduction methods results patients' age adjuvant chemotherapy postoperative complications linked to the ileostomy postsurgical complications in other places than the ileostomy site other medical/surgical interventions comorbidities patients' wishes discussions conclusions references sudan journal of medical sciences volume 13, issue no. 2, doi 10.18502/sjms.v13i2.2642 production and hosting by knowledge e research article attitude of a discrete group of nigerian male doctors towards prostate cancer screening e. v. ezenwa1 and v. y. adam2,3 1division of urology, department of surgery, ubth, benin city, edo state, nigeria 2department of community health, ubth, benin city, edo state, nigeria 3college of medicine, university of benin, benin city, edo state, nigeria abstract introduction: prostate cancer is the commonest cancer among nigerian males [1]. screening for prostate cancer is a topical issue among doctors as some studies have not conclusively shown higher survival rate among patients who had their pathology detected early. taking into consideration the uncertainty surrounding prostate cancer screening, coupled with the fact that doctors are most of the time overwhelmed with solving the problems of their patients while neglecting their personal health. this study assesses the attitude of a discrete group of nigerian doctors towards prostate cancer screening. objective: to assess the attitude towards prostate cancer screening of male medical doctors in public hospitals in benin city, nigeria. methodology: this was a cross-sectional study carried out over a period of six months at the university of benin teaching hospital (ubth) and the central hospital benin city. it involved all male doctors, 40 years and above. data were collected using a well-structured self-administered questionnaire, collated and subjected to statistical analysis. result: the study involved 214 male doctors. one hundred and fifty two of them practice in ubth, while 62 of them practice in central hospital. the mean (standard deviation) age of the respondents was 48.5 (6.3) years. ninety five percent (205) of the respondents had positive attitude towards prostate cancer screening. the main factors indicated by the respondents that affect individual decision to undergo prostate cancer screening were: the cost of screening [151 (70.6%)], lack of awareness [138 (64.5%)], fear of being stigmatized [97 (45.3%)] and fear of having a positive test [91 (42.5%)]. the least indicated was cultural barriers [42 (19.6%)]. conclusion: the attitude of the respondents for prostate cancer screening is good despite the challenges with recommendation against community screening by international health management system. the main factors identified by respondents as militating against screening should be given proper attention in order to reduce the scourge of this highly prevalent pathology among nigerians. keywords: prostate cancer, screening, attitude, male doctors, benin city how to cite this article: e. v. ezenwa and v. y. adam (2018) “attitude of a discrete group of nigerian male doctors towards prostate cancer screening,” sudan journal of medical sciences, vol. 13, issue no. 2, pages 114–124. doi 10.18502/sjms.v13i2.2642 page 114 corresponding author: e. v. ezenwa; email: x veze001@yahoo.com received 19 april 2018 accepted 15 june 2018 published 28 june 2018 production and hosting by knowledge e e. v. ezenwa and v. y. adam. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com veze001@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences e. v. ezenwa and v. y. adam 1. introduction when the hair greys and the eye dims, the prostate gland enlarges. prostate gland is a walnut-shaped gland located in the space between the bladder neck and the membranous urethra. the prostate gland can be afflicted by various pathologies such as prostatitis, benign and malignant enlargement. carcinoma of the prostate (cap) is common among men in their sixth decade of life. globally, prostate cancer is the fourth most common cancer in both sexes combined and the second most common cancer in men [2]. the incidence and mortality rates vary markedly among and within different countries. in nigeria, a recent study done in 2013 revealed a prevalence rate of 1046 per 100,000 men [3]. data on cancer morbidity and mortality in nigeria are unavailable due to the poorly kept national cancer registry. however, a review of cancer morbidity in adults from ibadan, southwest nigeria, showed that cap was the most common cancer in males [1]. early detection and refinements in the treatment of prostate cancer could lead to theoretical cure of this potentially disabling and deadly condition. prostate-specific antigen assay together with digital rectal examination (dre) is today the main tool used to identify men with a high probability of harbouring prostate cancer and thus indicating the need for a prostate biopsy to confirm the disease. the attitude of doctors to their personal health is poor as they engross themselves with solving patient’s problems while neglecting their personal healthcare [4]. increased knowledge does not always translate to positive change in behaviour and attitude concerning one’s health as seen in a study [5] among 100 saudi female physicians that revealed that the overall health status, lifestyle and attitude of these physicians towards their own health is suboptimal. the recommendation of the study was that even physicians need to improve their lifestyle behaviour and attitude towards their own health [5]. this poor attitude of doctors to their personal health and more specifically for prostate cancer may be compounded by the controversy surrounding prostate cancer screening with regards to the validity of the screening tool and paucity of evidence with regards to reduction in mortality from prostate cancer following early diagnosis and intervention. doctors are seen in the society as well-enlightened people especially when it comes to issues of health. they are seen by the public as role models who should be emulated when it comes to personal health care; however, they are usually occupied with the doi 10.18502/sjms.v13i2.2642 page 115 sudan journal of medical sciences e. v. ezenwa and v. y. adam maintenance of the health of the population rather than theirs. their attitude to personal health care is very poor despite the presumed high medical knowledge among them [5]. 2. methodology the study included all male medical doctors in ubth and central hospital benin, aged 40 years and above. the age 40 years and above was chosen as it is the recommended cut-off age for prostate cancer screening [53]. currently, the total number of male medical doctors aged 40 and above in all the departments of ubth [51, 54] and central hospital [52] is 257. a total population sampling was employed due to the small size of the population and the availability of a sampling frame. a self-administered questionnaire adapted from a previous similar study [4] was used. the questionnaire comprised of both openand close-ended questions. the questionnaire was divided into six parts: bio data, knowledge of prostate cancer, knowledge of prostate cancer screening, attitude towards prostate cancer screening, practice of prostate cancer screening and the factors affecting prostate cancer screening. after data collection, the questionnaires were appraised and answers to openended questions were coded. analysis was done using the spps software statistical package version 21.0. data was presented in the form of frequency tables and cross tabulations; charts and graphs were used where applicable. unadjusted associations were analysed using the chi-square and fishers exact test. adjusted associations were analysed using a regression model. the level of significance was set at p < 0.05. 3. results a total of 214 out of 257 male medical doctors participated in the study. the response rate for the study was 83.9%. one hundred and fifty two (71.0%) respondents practice in the university of benin teaching hospital, while 62 (29.0%) practice at the central hospital, benin city. the highest proportion [145 (67.8%)] of the respondents were in the age group 40– 49 years, while the least proportion [17 (7.9%)] were in the age group 60–69 years. the mean (standard deviation) age of the respondents was 48.5 (6.3) years. doi 10.18502/sjms.v13i2.2642 page 116 sudan journal of medical sciences e. v. ezenwa and v. y. adam the majority of the respondents were married [205 (95.8%)], practiced christianity [210 (98.1%)], and had spent 10 years and more [195 (91.1%)] in service. about half [108 (50.4%)] of the respondents were consultants. thirty five (16.4%) of the respondents were afraid of having dre, 40 (18.7%) were afraid of being told that their test results were positive, 47 (22.0%) were afraid of being stigmatised of having prostate cancer, while 14 (6.5%) felt that screening effort being made by the government is good. one hundred and forty six (96.1%) of the respondents who practised in ubth had good attitude towards prostate cancer screening compared to 59 (95.2%) of those in central hospital. the association between the place of medical practice and the attitude towards prostate cancer screening was not statistically significant (p = 0.721). one hundred and forty (96.6%) of the respondents in the age group 40–49 years had good attitude towards prostate cancer screening compared to 48 (92.3%) of those in the age group 50–59 years, and 17 (100.0%) of those in the age group 60–69 years. the association between age and attitude towards prostate cancer screening was not statistically significant (p < 0.349). one hundred and ninety seven (95.6%) of the respondents who were ever married (married, separated, divorced) had good attitude towards prostate cancer screening compared to eight (100.0%) of those who were never married (single). the association between marital status and the knowledge of prostate cancer screening was not statistically significant (p = 0.546). thirty five (92.1%) of the medical officers had good attitude towards prostate cancer screening compared to 67 (98.5%) of the resident doctors and 103 (95.4%) of the consultants. the association between designation and attitude towards prostate cancer screening was not statistically significant (p = 0.246). nineteen (100.0%) of the respondents with 0–9 years in service had good attitude towards prostate cancer screening compared to 186 (95.4%) of those who had 10 and more years in service. the association between the duration of service and the attitude towards prostate cancer screening was not statistically significant (p = 0.611). the variables in the model explained between 4.9% and 16.6% of the variation in the knowledge of prostate cancer screening among the respondents. after adjusting for other covariates in the model, the following adjusted associations were observed: the respondents who had their medical practice in ubth were 8.45 (95% ci: (1.00– 71.08) times likely to have good attitude towards prostate cancer screening compared to those in central hospital. doi 10.18502/sjms.v13i2.2642 page 117 sudan journal of medical sciences e. v. ezenwa and v. y. adam variables frequency (n = 214) percentage centre of medical practice ubth 152 71.0 central hospital 62 29.0 age group (years)* 40–49 145 67.8 50–59 52 24.3 60–69 17 7.9 marital status married 205 95.8 single 8 3.7 widowed 1 0.5 religion christianity 210 98.1 islam 4 1.9 designation consultants 108 50.4 resident doctors 68 31.8 medical officers 38 17.8 duration of service (years)** 0–9 19 8.9 10+ 195 91.1 departments surgery 29 13.6 obstetrics and gynaecology 27 12.6 orthopaedic 23 10.7 internal medicine 21 9.8 child health 19 8.9 pathology 18 8.4 anaesthesia 14 6.5 family medicine 14 6.5 dentistry 13 6.1 radiology 9 4.2 ent 7 3.3 mental health 7 3.3 ophthalmology 6 2.8 radiotherapy and oncology 5 2.3 community health 2 0.9 note: *mean (standard deviation) age: 48.5 (6.3) years; **median (range): 15 (3– 35) years. one hundred and ninety three respondents (90.2%) agreed that prostate cancer screening is necessary, 161 (75.2%) agreed that prostate cancer screening tools are effective in screening for prostate cancer, while 188 (87.9%) agreed that they would like to be informed if diagnosed with prostate cancer. table 1: socio-demographic characteristics of the respondents. doi 10.18502/sjms.v13i2.2642 page 118 sudan journal of medical sciences e. v. ezenwa and v. y. adam attitude items agree n (%) indifferent n (%) disagree n (%) prostate cancer screening is necessary 193 (90.2) 18 (8.4) 3 (1.4) prostate cancer screening tools are effective in screening for prostate cancer 161 (75.2) 45 (21.0) 8 (3.7) would like to be informed if diagnosed with prostate cancer 188 (87.9) 4 (1.9) 22 (10.3) table 2: attitude towards prostate cancer screening among the respondents. attitude items frequency (n = 214) percentage afraid of having digital rectal examination (dre) yes 35 16.4 no 179 83.6 afraid of being told that test results were positive yes 40 18.7 no 174 81.3 afraid of being stigmatised of having prostate cancer yes 47 22.0 no 167 78.0 screening effort being made by the government is good yes 14 6.5 no 200 93.5 table 3: respondents’ attitude and government effort towards prostate cancer screening. composite score categories* frequency (n = 214) percentage knowledge of prostate cancer good 204 95.3 poor 10 4.7 knowledge of prostate cancer screening good 204 95.3 poor 10 4.7 attitude towards prostate cancer screening positive 205 95.8 negative 9 4.2 practice of prostate cancer screening good 38 17.8 poor 176 82.2 nine of 10 respondents had positive attitude towards prostate cancer screening [205 (95.8%)]. table 4: composite scores for knowledge, attitude and practice of prostate cancer screening among the respondents. doi 10.18502/sjms.v13i2.2642 page 119 sudan journal of medical sciences e. v. ezenwa and v. y. adam variable attitude towards prostate cancer screening, n (%) p-value* positive negative frequency (%) centre of medical practice ubth 146 (96.1) 6 (3.9) 0.721 central hospital 59 (95.2) 3 (4.8) age group (years) 40–49 140 (96.6) 5 (3.4) 0.349 50–59 48 (92.3) 4 (7.7) 60–69 17 (100.0) 0 (0.0) marital status ever married 197 (95.6) 9 (4.4) 0.546 never married 8 (100.0) 0 (0.0) designation medical officers 35 (92.1) 3 (7.9) 0.246 resident doctors 67 (98.5) 1 (1.50 consultants 103 (95.4) 5 (4.6) duration of service 0–9 19 (100.0) 0 (0.0) 0.611 10+ 186 (95.4) 9 (4.6) note: *fisher’s exact test. table 5: unadjusted predictors of attitude towards prostate cancer screening among the respondents. the respondents in the age group 40–49 years were 1.19 (95% ci: (0.12–11.95) times likely to have good attitude towards prostate cancer screening compared to those in the age group 60–69 years. also, respondents in the age group 50–59 years were 3.31 (95% ci: 0.17–65.78) times likely to have good attitude towards prostate cancer screening compared to those in the age group 60–69 years. the respondents who were ever married were 4.57 (95% ci: 0.31–68.60) times likely to have good attitude towards prostate cancer screening compared to those who were never married. the respondents who were medical officers were 3.95 (95% ci: 0.37–42.56) times likely to have good attitude towards prostate cancer screening compared to those who were consultants. also, the respondents who were resident doctors were 6.43 (95% ci: 0.51–80.49) times likely to have good attitude towards prostate cancer screening compared to those who were consultants. the respondents who had spent 0–9 years in service were 0.18 (95% ci: 0.03–0.98) likely to have good attitude towards prostate cancer screening compared to those who had spent 10 years and above in service. doi 10.18502/sjms.v13i2.2642 page 120 sudan journal of medical sciences e. v. ezenwa and v. y. adam variable regression coefficient p-value or (95% ci) centre of medical practice ubth 2.13 0.05 8.45 (1.00–71.08) central hospital* 1 age group (years) 40–49 0.17 0.88 1.19 (0.12–11.95) 50–59 1.20 0.43 3.31 (0.17–65.78) 60–69* 1 marital status ever married 1.52 0.27 4.57 (0.31–68.60) never married* 1 designation medical officers 1.37 0.26 3.95 (0.37–42.56) resident doctors 1.86 0.15 6.43 (0.51–80.49) consultants* 1 duration of service 0–9 –1.71 0.05 0.18 (0.03–0.98) 10+* 1 note: *reference category, r2 = 4.9 – 16.6. table 6: adjusted predictors of attitude towards prostate cancer screening among the respondents. 4. discussion the response to the parameters used to assess individual’s attitude towards prostate cancer screening indicated good attitude by the studied population. over threequarters were not afraid of having dre, which is similar to the outcome of a study [4] among jamaican doctors that showed that 89% of respondents had no fear of having a dre done on them as part of screening for prostate cancer. also, a population survey [6] involving 13,580 healthy men in usa undergoing prostate-specific antigen (psa)—only screening to determine whether the use of dre results in decreased compliance with prostate cancer screening—revealed that only 78% of men would participate in screening that included both dre and psa. less than a quarter (22%) of the participants will abstain if dre is involved. dre was seen in that study as a significant barrier to participation in prostate cancer screening. the low number 35 (16.4% ) of respondents that are scared of dre in our study may be due to the fact that the study was carried out among doctors who have better knowledge of what dre entails, as culture was the main reason for abstinence in the earlier study. the fact that some doctors are scared of having dre suggests the need for further enlightenment doi 10.18502/sjms.v13i2.2642 page 121 sudan journal of medical sciences e. v. ezenwa and v. y. adam on the need for proper evaluation during prostate cancer screening, as some cancer may be missed when psa is used alone as the screening tool [7]. also, less than a quarter (22.0%) were afraid of being stigmatised of having prostate cancer, while 40 (18.7%) respondents were afraid of being told that their test result is positive. the percentage of those afraid of having a positive test found in this study is lower than what was obtained (39%) in a similar study [4] among male jamaican doctors. the low percentage recorded in the current study may be due to recent advances and positive outcomes of curative attempts for prostate cancer as the benefit of prostate cancer screening and early intervention was still highly debatable as at the time of earlier study. wood and colleagues [8] found that in a study of african american men, the majority of respondents identified fear-related barriers such as fear of cancer problems, fear of cancer treatment, fear of sexual dysfunctions and fear of a cancer diagnosis as the reason for not wanting to be tested for prostate cancer. the composite score for attitude was positive for prostate cancer screening in 205 (95.4%) respondents. this is much higher than 40.6% obtained in a cross-sectional study [42] involving 160 men aged between 50 and 80 years in a brazilian hospital. the high result obtained in the current study suggests a highly motivated group of respondents that fully support the concept of prostate cancer screening. multivariate regression analysis of the predictors of good attitude towards prostate cancer screening was statistically significant for ubth as a centre of practice and also for the duration of practice greater than 10 years. this suggests that more experienced doctors who practice in larger hospital are likely to have better attitude towards prostate cancer screening than those who practice in small hospital or have practiced for short duration. this finding may be attributed to more organised healthcare delivery system that is existent in such big centres like ubth, unlike what is obtainable in smaller centres like central hospital. in ubth, there is a centre for disease control where screening is a major service including that for prostate cancer, this must have contributed in refining the attitude of doctors that practice there towards prostate cancer screening. also, the increased duration of practice being a predictor may be due to the fact that as one gains more experience, the need for self-care increases, thus increasing one’s consciousness for cancer screening. this finding is in keeping the outcome of a cross-sectional study [9] among 204 primary care physicians in three tertiary centres in saudi arabia that showed that following multiple regression analysis for predictors of attitude, knowledge and age were the most significant determinants of physicians’ attitude towards prostate cancer counselling and screening in saudi arabia. the outcome of the current study is in contrast to what was reported by pendleton et doi 10.18502/sjms.v13i2.2642 page 122 sudan journal of medical sciences e. v. ezenwa and v. y. adam al. in 2006, where they noted that no demographic factor could independently predict prostate cancer attitude [8]. therefore, doctors who practice in smaller centres and with shorter duration of practice in our study are more likely to have poor attitude towards prostate cancer screening, thus necessitating more attitude-changing measures for this group of doctors. 5. conclusion the attitude of the respondents for prostate cancer screening is good despite the challenges with recommendation against community screening by some health management systems. the main factors identified by respondents as militating against cancer screening should be given proper attention in order to reduce the scourge of this highly prevalent pathology among nigerians. there is a need for middle-aged doctors that practice in smaller centres to be encouraged to have more positive attitude towards prostate cancer screening. references [1] ogunbiyi, j. o. (2000). epidemiology of cancer in ibadan: tumors in adults. archives of ibadan medicine, vol. 1, no. 2, pp. 9-12. [2] ferlay, j., soerjomataram, i., ervik, m., et al. (2013). globocan 2012: cancer incidence and mortality worldwide, vol. 1, pp. 1-2. international agency for research on cancer. [3] ikuerowo, s. o. (2013). prevalence and characteristics of prostate cancer among participants of a community-based screening in nigeria using serum prostate specific antigen and digital rectal examination. the pan african medical journal, vol. 15, p. 129. [4] mcnaughton, d., aiken, w., and mcgrowder, d. (2011). factors affecting prostate cancer screening behaviour in a discrete population of doctors at the university hospital of the west indies, jamaica. asian pacific journal of cancer prevention, vol. 12, pp. 1201-1205. [5] khateeb, m., khayat, s., radhwi, o., et al. (2012). attitude of 100 saudi female doctors towards their health. clinical medicine insights: women’s health, vol. 5, pp. 39-43. [6] nagler, h. m., gerber, e. w., homel, p., et al. (2005). digital rectal examination is barrier to population-based prostate cancer screening. urology, vol. 65, no. 6, pp. doi 10.18502/sjms.v13i2.2642 page 123 sudan journal of medical sciences e. v. ezenwa and v. y. adam 1137-1140. [7] ojewola, w., tijani, k. h., jeje, e. a., et al. (2013). an evaluation of usefulness of prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer in an unscreened population: experience in a nigerian teaching hospital. west african journal of medicine, vol. 19, no. 1, pp. 26-31. [8] woods, v. d., montgomery, s. b., and herring, r. p. (2006). social ecological predictors of prostate-specific antigen blood test and digital rectal examination in black american men. journal of the national medical association, vol. 98, pp. 492504. [9] arafa, a. m., rabah, d. m., and el-nimr, n. a. (2012). physicians’ behaviour and attitudes towards prostate cancer screening in riyadh, saudi arabia. journal of medicine and medical sciences, vol. 3, no. 1, pp. 043-048. doi 10.18502/sjms.v13i2.2642 page 124 introduction methodology results discussion conclusion references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5210 production and hosting by knowledge e research article hemogram abnormalities in apparently healthy first-time blood donors in libreville, gabon cyrille bisseye1, jophrette mireille ntsame ndong2, landry erik mombo1, hornéla christine minkoue mambéri1,2, guy mouelet migolet2, gemael cedrick taty-taty1, and bolni marius nagalo1,3 1laboratory of molecular and cellular biology (labmc), university of science and technology of masuku (ustm), p.o. box 943, franceville, gabon 2national blood transfusion center (nbtc), p.o. box 13895, libreville, gabon 3division of hematology and oncology, mayo clinic, 13400 e. shea blvd. scottsdale, 85259 az, usa abstract background: the objective of this study was to determine complete blood count (cbc) abnormalities in libreville blood donors to advocate for hemoglobin pre-donation implementation and to take into account cbc results in blood donation qualification. methods: this retrospective study was conducted with 4,573 blood donors in march 2016 and from january to april 2017. cbc was performed using sysmexxp-300tm hematology analyzer (sysmex corporation, kobe, japan). results: blood donors were predominantly males (83.7%) with an age ranging from 18 to 59 yrs. the abnormalities of leukocyte, platelet, and erythrocyte counts were determined in blood donors. leukopenia and thrombocytopenia were significantly more common in men than women (29.02% vs 24.4%, p = 0.011 and 16.2% vs 7.5%, p < 0.001). only 1.0% of women and 0.84% of men had leukocytosis, and 0.7% of women and 0.2% of men had thrombocytosis. anemia was significantly more common in women compared to men (69.4% vs 45.0%, p < 0.001). normocytic normochromic and normocytic hypochromic anemia were most common among libreville blood donors with 39.4% and 23.6%; followed by microcytic normochromic (18.7%) and microcytic hypochromic (13.2%) anemia. normocytic normochromic and normocytic hypochromic anemia were significantly more common in men than in women, whereas microcytic normochromic anemia was more prevalent among women compared to men (34.6% vs 13.9%, p < 0.001). conclusions: the results of this study clearly show the need to perform a pre-donation hemoglobin test in blood donors and to take into account their hemogram in the blood donation selection process at the libreville national blood transfusion center. keywords: hemogram, anemia, blood donors, libreville, gabon 1. introduction blood transfusion is a therapeutic procedure that saves lives by providing patients with the blood products they need according to their disease. it remains an essential how to cite this article: cyrille bisseye, jophrette mireille ntsame ndong, landry erik mombo, hornéla christine minkoue mambéri, guy mouelet migolet, gemael cedrick taty-taty, and bolni marius nagalo (2019) “hemogram abnormalities in apparently healthy first-time blood donors in libreville, gabon,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 103–115. doi 10.18502/sjms.v14i3.5210 page 103 corresponding author: cyrille bisseye; email: cbisseye@gmail.com received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e cyrille bisseye et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:cbisseye@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences cyrille bisseye et al component in the treatment of hemoglobinopathies, particularly sickle cell disease [1]. the stages of the transfusion chain that begin with the reception of the blood donor and end with the transfusion of the compatible blood product to the recipient are essential to observe in order to guarantee the quality of the transfused products [2]. one of these most important steps is the blood donation qualification by the transfusion physician during the pre-donation interview [3]. the qualification for blood donation is done by checking the donor for certain clinical and hematological parameters to evaluate their ability to donate. the measurement of hematological parameters in transfusion medicine is important in that it allows the detection of quantitative abnormalities of the cellular elements of the blood. however, according to the report of the transfusion research group in french-speaking africa, the measurement of these parameters is very little done in sub-saharan africa during the biological testing of a blood donation [4]. the measurement of hemoglobin is the only pre-donation screening preventing the occurrence of donation-induced anemia. it also avoids bleeding in an already anemic donor. various factors are known to cause changes in the rate of red blood cells in an individual, such as sex, age, pregnancy, altitude, and ethnicity [5]. the measurement of hemoglobin and the assessment of anemia should be corrected taking into account ethnicity. indeed, it has been shown that the average values of hemoglobin levels of african-american subjects are lower than those of american subjects of other ethnic origins [6]. a recent report has shown lower hemoglobin values in africans compared to caucasians [7]. most blood centers perform hemoglobin testing during the pre-donation interview using the copper sulfate method in relation to its very low cost. however, previous studies have shown that anemia was observed in 42% of blood donors in africa [8, 9]. while progress has been observed at the national blood transfusion center in libreville in terms of reducing the post-transfusion risk of transfusion-transmissible infections, measures taken to improve the blood donation qualification during the medical interview need to be improved [10–12]. indeed, the hematological parameters of the donor are verified post-donation and are only clinical information for the donor. the measurement of the hemoglobin level that represents the hematological parameter of eligibility for donation is not yet done during the pre-donation medical interview. this study was designed to evaluate the erythrocyte, leukocyte, and platelet counts of firsttime blood donors of libreville to determine the prevalence and characteristics of their abnormalities. doi 10.18502/sjms.v14i3.5210 page 104 sudan journal of medical sciences cyrille bisseye et al 2. methods 2.1. blood donors a cross-sectional analysis of blood donor data collected first in march 2016 and second between january and april 2017 was conducted at the national blood transfusion center (nbtc). all apparently healthy voluntary non-remunerated donors (vnrd) and family/replacement donors (frd) were selected after responding to a range of questions including medical history. individuals aged 18 to 59 yrs and weighing ≥ 50 kg were eligible for blood donations. all candidate donors responded to questions aiming at the exclusion of transfusion recipients, individuals who had jaundice or signs of hepatitis, pregnant women, and persons with unsafe sexual behavior during the six months prior to blood donation. blood donors signed a written informed consent forms prior to blood collection. venous blood was collected in the blood bags following standard procedures. 2.2. hemogram profile determination the complete blood count (cbc) was performed using an automated hematology analyzer sysmex xp-300tm (sysmex corporation, kobe, japan) according to the manufacturer’s instructions. the instrument automatically counts and gives a printout result of absolute numbers of erythrocytes (rbc) (1012/l), hemoglobin (g/dl), hematocrit (%), mcv (fl), mchc (g/dl), leukocytes (wbc) (109/l), and platelets (109/l). 2.3. statistical analysis statistical analyses were performed with the software epiinfo version 6 and spss version 20; p ≤ 0.05 was considered significant. 3. results 3.1. demographic characteristics of the study population this study involved 4,573 blood donors at the nbtc in libreville. blood donors were predominantly males (83.7%). the male/female sex ratio was 5/1. the age of blood doi 10.18502/sjms.v14i3.5210 page 105 sudan journal of medical sciences cyrille bisseye et al donors ranged from 18 to 49 yrs for women and 18 to 59 yrs for men. the age groups 20–29 and 30–39 yrs were the most represented in both women (52.2% and 34.9%) and men (48.4% and 35.8%) (table 1). table 1: repartition of blood donors by age groups. female male age groups number percentage number percentage < 20 yrs 12 1.6 37 1.0 20–29 yrs 389 52.2 1,851 48.4 30–39 yrs 260 34.9 1,369 35.8 40–49 yrs 84 11.3 504 13.2 50–59 yrs – – 67 1.8 total 745 3,828 3.2. mean values of the blood count in blood donors the mean values of hematological parameters such as rbc, hb, hct, mcv, mchc, wbc, and plt are presented in table 2. the mean values of erythrocyte parameters (rbc, hb, hct, and mcv) were significantly higher in men compared to women (table 2). only mchc was higher in women compared to men (p = 0.009). in contrast, the mean value of plt was significantly higher in women compared to men (p < 0.001), while the wbc average was similar for both sexes (p = 0.068). 3.3. abnormalities of blood donors’ blood count by gender the abnormalities of the hemogram of blood donors have been observed mainly in the erythrocytes. in fact, 69.4% and 84.4% of women had lower hb and hct levels, respectively, while 32.3% and 24.4% of them had mcv and mchc values lower than the lower limits, respectively. leukocyte and platelet counts showed little abnormality with 74.4% and 91.8% of female blood donors with wbc and plt levels between baseline values (table 3). in male blood donors, the abnormalities of the blood count mainly concerned erythrocytes with 45%, 52.2% and 28.6% with hb, hct, and mchc levels below the lower limit and only 0.2%, 0.5%, and 1.7% of these had hb, hct, and mchc levels above the upper limit (table 3). with respect to leukocytes and platelets, 29.02% and 16.2% of doi 10.18502/sjms.v14i3.5210 page 106 sudan journal of medical sciences cyrille bisseye et al table 2: comparison of mean values of complete blood count (cbc) in female and male blood donors. hematological parameters female male mean ± sd mean ± sd p-value* rbc x 1012/l 4.049 ± 0.531 4.878 ± 7.425 < 0.001 hb (g/dl) 10.802 ± 1.478 13.092 ± 1.538 < 0.001 hct (%) 32.860 ± 4.433 39.813 ± 4.538 < 0.001 mcv (ƒl) 81.294 ± 8.261 84.586 ± 6.953 < 0.001 mchc (%) 32.977 ± 2.804 32.975 ± 2.708 0.009 wbc x 109/l 5.035 ± 1.911 4.915 ± 1.512 0.068 plt x 109/l 239.168 ± 68.931 203.015 ± 59.690 < 0.001 rbc: red blood cell; hb: hemoglobin; hct: hematocrit; mcv: mean corpuscular volume; mchc: mean corpuscular hemoglobin concentration; wbc: white blood cell; plt: platelets. *mann–whitney test table 3: distribution of erythrocyte, leukocyte, and platelet parameters of female versus male blood donors according to reference and threshold values. hematological parameters reference values number of female vs male donors whose value is below the lower limit number of female vs male donors whose value is in the reference range number of female vs male donors whose value is greater than the upper limit numbers % numbers % numbers % rbc (x 1012/l) f: 4 < rbc < 5.3 m: 4.2 < rbc < 5.7 359/707 48.2/18.5 359/2859 48.2/74.7 27/262 3.6/6.8 hb (g/dl) f : 12 < hb < 16 m : 13 < hb < 18 517/1724 69.4/45.0 224/2098 30.0/54.8 4/6 0.6/0.2 hct (%) f : 37 < hct < 46 m : 40 < hct < 52 629/1998 84.4/52.2 112/1812 15.0/47.3 4/18 0.5/0.5 mcv (fl) 80 ≤ mcv ≤ 100 241/494 32.3/12.9 498/3302 66.8/86.3 6/32 0.8/0.8 mchc (%) 32 ≤ mchc ≤ 36 182/1094 24.4/28.6 527/2669 70.7/69.7 36/65 4.8/1.7 wbc (x 109/l) 4 < wbc < 10 183/1111 24.6/29.02 554/2685 74.4/70.14 8/32 1.0/0.84 plt (x 109/l) 150 < plt < 450 56/620 7.5/16.2 684/3199 91.8/83.6 5/9 0.7/0.2 rbc: red blood cell; hb: hemoglobin; hct: hematocrit; mcv: mean corpuscular volume; mchc: mean corpuscular hemoglobin concentration; wbc: white blood cell; plt: platelets. men had wbc and plt counts below the lower limit and only 0.84% and 0.2% of these showed wbc and plt rates above the upper limit (table 3). doi 10.18502/sjms.v14i3.5210 page 107 sudan journal of medical sciences cyrille bisseye et al 3.4. comparison of blood count abnormalities in blood donors by gender the three hematological parameters that have been taken into account are hemoglobin level (anemia), white blood cells (leukopenia and leukocytosis), and platelets (thrombocytopenia and thrombocytosis). the results show that women were significantly more frequently anemic than men (69.4% vs 45%, p < 0.001), while leukopenia and thrombocytopenia were significantly more common in men than women (29.02% vs 24.4%, p = 0.011 and 16.2% vs 7.5%, p < 0.001) (table 4). only 1.0% of women and 0.84% of men had leukocytosis, and 0.7% of women and 0.2% of men had thrombocytosis (table 4). table 4: comparison of erythrocytes, leucocytes, and platelets abnormalities in blood donors by gender. female male hematological parameters number percentage number percentage p-value hb (female: hb < 12 ; male: hb < 13) 517 69.4 1,742 45.0 < 0.001 wbc leukopenia (wbc < 4 x 109/l) 182 24.4 1,111 29.02 0.011 leukocytosis (wbc > 10 x 109/l) 8 1.0 32 0.84 0.778 plt thrombocytopenia (plt < 150 x 109/l) 56 7.5 620 16.2 < 0.001 thrombocytosis (plt < 450 x 109/l) 5 0.7 9 0.2 0.073 hb: hemoglobin; wbc: white blood cell; plt: platelets. 3.5. characterization of different levels and types of anemia in libreville blood donors anemia was significantly more frequent in women compared to men in the age groups < 20 yrs and 20–29 yrs (2.0% vs 1.1%, p = 0.039 and 52.6% vs 46.7%, p = 0.002) (table 5). in contrast, among blood donors aged 40 to 49 years, anemia was more prevalent in men compared to women (16.1% vs 11.2%, p < 0.001). with regard to the degree of anemia, slight anemia predominated in both women (63.2%) and men (84.8%). severe or moderate anemia was observed in 4.3% and 32.5% of women and 1.3% and 13.9% of men, respectively. they were significantly more frequent in women compared to men (p < 0.001 and p < 0.001) (table 5). doi 10.18502/sjms.v14i3.5210 page 108 sudan journal of medical sciences cyrille bisseye et al table 5: comparison of anemia level among blood donors by gender and age. female with anemia male with anemia parameters number % parameters number % p-value age groups < 20 yrs 10 2 < 20yrs 19 1.1 0.039 20–29 yrs 272 52.6 20–29yrs 802 46.5 0.002 30–39 yrs 177 34.2 30–39yrs 586 34 0.91 40–49 yrs 58 11.2 40–49yrs 278 16.1 < 0.001 50–59 yrs – – 50–59yrs 39 2.3 anemia level severe (hb < 8) 22 4.3 severe (hb < 9) 22 1.3 < 0.001 mild (8 < hb < 10) 168 32.5 mild (9 < hb < 11) 240 13.9 < 0.001 slight (10 < hb < 12) 327 63.2 slight (11 < hb < 13) 1,462 84.8 < 0.001 normocytic normochromic and normocytic hypochromic anemia were most common among libreville blood donors with 39.4% and 23.6%, respectively. they were followed by microcytic normochromic (18.7%) and microcytic hypochromic (13.2%) anemia. all types of hyperchromic anemia were found in 3.4% (77/2241) of blood donors. the different types of anemia were not associated with age of the blood donors (table 6). microcytic normochromic anemia was significantly more frequent in female blood donors compared to male blood donors (p < 0.001). while normocytic hypochromic or normochromic anemia were more prevalent in men than in women (p < 0.001 and p < 0.001) (table 6). 4. discussion this study was conducted with the aim of improving the qualification criteria for blood donation at the nbtc located in libreville by including the results of the cbc in the transfusion process. the measurement of hematological parameters in blood donors by cbc allows the diagnosis of certain existing blood abnormalities in the donor to establish a first barrier against transmitted-transfusion infections. in libreville blood donors, we observed that red cell parameters (rbc, hb, hct, and mcv) were higher in men compared to women. the mean of wbc was similar for both sexes. in contrast, the mean of plt was higher among women than men which is in agreement with previous doi 10.18502/sjms.v14i3.5210 page 109 sudan journal of medical sciences cyrille bisseye et al table 6: comparison of anemia type among blood donors by gender and age. type of anemia maha mahya mana miha mihya mina nha nhya nna n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) gender female 0 (0.0) 6 (1.2) 0 (0.0) 5 (1.0) 57 (11.0) 179 (34.6) 7 (1.4) 93 (18.0) 170 (32.9) male 1 (0.1) 28 (1.6) 3 (0.2) 15 (0.9) 239 (13.9) 240 (13.9) 49 (2.8) 435 (25.2) 714 (41.4) p-value nc ns nc ns ns < 0.001 ns < 0.001 < 0.001 age groups < 20 yrs 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.4) 3 (10.3) 8 (27.6) 1 (3.4) 8 (27.6) 8 (27.6) 20–29 yrs 0 (0.0) 17 (1.6) 1 (0.1) 12 (1.1) 147 (13.7) 211 (19.6) 28 (2.6) 231 (21.5) 427 (39.8) 30–39 yrs 0 (0.0) 9 (1.2) 1 (0.1) 4 (0.5) 87 (11.4) 148 (19.4) 17 (2.2) 188 (24.6) 309 (40.5) 40–49 yrs 1 (0.3) 6 (1.8) 1 (0.3) 3 (0.9) 56 (16.7) 47 (14.0) 9 (2.7) 87 (25.9) 126 (37.5) 50–59 yrs 0 (0.0) 2 (5.1) 0 (0.0) 0 (0.0) 3 (7.7) 5 (12.8) 1 (2.6) 14 (35.9) 14 (35.9) p-value nc ns nc ns ns ns ns ns ns maha: macrocytic hyperchromic anemia; mahya: macrocytic hypochromic anemia; mana: macrocytic normochromic anemia; miha: microcytic hyperchromic anemia; mihya: microcytic hypochromic anemia; mina: microcytic normochromic anemia; nha: normocytic hyperchromic anemia; nhya: normocytic hypochromic anemia; nna: normocytic normochromic anemia. studies [13–15]. the mean values of red cell parameters vary with age and sex [16]. indeed, values are higher in men compared to women, which is in agreement with the results of a recent report [7]. on the other hand, no difference between women and men was found for the leukocyte count as previously reported [17, 18]. leukocyte, platelet, and erythrocyte abnormalities of blood donors were assessed. cbc of blood donors showed that 70.8% of these showed no leucocyte abnormality. however, leukopenia was the most frequently observed wbc abnormality with a prevalence of 28.3%. two previous studies in nigeria and cameroon reported the prevalence of leukopenia of 12.5% and 14.96% in blood donors [19, 20]. leukopenia was significantly more prevalent in men than in women. leukocytosis was present in only 0.9% of libreville blood donors, while it was the most observed leukocyte abnormality in morocco with 5.27% [18]. with respect to platelet count, 84.9% of blood donors had no platelet count abnormalities. thrombocytopenia (14.8%) was the most observed abnormality compared to thrombocytosis (0.3%). thrombocytopenia was significantly higher in men compared to doi 10.18502/sjms.v14i3.5210 page 110 sudan journal of medical sciences cyrille bisseye et al women. thrombocytopenia may be central or peripheral due to destruction or excessive consumption of platelets. in this study, thrombocytosis was higher in women than in men as reported previously [21, 22]. but the difference observed was not significant. the observed thrombocytosis may be due in part to infections or iron deficiency [23]. with regard to the erythrocyte, anemia was found in 49% of blood donors. the prevalence of anemia found in our study is significantly higher than those of 36.5% and 28% observed, respectively, in congo and cameroon [20, 24]. lower anemia prevalences of 8.6% has been reported in north africa, particularly in tunisia [25]. the most anemic age group was 20 to 29 yrs, with rates of 52.6% and 46.5%, respectively, for women and men. in morocco, anemia rates of 43.5% and 42.5% were reported in the age group 30–39 yrs for both women and men [18]. in congo, however, the prevalence of anemia was higher in the 40–49 age group, with 42.7% in both sexes [24]. the high prevalence of anemia found in this study could be explained by the high prevalence of hemoglobinopathies in gabon such as alpha and beta thalassemias, sickle cell anemia, and glucose-6-phosphate deshydrogenase deficiency [26–28]. in this study, we found that women (69.4%) were more frequently anemic than men (45.0%). many studies in africa have also reported variable prevalence of anemia among women ranging from 49% in tanzania to 16.9% in tunisia [25, 29]. slight anemia was found in 84.8% of men and 63.2% of women. these results suggest that anemia, according to thresholds established by the who, is probably well tolerated by blood donors in gabon as few adverse events following blood donation in libreville have been reported among blood donors. therefore, it could be more appropriate to establish threshold hemoglobin values specific to the gabonese population in particular and to populations of color in sub-saharan africa in general to define anemia. in this study, the most common anemias in libreville blood donors were normocytic normochromic (39.4%) and normocytic hypochromic (23.6%). the highest prevalence of normocytic normochromic anemia observed in libreville blood donors is consistent with the prevalence of 46.74% reported previously in ghana [30]. the distribution of these two types of anemia was not identical in both sexes. normocytic normochromic and normocytic hypochromic anemia were significantly more frequent in men than in women. in contrast of the studies of bakrim et al. in morocco and nzengu-lukusa in democratic republic of congo (drc) [18, 24], who found high prevalence of microcytic anemia in blood donors, we observed microcytic normocytic and microcytic hypochromic anemia, respectively, in 18.7% and 13.2% of blood donors. microcytic normochromic anemia doi 10.18502/sjms.v14i3.5210 page 111 sudan journal of medical sciences cyrille bisseye et al was significantly more frequent in women (34.6%) than men (13.9%). in this study, we did not perform iron assessment. however, the prevalence of 13.2% microcytic hypochromic anemia observed in libreville blood donors may be associated with iron deficiency. indeed, previous studies in burkina faso, tunisia, and india have shown the association between microcytosis and iron deficiency anemia [25, 31, 32]. 5. conclusion the aim of this study was to provide reliable data to advocate for pre-donation hemoglobin measurement in libreville blood donors and to take into account cbc results in blood donation qualification. it appears that blood count abnormalities frequently encountered in blood donors were leucopenia, thrombocytopenia, and normocytic normochromic anemia. since anemia is present in about half of the blood donor population, a specific hemoglobin threshold in gabon from which a donation could be authorized should be defined. ethical approval this study was approved by the cnts ethics committee. acknowledgments the authors would like to thank all the participants of this study, the cnts’ staff ripaire mboumba and jpa for critically reading the manuscript. funding the authors are grateful to the nbtc for its financial support through le programme de support à la recherche. conflict of interest the authors declare that there is no conflict of interest. doi 10.18502/sjms.v14i3.5210 page 112 sudan journal of medical sciences cyrille bisseye et al references [1] de montalembert, m. 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(2014). complete blood count reference intervals and ageand sex-related trends of north china han population. clinical chemistry and laboratory medicine, vol. 52, no. 7, pp. 1025–1032. [7] omuse, g., maina, d., mwangi, j., et al. (2018). complete blood count reference intervals from a healthy adult urban population in kenya. plos one, vol. 13, no. 6, pp. e0198444. [8] world health organization. (2015). the global prevalence of anaemia in 2011. geneva: world health organization. [9] world health statistics. (2016). monitoring health for the sdgs indicators of overall progress. tables of health statistics by country, who region and globally en_whs201 _annexb © world health organization 2016. [10] rerambiah, l. k., rerambiah, l. e., bengone, c., et al. (2014). the risk of transfusiontransmitted viral infections at the gabonese national blood transfusion centre. blood transfusion, vol. 12, no. 3, pp. 330–333. [11] eko mba, j. m., ntsame ndong, m. j., and bisseye, c. 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(2016). iron deficiency and anemia among donors in kinshassa. pan african medical journal, vol. 23, pp. 174. [25] toumi, n. h., najjar, m. f., and boukef, k. (1992). blood donors and anemia. revue française de transfusion et d’hémobiologie, vol. 35, no. 4, pp. 295–298. doi 10.18502/sjms.v14i3.5210 page 114 sudan journal of medical sciences cyrille bisseye et al [26] mombo, l. e., ntoumi, f., bisseye, c., et al. (2003). human genetic polymorphisms and asymptomatic plasmodium falciparum malaria in gabonese schoolchildren. the american journal of tropical medicine and hygiene, vol. 68, no. 2, pp. 186–190. [27] nguetse, c. n., meyer, c. g., adegnika, a. a., et al. (2016). glucose-6-phosphate dehydrogenase deficiency and reduced haemoglobin levels in african children with severe malaria. malaria journal, vol. 15, no. 1, pp. 346. [28] mombo, l. e., mabioko-mbembo, g., kassa-kassa, r. f., et al. 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(2010). approach to blood donors with microcytosis. transfusion medicine, vol. 20, no. 2, pp. 88–94. doi 10.18502/sjms.v14i3.5210 page 115 introduction methods blood donors hemogram profile determination statistical analysis results demographic characteristics of the study population mean values of the blood count in blood donors abnormalities of blood donors' blood count by gender comparison of blood count abnormalities in blood donors by gender characterization of different levels and types of anemia in libreville blood donors discussion conclusion ethical approval acknowledgments funding conflict of interest references sudan journal of medical sciences volume 13, issue no. 2, doi 10.18502/sjms.v13i2.2639 production and hosting by knowledge e case report syringocystadenoma papilliferum of eye lid: a case report and review of literature in a tertiary eye hospital, nigeria k. f. monsudi1, k. a. suleiman2, and a. o. ayodapo3 1department of ophthalmology, federal medical centre, birnin kebbi, kebbi state nigeria 2department of pathology, federal medical centre, birnin kebbi, kebbi state nigeria 3department of family medicine, federal medical centre, birnin kebbi, kebbi state nigeria abstract a 58-year-old male with a one-year history of lower medial eyelid swelling and no other ocular and systemic abnormalities was examined. the examination revealed a medial bluish firm left lower eyelid mass. subsequently, he had an in toto excisional biopsy of a cystic mass, which was confirmed histopathologically to be syringocystadenoma papilliferum. a higher level of suspicion by the ophthalmologist and the histopathologist plays a vital role in the management of this tumour. 1. introduction syringocystadenoma papilliferum (sp) of the eyelid is a rare benign tumour of the moll’s glands equivalent to the sweat gland first reported in 1917 by john stokes [1]. the tumour is not so common in the eyelid, and is often misdiagnosed as cyst, bcc, or scc [2]. hence, histopathology evaluation is needed to confirm the diagnosis. syringocystadenoma papilliferum is mostly a childhood tumour [3] with 50% reported at birth and 15–35% presented at puberty [4]. however, it has been known to be associated with other benign tumours such as viral warts, nevus sebaceous, linear nevus verrucous, nevus comedonicus, apocrine poroma, apocrine hidrocystoma, tubulopapillary hidradenoma, hidradenoma papilliferum and papillary eccrine adenoma [5]. syringocystadenoma papilliferum can rarely transform into bcc, as has been reported [4]. a thorough review of the literature in google scholar, african journals online (ajol) and medline/pubmed yielded 17 cases of sp of the eyelid. we hereby report another interesting case of sp of the eyelid. how to cite this article: k. f. monsudi, k. a. suleiman, and a. o. ayodapo (2018) “syringocystadenoma papilliferum of eye lid: a case report and review of literature in a tertiary eye hospital, nigeria,” sudan journal of medical sciences, vol. 13, issue no. 2, pages 86–90. doi 10.18502/sjms.v13i2.2639 page 86 corresponding author: k. f. monsudi; email: kfmoshood@yahoo.com received 12 february 2018 accepted 15 june 2018 published 28 june 2018 production and hosting by knowledge e k. f. monsudi et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:kfmoshood@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences k. f. monsudi et al papillary projec!on fibrovascular core non-kera!nise squamous epithelium figure 1: microscopy section shows projected papillary, plasmacytic infiltrates and non-keratinised epithelium. 2. a case report a 58-year-old male with a non-progressing right lower eyelid swelling of one-year duration, unassociated with pain, bleeding, itching and eye lashes loss was examined. there is no preceding history of trauma and weight loss. visual acuity (va) in both eyes was 6/6. physical examination revealed medial bluish firm right eye (re) swelling measured 1.2cm x 0.6cm. other ocular findings were normal in both eye (be). there is no significant peripheral lymphadenopathy. the mass was excised in toto, and the wound was closed primarily. 3. histopathological report gross examination showed a round to oval mass 10mm x 5mmm. microscopic examination of tissue sections shows an acanthotic non-keratinised squamous epithelium overlying a cystic lesion composed of intra-cystic papillary structures lined by double layer of inner columnar and outer cuboidal cells (figure 1) with decapitation secretion seen within the luminal spaces. the fibrovascular cores show plasmacytic infiltrations with decapitation secretion within the luminal spaces. doi 10.18502/sjms.v13i2.2639 page 87 sudan journal of medical sciences k. f. monsudi et al 4. discussion syringocystadenoma papilliferum is a rare hamartoma benign tumour of the eyelid first reported [1] in 1917, believed to arise from sweat gland and mostly seen in head and neck region [1]. however, the occurrence of the tumour in other part of the body have been reported. from looking into the literature through google scholar, medline/pubmed and african journals online (ajol), 17 cases of eyelid sp have been reported as of today. the highest number was by barbarino et al. in 2009, who reported 14 number of cases, with age ranging 8–82years [6]. our case was a 58-year old similar to the age reported by behera & chatterjee [2]; however, older than the age reported by rao et al. [3] and jakobiec et al. [7] . a clinical differential diagnosis of this lid mass in our patient includes nevus sebaceous, hidradenoma, dermoid cyst, bcc, scc and keratoacanthoma. however, bcc and scc are unlikely because of the age of our patient. keratoacanthoma is a rapid-growth tumour, however, the nonrapid growth nature and age in our patient was not in favour of keratoacanthoma. the histopathological diagnosis of sp by jakobiec et al. [7] were all seen in our patient (cystic spaces within dermal, the dermis lined by non-keratinised epithelium, papillary projection and prominent plasmacystic infiltration). there are still arguments pertaining to the origin of sp: while some authors believe its apocrine origin, others call it eccrine gland origin [8]. in our patient, apart from the eyelid swelling no other ocular symptoms were noticed; however, there were previous reports of association of pruritic [9], verrucous and hyperkeratotic surface lesion [6] with sp. syringocystadenoma papilliferum is known to be associated with many other benign tumours such as apocrine cystadenoma [6], condyloma acuminatum [10], trichilemmoma [11], hidradenoma [12], trichoblastoma [13], verrucous cyst [14] and tubular apocrine adenoma [15], while our patient was associated with apocrine hydrocytoma. the malignant transition into bcc [2], ductal carcinoma and metastatic adenocarcinoma [16] have been reported in sp of other part of the body but none in the eyelid. the main treatment of sp of eyelid is excisional biopsy that was done in our case; however, carbon dioxide laser [17] and mohs micrographic surgery [18] have been used successfully in the treatment of sp. two cases of recurrences of eyelid sp following surgical excisional have been reported in the literature [19]. doi 10.18502/sjms.v13i2.2639 page 88 sudan journal of medical sciences k. f. monsudi et al 5. conclusion syringocystadenoma papilliferum of eyelid still remains a rare benign tumour that can be easily misdiagnosed as cyst, bcc and scc; hence higher index of suspicion by all practising ophthalmologist and histopathologist plays an important role in its diagnosis. references [1] shams, p. n., hardy, t. g., el-bahrawy, m., et al. (january-february 2006). syringocystadenoma papilliferum of the eyelid in a young girl. ophthalmic plastic & reconstructive surgery, vol. 22, no. 1, pp. 67-69. [2] behera, m. and chatterjee, s. (june 2015). a case of syringocystadenoma papilliferum of eyelid with literature review. indian journal of ophthalmology, vol. 63, no. 6, pp. 550-551. doi: 10.4103/0301-4738.162634. [3] rao, v. a., kamath, g. g., and kumar, a. (1996). an unusual case of syringocystadenoma papilliferum of the eyelid. indian journal of ophthalmology, vol. 44, no. 3, pp. 168-169. [4] karg, e., korom, i., varga, e., et al. (2008). congenital syringocystadenoma papilliferum. pediatric dermatology, vol. 25, no. 1, pp. 132-133. [5] felix, b. y., bang, r. l., and roshidah, b. (2010). syringocystadenoma papilliferum in an unusual location beyond the head and neck region: a case report and review of literature. dermatology online journal, vol. 16, no. 10, p. 4. [6] barbarino, s., mccormick, s. a., lauer, s. a., et al. (2009). syringocystadenoma papilliferum of the eyelid. ophthalmic plastic & reconstructive surgery, vol. 25, no. 3, pp. 185-188. [7] jakobiec, f. a., streeten, b. w., iwamoto, t., et al. (1981). syringocystadenoma papilliferum of the eyelid. ophthalmology, vol. 88, pp. 1175-1181. [8] perlman, j. i., urban, r. c., and edward, d. p. (1994). syringocystadenoma papilliferum of the eyelid. american journal of ophthalmology, vol. 117, no. 5, pp. 647-650. [9] mammino, j. j. and vidmar, d. a. (1991). syringocystadenoma papilliferum. international journal of dermatology, vol. 30, no. 11, pp. 763-766. [10] schewach-millet, m. and trau, h. 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(2004). syringocystadenocarcinoma papilliferum: successfully treated with mohs micrographic surgery. dermatologic surgery, vol. 30, no. 3, pp. 468-471. [19] xu, d., bi, t., lan, h., et al. (2013). syringocystadenoma papilliferum in the right lower abdomen: a case report and review of literature. oncotargets and therapy, vol. 6, pp. 233-236. doi 10.18502/sjms.v13i2.2639 page 90 introduction a case report histopathological report discussion conclusion references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5214 production and hosting by knowledge e research article obese family members of chronic renal failure patients are at higher risk for developing kidney diseases: in a cross-sectional study abozaid m elemam1, amar m ismail2, and maha i mohammed3 1department of clinical chemistry, faculty of medical laboratory science, omdurman islamic university, khartoum, sudan 2department of biochemistry and molecular biology, faculty of science and technology, alneelain university, khartoum, sudan 3department of medical biochemistry, faculty of medicine and public health, al-neelain university, khartoum, sudan abstract background: previously it has been demonstrated that, the obesity is one of the strongest risk factors for incident chronic kidney diseases (ckds). currently we examine the association between body mass index (bmi) and ckd in first degree relatives (fdrs) of renal failure patients on hemodialysis. materials and methods: in a cross-sectional study 135 fdrs of end stage renal disease (esrd) patients on hemodialysis were included. serum creatinine, urine creatinine and microalbumin were measured. estimated glomerular filtration rate (e-gfr) and albumin to creatinine ratio (acr) were calculated. the height in cm, weight in kg was measured, and the bmi was calculated. results: females 64% were found to have higher frequency than males 36%. the frequency of bmi categories was found to be 26.7% obese, 26.7% overweight and 46.6% normal weight. the mean bmi was (26.0 ± 6.62). the prevalence of ckds is 19.3% among relatives. ckds were more frequent 42.3% in obese, followed by 30.8% in overweight and 26.9% in normal weight relatives. obese and overweight relatives have significantly higher acr than normal weight (p= 0.012). gfr found to be significantly lower in obese and overweight relatives than normal weight (p = 0.000). gfr was negatively correlated with bmi (r = 0.430, p = 0.000). conclusion: obese and overweight renal failure relatives had higher acr and lower egfr. therefore, obese and overweight members are at higher risk for developing ckds. keywords: ckds, family members, bmi, obesity, acr, egfr. 1. introduction chronic kidney disease (ckd) is a global public health problem (1,2), that increasing rapidly worldwide and is gaining much attention in both the developed as well as how to cite this article: abozaid m elemam, amar m ismail, and maha i mohammed (2019) “obese family members of chronic renal failure patients are at higher risk for developing kidney diseases: in a cross-sectional study,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 143–154. doi 10.18502/sjms.v14i3.5214 page 143 corresponding author: abozaid mohammed hamid elemam; email: elemam69@hotmail.com amar mohamed ismail; email: amarqqqu@yahoo.com received 21 february 2019 accepted 12 may 2019 published 28 june 2019 production and hosting by knowledge e abozaid m elemam et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:elemam69@hotmail.com mailto:amarqqqu@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abozaid m elemam et al developing countries (3, 4). it is found in 10% of the global population (5,6), and it affects 10-16% of the adult population in china, asia, australia, europe and the united states (7). in sudan, as it was reported by hassan abu aisha in his pilot study at 2009, the prevalence range was 7.7 11% (8). ckd is considering as a health issue associated with increased morbidity, mortality and health care costs (5, 7). beside ckd, obesity is another worldwide pandemic problem; it is associated with various metabolic disorders such as ckd and results in a shortened life span related to adverse health consequences (9). in sudan, the high prevalence of obesity was observed, and it was found that; it is associated with diabetes and hypertension (10). epidemiological studies have demonstrated that obesity, a family history of esrd and high body mass index (bmi) are an essential risk factors for incident ckd and increased risk of esrd (11, 12), and associated with an increased risk of ckd development among adult individuals in the general population (13). several studies showed that; the fdrs of esrd patients with a family history are at risk to develop ckd (14, 15). furthermore, increased stocktickerbmi and obesity were found to be having direct impact on the development of ckd and esrd (12), through a compensatory mechanism of hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight and the increase in intraglomerular pressure which can damage the kidney structure and raise the risk of developing ckd in long term (12,16). recently, screening and early detection of ckds researches have performed to decrease the prevalence of ckd, minimize the incidence of esrd and to reduce their different health, social and economic effect (17, 18). therefore, in this study we investigated whether the study variables (age and bmi) associated with ckds, indeed, early detection and management of ckds in relatives at high risk. 2. materials and methods in a cross-sectional hospital based study during may 2017 – may 2018, 135 randomly selected family members (first degree relatives) of chronic end stage renal failure patients on hemodialysis attending different centers in khartoum state were included. ages ranged between 1760 years old. after informed consent blood samples were collected, under aseptic condition from relatives. subject with diabetes mellitus, hypertension, cancer, thyroid dysfunction, glucocorticoids therapy, hiv, pregnancy and hepatitis were excluded. the selection based on clinical history records. the demographic data were gathered using instructed questionnaire. the height in cm and weight in kg were doi 10.18502/sjms.v14i3.5214 page 144 sudan journal of medical sciences abozaid m elemam et al estimated, and then bmi was calculated. acr and e-gfr were measured. elevated acr (>30 mg/g) and/or reduced e-gfr (< 60 ml/min/1.73m2) considered as ckds. 2.1. ethical approval the study was approval by the local ethical committee of al-neelain university and ministry of health. written informed consent was obtained from all participants. 2.2. calculation of urine albumin to creatinine ratio (u. acr) brief according to manufacturer, mid-stream single spot urine sample was collected. urine albumin was measured by immunoturbidmetric assay method, which based on reaction of anti-albumin antibodies with antigen in the sample to form antigen/antibody complexes. the assay was performed using cobas auto analyzer instrument at central laboratory of east nile hospital. the concentration of albumin was calculated automatically by cobas c system turbidimetry assay. urine creatinine was estimated by kinetic jaffe reaction without deproteinization method, using cobas auto analyzer instrument. the creatinine concentration was calculated automatically by cobas c system and expressed in mg/dl. albumin creatinine ratio (acr) was calculated by medical, scy-med calculator, and expressed in mg/g. acr > 30 mg/gm was considered as albuminuria (19). 2.3. calculation of estimated glomerular filtration rate (egfr) estimated gfr was calculated by modification of diet in renal disease (mdrd) equation, using a 4-variable version (mdrd-4) that included age, sex, ethnicity, and serum creatinine, this 4-variable version was expressed using serum creatinine values that were standardized to reference methods (20 , 21). (reduced gfr was detected when egfr < 60 ml/min/1.73m2). gfr = 175 x serum creatinine (mg/dl) −1.154 x age (years) −0.203 x 1.212 (if patient is black) x 0.742 (if female) the serum creatinine was measured by photometric modified jaffe kinetic method (22), in which the concentration of creatinine was calculated automatically by mind ray bs200 auto analyzer. doi 10.18502/sjms.v14i3.5214 page 145 sudan journal of medical sciences abozaid m elemam et al 2.4. statistical analysis the statistical package for social sciences (spss), version 21.0 (spss inc., chicago, usa) was used for data analyses. results are presented as frequencies, percentage, mean ± sd and regression coefficient. the student’s t-test was used to compare mean levels between groups. chi-esquire was used for qualitative data. person’s correlation was employed to determine the association between continuous variables. p-value ≤ 0.05 was considered as the statistical significance. 3. results in this study 135 family members were participated.table1 show the demographic and characteristics data, table2 show the frequency and distribution of ckd and table3 show the mean levels of acr and e-gfr according to bmi categories, while figure1 show association of bmi with acr and e-gfr. 64% were females and 36% males. their mean age was (32.3 ± 14.1). the frequency of bmi categories was found to be 26.7% obese, 26.7% overweight, 39.2% normal weight and 7.4% underweight. the mean bmi was (26.0 ± 6.62). the prevalence of ckds is 19.3% among relatives. ckds were more frequent 42.3 % in obese, followed by 30.8 % in overweight and 26.9% in normal weight relatives. obese and overweight relatives have significantly higher acr than normal weight (p= 0.012). gfr found to be significantly lower in obese and overweight relatives than normal weight (p = 0.000). gfr was negatively correlated with bmi (r = 0.430, p = 0.000). a b figure 1: a: correlation between bmi and estimated -gfr, b: correlation between bmi and acr. doi 10.18502/sjms.v14i3.5214 page 146 sudan journal of medical sciences abozaid m elemam et al table 1: demographic and characteristics data of ckd relatives (n = 135). characteristics frequency (%) or mean ± sd variable frequency (%) or mean ± sd gender: n (%) age groups: n (%) male 49 (36 %) ≤ 20 years 32 (23.7 %) female 86 (64 %) 21 40 years 65 (48.1 %) age: (mean ± sd) (32.3 ± 14.1) > 40 years 38 (28.1 %) bmi: (mean ± sd) (26.0 ± 6.62) acr: n (%) bmi classification : n ( % ) >30 mg/gm. 23 (17.0 %) normal weight 63 (46.6 %) ≤ 30 mg/gm. 112 (83.0 %) overweight 36 (26.7 %) gfr – mdrd: n (%) obese 36 (26.7 %) < 60 ml/min/1.73m2 9 (6.70 %) > 60 ml/min/1.73m2 126 (93.3) table 2: frequency of chronic kidney disease and its distribution based on bmi and age categories among first degree relatives of hemodialysis patients (n = 135). characteristics frequency (%) chronic kidney disease 26 (19.3 %) bmi categories normal weight 7 (26.9 %) overweight 8 (30.8 %) obese 11 (42.3 %) total 26 (100 %) age group ≤ 20 years 5 (19.2 %) 21 40 years 9 (34.6 %) > 40 years 12 (46.2 %) total 26 (100 %) 4. discussion concurrent with several previous studies that showed increased prevalence of ckds (23, 24). this study has demonstrated higher prevalence (19.3%) of ckds among family members of renal failure patients. moreover, the frequency data showed that, ckds is more frequent in adults followed by adolescence and youngest. meanwhile, in 135 doi 10.18502/sjms.v14i3.5214 page 147 sudan journal of medical sciences abozaid m elemam et al table 3: the mean levels of acr and e-gfr based on bmi categories in total first-degree relatives. parameters bmi categories mean ± sd pvalue acr (mg /gm.) normal weight 12.0 ± 6.60 overweight 16.5 ± 9.80 obese 21.6 ± 8.90 0.012 gfr mdrd normal weight 90.7 ± 20.2 overweight 77.4 ± 21.6 obese 77.7 ± 25.8 0.000 of first-degree relatives, higher frequency of obesity was noted, followed by overweight and normal weight. several previous studies have reported similar findings, that increased bmi was independent risk factor for ckds in general population, diabetes and hypertension (25, 26, 27, 28, 29). indeed, obesity is known to affect hemodynamic, insulin resistance, adipokines changes, low grade inflammation, oxidative stress and endothelial dysfunction, therefore has been suggested to be a risk factor of ckds. previous studies have shown that, obesity lead to intraglomerular pressure, which damage the kidneys structure and raise the risk of developing ckd in long term (30, 31). whereas adiponectins from adipocyte are postulated to be involved in the pathogenesis and progression of ckd (32). in contrast few studies demonstrated an insignificant association between increased stocktickerbmi and ckd (33, 34). this contradiction attributed to obesity paradox, which suggested to have a protective effect against ckd progression and mortality (35). comparison analysis revealed that, obese and overweight relatives had significantly higher stocktickeracr and lower e-stocktickergfr levels than normal weight, therefore, have been suggested as potential risk factors of ckds among family members. these findings similar from those reported that, albumin excretion rate is increased in obese subjects, also obese non diabetic subjects had a greater risk for mircoalbuminuria (36, 37, 38). since the obesity increased renal plasma flow, hyperfiltration and promote renal injury, consequently proteinuria (39, 40, 41, 42). on the other hand the reduced level of e-stocktickergfr among individuals with increased stocktickerbmi, in addition some data in support of this finding that, the stocktickerbmi of 30 kg/m2 or more is associated with rapid loss of kidney function in patients with egfr of at least 60 ml/min /1·73 m2 (43, 44). doi 10.18502/sjms.v14i3.5214 page 148 sudan journal of medical sciences abozaid m elemam et al in the present study, the comparison analysis was further reinforced by person’s correlation of egfr and bmi that, egfr positively associated with bmi. in fact, the association of obesity with an increased acr-based ckd risk was previously reported (45). in contrast our results differ from those demonstrated that, the bmi is independent factor of ckd (46). 5. conclusion in conclusion, the prevalence of ckds is 19.3% among relatives. obese and overweight relatives had higher acr and lower egfr. meanwhile, bmi inversely associated with egfr. therefore, obese and overweight chronic renal failure relatives are at increased risk for developing ckds. 6. limitation of the study limited number of relatives, the diagnosis of albuminuria based on single laboratory measurement. acknowledgments the authors acknowledge this work to the family members. mr. ismail mohamed ismail, bsc, msc and marwan nori bsc, msc, for their help in statistical analyses. funding nil. conflict of interest the authors declare no conflict of interest. authors’ contribution all authors contribute equally doi 10.18502/sjms.v14i3.5214 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[44] lu jl, molnar mz, naseer a, mikkelsen mk, kalantar-zadeh k, kovesdy cp. association of age and bmi with kidney function and mortality: a cohort study. the lancet diabetes & endocrinology. 2015 sep 1;3(9):704-14. doi 10.18502/sjms.v14i3.5214 page 153 sudan journal of medical sciences abozaid m elemam et al [45] kim yj, hwang sd, oh tj, kim km, jang hc, kimm h, kim hc, jee sh, lim s. association between obesity and chronic kidney disease, defined by both glomerular filtration rate and albuminuria, in korean adults. metabolic syndrome and related disorders. 2017 oct 1;15(8):416-22. [46] zaman sb, hossain n, rahman m. associations between body mass index and chronic kidney disease in type 2 diabetes mellitus patients: findings from the northeast of thailand. diabetes & metabolism journal. 2018 aug 1;42(4):330-7. doi 10.18502/sjms.v14i3.5214 page 154 introduction materials and methods ethical approval calculation of urine albumin to creatinine ratio (u. acr) calculation of estimated glomerular filtration rate (egfr) statistical analysis results discussion conclusion limitation of the study acknowledgments funding conflict of interest authors' contribution references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6579 production and hosting by knowledge e research article gastric adenomyoma: an uncommon cause of dyspepsia and a rare endoscopic finding opeyemi folorunsho bamidele1, matthew olumuyiwa bojuwoye2, mudashiru lawal3, and ruth adabe bello4 1department of medicine, dalhatu araf specialist hospital, lafia, nigeria 2department of medicine, university of ilorin teaching hospital, ilorin, nigeria 3department of pathology, dalhatu araf specialist hospital, lafia, nigeria 4department of medicine, federal medical centre, keffi, nigeria abstract background: gastric adenomyoma (ga) is a rare benign lesion comprising of ducts and glands embedded in smooth muscle stroma. thirty-seven (37) cases of ga were identified until 1993, however, only 15 cases are said to have been reported from 1993 to 2016. oesophagogastroscopy has been widely used in evaluating ga. however, the diagnosis of ga remains exclusively histological. case: we report a 26-year-old nigerian woman who presented with recurrent dyspepsia with her endoscopic findings suggestive of ga. ga was confirmed by histology, and she was managed conservatively. conclusion: this report will contribute to creating awareness of this uncommon condition and also reminding physicians in considering ga as a possible differential of dyspepsia. keywords: gastric, adenomyoma, dyspepsia, endoscopy, nigerian, woman 1. introduction gastric adenomyoma (ga) is a rare benign lesion comprising of ducts and glands embedded in smooth muscle stroma [1]. ga was first described in 1903 by magnus-alsleben [2]. it has been characterized as a hamartomatous lesion, and even as heterotopic pancreas without an exocrine or endocrine function in some studies [3]. thirty-seven (37) cases were identified until 1993, however, only 15 cases are said to have been reported from 1993 to 2016 [4, 5]. it is commonly located in the gastrointestinal tract such as in the stomach (25–38%), duodenum (17–36%), and jejunum (15–21%) [6]. in the stomach, the most common location reported is in the antrum (85%) and the pylorus (15%). it is rarely found in the body [7, 8]. how to cite this article: opeyemi folorunsho bamidele, matthew olumuyiwa bojuwoye, mudashiru lawal, and ruth adabe bello (2020) “gastric adenomyoma: an uncommon cause of dyspepsia and a rare endoscopic finding,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 124–130. doi 10.18502/sjms.v15i2.6579 page 124 corresponding author: opeyemi folorunsho bamidele; consultant physician/gastroenterologist department of medicine. dalhatu araf specialist hospital, lafia email: opebamidele097@gmail.com tel: +2348035196624 received 19 may 2020 accepted 2 june 2020 published 30 june 2020 production and hosting by knowledge e opeyemi folorunsho bamidele et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:opebamidele097@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences opeyemi folorunsho bamidele et al ga can be found among patients between the ages of one month to eighty years, though, commonly seen between the fourth and sixth decade of life. it affects both male and female equally [5, 9]. ga can present as incidental findings during laparoscopic intervention or autopsy. however, non-specific symptoms such as nausea, vomiting, and epigastric pain have been reported. hematemesis, melena, and anemia have also been reported in some cases [10, 11]. the differential diagnosis of ga includes gastrointestinal stromal tumors, leiomyoma, hamartoma, and a reactive hypertrophic smooth muscle, especially when it presents as a solid submucosal mass or cystic lesion [4, 12]. oesophagogastroscopy, computer tomography (ct) scan, and endoscopic ultrasonography have been widely used in evaluating ga. despite the availability of these diagnostic modalities, diagnosing ga can still be difficult [10, 13]. nevertheless, the diagnosis of ga remains exclusively histological based on the identification of heterotopic tissues, the architectural pattern of the lesion, its relation with the surrounding tissues, and the exclusion of malignancy [4]. we report a case of a young woman with ga who presented with dyspepsia. 2. case report a 26-year-old nigerian woman presented to the gastroenterology clinic with a sixmonth history of recurrent epigastric pain. the pain was burning in nature and insidious in onset. it radiated to the left hypochondrium and was relieved by ingesting antacids. there were no known aggravating factors. the pain was associated with bloating and nausea, however, there was no history of heartburn or regurgitation. there was no history of jaundice, vomiting, abdominal swelling, weight loss nor change in bowel habit. there was no history suggestive of gastrointestinal bleeding. the patient’s systemic review was not contributory. there was no history of ingestion of non-steroidal anti-inflammatory drugs (nsaids) or herbal preparation. her family and past medical history were not contributory or significant. she neither smoked cigarette nor ingested alcohol. except for her tender epigastrium, her physical examination were unremarkable. doi 10.18502/sjms.v15i2.6579 page 125 sudan journal of medical sciences opeyemi folorunsho bamidele et al the platelet count was 180 x 109/l (reference: 150–450x 109/l); packed cell volume was 38% (reference: 35–45%); hemoglobin count was 14g/dl (reference: 13.5–17.5g/dl), and white blood cell count was 7.4 x 109/l (reference: 4–12x109/l). serum creatinine was 70 µmol/l (reference: 60–100 µmol/l), urea was 5.0 mmol/l (reference: 2.5–6.5 mmol/l), potassium was 3.8 mmol/l (reference: 3.5–5.0 mmol/l), and sodium was 138 mmol/l (reference: 135–145 mmol/l). serum alanine aminotransferase was 10iu/l (reference: 4–36iu/l), serum aspartate aminotransferase was 12iu/l (reference: 4–36iu/l), serum alkaline phosphatase was 90iu/l (reference: 45–146iu/l), and serum bilirubin was 12mmol/l (reference: 4–17mmol/l). viral screening for hepatitis b, c, and hiv were all negative. serum lipase was within normal limit. the patient’s chest x-ray, abdominopelvic ultrasound scan, and electrocardiography (ecg) findings were normal. urea breath test (ubt) was also negative. she had an oesophagogastroduodenoscopy (ogd) that revealed a small (1–2 cm), firm, circular, umbilicated subepithelial antral nodule (figure 1). the mucosa overlying the lesion appeared inflamed. the oesophagus, fundus, and corpus were normal. the duodenal mucosa also appeared normal. separate biopsies were taken from the antral nodule, fundus, and corpus. the histology of the biopsied nodule showed columnar epithelium overlying a lamina propria within which were nests of brunner glands that were separated by smooth muscle bundles and mucous glands. no cytologic atypia was seen (figure 2). the histological findings were diagnostic of a ga. no helicobacter pylori (h. pylori) was seen. the histological findings in the fundus, corpus, and duodenum were normal. endoscopic ultrasound (eus) and immunochemistry were not done as these were not available at the time this patient was managed. the patient was placed on proton pump inhibitors (ppi) for four weeks with the resolution of her symptoms after two weeks of medical therapy. the patient was referred to the general surgeons, who advised that patient should be followed-up and monitored due to the absence of dysplasia or malignant cells on a histology, the small size of the antral nodule, and resolution of symptoms with medical therapy. a repeat ogd and biopsy of antral lesion done six months after showed no significant change in the size of the nodule and no malignant transformation seen on histology. the patient is currently being followed-up in both gastroenterology and general surgery clinic and has remained asymptomatic. doi 10.18502/sjms.v15i2.6579 page 126 sudan journal of medical sciences opeyemi folorunsho bamidele et al 3. comments ga is a rare benign tumor first described by magnus-alsleben in 1903 [2]. since then, about 52 cases were reported until 2016 [15]. to the best of our knowledge, our case will be the first to be reported in nigeria. the index patient’s age was within the age range reported for ga; however, we could not ascertain if this lesion was present since childhood. our patient presented with only dyspepsia; however, other symptoms such as vomiting, melena, and even gastric outlet obstruction have been reported in other literatures [7, 11]. common associations of ga such as annular pancreas, gardner syndrome with duodenal adenomas, and gastric duplication reported in some cases were absent in our patient [12]. the long-term recurrent dyspepsia was the main indication for endoscopy in this patient. the ogd showed small, firm, circular, umbilicated subepithelial antral nodule. this lesion resembled heterotropic pancreas endoscopically, which was a differential diagnosis considered during the evaluation of our patient as ga was regarded as an abortive variant of the heterotopic pancreas in some studies [4]. ga was confirmed histologically with typical histological findings in keeping with this entity. eus and immunochemistry were not done as they were not available at the time of evaluation. however, histology remains the gold standard for the diagnosis of ga [4]. we believe the dyspeptic symptoms our patient had is most likely due to the presence of ga in the antrum, as the other possible causes of dyspepsia such as nsaid use and h. pylori were absent in this case. moreover, dyspeptic symptoms and even upper gastrointestinal bleeding have been reported in patients with ga [14]. our patient was managed conservatively with ppi with resolution of her symptoms. the lesion was not resected but rather monitored, and the patient is being followed-up in both gastroenterology and surgical clinic. treatment options for ga include endoscopic submucosal dissection, wedge resection of tumor to extensive surgical resections [11, 15]. the advent of frozen section has made intraoperative diagnosis of ga possible with reduction of unnecessary extensive operations [11]. in summary, ga is an uncommon cause of dyspepsia and unusual finding on ogd. this condition is rare in this part of the world, and its presentation can mimic common causes of dyspepsia. our patient had typical endoscopic and histology findings consistent with ga. we believe that our report of this uncommon condition will further raise doi 10.18502/sjms.v15i2.6579 page 127 sudan journal of medical sciences opeyemi folorunsho bamidele et al awareness and remind physicians to consider ga as a possible differential of dyspepsia, thus aiding its prompt diagnosis and treatment. figure 1: ogd showing a firm, circular, umbilicated subepithelial antral nodule. figure 2: nests of brunner glands (blue arrow) that are separated by smooth muscle bundles (yellow arrow). doi 10.18502/sjms.v15i2.6579 page 128 sudan journal of medical sciences opeyemi folorunsho bamidele et al author contribution opeyemi f bamidele was the patient’s gastroenterologist who reviewed and contributed to the final approval of the version of the manuscript to be published. matthew o bojuwoye contributed to the drafting of the manuscript, and mudashiru lawal was the patient’s pathologist who performed the pathological analysis and interpretation of sample and contributed to manuscript drafting. ruth a bello participated in the final drafting of the manuscript and all authors issued the final approval to the submission of this manuscript. conflict of interest the authors declare that they have no conflict of interest. references [1] ulich, t., kollin, m., simmons, g., et al. (1987). adenomyoma of the papilla of vater. arch path lab med, vol. 111, no. 4, pp. 388–390. [2] magnus-alsleben, e. (1903). adenomyome des pylorus. virchows arch, vol. 173, pp. 137–155. [3] erberich, h., handt, s., mittermayer, c., et al. (2000). simultaneous appearance of an adenomyoma and pancreatic heterotopia of the stomach. virchows arch, vol. 436, no. 2, pp. 172–174. [4] álvarez, m. a. d., lópez, j. r. g., and garijo, t. g. (2017). gastric adenomyoma: the unexpected mimicker. ge port j gastroenterol, vol. 24, no. 4, pp. 198–202. [5] vandelli, a., cariani, g., bonora, g., et al. (1993). adenomyoma of the stomach. surg endosc, vol. 7, no. 3, pp. 185–187. [6] ormarsson, o. t., gudmundsdottir, i., and mårvik, r. (2006). diagnosis and treatment of gastric heterotopic pancreas. world j surg, vol. 30, no. 9, pp. 1682–1689. [7] suma, m., jayalakshmy, p., resna, r., et al. (2016). gastric adenomyoma causing outlet obstruction. oncol gastroenterol hepatol rep, vol. 5, no. 1, p. 45. [8] yoon, k. h., eun, d. y., kim, j. h., et al. (2014). gastric adenomyoma in the stomach body: a case report. j med case rep, vol. 8, no. 1, p. 385. [9] sanchez garcia, s., rubio solis, d., anes gonzalez, g., et al. (2016). [gastric adenomyoma clinically simulating hypertrophic pyloric stenosis]. radiologia, vol. 58, no. 2, pp. 148–151. doi 10.18502/sjms.v15i2.6579 page 129 sudan journal of medical sciences opeyemi folorunsho bamidele et al [10] park, h. s., lee, s. o., lee, j. m., et al. (2003). adenomyoma of the small intestine: report of two cases and review of the literature. pathol int, vol. 53, no. 2, pp. 111–114. [11] zhu, h.-n., yu, j.-p., luo, j., et al. (2010). gastric adenomyoma presenting as melena: a case report and literature review. world j gastroenterol, vol. 16, no. 15, p. 1934. [12] ly, d. p., barnard, n. j., and schwarz, r. e. (2004). gastric adenomyoma: definitely benign or defiantly premalignant? digest dis sci, vol. 49, no. 11–12, pp. 1930–1934. [13] chu, k. (2002). endosonographic appearance of gastric adenomyoma. endoscopy, vol. 34, no. 8, p. 682. [14] kerkez, m. d., lekic, n. s., culafic, d. m., et al. (2011).gastric adenomyoma. vojnosanit pregl, vol. 68, no. 6, pp. 519–522. [15] wang, s., cao, h., zhang, y., et al. (2017). endoscopic submucosal dissection for gastric adenomyoma: a rare entity of 15 cases among 571 patients with gastric submucosal eminence lesions. medicine, vol. 96, no. 9. e6233 doi 10.18502/sjms.v15i2.6579 page 130 introduction case report comments author contribution conflict of interest references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article the path of undergraduate medical education in sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with undergraduate medical education (ume) stated in 1924 with one school, currently there are about 66 medical schools. during this period many local and global socioeconomic events took place and molded ume. this study was set to document the course and influencing factors that shaped sudanese ume. methods: an extensive literature search was conducted, all the relevant articles and websites were accessed, hard copy documents were reviewed and personal communications with eminent sudanese figures in the field were conducted. results: sudanese ume is meagerly documented and its history can be described in four phases. the establishment phase (1924-1974) one school was founded and it was influenced by the flexner’s era and sudanese independence. the provincial expansion phase (1975-1990) was influenced by sudan’s commitment to al-ma ata recommendations and current educational innovations. revolution in higher education (1991–2004,) led to mushrooming of public and private ume, was influenced by global trend in privatization and local sociopolitical turbulence. quality assurance and accreditation phase (2005-2019) was influenced by contradicting local factors and strong international directions. conclusion: sudan’s history and experience with ume is almost one century old during this time it experienced triumphs and setbacks. numerous lessons were learned and can contribute to facing the challenges of ume here and beyond. after december mighty revolution which changed the old political regime, the country entered a transitional stage devoted to rebuilding and repair in all sectors including education. studies such as this one will provide the needed data for reforming ume. keywords: sudan; medical education; reform, higher education; accreditation 1. introduction sudan is the third-largest country in africa with a total population of around 40 million [1]. it had borders with seven countries, and its capital is khartoum. sudan is a miniature representation of the diversity observed in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], how to cite this article: tahra al sadig al mahdi (2019) “the path of undergraduate medical education in sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences tahra al sadig al mahdi and the poverty percentage is around 46.5% [5]. the country suffers a marked shortage in health workforce worsened by poor distribution over the country and massive brain drain that depleted sudan of more than half its doctors and almost one-third of higher education teaching faculty [6, 7]. sudan medical education (me) is one of the oldest in the region [8] and has maintained high quality and good reputation. currently, it is witnessing unprecedented transformation and challenges that threaten its progression. sudan is one of the countries with greatest numbers of medical schools; that constitute about 23% of medical schools in subsaharan africa and 10% of that in emro region [9] yet, me literature from sudan represents only 2% of that reported from sub-saharan africa [10]. the sudanese health professionals had contributed massively to the development of education and medical and health practice and health systems organization in the region for a long time. this regional influence is deemed to increase; due to multiple reasons sudan is considered as one of the major exporting countries for health professionals [8]. this situation necessitates proper review and scrutiny of the history and influences that modeled the ume leading to the current state, and thereafter to take informed action for continuing its legacy. by reviewing the articles and collecting the relevant data the researcher was attempting to answer the following questions: 1. what is the chronological order of events? 2. what are the incidents that triggered or influenced each phase? objectives to document the path of undergraduate medical education in sudan from 1924 – 2019, and deduct the factors that contributed to its transformation throughout the years. 2. methods in the period between july 2018 to july 2019 an extensive literature search was conducted using pubmed, google scholar and african journals online using the term doi 10.18502/sjms.v14i4.5899 page 189 sudan journal of medical sciences tahra al sadig al mahdi “medical education in sudan”. moreover, relevant cited articles were searched by search engines and through direct contact to their authors. further information and documents were accessed from the ministry of higher education and scientific research website, also by reviewing the different medical schools’ websites and facebook pages. furthermore, the sudan medical council and sudan medical heritage foundation were consulted for more data on me. finally, personal communications with many national figures in me were conducted. the ethical clearance for this study was obtained from ahfad university for women’s ethical review board. 3. results in this study, 268 articles were retrieved and only 32 articles seemed relevant. 22 articles were retrieved as full articles, six as abstracts, and for four articles no abstracts were available. only three articles were of significance to the subject of this study [2, 11, 12]. 3.1. establishment of medical schools through the years me in sudan started in 1924 with the establishment of kitchener memorial school of medicine (ksm). in 1978 two provincial medical schools were established at juba in south sudan and gezira universities. in 1990 two more schools were established; one of them was the first private-not-for-profit school in sudan. in this same year, the government launched the “revolution in higher education” leading to a great expansion in ume. this brought about a lot of public and professional concerns, hence the regulators of me in sudan adopted the international basic standards for accreditation of ume. in 2005, 73% of these medical schools were public. however, private schools slowly followed. about 58% of the public schools were established in the period from 1990 to 2000, and about 67% of the private schools were established in the period 2011 to 2018. (fig 1) currently, there are about 66 medical schools in the country; they are equally divided as public and private ones. here its important to note that khartoum state hosts 51.5% of the medical schools in the country; nine of them are public, and 25 are private one (fig 2) doi 10.18502/sjms.v14i4.5899 page 190 sudan journal of medical sciences tahra al sadig al mahdi figure 1: the ms number, type and year of establishment. figure 2: the distribution of the medical school according to sudan states. 3.2. distribution of medical schools across the states governed by the stated philosophy of the “revolution in higher education”, there is now at least one public school in each state, this goal took about 26 years to materialize. however, there is no clear basis for the regional distribution of medical school especially when population density is considered. sudan is also divided into different regions that include the northern (two states), eastern (four states), southern (six states), western (three states) and central (three doi 10.18502/sjms.v14i4.5899 page 191 sudan journal of medical sciences tahra al sadig al mahdi states). the central region, composed mainly from khartoum and gezira and it possess about two-thirds of the medical schools (65%), and they constitute 43% of the public schools and 89% of the private schools in the country (tab.1 & fig.3). this region is populated by around one-third of the population. north kurdufan state is part of the central region, but its contribution to the above percentages is negligible. table 1: distribution of medical schools/region. regions central % north % south % west % east % total % public ms 14 42.4 4 12 8 24.2% 3 9 4 12 33 100 private ms 29 87.8 1 3 2 6% 0 0 1 3 33 100 tot n. ms 43 65 5 7.5 10 15 3 4.5 5 7.5 66 100 pop/mil 14.5 35.6 2.4 5.5 11.7 28.7% 4.3 10.5 7.8 19 40.7 100 figure 3: the distribution of medical schools according to their types and sudan regions /population. 4. discussion over one century, sudanese medical education has dramatically expanded. the path through which it evolved can be presented in four phases that were influenced by various local and global factors distinct to each phase. doi 10.18502/sjms.v14i4.5899 page 192 sudan journal of medical sciences tahra al sadig al mahdi 4.1. the establishment phase: 1924-1974 it is the longest phase, which is characterized by a slow and steady capacity building of teaching and administrative staff, infrastructure, stability and high quality of product [2]. throughout this phase, there was only one school in the country. it was thoroughly documented by haseeb in 1967 [12]. the kitchener memorial school of medicine was the second medical school in africa with a comprehensive syllabus (13,14). it started with a four years curriculum and gradually extended to six years to comply with the international standards. in 1946 ksm certificate became fully acknowledged by the different royal colleges of the united kingdom and it was part of the khartoum university college, which was part of the university of london. with sudan independence in 1956, khartoum university college obtained the full status of a university signaling the birth of the faculty of medicine, university of khartoum (fmuofk). global directions in me, as well as the local sociopolitical factors, have greatly influenced this phase. some of the factors were: • flexner’s report and its extending impact on me. this report was addressed to north american me but its impact resonated globally. it emphasized that clinical education should be grounded in scientific disciplines with a clear demarcation between the basic and clinical phases of the program [15], which should be done in teaching hospitals, and schools should abide by a highly selective students’ admission process [16]. • a relatively stable and functioning health delivery system that cooperated harmoniously with the medical school. this system was considered as a world model for health services in the 1940s and 1950s [17]. modern health services were introduced in the country since 1902 (13,14,18) but long before that time, between 1863-1866 there was a military hospital in each province of the turco-egyptian sudan (from 1821-1885) however, these hospitals were limited to military and government officials (14,17). • sudanese independence and the rise in national pride have influenced decisions about standards, and strategies for me. sudanese elites adopted western standards in areas such as civil services so as to be equivalent to the west and not doi 10.18502/sjms.v14i4.5899 page 193 sudan journal of medical sciences tahra al sadig al mahdi less. postgraduate training was pursued in prestigious institutes mainly in the uk before establishing local programs at the university of khartoum. the faculty of medicine at the university of khartoum had paid considerable attention to the standard of the teaching faculty and the quality of students’ training. thus the educational development center was established in 1970. the above factors have influenced the quality of graduates and contributed to the excellent reputation sudanese doctors continued to enjoy. 4.2. provincial expansion phase: 1975 -1990 the provincial expansion in higher education started in 1975 by the establishment of two regional public universities to foster fair distribution of services in the country. juba town in the south of sudan hosted “juba university” and medani town in the center accommodated “gezira university”. the initial plan for these medical schools was to start in 1976 by the same curriculum of fmuofk, but their direction was changed to adopt more innovative programs [19]. both schools launched their programs in 1978. the faculty of medicine in gezira university (fmgu) in particular, is famous for being one of the founding members of the international movement towards community oriented/based medical education (come) and as one of the world pioneers in problem based learning (pbl) [10]. in 1990 two medical schools were established at omdurman islamic university – a public institute and ahfad university for women. ahfad medical school was the first private, not-for-profit medical school with come mandate using pbl approach. in addition to delivering graduates well suited for their community, ahfad aspired to bridge the gender gap in the medical profession [20]. the phase was shaped by: • the who efforts in advancing public health, which culminated in the alma ata declaration in 1978. the sudanese government has committed itself to the declared recommendations and adopted community oriented/based medical education (come) in the newly founded schools. • the rise of constructivist views about learning, resulting in pbl as an efficient strategy for me. doi 10.18502/sjms.v14i4.5899 page 194 sudan journal of medical sciences tahra al sadig al mahdi by the end of this phase, there were five schools, four of them were public, and one private and three of them had innovative community-oriented curricula as recommended by alma ata declaration mandated reform. 4.3. higher education revolution phase: 1991 2004 the launching of the so-called “revolution in higher education” in the early 90s of the last century resulted in establishing numerous universities in different parts of sudan. some of the stated motives were to increase the number of graduates so as to keep up with the growing population numbers [21], to enhance the development of the different parts of sudan through establishing state universities, to promote context-sensitivity through islamizing and arabicizing of the curricula; and to encourage the establishment of private institutes. it was expected that it would solve the long-standing problem of poor distribution of doctors across the country by the enrollment of students from these states to retain them in their states after graduation (22,23). consequently, the number of medical graduates increased from around 600/year in 1990 to 5000/year in 2006 [2]. in these 15 years the number of medical schools stretched more than seven times to reach 30. eight of these schools were private and all of them located in khartoum state. the strategy of expanding the number of schools and graduating class seemed both wise and reliable and has been practiced in other parts of the world to deal with similar problems [24], in sudan the strategy was applied without proper planning or implementation [2]. some of the main influential events/threats were: • political turbulences and the increased instability of the population. • escalation of the civil war with its financial burden on the national budget. • the united states sanctions on sudan that acted as a barrier to international scientific interaction. • accelerating brain drain, mounting to what was considered as a national threat and severe worry to the plan of human resources for health (hrh), the health system and the quality of training for medical students [6]. • privatization of me, which started to appear in sudan and other parts of the world [25]. in the middle east, including sudan, privatization of medical schools is mainly doi 10.18502/sjms.v14i4.5899 page 195 sudan journal of medical sciences tahra al sadig al mahdi for-profit [10]. in principle privatization is quite acceptable and even welcomed, but in the absence of strict regulatory requirements and transparency, it can easily compromise quality [26] and may lead to the production of doctors not adequately representing the sudanese society. • the increasing dichotomy between health and education systems and arbitrary distribution of medical schools. • the concentration of medical schools in the capital, khartoum state hosted 16 schools that competed for almost the same training sites resulting in a severe problem for the clinical training. 4.4. quality control & accreditation phase: 2005 till now the proliferation of medical schools was not timely paralleled with a similar increase in the basic resources needed for reasonable me [2]. authorities in higher education were always very concerned with the quality of education, yet formal efforts started to appear in 2000 – which is relatively early in the region. since that time, many efforts have been put to regulate me and ensure its quality in relation to contextualized international standards. examples of these efforts are: development of “the model college” document in 2003 [27], formation of the national accreditation committee, which governs the national accreditation program [28], as well as the launching of the national accreditation program first round was in 2010 – 2012, and the second round started in 2018 [29]. currently, sudan medical council gained international recognition as an accrediting body by the wfme through its recognition program. this is considered a very positive development for sudanese me. moreover, sudan is one of the first ten countries in the world to obtain this recognition [30]. this phase coincided with and is still being molded by many influences. some of them are: • the global rise of accreditation culture due to changes in medical practice, health care delivery system, aspiration for quality assurance and the emphasis on humanitarian values. • the development of the international basic standards for undergraduate medical education by the who and the wfme. to deal with important challenges, they defined a new direction for me and advocated for the accreditation system that doi 10.18502/sjms.v14i4.5899 page 196 sudan journal of medical sciences tahra al sadig al mahdi is based on national and regional standards [27]. the international standards were proposed to act as a backbone for integrating the national and regional accreditation procedures [31]. • the signing of the comprehensive peace agreement (cpa) in sudan in 2005 that brought promises of the new prosperous era cpa has ended a 21-year-old civil war in sudan. at that time, sudan raised as oil-producing country and investments extended to private me. • escalation of privatization in ume; 25 new medical schools were established, and the majority of them were in khartoum. • separation of the south of sudan in 2011 and the significant economic hardship as sudan had lost great shares of its oil resources. this had direct implications on the financial support of education and health [7]. • increasing rates of migration resulting in severe shortage in hp, based on the who benchmark for the number of health workers per number of population; sudan was classified as a country with a critical shortage, resulting in sudan falling short from achieving any of the millennium development goals in 2015 [7]. • increased awareness about the need for formal training of medical teachers through faculty development programs of variable durations. currently there are five master’s degree programs for medical education in sudan. • rise in public dissatisfaction from the health system and service providers with increasing incidents of hostilities towards doctors. • the incidence of “december mighty revolution” that succeeded to change the political regime that ruled sudan for 30 years. presently, there is a transitional government with the mandate to prepare the country for the upcoming elections. meanwhile, professionals from different specialties are working on strategies to guide comprehensive reform in the country – this includes me. 5. recommendations and conclusion effort should be devoted to documenting the path of medical education and the existing obstacles and hurdles. this effort must involve all stakeholders, especially the public, must contribute to the discussion about the current status of ume and find contextsensitive strategies to improve the situation. doi 10.18502/sjms.v14i4.5899 page 197 sudan journal of medical sciences tahra al sadig al mahdi in conclusion, sudanese me has distinguished itself as a very dynamic and resilient entity that was shaped by local as well as global factors. in the quest to improve the health of sudanese people, various strategies and innovations in me were tried. in order to learn from its shortcomings and celebrate its triumphs, this experience needs more documentation and evaluation. december mighty revolution spirit and the wisdom of medical educators will act as a springboard for launching the comprehensive reform capable of addressing all the present challenges and place sudan back to where it belongs as a leading country that pioneered and excelled in me as well as many other fields. acknowledgement i would like to express my sincere thanks and gratitude to professor bashir hamad, professor ahmed al safi, professor zein a. karrar, professor mohamed yousif sukkar, professor dyaeldin elsayed, professor gasim badri and professor ahmed hassan fahal for offering their time, expertise and experience to assist me in writing this paper; may god bless them all. conflict of interest the author confirms no conflict of interest study financial support no financial support was received for this study. references [1] who sudan health profile. world health organization: regional office for the eastern mediterranean; 2015 (http://apps.who.int/iris/bitstream/handle/10665/254895/ emropub_2017_en_19610.pdf;jsessionid= 6ddbd5697492e24a1cbe65c52509a60c?sequence=1 accesses 28 september 2018). doi 10.18502/sjms.v14i4.5899 page 198 http://apps.who.int/iris/bitstream/handle/10665/254895/emropub_2017_en_19610.pdf;jsessionid=6ddbd5697492e24a1cbe65c52509a60c?sequence=1 http://apps.who.int/iris/bitstream/handle/10665/254895/emropub_2017_en_19610.pdf;jsessionid=6ddbd5697492e24a1cbe65c52509a60c?sequence=1 http://apps.who.int/iris/bitstream/handle/10665/254895/emropub_2017_en_19610.pdf;jsessionid=6ddbd5697492e24a1cbe65c52509a60c?sequence=1 sudan journal of medical sciences tahra al sadig al mahdi [2] fahal ah. medical education in sudan: its strengths and weaknesses. med teach. 2007; 29:910–914. 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[25] review of medical education in the eastern mediterranean region: challenges, priorities and a framework for action. regional committee for the eastern mediterranean; 2015 (http://apps.who.int/iris/bitstream/handle/10665/250489/ rc_technical_papers_2015_3_16502_ar.pdf?sequence=1, accessed 28 september 2018) [26] shehnaz si. privatisation of medical education: viewpoints with a global perspective. sultan qaboos univ. med. j. 2010; 10(1): 6-11. [27] sukkar my. accreditation of medical schools in sudan. khartoum med j 2008; 1(1): 49-50. [28] accreditation of medical schools, sudan medical council. sudan (http://www.sudmc. org/en/accreditation.html, accessed 28 september 2018) [29] karrar ez. sudan medical council: updates and recent initiatives; 2012 (https://www. youtube.com/watch?v=ehe7klzgkem, accessed 28 september 2018). doi 10.18502/sjms.v14i4.5899 page 200 http://med.uofg.edu.sd/en/about.aspx http://med.uofg.edu.sd/en/about.aspx http://www.ahfad.edu.sd/images/2017/pdf/auw-undergraduate-catalogue.pdf http://www.ahfad.edu.sd/images/2017/pdf/auw-undergraduate-catalogue.pdf http://apps.who.int/iris/bitstream/handle/10665/250489/ rc_technical_papers_2015_3_16502_ar.pdf?sequence=1 http://apps.who.int/iris/bitstream/handle/10665/250489/ rc_technical_papers_2015_3_16502_ar.pdf?sequence=1 http://www.sudmc.org/en/accreditation.html, http://www.sudmc.org/en/accreditation.html, https://www.youtube.com/watch?v=ehe7klzgkem, https://www.youtube.com/watch?v=ehe7klzgkem, sudan journal of medical sciences tahra al sadig al mahdi [30] agencies with recognition status. world federation for medical education (http: //wfme.org/publications/list-agencies-recognition-status-applying/?wpdmdl=1936 accessed 5 october 2018). [31] van zanten m, norcini jj, boulet jr, simon f. overview of accreditation of undergraduate medical education programmes worldwide. med. educ. 2008; 42(9): 930-937. doi 10.18502/sjms.v14i4.5899 page 201 http://wfme.org/publications/list-agencies-recognition-status-applying/?wpdmdl=1936 http://wfme.org/publications/list-agencies-recognition-status-applying/?wpdmdl=1936 introduction objectives methods results establishment of medical schools through the years distribution of medical schools across the states discussion the establishment phase: 1924-1974 provincial expansion phase: 1975 -1990 higher education revolution phase: 1991 2004 quality control & accreditation phase: 2005 till now recommendations and conclusion acknowledgement conflict of interest study financial support references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2952 production and hosting by knowledge e research article childhood steroid-sensitive nephrotic syndrome: characteristics and predictors of relapses (a study at a single center in khartoum) eltigani m. a. ali, nahla mohamed elhadi, mohamed b abdelraheem, and rashid a ellidir pediatric renal unit, soba university hospital, khartoum, sudan abstract background: childhood steroid-sensitive nephrotic syndrome (ssns) usually has a favorable outcome in spite of its relapsing course. the objective of the authors was to study the demographic and clinical characteristics, outcome and risk factors for relapses in children with ssns at a single center in khartoum, sudan. material and methods: in this cross-sectional, facility-based study, the authors retrospectively reviewed all the records of children with ssns, followed at the pediatric renal unit, soba university hospital, khartoum between 2001 and 2014. ssrns was defined as the remission of proteinuria within 4–6 weeks of corticosteroids. relapse is the recurrence of proteinuria after remission; frequent if ≥ 2 within initial six months or ≥ 4 within one year, and steroid dependence if 2 during therapy or within 14 days after stopping it. results: 330 children (males 220; 66.7%) with ssns were studied with a mean age of 5.2 ± 3.5 years of whom 42.4% aged 1–5 years. at the presentation, hypertension was detected in 31.8% and hematuria in 19.1%. serum cholesterol was elevated in all patients (mean 347.34 ± 117.87 mg/dl) and serum creatinine in 7.27% (mean 1.4 ± 0.35 mg/dl). renal histology showed mesangioproliferative glomerulonephritis (mespgn) in 57.5%, minimal change disease (mcd) in 35.5%, and focal segmental glomerulosclerosis (fsgs) and igm nephropathy in 3.5% each. during the course of the illness, 10.3% achieved long-term remission, 89.7% relapsed— of whom 52.3% had frequent relapsing/steroid-dependent (fr/sd) course and 37.7% had infrequent relapses. risk of frequent relapses were age of onset and low/moderate socioeconomic status (p = 0.015 and 0.019, respectively). infections were recorded in 71.8%, but not significantly associated with the risk of frequent relapses (p > 0.05). conclusions: the majority children with ssns at this single center in khartoum had a relapsing course with the majority being fr or sd. predictors of frequent relapses were young age at onset and low socioeconomic status. keywords: nephrotic syndrome, steroid sensitive, relapse, children, sudan how to cite this article: eltigani m. a. ali, nahla mohamed elhadi, mohamed b abdelraheem, and rashid a ellidir (2018) “childhood steroidsensitive nephrotic syndrome: characteristics and predictors of relapses (a study at a single center in khartoum),” sudan journal of medical sciences, vol. 13, issue no. 3, pages 133–143. doi 10.18502/sjms.v13i3.2952 page 133 corresponding author: eltigani m. a. ali; email: eltigani_ali@yahoo.com received 20 july 2018 accepted 10 september 2018 published 24 september 2018 production and hosting by knowledge e eltigani m. a. ali et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:eltigani_ali@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences eltigani m. a. ali et al 1. introduction the majority of children with nephrotic syndrome (ns) are steroid responsive referred to as steroid-sensitive nephrotic syndrome (ssns) [1]. more than 90% of these ssns patients have minimal change pathology and therefore have favorable long-term renal outcome [1]. in africa, children have a different pattern of ns with a paucity of minimal change disease (mcd), with the majority being steroid resistant with a higher risk of progression to ckd [2]. about 80–90% of ssns children experience one or more subsequent relapses that can be infrequent or frequent relapses (fr) or steroid dependence (sd) [3, 4]. the age of onset of the disease [5], time to respond to steroids [6], length of treatment [6, 7], infections [8, 9], rapid steroid tapering [10] were reported to be the predictors of the relapses and their frequency. prolonged use of steroids increases the risk of steroid toxic effects and infections with subsequent high morbidity and mortality. therefore, alkylating agents, levamisole, calcineurin inhibitors, mycophenolate mofetil and rituximab have been used as steroid-sparing agents. complications of ssns, occurring with variable frequencies were infections [11] (bacterial or viral), thromboembolism [12] (arterial or venous), renal insufficiency [13], hypovolemia [13], and drugs-related side effects. there are limited data on the long-term outcome of ssns, but multivariate analysis showed that renal function remains normal in adulthood and that long-term sequels are generally related to side effects of medications [14]. the aim of this study was to identify the demographic and clinical characteristics, and predictors of relapse and outcome of ssns in children at a single center in khartoum. 2. material and methods in this cross-sectional, facility-based study, the authors retrospectively reviewed the hospital records of all children (age > 1–18 years) with ssns who had been followed-up in the pediatric nephrology unit, soba university hospital, khartoum, between august 2001 and january 2012. the criteria for diagnosis of ns were serum albumin < 2.5 gm/dl) and urine albumin–creatinine ratio [uacr] ≥ 200 mg/mmol [15]. the inclusion criteria were: response to steroids (prednisolone 60 mg/m2/day) within 4–6 weeks [16], onset > 1 year, and follow-up ≥ 6 months. the exclusion criteria were: congenital or syndromic forms, family history of ns, ns with systemic disease and incomplete records. data were abstracted from the records using standard data collection sheet. demographic features, blood pressure, height and weight, and socioeconomic status doi 10.18502/sjms.v13i3.2952 page 134 sudan journal of medical sciences eltigani m. a. ali et al were recorded. laboratory data—urinalysis and culture, uacr, blood urea, serum creatinine, electrolytes, albumin, cholesterol, and kidney biopsy histology—were recorded. treatment protocols and responses, complications, and outcome were also recorded. 3. definitions definitions of remission, relapse, frequent relapse and steroid dependence were as per the international study of kidney disease in children (iskdc) [17]. remission: proteinuria < 4 mg/m2/hr or albumin negative or trace on urine dipsticks for three consecutive days. sustained remission: no relapse for at least six months. relapse: proteinuria > 40 mg/m2/hr or albumin 3+ on urine dipsticks for three consecutive days after having been in remission. infrequent relapse: less than two relapses in six months of response or less than four in twelve months. frequent relapse (fr): two or more relapses within six months of response or more than three in any twelve months. steroid dependence (sd): two consecutive relapses while on alternate-day steroids or within 14 days of its discontinuation. long-term remission: no relapse for at least three years. estimated glomerular filtration rate (e gfr) was calculated using the schwartz formula [18]. ckd was defined as gfr < 60 ml/min/1.73m2 for ≥ 3 months and ckd5 requiring renal replacement therapy (rrt) as gfr < 15 ml/min/1.73 m2 [19]. hypertension was defined as blood pressure above 95𝑡ℎ percentile for age [20]. hematuria was defined as > 3 rbcs/hpf in urine sediment [21]. 4. treatment protocols ns was treated with prednisolone 60 mg/m2/day divided doses for 4–6 weeks and then tapered to 40 mg/m2/day (single dose) on alternate days for 4–6 weeks [1]. in fr and sd ns, cyclophosphamide (cpm), levamisole, cyclosporine (csa), or mycophenolate mofetil (mmf) were used after induction of remission with prednisolone. doses and treatment durations were as follows: cpm: 2.5 mg/kg/day for 8–12 weeks, oral csa: 4–5 mg/kg/day in two divided doses for twelve months), mmf: 600 mg/m2 twice daily for 12 months and levamisole: 2 mg/kg/day for 12 months. outcome measures were remission (sustained, long-term), relapses (infrequent, fr, sd), ckd. doi 10.18502/sjms.v13i3.2952 page 135 sudan journal of medical sciences eltigani m. a. ali et al 5. data analysis data were organized into a master sheet using the statistical package for social sciences (spss), version 19. data were presented using frequencies and percentages for categorical variables and means ± standard deviation (sd) for numerical continuous variables. variables were compared using independent t-test for independent variables. for all statistical analysis, p-value less than 0.05 was considered as statistically significant. 6. results out of 460 children admitted with idiopathic ns, 330 (71.7%) had steroid-sensitive ns (ssns). of them, 220 (66.7%) were males and 110 (33.3%) females, with a male to female ratio of 2:1. the mean age at presentation was 5.2 ± 3.5 (range 1.5–16) years. the age spectrum was variable with 42.4% of patients being in the age range of 1–5 years. the mean age of onset of the disease was 5.4 ± 3.57 years with 62.7% being in the age range of 1–5 years. hypertension was detected in 105 patients (31.8%) and hematuria in 63 (19.1%). serum cholesterol was elevated in all patients (100%) with mean serum levels of 347.34 ± 117.87 (range 224–687) mg/dl. serum creatinine was elevated in 24 (7.3%) with a mean of 1.4 ± 0.35 (range 0.9–2) mg/dl, respectively. serum albumin was less than 2 gm/dl in 264 patients (80%) with a mean level of 2.18 ± 0.68 (range 0.9–3.3 gm/dl). renal biopsies were performed in 84 patients (25%), and indications were shift to csa in 44 fr/sd cases (52.4%), macroscopic hematuria 11 (13.1%), late age at onset 8 (9.5%) and persistent elevated serum creatinine in 4 (4.7%). types of histological lesions are shown in table 1. non-mcd lesions were the commonest types. during the follow-up period (mean 3.2 ± 2.6, range 1.5–13 years), 34 patients (10.3%) achieved long-term remission, 123 (37.3%) had fr/sd, and 173 (52.4%) had infrequent relapses. predictors of frequent relapses are shown in table 2. age of onset less than five years and low socioeconomic status were significantly associated with the risk of fr/sd course (p = 0.015 and 0.019, respectively). infections were recorded in 237 (71.8%) patients with ssns and in 232 (78.4%) with relapsing ns; 49.3% respiratory, 28% uti and 1.1% peritonitis. but infections were not significantly associated with frequency of relapses (p > 0.005). in about 87 (70.7%) patients with fr/sd nephrotic syndrome, steroid-sparing drugs were used, whereas in 36 (29.3%) small-dose alternate-day steroids were used. types and frequency of use of these drugs are shown in table 3. non-infectious complications were recorded in 32 (9.7%) doi 10.18502/sjms.v13i3.2952 page 136 sudan journal of medical sciences eltigani m. a. ali et al patients with ssns. frequency and types of these complications are shown in table 4. lastly, follow-up visit after a mean follow-up period of 3.2 ± 2.6 years (range 1.5– 13 years), 235 patients with ssns (71.2%) were in remission, 68 (20.6%) in relapse, 3 (0.9%) developed ckd, and 24 (7.3%) were lost to follow-up; table 5. t 1: types of histopathology lesions in studied patients with ssns underwent renal biopsy. histopathology lesion number percentage mesangial-proliferative glomerulonephritis 48 57.5% minimal change disease 30 35.5% focal segmental glomerulosclerosis 3 3.5% igm nephropathy 3 3.5% total 84 100.0% t 2: risk factors for relapses in studied children with ssns (frequent versus infrequent relapsing). risk factor fr/sd (n = 123) infrequent relapsing (n = 173) p-value gender male 85 (69.1%) 115 (66.5%) female 38 (30.9%) 58 (33.5%) 0.061 age at onset < 5 years 104 (84.6%) 86 (52.5%) > 5 years 9 (15.4%) 58 (47.5%) 0.015* time to initial response < 2 weeks 53 (43.1%) 71 (41%) > 2 weeks 70 (46.9%) 102 (59%) 0.091 socioeconomic status low 89 (64.2%) 78 (45.1%) high 5 (4.1%) 9 (5.2%) 0.019* initial mean serum albumin 1.17 ± 0.72 1.2 ± 0.64 0.588 infections respiratory 70 (47.9%) 76 (52.1%) 0.281 uti 40 (48.2%) 43 (51.8%) 0.211 * p-value is statistically significant. 7. discussion in developed countries, over 80% of children with idiopathic ns are steroid-sensitive [1]. in this series, children with steroid-sensitive ns (ssns) constituted 71.7% of all children with idiopathic ns who were followed in the center. in contrast, in developing doi 10.18502/sjms.v13i3.2952 page 137 sudan journal of medical sciences eltigani m. a. ali et al t 3: types of treatment used in studied children with relapsing ns. treatment number percentage cyclophosphamide (cpm) 42 34.2% alternate-day steroids 36 29.3% cyclosporine a (csa) 18 14.6% cpm followed by csa 14 11.4% mycophenolate mofetil (mmf) 7 5.7% levamisole 6 4.8% t 4: frequency and types of complications in studied children with ssns. complication number percentage cushingoid features 12 37.5% hypertension 8 25.0% glucosuria 5 15.6% short stature 4 12.50% ckd 3 9.40% total 32 100.00% t 5: outcome of studied children with ssns on last follow-up. outcome number percentage sustained remission 57 17.30% non-sustained remission 178 53.90% relapse 68 20.60% ckd 4 0.90% lost to follow-up 24 7.30% total 32 100.00% countries, especially in africa, the majority tend to have steroid-resistant disease [2, 22], which could be related to the predominance of non-mgd lesions among these populations. in this study, males were predominantly affected, which is consistent with the finding reported by the iskdc [23]. the mean age of presentation of children in this study was 5.2 years with 42.4% being in the age group 1–5 years. hypertension, hematuria, and elevated serum creatinine were recorded at presentation in 31.8%, 19.1% and 7.3% of them, respectively. similar finding was reported in other studies [24]. earlier and recent studies showed that about 80–90% of ssns children experience one or more subsequent relapses that can be infrequent or frequent relapses or steroid-dependent [3, 4]. among them, 35 to 50% relapse frequently [4, 26]. our series showed similar finding, as only 10.3% achieved sustained remission in the first 12 months, whereas the majority (89.7%) experienced relapses; among them 37.3% had doi 10.18502/sjms.v13i3.2952 page 138 sudan journal of medical sciences eltigani m. a. ali et al frequent relapses. however, other studies reported lower rate of infrequent and frequent relapses; om p. mishra et al. reported that 59.3% had relapses (52% infrequent, 7.3% frequent, and 0.6% steroid-dependent) [25]. noer reported 63.6% had relapsing ns, including 50.5% infrequent and 13.3% frequent relapses [26]. these variations in the frequency of relapses have been related to many factors. younger age at the onset of the disease was reported to be correlated with the frequency of relapse, with more frequent relapses in children younger than 4 years [27, 28]. the authors found that children in the age group 1–5 years had significantly more relapses in comparison to other age groups (p = 0.015). about 50–70% of relapses in ns are precipitated by a viral upper respiratory tract infection [29–31]. this is likely due to non-specific host response to infection rather than to viral antigen or antibody response [30]. therefore, other infections such as uti, peritonitis, and skin infections have also been reported as triggers of relapses [29, 32]. we found that the majority (71.8%) of relapses followed infections; upper respiratory (45.7%), uti (25.1%), and peritonitis (1%), and this association was statistically significant (p < 0.05). however, there was no statistically significant difference between patients with frequent and those with infrequent relapses regarding the frequency of infections (p = 0.211). low socioeconomic status was another risk factor for frequent relapses in this series (p = 0.019). this could be related to the fact that such children are vulnerable to infection and hence more likely to relapse. in this study, potential risk factors for relapse such as gender, time to initial response to steroids, and initial serum albumin, were not significantly associated with frequency of relapses (p = 0.061, 0.091 and 0.588, respectively) as reported in other studies. in conclusion, in a population of sudanese children, ssns is characterized by a relapsing course in the majority of patients. predictors of relapse were young at onset and had low socioeconomic status. although infections were documented in the majority of relapsing patients, they did predict the frequency of relapses. high rate of relapse and non-sustained remission on last follow-up despite the use of a wide spectrum of steroid-sparing drugs reflects the need for effective therapy to prevent morbidity and mortality. conflict of interests authors declare no conflict of interests. doi 10.18502/sjms.v13i3.2952 page 139 sudan journal of medical sciences eltigani m. a. ali et al ethical clearance the authors declare that the research protocol has been approved by the sudan medical specialization board research committee and soba hospital research committees, and that an informed consent was then obtained. they also declare that the results of this study have not been published before, except for the abstracts. acknowledgements this work is a part of a thesis submitted for partial fulfillment of clinical md in pediatrics, university of khartoum (2014). the authors would like to thank the staff at the pathology and medical records departments, soba university hospital, for their cooperation and help during data collection. they are also grateful to the staff in health statistics department, university of khartoum, for their help with data analysis. author contributions the authors declare that they all had significant contributions to the study and that they all agree with the content of the study. references [1] international study of kidney disease in children. (1981). the primary nephrotic syndrome in children. identification of patients with minimal change nephrotic syndrome from initial response to prednisolone: a report of the international study of kidney disease in children. the journal of pediatrics, vol. 98, pp. 561–564. [2] bhimma, r., coovadia, h. m., and adhikari, m. (1997). nephrotic syndrome in south african children: changing perspectives over 20 years. pediatric nephrology, vol. 11, pp. 429–434. [3] tarshish, p., tobin, j. n., bernstein, j., et al. (1997). prognostic significance of the early course of minimal change nephrotic syndrome: report of international study of kidney disease in children. journal of the american society of nephrology, vol. 8, pp. 769–776. [4] hodson, e. m., willis, n. s., and craig, j. c. (2008). non-corticosteroid treatment for nephrotic syndrome in children. cochrane database syst. rev, vol. 1, cd002290. doi:10.1002/14651858. cd002290. pub 3‘. doi 10.18502/sjms.v13i3.2952 page 140 sudan journal of medical sciences eltigani m. a. ali et al [5] kabuki, n., okugawa, t., hayakawa, h., et al. (1998). influence of age of onset on the outcome of steroid sensitive nephrotic syndrome. pediatric nephrology, vol. 12, pp. 467–470. [6] vivarelli, m., moscaritolo, e., tsalkidis, a., et al. (2010). time to initial response to steroids is a major prognostic factor in idiopathic nephrotic syndrome. the journal of pediatrics, vol. 156, pp. 965–971. [7] arbeitsgemeinschaft fur padiatrische nephrologie. (1988). short versus standard prednisolone therapy for initial treatment of idiopathic nephrotic syndrome in children. lancet, vol. 1, pp. 380–383. [8] abeyagunawardena, a. s. and trompeter, r. s. (2008). increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomized controlled trial. archives of disease in childhood, vol. 93, pp. 226–228. [9] gulati, a., sinha, a., sreenivas, v., et al. (2011). daily corticosteroids reduce infectionassociated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial. clinical journal of the american society of nephrology, vol. 6, pp. 163– 171. [10] hiraoka, m., tsukahara, h., matsubara, k., et al. (2003). a randomized study of two long-course prednisolone regimens for nephrotic syndrome in children. american journal of kidney diseases, vol. 41, p. 1155. [11] alwadhi, r. k., mathew, j. l., and rath, b. (2004). clinical profile of children with nephrotic syndrome not on glucorticoid therapy, but presenting with infections. journal of pediatrics and child health, vol. 40, pp. 28–32. [12] kerlin, b. a., blatt, n. b., fuh, b., et al. (2009). epidemiology and risk factors for thrombo-embolic complications of childhood nephrotic syndrome: a midwest pediatric nephrology consortium (mwpnc) study. the journal of pediatrics, vol. 155, pp. 105–110. [13] vande walle, j. g., donckerwolcke, r. a., van isselt, j. w., et al. (1995). volume depletion in children with early relapse of minimal change nephrosis with or without hypovolaemic symptoms. lancet, vol. 346, p. 148. [14] fakhouri, f., bocquet, n., taupin, p., et al. (2003). steroid sensitive nephrotic syndrome: from childhood to adulthood. american journal of kidney diseases, vol. 41, pp. 550–557. [15] report of workshop by the british association for pediatric nephrology and research unit, royal college of physicians. (1994). consensus statement on doi 10.18502/sjms.v13i3.2952 page 141 sudan journal of medical sciences eltigani m. a. ali et al management and audit potential for steroid responsive nephrotic syndrome. archives of disease in childhood, vol. 70, pp. 151–157. [16] kher, k. k., schnaper, h. w., and makker, s. p. (2007). clinical pediatric nephrology (second edition). uk: informa; health care. [17] international study of kidney disease in children. (1978). nephrotic syndrome in children. prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. a report of the international study of kidney disease in children. kidney international, vol. 13, pp. 159–165. [18] schwartz, g. j., muñoz, a., schneider, m. f., et al. (2009). new equations to estimate gfr in children with ckd. journal of the american society of nephrology, vol. 20, pp. 629–637. [19] national kidney foundation. (2008). k/doqi clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. american journal of kidney diseases, vol. 39, s1. [20] u.s. department of health and human services. national institutes of health national heart, lung and blood institute. the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. nih publication no. 05-5267 (originally printed on september 1996, revised may 2005). [21] grossfeld, g. d. and carroll, p. r. (1998). evaluation of asymptomatic microscopic hematuria. urologic clinics of north america, vol. 25, pp. 661–676. [22] olowu, w. a., adelusola, k. a., and adefehinti, o. (2010). childhood idiopathic steroid resistant nephrotic syndrome in southwestern nigeria. saudi journal of kidney disease and transplantation, vol. 21, pp. 979–990. [23] international study of kidney disease in children. (1997). nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. kidney international, vol. 13, pp. 159–165. [24] mishra, o. p., abhinay, a., mishra, r. n., et al. (2013). can we predict relapses in children with idiopathic steroid-sensitive nephrotic syndrome? journal of tropical pediatrics, vol. 59, pp. 343–349. [25] koskimies, o., vilska, j., rapola, j., et al. (1982). long term outcome of primary nephrotic syndrome. archives of disease in childhood, vol. 57, pp. 544–548. [26] noer, m. s. (2000). predictors of relapse in steroid-sensitive nephrotic syndrome. the southeast asian journal of tropical medicine and public health, vol. 36, pp. 1313– 1320. [27] lewis, m. a., davis, n., baildom, e. m., et al. (1989). nephrotic syndrome: from toddlers to twenties. lancet, vol. 86, pp. 255–259. doi 10.18502/sjms.v13i3.2952 page 142 sudan journal of medical sciences eltigani m. a. ali et al [28] kabuki, n., okugawa, t., hayakawa, h., et al. (1998). influence of age at onset on the outcome of steroid-responsive nephrotic syndrome. pediatric nephrology, vol. 12, pp. 467–470. [29] moorani, k. n. (2011). infections are common a cause of relapse in children with nephrotic syndrome. pakistan pediatric journal, vol. 35, pp. 213–219. [30] macdonald, n., wolfish, n., mclaine, p., et al. (1986). role of respiratory viruses in exacerbations of primary nephrotic syndrome. journal of pediatrics, vol. 108, pp. 378–382. [31] takahashi, s., wada, n., murakami, h., et al. (2007). triggers of relapse in steroiddependent and frequently relapsing nephrotic syndrome. pediatric nephrology, vol. 22, pp. 232–236. [32] afroz, s., khan hossain, m. a., roy, k. d., et al. (2010). urinary tract infection (uti) is associated with higher rate of relapse in children with nephrotic syndrome. ds (child) h j, vol. 26, p. 826. doi 10.18502/sjms.v13i3.2952 page 143 introduction material and methods definitions treatment protocols data analysis results discussion conflict of interests ethical clearance acknowledgements author contributions references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5209 production and hosting by knowledge e research article assessment of plasma von willebrand factor antigen in non-metastatic prostate cancer patients: a cross-sectional study of the sudanese population mohammed othman hashim1, gad allah modawe2, and ibrahim khider ibrahim1 1department of haematology, faculty of medical laboratory sciences, al neelain university, khartoum, sudan 2omdurman islamic university, faculty of medicine and health sciences, department of biochemistry abstract backgrounds: von willebrand disease (vwd) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (avws). these disorders arise due to defects and/or deficiency of the plasma protein von willebrand factor (vwf). high plasma vwf concentrations have been reported in patients with various types of cancer, such as prostatic cancer. metastasization may be associated with activation of hemostatic processes resulting in increased levels of circulating factor viii-related antigen (fviiirag) (von willebrand factor antigen). objective: to evaluate the status of vwf antigen in sudanese patients with prostate cancer attending rick hospital. methods: this is a cross-sectional study carried out in khartoum state at khartoum oncology (rick) hospital, during the period from april to june 2018, 45 samples were collected from patients with non-metastatic ca prostate, their ages ranged from 51 to 82 yr. the vwf level was measured using enzyme-linked immunosorbent assay (elisa). data were analyzed by the statistical package for social science (spss). results: serology for vwf antigen was done for 45 cases of prostate cancer. according to the age, 2 (8%) patients with age 51–66 yr had a high concentration of vwf, while 24 (92%) had normal vwf antigen concentration; of those with age 67–82 yr, 4 (21%) had high vwf antigen and 15 (79%) had normal antigen. conclusion: the study revealed that more than 80% of sudanese patients with nonmetastatic prostate cancer have a normal concentration of vwf. keywords: vwf, prostate cancer, age, elisa 1. introduction the glycoprotein von willebrand factor (vwf) mediates the adhesion of platelets to subendothelial surfaces in primary hemostasis in case of vascular injury [1]. plasma how to cite this article: mohammed othman hashim, gad allah modawe, and ibrahim khider ibrahim (2019) “assessment of plasma von willebrand factor antigen in non-metastatic prostate cancer patients: a cross-sectional study of the sudanese population,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 97–102. doi 10.18502/sjms.v14i3.5209 page 97 corresponding author: mohammed othman hashim received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e mohammed othman hashim et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammed othman hashim et al vwf levels vary over a very broad range extending from 40 to 240% of the mean value [2]. a major determinant of plasma vwf levels is the abo blood group, but several clinical conditions, such as myocardial infarction, diabetes mellitus, liver disease, and acute infections, induce increased plasma vwf concentrations [3–8]. there are some studies describing a correlation of vwf with different cancers like prostate cancer, cervical and ovarian cancer, head and neck cancer, larynx cancer, and colorectal cancer (crc) [9–15]. experimental models favor the hypothesis that vwf connects tumor cells to platelets and so assists during the pathogenesis of metastases. it is supposed that these vwf-tumor-cell-emboli are hardly detected by the immune system [16–18]. as vwf levels increase with progressive disease [14, 15], it is considered as a potential clinical marker in crc. metastasizing may be associated with activation of hemostatic processes resulting in increased levels of circulating von willebrand factor antigen. the objective of this study was to evaluate the status of vwf ag in sudanese patients with non-metastatic prostate cancer attending rick. 2. methods this is a retrospective cross-sectional study in which a total of 45 (non-metastatic) pc patients were recruited at the rick hospital, in the period from april to june 2018. a venous blood sample (3 ml) was taken from each subject into a tube containing 3.8% trisodium citrate, platelet poor plasma was prepared and used for the assessment of vwf level. the vwf level was measured using enzyme-linked immunosorbent assay (elisa) according to the manufacturer’s instructions (technozym, austria). 2.1. ethical consideration ethical clearance was obtained from the institutional review board at al neelain university. principal investigator obtained written informed consent from all participants prior to their inclusion in the study. 2.2. data analysis all obtained results were analyzed using statistical package for the social sciences (spss) version 20.0, with pearson’s chi-square test used to assess intergroup significance and t-test used to determine differences in means, other variables frequencies doi 10.18502/sjms.v14i3.5209 page 98 sudan journal of medical sciences mohammed othman hashim et al and odd ratio calculated for comparison and presented in form of figures and tables. p-value and odd ratio were used to assess the significance of the results. 3. results and discussion high-plasma vwf concentrations have been reported in patients with several types of cancers, such as prostatic cancer head and neck and laryngeal cancer, probably representing an acute phase reactant. in the present study, we evaluated the status of vwf antigen (vwf:ag) in 45 patients diagnosed with prostate cancer (non-metastatic). their mean age was 66.5 yr, 26/45 (58/%) patients were 51–66 years old, and 19/45 (42%) were 67–82 years old. the patient’s marital status: 34/54 (76%) of them were married and 11/45 (24%) were unmarried; 12/45 (27%) patients had hypertension and 4/45 (9%) had diabetes mellitus. serology for vwf antigen was done in 45 cases of prostate cancer. according to the age, 2 (8%) with age 51–66 yr had high concentration of vwf, 24 (92%) with same age had normal vwf antigen, and those with age 67–82 yr, 4 (21%) with high vwf antigen and 15 (79%) with normal antigen. in association with marital status: 5 (15%) of the married patients had high vwf antigen and 29 (85%) were normal. in unmarried men, 1 (9%) was found to have high ag level and 10 (91%) with normal ag level. in association with hypertension and diabetes mellites, 2 (17%) of the hyper-tensive patients had high antigen and 10 (83%) had normal antigen concentration. among the non-hypertensive patients, 4 (12%) had high concentration and the other 29 (88%) had normal ag concentration. of the diabetic patients, 4 (100%) had normal antigen concentration and among the non-diabetic patients, 6 (15%) had high concentration and other 35 (85%) had normal value. 4. conclusion the study revealed that more than 80% of sudanese patients with non-metastatic prostate cancer presented with a normal concentration of vwf. doi 10.18502/sjms.v14i3.5209 page 99 sudan journal of medical sciences mohammed othman hashim et al table 1: demographic and clinical data in the population study. variables frequency percentage (%) age 51–66 years 26 58 67–82 years 19 42 marital status married 34 76 unmarried 11 24 ht yes 12 27 no 33 73 dm yes 4 9 no 41 91 total 45 100 figure 1: distribution of von willebrand factor antigen in sudanese prostate cancer patients. references [1] ruggeri, z. m. (1991). structure and function of von willebrand factor: relationship to von willebrand’s disease. mayo clinic proceedings, vol. 66, pp. 847–861. [2] sadler, j. e., mannucci, p. m., berntorp, e., et al. (2000). impact, diagnosis and treatment of von willebrand disease. thrombosis and haemostasis, vol. 84, pp. 160–174. doi 10.18502/sjms.v14i3.5209 page 100 sudan journal of medical sciences mohammed othman hashim et al table 2: correlation between variables and study parameters. variables vwf ag p-value or ci lower ci upper high normal age 51–66 years 2 (8%) 24 (92%) 0.195 0.313 0.051 1.921 67–82 years 4 (21%) 15 (79%) marital status married 5 (15%) 29 (85%) 0.541 1.724 0.179 16.591 unmarried 1 (9%) 10 (91%) ht yes 2 (17%) 10 (83%) 0.541 1.450 0.230 9.160 no 4 (12%) 29 (88%) dm yes 0 (0.0%) 4 (100%) 0.552 1.171 1.032 1.330 no 6 (15%) 35 (85%) [3] gallinaro, l., cattini, m. g., sztukowska, m., et al. (2008). a shorter von willebrand factor survival in o blood group subjects explains how abo determinants influence plasma von willebrand factor. blood, vol. 111, pp. 3540–3545. [4] shima, m., fujimura, y., nishiyama, t., et al. (1995). abo blood group genotype and plasma von willebrand factor in normal individuals. vox sanguinis, vol. 68, pp. 236– 240. [5] lufkin, e. g., fass, d. n., o’fallon, w. m., et al. (1979). increased von willebrand factor in diabetes mellitus. metabolism, vol. 28, pp. 63–66. [6] giustolisi, r., musso, r., cacciola, e., et al. (1984). abnormal plasma levels of factor viii/von willebrand factor complex in myocardial infarction-expression of acute phase reaction or index of vascular endothelium damage? thrombosis and haemostasis, vol. 51, p. 408. [7] castillo, r., maragall, s., rodes, j., et al. (1977). increased factor viii complex and defective ristocetin-induced platelet aggregation in liver disease. thrombosis research, vol. 11, pp. 899–906. [8] sousa, n. c., anicchino-bizzacchi, j. m., locatelli, m. f., et al. (2007). the relationship between abo groups and subgroups, factor viii and von willebrand factor. haematologica, vol. 92, pp. 236–239. [9] ablin, r. j., bartkus, j. m., and gonder, m. j. (1988). immuno-quantitation of factor viiirelated antigen (von willebrand factor antigen) in prostate cancer. cancer letters, vol. 40, pp. 283–289. doi 10.18502/sjms.v14i3.5209 page 101 sudan journal of medical sciences mohammed othman hashim et al [10] facchini, v., gadducci, a., baicchi, u., et al. (1988). factor viiir:ag plasma levels in patients with cervical and ovarian carcinoma. european journal of gynaecological oncology, vol. 9, pp. 87–93. [11] gadducci, a., baicchi, u., marrai, r., et al. (1993). pretreatment plasma levels of fibrinopeptide-a (fpa), d-dimer (dd), and von willebrand factor (vwf) in patients with operable cervical cancer: influence of surgical-pathological stage, tumor size, histologic type, and lymph node status. gynecologic oncology, vol. 49, pp. 354–258. [12] sweeney, j. d., killion, k. m., pruet, c. f., et al. (1990). von willebrand factor in head and neck cancer. cancer, vol. 66, pp. 2387–2389. [13] paczuski, r., bialkowska, a., kotschy, m., et al. (1999). von willebrand factor in plasma of patients with advanced stages of larynx cancer. thrombosis research, vol. 95, pp. 197–200. [14] damin, d. c., rosito, m. a., gus, p., et al. (2002). von willebrand factor in colorectal cancer. international journal of colorectal disease, vol. 17, pp. 42–45. [15] wang, w. s., lin, j. k., lin, t. c., et al. (2005). plasma von willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. world j gastroenterology, vol. 11, pp. 2166–2170. [16] gasic, g. j., gasic, t. b., galanti, n., et al. (1973). platelet-tumor-cell interactions in mice. the role of platelets in the spread of malignant disease. international journal of cancer, vol. 11, pp. 704–718. doi 10.18502/sjms.v14i3.5209 page 102 introduction methods ethical consideration data analysis results and discussion conclusion references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4376 production and hosting by knowledge e case report acquired traumatic diaphragmatic hernia with delayed presentation in a child nader mutwakel osman omdurman islamic university, pediatric and child health department, sudan abstract a congenital diaphragmatic hernia occurs because of embryologic defects in the diaphragm. most patients with congenital diaphragmatic hernias present early rather than late in life, however, adults may present with a congenital hernia that was undetected during childhood. acquired diaphragmatic hernias result from all types of trauma with blunt forces accounting for the majority [1]. the author reports a case of acquired diaphragmatic hernia in a three-year-old boy with a prolonged history of recurrent attacks of vomiting and abdominal pain associated with cough. after taking in to account the full history and investigation, it was proved to be a case of acquired diaphragmatic hernia. keywords: congenital diaphragmatic hernia, acquired diaphragmatic hernia, trauma 1. introduction the vast majority of diaphragmatic hernias encountered by pediatric surgeons are congenital, with a reported prevalence rate of 1 to 3000–5000 live births. acquired or iatrogenic diaphragmatic hernias are probably under-reported in the pediatric population [2]. traumatic diaphragmatic herniation is rare in children. motor vehicle accidents are the most common cause of diaphragmatic herniation in children. as it is rare and overshadowed by associated injuries, the diagnosis of post-traumatic diaphragmatic rupture if often delayed [3]. diaphragmatic hernia requires a high level of suspicion to detect. patients can be asymptomatic in as many as 53% of hernias from blunt trauma and 44% of those from penetrating trauma. routine chest x-ray detects only 33% of hernia when interpreted by the trauma team [4]. missed injuries are associated with significant morbidity and mortality [5]. how to cite this article: nader mutwakel osman (2019) “acquired traumatic diaphragmatic hernia with delayed presentation in a child,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 9–14. doi 10.18502/sjms.v14i1.4376 page 9 corresponding author: nader mutwakel osman; email: nader_osman@hotmail.com received 23 january 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e nader mutwakel osman. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4376&domain=pdf&date_stamp=2019-03-31 mailto:nader_osman@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nader mutwakel osman 2. case report a three-year-old male saudi child was admitted to a governmental general tertiary hospital at ksa as he had recurrent episodes of vomiting over 12–18 months. the last attack was two days prior to admission. the vomiting was initially yellow in color which later became coffee ground. the vomiting was not projectile but associated with diffuse abdominal pain. he had a history of mild nonproductive cough with no signs of respiratory distress. he had no fever, alteration in his bowels, or other systemic symptoms. his past medical history was only remarkable for admission to the surgical ward at the age of 18 months following an accidental pistol shot by his brother while they were playing with their father’s pistol. an inlet injury wound on the left side of the chest with an entry site to the left anterior sixth intercostal space and an exit to the left posterior ninth intercostal space. investigations showed left-side hemothorax and ct chest did not show other complications. the hemothorax was drained and the patient was sent home shortly afterward. since discharge, he had recurrent attacks of unexplained abdominal pain and vomiting. no definite cause was found despite repeated investigations. 3. on examination the patient looked unwell with some signs of respiratory distress. his weight was 13.5 kg (50 centiles), and his observations were within normal. chest examination revealed a small scar at the lower side of the chest wall anteriorly and posteriorly and decreased air entry on the left side of the chest. systemic examination was otherwise unremarkable. 4. investigations hb 11.5 gm/dl (n 11.5 – 15.5 g/dl), wbc 10.2x109 (n 5 – 8x 109 cells/l), with normal differential, platelet 137x109 (n 150 – 400 x 109). bun 25 mg/dl (n 20 –40 mg/dl), creatinine 0.8 mg/dl (n 0.3 – 1 mg/dl), sodium 138 mmol/l (n 135 – 145), potassium 3.9 mmol/l (n 3.5 – 4.5), rbs 130 mg/dl, calcium 9.1 mg/dl (n8.5 –10 mg/dl), magnesium 2.0 mg/dl (n 1.5 – 2.3 mg/dl), abg : ph 7.458(n 7.350 –7.450), pco2 33.1, po2 50.1, hco3 24.3, oxygen saturation 96%. doi 10.18502/sjms.v14i1.4376 page 10 sudan journal of medical sciences nader mutwakel osman plain chest x-ray and with contrast suggest the diagnosis of left-side diaphragmatic hernia (figures 1 and 2), which was confirmed by the ct scan of the chest that showed a large portion of the stomach in the left side of the chest (figure 3). figure 1: cxr on presentation before operation. figure 2: cxr with contrast before operation. doi 10.18502/sjms.v14i1.4376 page 11 sudan journal of medical sciences nader mutwakel osman figure 3: ct scan chest with contrast before operation. 5. hospital course the patient underwent a surgical operation for repairing the defect of diaphragmatic hernia, and a rounded defect was seen in the posterior surface of the left side of the diaphragm, measuring around 5x4 cm. the stomach, splenic flexure of the colon, and omentum have herniated to the left side of the chest which was complicated with adhesions. his post-operative chest x-ray was normal (figure 4). the patient remained at the hospital after the operation for two weeks and was discharged home in good condition with no adverse events. his follow-up at the referred clinic showed no more complains or complications. 6. discussion the vast majority of diaphragmatic hernias are congenital and is rarely associated with a number of different syndromes including beckwith–weidman, goltz syndrome, and denys–drash syndrome. acquired diaphragmatic hernia is a rare occurrence. it can doi 10.18502/sjms.v14i1.4376 page 12 sudan journal of medical sciences nader mutwakel osman figure 4: cxr after operation. result from blunt, penetrating or inadvertent iatrogenic injury. when overlooked, it can potentially be catastrophic [2]. approximately 10% of blunt traumatic injuries in children involved the thorax. among these cases, a traumatic diaphragmatic hernia is a relatively uncommon injury. acute respiratory distress has been reported, and hypoxemia is a common feature in most cases. ventilator support can often be required because of associated pulmonary contusion [4]. despite the fact that chest x-ray can be highly suspicious, delay in diagnosis can occur. it is essential to combine diagnostic tests whenever there is a high index of suspicion [5]. about 30–50% of traumatic diaphragmatic ruptures are missed on initial presentation. only 25–50% of cases will be detected by initial chest radiograph, with an additional 25% with subsequent chest x-ray findings including distortion of diaphragmatic margin, elevated hemidiaphragm (> 4 cm higher on the left rather than the right), and bowel loops in the lung space [5]. conventional ct scan has been reported to have a sensitivity of 14–82% with a specificity of 87%. consistent ct findings include the ‘collar sign’, which is a focal constriction of abdominal viscera (most common), intrathoracic herniation of abdominal contents, and discontinuity in the diaphragm [5]. doi 10.18502/sjms.v14i1.4376 page 13 sudan journal of medical sciences nader mutwakel osman 7. conclusion acquired diaphragmatic hernia is extremely rare in children. however, a high index of suspicion is needed to diagnose this condition particularly if there is a history of trauma. it is therefore recommended that all tools of investigation should be used to detect the diagnosis. references [1] el-gohary, y., schuster, i., scriven, r. j., et al. (2014). iatrogenic diaphragmatic hernia in infants: potentially catastrophic when overlooked. journal of pediatric surgery case reports, vol. 2, no. 11, pp. 515–518. [2] rattan, k. n., magu, s., and agrawal, k. (2005). traumatic diaphragmatic herniation. indian journal of paediatrics, vol. november, no. 72, pp. 985–986. [3] west, k., weber, t., and grosfeld, j. (1981). traumatic diaphragmatic hernia in childhood. journal of paediatric surgery, vol. 3, no. 16, pp. 392–395. [4] kumar, k. and kumar, m. g. (2013). delayed presentation in traumatic diaphragmatic hernia. indian paediatrics, vol. 50, pp. 709–710. doi 10.18502/sjms.v14i1.4376 page 14 introduction case report on examination investigations hospital course discussion conclusion references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5901 production and hosting by knowledge e research article self-care practices of type 2 diabetes patients by socio-demographic and clinical factors: an ordered probit model imran hameed khaliq1, hafiz zahid mahmood2, nusrat manzoor3, farhan hameed khaliq4, khadija asim1, yaseen abdullah1, itzaz aslam5, and shakila zaman1 1department of public health, university of health sciences, lahore, pakistan 2department of economics, comsats university islamabad, lahore campus, pakistan 3department of obstetrics and gynaecology, rai medical college, sargodha, pakistan 4hussain college of health sciences, lahore, pakistan 5johar institute of professional studies, lahore, pakistan abstract background: diabetes prevalence has risen more rapidly in middleand low-income countries and has emerged as the seventh highest cause of death in such countries. socio-demographics, patient knowledge and clinical factors, such as family history of diabetes, have a vital effect on the disease outcomes. this study assessed self-care practices among patients with type 2 diabetes to determine the probability of self-care by predictor variables, including socio-economic and clinical factors, and quantify the marginal effects of these independent variables on different self-care practices among diabetic patients. methods: this exploratory study collected data from 200 type 2 diabetes patients at a branch of private pharmacy in pakistan using a convenient sampling technique and a semi-structured questionnaire. an ordered probit regression model was used to analyze the different self-care practices among diabetic patients. with self-practices ordered in four classes from poor to good, the marginal effects of each socio-economic and clinical factors were also calculated on the likelihood of aforesaid self-care practices among diabetic patients. results: results showed that the relationships of household income, patient’s choice of private or public hospital for treatment, and patient’s weight with selfcare probability were statistically significant. these socio-demographics and clinical indicators significantly influenced each category of self-care practices. conclusion: socio-demographic and clinical factors played a decisive role in the healthcare practices among type-2 diabetes patients. monthly household income, patient’s choice of private or public hospital for treatment, and patient’s weight influenced different levels of self-care practices. income had a negative contribution in poor and fair self-care levels of practices, whereas it had a positive role in average and good self-care levels of practices. keywords: type 2 diabetes; self-care practices; socio-economic factors; developing country how to cite this article: imran hameed khaliq, hafiz zahid mahmood, nusrat manzoor, farhan hameed khaliq, khadija asim, yaseen abdullah, itzaz aslam, and shakila zaman (2019) “self-care practices of type 2 diabetes patients by socio-demographic and clinical factors: an ordered probit model,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 210–224. doi 10.18502/sjms.v14i4.5901 page 210 corresponding author: imran hameed khaliq; department of public health, university of health sciences, khayaban-e-jamia punjab, lahore-54600, pakistan tel: +923227171089 email: imranham90@gmail.com imranhameed@uhs.edu.pk received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e imran hameed khaliq et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:imranham90@gmail.com mailto:imranhameed@uhs.edu.pk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences imran hameed khaliq et al 1. introduction worldwide, diabetes is a chronic disease affecting 450 million people [1]. the global prevalence of diabetes among adults over 18 years of age was 8.5% in 2014 [2]. in 2015, complications related to diabetes resulted in 1.5 million deaths worldwide, and high blood glucose was the cause of another 2.2 million deaths in 2012 [3]. diabetes prevalence has been rising more rapidly in middleand low-income countries and has emerged as the seventh highest cause of death in such countries [4]. the prevalence rate of diabetes in pakistan is 9.8%, with the disease affecting males (10.0%) and females (9.7%) nearly equally [5]. in 2017, there were 7,474,000 cases of diabetes in pakistan [1]. pakistan has a high prevalence of diabetes and is expected to experience further rises in the disease with advancing urbanization and associated factors of unhealthy lifestyles, genetic predisposition, maternal and fetal malnutrition, reduced physical activity, obesity, increased caloric intake and increased smoking rates [6–8]. in addition, management of diabetes and its risk factors remains suboptimal in pakistan [9, 10]. in 2016, complications related to diabetes were responsible for 7,210 male and 9,180 female deaths among persons aged 30–69 years and 9,560 male and 12,800 female deaths among persons aged 70 years and older [11]. diabetes is not a curable disease, but it is controllable; however, if the disease is not controlled, it can lead to poor health, multiple systematic complications and premature death [11]. appropriate self-care practices are critical if individuals with the condition are to minimize their risk of diabetes complications and ensure improved overall health outcomes irrespective of the type of diabetes [12]. these self-care practices relate to age, gender, marital status, education, rural background, family system and socioeconomic status among persons with diabetes [13–16]. socio-demographics, patient knowledge and culture have a vital effect on the disease outcomes [17]. moreover, clinical factors also affect the self-care management among diabetes patients, including glycated hemoglobin levels, treatment received according to the type of diabetes, proper compliance to medication, proper follow-up visits to diabetes clinics and presence of risk factors [18]. both the immediate and life-long impact of diabetes represents a significant burden for healthcare settings. in pakistan, current health expenditure per capita is us $37, which is below the who recommended standard of us $44; as a result, a number of ill persons struggle to accomplish healthy outcomes through the internationally recommended lifestyle modifications [19]. given the rapidly increasing prevalence of diabetes in pakistan, a focus on treatment is crucial. unfortunately, only 58% of pakistani doi 10.18502/sjms.v14i4.5901 page 211 sudan journal of medical sciences imran hameed khaliq et al citizens have an education level of 10 years and above [19]. indeed, diabetes is a chronic disease for which self-care and socio-demographic and clinical factors must be addressed. therefore, the objectives of this study were to assess the self-care practices among diabetic patients, determine the probability of self-care among the target patients by socio-economic and clinical factors and quantify the marginal effects of these independent variables on different self-care practices among diabetic patients. 2. methods 2.1. ethical approval the survey was approved by the ethical review committee, hussain college of health sciences/hussain memorial hospital, lahore (no. hcsc/18/erc/105). all patients in the study provided written informed consent. 2.2. study design and setting this exploratory study was conducted between april and june 2018 at the hussain memorial hospital pharmacy and a branch of clinix pharmacy, lahore, pakistan. moreover, this study protocol adhered to international ethical guidelines for health-related research involving humans [18]. 2.3. inclusion/exclusion criteria inclusion criteria consisted of individuals who were 18 years of age or older, diagnosed with type 2 diabetes at least three years prior at the time of interview and able to provide informed consent. patients who were unable to understand and speak english, urdu, saraiki or punjabi were excluded from the study. 2.4. sample size and sampling technique all patients who fulfilled the inclusion criteria during the study period were included in the study using a purposive sampling technique. doi 10.18502/sjms.v14i4.5901 page 212 sudan journal of medical sciences imran hameed khaliq et al 2.5. study instrument development the multi-disciplinary team of authors developed a semi-structured questionnaire based on literature [20, 21]. the questionnaire was validated in two steps. first, the questionnaire was sent to a diabetes and endocrinology consultant of a private hospital situated in lahore, who provided his expert opinion on the elements of the instrument with respect to importance, simplicity and relativity. second, the survey instrument was pre-tested with 10 diabetic patients to assess presentation, acceptability and ease of understanding of the questions. according to feedback, the questionnaire was slightly modified prior to use. 2.6. data collection the instrument was consisted of three parts: demographic characteristics: eight survey items assessed demographic information of the target patients. respondents were asked to describe their age in years (below 21, 21–30, 31–40, 41–50, 51 and above), gender (male, female), highest level of education (illiterate, literate with no formal education, high school/10th standard, intermediate/12th standard, graduate, post graduate/doctorate), marital status (married, unmarried), monthly household income in pakistani rupees (10,000–20,000, 20,001– 30,000, 30,001–40,000, 40,001–50,000, above 50,000), patient family system (joint family system, nuclear family system), rural background of the patient (yes, no) and preferable patient care center (government hospitals, private hospitals, private clinics). medical characteristics: two open-ended questions assessed the medical characteristics of the patients: duration of diabetes mellitus in years and patient weight in kilograms. variables to measure the self-care practices of diabetic patients: three survey items were included in the questionnaire to compute the self-care practices of diabetic patients by adding binary variables of regular exercise (yes = 1, otherwise 0), cereal foods intake (yes = 1, otherwise 0) and regular self-diabetes check at home (yes = 1, otherwise 0). 2.7. statistical analysis descriptive statistics were rendered for the key variables by estimating frequencies, percentages and measures of central tendencies. doi 10.18502/sjms.v14i4.5901 page 213 sudan journal of medical sciences imran hameed khaliq et al econometric model: an ordered probit model was used to analyze the different selfcare practices among diabetic patients. this model accounted for interdependencies among explanatory variables, marginal effects and statistical significance of variables to demonstrate the comparative degrees to which different factors and combinations of factors account for the different levels of self-care practices of diabetic patients. a set of demographic and medical indicators was chosen as explanatory variables, including age, gender, marital status of the diabetic patients, household income, dummy of rural background of patients (rural area = 1, otherwise 0), patient’s family system (joint family = 1, otherwise 0), duration of diabetes mellitus (in years), patient’s weight (in kilograms), duration of diabetes in other family members (in years), dummy of private hospital treatment (yes = 1, otherwise 0), dummy of private clinic treatment (yes = 1, otherwise 0), dummy of government hospital treatment (yes = 1, otherwise 0), which were denoted by x1, x2, x3, x4, x5, x6, x7, x8, x9, x10, and x11, respectively. different self-care practices of diabetic patients were taken as the dependent variable (y) that showed different self-care practices. the levels of self-care were scored as the following: poor self-care practices = 0, fair self-care practices = 1, average self-care practices = 2 and good self-care practices = 3. self-care practices were computed by adding dummy variables of regular exercise (yes = 1, otherwise 0) cereal foods intake (yes = 1, otherwise 0) and regular self-diabetes check (yes = 1, otherwise 0) at home. stata 10 (statacorp llc texas, usa) was employed to render econometric analysis to achieve the results of the study. 3. results table 1 shows that 64.5% of the diabetic patients were females. fifty-five per cent of patients were 41–50 years of age, followed by 31–40 years (34.5%), 51 years and above (7.5%), 21–30 years (2.5%) and below 21 years (0.5%). sixty-five per cent of patients were married, and 74% patients were living in joint family systems. fifty-six per cent of patients’ families had rural backgrounds, and patients had been suffering from diabetes for 7.46 years on average (sd = 2.75) at the time of data collection. table 2 shows the ordered probit regression results, which describe the impact of independent variables on the probability of self-care practice levels. there were insignificant relationships of demographic indicators, including age, gender, marital status, rural background of patients and family system, with the probabilistic change in self-care practices among diabetic patients. income was statistically significant at the highest level (less than 1%) and positively affected the probability of self-care practices doi 10.18502/sjms.v14i4.5901 page 214 sudan journal of medical sciences imran hameed khaliq et al table 1: demographic/clinical characteristics of diabetes patients [n = 200]. variable frequency percent [%] mean standard deviation age [in years] below 21 1 0.5 – – 21 – 30 5 2.5 – – 31 – 40 69 34.5 – – 41 – 50 110 55 – – 51 and above 15 7.5 – – gender male 71 35.5 – – female 129 64.5 – – marital status unmarried 71 35.5 – – married 129 64.5 – – educational qualification [in years] illiterate 51 25.5 – – literate with no formal education 37 18.5 – – high school / 10th standard 41 20.5 – – intermediate / 12th standard 40 20 – – graduate 21 10.5 – – post graduate / doctorate 10 5 – – household income [in rs.] 10,000 – 20,000 5 2.5 – – 20,001 – 30,000 21 10.5 – – 30,001 – 40,000 53 26.5 – – 40,001 – 50,000 51 25.5 – – patient family system nuclear family system 52 26 – – joint family system 148 74 – – rural background of patient — 111 55.5 – – preferable patient care center government hospital 70 35 – – private hospital 84 42 – – private clinic 46 23 – – duration of diabetes mellitus [in years] – – – 7.46 2.75 patient weight [in kilograms] – – – 71.63 14.66 doi 10.18502/sjms.v14i4.5901 page 215 sudan journal of medical sciences imran hameed khaliq et al among the diabetic patients. specifically, a rise in income by one pakistani rupee (pkr) increased the probability of self-care practices by 0.23%. table 2: probability of self-care practices change due to demographic and medical factors [n = 200] using [statistical procedure]. indicators coefficient standard error p-value 95% confidence interval age 0.06 0.12 0.611 –0.17217 0.29307 gender 0.31 0.33 0.344 –0.33203 0.95190 dummy-marital status –0.27 0.32 0.405 –0.91055 0.36740 household income 0.23 0.07 0.001 0.10398 0.39458 rural background of patient 0.18 0.16 0.265 –0.13575 0.49301 family system 0.05 0.18 0.760 –0.29609 0.40520 duration of diabetes mellitus –0.05 0.03 0.057 –0.11131 0.00167 patient’s weight 0.01 0.01 0.048 0.00010 0.02143 duration of diabetes to other family members 0.03 0.14 0.818 –0.24415 0.30911 dummy-private hospital treatment 0.50 0.18 0.006 0.14635 0.85385 dummy-private clinic treatment 0.18 0.21 0.395 –0.23754 0.60244 lr chi2 [11] = 25.62; prob > chi2 = 0.0074; and pseudo r2 = 0.0500 table 2 also shows the impact of clinical attributes of the diabetic patients on the probability of change in self-care practices. the relationships of diabetes of other family members (p = 0.818) and dummy of patient’s choice of private clinic for treatment compared with public sector hospitals (p = 0.395) with self-care practices were statistically insignificant, and the relationship of duration of diabetes with self-care practices (p = 0.057) was near to significant. in contrast, household income (p = 0.001), patient’s weight (p = 0.048) and dummy of patient’s choice of private hospitals for treatment compared with public sector hospitals (p = 0.006) with the probability of change in selfcare practices were statistically significant. moreover, there was a negative relationship between duration of diabetes and probability of self-care practices (coefficient = -0.05), which showed that an increase of one year in the duration of diabetes resulted in a decline of 0.05% in the probability of self-care practices by the targeted patients. on the other hand, there was a positive relationship between patient’s body weight and probability of self-care practices (coefficient = 0.01) by the patients, which was witnessed as significant at 5%. table 2 further shows that a rise of self-care practices by approximately 0.01% augments the probability of an increase in the patient’s body weight by approximately 1 kg. regression analysis used the dummy of patients’ choice of private clinic and private hospitals for treatment reference to public sector hospitals. patients who visited doi 10.18502/sjms.v14i4.5901 page 216 sudan journal of medical sciences imran hameed khaliq et al private hospitals had a higher probability of self-care practices as compared with the patients seeking treatment from public sector hospitals. furthermore, the regression model showed acceptable goodness of fit and was statistically significant as per given values of probability of chi square (prob > chi2 = 0.0074). table 3: marginal effects of predictors on different self-care practices of diabetic patients [n = 200]. indicators dy/dx s. error z p-value 95% confidence interval poor self-care practices of diabetic patients age –0.0143 0.0281 –0.51 0.611 –0.06930 0.04072 gender –0.0767 0.0848 –0.90 0.366 –0.24286 0.08948 dummy–marital status 0.0616 0.0710 0.87 0.386 –0.07761 0.20076 household income –0.0589 0.0182 –3.24 0.001 –0.09462 –0.02323 rural background of patient –0.0426 0.0387 –1.10 0.271 –0.11856 0.03330 family system –0.0131 0.0434 –0.30 0.764 –0.09819 0.07206 duration of diabetes mellitus 0.0130 0.0069 1.88 0.060 –0.00054 0.02645 patient’s weight 0.0025 0.0013 –1.95 0.051 71.60800 0.00001 duration of diabetes to other family members 76774 0.0334 0.23 0.818 –0.07310 0.05775 dummy-private hospital treatment –0.1133 0.0403 –2.81 0.005 –0.19228 –0.03442 dummy-private clinic treatment –0.0410 0.0457 –0.90 0.370 –0.13053 0.04858 fair self-care practices of diabetic patients age –0.0097 0.0192 –0.51 0.612 –0.04747 0.02797 gender –0.0464 0.0456 –1.02 0.309 –0.13576 0.04298 dummy-marital status 0.0457 0.0571 0.80 0.424 –0.06626 0.15758 household income –0.0402 0.0141 –2.85 0.004 –0.06785 –0.01257 rural background of patient –0.0284 0.0256 –1.11 0.268 –0.07852 0.02181 family system –0.0086 0.0279 –0.31 0.756 –0.06328 0.04599 duration of diabetes mellitus 0.0088 0.0049 1.79 0.074 –0.00085 0.01853 patient’s weight –0.0017 0.0009 –1.86 0.063 –0.00357 0.00009 duration of diabetes to other family members –0.0052 0.0228 –0.23 0.818 –0.04987 0.03940 dummy-private hospital treatment –0.0827 0.0333 –2.49 0.013 –0.14788 –0.01747 dummy-private clinic treatment –0.0311 0.0387 –0.80 0.422 –0.10700 0.04478 average self-care practices of diabetic patients age 0.0126 0.0249 0.51 0.612 –0.03611 0.06136 gender 0.0677 0.0745 0.91 0.364 –0.07838 0.21377 dummy-marital status –0.0534 0.0602 –0.89 0.375 –0.17126 0.06455 household income 0.0521 0.0176 2.95 0.003 0.01751 0.08663 rural background of patient 0.0376 0.0345 1.09 0.276 –0.03003 0.10530 family system 0.0116 0.0386 0.30 0.764 –0.06406 0.08721 duration of diabetes mellitus –0.0115 0.0063 –1.82 0.069 –0.02380 0.00090 doi 10.18502/sjms.v14i4.5901 page 217 sudan journal of medical sciences imran hameed khaliq et al indicators dy/dx s. error z p-value 95% confidence interval patient’s weight 0.0022 0.0012 1.89 0.059 –0.00009 0.00459 duration of diabetes to other family members 0.0068 0.0295 0.23 0.818 –0.05103 0.06460 dummy-private hospital treatment 0.0964 0.0352 2.74 0.006 0.02733 0.16545 dummy-private clinic treatment 0.0126 0.0249 0.51 0.612 –0.03611 0.06136 good self-care practices of diabetic patients age 0.0114 0.0225 0.51 0.611 –0.03259 0.05541 gender 0.0554 0.0558 0.99 0.321 –0.05395 0.16473 dummy-marital status –0.0539 0.0681 –0.79 0.429 –0.18737 0.07962 household income 0.0471 0.0149 3.15 0.002 0.01781 0.07631 rural background of patient 0.0334 0.0298 1.12 0.264 –0.02514 0.09185 family system 0.0101 0.0327 0.31 0.757 –0.05399 0.07426 duration of diabetes mellitus –0.0103 0.0056 –1.86 0.063 –0.02125 0.00055 patient’s weight 0.0020 0.0011 1.93 0.054 –0.00003 0.00410 duration of diabetes mellitus to other family members 61317 0.0267 0.23 0.818 –0.04612 0.05838 dummy-private hospital treatment 0.0996 0.0392 2.54 0.011 0.02283 0.17644 dummy-private clinic treatment 0.0365 0.0455 0.80 0.422 0.05267 0.12576 table 3 shows the marginal effects of different independent variables on the individual self-care levels of the target patients. it showed that household income (p = 0.001) and dummy of patient’s choice of private hospitals for treatment compared with public sector hospitals (p = 0.005) were significantly influencing each category of the patients with poor self-care practices. income had a negative contribution in poor (dy/dx = -0.0589, z = -3.24) and fair (dy/dx = -0.0402, z = -2.85) self-care level of practices, whereas it had a positive role in average (dy/dx = 0.0521, z = 2.95) and good (dy/dx = 0.0471, z = -0.79) self-care levels of practices. table 3 further shows the marginal effects of different independent variables on the fair, average and good self-care practices of diabetic patients. 4. discussion the results of our study showed that household income was the only socio-economic indicator that was statistically significant and positively affected the probability of selfcare practices among diabetic patients. additionally, patient’s choice of hospital for treatment and clinical factors, including duration of diabetes, as well as patients’ weight all showed a statistically significant relationship with self-care probability. moreover, household income, duration of diabetes, body weight of the patients and patient’s choice doi 10.18502/sjms.v14i4.5901 page 218 sudan journal of medical sciences imran hameed khaliq et al of private hospitals for treatment in comparison to public sector hospitals significantly influenced each category of self-care practices exercised by the patients. income had a negative contribution in poor and fair self-care practices, whereas it positively affected average and good self-care practices. the results of our study were consistent with previous studies that showed a positive and significant relationship between probability of self-care practices and household income [22–24]. the economic foundation of health and self-care practices (i.e. monthly household income) conforms to maslow’s hierarchy of needs that places meeting basic physiological needs ahead of the pursuit of higher-level health needs [23]. therefore, patients with higher income might have better self-care health practices owing to better education, access to healthcare resources, economic capacity to develop their own way of life actively and nutritive diets [23, 25]. conversely, the self-reported poor self-care practices of low-income patients might be due to low-education and a high dependency on the household breadwinner with their main consumption focused on clothing, food and other physiological needs, which leads them to pay less attention to their health [22, 23]. although patients have reported low quality of services and longer wait times in public hospitals for appointments, treatment and follow-up, these disadvantages did not lead them to distrust public hospitals [26]. on the other hand, patients who provided positive feedback related to shorter wait times and higher quality of healthcare services in private hospitals generally indicated a distrust of public hospitals [26]. these results were consistent with a previous study conducted in lahore, which showed that private hospitals were delivering better quality of services to their patients as compared to public hospitals [27]. however, contradictory results from a study conducted in islamabad indicated that patients felt public hospitals were providing better services concerning lethal diseases, such as diabetes, when compared with private hospitals [28]. in the systematic review by xiaoping et al., although many studies found that patients with longer duration of disease managed diabetes better [29], this was not supported by others [29, 30]. it is an established fact that diabetes can be controlled by taking various cautionary measures but is not curable. the reason behind this negative relationship might be due to the persistency and chronicity of diabetes [31]. owing to longer duration of diabetes, patients might become frustrated and relax their cautionary attitude towards self-care practices [31]. moreover, a previous study also showed that patients with chronic type 2 diabetes who administered insulin as part of their good self-care practices were more likely to gain weight [32]. doi 10.18502/sjms.v14i4.5901 page 219 sudan journal of medical sciences imran hameed khaliq et al generally, the intelligent quotient and decision power of two people is thought to be higher when compared with an individual [34]. thus, married people may have better level of self-care practices as compared with those who are single. as far as self-care practices and gender nexus is concerned, the probability of good self-care practices is expected to be higher in males compared with females. as pakistani society is male-centric with relatively high education and free mobility afforded to males only, they might have better opportunities to interact with various community members, understand, learn and practice good self-care [34]. it might be the reason for better selfcare levels of male patients than their women counterparts. a previous study showed significant relationship between socio-economic indicators including age, gender and marital status with different levels of self-care practices [29]. however, the results of our study showed contradictory results in line with the results of previous studies regarding age [22]. another study showed that there was no significant relationship between quality of life of diabetic patients and their age, gender and marital status [24]. the strengths of this study include its use of well-validated measures of different levels of self-care practices to cope with diabetes. another strength is using the interview method for data collection, which is a more appropriate method compared with selfcompletion of a questionnaire method due to the low literacy level of the participants. however, the limitations of this study include the cross-sectional nature of the study, which makes us cautious about causal relations. this study may be supplemented in the future with larger-scale surveys to strengthen the conclusions drawn about the socio-economic and clinical factors influencing self-care practices of diabetic patients. 5. conclusion in conclusion, socio-demographics and clinical indicators, including monthly household income, patient’s choice of private hospitals for treatment in comparison to public sector hospitals and patient’s weight, influence different levels of self-care practices among diabetic patients. briefly, socio-demographic and clinical indicators played a decisive role in the health and self-management among type 2 diabetes patients. income had a negative contribution in poor and fair self-care levels of practices, whereas it had a positive role in average and good self-care levels of practices. doi 10.18502/sjms.v14i4.5901 page 220 sudan journal of medical sciences imran hameed khaliq et al acknowledgements the authors sincerely thank kathleen and jennifer l. who supported in the proof-reading and content reviewing of the manuscript. references [1] international diabetes federation. 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(2013). role of self-care in management of diabetes mellitus. journal of diabetes & metabolic disorders, vol. 12, no. 1, p. 14. doi: 10.1186/2251-6581-12-14. doi 10.18502/sjms.v14i4.5901 page 224 introduction methods ethical approval study design and setting inclusion/exclusion criteria sample size and sampling technique study instrument development data collection statistical analysis results discussion conclusion acknowledgements references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5909 production and hosting by knowledge e research article the irrational use of antibiotics among doctors, pharmacists and the public in river nile state, sudan sara h oleim1, sufian k noor2, sarra o bushara2, m h ahmed3, and wadie elmadhoun4 1department of pharmacology, faculty of medicine and health sciences, nile valley university, atbara, sudan 2department of medicine, faculty of medicine and health sciences, nile valley university, atbara, sudan 3department of medicine and hiv metablolic clinic, milton keynes university hospital nhs foundation, eaglestone milton keynes, buckinghamshire, uk 4department of pathology, faculty of medicine and health sciences, nile valley university, atbara, sudan abstract background: inappropriate antibiotic prescription, dispensing and self-medication are alarmingly high worldwide. the problem is more so in developing countries, including sudan, where resistance to life-saving drugs is emerging. objective: to assess the prevalence of irrational use of antibiotics among doctors, pharmacists and the public in river nile state (rns), sudan. methodology: a descriptive cross-sectional study was conducted, in march 2014 through april 2014. the study population was 278 individuals, composed of 100 doctors, 78 pharmacists selected randomly from hospitals, pharmacies and health centers, besides 100 adults from the community. three different intervieweradministered standardized pre-tested questionnaires were used for data collection. results:antibiotic misuse is common practice among both medicals as well as the public in rns. this was evidenced by the facts that 92% of doctors prescribed antibiotics without culture and sensitivity results, more than 93% of pharmacists dispensed antibiotics as over the counter medications and that 89% of participants used antibiotics without consulting a doctor. more than 90% of the misused antibiotics werebeta-lactams and macrolides and the most common indication for their use was cough and common cold. conclusion: irrational use of antibiotics is a widespread practice in rns among all stakeholders. therefore, health care policy makers and care providers should have antibiotic policy and clear to follow obligatory guidelines and to ensure that the public and every prescriber/dispenser conforms to that policy. moreover, increasing awareness about the appropriate antibiotic use among all stakeholders is of paramount importance. how to cite this article: sara h oleim, sufian k noor, sarra o bushara, m h ahmed, and wadie elmadhoun (2019) “the irrational use of antibiotics among doctors, pharmacists and the public in river nile state, sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 276–288. doi 10.18502/sjms.v14i4.5909 page 276 corresponding author: sara h oleim received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e sara h oleim et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sara h oleim et al 1. introduction since their discovery in the 1940s, antibiotics have been imperative to the modern health care system. they are not only used to treat serious infections but also to prevent surgical wound infection and as prophylaxis forimmune-compromised individuals [1]. there is a worldwide progressive increase in antibiotic consumption, particularly in developing countries [1]. in fact, antibiotics are the most commonly used and misused medications [2, 3]. in some developing countries, it is estimated that 20 percent of antibiotics are used in hospitals and other healthcare facilities, whereas, 80 percent are used in the community, either prescribed by healthcare providers or purchased directly by consumers or caregivers without prescription [4]. it is a known fact that the greater the volume of antibiotics used, the greater the bacterial resistance prevails. this is evidenced by the decline in the stock of effective antibiotics available for treating serious infections. unfortunately, resistance to all first-line and last-resort antibiotics is rising [1]. the irrational use of antibiotics is not only lethal to some patients but also jeopardizing to the economy of the country; as the cost of antibiotic resistance is huge even in developed countries, let apart low and middle-income countries(lmics). for instance, in the u.s., the direct and indirect costs of microbial resistance is estimated as more than 50 $ billion annually [1]. in a resource-limited country, such as sudan, reducing the health care expenses for irrationally used antibiotics is of paramount importance for health economics as well as for individual patients. investigating irrational use of antibiotics implies monitoring, evaluation, and suggesting modifications in doctor’s prescription habits, pharmacist’s dispensing practice and the community usage at large, so as to rationalize the use of antibiotics [5, 6]. to achieve this goal in antibiotic usage, it is important to provide health policy makers by high-quality research addressing this topic. therefore, we aimed by this study to determine the magnitude of the irrational use of antibiotics among all stakeholders in river nile state, sudan and to urge recommendations that help solve this challenge. 2. methods 2.1. settings the study was conducted in the main cities of rns, namely atbara, ed damer, berber and abu hamadduring the period from the 1st of march through april, 30th, 2014. rns doi 10.18502/sjms.v14i4.5909 page 277 sudan journal of medical sciences sara h oleim et al covers an area of 124,000 km2 and is populated by about 1,300,000 individuals, 60% are residing in rural areas.there are about 11 referral hospitals, 15 rural hospitals and more than 80 health centers and dispensaries. besides, there are about 300 pharmacies in rns. the workforce is about 400 doctors with different career grades, whereas the pharmacists are about 100. 2.2. study population this descriptive cross-sectional study included 278 participants, consisting of 100 doctors selected randomly from the five hospitals in rns, namely, atbara teaching hospital, alsalam university hospital, the military hospital, the police hospital , atbara medical complex, ed damer hospital, berber hospital, as well as many health centers. these health facilities were selected by simple tossing technique from the list of facilities in rns.seventy-eight pharmacistsworking in rns pharmacies, both public and private, were also included. besides, one hundred individuals, aged 20 years and above, were selected randomly from the community of rns.it is to be mentioned that, antibiotics are commonly dispensed as over the counter (otc) medications inboth public as well as private pharmacies. 2.3. data collection tools three different questionnaires were constructed for doctors, pharmacists, and patients to gather socio-demographic characteristics, knowledge, attitudes and practices towards prescription, dispensing and self-medication of antibiotics respectively. the questionnaires were standardized, pre-tested and validated to gather the required data from participants. 2.4. data analysis methods obtained data were validated, entered and double checked and analyzed using spss v.20 computer program.descriptive statistics was applied to data. frequencies, means, and standard deviations were calculated. doi 10.18502/sjms.v14i4.5909 page 278 sudan journal of medical sciences sara h oleim et al 2.5. ethical issues an informed written consent was obtained from each participant prior to enrollment. the objective of study was fully explained and that participation was optional.confidentiality of participants and data was secured. an ethical approval was obtained from the ethical committee of faculty of medicinenile valley university. 3. results 3.1. overview this study included 100 treating doctors, 78 dispensing pharmacists and 100 individuals from the local community of rns. individuals were interviewed separately for their practices about the irrational use of antibiotics. overall, there was high prevalence of antibiotic misuse by both medicals as well as the public. this was evidenced by the facts that92% of doctors prescribe antibiotics without culture and sensitivity results, more than 93% of pharmacists dispense antibiotics as over the counter medications and that 89% of participants use antibiotics without consulting a doctor. 3.2. socio-demographic characteristics of study population there were 171 (62.5%) females and 107 (37.5%) males, giving a female to male ratio of 1.7:1. most practicing doctors (92%) and pharmacists (96.0%) were baccalaureate holders, the rest were masters or ph.d. holders. while most doctors were working at public hospitals (78.0%), most pharmacists (91.1%) were working at private pharmacies. moreover, all pharmacists were assisted by drug sellers, among them, 50.0% had neither license nor certificate for practice (drug sellers were not interviewed). table 1 displays the socio-demographic characteristics of study population. 3.3. antibiotic practices among doctors among participating doctors, 87.0% prescribe antibiotics based on clinical judgment, while only less than 10.0% used culture and sensitivity results to guide treatment. therefore, broad-spectrum antibiotics were preferable for 64.0% of doctors vs. 8.0% for narrow spectrum antibiotics. beta-lactams were the most commonly prescribed doi 10.18502/sjms.v14i4.5909 page 279 sudan journal of medical sciences sara h oleim et al antibiotics (89.0%). table 2 shows the common practices of treating doctors towards antibiotic prescription. 3.4. antibiotic practices among pharmacists most pharmacists (93.6%) dispensed antibiotics without prescriptions, or based on their own diagnosis (93.5%) for patients’ complaints. moreover, 89.8% of pharmacists stated that they permit their assistants to dispense antibiotics without prescription. more than 60% of pharmacists admitted that they dispensed antibiotics as incomplete dose based on patients’ request. table 3 reveals the common practices of pharmacists towards antibiotics dispensing. 3.5. antibiotic practices among the public a minority of participants from the community (11.0%) obtained their antibiotics through prescription by doctors, while 55.0% got them directly from pharmacies. the most common cause for using antibiotics (82.0%) was cough and common cold. in addition, 43.0% discontinued their treatment when improved, whereas, 41.0% shifted to another antibiotic when there had been no response to their illness (table 4). 4. discussion in sudan, there are few published studies about the irrational use of antibiotics [7, 8]. while, in river nile state, this is the first investigation uncovering the magnitude of this health-threatening problem. it is obvious, in this study, that antibiotics are widely misused in our settingsby all stakeholders, including physicians, pharmacists and the public. reported promoters for antibiotic misuse include lack of knowledge, absence of clear antibiotic policies and regulations, in addition to the powerful pharmaceutical marketing [9, 10]. these same factors may be applied to our situation. doctors should be aware to prescribe antibiotics according to the principles of antimicrobial stewardship.the antimicrobial stewardship clinical care standard aims to ensure that a patient with a bacterial infection receives optimal treatment with antibiotics. optimal treatment means treating patients with the right antibiotic to treat their condition, the right dose, by the right route, at the right time and for the right duration based on accurate assessment and timely review [11]. doi 10.18502/sjms.v14i4.5909 page 280 sudan journal of medical sciences sara h oleim et al table 1: the socio-demographic characteristics of study population. river nile state, sudan 2014 (n=278). category characteristic variable n % doctors sex male 38 38.0 female 62 62.0 age group 20 – 29 62 62.0 30 39 28 28.0 40-49 5 5.0 50-59 4 4.0 > 60 1 1.0 professional career specialist 8 8.0 registrar 8 8.0 dentist 15 15.0 general practitioner 42 42.0 house officer 27 27.0 place of work public hospital 78 78.0 private hospital 10 10.0 primary health care center 12 12.0 pharmacists sex male 26 33.3 female 52 66.7 age group 20 – 29 42 53.6 30 39 25 32.1 40-49 6 7.2 50-59 5 7.1 place of work hospital pharmacy 7 8.9 private pharmacy 71 91.1 qualifications bachelor degree 75 96.0 masters degree 3 4.0 employing drug sellers yes 78 100.0 qualifications of drug sellers diploma of pharmacy 39 50.0 no license/certificate 39 50.0 participants from community sex male 43 43.0 female 57 57.0 age group 20 – 29 56 56.0 30 39 24 24.0 40-49 13 13.0 50-59 5 5.0 more than 60 2 2.0 level of education illiterate 15 15.0 secondary 35 35.0 college 50 50.0 doi 10.18502/sjms.v14i4.5909 page 281 sudan journal of medical sciences sara h oleim et al table 2: the common practices of treating doctors towards antibiotic prescription in river nile state, sudan 2014 (n=100). practice variable n % basis for antibiotic prescription in your practice clinical diagnosis 87 87.0 culture result 8 8.0 experience/trend in hospital 5 5.0 basis for antibiotic selection for a specific patient/illness your own experience in dealing with the disease 60 60.0 use the most potent antibiotic at hand 17 17.0 culture result 7 7.0 senior’s experience 15 15.0 preference of antibiotic spectrum broad spectrum 64 64.0 narrow spectrum 8 8.0 no specific preference 28 28.0 the most commonly prescribed group of antibiotics in your everyday practice beta-lactams 89 89.0 macrolides 8 8.0 quinolones 2 2.0 aminoglycosides 1 1.0 estimated frequency of using culture and sensitivity in everyday practice never requested before 15 15.0 less than 25% of cases 45 45.0 more than 25%and up to 50% 27 27.0 more than 50% and up to 75% 11 11.0 more than 75% 2 2.0 indications for requesting culture and sensitivity in your everyday practice failure to find out a clinical diagnosis 38 38.0 poor or no response to prescribed antibiotic 47 47.0 never request culture 15 15.0 barriers for using culture and sensitivity services unsatisfactory laboratory results 43 43.0 poor economic status of patients 38 38.0 no specific cause 19 19.0 more than half of doctors in this study were females this may reflect the current situation of female predominance in the medical professions. whether gender has an effect on pattern of prescription is a point that is to be determined by further research. younger age groups (below 30 years) constituted more than half of study population, and most of them were either house officers or general practitioners. this fact may attribute to their improper prescription practices due to lack of adequate knowledge and experience in the absence of training workshops about the rational use of antibiotics; doi 10.18502/sjms.v14i4.5909 page 282 sudan journal of medical sciences sara h oleim et al table 3: the common practices of pharmacists towards antibiotic dispensing in river nile state, sudan 2014 (n=78). practice variable n % frequency of dispensing antibiotics without prescription yes 73 93.6 no 5 6.4 permission for drug sellers to dispense antibiotics without prescription yes 70 89.8 no 8 10.2 frequency of dispensing antibiotics based on pharmacist’s own diagnosis for patients yes 73 93.6 no 5 6.4 frequency of pharmacists allowing drug sellers to dispense antibiotics based on seller’s diagnosis for patients yes 70 89.7 no 8 10.3 the most common dispensed antibiotics without prescription beta-lactams 61 78.2 macrolides 17 21.8 pharmacist’s estimation for patients getting antibiotics without prescription less than 25% 16 20.5 26%-50% 34 43.6 51%-75% 25 32.1 more than 75% 3 3.8 pharmacists specifying duration of antibiotic course yes 62 79.5 no 16 20.5 pharmacists dispensing antibiotic as incomplete dose yes 48 61.5 no 30 38.5 therefore, empirical coverage by broad spectrum antibiotic may seem a safe way for some of them. in this study, most of participant doctors were public employees in hospitals or health centers, where most patients were covered by health insurance, facilitating access to low price antibiotics. this, seemingly, low economic burden on patients may encourage doctors to prescribe irrationally. however, the overall cost of this practice on the health system economy is devastating.it is also evident from this study that only a minority of doctors request culture and sensitivity services, whereas the majority use only their clinical judgment when prescribing antibiotics to their patients. moreover, 15% of doctors had never requested culture and sensitivity test for their patients before. for instance, the culture and sensitivity test is available and costs lesser than one dose of a commonly prescribed antibiotic (ceftriaxone). therefore, about two third of doctors prescribe broadspectrum antibiotics, mostlybeta-lactams and macrolides, for their patients, a situation doi 10.18502/sjms.v14i4.5909 page 283 sudan journal of medical sciences sara h oleim et al table 4: the common practices of community participants for antibiotics in river nile state, sudan 2014 (n=100). practice variable n % the main source for getting antibiotics doctor 11 11.0 same antibiotic used for a similar previous illness 25 25.0 directly from pharmacy 55 55.0 any antibiotic available at home 9 9.0 the most common indications for using antibiotics cough and common cold 82 82.0 wounds 13 13.0 other illnesses (e.g. sore throat and tonsillitis). 5 5.0 the most commonly used antibiotics azithromycin 27 27.0 amoxicillin 20 20.0 the combination of amoxicillin with clavulanic acid 11 11.0 do not know/remember 42 42.0 preference for route of administration oral 63 63.0 parentral 37 37.0 no specific preference 10 10.0 patients on chronic medications yes 16 16.0 no 84 84.0 time for treatment discontinuation when feels better 43 43.0 when stock finishes 24 24.0 based on doctor’s prescription 33 33.0 what to do if first used antibiotic was not effective refer to doctor 49 49.0 shift to another antibiotic 41 41.0 repeat the same course of antibiotic 10 10.0 that is similar to doctors’ practice in greece [12]. this high antibiotic prescription practice is higher than that reported in the u.s and canada, where over-prescription is about 50% [13]. we believe that, this empirical and irrational use of antibiotics basically violates the hippocratic oath for doctors that states “i will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone”, because by so doing doctors would harm not only individual patients but also the whole community. the role of pharmacists in antibiotic misuse in this study is remarkable. pharmacists in rns were mostly bachelor holders, most of them were working in private pharmacies, doi 10.18502/sjms.v14i4.5909 page 284 sudan journal of medical sciences sara h oleim et al and half of pharmacists were assisted by non-qualified drug sellers. these facts may attribute to antibiotic misuse: indicating lack of appropriate knowledge.profitability was a major concern for private pharmacies rather than rationalizing antibiotic use. this was evidenced by the fact that almost all pharmacists (93.6%) and drug sellers dispensed antibiotics not only without prescription but also based on their own diagnosis for individual patient’scomplain. this high inappropriate prescription was similar to a study in india (94%) [14] and veitnam (90%) [10] but higher than that reported from zimbabwe (39%) [15], saudi arabia (78%) [16] and syria (87%) [17]. added to this malpractice, is dispensing of incomplete dosage of antibiotics, which they justified by patient’s convenience. this is similar to the practice reported from egypt [18]. in this study, more than half of community individuals obtained antibiotics directly from pharmacies, a situation that is similar in khartoum, sudan [7], and many other countries [19–23]. in this regard, the presence of regulations prohibiting malpractice would help reduce easy access to life-saving medications. cough and common cold were the most indications for using antibiotics in this study, a situation that is similar to other developing countries [24–29]. this practice hinders the fact that antibiotics should not be used to treat mild ailments, but rather to treat serious infections [1]. this misconception for using antibiotics for common cold and other viral infections may be rectified by health education for the community. almost half of public participants discontinued medications when symptoms improved, but if not improved, more than 40% shifted to another antibiotic through selfmedication. self-medication in this study is similar to a study conducted in khartoum [8]. this study has some limitations. the small sample size, especially for the public, may not allow generalizability of the results to the whole population of rns. this limited sample size was mainly due to logistic shortages. however, this sample size included 20%-25% of the doctors’ working force and almost 90% of practicing pharmacists in rns. therefore, we assume that these two important cohorts were representative for their populations. however, a study with a larger sample size is recommended.other limitationswere the subjectivity of the questions, recall problems and the effect of social norms. in this regard, the researchers assured participants about the voluntariness nature of the study, absence of identifiers for participants and confidentiality of their responses.it would be more objective if prescriptions from treating doctors, who participated in this study, were revised for the frequency of antibiotics prescribed for patients, and that pharmacists dispensing practices were assessed in reality. despite doi 10.18502/sjms.v14i4.5909 page 285 sudan journal of medical sciences sara h oleim et al these limitations, this study is comprehensive and novel, as it investigated antibiotic practices among all stakeholders: doctors, pharmacists, and the public.the second point of strength is that this study is the first one documenting the irrational use of antibiotics in rns, therefore, it may constitute a database for many studies to come. in conclusion, irrational use of antibiotics is a widespread practice in rns among all stakeholders. therefore, health care policy makers and care providers should have antibiotic policy and clear to follow obligatory guidelines and to ensure that the public and every prescriber/dispenser conforms to that policy. moreover, increasing awareness about the appropriate antibiotic use among all stakeholders is of paramount importance. references [1] center for disease dynamics, economics & policy. 2015. state of the world’s antibiotics, 2015. cddep: washington, d.c. 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[21] skliros e,merkourisp, papazafiropoulou a, gikas a,matzouranisg, papafragos c et al.self-medication with antibiotics in rural population in greece: a cross-sectional multicenter study. bmc fam. pract. 2010; 11. doi:10.1186/1471-2296-11-58. [22] al-azzamsi , al-huseinba, alzoubi f, masadeh mm, al-horanimas. self-medication with antibiotics in jordanian population. int. j. occup. med. environ. health2007; 20: 373–80. doi 10.18502/sjms.v14i4.5909 page 287 sudan journal of medical sciences sara h oleim et al [23] widayati a, suryawati s, de crespigny c, hiller j.e. self medication with antibiotics in yogyakarta city indonesia: a cross sectional population-based survey. bmc res. notes 2011:4, doi:10.1186/1756-0500-4-491. [24] bi p, tong sl, parton ka: family self-medication and antibiotics abuse for children and juveniles in a chinese city. socsci med 2000,50:1445–50. [25] remesh a, samna salim am, gayathri un, retnavally kg. antibiotics prescribing pattern in the in-patient departments of a tertiary care hospital. pharmapract 2013,4:71–6. [26] okumura j, wakai s, umenai t. drug utilisation and self-medication in rural communities in vietnam. socsci med2002;54:1875–86. [27] murphy mc, bradley c, byrne s.antibiotic prescribing in primary care, adherence to guidelines and unnecessary prescribing-an irish perspective, bmc family practice 2012; 13(1): 43. [28] muhammad s, muhammad f, mariah i, amjad h. evaluation of antibiotic use behavior in cold and flu amongst the students of bahauddinzakariya university multan pakistan.pak j pharm 20-23 (1&2) 15-2, 2007-2010 [29] sun q, dyar o, zhao l, tomson g, nilsson l,grape m et al. overuse of antibiotics for the common cold – attitudes and behaviors among doctors in rural areas of shandong province, china. bmc pharmacoltoxicol 2015; 16: 6. doi 10.18502/sjms.v14i4.5909 page 288 introduction methods settings study population data collection tools data analysis methods ethical issues results overview socio-demographic characteristics of study population antibiotic practices among doctors antibiotic practices among pharmacists antibiotic practices among the public discussion references sudan journal of medical sciences volume 13, issue no. 1, doi 10.18502/sjms.v13i1.1687 production and hosting by knowledge e research article knowledge, practice and acceptability of hpv vaccine by mothers of adolescent girls in ilorin, nigeria kikelomo t. adesina1 , aishat saka2, salamat a. isiaka-lawal3, omotayo o. adesiyun4, a. gobir4, adebunmi o. olarinoye1, and grace g. ezeoke1 1senior lecturer/honorary consultant, department of obstetrics and gynaecology, university of ilorin/university of ilorin teaching hospital, nigeria 2senior lecturer/honorary consultant, department of paediatrics and child health, university of ilorin/university of ilorinteaching hospital, nigeria 3consultant obstetrician and gynaecologist, department of obstetrics and gynaecology, sobi specialist hospital, ilorin, nigeria 4associate professor/honorary consultant, department of paediatrics and child health, university of ilorin/university of ilorinteaching hospital, nigeria abstract background: human papilloma virus (hpv) is a sexually transmitted cause of carcinoma of the cervix. an important determinant of the success of a primary preventive strategy like hpv vaccination is the knowledge and willingness of parents to vaccinate adolescents before sexual debut. materials and methods of study: a cross sectional descriptive survey of mothers of girls in 8 secondary schools in ilorin was carried out from february to april 2015. schools were selected using multi staged sampling. descriptive and inferential statistics were performed with chi square and anova. results: there were 470 questionnaires returned for analysis out of 600, giving a response rate of 78.3%. one hundred and sixty-one (34.3%) knew hpv to be sexually transmitted infection and 40.4% knew it was the cause of cervical cancer. while 35.1% were aware of hpv vaccine, only 1.9% had ever vaccinated their children. less than half (44.9%) were willing to vaccinate their children. women with good knowledge of hpv and cervical cancer were more willing to vaccinate their children than women with poor knowledge (p <0.001). conclusion: there is poor knowledge of hpv and practice of vaccination among mothers in llorin. willingness of mothers to vaccinate their daughters is suboptimal. mother’s knowledge is an important determinant of hpv vaccination of adolescents. keywords: human papilloma virus, hpv vaccine, prepubertal hpv vaccination, adolescent girls’ vaccine, ilorin how to cite this article: kikelomo t. adesina, aishat saka, salamat a. isiaka-lawal, omotayo o. adesiyun, a. gobir, adebunmi. o. olarinoye, and grace g. ezeoke, (2018) “knowledge, practice and acceptability of hpv vaccine by mothers of adolescent girls in ilorin, nigeria,” sudan journal of medical sciences, vol. 13 (2018), issue no. 1, 33–49. doi 10.18502/sjms.v13i1.1687 page 33 corresponding author: k. t. adesina; email: teminikike@yahoo.com received 6 december 2017 accepted 10 march 2018 published 14 march 2018 production and hosting by knowledge e kikelomo t. adesina et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0001-9741-3968 mailto:teminikike@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences kikelomo t. adesina et al 1. introduction the global burden of cervical cancer has reached epidemic rates and as such calls for primary prevention especially in areas of high prevalence. carcinoma of the cervix is the leading gynecological cancer in our environment and the second commonest female cancer worldwide [1]. it is responsible for over 8,000 deaths annually from advanced disease and late presentation [2, 3]. studies have shown that many of our women are aware of the disease and there is an increasing level of awareness about its prevention through screening for its premalignant state. a survey conducted among women seeking gynecological and family planning services in university of ilorin teaching hospital (uith), showed that 78.2% of the respondents were aware of cervical cancer, half of them knew it can be prevented but over two-thirds had no idea of the cause [4]. similarly, there is a higher prevalence of human papilloma virus( hpv) infection in women with cervical lesions than those not affected [5]. the discovery of the etiological role of the sexually transmitted hpv in carcinoma of the cervix has redirected the preventive strategies towards vaccination against the virus before exposure to the infection [6]. the vaccination of pre-pubertal girls and women of 12-26 years is the current primary preventive strategy in lime light; this has by no means de-emphasized screening for the pre malignant state of the disease. unfortunately, knowledge and practices concerning the hpv infection and prevention; its effect and role in the primary prevention of cervical cancer are very low and not encouraging [4, 7]. estimates suggest that introducing hpv vaccination at 12 years of age alongside the current u.s. screening program for cervical cancer could reduce lifetime cervical cancer incidence by up to 94% [8]. the safety and efficacy of prophylactic hpv vaccines against types 16, 18 , 11,6 and even 16/18 related cin2/3 and adenocarcinoma in situ are well established [9– 11]. worldwide, the available preparations of the prophylactic vaccines are expensive and there is need to educate the populace on the importance and justify the long term cost effectiveness. in the united kingdom, united states of america, netherlands, some parts of australia and new zealand, hpv vaccine has been included in the school vaccination program for girls. in the developed world, studies have shown the varying attitudes of parents and guardians towards hpv vaccination of their children and wards; this is not unrelated to the general pervasive lack of knowledge of hpv as a sexually transmitted infection (sti) and a cause of cervical cancer [12]. doi 10.18502/sjms.v13i1.1687 page 34 sudan journal of medical sciences kikelomo t. adesina et al an important determinant of uptake of this primary prevention strategy is the attitude and willingness of parents of these girls to the vaccine. their knowledge remains an important pivotal to acceptance of the vaccine. in a developing society like ours most vaccination programmes are highly subsidized or provided freely by donor agencies, in order to have a wide coverage. hpv vaccine has not yet been subsidized. the socioeconomic capacity of parents may also determine acceptability [5] as documented by dahlstrom et al in a population based survey in sweden [12]. since the vaccine is currently available for girls below 18 years, parents have to give consent for the child to be vaccinated. parental knowledge and attitude would influence parental willingness which will indirectly translate to the uptake of the vaccine. baseline data are therefore necessary for national and local awareness and campaign programmes to ensure the acceptability and uptake of the vaccine. this study was to determine the knowledge of parents about hpv infection, their awareness about hpv vaccine and willingness to vaccinate their daughters. hopefully, it would be an important foundation for the incorporation of hpv vaccine into the national immunization programme in nigeria. 2. materials and methods this was a cross sectional descriptive survey involving mothers of selected secondary school girls. it was carried out in ilorin from february to april 2015. ilorin is the capital of kwara state in nigeria. it is located in the north central geopolitical zone of the country. it has three local government areas and the settlement is semi-urban. the main ethnic groups in the city are yorubas, fulanis and hausas. the sample size was determined by fischer’s formula using a prevalence rate of 14% according to nnondu et al,7 20% of the calculated sample size was added to cater for incomplete and non-responses. the minimum sample size calculated was 250 participants (parent/daughter pair). the list of the registered secondary schools in ilorin was obtained from the state ministry of education after obtaining permission from the ministry and ethical approval from the ethical review board of the university of ilorin teaching hospital, ilorin. a multi stage sampling method was utilized to select secondary schools from the list of schools which included both public and private secondary schools. at the selected schools, girls between 10 and 15 years were randomly selected from junior secondary classes of these schools until the calculated sample size was reached. doi 10.18502/sjms.v13i1.1687 page 35 sudan journal of medical sciences kikelomo t. adesina et al a minimum of 40 girls were randomly sampled from each school. their parents were invited to participate voluntarily in the study during open / visiting days for the boarding students while invitations were sent through the day students to their parents. the invitation included an information sheet, consent form and the questionnaire. a week after the distribution, the researchers returned to collect the completed questionnaires from the girls through their class teachers. the instrument for this survey was a close ended (multiple choice) self administered questionnaire designed to determine the knowledge, attitude and willingness of participants to hpv vaccination. the study respondents were assured of anonymity and confidentiality and first part of the questionnaire provided socio-demographic information of the mothers. the second part assessed their knowledge of hpv infections, vaccines and their willingness to accept hpv vaccine for daughters. there was no health education on the subject for the participants before completion of the questionnaire. mothers completed the survey items for this study only once, even if they had more than 1 child enrolled in the schools. the questionnaire was pre-tested in a similar population for validity and reliability using 20% of the calculated size. data analysis was done using spss version 20 with both descriptive and inferential statistics. in particular, chi-square statistics were used to estimate the degree of correlation between the variables and nature of the independent variables in this study. p values less than 0.05 were considered significant. 3. results 3.1. socio-demographic characteristics of respondents six hundred questionnaires were distributed to mothers of female students from selected secondary schools however, 470 questionnaires were returned for analysis, giving a response rate of 78.3%. majority of the respondents (61.9%) were between 31 and 50 years, 83.6% were of yoruba ethnicity. the parents were either christians or muslims and 58.1% had at least secondary school education. among the respondents, 70.2% were employed out of which 171(51.8%) were civil servants. among the 91.9% of the respondents whose social class could be determined, 22.8% (107) belonged to the upper social class. (table 1). doi 10.18502/sjms.v13i1.1687 page 36 sudan journal of medical sciences kikelomo t. adesina et al 3.2. knowledge of hpv infection one hundred and sixty-one (34.3%) of the respondents knew that hpv can be sexually transmitted and 34.5 percent knew that it could be prevented by use of condoms. sexual abstinence and having one sexual partner were suggested as preventive measures for hpv infection by 27.9% and 37.7% of the respondents, respectively. even though 40.4% knew that hpv can cause cervical cancer, a higher percentage of 47.7% did not know that hpv can cause cervical cancer (table 2). 3.3. knowledge of hpv vaccine out of the study participants, 35.1% were aware of hpv vaccine and majority (58.7%) has not heard of the vaccine. the hospital/medical personnel were the sources of information in 28.1% while other sources such as mass media, health talks, journal/magazines accounted for approximately 15-21% (table 3). hpv vaccine was known to prevent hpv infection by only 29.1% of the respondents, 25.5% knew it prevented cervical cancer while only 9.6% knew it could prevent genital warts (table 3). among the respondents, 33.8% knew it was available in nigeria. as many as 83% of the respondents gave no response about the available types of hpv vaccine but 15.3% had no knowledge whatsoever about the types of vaccine. among the study participants, only 1% knew that cervarix and/or gardasil are hpv vaccines, while two mothers wrongly considered the routine immunization schedule as the vaccine. some respondents, 32.3% answered that all girls should be vaccinated while 6.4% thought otherwise; 11.3% responded that it should be given to only sexually active girls and 1.1% opined that boys should also be vaccinated. 4. practice and willingness to accept hpv immunization majority (91.9%) of the parents responded that their girls have not been immunized with hpv vaccine. of the 9 respondents (1.9%) whose children have been immunized, immunization was given between 11and 20 years in 77.8% of them. among the 7% of women that knew hpv immunized persons, only few (2.3%) reported abdominal cramps, body pains, lethargy as side effects of the vaccine in them (table 4). doi 10.18502/sjms.v13i1.1687 page 37 sudan journal of medical sciences kikelomo t. adesina et al in this survey, 44.9% of the women were willing to vaccinate their children with hpv vaccine even when only 13% had enough information to decide on acceptance of the vaccine. furthermore, 37.9% would like further consultation with a doctor or any health care provider before accepting the vaccine. in terms of cost, 22.3% would accept the vaccine only if free, 33. % of the respondents will do so even if vaccine is not free. one hundred and fifty two (32.3%) of the respondents are willing to give the vaccines to all girls while 11.3% of them would be willing to give the vaccine to sexually active girls only (table 5). respondents that were willing to vaccinate their girls had a mean score of 5.00 ±3.32 about the knowledge of hpv while those not willing had a score of 4.92± 2.93. similarly, the knowledge score of hpv vaccination was higher among half of those willing to vaccinate and it was significant statistically (p 0.0001) tables 6&7. 5. discussion the age distribution of the study population ranged from the highly reproductive age to peri-menopausal age; most respondents were between 31 and 50 years. their demographic characteristics showed a variation in terms of age, education, marital status, social class among others. mothers in the upper social class were the least when compared with those in the lower and middle classes. this is most likely a representation of the semi-urban pattern of the population of ilorin, nigeria. there was poor knowledge of hpv infection and practice of vaccination among mothers. the willingness to accept hpv vaccine was low and there was a significant statistical relationship between acceptability of hpv vaccine and knowledge of hpv infection, vaccination and cervical cancer. 6. knowledge of hpv infection and vaccine the mothers of girls in this study demonstrated poor knowledge of human papillomavirus infection and vaccine as 34.5% of the respondents had a score of 5 or more (correct knowledge).this is similar to findings from some developing countries [13–17]. for example, in ghana and cameroon, parents of adolescents had poor knowledge of hpv and its vaccination [16, 17]. our findings indicate that women in ilorin are poorly informed about hpv and cervical cancer, this is similar to those of other developing countries. doi 10.18502/sjms.v13i1.1687 page 38 sudan journal of medical sciences kikelomo t. adesina et al this is however, in contrast to findings among cameroonian adolescents who displayed high level of awareness on hpv, cervical cancer and hpv vaccine [18]. prior sensitization and health education was found to result in the high level of awareness among the girls when compared with the poor knowledge and awareness among mothers in our study. also, standard educational script on risk factors and prevention of hpv infection and cervical cancer was given to the women that participated in a similar survey in zambia and this positively influenced their acceptability of the vaccine [14]. education on hpv and cervical cancer prevention would increase access to screening and other preventive measures [19]. it was concluded that community education was the effective strategy for acceptability of hpv immunization in the setting. the practice of hpv vaccination was very low in this study; poor knowledge of the vaccine and the role of the virus in the widely prevalent cervical cancer in the environment is a contributory factor. in addition to the poor knowledge of the etiological role of hpv in carcinoma of cervix, majority knew little to nothing about availability and types of hpv vaccines. this is rather unacceptable, knowing that the vaccine has been licensed for use in the u.s.a, since 2006 [20] and has even become part of some national immunization programs in both developing and developed worlds [10, 11, 14, 15, 19, 20]. this probably explains the very low percentage of hpv immunized girls in this study. the roles hpv vaccines in the prevention of cervical cancers and genital warts are well established. cervarix is a bivalent hpv vaccine that prevent hpv types 16 and 18 serotypes responsible for 70% of cervical cancers. the other quadrivalent hpv vaccine is gardasil. it prevents hpv types 6, 11, 16 and 18. hpv 6 and 11 cause 90% of genital warts. gardasil also protects against cancers of the anus, vagina and vulva. who recommends that settings like nigeria where there is high prevalence and mortality from cervical cancer should include hpv vaccines into routine national immunization programmes [21]. the role of governmental policy in the implementation of the vaccine is relevant as some women even reported it wrongly as being part of the current national immunization programme in nigeria. more women knew that it can prevent cervical cancer while 9.6% knew it prevents genital warts. it may be that the awareness on cervical cancer is greater than genital warts in our environment because of its high prevalence and associated mortality and morbidity. however, it may be more important to educate the populace on the role of hpv in other gynecological and anogenital cancers; its mode of spread and transmission which is of more public health importance [10, 20]. doi 10.18502/sjms.v13i1.1687 page 39 sudan journal of medical sciences kikelomo t. adesina et al in addition, there was significant relationship between practice and knowledge of the vaccine. obviously, health education programs on the condition are either lacking or the education is not targeted at the population at risk. the willingness to accept hpv vaccine was low and there was a significant statistical difference between acceptability and knowledge of hpv infection and vaccination, and cervical cancer. where others reported high acceptability [18-24] 44.9% of mothers indicated willingness to accept the vaccine despite the poor knowledge. most likely, differences in methodology, prior health education on risk factors and prevention of hpv and cervical cancer before survey and differing study populations are reasons for differences between vaccine acceptability. thus, health education programmes on hpv infection as a risk factor for cervical cancer and other important related public health matters should form the core strategy for implementation of hpv vaccine in our society and not just merely making the vaccines available. another obvious problem with the acceptance of any vaccine is the cost. approximately, one third of the women were willing to vaccinate their daughters even if the vaccine is not free while a lower percentage of 22% would accept it only if free. a related survey among kenyan women showed that most would prefer making the vaccine much lower cost if not free [13]. in israel, cost of the vaccine was identified as one of the barriers to acceptability of the vaccine among others [2]. currently currently, hpv vaccines (gardasil and cervarix) are available in nigeria but their cost is not within reach for an average nigerian; it is about the recommended minimum wage of any employee in the country, implying that it is unaffordable by majority. although undocumented verbal reports are suggesting that more women are requesting to be immunized, it is costly, not affordable and not within reach of all women especially when compared with other vaccine preventable diseases. until, hpv vaccine is implemented as a national programme, it may never have wide coverage and may never be available to adolescents at future risk of cervical cancer. this strategy would eliminate cost as a factor that may limit the acceptability and willingness of parents to vaccinate their wards and children. 7. conclusion one third of the respondents had correct knowledge of hpv infection, immunization and its role in prevention of cervical cancer; 44.9% of the mothers were willing to vaccinate, while 10.6% were not. 41.3% did not respond probably because of the poor knowledge of hpv. this study has demonstrated the relationship between knowledge doi 10.18502/sjms.v13i1.1687 page 40 sudan journal of medical sciences kikelomo t. adesina et al variable frequency (n=470) percent age group (years) < 20 60 12.8 20-30 20 4.3 31-40 131 27.9 41-50 160 34.0 51-60 28 6.0 >60 71 15.1 nationality nigeria 430 91.5 cameroon 1 0.2 nr 39 8.3 ethnicity yoruba 393 83.6 igbo 12 2.6 hausa 5 1.1 fulani 4 0.9 others 19 4.0 nr 37 8.9 religion christianity 209 44.5 islam 218 46.4 nr 43 9.1 educational status < secondary school 159 33.8 secondary or equal 99 21.1 > secondary school 174 37.0 nr 38 8.1 employment yes 330 70.2 no 83 12.1 nr 57 12.1 social class lower 174 37.0 middle 151 32.1 upper 107 22.8 nr 38 8.1 family types monogamy 312 66.4 polygamy 53 11.3 single mothers 105 22.3 number of children of respondents 1 15 3.2 2 42 8.9 ≥ 3 316 67.2 t 1: socio-demographic parameters of respondents. doi 10.18502/sjms.v13i1.1687 page 41 sudan journal of medical sciences kikelomo t. adesina et al variable frequency (n=470) percent hpv is sexually transmitted yes 161 34.3 no 66 14.0 i don’t know 186 39.6 nr 57 12.1 hpv can be prevented by use of condom yes 162 34.5 no 77 16.4 i don’t know 169 36.0 nr 62 13.2 hpv can be prevented by having only one sexual partner yes 177 37.7 no 58 12.3 i don’t know 169 36.0 nr 66 14.0 hpv can be prevented by abstinence from sex yes 131 27.9 no 72 15.3 cervical cancer is caused by hpv yes 190 40.4 no 30 6.4 i don’t know 224 47.7 nr 26 5.5 t 2: respondents’ knowledge of hpv. of hpv, willingness and acceptability of hpv vaccines in a semi-urban population in nigeria, a developing country with high prevalence and mortality from cervical cancer. there is poor knowledge of hpv and its vaccines among mothers in ilorin; and they are important determinants of acceptability/ willingness of parents to vaccinate their pre-pubertal girls. a core preventive strategy is the implementation of the vaccine into national immunization program after adequate and widespread community education. addressing doi 10.18502/sjms.v13i1.1687 page 42 sudan journal of medical sciences kikelomo t. adesina et al variable frequency (n=470) percent have you heard of hpv vaccine? yes 165 35.1 no 276 58.7 nr 29 6.2 sources of information* mass media 61 21.4 hospital/medical personnel 80 28.1 newspaper/journals/magazines 43 15.1 health talk 60 21.1 peer group/parents 11 3.9 others internet 18 6.3 relativ es 2 0.7 social media 10 3.5 prevents hpv infection yes 137 29.1 no 60 12.8 i don’t know 261 55.5 prevents cervical cancer yes 120 25.5 no 84 17.9 i don’t know 256 54.5 nr 10 2.1 prevents genital warts yes 45 9.6 no 88 18.7 i don’t know 261 55.5 nr 76 16.2 is hpv available in nigeria? yes 159 33.8 no 69 14.7 i don’t know 151 32.1 nr 91 19.4 what type of hpv do you know? none 72 15.3 abnormal pap’s 1 0.2 gardasil&cervarix 3 0.6 cervarix 2 0.4 dpt, bsg, oral polio 1 0.2 mycotine 1 0.2 nr 390 83.0 nr: no response *multiple responses t 3: respondents’ knowledge of hpv vaccine. doi 10.18502/sjms.v13i1.1687 page 43 sudan journal of medical sciences kikelomo t. adesina et al variable frequency (n=470) percent have you immunized your daughter with hpv vaccine? yes 9 1.9 no 432 91.9 nr 29 6.2 if yes, at what age? (n = 9) 11 – 20yrs 7 77.8 > 20yrs 2 22.2 is there anyone who had hpv vaccine that you know? yes 33 7.0 no 315 67.0 i don’t know 98 20.9 nr did the person experience any side effects?(n = 33) 24 5.1 yes no 11 2.3 i don’t know 12 2.6 10 2.1 nr: no response t 4: practice of hpv vaccination among respondents. mothers of adolescent girls would be a desirable target population for implementing other primary preventive measures such as screening for premalignant condition, hpv infection and stis. 8. recommendations there is need for intense public campaigns and enlightenment programmes on cervical cancer, hpv and immunization to prevent cervical cancer. without this, the reduction in cervical cancer mortality may not be realized in the nearest future. doi 10.18502/sjms.v13i1.1687 page 44 sudan journal of medical sciences kikelomo t. adesina et al variable frequency (n=470) percent hpv vaccine should be given to all girls 152 32.3 it should be given to sexually active girls only 53 11.3 hpv vaccine should be given to boys 89 1.1 i have enough information to decide for or against accepting the vaccine for my child 61 13.0 i need to ask doctor or health worker before accepting vaccine 178 37.9 are you willing to vaccinate your child? 211 44.9 willing only if vaccine is free 105 22.3 willing even if vaccine is not free 148 31.5 t 5: parents’ willingness to accept hpv vaccine. willing to vaccinate child n knowledge score f p value yes 211 5.00 ± 3.32𝑎 65.922 <0.001 no 50 4.92 ± 2.93𝑎 i don’t know 194 1.69 ± 2.71𝑏 f: anova (analysis of variance); *: statistically significant (i.e. p value <0.05); mean with different alphabets indicate significant difference t 6: mean score of respondents’ knowledge of hpv and willingness to vaccinate child. this should be foremost if any hpv immunization programme would be successful in our environment. the cost of the vaccine should be heavily subsidized if not made freely available by the government. the long term benefits are worthwhile. willingness to vaccinate child knowledge score yes no i don’t know total 𝜒2 p value n (%) n (%) n (%) n (%) 0 – 4 106(50.2) 24(48.0) 168(86.6) 298(65.5) 69.118 <0.001* 5 – 9 78(37.0) 22(44.0) 22(11.3) 122(26.8) ≥ 10 27(12.8) 4(8.0) 4(2.1) 35(7.7) total 211(100.0) 50(100.0) 194(100.0) 455(100.0) t 7: relationship between willingness to vaccinate child and the respondents’ knowledge of hpv and vaccination doi 10.18502/sjms.v13i1.1687 page 45 sudan journal of medical sciences kikelomo t. adesina et al 9. limitation this survey was conducted among mothers who were reached through their daughters and not a community based survey which would have identified mothers directly. there was no preceding health education on the subject like earlier similar surveys which probably explains the high poor response to many questions. in another instance, this serves as the strength of the study because the poor knowledge was demonstrated distinctively. 10. declarations 11. acknowledgements we hereby acknowledge parents of secondary girls who gave consent to participate in the study and the school authorities that ensured due completion of questionnaires. we also acknowledge the support of prof.t.m akande in terms of positive critique of the manuscript. 12. ethical approval ethical approval for this study was obtained from ethical review committee of the university of ilorin teaching hospital, ilorin as well as permission from the ministry of education, kwara state. 13. competing interests authors hereby declaring no competing or conflict of interests. 14. availability of data and material data and instruments for this study are available and kept confidential by authors. 15. funding this work was funded by all authors. doi 10.18502/sjms.v13i1.1687 page 46 sudan journal of medical sciences kikelomo t. adesina et al 16. list of abbreviations hpv human papilloma virus u.i.t.h university of ilorin teaching hospital u.s.a united states of america cin cervical intraepithelial neoplasia sti sexually transmitted infection spss statistical package for social sciences who world health organization references [1] parkin dm, bray f. the burden of hpvrelated cancers. vaccine 2006;24:11-25. [2] who/ico. information on hpv and cervical cancer (hpv information centre). summary report on hpv and cervical cancer statistics in nigeria. 2007 [cited 2013 feb 12]. available from:www.who.int/hpvcentre. [3] kolawole ao. cervical cancer prevention in nigeria: issues arising. internet journal of gynecology and obstetrics. 2012 jan[cited feb 11];16(1). doi: 10.5580/2b20.available from at: http://www.ispub.com/journal/the-internetjournal-of-genomics-and-proteomics. [4] adesina k, saidu r, aboyeji a, fawole a, olarinoye a, ibrahim k. factors contributing to low cervical cancer screening in a population at risk. nig j health sci.2010;10:2125. [5] ault ka. effect of prophylactic human papillomavirus l1 virus-like particle vaccine on risk of cervical intraepithelial neoplasia grade 2,grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. lancet 2007;369:1861– 1868. [6] nnodu o, erinosho l, jamda m, olaniyi o, adelaiye r,lawson l et al. knowledge and attitudes towards cervical cancer and human papillomavirus: a nigerian pilot study. african journal of reproductive health 2010; 14:95-108. [7] goldie sj, kohli m, grima d, weinstein mc, wright tc, xavier bosch f ,franco e . projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. j natl cancer inst 2004;96:604–15. [8] moraros j , bird y, barney d.d ,king s.c ,banegas m, suarez-toriello e. a pilot study: hpv infection knowledge & hpv vaccine acceptance among women residing in doi 10.18502/sjms.v13i1.1687 page 47 sudan journal of medical sciences kikelomo t. adesina et al ciudad juárez, méxico. californian journal of health promotion 2006; 4:177-186. [9] garland sm, hernandez-avila m, wheeler cm, perez g, harper dm, leodolter s, et al. quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. n engl j med 2007;356:1928–1943. [10] d. paavonen j, jenkins d, bosch fx, naud p, salmeron j, wheeler cm, et al. efficacy of a prophylactic adjuvanted bivalent l1virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase iii double-blind, randomised controlled trial. lancet 2007;369:2161–2170. [11] thomas jo, hererro r, omigbodun aa, ojemakinde k, ajayi io, fawole a et al. prevalence of human papilloma virus infection in women in ibadan,nigeria: a population-based study. br j cancer 2004;90:638-645. [12] bosch fx, lorincz a, munoz n, meijer cj, shah kv. the causal relation between human papillomavirus and cervical cancer. j clin pathol. 2002;55: 244-265. [13] becker-dreps s, otieno wa, brewer nt, agot k, smith js.hpv vaccine acceptability among kenyan women. vaccine2010;28: 4864–4867. [14] liu fw, vwalika b, hacker mr, allen s, awtrey cs. cervical cancer and hpv vaccination: knowledge and attitudes of adult women in lusaka, zambia. journal of vaccines & vaccination 2012 doi: 10.4172/2157-7560.1000138 [15] francis sa, nelson j, liverpool j, soogun s, mofammere n, thorpe rj. examining attitudes and knowledge about hpv and cervical cancer risk among female clinic attendees in johannesburg, south africa. vaccine 2010;28: 8026–8032 [16] coleman ma, levison j, sangi-haghpeykar h . hpv vaccine acceptability in ghana, west africa. vaccine.2011; 29: 3945–3950. [17] wamai rg, ayissi ca, oduwo go, perlman s, welty e, manga s et al. assessing the effectiveness of a community-based sensitization strategy in creating awareness about hpv, cervical cancer and hpv vaccine among parents in north west cameroon. journal of community health.2012; 37: 917–926. [18] ayissi ca, wamai rg, oduwo go, perlman s, welty e, welty t et al. awareness, acceptability and uptake of human papilloma virus vaccine among cameroonian school-attending female adolescents. journal of community health2012; 37: 1127– 1135. doi: 10.1007/s10900-012-9554-z [19] perlman s, wamai rg, bain pa, welty t, welty e, ogembo jg. knowledge and of hpv vaccine and acceptability to vaccinate in sub-saharan africa: a systematic review. plos one2014; 9: e90912. doi:10.1371/journal.pone.0090912. [20] markowitz le, dunne ef, saraiya m, lawson hw, chesson h, unger er. centers for disease control and prevention (cdc); advisory committee on munization doi 10.18502/sjms.v13i1.1687 page 48 sudan journal of medical sciences kikelomo t. adesina et al practices (acip) quadrivalent human papillomavirus vaccine: recommendations of the advisory committee on immunization practices (acip) mmwr recomm rep.2007;56(rr-2):1–24. [21] fisher wa, laniado h, shoval h, hakim m, bornstein j. barriers to human papillomavirus vaccine acceptability in israel. vaccine 2013; 31: 153-157. doi 10.18502/sjms.v13i1.1687 page 49 introduction materials and methods results socio-demographic characteristics of respondents knowledge of hpv infection knowledge of hpv vaccine practice and willingness to accept hpv immunization discussion knowledge of hpv infection and vaccine conclusion recommendations limitation declarations acknowledgements ethical approval competing interests availability of data and material funding list of abbreviations references page 1 research article fatigue, nonrestorative sleep and associated factors among sudanese patients with type 2 diabetes: a case-control study hyder osman mirghani medical department, faculty of medicine, university of tabuk, saudi arabia abstract: background: fatigue, nonrestorative sleep, and other sleep disorders could be pointers to serious medical problems like obstructive sleep apnea; when present in patients with diabetes, they exacerbate each other deleterious consequences. the present study aimed to assess fatigue, nonrestorative sleep, sleep duration, and daytime sleepiness among patients with type 2 diabetes. methods: this cross-sectional descriptive study was conducted among 103 consecutive patients with type 2 diabetes and 121 healthy controls attending an outpatient clinic in omdurman, sudan during the period from december 2015 to june 2016. all participants signed a written informed consent and were interviewed using a questionnaire based on epworth sleepiness scale to assess subjective nonrestorative sleep, sleep duration, and snoring. a blood sample was taken for the hba1c. the local ethical committee approved the research, and chi-square test and t-test were used for data analysis. results: highly significant statistical differences were observed between the diabetic patients and the control subjects regarding fatigue, nonrestorative sleep, sleep duration, snoring, and excessive daytime sleepiness (p < 0.001). patients with fatigue had higher nonrestorative sleep than those without, no significant differences were found between patients with the symptoms of fatigue and those without regarding excessive daytime sleepiness, snoring, sleep duration, and the hba1c (p > 0.05). conclusions: fatigue, nonrestorative sleep, sleep duration, excessive daytime sleepiness, and snoring were common among patients with type 2 diabetes than their healthy counterparts, diabetic patients with fatigue had more nonrestorative sleep than those without. the reliance on a self-administered questionnaire is a limitation of the study. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6696 production and hosting by knowledge e how to cite this article: hyder osman mirghani (2019) “fatigue, nonrestorative sleep and associated factors among sudanese patients with type 2 diabetes: a case-control study,” sudan journal of medical sciences, vol. 15, issue no. 1, pages 1–9. doi 10.18502/sjms.v15i1.6696 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: s.hyder63@hotmail.com. received 11 january 2020 accepted 02 march 2020 published 31 march 2020 production and hosting by knowledge e cc hyder osman mirghani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: fatigue, nonrestorative sleep, excessive daytime sleepiness, diabetes mellitus, sudan introduction diabetes mellitus is a lifelong morbid disorder causing a lot of mortality and morbidity. overall, 6% of the world population is affected by the disease, and the number is projected to reach 438 million by the year 2030. currently, 7.7% of adult population is affected by diabetes mellitus in sudan, and the level is rising at an alarming rate [1–3]. mailto:s.hyder63@hotmail.com sudan journal of medical sciences hyder osman mirghani doi 10.18502/sjms.v15i1.6696 page 2 chronic fatigue is common among patients with diabetes and can be reported in more than half of them. fatigue can affect adversely the quality of life, compromise the self-management of diabetes, and increase complications that come with the disease. the pathophysiology of diabetes mellitus and fatigue could be shared in some respects [4, 5] (the release of inflammatory markers like tumor necrosis factor, interleukins, and increased c-reactive proteins are to blame for both conditions). fatigue can be acute and fluctuating during the day or a chronic persistent with functional impairment. hyperglycemia in patients with diabetes precipitates fatigue, while sleep disorders, depression, and pain perpetuate it [6–9]. previous literature indicated a u-shaped relationship between diabetes and sleep with an increasing incidence among those who sleep less than six or more than eight hours per night [10]. physiological studies have documented the activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis leading to an increase in the heart rate and impairment of its variability among patients with insomnia who met the objective and subjective criteria during polysomnography. an increase in the metabolic rate was also observed in those patients [11–13]. nonrestorative sleep is the subjective feeling of unrefreshing sleep, up to 10% of the healthy individuals could be affected by this disorder. nonrestorative sleep may be associated with insomnia, unhealthy lifestyles, and gastroesophageal reflux disease [14, 15]. excessive daytime sleepiness and snoring are clinical indicators of obstructive sleep apnea and have been linked to an increasing morbidity and mortality in various clinical setting including diabetes mellitus. excessive daytime somnolence could impair diabetes self-management and increase the glycated hemoglobin and lead to higher rate of microvascular complications [16]. not many researchers have studied fatigue, insomnia, and excessive daytime sleepiness in sudan and the studies conducted on this factors in the western countries may not apply to sudan. thus, the present research was conducted to assess fatigue, excessive daytime sleepiness, and insomnia among patients with type 2 diabetes mellitus in sudan. materials and methods this case-control study was conducted among 102 consecutive patients with type 2 diabetes mellitus and 121 healthy controls during the period from december 2015 to june 2016. the participants were attending an outpatient diabetes clinic at the omdurman teaching hospital, omdurman, sudan; the diabetic patients were chosen from amongst the regular follow-up patients, and the control subjects were chosen from sudan journal of medical sciences hyder osman mirghani doi 10.18502/sjms.v15i1.6696 page 3 the relatives and co-patients to address the confounding factors like socioeconomic factors and level of education [17]. the sample size was calculated using the formula: n = z2 p – q/d2, where z = 95% confidence (1.96), p = prevalence of diabetes mellitus in sudan [3], q = 100–prevalence, and d = tolerated error. all participants signed a written informed consent and were then interviewed using a structured questionnaire to collect demographic data on subjective sleep duration, non-restorative sleep during the past month, and fatigue that persisted during the day with the disturbance in function [6]. those with chronic medical conditions like rheumatic disorders as well as those with psychological diagnosis, cigarettes smokers, and alcohol consumers were excluded. the epworth sleepiness scale (ess) was used [18] to assess patients’ likelihood of falling asleep during the course of the day, the scale is an eight component choice questions with a total score of 24; these eight components are: how likely are you to fall asleep when: watching tv, sitting and reading, sitting inactively in public places, as a passenger in a car for one hour without a break, lying down to rest in the afternoon when circumstances permit, sitting talking to someone, sitting quietly after a lunch without alcohol, and in a car, while stopping for a few minutes in traffic. each component is scored between 0 and 3 with 0 indicating no tendency for dosing off and 3 being severe dysfunction. a person who scores 10 or more is regarded as an excessive daytime sleeper. weight and height were also measured, and the body mass index (bmi) was measured using the formula: weight in kg/height in meter square. a bmi ≥ 30 was regarded as obesity, 25–29 as overweight, and 18–25 as normal. blood sample was taken to assess the glycemic control (hba1c%). the research was approved by the local ethical committee. data were analyzed using the statistical software (spss version 20), chi-square test, and t-test and p < 0.05 was considered as statistically significant. results overall, 102 patients with type 2 diabetes and 121 control subjects were included in the study, with ages 58.39 ± 8.74 and 50.58 ± 10.17 years, respectively, p < 0.001; female dominance was apparent in both patients (71.6%) and controls (64.5%), p = 0.314; fatigue was reported in the majority of the patients (70.5% vs 36.3% among control subjects) with a high significant statistical difference, p < 0.001; non-restorative sleep was evident in 91.1% of the patients and 74.3% of the controls with a significant statistical difference, p = 0.001; while regular snoring was found in 56.9% and 28.1% of patients and controls, respectively, p < 0.001. table 1 shows the comparison between patients with type 2 sudan journal of medical sciences hyder osman mirghani doi 10.18502/sjms.v15i1.6696 page 4 table 1: comparison between patients with type 2 diabetes and control subjects. characteristics diabetic patients control subjects p value* sex males females 29 (28.4%) 73 (71.6%) 43 (35.5%) 78 (64.5%) 0.314 regular snoring 58 (56.9%) 34 (28.1%) 0.000 non-restorative sleep 93 (91.1%) 90 (74.3%) 0.001 fatigue 72 (70.5%) 44 (36.3%) 0.000 excessive daytime sleepiness 41 (40.2%) 13 (10.7%) 0.000 sleeping hours <6 hours/night mean ± sd 57 (55.9%) 5.29 ± 1.20 18 (14.9%) 5.29 ± 1.20 0.000 *chi-square test table 2: a comparison between diabetic patients with and without fatigue. characteristics fatigue present fatigue not present p value* sex males females 22 (30.5%) 50 (69.5%) 7 (23.3%) 23 (76.6%) 0.461 snoring 42 (58.3%) 16 (53.3%) 0.666 non-restorative sleep 71 (98.6%) 22 (73.3%) 0.000 *chi-square table 3: t-test comparing diabetic patients with and without fatigue. characteristics fatigue present fatigue not present p value* age 58.01 ± 8.84 59.30 ± 8.59 0.501 daytime sleepiness 7.37 ± 5.11 7.23 ± 4.39 0.895 hba1c 9.44 ± 1.88 8.89 ± 1.90 0.186 bmi 31.50 ± 4.80 30.00 ± 4.16 0.139 sleep duration 5.30 ± 1.26 5.26 ± 1.04 0.882 *t-test diabetes and healthy control subjects. table 2 illustrates a comparison between patients with and without fatigue in which snoring was found in 58.3% of the diabetic patients with fatigue and 53.3% of their counterparts with no significant statistical difference, p = 0.666; non-restorative sleep was higher among patients with fatigue at 98.6% vs 73.3% in controls with a high significant statistical difference, p < 0.001. as shown in table 3, no significant differences were found between the diabetic patients with chronic fatigue and those without the abnormality regarding age (58.01 ± 8.84 vs 59.30 ± 8.59, p = 0.501), excessive daytime sleepiness (7.37 ± 5.11 vs 7.23 ± 4.39, p = 0.895), the hba1c (9.44 ± 1.88 vs 8.89 ± 1.90, p = 0.186), bmi (31.50 ± 4.80 vs 30.00 ± 4.16, p = 0.139), and sleep duration (5.30 ± 1.26 vs 5.26 ± 1.04, p = 0.882). sudan journal of medical sciences hyder osman mirghani doi 10.18502/sjms.v15i1.6696 page 5 discussion in the present study, majority of the patients with diabetes mellitus presented with fatigue and non-restorative sleep with a highly significant statistical difference between the patients and control subjects. patients with type 2 diabetes mellitus had shorter sleep duration than controls and patients with chronic fatigue had higher non-restorative sleep than others without the diagnosis, while no significant difference was found between the two groups regarding the hba1c, excessive daytime sleepiness, body mass index, and the duration of sleep. there are complex discrepancies between causes and indicators of fatigue, so it’s hard to define fatigue or transform it into a quantifiable measure. due to the complex management strategies in diabetes, the importance of fatigue may be greater. in the present study, fatigue was more common among patients with type 2 diabetes than the healthy control subjects (70.5% vs 36.3%) in line with previous observations [19]. another epidemiological study concluded fatigue in 61% of patients with type 2 diabetes, also in line with the current observations [20]. various physiological and pathological disorders associated with diabetes mellitus like hyperglycemia, hypoglycemia, neuropathic pain, polypharmacy, and sleep disorders may result in fatigue [21–23]. irrespective of the cause of death, both short and long sleep durations were associated with an increasing mortality. the growing rate of death might be free of diabetes and hypertension [24], in the current data, patients with type 2 diabetes mellitus slept for a short period and had a non-restorative sleep more than the controls, as in the cespedes et al.’s study, who concluded the association between diabetes mellitus, short sleep duration, and insomnia [25]. nonrestorative sleep may be a potential risk for various clinical outcomes related to sleep disorders even in the general population. however, factors involving nonrestorative sleep remain to be elucidated. recent literature concluded the association of nonrestorative sleep with insomnia, psychiatric disorders, and gastroesophageal reflux disease [26]. in the present study, non-restorative sleep was present in 91.1% of patients with type 2 diabetes mellitus and 74.3% of control subjects with highly significant statistical difference; similarly, a study conducted among patients with the metabolic syndrome concluded the high rate of non-restorative sleep [27]. however, the relationship between fatigue and non-restorative sleep remains significant after controlling for age, sex, bmi, snoring, and excessive daytime sleepiness. the present observation calls for further larger multicenter studies to assess further possible sudan journal of medical sciences hyder osman mirghani doi 10.18502/sjms.v15i1.6696 page 6 consequences of nonrestorative sleep among patients with type 2 diabetes mellitus in general and particularly those who present with the symptoms of fatigue. excessive daytime sleepiness and snoring are predictors of obstructive sleep apnea, a common sleep problem among patients with type 2 diabetes which when co-exist might increase each other’s deleterious consequences [28]. in the present study, snoring and excessive daytime sleepiness were evident in 56.9% and 40.2% of diabetic patients with a high significant statistical difference between patients and control subjects similar to kelly et al. [29] who found daytime sleepiness in 56% of hospitalized diabetic patients. similarly, marchiseni et al. [30] reported habitual snoring in 56.1% of obese patients. fatigue could be a result of increasing bmi or lack of physical activity, but we did not assess the level of exercise as an important factor [31]. also, we did not study other important factors like depression and diabetes distress that could contribute to the symptom of fatigue. conclusion the present study concluded a high rate of fatigue, non-restorative sleep, short sleep duration, snoring and excessive daytime sleepiness, and a highly significant statistical relation between fatigue and non-restorative sleep. more larger studies using objective measure for the diagnosis of obstructive sleep apnea and assessing various possible causes of non-restorative sleep need to be conducted to improve diabetes care and quality of life because the above factors could impair the diabetes complex selfmanagement. declaration: the views expressed in the submitted article are author’s own and not an official position of the institution or funder. authors contribution • concept and design: dr. hyder mirghani • data collection: dr. hyder mirghani and dr. fathiya • data analysis: dr. hyder mirghani • manuscript drafting and critical revision for important intellectual content: dr. hyder mirghani sudan journal of medical sciences hyder osman mirghani doi 10.18502/sjms.v15i1.6696 page 7 references [1] acharya kg, shah kn, solanki nd et al. 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[31] telford rd (2007). low physical activity and obesity: causes of chronic disease or simply predictors? medicine & science in sports & exercise. 39(8): 1233–1240. sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13607 production and hosting by knowledge e narrative review the impact of incisional hernia repair on the quality of life: a narrative review mara ioana pătrașcu1, daniel ion1,2, alexandra bolocan1,2, dan nicolae păduraru1,2, and octavian andronic1,2 1carol davila university of medicine and pharmacy, bucharest, romania 2university emergency hospital of bucharest, romania orcid: octavian andronic: https://orcid.org/0000-0002-9053-0018 abstract background: incisional hernias represent a common complication following a midline incision, generating impairment, lower quality of life, and social costs. the aim of this narrative review is to determine in which manner risk factors – such as age, gender, postoperative complications, and even the overall health system – impact the satisfaction and expectations of the patients. methods: a literature search was performed through pubmed, web of science, and springerlink, addressing both international and national articles. only full-text articles published in the last 12 years were chosen. each individual positive or negative factor was then targeted. results: statistically, the majority of patients were satisfied with the outcomes of the reparative surgery. even so, complications can still occur, which are more likely to appear in the early postoperative stages. in most of these cases, the patients complained of strenuous movement, chronic pain, or recurrence, leaving the option of another surgical repair up to the patient’s wishes. on the one hand it seems that robotic-assisted surgery (ras), absorbable sutures, suture fixation without tacks, and the male gender were associated with a better quality of life and less recurrence or other complications. on the other hand, lack of communication between patients and health personnel, chronic health diseases, and the female gender were linked to a tendency of developing more complications and therefore, a lower quality of life. conclusion: statistically, in most of the cases, the patients were satisfied with the results. while it is safe to say that an incisional hernia repair increases the quality of life, there is still a small, but significant percentage of people that do not benefit from it as much as they expected. more awareness should be raised and the communication between patients and health personnel improved. keywords: incisional hernia, postoperative hernia, incisional hernia repair, quality of life how to cite this article: mara ioana pătrașcu, daniel ion, alexandra bolocan, dan nicolae păduraru, and octavian andronic (2023) “the impact of incisional hernia repair on the quality of life: a narrative review,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 242–256. doi 10.18502/sjms.v18i2.13607 page 242 corresponding author: octavian andronic; email: octavian.andronic@umfcd.ro received 29 august 2022 accepted 16 january 2023 published 30 june 2023 production and hosting by knowledge e mara ioana pătrașcu et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mara ioana pătrașcu et al 1. introduction abdominal hernias can be primary or acquired: while the former group refers to primary ventral hernias ( midline as epigastric and umbilical, and lateral as spigelian and lumbar), the latter consists of incisional hernias, which are acquired forms on previous incisions. reparative techniques are performed with prosthetic (alloplastic) materials that can be synthetic (polypropylene, polyester, ptfeand composite) or biological (porcine dermis, bovine pericardium) [1]. the symptomatology of an ih is quite diverse, depending on its characteristics, however, most studies are pointing toward pain, discomfort, and altered emotional health, most probably due to a low self-perceived body image and lack of ease in performing daily duties. other elements could be insomnia, dyspnea, constipation, diarrhea, fatigue, and more. individuals with a bmi > 25 kg/m2 or a subsequent pregnancy are prone to developing ih [2], whereas young patients and those that suffer from recurrences and smokers are prone to chronic pain [3, 4]. it is estimated that 13% and 22% of patients will develop an incisional hernia in the next two and three years following a midline incision, respectively, therefore leading to considerable social costs and impairment. while not every hernia is symptomatic, in 80% of cases it will require surgical repair [5, 6]. the quality of life after incisional hernia repair is yet to be thoroughly documented. so far, most studies have focused on the cost-effectiveness of the surgical technique, duration of surgery, or even the time span needed for a surgeon to master that certain technique. in the last few years, a number of studies have been conducted, focusing on the qol or short/long-term complications. whilst this brings new horizons for this particular topic, there has not been a standardized protocol, leading to research that uses different types of criteria to define their patient population or assess the qol. therefore, when it comes to evaluating a greater mass of results, these might not be conclusive, needing to approach this subject in a fragmented way. the aim of this narrative review is to provide the latest information concerning the quality of life in patients that underwent an incisional hernia repair surgery. 2. materials and methods a thorough search through pubmed, web of science, and springerlink was performed, using the following search formula: ([{incisional or ventral or postoperative}and hernia] and [quality of life]). we included cross-sectional, retrospective, and prospective doi 10.18502/sjms.v18i2.13607 page 243 sudan journal of medical sciences mara ioana pătrașcu et al cohorts, and controlled trials published in the last 13 years in order to choose the most relevant and recent data. the studies must assess the quality of life among different groups of patients in order to achieve a broad image over the subject. to be included, the studies have to focus on differences between the given cohorts, which are grouped into general aspects, such as age, gender, health status, and more topic-related aspects – classic, laparoscopic, or (ras), type of mesh used, onlay or sublay placement of the mesh, symptoms accused preoperatively by the patients, and expectations prior to the surgery. in addition, the outcomes relevant to the quality of life are to be observed, that being convalescence period, performance reported by the patient for daily and more strenuous activities, and acute and chronic reported complications. for the acute complications, we decided to focus on acute postoperative pain, mesh-associated infections, mesh removal, ileus, seroma formation, enterocutaneous fistula, recurrence up to the first 30 postoperative days, hemorrhage and sepsis, and for the chronic complications we chose chronic postoperative pain, recurrence following 30 postoperative days, late enterocutaneous fistula and mesh-associated complications, such as mesh migration, mesh shrinkage, intraperitoneal adhesions that can predispose to small bowel obstruction, and inflammatory local reactions that can develop into fibrosis. moreover, risk factors for each of these complications were observed – age, gender, physical health status, bmi, smoking, stress, emotional health. typical qol assessment questionnaires, such as ccs, sf-36, herqles (herniarelated quality-of-life assessment) tool, gillman pain test and vas (visual analogue scale) were searched for. in addition, to broaden the range of the data that was included, personalized surveys created by the surgeons for those particular studies were added as long as they were targeting our previously mentioned long-term and short-term outcomes. lastly, a total of 25 articles were selected. 3. results & discussion typical qol assessment questionnaires are the ccs, sf-36, herqles – hernia-related quality-of-life assessment tool, gillman pain test, and specific personalized surveys created by the surgeons conducting the study. the ccs (carolina comfort scale) is a validated hernia specific survey that uses a 0–5 scale to evaluate the pain, mesh sensation, and mobility of the patient after the doi 10.18502/sjms.v18i2.13607 page 244 sudan journal of medical sciences mara ioana pătrașcu et al surgery [7]. it is one of the most commonly used scores. the higher the score, the lower is the health-related qol, ranging between 0 and 115. the sf-36 (short form 36) is another survey, quite often used for many other health conditions, but mostly used in the us to assess patients after an incisional hernia repair. it is based on 36 graded questions that define eight other domains: physical functioning (pf), role physical (rp), bodily pain (bp), general health (gh), vitality (vt), social functioning (sf), role emotional (re), and mental health (mh). each of these subscales can receive a score between 0 (poor health) and 8 (good health), based on their own set of questions, therefore resulting in two major subscales: physical health and mental health. a study can choose to focus on certain scales or use them all in an integrated manner [7]. the karnofsky performance status scale (kps) is used to measure functional performance by assessing the patient and giving a score in the form of increments between 100 (perfect health condition, the patient can perform multiple activities, without the aid of other people ) and 0 (death) [8]. the herqles – hernia-related quality-of-life assessment tool – is a 12-phrase survey in which the patient has to pick an answer that ranges between “strongly disagree” and “strongly agree.” the higher the score, the more the patient’s qol affected [1]. the mcgill pain score is also worth mentioning. it is administered by an interviewer and for each subclass of words, the patient has to choose one word that describes the pain in the best way, each word having an already established value. in the end, the value of these words is summed up and a score between 0 and 78 is the final result. the higher the score is, the greater the pain [9]. supposedly, an ihr should bring the functionality of the abdominal wall to levels similar to the general population after one year postoperatively, but never as good as theirs, as another study shows [10]. 3.1. laparoscopic vs open vs robotic-assisted surgery it is widely accepted that an open repair technique poses more threats than a minimally invasive one, such as greater risk of infection, longer hospitalization time, and harder postoperative recovery. even so, in the case of larger, more complex hernias it is recommended [11]. certain surgical procedures can be done in an open or minimally invasive manner depending on the size of the hernia, the latter being the most preferred. ipom plus (and the classic ipom) is one such technique. the ipom-plus technique needs four ports, each being used for different purposes during the stages of the doi 10.18502/sjms.v18i2.13607 page 245 sudan journal of medical sciences mara ioana pătrașcu et al surgery. pneumoperitoneum is achieved using a veress needle. after adhesiolysis, the hernia sac is excised and a composite mesh is used to close the intra-peritoneal defect. five transfascial sutures are needed, one in the center, and four in the corners. another option to better center the mesh is by having a central suture and four peripheral sutures in a cross shape. this technique seems to present the most benefits, as it has a lower postoperative recovery time and the seroma heals faster compared to the ipom technique [12, 13]. in a study conducted by saijo et al. [12], these two methods were compared. in total, 33 patients were included in this study – 14 undergoing ipom and 19 undergoing ipom plus. the qol was assessed preand postoperatively using the sf36. seroma formation was associated more often with ipom, whereas chronic pain was accused by the ipom plus group. regarding the sf-36 at one-year postoperatively, five out of eight subscales were improved in both groups (pf, rp, gh, sf, re) and between the two groups, there were no statistically significant differences. another study is addressing the onlay placement of the mesh, observing patients after five years from an onlay ihr repair [14]. the results were quite satisfying, with only 24 patients (33%) accusing recurrences, and among them, only 8 out of the 24 patients refusing the surgery, because they were asymptomatic. as expected, patients suffering from recurrences had a lower qol than the ones without. as it was already mentioned, minimally invasive procedures are preferred by both patients and surgeons, however, in certain cases open ihr surgeries need to be performed. tar is one sequence that is associated most of the time and sadava et al. [15] conducted a study where they assessed the qol at 60 days postoperatively. only 4% had a recurrence and the overall 30-day morbidity was 24%, including surgical site infections, seromas, and one mesh removal. the herqles questionnaire results at six months postoperatively showed significant improvements, the mean preoperative cohort score being 50.9 ± 22.9, whereas the postoperative cohort score was 91.8 ± 18.0. another open surgery technique is the classic chevrel technique, and even more importantly, the modified chevrel technique presented in this particular study by mommers et al. [16]. it was shown that a modified chevrel technique is superior to the original one, leading to low recurrence rates and an optimized qol. the process begins with antibiotic prophylaxis and an incision across the scar tissue. the layers above the anterior rectus abdominis fascia are dissected up until 2–3 cm lateral of the rectus muscle. an incision up to 5 cm is made across the fascia, depending on the size of the hernia. the medial part of the anterior fascia is then separated from the adjacent tissue and turned over the midline. the content of the sac is excised or left as it is. “both the left and right ‘turned over’ anterior fascia can now be sutured in the midline with a doi 10.18502/sjms.v18i2.13607 page 246 sudan journal of medical sciences mara ioana pătrașcu et al continuous 2/0 polydioxanone (pds) suture using small bites. this suture ‘closes’ the abdomen and provides the first ‘layer’ of the repair.” the second layer is a polypropylene mesh, sutured to the lateral side of the anterior fascia. “one tied suture fixes the mesh at the cranial and one at the caudal meeting point of the left and right lateral part of the anterior rectus fascia. with small bites, the mesh is sutured to the edge of the anterior fascia running from cranial and caudal, thereafter, meeting halfway where the cranial and caudal suture are tied together.” the mesh has to be flat on the surface. “the excess mesh is trimmed with scissors to leave a rim of approximately 1.5 cm lateral to the continuous suture. this rim is then sutured to the ventral side of the anterior rectus fascia using single prolene® 2/0 sutures.” this technique has the original chevrel one as its base but it “does not require such large subcutaneous dissection since the mesh is sutured to the remnant of the anterior rectus fascia with only one-and-a-half centimeters overlap.” in this study, there were 155 patients included. among these, only 110 presented themselves to the long-term follow-up and two patients had a recurrence after 13 and 15 months. this study also performed a literature review, concluding that in the modified chevrel technique group the recurrence rate was between 0% and 2% and in the original group between 0% and 33%. in the first 30 postoperative days, 36 out of 155 patients had complications, but mostly seromas. after 35 months, the qol was assessed via de ccs, and 60% reported a score of 0, meaning perfect health condition. however, generally speaking, between the ras, laparoscopic, and open surgery, ras seems to offer the best results for the patient [17]. leblanc et al. showed in their study that the lowest complication rates were among the ras group with a clavien-dindo grade i compared to grades ii–iii for the open technique. patients could also return to work faster, and the highest painkillers prescription demand was in the open group, but even so, between patients that were taking analgesics, the dosage was similar. regarding the herqles questionnaire, in the first three months postoperatively, there were no major differences recorded, but afterward the ras group seemed to score higher than the open and laparoscopic groups. preoperatively, the mean cohort score in the ras group was 47.0 ± 26.0 and postoperatively the value was 71.7 ± 23.9. for the open and laparoscopic groups, the preoperative values were 52.5 ± 27.6 and 46.8 ± 27.55 , respectively, and the postoperative mean cohort values were 70.0 ± 26.5 and 73.9 ± 22.0, 𝑟𝑒𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒𝑙𝑦. therefore, it is safe to say that all three options brought a better qol to the patients, however, ras showed the best improvements. these results are slightly different than the findings from another study [18]. in this particular study, there is a comparison between the open and ras groups at one year postoperative. in terms of age, bmi, and type of mesh or size, there are no statistically significant doi 10.18502/sjms.v18i2.13607 page 247 sudan journal of medical sciences mara ioana pătrașcu et al differences. although both groups showed an increase in the qol, the open and ras median scores at one year were 88 and 90, respectively, and the recurrence rates were 20% and 24%, respectively. in order to determine if these results are statistically significant, a multivariate analysis was performed, showing that no technique was superior over the other. therefore, homogenous research should be done in order to reach a consensus. 3.2. method of fixation the placement of the mesh is not the only important variable, but the method of fixation as well. in an rct study conducted by eelco wassenaar et al. [19], different methods of fixation techniques were evaluated to determine which one carries the best results. these are “absorbable sutures (as) with tacks; double crown (dc), which involved two circles of tacks and no sutures; and nonabsorbable sutures (ns) with tacks” and a qol survey both preoperatively and three months postoperatively. the end results determined that the postoperative pain in these three groups was similar, but slightly higher in the ns and dc groups, most probably due to a more secure fixation than needed. regarding the qol, the results were obtained after completing a preoperative and postoperative sf-36 survey and extracting the preoperative value from the postoperative value for each of the eight subscales of this form, therefore resulting in only one value. between the as, dc, and ns groups, as registered better post-hoc analysis results in the role limitation due to physical problems (8.6 vs 10.8 vs 9.2) and physical function (13.5 vs 2.4 vs 9.2). therefore, in all three groups, the qol was improved at three months postoperatively, but statistically, there are no major differences between the three techniques, therefore none is superior over the other. contrarily, in another study, they compared suture fixation with or without tacks [20]. the cost of the procedure was higher in the tacker group. postoperative recovery was faster in the suture group and the intensity of the pain was higher in the tacker group up until one month postoperatively. at the three-month follow-up, the intensity of the pain between the two groups was similar, decreasing for all but five patients. these were observed for the next two years, with four patients still complaining about surges of pain associated with sudden abdominal movement – two patients from the tacker group and two from the suture group. the qol assessment via the sf-36 survey showed no major differences between the two groups, however, what is surprising is that the suture group showed no improvements in the physical function compared to the tacker group. doi 10.18502/sjms.v18i2.13607 page 248 sudan journal of medical sciences mara ioana pătrașcu et al overall, all patients had an improved qol, both physically and emotionally. regarding the patient satisfaction, the suture group recorded better results. 3.3. types of mesh the mesh used can also contribute to the overall results. a biological mesh has more benefits over other types, such as less chances of a postoperative infection, however, they are costly and when treating a larger or complex hernia the recurrence rate is higher than the other available choices. in a recent study [21], outcomes of long(ltd) and midterm degradable (mtd) meshes were analyzed. it was observed that in the group with mtd the patients had no need for removing the mesh in case it got contaminated, compared to the ltd meshes, where nine patients had it done. the recurrence rate was similar at the follow-up. similarly, in an observational study, the outcomes and qol associated with the use of biosynthetic meshes were assessed [1]. having a multitude of materials for a mesh gives surgeons the choice to decide the best option for them, but due to inconsistent data, the results are conflicting, therefore facing a great deal of subjectivity regarding this matter. in this study, 275 patients were included and observed for 36 months postoperatively, leaving enough time for the mesh to absorb. during the first eight days the patients did not report any changes different from prior to the surgery. while 8% reported a recurrence, 6.7% had a seroma that needed to be drained. considering infections, 4% had superficial infections that required surgical intervention, there were no deep or organ infections and 1.3% needed a mesh removal. regarding the qol, as mentioned, there were no major improvements at eight days postoperatively, however, gradually, the functional status of all patients improved, reaching a peak in this study after 36 months (due to the study ending, therefore a longer follow-up would be needed) and being able to perform daily chores quite reasonably. their pain and anxiety decreased as well. the hernia size is another important factor that should be taken into account when analyzing the best surgical option. baccari et al. [11] in their study analyzed this aspect, comparing midand long-term outcomes of hernias below and above 15 cm. all patients were laparoscopically operated. the patients with hernias above 15 cm had higher recurrence rates, but it was acceptable, when comparing it with the recurrence rate of smaller hernias. what is surprising is that the qol assessed with the mcgillman pain score was better in the larger hernia group than in the smaller one. complications such as seroma, polmonitis, or prolonged ileus were rare. doi 10.18502/sjms.v18i2.13607 page 249 sudan journal of medical sciences mara ioana pătrașcu et al as more surgeons started to be interested in the postoperative qol of the patient, rather than just reconstructing the abdominal wall, more studies were carried out in this direction, finding similar results. in a study by rogmark et al. [5], which included 217 patients, among which 103 presented themselves for a clinical examination, it was stated that by measuring the qol before and a few weeks after the surgery, the patients agreed to an improved function. a patient database was searched, picking all the discharged patients that underwent an ihr between 1998 and 2006 in order to define the population of this study. between 2010 and 2012, the clinical exams were performed and in 2015 the medical records were reviewed again to check for any other recurrences. data collected at one year postoperatively was similar to prior ones, finding differences only in the long run. the qol of the patients that were operated was higher than of the ones that refused surgery. all of the scales of the sf-36 questionnaire were improved, other than the role function, bodily pain, and emotional pain. roughly, 80% of the patients were satisfied with the results. the recurrence rates between the primary and secondary incisional hernia repair were similar (7.1% vs 10.9%), even though a secondary ih carries more complications and therefore is more complex. though if the hernia was asymptomatic, there was no need for another repair. patients who suffered from recurrence, chronic pain, or altered bodily function had lower qol. this is one of the most longevous studies, assessing the patients for over 11 years. it is also worth mentioning that patients with recurrences had more intense pain and lower physical function than patients without [3]. in another study [22], similar results were found, having 80% of the patients satisfied with their overall results, and chronic pain or recurrence being the main complaints at seven years postoperatively. complications were registered for 27% of the patients, but mostly between the clavien-dindo grades i and ii. additionally, 9% were operated within 90 days for various complications, such as deep wound infection or an arterial bleeding, but no mesh was explanted. the results of the sf-36 questionnaire were comparable to that of people who suffer from one or two chronic diseases. what is surprising is that even if the qol could be considered quite low in this case, most patients were pleased with the results. this makes us believe that the qol is not entirely influenced by the operation itself, but also by additional health problems. around 9.8% were taking painkillers on a daily basis due to the pain. among the patients that were not pleased, all of them suffered from chronic pain and only a half had a recurrence. at the follow up at 11 years, the registered recurrence rate was 8.1%. as highlighted by this study, in several other scientific papers, different recurrence rates were reported, usually varying doi 10.18502/sjms.v18i2.13607 page 250 sudan journal of medical sciences mara ioana pătrașcu et al between 8% and 30%. the recurrence tends to appear in the very first years after the surgery and then gradually decrease. similar results were found in another study [8], where patients that underwent an ihr were matched with a control group and observed for 10 years. overall, the outcomes of the surgery were excellent, 75% being satisfied with the end results. the sf-36 form showed no actual differences between the two groups, however, the physical function was slightly altered, with a karnofsky scale of 75. between the patients who had a previous abdominal surgery and the ones who had no one at that point, no differences were reported. mental health showed no alteration. therefore, it is safe to say that an ihr should improve the hrql. as shown in another article [23], the ihr impacts life on many of its dimensions. in this study, lee et al. had them grouped in 10 parts. one of them was the impact on daily life, where patients complained that due to chronic pain or fear of a recurrence they cannot perform activities such as playing with the nephews or having a job anymore. similarly, the other dimensions were affected, such as the emotional health, where the main concern was a continuous state of anxiety on a daily basis, even years after the surgery, because of any potential complications that could arise. pain was another concern, simply because it was harder than usual to pinpoint the exact cause and it took a toll on the patients’ emotional status. even so, in most cases, a visit to the doctor could pinpoint the exact problem. consumption of analgesics is another problem for patients who suffer from chronic pain, for both the financial and health status. moreover, many participants expressed a need for better communication with the health personnel, to the extent of even asking questions regarding the risks and benefits of the procedure, to ensure that the patients have a correct understanding. support groups are also a wish for many of them. having the ability to share their experiences and give advice to others could aid their recovery, both mentally and physically. similar results were found in a study by langbach et al. [24], but what is interesting is that they also made a comparison between men and women. the differences were not that significant, however, it seems that women have a better tolerance to pain if a positive attitude is maintained. between the ovhr and lvhr there were no major differences, this being in accordance with another study [3]. both improved physical function and mental health, but women seemed to have lower scores than men. moreover, another study [25] showed that despite the patients confirming an improved function, up to 63% indicated postoperative symptoms, such as pain or discomfort associated with both rest and movement. a fifth of them saw no actual improvements and another fifth considered their state to be worsened, confirming data doi 10.18502/sjms.v18i2.13607 page 251 sudan journal of medical sciences mara ioana pătrașcu et al from previous studies. the main disappointment that was stated is the lack of proper preoperative counselling, where all possible outcomes should have been presented. by knowing such information, some patients (10%) said that they would have denied the surgery. having up to 30% complaining of feelings of discomfort is quite disheartening, considering that the ihr is presented as the very solution to such complaints. another interesting point that is made in this study is the discrepancy between what a surgeon and a patient take into account when considering the success of the surgery. the surgeon is more interested in restoring the integrity of the abdominal wall, whereas the patient’s wishes are based on ceasing the pain, receiving visually pleasing results, and performing daily activities with the same ease as before the hernia occurrence. as shown in another study [4], indeed, an altered abdominal wall changes the distribution of the forces, affecting the neuromuscular system. the movements and the gait of such a person would be altered. such consequences would be assessed using a barycenter variation evaluation, and eventually the poma scale. as observed in this research, the patient who had an ihr done showed improvements in both these scores. therefore, better communication should be adopted between the two sides, and even though there is no actual tool to determine the success of an ihr, a set of values agreed upon by both surgeons and patients should be the key. therefore, after analyzing the information presented in this study, the following factors have been shown to influence the qol after ihr in a positive or negative manner. table 1: factors influencing the qol after ihr in a positive or negative manner. positive factors negative factors robotic-assisted surgery [17] ltd mesh [21] modified chevrel technique [16] female gender [24] absorbable sutures [19] chronic health diseases [22] suture fixation without tacks [20] lack of communication between patients and health personnel [23] mtd mesh [21] hernia size > 15 cm [11] male gender [24] thorough communication between patients and health personnel [23] 4. conclusion statistically, in most of the cases, the patients were satisfied with the results, whereas a small yet significant percentage were accusing chronic pain, strenuous movement, and doi 10.18502/sjms.v18i2.13607 page 252 sudan journal of medical sciences mara ioana pătrașcu et al recurrence. the recurrence is bound to appear in the earlier postoperative stages and if it is asymptomatic, it is up to the patient to decide whether it should be operated or not. while it is safe to say that the ihr is resulting in an increased qol, both physically and mentally, it is important to take into account the smaller percentage of people that do not end with such good results. therefore, better communication between health professionals and patients is needed. acknowledgements none. ethical considerations the current narrative review does not include any research on humans or animals published by the authors. competing interests the authors declare that they have no competing interests. availability of data and materials the dataset used in this narrative review is cited and available online. funding none. references [1] rognoni, c., cuccurullo, d., borsoi, l., bonavina, l., asti, e., crovella, f., bassi, u. a., carbone, g., guerini, f., de paolis, p., pessione, s., greco, v. m., baccarini, e., soliani, g., sagnelli, c., crovella, c., trapani, v., de nisco, c., eugeni, e., . . . piccoli, m. 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(2021). outcomes of mid-term and long-term degradable biosynthetic meshes in single-stage open complex abdominal wall reconstruction. hernia, 25(6), 1647– 1657. https://doi.org/10.1007/s10029-021-02415-7 [22] licari, l., campanella, s., carolla, c., madonia, c., canino, b., & salamone, g. (2021). abdominal wall incisional hernia repair improves respiratory function: results after 3 years of follow-up. hernia, 25(4), 999–1004. https://doi.org/10.1007/s10029-02002302-7 [23] lee, t. j., ulisney, k. l., choudhuri, a. k., swiger, j. l., & gibeily, g. j. (2019). understanding the patient perspective after ventral hernia repair. hernia, 23(5), 995–1001. https://doi.org/10.1007/s10029-019-02015-6 [24] langbach, o., bukholm, i., benth, j. š., & røkke, o. (2016). long-term quality of life and functionality after ventral hernia mesh repair. surgical endoscopy, 30(11), 5023– 5033. https://doi.org/10.1007/s00464-016-4850-9 [25] van veenendaal, n., poelman, m. m., van den heuvel, b., dwars, b. j., schreurs, w. h., stoot, j. h. m. b., & bonjer, h. j. (2021). patient-reported outcomes after incisional hernia repair. hernia, 25(6), 1677–1684. https://doi.org/10.1007/s10029-021-02477-7 doi 10.18502/sjms.v18i2.13607 page 256 introduction materials and methods results & discussion laparoscopic vs open vs robotic-assisted surgery method of fixation types of mesh conclusion acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4378 production and hosting by knowledge e research article hematological changes in sudanese patients with falciparum malaria attending elnihoud teaching hospital abdelnassir m. ahamed1, hafiz ahmed hobiel2, gad allah modawe3, and mohammed saeed elsammani4 1department of pathology, faculty of medicine and health sciences, university of west kordufan, elnihoud, sudan 2department of biochemistry, faculty of medicine and health sciences, university of west kordufan, elnihoud, sudan 3department of biochemistry, faculty of medicine and health sciences, omdurman islamic university, omdurman, sudan 4department of pathology, faculty of medicine, university of albaha, saudi arabia abstract backgrounds: malaria is a major public health problem in the tropical and subtropical areas of the world, including africa. most cases of malaria in africa are caused by plasmodium falciparum. objectives: this study was aimed to assess the hematological changes in patient with falciparum malaria and to estimate the incidence of leucopenia, thrombocytopenia, and its response to anti-malaria therapy, and to correlate the association of the hematological changes with p. falciparum-positive (study group) and p. falciparumnegative (control group). methodology: a total of 453 participants (353 cases and 100 as control group) were enrolled in this study, all of them were randomly selected from elnihoud teaching hospital, elnihoud locality, west kordufan state, sudan. questionnaire was filled by every participant and thick and thin blood films for malaria were prepared and stained by giemsa stain and the cbc was done by sysmex automated hematological analyzer. results: thrombocytopenia, leucopenia, microcytic hypochromic red blood cells and relative lymphocytosis have significant association with falciparum malaria with pvalues 0.008, 0.001, 0.008, and 0.004, respectively. conclusion: patients with thrombocytopenia and/or leucopenia with malaria should receive anti-malaria therapy and follow-up by cbc, and shouldn’t be hurried for a bone marrow examination. keywords: falciparum malaria, thrombocytopenia, leucopenia, relative lymphocytosis how to cite this article: abdelnassir m. ahamed, hafiz ahmed hobiel, gad allah modawe, and mohammed saeed elsammani (2019) “hematological changes in sudanese patients with falciparum malaria attending elnihoud teaching hospital,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 24–30. doi 10.18502/sjms.v14i1.4378 page 24 corresponding author: hafiz ahmed hobiel; email: hebiel78@yahoo.com received 15 january 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e abdelnassir m. ahamed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4378&domain=pdf&date_stamp=2019-03-31 mailto:hebiel78@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdelnassir m. ahamed et al 1. introduction malaria is a major public health problem in the tropical and subtropical parts of the world [1]. it is one of the most common dangerous protozoan disease in which most cases in africa are caused by p. falciparum, with a relatively small proportion attributable to p. malariae or p. ovale, while p. vivax is known to occur in only some areas of the region [2]. an estimated 219 million cases of malaria occurred worldwide in 2017 compared with 239 million cases in 2010 and 217 million cases in 2016. the who african region still bears the largest burden of malaria morbidity, with 200 million cases (92%) in 2017, followed by the who south-east asia region (5%) and the who eastern mediterranean region (2%) [3]. the clinical manifestation of falciparum malaria varies from mild acute febrile illness to life-threatening severe systemic complications involving one or more organ systems [4]. it causes significant hematological changes ranging from hemolytic anemia (hb < 10 g/dl.), defective erythropoiesis, and reticulocyte production, leukocytosis (wbc > 11 x 103/microliter), leukocytopenia (wbc < 4 x103/microliter), thrombocytopenia (tcp) platelets count less than 150 x103/microliter, platelet dysfunction in severe malaria, and disseminated intravascular coagulation (dic) (5). severe tcp is frequently noticed with p. falciparum malaria [5]. tcp during malarial infection may appear even before fever, anemia, and splenomegaly become manifest [6]. during early stages of malaria, platelet agglutination as a result of endothelial cell activation and release of activated von willebrand factor occur which may cause thrombocytopenia [7]. direct invasion of platelets by malarial parasites may occur. thrombocytopenia in malaria is usually mild and treated by eradication of malaria parasite [8]. thrombocytopenia is an early and consistent feature of malaria, but its pathogenesis remains incompletely understood [9]. the causes of thrombocytopenia in falciparum malaria are increased platelet consumption as evidenced by shortened survival of platelets and the finding of increased megakaryocytes in patient’s bone marrow and elevated plasma thrombopoietin levels [10], and systemic microvascular sequestration and endothelial activation may play a pathophysiological role, a hypothesis supported by the observation that the radiolabelled platelets of patients with falciparum malaria are diffusely sequestered rather than pooling in the liver or spleen [11]. population studies have shown an association between thrombocytopenia and outcome, and a recent study from india proposed that thrombocytopenia should be added to the world health organization (who) criteria for the definition of severe malaria [12]. this study was aimed to assess the hematological changes in patients with falciparum malaria. doi 10.18502/sjms.v14i1.4378 page 25 sudan journal of medical sciences abdelnassir m. ahamed et al 2. materials and methods this study was an analytical cross-sectional study, carried out in elnihoud teaching hospital, elnihoud locality, west kordufan state, sudan, from april 2015 to april 2016. elnihoud teaching hospital is tertiary referring hospital receiving approximately about 15,000 patients suffering from malaria annually. a total of 453 participants (353 cases and 100 as control group) were enrolled in this study, all of them were randomly selected. participants with positive blood film for malaria were taken as cases group, and febrile patients with a negative result for malaria were taken as control group, any patient with hematological disorders was excluded. the institutional research and ethics approval was obtained before the commencement of the study. all participants spoke sufficient arabic to provide informed consent. questionnaires were filled, blood samples were obtained for the detection of malaria using giemsa-stained thickand thin blood films and stander diagnostic (sd) ict for malaria antibodies. full blood count was done for the patients with abnormal blood count two weeks after completing the anti-malaria therapy; the complete blood count (cbc) was analyzed by automated hematological analyzer (sysmex xp-300); also the peripheral blood film was stained by leishman’s stain and screened by an expert hematologist. the data were analyzed by spss program version 20. 3. results the distribution of the ages of the study participants were between 4 months and 75 years with the mean of 29 +/– 3.4 years. of the total participants, 216 (88.5%) were rural while 28 (11.5%) were urban. the study results show that the incidence of pancytopenia among study group was 6 out of 353 (1.7%) (table 1). the incidences of anemia, leucopenia, and thrombocytopenia among the study group were: 77 out of 353 (21.8%), 22 out of 352 (6.3%), and 75 out of 353 (21.3%), respectively. whereas, on the other hand, the incidences of microcytic hypochromic red blood cells and relative lymphocytosis (the absolute lymphocyte count is normal but it is more than neutrophil count) among study group were 140 out of 353 (39.7%) and 51 out of 267 (19.1%), respectively. there was a statistically significant positive association between p. falciparum malaria and leucopenia, relative lymphocytosis, thrombocytopenia and microcytic hypochromic red blood cells with p-values 0.001, 0.004, 0.008, and 0.008, respectively (table 2). two weeks’ follow-up after completing the treatment, 90.7% of thrombocytopenic and 90.9% of thrombocytosis patients showed normal platelet count. doi 10.18502/sjms.v14i1.4378 page 26 sudan journal of medical sciences abdelnassir m. ahamed et al for wbcs, 90.9% of leukopenia and 86.5% of leukocytosis patients revealed normal value (table 3). table 1: characteristics and description of the study groups. characteristic patient control total p-value age under 5 years 37(12%) 33(24.7%) 70(17.3%) 5 to 14 years 46(14.9%) 12(12.6%) 58(14.4%) 15 to 50 years 164(53.1%) 34(35.8%) 198(49%) < 0.001 above 50 years 62(20.1%) 16(16.8%) 78(19.3%) total 309(100%) 95(100%) 404(100%) sex male 188(76.7%) 57(23.3%) 245(54.2%) female 165(79.7%) 42(20.3%) 207(45.8%) 0.128 total 353 (100%) 99(100%) 452(100%) residence area rural 216(88.5%) 68(81.9%) 284(86.9%) urban 28(11.5%) 15(18.1%) 43(13.1%) 0.135 total 244(100%) 83(100%) 327(100%) incidence of pancytopenia present 6(1.7%) 0(0.00%) 6(1.3%) absent 347(98.3%) 100(100%) 347(98.7%) 0.346 total 353 (100%) 100 (100%) 453 (100%) 4. discussion this study sets out to describe the hematological changes in p. falciparum patients in elnihoud teaching hospital, the study results revealed that there was a significant positive association between thrombocytopenia and p. falciparum malaria (p-value 0.008), which is consistent with [7, 13, 14], who stated that the most common complications of falciparum malaria is thrombocytopenia and platelet dysfunction. the thrombocytopenia is usually not associated with bleeding even in patients with very severe form (platelets less 10 x 103/microliter), and there was a complete recovery after treatment, so thrombocytopenia is a significant indicator for malaria, especially in correlation with typical fever and hypotension. also, the study shows a significant positive association between leucopenia and p. falciparum malaria (p-value 0.001), which is in agreement with ladhani et al. [15], who reported that leucopenia and thrombocytopenia occurred with p. falciparum malaria, but these were not associated with death. the leucopenia occurred most probably due to a bone marrow suppression, resulting from cytokines doi 10.18502/sjms.v14i1.4378 page 27 sudan journal of medical sciences abdelnassir m. ahamed et al table 2: comparison of hematological parameters of the study groups. characteristic patient control total p-value hb normal 275(77.9%) 85(85%) 360(79.5%) anemia 77(21.8) 15(15%) 92(20.3%) polycythemia 1(0.3%) 0(0%) 1(0.2%) 0.278 total 353(100%) 100 (100%) 453(100%) twbc normal 293(83.2%) 69(69%) 362(80.1%) leucopenia 22(6.3%) 5(5%) 27(6%) < 0.001 leukocytosis 37(10.5) 26(26%) 63(13.9%) total 352(100%) 100(100%) 452(100%) plt normal 267(75.6%) 79(79%) 346(76.4%) thrombocytopenia 75(21.3%) 12(12%) 87(19.2%) thrombocytosis 11(3.1%) 9(9%) 20(4.4%) 0.008 total 353 (100%) 100 (100%) 453 (100%) mcv normal 210(59.5%) 42(42%) 252(55.6%) microcytic 140(39.7%) 57(57%) 197(43.5%) 0.008 macrocytic 3(0.8%) 1(1%) 4(0.9%) total 353 (100%) 100 (100%) 453 (100%) relative lymphocytosis yes 51(19.1%) 1(2.3%) 52(16.8%) 0.004 no 216(80.9%) 42(97.7%) 258(83.2%) total 267(100%) 43 (100%) 310 (100%) table 3: patients response to anti-malaria therapy. characteristic patient before the therapy patient two weeks after the therapy normal values two weeks after the therapy p-value leucopenia 22(37.3%) 2 (28.6%) 20 (38.5%) leukocytosis 37(62.7%) 5 (71.4%) 32 (61.5%) 0.001 total 59 (100%) 7 (100%) 52 (100%) thrombocytopenia 75 (87.2%) 7 (87.5%) 68 (87.2%) thrombocytosis 11 (12.8%) 1 (12.5%) 10 (12.8%) 0.001 total 86 (100%) 8 (100%) 78 (100%) production and/or folate deficiency when associated with pancytopenia. there was a significant positive association between microcytic hypochromic red blood cell and p. falciparum malaria (p-value 0.008) as it is stated by who [8] which reported the same point. microcytic hypochromic red cells might due to either hepcidin production or loss of appetite and poor diet especially in childhood period. the study revealed doi 10.18502/sjms.v14i1.4378 page 28 sudan journal of medical sciences abdelnassir m. ahamed et al a significant positive association between relative lymphocytosis and p. falciparum malaria (p-value 0.004), same result reported by ladhani et al. [15]; this might be a part of the bone marrow failure which is associated with neutropenia because neutrophil has short half-life compared with lymphocytes and its deficiency appears early. there was no significant association with anemia and so pancytopenia because hemoglobin can take time to show a significant drop. two weeks after completing the treatment, patients with abnormal blood counts showed normal values that indicates that these patients should receive anti-malaria therapy irrespective of malaria-parasite results. 5. conclusion the study findings demonstrate that p. falciparum malaria is one of the common causes of hematological changes. the results showed that there was a statistically significant positive association between p. falciparum malaria and each of leucopenia, relative lymphocytosis, thrombocytopenia, and microcytic hypochromic red blood cells. acknowledgement the authors would like to thank the members of the department of pathology, their colleagues, and the staff workers in medical laboratory of elnihoud teaching hospital for their contribution and support. references [1] kidist. m and zerihun, z. 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(2002). changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome. british journal of haematology, vol. 119, no. 3, pp. 839–847. doi 10.18502/sjms.v14i1.4378 page 30 introduction materials and methods results discussion conclusion acknowledgement references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13605 production and hosting by knowledge e research article assessment of cardiovascular risk factors among sudanese patients with type 2 diabetes hisham mohammed abdelrahim1, abdelhaleem mustafa madani2,3, and tarig mohammed el-hadiyah2 1department of endocrinology, faculty of medicine, university of national ribat, khartoum, sudan 2pharmacology department, faculty of pharmacy, international university of africa, khartoum, sudan 3department of clinical pharmacy, ibn-elnafees cardiac center, omdurman teaching hospital, omdurman, sudan abstract background: individuals with type 2 diabetes who have optimum condition management are exposed to a significantly higher risk of developing cardiovascular disease (cvd) compared to those who do not have diabetes. people with diabetes are estimated to have a fourfold greater risk of developing cvd than people without diabetes. cvd risk factors other than diabetes include older age, obesity hypertension, dyslipidemia, smoking, and a family history of coronary or kidney diseases. objectives: the study aims to assess the cardiovascular risk factors among type2 diabetes at ribat hospital diabetes clinic, sudan. methods: t2 dm patients were evaluated for the presence of cvd risk factors by using data collecting form to extract data verbally and from patients’ files. results: out of 147 t2 dm files, 92 (61.7 %) were female, 57 (38.3 %) were male, and 58 (38.9 %) patients were ≥ 60 year old. patients who had poor glycemic control were 112 (75.2 %) and those who met the glycemic target were only 37 (24.8 %). older age (p = 0.01) and diabetes duration (p = 0.026) were associated with poor glycemic control. prevalence of hypertension was 61 (40.9 %), dyslipidemia 31 (20.8 %), and physical inactivity 112 (75.2 %). all patients had at least one cvd risk factor and those having all three risk factors were 48 (32.2 %). conclusion: all t2 dm diabetic patients in rhdc had at least one cvd risk factor and almost a third of them had all three risk factors. poor glycemic control, physical inactivity, hypertension, and age ≥ 60 had the higher prevalence of cvd risk factors. how to cite this article: hisham mohammed abdelrahim, abdelhaleem mustafa madani, and tarig mohammed el-hadiyah (2023) “assessment of cardiovascular risk factors among sudanese patients with type 2 diabetes,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 221–230. doi 10.18502/sjms.v18i2.13605 page 221 corresponding author: abdelhaleem mustafa madani; email: madani70011@gmail.com received 22 november 2021 accepted 5 march 2023 published 30 june 2023 production and hosting by knowledge e abdelhalim madani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdelhalim madani 1. introduction type 2 diabetes mellitus (t2dm) is very widespread and is responsible for enormous morbidity and mortality. moreover, it is a major financial exhaustion on individuals, families, health systems, and societies in general. the prevalence of dm globally continues to increase, rising to 10% of the population in many countries such as india and china, which are now, starting to simulate western lifestyles. this substantial increment in the number of diabetics has led the experts to set the prediction that by 2045 >600 million individuals would be developing t2dm globally [1]. t2dm patients with optimum treatment conditions are prone to have a significantly higher risk of cardiovascular diseases (cvd) compared to those not having diabetes [2]. it has been estimated that people with diabetes have a fourfold greater risk of developing cvd than people without diabetes [3, 4]. in a systematic review among individuals with t2dm, the estimated prevalence of cvd was 32.2% and concluded that cvd was responsible for 50.3% of all deaths in patients with t2dm [5]. several studies of patients with diabetes have revealed that close monitoring of glycemia substantially reduced cvd morbidity and mortality [6, 7]. the famous united kingdom prospective diabetes study (ukpds) reported that 1% reduction in hba1c concentration decreased micro and macro-vascular long-term diabetes-related complications and mortality [8]. intensive glycemic control substantially lowers the risk of cvd, whilst poor control increases risk factors for cvd and other risk of diabetes complications and mortality [9, 10]. american diabetes association specifies hba1c to be less than 7% in most patients with diabetes as an optimum target for glycemic control [9]. many factors are linked to diabetes poor control such as older age, long duration of diabetes, sedentary lifestyle, non-adherence to medications, and patients awareness of diabetes and the disease treatment [10]. cvd risk factors other than diabetes include older age, obesity [11], hypertension, dyslipidemia, smoking, a family history of coronary diseases, chronic kidney disease, and the presence of albuminuria [12]. intensive glycemic control together with appropriate management of other risk factors for cvd substantially reduced cvd morbidity and mortality [1, 6, 13]. risk factors of developing cvd are more frequent in clinics treating diabetes in sudan; however, studies regarding the actual proportion of diabetic patients with those risks are rare, therefore the present study was undertaken to specify the prevalence of risk factors for cvd among diabetic patients at ribat university hospital diabetic clinic (ruhdc), sudan. doi 10.18502/sjms.v18i2.13605 page 222 sudan journal of medical sciences abdelhalim madani 2. materials and methods 2.1. study design, setting, and participants this is a cross-sectional hospital based, single center study conducted at ruhdc, sudan during april-may 2017 for two months. records of 147 patients were registered in this study. 2.2. inclusion and exclusion all t2dm patients’ records were selected for this study. the eligibility criteria for patients to participate in the study included their complete records, age ≥ 18, and regular medication from the past three months. the pregnant women and patients who refused to participate were excluded. 2.3. sample size records of 187 patients attending ruhdc during the study period were examined. after the fast screening, 149 completed records were selected for this study. 2.4. tools of data collection the data collecting form was prepared in collaboration with staff members in ribat university; faculty of pharmacy from recently updated literature. finally, data collecting form was further revised by researchers who are experts in diabetes treatment to ensure validity for the study objectives. patients were informed about the aim of the study. data collecting form included socio-demographic characteristics, most recent blood pressure measurement, and most recent serum concentrations of low-density lipoprotein (ldl), high-density lipoprotein (hdl), total cholesterol, triglycerides, and glycated hemoglobin (hba1c). cvd risk factors are considered elevated as shown in table 5. for precise assessment of the current status of control of cvd risk factors, the most recent, available during the last three months, hga1c, lipid profile, and bp values were used. if any of them were unavailable, that file was excluded. information including socio-demographic characteristics and physical inactivity was taken verbally from the patients. physical activity was specified as performing of =150 min of moderate to vigorous-intensity exercise per week for the fit patients. doi 10.18502/sjms.v18i2.13605 page 223 sudan journal of medical sciences abdelhalim madani 2.5. data analysis the process of analysis was conducted using spss version 16. descriptive analysis was conducted for data and representation in tables as frequency and percentage. binary logistic regression was carried out to specify factors that are associated with poor glycemic control. p value < 05 was estimated as statistically significant. 3. results in the current study, 147 t2dm patients’ records were introduced for analysis. females were 92 (61.7%), males 57 (38.3%), patients ≥ 60 years old were 58 (38.9 %), and < 60 were 91 (61.1%). the majority having a basic education level were 70 (47%), illiterate were 19 (12.8%), non-worker were 110 (73.8 %), officers were 32 (21.5%) (table 1). a total of 112 (75.2%) patients had poor diabetes control (hba1 c > 7%) and those who met the glycemic target were 37 (24.8%). age (p = 0.01) and diabetes duration (p =0.026) were associated with glycemic poor control (table 4). prevalence of hypertension was 61 (40.9%), dyslipidemia 31 (20.8%), physical inactivity 112 (75.2%), and smoking was 6 (4%) (table 2). all patients had at least one cvd risk factor; three risk factors were 48 (32.2%) and five risk factors were 6 (4%) (table 3). 4. discussion patients with diabetes are known to be at a greater risk for cardiovascular diseases than non-diabetic individuals, however intensive monitoring of recommended glycemic (hb a1c) target to be in less than 7% together with appropriate management of other cardiovascular risk factors, reduce or delay development of cvd and other complications of diabetes. this study revealed that almost quarter of the patients achieved the glycemic control target and this finding was comparable to alramadanet alstudy who reported 24.1% [10], alzahebet alstudy exhibited 25.1% [14] and khattab et al study who showed 34.9% of the patients had attained the target level of glycemic control [15]. age ((p-value: 0.010) and longer duration of diabetes (p-value: 0.026) in this study was associated of poor glycemic control and this result was consistent with that reported by many studies [10, 15, 16]. hypertension is linked to cardiovascular mortality and morbidity risks which are twicefold in the presence of diabetes; thus, intensifying t2dm cardiovascular complications [17]. hypertension is predominant in individuals with diabetes [18] and considered a doi 10.18502/sjms.v18i2.13605 page 224 sudan journal of medical sciences abdelhalim madani major cause of cvd. in this work, almost 41% of our patients had hypertension and this result was less than salman et al’s study who reported 54.2% [17]. physical activity is known to be a vital component of standard diabetes management [19], it protects individuals against hazards of cvd risk factors, long-term diabetes complications and strengthens the general health of the patients [20, 21]. despite the positive effects of physical activity, a vast number of patients with diabetes are physically inactive [22]. most patients in this work were physically inactive and these findings are in line with many studies [23, 24, 25]. dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus and this is attributed to the fact that diabetes can cause a variety of disarrangement in oxidative/reduction in lipid metabolic and regulatory mechanisms that might be responsible for the accumulation of lipids particles [26]. this study showed that almost one-fifth of patients had dyslipidemia and this result was better than haile and his colleague’s study in ethiopia which reported 68.1% [27]. moreover, chamba et al.’s study from tanzania reported 83% [28] and hussein et al.’s study from egypt exhibited that 60.7% had dyslipidemia [29]. the incidence of cvd, diabetes, and other complications related to diabetes arise among individuals aged older than 65 [30]. this work revealed that 60-year-old patients were linked to poor glycemic control (hb a1c) and this increases the risk of cvd. almost 39% of patients in this study aged 60 and this was higher than that reported by hussein et al. [29] and bello et al. [31] studies who reported 22.5% and 28.9% respectively. although one cvd risk factor increases the risk of morbidity and mortality, the effect is enhanced when the combination is more than one [32]. in this study, all patients had at least one cvd risk factor and 32.2 % had three risk factors. the study by hussien et al. from egypt reported that all his patients had at least one cvd risk factor and 24.5% had three risk factors [29]. a study carried out in saudi arabia by al slail et al. showed that 31% of the patients had three cvd risk factors [33]. these findings from this group of patients need to be further authenticated by large and multicenter study, in particular, it needs to be determined whether having multiple cvd risk factors varies by socioeconomic status. 5. conclusion all t2 dm diabetic individuals in rhdc had at least one cvd risk factor and almost a third of them had three risk factors. poor glycemic control, physical inactivity, hypertension, and age ≥ 60 had higher prevalence of cvd risk factors. multiple cvd risk factors lead to a high burden on both the patients and the health system, especially in a doi 10.18502/sjms.v18i2.13605 page 225 sudan journal of medical sciences abdelhalim madani country such as sudan. therefore, it is essential that the healthcare system focuses on raising awareness among the population, and implements appropriate measures for prevention, early detection, and suitable management of cvd risk factors among patients with t2dm. acknowledgments we would like to acknowledge the study participants who volunteered to give all relevant information for the study. we are grateful to ruhdc staff members for their support during the data collection. ethical considerations all t2dm individuals who volunteered to take part in this study were enrolled after signing a written agreement. the protocol and the written consent were approved by research board faculty of pharmacy, national ribat university. conflict of interest none declared. availability of data and materials all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding none. references [1] cosentino, f., grant, p. j., aboyans, v., bailey, c. j., ceriello, a., delgado, v., federici, m., filippatos, g., grobbee, d. e., hansen, t. b., huikuri, h. v., johansson, i., jüni, p., lettino, m., marx, n., mellbin, l. g., östgren, c. j., rocca, b., roffi, m., . . . wheeler, d. c., & the esc scientific document group. 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(2013). physical activity in adults with and without diabetes: from the ‘high-risk’ approach to the ‘populationbased’ approach of prevention. bmc public health, 13, 1002. [25] parajuli, j., saleh, f., thapa, n., & ali, l. (2014). factors associated with nonadherence to diet and physical activity among nepalese type 2 diabetes patients: a cross sectional study. bmc research notes, 7, 758. [26] hirano, t. (2018). pathophysiology of diabetic dyslipidemia. journal of atherosclerosis and thrombosis, 25, 771–782. [27] haile, k., & timerga, a. (2020). dyslipidemia and its associated risk factors among adult type-2 diabetic patients at jimma university medical center, jimma, southwest ethiopia. diabetes, metabolic syndrome and obesity, 13, 4589–4597. [28] chamba, n. g., shao, e. r., sonda, t., & lyaruu, i. a. (2017). lipid profile of type 2 diabetic patients at a tertiary hospital in tanzania: cross sectional study. journal of endocrinology and diabetes, 4, 1–6. [29] hussein, a., mahmoud, s. e. d., awad, m. s., & mahmoud, h. e. m. (2020). assessment of cardiovascular risk factors in patients with type 2 diabetes in upper egypt villages. diabetes, metabolic syndrome and obesity, 13, 4737–4746. [30] halter, j. b., musi, n., mcfarland horne, f., crandall, j. p., goldberg, a., harkless, l., hazzard, w. r., huang, e. s., kirkman, m. s., plutzky, j., schmader, k. e., zieman, s., & high, k. p. (2014). diabetes and cardiovascular disease in older adults: current status and future directions. diabetes, 63, 2578–2589. [31] bello-ovosi, b. o., ovosi, j. o., ogunsina, m. a., asuke, s., & ibrahim, m. s. (2019). prevalence and pattern of dyslipidemia in patients with type 2 diabetes mellitus in zaria, northwestern nigeria. the pan african medical journal, 34, 123. [32] kalofoutis, c., piperi, c., kalofoutis, a., harris, f., phoenix, d., & singh, j. (2007). type ii diabetes mellitus and cardiovascular risk factors: current therapeutic approaches. experimental and clinical cardiology, 12, 17–28. doi 10.18502/sjms.v18i2.13605 page 229 sudan journal of medical sciences abdelhalim madani [33] al slail, f. y., abid, o., assiri, a. m., memish, z. a., & ali, m. k. (2016).cardiovascular risk profiles of adults with type-2 diabetes treated at urban hospitals in riyadh, saudi arabia. journal of epidemiology and global health, 6(1): 29–36. doi 10.18502/sjms.v18i2.13605 page 230 introduction materials and methods study design, setting, and participants inclusion and exclusion sample size tools of data collection data analysis results discussion conclusion acknowledgments ethical considerations conflict of interest availability of data and materials funding references sudan journal of medical sciences volume 18, issue no. 2, doi 10.18502/sjms.v18i2.13603 production and hosting by knowledge e research article serum cytokine levels as critical parameters in early diagnosis of disease progression in covid-19: a pilot study walaa mohammedsaeed1, ziab zakey alahmadey2, and nikhat manzoor3 1clinical biochemistry, department of medical laboratory technology, faculty of applied medical sciences, taibah university, madinah, saudi arabia 2laboratory department, ohud hospital madinah, saudi arabia 3medical mycology lab, department of biosciences, jamia millia islamia, new delhi, india orcid: walaa mohammedsaeed: https://orcid.org/0000-0002-6696-5441 abstract background: the severity of coronavirus disease 2019 (covid-19) has been proposed to be associated with cytokine dysregulation. a significant number of patients become serious and need intensive care in hospitals. methods: the concentrations of cytokines interleukin (il-6, il-10) and tumor necrosis factor (tnf) were estimated using enzyme-linked immunosorbent assay (elisa) in serum samples of 60 adult patients infected with sars-cov-2 along with 50 healthy controls of the same age. the mean age of the subjects was 50-52 years and included an equal number of males and females. the patients were further grouped as severe (38 patients) and non-severe cases (22 patients). results: the mean serum cytokine levels were significantly higher in the covid-19 patients than in the healthy controls. il-6 was excessively elevated in comparison to il-10 and tnf. comparative analysis of severe versus non-severe cases revealed only slight alterations in the cytokine levels: il-6 being the most elevated in severe cases. the concentration of the liver enzyme alt was higher than ast in both severe and non-severe cases. the mean concentration of serum electrolytes (na, k, and ca) did not vary much between the patients and healthy controls. conclusion: there was a significant positive correlation between the levels of cytokines serum biomarkers in covid-19 patients. it may be suggested that early detection of cytokines, especially il-6 and serum biomarkers can help predict disease prognosis and severity in covid-19 patients. keywords: covid-19, cytokines, disease severity, diagnosis, liver function, kidney function how to cite this article: walaa mohammedsaeed, ziab zakey alahmadey, and nikhat manzoor (2023) “serum cytokine levels as critical parameters in early diagnosis of disease progression in covid-19: a pilot study ,” sudan journal of medical sciences, vol. 18, issue no. 2, pages 190–202. doi 10.18502/sjms.v18i2.13603 page 190 corresponding author: walaa mohammedsaeed; email: wmohammedsaeed@taibahu.edu.sa received 15 january 2023 accepted 12 march 2023 published 30 june 2023 production and hosting by knowledge e walaa mohammedsaeed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. nazik elmalaika obaid seid ahmed husain, md, m.sc, mhpe, phd. http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences walaa mohammedsaeed et al 1. introduction the sars-cov-2 infection (covid-19) has been wreaking havoc since its outbreak in december 2019. more than 660 million infections and 6.7 million deaths have been reported to date. the virus has not only spread worldwide but has also mutated several times [1]. the disease has pneumonia-like symptoms affecting the lungs with varying degrees of severity. from the infected lungs, it may spread to other parts of the body, sometimes leading to multiple organ failure [2]. acute lung injury in covid-19 patients may be triggered by the release of inflammatory molecules, activated immune cells, overproduction of cytokines, and the presence of adhesins [3]. the damage caused to the lungs and other body organs has been linked to the abnormally strong proinflammatory host immune response. described as the ‘cytokine storm syndrome,’ it plays an important role in the pathophysiology of covid-19. the clinical symptoms vary among individuals from asymptomatic and non-specific to more serious, where patients need hospitalization [4]. the severity of covid-19 disease depends on several factors imparting poor prognoses, such as high viral load, old age, and comorbidities (cancer, coronary heart disease, diabetes, and hypertension) [5, 6]. the disease pathogenesis is not clearly understood and comprises several intricate and complex physiological processes. cytokines are released by immune cells to regulate inflammatory responses during tissue damage and infections. it has been shown that some proinflammatory cytokines, namely, tumor necrosis factor-alpha (tnf-α), transforming growth factor-beta (tgf-β), interferon gamma (ifnγ), interleukins (il-1, il-8, and il-6), play a crucial role in several pathological conditions [7, 8]. the involvement of tnf-α is an intermediary in the pathogenesis of certain viral infections like influenza [9]. some other cytokines, like il-4 and il-10, help reduce inflammation [10]. the role of cytokines in disease pathogenesis is still unclear, but reports suggest that their excessive outburst may be responsible for disease progression and sometimes death of the patient [11, 12]. the serum cytokine levels must be regulated, but whether anti-cytokine therapy has any benefit needs further evaluation [13]. the liver, heart, and kidneys are vital organs of the human body that perform some critical functions. detection of specific biomarkers and their appropriate concentrations in the blood helps investigate these organs’ health status [14]. a strong connection has been observed between the severity of covid-19 and chronic liver diseases accompanied by inflammation and dysregulation of immune responses. patients suffering from underlying conditions carry a greater risk of adverse consequences after contracting covid-19. moreover, when infected, healthy individuals exhibit abnormal liver function, directly implicating the virus in damaging the liver and doi 10.18502/sjms.v18i2.13603 page 191 sudan journal of medical sciences walaa mohammedsaeed et al metabolism [15]. aspartate aminotransferase (ast) and alanine aminotransferase (alt) are biomarkers for hepatocellular damage. bilirubin and albumin levels assess the liver’s secretory and synthetic capacities, respectively [16]. increased levels of serum creatinine can indicate renal dysfunction. serum ferritin, creatine kinase (ck), lactate dehydrogenase (ldh), inflammatory factors, and electrolytes (sodium, potassium) can be used as indicators for covid-19 [17]. as observed with other viral infections, increasing cytokine levels have emerged as early parameters in covid-19 disease advancement [18]. hence, estimating increased serum cytokine levels and abnormalities in the hepatic, renal, and cardiac biomarkers can be important in predicting poor outcomes in covid19 patients. the levels of il-6, il-10, and tnf in the serum can also predict the severity of the disease, as cytokines play an important role in host immunity and immunopathology during the infection. the present study thus attempts to correlate cytokine levels with biomarkers of vital body organs in covid-19 patients. 2. methods 2.1. patients and data collection a total of 60 covid-19 patients were randomly selected from the ohud hospital, madinah, saudi arabia. a healthy control group of similar age (50 subjects) was selected from taibah university, madinah, saudi arabia. the clinical and laboratory data of the patients were analyzed and documented. all the cases were assessed according to the inclusion and exclusion criteria. individuals with a history of endocrine diseases were excluded. patients with confirmed covid-19 were categorized into two groups (severe and non-severe) based on clinical characteristics, symptoms, and results obtained from chest radiography [19]. blood samples (3 ml) were collected in serum separator tubes and allowed to clot for 2 h at room temperature before centrifugation at 1000×g for 15 min. serum was collected and stored at -80∘c. the serum concentrations of tnf-α, il-10, and il-6 were determined in the subjects. biochemical assays (kidney and liver function tests) were performed to estimate the concentration of creatinine, urea, na, k and ca, troponin i, c-reactive protein (crp), ldh, ck, alt, ast, bilirubin, albumin, and ferritin using the automated architect c4000, as per the manufacturer’s guidelines. doi 10.18502/sjms.v18i2.13603 page 192 sudan journal of medical sciences walaa mohammedsaeed et al 2.2. enzyme-linked immunosorbent assays (elisa) cytokine concentrations were determined using elisa development kits (cusabio technology llc, houston, usa) in adherence with the manufacturer’s instructions for tnf-α, il-10, and il-6. the antibody specific for each cytokine was pre-coated onto a microplate. the optical density was verified using a mindray mr-96a/mindray elisa reader microplate reader (mindray, guangdong, china) set at 450 nm. the experiment was carried out twice, with duplicate samples within each experiment. 2.3. statistical analysis quantitative data were normally distributed and expressed as mean with standard deviations (± sd). student’s t-test evaluated differences between groups. the spearman correlation coefficient calculations were used to investigate the association between the different parameters. all statistical analyses were performed using the statistics package of social science (spss 20, spss inc., chicago, il) and two-tailed p-values. 3. results 3.1. patient characteristics and cytokine levels the mean age of the covid-19 patients was comparable (50 ± 10.6 years) to that of the healthy controls (52 ± 12.8 years) and included subjects from both genders equally. the serum concentrations of liver enzymes alt and ast in the patients were high (60.44 ± 33.07 u/l and 49.20 ± 25.17 u/l) in comparison to healthy controls, where the values were 10.8 ± 4.6 u/l and 15.7 ± 7.3 u/l, respectively. similarly, in covid-19 patients the concentrations of albumin and bilirubin were 45 ± 15.35 g/l and 50.34 ± 21.80 mg/dl, respectively, while healthy controls were 40.7 ± 31.9 g/l and 1.4 ± 0.8 mg/dl, respectively. thus, the serum concentrations of liver function biomarkers in covid-19 patients were much higher than in healthy controls. the serum levels of creatinine, urea, na, k, and ca (biomarkers of renal function) in covid-19 patients were 292.95 ± 86.73 µmol/l, 20.83 ± 10.98 mmol/l, 149.35 ± 22.96 mmol/l, 1.33 ± 1.2 mmol/l, and 2.15 ± 0.87 mmol/l, respectively. serum concentrations for the same in healthy controls were 55.67 ± 20.93 µmol/l, 8.10 ± 5.13 mmol/l, 130.87 ± 8.77 mmol/l, 3.77 ± 0.77 mmol/l, and 2.10 ± 0.52 mmol/l, respectively. except for ca and k, the concentrations of renal function biomarkers were significantly higher in doi 10.18502/sjms.v18i2.13603 page 193 sudan journal of medical sciences walaa mohammedsaeed et al covid-19 patients compared to controls. the serum levels of ldh (391.84 ± 75.9 u/l), ck (393.88 ± 75.27 u/l), crp (50 ± 15.35 mg/l), and ferritin (599.64 ± 51.90 ng/ml), although not troponin (0.5 ± 0.20 ng/l), were significantly increased in the patients in comparison to healthy controls where these values were respectively, 110.57 ± 27.6 u/l, 50.44 ± 40.17 u/l, 6.9 ± 3.35 mg/l, 107.69 ± 55.80 ng/ml, and 0.2 ± 0.10 ng/l (table 1). also, the levels of cytokines il-6 (0.8 ± 0.75 pg/ml), il-10 (3.2 ± 2.05 pg/ml), and tnf (6.1 ± 3.32 pg/ml) in healthy controls were found to increase to 30.27 ± 13.35 pg/ml, 17.6 ± 7.2 pg/ml and 15.4 ± 6.4 pg/ml in the diseased individuals, p < 0.001**. table 1: clinical characteristics and cytokine levels in covid-19 patients and the healthy population. parameters covid-19 patients n = 60) control (n = 50) p-value age 50 ± 10.6 52 ± 12.8 sex (number) male = 30 male = 25 female = 30 female = 25 alt (u/l) 60.44 ± 33.07 10.8 ± 4.6 0.01* ast (u/l) 49.20 ± 25.17 15.7 ± 7.3 0.02* bilirubin (mg/dl) 50.34 ± 21.80 1.4 ± 0.8 <0.001** albumin (g/l) 45 ±15.35 40.7 ± 31.9 0.06 creatinine (µmol/l) 292.95 ± 86.73 55.67 ± 20.93 0.01* urea (mmol/l) 20.83 ± 10.98 8.10 ± 5.13 0.06 na (mmol/l) 149.35 ± 22.96 130.87 ± 8.77 0.04* k (mmol/l) 1.33 ± 1.2 3.77 ± 0.77 0.04* ca (mmol/l) 2.15 ± 0.87 2.10 ± 0.52 0.072 ck (u/l) 393.88 ± 75.27 50.44 ± 40.17 <0.001** ldh (u/l) 391.84 ±75.9 110.57 ± 27.6 0.002** troponin (ng/l) 0.5 ± 0.20 0.2 ± 0.10 0.08 ferritin (ng/ml) 599.64 ± 51.90 107.69 ± 55.80 <0.001** crp (mg/l) 50 ± 15.35 6.9 ± 3.35 0.003* il-6 (pg/ml) 30.27 ± 13.35 0.8 ± 0.75 <0.001** il-10 (pg/ml) 17.6 ± 7.2 3.2 ± 2.05 <0.001** tnf (pg/ml) 15.4 ± 6.4 6.1 ± 3.32 <0.001** data are presented as mean ± sd. *p < 0.05, **p < 0.001. 3.2. cytokine levels and other biomarkers in severe and non-severe covid-19 patients table 2 shows the comparative variations in the concentrations of hepatic, renal, and cardiac biomarkers with that of cytokines (il-6, il-10, and tnf) between severe and non-severe covid-19 cases. the mean il-6 concentration in severe covid-19 patients was 20.17 ± 10.35 pg/ml, statistically greater than in non-severe patients (10.8 ± 5.75 doi 10.18502/sjms.v18i2.13603 page 194 sudan journal of medical sciences walaa mohammedsaeed et al pg/ml). similarly, the mean concentrations of il-10 (15.03 ± 5.62 pg/ml) and tnf (17.25 ± 6.47 pg/ml) in severe covid-19 patients were again significantly higher than in nonsevere patients (10.21 pg/ml and 11.21 ± 4.32, respectively). compared to non-severe covid-19 patients, the severe cases showed significantly higher levels of serum alt, ast, and bilirubin, which were 65.22 ± 50.91 mmol/l and 53.95 ± 46.50 mmol/l and 50.89 ± 32.62 mg/dl, respectively. in the case of non-severe cases, the serum levels of alt, ast, and bilirubin were 12.8 ± 8.6, 15.7± 7.3, and 20.4 ± 1.5, respectively. the serum levels of creatinine and na were significantly higher (184.28 ± 34.89 µmol/l and 148.10 ± 20.71 mmol/l, respectively) in severe cases, while the values in non-severe cases were 78.45 ± 50.99 and 138.17 ± 78.99, respectively. the concentration of k was slightly higher (2.99 ± 2.92 mmol/l) in non-severe cases than in severe ones (1.25 ± 0.92 mmol/l). the levels of cardiac biomarkers were again significantly higher in severe cases compared to non-severe patients (table 2). the concentrations of ck, ldh, ferritin, and crp were 55.94 ± 100.07 u/l, 100.54 ± 25.9 u/l, 100.64 ± 45.80 ng/ml, and 15.9 ± 4.35 mg/l in non-severe cases. the concentration of the same biomarkers was considerably increased in severe covid-19 cases. in patients with severe disease, the serum concentration values for ck, ldh, ferritin, and crp were 350.88 ± 45.17 u/l, 362.44 ± 45.9 u/l, 750.60 ± 81.80 ng/ml, and 29 ± 9.35 mg/l, respectively. table 2: alterations in cytokine levels and other biomarkers in severe and non-severe covid-19 patients. biomarkers non-severe cases, n = 22 severe cases, n = 38 p-value mean ± sd mean ± sd il-6 10.8 ± 5.75 20.17 ± 10.35 0.01* il-10 10.21 ± 4.05 15.03 ± 5.62 0.03* tnf 11.21 ± 4.32 17.25 ± 6.47 0.01* alt 12.8 ± 8.6 65.22± 50.91 0.001** ast 15.7 ± 7.3 53.95 ± 46.50 0.001** bilirubin (mg/dl) 20.4 ± 1.5 50.89 ± 32.62 0.002** creatinine(µmol/l) 78.45 ± 50.99 184.28 ± 34.89 0.003** na(mmol/l) 138.17 ± 78.99 148.10 ± 20.71 0.04* k(mmol/l) 2.99 ± 2.92 1.25 ± 0.92 0.06 ck (u/l) 55.94 ± 100.07 350.88 ± 45.17 0.003** ldh (u/l) 100.54 ± 25.9 362.44 ± 45.9 0.001** ferritin (ng/ml) 100.64 ± 45.80 750.60 ± 81.80 0.0001** crp (mg/l) 15.9 ± 4.35 29 ± 9.35 0.05* data were analyzed using t-test. the values indicate statistical significance (p < 0.001** and p < 0.05*) doi 10.18502/sjms.v18i2.13603 page 195 sudan journal of medical sciences walaa mohammedsaeed et al 3.3. correlation between cytokine levels and biochemical markers in covid-19 patients the relationship between serum cytokines and other biochemical markers in covid-19 patients is in table 3. the values indicated that serum il-6 showed significant positive correlations with alt (r = 0.750, p = 0.02), ast (r = 0.659, p = 0.04), ck (r = 0.569, p = 0.04), ferritin (r = 0.704, p = 0.02), and crp (r = 0.859, p = 0.001). on the other hand, il-10 showed significant positive correlations with only alt (r = 0.636, p = 0.04) and ast (r = 0.672, p = 0.5). interestingly, tnf showed a positive correlation with alt (r = 0.726 p = 0.05), ast (r = 0.682 p = 0.03), ck (r = 0.619 p = 0.04), ferritin (r = 0.604 p = 0.02) and crp (r = 0.784, p = 0.03). our results showed no significant positive correlations between serum cytokines with biological parameters like bilirubin, creatinine, na, and ldh. table 3: relationship between serum cytokine levels and other biochemical parameters in covid-19 patients. il-6 il-10 tnf r p r p r p alt 0.750 0.02* 0.636 0.04* 0.726 0.05* ast 0.659 0.04* 0.672 0.05* 0.682 0.03* bilirubin 0.210 0.060 0.329 0.07 0.043 0.08 creatinine 0.082 0.073 0.257 0.06 0.257 0.09 na 0.201 0.025 0.078 0.08 0.068 0.06 ck 0.569 0.04* 0.319 0.07 0.619 0.04* ldh 0.122 0.06 0.136 0.07 0.123 0.09 ferritin 0.704 0.02* 0.257 0.08 0.604 0.02* crp 0.859 0.001** 0.426 0.06 0.646 0.03* il-6 0.741 0.002** 0.784 0.003** il-10 0.741 0.002** 0.604 0.02* tnf 0.784 0.003** 0.604 0.02* correlation is statistically significant (p < 0.05* and p < 0.001**) 4. discussion under normal conditions, cytokines coordinate the host’s immune response against microbial infections. insufficient cytokines are incapable of modulating inflammation and dealing with pathogenic invasion. similarly, excessively high amounts can sometimes cause irreparable damage. covid-19 patients discharged from the icu seem to have more elevated levels of inflammatory cytokines than individuals who are less severely doi 10.18502/sjms.v18i2.13603 page 196 sudan journal of medical sciences walaa mohammedsaeed et al infected. cytokine storm generation is not a universal feature of all infections. it has been observed to be triggered by the influenza a virus and may have been the cause of death during the 1918 influenza pandemic [20]. immunotherapy, organ transplantation, cancer therapy, aids, and sepsis are some conditions that can trigger the overproduction of cytokines and inflammatory molecules, affecting multiple organs and become lifethreatening [21]. in the case of covid-19, the selective behavior of the host response toward the virus needs to be investigated. although unclear, the expression of specific genes may generate a cytokine storm besides other factors [22]. the severity of the disease depends on underlying health conditions like diabetes, heart disease, hypertension, and other comorbidities. early diagnosis can be made by estimating the level of cytokines before the body organs are affected, specifically the heart, liver, and kidneys. elevated cytokine levels and anomalies in the blood profiles of patients can be helpful indicators of disease progression [23] . previous reports have implicated excessively high levels of il-6 in disease severity and high mortality in covid19 patients [24]. the available clinical data have indicated that moderate and severe covid-19 patients display abnormal liver function with increased levels of ast and alt [25]. however, the impact of covid-19 on liver and kidney function is yet to be completely understood. studies have shown that cytokine storms generated in noncovid-19 cases also lead to acute liver injury [26-27]. early measurement of serum cytokines is thus a reliable predictor of disease outcome and, hence, is critical for early diagnosis and treatment. a model based on cytokine levels can help optimize therapeutic strategies and design clinical trials to modulate the released inflammatory molecules [28]. increased amounts of ldh and ck enzymes in the blood indicate cellular damage. similarly, the release of cardiac biomarkers (ck, troponin, myoglobin) in the blood indicates a damaged heart. their levels can be estimated in diagnosing cardiac ischemia, a condition common in sars-cov2 infection. the protein troponin is the most commonly used biomarker, with very high sensitivity as it remains in the blood for longer periods. although not specific, the concentration of ck often doubles when the heart is damaged [25]. in the present study, the serum concentrations of cytokines il-6, il-10, and tnf were all found to be elevated in covid-19 patients. the concentration of il-6 was found to be elevated 37-fold, which is extremely high in comparison to the other two cytokines. ferritin and il-10 were elevated by 5.5-fold, while tnf was only 2.5-fold higher compared to the healthy controls. tnf is a proinflammatory cytokine largely released by activated macrophages, t lymphocytes, and natural killer cells. it displays a complex network of interactions with other cytokines and further stimulates their release. il-10, on the other hand, is an inhibitor of pro-inflammatory doi 10.18502/sjms.v18i2.13603 page 197 sudan journal of medical sciences walaa mohammedsaeed et al cytokine production and antigen presentation in activated monocytes/macrophages [29]. along with elevated serum cytokine levels, covid-19 patients displayed increased levels of liver enzymes (alt and ast). interestingly, alt, a more specific indicator of liver inflammation [15], was found in higher concentrations than ast. compared to healthy individuals, the serum of covid-19 patients showed elevated levels of ast, alt, bilirubin, creatinine, urea, k, ck, ldh, troponin, ferritin, and crp. elevation of serum ast and alt levels (3-5-fold) can be due to hepatocellular damage, but a 36-fold higher bilirubin level in covid-19 patients suggests obstruction of bile flow (cholestasis). we also found the patients’ ck and crp levels to be 7-8-fold elevated. although there was no change in the na and ca ion concentrations, the level of k was slightly lower, which may be due to its loss in urine [30]. ferritin is a cytosolic protein that is released into the serum. usually, it is used as a diagnostic marker for anemia, but high serum ferritin levels may indicate acute inflammatory reactions. ferritin, crp, and il-6 have been considered possible immunological biomarkers for severe covid-19 and probable tools for screening and early diagnosis [23]. as expected, the comparison of severe and nonsevere covid-19 cases revealed that the serum cytokine levels and biomarkers were slightly higher in the former cases. severe cases showed around 7.5 times higher levels of ferritin. the liver enzyme alt and ck concentrations were 5-6 times higher in severe cases indicating greater liver damage here. 5. conclusion managing the host’s immune status and other biological parameters can significantly combat the sars-cov-2 infection. screening patients for hyperinflammation and managing cytokine storms in immunocompromised patients, along with other biomarkers of vital organs, can improve the mortality rate. therapeutic strategies may include a combination of antibiotics, immunoglobulins, and inhibition of cytokine overproduction. in order to understand the mechanisms and factors involved in covid-19 disease progression, a comparative analysis of the serum cytokine levels should be done in patients and healthy individuals. estimating increased serum cytokine levels and abnormalities in the hepatic, renal, and cardiac biomarkers can play an important role in predicting poor outcomes in covid-19 patients. the levels of il-6, il-10, and tnf in the serum can also predict the severity of the disease, as cytokines play an important role in host immunity and immunopathology during the infection. since there is no effective treatment for covid-19 to date, the estimation of cytokine levels and biomarker doi 10.18502/sjms.v18i2.13603 page 198 sudan journal of medical sciences walaa mohammedsaeed et al molecules in patients may be used as indicators for early detection and appropriate treatment. acknowledgments we highly appreciate the hospital team’s efforts in treating the patients and the laboratory staff for data and sample collection. our sincere thanks are also extended to dr. bander suliman and his team (ms. araig aljohani, bioscience and technologist) from bander gene center, madinah, ksa, for dedicating their time to analyzing the laboratory experiments. ethical considerations the study was approved by the ethics committee, faculty of applied medical sciences, taibah university (srec/ams 2020/63/cld) and saudi arabia ministry of health, general administration for research & studies (irb 452). competing interests the authors declare no conflict of interest. availability of data and material the data supporting this study’s findings are available in the ministry of health, madinah, saudi arabia. restrictions apply to the availability of these data, which were used under license for this study. data are available from the authors, with the permission of the ministry of health, saudi arabia. funding the author declares that this research received no specific grant from funding agencies. references [1] wang, c., wang, z., wang, g., lau, j. y., zhang, k., & li, w. 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[29] islam, h., chamberlain, t. c., mui, a. l., & little, j. p. (2021). elevated interleukin-10 levels in covid-19: potentiation of pro-inflammatory responses or impaired antiinflammatory action? frontiers in immunology, 12, 677008. [30] alfano, g., ferrari, a., fontana, f., perrone, r., mori, g., ascione, e., magistroni, r., venturi, g., pederzoli, s., margiotta, g., romeo, m., piccinini, f., franceschi, g., volpi, s., faltoni, m., ciusa, g., bacca, e., tutone, m., raimondi, a., . . . guaraldi, g., & the modena covid-19 working group (moco19). (2021). hypokalemia in patients with covid-19. clinical and experimental nephrology, 25, 401–409. https://doi.org/10.1007/s10157-020-01996-4 doi 10.18502/sjms.v18i2.13603 page 202 introduction methods patients and data collection enzyme-linked immunosorbent assays (elisa) statistical analysis results patient characteristics and cytokine levels cytokine levels and other biomarkers in severe andnon-severe covid-19 patients correlation between cytokine levels and biochemical markers in covid-19 patients discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2954 production and hosting by knowledge e research article human beta defensin 1 (hbd1) levels in sputum and lysate of mononuclear blood cells of drug-sensitive and drug-resistant pulmonary tuberculosis patients attending a tertiary hospital in ibadan, nigeria musa solomon ekhegbai, onifade abdulfatai adekunle, and arinola olatunbosun ganiyu immunology training and research unit, department of chemical pathology, college of medicine, university of ibadan, nigeria abstract background: mycobacterium tuberculosis (m. tb) that causes pulmonary tuberculosis (ptb) occupies the lungs, while human β-defensin-1 (hbd1) is expressed in all human epithelial tissues as one of the products of phagocytic leucocytes, especially at the site of microbial colonisation such as the lungs. the involvement of hbd1 in mycobacterial infection has not been extensively studied, thus there is the need to measure the levels of the hbd1 in mononuclear cell lysates and sputum of ptb patients at diagnosis. materials and methods: ninety participants aged between 15 and 64 years were recruited as follows: 30 newly diagnosed multi-drug-resistant tb (mdr-tb) patients and 30 newly diagnosed drug-sensitive tb patients (ds-tb) from mdr-tb treatment centre and the medicine outpatient clinic at university college hospital (uch) ibadan, nigeria. thirty (30) non-tb apparently healthy individuals served as controls. the analytical method employed for the measurement of hbd1 in the sputum and lysate was the enzyme-linked immunosorbent assay (elisa). the data were expressed as mean and standard deviation, and the differences between the means were established using student (t) test. p-value ≤ 0.05 indicated statistical significance. results: the mean levels of lysate and sputum hbd1 were not significantly different in newly diagnosed ds–tb patients (d0)compared with control (p > 0.05). whereas, the mean levels of lysate and sputum hbd1 were significantly higher in newly diagnosed mdr–tb patients (m0) compared with newly diagnosed ds–tb patients (d0)or control (p < 0.05). conclusion: due to the higher levels of hbd1 in the sputum and lysate of m0 than in d0, one might conclude that there is a relationship between chronicity of ptb and hbd1 level. keywords: defensins, tuberculosis, lysate how to cite this article: musa solomon ekhegbai, onifade abdulfatai adekunle, and arinola olatunbosun ganiyu (2018) “human beta defensin 1 (hbd1) levels in sputum and lysate of mononuclear blood cells of drug-sensitive and drug-resistant pulmonary tuberculosis patients attending a tertiary hospital in ibadan, nigeria,” sudan journal of medical sciences, vol. 13, issue no. 3, pages 168–174. doi 10.18502/sjms.v13i3.2954 page 168 corresponding author: arinola olatunbosun ganiyu received 23 july 2018 accepted 15 september 2018 published 24 september 2018 production and hosting by knowledge e musa solomon ekhegbai et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences musa solomon ekhegbai et al 1. introduction tuberculosis (tb) is an infectious disease caused in humans by several strains of mycobacterium, especially mycobacterium tuberculosis (m. tb) [1]. globally, tb has remained a major health problem that is endemic in most developing countries of the world and responsible for ill health among millions of people. nigeria is ranked fourth among the 22 countries with a high burden of tb in the world with a prevalence of 330 per 100,000 [2]. there is also an increasing incident of mdr-tb in nigeria which is jeopardising the efforts of tb control [2]. among reasons why m. tb is a major health problem globally is due to the occurrence of drug resistant strains of m. tb [3]. resistance to tb drugs could result from inappropriate treatment with a single antitb drug (usually isoniazid), wrong-drug prescription leading to ineffective treatment and may also be due to the patient not taking the medication correctly, which can be due to a variety of reasons, including cost or scarcity of medicines, patient’s forgetfulness, or patient stopping treatment early because they feel better [4]. none of these reasons addressed innate intracellular components of cells involved in combating m. tb infection. transmission of m. tb is via inhaled air and as m. tb reaches the pulmonary alveoli, phagocytosis by alveolar macrophages and dendritic cells (dcs) is the first event in the non-specific host–pathogen interaction [5, 6]. alveolar macrophages and dcs recognize m. tb through pattern recognition receptors (prrs), such as pathogen-associated molecular patterns (pamps), which trigger an intracellular signalling cascade in the alveolar macrophages, leading to phagocytic activity [7, 8]. anti-microbial peptides (amps), which include defensins, have been identified as key elements in the innate host defence against infections [9]. defensins possesses and exerts antimicrobial and cytotoxic activities against microorganisms especially during mycobacterium infection [10]. apart from their antimicrobial abilities, defensins also act as chemo-attractants to immature dcs and t cells [11]. human β-defensins (hbd) are expressed in all human epithelial tissues [12] as one of the products of phagocytic leucocytes, especially at the site of microbial colonisation [13]. both hbd1 and hbd2 genes are also expressed in human trachea and lung and are believed to contribute to antimicrobial defence in the respiratory tract [14]. since m. tb inhabit lungs and certain leucocytes where defensins are produced, there is a need to determine the levels of human defensin in the local environments (monocytes and sputum), where m. tb normally infect. doi 10.18502/sjms.v13i3.2954 page 169 sudan journal of medical sciences musa solomon ekhegbai et al 2. materials and methods 2.1. study participants this is a case-control study that involved the recruitment of 90 participants aged between 15 and 64 years. after obtaining a written informed consent for this study, the participants were divided into three groups that comprised of 30 multi-drug-resistant tb (mdr-tb) patients, 30 drug-sensitive tb patients (ds-tb), and 30 non-tb, apparently healthy, individuals as controls. the mdr-tb patients were diagnosed as being infected with isoniazid and rifampicin-resistant strains of m. tb with the aid of their clinical history, chest x-ray and gene xpert® test. after which they were admitted into the mdr-tb centre, university college hospital (uch) ibadan, nigeria for antitb treatment. as for the ds-tb patients, they were recruited from the medicine outpatient clinic at uch, ibadan, nigeria, by a consultant chest physician after laboratory tests and chest x-rays were performed and from the clinical history presented. the study protocol was reviewed and approved by the university of ibadan/university college hospital joint institutional research ethics committee. three millilitres (3 ml) of blood was drawn from the antecubital vein of each participant into lithium heparin tube and mixed with 3ml of phosphate buffered saline (pbs). lymphoprep (6ml) carefully layered on it and was at 600g for 15 mins to obtain mononuclear cells above the mixture of polymorphonuclear cells and red blood cells. mononuclear cells obtained were washed, resuspended in ringers solution, counted and adjusted to 0.5 x 106 cells/ml. mononuclear cell lysate was obtained by freeze thaw method. cell suspension was frozen for 15 mins at –20∘c and thawed at 4∘c for 30 mins. this procedure of freezing (–20∘c, 15 mins) and thawing (4∘c, 30 mins) was repeated to make three cycles. microscopic examination confirmed complete disruption of mononuclear cells. lysate was stored at –20∘c until analysis. early-morning sputum samples were collected into sterile bottles to avoid contamination. sputum samples were diluted in phosphate buffer saline (pbs) in a ratio 1:1 dilution factor. the mixture was centrifuged and the clear supernatant was collected and stored for analysis at –20ºc. enzyme-linked immunosorbent assay (elisa) method was used for the determination of mononuclear cell lysate and sputum concentrations of hbd 1 as specified by kit manufacturer (elabscience biotechnology co., ltd, p.r.c). student t-test was used to compare two mean values; p-value less than 0.05 was considered significant. doi 10.18502/sjms.v13i3.2954 page 170 sudan journal of medical sciences musa solomon ekhegbai et al 3. results as shown in table 1, the mean levels of mononuclear cell lysate and sputum hbd1 in control, d0and m0 were compared in table 1. the mean levels of lysate and sputum hbd1 were not significantly different in d0when compared with the controls. the mean levels of wbc lysate and sputum hbd1 were significantly higher in m0 compared with d0 or control. however, the mean concentration of sputum hbd1 in m0 was higher than the level in the lysate. the reverse was the case in other groups. t 1: mean levels of hbd 1 in mononuclear cell lysate and sputum hbd1 levels in controls, d0 and m0 at diagnosis. variables control (n = 30) d0 (n = 30) m0 (n = 30) f wbc lysate hbd1(pg/ml) 57.08 ± 12.71 57.58 ± 13.75 70.71 ± 21.27#+ 3.898 sputum hbd1(pg/ml) 19.1 ± 4.7 35.5 ± 30.7 171.4 ± 210.4#+ 13.561# #significantly different when compared with controls, #significantly different when compared with controls, +significantly different when compared with d0 4. discussion defensins, especially β-defensins, are known as endogenous antibiotics [15] that are involved in antimycobacterial defence in the local environment, especially during the inflammation and colonisation phase of mycobacterial infection [13]. yet, studies on the levels of hbd 1 in the lysate and sputum in tb patients is lacking, though reported in the fluids of patients having other conditions apart from tb [16–18]. our finding of increased levels of sputum and lysate hbd1 in m0 compared with d0 and control might be due to chronic nature of m. tb infection in the m0 group, which would have led to increased recruitment and activation of immune cells (macrophages and dcs), pro-inflammatory cytokines (tnf-α, ifn-γ, il-1β and il-6) and chemoattractant. secretion of pro-inflammatory cytokines, especially tnf-α, is a contributory factor to increased inflammation in situ. this is further exacerbated by the consistent replication and imminent necrotic activity of the m. tb within the macrophage leading to increased leucocyte activation. this increased activation consequently cause production of large amount of hbd1 from the epithelial cells in m0 with a view to inhibiting the mycobacterial growth in the alveolar macrophages and defending other alveolar cells from being infected. doi 10.18502/sjms.v13i3.2954 page 171 sudan journal of medical sciences musa solomon ekhegbai et al non-significant differences observed when the mean levels of lysate and sputum hbd1 in d0 were compared with the control could be attributed to the early or nonsevere phase of the m. tb infection in the patients. there is supporting evidence from the studies conducted by ertugrul et al [19] and kaltsa et al [20], which reported higher levels of hbd1 in chronic periodontitis patients compared with patients having gingivitis and elevated levels of hbd1 in patients with cirrhosis when compared with hepatitis patients and control. one of the sites of β-defensins production is the epithelial cells of the lungs where it acts as defence to mycobacterial infection and furthermore inhibits mycobacterial growth. defensins also act as chemoattractant to antigen specific t-cells and immature macrophages with the aid of il-2 and ifn-γ that induce macrophage activation towards the development of a microbicidal granuloma via host-specific cell-mediated immune response to the end of halting the replication and spread of the infection to other parts of the body. in an earlier study, schwander et al. [21] reported high number of polymorphonuclear (pmn) cells and immature macrophages in bal fluids from the lungs of tb patients. thus, the observed elevated levels of sputum hbd1 in m0compared with d0 and controls could indicate that there is heightened production of hbd1 in the lungs of m0 that probably resulted in high level of sputum hbd1 as observed by this study. hbd1 is mainly expressed by epithelial cells, tissues and salivary glands, especially in the local environment of the infection, which is in the epithelial of the lungs. this could also account for higher level of sputum hbd1 compared with monocyte lysate hbd1. 5. conclusion 1. since the levels sputum and lysate hbd1 were higher in tb patients than normal individuals, it shows that hbd1 might be involved in combating tb and may be used as a therapeutic target for treating tb. 2. there is an association between and tb severity and hbd1. references [1] kumar, v., abbas, a. k., fausto, n., et al. (2007). robins basic pathology (eighth edition), pp. 516–522. saunders: elsevier. [2] world health organization. (2015). global tuberculosis report (twentieth edition). geneva. retrieved from http://www.who.int/tb/publications/global_report/en/ (accessed on 4 february 2016). doi 10.18502/sjms.v13i3.2954 page 172 http://www.who.int/tb/publications/global_report/en/ sudan journal of medical sciences musa solomon ekhegbai et al [3] world health organization. (2014). global tuberculosis report (nineteenth edition). geneva, switzerland. retrieved from http://www.who.int/tb/publications/ global_report/en (accessed on 4 february 2016). [4] adams, l. and woelke, g. (2014). understanding global health: tuberculosis and hiv/aids (twelfth edition), p. 10. new york, ny: mcgraw-hill. [5] gupta, a., kaul, k., tsolaki, a. g., et al. (2012). mycobacterium tuberculosis; immune evasion, latency and reactivation. immunobiology, vol. 217, pp. 363–374. [6] bafica, a. and aliberti, j. (ed.). (2012). mechanisms of host protection and pathogen evasion of immune responses during tuberculosis, in control of innate and adaptive immune responses during infectious disease. new york, ny: springer science, business media, llc. doi: https://doi.org/10.1007/978-1-4614-0484-2_2 [7] liu, p. t. and modlin, r. l. (2008). human macrophage host defence against mycobacterium tuberculosis. current opinion in immunology, vol. 20, pp. 371–376. [8] persson, y. a., blomgran-julider, r., rahman, s., et al. (2008). mycobacterium tuberculosis induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat-shock protein 72, acting in synergy with the bacteria. microbes and infection, vol. 10, pp. 233–240. [9] zaiou, m. (2007). multi-functional antimicrobial peptides; therapeutic targets in several human diseases. journal of molecular medicine, vol. 85, pp. 317–329. [10] cole, a. m. and waring, a. j. (2002). the role of defensins in lung biology and therapy. american journal of respiratory and critical care medicine, vol. 1, pp. 249– 259. [11] yang, d., biragyn, a., kwak, l. w., et al. (2002). mammalian defensins induced in immunity: more than just microbicidal. trends in immunology, vol. 23, pp. 291–296. [12] lehrer, r. i. and ganz, t. (2002). defensins of vertebrate animals. current opinion in immunology, vol. 14, pp. 96–102. [13] dong-min, s. and eun-kyeong, j. (2011). immune network, vol. 11, no. 5, pp. 245–252. [14] oppenheim, j. j., biragyn, a., kwak, l. w., et al. (2003). roles of antimicrobial peptides such as defensins in innate and adaptive immunity. annals of the rheumatic diseases, vol. 62, no. 2, pp. 17–21. [15] ganz, t. (2003). defensins: antimicrobial peptides in innate immunity. nature reviews immunology, vol. 3, no. 9, pp. 710–720. [16] hiratsuka, t., mukae, h., iiboshi, h., et al. (2003). increased concentrations of human β-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. thorax, vol. 58, pp. 425–430. doi 10.18502/sjms.v13i3.2954 page 173 http://www.who.int/tb/publications/global_report/en http://www.who.int/tb/publications/global_report/en https://doi.org/10.1007/978-1-4614-0484-2_2 sudan journal of medical sciences musa solomon ekhegbai et al [17] abiko, y., mitamura, j., nishimura, m., et al. (1999). pattern of expression of betadefensins in oral squamus cell carcinoma. caneur letter, vol. 143, pp. 37–43. [18] mizukawa, n., sugiyima, k., veno, t., et al. (1999). levels of human defensin-1 an antimicrobial peptide in saliva of patients with oral inflammation. oral surgery, oral medicine, oral pathology, and oral radiology, vol. 87, pp. 539–543. [19] ertugrul, a. s., dikilitas, a., sahin, h., et al. (2012). gingival crevicular fluid levels of human beta-defensins 1 and 3 in subjects with periodontitis and/or type 2 y. diabetes mellitus: a cross-sectional study. journal of periodontal research, vol. 48, no. 4, pp. 475–482. [20] kaltsa, g., bamias, g., siakavellas, s. i., et al. (2016). systemic levels of human βdefensin 1 are elevated in patients with cirrhosis. annals of gastroenterology, vol. 29, pp. 63–70. [21] schwander, s. k., sada, e., torres, m., et al. (1996). t lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis. the journal of infectious diseases, vol. 173, pp. 1267–1272. doi 10.18502/sjms.v13i3.2954 page 174 introduction materials and methods study participants results discussion conclusion references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.5027 production and hosting by knowledge e research article clinical evaluation of non-functional invasive hypophysis adenomas feyzi gokosmanoglu1, ceyhun varim2, and kenan evren oztop3 1department of endocrinology, medical park hospital, ordu, turkey 2department of internal medicine, sakarya university medicine faculty, sakarya, turkey 3department of internal medicine, konak hospital, sakarya, turkey abstract background: there are ongoing studies to predetermine non-functional invasive pituitary adenomas that may show aggressive behavior. our aim is to discuss whether there is a relationship between the immunohistochemical presence of gh, fsh, lh, prl, acth, tsh and their aggressive clinical course in non-functional pituitary adenomas. materials and methods: in this study, we evaluated retrospectively the files of the patients who were diagnosed with the sellar or parasellar tumor in our endocrinology clinic between the years of 2004 and 2014. the patients were divided into two groups as non-invasive pituitary adenomas and non-functional invasive pituitary adenomas. the immunohistochemical staining characteristics were compared between the two groups. results: in this study, we scanned the data of 70 patients who were followed for non-functional sellar or parasellar mass; 47.1% of the patients were female and 52.9% were male. of them, 39 patients had a non-functional pituitary adenoma whereas 20.5% of them had non-functional invasive adenoma. while there was a significant relationship between the immunohistochemical positivity of gh, fsh, lh and the aggressive behavior of non-functional invasive adenomas. no significant relationship was found between the immunohistochemical positivity of prl, acth, tsh and the aggressive behavior of non-functional invasive adenomas. conclusion: we found silent gh and gonadotropin adenomas as non-functional aggressive pituitary adenoma. more aggressive treatment and close clinical monitoring should be performed because atypical pituitary adenomas are characterized by invasive growth and aggressive clinical course. keywords: pituitary adenoma, non-functional, invasive 1. introduction hypophysis adenoma, contrary to common belief, is quite widespread. it is found in the normal population at a rate of 20%. shedding light on the embryological development of adenohypophysis and transcription factors related to molecular cell differentiation how to cite this article: feyzi gokosmanoglu, ceyhun varim, and kenan evren oztop (2020) “clinical evaluation of non-functional invasive hypophysis adenomas,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 106–113. doi 10.18502/sjms.v15i2.5027 page 106 corresponding author: ceyhun varim, md; adnan menderes caddesi, sağlık sokak, no: 195-54000, adapazarı/sakarya. tel: +90 264 255 21 06. fax number: +90 264 255 21 05. email: ceyhunvarim@sakarya.edu.tr received 15 april 2020 accepted 12 june 2020 published 30 june 2020 production and hosting by knowledge e feyzi gokosmanoglu et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ceyhunvarim@sakarya.edu.tr https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences feyzi gokosmanoglu et al pathways has led to innovations in the diagnostic approach for adenomas. to that end, a number of different classification models have been developed, which may be classified as functional, anatomic, radiological, histological, immunohistochemical, ultrastructural, or clinicopathological [1]. invasive hypophysis adenomas are very large, treatment-resistant adenomas that exhibit common and extensive invasion of peripheral anatomic structures while growing rapidly and recurring quickly in the wake of treatment. their biological behavior falls between hypophysis adenomas and hypophysis cancers. about 2.7% of hypophysis adenomas are invasive tumors [2]. in 2004, the world health organization classified atypical hypophysis adenomas as tumors showing invasive growth and increased mitotic activity, with those having an mib.1 proliferative index > 3% and p53 immunoreactivity being atypical [3]. in this study, we aimed to retrospectively evaluate the clinical results of cases of non-functional invasive hypophysis adenoma in patients followed-up within our clinic. 2. materials and methods in this study, the medical files of the patients who were followed-up with the diagnosis of sellar and parasellar tumors in the samsun ondokuz may𝚤s university medicine faculty endocrinology clinic between the years 2004 and 2014 were retrospectively examined by us. hypophysis adenomas were separated from the tumoral lesions, which are seen rarely in the other sellar and parasellar regions. detailed anamnesis and demographic characteristics of the patients, as well as their reasons for presenting at the hospital and the frequency of applications, were recorded from their medical files (table 1). the clinical and radiological images of the cases and dynamic test data regarding hormones were obtained from the patient files. adenomas were divided into two groups, namely functional and non-functional. as for hypophysis adenomas, the functional ones were determined according to the hormone content in the foreground and excluded from the study. table 1: the distribution of the symptoms of the cases at the time of diagnosis. symptoms and findings the number of patients and percentages headache 34.2% (n =34) visual impairment 21,4% (n =15) sexual anorexia, infertility 5,7% (n =5) non-specific symptoms 12,8% (n =9) asymptomatic, incidental detections 10% (n =7) doi 10.18502/sjms.v15i2.5027 page 107 sudan journal of medical sciences feyzi gokosmanoglu et al table 2: clinicopathological and immunohistochemical staining results of the patients. type of adenoma, immunohistochemical classification number of cases hypophysis adenoma, plurihormonal 20 cystic lesions 12 hypophysis adenoma, staining-negative 8 hypophysis adenoma, blood and blood clot 7 gh (+) 2 lh (+) 1 acth (+) 1 craniopharyngioma 5 meningioma 3 neurofibroma 1 registries missing 10 total 70 table 3: immunohistochemical staining characteristics of non-functional invasive hypophysis adenomas. type of adenoma, immunohistochemical classification group 1 group 2 p-value hypophysis adenoma, plurihormonal 20 5 fsh, lh 11 6 0.013 prl 8 3 0.306 gh 7 5 0.009 acth 12 1 0.298 tsh 5 – hypophysis adenoma, staining-negative 8 1 hypophysis adenoma, blood and blood clot 7 – total 39 8 group 1: non-invasive adenomas, group 2: invasive adenomas table 4: immunohistochemical classification and distribution of invasive adenomas type of adenoma immunohistochemical staining number of cases hypophysis adenoma, plurihormonal fsh, lh, estrogen 2 sf1 1 fsh, lh, gh, prl 1 gh, prl, acth 1 gh, prl hypophysis adenoma, staining-negative null cell 1 gh (+) gh (+) 2 total 8 doi 10.18502/sjms.v15i2.5027 page 108 sudan journal of medical sciences feyzi gokosmanoglu et al in our research, sellar and parasellar regional lesions were classified as either nonfunctional hypophysis adenomas or other lesions (cyst, teratoma, metastasis, infectious and inflammatory lesions, glioma, germinoma, neurofibroma, meningioma and craniopharyngioma) using immunohistochemical staining data. non-functional non-invasive hypophysis adenomas and non-functional invasive hypophysis adenomas were separated into two groups: group 1 and group 2. the immunohistochemical staining characteristicsof both groups were compared as well (table 2). hypophysis adenomas were specified as microadenoma (< 10 mm) and macroadenoma (≥ 10 mm) according to their hypophysis/pituitary sizes on mri. all the data were determined as mean (±) standard deviation (sd). the statistical analyses were performed through spss 16.0 (spss inc., chicago, il) programme. the statistical analyses of their mean comparisons were performed via independent two sample t-test and chi-square test. numeric values and percentages of all the determinants were evaluated via frequency analyses. as the p-value was < 0.05 during the comparison process, it was accepted as statistically significant. 3. results research was carried out in the endocrinology clinic of our hospital between 2004 and 2014 by retrospectively examining the data of 70 patients who were followed-up due to non-functional sellar and parasellar lesions following hypophysis; 47% of the patients (n = 33) were female while 53% of them (n = 37) were male. the mean age was 48 years and 90% of the patients (n = 63) were asymptomatic at the time of diagnosis. in our study, 18.5% of the patients (n = 13) had microadenoma, while 81.4% of them (n = 57) had macroadenoma. at the first admission to the hospital, 57 patients were followedup through the treatment process while 13 of them through an unmedicated method. all patients who went through an unmedicated follow-up process had microadenomas. fifty surgical patients underwent transsphenoidal surgery and seven patients underwent transcranial surgery. a remission rate of 80.7% (n = 46) was detected along with surgical treatment; however, a 19.2% (n = 11) residual tumor rate was detected despite surgical treatment. during clinicopathological and immunohistochemical examinations of the cases, no record could be found for 55.8% (n = 39) of hypophysis adenoma, 30% (n = 21) of cystic lesions, craniopharyngioma, meningioma, neurofibroma, or 14.2% (n = 10) of immunohistochemical staining (table 3). the clinicopathological and immunohistochemical staining results of 39 cases that were followed-up with a diagnosis of non-functional hypophysis doi 10.18502/sjms.v15i2.5027 page 109 sudan journal of medical sciences feyzi gokosmanoglu et al adenoma are given in table 3. a treatment-resistant invasive growth that progressed aggressively was found in eight cases. no remission was achieved, despite the fact that five of these cases had been operated on twice and three of them had been operated on thrice, and the gamma knife treatment was provided during the post-operative period. the immunohistochemical staining results of eight adenomas showing a treatmentresistant invasive growth with an aggressive course are shown in table 4. statistically, we ascertained a significant relationship between gh presence in the immunohistochemical staining process and invasive and aggressive behavioral patterns of non-functional adenomas (p = 0.009). the fsh, lh positivity in adenomas caused adenomas to demonstrate invasive and aggressive behavior (p = 0.013). during the immunohistochemical staining process of non-functional hypophysis adenomas, no significant relationship could be found between the presence of prl, acth, tsh and the invasive, aggressive behavioral patterns of adenomas. 4. discussion the prevalence rate of hypophysis adenomas is approximately 20% [4]. however, > 90% of the patients operated on with the diagnosis of hypophysis tumor were diagnosed with hypophysis adenoma [4]. other kinds of hypophysis tumors are rathke’s cleft cyst (28%), craniopharyngioma (14%), metastatic carcinoma (12%), chordoma (11%), and meningioma (10%) [4]. in our research, 55.8% of the non-functional sellar and parasellar regional tumoral lesions were regarded as hypophysis adenoma in the wake of the operation, whereas 30% of them were considered as cystic lesions, craniopharyngioma, meningioma, and neurofibroma. the reason for the low percentage in the diagnosis of post-operative hypophysis adenoma in our study may be due to the exclusion of functional adenomas from the study and the missing immunohistochemical staining records in 14.2% of cases. apart from being slowly growing benign tumors, hypophysis adenomas tend to lead to an invasion of the cavernous sinus and even the sphenoid sinus by causing pressure against the optic chiasm after surpassing the sella. it is also possible that invasive adenomas infiltrate bone, and more rarely the brain (5). in our study, all invasive adenomas were macroadenomas, and radiological reports showed that they had invaded the sellar and suprasellar region. in the literature, the incidence of atypical hypophysis adenoma was reported as ranging from 2.7 to 15%. [6–8]. in half of these cases, a non-functional hypophysis adenoma was detected [6]. in our research, we detected a treatment-resistant invasive doi 10.18502/sjms.v15i2.5027 page 110 sudan journal of medical sciences feyzi gokosmanoglu et al adenoma exhibiting invasive growth with an aggressive course in 20.5% of 39 cases (n = 8) with non-functional hypophysis adenoma. the fact that we detected a high level of invasive adenoma in non-functional hypophysis adenomas may be explained by the fact that the cases incorporated into the study were complicated and the challenging ones were followed-up through a multidisciplinary approach. in 2004, the world health organization classified hypophysis adenomas as atypical adenoma and carcinoma in accordance with the classification of endocrine tumors. cases demonstrating an apparent mitotic activity, a ki-67 proliferative index over 3%, and a common nuclear p53 protein positivity are defined as atypical hypophysis adenoma (3). differing from the criteria of the world health organization as to atypical adenomas, we determined in our research that positive adenomas had shown an atypical and aggressive course through gh positivity and fsh, lh, and immunohistochemical staining. recurrences and aggressiveness are very rare in cases of ki-67 proliferative index and p53 protein positivity after surgery [9]. separately, aggressive behavior can also be seen in the absence of these immunohistochemical findings [9]. it was shown that silent gh and gonadotroph adenoma tended to be invasive macroadenomas or giant adenomas [10]. also, in our research we ascertained that silent gh and gonadotroph adenomas had progressed aggressively. we detected an estrogen receptor positivity in 25% of cases with non-functional invasive hypophysis macroadenoma during the immunohistochemical staining process. during the research, estrogen receptor alpha positivity was determined to be prominently higher (80%) in invasive macroadenomas than in microadenomas (3.33%) [11]. the estrogen receptor alpha in non-functional invasive adenomas was reported to have been stained more intensely than in the non-invasive ones [12]. the estrogen receptor alpha was shown to have been expressed more in fsh-lh, gh, and null cell adenomas than acth adenomas (13). in our study, we demonstrated an estrogen receptor in invasive fsh-lh adenomas. in the literature, < 70% of atypical adenomas were reported to have formed ghsecreting, null cell, and silent acth adenomas. recently, it has been reported that nonfunctional gonadotropin adenomas exhibit invasive behavioral patterns [6]. however, in our research, silent gh adenoma and non-functional gonadotropin adenomas were seen to have progressed in an aggressive manner. we determined that acth, tsh, and prl positivity, which are among the histopathological sub-types, and also null cell adenomas act as typical adenomas. doi 10.18502/sjms.v15i2.5027 page 111 sudan journal of medical sciences feyzi gokosmanoglu et al we ascertained that 20.5% of non-functional hypophysis adenomas were atypical, invasive macroadenomas that acted aggressively. silent gh adenomas and gonadotropin adenomas comprised a majority of these tumors. since atypical hypophysis adenomas are characterized by invasive development and an aggressive clinical course, close clinical follow-up of these cases must be performed in terms of their recurrence or distant metastasis. contributing to the development of target-specific treatments, we are of the opinion that the sub-types of hypophysis adenomas should be specified by taking current approaches into consideration, and that the treatment and follow-up of particular sub-types should follow aggressive courses that must be performed more carefully. conflict of interest the authors declared that there is no conflict of interest. author contribution fg found the subject and collected data, cv wrote the article and searched the references, and keo translated the article to english and created the tables. references [1] asa, s. l. (2008). practical pituitary pathology. what does the pathologist need to know? archives of pathology & laboratory medicine, vol. 132, pp. 1231–1240. [2] buchfelder, m. (2009). management of aggressive pituitary adenomas: current treatment strategies. pituitary, vol. 12, pp. 256–260. [3] delellis, r., lloyd, r. v., heitz, p., et al. (eds). (2004). world health organization classification of tumours: tumours of endocrine organs, pp. 10–35. lyon: iarc press. [4] davis, j. r., farrell, w. e., and clayton, r. n. (2001). pituitary tumours. reproduction, vol. 121, no. 3, pp. 363–371. [5] botelho, c. h., magalhaes, a. v., mello, p. a., et al. (2006). expression of p53, ki67 and c-erb b2 in growth hormoneand/or prolactin-secreting pituitary adenomas. arquivos de neuro-psiquiatria, vol. 64, no. 1, pp. 60–66. [6] zada, g., woodmansee, w. w., ramkissoon, s., et al. (2011). atypical pituitary adenomas: incidence, clinical characteristics and implications. journal of neurosurgery, doi 10.18502/sjms.v15i2.5027 page 112 sudan journal of medical sciences feyzi gokosmanoglu et al vol. 114, pp. 336–344. [7] tortosa, f. and webb, s. m. (2015). atypical pituitary adenomas: 10 years of experience in a reference centre in portugal. neurología, vol. 31, no. 2, pp. 97–105. [8] saeger, w., lüdecke, d. k., buchfelder, m., et al. (2007). pathohistological classification of pituitary tumors: 10 years of experience with the german pituitary tumor registry. european journal of endocrinology, vol. 156, pp. 203–216. [9] gejman, r., swearingen, b., and hedley-whyte, e. t. (2008). role of ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. human pathology, vol. 39, pp. 758–766. [10] gomez-hernandez, k., ezzat, s., asa, s. l., et al. (2015). clinical implications of accurate subtyping of pituitary adenomas: perspectives from the treating physician. turkish journal of pathology, vol. 31, pp. 4–17. [11] pereira-lima, j. f., marroni, c. p., pizarro, c. b., et al. (2004). immunohistochemical detection of estrogen receptor alpha in pituitary adenomas and its correlation with cellular replication. neuroendocrinology, vol. 79, no. 3, pp. 119–124. [12] zhou, w., song, y., xu, h., et al. (2011). in nonfunctional pituitary adenomas, estrogen receptors and slug contribute to development of invasiveness. the journal of clinical endocrinology and metabolism, vol. 96, no. 8, pp. e1237–e1245. [13] manoranjan, b., salehi, f., scheithauer, b. w., et al. (2010). estrogen receptors alpha and beta immunohistochemical expression: clinicopathological correlations in pituitary adenomas. anticancer research, vol. 30, no. 7, pp. 2897–2900. doi 10.18502/sjms.v15i2.5027 page 113 introduction materials and methods results discussion conflict of interest author contribution references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5213 production and hosting by knowledge e research article high sensitive c reactive protein in sudanese type 2 diabetic patients hala abdalazeem aljack (phd)1,2, omer fadul edris (phd)3, amar mohamed ismail (phd)3 1department of clinical chemistry, faculty of medical laboratory science, omdurman islamic university, khartoum-sudan 2department of clinical chemistry, faculty of medical laboratory science, al-neelain university, khartoum-sudan 3department of biochemistry and molecular biology, faculty of science and technology, alneelain university, khartoum-sudan abstract background: researchers proved the association between inflammatory condition, high sensitive c reactive protein (hs-crp), and cardiovascular diseases (cvds) in type 2 diabetes mellitus (dm). therefore, this study aimed to assess the hs-crp level in type 2 dm patients and their relation to diabetes cardiovascular complications. materials and methods: in a case-control study, 205 previously diagnosed type 2 dm patients and 100 controls were included. serum high sensitive c reactive protein (hs-crp) was estimated immune-turbidimetrically using cobas c-311® fully automated analyzer. also, triglyceride (tg), total cholesterol (tc), high-density lipoprotein (hdl-c), and low-density lipoprotein (ldl-c) were measured. results: type 2 dm patients had an increased level of hs-crp (p-value 0.020). females had higher levels of hs-crp, tc, hdl-c, and ldl-c than males (p-value 0.005, 0.000, 0.000, and 0.000, respectively). moreover, patients who received statin drugs had decreased levels of hs-crp, tc, and ldl-c (p-value 0.030, 0.000, and 0.000, respectively). the correlation analysis revealed hs-crp correlates positively with bmi (r: 0.56, p-value 0.000). conclusion: the data showed that type 2 dm patients had higher hs-crp. moreover, hs-crp positively associated with bmi. therefore, obesity might be related to cvds in type 2 dm patient. keywords: high sensitive c reactive protein, cardiovascular diseases, type 2 dm, obesity, sudan. 1. introduction diabetes mellitus (dm) is a chronic metabolic disorder, characterized by hyperglycemic condition due to a defect in secretion of insulin by β cells of pancreas or defect in how to cite this article: hala abdalazeem aljack (phd), omer fadul edris (phd), amar mohamed ismail (phd) (2019) “high sensitive c reactive protein in sudanese type 2 diabetic patients,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 132–142. doi 10.18502/sjms.v14i3.5213 page 132 corresponding author: hala abdalazeem aljack; department of clinical chemistry, omdurman islamic university, faculty of medical laboratory science, alshigla street, khartoum, 11111, sudan. tel: 00249915503549 fax: 382 email: hala.abdalazeem@yahoo.com received 21 february 2019 accepted 12 may 2019 published 28 june 2019 production and hosting by knowledge e hala abdalazeem aljack et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hala.abdalazeem@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hala abdalazeem aljack et al insulin action. [1-3]. recently, dm become the most common chronic disorder, (4) with increasing prevalence worldwide (5). it was estimated that 425 million people had dm in 2017, and the number is expected to rise to 629 million by 2045 [6]. in sudan, the prevalence of dm is rising from 9.3% in 2010 to 10.6 % in four states in 2013 [7]. type 2 diabetes mellitus is a complex condition, results from the resistance of insulin action combined with impaired pancreatic function [8]. if left uncontrolled, type 2 dm can cause chronic microvascular and macrovascular complications [9]. some previous studies confirmed that type 2 dm gradually causes chronic low-grade inflammation, which plays a vital role in the progression of diabetic complications [10]. type 2 dm patients are at a high risk to develop cvds, and the risk increased when patients suffer from nephropathy [11]. the cvds are observed to increase in type 2 dm with elevated inflammatory markers [12]. the inflammatory marker hs-crp is a pentameric protein synthesized by hepatic cells under the control of cytokines [11]. it has been identified as a reliable predictor marker for cvds [13-15]. previous studies documented that, diabetic patients undergo high serum hs-crp level [16], that lead to the activation of inflammatory pathways and progression of cvd [17, 18]. accordingly, this study was conducted to determine whether the hs-crp is associated with cvds in type 2 dm patients. 2. materials and methods this case-control study was conducted in the military hospital at khartoum state during period from 2015 to 2019. randomly 205 type 2 dm patients (111 females and 94 males), and 100 apparently healthy control matched in age and gender were selected. dm patients with inflammatory, liver, and/or renal diseases were excluded. after written informed consents, 5 ml venipuncture blood was collected. the study was approved by the local committee of al-neelain university, sudan (issued in may 2015). 2.1. measurement of bmi body mass index (bmi) was calculated using (weight kg/hight m2) formula. doi 10.18502/sjms.v14i3.5213 page 133 sudan journal of medical sciences hala abdalazeem aljack et al 2.2. measurement of hs-crp serum level of hs-crp were measured by cobas c-311® (roche diagnostics, germany) using the particle enhanced immunoturbidimetric method human crp agglutinates with latex particles coated with monoclonal anti-crp antibodies, and then the precipitate was determined turbidimmetrically. 2.3. measurement of lipid profile serum tg, tg, and hdl-cholesterol were estimated by cobas c-311® automated chemistry analyzer (roche diagnostics, germany). 2.4. tg measurement using the principle enzymatic colorimetric method which based on complete hydrolysis of triglycerides by lipoprotein lipase to glycerol, followed by oxidation and peroxidation process to form a red dyestuff. the color intensity of the red dyestuff formed is directly proportional to the triglyceride concentration and can be measured photometrically. 2.5. tc measurement estimation of total cholesterol based on serial enzymatic reactions leads to the formation of red quinone-imine dye, which can be measured photometrically. the color intensity of the dye formed is directly proportional to the cholesterol concentration. 2.6. hdl-c measurement in the presence of magnesium ions, dextran sulfate selectively forms water-soluble complexes with ldl, vldl, and chylomicrons. the cholesterol concentration of hdlcholesterol is determined enzymatically after the formation of a purple-blue dye. the color intensity of this dye is directly proportional to the cholesterol concentration and is measured photometrically. doi 10.18502/sjms.v14i3.5213 page 134 sudan journal of medical sciences hala abdalazeem aljack et al 2.7. ldl-c measurement levels of ldl-c were calculated using the friedwald equation [19] as follow: 𝐿𝐷𝐿 − 𝐶 = 𝑇𝐶 − (𝐻𝐷𝐿 − 𝐶 + 𝑇𝐺 5 ) 2.8. statistical analysis all statistical analyses were performed using the spss software (statistical package for the social sciences) (version 21.0; spss inc.). descriptive statistic (frequency and percentage) were obtained. independent t-test was employed to compare mean between groups. pearson’s correlation was used to correlate between study parameters and variables. quantitative variables were demonstrated as mean±sd; significant differences were considered as p-value ≤ 0.05. 3. results the study comprised of 205 type 2 diabetic patients and 100 subjects as control. the demographic and general characteristics of the population are shown in (table 1). the mean level of hs-crp was significantly increased in the diabetic group (4.83±0.42) compared with non-diabetic (3.48±0.38) with (p-value 0.020), while there was a significant decrease in hdl-c level in diabetic (39.4±8.88) compared with nondiabetic group (45.2±12.4) with (p-value 0.000). also, the mean levels of tg, tc, and ldl-c, showed insignificant differences when the diabetic group compared to the non-diabetic group (table 2). the results of the study showed the mean level of hs-crp was significantly higher in female (5.91±2.61) compared with male (3.54±2.55) with (p-value 0.005). furthermore, the lipid profile results showed a significant increase in tc, hdl-c, and ldl-c mean levels in female compared with male (p-value 0.000) as shown in (table 3). patients group who take cholesterol-lowering agent (statin) had significantly lower levels of hs-crp, tc and ldl-c as compared with untreated patients (p-value 0.030, 0.000 and 0.000, respectively), while other parameter showed insignificant differences between two groups (table 4). doi 10.18502/sjms.v14i3.5213 page 135 sudan journal of medical sciences hala abdalazeem aljack et al in correlation analysis, hs-crp level correlates positively with bmi (r: 0.56 p-value 0.000), while no correlation observed according to age, duration of disease and lipid profile as in (table 5). table 1: general baseline characteristics of patients and control groups. characteristics diabetic group non-diabetic group bmi 28.0±4.60 25.8±4.66 control of diabetes controlled: 64 (31.2%) uncontrolled: 141 (68.8%) education status low: 36 (18%) moderate: 132 (65%) high: 35 (17%) low: 33 (33%) moderate: 50 (50%) high: 15 (15%) life style low: 69 (35.0%) moderate: 113 (57.4%0) good: 15 (7.6%) low: 52 (53.1%) moderate: 41 (41%) good: 5 (5.0%) cholesterol lowering agent yes: 84 (47.2%) no: 94 (52.8%) table 2: compersion of serum hs-crp and lipid profile in diabetic and non-diabetic groups. parameter diabetic group (mean±sd) non-diabetic group (mean±sd) p-value hs-crp (mg/l) 4.83±0.42 3.48±0.38 0.020 tg (mg/dl) 117±48.3 114±60.4 0.620 t.cholestrol (mg/dl) 171±33.7 163±42.2 0.055 hdl-cholestrol (mg/dl) 39.4±8.88 45.2±12.4 0.000 ldl-cholestrol (mg/dl) 101±35.8 103±31.1 0.647 the results expressed as (mean±sd) and p value less than 0.05 was considered statistically significant. doi 10.18502/sjms.v14i3.5213 page 136 sudan journal of medical sciences hala abdalazeem aljack et al table 3: compersion of study parameters in patients groups classified according to gender. parameters male (mean±sd) female (mean±sd) p-value hs-crp (mg/l) 3.54±2.55 5.91±2.61 0.005 tg (mg/dl) 119±60.2 121±62.7 0.794 t.cholestrol (mg/dl) 150±39.1 171±40.1 0.000 hdl-cholestrol (mg/dl) 37.1±7.51 41.4±9.49 0.000 ldl-cholestrol (mg/dl) 91.3±34.5 109±35.0 0.000 the results expressed as (mean±sd) and p-value less than 0.05 was considered statistically significant. table 4: compersion of study parameters in the patient groups classified according to intake of cholesterollowering agent. parameters cholesterol-lowering used (mean±sd) cholesterol-lowering nonused (mean±sd) p-value hs-crp (mg/l) 3.52±3.23 4.98±5.43 0.030 tg (mg/dl) 121±69.1 125±58.8 0.706 t.cholestrol (mg/dl) 146±38.2 176±40.7 0.000 hdl-cholestrol (mg/dl) 38.8±8.71 39.0±8.35 0.847 ldl-cholestrol (mg/dl) 85.8±32.1 114±33.9 0.000 the results expressed as (mean±sd) and p-value less than 0.05 was considered statistically significant. table 5: pearson’s correlation of hs-crp with bmi, age, duration of disease and lipid profile. correlation r p-value bmi 0.56** 0.000 age -0.12 0.094 duration of disease -0.01 0.942 tg -0.020 0.778 t.cholestrol 0.046 0.512 hdl-cholestrol -0.043 0.544 ldl-cholestrol 0.66 0.350 (r): pearson correlation test, (-) negative correlation. a p-value of less than 0.05 was considered statistically significant. doi 10.18502/sjms.v14i3.5213 page 137 sudan journal of medical sciences hala abdalazeem aljack et al 4. discussion in this study, we found that type 2 dm is prevalent in females than males. the predominance of females with diabetes is attributed to the hormonal effects, the higher ability of the body to store iron and physical inactivity; indeed, most of them were housewives [20]. in our study, the majority of patients are elderly and overweight. thus postulated combination of genetic predisposition, environmental, nutritional factors, obesity, physical inactivity, stress, and aging [21], might be involved in sudanese type2 dm. moreover, patients personal data revealed low to moderate education and socioeconomic status. a previous study observed low educational level correlate with dm, and socioeconomic status inversely associated with dm prevalence [22]. serum hs-crp level was significantly higher in type 2 dm patients than non diabetic group. this finding in agreement with the previous study that, pro-inflammatory cytokine hs-crp was significantly higher in type 2 diabetic patients [23, 24]. recently, the inflammatory pathway plays a critical role in type 2 pathogenesis, development, and progression of diabetes complications [11]. on the other hand, in accordance with previous reports [25, 26], we found that women had higher hs-crp levels than with men. in fact that gender difference has not yet completely understood, many studies speculated that adiposity, hormones replacement therapy, postmenopausal are associated with higher levels of crp in women [26]. furthermore, female type 2 dm patients had higher levels of tc, hdl-c, and ldl-c than the diabetic males which is in line with previous studies [27]. the findings may attributed to the effect of sex hormones and distribution of body fat leading to these differences [27]. moreover, patients who received statin treatment revealed lower levels of hs-crp, tc, and ldl-c. a previous evidence suggest that, therapy with atorvastatin lead to reduced hs-crp and ldl-c levels in patients with type 2 dm [28]. likewise, previous reports revealed proportional association between hs-crp level and bmi [29], our study showed a positive relationship between hs-crp and bmi. meanwhile, no correlations noted with lipid profile. since crp used to predict cvds even in patients with low ldl-c, indeed its stability in blood and not affecting by food intake [30]. the limitations of this study are frist the number controls is not equal to patients. second there are no pre-investigations done to patients, therefore the selection depend on previous clinical investigation. doi 10.18502/sjms.v14i3.5213 page 138 sudan journal of medical sciences hala abdalazeem aljack et al 5. conclusion the study concludes that, the hs-crp level is increased in type 2 dm patients. females had higher hs-crp than males. furthermore, atorvastatin reduces hs-crp level. also, hs-crp correlates positively with bmi therefore, monitoring of hs-crp is recommended, especially for females, overweight and obese type 2 dm patients, consequently early intervention. acknowledgment the authors gratefully acknowledge dr. nazik mahmoud (specialist of diabetes and endocrinology) at the diabetic center of military hospital for her valuable assistance in this study. conflict of interest all authors have declared that no conflict of interest exists. references [1] khodaeian m, enayati s, tabatabaei-malazy o, amoli mm. association between genetic variants and diabetes mellitus in iranian populations: a systematic review of observational studies. journal of diabetes research. 2015;2015:21. 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[26] qasim an, budharaju v, mehta nn, st clair c, farouk s, braunstein s, et al. gender differences in the association of c−reactive protein with coronary artery calcium in type−2 diabetes. clinical endocrinology. 2011;74(1):44-50. [27] zeqollari a, spahiu k, vyshka g, çakërri l. lipid profile in diabetes mellitus type 2 patients in albania and the corellation with bmi, hypertension, and hepatosteatosis. journal family medicin community health. 2014;1(4):1018. [28] son jw, kim dj, lee cb, oh s, song kh, jung ch, et al. effects of patient−tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low−density lipoprotein cholesterol in patients with type 2 diabetes. journal of diabetes investigation. 2013;4(5):466-74. [29] amanullah s, jarari a, govindan m. association of hs-crp with diabetic and nondiabetic individuals. jordan journal of biological sciences. 2010;3(1):7-12. doi 10.18502/sjms.v14i3.5213 page 141 sudan journal of medical sciences hala abdalazeem aljack et al [30] bandyopadhyay r, paul r, basu ak, chakraborty pp, mitra s. study of c reactive protein in type 2 diabetes and its relation with various complications from eastern india. journal of applied pharmaceutical science. 2013;3(7):156-9. doi 10.18502/sjms.v14i3.5213 page 142 introduction materials and methods measurement of bmi measurement of hs-crp measurement of lipid profile tg measurement tc measurement hdl-c measurement ldl-c measurement statistical analysis results discussion conclusion acknowledgment conflict of interest references sudan journal of medical sciences volume 14, issue no. 1, doi 10.18502/sjms.v14i1.4380 production and hosting by knowledge e research article microbiological profile of neonatal sepsis at a maternity hospital in omdurman, sudan manal abdelaziz1, yassir hamadalnil1, omaima hashim2, tahane bashir3, and e. s. mahjoub4 1department of microbiology, maternity hospital, khartoum 2department of microbiology and virology, national center for gastrointestinal & liver diseases, khartoum 3department of microbiology, radioisotope center khartoum, sudan 4department of microbiology, red sea university, port sudan 5department of microbiology, university of khartoum, khartoum, sudan abstract background: neonatal sepsis is a clinical syndrome characterized by systemic signs of infection and accompanied by bacteremia in the first month of life. it is a major cause of morbidity and mortality in neonatal period. the study was conducted to determine microbiological profile and antibiogram of neonatal sepsis at omdurman maternity hospital. methods: this was a cross-sectional hospital-based study involving 202 neonatal blood cultures at omdurman maternity hospital during the period from april 2017 to april 2018. specimens were cultured in brain heart infusion broth followed by subculture of isolates on blood agar, macconkey agar, and chocolate agar and incubated aerobically at 37ºc for 24 h. the isolates were tested for their susceptibility to antimicrobial agents using the kirby bauer disc diffusion method. results: of 202 positive blood cultures, 130 cases (64.4%) were early onset and 72 cases (35.6%) were recorded for late onset sepsis. gram-negative pathogens approaching (123, 60.9%). staphylococcus aureus was the most common organism in both groups of neonatal sepsis being isolated from (71, 35.7%), followed by klebsiella pneumoniae (43, 21.2%). gram-negative organisms were sensitive to imepenem (97.3%) and meropenem (80.5%) and resistant to third-generation cephalosporins (65.3%) and amoxicillin/clavulanic acid (91.4%). gram-positive organisms were resistant to cefotaxime (75%), amoxicillin/clavulanic acid (65.4%), and clindamycin (68.2%); 91.6% of gram-positive isolates were sensitive to vancomycin. conclusion: gram-negative pathogens took the major spectrum of isolates. klebsiella pneumoniae (21.2%) was the most frequent gram-negative organism. methicillinresistant staphylococcus aureus (mrsa) (33.7%) was the most common isolate. most of the isolates were multidrug resistant. the best choice for treatment is vancomycin (8.4%) and imepenem (2.7%) for gram-positive and gram-negative, respectively. adherence to antibiotic policy, antimicrobial surveillance, and policy updating is necessary. keywords: neonatal sepsis, mrsa, esbl how to cite this article: manal abdelaziz, yassir hamadalnil, omaima hashim, tahane bashir, and e. s. mahjoub (2019) “microbiological profile of neonatal sepsis at a maternity hospital in omdurman, sudan,” sudan journal of medical sciences, vol. 14, issue no. 1, pages 45–51. doi 10.18502/sjms.v14i1.4380 page 45 corresponding author: manal abdelaziz; email: manalhassieb@gmail.com received 10 february 2019 accepted 26 march 2019 published 31 march 2019 production and hosting by knowledge e manal abdelaziz et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v14i1.4380&domain=pdf&date_stamp=2019-03-31 mailto:manalhassieb@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences manal abdelaziz et al 1. introduction neonatal sepsis is considered one of the major causes of morbidity and mortality among term and preterm infants in neonatal intensive care units (nicu) [1]. neonatal sepsis is a systemic infection occurring in infants less than 28 days of life and is classified into early onset and late onset neonatal sepsis. early-onset neonatal sepsis (eos) occurs within seven days of birth, while late-onset neonatal sepsis (los) occurs after the first seven days of life [2]. neonatal infections are responsible for about 1.6 million deaths every year in developing countries [3]. sepsis and meningitis are considered the most common causes of these deaths [4]. in developed countries, streptococcus agalactiae (gbs) and escherichia coli were the most common pathogens isolated in severe cases [5]. eos is caused by gbs, e. coli, streptococcus viridans, staphylococcus aureus, and haemophilusinfluenzae [6]. the infant may acquire the pathogen either in utero or intrapartum [7]. according to the world health organization (who), there were around four million neonatal deaths every year, about a quarter of them is due to neonatal sepsis/pneumonia alone [8]. in sudan, the prevalence of neonatal sepsis is 17.5% and the mortality is 14.5% [9]. this study was conducted to determine the microbiological profile and antibiogram of neonatal sepsis at omdurman maternity hospital. 2. materials and methods the present study was a cross sectional, hospital-based study, conducted at omdurman maternity hospital during the period april 2017–april 2018. in this period, a total of 202 positive blood samples were analyzed. two ml of blood from neonate was dispensed into a sterilized universal bottle containing brain heart infusion broth to make a 1:10 dilution. it was collected from neonates under aseptic condition. each sample was cultured in blood culture bottle and incubated aerobically at 37c up to seven days. regular observation of the bottle color, and turbidity, direct gram stain, and subculture were done to detect the positive ones. regular subculture was done after one day of incubation, at 48 hours, and then at 96 hours. each sample was subcultured on blood agar, macconkey agar, and chocolate blood agar and incubated aerobically at 37ºc for 24 h. if there was no broth change or negative subculture for up to seven days, blood culture was considered as negative. identification was done based on colonial morphology, gram stain, and standard biochemical tests. antimicrobial susceptibility of isolated organisms was detected by using the kirby bauer disc diffusion method according to the clinical and laboratory standard institute (clsi) [10]. pure colonies doi 10.18502/sjms.v14i1.4380 page 46 sudan journal of medical sciences manal abdelaziz et al of isolates were emulsified in distilled water and inoculated on muller hinton agar. antimicrobial discs were placed on the inoculated agar and incubated for 24 h at 37ºc; then they were observed for zones of inhibition and determined as susceptible, intermediate, or resistant according to the clsi [10]. the applied antibiotic for grampositive cocci included oxacillin to check mrsa and for gram-negative rods e. coli attcc 25922 was used as control strain. data were analyzed by statistical package for social science spss software version 24. chi-square tests were done. p-value < 0.05 was considered significant in comparative data. 3. results a total of 202 newborn babies were enrolled in this study. there were 130 cases (64.4%) of early-onset sepsis and 72 cases (35.6%) of late-onset sepsis, see table 1. among the positive blood cultures, gram-negative septicemias were 123(60.9%), while gram-positive were 75(37.1%). staphylococcus aureus was isolated from 71(35.7%) in both groups of neonatal sepsis, followed by klebsiella pneumoniae 43(21.2%) table 2. tables 3 and 4 show the result of antibiotics sensitivity tests. table 1: distribution of isolated organisms in an eos and los. frequency of isolation early onset late onset bacteria streptococcus pyogenes 1 1 0 klebsiella oxytoca 1 1 0 candida albicans 4 0 4 enterococcus faecalis 2 0 2 proteus mirabilis 1 1 0 salmonella spp. 6 3 3 s. epidermidis 1 0 1 enterobacter spp. 6 5 1 acinetobacter baumannii 5 2 3 serratia marcescens 7 7 0 citrobacter spp. 4 1 3 pseudomonas aeruginosa 18 12 6 mrsa 68 43 25 staphylococcus aureus 3 2 1 klebsiella esbl 11 8 3 klebsiella pneumonae 32 19 13 e.coli esbl 9 7 2 e. coli 23 18 5 total 202 130 72 doi 10.18502/sjms.v14i1.4380 page 47 sudan journal of medical sciences manal abdelaziz et al table 2: frequencies of bacteria that cause neonatal sepsis in which mrsa is the most common organism (n = 202). frequency percent type of bacteria mrsa 68 33.7 klebsiella pneumonae 32 15.8 e. coli 23 11.4 pseudomonas aeruginosa 18 8.9 klebsiella esbl 11 5.4 e. coli esbl 9 4.5 serratia marcescens 7 3.5 enterobacter spp. 6 3.0 salmonella spp. 6 3.0 acinetobacter baumannii 5 2.5 citrobacter spp. 4 2.0 candida albicans 4 2.0 staphylococcus aureus 3 1.5 enterococcus faecalis 2 1.0 s. epidermidis 1 .5 proteus mirabilis 1 .5 klebsiella oxytoca 1 .5 streptococcus pyogenes 1 .5 total 202 100.0 table 3: frequencies of antibiotic susceptibility of the gram-negative organisms. antibiotics sensitive resistant imipenem 110 (97.3%) 3 (2.7%) meropenem 95 (80.5%) 23 (19.5%) cefotaxime 43 (40%) 66 (60%) amikacin 45 (46.9%) 51 (53.1%) ceftazidime 36 (34.7) 68 (65.3%) gentamicin 32 (39.5%) 49 (60.5%) amoxicillin/clavulanic acid 6 (8.6%) 64 (91.4%) penicillin 7 (13.5%) 45 (86.5%) 4. discussion neonatal sepsis can be defined as a clinical syndrome characterized by systemic signs of infection and accompanied by bacteremia in the first month of life [11]. it is considered one of the major causes in neonatal morbidity and mortality [1]. the pathogens causing neonatal sepsis in developing countries differ from those in developed countries [12]. but overall the gram-negative organisms are more common [13]. doi 10.18502/sjms.v14i1.4380 page 48 sudan journal of medical sciences manal abdelaziz et al table 4: frequencies of antibiotic susceptibility of the gram-positive organisms. antibiotics sensitive resistant penicillin 6 (9%) 61 (91%) vancomycin 66 (91.6%) 6 (8.4%) amoxicillin/clavulanic acid 12 (34.6%) 40 (65.4%) ciprofloxacin 26 (43.3%) 34 (56.7%) cefotaxime 2 (25%) 6 (75%) clindamycin 7 (31.8%) 15 (68.2%) gentamicin 45 (60.8%) 29 (39.2%) in this study, gram-negative and gram-positive organisms encountered 60.9% and 37.1%, respectively, which is comparable to a study conducted in india [12], which reported that gram-negative and gram-positive organisms were 56% and 44%, respectively. similar results were reported in iraq [14] and tanzania [15]. in this study, the eos and los were 64.6% and 35.4%, respectively. this result is also comparable to a study conducted in india [16], which reported that eos and los were 61.41% and 38.59%, respectively, further supported by another study done in india [17]. however, it differs from the study conducted in tanzania [15] and iraq [14]. staphylococcus aureus was the most common isolate (35.1%) in both eos and los in the current study, and 95% of s. aureus were methicillin-resistant staphylococcus aureus (mrsa). this result is similar to a study conducted by zaidi et al. [18]. the second most common isolate was klebsiella pneumoniae (21.2%), from which 25.58% were extended spectrum beta lactamase (esbl). high resistance rate to cephalosporins can be contributed to the irrational use of these antibiotics. the presence of proteus mirabilis, serratia marcescens, klebsiella oxytoca, and streptococcus pyogenes isolates in the eos and the absence of these isolates in the los was noted in this study. antimicrobial resistance now is worldly distributed and multidrug-resistant organisms are a global concern. antibiotics susceptibility patterns differ from one country to another, so it is difficult to compare the susceptibility patterns between countries. in this study, gram-negative organisms showed a high sensitivity to imepenem (97.3%) which is consistent to the local study conducted at soba hospital in khartoum (100%) [19]. imepenem sensitivity was 80.5%. this study reflected moderate resistance to amikacin (53.1%) and gentamicin (60.5%), which differs from the local study that showed low resistance to amikacin (10.5%) and high resistance to gentamicin (89.5%) [19]. this study reflected a moderate resistance to third generation cephalosporin 60% when it’s compared to the local study that reflected high resistance (89.5%) [19]. the best sensitivity of gram-positive organisms was to vancomycin (91.6%), most of these isolates doi 10.18502/sjms.v14i1.4380 page 49 sudan journal of medical sciences manal abdelaziz et al were mrsa. this result was comparable to soba study (92%) [19]. gentamicin showed moderate sensitivity (60%), which is also comparable to the soba study (50%) [19]. also, for the gram-positive organisms, the third generation cephalosporin showed a moderate resistance (75%). most probably the overuse of third-generation cephalosporin is a main cause of the wide range resistance. 5. conclusion from this study, gram-negative pathogens took a major spectrum of isolates. klebsiella pneumoniae was the most frequent gram-negative organism. methicillin-resistant staphylococcus aureus (mrsa) was the most common isolate. most isolates were multidrug resistance. therefore, the surveillance for antimicrobial resistance was necessary. adhering to and updating the antibiotic policy contributes to containing this problem. references [1] camacho-gonzalez, a., spearman, p. w., and stoll, b. j. (2013). neonatal infectious diseases: evaluation of neonatal sepsis. pediatric clinics of north america, vol. 60, pp. 367–389. [2] verani, j. r., mcgee, l., schrag s. j. (november 19, 2010). prevention of perinatal group b streptococcal disease: revised guidelines from cdc. mmwr recommendations and reports, vol. 59, pp. 1–32. [3] brye, j, boschi, pinto, c., et al. (2005). who estimate of the causes of death in children. lancet, vol. 365, p. 1147. [4] nbs, s., menezes, r. p., brito, m. o., et al. (2017). sepsis neonatal: epidemiology, etiology and risk factors. advances in biotechnology and microbiology, vol. 4, no. 2, pp. 7–8. [5] le doare, k. and heath, p. t. (2013). an overview of global gbs epidemiology. vaccine, vol. 31s, pp. d7–12.2. [6] weston, e. j., pondo, t., lewis, m. m., et al. (november 2011). the burden of invasive early-onset neonatal sepsis in the united states, 2005-2008. the pediatric infectious disease journal, vol. 30, no. 11, pp. 937–941. [7] simonsen, k. a., anderson-berry, a. l., delair, s. f., et al. (january 1, 2014). earlyonset neonatal sepsis. clinical microbiology reviews, vol. 27, no. 1, pp. 21–47. [8] world health organiation. (2011). neonatal sepsis a major killer to be tackled in communities. who. doi 10.18502/sjms.v14i1.4380 page 50 sudan journal of medical sciences manal abdelaziz et al [9] kheir, a. e. m. and khair, r. a. (2014). neonatal sepsis: prevalence and outcome in a tertiary neonatal unit in sudan. time journals of medical sciences report and research, vol. 2, no. 1, pp. 21–25. [10] clinical & laboratory standards institute. (2011). performance standards for antimicrobial susceptibility testing: twenty-first informational supplement. clsi document m100-s21. wayne, pa: clinical and laboratory standards institute. [11] verma, p., berwal, p. k., nagaraj, n., et al. (2015). neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. international journal of contemporary padiatrics, vol. 2, no. 5, pp. 176– 180. [12] jyothi, p., basavaraj, m. c., and basavaraj, p. v. (2013). bacteriological profile of neonatal septicemia and antibiotic susceptibility pattern of the isolates. journal of natural science, biology and medicine, vol. 4, no. 2, pp. 306–309. [13] vergnano, s., sharland, m., kazembe, p., et al. (2005). neonatal sepsis: an international perspective. archives of disease in childhood fetal and neonatal edition, vol. 90, pp. f220–f224. [14] ibrahim, s. a. and rahma, s. (2012). microbiological profile of neonatal septicemia. the iraqi postgraduate medical journal, vol. 11, no. 1. [15] kayange, n., kamugisha, e., mwizamholya, d. l., et al. (2010). predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, mwanzatanzania. bmc pediatrics, pp. 1471–2431. [16] lamba, m., sharma, r., sharma, d., et al. (2016). bacteriological spectrum and antimicrobial susceptibility pattern of neonatal septicaemia in a tertiary care hospital of north india. journal of maternal-fetal and neonatal medicine, vol. 29, pp. 3993– 3998. [17] agnihotri, n., kaistha, n., and gupta, v. (december 2004). antimicrobial susceptibility of isolates from neonatal septicemia. japanese journal of infectious diseases, vol. 57, pp. 273–275. [18] zaidi, a. k., thaver, d., ali, s. a., et al. (2009). pathogens associated with sepsis in newborns and young infants in developing countries. the pediatric infectious disease journal, vol. 28, pp. s10–s18. [19] babiker, w., ahmed, a., babiker, t., et al. (2018). prevalence and causes of neonatal sepsis in soba university hospital, sudan. medical microbiology reports, vol. 1, 2. doi 10.18502/sjms.v14i1.4380 page 51 introduction materials and methods results discussion conclusion references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2956 production and hosting by knowledge e case report a case report of duodenal psammomatous somatostatinoma ayman fisal ahmed foad1 and hyder osman mirghani2 1department of pathology, faculty of medicine, university of tabuk, saudi arabia 2department of internal medicine and endocrine, faculty of medicine, university of tabuk, saudi arabia abstract somatostatinoma is a neuroendocrine tumor; its incidence in the duodenum around the ampulla of vater is rare, and it is often not associated with secretory manifestation. the authors report a case of a female with an ampullary (vater) tumor displaying neuroendocrine nuclear features, psammoma bodies, and the positivity for immunohistochemical panel of neuroendocrine tumors. the patient was presented with some features compatible with somatostatin secretion-associated syndrome; albeit with normal serum levels of the hormone. initial attempt of complete resection failed, and the involved margins were revised with a subsequent surgery, and the patient showed an uneventful course on follow-up for two years. 1. introduction neuroendocrine tumors are a group of tumors with a variable malignant potential. in the gastrointestinal tract, they are classified topographically into fore, mid and hindgut tumors. most of the tumors arise in the mid-gut, distally more than proximally [1]. only 2% of neuroendocrine tumors occur in the duodenum. five types have been recognized in the duodenum and the upper jejunum: g-cell tumor (gastrinoma), d-cell tumor (somatostatinoma), well-differentiated tumors, poorly differentiated tumors/small cell carcinoma, and gangliocytic paraganglioma [1–3]. according to the iarc-who blue book, neuroendocrine tumors span a spectrum from well to poorly differentiated tumors. mitosis and tumor necrosis dictate the classification [1]. the somatostatinoma syndrome is defined by a pentad of clinical features; diarrhea, cholelithiasis, diabetes mellitus, weight loss and hypochlorhydria. somatostatinoma syndrome is often associated with pancreatic neuroendocrine tumors; duodenal tumors are mostly asymptomatic, and only a small fraction of cases (10%) is symptomatic [3]. how to cite this article: ayman fisal ahmed foad and hyder osman mirghani (2018) “a case report of duodenal psammomatous somatostatinoma,” sudan journal of medical sciences, vol. 13, issue no. 3, pages 187–195. doi 10.18502/sjms.v13i3.2956 page 187 corresponding author: ayman fisal ahmed foad; email: a.foad@ut.edu.sa received 10 august 2018 accepted 18 september 2018 published 24 september 2018 production and hosting by knowledge e ayman fisal ahmed foad and hyder osman mirghani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:a.foad@ut.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani duodenal somatostatinoma arises exclusively in or in the vicinity of the ampulla of vater. these tumors are solitary in 90% of cases, while familial tumors and syndromeassociated tumors might be multiple [2]. 2. case report 2.1. history and examination a 39-year-old female from west kordofan state/sudan presented in july 2012 to a private clinic run by a general physician in alnohod city complained of vague abdominal pain and indigestion for two-month duration. she has been diagnosed with irritable bowel syndrome (ibs) and received antispasmodic medications since. she has no diarrhea or steatorrhea. on examination, she was found as obese with bmi (31), not pale jaundiced or cyanosed. her abdomen was soft and pendulous. the liver and the spleen were not palpable. other clinical examinations were unremarkable. blood chemistry revealed adverse lipid profile with high cholesterol = 260mg/dl, ldl cholesterol = 150mg/dl, hdl cholesterol = 42mg/dl, normal bilirubin, alkaline phosphatase x3 upper normal level (done one week postoperatively), post prandial glucose = 14 mmol/l, normal bicarbonate and electrolytes levels. the fasting serum somatostatin level = 7.9pmol/l, which falls within the normal reference range for adults (10–22 pg/ml) [4] (in two different occasions in two different labs two-weeks apart). abdominal ultrasonography revealed two small echogenic gallstones with a thinwall gall bladder. no features consistent with cholecystitis were seen. the liver showed no echogenic masses. with the persistent of her symptoms, the patient was referred to khartoum teaching hospital (a reference hospital in sudan) in august 2012. the attending gastroenterologist planned for upper git endoscopy. the procedure showed a 2.7 cm polypoid mass with a smooth glistening surface at the level of the 2nd duodenal segment protruding from the ampulla of vater, and the surrounding duodenal mucosa was unremarkable. an incisional biopsy was obtained and sent to the authors’ lab (central laboratory administration, histopathology-lab). the received specimen was tiny, fragmented and poorly preserved with crush artifacts and was not optimal for a proper histopathological interpretation, nevertheless the ghosted outlines of the nested growth gave the impression of a neuroendocrine tumor. doi 10.18502/sjms.v13i3.2956 page 188 sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani a definitive surgery was planned after four-weeks interval (october 2012) for the attempt of complete surgical resection. the tumor was approached through laparotomy, excisional attempt succeeded via ampullectomy (including the polypoid tumor) with electrocautery dissector, intraoperative examination of the duodenum revealed increased thickness overlying the affected area. 2.2. gross description the specimen received were fixed in formalin; the external surface was grayish white in color with small punctate hemorrhage on its surface. the mass measured 2.7 cm and consisted of a polyp with a small segment of its base, with three accompanying lymph nodes, sized 1x, 6x, and 7x each. serial longitudinal sections were done to reveal relation with the deep surgical margin. the cut sections showed a yellowish white surface with a slight gritty sensation upon trimming. no cystic degeneration, necrotic or hemorrhagic central foci noted. the tumor specimen were all processed for microscopic examination. the third subsequent margin revision biopsy was composed of a pancreatico-gastroduodenectomy resection specimen. 2.3. microscopic description microscopic examination of the polypoid mass revealed a circumscribed mass composed of glandular structures and packets of cells surrounded by abundant, delicate vasculature. glandular lumen showed psammomatous bodies about 25–60 um in diameter. periodic acid schiff luminal secretions were detected focally. the constituent tumor cells are columnar, with basally oriented nuclei. the cytoplasm ranges from eosinophilic to clear. the nuclei showed monotony; some are vesicular with prominent nucleoli. no mitotic activity or necrotic foci were appreciated in the adequate biopsy submitted (figure 1). immunohistochemical studies were positive for synaptophysin, cd56, chromogranin, ck and weakly for cdx-2; a collective of a neuroendocrine differentiation markers. the deep surgical margin was involved, the base of the polypoid mass showed infiltrating glands traversing and dissecting through pancreatic acini (figure 2). doi 10.18502/sjms.v13i3.2956 page 189 sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani figure 1: the upper microscopic slide (h&e) shows nests, trabeculae, and ribbons of columnar cells with clear to eosinophilic cytoplasm surrounded by a rich vascular network. the lower shows psammoma body in the center of the field. the tumor is well-differentiated, grade 1 – according to the who criteria (< 2mitoses/10 hpf (50 fields were counted using x40), and no necrosis). the world health organization criteria for diagnosing malignancy are a size > 2 cm, increased mitosis, and the presence of tumor necrosis [3]. the ptnm (pathological tumor, node, metastasis staging system) staging according to the ajcc manual [5] is t3 (tumor invades the pancreas), n0 (no regional lymph node doi 10.18502/sjms.v13i3.2956 page 190 sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani figure 2: the upper histopathological slide shows the invasive front of the tumor traversing and dissecting through pancreatic acini. the lower slide shows the tall columnar clear tumor cells forming trabecula and nests with small punctate classifications. metastasis, three were obtained), m0 (no distant metastasis), and r1 (surgical margin is grossly negative, microscopically positive). surgical revision for the deep margin was advised, and a second pancreatico-gastroduodenectomy procedure performed two month later, and all the surgical margins and accompanying lymph nodes (= 6 nodes) were negative of tumor deposits. doi 10.18502/sjms.v13i3.2956 page 191 sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani 3. discussion the first case of duodenal somatostatinoma was reported in 1979. duodenal somatostatin-producing endocrine tumors, which belong to the group of gastrointestinal, endocrine tumors, are rare neoplasms that have a prevalence of 1 in 40 million [6, 7]. due to the relatively large number of d cells, 40% of the reported somatostatinoma originated from the upper intestinal tract (50% in the duodenum and 50% in the ampulla with only one case reported in the jejunum) [6]. the peri-ampullary of vater region is a specialized anatomical structure in the 2nd part of the duodenum composed of both ampulla and papilla. the ampulla constitutes common bile duct and pancreatic duct with variable anatomical combination patterns. the papilla is observed as a mucosal protrusion into the duodenal lumen. the area showed multiple intersections of different types of mucosa (small intestine, pancreatic duct, and biliary duct epithelia) and associated underlying supporting tissue [8]. about 105 case reports hits in pubmed (accessed december 7, 2016), about 93% are sporadic and 7% familial. familial cases are usually associated with neurofibromatosis1, multiple endocrine neoplasia-1, tuberous sclerosis or vhon hippel lindau syndromes [9–13], all of which were excluded in the patient. duodenal tumors tend to be smaller averaging between 13 and 75 mm and 18 mm as a medium size, compared to pancreatic tumors with a median size of 42.5 mm. in this case, the tumor size was 2.7 cm. there is a strong correlation between the size of the tumor and its behavior; larger tumors tend to have lymph node and liver metastasis that were not observed in this case supporting the previous findings [14]. in the current case, some features of somatostatinoma syndrome were evident (diabetes mellitus and gallstones), but not yet fulfilling the criteria for the diagnosis. somatostatin is an inhibitory hormone to various endocrine and exocrine hormones but due to the binding proteins in the plasma that rapidly inactivate the hormone it mainly acts in paracrine fashion [15]. accordingly, the somatostatinoma syndrome is rare in duodenal somatostatinomas. the diabetic range plasma glucose observed in this case could be explained by the inferential inhibition of somatostatin on insulin and diabetogenic hormones leading to a mild degree of diabetes and less ketoacidosis that could be observed in patients with somatostatinoma. another plausible explanation is the coincidental dm in the patient, reflecting the high prevalence of diabetes mellitus in sudan [16]. in this case, doi 10.18502/sjms.v13i3.2956 page 192 sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani the fasting somatostatin level was within normal reference range. and the postprandial plasma glucose was diagnostic for diabetes. the patient had many features of the metabolic syndrome, consolidated by a high postprandial glucose, adverse lipid profile, and bmi. in the literature most of the duodenal somatostatinoma are non-secretory [1]. episodic secretion of the somatostatin hormone or decline in the secretory function of the tumor with the tumor advancement is a likely remote possibility. gallstones are observed in 27% of duodenal somatostatinoma together with a massively dilated gallbladder [15]. although gallstones were detected in our patient, the gallbladder was not dilated and showed normal wall thickness. in a subset of cases, metastatic disease is evident at diagnosis mainly in the liver (10%) and lymph nodes (35%). this might be related to the late presentation at the diagnosis due to non-secretory attribute of the tumor [17]. liver and lymph nodes metastasis in the present case were excluded by clinical, ctabdomen, ultrasonic and surgical exploration; however, endoscopic ultrasonography was not done due to limited accessibility of this important diagnostic imaging in the authors’ country. the long follow-up disease free survival supports the absence of metastasis and lymph node involvement notion. the deep surgical margin was involved, and review of the surgical margin was advised. subsequent radical surgery was done through whipple pancreatico-gastroduodenectomy after two months’ interval. the revised surgical margin was free. the patient showed no features of recurrence at six, twelve months and two years’ followup visits (last visit in may 2014). forty percent of patients with somatostatinomas died at intervals ranging from 1 week to 14 months after diagnosis, whereas 60% of patients were alive from 6 months to 5 years after diagnosis. thus, the syndrome is associated with a high malignant potential, and it is important to be approached aggressively in management and to attempt to remove all tumor tissue with a clear surgical margin. surgical extirpation of the tumor provides the only chance of cure [18]. acknowledgements the views expressed in this article are authors’ own and not an official opinion of the institution or funder. the authors are accountable for the accuracy and integrity of all aspects of this work. doi 10.18502/sjms.v13i3.2956 page 193 sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani author contributions both authors contributed equally and significantly to the entire work—including concept and design of the work, data collection, data analysis, and manuscript drafting and critical revision for important intellectual content. references [1] bosman, f. (2010). who classification of tumours of the digestive system. lyon: international agency for research on cancer. [2] medscape. (2018). somatostatinomas: background, pathophysiology, epidemiology. retrieved from http://emedicine.medscape.com/article/182841-clinical (accessed on september 4, 2018). [3] cooper, h. s. (2015). intestinal neoplasms, in s. e. mills and s. s. sternberg. sternberg’s diagnostic surgical pathology, p. 1552. philadelphia, pa: lippincott williams et wilkins. [4] medscape. (2018). somatostatin: reference range, background/interpretation, collection and panels. retrieved from https://emedicine.medscape.com/article/ 2089466-overview (accessed on september 4, 2018). [5] pathologyoutlines.com. (2018). tnm staging. retrieved from: http://www. pathologyoutlines.com/topic/ampullatnmamp.html (accessed on september 4, 2018). [6] kaneko, h., yanahira, n., ito, s., et al. (1979). somatostatinoma of the duodenum. cancer, vol. 44, pp. 2273–2279. [7] yamamoto, r., kato, s., maru, t., et al. (2016). the coexistence of somatostatinoma and gastrointestinal stromal tumor in the duodenum of a patient with von recklinghausen’s disease. internal medicine, vol. 55, no. 6, pp. 617–622. doi: 10.2169/internalmedicine.55.5761 [8] kim, t. u., kim, s., lee, j. w., et al. (2008). ampulla of vater: comprehensive anatomy, mr imaging of pathologic conditions, and correlation with endoscopy. european journal of radiology, vol. 66, no. 1, pp. 48–64. doi:10.1016/j.ejrad.2007.04.005 [9] kainuma, o., ito, y., taniguchi, t., et al. (1996). ampullary somatostatinoma in a patient with von recklinghausen’s disease. journal of gastroenterology, vol. 31, pp. 460–464. doi 10.18502/sjms.v13i3.2956 page 194 http://emedicine.medscape.com/article/182841-clinical https://emedicine.medscape.com/article/2089466-overview https://emedicine.medscape.com/article/2089466-overview http://www.pathologyoutlines.com/topic/ampullatnmamp.html http://www.pathologyoutlines.com/topic/ampullatnmamp.html sudan journal of medical sciences ayman fisal ahmed foad and hyder osman mirghani [10] karasawa, y., sakaguchi, m., minami, s., et al. (2001). duodenal somatostatinoma and erythrocytosis in a patient with von hippel-lindau disease type 2. internal medicine, vol. 40, pp. 38–43. [11] sreenarasimhaiah, j., armstrong, l. a., tang, s.-j., et al. (2009). pancreatic somatostatinoma and tuberous sclerosis: case report of an exceedingly rare association. gastrointestinal endoscopy, vol. 69, no. 2, pp. 379–381. [12] nhs choices. department of health. tuberous sclerosis. retrieved from http:// www.nhs.uk/conditions/tuberous sclerosis/pages/introduction.aspx (accessed on january 8, 2017). [13] marini, f., falchetti, a., luzi, e., et al. (2009). multiple endocrine neoplasia type 1 (men1) syndrome, in d. l. riegert-johnson, l. a. boardman, t. hefferon, et al. (eds.) cancer syndromes. bethesda (md): national center for biotechnology information (us). retrieved from: https://www.ncbi.nlm.nih.gov/books/nbk7029/ (accessed on july 18, 2008 [updated august 9, 2008]). [14] garbrecht, n., anlauf, m., schmitt, a., et al. (2008). somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. endocrinerelated cancer, vol. 15, pp. 229–241. [15] vinik, a., feliberti, e., perry, r. r. (2000). somatostatinoma, in l. j. de groot, g. chrousos, k. dungan, et al. (eds.) endotext. south dartmouth (ma): mdtext.com, inc. retrieved from: https://www.ncbi.nlm.nih.gov/books/nbk279034/ (accessed on november 28, 2013). [16] international diabetes federation, sudan. (n.d.). retrieved from http://www.idf. org/membership/mena/sudan (accessed on january 18, 2017). [17] duodenum (psammomatous) somatostatinoma. (n.d.). retrieved from http://surgpathcriteria.stanford.edu/gitumors/duodenum-somatostatinomapsammomatous/printable.html (january 18, 2017). [18] vinik, a., feliberti, e., and perry, r. r. (2000). somatostatinoma, in l. j. de groot, g. chrousos, k. dungan, et al. (eds.) endotext. south dartmouth (ma): mdtext.com, inc. retrieved from: https://www.ncbi.nlm.nih.gov/books/nbk279034/ (accessed on november 28, 2013). doi 10.18502/sjms.v13i3.2956 page 195 http://www.nhs.uk/conditions/tuberous http://www.nhs.uk/conditions/tuberous https://www.ncbi.nlm.nih.gov/books/nbk7029/ https://www.ncbi.nlm.nih.gov/books/nbk279034/ http://www.idf.org/membership/mena/sudan http://www.idf.org/membership/mena/sudan http://surgpathcriteria.stanford.edu/gitumors/duodenum-somatostatinoma-psammomatous/printable.html http://surgpathcriteria.stanford.edu/gitumors/duodenum-somatostatinoma-psammomatous/printable.html https://www.ncbi.nlm.nih.gov/books/nbk279034/ introduction case report history and examination gross description microscopic description discussion acknowledgements author contributions references sudan journal of medical sciences volume 13, issue no. 4, doi 10.18502/sjms.v13i4.3596 production and hosting by knowledge e research article frequency of methicillin resistance among staphylococcus aureus clinical isolates in khartoum state, sudan najem aldin mohammed osman1, intisar elhag elraya2, yassir mahgoub mohamed3, muataz mohamed eldirdery3, salaheldein gumaa elzaki4, abdallah elssir ahmed5, and ali mohamed elhassan eleragi6 1department of biotechnology, faculty of science and technology, omdurman islamic university, sudan 2college of applied medical science, shaqra university, ksa 3department of microbiology, tropical medicine research institute, national center for research, sudan 4department of epidemiology, tropical medicine research institute, national center for research, sudan 5institute of endemic diseases, university of khartoum, sudan 6department of microbiology, faculty of medicine, university of bisha, ksa abstract background: methicillin-resistant staphylococcus aureus (mrsa) have emerged as an important cause of nosocomial and community-acquired infections ranging from mild to severe life-threatening infections. therefore, a reliable detection of such strains is required for effective treatment. objectives: to determine the frequency and the antibiogram of mrsa among different clinical isolates. study design: a cross-sectional, descriptive study. materials and methods: standard bacteriological methods, disk diffusion and pcr were performed to determine the frequency of mrsa among different clinical isolates. results: the overall results showed 96/210 (45.7%) of isolates were mrsa mostly recovered from wounds and blood stream. high percentage was detected in hospitalassociated (ha) strains (64.2%) rather than community (ca) (37.1%) (p-value < 0.001). from the generated antibiogram, co-trimoxazole was the most active (80.2%), while penicillin was the least one (6.2%). conclusion: as mrsa strains were mostly isolated from hospitals, clinicians should be aware of such burden strains. local frequency investigation of mrsa is recommended for perfect diagnosis and treatment. keywords: mrsa, s. aureus, meca, sudan how to cite this article: najem aldin mohammed osman, intisar elhag elraya, yassir mahgoub mohamed, muataz mohamed eldirdery, salaheldein gumaa elzaki, abdallah elssir ahmed, and ali mohamed elhassan eleragi (2018) “frequency of methicillin resistance among staphylococcus aureus clinical isolates in khartoum state, sudan,” sudan journal of medical sciences, vol. 13, issue no. 4, pages 240–250. doi 10.18502/sjms.v13i4.3596 page 240 corresponding author: najem aldin mohammed osman; email: najemosman@hotmail.com received 13 october 2018 accepted 3 december 2018 published 26 december 2018 production and hosting by knowledge e najem aldin mohammed osman et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v13i4.3596&domain=pdf&date_stamp=2018-12-26 mailto:najemosman@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences najem aldin mohammed osman et al 1. introduction the staphylococcus aureus has been recognized as one of the major human pathogens. it has been reported as the cause of spectrum of infections in hospitals and throughout the communities [1]. humans and animals are the natural reservoirs of s. aureus. it has been reported that from 10 to 40% of people not associated with hospitals are carriers of s. aureus and the predominant sites of its colonization were the throat and anterior nares [2]. it is considered as one of the most common causes of soft tissues and skin infections such as carbuncles, abscesses, furuncles, folliculitis, impetigo, cellulitis, and bullous impetigo [3]. other than skin and soft tissue infections, s. aureus is known to cause bone and joint infections, pneumonia, endocarditis, and scalded skin syndrome [4]. methicillin-resistant s. aureus (mrsa) was first reported from the united kingdom (uk) in 1961 [5]. in the following decades, mrsa had been established as a major nosocomial pathogen worldwide with a significant economic impact on healthcare systems [6]. several reports indicated that mrsa infections have been associated with high mortality, morbidity, and high treatment cost. furthermore, failure to identify mrsa in patients results in therapy failure and thus increases overall morbidity and mortality as well as the cost effectiveness [7–9]. mrsa resistance to methicillin has been attributed to a number of mechanisms, but the chief factor is supposed to be its ability to produce specific penicillin-binding protein 2a (pbp-2a) that renders β-lactamase-resistant penicillin ineffective including all other β-lactam drugs [10]. the pbp-2a has shown a usual low binding affinity for almost all beta-lactam antibiotics as compared to native pbps [11]. the pbp-2a is coded and induced by the meca gene, a part of staphylococcal cassette chromosome (sccmec). the sccmec is known to be present in mrsa but not in the methicillin-susceptible s. aureus (mssa) strains [12–14]. according to their origin, mrsa strains were classified into two main types: community-associated mrsa (camrsa) and hospital-associated mrsa (ha-mrsa). however; the prevalence varies from country to country, where most mrsa strains have been hospital-associated (ha-mrsa) [15, 16]. for most countries affected by mrsa, there have been many years of debate about its relative virulence compared with methicillin-susceptible s. aureus (mssa) and whether it could be controlled. mrsa is endemic in the majority of hospitals around the world, and it is now considered as an additional burden of healthcare-acquired infection [8]. in the current study, the presence of meca gene was investigated in s. aureus strains isolated from three khartoum major hospitals. this cross-sectional study was designed to determine the frequency of mrsa strains and to elucidate their distribution among community and hospital strains. doi 10.18502/sjms.v13i4.3596 page 241 sudan journal of medical sciences najem aldin mohammed osman et al 2. methods the current study was performed mainly in khartoum state; during the period from 2013 to 2015. the specimens were collected from three khartoum major hospitals – khartoum teaching hospital, alribat teaching hospital, and the military hospital. study subjects were patients presented with any s. aureus-suspected infections. scientific and ethical approval of the study was obtained from the ethical committee of tropical medicine research institute (sudan). 2.1. bacterial identification the isolation and identification of bacterial isolates was done as described previously by cowan et al. (1993) [17] and collee et al. (1996) [18]. two hundred and ten s. aureus isolates were recovered from different sites of infections. s. aureus atcc 25923 was used as control strain in all procedures. 2.1.1. criteria for labeling isolates as community associated (ca) or hospital associated (ha) the isolates were differentiated into community or hospital strains according to the cdc standardized definition [19]. 2.2. antibiotic susceptibility testing muller-hinton agar was used to test the isolates to different antibiotics according to clsi, (2006) [20]. 2.2.1. testing isolates for methicillin resistance standard disk diffusion was done using oxacillin 1μg to differentiate mrsa from mssa strains. a zone size of ≥ 10 mm was considered resistant; a zone size of ≥13 mm was considered susceptible [20]. 2.3. molecular detection of meca gene doi 10.18502/sjms.v13i4.3596 page 242 sudan journal of medical sciences najem aldin mohammed osman et al 2.3.1. dna extraction dna extraction was performed using dneasy kit (qiagen). pretreatment of bacterial cells was done according to the manufacturer instructions. 2.3.2. pcr amplification meca specific primers were used (metabion international-germany) as follows: meca1 (5 -aaa atc gat ggt aaa ggt tgg c3), meca-2 (5 -agt tct gca gta ccg gat ttg c3) for detection of the methicillin-resistant gene. single pcr amplifications were performed in 25 µl reaction mixture (maxime pcr premix kit i-taq 5 µl) (intron biotechnology, south korea), containing 3µl of bacterial dna template, 1 µl of 5 pmol/µl from each primers, and the mixture was completed with 15 µl of sterile distilled water in a 0.2 eppendorf (pcr) tube. amplifications were performed by using the thermalcycler as follows: an initial denaturing step at 94ºc for 3 min followed by 30 cycles of amplification with 94ºc for 30 s, annealing at 55ºc for 30 s, and extension at 72ºc for 30 s, except for the final cycle which had an extension step of 4 min. the size of the pcr product was 532 bp [21]. 3. results 3.1. oxacillin disk diffusion result 80/210 (38.1%) of the s. aureus isolates were found to be mrsa while the remainder 130 (61.9%) were found to be mssa. 3.2. pcr result it is observed that 96/210 (45.7%) of isolates were meca positive (mrsa), while 114 (54.3%) were meca negative (mssa) (figure 1). 3.3. distribution of mrsa according to the site of infection according to the anatomical site of infection, the distribution of the encountered mrsa isolates was as follows: surgical wound infection 40 (63.5%), skin and soft tissues 15 doi 10.18502/sjms.v13i4.3596 page 243 sudan journal of medical sciences najem aldin mohammed osman et al (34.1), paronychia 10 (37.0%), bone 8 (44.4%), urinary tract 5 (45.5%), ear infection 3 (37.5%), blood stream 5, others 7 (53.8%) (table 1). 3.4. frequency of mrsa according to the source among the total isolated community strains (143), the meca positive (ca-mrsa) were 53 (37.1%), while among the total isolated hospital strains (67), the meca positive (hamrsa) were 43 (64.2%) with significant difference (p-value < 0.001) (table 2). 3.5. antibiotics sensitivity pattern of mrsa isolates with regard to mrsa isolates, we found that the most active antibiotic was cotrimoxazole (80.2%), while the penicillin was the least active (6.2%) (table 3). figure 1: number and percentage of detected mrsa and mssa strains by disk diffusion and pcr (meca detection). 4. discussion in the last few years mrsa have emerged as one of important medical pathogens. hence, their rapid and accurate detection is of vital importance to formulate strategic interventions such as effective treatment regimens and sound control measures to combat and hinder their spread. however, the present study demonstrated that encountered mrsa strains are less frequent than mssa while using standard disk diffusion and pcr procedures. this may be attributed to the more frequent mssa doi 10.18502/sjms.v13i4.3596 page 244 sudan journal of medical sciences najem aldin mohammed osman et al figure 2: detection of meca gene by pcr in 1.5% agarose gel electrophoresis. m: 100 bp molecular ladder; lane (1 & 13): positive control; lane 2: isolate 131; lane 3: isolate 174; lane 4: isolate 175; lane 5: isolate 176; lane 6: isolate 177; lane 7: isolate 178; lane 8: isolate 179; lane 9: isolate 180; lane 10: isolate 181; lane 11: 182; lane 12: negative control. (isolates 131, 175, 176, 177, 180, and 182 were meca gene positive (mrsa) with product size 532 bp, while isolates 174, 178, 179 and 181 were meca gene negative mssa.) t 1: distribution of isolated mrsa and mssa strains according to the site of infection. site of infection number (n) mrsa (%) mssa (%) surgical wound 63 40 (63.5) 23 (36.5) skin and soft tissues 44 15 (34.1) 29 (65.9) paronychia 27 10 (37.0) 17 (63.0) bone 18 8 (44.4) 10 (55.6) urinary tract 11 5 (45.5) 6 (54.5) ear 8 3 (37.5) 5 (62.5) ∗aspiration 7 0 7 (100) blood stream 7 5 (71.4) 2 (28.6%) throat 5 3 (60.0) 2 (40.0%) nasal cavity 5 0 5 (100) respiratory tract 2 0 2 (100) ∗∗others 13 7 (53.8) 6 (46.2) total 210 96 114 notes: ∗aspiration include: peritoneal (3), pleural (2), knee (2); **others include: tracheal swab (3), breast infection (2), umbilical swab (2), uterus swab (1), tissue biopsy (1), vaginal discharge (1), myositis (1), bacteremia (1) and semen (1). t 2: frequency of mrsa and mssa community (ca) and hospital (ha) strains. type of isolate ca–s. aureus (n = 143) has. aureus (n = 67) ∗p-value mrsa 53 (37.1%) 43 (64.2%) < 0.001 mssa 90 (62.9%) 24 (35.8%) — notes: *p-value calculated using chi-square test; ca = community associated; ha= hospital associated. strains rather than mrsa. similar results were reported by different previous studies as that of butt et al. (2004) and durmaz et al. (1997) [22, 23]. our finding showed that 16 isolates of the 130 mssa isolates were phenotypically susceptible when tested by doi 10.18502/sjms.v13i4.3596 page 245 sudan journal of medical sciences najem aldin mohammed osman et al t 3: antibiogram of some antibiotics used against mrsa isolates (total number 96 isolates). type of antibiotic susceptible isolates (%) resistant isolates (%) intermediate susceptible isolates (%) co-trimoxazole 77 (80.2%) 18 (18.8%) 1 (1%) ciprofloxacin 44 (45.9%) 23 (23.9%) 29 (30.2%) gentamicin 39 (40.6%) 49 (51.1%) 8 (8.3%) cefazolin 33 (34.4%) 50 (52.1%) 13 (13.5%) ∗amoxiclav 22 (22.9%) 74 (77.1%) – penicillin g 3 (3.1%) 93 (96.9%) – note: ∗amoxiclav = amoxicillin clavulanic acid. oxacillin disk diffusion, but when subjected to pcr they were found to be meca gene positive. the remaining 80 isolates were detected as mrsa by both disk diffusion and pcr. no one of the phenotypically resistant isolates was found to be negative by pcr. however, the molecular assays now considered as standard method for genes detection including meca gene and for discrimination of s. aureus from other species through multiplex pcr [24]. even the pcr technique is used now as gold standard technique to evaluate the other conventional methods as done by perez et al. [11]. moreover, ha-mrsa (64.2%) were detected in a higher rate than the ca-mrsa strains significantly (p-value < 0.001) which supported our general impression. this finding was in consistence with that of huang et al. (2006) who reported that mrsa strains were detected more frequently (55.1%) in hospital isolates [25]. on the other hand, the detected number of ca-mrsa strains may support the possibility that ca-mrs infections are in increase as observed in some other countries [19 26]. furthermore, in the present investigation, mrsa infections were found to be distributed in different anatomical positions (table 2). this may explain the increasing incidence of mrsa infections, which may be reflected by the increased duration of hospitalization and therefore increase in the overall treatment expenditure as stated by cosgrove et al. [27]. with regard to antibiotics-susceptibility profile of mrsa, co-trimoxazole was found to be the most effective one (80.2%), followed by vancomycin (47%), ciprofloxacin (45.8%), and gentamicin (40.6%). these results explain why the cotrimoxazole was considered as one of the drugs used to treat mrsa infections [28– 31]. for ciprofloxacin and gentamicin, the generated results are comparable to those reported in india where less than 30% were found to be resistant to ciprofloxacin, while about 40–50% were found to be resistant to gentamicin [32]. the susceptibility of mrsa isolates to β-lactam antibiotics was found to be 34.4%, 22.9%, and 3.1% for cefazolin, amoxicillin clavulanic acid, and penicillin, respectively. the high resistance doi 10.18502/sjms.v13i4.3596 page 246 sudan journal of medical sciences najem aldin mohammed osman et al may be due to the production of additional β-lactamase by mrsa strains rendering them to resist improved antibiotics such as cefazolin and amoxicillin clavulanic acid. schweizer et al. (2011) stated that cefazolin does not work in case of mrsa [33]. the current study had certain limitations. first, the study was done in only three major hospitals in the study area. second, some sites of infection which can be infected by s. aureus were not represented here. in conclusion, this study reported significant high frequency of mrsa in hospital isolates. moreover, these strains were mostly isolated from surgical wounds and blood stream. it is recommended that clinicians should be aware of the most active antibiotics against mrsa such as co-trimoxazole, vancomycin and ciprofloxacin. acknowledgement the authors would like to thank the staff of tropical medicine research institute, sudan. they would also like to acknowledge mr. esam bashab and ms. mona from alribat hospital and ms. hiba from khartoum hospital for their support in specimens collection. conflict of interest the authors have no competing interests. references [1] holmes, a., ganner, m., mcguane, s., et al. 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(june 04, 2013). prevalence and antibiotic susceptibility pattern of methicillin-resistant staphylococcus aureus (mrsa) among primary school children and prisoners in jimma town, southwest ethiopia. annals of clinical microbiology and antimicrobials, vol. 12, no. 11. [30] rayner c, munckhof wj. antibiotics currently used in the treatment of infections caused by staphylococcus aureus. internal medicine journal. 2005;35(s2):s3-s16. [31] brooks, g. f., butel, j. s., and morse, s. a. (1998). jawetz, melnick & adelberg‘s medical microbiology (twenty-first edition). london: appleton & lange. [32] pai, v., rao, v. i., and rao, s. p. (july 2010). prevalence and antimicrobial susceptibility pattern of methicillin-resistant staphylococcus aureus [mrsa] isolates at a tertiary care hospital in mangalore, south india. journal of laboratory physicians, vol. 2, no. 2, pp. 82–84. [33] schweizer, m. l., furuno, j. p., harris, a. d., et al. (2011). comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible staphylococcus aureus bacteremia. bmc infectious diseases, vol. 11, p. 279. doi 10.18502/sjms.v13i4.3596 page 250 introduction methods bacterial identification criteria for labeling isolates as community associated (ca) orhospital associated (ha) antibiotic susceptibility testing testing isolates for methicillin resistance molecular detection of meca gene dna extraction pcr amplification results oxacillin disk diffusion result pcr result distribution of mrsa according to the site of infection frequency of mrsa according to the source antibiotics sensitivity pattern of mrsa isolates discussion acknowledgement conflict of interest references sudan journal of medical sciences volume 13, issue no. 3, doi 10.18502/sjms.v13i3.2961 production and hosting by knowledge e research article the response, operability, and type of surgery following neoadjuvant chemotherapy in sudanese patients with locally advanced breast cancer abdelsamie abdalla mohamed, kamal eldein h. mohamed, eltaib a. saad, and shadad m. mahmoud department of surgery, faculty of medicine, university of khartoum abstract background: neoadjuvant chemotherapy (nact) treatment has become the standard treatment for locally advanced breast cancer (labc) in many centers worldwide. objectives: this study evaluates the short-term response of patients with labc to nact and its impact on operability and the type of surgery. patients and methods: this is a descriptive analytical hospital-based study including 147 patients with labc who were presented to plastic and reconstructive surgery unit at soba university hospital (suh), between january 2012 and december 2014, and were treated with nact. clinical and pathological responses to neoadjuvant chemotherapy were evaluated according to union for international cancer control criteria, operability, and the type of surgery performed was also recorded. results: all patients were females, the mean age was 43 ± 7 years, of them 53.7% were pre-menopausal, 51% presented with a breast lump, 19.7% with nipple discharge, and 19% with skin changes and ulceration. the mean initial tumor size was 7 cm ± sd. following nact, complete clinical response was reported in 30 patients (20.4%), partial clinical response in 92(62.6%), stable clinical response in 20 (13.6%), and five (3.4%) had progressive clinical response. initial smaller tumors (size < 5 cm) showed a better clinical response to nact as 76.7% of complete clinical response was achieved. pathological complete response was achieved in 25(17%) patients, pathological partial response in 102(74.1%), and pathological stable disease in 13(8.8%). following nact, breast conserving surgery was performed in 78(53.1%) patients, modified radical mastectomy in 64(43.5%), 25 of them had latissimus dorsi, and five patients were not offered surgery as they developed progressive disease during the study period. conclusion: following nact, it was possible to perform surgery in more than 96% of patients with labc. keywords: locally advanced breast cancer, neoadjuvant chemotherapy treatment, clinical response, pathological complete response, operability how to cite this article: abdelsamie abdalla mohamed, kamal eldein h. mohamed, eltaib a. saad, and shadad m. mahmoud (2018) “the response, operability, and type of surgery following neoadjuvant chemotherapy in sudanese patients with locally advanced breast cancer,” sudan journal of medical sciences, vol. 13, issue no. 3, pages 219–229. doi 10.18502/sjms.v13i3.2961 page 219 corresponding author: abdelsamie abdalla mohamed; email: abdelsamieabdalla@gmail.com received 15 august 2018 accepted 20 september 2018 published 19 september 2018 production and hosting by knowledge e abdelsamie abdalla mohamed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abdelsamieabdalla@gmail.com mailto:abdelsamieabdalla@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdelsamie abdalla mohamed et al 1. introduction neoadjuvant chemotherapy treatment (nact) is now the standard treatment for locally advanced breast cancer (labc) in several centers worldwide [1–3]. it reduces the size of the primary tumor, thus offering the option of breast-conserving surgery in patients who couldn’t have this advantage before [4]. by down-staging tumors, nact may likely improve available surgical options. numerous randomized clinical trials confirmed the equivalence of neoadjuvant and adjuvant chemotherapy in terms of disease-free and overall survival rates [5]. pathological complete response (pcr), which is defined as absence of residual and in-situ disease in the breast and the axillary nodes, has recently emerged as a powerful prognostic marker for overall and disease-free survival following nact [6, 7]. attaining a pcr after nact has been shown by several investigators to be a good marker for improved long-term outcome [8–10]. labc is not a usual presentation among females in the western world; however, in sudan, this stage is not only uncommon, but it also more prevalent among younger patients [11]. 2. objectives this work aimed to assess the short-term response of sudanese patients with labc to nact and its impact on operability and the types of the surgery performed. 3. patients and methods this is a descriptive analytical hospital-based study. a consecutive one hundred fortyseven (147) patients who were presented with labc to the plastic and reconstructive surgery unit at soba university hospital (suh) from january 2012 to december 2014 were reviewed. they were assessed initially at suh and then referred to radio-isotope center, khartoum (rick) for receiving nact. the study was approved by the scientific and research committee of soba university hospital (suh). labc is defined as stage iiia (t0-n2; t1/2-n2; t3-n1/2), stage iiib (t4, n0-2), and stage iiic disease (any t, n3). patient with early breast cancer (stage i/ii), metastatic breast cancer (stage iv) proven clinically and/or radiologically and those who haven’t had regular follow-up during the study period in both rick and suh were excluded from study. doi 10.18502/sjms.v13i3.2961 page 220 sudan journal of medical sciences abdelsamie abdalla mohamed et al according to the national protocol of neoadjuvant chemotherapy, the aim of the treatment was standardized. for patients with operable lesions and not suitable for breast conserving surgery (bcs), the chemotherapy was delivered until bcs could be performed. for patients with inoperable lesions, the chemotherapy was delivered until curative surgery could be achieved. the clinical response was assessed at the start, after each two cycles and at the end of the treatment to document and classify the response. assessment of the clinical response was based on union for international cancer control (uicc) criteria with definitions as follows: complete response (cr) = complete clinical resolution of tumor; partial response (pr) = 50% or greater diminution of bi-dimensional tumor; minimal response (mr) = 25% to 50% diminution of tumor; stable disease (sd) = no more than 25% increase or decrease in tumor size; progressive disease (pd) = more than 25% increase in tumor [12]. the pathological response was also assessed. complete pcr was defined as a complete disappearance of invasive breast cancer in the final histological specimen of the primary tumor. partial pathological response was defined as a reduction of more than 50% of the initial tumor size, whereas stable pathological disease was defined as a reduction of less than 50% of the initial tumor size, and progressive disease was defined as any increase in initial tumor size during cycles of chemotherapy [12]. data were processed and analyzed using the spss software package (version 21 windows). to determine the statistical significance of differences, the pearson test was used and probability test (p-value) with p <0.05 was considered as significant at 95% confidence interval. 4. results one hundred forty-seven (147) patients receiving neoadjuvant chemotherapy for labc were reviewed. all were females, the mean age of the patients at the time of diagnosis was 43 ± 7 years and 79 patients (53.7%) were pre-menopausal. more than half of the patients (51%) were presented with a breast lump, 29(19.7%) patients had nipple discharge as a chief complaint, whereas 28(19.0%) were presented initially with skin changes and ulcers and 15 patients (10.2%) were presented primarily with axillary changes and swelling. the mean tumor diameter measured clinically before neoadjuvant chemotherapy was 7 ± 3 cm (range 3–15 cm). tumor stage and nodal status were summarized in (tables 1 and 2, respectively). no association was found between age and tumor size (p = 0.11); however, a significant association was observed between doi 10.18502/sjms.v13i3.2961 page 221 sudan journal of medical sciences abdelsamie abdalla mohamed et al age and nodal status (p = 0.0002) with 53% of those aging more than 45 years having a late nodal stage (n2 and n3). regarding histopathological type of the tumors, 132 patients (88.2%) had invasive ductal carcinoma (idc) and only 15 patients had invasive lobular carcinoma. other less common histopathological variants were not reported in this series. estrogen receptors (er) showed positivity in 80 patients (54.4%) with 55(68.8%) of those with positive er being below 45 years of age, and progesterone receptors being positive in 78 patients (45%). based on clinical evaluation and echocardiographic findings, patients were classified into three groups. group a consisted of 52 patients who received 5-fluorouracil 500mg/m2 i.v, adiramycin (doxorubicin) 50mg/m2 i.v, and cyclophosphamide 500mg/m2 (fac) for six cycles on a 21-day period, followed by paclitoxel800 mg/m2 for 12 weeks; group b includes 47 patients who were treated with the 5-flurouracil 500mg/m2 i.v, epirubricin90mg/m2 i.v, and cyclophosamide 600mg/m2 (fec) for four cycles with three weeks off, and then they received paclitaxel 100mg/m2 for six weeks; group c were patients who received doxorubicin 600mg/m2 cyclophosamide 600mg/m2 i.v and taxanes (doxetaxel) 100mg/m2(tac) regimen and included patients with cardiac diseases based on echocardiography reports in whom other regimens were contraindicated. in addition, prednisolone, antiemetic, and antibiotics were given when they were clinically indicated. thirty (20.4%) patients achieved a clinical complete response (cr). complete clinical response (cr) was associated significantly with initial tumor sizes; 56.7% of cr was achieved in patients with tumor stages (t1 and t2 with tumor size < 5 cm). partial response was observed in 92 (62.6%) patients, while static response was achieved in 20 (13.6%) patients, and five (3.4%) patients had developed a progressive disease (table 3). clinical response was not found to be affected by the age and tumor histopathology type. complete pathological response (pcr) was achieved in 25 (17%) patients in whom no residual disease was seen in postoperative pathological specimens. a significant association was found between pcr and nodal disease and negativity of er (p < 0.001 in both) (table 4). the type of chemotherapy regimen used was neither found to affect clinical response nor pathological response (p-values were 0.196 and 0.087. respectively). following nact, bcs was performed in 78 patients (53.1%) who had sufficient reduction to allow bcs, while 64 (43.5%) patients had modified radical mastectomy, and in 25 patients (39.1%) latissimus dorsi flap (ld) was used to close the defect following mastectomy, myo-cutaneous flap in 16 patients and muscle flap in 9 patients. a curative surgery could not be achieved in five patients who had developed a doi 10.18502/sjms.v13i3.2961 page 222 sudan journal of medical sciences abdelsamie abdalla mohamed et al t 1: relation between age with initial tumor size (t stage) (n = 147). age (years) initial tumor size (t stage)* t1 t2 t3 t4 total < 35 1 4 16 5 26 35–45 0 10 21 21 52 > 45 2 13 41 13 69 total 3 27 78 39 147 note: *p = 0.11 (> 0.05). t 2: relation between age with nodal status (n stage) (n = 147). age (years) nodal status (n stage)* n0 n1 n2 n3 total < 35 0 13 6 7 26 35–45 7 6 32 7 52 > 45 3 29 28 9 69 total 10 48 66 23 147 note: *p = 0.0002 (< 0.05). t 3: association between clinical response and initial tumor size (t stage) (n = 147). clinical response complete partial stable progressive total initial tumor size (in cm)* t1 < 2 2 1 0 0 3 t2 2–5 15 10 2 0 17 t3 > 5 12 57 9 0 78 t4 (any size, skin/chest involvement) 1 24 9 5 39 total 30 92 20 5 147 note: *p < 0.001. t 4: association between pathological complete response (pcr) and nodal status and er status (n = 147). pathological response complete partial stable total nodal status* n0 7 3 0 10 n1 10 32 6 48 n2 5 58 3 66 n3 3 16 4 23 total 25 109 13 147 er status** positive 3 72 6 83 negative 22 37 7 64 total 25 109 13 147 note: *p < 0.001; **p < 0.001. doi 10.18502/sjms.v13i3.2961 page 223 sudan journal of medical sciences abdelsamie abdalla mohamed et al progressive disease during the course of neoadjuvant therapy. hormonal therapy was given to all patients with positive er receptors. 5. discussion nact permits breast conservation in some patients who would otherwise require mastectomy [12]. the median age of patients in this study was 43 years and 42% of the patients were premenopausal, which is comparable to other reports [13–15]. the average number of nact cycles ranged from four to six cycles depending on patient’s response. however, the literature reported considerable variations in numbers of cycles of chemotherapy that are usually given in neoadjuvant setting [16, 17]. three regimens of nact were employed in this study. however, both clinical and pathological responses were not found to be affected by the type of regimen used (p-values are 0.196 and 0.087, respectively); this is similar to many series [18, 19], in contradiction to others that showed a better response with taxanes-based regimens [20, 21]. complete pathological response (pcr) was achieved in 17%, which is in the range of other series [18, 22], although significant variations exist in pcr values in the literature ranging from 4% to 40% [23–25]. these variations could be attributable to the use of different chemotherapy regimens and or the ethnical and racial differences [26, 27]. age and family history were not associated with complete pathological response in this series, which is in line with what was reported in the previous studies [28–30]. on the other hand, the authors found an association between the nodal stage and pcr (p < 0.001) as the late nodal disease (n2, n3) was associated with poor pathological response, a finding which is similar to what was found by many other workers [30, 31]. complete clinical response (cr) was achieved in 20.4% of the patients; it was significantly associated with initial tumor size (t stage) as 56.7% of complete clinical response was observed among patients with an initial tumor size of less than 5 cm (t1 and t2) (p = 0.001). these findings are in agreement with previous reports that proved better clinical responses with smaller tumors [27, 29]. clinical response was not found to be affected by the age and tumor histopathology type which is comparable to the previous series [29, 30]. estrogen receptor (er) status was associated with a better pcr, as 65% of patients with pcr had a negative er (p < 0.001) in keeping with previous reports [31, 32]; however, this finding disagrees with other reports that found a better pcr with erpositive tumors [13]. nevertheless, there is an evidence to suggest that er-negative doi 10.18502/sjms.v13i3.2961 page 224 sudan journal of medical sciences abdelsamie abdalla mohamed et al tumors are more likely to achieve better pcr, following nact in comparison to erpositive ones, as an inverse relationship exists between er expression and tumor proliferation; with er-positive cancers showing a low proliferation rate, whereas ernegative breast cancers having a high proliferation rate, which is correlated with a better short-term response to nact [29, 30]. seventy-eight (53.1%) patients had achieved a sufficient clinical down-staging to allow bcs; these results are quite comparable with other international reports [33– 35], but higher than that reported previously in one study from sudan (33.3%) [13]. in fact, the literature has reported different rates of bcs after nact ranging from 16% to 80% [15]. these variations could be attributable to the differences in the types of chemotherapy regimens used, the studied population, and the study designs [36]. nevertheless, there are certain factors that predict eligibility of a conserving surgery after nact, with the tumor size being the most important one [37]. it is interesting to note that some workers have designed validated nomograms to predict the probability of residual tumor size and eligibility for a conserving surgery after nact; 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(2006). development and validation of nomograms for predicting residual tumor size and the probability of successful conservative surgery with neoadjuvant chemotherapy for breast cancer. cancer, vol. 107, pp. 1459–1466. doi 10.18502/sjms.v13i3.2961 page 229 introduction objectives patients and methods results discussion conclusion conflict of interest funding references sudan journal of medical sciences volume 13, issue no. 4, doi 10.18502/sjms.v13i4.3641 production and hosting by knowledge e research article prognostic roles of c-reactive protein and erythrocyte sedimentation rate as acute phase reactants in mentally challenged subjects adedeji david atere1,3, bashiru s. a. oseni2, ifelola patience adebua3, joshua seun fapohunda1, and idomeh festus aigbokheo4 1department of medical laboratory science, university of benin, benin city, edo state, nigeria 2department of biomedical sciences, ladoke akintola university of technology, osogbo, osun state 3department of medical laboratory science, achievers university, owo, ondo state, nigeria 4university of benin teaching hospital, benin city, edo state, nigeria abstract background: a mental disorder is a psychiatric disease that presents as mild or severe disturbances in a person’s behavior, mood, or thought. mental illnesses are very common because of excessive stress. recent studies show that mental illnesses are on the rise generally because of increasing stress. in nigeria, medical records suggest an upsurge in mental health cases since the onset of the country’s economic downturn and the consequent trauma following it. the erythrocyte sedimentation rate (esr) is an indirect marker of serum acute-phase protein concentrations, whereas c-reactive protein (crp) is a direct protein measurement and it is inherently more well-defined. this study thus evaluated the roles of esr and crp as sensitive markers of inflammation and correlated their levels with severity stratification and prognosis in schizophrenic patients. materials and methods: this is a case-control study, and it was carried out on 40 patients diagnosed with schizophrenia. thirty (30) controls were matched for age and sex; 8 millimeters of venous blood was collected from each participant using ante-cubital veins. samples collected were dispensed into appropriate bottles for analysis of crp and hematological parameters using standard laboratory procedures. statistical analysis of the data was done appropriately and p-value of less than 0.05 was considered as significant. results: at the end of the study, the mean granulocytes, esr, and crp were significantly higher in schizophrenia cases than in the controls, while the mean pcv, rbc, and hemoglobin were significantly lower in the subjects. crp had a higher area than esr under the roc curve (auroc). conclusion: this study thus evaluated the role of esr and crp as sensitive markers of inflammation and acute phase reactants in schizophrenic patients. the findings showed that crp was a better diagnostic or predictor treatment outcome of schizophrenia. how to cite this article: adedeji david atere, bashiru s. a. oseni, ifelola patience adebua, joshua seun fapohunda, and idomeh festus aigbokheo (2018) “prognostic roles of c-reactive protein and erythrocyte sedimentation rate as acute phase reactants in mentally challenged subjects,” sudan journal of medical sciences, vol. 13, issue no. 4, pages 311–323. doi 10.18502/sjms.v13i4.3641 page 311 corresponding author: adedeji david atere; email: ateread@gmail.com received 12 november 2018 accepted 17 december 2018 published 26 december 2018 production and hosting by knowledge e adedeji david atere et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v13i4.3641&domain=pdf&date_stamp=2018-12-26 mailto:ateread@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences adedeji david atere et al keywords: schizophrenia, acute phase reactants, c-reactive protein, erythrocyte sedimentation rate, inflammation 1. introduction schizophrenia is a mental disorder that is characterized by a breakdown of thought processes and by poor emotional responsiveness, with mild or severe disturbances in a person’s behavior, mood, or thought [1]. even though schizophrenia has long been described as a disease of ‘unknown etiology’ [2], it had been documented to be associated with multiple genetic and environmental risk factors, including drug and alcohol abuse, prenatal infections, and malnutrition [1, 3]. generally, a mental disorder appears in late adolescence or early adulthood. however, it can emerge at any time in life. its common features include auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, accompanied by significant social or occupational dysfunction [1, 4]. most people feel that mental disorders are rare and would not happen to them or the members of their family. this is largely incorrect! mental illnesses are very common. about 30% of nigerians suffer from or are liable to different mental disorders, but the majority of them are undiagnosed [5]. nigeria with a population of nearly 170 million has about 1.7 million people suffering from schizophrenia [6]. this figure reached before 2014 has risen to a new level following the economic slump and the accompanying stress the country has suffered since 2016 which can lead to a state of depression. depression is a state of low mood and aversion to activity that affects thoughts, behavior, and physical well-being [7]. it remains a health issue of public importance. it affects about 121 million people and is recognized as the leading cause of disability worldwide [8]. absolute poverty, limited public health services, civil unrest, gender inequality, and multiple medical problems are some of the identified causes of depression [9]. despite decades of intensive research, diagnosis, and identification of patients with severe form of depression, it still remains a challenge due to the lack of routinely effective laboratory tests. this is further compounded by the unfavorable prognosis of depression as relapse/recurrence rate could be as high as 87% over 15 years with at least 40% not responding to initial treatment [10]. the search for serumbased biological marker for the diagnosis of depression or schizophrenia has been on since 1960 when urinary excretion of metabolites of catecholamines, particularly doi 10.18502/sjms.v13i4.3641 page 312 sudan journal of medical sciences adedeji david atere et al norepinephrine, was used to classify major mood disorders [11]. laboratory investigations have linked mental problems with excessive stress. high cortisol levels reflect a higher degree of stress, but are dependent on the integrity of the hpa-axis [12]. also, elevated plasma levels of arginine vasopressin (avp) which is another stress hormone produced through hpa axis activity has been reported in schizophrenic patients [13]. copeptin is a sensitive and stable surrogate marker for avp release. it reflects the individual stress level that plays a major role in depression and schizophrenia [5, 14]. acute phase proteins (app) are blood proteins primarily synthesized by hepatocytes as part of the acute phase response (apr). the apr is a part of the early defense or innate immune system, which is triggered by different stimuli including trauma, infection, stress, neoplasia, and inflammation. the apr results in a complex systemic reaction with the goal of re-establishing homeostasis and promoting healing [15]. crp has been inherently well-defined as a direct marker of acute protein measurement, while erythrocyte sedimentation rate (esr) is an indirect biomarker of serum acutephase protein concentrations. crp is an acute phase reactant. it is a protein made by the liver and released into the bloodstream within 24–48 hours after tissue injury, at the start of an infection, or any inflammatory condition [16]. the level of crp can rise a thousand-fold in response to an inflammatory condition, and its rise in the blood can precede pain, stress, or other clinical indicators [17]. crp is not diagnostic of any condition, but it can be used together with symptoms and other tests to evaluate an individual for an acute or chronic inflammatory condition [18, 19]. crp is a ‘marker’ for systemic inflammation [20], and thus would be useful as a prognostic marker in management of schizophrenic subjects. esr is a laboratory test that measures erythrocytes distance in a vertical tube (in millimeters) under the influence of gravity force in one hour. it is a simple and an inexpensive test for an indirect measurement of serum acute-phase protein concentrations that responds slowly to inflammatory stimuli. the esr depends on the aggregation of red blood cells (rbcs) and rouleaux formation [21]. as a patient’s condition worsens or improves, the esr responds slowly, because fibrinogen, the major contributor to the short-term increase in esr, has a halflife of days (depending on other hemostatic factors), and immunoglobulins (strongly contributing to the elevation of esr in chronic inflammatory states) have half-lives of weeks under normal physiologic states. this process can result in a significant lag between clinical changes and esr values [21]. this study will thus evaluate the roles of esr and crp as both sensitive markers of inflammation and correlate their levels with severity stratification and prognosis in mentally challenged patients. doi 10.18502/sjms.v13i4.3641 page 313 sudan journal of medical sciences adedeji david atere et al 2. materials and methods 2.1. study design this is a case control study. 2.2. subjects the ethical approval with registration number erc/2018/04/04/116b from the federal teaching hospital, ido-ekiti (fthi) ethics and research committee was duly obtained for this study and also the informed consent or otherwise assent was taken from each participant or relative, respectively. thereafter, forty (40) schizophrenic subjects and thirty (30) ageand sex-matched controls were randomly recruited into the study. all the participants were between the ages of 18 and 70 years. the schizophrenic patients were recruited from the psychiatry clinic of the fthi, while the control group comprised the members of the staff of the hospital who had no symptoms of schizophrenia. the schizophrenia group was diagnosed according to the diagnostic and statistical manual of mental disorders, fourth edition, text revision (dsm-4tr) by clinically trained and experienced psychiatrists. a trained psychiatrist administered the positive and negative syndrome scale (panss) and recorded scores appropriately. panss is a medical scale used for measuring symptom severity of patients with schizophrenia [22]. 2.3. inclusion criteria (cases and controls) the criteria for the inclusion of cases were participants that gave informed consent, satisfied panss for the diagnosis of schizophrenia, subjects whose positive and negative scales were ≤ 7 x ≥ 49 (schizophrenia) and aged 18 to 70 years. the criteria for the inclusion of controls were participants aged 18 to 70 years and whose panss scale score was less than 7 (schizophrenia). 2.4. exclusion criteria (cases and controls) the criteria for the exclusion of cases and controls were geriatric subjects (> 70 years) and subjects less than 18 years, subjects with concurrent use of non-steroidal antiinflammatory agents, steroids, antidepressants, antipsychotic medications, and anticonvulsants 3 weeks before presentation, subjects with previous history of mania or doi 10.18502/sjms.v13i4.3641 page 314 sudan journal of medical sciences adedeji david atere et al hypomania, or any concurrent psychotic symptoms, subjects with pregnancy, presence of serious and/or unstable medical disorders, previous history of addison’s disease, cushing’s disease or thyroid diseases or diabetic and hypertensive subjects. 2.5. collection/sampling technique and storage of sample eight milliliters (8 ml) of venous blood was collected from each subject using aseptic procedure. two (2 ml) of venous blood was dispensed into a sterile esr bottle containing 3.2% tri-sodium citrate solution in a ratio of blood-citrate, 5:1 (v/v) as an anticoagulant and gently mixed by inverting the container several times for the determination of esr; 3 ml of the samples collected was dispensed into plain bottles and allowed to retract. each sample was spun at 4000 rpm for 5 minutes to obtain serum that was stored at –20c until analysis. similarly, three milliliters (3 ml) of venous blood left over was dispensed into ethylene diamine acetate bottle for hematological parameters analysis. 2.6. analytical methods and procedures the serum level of crp was determined using enzyme immunosorbent assay (elisa) as described by johnson et al. [23], and standard methods were employed to determine esr and full blood count (fbc), using westergren method and hematological analyzer, respectively. 2.7. statistical analysis a statistical package for social scientist (spss) 23.0 version was used for the appropriate analysis of the data. the distribution of the variables was assessed using histogram with standard curve. variables with gaussian distribution were compared between groups using student’s t-test. however, to adjust for confounding factors, analysis of variance (anova) was used to compare differences between the schizophrenic groups based on the year of diagnosis. a graphical plot of sensitivity (receiver operating curve; roc) was done and an area under roc (auroc) of each marker (crp and esr) was compared using pair-wise comparison. spearman correlation was used to test the association between inflammatory markers (crp and esr) and other variables in exposed groups. p-values less than 0.05 was considered significant. doi 10.18502/sjms.v13i4.3641 page 315 sudan journal of medical sciences adedeji david atere et al 3. results a total number of 70 subjects were studied. they comprised 40 schizophrenic subjects with mean age of 40.65 ± 12.32 years and 30 controls with mean age of 38.33 ± 11.93 years. figure 1 shows the age and sex distribution of the recruited population in percentage (%). there were 16 females and 24 males in the schizophrenic group, and 13 females and 17 males in the non-schizophrenic groups. thus, females constituted 41.42%, while males constituted 58.58% overall. comparing the mean hematological parameters and crp in schizophrenic subjects and controls using independent student t-test, the mean gra, esr, and crp were significantly higher among schizophrenia, while the mean pcv, rbc, and hbg were significantly lower (table 1). the schizophrenic subjects were further classified into five groups based on the years of diagnosis. it was observed, as shown in table 2, that there were no significant differences in the mean of hematological indices and crp within the three groups, using one way analysis of variance (anova). table 3 shows spearman correlation between hematological parameters with esr and crp schizophrenic subjects. crp showed positive correlation with gra and negative correlation with lymp, while esr only had inverse correlation with pcv, rbc, and hgb. the diagnostic performance of esr and crp were determined. crp had higher area under the roc curve (auroc) than esr as shown in figure 2. figure 1: age and sex distribution of the recruited population in percentage (%). 4. discussion and conclusion doi 10.18502/sjms.v13i4.3641 page 316 sudan journal of medical sciences adedeji david atere et al t 1: comparison of mean age, hematological parameters, and crp among schizophrenic and nonschizophrenic subjects. parameters schizophrenic subjects (n = 40) non-schizophrenic subjects (n = 30) p-value rmk age (years) 40.65 ± 12.32 38.33 ± 11.93 0.433 ns pcv(%) 38.34 ± 4.09 40.89 ± 2.85 0.005 s rbc (x 1012/l) 4.38 ± 0.50 4.76 ± 0.49 0.003 s hbg (g/dl) 12.83 ± 1.38 13.49 ± 1.17 0.040 s mcv (fl) 88.28 ± 6.00 85.80 ± 4.87 0.069 ns mch (pg) 29.18 ± 2.75 28.46 ± 2.20 0.243 ns mchc (g/dl) 32.93 ± 1.21 33.00 ± 0.98 0.792 ns twbc (x 109/l) 6.30 ± 1.91 6.07 ± 1.57 0.591 ns lymp (%) 40.37 ± 10.22 44.05 ± 10.13 0.139 ns gra (%) 48.32 ± 9.53 43.91 ± 8.22 0.046 s plt (x 109/l) 178.53 ± 59.06 205.30 ± 61.45 0.069 ns esr (mm/hr) 37.73 ± 23.33 12.20 ± 9.06 0.000 s crp (µg/ml) 1.27 ± 0.32 1.07 ± 0.12 0.002 s note: *significant at p ≤ 0.05. pcv = packed cell volume; rbc = red blood cell; hgb = hemoglobin concentration; mcv = mean cell volume; mch = mean cell haemoglobin; mchc = mean cell hemoglobin concentration; twbc = total white blood cell; lymp = lymphocyte; gra = granulocytes; plt = platelets; esr = erythrocytes sedimentation rate; crp = c-reactive protein; rmk = remark; s = significant; and ns = not significant. t 2: comparison of mean hematological indices and crp based on years of diagnosis among the schizophrenic subjects. years of diagnosis parameters 0–5 (n = 20) 6–10 (n = 7) 11–15 (n = 4) 16–20 (n = 6) > 20 (n = 3) p-value age (years) 38.75 ± 12.20 38.71 ± 14.44 39.25 ± 14.32 47.17 ± 3.66 46.67 ± 18.61 0.562 pcv (%) 38.58 ± 4.47 37.40 ± 4.45 37.28 ± 2.94 39.57 ± 2.58 37.90 ± 6.00 0.877 rbc (x 1012/l) 4.42 ± 0.56 4.30 ± 0.54 4.31 ± 0.29 4.36 ± 0.45 4.48 ± 0.64 0.978 hbg (g/dl) 13.00 ± 1.54 12.34 ± 1.71 12.58 ± 0.95 13.12 ± 0.99 12.63 ± 0.74 0.824 mcv (fl) 88.90 ± 5.85 86.71 ± 9.09 86.25 ± 4.57 90.17 ± 4.07 86.67 ± 4.73 0.763 mch (pg) 29.68 ± 2.61 28.64 ± 3.93 28.20 ± 2.11 29.63 ± 1.55 27.50 ± 3.55 0.625 mchc (g/dl) 33.19 ± 1.16 32.90 ± 1.28 32.83 ± 0.97 32.73 ± 0.84 31.77 ± 2.21 0.443 twbc (x 109/l) 6.24 ± 1.78 6.71 ± 2.47 5.71 ± 1.42 6.55 ± 2.35 5.96 ± 2.06 0.929 lymp (%) 39.50 ± 10.96 42.71 ± 9.87 33.93 ± 10.13 45.38 ± 6.59 39.23 ± 12.41 0.483 gra (%) 48.19 ± 10.78 47.10 ± 8.56 54.33 ± 6.06 44.70 ± 6.41 51.20 ± 12.65 0.604 plt (x 109/l) 181.45 ± 65.17 176.00 ± 63.70 182.50 ± 80.69 175.50 ± 46.12 165.67 ± 2.52 0.994 esr (mm/hr) 32.50 ± 22.96 41.86 ± 24.51 34.50 ± 23.24 42.00 ± 22.76 58.67 ± 23.69 0.432 crp (µg/ml) 1.33 ± 0.31 1.25 ± 0.44 1.19 ± 0.19 1.18 ± 0.23 1.17 ± 0.32 0.865 note: *significant at p ≤ 0.05. doi 10.18502/sjms.v13i4.3641 page 317 sudan journal of medical sciences adedeji david atere et al t 3: correlation between inflammatory markers, weight, body mass index, fasting blood sugar, and oxidative stress parameters in exposed groups. esr r-value p-value crp r-value p-value age (years) 0.071 0.662 –0.186 0.249 pcv (%) –0.566 0.000* –0.032 0.845 rbc (x 1012/l) –0.578 0.000* 0.049 0.766 hbg (g/dl) –0.523 0.001* 0.043 0.793 mcv (fl) 0.171 0.292 –0.072 0.660 mch (pg) 0.064 0.696 –0.029 0.857 mchc (g/dl) –0.126 0.437 0.138 0.396 twbc (x 109/l) 0.234 0.146 –0.184 0.256 lymp (%) –0.049 0.766 –0.264 0.027* gra (%) 0.171 0.292 0.262 0.029* plt (x 109/l) –0.046 0.778 –0.044 0.790 esr (mm/hr) 1.000 –0.213 0.186 note: *correlation is significant at the 0.05 level (2-tailed). figure 2: the roc curve of blood levels of crp and esr schizophrenic subjects. doi 10.18502/sjms.v13i4.3641 page 318 sudan journal of medical sciences adedeji david atere et al 4.1. discussion figure 1 shows the age and sex distribution of the recruited population in percentage (%). a total number of seventy (70) subjects consisted of forty (40) schizophrenic subjects with mean age of 40.65 ± 12.32 years and thirty (30) control groups with mean age of 38.33 ± 11.93 years were studied. the subjects constituted of 41.42% and 58.58% females and males, respectively, overall; 31.42% of schizophrenic subjects in this study were youths within the age bracket of 18–40 years. the major cause of mental challenge in nigeria is traceable to either drug abuse, abject poverty, or any daily activities that could lead to depression [6]. despite decades of intensive research, diagnosis, and identification of patients with severe form of mental disorders, it remains a challenge due to the lack of routinely useful laboratory test. there remains an urgent need to identify biomarkers that can determine the severity, aid in diagnosis, and probably predict the outcome of the treatment of these disorders. the data in this study showed that the mean levels of granulocytes (gra), esr and c-reactive protein (crp) were significantly higher in schizophrenic group in comparison with non-schizophrenic groups, while the mean pcv, rbc, and hbg were significantly lower among schizophrenic group. crp is an acute phase reactant, produced by some inflammatory stimuli in the liver. it is mainly induced by interleukin 6 (il-6), which is pro-inflammatory cytokines released into the bloodstream [16, 24]. crp is a ‘marker’ for systemic inflammation [20], and thus would be useful as a prognostic marker in the management of schizophrenic subjects. increase in the mean levels of crp in schizophrenia cases observed in this work is consistent with recent work where elevated levels of some inflammatory biomarkers, such as tnf-α, was reported in schizophrenic patients [25, 26]. in the same vein, increase in mean levels of esr observed among schizophrenia cases in comparison with control group confirms esr roles as indirect marker of app even though its response to inflammatory stimuli might be slow [27]. as a patient’s condition worsens or improves, the esr responds slowly, and thus elevated esr has been reported to strongly contribute to chronic inflammatory states of the condition [21]. melamed and sirota [28] revealed that esr increased in 17% of the patients with acute psychosis, which decreased to normal values after eight weeks of antipsychotic treatment in two-thirds of those patients, with the reduction of psychopathological manifestations. here, using esr with other markers, having a high esr without a known physical illness might possibly serve as a biological indication of the remission and relapse of the disease. doi 10.18502/sjms.v13i4.3641 page 319 sudan journal of medical sciences adedeji david atere et al results showed that crp had a positive correlation with gra, and esr had a negative correlation with packed cell volume (pcv), red blood cells (rbc), and hemoglobin (hgb). immune system dysfunctions and inflammatory processes show a link with the pathogenesis of schizophrenia as reported by richard and brahm [29]. granulocytes are leukocytes of the innate immune system that have granules in their cytoplasm and they are neutrophil, basophil, and eosinophil. we could speculate that positive correlation between crp and granulocytes are up-regulated as a compensatory mechanism to cope with the condition or response to treatment. this confirms the roles of crp and granulocytes as acute protein reactant and immune system functions, respectively, in the management of mentally challenged subjects. on the contrary, esr had negative correlation with pcv, rbc, and hemoglobin (hgb), and this corroborated the dependence of esr on the aggregation of rbcs and rouleaux formation as documented by calderon and wener [21]. the diagnostic performance of esr and crp was determined using area under the roc curve (auroc). crp had higher area under the roc curve (auroc) than esr as shown in figure 2. even though esr and crp are both sensitive markers of inflammation and correlate with severity of inflammation, they are not specific to any particular illness [21]. the high levels of crp in central nervous system have been reported to play an important role in some psychiatric dysfunctions, such as schizophrenia [30]. similarly, wang et al. [24] also reported that sensitivity analysis showed that serum and plasma crp levels were increased moderately in studies involving only highsensitivity crp assay. however, our finding, when we determined the diagnostic and prognostic performance of crp and esr using auroc, showed that crp, compared with esr, had better performance. thus, this finding is certainly of clinical importance since the measurement of crp is widely available and affordable. using crp with symptoms and other laboratory tests to predict or monitor the treatment of schizophrenia would certainly improve the treatment condition of schizophrenic patients. 4.2. conclusion and recommendation this study thus evaluated the roles of esr and crp as sensitive markers of inflammation and acute phase reactants in schizophrenic patients. also, crp was found to be a better diagnostic or predictor treatment outcome of schizophrenia. this would definitely improve the treatment of psychiatric patients as well as prevent relapse and recurrence in the long term. doi 10.18502/sjms.v13i4.3641 page 320 sudan journal of medical sciences adedeji david atere et al acknowledgments the authors would like to thank all the participants, resident doctors, and staff of the department of psychiatry clinic, the federal teaching hospital, ido-ekiti (fthi) for their support. funding the research was self-sponsored. conflict of interest the authors declare that this manuscript was approved by all authors in its form and has no competing interests. references [1] gonzalez-liencres, c., tas, c., brown, e. c., et al. 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(2012). erythrocyte sedimentation rate and creactive protein. hospital medicine clinics, vol. 1, pp. 313–337. doi 10.18502/sjms.v13i4.3641 page 322 sudan journal of medical sciences adedeji david atere et al [22] stefanović, v., mihajlović, g., nenadović, m., et al. (2015). the effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia. vojnosanitetski pregled, vol. 72, no. 12, pp. 1085–1092. doi: 10.2298/vsp140526016s. [23] johnson, h. l., chiou, c. c., and cho, c. t. (1999). applications of acute phase reactants in infectious diseases. journal of microbiology, immunology and infection, vol. 32, no. 2, pp. 73–82. [24] wang, z., li, p., chi, d., et al. (2017). association between c-reactive protein and risk of schizophrenia: an updated meta-analysis. oncotarget, vol. 8, no. 43, pp. 75445– 75454. [25] miller, b. j., buckley, p., seabolt, w., et al. (2011). meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic eects. biological psychiatry, vol. 70, pp. 663–671. [26] boll, k. m., noto, c., bonifácio, b. l., et al. (2017). oxidative and nitrosative stress biomarkers in chronic schizophrenia. psychiatry research, vol. 253, pp. 43–48. [27] pavlovic, m., babic, d., rastovic, p., et al. (2013). association of erythrocyte sedimentation rate and fibrinogen concentration with metabolic syndrome in a schizophrenic patients. psychiatria danubina, vol. 25, no. 1, pp. 51–55. [28] melamed, y. and sirota, p. (2000). erythrocyte sedimentation rate in patients with schizophrenia. the canadian journal of psychiatry, vol. 45, no. 10, p. 938. [29] richard, m. d. and brahm, n. c. (2012). schizophrenia and the immune system: pathophysiology, prevention, and treatment. american journal of health-system pharmacy, vol. 69, pp. 757–766. [30] najjar, s., pearlman, d. m., devinsky, o., et al. (2013). neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence. journal of neuroinflammation, vol. 10, p. 142. doi 10.18502/sjms.v13i4.3641 page 323 introduction materials and methods study design subjects inclusion criteria (cases and controls) exclusion criteria (cases and controls) collection/sampling technique and storage of sample analytical methods and procedures statistical analysis results discussion and conclusion discussion conclusion and recommendation acknowledgments funding conflict of interest references sudan journal of medical sciences volume 13, issue no. 4, doi 10.18502/sjms.v13i4.3599 production and hosting by knowledge e research article evaluation of antimicrobial activity of a sudanese herbal plant (piliostigma reticulatum) shamsoun khamis kafi1, fatima mekki abdalla2, and mohamedelfateh salaheldin eljack3 1department of microbiology, faculty of medical laboratory science, the national ribat university 2department of microbiology, national ribat teaching hospital 3medical parasitology department, faculty of medical laboratory science, national ribat university abstract background: piliostigma reticulatum is a plant that is found in a wide area of sahelosudanian region of africa. it is widely used in africa as a traditional medicine for the treatment of a wide range of diseases including epilepsy, anxiety, and agitation. the leaf extract was found to have antimicrobial activity. in sudan (nuba mountains in particular), it is widely used to dress new wounds and as well puerperal sepsis. moreover it’s fruit is eaten and used to prepare juice. reported studies concerning antimicrobial activity of the plant in sudan could not be found. this study therefore aimed to evaluate the antimicrobial action of ethanolic and aqueous extract of leaves and barks of the plant. methods: barks and leaves of p. reticulatum were obtained from north kordofan state. they were then air dried in the shade and milled into powder using mortar. methanolic and water extract of each part of the plant was prepared using a soxhlet apparatus. the following concentrations of extracts of each part (bark and leaves) of the plant were prepared using distilled water (50 mg/ml, 25 mg/ml, 12.5 mg/ml, 6.25 mg/ml, 3.125 mg/ml, and 1.56 mg/ml). antimicrobial action of the different concentrations of the extracts of the two parts of the plant on selected bacterial and fungal species was performed using well diffusion technique. antimicrobial susceptibility of the tested organisms to serial concentrations (40 µg, 20 µg, 10 µg, and 5 µg) of three antibacterial (gentamicin, ampicillin, and tetracycline) and 2 antifungal (nystatin and clotrimazole) was evaluated using well diffusion method. results: the methanolic extract of p. reticulatum leaves showed high antibacterial activity against bacillus subtilis (inhibition zone 22 mm), s. aureus (25 mm), p. aeruginosa (23 mm), and e.coli (20 mm). the extract also showed antifungal activity against a. niger (23 mm) and c. albicans (23 mm). the aqueous extract revealed low activity against p. aeruginosa (10 mm) and no action on the rest of the microorganisms. how to cite this article: shamsoun khamis kafi, fatima mekki abdalla, and mohamedelfateh salaheldin eljack (2018) “evaluation of antimicrobial activity of a sudanese herbal plant (piliostigma reticulatum),” sudan journal of medical sciences, vol. 13, issue no. 4, pages 264–276. doi 10.18502/sjms.v13i4.3599 page 264 corresponding author: mohamedelfateh salaheldin eljack; email: m.elfatehsalah@gmail.com received 15 september 2018 accepted 9 december 2018 published 26 december 2018 production and hosting by knowledge e s. k. kafi et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://crossmark.crossref.org/dialog/?doi=10.18502/sjms.v13i4.3599&domain=pdf&date_stamp=2018-12-26 mailto:m.elfatehsalah@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences s. k. kafi et al conclusion: in this study, the methanolic extract of the leaves inhibited the growth of all the tested bacteria and fungi but with varied activity (inhibition zones between 8 mm and 20 mm). the highest activity was against b. subtilis (inhibition zone 20 mm), followed by a. niger and c. albicans (19 mm each), then p. aeruginosa (18 mm). methanolic extract of the leaves revealed moderate activity against e. coli(13 mm) and low activity against s. aureus (8 mm). keywords: 1. introduction piliostigma reticulatum is a plant that occurs in the sahelo-sudanian region of africa from senegal, mauritania to sudan and has been introduced to mozambique (fibres, 1846). the plant is a dioeciously shrub or small tree up to 10–15 meters tall, bole short, rarely straight, up to 30 cm in diameter. the outer bark is deeply fissured, cracked grey to brown, and the inner bark pink to red crown rounded and dense. the branches are grey, waxy, and glabrous. the leaves alternate conspicuously bilobed, petiole 1–3.5 cm long, swollen at both ends, blade 5–12 cm x 4–18 cm, chordate or rounded at base, lobes rounded more or less cuneate (figure 1). the flowers are unisexual, 2.5 cm in diameter, calyx 5 toothed, 15–20 cm long, petals 5 obovate, white with pink stripes, male flowers with 10 stamens, anthers brown (figure 2). fruit an oblong pod 15–30 cm x 2.5–5 cm, straight undulate woody, hard, glabrous, or sparsely pubescent, brown flat, pruinose, sometimes twisted and cracked, indehiscent and persisting, many seeded [1]. the plant is used widely in africa as a traditional medicine for the treatment of many diseases, such as malaria, tuberculosis, and diarrhea [2]. piliostigma reticulatum is used in traditional medicine in cameron to treat epilepsy, anxiety, and agitation. in fact the results of a study done in cameron suggested that it possesses anxiolytic and antipyretic properties in mice and could really be helpful in the treatment of anxiety [3]. the leaf extract from the plant was found to exhibit anti-microbial activity against some bacteria and fungi such as staphylococcus aureus (nctc 6571, escherichia coli (nctc 10418), bacillus subtilis (nctc 8236), proteus vulgaris (nctc 4175), aspergillus niger (atcc 10578), and candida albicans (nctc 10231) [4]. vibriocidal action of p. reticulatum doi 10.18502/sjms.v13i4.3599 page 265 sudan journal of medical sciences s. k. kafi et al among other medicinal plants was studied and proved to be effective in killing vibrio spp. [5]. in nuba mountains in sudan, the plant is widely used. the young leaves with their acidic taste are eaten. the fruits after maturation and drying is also eaten for its sweet taste and nowadays used for preparation of juice. the fresh bark of the plant is used for fresh wound dressing as it coagulates blood and is believed to enhance healing of the wound by keeping it clean. in the old days before the introduction of primary healthcare and midwifery facilities, the inner soft bark of p. reticulatum was widely used after delivery to cover the episiotomy wound (based on personal observation, one of the authors being part of the nuba community). this study was conducted to evaluate the antimicrobial activity of p. reticulatum on selected bacterial and fungal spp. figure 1: fruits and leaves of p. reticulatum. doi 10.18502/sjms.v13i4.3599 page 266 sudan journal of medical sciences s. k. kafi et al figure 2: leaves and flowers of p. reticulatum. 2. materials and methods 2.1. preparation of the different plant’s parts barks and leaves of p. reticulatum were obtained from north kordofan state. the bark and leaves of the plant were dried in the shade and then milled using mortar and pestle to prepare a powder. 2.2. preparation of the extracts eighty five grams of the air-dried and coarsely powdered material of each plant part was exhaustively extracted for 20 hours with methanol (40–60ºc) in a soxhlet apparatus. the methanolic extract was filtered and evaporated under reduced pressure again using rota-vapor. each residue was weighed and the yielded percentage was determined. the methanol residue was redissolved or suspended in methanol. the final volume was adjusted to give the specific concentration (100 mg/ml) and kept in a refrigerator until used. aqueous extract of each dried, ground plant part (10 g) was prepared by infusion using boiled distilled water. it was allowed to soak in a beaker on water bath with occasional shaking for four hours. the residue was then dried and weighed and the yield percent was obtained. the final volume of the residue was adjusted to 10 ml sterile distilled water, and used immediately. doi 10.18502/sjms.v13i4.3599 page 267 sudan journal of medical sciences s. k. kafi et al 2.3. preparation of the standard test organisms the standard organisms were obtained from the department of microbiology and parasitology, medicinal and aromatic plant research institute, khartoum and inoculated into broth that was then incubated at 37ºc aerobically for 24 hours. 2.4. preparation of the standard bacterial suspensions one ml aliquots of a 24-hours broth culture of the test organisms were aseptically distributed onto nutrient agar slopes and incubated at 37ºc for 24 hours. the bacterial growth was harvested and washed off with 100 ml sterile normal saline, to produce a suspension containing about 108–109 colony forming units per ml. the suspension was stored in the refrigerator at 4ºc till used. the average number of viable organisms per ml of the stock suspension was determined by the means of the surface viable counting technique. serial dilutions of the stock suspensions were made in sterile normal saline solution and 0.02 ml volumes of the appropriate dilution were transferred by micropipette to the surface of dried nutrient agar plates. the plates were allowed to stand for 2 hours at room temperature for the drops to dry, and then incubated at 37ºc for 24 hours. after incubation, the number of developed colonies in each drop was counted. the average number of the colonies per drop (0.02ml) was multiplied by 50 and by the dilution factor to give the viable count of stock suspensions, expressed as the number of colony forming unit per ml of suspension. each time fresh stock suspension was prepared, all the aforementioned experimental conditions were maintained constant so that suspensions with very close viable count would be obtained [6, 7]. 2.5. preparation of standard fungal organisms the standard fungi were obtained from the department of microbiology and parasitology, medicinal and aromatic plant research institute, khartoum and were maintained on sabouraud’s dextrose agar, incubated at 25ºc for 4 days. the fungal growth were harvested and washed with sterile normal saline and finally suspended in 100 ml of sterile normal saline and the suspension was stored in refrigerator till used. doi 10.18502/sjms.v13i4.3599 page 268 sudan journal of medical sciences s. k. kafi et al 2.6. testing of antibacterial susceptibility the paper disc diffusion method was used to screen the antibacterial activity of plant extracts and performed by using mueller hinton agar (mha). the experiment was carried out according to the national committee for clinical laboratory standards guidelines [8]. bacterial suspension was diluted with sterile physiological solution to 108cfu/ml (turbidity = mcfarland standard 0.5). one hundred microliters of bacterial suspension were swabbed uniformly on surface of mha and the inoculum was allowed to dry for 5 minutes. sterilized filter paper discs (whatman no.1, 6 mm in diameter) were placed on the surface of the mha and soaked with 20 µl of a solution of each plant extracts. the inoculated plates were incubated at 37 ºc for 24 h in the inverted position. the diameters (mm) of the inhibition zones were measured. 2.7. testing for antifungal activity the same method as for antibacterial activity was used. sabouraud dextrose agar was used instead of nutrient agar. the inoculated medium was incubated at 25ºc for three days for the a. niger and two days for c. albicans. 2.8. determination of minimum inhibitory concentration (mic) by agar plate dilution method the principle of the agar plate dilution is the inhibition of growth on the surface of the agar by the plant extracts incorporated into the medium. plates were prepared in the series of increasing concentrations of the plant extract. the bottom of each plate was marked off into six segments. the organisms tested were inoculated into broth media over night to obtain 109 cfu/ml. a loop-full of diluted culture was spot with a standard loop that delivers 0.001 ml on the surface of each segment and then incubated at 37ºc for 18 hour (9). piliostigma reticulatum extract was prepared in the series of decreasing concentrations in the following order 50, 25, 12.5, 12.5, 6.25, 3.125, and 1.56 mg/ml. the end point (mic) is the least concentration of antimicrobial agent that completely inhibits the growth. mic for each microbe was reported in term of mg/ml. doi 10.18502/sjms.v13i4.3599 page 269 sudan journal of medical sciences s. k. kafi et al 2.9. antibacterial activity of reference drugs in the present work, three antibiotics (ampicillin, gentamicin, and tetracycline) were used as reference drugs. antibacterial drugs were tested at different concentrations obtained by dissolving 0.1 g of each powdered drug in 100 ml sterile distilled water to give a concentration of 1000 μg/ml followed by serial dilutions to give concentrations of 40, 20, 10, and 5 μg/ml. these drugs were tested against reference bacteria, that is, bacillus subtilis, staphylococcus aureus, escherichia coli, and pseudomonas aeruginosa. 2.10. antifungal activity of reference drugs in the present work, two antifungal agents (nystatin and clotrimazole) were used as reference drugs. antifungal drugs were tested at different concentrations obtained by dissolving 0.1 g of each powdered drug in 100 ml sterile distilled water to give a concentration of 1000 μg/ml followed by serial dilutions to give concentrations of 40, 20, 10, and 5 μg/ml. these drugs were tested against reference fungi. a. niger and c. albicans. 3. results 3.1. screening for antimicrobial activity of methanolic and aqueous extracts of bark and leaves of p. reticulatum (kharoub) the methanolic leaves extract of p. reticulatum showed high antimicrobial activity against gram positive and negative bacteria with inhibition zone of 20 mm against b. subtilis, 18 mm against p. aeruginosa. it also showed high activity against c. albicans and a. niger (inhibition zone 19 mm against each one). the methanolic leaves extract revealed moderate activity against e. coli and low activity against s. aureus (inhibition zones of 13 mm and 8 mm, respectively) (plates 2–3). the aqueous extract showed moderate activity against a. niger (inhibition zone 12 mm) and no activity against the rest of the tested organisms (table 1). the methanol bark extract of piliostigma reticulatun showed pronounced activity against s. aureus (inhibition zone 25 mm), and high activity against p. aeruginosa, b. subtilis, and e.coli (inhibition zones of 23 mm, 22 mm, 20 mm, respectively). the methanolic bark extract also showed pronounced activity against a. niger and high doi 10.18502/sjms.v13i4.3599 page 270 sudan journal of medical sciences s. k. kafi et al activity against c. albican (inhibition zones of 24 mm and 23 mm, respectively) (table 1 and plate-1). the aqueous extract showed low activity (10 mm) against p. aeruginosa and inactive against the rest of the organisms (table 1). 3.2. comparison between the antimicrobial activity of the most active bark and leaves methanolic extracts with standard reference drugs e. coli was found to be resistant to all the three drugs (ampicillin, gentamicin, and tetracycline) at all concentrations while sensitive to the leaves and bark ethanolic extract of the plant. it was also found to be resistant to tetracycline and ampicillin at all concentrations but sensitive to leaves and bark ethanolic extracts of p. reticulatum (table 2). bacillus subtilis revealed sensitivity to all the three antibiotics used and the ethanolic leaves and bark extracts of the plant but resistant to the aqueous extracts (tables 1 and 2). candida albicans was found to be sensitive to both antifungal used in all concentrations and as well methanolic leaves and bark extract of the plant but resistant to aqueous extracts. aspergillus niger showed sensitivity to all extracts except the aqueous bark extract. it also revealed sensitivity to nystatin and clotrimazole except in low concentration (tables 1 and 3). the leaves methanolic extract of p. reticulatum activity against b. subtilis was equivalent to the activity 10 μg/ml gentamicin. the bark methanol extract of p. reticulatum activity against b. subtilis was similar to the activity of 20 μg/ml gentamicin. the methanol bark extract activity against s. aureus was similar to that of 40 μg/ml tetracycline. the diameter of the inhibition of methanolic bark extract against c. albicans was similar to that caused by 12.5 μg/ml nystatin (tables 2 and 3). 3.3. determination of the minimum inhibitory concentrations the minimum inhibitory concentrations of the bark methanolic extracts of p. reticulatum was found to be 3.125 mg/ml for s. aureus and p. aeruginosa and 1.56 mg/ml for b. subtilis, e. coli, a. niger, and c. albicans. regarding the methanolic leaves extract, mic for s. aureus was 50 mg/ml, 6.25 mg/mg for c. albicans, and 3.125 mg/ml for b. subtilis, p. aeruginosa, and a. niger (table 4). doi 10.18502/sjms.v13i4.3599 page 271 sudan journal of medical sciences s. k. kafi et al t 1: the diameter of the inhibition zone in mm of the methanolic and water extracts of p. reticulatum against standard tested organisms. type of extract the size of inhibition zone (mm) against the different standard organisms e. coli p. aeruginosa b. subtilis s. aureus a. niger c. albicans leaves methanolic extract 13 18 20 8 19 19 leaves water extract resistant resistant resistant resistant 12 resistant bark methanolic extract 20 23 22 25 24 23 bark water extract resistant 10 resistant resistant resistant resistant interpretation of results: mean diameter of inhibition zone in mm (mdiz): (> 8 mm: sensitive, 12–15 mm: intermediate : < 8 mm: resistant. t 2: antibacterial activity of reference drugs against standard bacteria. type of the antibiotic concentration of the drug in the antibiotic disc the diameter of the inhibition zone in mm e. coli p. aeruginosa b. subtilis s. aureus ampicillin 40 resistant resistant 15 25 20 resistant resistant 14 20 10 resistant resistant 13 18 5 resistant resistant 12 15 gentamicin 40 resistant 29 9 35 20 resistant 21 22 33 10 resistant 20 20 30 5 resistant 19 17 28 tetracycline 40 resistant resistant 25 25 20 resistant resistant 23 resistant 10 resistant resistant 19 resistant 5 resistant resistant 18 resistant 4. discussion the methanol and aqueous extracts of the leaves and bark of p. reticulatum were screened for their anti-microbial activity against six microorganisms, two standard gram-positive bacteria (s. aureus and b. subtilis), two gram-negative bacteria (e. coli and p. aeruginosa) and two standard fungi (a. niger and c. albicans) using disc diffusion method. in this study, the methanolic extract of p. reticulatum bark and leaves extracts were found to have broad spectrum antimicrobial activity against the gram-positive and negative bacterial species tested as well as the two fungal species. the bark ethanolic doi 10.18502/sjms.v13i4.3599 page 272 sudan journal of medical sciences s. k. kafi et al t 3: antifungal activity of reference drugs against standard fungi. the antifungal drugs conc. used μg\ml the diameter of the inhibition zone in mm a. niger c. albicans nystatin 500 27 32 50 17 28 25 14 26 12.5 resistant 23 clotrimazole 40 30 42 20 22 40 10 20 31 5 resistant 28 t 4: minimum inhibitory concentrations (mic) of p. reticulatum methanolic extracts against the standard microorganisms. part used solvent conc. used mg/ml the diameter of the inhibition zone in mm b. subtilis s. aureus e. coli p. aeruginosa a. niger c. albicans bark methanol 50 22 20 16 13 14 16 25 14 19 15 12 14 14 12.5 14 11 14 11 14 13 6.25 14 11 13 11 13 13 3.125 11 0 10 0 10 11 1.56 0 0 0 0 0 0 leaves methanol 50 18 8 13 17 17 18 25 17 0 12 15 13 16 12.5 14 0 11 15 13 14 6.25 13 0 11 14 13 12 3.125 11 0 0 11 10 0 1.56 0 0 0 0 0 0 extract showed higher activity against all tested bacteria and fungi compared to leave extract. based on microbial species, the bark ethanolic extract showed higher effect on s. aureus inhibition zone of 25 mm followed by a. niger (24 mm), then p. aeruginosa and c. albicans (23 mm each). contrary to our results, daniel and malomo reported that p. reticulatum was not active against p. aruginosa but showed high activity (with inhibition zone 22 mm against b. subtilis and 20 mm against e. coli [11]. the antimicrobial effect of the methanolic bark and leave extract were even better than the drugs used (ampicillin, gentamicin, and tetracycline). doi 10.18502/sjms.v13i4.3599 page 273 sudan journal of medical sciences s. k. kafi et al plate 1: invitro antimicrobial activity of p. reticulatum bark extract (m) methanol extract (w) water extract against staphylococcus aureus. plate 2: invitro antimicrobial activity of p. reticulatum bark extract (m) methanol extract (w) water extract against pseudomonas aeruginosa. the aqueous extract of the plant showed low antibacterial activity against p. aeruginosa (inhibition zone10 mm), while inactive against rest bacterial and fungal organisms tested. similar results were reported by a study done in 2009 in which the hot and cold aqueous extracts of p. reticulatum exhibited low antimicrobial activity against e. coli, shigella dysenteriae, salmonella typhimrium, staphylococcus aureus, and pseudomonas aruginosa with zones of inhibition ranging between 8–10 mm and 4–7 mm for bacterial and fungal species, respectively [12]. however, one of the previous studies found no difference between the methanolic and aqueous extract of the plant [10]. the active ingredient is possibly alcohol soluble and water insoluble resulting in the variation in the antimicrobial effect of the two doi 10.18502/sjms.v13i4.3599 page 274 sudan journal of medical sciences s. k. kafi et al plate 3: invitro antimicrobial activity of p. reticulatum leaves extract (m) methanol extract (w) water extract against a. niger. types of extract, moreover the concentration of the active ingredient is probably higher in the bark than the leaves. this can explain why bark extract was more effective than the leave extract. in conclusion, the methanolic extract of bark showed more anti-microbial activity than leaves extract. acknowledgement the authors are indebted to and appreciate the role of staff members of the departments of microbiology and parasitology of the medicinal and aromatic plant research institute for their help in preparation of the extracts. references [1] fibres. (1846). description, original, geographic distribution, uses and production and international trade of p. reticulatum. prota (plant resourcer of tropical africa) vol. 29, p. 299. [2] dosso, k., n’guessan, b. b., bidie, a. p., et al. (2011). antidiarrheal activity of an ethanol extract of the stem bark of piliostigma reticulatum (caesalpiniaceae) in rats. african journal of traditional, complementary and alternative medicines, vol. 9, no. 2, pp. 242–249. doi 10.18502/sjms.v13i4.3599 page 275 sudan journal of medical sciences s. k. kafi et al [3] sidiki, n., djafsia, g., njapdounke, k. j. s., et al. (january–march 2013). anxiolytic and antipyretic activities in the decoction of leaves of piliostigma reticulatum. asian journal of pharmaceutical and health sciences (ajphs), vol. 3, no. 1. [4] olalekan, j., babajide, et al. (2008). flavonols and an oxychromonol from piliostigma reticulatum. phytochemistry, vol. 69, no. 11, pp. 2245–2250. [5] akinsinde, k. a. and olukoya, d. k. (1995). vibriocidal activities of some local herbs. journal of diarrhoeal diseases research, vol. 13, no. 2, pp. 127–129. [6] miles, m. and misra, s. s. (1938). the estimation of the bacterial power of the blood. journal of hygiene, vol. 38, pp. 7–32. [7] collee, j. g., barrie, p. m., andrew, g. f., et al. (1996). practical medical microbiology. specimen collection, culture container and media (fourteenth edition), section a, vol. 5, pp. 95–109. singapore: longman singapore publisher ltd. [8] nccls. (1999). methods for determining bactericidal activity of antibacterial agents: approved guideline. nccls document m26-a. villanova, pa: nccls. [9] abd-ulgadir, k. s., suliman, s. i., zakria, i. a., et al. (2015). antimicrobial potential of methanolic extracts of hibiscus sabdariffa and ricinus communis. advancement in medicinal plant research, vol. 3, no. 1, pp. 18–22. [10] aderogba, m. a., okoh, e. k., okeke, i. n., et al. (2006). antimicrobial and antiinflammatory effects of piliostigma reticulatum leaf extract. international journal of pharmacology, vol. 2, no. 1, pp. 70–74. [11] daniels, a. o. and malomo, o. (2014). preliminary studies on the antimicrobial effect and phytochemicals studies of some nigerian medicinal plant on some human pathogens. international journal of current microbiology and applied science, vol. 3, no. 3, pp. 910–923. [12] awe, s. and omojasola, p. f. (2009). a comparative study of the antibacterial activity of piliostigma reticulatum bark extract with some antibiotics. ethnobotanical leaflets, vol. 2009, no. 9, article 11. doi 10.18502/sjms.v13i4.3599 page 276 introduction materials and methods preparation of the different plant's parts preparation of the extracts preparation of the standard test organisms preparation of the standard bacterial suspensions preparation of standard fungal organisms testing of antibacterial susceptibility testing for antifungal activity determination of minimum inhibitory concentration (mic) by agar plate dilution method antibacterial activity of reference drugs antifungal activity of reference drugs results screening for antimicrobial activity of methanolic and aqueous extracts of bark and leaves of p. reticulatum (kharoub) comparison between the antimicrobial activity of the most active bark and leaves methanolic extracts with standard reference drugs determination of the minimum inhibitory concentrations discussion acknowledgement references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.6703 production and hosting by knowledge e research article hematological parameters in apparently healthy eritrean blood donors at the national blood transfusion center, asmara, eritrea faris m. abdon1, elias t. adgoy2, nahom y. berhane3, senet a. ibrahim3, adil k.h. khalil4, yemane seyoum5, and osama s. abbadi6 1department of biochemistry, orotta college of medicine and health sciences, asmara, eriteria 2community medicine and primary health care, orotta college of medicine and health sciences, asmara 3department of laboratory medicine, national blood transfusion service (nbts), eritrea 4department of basic medical science, college of medicine, dar al uloom university, riyadh, kingdom of saudi arabia 5dean, orotta college of medicine and health sciences, asmara, eritrea 6department of biochemistry, faculty of medicine, omdurman islamic university, sudan abstract background: this study was conducted to measure the hemoglobin (hb) levels, erythrocytes, and related measurements (particularly mean corpuscular volume [mcv], mean corpuscular hemoglobin [mch], mean corpuscular hemoglobin concentration [mchc], and hematocrit) in healthy individuals donating blood at the national blood transfusion center (nbts) in asmara city, eritrea. methods: venous blood samples were taken from the candidates’ peripheral veins into the edta tube and examined for red blood cell(rbc) count, hb, hematocrit (%),mcv, mch, mchc, and red cell distribution width (rdw), analyzed and measured by automated blood analyzer. results: the mean hb level was 14.428±1.485g/dl, rbcs count was 4.744±0.482×1012/l, hct was 41.929 ±3.75%, rdw mean was 13.571±0.744%, mcv was 88.582± 4.0558 femtoliter, mch was 30.470±2.188picogram, and mchc was a mean of 34.393±1.347g/dl. the difference between males and females in mcv and mchc was significant in favor of female donors. a correlation of a weak positive naturewas found between the ages and genders of donors and the hb level. all measured values were found to be within the global referenced ranges. conclusion: hb, rbcs count, and rbcs indices of apparently healthy eritrean blood donors were measured for reference, and all values were found to be within the normal reference ranges. keywords: blood donors, hemoglobin, rbcs, rbcs indices 1. introduction the red blood cells (rbcs) are a type of cells primarily composed of the quaternary protein hemoglobin (hb) that serves as the carrier of oxygen to the tissues, carbon how to cite this article: faris m. abdon, elias t. adgoy, nahom y. berhane, senet a. ibrahim, adil k.h. khalil, yemane seyoum, and osama s. abbadi (2020) “hematological parameters in apparently healthy eritrean blood donors at the national blood transfusion center, asmara, eritrea,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 290–299. doi 10.18502/sjms.v15i3.6703 page 290 corresponding author: osama s. abbadi; department of biochemistry, faculty of medicine, omdurman islamic university, sudan. current address: riyadh city, saudi arabia. p.o. box: 22490, riyadh 11426. tel: 00966531549824. email: aslikhalis@yahoo.com received 12 june 2020 accepted 19 july 2020 published 30 september 2020 production and hosting by knowledge e faris m. abdon et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:aslikhalis@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences faris m. abdon et al dioxide, bicarbonates, and proton (h+) to the lungs [1]. most rbcs are round and flattened at the center, probably due to the absence of nuclei and most of the cell organelles [2]. through a process known as erythropoiesis, couple million erythrocytes are formed within the human bone marrow each second [3, 4]. an adult human body has an estimated 2–3 ×1013 rbcs in total, with males having the higher average count due to physiological and hormonal causes [ 4,5]. people living at high altitudes with low oxygen tension will have higher erythrocyte level [6]. except for 2% of the dissolved oxygen in plasma, rbcs carry the majority of molecular oxygen in the blood [ 1]. the rbcs of an average adult human male store collectively about 2.5 gram of iron, which is two-thirds of the total body iron, in the heme of erythrocytes [ 4, 5]. some important terms were developed to describe the physiological and pathological parameters of erythrocytes: measured in femtolitres (fl), the average volume oferythrocytes is known as mean corpuscular volume (mcv). if the majority of rbcs in a sample are smaller or larger than the population mcv, this implies that there is micro or macrocytic anemia, respectively.variable sizes of erythrocytes are measured through the rdw.hb in rbcs is either described inpicograms for the amount in rbcs;in this case, the measurement is called mean corpuscular hemoglobin (mch) and otherwise, it could be measured as a fraction of hb in the erythrocyte, which is called mch concentration. either described in g/dl or percentage, the mchc is the same index [ 4]. blood transfusion is an essential component of quality healthcare service package. voluntary blood donors are the main contributor to safe blood to be transfused. the availability and accessibility of safe blood and blood products save life, mainly in emergencies such as hemorrhagic anemia due to obstetric and gynecological emergencies, general surgeries, accidents, conflicts, and complex medical and surgical conditions for improving the life expectancy and quality of life. sufficient and safe blood donation/transfusion service is an essential component of the healthcare system of a nation. those who are selected for blood donation should be from a group of population with low risk of infection and prevalence of infectious diseases. according to different studies and clinical trials, hb level and rbc count are commonly and routinely used in clinical diagnostic measures. to the best of the researchers’ knowledge, so far, no study has been conducted on the hb level and rbc indices in apparently healthy eritrean blood donors. therefore, this study will help in establishing the reference ranges of hb level and erythrocytes count in eritrean people and to correlate them with genders and ages of the participants. doi 10.18502/sjms.v15i3.6703 page 291 sudan journal of medical sciences faris m. abdon et al 2. materials and methods 2.1. study design and area this study was a descriptive cross–sectional study performed at the national blood transfusion center (nbts) of eritrea between october and december 2019. the nbts is the only blood bank in the country that is situated around the national referral hospitals of the country. 2.2. study participants voluntary donors were chosen according to specific health parameters – including suitable age, average weight and body mass index (bmi); passing a general physical examination; the absence of non-communicable chronic diseases, namely diabetes mellitus and hypertension; and the absence of blood-transmitted infections, particularly syphilis, hepatitis b, hepatitis c, and hiv. hb level assessment was performed using the hemocue 201 hemoglobinometre®, and donors were reported as fit for the donation if a drop of blood sankin a copper sulphatesolution, of a certain specific gravity. the sample size was determinedusing anonline software available at: https://www.surveysystem. com/sscalc.htm. putting a confidence level of 95% and confidence interval 4.0, and previously knowing that the population of eritrea is 3,200,000 (according to a 2010census), the calculated sample size was 601 participants.accordingly, a total of 610 volunteered blood donors –205 females and 405 males –between the ages of 16 and 65 years consented to participate in the study. 2.3. data collection methods 2.3.1. questionnaire a standard donor questionnaire, designed by the enbts for counseling purposes, was used to collect information such asthe demographic data, social habits, current health status, and past medical history of each blood donor. 2.3.2. laboratory investigations the required blood samples were taken during the donation process. blood sampling was performed by trained staff working in the enbts, following a standard operating doi 10.18502/sjms.v15i3.6703 page 292 https://www.surveysystem.com/sscalc.htm. https://www.surveysystem.com/sscalc.htm. sudan journal of medical sciences faris m. abdon et al procedure for blood sample collection. moreover, 4 ml of blood from peripheral veins was collected into the k3edta tubes (becton dickinson, plymouth, uk) and 6ml venous blood was collected into serum tube from all participants of the study. blood samples collected into the edta tubes were examined for hb, erythrocytes count, packed cell volume (hct%), rdw, mcv,mch, and mchc by automated blood analyzer: beckman coulter dxh500 series, within the first 4 hr of sample collection. the 6ml venous blood collected were analyzed using the cobas-e 411 for the screening hiv, syphilis, hepatitis b virus surface antigen (hbsag), and hepatitis c virus antibodies (hcabs). both instruments participate in an external quality assurance program, and routine internal quality control product was run before analyzing each sample. 2.3.3. data analysis the basic datasheet, descriptive statistics, and tests of significance were all performed usingthe microsoft® 2007 excel software. 3. results the study participants (n=601) were found to have a mean weightof 60.633 ± 10.312kg and aged between 16 and 71 years. the hb level was14.428 ± 1.485g/dl; rbcs count 4.744 ± 0.482×1012/l; hct 41.929 ± 3.75%; rdw mean 13.571 ± 0.744%; mcv 88.582 ± 4.0558 fl; mch 30.470 ± 2.188 pg; and mchc mean 34.393 ± 1.347 g/dl (see table 1).the differences between female(n=205) and male (n=405) donors in mcv and mchc were found to be significantly higher in female donors when compared to males. however, the differences in the rbcs counts, hb levels, and hematocrits were found to be insignificant (table 2).a positive correlation was observed between the weight and age of the apparently healthy blood donors with rbcs count, and also a correlation between weight and age with hb level (table 3). while figure 1 shows a line chart of rbcscount comparing the male and female donors,figure 2 shows a line chart of hb levels comparing the twodonor groups. 4. discussion thecurrentstudy of blood parameters is considered as the first to be performed among theeritrean blood donors. the study revealed the hematological values that includehb, erythrocytes count, hematocrit, and other rbc indices, namely mcv, mch and mchc to doi 10.18502/sjms.v15i3.6703 page 293 sudan journal of medical sciences faris m. abdon et al table 1: the results calculated to eight variables in erythrocytes and hemoglobin. variable mean median mode standard deviation standard error sample variance range minimum maximum confidence level (95.0%) weight in kg 60.633 57 55 10.312 0.4175 106.331 60 50 110 0.82 age in years 22.5 17 16 10.808 0.438 116.808 45 16 61 0.859 hb level g/dl 14.428 14.36 15.25 1.485 0.06 2.204 8.54 11.14 19.68 0.118 rbcs count 1012/liter 4.744 4.73 4.8 0.482 0.02 0.232 3.04 3.45 6.49 0.038 hct % 41.929 41.7 40 3.75 0.152 14.066 24.7 32.8 57.5 0.298 mcv (fl/cell) 88.582 88.4 86.7 4.056 0.164 16.45 36.1 72 108.1 0.322 mch (pg/cell) 30.47 30.2 30.2 1.88 0.076 3.535 14.7 23.2 37.9 0.15 mchc (g/dl rbcs) 34.393 34.1 33.9 1.347 0.055 1.814 10.5 29.5 40 0.107 rdw (%) 13.57 13.45 13.4 0.744 0.03 0.554 6.7 11.9 18.6 0.0592 figure 1: diagram demonstrating rbcs count in male and female donors. *population limitation is from the software. table 2: the significance of the difference between male and female donors in regards to rbcs count, hemoglobin level, and hematocrit (hct). parameter male mean female mean statistic t critical two-tailed t difference status rbcs count 4.913 4.408 –14.0369 1.963886 insignificant hb level 15.008 13.266 –16.417 1.963886 insignificant hct 43.341 39.128 –15.3919 1.963886 insignificant mcv 88.394 89.092 2.045407 1.963886 significant mch 30.609 30.197 –2.56531 1.963873 insignificant mchc 34.012 35.146 10.69728 1.963873 significant rdw 13.618 13.479 –2.18499 1.963873 insignificant be within the referenced normal ranges [6], although the mcv and mchc in the female donors were higher than the male donors by 0.7fl/cell and 1.13pg/cell, respectively. doi 10.18502/sjms.v15i3.6703 page 294 sudan journal of medical sciences faris m. abdon et al figure 2: a line chart representing the hemoglobin levels in males and females of the study population. *population limitation is from the software. table 3: correlations ofthe weight and age to both rbcs count and hemoglobin level. parameter correlations withthe rbcs count comment correlationswith thehb level comments weight 0.146203767 very weak positive 0.231729022 weak positive age 0.091116727 very weak positive 0.276022551 weak positive this is the only parameter which was found to have statisticallysignificant difference between the two genders. these results might be due to a compensatory response to the absenceof testosterone hemopoietic effect in females [7]. however, both the mcv and mhch values were found to be within the normal range of hematologicreferences. some studies documented increased mcvdue to aplastic anemia, liver disease, myelodysplastic syndrome, and chemotherapy [8]. a population-based study in eritrea, which was performed in 2018, revealed that the mean hb level was 15.4 g/dl for males, whereas females scored 14.9 g/dl; males had a mean rbcs count of 5.3×1012/l and females 4.7×1012/l.the hematocrit in that study was 49.3% and 44.2% for males and females, respectively;the mean mcv in males was 93.8 fl/cell, while females gave a mean of 93.6 fl/cell. also, the mch value for males was 30.8pg/celland for females 30.4pg/cell and the mean mchc for males was 32.8, whereas the females scored a mean of 32.4g/dl rbcs[9]. one can notice that apart from the mchc, all the current results are lower than the population-based study. according to another hematologic study conducted on apparently healthy male donors in sudan by abbas et al, the results were documented with a mean hb level of 14.509±1.2076 g/dl, mean rbcs count of 5.1515±0.45432×1012/l, mean mcv of 85.08±5.7391fl, mean mch of 28.244± 2.1959 pg, and mchc of 32.218±1.9002 g/dl doi 10.18502/sjms.v15i3.6703 page 295 sudan journal of medical sciences faris m. abdon et al [4],which are relatively consistent to this study. besides, two another studies in ethiopia (1979[10] and 1999[11]) and one in tanzania (2008 [12]) have also been documented and summarized in table 4. table 4: comparison between the studies done in healthy population within sudan, eritrea, tanzania, and ethiopia with regards tohemoglobin, rbcs count, and rbcs indices. parameter eritrea 2019 (current study) eritrea 2018 populationbased study sudan 2015 study ethiopia 1979 study ethiopia 1999 study tanzania 2008 study williams manual of hematology. hemoglobin ± sd (g/dl ) males : 15.008 (sd ± 1.228) females: 13.266 (sd ± 1.026) males : 15.4 females: 14.9 14.509 (sd ± 0.208) 16.4 (sd ± 1.5) males: 16.1 (sd ± 1.1) females: 14.3 (sd ±1.2 ) males: 15.4 females: 13.5 range: m = 14–18 f = 12–15 rbcs count ±sd (1012/l) males: 4.913 (sd ± 0.428) females: 4.408 (sd ± 0.401 ) males: 5.3 females:4.7 5.152 (sd ± 0.454) ___________ males: 5.1 6 (sd ± 0.4) females: 4.5 6 (sd ± 0.4 ) males: 5.21 females: 4.69 range: m = 4.5–6.0 f = 4.1–5.1 hct±sd (percentage) males: 43.341 (sd ± 3.364 females: 39.128 (sd ±2.801 males:49.3 females:44.2 43.625 (sd ± 3.775) 47.3 (sd ± 3.5) males: 48.3 (sd ± 3.4) females: 42.0 (sd ±3.2) males: 46.6 females: 41.5 range: m = 42–51 f = 36–46 mcv±sd (fl/cell) males: 88.394 (sd ± 3.77) females: 89.092 (sd ± 4.338) males:93.8 females:93.6 85.08 (sd ± 5.7391) __________ ___________ males: 89.3 females: 89.5 range: m = 80–96 f = 79–94 mch±sd (pg/cell) males: 30.609 (sd ± 1.886 ) females: 30.197 (sd ± 1.843) males:30.8 females:30.497 28.244 (sd ± 2.1959) __________ __________ males: 30.0 females: 29.3 range: 27–33 mchc±sd (g/dl rbcs) males: 34. 012 (sd ± 0.663) females: 35.146 (sd ± 1.92) males:32.8 females:32.4 32.218 (sd ± 1.9002) ___________ ___________ males: 33.3 females: 32.7 range: 33–36 the hematologic values of this study are in between those reported by the ethiopia and sudan studies. knowing the fact that both countries are within the range of the ethiopian plateau, where high altitude induces polycythemic changes, it is suspected that the participants of this study, eritreans, have the same hb and rbcs readings as that of ethiopia (1979); however,thedifference with the study of 1999 may be attributed to the nutritional causes [13]. our study has the advantage of recruiting both genders and adding a broader range of variables with a representative sample size (n=601). in this study, the microscopic examination was not performed; therefore we have no insight about the rbcs’ descriptive remarks. according to abbas et al. (2015), erythrocytes microscopy showed that 3% of the sudanese blood donors exhibited anisocytosis (unequal rbcs sizes), 18% showed microcytichypochromic rbcs, and 2% showed macrocytic rbcs in their samples [4]. the study recommends a further populationbased research of hematological parameters including erythrocytes microscopy with multi-regional recruitment of healthy blood donors throughout the country. doi 10.18502/sjms.v15i3.6703 page 296 sudan journal of medical sciences faris m. abdon et al 5. conclusion this descriptive cross–sectional study was performed at the national blood bank of eritrea, where blood samples of 610 healthy voluntary blood donors were taken to be measured for the hb level, rbcs count, and rbcs indices. the results were found to be within the normal range of the international reference value. the mean hb level and rbcs count were recorded at values lower than those measured in ethiopian donors and higher than the sudanese, whereas the values differences with regard to gender might be due to physiological causes. declaration section acknowledgements the authors would like to thank the medical director of the national blood bank of eritrea. ethical considerations all study participants filled an informed consent to participate in the study. ethical approval for the research was obtained from the deanship of orotta college of medicine and health sciences and the national blood transfusion service (nbts) of eritrea. competing interests the authors declare that there are no competing interests. availability of data and material data recorded and collected for this study is available in excel files and questionnaire papers. funding none. doi 10.18502/sjms.v15i3.6703 page 297 sudan journal of medical sciences faris m. abdon et al authors’contributions fmaa and eta designed the study; nyb and sai performed the practical procedure and data collection; akhk is the counsellor and the critical reviewer of the experiment; ysreviewed the draft for final approval; and osa performed the statistical analysis and prepared the final manuscript. references [1] murray, r. k., granner, d. k., mayes, p. a., et al. (2003). harper’s illustrated biochemistry(26𝑡ℎ ed). toronto (ontario): mcgraw-hill inc. [2] ford, j. (2013). red blood cell morphology. international journal of laboratory hematology, vol. 35, no. 3, pp. 351–357. doi: 10.1111 /ijlh.12082. [3] catovsky, d.,hoffbrand, v., tuddenham, e. g. d., (eds.) (2005). postgraduate hematology (5𝑡ℎ ed.). oxford, uk : john wiley and sons ltd. [4] abbas, a. a., khalil, a. k. h., yasir, h., et al. (2015). hemoglobin level and red blood cell indices in apparently healthy sudanese blood donors in gezira state (sudan). pyrex journal of biomedical research, vol. 1, no. 6, pp. 91–94. [5] dacie, j.v. and lewis, s. m. (2006). practical haematology (10𝑡ℎ ed). london, uk: churchill livingstone. [6] lichtman, m. a., kaushansky, k., prchal, j. t., et al. (2015). williams manual of hematology(9𝑡ℎ ed.). new york,ny: mcgraw-hill. [7] bachman, e., travison, t. g., basaria, s., et al. (2014). testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. the journals of gerontology series a biological sciences and medical sciences, vol. 69, no. 6, pp. 725–735. [8] ravi sarma, p. (1990). red cell indices. in: h. k.walker, w. d.hall, j. w.hurst,(eds.).clinical methods: the history, physical, and laboratory examinations (3rd ed.). boston, ma: butterworths; chapter 152. [9] siraj, n., issac, j., anwar, m., et al. (2018). establishment of hematological reference intervals for healthy adults in asmara. bmc research notes, vol. 11, p. 55. doi: 10.1186/s13104-018-3142-y. [10] abdulkadir, j., bolodia, g., tegene, n., et al. (1979). haemoglobin and haematocrit levels in young adult ethiopian males in addis ababa. ethiopian medical journal, vol. 17, no. 1, pp. 5–7. doi 10.18502/sjms.v15i3.6703 page 298 sudan journal of medical sciences faris m. abdon et al [11] tsegaye, a., messele, t., tilahun, t., et al. (1999). immunohematological reference ranges for adult ethiopians. clinical and diagnostic laboratory immunology, vol. 6, no. 3, pp. 410–414. [12] saathoff, e., schneider, p., kleinfeldt, v., et al. (2008). laboratory reference values for healthy adults from southern tanzania. tropical medicine and international health, vol. 13, no. 5, pp. 612–625. [13] malik, b. y. (2017). state-induced famine in eritrea: persecution and crime against humanity. journal of politics and law, vol. 10, no. 4, pp. 1–14. doi 10.18502/sjms.v15i3.6703 page 299 introduction materials and methods study design and area study participants data collection methods questionnaire laboratory investigations data analysis results discussion conclusion declaration section acknowledgements ethical considerations competing interests availability of data and material funding authors'contributions references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5207 production and hosting by knowledge e research article pink1 type of early onset parkinson’s disease (eopd) in sudanese patients, 2018 etedal ahmed a. ibrahim1,2 and samer abdalaziz albasher2 1al neelain university, khartoum, sudan 2national center of neurological sciences, khartoum, sudan abstract background: parkinson’s disease (pd) is a neurodegenerative disorder affecting the motor system. it is a chronic progressive disorder that leads to long standing disability. objective: to study the presentations and pink1 gene in young sudanese patients with pd. methods: a prospective study was conducted among 31 pd patients at the national center for neurological science (ncns) at khartoum state. a structured questionnaire was used for data collection. this consisted of personal data, clinical presentations, and investigations. rt-pcr technique was done using g-spintm kit. pink1 gene was detected in most of the samples and was strongly positive. data was analyzed using spss version 21. results: the majority of them, 19 (61%), were located in age group 41–50 years; the mean age of onset was 33.4 ± 12 yr; our of the total number of subjects, 19 (61%) were male and 12 (39%) were female with a ratio 1.6:1 (m:f); 20 (64.5%) were married and 8 (40%) were endogamous married; 5 (62.5%) were second degree and 3 (37.5%) were third degree, 17 (85%) had children and 2 (10%) had children with pd; 22 (71%) had duration more than 12 months and 12 (39%) were more than 40 years old; 29 (93.5%) had tremor, 27 (87.1%) had rigidity, 23 (74.2%) had bradykinesia, and 14 (45%) had positive family history of pd. pink1 gene expression was detected in 28 (90.3%) patients. no significant associations were found between pink1 expression and age, gender, age at onset, and family history (p > 0.05). conclusion: this study concludes that early onset pd was common among males than females. the most affected age group was found to be 41–50 years and the mean age of onset was 33.4 yr. also, the patterns of the clinical features were generally similar to literature. pink1 expression was predominant with no significant associations between pink1 expression with age, gender, age at onset, and family history. keywords: early onset, parkinson’s disease, pink1 gene, sudan 1. introduction parkinson’s disease (pd) is a progressive neurodegenerative illness. it was first described by james parkinson in his classic 1817 monograph, “an essay on the shaking how to cite this article: etedal ahmed a. ibrahim and samer abdalaziz albasher (2019) “pink1 type of early onset parkinson’s disease (eopd) in sudanese patients, 2018,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 78–90. doi 10.18502/sjms.v14i3.5207 page 78 corresponding author: etedal ahmed a. ibrahim; email: eetedalibrahim@yahoo.com received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e etedal ahmed a. ibrahim and samer abdalaziz albasher. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:eetedalibrahim@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher palsy” [1], pd, also known as paralysis agitans, is a progressive neurodegenerative disease that affects between 100 and 200 per 100,000 people over 40, and over 1 million people in north america alone [2, 3]. it is uncommon in people younger than 40, and the incidence of the disease increases rapidly over 60 years, with a mean age of 70.5 yr at the time of diagnosis [4]. while pd has traditionally been considered a motor system disorder, it is now recognized to be a complex condition with diverse clinical features that include neuropsychiatric and other non-motor manifestations in addition to its motor symptomatology (5). young-onset parkinson’s disease (yopd) is a subtype of pd, occurring at a younger age, with specific symptoms, genetic correlation, and treatment strategies. yopd is defined as a diagnosis of pd between the ages of 21 and 40 [6]. a positive pd diagnosis under the age of 21 is referred to as “juvenile parkinson’s” (jp). between 3 and 6% of all pd cases are reported to be yopd [7]. although most clinical features of jp and yopd are the same, increased occurrence of dystonia and pd are found in patients with jp [8]. the overall age and gender adjusted incidence of pd is 13.4 per 100,000, whereas the incidences for people between the ages of 30 and 39, 40 and 49, and 50 and 59 are 0.5, 2.5, and 9.8 per 100,000, respectively [4]. approximately 20% of yopd patients have at least one firstor second-degree relative with pd either in the same or antecedent generation [4]. the cardinal features of pd are tremor, bradykinesia, and rigidity. a fourth feature, postural instability, is commonly mentioned, although it does not generally occur until much later in the course of the disease and is thus not included in any published diagnostic criteria for pd [8]. women and men are affected equally. age at onset is highly variable, even in individuals with the same pathogenic variant [9]; onset is usually in the third or fourth decade [10]. in the study by marongiu et al. (2008), the average age at onset in those with two pink1 pathogenic variants was 41 yr [11]. bradykinesia and tremor are the most common presenting signs. in some individuals, the symptoms at onset are symmetric. dystonia and hyperreflexia may also be present [10]. in addition to parkinsonism, individuals with the pink1 type of yopd may be prone to psychiatric involvement. abnormal behavior and/or psychiatric manifestations (in particular, depression and anxiety) occur in about 30 and 15% of affected individuals, doi 10.18502/sjms.v14i3.5207 page 79 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher respectively. other features include hallucinations and dementia [12]. non-motor symptoms are also frequent, and overall, the clinical signs at examination are also variable [12]. on average, the response to levodopa is better than in other forms of parkinson disease [13]; however, the incidence of levodopa-induced dyskinesia may be greater in individuals with pink1-associated yopd than in those with parkinsonism of different etiologies [14]. 1.1. problem statement there are several genes that have been implicated in pd. some rare mutations are implicated in the onset of pd in a young age, usually before the age of 30; these genes are park2, park6, and park7. their abnormal gene products appear to affect the function of the energy factory of the cell-the mitochondrion. well understanding of clinical presentation and causes of pd will lead to early diagnosis and give new ideas about new modality of treatment. 1.2. objective to study pink1 gene in early onset pd and its clinical presentations in sudanese patients at the national center for neurological science (ncns). 2. methods this was a prospective study conducted at the ncns between december 2016 and december 2018. sudanese patients aged < 50 yr and diagnosed with pd were included. patients developing pd at age > 50 yr, patients with idiopathic pd, non-sudanese patients, and those who were unable or refused to answer the questionnaires were excluded from the study. the sample size was 31 patients and data were collected through a questionnaire. 2.1. study variables patient’s age, gender, cause of disease, severity of symptoms, duration of the disease, and motor abnormalities. doi 10.18502/sjms.v14i3.5207 page 80 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher 2.2. techniques 2.2.1. blood collection 5 ml of venous blood was collected in sterile containers and put in vaccination containers and transported to laboratory for performance of genetic analysis. 2.2.2. genetic analysis (pink1) dna extraction: the extraction of dna was carried out by using g-spintm total dna extraction kit. briefly, 20 μl of proteinase k and 5 μl of rnase solution were added to 200 μl of the whole blood sample. then, 200 μl of buffer bl was added, mixed thoroughly, incubated at 56°c for 10 min and centrifuged; 200 μl of absolute ethanol was added to the mixture and mixed gently by pipette (5–6 times) and then centrifuged; 700 μl of buffer wa was added and centrifuged (repeated twice). and then 100 μl of buffer ce was added for elution. real-time pcr process: extracted dna samples were then amplified by adding 2 μl of dna, 1 ml of forward primer, 1 ml of reverse primer, and 20 ml of water. then, the mixture was put in tubes placed in thermal cycler and amplification was performed. the collected data were organized into a master sheet and then entered in the computer using the statistical package for social sciences (spss) version 21. the results obtained were presented in tables and figures. chi-square test was used as significance test and the level of significance was considered as p-value < 0.05. 2.3. ethical consideration consent was taken from all participants and from the national centre for neurological science. participation to the study was completely voluntary and confidentiality was considered. 3. results of the total of 31 patients, the majority of them were located in age group 41–50 yr, 19 (61%) of the subjects were male and 12 (39%) were female with a ratio 1.6:1 (m: f), doi 10.18502/sjms.v14i3.5207 page 81 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher 22 (71%) had duration more than 12 months and 12 (39%) had age more than 40 yr, followed by 11 (35%) in age group 20–40 yr and 8 (26%) less than 20 yr. mean 33.6 ± 12.9 yr (figures 1–3). figure 1: age distribution among pink1 early onset pd patients (n = 31). figure 2: gender distribution among study group (n = 31). pink1 gene expression: 28 (90.3%) patients showed positive result and 3 (9.7%) showed negative results (figure 4). doi 10.18502/sjms.v14i3.5207 page 82 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher figure 3: gender distribution among study group (n = 31)the age of onset of pink1 type early onset pd (n = 31). figure 4: pink1 gene expression distribution among the study group. the association between pink1 gene and age at onset: 100% of the patients in age group less than 20, 81.8% in age group 20–40 yr, and 91.7% of the patients in age group 40–50 ys expressed pink1 gene. but the difference was statistically insignificant (p = 0.408; figure 5). doi 10.18502/sjms.v14i3.5207 page 83 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher figure 5: pink1 gene expression according to the age at onset. symptoms: 29 (93.5%) patients had tremor, 27 (87.1%) had rigidity, 23 (74.2%) had bradykinesia, and 24 (77.4%) had tremor as initial symptoms. 27 (87.1%) patients had hand tremor, it was bilateral in 24 (85.7%) and symmetrical in 6 (25%), 12 (54.5%) had both types of rigidity (cogwheel and lead pipe), 30 (97%) had monotonous speech (tables 1 and 2); 20 patients (64.5%) were married, 8 (40%) were endogamous married and 5 (62.5%) were second-degree and 3 (37.5%) were thirddegree relative; 17 (85%) patients had children, 2 (10%) had children with pd table(3). table 1: the symptoms of pink1 type early onset pd. symptoms n % tremor 29 93.5 rigidity 27 87.1 bradykinesia 23 74.2 other 4 12.9 family history: all of the patients have positive family history (100%) of pd and had 1–3 members of family with pd: 8 (57.1%) of them were first-degree members; 28.6% were firstand second-degrees members, and 14.4% were third degree (table 4). family members’ symptoms: 14 (100%) had rigidity, 13 (92.2%) had tremor, and 4 (28.6%) had bradykinesia. doi 10.18502/sjms.v14i3.5207 page 84 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher table 2: the signs of pink1 early onset pd among the patients. signs n % tremor site • hand 27 87.1 • head 1 3.2 bilateral hand tremor 24 85.7 • symmetrical 6 25 • non-symmetrical 18 75 rigidity type (n = 22) • cog-wheel 9 40.9 • lead pipe 1 4.5 • both 12 54.5 table 3: distribution of marital status, endogamous marriage and degree of relativity in endogamous marriage among the study group. n % marital status (n = 31) • married 20 64.5 • unmarried 11 35.5 endogamous marriage (n = 20) • yes 8 40 • no 12 60 degree of relativity in endogamous marriage (n = 8) • second degree 5 62.5 • third degree 3 37.5 initial symptoms: 12 (85.7%) of them developed tremor and 2 (14.3%) developed rigidity. age and gender of the family members: 9 (64.3%) were in age group 20–35 yr, followed by 21.4% that were in age group 36–50 yr and 14.3% > 50 years; 7 (50%) were males. brain imaging: 20 (64%) patients underwent ct brain, which was normal, 11 (36%) underwent mri brain, which was also normal. types of treatment: 23 (74%) patient used combined akisol and levocare, 5 (16%) used akisol, and 3 (10%) used levocare alone. association between pink1 gene expression age: all of the patients (100%) in age group –40 yr expressed pink1 gene, followed by 89.5% in the age group 41–50 yr, and 88.9% in age group 20–30 yr, the difference was statistically insignificant (p = 0.836). gender: doi 10.18502/sjms.v14i3.5207 page 85 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher table 4: characteristics of family members of pink1 early onset pd. n % affected members (n = 14) • 1–3 members 14 100 degree of relativity (n = 14) • first degree 8 57.1 • third degree 2 14.4 • first and second degrees 4 28.6 age (n = 14) • 20–35 9 64.3 • 36–50 3 21.4 • > 50 2 14.3 gender (n = 14) • male 7 50.0 • female 4 28.6 • both 3 21.4 family blood genetic screening (n = 14) no 14 100 91.7% of the female patients and 89.5% male expressed pink1 gene, the difference was statistically insignificant (p = 0.672). expression of pink1 gene according to the family history: 92.9% of those with positive family history and 88.2% with negative family history group expressed pink1 gene. the difference was statistically insignificant (p = 0.575). also, all the patients had third-degree memberand firstand second-degree member-expressed pink1 gene, 85.7% of the patients had first-degree relative-expressed pink1 gene. the difference was statistically insignificant (p = 0.629) (tables 5 and 6). 4. discussion this study included 31 pd patients, among them males (61%) were affected more than females (39%) with male to female ratio of 1.6:1; this is similar to other study conducted by khalda et al. in sudan who found that male:female in pd was 1.5:1 [14]. the peak incidence of pd was found to be in the age group 41–50 yr (61%), mean age was 33.4 yr, which was similar to the literature and witjas et al. [4, 15]. also, our study showed that most patients had tremor (93.5%), rigidity (87.1%), and bradykinesia (74.2%); 77.4% had tremor as initial symptoms, this similar to the findings of khalda et al. [14] and goes well with what was mentioned in the literature [15]. doi 10.18502/sjms.v14i3.5207 page 86 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher table 5: shows the association between pink1 gene expression and demographic data of the study group. pink1 gene expression p-value yes (%) no (%) age 0.836 • 20–30 8 (88.9) 1 (11.1) • 31–40 3 (100) 0 (0) • 41–50 17 (89.5) 2 (10.5) gender 0.672 • male 17 (89.5) 2 (10.5) • female 11 (91.7) 1 (8.3) marital status 0.719 • married 18 (90) 2 (10) • unmarried 10 (90.9) 1 (9.1) chi-square test was used. table 6: shows the association between pink1 gene with affected family members. pink1 gene expression p-value yes (%) no (%) positive family history 0.575 • yes 13 (92.9) 1 (7.1) • no 15 (88.2) 2 (11.8) degree of relativity (n = 14) • first degree 6 (85.7) 1 (14.3) 0.629 • third degree 2 (100) 0 (0) • first and second degrees 4 (100) 0 (0) regarding the pd signs, the majority of the subjects (87.1%) had hand tremor, it was bilateral in 85.7% and symmetrical in 25%; 54.5% had both types of rigidity (cogwheel and lead pipe) and this was in favor with what was mentioned in the literature [15]. the current study revealed that 45% of the patients had positive family history to pd, this result was similar to bentio et al.’s in denmark [16], and differ from the study of khalda et al. [14] who found that small percentage of the pd patients (11.7%) had positive family history. regarding pink1 gene expression, this study presented that 90.3% of the patients showed positive result. this is similar to those reported by koziorowski et al who found that mutations were identified only in the park2 and pink1 genes with the frequency of 84.7% and 82.7% of subjects, respectively, and they conclude that the frequency of the park2 and pink1 mutations among polish eo–pd patients seems to be high [17]. also, mutations in pink1 were initially identified in early onset, autosomal recessive kindreds. point mutations, frame shift mutations, and truncating mutations have been reported doi 10.18502/sjms.v14i3.5207 page 87 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher throughout the gene. in addition, no significant associations were found between pink1 expression and age, gender, age at onset, and family history (p > 0.05). these findings go in line with what was mentioned in literature [18]. 5. conclusion this study concludes that pink1 gene seems predominant in sudanese patients. it was common among males than females. the most affected age group was found to be in the third and fourth decades. the patterns of the clinical features were generally similar to the literature. pink1 expression was predominant with no significant associations between pink1 expression and age, gender, age at onset, and family history. pink1 gene testing is recommended in all eopd sudanese patients. funding this study was not funded by any organization or institution. conflicts of interest the authors declare that there is no conflict of interest. references [1] parkinson, j. (1817). an essay on the shaking palsy. medical classics, vol. 10, pp. 964–997. [2] charcot, j. m. (1879). lecture v. on paralysis agitans. in: g sigerson g (trans.), lectures on diseases of the nervous system. philadelphia: hc lea. [3] greenfield, j. g. and bosanquet, f. d. (1953). the brain-stem lesions in parkinsonism. journal of neurology, neurosurgery, and psychiatry, vol. 16, pp. 213–226. [4] barbeau a. (1962). the pathogenesis of parkinson’s disease: a new hypothesis. canadian medical association journal, vol. 87, pp. 802–807. [5] birkmayer, w. and hornykiewicz, o. (1962). the l-dihydroxyphenylalanine (l-dopa) effect in parkinson’s syndrome in man: on the pathogenesis and treatment of parkinson akinesis. arch psychiatr nervenkr z gesamte neurol psychiatr, vol. 203, pp. 560–574. doi 10.18502/sjms.v14i3.5207 page 88 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher [6] cotzias, g. c., van woert, m. h., and schiffer, l. m. (1967). aromatic amino acids and modification of parkinsonism. the new england journal of medicine, vol. 276, pp. 374–379. [7] speelman, j. d. and bosch, d. a. (1998). resurgence of functional neurosurgery for parkinson’s disease: a historical perspective. movement disorders, vol. 13, pp. 582–588. [8] jankovic, j. (2001). parkinson’s disease therapy: treatment of early and late disease. chinese medical journal, vol. 114, pp. 227–234. [9] hedrich, k., hagenah, j., djarmati, a., et al. (2006). clinical spectrum of homozygous and heterozygous pink1 mutations in a large german family with parkinson disease: role of a single hit? archives of neurology, vol. 63, pp. 833–838. [10] bonifati, v., rohé, c. f., breedveld, g. j., et al. (2005). early-onset parkinsonism associated with pink1 mutations: frequency, genotypes, and phenotypes. neurology, vol. 65, pp. 87–95. [11] marongiu, r., ferraris, a., ialongo, t., et al. (2008). pink1 heterozygous rare variants: prevalence, significance and phenotypic spectrum. human mutation, vol. 29, p. 565. [12] ricciardi, l., petrucci, s., guidubaldi, a., et al. (2014). phenotypic variability of pink1 expression: 12 years’ clinical follow-up of two italian families. movement disorders, vol. 29, pp. 1561–1566. [13] nishioka, k., kefi, m., jasinska-myga, b., et al. (2010). a comparative study of lrrk2, pink1 and genetically undefined familial parkinson disease. journal of neurology, neurosurgery, and psychiatry, vol. 81, pp. 391–395. [14] prestel, j., gempel, k., hauser, t. k., et al. (2009). clinical presentation of parkinson’s disease among sudanese patients. sudan journal of medical sciences, vol. 4, no. 3, pp. 47–51. [15] witjas, t., kaphan, e., azalay, j. p., et al. (2002). non motor fluctuation in pd frequent and disability. neurology, vol. 59, pp. 408–413. [16] adkin, a. l., frank, j. s., and jog, m. s. (2003). fear of falling and postural control in parkinson’s disease. movement disorders, vol. 18, pp. 496–502. [17] bentio-leon, j., bermejo-pareja, f., rodriguez, j, et al. (2003). prevalence of pd and other types of parkinsonism in three elderly populations of central spain. movement disorders, vol. 18, no. 3, pp. 267–274. [18] koziorowski, d., hoffman-zacharska, d., sławek, j., et al. (2013). incidence of mutations in the park2 and pink1 genes in polish early-onset parkinson disease patients. neurologia i neurochirurgia polska, vol. 47, no. 4, pp. 319–324. doi 10.18502/sjms.v14i3.5207 page 89 sudan journal of medical sciences etedal ahmed a. ibrahim and samer abdalaziz albasher [19] piccoli, c., ripoli, m., quarato, g., et al. (2008). coexistence of mutations in pink1 and mitochondrial dna in early onset parkinsonism. journal of medical genetics, vol. 45, pp. 596–602. [20] al-mubark, b. r., bohlega, s. a., alkhairallah, t. s., et al. (2015). parkinson disease in saudi patients. agenetic study. plos one. doi 10.18502/sjms.v14i3.5207 page 90 introduction problem statement objective methods study variables techniques blood collection genetic analysis (pink1) ethical consideration results discussion conclusion funding conflicts of interest references page 56 research article evaluation of the sensitivity of staphylococcus aureus isolated from nasal swabs to natural honey a molanaei1, sa seyedoshohadaei2 , s hasani3, p sharifi4, m rashidian5, a taherpour5, s tozandehjani6 , s hasani7* 1. department of internal medicine, kurdistan university of medical sciences, sanandaj, iran 2. department of psychiatry, kurdistan university of medical sciences, sanandaj, iran 3. department of microbiology sciences, islamic azad university, sanandaj branch, sanandaj, iran 4. department of microbiology sciences, liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran 5. department of microbiology sciences, kurdistan university of medical sciences, sanandaj, iran 6. department of biology, faculty of sciences, university of kurdistan, sanandaj, iran 7. lung diseases and allergy research center, kurdistan university of medical sciences, sanandaj, iran abstract introduction: bacterial resistance to antibacterial agents is a very serious threat to public health. where some antibacterial agents prove ineffective, the antibacterial properties of honey have been shown to be highly efficacious against several human bacterial pathogens. the purpose of this study is to investigate the sensitivity of staphylococcus aureus isolated from the nursing staff of a hospital to natural honey. methods: in this study, 35 strains of methicillin-resistant s. aureus samples were selected from hospital staff’s nasal swabs. two strains were vancomycin-resistant. the serial dilution tube test methodwas used to determine minimum inhibitory concentration (mic). the susceptibility of each strain of staph bacteria to natural honey without wax was determined and compared with that of a glucose solution with the same density. results: in all strains, except for the two strains resistant to vancomycin, mic level was <8.3% (v/v). the mic of glucose as dense as honey was four times higher. the two vancomycin-resistant strains were completely resistant to natural honey. conclusions: this study has therefore demonstrated that inhibiting bacterial growth is not merely done by purely natural honey not because of osmolality, but vancomycinresistant bacteria are not sensitive to natural honey. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6705 production and hosting by knowledge e how to cite this article: s hasani (2019) “evaluation of the sensitivity of staphylococcus aureus isolated from nasal swabs to natural honey”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 56-64. doi 10.18502/sjms.v15i1.6705 corresponding author: s.hasani@muk.ac.ir. received 09 november 2019 accepted 10 march 2020 published 31 march 2020 production and hosting by knowledge e cc s hasani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: sensitivity, staphylococcus aureus, natural honey, minimum inhibitory concentration sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 57 introduction increased use of complementary medications has led to a lot of interest in traditional treatments. one treatment that has attracted a lot of interest is honey [1]. research shows that honey has functional properties in promoting human health, which can be attributed to its osmolarity and antibacterial characteristics [2]. honey collected from different geographical areas has shown different activities [3], and it has traditionally been used to treat burns, infected and untreated wounds, stomach ulcers, pimples, peptic ulcers, [4], and decrease cough symptoms [5]. it has also been reported that honey has anti-inflammatory, antibacterial, antifungal, and antioxidant effects and is effective against several human bacterial pathogens including escherichia coli, salmonella typhimurium, and staphylococcus aureus [6]. scientists first reported the ability of honey to eliminate microbial diseases in the late 1800s, but with the emergence of antibiotics in the early 1900s, scientists’ interest in honey diminished [7]. however, as resistant pathogens developed, the effect of antibiotics reduced. this kind of bacterial resistance to antibacterial agents is a very serious public health threat [8]. the number of newly developed antibiotics is limited when compared with the increase in the preponderance of bacterial resistance, and there is an increasing need for the development of alternative antimicrobial strategies [9]. therefore, our ability to treat disease effectively depends on the development of new drugs and one potential source of new drugs is traditional medicine [10]. honey has long been offering a wide range of antibacterial properties [11, 12], although the specific anti-bacterial mechanism is unclear [13] and perhaps hydrogen peroxide, organic acids, flavonoids, nectar, bee wax, pollen are the important chemical factors for this property. regardless, it can be considered as an appropriate and safe source of medicinal treatment for humans [14]. therefore, the aim of this study was to investigate the sensitivity of s. aureus to natural honey in samples taken from nursing staff. methods in this laboratory-controlled study, 35 different types of s. aureus with antibiotic properties were collected. the study investigates the sensitivity of s. aureus to natural honey. the honey used in this study was obtained from a farm in a mountainous area. bees produce honey from the dominant plant species. the honey samples used in this investigation were refined and without wax. sugar was used in the study as control for comparison with honey, in the form of glucose. sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 58 sample size: 33 species of these bacteria were resistant to methicillin and 2 species were vancomycin-resistant. the details of vancomycin-resistant strains sensitive are as follows: antibiotic susceptibility of vancomycin-resistant strains and determination of mic and mbc. sample dilution 409820481024512256128643216840 6-----------29-----------determining mic in this study, the minimum inhibitory concentration (mic) of honey was investigated using the test tube serial dilution method [15]. data were collected through tube medium, adding different concentrations of honey and sugar solutions into the tubes and assessing the bacterial growth. each sample comprised of three series of 10 tubes. when the concentration was created, a bacteria culture was produced. this allowed us to determine the mic for bacterial growth in the presence of honey and sugar solution. the test tube serial dilution method is very accurate and sensitive, but it is not routinely used in clinical laboratories. this procedure is done in two micro tubes, in which the mic of a certain bacteria can be calculated. using this method, 10 sterile tubes (dimensions mm 100 × 13) were numbered and one of the tube was considered as the control group. in each of the tubes from 2 to 10, and control tube, 1cc of mullerhinton broth was poured into a sterilized medium and then a sterilized solution made from honey (1 g per 1 ml) (sterilized disposable filter with a pore diameter of 0/45 µm) was added. in tube no 1, 2 ml of culture medium was poured and from tube 1, 1 ml was removed and then added to tube 2 to make 5.0 dilutions; similarly serial dilutions were prepared (twice less than the previous tube); 1 ml of solution was removed from the last tube and thrown away. the control tube had no honey inside. all tubes and pipes were then provided with 1 cc of suspension of bacteria (s. aureus). the complex was incubated for 24 hr at 37ºc. after 24 hr, the tubes were examined. determining mbc the mbc (minimum bactericidal concentration) is obtained in relation to the mic. mbc is usually two to four times as much as mic. the last tube in which bacteria did not grow was considered as the mic. then from the mic tube and the three tubes before that sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 59 (001/0 ml volume) was removed and cultured (such as blood agar newest garya) on a solid medium. after incubation, investigation of mbc’s plates was determined including the density of antibiotics with < 99% growth. as mentioned previously, mbc is usually two to four times of mic. this method was used to evaluate the mic and mbc of honey. to compare the effects of honey and glucose, mic and mbc for glucose were calculated to determine the osmotic effect of honey on the property or its ingredients. in the dilution of glucose as the dilution g/ml 1 was not possible, therefore, a series of tube no. 3 were prepared. data analysis data were analyzed using the spss 18 software and the chi-square test. results the staphylococcus species used in this study were all resistant to glucosacchillin; 33 species of these bacteria were resistant to methicillin and 2 to vancomycin (table 1). table 2 describes the determination of mic and mbc of vancomycin-resistant strains in an antibiotic. the mic for these two species was 0.512 for vancomycin; 35 species were at concentrations of 66/7%, 33/3%, 16/7%, 8/3%, 4/2%, 2/08%, 1/04%, 0/52%, 0/26% (v/v%). honey tube was cultured in vitro and the results of the development and growth of this species are shown in table 3. the 35 species at concentrations of 16/7%, 8/3%, 4/2%, 2/08%, 1/04%, 0/52%, 0/26% of glucose in the culture medium were cultured in tubular environments. table 1: the prevalence of antibiotic of staphylococcus aureus isolated from the nasal  swabs of tohid hospital staff. antibiotic results resistant semi-sensitive sensitive total percentage number percentage number percentage number percentage number glucosaccholine 97 65 1.5 1 1.5 1 67 100 vancomycin 3 2 0 0 97 65 67 100 rifampin 4.5 3 0 0 95.5 64 67 100 erythromycin 4.5 3 9 6 86.5 58 67 100 gentamicin 6 4 0 0 94 63 67 100 penicillin 100 67 0 0 0 0 67 100 ciprofloxacin 1.5 1 0 0 98.5 66 67 100 cefalexin 1.5 1 4.5 3 94 63 67 100 sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 60 table 2: antibiotic susceptibility of vancomycin-resistant strains and determination of mic and mbc. sample dilution 048163264128256512102420484096 6-----------39-----------table 3: growth rate of 35 strains of staphylococcus aureus in different concentrations of natural honey in tubular culture. result concentration (v/v%) growthno growth percentagenumberpercentagenumber 66.75.7294.333 33.311.5488.531 16.714.3585.730 8.334.31265.723 4.21003500 2.081003500 1.041003500 0.521003500 0.261003500 except for concentrations of 1, 0.5, and 0.25, they were grown in all concentrations of glucose. the susceptibility of 35 strains of mic s. aureus are shown in table 4. based on the results, 69/7% of mic species had 8/3% (v/v%). two types of samples of staphylococcus used in the study previously had antibiotic resistance to vancomycin. they showed full resistance to natural honey and grew at all concentrations. in a study of 33 strains of s. aureus which were susceptible to natural honey from the results (table 4), 17 species of staphylococcus (51/8%) had 8.3% mbc (v/v%). in comparison of mic and mbc of staphylococcus species in a medium containing honey and glucose, a significant difference was seen. mic and mbc of honey was at least a quarter of glucose (table 5). table 4: frequency of mic of 33 species of honey-sensitive staphylococcus aureus. percentage (v/v)percentagenumber 66.762 33.33.11 16.721.27 8.369.723 4.200 10033 sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 61 table 5: frequency of mbc of 33 species of honey-sensitive staphylococcus aureus. concentration (v/v)percentagenumber 66.793 33.3124 16.727.29 8.351.817 4.200 10033 discussion based on this study, 94.3% of the tested strains did not grow in 66.7% (v/v%) of honey, and the mic of honey as an antibacterial solution (v/v%) was 8.3%. in the shimaa t. omara study, honey had antibacterial activity and the mic (v/v%) was 5 and 2.5 [16]. in a study by aamer and colleagues, all tested honey showed antibacterial activity against multi-drug-resistant bacterial strains [17]. due to the fact that in the concentration of 8.3% of honey, 94.2% of the bacteria did not grow, but in the case of glucose, all bacteria have grown in this concentration, and even in the concentration of four times this concentration there has been growth of the bacterium in glucose, this study concludes that the lack of growth of the bacterium in the concentration (v/v%) of 8.3% honey is not related to the effect of the concentration and osmotic properties of honey, because in the same concentration of glucose, despite the presence of osmotic, bacterial growth occurred. instead, this study demonstrates that the limited bacterium growth is based on the antibacterial properties of honey, which, according to the af henriques study, can affect cell division in s. aureus [18]. in the study of r. a. cooper et al., honey bacterial inhibition was not exclusively related to honey osmolarity [19]. in a study by mulhouse vebert, the mic of honey in the case of staphylococcus coagulase positive 25% (v/v) has been reported [20], which is not consistent with our study. this difference can be due to other honey or honey-producing plant material [21]. in our study, the two strains that had a complete resistance to vancomycin also completely resisted natural honey. however, in the study of mulan and colleagues, which compared antibiotic susceptible strains with antibiotic-resistant strains, there was no significant difference in the presence of honey [19]. the results of the present study indicate that honey has an antibacterial effect similar to vancomycin, and 33 species of s. aureus are susceptible to honey from amongst the 35 species susceptible to sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 62 vancomycin, but the two species resistant to vancomycin are also resistant to honey, which can be used as substituting vancomycin for s. aureus and studying it. as noted in the study, honey can be considered as a substitute therapy against specific bacteria [22] and the separation of active ingredient honey is a good way to deal with infection [23]. recommendations our study shows that honey has antimicrobial effects similar to vancomycin, so honey can be considered as an alternative to vancomycin in staphylococcus infection and it can also be studied further. conflict of interest the authors report no conflict of interest or any source of financial support for the research. data availability the data used to support the findings of this study are included within the article. references [1] lusby pe, coombes al, wilkinson jm (2005). bactericidal activity of different honeys against pathogenic bacteria. archives of medical research. 36(5): 464–467. [2] estevinho l, pereira ap, moreira l et al. (2008) antioxidant and antimicrobial effects of phenolic compounds extracts of northeast portugal honey. food and chemical toxicology. 46(12): 3774–3779. [3] noori a, al ghamdi a, ansari mj et al. (2013). differences in composition of honey samples and their impact on the antimicrobial activities against drug multiresistant bacteria and pathogenic fungi. archives of medical research. 44(4): 307–316. [4] yaghoobi r, kazerouni, a (2013). evidence for clinical use of honey in wound healing as an anti-bacterial, anti-inflammatory anti-oxidant and anti-viral agent: a review. jundishapur journal of natural pharmaceutical products. 8(3): 100. [5] oduwole o, udoh ee, oyo-ita a et al. (2018). honey for acute cough in children. cochrane database system review. 4(3): cd007094. sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 63 [6] jantakee k, tragoolpua y (2015). activities of different types of thai honey on pathogenic bacteria causing skin diseases, tyrosinase enzyme and generating free radicals. biological research. 48(1): 4. [7] mcloone p, warnock m, fyfe l (2016). honey: a realistic antimicrobial for disorders of the skin. journal of microbiology, immunology and infection. 49(2): 161–167. [8] mandal md, mandal s (2011). honey: its medicinal property and antibacterial activity. asian pacific journal of tropical biomedicine. 1(2): 154–160. [9] iqbal mn, anjum aa, ali ma et al. (2015). assessment of microbial load of unpasteurized fruit juices and in vitro antibacterial potential of honey against bacterial isolates. the open microbiology journal. 9: 26–32. [10] moussa a, noureddine d, abdelmelek m et al. (2012). antibacterial activity of various honey types of algeria against pathogenic gram–negative bacilli: escherichia coli and pseudomonas aeruginosa. asian pacific journal of tropical disease. 2(3): 211–214. [11] cooper r, halas e, molan p (2002). the efficacy of honey in inhibiting strains of pseudomonas aeruginosa from infected burns. the journal of burn care & rehabilitation. 23(6): 366–370. [12] majtan j (2014). honey: an immunomodulator in wound healing. wound repair and regeneration. 22(2): 187–192. [13] nassar hm, li m, gregory rl (2012). effect of honey on streptococcus mutans growth and biofilm formation. applied and environmental microbiology. 78(2): 536–540. [14] omoya f, akharaiyi f (2011). mixture of honey and ginger extract for antibacterial assessment on some clinical isolates. international journal of pharmaceutical and biomedical research. 2(1): 39–47. [15] wasihun ag, kasa bg (2016). evaluation of antibacterial activity of honey against multidrug resistant bacteria in ayder referral and teaching hospital, northern ethiopia. springerplus. 5(1): 842. [16] omara st (2017). mic and mbc of honey and gold nanoparticles against methicillinresistant (mrsa) and vancomycin-resistant (vrsa) coagulase-positive s. aureus isolated from contagious bovine clinical mastitis. journal of genetic engineering and biotechnology. 15(1): 219–230. [17] aamer a, abdul-hafeez, m, sayed s (2014). minimum inhibitory and bactericidal concentrations (mic and mbc) of honey and bee propolis against multi-drug resistant (mdr) staphylococcus sp. isolated from bovine clinical mastitis. alternative & integrative medicine. 3(4): 1–9. sudan journal of medical sciences a molanaei et al. doi 10.18502/sjms.v15i1.6705 page 64 [18] henriques a, jenkins r, burton n et al. (2010). the intracellular effects of manuka honey on staphylococcus aureus. european journal of clinical microbiology & infectious diseases. 29(1): 45. [19] cooper r, molan p, harding k (2002). the sensitivity to honey of gram‐positive cocci of clinical significance isolated from wounds. journal of applied microbiology. 93(5): 857–863. [20] molan p, brett m eds. (1998). honey has potential as a dressing for wounds infected with mrsa. the second australian wound management association conference brisbane, australia. [21] mullai v, menon t (2007). bactericidal activity of different types of honey against clinical and environmental isolates of pseudomonas aeruginosa. the journal of alternative and complementary medicine. 13(4): 439–442. [22] al-naama rt (2009). evaluation of in-vitro inhibitory effect of honey on some microbial isolate. african journal of bacteriology research. 1(6): 64–67. [23] noori a, al-ghamdi a, ansari mj et al. (2012). synergistic effects of honey and propolis toward drug multi-resistant staphylococcus aureus, escherichia coli and candida albicans isolates in single and polymicrobial cultures. international journal of medical sciences. 9(9): 793. sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.5503 production and hosting by knowledge e research article comparison between students’ perception toward an examination and item analysis, reliability and validity of the examination assad ali rezigalla1, ali mohammed elhassan eleragi1, masoud ishag elkhalifa2, and ammar mohammed ali mohammed3 1department of basic medical sciences, college of medicine, university of bisha, bisha 61922, p.o. box 551, saudi arabia 2department of medical education, college of medicine, university of bisha, bisha 61922, p.o. box 551, saudi arabia 3department of anatomy, faculty of medicine, international university of africa, khartoum, sudan. abstract introduction: while student’s perception of an exam is a reflection of their feelings toward the exmination items, item analysis is a statistical analysis of their responses to examination items. the study aims to compare students’ perception toward the difficulty of an examination with the results of item analysis and examination reliability and validity. materials and methods: this is a cross-sectional study conducted in the college of medicine between january and april 2019. the study uses a structured questionnaire and standardized item analysis of students’ examination. results: overall, 80 items were analyzed in this study. kuder–richardson formula 20 of the examination was 0.906. the average difficulty index of the examination items was 69.4 (± 21.86). the response rate of the questionnaire was 88.9% (40/45). students considered the examination as easy (70.4%). students’ perception toward the difficulty of the individual items shows a moderate positive correlation between easy perception and difficulty index (r = 0.7033, p = 0.00001), which means there is a tendency for high difficulty index to go with high easy perception (and vice versa). moderate negative correlations were reported between moderate (r = –0.2969, p = 0.008082) and difficult (r = –0.6094, p = 0.00001) perception to individual items’ difficulty and difficulty index. a significant moderate positive correlation (r = 0.615, p = 0.00001) was reported between the difficulty index and items covered within the specific learning outcomes. conclusion: students’ perception toward items difficulty is aligned with the standard difficulty index of items. their perception can support the evidence of examination validity. the constructions of items from the covered outcomes result in an acceptable level of item and examination difficulties. keywords: students’ perception, item analysis, assessment, difficulty index, internal consistency how to cite this article: assad ali rezigalla, ali mohammed elhassan eleragi, masoud ishag elkhalifa, and ammar mohammed ali mohammed (2020) “comparison between students’ perception toward an examination and item analysis, reliability and validity of the examination,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 114–123. doi 10.18502/sjms.v15i2.5503 page 114 corresponding author: assad ali rezigalla; email: assadkafe@yahoo.com received 24 april 2020 accepted 15 june 2020 published 30 june 2020 production and hosting by knowledge e rezigalla et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:assadkafe@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences rezigalla et al 1. introduction students’ perception of an examination is defined as a reflection of their feelings toward the examination items. while item analysis refers to a statistical analysis of students’ responses to examination items. the two represent different perspectives about examination items. the assessment is considered to be valid if it measures what is intended to be measured and reflects the educational contents [1, 2]. construct validity denotes ”a unitary concept, requires multiple lines of evidence, to support the appropriateness and meaningfulness of the specific inferences made from test scores” [3]. the validity and reliability of exmination can be adversely impacted by the mismatch between the level of cognition in the assessment and the educational task [1, 4]. this mismatch can appear in the form of too many easy or difficult items. item analysis is used to evaluate the quality of items and consequently helps in the improvement of the assessment process. an assessment can be improved by refining the defective items or deleting the poorly constructed ones from the question bank [5–7]. the parameters of item analysis include the difficulty index (dif) as well as the index of the internal consistency, that is, kuder–richardson formula 20 (kr-20). the dif refers to the percentage of the examinees who answered the item correctly. it ranges from 0 to 100%, with a higher value indicating an easy item index (8). meanwhile, internal consistency is commonly measured through cronbach’s α (coefficient alpha) [5, 9, 10]. coefficient alpha is known to be identical to the kr-20 in the case of type a mcqs [5, 11, 12]. different ranges and interpretations of item analysis parameters, as well as internal consistency, have been published in extant literature [9, 12–17]. the college of medicine, university of bisha, saudi arabia (ubcom) has adopted innovative student-centered teaching, problem-based learning, an integrated curriculum, community-based teaching, electives with core, and the use of a systematic methods curriculum (spice). problem-based learning is the principle educational strategy in addition to the team-based learning, seminars, case-based learning, and practical. the program offers bachelor of medicine, bachelor of surgery (mb, bs) following the successful completion of 12 semesters (six years) [18, 19]. students’ perception is widely used and recommended in the field of medical education. data generated from students’ perception can provide valuable information about faculty, the achievement of educational objectives, and instructional methods [20, 21] besides being considered as a reliable and valid indicator of effective teaching [22]. doi 10.18502/sjms.v15i2.5503 page 115 sudan journal of medical sciences rezigalla et al the study aims to compare students’ perception toward the difficulty index of an examination with the results of the item analysis and examination reliability and validity. 2. materials and methods 2.1. study area the study was conducted at ubcom between january and april 2019. 2.2. study design the study desgin is cross sectional study [23]. 2.3. study population all students registered for the course of principles of human diseases (2016–2017) were included in the study (n = 40). the exclusion criteria of the study included students who refused to participate or those who did not fill the questionnaire. the particpating students filled the questionnaire immediately after completing the examination without identification. 2.4. sample size the sample size is the total coverage. 2.5. materials the study used a standardized item analysis of the final course examination and a questionnaire. the examination used in this study was from the course of principles of human diseases. it is conducted in semester two of the second year (n = 45). the course is integrated and multidisciplinary. the course examination was developed by the course committee using course blueprint and then approved by the students’ assessment committee (sac) of ubcom. it was comprised of type a mcqs. the number of examination items (n = 80) was adjusted according to the course blueprint and the tested domains [24]. each item is composed of stem and four options, three distractors, and a single doi 10.18502/sjms.v15i2.5503 page 116 sudan journal of medical sciences rezigalla et al best answer. the correct answer is awarded one mark and no marks for blank or wrong selection. the examination was marked automatically (datalink 1200 – apperson system) and double-checked by the examination officer and course coordinator. standard item analysis was obtained and processed for the study. the study used a questionnaire to evaluate students’ perception of the examination items and standard item analysis of the examination. the questionnaire was developed to gain a deep understanding of students’ perception toward the examination in general and examination items in particular. it was developed by the authors in consultation with medical education experts and statisticians and consisted of two parts. part consisted of a three-point likert scale (easy, moderate, and difficult). the mode of covering specific learning outcomes (slo) from which the items were constructed was assessed through a two-point likert scale (covered or not covered). the second part encompassed the number of items, their mode of covering the course contents, and the ability of examination to assess students. this part was evaluated through a three-point likert scale (yes, not sure, and no). the questionnaire was tested through a pilot study. the internal consistency of the questionnaire was 0.79. data generated from the pilot study were not included in the study. 2.6. data collection the questionnaire was distributed to students in the last five min of the examination, and those who finished early were given the questionnaire after they left the examination hall. the data was collected by the authors. all students were informed that participation in the study had no impact on their academic performance in the long or short term. 2.7. statistical analyses the data obtained from the questionnaires and the standard item analysis were analyzed using spss, version 20 (armonk, ny: ibm corp, usa). descriptive statistics and pearson correlation coefficient were applied to measure the significance of difference and correlation among different variables. the level of significance was fixed at 95%, confidence interval and p-value < 0.05 was considered as significant. doi 10.18502/sjms.v15i2.5503 page 117 sudan journal of medical sciences rezigalla et al 2.8. ethical consideration the study was approved by the research and ethics committee. all students who participated in the study gave a written consent. 3. results 3.1. item analysis the total number of the analyzed items was 80. the average class score was 55.5 (69.38%). class median was 56.0 (70.0%). kr-20 of the examination was 0.906. students’ passing rate was 32.5% (passing marks = 60). the average dif of the examination was 69.4 (±21.86). the exmination items were classified into difficult, moderate (acceptable), and easy (table 1). table 1: classification of examination items according to difficulty index. parameters ubcom pande et al., 2013 [13] mitra et al., 2009 [16] interpretation % interpretation % interpretation % easy > 80 35 easy ( >70) 52.5 easy ( >80) 35 moderate (25–80) 62.5 acceptable (30–70) 42.5 acceptable (30–80) 60di difficult (0–25) 2.5 difficult (< 30) 5 difficult (< 30) 5 di, difficulty index figure 1: correlation of student’s perception toward item difficulty and the standard difficulty index of items. doi 10.18502/sjms.v15i2.5503 page 118 sudan journal of medical sciences rezigalla et al figure 2: correlation between the difficulty index of items and the specific learning outcome. 3.2. students’ perception the response rate of the questionnaire was 72.5% (29/40) and 11 students refused to participate in the study. the averages of students’ perception toward items’ difficulty were easy (70.4%), moderately difficult (18.5%), and difficult (11.1%). for 57% of the students, the examination coveredthe entire course. the distribution of examination items across the course content was equal for 64% of the students. while only 38% thought that the examination could assess them, 70% of the students reported that the number of questions was adequate to assess them. the majority of students (92%) believe that the examination items were covered during course instruction. a moderate positive correlation was reported between easy perception and dif (r = 0.7033, p = 0.00001), which means high dif is associated with high easy perception. high dif of an item indicates its easiness. moderate negative correlation was reported between moderate (r = –0.2969, p = 0.008082) and difficult (r = –0.6094, p = 0.00001) students’ perception and dif (figure 1). a significant moderate positive correlation (r = 0.615, p = 0.00001) was reported between dif and items from covered slos (figure 2). doi 10.18502/sjms.v15i2.5503 page 119 sudan journal of medical sciences rezigalla et al 4. discussion the kr-20 of the examination (reliability coefficient) was 0.906, and the majority of examination items were within the acceptable range of difficulty (62.5%). these findings support the validity of the examination. according to some authors [1, 9, 14, 17, 25], kr-20 value of 0.8 or above is ideal and demonstrate excellent reliability of the examination. it has been reported that the presence of too many easy or difficult items can affect both examination validity and reliability [1, 4]. the average class score and class median were 55.5 and 56.0, respectively. these values suggest that the number of students who performed very well was the same as those with low performance. examination set-up, such as the construction of the examination by the expert staff who were involved in teaching and using the blueprint, supports the content form of validity [1, 2, 15, 24]. also, the presence of an acceptable percentage of students who pass the examination supports the construct form of validity [26]. students reported that the examination covered the course contents in a wellbalanced manner, and the number of items was adequate to assess them. these findings of students’ perception support the validity of the examination since an examination is considered valid if it measures what is intended to measure and reflects the educational contents. these findings are supported by the previous works of carmines et al. and brown et al. [15, 27] who reported that the validity is based on the extent to which a measurement reflects the specific intended content. the average dif of examination, according to the standard item analysis, was 69.4. the average student’s perception of examination difficulty is easy (70.5%) and shows a significant positive correlation (r = 0.7033, p = 0.00001) with dif. the average examination difficulty is considered good and acceptable according to the college assessment policy and literature [13, 14, 16]. in any examination or test, the average difficulty of items is adjusted according to the required competencies and student-level [1]. the current findings of students’ perception toward examination difficulty suggested that they underestimated the examination difficulty. students commonly underestimate their performance rather than the examination difficulty [1, 28, 29]. van de watering reported that students’ perception toward examination difficulty differs according to their performance in the examination and students with higher scores underestimate their performance while students with lower scores have more accurate estimations [1]. according to the examination result, the upper students represent 72.5%. however, the class mean and average are relatively similar (55.5 and 56.0, respectively). the result doi 10.18502/sjms.v15i2.5503 page 120 sudan journal of medical sciences rezigalla et al suggested a good student’s performance. these findings support the work of van de watering [1]. the limitation of the study includes the fewer number of students and the application of the study on one course. the strength of the study is that the test is considered valid and reliable through several pieces of evidence. 5. conclusion students’ perception toward items difficulty is aligned with the standard dif of the examination items. their perception support the evidence of examination validity. the constructions of items from the covered outcomes result in an acceptable level of item and examination difficulties. acknowledgments the authors would like to thank the students who participated in the study. they are also thankful to dr elwathiq khalid, dr k. salih, dr e. miskeen, dr i. jack, dr m. elhassan and all their colleagues. they are especially thankful to mr. m. k. abid for the statistical analysis and helpful comments and to the college dean and administration for their help and allowing the use of facilities. references [1] van de watering, g. (2006). teachers’ and students’ perceptions of assessments: a review and a study into the ability and accuracy of estimating the difficulty levels od assessment items. educational research review, vol. 2, no. 1, pp. 133–147. [2] mcmillan, j. h. (2012). sage handbook of research on classroom assessment. sage. [3] american educational research association, american psychological association, and national council on measurement in education. (1985). standards for educational and psychological testing. washington dc: american educational research association. [4] linn, r. l. (1993). educational measurement. american council on education series on higher education. oryx pr. [5] considine, j., botti, m., and thomas, s. (2005). design, format, validity and reliability of multiple choice questions for use in nursing research and education. collegian, doi 10.18502/sjms.v15i2.5503 page 121 sudan journal of medical sciences rezigalla et al vol. 12, no. 1, pp. 19–24. 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(2009). the levels of difficulty and discrimination indices in type a multiple choice questions of pre-clinical semester 1, multidisciplinary summative tests. iejsme, vol. 3, no. 1, pp. 2–7. [17] streiner, d. l. (2003). starting at the beginning: an introduction to coefficient alpha and internal consistency. journal of personality assessment, vol. 80, no. 1, pp. 99– 103. [18] ibrahim, m. e. and al-shahrani, a. m. (2018). implementing of a problem-based learning strategy in a saudi medical school: requisites and challenges. international journal of medical education, vol. 9, p. 83. doi 10.18502/sjms.v15i2.5503 page 122 sudan journal of medical sciences rezigalla et al [19] ibrahim, m. e., al-shahrani, a. m., abdalla, m. e., et al. (2018). the effectiveness of problem-based learning in acquisition of knowledge, soft skills during basic and preclinical sciences: medical students’ points of view. acta informatica medica, vol. 26, no. 2, p. 119. [20] aleamoni, l. m. (1999). student rating myths versus research facts from 1924 to 1998. journal of personnel evaluation in education, vol. 13, no. 2, pp. 153–166. [21] zhao, j. and gallant, d. j. (2012). student evaluation of instruction in higher education: exploring issues of validity and reliability. assessment & evaluation in higher education, vol. 37, no. 2, pp. 227–235. [22] marsh, h. w. (1984). students’ evaluations of university teaching: dimensionality, reliability, validity, potential baises, and utility. journal of educational psychology, vol. 76, no. 5, p. 707. [23] rezigalla, a. a. (2020). observational study designs: synopsis for selecting an appropriate study design. cureus, vol. 12, no. 1. [24] abdellatif, h. and al-shahrani, a. m. (2019). effect of blueprinting methods on test difficulty, discrimination, and reliability indices: cross-sectional study in an integrated learning program. advances in medical education and practice, vol. 10, p. 23. [25] sullivan, g. m. (2011). a primer on the validity of assessment instruments. chicago, il: the accreditation council for graduate medical education. [26] van der vleuten, c. (2000). validity of final examinations in undergraduate medical training. bmj, vol. 321, no. 7270, pp. 1217–1219. [27] brown, s. and knight, p. (2012). assessing learners in higher education. abingdon, united kingdom: routledge. [28] rezigalla, a. a. (2015). angoff’s method: the impact of raters’ selection. saudi journal of medicine and medical sciences, vol. 3, no. 3, p. 220. [29] dochy, f. j. r. c. (1992). assessment of prior knowledge as a determinant for future learning: the use of prior knowledge state tests and knowledge profiles. centre for educational technology and innovation, open university. doi 10.18502/sjms.v15i2.5503 page 123 introduction materials and methods study area study design study population sample size materials data collection statistical analyses ethical consideration results item analysis students' perception discussion conclusion acknowledgments references sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5211 production and hosting by knowledge e research article prevalence and risk factors for hepatitis b infection among pregnant women attending antenatal clinic in um dafog area, south darfur state, sudan abdalla hassan mudardum1 and abbakar adam mohammed2 1health officer, ministry of heath, south darfur state, sudan/zoa international, nyala office 2epidemiology and public health, department of preventive medicine & public health, faculty of veterinary science, university of nyala abstract background: sudan is an endemic country for hepatitis b virus (hbv). screening for hbv during pregnancy may help in instituting interventions to minimize vertical transmission. hbv in pregnant women in remote areas of darfur were uncovered by the previous studies in sudan, objectives: this study was aimed to determine the seroprevalence of hbv and the possible risk factors for its acquisition among antenatal care attendants in um dafog area, south darfur state, sudan. methods: a cross-sectional study was conducted between july 2018 and january 2019 in um dafog area. blood samples were collected from 165 (143 from sudan and 22 from central african republic) pregnant women attending the antenatal um dafog clinic. serum was separated and tested for hbv marker using rapid hbsag test. information on socio-demographic and other pertinent data was collected using a structured questionnaire. informed consent was obtained and confidentiality of personal data was assured. results: hbsag was detected in 8.5% of study population. participants from central african republic recorded higher prevalence (18.2%) than those from sudan (7%). however, there was no significant association (p > 0.05) between prevalence of hbsag and residence, history of blood transfusion, tattooing, circumcision, surgical procedure, cupping therapy, caesarean section, ear piercing, unsafe injection, and jaundice or liver problems. conclusion: the study concluded that the prevalence of hbv among pregnant women in um dafog area is of high endemicity according to the who, hence the need for established public health interventions that lead to reduction of hbv transmission. keywords: hepatitis b, pregnant women, um dafog, sudan how to cite this article: abdalla hassan mudardum and abbakar adam mohammed (2019) “prevalence and risk factors for hepatitis b infection among pregnant women attending antenatal clinic in um dafog area, south darfur state, sudan,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 116–125. doi 10.18502/sjms.v14i3.5211 page 116 corresponding author: abbakar adam mohammed; email: abbakarad67@yahoo.com received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e abdalla hassan mudardum and abbakar adam mohammed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abbakarad67@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed 1. introduction hepatitis b virus (hbv) infection is a serious public health problem worldwide. it is caused by the hbv that infects the liver and causes hepatocellular necrosis, carcinoma, and inflammation [1]. many of the carriers do not realize that they are infected with the virus rendering the hbv to be known as a silent killer [1].the main modes of horizontal transmission of hbv are unprotected sexual contact with an infected individual, inadvertent percutaneous or mucosal contact with blood or infectious body fluids among people in close daily contact (household members) through ear piercing, cupping therapy, or sharing needles and syringes among injecting drug users, or from an infected mother to her baby at birth [2, 3]. hbv poses a risk to healthcare workers who sustain accidental needle stick injuries while caring for hbv-infected people [4]. uncommon vertical transmission is generally associated with antepartum hemorrhage and placental tears [4], and it depends on the time at which a pregnant woman acquired the hbv infection [5]. unsafe blood transfusion, female circumcision, surgical and dental procedures, intravenous drug abuse, and some socio-demographic factors are the common risk factors but vary globally depending on religious and cultural backgrounds of the communities [6]. worldwide, hepatitis b surface antigen (hbsag) seroprevalence varies markedly by geographical region, with the highest prevalence (> 5%) in sub-saharan africa, east asia, some parts of the balkan regions, the pacific islands, and the amazon basin of south america, while prevalence below 2% is in central latin america, north america, and western europe [1]. the prevalence of hbv among pregnant women referring to prenatal healthcare or admitted for birth in some african countries was found to be 3.2% in eritrea [7], 6.9% in ethiopia [8], 11.8% in northern uganda [9], 10.6% in central african republic [10], 11% in south sudan[11], and 9.0% in nigeria [12]. studies on prevalence and risk factors associated with hbv acquisition among pregnant women attending antenatal care clinics in different parts of the sudan revealed a prevalence of 7.5% among pregnant sudanese women attending antenatal clinic at the khartoum teaching hospital [13], 6.8% in central sudan [14], 5.6% in the omdurman maternity hospital [15], 5.1% in the wad medani maternity hospital [16], and 18% in al fashir town [17]. on other cross-sectional studies conducted in nyala, a prevalence of 6.25% was reported among blood donors [18]. antenatal screening for hbsag to all pregnant women and treating those hbv-infected before delivery and vaccination of their babies at birth has been recommended widely to prevent transmission around birth, yet it is not a routine practice in most health settings of sudan [1]. doi 10.18502/sjms.v14i3.5211 page 117 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed information on the situation of the disease in remote marginalized areas of the sudan with limited healthcare facilities is scarce, therefore this study is focused to determine the seroprevalence and to evaluate the risk factors associated with hepatitis b infection among pregnant women attending the antenatal care clinic (anc) in the um dafog area, south darfur state. 2. methods 2.1. study area the study was carried out in the um dafog area, south darfur state, at the um dafog clinic which is the only health facility including the reproductive health service. it serves around 400 pregnant women visiting the anc annually. the reproductive health service is operated by the rufida health foundation(rhf), a non-governmental organization. um dafog town (approximately 350 km far from nyala, the capital of south darfur state) is the headquarter of the um dafog locality, which is located in the southern west of south darfur state, sharing the border with central african republic (figure 1). the estimated number of population of the town is around 30,000. the livelihood activities include cash crop farming, pastoral farming, fishing, border trade, and seasonal labor. 2.2. study design and data collection the study was a descriptive cross-sectional study conducted for six months period extending from july 2018 to january 2019. the study population consisted of all pregnant women attending the anc for routine check-up and those that matched the inclusion criteria (confirmed pregnancy, had not been vaccinated against hepatitis b, and did not know their hepatitis b status) during the study period. all pregnant women who were vaccinated against hbv or had previously tested positive for any hepatitis b sero-markers were excluded. pregnant mothers who attended the clinic for more than one visit during the study period were excluded for subsequent visits using a unique mark on their cards. finger stick whole blood drop was aseptically collected by using sterile lancet and sample dispensing plastic dropper, and serum was separated and tested for hbsag using rapid hbv surface antigen test (advanced quality one step hbsag test); the result was red according to the manufacturer’s instructions (ith biotech company, 2016). doi 10.18502/sjms.v14i3.5211 page 118 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed information on socio-demographic and other pertinent data were collected using a structured questionnaire that was adapted from the standard who protocol for the assessment of hepatitis b infection in antenatal patients. 2.3. ethics approval and consent to participate the study was approved by the research directorate, ministry of health, south darfur state (ref. 1/b/50:n) and informed consent was obtained from all participants before the collection of samples and data. 2.4. data processing and analysis the data was processed and analyzed by using statistical package for social sciences (spss) version 21. chi-square and fisher exact test were used to test if there is significant association between the occurrence of hbv and different variables at 95% confidence level. odds ratio (or) with their 95% confidence intervals (ci) was calculated to estimate the magnitude of the association between hbsag positivity and the study variables as possible risk factors; p < 0.05 was considered significant. 3. results a total of 165 eligible study participants were recruited into the study with their consent, 143 (87%) were from sudan and 22 (13%) from central african republic. of the 165 subjects, 14 (8.5%) were tested positive for hepatitis b infection using advanced quality hbsag rapid test (figure 2). most of the pregnant women enrolled in the study were in the age group 20– 30 yr (57.6%). the youngest age noted during the study period was 15 yr, while the oldest being 40 yr (86%), with mean age ± sd of 27.64 ± 4.53. the distribution of hbsag positive pregnant women according to their socio-demographic characteristics including age, residence, marital status, occupation, and level of education is shown in table 1. different potential risk factors for hepatitis b infection including the history of blood transfusion, surgical procedure, dental procedure, tattooing/traditional mark, cupping therapy, unsafe injection, caesarean section, ear piercing, jaundice, jaundice among husbands of participants, and female genital circumcision were assessed. the statistical doi 10.18502/sjms.v14i3.5211 page 119 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed figure 1: a map of south darfur state showing the study area. analysis of data revealed no significant association (p > 0.05) between the prevalence rate of hbsag and studied potential risk factors (table 2). 4. discussion this descriptive cross-sectional hospital-based study was carried out at the um dafog clinic, south darfur state to determine the prevalence and evaluate the risk factors of hepatitis b viral infection among pregnant women attending the anc. the present findings were believed to be the first data of hbv seroprevalence among pregnant women in south darfur state. the overall prevalence rate of hepatitis among pregnant women in the um dafog area was found to be 8.5%, which is higher than the who cut-off level of endemicity (8%), hence classifying the area as highly endemic. this result is close similar to 8.2% in the central african republic that was reported by doi 10.18502/sjms.v14i3.5211 page 120 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed figure 2: the test result of hbsag among pregnant women attending antenatal care (anc) clinic at the um dafog area, south darfur state, sudan during july 2018 to january 2019. komas et al. [19], but it is higher than 5.6%, 5.1%, and 7.5% that reported by elsheikh et al., osman et al., and abuelgasim [13, 15, 16] at the omdurman maternity hospital, central sudan and khartoum teaching hospital, respectively. however, it is much lower that the result of el gasim et al. [17] who found 18% positive cases for hbsag among pregnant women attending antenatal clinics in al fashir, north darfur state. these variations in the prevalence rate may be due to the differences in efficiency of exposure and cultural backgrounds of the communities or to the sensitivity of different diagnostic tests used. the age-specific prevalence of hbv showed that women < 20 yr old were with the highest hbv prevalence (9.4%), while the age group 31–40 yr was found free of hbv. the community under the study is semi-nomadic community, and usually young girls are married at a very tender age, this could explain why we have included this age group. this result is similar to that recorded by bayo et al. [9] in uganda who found the highest hbsag positivity (20%) in women aged 20 yr or less, but in contrast with the result of abioye et al. [12] who recorded the highest hbsag positivity (15.78%) for those aged 37–48 yr. this could be due to community exposure to risk factors. the prevalence rate among pregnant women residing in the central african republic was found to be higher (18.2%) than among those from sudan (7%). this might be attributed to geographical variations and the cultural and behavioral differences regarding the exposure to possible risk factors of hbv infection. doi 10.18502/sjms.v14i3.5211 page 121 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed table 1: distribution of hbsag-positive pregnant women according to their socio-demographic characteristics. characteristic no. tested hbsag +ve frequency % age/years > 20 64 6 9.4 20–30 95 8 8.4 31–40 6 0 0.0 residence area sudan 143 10 7.0 central african republic 22 4 18.2 marital status single 6 1 16.7 married 158 13 8.2 divorced 1 0 0.0 occupation house wife 107 10 9.3 business 2 0 0.0 farmer 55 4 7.3 employee 1 0 0.0 educational level illiterate 63 5 7.9% khalwa (school of holy quran) 27 3 11.1% primary (basic) school 57 5 8.8% secondary school 17 1 5.9% university graduate 1 0 0.0% total 165 14 8.5 several potential risk factors for contracting hbsag were evaluated including the history of blood transfusion, surgical and dental procedures, ear piercing, tattooing, cupping therapy, unsafe injection, caesarean section, female genital circumcision, liver problem or jaundice, husband’s history of jaundice, and abortion or miscarriage. no significant association was observed between the studied risk factors and hbsag. this agrees with the results of elsheikh et al. [15] in omdurman, however, significant relationship between hbsag positivity and mother’s history of surgery, jaundice, blood transfusion and jaundice in the husbands was seen in a study carried out in khartoum [13]. a study carried out in al fashir found a significant association between hbv infection and some factors included residence, income, occupation, bloodletting, and ear piercing [17]. these variations may be attributed to the sensitivity of diagnostic tests used or cultural and behavioral differences. doi 10.18502/sjms.v14i3.5211 page 122 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed table 2: p-value and odds ratio analysis of the possible risk factors for hbsag among the study population. variable no. studied no. +ve (%) *p-value odds ratio 95% confidence interval blood transfusion 7 0 0.00 0.41 0.69 0.3–1.86 surgical procedure 11 1 9.09 0.94 0.78 0.7–2.5 dental procedure 10 1 10.00 0.86 0.82 0.6–1.9 tattooing 20 0 0.00 0.15 0.98 0.5–2.3 cupping therapy 23 1 4.35 0.44 0.79 0.3–1.84 unsafe injection 7 0 0.00 0.41 0.96 0.6–1.7 caesarean section 9 0 0.00 0.35 1.0 0.5–1.88 ear piercing 159 12 7.55 0.10 0.99 0.6–2.7 liver problem or jaundice 50 5 10.00 0.65 0.93 0.3–1.7 husband’s jaundice 27 4 14.81 0.20 0.66 0.6–2.1 abortion or miscarriage 45 5 11.11 0.46 0.70 0.4–1.2 female circumcision 149 13 8.72 0.74 0.87 0.5–2.4 *p-value < 0.05 is considered significant. 4.1. limitations of the study regarding the high prevalence of hbsag in the current study; the duration of the study is short, based only on the detection of hbsag by rapid test, and the population investigated consisted only of women who were able to access antenatal care, thus the prevalence reported here may have underestimated the true prevalence among pregnant women in the larger community. 5. conclusion the study concluded that hbv infection is prevalent among pregnant women in the um dafog area and classifies it as high zone of endemicity according to the who, so further studies covering larger community using robust diagnostic techniques are highly recommended to support these findings. furthermore, all pregnant women should be screened for hbv, treated if necessary to reduce their viral loads, and their children being should be vaccinated at birth with the single-dose hepatitis b vaccine to break the cycle of mother-to-child transmission. acknowledgements the authors are grateful to the participants for their participation and co-operation. the authors are indebted to the laboratory staff of the um dafog clinic for their assistance doi 10.18502/sjms.v14i3.5211 page 123 sudan journal of medical sciences abdalla hassan mudardum and abbakar adam mohammed during data collection and operating procedures for the laboratory tests. provision of some laboratory materials by the ministry of health, south darfur state, is acknowledged. references [1] who. 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[17] el gasim, r. a., eltayeb, n., and el khidir, i. (2019). hepatitis b virus infection in pregnant women, in al fashir town, north darfur state, sudan. open journal of medical microbiology, vol. 9, pp. 28–36. [18] abou, m. a., eltahir, y. m., and ali, a. s. (2009). seroprevalence of hepatitis b virus and hepatitis c virus among blood donors in nyala, south darfur, sudan. virology journal, vol. 6, p. 146. retrieved from: https://doi.org/10.1186/1743-422x-6-146 [19] komas, n. p., ghosh, s., abdou-chekaraou, m., et al. (2018). hepatitis b and hepatitis d virus infections in the central african republic, twenty-five years after a fulminant hepatitis outbreak, indicate continuing spread in asymptomatic young adults. plos neglected tropical diseases, vol. 12, no. 4. doi: 10.1371/journal.pntd.0006377. doi 10.18502/sjms.v14i3.5211 page 125 https://doi.org/10.1186/1743-422x-6-146 introduction methods study area study design and data collection ethics approval and consent to participate data processing and analysis results discussion limitations of the study conclusion acknowledgements references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5905 production and hosting by knowledge e research article ceftriaxone drug utilization evaluation (due) at prince abdulaziz bin moussae’ed hospital, arar, kingdom of saudi arabia muhammad jan shamsur rehman1, majed alrowaili2, abdul wajed abdul rauf3, and elhassan hussein eltom1 1department of pharmacology, college of medicine, northern border university, arar, kingdom of saudi arabia 2department of orthopedic, prince abdulaziz bin mossae’ed hospital & college of medicine, northern border university, arar, kingdom of saudi arabia 3internal medicine, prince abdulaziz bin moussae’ed hospital, arar, ksa abstract introduction: bacterial resistance to the most commonly used drug ceftriaxone and its adverse effects have increased due to its injudicial use. drug utilization evaluation (due) is an ongoing, systematic process designed to promote the appropriate and effective use of drugs. the purpose was to detect potential problems and search out solution. methods: data were collected in structured preform specific for due and were represented as numbers and percentages. for comparing numerical data, mann– whitney u-test was used as the data were non-parametric in distribution for ages and bmi, while fisher exact test was used for categorical data comparison. multivariate multi-logistic regression models to study the overlapped effect of the variables in development of ceftriaxone induced liver functions derangement. data were processed and analyzed using spss16 for statistical analysis. significance was considered as p < 0.05. results: our study showed that ceftriaxone use was more. high dose was used and for more than 10 days were the result of adverse effects and liver insult. conclusion there is need for awareness among the general practitioners and clinicians to ensure rational use of antibiotics. this will minimize bacterial resistance to drug, adverse effects and save national economy. keywords: ceftriaxone, drug utilization evaluation 1. introduction antibiotics are the most frequently prescribed drugs and more likely to be used inappropriately. the irrational use of antibiotics can lead to microbial resistance, patient morbidity and mortality, prolonged hospital stay, and wastage of resources. out of many antibiotics, ceftriaxone, one of the third-generation cephalosporin, is a very commonly used and more commonly misused antibiotic. as per the who recommendations, drug how to cite this article: muhammad jan shamsur rehman, majed alrowaili, abdul wajed abdul rauf, and elhassan hussein eltom (2019) “ceftriaxone drug utilization evaluation (due) at prince abdulaziz bin moussae’ed hospital, arar, kingdom of saudi arabia,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 266–275. doi 10.18502/sjms.v14i4.5905 page 266 corresponding author: muhammad jan shamsur rehman; tel: 00966-0569100195 email: rmuhammadjansmc@gmail.com received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e muhammad jan shamsur rehman et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:rmuhammadjansmc@gmail.com mailto:rmuhammadjansmc@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences muhammad jan shamsur rehman et al utilization evaluation (due) studies should be conducted for such commonly used drugs in order to detect their irrational use and suitable measures should be adopted for their safe prescription and to avoid any harmful sequels. the due studies are meant to promote the appropriate and effective use of drugs. the main idea behind is to find out the possible problems in the prescription , administration of drugs and adopt strategies for their rational use. due studies are based on some qualitative measures for the detection of the problems in the use of drugs, as well as emphasize on the outcomes and cost-effectiveness of drug therapy. the purpose is to ensure rational drug use. due contains qualitative measures and emphasizes the outcomes and cost-effectiveness of drug therapy [1]. due is performed in patient settings to identify trends of over use and in-appropriate prescribing. surveys have shown that 22-65% antibiotics prescriptions are either in-appropriate or incorrect. taking this in account targeting the antibiotics that are prescribed frequently for due would be important to extend the useful life of the antimicrobial agents [2]. limiting the emergence and spread of antibiotic resistance, managing medicines costs and improving medical care, all are the leading reasons to evaluate specific drug use. cephalosporin are the most widely used antibiotics for treating common infections [3]. these are large group of related beta-lactam antimicrobial agents with broad spectrum of activity, low rates of toxicity and ease of administration [4]. during the past several years, the problem of antibiotic resistance has noticeably worsened in korea [5]. ceftriaxone is one of the most commonly used antibiotics compared to infections caused by susceptible pathogens. diseases caused by resistant pathogens are associated with higher rates of morbidity and mortality [6]. inappropriate utilization of ceftriaxone, however, including continued empiric use for presumed infections and prophylactic perioperative injection remained high [7]. data collection is done in structured preform based on criteria for due of the american society of health system pharmacist [7] and who criteria for due [8]. in a study, ceftriaxone was most frequently prescribed (64%) third generation cephalosporin in parenteral form [9]. third generation cephalosporin are the most commonly prescribed broad spectrum antibiotic even before the culture sensitivity results arrives [10]. due has been defined by the american society of health system pharmacists [11]. due are conducted in patient settings to identify trends of over use, underuse, or inappropriate prescribing. inappropriate use of antibiotics leads to the emergence of microbial resistance, patient’s morbidity & mortality, prolonged hospital stay and wastage of financial and other resources. unscientific use of drugs may lead to many problems like side effects, toxic effects, drugs interactions & occurrence of drugs doi 10.18502/sjms.v14i4.5905 page 267 sudan journal of medical sciences muhammad jan shamsur rehman et al induced diseases. considering all these factors, it is of immense importance to conduct due studies on antibiotics, which are being prescribed quite frequently. amongst the antibiotics, cephalosporin is the most widely used for the treatment of common infections. cephalosporin comprises a large group of beta-lactam drugs ranging from first to fifth generation with broad spectrum of activity. out of cephalosporin, ceftriaxone is one of the most commonly prescribed drugs for treatment of different types of bacterial infections. it is cephalosporin especially effective against gram negative bacteria. inappropriate use of ceftriaxone is also common to occur and may include overuse, underuse, frequent empiric use for presumed infections and prophylactic perioperative injections. who has recommended that due studies must be done for the commonly used drugs to find out their possible irrational use and to take appropriate measures to prevent the undesirable outcomes. in the present study due of ceftriaxone was conducted at the prince abdulaziz bin moussa’ed hospital, arar, which is a tertiary care hospital in the northern border region of saudi arabia, it was designed to perform due of ceftriaxone in order to get useful information about the irrational use of drug in the form of low dose, very high dose, use for very small duration or very long duration. it will to prevent the spread of microbial resistance, minimize adverse drug reactions. this will create more awareness among general practitioners, clinicians to ensure rational use of the drug & save national economy. 2. materials and methods a retrospective due of ceftriaxone was carried out in prince abdulaziz bin moussa’ed hospital at arar which is the capital of northern borders province in saudi arabia that has a population of 145,237. data was collected in structured preform, based on the criteria for due of the american society of health system pharmacist [7] and the who criteria for due [8]. medical records of patients who received ceftriaxone during hospitalization between 1st january 2018 to 31st december 2018, were scrutinized and the relevant information were entered in the prescribed preform. according to the standard criteria the justification of drug use, process indicators, and outcome measures were investigated along with patient’s demographic data. data was entered in excel file and represented as numbers and percent. for comparison of numerical data mann-whitney u test was used as the data was non parametric in distribution for ages and bmi. while fisher exact test was used for categorical data comparison. multivariate multi-logistic regression models to study the overlapped effect of the variables in development of doi 10.18502/sjms.v14i4.5905 page 268 sudan journal of medical sciences muhammad jan shamsur rehman et al ceftriaxone induced liver functions derangement. the data was processed and analyzed using spss16 for statistical analysis. significance was considered with p<0.05. 3. results due of ceftriaxone for the period of january 1st 2018 to december 31th 2018, 1141 patients admitted to prince abdualaziz bin mussa’ed hospital in arar city were prescribed ceftriaxone for different indications. table (1) represent the demographic data of those patients, 609 (53.4 %) male and 532 (46.6 %) female, the age group 20 – 39 years old constitute the majority of cases 421 (36.9 %). saudi patient were 989 (86.7 %) while non-saudi were 152 (13.3 %), allergy to medications was reported in 11 (1.1 %) patients. table 1: demographic data of ceftriaxone encounters (total of 1141). gender no. % m 609 53.4 f 532 46.6 age no. % <20 255 22.3 20-39 421 36.9 40-59 219 19.2 60-79 187 16.4 >80 59 5.2 nationality no. % saudi 989 86.7 non-saudi 152 13.3 allergies no. % allergies penicillin (4) ciprofloxacin (1) metoclopramide (3) ibuprofen (3) 11 1.0 no allergies 1130 99.0 table (2) shows the justification of ceftriaxone use, this drug had been used prophylactically in 106 (9.3 %), based on culture and sensitivity (c/s) in 13 (1.1 %), and prescribed empirically in 1022 (89.6 %). this table also represents dose, duration, and route of administration of ceftriaxone, there were 18 (1.6 %) patient prescribed the drug for more doi 10.18502/sjms.v14i4.5905 page 269 sudan journal of medical sciences muhammad jan shamsur rehman et al than 14 days. the frequent dose was 2 grams/day in 1053 (92.3 %) while 41 (3.6 %) had taken a dose of 4 grams/day. table 2: justification of ceftriaxone use (total of 1141). justification 4 no. % prophylactic 106 9.3 culture: bronchitis (3) pneumonia (4) tonsillitis (1) chronic gastritis (1) diabetic complication (2) septic wound (2) 13 1.1 empirical 1022 89.6 course duration no. % 1 day 150 13.1 2 to 7 days 780 68.4 8 to 14 days 193 16.9 >14 days 18 1.6 dosage (gram/day) no. % 0.5 4 0.4 1 35 3.1 1.5 5 0.4 2 1053 92.3 3 3 0.3 4 41 3.6 route of administration no. % iv 886 77.7 ivi 255 22.3 iv: intravenous, ivi: intravenous infusion in table (3), process indicators of ceftriaxone use had been summarized, we observed that c/s had been done only for 13 (1.1 %) patients, for the rest of the patient ceftriaxone either used empirically or prophylactically. table (4), shows trauma and fractures which were the highest and constitute 254 (22.3 %), followed by upper respiratory tract infection 154 (13.5 %), gastritis and gastroenteritis 132 (11.6 %), appendicitis 115 (10.1 %). table (5) shows the most common adverse drug reactions and safety profile of ceftriaxone in the studied cases, with remarks to liver function, renal function and complete blood count were extracted. accordingly, 79 (6.9 %) of patients showed sgpt elevation, adjusted to those with normal sgpt on admission, 112 (9.8 %) of patients doi 10.18502/sjms.v14i4.5905 page 270 sudan journal of medical sciences muhammad jan shamsur rehman et al table 3: process indicators of ceftriaxone encounters (total of 1141). process indicator no. % appropriate c&s obtained within 48 hours before initial ceftriaxone dose 13 1.1 complete blood count (cbc) with differential obtained before initial ceftriaxone dose 1141 100 renal function obtained if sever hepatic and renal impairment occurs 1141 100 liver function obtained before initial ceftriaxone dose 1141 100 vital signs monitored at least three time daily until patient becomes afebrile and at least once daily thereafter during ceftriaxone therapy 1141 100 table 4: distribution of ceftriaxone encounters (total of 1141), according to diagnosis. diagnosis number % abscesses 37 3.2 appendicitis 115 10.1 biliary infections 85 7.4 copd 92 8.1 diabetic coma and diabetic foot 96 8.4 gastritis & gastroenteritis 132 11.6 meningitis 11 1.0 pneumonia 63 5.5 trauma and fractures 254 22.3 upper respiratory tract infections 154 13.5 uti 102 8.9 total 1141 100 showed sgot elevation, adjusted to those with normal sgot on admission, 15 (0.12 %) of patients show serum creatinine level elevation, adjusted to those with normal levels on admission, 9 (2.2 %) showed thrombocytosis with exclusion of post-operative and trauma cases, and those treated with ceftriaxone for more than 8 days. table (6) represents the univariate and multivariate of our data, we found that age, body mass index (bmi), duration of treatment, and iv bolus route had significant correlation with ceftriaxone liver insult, with p. value of 0.0002, 0.0008, 0.0001, and 0.0001 respectively. figure (1) assure the same result using man-whitney u test for age and bmi because the data were non parametric at those level, while fisher exact was used for the four rest categorical variables. for duration & route, the p value was very highly significant of all the parameters (p<0.0001). doi 10.18502/sjms.v14i4.5905 page 271 sudan journal of medical sciences muhammad jan shamsur rehman et al table 5: ceftriaxone safety profile on remarks to liver function, renal function and complete blood count. laboratory parameters number of cases % of cases reference range level on increase high sgpt in cases with previously normal sgpt 79 6.9 15-65 ≤130 (43) 131-260 (71) >260 (38) high sgot in cases with previously normal sgot 112 9.8 15-37 ≤74 (84) 75-144 (42) >144 (26) high serum creatinine in cases with previously normal serum creatinine 15 0.12 49-115 ≤230 (12) 231-462 (3) thrombocytosis with exclusion of postoperative and trauma cases (in cases with treatment duration <8 days) 9 2.2 150-400 ≤600 (5) >600 (4) table 6: correlation of 6 independent variables with ceftriaxone liver insult using univariate and multivariate analysis. variables univariate multivariate sig. or age 0.0002 .021 1.617 bmi 0.0008 .003 1.205 dose(1) 0.5 .030 1.372 duration(1) <0.0001 .010 2.123 gender(1) 0.662 .791 0.210 route(1) <0.0001 .121 0.417 4. discussion drug use evaluation (due) is an on-going, authorized and systematic quality improvement process, which is designed to review drug use and/or prescribing patterns, provide feedback of results to clinicians and other relevant groups, develop criteria and standards which describe optimal drug use and promote appropriate drug use through education and other interventions. cephalosporin is the most commonly used antibiotics. in a study in arab emirate, it was observed that 3rd generation cephalosporin doi 10.18502/sjms.v14i4.5905 page 272 sudan journal of medical sciences muhammad jan shamsur rehman et al constituted 83.6 % of the prescriptions, with ceftriaxone being the most commonly used one (81.1 %). in another study it was 87 %. they were mainly prescribed for the treatment of the lower respiratory tract infections (60.2 %). seven (3.5 %) different adrs linked to cephalosporin use were observed ranging from oral thrush to clostridium difficile infection. the 3𝑟𝑑 generation cephalosporin was commonly prescribed by parenteral route [12]. our study is in complete agreement with the above study that states that ceftriaxone is the most commonly used drug in saudis (86.7%) & in above study it was 81.1%. the percentage is more for saudi people because as compared to non-saudis, most of the patients coming to the government hospital are saudis. similarly, in above study adverse drug reactions to ceftriaxone were 3.5 % but in our study they were 1.1 %. likewise, the most common route of administration was parenteral in our study which is in agreement with the above mentioned study. demographic details of a study for due of ceftriaxone shows that males were 54.5% and females were 45.5% [13]. our study is in complete agreement with above study which shows male 53.4 % & female 46.6%. in our study we found that dose & duration of ceftriaxone were 1.6 % in patients prescribed the drug for more than 14 days. the frequent dose was 2 grams/day in 92.3 % while 3.6 % had taken a dose of 4 grams/day. this overdose & long duration may lead to increased side effects & wastage of drug. in a cross sectional study, it was found out that in 56% patients, ceftriaxone was prescribed without indication [14]. antimicrobial drug resistance has been projected to add between $100 million and $30 billion annually to health-care costs [15]. in a study it was observed that use of the drug was 89 % in age 15-65 years & 2.3% in patients above 65 years [14]. our study is consistent with this study in which we found the same as 36.9 % for age 20-39 years & 5.2 % in patients above 80 years. our study showed most common adverse drug reactions and safety profile of ceftriaxone with remarks to liver function, renal function and complete blood count. the patients showed 6.9 %) sgpt elevation, 9.8 % of patients showed sgot elevation, 0.12 %) of patients showed serum creatinine level elevation, 2.2 %) showed thrombocytosis all treated with ceftriaxone for more than 8 days. so, these side effects will be controlled if the drug is not used for unnecessary long duration. similarly, in our study we observed that c/s had been done only for 1.1 % patients, for the rest of the patients ceftriaxone either used empirically or prophylactically. so, culture & sensitivity if done for all the patients will ensure required & judicial use of drug. in our study trauma and fractures were the highest and constitute 22.3 %, for which ceftriaxone was prescribed. similarly, in our study we found that age, body mass index (bmi), duration of treatment, and iv bolus route had significant correlation with ceftriaxone liver insult, with p. value of 0.0002, 0.0008, 0.0001, and 0.0001 respectively. for duration & route, doi 10.18502/sjms.v14i4.5905 page 273 sudan journal of medical sciences muhammad jan shamsur rehman et al the p value was very highly significant of all the parameters (p<0.0001). in many other studies it is clear that high dose & duration of treatment for more than 10 days will lead to more side effects. 5. conclusion our study emphasized the need for creating more awareness among the general practitioners and clinicians to ensure rational use of antibiotics to minimize resistance, adverse drugs reactions & save national economy. therefore, we recommend that a team, particularly the clinical pharmacists in all wards should monitor & ensure the judicial use of ceftriaxone and other antibiotics. acknowledgement this project was funded by deanship of scientific research, northern border university for their financial support under grant no. (6984-med-2017-1-7-f) .the authors, therefore, acknowledge with thanks dsr technical and financial support. authors’ contribution author nos. 1–3 handled the design, data collection, interpretation , arranging & rechecking. author no.4 handled the statistical analysis and typing grant & support the study has been funded by the deanship of research, northern border university, arar, kingdom of saudi arabia. references [1] qingping, s., feng, d., ran, s., et al. (2013). drug use evaluation of cefepime in the first affiliated hospital of bengbu medical college: a retrospective and prospective analysis. bmc infectious diseases, vol. 13, no. 1, p. 160. [2] lee, h., jung, d., yeom, j. s., et al. (2009). evaluation of ceftriaxone utilization at multi-center study. korean journal of internal medicine, vol. 24, no. 4, pp. 374–380. doi 10.18502/sjms.v14i4.5905 page 274 sudan journal of medical sciences muhammad jan shamsur rehman et al doi: 2009;10, 3904.kjim [3] laxminarayan, r., bhutta, z., duse, a., et al. (2005). drug resistance, in disease control priorities in developing countries, pp. 1031–1051. [4] william, f. and janis, e. (1996). the cephalosporins. mayo clinic proceedings, vol. 74, pp. 187–195. [5] chong, y. and lee, k. (2000). present situation of antimicrobial resistance in korea. journal of infection and chemotherapy, vol. 6, pp. 189–195. [6] holmberg, s. d., solomon, s. l., and blake, p. a. (1987). health and economic impacts of antimicrobial resistance. reviews of infectious diseases, vol. 9, pp. 1065–1078. [7] american society of health-system pharmacists. (1996). ashp guidelines on medication-use evaluation. american journal of health-system pharmacy, vol. 53, pp. 1953–1955. [8] holloway, k. and green, t. (2003). drug and therapeutics committees a practical guide. geneva, switzerland: world health organization, department of essential drugs and medicines policy. [9] panavila, l., ninan, n., and pratima, k. c. (2016). drug use evaluation of third generation cephalosporin in a tertiary care teaching hospital . international journal of therapeutic applications, vol. 32, pp. 81–85. [10] kaliamoorthy, k., sankaralingam, r., punniyakotti, s., et al. (2012). drug utilization evaluation of third generation cephalosporins using core drug use indicators. pakistan journal of pharmaceutical sciences, vol. 25, no. 2, pp. 339–342. [11] amos, m. y., yitzhack, s., yechiel, s., et al. (2000). cefuroxime utilization evaluation: impact of physician education on prescribing patterns. imaj, vol. 2, pp. 187–191. [12] abou-shaaban, m., ali, a. a., rao, p. g., et al. (2016). drug utilization review of cephalosporins in a secondary care hospital in united arab emirates. international journal of clinical pharmacy, vol. 38, no. 6, pp. 1367–1371. [13] naveen, v., abubakar, s., and chandana, g. (2018). drug utilization pattern of cephalosporin. international journal of current pharmaceutical research, vol. 10, no. 3, pp. 33–36. [14] hafte, k., tefera, k., azeb, w., et al. (2018). assessment of ceftriaxone use in eastern ethiopian referral hospital: a retrospective study. journal of infectious diseases and medical microbiology, vol. 2, no. 3, pp. 26–29. [15] phelps, c. e. (1989). bug/drug resistance: sometimes less is more. medical care, vol. 27, pp. 194–203. doi 10.18502/sjms.v14i4.5905 page 275 introduction materials and methods results discussion conclusion acknowledgement authors' contribution grant & support references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5903 production and hosting by knowledge e research article insurgency in northern nigeria: implication for polio eradication in nigeria dr olorunfemi akinbode ogundele1, dr christianah adeola adeyanju2, and dr ayodeji andrew omotoso2 1department of community medicine, university of medical sciences, ondo city, ondo state 2department of community health, university of medical sciences teaching hospital, ondo city, ondo state abstract northern nigeria is currently threatened by two wars, the disease called polio and insurgency caused by the fierce group that rejects the influence of western education. the increased insurgency experienced in the last decade in the form of violent conflicts and criminality has created a community of poor internally displaced people at risk of infectious diseases such as polio. despite efforts by the government to eradicate polio in nigeria insurgency remain a major obstacle. there is a need to urgently tackle insurgency to achieve polio eradication. 1. introduction northern nigeria is confronted by two wars, the disease, and the insurgency caused by the brutal rebels who reject the influence of western education [1]. insurgency is defined as an organized movement aiming at overthrowing a constituted authority or government through a disruptive means and armed conflict [2]. this definition means that insurgent groups employ unlawful means towards achieving an end, which could be political, religious, social or even ideological. the disease is polio a plague on the poor, a paralyzing, disabling brute of a virus, it deforms the limbs and wastes the muscles. children under five are most at risk and places with poor sanitation are favoured feeding grounds for the virus, which spreads through infected faeces [1]. the increased insurgency experienced in the last decade in form of violent conflicts and criminality has created a community of poor internally displaced people that runs into millions. this community is a veritable ground where polio can thrive. the major insurgency group is boko haram. the group started in 2009 as an agitation against western influence of any kind. the sect which started it activities in one of the state now holds a great swath of territory in north-east nigeria. aside resisting western civilization and education the sect shield people in its territory and keep vaccination teams seen as a western influence out. their leaders also share distrust with repeated allegations that the polio vaccine was a western plot to sterilize the people. it is to this area that polio has returned, and how to cite this article: dr olorunfemi akinbode ogundele, dr christianah adeola adeyanju, and dr ayodeji andrew omotoso (2019) “insurgency in northern nigeria: implication for polio eradication in nigeria,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 252–256. doi 10.18502/sjms.v14i4.5903 page 252 corresponding author: dr olorunfemi akinbode ogundele; email: femiaoo@yahoo.com received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e dr olorunfemi akinbode ogundele et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:femiaoo@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dr olorunfemi akinbode ogundele et al the fear is that those fleeing their violence could bring the virus back into the wider country. nigeria was on track to be declared polio-free in 2017 among the remaining three host counties, others being afghanistan and pakistan. but just as it was ready to celebrate, the disease recurred. for every one person paralyzed by polio, there is a contagious pool somewhere in the community. findings show that health indices such as maternal and child health are worst in the northern zone compared to other region in nigeria [3]. the 2016 humanitarian response plan report shows that about 14.8 million people in four states (borno, yobe, adamawa, gombe) were affected by the insurgency with about 7 million in need of humanitarian assistance. of these, about 3.7 million are in need of health interventions [4]. in 2018, nearly 2 million people are internally displaced with over 80% of these being in borno state, the epicenter of the crisis and over 60% living in host communities [5]. the conflict has no doubt impacted on child health through many pathways especially the breakdown of infrastructures such as health facilities, markets, water supply and sewage systems. in countries like uk, where polio has long been wiped out, sewers are regularly tested to ensure that polio does not sneak back into the population compared to a displaced population without access to good quality infrastructure, the risk that polio or any other disease would thrive if uncontrolled is increased. 2. poliovirus and vaccine there are 3 serotypes of wild polioviruses and are mainly transmitted through the faecooral route (via stool contaminated food and water) and also by person to person contact. polio has no cure, clinical cases can only be managed with supportive care. therefore, prevention is the mainstay of management of polio. vaccination is the primary mode of prevention, although improvement in hygiene and sanitation standards also play a role. primary and booster doses of polio vaccine protects most vaccinees for life [6]. two vaccines are currently available for prevention namely the live attenuated oral polio vaccine (opv) and the inactivated (killed) polio vaccine (ipv). opv is safe, but has a rare adverse event called vaccine-associated paralytic polio (vapp) that could occur when opv virus revert to a live virus called circulating vaccine-derived polio viruses (cvdpvs) resulting in paralysis similar to wild polio viruses. on the other hand, ipv has no risk of vapp and confers immunity against 3 serotypes. doi 10.18502/sjms.v14i4.5903 page 253 sudan journal of medical sciences dr olorunfemi akinbode ogundele et al 3. insurgency implication on polio eradication nigeria as a country share boundary with other african countries; lake chad, benin republic, niger republic and cameroun. this gives access to the spread of disease outbreak through migration in and out of the country. immunization activities in northern nigeria have been significantly limited by security concerns over insurgency which prevented vaccinators from reaching multiple northern villages over the years, and consequently, many children may not have been immunized. lack of access to people who settled in the inaccessible area following insurgent attack reduce the immunity in the area compared to other areas thus making large population of children susceptible to the disease. this has led to the build-up of a large susceptible population of children, estimated between 500,000 and 1,000,000 in the inaccessible areas which could serve as a source of transmission [4]. cases of afp could go unnoticed as large displaced populations are continuously moving between cities and camps hindering surveillance efforts and pose a risk of transmission to new susceptible individual in the community. this also prevents the ability to track children’s vaccination status as many could not be located. findings revealed that 3 cases detected in 2016 were found in the area under insurgency control and have the same genetic resemblance to 2011 strain detected in the same area. this shows that the case had been in circulation undetected for five years [7]. difficulty in reaching mobile population who had moved out of the temporary camps to their original homes following regain of territory by military pose a challenge to polio eradication as opv doses are supposed to be administered at regular intervals to be effective. northern states are the home of nomadic groups who graze their cattle across the country and neighboring countries [8]\ it, therefore, serves as a means of spreading poliovirus and other diseases to neighboring countries or acquiring a new strain into the country. this situation introduce some complexity into the eradication agenda as it’s so difficult to curtail such movement. there is therefore increased risk of re-introduction into a previously free zone in the countries and neighbouring countries .the stumbling block here therefore is not a lack of effort neither is it the drive to vaccinate by nigeria, but rather the problem of insurgency complicated by underlying culture and religious beliefs which no doubt might delay the polio eradication agenda. doi 10.18502/sjms.v14i4.5903 page 254 sudan journal of medical sciences dr olorunfemi akinbode ogundele et al 4. conclusion in spite of efforts by the government on polio eradication in nigeria insurgency remain a major barrier. it may be difficult for polio to be eradicated in nigeria due to persistent insurgency in northern nigeria and the impact on health, infrastructure and socioeconomic situation of the populace. urgent attention is required. the government should intensify efforts in curbing the spate of attacks and insecurities and complete restoration of peace and tranquility to the affected communities and states. it is only when there is security of lives and properties together with freedom of movement that success can be recorded on surveillance, tracking of children vaccination status and immunization schedule on poliomyelitis disease. therefore, access constraints related to insecurity must be effectively tackled for global effort on total polio eradication in nigeria to be an achievement. references [1] mcveigh, t. (2017). northern nigeria is the frontline in two wars: the disease and the brutal rebels who reject the west’s influence, the guardian international edition, may 7. retrieved from: https://www.theguardian.com/global-development/2017/may/ 07/nigeria-polio-vaccination-boko-haram (accessed 5 september 2019). [2] united state department of defence. (2007). retrieved from: http//www.wikipedia. org (accessed 1 september 2019). [3] national population commission, icf international. (2014). nigeria demographic and health survey 2013. abuja: national population commission and icf international. [4] polio global eradication initiatives: nigeria and lake chad polio outbreak appeal (2016). retrieved from: http//www.humanitarianresponse.info or http//www. polioeradication.org [5] the independent monitoring board of the global polio eradication initiative on progress in afghanistan, nigeria and pakistan. (2018). a review of polio endemic countries report. retrieved from: http://polioeradication.org/wp-content/uploads/ 2018/10/review-of-polio-endemic-countries-2018.pdf (accessed 1 september 2019). [6] tagbo, b. n. (2013). achieving polio eradication in nigeria: prospects and challenges. nigerian journal of paediatrics, vol. 1, pp. 15–23. doi: http://dx.doi.org/10.4314/njp. v40i1.3 [7] mckenna, m. (2016). polio returns to nigeria for the first time in years. retrieved from: https://www.nationalgeographic.com (accessed 1 september 2019). doi 10.18502/sjms.v14i4.5903 page 255 https://www.theguardian.com/global-development/2017/may/07/nigeria-polio-vaccination-boko-haram https://www.theguardian.com/global-development/2017/may/07/nigeria-polio-vaccination-boko-haram http//www.wikipedia.org http//www.wikipedia.org http//www.humanitarianresponse.info http//www.polioeradication.org http//www.polioeradication.org http://polioeradication.org/wp-content/uploads/2018/10/review-of-polio-endemic-countries-2018.pdf http://polioeradication.org/wp-content/uploads/2018/10/review-of-polio-endemic-countries-2018.pdf http://dx.doi.org/10.4314/njp.v40i1.3 http://dx.doi.org/10.4314/njp.v40i1.3 https://www.nationalgeographic.com sudan journal of medical sciences dr olorunfemi akinbode ogundele et al [8] mcneil, d. g., jr. (2016). polio response in africa to be fast, difficult and possibly dangerous, the new york times, august 12, 2016. retrieved from: http://ift.tt/ 2ax6djv (accessed 1 september 2019). doi 10.18502/sjms.v14i4.5903 page 256 http://ift.tt/2ax6djv http://ift.tt/2ax6djv introduction poliovirus and vaccine insurgency implication on polio eradication conclusion references sudan journal of medical sciences sjms special issue 2020: competing with covid-19 in sudan, doi 10.18502/sjms.v15i5.6880 production and hosting by knowledge e guest editorial covid-19: an accelerated learning challenge for developing & developed countries alike professor hassan bella senior advisor, sudan medical specialization board former director, the world association of medical editors former editor-in-chief, saudi journal of medicine & medical sciences former a faculty, johns hopkins university, baltimore, usa covid-19 is the fastest evolving and most horrific pandemic in the recent global history. it is perhaps the greatest and most daunting challenge humanity has faced since world war ii and could bring on so many sequelae and a ‘recession with no parallel in the recent past’ [1]. the editors of the sudan journal of medical sciences have commissioned this timely issue of the journal to assess the implications of this unprecedented event on sudan’s healthcare sector. researching the literature for the purpose of this editorial, using google scholar and other authentic search engines, produced a seemingly infinite number of titles. never in my career as medical teacher and researcher i have encountered such a vast volume of literature produced on one subject in such a very short time. apart from the fake and the undocumented information, there are so many conflicting and contradictory views in both the scientific writings and the media. one author remarked that: things are changing so fast that even the solid certainties that we thought we were sure of – the reproductive rate, the symptoms of the infection, the key to making a good quarantine – are suspect and need to be re-evaluated. [2] in hospitals around the world, case definitions are changed on daily basis – sometimes twice in a day. there is also controversy regarding management. while some countries are considering hydroxy chloroquine – upon scientists’ advice – for a treatment, scientists in other countries are warning against its use. some authors view herd immunity as a possible preventive strategy, while others believe it is not. at present, there is no clear answer about the best way to deal with this pandemic, the data is varied and limited, and the science is unclear. this has led the editor-in-chief of the lancet to call the response by the uk’s national health service (nhs) ‘a national scandal’ and he urged the board ’to resign after the dust settles’. he commented: we shouldn’t be in this position. we knew in the last week of january that this was coming. we wasted february when we could’ve acted. time when we could’ve ramped up testing. time when we could’ve got personal protective equipment ready and disseminated. the hypocrisy of clapping nhs workers how to cite this article: professor hassan bella (2020) “covid-19: an accelerated learning challenge for developing & developed countries alike,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 1–4. doi 10.18502/sjms.v15i5.6880 page 1 corresponding author: hassan bella; email: hassanbella@yahoo.com received 1 april 2020 accepted 20 april 2020 published 23 april 2020 production and hosting by knowledge e hassan bella. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hassanbella@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hassan bella and yet the government not supporting them to go into that frontline is tragic and it was preventable. [3] one fact cannot be disputed: the economic impact of the pandemic in sudan and similar countries will be devastating if the infection rate follows that seen in developed western countries. we do not yet feel it because we are in the shock stage. social media during the pandemic has been described as both a blessing and curse. despite the information chaos, both the internet and social media have proved to be invaluable vehicles providing scientific and health education material for both health workers and the public. some respectable institutions recommended the careful use of social media and some have created corona virus apps. i would like to take this opportunity to urge my colleagues not to post anything on the social media which is not authentic and accurate. the good news is that many highly-regarded international institutions have launched websites and search engines for covid-19. for example, johns hopkins university have created ‘global health now’ [4]. they have also produced a free teach-out ‘fighting covid-19 with epidemiology’ [5]. meanwhile, the stephen b. thacker cdc library is collecting covid-19 research articles and compiling them into an easily accessible and downloadable data base – updated every day – to help researchers find the latest covid-19 research [6]. the world health organisation (who) regions provided guidance notes on covid-19 [7] and also introduced the who health alert on whatsapp in the 3 main languages [8]. at the time of writing this editorial, the number of cases of covid-19 is still on the increase. however, we have already learnt many lessons and we will certainly continue to learn more as the pandemic progresses or regresses. china has illustrated that covid-19: [c]an be limited when public health outbreak response strategies and tactics are implemented early. in low and middle income countries (limics) programs must be strengthened by ensuring that at least minimum requirements for infection prevention and control (ipc) are in place as soon as possible. [9] another lesson to learn – particularly pertinent to sudan – is that meagre resources should not stop us fighting the corona virus. recent events have revealed that no single health system anywhere in the world was ready for a pandemic of this scale. we can learn from the mistakes made by healthcare systems in other countries. one good thing we learned from this pandemic is the importance of collaboration. unlike politicians, researchers all over the world opened their doors in an unprecedented act of global collaboration. research secrecy and competition are no longer the priority, saving lives is. a harvard professor working on a corona virus trial recently noted that the ‘ability to work collaboratively, setting aside your personal academic progress, is occurring right now because it is a matter of survival’ [10]. evidence of this ethos in our part of the world is visible in the establishment of an african taskforce for corona virus preparedness & response (aftcor). the pandemic has revealed the inadequacy and fragility of the health systems across the world. we should learn from the experiences of others, and gather together data concerning the numbers of all health personnel in our country, together with hospital doi 10.18502/sjms.v15i5.6880 page 2 sudan journal of medical sciences hassan bella readiness checklists, so we can know if we are prepared for covid-19 or any other epidemic/pandemic that might occur in the future. while it is true that malaria and other tropical diseases have a higher mortality rate than covid-19, the difference is that these diseases do not require icus or ventilators to manage and therefore do not crowd hospitals. moreover, the corona crisis has shown the value of some medical specialties that are not usually known to the public and even to some health professionals, namely epidemiologists and physician scientists. these are now widely recognized as crucial members of the health team. perhaps the most important lesson which covid-19 has taught us is the importance of allocating enough budget and resources for our national health services. until recently (before the december revolution), expenditure on healthcare in the sudan was outrageously low. most of the annual budget used to go to the army and security forces, and the doctors and health personnel – who are now risking their lives to wage war against this treacherous virus – are poorly funded and poorly equipped. in the grip of this pandemic, every government is forced to acknowledge the vital importance of healthcare professionals to the strength and stability of the nation. since it has been demonstrated that that health workers alone cannot fight the virus, the role of other humanitarian workers is immensely important. a new culture of voluntary work in sudan needs to be implemented and promoted across all levels of education. moreover, in view of our limited resources, especially in the numbers of icu beds and staff, the only strategy for sudan in dealing with this calamity is prevention and possibly containment of the pandemic. corona is not all evil. in a televised speech, the who director general remarked that, ‘covid-19 is taking so much from us. but it is also giving us something: the opportunity to come together as one against a common threat, and to build a common future’ [11]. the awareness revolution created by the corona health crisis encourages governments, healthcare organizations and the general population to listen to some wise people from all walks of life. it is good to hear some rational voices speak up in a world dominated by corrupt politicians. bill gates is one of those sane and wise people who contributed to the corona talks. he imparted some thought-provoking messages. he strongly believes that ‘there is a spiritual purpose behind everything that happens’. it is worth quoting here few of his messages: • ‘covid-19 reminds us that we are all equal, regardless of our culture, religion, occupation, financial situation or how famous we are’ • ‘it is reminding us how precious our health is’ • ‘it is reminding us of how materialistic our society has become’ • ‘it is reminding us of how important our family and home life is’ • ‘it is reminding us to keep our egos in check and that no matter how great we think we are or how great others think we are; a virus can bring our world to a standstill’ • ‘it is reminding us that after difficulty, there is always ease’ doi 10.18502/sjms.v15i5.6880 page 3 sudan journal of medical sciences hassan bella he concludes that ‘whereas many see corona covid-19 virus as a great disaster’, he sees it as ‘a great corrector’ [12]. finally, we need to remember the psychological aftermath of the pandemic. one author rightly observed that ‘wuhan’s covid-19 crisis is easing; its mental health disaster is just beginning’ [13]. this in fact provides a great opportunity for our researchers to investigate the psychological effects of the pandemic. the existing vast and increasing literature on all aspects of the pandemic also provides a chance for writing review articles if not meta-analysis and systematic reviews. references [1] schwartz, n.d. (2020, march). coronavirus recession looms, its course ’unrecognizable’. the new york times. [2] meyerowitz-katz, g. (2020, march). here’s why herd immunity won’t save us from the covid-19 pandemic. science alert, retrieved from https://www.sciencealert.com/why-herd-immunity-will-notsave-us-from-the-covid-19-pandemic] [3] (2020, march). medical journal editor slams uk coronavirus response. the canary, retrieved from https://www.thecanary.co/trending/2020/03/27/medical-journal-editor-slams-uk-coronavirusresponse-live-on-the-bbc/ [4] johns hopkins bloomberg school of public health. (2020, march). global health now. retrieved from https://www.globalhealthnow.org/ [5] johns hopkins bloomsberg school of public health. (2020, march). fighting covid-19 with epidemiology. retrieved from https://www.globalhealthnow.org/ [6] center for disease control and prevention. (2020, march). covid-19 research downloadable articles. stephen b. thacker cdc library. retrieved from https://www.cdc.gov/library/researchguides/ 2019novelcoronavirus/researcharticles.htm [7] world health organisation. (2020, march). african countries move for covid-19 readiness to response as many confirm cases. who regions guidance notes on covid-19. retrieved from afro.who.int. [8] world health organization. the who launches who alert on whatsapp wa.me/41225017023? (arabic) [9] hopman, j., et al. (2020). managing covid-19 in lowand middle-income countries. jama, march 16, 2020. [10] covid-19 changed how the world does science, together. in the new york times, retrieved on april 2, 2020 from johns hopkins, global health now. [11] adhanom, t. (2020, march). who director general’s remarks at the g20 extraordinary leaders’ summit on covid-19 26 march 2020. retrieved from https://www.who.int/dg/speeches/detail/who-directorgeneral-s-remarks-at-the-g20-extraordinary-leaders-summit-on-covid-19---26-march-2020. [12] auburn volkswagen. (2020, march). bill gates on covid-19. what is the corona/covid-19 virus really teaching us. retrieved from https://www.auburnvw.com/bill-gates-on-covid-19/. [13] walsh, m., danmerg, m. and muting, j. (2020, april). wuhan’s covid-19 crisis is easing; its mental health disaster is just beginning. caixin global podcasts. retrieved from https://www.caixinglobal.com/202004-01/wuhans-covid-19-crisis-is-easing-its-mental-health-disaster-is-just-beginning-101537465.html. doi 10.18502/sjms.v15i5.6880 page 4 https://www.sciencealert.com/why-herd-immunity-will-not-save-us-from-the-covid-19-pandemic https://www.sciencealert.com/why-herd-immunity-will-not-save-us-from-the-covid-19-pandemic https://www.thecanary.co/trending/2020/03/27/medical-journal-editor-slams-uk-coronavirus-response-live-on-the-bbc/ https://www.thecanary.co/trending/2020/03/27/medical-journal-editor-slams-uk-coronavirus-response-live-on-the-bbc/ https://www.globalhealthnow.org/ https://www.globalhealthnow.org/ https://www.cdc.gov/library/researchguides/2019novelcoronavirus/research articles.htm https://www.cdc.gov/library/researchguides/2019novelcoronavirus/research articles.htm https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-g20-extraordinary-leaders-summit-on-covid-19---26-march-2020. https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-g20-extraordinary-leaders-summit-on-covid-19---26-march-2020. https://www.auburnvw.com/bill-gates-on-covid-19/ https://www.caixinglobal.com/2020-04-01/wuhans-covid-19-crisis-is-easing-its-mental-health-disaster-is-just-beginning-101537465.html. https://www.caixinglobal.com/2020-04-01/wuhans-covid-19-crisis-is-easing-its-mental-health-disaster-is-just-beginning-101537465.html. references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6984 production and hosting by knowledge e letter to the editor a systems thinking approach for creating super clinicians using a competency-based medical education framework imad hassan, md (uk) facp frcpi memacadmed (uk), msc (uk), mbbs section head, internal medicine, department of medical protocol, king abdulaziz medical city, riyadh, ksa dear sir, we think that the article titled “national competency frameworks for medical graduates: is it time for the “sudanmeds”? published in the sudan journal of medical sciences [1] is a timely publication. competency-based medical education (cbme) is considered as a paradigm shift in medical education, the ultimate aim of which is the improvement of patient and society’s quality of care by training and creating highly skilled clinicians. a paradigm as defined by the cambridge dictionary is a situation in which the usual and accepted way of doing or thinking about something changes completely. the magnitude of change is so profound to the extent that it leads to a fundamental change in the approach or underlying assumptions, an example being the introduction of the internet. several such major “contemporary” shifts have colored the thinking processes and actions of healthcare professionals and leaders. for example, the patient safety paradigm and the evidence-based practice paradigm. the challenge of cbme in sudan and the creation of a sudanmeds (capitalized as per the canmeds counterpart-the canadian medical education directives for specialists), is in its adaptation and adoption into the “system” of medical education. we hereby advocate for a systems thinking approach for the creation of highly skilled clinicians using a cbme framework or sudanmeds. adaptation is the process of change by which the curricular content becomes better suited to sudan’s healthcare needs thereby truly becoming a sudanmeds framework. for example, the canmeds framework [2] has seven competency domains, namely the medical expert, communicator, collaborator, scholar, advocate, leader, and professional. additions to better suit sudan’s population health needs would entail adding extra domains such as spirituality/religious beliefs competency domains. the adoption component, that is, its incorporation into the “system” of training necessitates a special approach, the so-called “systems thinking approach” – an approach advocated by the world health organization [3]. systems thinking is yet another paradigm shift how to cite this article: imad hassan, md (uk) facp frcpi memacadmed (uk), msc (uk), mbbs (2020) “a systems thinking approach for creating super clinicians using a competency-based medical education framework,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 195–198. doi 10.18502/sjms.v15i2.6984 page 195 corresponding author: imad hassan; email: hassani@ngha.med.sa received 17 april 2020 accepted 11 june 2020 published 30 june 2020 production and hosting by knowledge e imad hassan. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hassani@ngha.med.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences imad hassan table 1: proposed sudanmeds competency-based training program biomatrix elements and administrative actions biomatrix item description administrative component or action aims (vision) the outcome(s): the results that the system wants to achieve. aims create focus. outcome-oriented ethos organizational culture: its unique expectations and values and is expressed in its self-image“as you think, so you will become.” super-skilled structure the organogram: the anatomy of a system. sudanmeds training committee, training curriculum, faculty training program, educationalist, simulation lab., monitoring & assessment unit process the activities: describes the activities of the system – the activities involved in the delivery of services (training) to the customers. 1. sudanmeds induction program for faculty and first-year trainees, teachable moments, competency presentations & workshops, e.g., in the communicator role, professionalism, etc. 2. scholar role activities: such as evidence-based literature searching workshops in a computer lab. 3. professional role activities: ethical practice/case vignettes, self-care, etc. 4. leadership role activities: for instance, leadership skills, service improvement skills (quality and safety improvement tools like audit). 5. communication role activities: written (h&p, follow-up, discharge summaries, etc.), patient-centered communication, hand-over, breaking-bad news, etc. 6. new non-clinical rotations: ebm rotation, research & audit, medical technology, medical bioethics, community health, medical education, etc. resources material and intellectual assets: refer to the resources of the organization, such as its capital equipment, financial resources, intellectual property, staff capabilities, etc. sudanmeds skilled faculty, audiovisual resources, case vignettes, website, blogs, etc. environment local & surrounding facilitators & barriers: (the latter need to be resolved at the outset). 1. incentive and championship program for faculty and trainees. 2. simulation lab. 3. collaboration with research centers, technology and innovation centers, evidence-based practice centers, quality improvement organizations, international competency-based training programs, etc. governance regulation & monitoring: the function of governance in an organization is to set aims and to monitor and regulate the movement of the organization toward the attainment of these aims. assessment program for faculty & trainees. doi 10.18502/sjms.v15i2.6984 page 196 sudan journal of medical sciences imad hassan in human thinking. it first appeared in the business and management arena but has spread to all disciplines or “systems” especially when the human factor is a pivotal element, for example, in social systems. it was first publicized by a nobel prize winner, professor peter senge in his book, the fifth discipline [4]. systems thinking as a foundational element together with team learning, personal mastery, mental models, and building shared vision comprise the building blocks of the five disciplines of a successful learning organization. a critical component underscoring the success of the systems thinking approach is its focus on staff rather than the service, the so-called system intelligence. a system is defined as an entity with interrelated and interdependent parts that are working together to achieve a common purpose. anything that has a name qualifies as a system – be it a chair, a car, or a company. any change in a part of the system, for instance, creation of a highly competent workforce, not only affects that particular but also the whole system. healthcare is considered as a system with numerous structures and processes that are integrated to achieve wellness as an ultimate purpose. systems thinking is a holistic approach to better understand how the system elements interact with each other over time, the root causes of system defects, and the right approach for a highly effective problem-solving intervention. systems thinking facilitates an in-depth understanding of system dynamics. its tools enable its users to redesign their systems and radically create the results they truly desire, thanks to a methodology for selecting and focusing on the right “high-leverage areas.” one of the tools for identifying and selecting high-leverage areas is called the biomatrix tool, a tool emanating from the science of the biomatrix systems theory. its seven components constitute the building blocks for any effective system, be it a clinical unit, department, hospital, organization, government, etc. unlike the classic description of a system with its three basic components: the structure, process, and outcome, the biomatrix tool smartly incorporates four extra indispensable elements for a comprehensive and successful system design or redesign. one may thus utilize it to build a competency-based training program. table 1 depicts the seven elements and their relevant practical administrative components or actions for a competency-based program. the canmeds committee in the department of medicine, king abdulaziz medical city in riyadh, saudi arabia has endorsed all seven elements in its endeavor to energize and activate its competencytraining program. a major and deterministic “leverage-point” for this program is purely administrative. the proposed sudanmeds cbme framework, if adapted and adopted in the medical education arena, will undoubtedly revitalize, reshape, and modernize the doi 10.18502/sjms.v15i2.6984 page 197 sudan journal of medical sciences imad hassan practice of medicine in sudan. what is urgently needed is more than just “putting more pressure on the gas pedal.” it requires a shifting of gears. references [1] azeem, a. a. (2019). national competency frameworks for medical graduates: is it time for the “sudanmeds”? sudan journal of medical sciences, vol. 15, no. 1, pp. 20–34. [2] royal college of physicians and surgeons of canada. canmeds framework. retrieved from: http://www.royalcollege.ca/rcsite/canmeds/canmeds-framework-e [3] de savigny, d. and adam, t. (eds.). (2009). systems thinking for health systems strengthening. alliance for health policy and systems research, world health organization. retrieved from: https://www.who.int/alliance-hpsr/resources/ 9789241563895/en/ [4] senge, p. (1990). the fifth discipline: the art and practice of the learning organizations. new york: doubleday. doi 10.18502/sjms.v15i2.6984 page 198 http://www.royalcollege.ca/rcsite/canmeds/canmeds-framework-e https://www.who.int/alliance-hpsr/resources/9789241563895/en/ https://www.who.int/alliance-hpsr/resources/9789241563895/en/ references page 20 research article national competency frameworks for medical graduates: is it time for the “sudanmeds”? ahmad abdulazeem abdullah, mbbs, msc, md, mrcsed, mmed department of surgery, college of medicine, prince sattam bin abdulaziz university, alkharj 11942, saudi arabia abstract competency-based medical education has emerged recently as a novel model of medical training driven by its ability to reconcile the desired attributes in future physicians and address the overarching and demanding issues of the discipline in this century. the rising concerns of social accountability, patient safety, and cost effectiveness of medical education programs have contributed significantly to the popularity of this paradigm worldwide. this is translated in turn to the evolution of national competency frameworks for medical graduates that are increasingly implemented in different jurisdictions to standardize and ensure equivalent outcomes of medical curricula and readiness of their graduates to better serve their communities. medical education in sudan is deeply rooted in the history of the nation and the continent and is tinged with remarkable success and achievements. it is challenged nowadays with unprecedented expansion in basic medical education which may hinder the quality of medical schools’ programs and their graduates. this article explores the feasibility of one such framework in sudan: the “sudanmeds” to ensure minimum standards and comparability of medical schools’ curricula and their outcomes across the country. the framework would also arm the regulatory bodies with a tool for accreditation and recognition of basic medical education programs in sudan and reflect quality assurance in their settings. once this approach is deemed feasible, the contribution of all stakeholders from the highest top to the bottom – the government, the regulatory bodies, the public and civil organizations, and the medical schools’ community – is required to allow for creation, implementation, and follow-up of the “sudanmeds” framework. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6699 production and hosting by knowledge e how to cite this article: ahmad abdul azeem (2019) “national competency frameworks for medical graduates: is it time for the “sudanmeds”?”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 20–34. doi 10.18502/sjms.v15i1.6699 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: a.omer@psau.edu.sa. received 11 november 2019 accepted 02 february 2020 published 31 march 2020 production and hosting by knowledge e cc ahmad abdulazeem abdullah. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: sudan, competency-based medical education, national competency frameworks, medical schools, basic medical education introduction a global drive for competency-based medical education (cbme) the trajectory of medical education has been marked in the last few decades with growing enthusiasm in competency-based education [1–5]. this paradigm came at the sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 21 forefront of interests of many medical schools worldwide driven by the increasing complexity and changing roles of physicians in this century [3, 6]. the interest in cbme has spiked recently in response to the rising awareness and expectations of the community of what physicians should be able to do to meet their needs in addition to the increased concerns of patient safety in todays’ practice of medicine [7–9]. enthusiasm for social accountability and cost-effectiveness of medical programs was also pressing and augmented by the rapid expansion in knowledge currently witnessed in the field of medicine [10–12]. it is not surprising therefore that many medical programs at undergraduate and postgraduate levels have adopted cbme in their curricula in expression of the set of aforementioned influences and to provide an evidence of their efforts to produce graduates who are qualified to meet the demands of their expected roles [4]. organizing learning around a predetermined set of competencies encourages students and teachers to move toward common goals and promote active learning and student-centered approaches that are always sought and admired in modern medical education [5, 13, 14]. characteristics of cbme cbme is different from traditional approaches of medical teaching in two prominent features. firstly, while the traditional approach starts with a description of objectives and teaching intentions and the pedagogical methods to accomplish these, cbme starts with the end-product (graduate’s abilities) in mind and then retrospectively defines the teaching and assessment strategies to ensure the achievement of these capabilities [13, 15]. secondly, while the duration of studies and credit hours are the means of merit in traditional approaches, cbme conceptually de-emphasizes time and entails that learning is centered around the demonstration of achievement of competency regardless of the time spent in the class [1, 2]. despite the overwhelming popularity of cbme in current medical education programs, there are some obstacles yet to be addressed, particularly the definition of competencies and the development of authentic methods for their assessment [7]. national competency frameworks for medical graduates the likelihood of cbme to endorse the desired professional competences of the twentyfirst-century physician in addition to the other benefits that it brought to the realm of medical education have endeared its use to ensure that medical graduates are well sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 22 trained to suit the needs of their local communities [4]. the expansion in the number of medical schools, which is a global phenomenon mandated by growth in the population, and the changing criteria of health care systems have as well triggered the regulatory bodies in different parts of the world to think of ways to standardize and ensure equivalent outcomes of medical programs under their jurisdiction, particularly that fragmented curricula were claimed to hamper the quality of medical programs and their graduates in some countries [16]. this is translated in the yield of national competency frameworks that, although started in some parts of the world, are steadily expanding over other regions and courtiers [17, 18]. examples of such frameworks include: the canadian medical education directives “canmeds,” the “tomorrow’s doctor,” the “scottish doctor” of the uk, the milestones of the accreditation council of graduate medical education (acgme) of the usa, and the framework for undergraduate medical education in the netherlands [13, 18]. furthermore, many countries have attempted to embrace such initiatives in their basic as well as advanced medical training programs and the “saudi meds” is a notable example in the middle east and the arab region [19–24]. such approach is deemed necessary to provide evidence that all medical graduates within a country are prepared to meet their expected roles according to a predefined set of national standards and to reflect quality assurance measures to internal and external relevant bodies [20, 24]. however, these frameworks are not meant to serve as curricula for medical schools, instead they are supposed to establish a common platform against which all basic medical curricula in a country can be compared and standardized [23, 24]. thus, autonomy is preserved and as far as the standard competencies are addressed, medical schools are free to choose the teaching approaches appropriate to their settings and to include in their curricula topics which might be essential to suit their individual needs [24]. some reports have shown that competency frameworks can be incorporated in the teaching strategy of medical programs regardless of the curriculum design and setup, be it traditional course-based, problem-solving-based, or community-oriented, as long as the essential competencies and authentic methods of their assessment are laid down [2, 25–27,]. this serves as another advantage of these frameworks and demonstrates their flexibility to be assimilated in different curricular approaches without affecting the integrity of the curriculum accustomed in a given educational setting. initial evaluative studies of the implementation of competency frameworks have asserted some degree of success and increased the fortitude of adopting the strategy in many parts across the globe [28, 29]. sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 23 the arena of medical education in the sudan medical education in sudan is deeply rooted in the history of the country and the content of africa beginning with the establishment of kitchener medical school in 1924 [30, 31]. since that memorial event and for years later, the number of medical schools have increased gradually with the increased number of citizen practitioners and concomitant increase in the number of hospitals and other health facilities [30]. with an early generation of dedicated physicians who were trained inside and outside the sudan in addition to the availability of opportunities for immense clinical training in rural and urban areas, the quality of medical training and its graduates have enjoyed a stance of an international reputation and a prestigious status for long time [30, 32, 33]. the burst of medical schools in the sudan following an interesting period of constancy and good outcomes of basic medical education as mentioned earlier, the field has witnessed dramatic changes thereafter and with the constitution of the so-called “higher education revolution,” the number of medical schools rose to 23 in 1990 and further spiked to 32 in the year 2014 [34]. however, that was only a part of the story, and in 2019 the number of medical schools drastically flared up to 74 (29 public and 45 in the private sectors; as retrieved from the website of the general administration of admission, evaluation and documentation of higher education certificates – part of the ministry of higher education and scientific research) [35], which means that the count of medical schools has exceeded the double in only five-year time. moreover, those new medical schools are maldistributed across the country with the majority being located in the capital city of khartoum while some are hosed in remote areas where the necessary infrastructure is almost non-existent [30, 32]. one wonders about the justification of this massive increase in the number of medical schools in the absence of appropriate social and population studies and job market needs and, more importantly, the availability of enough clinical sites for training this huge and out-of-proportion number of medical students [6, 8, 36]. the unprecedented florid increase in the number of medical schools in sudan that was once described as haphazard [32] will risk the whole phenomenon to be marked as a trade rather than natural professional development [34, 37, 38], bearing in mind that the establishment of a new medical school is a thoughtful and relatively long process that should involve careful planning and participation of all stakeholders [6, 39, 40]. sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 24 implications to the quality of basic medical education it is well-known that clinical teaching lies at the heart of physicians’ training as dictated by the apprenticeship model that is historically popular and well-grounded in the medical discipline [8]. however, with this unbalanced formula, the conditions of clinical training that was already in misery [41] is further jeopardized where the hospitals and other clinical sites suitable for training are stifled in the midst of the plethora of medical schools particularly around the city of khartoum [32, 36, 42]. this perplexing situation is complicated with political and economic conflicts and has adversely affected the quality of clinical training and limited the clinical knowledge and skills of our medical graduates on whom we count for the well-being of the coming generations [41–43]. regrettably, calls for thoughtful and commensurate expansion in the number of medical schools and medical students was reported almost 40 years ago with a visionary report about the directions of medical education in sudan [44]. considering the high rate of migration of sudanese medical graduates seeking work and training outside and what is known as the “brain drain” phenomenon, it should be noted that expansion in medical education would not suffice alone to solve the shortage of physicians in the country unless accompanied with strategies to retain them in the health workforce [6, 36, 45, 46]. to this end, a clear and compelling evidence is apparent more than any time before for the medical education community and other stakeholders in sudan to find robust mechanisms that guarantee quality and standardized medical training throughout the country. i believe that invention and implementation of a national competency framework for medical graduates in sudan “sudanmeds” is one step forward in this long yet promising journey. in the following paragraphs, an account on the expected advantages of the proposed “sudanmeds” to the field of medical education in sudan will be provided, in addition to some of the expected challenges and suggestions to overcome them. the promises of the “sudanmeds” the proposed national competency framework “sudanmeds” is expected to contribute positively to the realm of medical education in sudan in many aspects that include but are not limited to improving the curricula of medical schools and aid the process of accreditation and quality assurance of their programs, ensuring minimum standards and equivalent products of medical education in the country, and facilitate transition of medical graduates to higher specialty training. these will be discussed later in further details. sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 25 informing undergraduate medical curricula curriculum development plays an important role in defining the quality of medical programs and their graduates [27, 45]. the proposed competency framework would specify the competencies that should be mastered by all medical graduates in sudan and consequently guide the process of identification of the important topics that should be covered in the curriculum. decision on such topics should be tailored to encompass the pervasive health and environmental problems with intimate consideration of the social and cultural norms that are dominant in the country [6]. this is particularly essential considering the wide geographical area and the diverse ethnic and sociocultural backgrounds with which sudan is endowed [30]. for instance, sudan is characterized by the prevalence of communicable diseases (e.g., malaria, leishmania, tuberculosis) and non-communicable diseases (e.g., cancer and malnutrition), and it sometimes experiences environmental disasters like floods and sanitation problems [42]. therefore, these topics should contribute to the core of the curriculum of medical schools in the country. once the desired competencies of sudanese medical graduates are defined, a list of enabling learning outcomes of knowledge and skills can be derived for each domain of the competency. in such a way a curriculum matrix of a minimum standard of knowledge/topics and skills domains can be created and used to inform development and standardization of basic medical curricula and ensure consistency in the outcomes of all medical schools in the country [24, 29, 47]. fortunately, appreciable efforts are currently being made by some medical schools in sudan in order to gain insight, analyze, and reform their curricula in a way that better suits their communities and serves their needs and one that may in turn set the stage for vigilant consideration of the proposed national competency framework [27, 30, 33, 48–50]. guard against significant omissions in the curriculum “sudanmeds” would also guard against significant omissions in the teaching program of medical colleges where the taught topics can be compared to a corresponding set of national standards [23, 24, 51]. such omissions may create deficiencies in some vital skills and limit graduates’ abilities to perform their expected roles as medical practitioners [51]. this is best exemplified by the report of the medical council in sudan that affirmed significant deficiency and inconsistency in teaching professionalism across all medical schools [8]. a similar report has addressed inconsistencies in psychiatry and mental health teaching among medical schools with lack of either a separate disciplinary sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 26 approach or appropriate clinical training [45]. such deficiencies may only be examples of others [48, 52, 53], particularly in view of the dilemma of the extremely rapid increase in the number of medical schools in the country as mentioned earlier. considering the practice of adoption of old schools’ curricula by new medical schools, a strategy that is well-known and practiced in sudan [25, 27, 40], such significant omissions would lead to the reiteration of the same mistakes if those curricula were transferred without being compared to a national reference of standards [39]. once “sudanmeds” is developed, all medical schools would be encouraged to map and cross-reference their curricula to the national standard, an exercise that would have a twofold advantage. it would offer medical colleges an opportunity for attentive foresight into their teaching practices and what they have been doing previously and simultaneously delineate and compensate for any deficiencies in their curricula [23, 51, 54]. it should be noted that the proposed “sudanmeds” does not intend to replace curricula that are already administered in the medical colleges in sudan, as it is not a formal curriculum. instead, it would build on them and inform their reconstruction in a way that levers their capacities to produce competent graduates who are better prepared to serve their communities. such variations in the curricula of medical colleges reflects diversity in a wide country like the sudan and is something that should be encouraged and consolidated. relation to accreditation and quality assurance recognition of medical programs by local, regional, and international regulatory bodies is steadily increasing and becoming a standard practice in the field exacerbated by the increasing concerns of quality assurance and cross-border migration of healthcare providers [38]. medical schools are increasingly seeking recognition of their programs to provide an evidence of such quality requirements and to facilitate acceptance and engagement of their graduates in local, regional, and international jobs and training posts [54–56]. this process is gradually becoming mandatory not only in the western world (e.g., the liaison committee of medical education in the usa and the general medical council in the uk) but also in some regional countries like saudi arabia, where medical schools are obliged to comply with the national competency framework, the “saudi meds” and the specifications of the national centre for academic accreditation and assessment (ncaaa) for their programs to be recognized in saudi arabia [21, 23, 29, 54]. sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 27 the sudan medical council (smc) and the ministry of higher education and scientific research are the two regulatory bodies responsible for overseeing and accreditation of medical schools in sudan [8]. the smc, which was recently empowered by the recognition of the world federation for medical education (wfme), currently applies the concept of the “model medical school” based on the international standards set by the wfme in accreditation and recognition of basic medical programs in the country [41, 55, 58]. although the wfme standards provide a comprehensive and internationally accepted platform for the accreditation of undergraduate medical programs, it neither recognizes individual medical colleges nor dictates what should be taught in the curriculum domain which is left to be decided based on the local health circumstances and traditional values prevalent within medical schools [38, 55, 56]. of course, this is understood to confer flexibility since the wfme standards are intended to serve as a universal system for accreditation of basic medical education. the proposed “sudanmeds” would contribute here with a provision of a national skeleton of knowledge and skill domains; a curriculum content that should be assimilated in all basic medical programs as per the predefined set of competencies desired in sudanese medical graduates [38]. therefore, the framework is expected to offer a legitimate tool through which decisions on the content and coverage of basic medical programs’ curricula can be determined and thus aid in the process of accreditation of medical schools in the sudan [56]. facilitation of transition to training and job opportunities within the continuum of medical education in the sudan it has been shown that national frameworks can be integrated horizontally across all medical schools and other allied health sciences and also vertically to involve higher specialty training programs [6]. in fact, national competency frameworks were introduced first in the setting of postgraduate medical training before being later incorporated in basic medical education [23, 29]. where national frameworks are integrated at all levels of medical training from basic to higher specialty onto continuing professional development, the trajectory of training in terms of competences is perceived as a journey through a continuum rather than movement between unrelated and isolated slots of learning [59]. as such, the transition of graduates from one level to the other, which is often associated with stress and difficulties [60], will be facilitated with the homogenous training environment created by adoption of well-developed and integrated national competency frameworks at all levels of medical education [14, 16]. sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 28 in relation to training and work outside the sudan considering the experiences of development and adoption of national competency frameworks in some jurisdictions, it was evident that competency frameworks were first imparted from another country but then modified to suit the health and sociocultural characteristics prevailing in the place in which they will be applied [3, 13–15, 23, 29, 61]. as such, a bunch of similarity is expected between some local and international competency frameworks in terms of the capabilities and attributes of their trainees which may count to an easier transition of medical graduates should they decide to proceed for further training or work abroad [21, 62, 63]. such similarities in the nature of the training and job requirements would create a sense of camaraderie; feeling of friendliness or having spent some time together, between trainees or healthcare providers when they join a clinical environment of similar training and work demands and standards. such factor may be of interest to the community of medical schools and other stakeholders in sudan in view of the high rate of migration of their graduates to pursue further studies or work outside the country as mentioned earlier. it should be expected that the development of “sudanmeds” in itself would reflect the quality of basic medical education in sudan and provide a firm basis on which decisions about the opportunities of sudanese medical graduates for work and further training by regional and international bodies can be taken. challenges to “sudanmeds” having discussed some of the tenets and the expected benefits of the proposed “sudanmeds,” it should be mentioned that some difficulties are also expected along the way. apparently, the most critical challenge revolves around inducing an institutional and individual shift in the views and practices in the medical education community in sudan to embrace competency-based teaching and buy-in the process of reforming curricula of medical schools accordingly [3, 14]. arguments like “if the old curriculum works, why should we change it” has been reported in some settings and should not be denied but refuted with the growing evidence of the benefits and applicability of national competency frameworks in the medical field worldwide [14]. communication of the goals of such an intervention in addition to faculty development programs are among the strategies that can be used to decrease contention and resentment that may evolve among faculty and administrators [3, 4, 29, 64]. other constraints include addressing sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 29 the pressures of time and shortage of staff and the need for new educational technologies to teach and assess the desired learning outcomes and financial concerns tied to all of these aspects [3, 4, 6, 29, 43]. the way forward consideration of ready-made competency frameworks set in regional and international countries as examples to be later modified to suit the circumstances of sudan in addition to seeking the help of experts in the field could be illuminative initial steps in the road [15, 24]. intuitively, a firm support to provide the necessary financial and logistical backup is essentially required from the top to the button of all those who are concerned including the government, the regulatory bodies, the civilian and public constitutions, and of course the medical school communities. experiences from other parts of the world have shown that stunning and seamless achievements can be produced in such initiatives with collaboration of all stakeholders in the public and private sectors and their belief and perseverance to pursue the envisaged outcomes [14, 15, 23, 24, 28]. although the road toward “sudanmeds” may appear long and daunting particularly within the intricate circumstances that sudan is currently experiencing, the count is on the long heritage of courage and motivation of the sudanese medical educators inside and outside sudan to put-in the necessary efforts that would give birth to ‘sudanmeds” and nourish it to grow and survive. conclusion resurgence of cbme in contemporary medical education programs is mandated by the changing roles and societal needs that physicians are currently facing. national competency frameworks for medical graduates are increasingly emerging and applied in different countries to ensure minimum standards in medical programs and equivalence of their outcomes based on the local needs of their communities. the “sudanmeds” is an initiative in the same direction necessitated by the unprecedented expansion in the number of medical schools ever seen in the country. the framework is expected to inform and standardize curricula of medical schools in sudan and help with the accreditation of their programs with implications to quality assurance and readiness of their graduates to serve their communities. the development and implementation of such a framework is a challenge that requires contribution of all those who are concerned with medical education in sudan, yet is promising in many aspects. sudan journal of medical sciences ahmad abdulazeem abdullah doi 10.18502/sjms.v15i1.6699 page 30 this article calls for initiation of a discussion among all stakeholders about the feasibility, the perils, and the promises of a national competency framework for medical graduates in sudan; the “sudanmeds.” conflict of interests the author declares no conflict of interest. acknowledgement the author would like to express his sincere gratitude to 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(2015). competency-based medical education: developing a framework for obstetrics and gynaecology. journal of obstetrics and gynaecology canada. 37(12): 1104–1112. sudan journal of medical sciences volume 14, issue no. 3, doi 10.18502/sjms.v14i3.5215 production and hosting by knowledge e research article quantitative analysis of serum levels of trace elements in sudanese snuff dippers abdel azim alsanousi1, abdel raouf ahmed1, 2, and gadallah modawe1 1omdurman islamic university, faculty of medicine and health sciences, biochemistry department, omdurman,sudan 2omdurman islamic university, faculty of sciences and technology abstract background: oral cancer in sudan has high incidence rate due to the use of toombak, a homemade smokeless tobacco, rich in tobacco specific nitrosamines.there have been calls for continuous monitoring on toombak users to discover very early the carcinogenic changes to avoid mortality, and morbidity. objective: the purpose of this study was to assess technically, and financially affordable methodologies, that are reliable, reproducible, sensitive, specific and cost effective valid for use in mass screening amongst the high risk groups. (the toombak users). the present study was done to evaluate the levels of copper, zinc and magnesium in serum of toombak dippers. materials and methods: the levels of copper, zinc, and magnesium were estimated in the serum of 150 toombak dippers. the values were compared with 50 normal age matched, healthy control subjects and 50 patients with oral squamous cell carcinoma, using atomic absorption spectrophotometry. results: there was significant difference of the mean serum copper, zinc, and magnesium levels of toombak dippers when compared to the normal controls. in oral cancer patients there was significant difference in the copper, zinc, and magnesium levels. copper level was found increased gradually starting from control through toombak dippers to oral squamous cell carcinoma patients, while the level of zinc and magnesium was found decreased in the same sequence. conclusion: serum may be used as a potential diagnostic tool, which can be efficiently employed to evaluate the copper, zinc and magnesium levels in sudanese snuff dippers for population based mass screening.serum trace elements levels could be used as potential diagnostic markers for early changes caused by toombak dipping. keywords: atomic absorption spectrophotometry, copper, magnesiumm, zinc, oral squamous cell carcinoma, tobacco specific nitrosamines, serum, toombak. 1. introduction oral cancer is the 6𝑡ℎ most common cancer in the world, and the most common cancer in head and neck.500,000 new cases are added annually worldwide, with increasing how to cite this article: abdel azim alsanousi, abdel raouf ahmed, and gadallah modawe (2019) “quantitative analysis of serum levels of trace elements in sudanese snuff dippers,” sudan journal of medical sciences, vol. 14, issue no. 3, pages 152–161. doi 10.18502/sjms.v14i3.5215 page 152 corresponding author: abdel azim alsanousi; email: aalsanoocy@yahoo.com received 21 february 2019 accepted 12 may 2019 published 30 september 2019 production and hosting by knowledge e abdel azim alsanousi et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:aalsanoocy@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdel azim alsanousi et al rate of incidence in under developed countries [1]. the world cancer report of 2008 ranked oral cancer as the fifth most common cancer type among males in the less developed countries [2]. oral cancer is the 5𝑡ℎ most common cancer in the sudan with incidence rate of (920/year) comprising 9 % of the cases reported annually in africa. this is strongly attributed to the use of local type of snuff known as toombak, a very popular material in the sudanese community [3]. toombak, is home-made from finely ground leaves of nicotiana rustica, a tobacco species with a particularly high content of nicotine and minor alkaloids. this tobacco is mixed with natron or atron (sodium bicarbonate) (about 4:1), to raise the ph for rapid absorption of nicotine then water is added to the mixture, and after a period of about 2 hours or longer the mixture is ready for use [4]. snuff is habitually used orally by insertion between lower gum and cheek or lip (dipping) [5]. nicotine ranges (8-102) mg/g. dry weight. tobacco specific nitrosamines. tsna ranges (420-550) μg/g.for n-nitroso nor nicotine.nnn, and (620780) μg/gm. for 4(n –nitrosomethylamino)1(3pyridyl)1butanone.nnk, dry weight respectively, the highest ever reported tsna concentration in a tobacco product [6]. the toombak habituate is exposed minimally to (0.12-0.44 mg) of nnk per day, the highest documented uptake of a non occupational carcinogen [7]. the world health organization who. recommended less than (2.0 μg /g) dry weight combined nnn and nnk,in smokeless tobacco [8]. toombak contains 100-fold higher levels of tobacco specific nitrosamines tsna than commercial snuff in the u.s. and sweden [9]. the tsna content in the saliva of toombak dippers is at least ten times higher than that reported in the saliva of dippers of commercial snuff in usa or sweden [10]. the abnormally high concentration of tobacco specific nitrosamines in toombak is attributed first to the use of species nicotiana rustica that contains nicotine (8–10) times the nicotine in the nowadays universally used species nicotiana – tabaccum, as well as a high level of alkaloids [11]. curing of snuff by fermentation is another major factor as it accelerates production of tsna out of the tobacco leaves alkaloids, as well as the high temperature during storing [12] in addition to contamination, and poor hygiene environment during, processing, and the highly alkaline ph [13]. toomback trade is legal in the sudan, without any sort of control, or supervision on manufacturing process by health care authorities. attempts should be made to reduce exposure to tsna in oral snuff users in sudan [14]. toombak dipping is considered social stigma in sudan for females, 95% of toombak users are males, [15] although oral cancer is associated with documented risk factors, yet no comprehensive screening program [16, 17]. there is need for screening and continuous monitoring for toomback users, as a high risk group [14]. the short in budget hinders the national cancer control plans for oral doi 10.18502/sjms.v14i3.5215 page 153 sudan journal of medical sciences abdel azim alsanousi et al cancer screening [18]. taking biopsy is not suitable for screening purposes of high risk individuals for early oral cancer detection due to its invasive nature, high cost, need for specially trained medical person, and equipment [19]. biopsy for detection of early oral cancerous signs, suffers from the reliability for the appropriate site for the obtainment of specimen to be conclusive, that leads to multiple follow up biopsies while repeated surgical biopsies can discourage the habituate from agreeing to further diagnostic biopsies as it causes fear, and stress, pain, and damage to healthy tissues in addition to risk of infection, and temporary disability, and discomfort [19]. considering that the habituate is not motivated to co operate with the test idea as he believes no need for it as long as there is no pain or swelling.toludine blue, rose bengal, iodine stain, 6 tolonium chloride stain have been used as detectors for early carcinogenic changes, but inexperienced practitoners can not use these techniques to diagnose such changes, besides low specificity [20–23]. the imaging diagnostic techniques such as radiographic techniques, nuclear medicine, magnetic resonance, or ultrasonography, need equipments, and trained staff, which is hard to provide by the health care system, suffering already from limited resources, and escalating costs. the who guidelines for screening programs in developing countries, put the cost of any test as a very important consideration.the national screening programs should avoid imposing the high technology of the developed world on countries that lack the infrastructure, and resources to use the technology appropriately, or to achieve adequate coverage of the population [18]. the trace elements have been extensively studied in recent years, to assess whether they had any role in the aetiology of cancer. magnesium and zinc are the elements which have essential roles in the regulation of the cell growth, division and differentiation. high levels of copper have been observed to protect against a chemical induction of tumours [24]. the present study was done to evaluate the levels of copper, zinc and magnesium in serum of toombak dippers. 2. materials and methods randomized cross sectional study was conducted involving 250 subjects (all males) from khartoum state,sudan.this study was approved by concerned institution’s ethics committees. study subjects were divided into 3 groups. first group 150 toombak dippers in an age range 27 to 79 years mean age (50 ± 11.85).years with history of toomback use for more than 10 years, non smokers or alcohol drinkers. with no diagnosable change in oral mucousa. the second group 50 healthy non tobacco users control with the same age range.the third group oral squamous cell carcinoma oscc. patients with doi 10.18502/sjms.v14i3.5215 page 154 sudan journal of medical sciences abdel azim alsanousi et al age ranges between (30 to 82 years), with history of toombak use, and no previous history of malignancy. the study protocol was explained for the subjects involved, and a consent was obtained.5 ml of venous blood were collected from each subject in a plain polyethylene tube, the tubes were left for 30 minutes at room temperature. samples were centrifuged at 3,000 rpm for10 minutes to separate serum.2 ml of serum from each sample was put in a labeled cryotube kept in liquid nitrogen tank (-196 c), till the time of estimation. 2.1. methodology for trace elements estimation trace elements were estimated using full automatic device. (buck scientific 210 /211 vgp atomic absorption spectrophotometer.usa) at national center for research. khartoum, sudan. the estimation of copper was done according to the method of weinstock, and uhleman, 1981 [25]. the estimation of zinc was done according to the method of butrimovtz, and purdy, 1977 [26]. estimation of magnesium was done according to the method of amino, 1964 [27]. 2.2. statistical analysis statistical analysis was performed using the statistical package for the social sciences (spss version 21) software. values are expressed as (means ± sd) and p (probability) values of 0.05 were considered to be significant with a 95% confidence interval. serum levels of different parameters were statistically analyzed in all the three groups included in the study using analysis of variance (anova) test, and intergroup relationship was analyzed using ttest. relationships between variables were evaluated by pearson correlation coefficient. p value of 0.05was considered to be statistically significant. 3. results the trace elements in the present study were found to be related to toomback dipping, as well as to duration of habit, frequency of dipping/day, and consumption of toombak in grams/day. the present study showed that the mean serum copper level in control group was:0.78 0 ± 0.27 mg/l. (mean ± sd).the serum copper level in toombak dippers group was 0.83 ±0. 22 mg / l (mean ± sd), while it was found to be 0.69 ± 0.23 mg / l. (mean ± sd) in the oscc patients group. (table 2). the difference between serum copper level in the toombak dippers group, and the level in the control group was significant (p doi 10.18502/sjms.v14i3.5215 page 155 sudan journal of medical sciences abdel azim alsanousi et al < 0.002).the mean serum copper level increased in toombak dippers group. toombak in gram/day (r=0.221 p=0.006) (figure 1). the mean serum zinc level in control group was 0.83 ±0.33 mg / l (mean ± sd).the serum zinc level in toombak dippers group was 0.79 ± 0.27 (mean ± sd), while it was found to be 0.69 ± 0.25 mg / l. (mean ± sd) in the oscc patients group. (table 3). the difference between serum zinc level in the toombak dippers group, and the level in the control group was significant (p 039).the mean serum zinc level showed a decreasing trend from control group through toombak dippers group to oscc patients group. the mean serum magnesium level in control group was 26.1 ± 5.10 mg / l (mean ± sd). the serum magnesium level in toombak dippers group was 24.8 ± 4.56 mg / l. (mean ± sd), while it was found to be 21.7 ± 5.60 mg / l. (mean ± sd) in the osccpatients group. (table 4). the difference between serum magnesium level in the toombak dippers group, and the level in the control group was highly significant (p < 0001). the mean serum magnesium level showed a decreasing trend from control group through toombak dippers group to oscc patients group. table 1: general characteristics of toombak users. study variable minimum maximum mean std. deviation duration of habit (year) 10.0 55.0 26.63 10.98 consumption in grams/day 30.00 70.00 46.50 9.65 frequency of dipping/day 10.0 30.0 14.18 3.065 time the quid kept in the mouth (minute) 5.00 25.0 9.373 2.539 age (year) 27.0 79.0 50.90 11.86 table 2: shows copper results of subjects with oscc, and toombak dippers as compared to healthy control. parameter group mean s±d p-value serum copper mg / l 1-toombak dippers 0.83 ± 0.22 2-healthy control 0.78 ± 0.27 3-oscc patients 0.69 ± 0.23 0.002 table 3: shows serum zinc results of subjects with oscc., and toombak dippers as compared to healthy control. parameter group mean ± sd p-value serum zinc mg / l 1-toombak dippers 0.79 ± 0.27 2-healthy control 0.83 ± 0.33 2-oscc patients 0.69 ± 0.25 0.039 doi 10.18502/sjms.v14i3.5215 page 156 sudan journal of medical sciences abdel azim alsanousi et al table 4: shows magnesium results of subjects with oscc., and toombak dippers as compared to healthy control. parameter group mean ± sd p-value serum magnesium mg / l 1-toombak dippers 24.8 ± 4.56 2-healthy control 26.1 ± 5.10 3-oscc patients 21.7 ± 5.60 0.000 table 5: descriptive statistics of serum copper level in toombak dippers compared to healthy control. serum copper mg/l minimum maximum mean std. deviation 1-toombk dippers 0.10 1.65 0.87 0.22 2-healthy control 0.35 1.38 0.78 0.27 table 6: descriptive statistics of serum zinc level in toombak dippers compared to healthy control. serum zinc mg/l minimum maximum mean std. deviation 1-toombk dippers 0.22 1.70 0.79 0.28 2-healthy control 0.39 1.61 0.83 0.33 table 7: descriptive statistics of magnesium level in toombak dippers compared to healthy control. serum magnesium mg/l minimum maximum mean std. deviation 1-toombk dippers 15.3 37.5 24.8 4.56 2-healthy control 15.8 35.5 26.1 5.10 4. discussion serum copper level of toombak dippers group in the present study was high compared to the level of control group serum copper (table 2) the difference was statistically significant. the serum copper level of squamous cell carcinoma was found to be high compared to healthy control.the results agreed with the findings of tudek, et al [28] darna, et al [29] and with sreelatha, et al [30] who reported increased level of serum copper in oral squamous cell carcinoma patients group compared to control group. varhgese et al. [31], studied the serum copper level in leukoplakia, they found high level of copper in leukoplakia group compared to control group with a statistical significance silverman, and thompson. [32] reported significant increase in serum copper in head, and neck squamous cell carcinoma. serum zinc in the present study had shown lower level in toombak dippers, and squamous cell carcinoma patients compared to control group. (table 3). there was statistically significant difference. darna, etal [29] reported statistically significant difference between low serum zinc of oral squamous cell carcinoma patients group, and the higher level of zinc of the control group sreelatha,et al. [30] reported similar results. the results of the present study disagreed with the study of boliniarz, et al [33], who had found higher zinc level in doi 10.18502/sjms.v14i3.5215 page 157 sudan journal of medical sciences abdel azim alsanousi et al oral squamous cell carcinoma patients group compared to healthy control group, and also contradicted with the results of silver,and thompson [32] who had found higher level of zinc in cancer patients compared with controls. magnesium levels in serum of the groups of the present study had shown statistically significant variation (table 4). the level in toombak dippers group was found to be (21.6 ± 4.56 mg/l),while it was (26. ± 15.1 mg /l), in healthy control group.these results agreed with what was reported by (deheinzelin, et al [34] who had found hypo magnesemia in oral cancer patients confirming the earlier results of (chernow, et al (1995), and (guern, et al (1996) who both found low magnesium level in oral squamous cell carcinoma patients compared to healthy control group. sreelatha, et al [30] found decreased serum magnesium level in oral squamous cell carcinoma patients group compared to healthy control group. taysi s, etal [34] also reported lower serum magnesium level in cancer patients compared to controls. vyas rk et al [36] concluded that the zinc, and serum magnesium levels were found to be low in the patients with malignancies. the results of the present study disagreed with the findings of akinmoladunm, etal [37] as they reported higher serum magnesium level in cancer patients compared to controls. trace elements assessment in serum, is a highly appreciated parameter in diagnosis, and prognosis processes concerning oral squamous cell carcinoma. 5. conclusion the present study is a trial to assess the effects of toombak on dippers depending on biochemical markers, with the advantage of detecting the anticipated changes before being displayed by the affected cells. the results of the three groups studied (toombak dippers, control group, oscc group) had shown clear variation between the 3 groups members. the change in the level of these elements can be used as marker that reflects susceptibility towards cancer. references [1] hanspal s, pushaparja s, sreelatha sv, madvikha p. analysis of salivary antioxidant levels in different clinical staging and histological grading of oscc:noninvasive technique in dentistry. j clin diagn res.2014 aug (8) zc08-zc11. 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[36] vyas rk, gupta ap, gupta a, aeron ak. serum copper, zinc, magnesium and calcium levels in various human diseases. indian j. medical res. 1982;76:301–04. [37] akinmoladun v i, owotade f j, olusanya a a.(2013).trace metals and total antioxidant potential in head and neck cancer patients.annals afromed.org; may.(2013). doi 10.18502/sjms.v14i3.5215 page 161 introduction materials and methods methodology for trace elements estimation statistical analysis results discussion conclusion references sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5900 production and hosting by knowledge e research article isolation of jatropha curcas seeds isolectins with variable affinity for human and animal blood types abeer al gaali1, gadallah modawe2, reem m. ahmed3, and emadeldin h. e. konozy3 1ahfad university for women, faculty of pharmacy, department of pharmaceutical biotechnology 2omdurman islamic university, faculty of medicine and health sciences, biochemistry department, khartoum, sudan 3biotechnology department, africa city of technology, khartoum, sudan abstract background: lectins are carbohydrate-binding protein which agglutinate glycoconjugates in a reversible way, they are with wide applications in biological and medical sciences. jatropha curcas belongs to the family euphorbiaceae and is distributed in many tropical and subtropical countries. the toxicity of this plant is known for long ago and has been attributed to several components among which is a protein called curcin. methods: jatropha curcas seeds were pulverized and protein was extracted with suitable buffer. protein extract thus obtained had undergone successive protein precipitations by salting-out using (nh4)2so4 (as) at 40, 60, and 80% saturations. lectin activity was detected by hemagglutination method using humanand animal blood types. as-precipitated protein fractions that possess lectin activity were tested for their antimicrobial activity against the pathogenic staphylococcus aureus, escherichia coli, bacillus aueras, and candida albicans. results: at least three isolectins (lec40, lec60, and lec80) were detected by hemagglutination (ha) and isolated by as fractionation from the crude jatropha curcas seed extract (cext). the isolectins exhibited different tendency toward human and animal blood types. none of the isolectins could inhibit any of the used bacterial strains and candida albicans. conclusions: in this study, though the detected lectins resemble their counterpart legume lectins, they, however, showed apparently unique and variable behavior toward human and animal blood types. which might emphasize on the need for further structural analysis on the affinity sites of these proteins. keywords: jatropha curcas; euphorbiaceae; lectin; hemagglutination; antimicrobial activity how to cite this article: abeer al gaali, gadallah modawe, reem m. ahmed, and emadeldin h. e. konozy (2019) “isolation of jatropha curcas seeds isolectins with variable affinity for human and animal blood types,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 202–211. doi 10.18502/sjms.v14i4.5900 page 202 corresponding author: emadeldin h. e. konozy; phone: +249 (0) 912387107 email: ehkonozy@yahoo.com received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e abeer al gaali et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ehkonozy@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abeer al gaali et al 1. introduction lectins are carbohydrate-binding proteins that recognize and bind reversibly to specific mono and oligosaccharides on cell surfaces, the extra cellular matrix, and secreted glycoprotein [1]. due to lectin selective glycoconjugates binding property they have gained much of scientists’ attention [2]. plant lectins have been routinely used in research as a tool for glycoconjugates purification, and as bioactive agents for exploring some particular processes in cells or organisms. the current progress in plant lectin research, especially with respect to the study of the structure/ specificity/ function relationships of the different lectin categories will certainly refine and extend these molecules applications with emphasis to biomedical uses [3]. much like other members of the family euphorbiaceae, members of the genus jatropha contain several toxic compounds [4]. in particular, the seeds contain the highly poisonous curcin, a dimeric lectin [5]. however, though of jatropha apparent toxicity, its different parts have been used as medicine in certain geographic region [6] and is shown to exhibit antimicrobial activities [7]. lectins have long been proven to be quite useful for clinical blood typing and structural studies of blood group substances [8]. the use of lectins as a tool for blood typing is known for years ago. in our laboratory, we have detected more than a single lectin in the seeds of jatropha curcas and since no work has been done to characterize the affinity of these lectins towards human and animal blood types, this work was undertaken. furthermore, since the previous work on the antimicrobial activity of j. curcas was focused on secondary metabolites we intended to fractionate seeds protein and study their antimicrobial effects on pathogenic bacterial and yeast strains. 2. methods good and mature jatropha curcas seeds were brought from north kordofan state, khartoum, sudan. 2.1. erythrocytes human blood samples (a, b, ab and o) were obtained from blood bank of aldwali hospital, khartoum, sudan. while animals blood (cow, goat, donkey and sheep) were obtained from veterinary hospital bahri university, khartoum, sudan. doi 10.18502/sjms.v14i4.5900 page 203 sudan journal of medical sciences abeer al gaali et al 2.2. protein estimation protein content was determined according to ref [9] using bovine serum albumin (bsa) as the standard. 2.3. preparation of defatted acetone dried powder (adp) jatropha curcas seeds were ground by coffee blender to obtain fine powder. seeds powder was defatted with 500 ml petroleum ether and dehydrated with cold acetone and left at room temperature for drying. the obtained acetone dried powder (adp) was quantified and used for protein extraction. 2.4. preparation of crude extract (cext) to thirty five gram of the adp, 170 ml of child physiological saline (0.145m) (phs) was added and extracted for four hours under cold conditions. the extract was filtrated through cheesecloth. the clear protein supernatant obtained after removal of small cell debris by centrifugation was named as crude extract (cext). hemagglutination unit and specific activity were calculated for cext and further fractions as described earlier [10]. 2.5. ammonium sulphate (as) protein fractions preparation cext protein was subjected to varying successive fractionations by addition of solid as at 40%, 60%, and 80% saturations [11]. precipitated proteins by salting-out were dissolved in minimal amount of phs. the resultant protein fractions obtained after the suspension of precipitates in phs were denoted here forth as fr40, 60, and 80, respectively. and the lectin activities detected in these as fractions were named as lec40, 60, and 80 respectively. 2.6. characterization of fr40, 60, and 80 2.6.1. erythrocytes suspension collected edta-treated blood samples (human and animal) were taken, washed with several folds of phs, 2% (v/v) erythrocytes suspension were prepared in physiological saline (0.145m). trypsinized erythrocytes were prepared by addition of 0.05% trypsin to doi 10.18502/sjms.v14i4.5900 page 204 sudan journal of medical sciences abeer al gaali et al rbcs suspension and the mixer was incubated at 37°c for an hour. trypsinized rbcs were washed with four folds of phs. final rbcs suspension at 2% (v/v) was prepared as previously shown and used for all assays. 2.6.2. hemagglutination activity assay (ha) hemagglutination test was performed in elisa 96-well microtiter (u-shaped) plates, in a final volume of 100 μl. agglutination was assessed after one hour incubation at room temperature. hemagglutinating activity was expressed as titer, namely, the reciprocal of the highest dilution that gave a clear agglutination. the specific hemagglutinating activity was defined as titer (unit) per mg protein [12, 13]. 2.6.3. anti-microbial activity of protein fractions for the disc diffusion antimicrobial tests, the test pathogens (100 μl/plate) (table 1) were spread on muller hinton agar plates. sterile paper discs of (6 mm diameter, 0.09 mm thickness, 5 discs/plate) were aseptically transferred on agar plates and were then soaked with equal volume 5 μl of 0.2 g/ml (w/v) fixed concentration of lec40, 60, and 80. the zone of inhibition was examined after the plates were incubated at 37°c for 24–48 h. the pathogens were also tested with both a standard antibiotic tetracycline (30 μg as positive control) and negative controls (solvents) [14]. 3. results and discussion 50 gram of jatropha curcas seeds were pulverized and extensively defatted with petroleum ether and extracted with suitable amount of phs. the obtained clear protein solution was fractionated by the classical salting out technique using as salt at 40, 60 and 80% saturations. the resultant precipitants were dissolved in minimal amount of phs. almost equal quantities of protein was precipitated in each as fraction. upon testing these fractions for lectin activity by ha, each faction exhibited detectable hemagglutinating activity, indicating the presence of lectin in multiform. these findings are similar to the one obtained by osman et al [12] from seed extract of tamarindus indica [12]. whereas in contrary to de oliveira et al in which only one lectin was present in seeds [15]. maximum lectin activity was detected in fra80 followed by fra60 and finally fra40. by this step the isolectin collectively were purified by almost 10 times (table 2). precipitation of euphorbiaceae family lectins with salting out using as is reported in doi 10.18502/sjms.v14i4.5900 page 205 sudan journal of medical sciences abeer al gaali et al several publications [16-19]. however, none of these groups detected the presence of isolectins separated by their order of as solubility. these results could be attributed to the fact that in these reports cext was brought in a single addition of as to 60 [20] and 100% saturations [21] and no systematic protein fractionation, as in the current investigation, was done. moreover, since lec40 is none reactive towards human blood types, these authors might have missed its detection. the affinity purified toxic lectin, curcin, from j. curcas seeds, was initially precipitated from its crude extract by as at 60% saturation. single lectin, the curcin, was obtained with a pi 8.54 [20]. whereas a pi of 4.4 for a single lectin from the latex of synadenium carinatum was reported [22]. 3.1. behavior of lectin toward human and animals blood types of the several distinct properties of lectins is their erythrocytes hemagglutinating. therefore, it’s routine laboratory work to detect lectin activity by the hemagglutinating assay. most researchers have focused their research on human erythrocytes abo system antigens [23] which could be due to their ease to obtain and higher stability in comparison to animal erythrocytes. all human (a, ab, b and o) or animal (cow, goat, horse and sheep) blood types were either used raw or trypsin-treated. the lectin isoforms (lec40, lec60, and lec80) exhibited variable interaction patterns with the blood types used. like most of other euphorbiaceae lectins, j. curcas seed lectins agglutinated human and animal bloods differently. lec60 and 80 agglutinated poorly human a, b and o blood types, whereaslec40 didn’t clump any of the used human blood type. interestingly, none of these isolectins could agglutinate ab blood type. on the other hand, agglutination was induced or enhanced when human blood types were treated with trypsin (table 3). treatment of rbcs with proteases such as trypsin, neuraminidase, pronase, and papin is known to increase sensitivity of rbcs agglutination by several folds. treatment of rbcs with protease leads to the removal of polypeptides on the surface of erythrocytes and exposing number of lectins surface receptors [24]. these preferential agglutinations of human blood types with this lectin confirm the presence of this lectin in multiform. our results of agglutination of human blood types with jatropha curcas isolectins, are in accordance with some published papers on euphorbiaceae family lectins [18, 19] whereas in contrary to some other reports [21]. these differences might highlight interesting variability in the affinity sites of these isolectins and through some light doi 10.18502/sjms.v14i4.5900 page 206 sudan journal of medical sciences abeer al gaali et al on the apparent distinct, thought yet to be disclosed, physiological role of these proteins. when blood of animals like cow, goat, horse and sheep were used, none were agglutinated by jatropha curcas isolectins. however, interestingly, upon treatment of rbcs with trypsin, lec40 could only agglutinate, to good extend, cow and sheep bloods, whereas no effect was shown by lec60 and 80 (table 3). jawada et al in their work e. tithymaloides leaves lectin had shown that among the different animal blood types they used, only cow erythrocytes were agglutinated [21]. 3.2. antimicrobial activity of lectin the evaluation of the antimicrobial activity of lec40,60 and 80 was conducted using 3 strains of bacteria, in which two were gram negative, one was gram positive and fungi cultivated in mueller – hinton medium, with different concentrations of protein 100, 200 and 300ug, the antibiotic gentamycin was used as control. none of the isolectins lec30, 60 or 80 showed any inhibitory effect against the used bacterial and fungal strains (data not shown). a lectin from e. helioscopia was shown to express strong inhibitory effect on pseudomonas aeruginosa, klebsiella pnuemoniae and escherichia coli [25]. previous work with jatropha curcas seed extract had shown inhibitory effect of j. curcas extract against fusarium oxysporum however, since they didn’t use candida albicana, which we used in the present study, we couldn’t correlate our results with theirs [14] 4. conclusion though jatropha curcas seed lectin is a typical legume family lectin in term of its presence in multiform, these lectins behaves differently from other lectins of the same family. with regards to rbcs hemagglutination, unlike majority of legume lectin, jatropha curcas seed lectins agglutinated poorly tyrosinated or untyrosinated human and animal rbcs. these results conclusively indicate the peculiar active site of these proteins. therefore, further studies on the affinity site of these lectins as well as their secondary and tertiary structure may pave explaining these interesting features of these proteins. doi 10.18502/sjms.v14i4.5900 page 207 sudan journal of medical sciences abeer al gaali et al abbreviations used as: ammonium sulphate fr40: protein precipitate obtained after 40% as saturation of crude extract fr60: protein precipitate obtained after 60% as saturation of crude extract fr80: protein precipitate obtained after 80% as saturation of crude extract lec40: lectin activity detected in protein fraction precipitated at 40% as saturation lec60: lectin activity detected in protein fraction precipitated at 60% as saturation lec80: lectin activity detected in protein fraction precipitated at 80% as saturation ha: hemagglutination cext: jatropha curcas seeds crude extract adp: acetone dried powder phs: physiological saline (0.145m) na: no agglutination observed table 1: the standard microorganism used in the assay. organism standard code bacillus subtilis nctc 8236 (gram +ve bacteria) escherichia coli atcc 25922 (gram -ve bacteria) staphylococcus aureus atcc 25923 (gram +ve bacteria) candida albicans atcc 7596 table 2: partial purification of isolectins from jatropha curcas seeds. stage total volume (ml) total protein (mg) lectin activity (unit) activity (unit/ml) specific activity (unit/mg) purification fold cext 100 70 16 160 11 1 lec40 5 3 4 20 6 2 lec60 5 3 16 80 32 3 lec80 7 3 16 112 40 3 trypsin-treated b blood was used for all assays doi 10.18502/sjms.v14i4.5900 page 208 sudan journal of medical sciences abeer al gaali et al table 3: agglutination study of lec40, 60 and 80 of jatropha curcas with human and animal erythrocytes. blood type hemagglutination activity titer (unit) human lec40 lec60 lec80 trypsin-untreated a na* 22 2 ab na na na b na 22 2 o na 22 24 trypsin-treated a 22 24 24 ab 24 24 24 b na 24 24 o na 24 24 animal lec40 lec60 lec80 trypsin-untreated cow na na na goat na na na horse na na na sheep na na na trypsin-treated cow 23 na na goat na na na horse na na na sheep 24 na na *na= no agglutination. references [1] giacometti, j. 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(2014). eutirucallin, a rip-2 type lectin from the latex of euphorbia tirucalli l. presents proinflammatory properties. plos one, vol. 9, no. 2, e88422. doi 10.18502/sjms.v14i4.5900 page 210 sudan journal of medical sciences abeer al gaali et al [19] nsimba-lubaki, m., peumans, w. j., and carlier, a. r. (1983). isolation and partial characterization of a lectin from euphorbia heterophylla seeds. biochemical journal, vol . 215, no. 1, pp. 141–145. [20] juan, l., xin, z., jinya, w., et al. (2010). purification and characterization of curcin, a toxic lectin from the seed of jatropha curcas. preparative biochemistry & biotechnology, vol. 40, no. 2, pp. 107–118. [21] aruna, a. j., shubhangi, k. p., rajani, g. t., et al. (2016). isolation and characterization of lectin from the leaves of euphorbia tithymaloides (l.). tropical plant research, vol. 3, no. 3, pp. 634–641. [22] souza, m. a., amâncio-pereira, f., cardoso, c. r. b., et al. (2005). isolation and partial characterization of a d-galactose-binding lectin from the latex of synadenium carinatum. brazilian archives of biology and technology, vol. 48, no. 5, pp. 705–716. [23] aumiev, a. k., cuhatdullin, i. i., baimev, a. k. h., et al. (2007). site directed mutagenesis of sugar binding lectin fragment of legume plant with the help of inverse pcr. molekuliarnain biology, vol. 41, pp. 940–942. [24] mukhammadiev, r. s. and bagaeva, t. v. (2015). fungal lectins of fusarium and the dynamics of their formation. research journal of pharmaceutical, biological and chemical sciences, vol. 6, no. 6, pp. 1769–1775. [25] shaista, r., qadir, s., hussain, i., et al. (2014). purification and partial characterization of a fructose-binding lectin from the leaves of euphorbia helioscopia. pakistan journal of pharmaceutical sciences, vol. 27, no. 6, pp. 1805–1810. doi 10.18502/sjms.v14i4.5900 page 211 introduction methods erythrocytes protein estimation preparation of defatted acetone dried powder (adp) preparation of crude extract (cext) ammonium sulphate (as) protein fractions preparation characterization of fr40, 60, and 80 erythrocytes suspension hemagglutination activity assay (ha) anti-microbial activity of protein fractions results and discussion behavior of lectin toward human and animals blood types antimicrobial activity of lectin conclusion abbreviations used references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6787 production and hosting by knowledge e research article prevalence of transfusion transmissible infection among healthy blood donors at dongola specialized hospital, sudan, 2010–2015 mohamed osman abdelaziz department of medicine, faculty of medicine & health sciences, university of dongola abstract background: blood transfusion saves lives but carries the risk of transmission of infections. screening donors for transfusion transmissible infection (tti) is mandatory. objectives: to study the prevalence of tti among blood donors at dongola specialized hospital, northern state, sudan. materials and methods: retrospective study performed on blood donors at the blood bank of dongola specialized hospital during the period 2010–2015. demographic data and results of screening tests for all donors in the study period were included. data were analyzed using spss and results were presented in percentages. results: the total number of donors were 6,489, of which 6,433 (99.1%) were included in the study. all donors were males and family donors. mean age (sd) was 27.9 (6.516) years. hepatitis b virus was detected in 85 (1.3%), syphilis in 68 (1.1%), hepatitis c virus in 45 (0.7%), and human immunodeficiency virus in 3 (0.05%) donors. coinfections of hepatitis b with syphilis and hepatitis b with hepatitis c were found in 0.05% and 0.03% of the donors, respectively. conclusion: the prevalence of tti is low compared to national and international figures. these findings may reflect low prevalence rates of the studied infections in the community. keywords: blood donors, northern state, sudan, transfusion transmissible infection 1. introduction the history of blood transfusion originated with william harvey who discovered blood circulation in 1628. the earliest known blood transfusion in dogs occurred in 1665, and 1966 witnessed the first transfusion of blood from lambs to humans that was stopped due to serious interactions. the first human blood transfusion was performed by dr. philip syng physick in 1795. the first blood bank was established in leningrad in 1932 [1]. how to cite this article: mohamed osman abdelaziz (2020) “prevalence of transfusion transmissible infection among healthy blood donors at dongola specialized hospital, sudan, 2010–2015,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 163–170. doi 10.18502/sjms.v15i2.6787 page 163 corresponding author: mohamed osman abdelaziz; department of medicine, faculty of medicine & health sciences, university of dongola, po box 47, dongola 41111, sudan. mobile: +249912634357+249123166669 email: mosmanomda@uofd.edu.sd dralomda34@gmail.com received 12 may 2020 accepted 9 june 2020 published 30 june 2020 production and hosting by knowledge e mohamed osman abdelaziz. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mosmanomda@uofd.edu.sd mailto:dralomda34@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed osman abdelaziz blood donation saves lives; one pint of donated blood saves an average of three lives. someone needs blood every 2–3 sec, and about 117.4 million blood donations are collected worldwide [2]. there are three types of blood donors: voluntary unpaid donors, family donors, and paid donors. voluntary unpaid donors account for 50–90% of all donors globally. whole blood donation is the most common type of donation followed by donation of specific type of blood components such as plasma which is known as apheresis. autologous blood donation refers to donation for the donor’s own use later for elective surgery. average age of donors ranges from 18 to 65 years and males are more likely to donate blood as only about 30% of donors are females [3]. donation of blood is not without risks. transfusion transmissible infection (tti) remains the major challenge to transfusion services in the world, particularly in developing countries like sudan, where these infections tend to be more prevalent and the need for blood transfusion services is high. many infectious agents like viruses, bacteria, and parasites can be transmitted through blood transfusion. major ttis include hepatitis b virus (hbv), hepatitis c virus (hcv), human immunodeficiency virus (hiv), and syphilis. who recommends that all blood donations should be screened for evidence of infections prior to the release of blood and blood components for use. screening of all blood donations should be mandatory for ttis; hbv, hcv, hiv, and syphilis [4]. literature review revealed no studies concerning the prevalence of tti among blood donors in the northern state. the aim of this study was to determine the prevalence of ttis; hbv, hcv, hiv, and syphilis among healthy blood donors at dongola specialized hospital, northern state, sudan during the period 2010–2015. 2. materials and methods this study is a retrospective hospital-based study. records of all donors who were seen at the blood bank of dongola specialized hospital, the main hospital of the northern state of sudan were included. the study was carried out between the 1st of january 2010 to 31st of december 2015. permission was obtained from the director general of the hospital and the director of the blood bank to use data from the records of the blood bank. after taking informed consent, the donors were seen by the laboratory staff of the blood bank and a sample of blood was taken for assessment of hemoglobin level and screening for hbv, hcv, hiv, and syphilis using rapid diagnostic tests. donors who had normal hemoglobin and negative screening for infections were seen by the emergency doi 10.18502/sjms.v15i2.6787 page 164 sudan journal of medical sciences mohamed osman abdelaziz room doctors for medical fitness for donation. donors who had positive screening tests for either one or more of hbv, hcv, hiv, or syphilis were referred for counseling and further confirmatory tests. data including donors’ age, gender, and results of screening tests were extracted from the records of the blood bank using data sheet and analyzed using spss statistics software version 24 (armonk, ny: ibm corp, usa). results were shown as percentages. 3. results the total number of donors during the study period was 6,489, 56 were excluded due to missing or incomplete results of screening tests and 6,433 (99.1%) were included in the study. the age of donors ranged from 17 to 46 years with a mean age of 27.9 years and standard deviation of 6.516, and the median age was 27 years. all donors were males and were family donors. of the 6,433 donors, 201 (3.1%) were seropositive for one or more ttis. table 1 shows the prevalence of ttis among healthy blood donors in dongola specialized hospital. hbv infection was the most common type in the study with a prevalence of 1.3%, while hiv infection had the lowest prevalence of 0.05%. three donors had hbv and syphilis coinfections, and two donors demonstrated hbv and hcv coinfections. table 1: prevalence of transfusion transmissible infections among healthy blood donors in dongola specialized hospital, 2010–2015 type of infection positive no. (%) negative no. (%) total no. (%) hepatitis b virus infection 85 (1.3) 6348 (98.7) 6433 (100) hepatitis c virus infection 45 (0.7) 6388 (99.3) 6433 (100) hiv infection 3 (0.05) 6430 (99.95) 6433 (100) syphilis 68 (1.1) 6365 (98.9) 6433 (100) hbv and hcv coinfection 2 (0.03) 6431 (99.97) 6433 (100) hbv and syphilis coinfection 3 (0.05) 6430 (99.95) 6433 (100) hbv, hepatitis b virus; hcv, hepatitis c virus; hiv, human immunodeficiency virus figure 1 demonstrates the distribution of ttis among the 201 seropositive donors. hbv is the most common infection followed by syphilis and hcv, whereas hiv is the least common among seropositive donors. table 2 demonstrates the distribution of ttis among healthy blood donors in dongola specialized hospital by years of study. the highest rates of hbv was recorded in 2012 and 2014, while the lowest rate was reported in 2010. for hcv, the highest rate occurred in 2014 while the lowest rate in 2010. with regard to syphilis, the highest rate occurred in doi 10.18502/sjms.v15i2.6787 page 165 sudan journal of medical sciences mohamed osman abdelaziz n = 201 figure 1: distribution of hepatitis b virus (hbv), hepatitis c virus (hcv), human immunodeficiency virus (hiv), and syphilis among seropositive blood donors at dongola specialized hospital, sudan, 2010–2015. 2014 and the lowest rate in 2015. fluctuations in the prevalence of the ttis in different years may be due to many factors including variations in the brands of testing devices used from different manufacturers as well changes in laboratory staff with different levels of skills to perform the tests. table 2: distribution of transfusion transmissible infections by years among healthy blood donors in dongola specialized hospital from 2010 to 2015 year total no. hbv no. (%) hcv no. (%) hiv no. (%) syphilis no. (%) hbv/hcv coinfection no. (%) hbv/ syphilis coinfection no. (%) 2010 1085 6 (0.6) 1 (0.09) 0 9 (0.8) 0 0 2011 1177 15 (1.3) 10 (0.8) 1 (0.08) 12 (1.0) 1 (0.8) 1 (0.08) 2012 1089 18 (1.7) 10 (0.9) 0 9 (0.8) 1 (0.9) 2 (0.18) 2013 1019 14 (1.4) 9 (0.9) 1 (0.1) 10 (1.0) 0 0 2014 1042 18 (1.7) 14 (1.3) 1 (0.1) 22 (2.1) 0 0 2015 1021 14 (1.4) 1 (0.1) 0 6 (0.6) 0 0 total (%) 6433 85 (1.3) 45 (0.7) 3 (0.05) 68 (1.1) 2 (0.03) 3 (0.05) hbv, hepatitis b virus; hcv, hepatitis c virus; hiv; human immunodeficiency virus 4. discussion blood donation has life-saving benefits but also carries risks. prevention of tti depends on proper selection of healthy donors followed by screening for the infections. doi 10.18502/sjms.v15i2.6787 page 166 sudan journal of medical sciences mohamed osman abdelaziz the prevalence rates of both hepatitis b and c viruses were low among blood donors of the northern state compared to the overall prevalence in sudan. hepatitis b surface antigen (hbsag) seroprevalence was 6.8% in sudan whereas the prevalence of hcv was 2.2–4.8% [5]. the prevalence rate for hiv was also lower compared to the national rate of 0.3% for adult males [6]. no studies could be found regarding the prevalence of syphilis in adult males, however, a study in pregnant women revealed a prevalence rate of 3%, which was high compared to the prevalence in this study [7]. the prevalence rates of hbv, hiv, and syphilis in this study were low compared to four previous studies from different parts of sudan, whereas the prevalence rate of hcv was high compared to three of those studies but low compared to one. the study from khartoum, central sudan by ahmed et al. showed prevalence rates of hbv, hcv, hiv, and syphilis as 6.0%, 0.2%, 0.4%, and 5.4%, respectively [8]. the prevalence rates from kassala, eastern sudan by abdalla et al. were 4.3%, 3.1%, 3%, and 2.6% for hbv, hcv, hiv, and syphilis, respectively [9]. the third study from port sudan, eastern sudan by mohammed et al. showed the prevalence rates of 11.7%, 0.4%, 0.4%, and 6.6%, for hbv, hcv, hiv, and syphilis respectively [10]. the fourth study from elobeid, western sudan revealed the prevalence rates of 10%, 0%, 0.8%, and 15% for hbv, hcv, hiv, and syphilis, respectively [11]. the much lower prevalence rates of ttis in the northern state compared to the rest of the country might be explained by the fact that this is a stable indigenous population with a minority of immigrants from areas with high prevalence rates. it might also be due to the conservative life style and behavior of the population. the low prevalence rates have favorable implications on blood safety and donation rates. this might also reflect low prevalence rates of these infections in the community of the northern state but further community-based studies are indicated. the author compared the study findings with studies from neighboring and some african countries. compared to a study from egypt, the prevalence rates for hbv and syphilis were high (1.22% vs 1.3% and 0.13% vs 1.1%, respectively) but the rates for both hcv and hiv were low (4.3% vs 0.7% and 0.13% vs 0.05%, respectively) [12]. the prevalence rates for hbv, hcv, and hiv were low, while that of syphilis was high in this study compared to a study from hail, saudi arabia [13]. a study from ethiopia showed higher prevalence rates for hbv and syphilis but lower rates for hcv and hiv compared to the findings of this study [14]. the prevalence rates of this study were higher for hbv and hcv but lower for hiv compared to a study from south africa that did not include syphilis [15]. doi 10.18502/sjms.v15i2.6787 page 167 sudan journal of medical sciences mohamed osman abdelaziz this study is the first to release data from this area of sudan, which gives it strength and importance, but this study is not without limitations. the limitations of this study includes: first, the study was carried out on secondary data from a blood bank, which resulted in the absence of some important data such as occupation and residence for most of the donors and of screening results for some donors. second, the study was based on screening donors by rapid diagnostic tests and no confirmatory tests were included for those donors with positive screening tests to tti. most of the rapid diagnostic tests have sensitivity and specificity below the who recommendations and demonstrate great variations in results without quality assurance, yet they are widely used in low-income countries that lack the capacity to support the routine use of more sophisticated techniques like elisa and nucleic acid testing devices [16, 17]. third, it included data from only one hospital. 5. conclusion this study reveals that the prevalence of tti is low in sudan compared to national and international figures. these findings may reflect low prevalence rates of the studied infections in the community but large-scale community-based studies are needed to determine the prevalence of these infections among potential healthy blood donors in the northern state. ethical approval verbal consent was taken from the director general of the hospital and the director of the laboratory department. to guarantee confidentiality, the names of donors were not taken from the records. acknowledgement the author would like to thank the laboratory personnel of the blood bank at dongola specialized hospital for their help in the data collection. conflicts of interest the author declares that there are no conflicts of interest. doi 10.18502/sjms.v15i2.6787 page 168 sudan journal of medical sciences mohamed osman abdelaziz references [1] highlights of transfusion medicine history. retrieved from: file:///d:/donors/ highlights%20of%20transfusion%20medicine%20history.htm accessed on 27/03/2020. 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(2018). prevalence and factors associated with syphilis among pregnant women attending antenatal care, khartoum state, sudan. international journal of advances in medicine, vol. 5, no. 2, pp. 218–223. [8] ahmed, n. o. a., omer, e. d., and mohammed, m. a. a. (2016). sero-prevalence of transfusion transmissible infections among blood donors in khartoum central sudan. european academic research, vol. iv, no. 3, pp. 2234–2246. [9] abdallah, t. m. and ali, a. a. a. (2011). sero-prevalence of transfusion-transmissible infectious diseases among blood donors in kassala, eastern sudan. journal of medicine and medical science, vol. 2, no. 11, pp. xxx-xxx. retrieved from: http: //www.interesjournals.org/jmms [10] mohammed ba, badneen ma, gibreel mo, othman sa. prevalence of transfusiontransmissible infections among blood donors in port sudan. egypt j haematol 2019; 44(1):72-6. [11] elfaki, a. m. h., agab eldor, a. a., and elsheikh, n. m. h. 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(2014). blood donor recruitment strategies and their impact on blood safety in egypt. transfusion and apheresis science, vol. 50, no. 1, pp. 63–67. [13] sarah, a. e., sabry, a. e. e., and maryam, a. a. s. (2016). seropositivity of ttis among blood donors in hail, saudi arabia, from 2014 to 2015. asian pacific journal of tropical disease, vol. 6, no. 2, pp. 141–146. [14] shiferaw, e., tadilo, w., melkie, i., et al. (2019). sero-prevalence and trends of transfusion-transmissible infections among blood donors at bahir dar district blood bank, northwest ethiopia: a four year retrospective study. plos one, vol. 14, no. 4, e0214755. retrieved from: https://doi.org/10.1371/journal.pone.0214755 [15] vermeulen, m., swanevelder, r., chowdhury, d., et al. (2017). use of blood donor screening to monitor prevalence of hiv and hepatitis b and c viruses, south africa. emerging infectious diseases, vol. 23, no. 9, pp. 1560–1563. [16] pruett, c. r., vermeulen, m., zacharias, p., et al. (2015). the use of rapid diagnostic tests for transfusion infectious screening in africa: a literature review. transfusion medicine reviews, vol. 29, no. 1, pp. 35–44. [17] mbanya, d. (2012). use of quality rapid diagnostic testing for safe blood transfusion in resource-limited settings. clinical microbiology and infection, vol. 19, no. 5, pp. 416–421. doi 10.18502/sjms.v15i2.6787 page 170 https://doi.org/10.1371/journal.pone.0214755 introduction materials and methods results discussion conclusion ethical approval acknowledgement conflicts of interest references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7007 production and hosting by knowledge e research article lockdown as a preventive strategy against covid-19: socioeconomic implications on nigerians dr ismaila isiaka alani and dr raji saheed olanrewaju institution: sarkin maska shehu hospital (smash), pmb 6027, funtua, katsina state, nigeria. disclaimer statement: views expressed in the article are authors’ opinions and not necessarily the official position of sudan journal of medical sciences. authors’ contribution: both authors contributed to concept, design, write up and final approval of the final version of the manuscript before submission for publication. both authors agreed to be accountable for accuracy and integrity of the work abstract background: lockdown is a strategy employed worldwide to limit the spread of covid19. social and economic activities were markedly affected in nigeria and other parts of the world. the piece is a short communication to spotlight the social and economic implications of lockdown on africans and other lowand middle-income countries, using nigeria as a case study. method: to analyze the documented evidence of social and economic events arising from lockdown strategy to combat spreading cases of covid-19. result: creative potentials of so many nigerians were brought to the limelight as a positive effect. worsening security problems, corruption, poverty, and hunger were highlighted as negative socioeconomic effects of lockdown strategy on nigerians. conclusion: lockdown impacts significantly on social and economic activities of nigerians. moderation and appropriate control of the strategy are suggested as “total lockdown” is not feasible in nigeria. 1. introduction the current covid-19 outbreak which started in wuhan, china around december 2019 has resulted in unprecedented morbidity and mortality all over the world, killing people in hundreds of thousands. as at mid-may 2020, more than four million cases had been reported worldwide with over 250,000 deaths. africa has not been spared either, with over 40,000 cases and 1,500 deaths, we are still counting [1]. although the mortality figures in nigeria are not as terrifying as in some other affected african countries, 164 deaths recorded so far [2] can rise if current measures being implemented are not accorded required seriousness by those at the helm of affairs and the populace. as death toll continue to surge exponentially, hunger and restiveness occasioned by lockdown imposed by governments across the world have also increased arithmetically. this is worse in some african countries affected by covid-19, notably kenya, south how to cite this article: dr ismaila isiaka alani and dr raji saheed olanrewaju (2020) “lockdown as a preventive strategy against covid-19: socioeconomic implications on nigerians,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 123–126. doi 10.18502/sjms.v15i5.7007 page 123 corresponding author: dr ismaila isiaka alani phone number:+2347039382001 institution: sarkin maska shehu hospital (smash), pmb 6027, funtua, katsina state, nigeria. email: ishaqbola@yahoo.com received 22 may 2020 accepted 27 july 2020 published 1 october 2020 production and hosting by knowledge e dr ismaila isiaka alani and dr raji saheed olanrewaju. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ishaqbola@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dr ismaila isiaka alani and dr raji saheed olanrewaju africa, rwanda, and zimbabwe [3]. according to the world health organization (who), lockdown is one of several physical distancing measures aimed at slowing down the spread of the coronavirus, but not to completely eradicate it. if well implemented, it can buy time and allow governments of the affected countries to develop effective strategies to attack the virus and to subsequently eradicate it [4]. 2. social and economic consequences apart from the loss of lives and illness associated with the pandemic, people’s lifestyle has been affected in one way or the other, some positive while others negative. positively, some businesses, especially those rendering essential services (food, medications, and other consumables such as face masks, sanitizers, and hand gloves) have recorded a huge increase in sales, many african countries have been ”forced” naturally to manufacture improvised healthcare equipment such as ventilators and other consumables including protective gowns, face masks, sanitizers, and hand gloves which are relevant in prevention and treatment of covid-19, using locally sourced materials [5]. on the other hand, a major negative aspect of the pandemic is the current lockdown in some parts of the country, notably federal capital territory (fct) abuja, ogun, and lagos state which are the current epicenter of the pandemic in nigeria. lockdown is one of the tools employed by the nigerian government to curtail the spread of covid-19. this tool has, to a large extent, locked down economic activities [6] in affected areas and has probably led to increased hunger among the populace, as well as unrest, hooliganism, armed robberies, and other social vices perpetrated by street urchins. these street urchins, referred to as ”area boys” in local parlance, survive on daily extortion from commercial vehicle operators, commercial motorcyclist and tricyclists, food vendors, market women, and street hawkers. with lockdown in place, it is no longer business as usual. it has become pretty difficult for street urchins to survive, hence the majority of them have resorted to armed robbery attacks on hungry residents [7]. enforcement of ”stay at home” order by security agents is another cog in the wheel of progress. in nigeria alone, more people were reportedly killed by security men than coronavirus between march 30, 2020 and april 13, 2020 [8]. despite the excellent motive behind lockdown in some states in nigeria, people are still sneaking in and out of these highburden areas (mainly for economic activities) aided by unscrupulous and corrupt security agents who collect bribes from motorists in exchange for illegal entry and exit. refusal to abide by restriction order is probably a subtle way by which the nigerian populace are saying ”no” to the lockdown because it is an infringement on peoples’ right to freedom of movement and social gathering. even in advanced countries such as the united states of america, protest against lockdown have been demonstrated in some parts of that country [9]. in the long run, how effective will lockdown be if the nigerian factor –corruption, is not eliminated from our strategic planning against coronavirus; if the security of lives and properties are not guaranteed; if the populace refuses to abide by rules and regulations guiding restrictions? doi 10.18502/sjms.v15i5.7007 page 124 sudan journal of medical sciences dr ismaila isiaka alani and dr raji saheed olanrewaju 3. suggestions and recommendations since the detection of nigeria’s first case of coronavirus infection early this year and till date, government’s efforts at halting the spread of the virus are applaudable [10], however, a lot more needs to be done. in lowand middle-income countries such as nigeria, a total lockdown may not be feasible and may even become counter-productive vis-a-vis the peculiar situation of this country: high level of ignorance, poverty, and corruption. a partial lockdown may be advisable in our setting, with subtle enforcement (devoid of extrajudicial killing) of social distancing and public hygiene rules. handwashing basin should be placed at strategic points in the community like grocery stores, hospitals, etc. compulsory face mask use can be introduced if the government can engage in mass production and distribution of quality face masks to the citizens. nosocomial transmission can be minimized by screening all patients at the entrance gate of the health facilities with a brief questionnaire. patients with a high index of suspicion for the disease should be attended to and reviewed in a special setting, before the laboratory investigation. this will prevent disease transmission between patients and reduce infection rate amidst healthcare workers. ongoing research works on preventive vaccines, palliative care measures, and therapeutic products should be pursued with vigor. security of lives and properties should be stepped up and the security agents should be charged to shelf their corrupt tendencies and do the needful. palliative measures put in place by government to cushion the harsh effects of the current lockdown should be monitored to ensure that they reach desired targets in the country. much more importantly, public education on the need to abide by the rules and regulations of restrictions and to make necessary reasonable adjustments in their lifestyle is desired now, more than ever before . acknowledgement none authors’ contribution both authors contributed to the concept, design, write-up, and approval of the final version of the manuscript before submission for publication conflict of interests none doi 10.18502/sjms.v15i5.7007 page 125 sudan journal of medical sciences dr ismaila isiaka alani and dr raji saheed olanrewaju references 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(2020). lockdowns: security men killed more nigerians in two weeks than coronavirus-commission. premium times nigeria, april 20, 2020. retrieved from: https: //www.premiumtimesng.com/news/top-news/387999-lockdown-security-agents-killed-morenigerians-in-two-weeks-than-coronavirus-commission.html [accessed april 20, 2020]. [9] marcus, p. (2020). protest erupts against coronavirus lockdowns around the world. the telegraph, april 21, 2020. retrieved from: https://www.telegraph.co.uk/news/2020/04/20/protests-erupt-againstcoronavirus-lockdowns-around-world/ [accessed april 25, 2020]. [10] adepoju, p. 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https://www2.deloitte.com/us/en/insights/economy/covid-19/economic-impact-covid-19.html https://www2.deloitte.com/us/en/insights/economy/covid-19/economic-impact-covid-19.html https://www.thenigerianvoice.com/news/286966/covid-19-lockdown-the-rising-threat-of-armed-robbers-in-lag.html https://www.thenigerianvoice.com/news/286966/covid-19-lockdown-the-rising-threat-of-armed-robbers-in-lag.html https://www.premiumtimesng.com/news/top-news/387999-lockdown-security-agents-killed-more-nigerians-in-two-weeks-than-coronavirus-commission.html https://www.premiumtimesng.com/news/top-news/387999-lockdown-security-agents-killed-more-nigerians-in-two-weeks-than-coronavirus-commission.html https://www.premiumtimesng.com/news/top-news/387999-lockdown-security-agents-killed-more-nigerians-in-two-weeks-than-coronavirus-commission.html https://www.telegraph.co.uk/news/2020/04/20/protests-erupt-against-coronavirus-lockdowns-around-world/ https://www.telegraph.co.uk/news/2020/04/20/protests-erupt-against-coronavirus-lockdowns-around-world/ https://www.nature.com/articles/d41591-020-00004-2 introduction social and economic consequences suggestions and recommendations acknowledgement authors' contribution conflict of interests references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6693 production and hosting by knowledge e research article fraud and misconduct in publishing medical research dya eldin m. elsayed, md department of community medicine, faculty of medicine, alzaiem alazhari university, sudan abstract one of the important feature of scientific research is scrutinizing truth. investigators strive for honesty and integrity in all scientific communications. candidly reported methods and procedures, data and results, and their publication status should reflect authenticity. publication of fake data diverts the search from truth. the aim of studying human subjects should be advancing research and scholarship and not just the researcher’s own career. misconduct in medical research is any intentional deviation from acceptable ethical principles. intentional misconduct is a serious observation, and misconduct such as falsification and fabrication of data and plagiarism are the most common fraud practices in medical research. misconduct can occur at any stage of the research process; however, it particularly occurs in the results section of the research as researchers try to avoid negative findings. data falsification occurs when investigators attempt to alter data to meet their own expectations. falsification could involve altering data and results on research participants’ record to fit research report. data fabrication occurs when researchers report data that were completely constructed and never occurred when running the research. plagiarism is using—either deliberate or inattentive—other researchers’ ideas and words without clearly acknowledging the source of that information. although fraud and misconduct have serious consequences, they are not uncommon among research publications in scientific journals. institutions have to develop a mechanism to discover research misconduct and to prevent it. editors and reviewers are required to introduce some commentaries in the regulations to impose sanctions on those found guilty of research misconduct. keywords: research, fraud, misconduct 1. introduction advances in medical and health sciences, and indeed all fields of academic and scientific research, depend on the reliability of the research records. a key foundation of scientific research is the search for truth. investigators strive for honesty and integrity in all scientific communications (data, results, methods and procedures, and publication status). how to cite this article: dya eldin m. elsayed, md (2020) “fraud and misconduct in publishing medical research,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 131–141. doi 10.18502/sjms.v15i2.6693 page 131 corresponding author: dya eldin m. elsayed, md; email: delsayed@aau.edu.sd received 12 march 2020 accepted 9 june 2020 published 30 june 2020 production and hosting by knowledge e dya eldin m. elsayed, md. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:delsayed@aau.edu.sd https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dya eldin m. elsayed, md researchers, university staff and graduate students are expected to conduct their research in accordance with the highest ethical standards, adhering to all relevant institutional, national, and international guidelines. conducting and reporting research ethically is a priority. moreover, ethical conduct not only fulfils a moral imperative but also leads to better research results. researchers should pay attention to the details of research, including quantitative and statistical techniques, and predictable collaboration among investigators. the credibility of the research process and the results depend on adherence to the highest ethical standards throughout the whole research process [1]. publication of fake data diverts this search from the truth. when conducting research, the aim should be advancing research and scholarship, and not just advancing just one’s career [2]. intentional misconduct is considered a serious breach of scientific honesty and integrity. allusion to misconduct in scientific research has been made as early as in 1830 when the mathematician and inventor charles babbage (1791–1871) wrote about the unethical practices he had observed in scientific writing in britain. he used terms such as ‘hoaxing’, ‘forging’, ‘trimming’, and ‘cooking of data’. according to babbage, hoaxing and forging occur when one makes up data. trimming occurs when one clips off pieces of data that do not agree with one’s hypothesis, and cooking occurs when one manipulates data to make them appear to be more accurate than they are [3]. in contemporary science and ethics, terms like hoaxing, forging, trimming, and cooking are replaced by falsification and fabrication of data and plagiarism. these are the most common fraud practices in medical research. although, misconduct can occur at any stage of the research process, it particularly occurs in the results section when researchers attempt to avoid reporting negative findings [4]. fraud and misconduct in scientific research appear to be on the rise among the scientific community throughout the whole world, with instances committed by individuals, institutions, and corporations alike [5]. the scientific community started to become concerned about research fraud and misconduct in the early 1980s. prior to this, research institutions sometimes ignored or covered up potential misconduct rather than investigate it [6]. it should be noted, however, that research misconduct does not include an accidental error or honest misinterpretation of results and honest error or differences of opinion [7]. fraud and misconduct are the two terminologies often used to describe deviation from ethical principles in conducting or reporting the research. they are often used interchangeably. however, there is a gross distinction between the two. misconduct/fraud is a violation of the ethical standard and/or codes of conduct in scientific research. “fraud doi 10.18502/sjms.v15i2.6693 page 132 sudan journal of medical sciences dya eldin m. elsayed, md is an intentional deception made for personal gain or to damage another individual, for instance, intentionally falsifying and/or fabricating research data, and misleading reporting of the results.” in contrast to fraud, which is intentionally committed, misconduct may not be an intentional action, rather an act of poor management including failure to follow predetermined protocols whenever the failure causes unreasonable risk or harm to humans.… so, fraud is usually deliberately committed. it should have an element of celebrate action, which is not the case with misconduct [8, 9]. however, in this article the author has used the term “research misconduct” to mean both fraud and misconduct. several studies have found that more than 40% of surveyed researchers were aware of misconduct but did not report it [9]. sheehan et al. reported that 17% of surveyed authors of clinical drug trials reported that they personally knew of fabrication in research occurring over the previous 10 years [10]. the objective of this article is to present the most important types of research misconduct and fraud. to our knowledge many graduate students, young researchers, and even some researchers in universities and research centers are unfamiliar and unaware of the danger of research misconduct and fraud. the author wants to empower researchers with sufficient knowledge concerning research misconduct; hopefully this might help them avoid such misconduct whether deliberately or accidentally. 2. materials and methods the author surveyed similar articles published in medicaland health-related journals regardless the place and time of publication using keywords such as “research misconduct,” “fraud,” “fabrication,” “falsification and plagiarism.” the purpose of the search was to find what has been written on the topic and how it has been written. our search focused on history, definition, and common types of misconduct. it also includes the identification of ways to prevent research misconduct and fraud. besides medical journals, the search covered books and periodicals of some scientific and research institutions. during the research, the author obtained many publications covering the topic of our intended manuscript. nineteen publications were eligible for the research misconduct. one of the publications was an online course on research misconduct, two were text books, and sixteen were journal articles published by individuals or a group of authors. two of the articles were published by health institutions. doi 10.18502/sjms.v15i2.6693 page 133 sudan journal of medical sciences dya eldin m. elsayed, md 3. common types of fraud in research fabrication, falsification, plagiarism or deception in proposing, carrying out, or reporting results of research are the most common forms of fraud. 3.1. data falsification sometimes the results of a study do not match the investigator’s predictions. so, some investigators might modify these research results to improve the outcome and have reported results they “knew to be untrue” [9]. falsification occurs when investigator attempts to alter data to meet theirown expectations. falsification could involve altering data and results on research records to fit research report. for example, altering the results of interview, observation, or claiming to have performed a procedure on a research participant who had not undergone that procedure [11]. examples of common forms of data falsification: • exchanging records for different research participants • falsely reporting that certain research team members, who were supposed to perform certain procedures during the research course, had done so when they had not; altering the dates of visits • altering the data on patients screening records and/or submitting the same records with mild or moderate altered dates on multiple occasions • failing to update the patients’ status and representing data from prior screening or survey as being current • altering the results of particular tests on blood samples (or any biologic materials) to show that the test accurately predicted the disease under study • backdating follow-up interviews to fit the predetermined time by the study protocol. 3.2. fabrication data fabrication occurs when the researcher reports data that was completely constructed and had never occurred during the course of the study. for example, reporting an interview that had never taken place or providing data on blood samples that were not taken. the researcher might also report data on patients who do not exist, insert fabricated data into medical records, or include progress data for a person who had doi 10.18502/sjms.v15i2.6693 page 134 sudan journal of medical sciences dya eldin m. elsayed, md died. fabrication is more serious than any other form of fraud or misconduct. we could summarize data fabrication in the following points: • creating records of interviews, observation, or review of medical records that never took place • making up progress notes for patients who have not been visited or reporting records on patients who had already died. the difference between fabrication and falsification is that fabricating data involves creating entirely new records, whereas data falsification involves altering existing records. 3.3. plagiarism in the course of research, it is advisable to review the available published literature. this allows the researcher to see what has already been done in the field, how it has been done, and to collect information that might help in creating new insights. knowledge is built on previous publicly available knowledge, that is, we use each other’s previous works as foundation for building new knowledge. however, it is equally important to give credit to the source of this information. failure to acknowledge others’ work can be classed as plagiarism. plagiarism is the deliberate or inadvertent use of others’ ideas and words without clearly acknowledging the source of that information [12]. the availability and ease of access to electronic information make using it easier. unfortunately, open access to electronic media may contribute to the spread of plagiarism (copy/paste). to avoid plagiarism, one should always cite the source when using ideas, opinions, facts, statistics, or any information that is not common knowledge (widely known facts). for example, the statement “research involving human subjects should be conducted by essential ethical principles” describes something that everyone knows. it is therefore common knowledge and does not require a citation and source reference. contrastingly, content that is not common knowledge must have its source acknowledged and cited. for example, international ethical guidelines require some forms of informed consent in research with humans to ensure that research is informed, voluntary, and competent, thereby minimizing the chance of exploitation of study subjects (coughlin) [13]. other forms of research misconduct include unethical research. this is research that failed to fulfil some or all ethical values. defective data description, image manipulation, inadequate author, undeclared conflict of interest, and redundant publication are less serious. doi 10.18502/sjms.v15i2.6693 page 135 sudan journal of medical sciences dya eldin m. elsayed, md 4. why does misconduct occur? an action is considered to be a misconduct when it represents a significant departure from accepted practices and has been committed intentionally, or recklessly. the motivating factors for research misconduct vary, however, ambition is one of the most common. university staff gain career advancement by conducting research and publishing. some researchers want and hope for professional recognition within their institution and within the wider international scholarly community. it could also occur due to innocent ignorance or laziness of the investigators or other research staff, for complex studies needing repeated assessments for instance, repeating blood drawing or continuous monitoring (blood pressure, pulse or temperature readings). misconduct may also occur when an investigator strongly believes intuitively in the “right” answer although the right answer may be contrary [4, 7, 8, and 13]. cultural differences and personality and character issues are other factors that can influence the involvement of investigators in research misconduct. usually, many people cheat, lie, or steal for money or financial interests. but in research, money may not be the prime motivator. investigators may commit fraud for glory, for the desire to be the first and be famous and known as prominent investigator [10]. there could also be associated institutional factors such as the number of research studies at a time (workload), the existence of explicit versus implicit rules, penalties and rewards attached to such rules, training of investigators, regulations involved, and closed supervision. also, lack of resources needed for ethical research conduct can foster misconduct [14]. to the best of our knowledge, there is no documented case of research misconduct in sudan. however, in the international literature many cases were discussed. one of the prominent cases of publishing fabricated research is the case of eric poehlman from the university of vermont in burlington, usa. he had published fabricated research in 10 articles, each in a different journal. the case was investigated by the office of integral research. he was found guilty and all fabricated research was retracted from the journals [2]. 5. how is misconduct identified? it is very important to identify misconduct. warning signals, during the peer review of a research paper, should prompt the reviewer to be more vigilant and look at the data with a magnifying glass. the widespread phenomenon of research fraud makes us doi 10.18502/sjms.v15i2.6693 page 136 sudan journal of medical sciences dya eldin m. elsayed, md reconsider that it is appropriate to look at every article as suspect until proven otherwise. for example, a 100% response rate and excessive instances of perfect attendance could be signs of falsified data. the most important identifiers include implausible trends, for example, in clinical trials, 100% drug compliance, identical laboratory results, no serious adverse events reported, and subjects adhering perfectly to a visit schedule can all be evidence that the results are being manipulated [15]. a good research study leads to further studies. failure to reproduce and repeat a study by other investigators indicates fraud data. failure to confirm research results by the researcher’s laboratory or others is another indicator that could indicate research misconduct. the current procedures for detecting misconduct in research, which are often discovered by chance, are not sufficient. hence, more rigorous procedures are desperately needed. first, it is necessary to train researchers to avoid fraud and misconduct in medical research. it is their responsibility to conduct ethically sound research and to report misbehavior by colleagues. 6. what to do when misconduct is discovered? misconduct is a serious offence that requires effective and rapid reactions and sanctions against researchers who commit it. when an accusation or suspicion of fraud occurs, the institute or university must follow the institutional steps in determining the fraud. a thorough investigation is required. to determine the fraud, its type, who is responsible for its occurrence, how did it occur, and identifying its consequences are important. once a case of fraud is established, first, the punishment should be determined and the research should be ceased, irrespective of the stage the study is, retracting the published papers from scientific journals and conference proceedings. second, punishment may include reprimanding, rank, and salary reduction, and even the dismissal of persons involved in misconduct. in medical research with misconduct, junior employees may bear the burden of sanction for scientific misconduct [16–18]. 7. what is the possible impact of research misconduct? adhering to proper ethical standards helps promote medical and health research, encourages public support, and reminds researchers of their accountability to the public. misconduct can destroy the values of cooperation and collaborative work between colleagues and partners, and also undermine moral and social values [19]. misconduct doi 10.18502/sjms.v15i2.6693 page 137 sudan journal of medical sciences dya eldin m. elsayed, md in medicaland health-related research affects the validity of data and impacts adversely the core of good clinical practice by threatening the rights, safety, and well-being of research participants. on a broader scale, it can lead to wrong, ineffective, or even harmful medical practices and pharmaceutical products [21]. misconduct can give a bad name to the university or research institution and might result in funding and sponsorship cuts [20]. 8. mechanisms to prevent misconduct 8.1. primary and secondary prevention prevention of research misconduct requires certain characters and procedures. mechanisms to preventing research misconduct can include primary as well as secondary measures. primary prevention aims at identifying and removing causes of misconduct prior to its occurrence. first, the author thinks that the establishment of guidelines and regulations would help a lot to prevent research misconduct. they should be steeled at institutional and national levels. regulations should include articles on punishment for misconduct. second, joiner investigators and graduate students should receive appropriate training in both research methodology and research ethics. third, thorough review of submitted manuscripts should be done. editors may ask specialists to review manuscripts prior to acceptance. reviewers can make use of internet and available technologies to review and compare submitted manuscripts with previously published literature. editors won’t publish when misconduct is discovered. fourth; investigators should be required to share data, results, ideas, tools, resources with colleagues, senior as well as junior. colleagues should help one another to discover mistakes including misconduct and the investigators should be open to criticism and new ideas. finally„ for the secondary prevention of research misconduct, that is, early detection and discovery of cases of misconduct, each suspected case should be investigated and sanctions be delivered to those revealed to be responsible for the misconduct. sanctions involve retraction of fraudulent articles and punishment to those found guilty of fraud [21]. 9. national rules and regulations the foundations, controls, and standards that define the levels of health services and health research in the republic of the sudan are the responsibility of the federal ministry doi 10.18502/sjms.v15i2.6693 page 138 sudan journal of medical sciences dya eldin m. elsayed, md of health (fmoh) and the institutions affiliated with the organ [22]. for research governance, the fmoh has established the “national health research ethics committee,” which has developed the national guidelines for research ethics (2008 amended 2017). at the national level, sudan has established the “national board for medicines and poisons,” which is responsible, among other responsibilities, for clinical trials. yet, none of the two national bodies has designed a system for evaluating allegations of scientific fraud. the author believes that at this time, with the spread of fraud in medical research, we need to create a national body for research integrity that is concerned with medical research issues and establish a system for identifying and evaluating fraudulent research and punish researchers who commit research misconduct [23, 24]. 10. conclusion fraud and misconduct, if not identified, have serious consequences. they may lead investigators to the wrong directions if they cite and use such published fraud data. bad consequences can also extend to the management of patients and science. universities and research institutions are required to develop a mechanism to discover and prevent fraud in research. institutional and national research ethics guidelines in sudan do not prescribe specific sanctions on those found guilty. so, institutions are required to introduce some articles in the regulations to impose sanctions on those found guilty of research misconduct. the author would also like to recommend the following: 1. creating a national body (like an office) for research integrity 2. training on research ethics, research integrity, and research misconduct has to be integrated into the curriculum of undergraduate and postgraduate students 3. provision of training on research ethics should be made for in-service training of researchers 4. conducting research studies aimed at determining the occurrence of scientific misconduct among academic researchers in sudan 5. research misconduct committees should have preventive as well as investigative roles doi 10.18502/sjms.v15i2.6693 page 139 sudan journal of medical sciences dya eldin m. elsayed, md acknowledgement the author would like to thank professor suad suliman for her assistance in developing this work. she revised and corrected the early draft. conflict of interest the author declares that there is no conflict of interest. references [1] shahnazarian, d., rose, s. l., hagemann, j., et al. avoiding being penalized: research misconduct. usc online course. retreived from: www.citiprogram.org [accessed april 1, 2016]. [2] sox, h. c. and rennie, d. (2006). research misconduct, retraction, and cleansing the medical literature: lessons from the poehlman case. annals of internal medicine, vol. 144, no. 8, pp. 609–613. [3] baggage, c. (1970 {1830}). reflections on the decline of science in england. new york, n.y.: andesite press. [4] weir, c. and murray, g. (2011). fraud in clinical trials: detecting it and preventing it. significance, pp. 164–168. [5] catano, v. m. and turk, j. (2007). fraud and misconduct in scientific research: a definition and procedures for investigation. med law, vol. 26, no. 3, pp. 465–476. [6] institute of medicine, national academy of sciences, and national academy of engineering. ”research misconduct.” on being a scientist, chapter 6. retrieved from: http://www.nap.edu/read/12192/ [accessed april 12, 2016]. [7] us department of health. definition of research misconduct. retrieved from: http://ori.hhs.gov/definition-misconduct [accessed march 30, 2016]. [8] bhatt, a. (2011). quality of clinical trials: a moving target. perspectives in clinical research, vol. 2, pp. 124–128. [9] gupta, a. (2013). fraud and misconduct in clinical research: a concern. perspectives in clinical research, vol. 4, no. 2, pp. 144–147. [10] sheehan, j. g. (2007). fraud, conflict of interest, and other enforcement issues in clinical research. cleveland clinic journal of medicine, vol. 74, pp. s63–s67. [11] elsayed, d. m. (2013). manual for research ethics in medical and health sciences. saarbrücken, germany: lap lambert academic publishing. doi 10.18502/sjms.v15i2.6693 page 140 www.citiprogram.org http://www.nap.edu/read/12192/ sudan journal of medical sciences dya eldin m. elsayed, md [12] das, n. and panjabi, m. (2011). plagiarism: why is it such a big issue for medical writers? perspectives in clinical research vol. 2, no. 2, pp. 67–71. [13] kumar, p. m., priya, n. s., musalaiah, s., et al. (2014). knowing and avoiding plagiarism during scientific writing. annals of medical and health sciences research, vol. 4, no. 3, pp. s193–s198. [14] habermann, b., broome, m., pryor, e. r., et al. (2010). research coordinators’ experiences with scientific misconduct and research integrity. nursing research, vol. 59, no.1, pp. 51–57. [15] jessen, j., robinson, e., bigaj, s., et al. (2007). unreported clinical research fraud and misconduct. journal of clinical research best practices, vol. 3, no. 1, pp. 1–5. [16] reynolds, s. m. (2004). ori findings of scientific misconduct in clinical trials and publicly funded research, 1992–2002. clin trials, vol. 1, no. 6, pp. 509–516. [17] fanelli, d. (2009). how many scientists fabricate and falsify research? a systematic review and meta-analysis of survey data. plos one, vol. 4, no. 5, p. e5738. [18] elsayed, d. m. and elamin, r. (2009). medical ethics: what is it? why is it important? slovenian journal of public health, vol. 4, no. 2, pp. 284–287. retrieved from: http: //www.sjph.net.sd [19] al-marzouki, s., roberts, i., marshall, t., et al. (2005). the effect of scientific misconduct on the results of clinical trials: a delphi survey. contemporary clinical trials, vol. 26, pp. 331–337. [20] ghooi, r. b. (2014). expert committee to formulate policy and guidelines for approval of new drugs, clinical trials and banning of drugs-comments. perspectives in clinical research, vol. 5, no. 3, pp. 100–107. [21] weed, d. l. (1998). preventing scientific misconduct. american journal of public health, vol. 88, no. i, pp. 125–129. [22] sudan: national public health law of 2008. [23] eldin mohammed elsayed, d. (2006). national framework for ethics in health research involving human subjects. sudanese journal of public health, vol. 1, no. 3, pp. 192– 196. retrieved from: http://www.sjph.net.sd [24] eldin mohammed elsayed, d. (2007). national health research system: for better health. j.c. tech, vol. 8, no. 1, pp. 88–96. doi 10.18502/sjms.v15i2.6693 page 141 http://www.sjph.net.sd http://www.sjph.net.sd http://www.sjph.net.sd introduction materials and methods common types of fraud in research data falsification fabrication plagiarism why does misconduct occur? how is misconduct identified? what to do when misconduct is discovered? what is the possible impact of research misconduct? mechanisms to prevent misconduct primary and secondary prevention national rules and regulations conclusion acknowledgement conflict of interest references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7747 production and hosting by knowledge e editorial article keyword selection keyword selection is the second sudan journal of medical sciences (sjms) short guidance piece on the international academic standards. as a section editor at sjms, i am honored to be invited to write in this series. in future, i can see sjms leading the way to improving the publishing standards in sudan’s medical field. and with the current practice and unique services that sjms provides for their readers and authors, it marks its step to be one of the best regional journals in the discipline. the importance of keywords as authors, we aspire to share our work among the readers in our field and get appropriately cited. here comes the volume for the authors’ keywords. the first journey for each manuscript begins with a literature review in which the indexing databases such as scopus and pubmed are searched for any present work related to our ideas. this ends by the citation of most of those works in our reference list. it is curial to select your keywords so that it acts as a promoter for your work among your colleagues. apart from being used by the indexing service to classify your work, keywords for the publisher and the editorial board serve as a guidance for choosing the referee for your article and your paper’s subject. how to choose your keyword? 1. first, make a list of words from the manuscript, which you believe represents the work’s essential idea. they could also be a phrase (e.g., colon cancer). most researchers use sentences or phrases in search engines. do not use words from your title, as this will decrease the chances of the article appearing during the logarithmic search. there is also a word generator engine like mesh on demand, a google keyword planner. each journal has its own maximum number of keywords; for sjms, the number of keywords are specified according to the article types. 2. next, have a look at the standard term used for indexing in the medical field (mesh, psycinfo, and others) and ensure that the keyword of your choice is listed there. page 215 received 15 september 2020 accepted 25 september 2020 published 30 september 2020 production and hosting by knowledge e editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com sudan journal of medical sciences 3. lastly, go through the standard search engine used commonly by professionals in your field and type it to see if the same titles as yours come up. to publish means to be known. i believe each article’s minor part deserves the same input as a significant section. dr. abduelbagi d.a altayb, mrcp. section editor, sjms. aaaldesogi@icloud.com doi 10.18502/sjms.v15i3.7747 page 216 the importance of keywords how to choose your keyword? sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6727 production and hosting by knowledge e research article assessment of dehydration in children with acute gastroenteritis: a narrative review of international guidelines mohammed alhassan, md department of pediatric, college of medicine, prince sattam bin abdulaziz university, alkharj 11942, saudi arabia abstract background: acute gastroenteritis (age) is a major cause of presentation to hospital in children. detection and classification of the degree of dehydration are vital for proper treatment. methods: the authors reviewed six international guidelines on age in children. the aim was to equip clinicians working in a hospital setting with practical and readily applicable clinical handles to assist them in detecting and classifying dehydration. results: published international guidelines on age vary in their recommendations on the assessment of dehydration as well as their classification of dehydration severity. nevertheless, a practical scheme utilizing a combination of these guidelines could be devised. conclusion: in addition to the world health organization classification of dehydration in children, several clinical handles were suggested. keywords: acute gastroenteritis, children, dehydration, diarrhea 1. introduction acutegastroenteritis (age) and its complications remain one of the leading causes of mortality in children worldwide [1]. in underdeveloped countries, the disease poses a particular burden on the resource-limited healthcare systems; enormously higher mortality rates from the disease in sub-saharan africa, for example, is not unexpected [2]. in some regions of africa, diarrheal diseases remain the leading cause of hospital presentation and the second most common cause of death in children under five years of age (excluding the neonatal period) [3]. in places with underdeveloped, underresourced, and overburdened community and primary care services, a considerable percentage of patients with age present to the emergency departments (eds) of large hospitals without passing through primary healthcare services. this necessitates an easy and reliable tactic to quickly and efficiently detect and classify dehydration in children in a busy and understaffed ed. the aim of this article is to equip clinicians how to cite this article: mohammed alhassan, md (2020) “assessment of dehydration in children with acute gastroenteritis: a narrative review of international guidelines,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 142–152. doi 10.18502/sjms.v15i2.6727 page 142 corresponding author: mohammed alhassan, md; +966505198904 email: mhmdarhafeez@yahoo.com received 26 april 2020 accepted 18 june 2020 published 30 june 2020 production and hosting by knowledge e mohammed alhassan, md. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mhmdarhafeez@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammed alhassan, md working in a hospital setting with practical and readily applicable clinical handles to assist them in detecting and classifying dehydration. the article may be useful mainly for physicians working at moderately to markedly under-resourced pediatric eds. clinical practice guidelines have been defined as “statements that include recommendations intended to optimize patient care, and that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options” [4]. it has been demonstrated that adherence to robust clinical practice recommendations and guidelines improves the outcomes, lowers the rate of hospital admissions, reduces the duration of hospital stay, and lowers the financial costs attributable to diarrheal diseases in children [5, 6]. however, when individual guidelines cannot provide satisfactory answers to all practice ambiguities across all settings, poor adherence to these guidelines is an expected outcome [7]. inconsistencies in recommendations among different guidelines further complicate things for practicing physicians. classifying dehydration into subgroups is an “essential basis” for appropriate rehydration [8]. this review of the international guidelines aims at providing practical answers to the following clinical questions relevant to the management of age in children. • what is the utility of individual clinical signs and symptoms in detecting and categorizing dehydration? • what is the most convenient and practical way of classifying the degree of dehydration in an ed? this has been done after reviewing, utilizing, and combining practical recommendations from international guidelines, taking into consideration the peculiarities of the organization of services, processes, and setting of a typical resource-limited yet busy hospital’s ed. 2. materials and methods 2.1. selecting, retrieving, and reviewing the guidelines in addition to the existing world health organization (who) guidelines for treating diarrhea in children, five international guideline documents addressing acute diarrhea/gastroenteritis and dehydration were retrieved from the websites of the relevant professional organizations and institutions. the guidelines are: • the who guidelines on the treatment of diarrhea in children [9–11]. • national institute for health and care excellence (nice) guidelines [12, 13]. doi 10.18502/sjms.v15i2.6727 page 143 sudan journal of medical sciences mohammed alhassan, md • cincinnati children’s hospital (cch) medical center’s guidelines on age in children aged 2 months through 5 years [14]. • guidelines for the management of acute gastroenteritis in children in europe (esp) [15]. • canadian pediatric society (cps) position statement on “oral rehydration therapy and early refeeding in the management of childhood gastroenteritis” [16]. • “managing acute gastroenteritis among children” from the centers for disease control and prevention (cdc) [17]. these guidelines were chosen based on their international reputability in addition to their quality being critically appraised previously by van den berg and berger [18]. no further critical appraisal of data has been done in this article. the author initially formulated the clinical practice questions mentioned previously (in the introduction section). each guideline document was then thoroughly reviewed with a focus on fetching recommendations that answer the research questions. these recommendations were first assessed on whether they were based on evidence of an acceptable level or were graded as strong recommendations. this was partly based on the information extracted from [18] in addition to the guidelines themselves where available. next, a decision about each recommendation applicability to the practice area of concern (i.e., a large hospital ed) was made based on the author’s judgment and experience in working in the same setting for around six years in sudan. finally, practical conclusions were suggested building on one or more corresponding recommendations from the international guidelines. 2.2. target patients age has been defined as a diarrheal disease of acute onset “with or without accompanying nausea, vomiting, fever, or abdominal pain” [14]. diarrhea is the passage of unusually loose or liquid stool, typically ≥ 3 times per 24 hr. however, “a change in stool consistency versus previous stool consistency” is more indicative of diarrhea than the frequency of defecation [9, 15]. this review is intended primarily for use in children aged one week to five years with clinically confirmed age. it is important to note that the review does not apply to the following categories: • age in a severely malnourished child (see the who definition of severe acute malnutrition [19]. doi 10.18502/sjms.v15i2.6727 page 144 sudan journal of medical sciences mohammed alhassan, md • acute diarrhea with or without vomiting as a result of non-gastrointestinal illness, for example, sepsis, urinary tract infection, and meningitis. • iso-, hypo-, or hypernatremic dehydration resulting from causes other than age, for example, acute adrenal crisis and vomiting with no diarrhea. 2.3. audience this review will be helpful primarily to practicing pediatricians, pediatric, and pediatric emergency medicine (pem) trainees working in an ed setting. although it is more directed to a resource-limited hospital, clinicians in all ranges of eds may find it useful. 3. results and discussion almost all reviewed guidelines agreed on using a three-category classification of no (< 5%) dehydration, some (mild to moderate) (5 to 9%) dehydration, and severe (≥ 10%) dehydration (the quoted percentages of loss are the ones used by the who). the fourcategory classification has mostly been avoided [20] because of poor interobserver reliability. the guidelines, however, vary in the use of clinical symptoms and signs to assess dehydration. measuring the child’s weight and comparing it to a recent measurement to calculate the percentage fluid loss was not used by any guideline to classify dehydration because of impracticality and accuracy issues. the who and nice guidelines emphasized on hypovolemic shock as a clinical entity with a greater percentage of body fluid loss and higher fluid requirement than “severe dehydration” [11, 21]. both guidelines stressed the crucial importance of early recognition and emergency treatment of hypovolemic shock. the who characterizes shock diagnosis as based on the clinical signs of cold hands, prolonged capillary refill time of > 3 sec, and weak pulses on top of signs of severe dehydration. nice guidelines pointed out that a child with shock might have a more profound depressed level of consciousness and more pronounced tachycardia than dehydration. they restated that the manifestations of advanced shock would be unequivocal, however, milder degrees of shock might be challenging to distinguish from severe dehydration, concluding that “when there was uncertainty, the safe approach would be to treat as though shock was present.” importantly also, nice suggested that, in some cases, when an infant develops rapid fluid losses, shock may ensue before the signs of severe dehydration (e.g., slow skin pinch and dry tongue) are manifested. other guidelines did not define doi 10.18502/sjms.v15i2.6727 page 145 sudan journal of medical sciences mohammed alhassan, md the “shock” category. hypotension was agreed on to be a late sign of severe shock. the presence of normal blood pressure does not rule out shock [22]. some individual signs have increased the likelihood in detecting ≥ 5% dehydration, that is, ”some dehydration” and worse. the best “individual” signs to indicate dehydration were abnormal skin turgor, absent tears, abnormal (deep/rapid/acidotic) respiratory pattern, and prolonged capillary refill (esp, cch, and nice citing the study of steiner et al. [23]). these were the highest in specificity (and likelihood ratio (lr)) for detecting ≥ 5 % (some or severe) dehydration. this means that the finding of any one of these signs is likely indicative that the child is dehydrated, but without taking the degree of dehydration into account (see page 9 in [14] and table 4.1 in [18]). an altered mental status of any degree (irritability, restlessness, lethargy, coma), sunken eyes, and dry mucus membranes (except for mouth breather) were also consistent individual signs of dehydration across all guidelines, except the who that did not assess for mucus membranes. however, their individual lrs for detecting dehydration were less than those for the signs mentioned previously [23]. poor general appearance, dry mucous membranes, and sunken eyes also had the highest individual sensitivity for detecting ≥ 5% dehydration [21]. more importantly, the absence of these signs individually had the lowest lr (negative lr = 0.46, 0.41, 0.49, respectively [23]). this implies that children with age are likely not dehydrated if they appear well, do not have sunken eyes, or have moist mucous membranes (when no recent drinking). tachycardia, although a consistently mentioned sign of dehydration in all reviewed guidelines, may also occur in a well-hydrated child with coexisting fever, abdominal pain, or anxiety [24]. this markedly lowers its utility in detecting dehydration (positive lr of 1.3 [23]). however, this consistency in guidelines might make the absence of tachycardia a reasonable indicator that a child is not severely dehydrated. the heart rate in some children with no or some dehydration may be normal (cdc, cps, cch, nice). cch and cdc guidelines also drew attention to the fact that bradycardia can occur in the most severe cases (of dehydration or shock). assessment of tears was not part of the evaluation of dehydration in three out of six guidelines (who, cps, nice). however, the presence of normal tears would argue against severe (≥ 10%) dehydration. assessment of the anterior fontanelle was used only by cch and cps guidelines, and its use was deemed “unreliable and misleading” by the cdc. parental reports of symptoms/signs of dehydration were not part of the assessment in all but one (nice) guidelines. parental reporting was stated as being not clinically useful by esp guidelines. the latter, however, strongly recommends that “parental report of normal urine output decreases the likelihood of dehydration” [15]. doi 10.18502/sjms.v15i2.6727 page 146 sudan journal of medical sciences mohammed alhassan, md at the same time, nice guidelines stated that “some reassurance could be taken if the urine output was said to be normal” [13] (see table 1). table 1: assessment and classification of dehydration.𝐴 parameter no dehydration (< 5%) some dehydration (5– 9%)𝐵 severe dehydration (≥ 10%)𝐵 hypovolemic shock (>> 10%) comment mental status and general condition well, alert𝐶 restless, irritable lethargic or unconscious𝐷 lethargic or unconscious𝐷 a well-appearing alert child decreases the likelihood of dehydration. (sensitivity of abnormal general appearance = 0.80)𝐸 eyes normal𝐶 sunken eyes** sunken eyes** sunken eyes** normal eye (not sunken) decreases the likelihood of dehydration. (sensitivity of sunken eyes = 0.75)𝐸 skin pinch goes back quickly goes back slowly𝐹 goes back very slowly (≥ 2 sec)𝐹 goes back very slowly (≥ 2 sec)𝐹 abnormal skin pinch alone increases the likelihood of ≥ 5% dehydration (not in the severely malnourished child) thirst drinks normally, no excessive thirst thirsty, drinks eagerly drinks poorly or is unable to drink drinks poorly or is unable to drink hands/extremities – 𝐺 – – cold ± pale and mottled if hands are warm, the child probably does not have hypovolemic shock (distributive types of shock may cause warm hands). breathing𝐹 acidotic breathing alone in the context of age increases the likelihood of >> 5% dehydration.𝐻 capillary refill time (crt) – – – delayed > 3 sec𝐹 a delayed crt alone in the context of age increases the likelihood of >> 5% dehydration. doi 10.18502/sjms.v15i2.6727 page 147 sudan journal of medical sciences mohammed alhassan, md parameter no dehydration (< 5%) some dehydration (5– 9%)𝐵 severe dehydration (≥ 10%)𝐵 hypovolemic shock (>> 10%) comment pulse rate – – – increased (decreased in most severe cases) poor discriminatory sign for dehydration as coexisting fever, pain, anxiety may also cause tachycardia. a normal pulse rate decreases the likelihood of severe dehydration. pulse volume – – – weak if the pulse is strong and not fast, the child is not in shock [11]. mucous membranes moist (not after a drink)𝐶 – – – moist tongue decreases the likelihood of ≥ 5% dehydration. (sensitivity of dry mucous memb. = 0.86)𝐸 tears normal – absent𝐹 absent absent tears alone increases the likelihood of ≥ 5% dehydration (not in severely malnourished children). normal tears decreases the likelihood of severe dehydration. (sensitivity of absent tears = 0.63)𝐸 𝐴this table is a modification and expansion of the who classification of dehydration in children. the shaded cells represent the who classification of dehydration. use these first to classify dehydration. if in doubt, supplement clinical judgment by using unshaded cells. 𝐵two or more signs classify children in this category. 𝐶any one negative (normal) sign makes ≥ 5% dehydration unlikely. 𝐷lethargy here means dull mental status, and the child cannot be fully awakened. 𝐸data from [23]. 𝐹 any one positive sign indicates a high likelihood of ≥ 5% dehydration. 𝐺a dash (–) means the presence or absence of the sign is not very useful in detecting or classifying this category of dehydration. 𝐻acidotic = deep ± rapid breathing **“in some infants and children, the eyes normally appear somewhat sunken. it is helpful to ask the mother if the child’s eyes are normal or more sunken than usual.” [9] 3.1. practice bottom line • it is recommended to use the who guidelines for the assessment and classification of dehydration in a pediatric ed setting, particularly a resource-limited one. • hypovolemic shock represents a higher fluid deficit than severe dehydration. – hypovolemic shock should be strongly considered if a child has features of severe dehydration and, in addition, has decreased level of consciousness, cold hands, prolonged capillary refill time, and weak and markedly fast pulses. – if the pulse is strong and not fats, the child is not in shock. – if in doubt, the child should be treated as if shock was present. doi 10.18502/sjms.v15i2.6727 page 148 sudan journal of medical sciences mohammed alhassan, md • in addition to the who classification of dehydration, the following general guides may provide clinical handles to supplement the assessment process and remove potential uncertainty. – the presence of any one of the following signs increases the likelihood of at least some (≥ 5%) dehydration (note that these signs do not indicate the degree of dehydration [some versus severe] when used individually). * prolonged capillary refill time * slow return of skin pinch (except in severe malnutrition) * acidotic (deep ± rapid) breathing * absent tears (except in severe malnutrition) – a child with any one of the following signs is likely not dehydrated. * well appearing and alert * eyes not sunken * moist mucus membranes (except after a drink) – a child with any one of the following signs is likely not severely dehydrated. * normal tears * normal pulse rate (bradycardia can occur in most severe cases of shock) • the examination of anterior fontanel is not reliable in the assessment of dehydration. • parental reporting of normal urine output decreases the likelihood of ≥ 5% dehydration. 4. conclusion the who classification of dehydration in children with age seems simple yet practical. with a supplement of clinical handles from other international guidelines, as suggested in this article, a clinician may find himself better equipped for a more accurate and quicker clinical assessment in a busy hospital ed setting. conflict of interest the author declares that there is no conflict of interest. doi 10.18502/sjms.v15i2.6727 page 149 sudan journal of medical sciences mohammed alhassan, md references [1] troeger, c., blacker, b. f., khalil, i. a., et al. 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(2009). severe acute malnutrition. who. retreived from: https://www.who. int/nutrition/topics/malnutrition/en/ [accessed march 26, 2020]. [20] nazarian, l. f., berman, j. h., brown, g., et al. (1996). practice parameter: the management of acute gastroenteritis in young children. pediatrics, vol. 97, pp. 424–436. [21] national collaborating centre for women’s and children’s health. (2009). assessing dehydration and shock. london, uk: rcog press. retreived from: https://www.nice.org.uk/guidance/cg84/documents/cg84-diarrhoea-and-vomitingin-children-under-5-evidence-tables2 [accessed march 23, 2020]. [22] advanced medical certification. diagnosing shock pals online handbook. retreived from: https://advancedmedicalcertification.com/lesson/diagnosing-shockpals-online-handbook/ [accessed march 22, 2020]. [23] steiner, m. j. and dewalt, d. (2004). is this child dehydrated? clinical scenarios: jama, vol. 291, no. 22. pp. 2746–2754. [24] fleming, s., thompson, m., stevens, r., et al. (2011). normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. lance, vol. 377, no. 9770, pp. 1011–1018. doi 10.18502/sjms.v15i2.6727 page 152 https://www.who.int/nutrition/topics/malnutrition/en/ https://www.who.int/nutrition/topics/malnutrition/en/ https://www.nice.org.uk/guidance/cg84/documents/cg84-diarrhoea-and-vomiting-in-children-under-5-evidence-tables2 https://www.nice.org.uk/guidance/cg84/documents/cg84-diarrhoea-and-vomiting-in-children-under-5-evidence-tables2 introduction materials and methods selecting, retrieving, and reviewing the guidelines target patients audience results and discussion practice bottom line conclusion conflict of interest references page 73 research article assessment of serum copper level among sudanese patients with vitiligo mehad muawia1, suad h h2, gad allah modawe3* 1. department of clinical chemistry, faculty of medical laboratory sciences, al neelain university, omdurman, sudan 2. department of dermatology, faculty of medicine and health sciences, omdurman islamic university, omdurman, sudan 3. department of biochemistry, faculty of medicine and health sciences, omdurman islamic university, omdurman, sudan abstract background: vitiligo is a common skin disease of unknown etiology characterized clinically by depigmented patches, which can be localized or generalized; it usually runs a chronic course with an un predictable outcome and failure of complete cure in many affected individuals. many communities consider it a contagious disease which leads to a great psychological and social stigma for patients; previous studies showed that copper might be associated with the pathogenesis of vitiligo. the aim of this study was to assess copper level in sudanese vitiligo patients. methods: this is a case-control study conducted in dermatology clinics in khartoum state during the period from november 2018 to february 2019. blood samples were obtained from 100 participants, 50 from vitiligo patients and 50 from non-vitiligo subjects representing a control group. serum copper was measured by mind-ray (automation). results: a highly significant increase (p = 0.000) in the copper level was seen in vitiligo patients compared with the control group. of the total number of patients, 17 (34%) were females and 33 (66%) were males. according to the duration of the disease, the copper level was significantly increased in patient group with a disease duration of > one year compared to the patient group six months – one year and patient group < 6 months; we found no significance of the family history, 18% of the case group had a family history while 42 (82%) had no family history. discussion: the relationship between the serum level of copper and vitiligo has been assessed by many studies. copper is one of the trace elements that was found to be important for tyrosinase enzyme that catalyzes the first steps in melanin synthesis in the skin. some studies showed that the disease was associated with low serum levels of copper and since vitiligo is a disease that is characterized clinically by white areas of skin with no melanin, these studies seem to be logical. however, in this study, the serum level of copper was found to be high in vitiligo patients which might be justified by the release of copper from the destroyed melanocytes. another justification might be a defect in the carrier protein for copper. conclusion: the study found that the serum copper was significantly increased in vitiligo patients compared to the control and it is recommended that serum copper level and copper profile should be assessed routinely in vitiligo patients. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6707 production and hosting by knowledge e how to cite this article: gad allah modawe (2019) “assessment of serum copper level among sudanese patients with vitiligo”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 73–84. doi 10.18502/sjms.v15i1.6707 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: gadobio77@hotmail.com received 02 january 2020 accepted 17 march 2020 published 31 march 2020 production and hosting by knowledge e cc gad allah modawe. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 74 key words: vitiligo; depigmentation; copper, sudanese introduction vitiligo is a chronic idiopathic skin disease, characterized by sharply marginated depigmented patches [1]. lesions often start on sun-exposed areas [2]. both genetic and environmental factors are believed to play a role in the pathogenesis of the disease [1, 2]. the distribution of the disease can be unilateral segmental or non-segmental [1]. vitiligo is estimated to account for 1% of the general population globally [3], however, in some populations, the incidence has reached 2–3% [4]. patients who are stigmatized for the disease can experience depression and other psychological mood disorders [5]. the risk factors for developing vitiligo include family history and other autoimmune diseases [2]. the disease is usually diagnosed clinically. the diagnosis is confirmed by tissue biopsy and histopathological study [2]. vitiligo should be differentiated from other skin conditions in which there is decrease in or loss of pigment, for example, tinea versicolor, piebaldism, idiopathic guttate hypomelanosis, etc. [6]. there is no cure for vitiligo [1], but it can be treated with the many available options, including topical steroids, sunscreens, phototherapy, etc. [1, 2]. melanin is the pigment majorly responsible for skin color; it is synthesized from amino acid tyrosine in the melanosomes that are found within epidermal melanocytes. tyrosinase enzyme catalyzes the first two reactions in the pathway of melanogenesis [7]. it is found in animal and plant tissues responsible for the production of melanin as well as other pigments in these tissues [8]. melanin is an effective absorbent of ultraviolet rays (uv) [10] and prevents the skin from its harmful effects. some studies have shown that there is a reduced incidence of some types of skin cancers in individuals with dark skin compared to others, but the relationship between photo protection and the incidence of skin cancer is not clearly understood [11]. tyrosinase is a copper-containing enzyme encoded by the tyr gene in humans [9]. copper is a trace element needed in small amount in the diet, the proximal small intestine is recognized as the main site of dietary copper absorption in mammals. the transport of copper from the intestinal lumen into the intestinal mucosa is a carriermediated process involving a saturable transport component. the overall intestinal copper uptake is influenced by amino acids, ascorbic acid, and other dietary factors [12]. once in mucosal cells, approximately 80% of the newly absorbed copper is in the cytosol, mainly bound to metallothionein (mts). these are low-molecular weight-inducible proteins with many functions including homeostasis, storage, transport, and detoxification of metals. the mts bind to many metals, but in normal circumstances only zn, cu, and cd binding is https://www.humpath.com/spip.php?article23324 sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 75 significant [13]. after passing through the enterocytes, copper enters the portal circulation where it is bound to carrier proteins (primarily albumin), peptides, and amino acids and is transported to the liver, with lesser amounts entering the kidneys. recently, many studies have been conducted to show that copper plays an important role in pigmentation, it accelerates the oxidation of dopa by skin extracts containing dopa-oxidase. furthermore, the action of copper in pigmentation was not clear until gorter [14], in 1935, conclusively demonstrated the fact that copper-free diets resulted in depigmentation of the hair of rats, rabbits, and cats and that this depigmentation disappeared following the administration of copper. on the other hand, no effect on melanogenesis was obtained if other minerals or vitamins were added to the diet [14]. in an old study submitted in philadelphia 1931, cunningham [15] made an observation relevant to this problem; he noted that the skin of black-coated animals contained more copper than the white-coated ones and that copper was concentrated mainly in the epidermis and “in vitro” experiments demonstrated the fact that copper accelerated the oxidation of dopa by skin extracts containing dopa-oxidase [15]. in the same year, sarata [15] made the first definite attempt to correlate the copper content of skin with its degree of pigmentation. a study carried out in mottled dogs and cats showed that the copper content of pigmented hair was much higher than that of the nonpigmented hair of the same animal. moreover, generally speaking, copper was found to be present in greater amounts in a skin covered by dark hair than the skin underlying the colorless hairs [15]. in 1934, schroeder, gruenberg, and schade, quoted by cornbleet [16], demonstrated that vitamin “c” inhibits the dopa reaction. cornbleet [16] found that pigmentary precipitates can occur in a solution of dopa under the action of uv light alone, buthe was able to accelerate this reaction considerably by adding copper to the solution. on the other hand, the addition of vitamin c tended to slow down the reaction or, in other words, to neutralize the catalytic effect of copper. cornbleet concluded that the presence of these two substances, having antagonistic actions, so far as the oxidation rate of dopa is concerned, makes pigment formation susceptible to ready physiologic control [16]. also, a study conducted at the faculty of medicine, fayoum university showed that serum zn levels were lower in different studied groups but it was much lower in the vitiligo group and that the serum cu levels in the vitiligo group were insignificantly higher compared to the control group. hence, serum zn and cu may have an effect on the vitiligo disease as zn in combination with other micronutrients such as cu, cobalt, nickel, iron, manganese, and ca++ plays an important role in the process of melanogenesis [17]. sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 76 in another study conducted at the central south university, changsha, china in 2014, it was noted that that out of the 16 studies that detected serum cu level, 6 reported no statistically significant cu level change in both the groups while 10 presented a significant decrease in the cu levels in the vitiligo group. thereafter, a random effect model was used for meta-analysis. in the pooled analysis, there was a significant decrease in the cu levels in the vitiligo group [16]. copper is essential for human heath, it is crucial for growth and brain development and helps fight dangerous infections, according to some reports in the literature review, lower copper increases the susceptibility to vitiligo, vitiligo is one of the most common skin diseases, it can persist for years and result in disfigurement and permanent scarring, it can cause serious adverse effects on psychological development resulting in emotional problems like withdrawing from society and depression. however, most of the researches were directed to determine the pathological effect due to changes in the level of copper, since there is a strong relationship between serum copper level and vitiligo, hence this study was designed to highlight the relation between serum copper level and vitiligo in sudanese patients. the aim of this study was to assess the serum copper level in patients with vitiligo. materials and methods this study is a case-control hospital-based study carried out at sudanese dermatology clinics and the khartoum teaching hospital for dermatology, khartoum city, khartoum state. the study was conducted during november 2018 to january 2019. the study population was 100, with 50 vitiligo patients and 50 non-vertigo patients representing the control group. the study populations were matched in age and sex, the age ranged between 16 and 60 years, the number of males studied was 33 (66%) and females 17 (34%). sudanese patients with any type of vitiligo were included in the study. whereas, all subjects with leukoderma secondary to other causes, subjects with a history of other obvious skin diseases, patients undergoing treatment with copper or any history of copper intake for six weeks before this study, and subjects who suffered from any other systemic diseases such as hepatic cirrhosis, viral hepatitis, neoplastic condition, myocardial infarction, steatorrhea, renal failure, pregnancy, consumption of oral contraceptive pills, and git troubles (like dyspepsia, diarrhea, etc.) were excluded from the study. sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 77 a blood sample of 3 ml was collected in plain containers from each volunteer under optimum condition. the blood was centrifuged at 5000 r.p.m for 10 min which was stored in small aliquots and kept in a deep freezer (–20ºc) until analyzed. data were collected from patients using questionnaire forms. after explaining the aim of the study, verbal consent was taken from all participants before sample collection. serum copper level was analyzed through spectrophotometric method using mindray. the precision and accuracy of the methods used in this study were checked each time using a control material. this study was approved by the committee of department of clinical chemistry, faculty of medical laboratory sciences, al-neelain university, khartoum, sudan. the collected data were analyzed using the statistical package of social sciences (spss) version 21.0. the results were expressed using (mean ± sd) figures and tables. results the study enrolled 50 vitiligo patients and 50 healthy subjects as a control group with matched age and sex. it was conducted at different dermatology clinics in khartoum city, khartoum state. the aim was to assess the serum copper level and to compare the results of the case and control groups of the study populations. figure 1 shows the distribution of patients according to gender. the number of males among the vitiligo patients was 33 (66%) and females 17 (34%). figure 1: distribution of patients according to the gender. sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 78 figure 2 shows the distribution of patients according to family history. nine vitiligo patients (18%) had a family history of the disease while 41 (82%) had no family history. figure 2: distribution of patients according to the family history of vitiligo disease. figure 3 shows the distribution of patients according to the duration of the disease. the patient group (6 months–1 year) had the longest duration of the disease, 27 (54%) followed by the group with > 1 year duration comprising 15 (30%) and the group with < 6 months duration comprising 8 (16%). figure 3: distribution of patients according to the duration of vitiligo disease. table 1 shows a mean comparison of age in the study populations, the age was matched between the case and control groups, the age ranged between 16 and 60 years. sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 79 table 1: mean comparison of study parameter across age. variable group min. max. mean ± sd age (years) case 16.00 60.00 32.52 ± 11.86 control 16.00 60.00 32.72 ± 10.31 table 2 shows the mean comparison of study parameter in case versus control group. the copper level in the case and control groups was 21.69 ±5 .17 mμol/l and 18.05 ± 3.51 mμol/l, respectively). the serum copper was significantly increased in vitiligo patients compared to the control group (p value = 0.000). table 2: mean comparison of study parameters in case versus control groups. parameter group mean ± sd p value copper level mμol/l case 21.69 ± 5.17 0.000 control 18.05 ± 3.51 table 3 shows mean comparison of study parameter across gender. there is no difference between males and females. table 3: mean comparison of study parameter across gender. parameter gender mean ± sd p value copper level mμol/l male 22.18 ± 5.91 0.274 female 20.74 ± 3.27 table 4 shows mean comparison of study parameter across family history. the copper levels in family history were 22.48 ± 5.53 mμol/l and 22.48 ± 5.53 mμol/l, respectively, there were insignificant differences with p value = 0.612. table 4: mean comparison of study parameter across family history. parameter family history mean ± sd p value copper level mμol/l yes 22.48 ± 5.53 0.612 no 22.48 ± 5.53 table 5 shows the mean comparison of study parameter across the duration of vitiligo disease. there was no significant difference of serum copper level regarding the duration of the disease. table 5: mean comparison of study parameter across the duration of disease. duration mean ± sd p value <6 months 20.66 ± 4.05 6months–1 year 20.91 ± 4.52 0.905 >1 year 23.63 ± 6.47 0.192 sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 80 figure 4 shows the correlations between the age and the serum copper level. there was a negative correlation between age and serum copper level (r = 0.230, p = 0.108). figure 4: the correlations between age and serum copper level in the study group. discussion vitiligo is a chronic skin disease that is considered as a stigma to patients in certain communities, it is wrongly believed to be contagious. the etiology of vitiligo is still not known and the effect of all therapies till now doesn’t seem promising. many studies have been conducted on vitiligo pathogenesis but it is still idiopathic and no result was conclusive. some studies have demonstrated the role of trace elements such as copper, zinc, iron, etc. in melanogenesis with different results and conclusions. the role of copper in melanogenesis has been studied since 1931 when keil and nelson had observed that the color of the hair of experimental rats had turned white when they were fed with only milk, which is a copper-deficient diet while being studied for milk anemia [1]. cunningham in the same year found that the white-coated animals have lower copper levels in their skin than the black-coated ones, he also found that copper is concentrated mainly in the epidermis [2]. this observation is very important. the first observation pointed to the possible role of copper in melanin synthesis and the second is more supportive to this hypothesis since melanogenesis occurs in the epidermis, but of course till that time no one had talked about the nature of melanocytes and their location within epidermal keratinocytes. since melanogenesis takes place in the skin of animals and humans, researchers started to study the role of copper and other sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 81 trace elements in animals. these studies had raised the suspicion of the role of copper in the pathogenesis of vitiligo in humans and since that time many other researches had talked about the possible role of trace elements in the etiology of vitiligo with the hope of finding promising treatment for this condition which is still idiopathic and all the possible etiologies are stated as hypotheses. the results of this study pointed to slightly increased incidence of vitiligo in male 22.18 ± 5.91 versus female 20.74 ± 3.27 with a p-value of 0.274, in agreement with wang et al. [18] who found a higher prevalence of the disease in male than in female. the male to female ratio was 1.6:1, which is similar to that reported by mcburney [19] but in disagreement with lu et al. [20] who reported that vitiligo is distributed equally in men and women. the present study was conducted on the age group ranging from 16–60 years with a mean age of 31 years, similar to marwa salem et al.’s study [21], in which she included 50 patients with vitiligo of both sexes: 33 females (60%) and 17 males (34%). fifty volunteers were included as a control group. the age in vitiligo group ranged between 15 to 60 years with a mean ± sd of 36.74 ± 14 years and in control group ranged from 15 to 60 years with a mean ± sd of 31.28 ± 9.49 years, and disagreed with a study which reported that the mean age of onset was 18.9 years, while another study found that the mean age of onset was 23.7 years old. the present findings observed that there is a high concentration of copper in vitiligo patients as compared to healthy controls, agreed with helmy et al. [22], who showed that cu levels were significantly higher in active vitiligo patients compared to the control. on the contrary, wasan and al-rubayee [23], wu et al. [24], kang et al. [27], wang et al. [18], shi et al. [25], and li et al. [26] reported no statistically significant cu level change between the vitiligo patients and the control group and all of them agreed with marwa salem et al. (26), who also reported that serum cu was insignificantly higher in vitiligo group compared to the control group. of the 16 studies that detected the serum cu level, six studies [24, 25, 28, 32, 37] reported no statistically significant cu level change between the vitiligo and the healthy groups. the others presented significant decrease of cu level in the vitiligo group (18). melanin’s are colloidal pigments and have a high affinity for metal ions; therefore, cu is found in high levels in pigmented tissues involved in melanin synthesis. as melanocytes degenerate in vitiligo patients, less cu is utilized for the melanin synthesis, which consequently raise levels of cu in serum in vitiligo patients (18). according to the results of the study we reported that the disease has no association with family history, in the mean comparison of study parameter across family history. the copper levels in family history were (22.48 ± 5.53 μμol/l and 22.48 ± 5.53 μμol/l, respectively). the p value = 0.612 sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 82 showed no significant differences, disagreeing with a chinese study that reported 20% of the patients with positive family history in first-degree relatives [18]. conclusions this study concluded that serum copper was highly and significantly increased in sudanese vitiligo patients studied compared to the control group. recommendation in our study, we recommend encouragement of healthy diets containing copper and all other trace elements important for enzymatic actions to prevent serious diseases, for example, vitiligo, measurement of copper profile, routine investigations for copper, and other trace elements for vitiligo patients, and further studies regarding the role of other trace elements need to be performed in vitiligo patients because the etiopathogenesis of the disease is still unclear and also the treatment of vitiligo still represents a great challenge. references [1] ezzedine k, eleftheriadou v, whitton m et al. (2015). vitiligo. lancet. 386(9988): 74–84. [2] niams (2014). archived from the original on 21 august 2016. retrieved 11 august 2016. [3] whitton m, pinart m, batchelor jm et al. (2016). evidence-based management of vitiligo: summary of a cochrane systematic review. the british journal of dermatology. 174(5): 962–969. [4] krüger c, schallreuter ku (2012). a review of the worldwide prevalence of vitiligo in children/adolescents and adults. international journal of dermatology. 51(10): 1206–1212. [5] picardi a, pasquini p, cattaruzza ms et al. (2003). stressful life events, social support, attachment security and alexithymia in vitiligo. a case-control study. psychotherapy and psychosomatics. 72(3): 150–158. [6] birlea sa, spritz ra, norris da (2007). vitiligo. in l. a. goldsmith, s. i. katz, b. a. gilchrest, a. s. paller, d. j. leffell, and k. wolff (eds.), fitzpatrick’s dermatology in general medicine (7th ed.). new york: mcgraw-hill professional. https://web.archive.org/web/20160821083604/http:/niams.nih.gov/health_info/vitiligo/default.asp sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 83 [7] kumar cm, sathisha uv, dharmesh s et al. (2011). interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis. biochimie. 93(3): 562–569. [8] stevens lh, davelaar e, kolb rm et al. (1998). tyrosine and cysteine are substrates for blackspot synthesis in potato. phytochemistry. 49(3): 703–707. [9] barton de, kwon bs, francke u (1988). human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7. genomics. 3(1): 17–24. [10] meredith p, riesz j (2004). radiative relaxation quantum yields for synthetic eumelanin. photochemistry and photobiology. 79(2): 211–216. [11] brenner m, hearing vj (2008) [12] fuentealba ic, aburto em (2003). animal models of copper-associated liver disease. comparative hepatology. 2(1): 5. [13] ligoxygakis p (2001). copper transport meets development. trends in genetics. 17(8): 442. [14] becker sw (1933). arch derm syph. 28: 497. [15] knin hl, nelson vh (1931). journal of biological chemistry. 93: 49; cunningham ij (1931). some biochemical and physiological aspects of copper in animal nutrition. biochemical journal. 25(4): 1267–1294. [16] mabson p (1935). bull. soc. franc. de dermat. et syph. (reunion dermat., stras-bourg). 42: 1112. [17] pillsbury dm, kulchar gv (1933). arch derm syph. 27: 36. [18] wang x, du j, wang t et al. (2013). prevalence and clinical profile of vitiligo in china: a community-based study in six cities. acta dermato-venereologica. 93(1): 62–65. [19] mcburney ei (1979). vitiligo. clinical picture and pathogenesis. archives of internal medicine. 139(11): 1295–1297. [20] lu t, gao t, wang a et al. (2007). vitiligo prevalence study in shaanxi province, china. international journal of dermatology. 46(1): 47–51. [21] (2018). the egyptian journal of hospital medicine. 70(2). [22] salem m, abd el-raheen ta, aboraia nm (2018). serum copper and zinc levels in vitiligo patients. the egyptian journal of hospital medicine. 70(3): 364–370. [23] helmy mi, gayyar el, hawas s et al. (2004). role of oxidative stress in the pathogenesis of vitiligo. journal of pan-arab league of dermatologists. 15(3): 97–105. sudan journal of medical sciences mehad muawia et al. et al. doi 10.18502/sjms.v15i1.6707 page 84 [24] wasan ts, al-rubayee w (2011). trace elements levels in serum and hair of patients with vitiligo and alopecia areata. karbala journal of medicine. 4(2): 1117–1121. [25] wu y, he n, li js et al. (2010). the zinc and copper levels in serum of 70 vitiligo patients from guangxi province. chinese journal of dermatology venereology. 24: 722. [26] shi dr, pu xm, ha ls (1993). a correlative study on serum copper and zinc in patients with vitiligo. journal of clinical dermatology. 5: 241–243. [27] li yg, zhou jg, shao zh (1988). determination of the levels of copper and zinc in plasma of serum of some patients. journal of tianjin university of commerce. 4: 24–30. [28] kang aj, su bs, xu hq (2002). research on the melanocytes apoptosis in vitiligo caused by oxygen free radicals and microelement. journal of chinese clinical medicine. 3: 4–7. sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.6211 production and hosting by knowledge e research article association of subpubic angle measurement with age and gender in a group of adult sudanese patients rabab a. mohammed and khalid a. awad department of anatomy, faculty of medicine, university of khartoum, khartoum, sudan abstract background: the measurement of the subpubic angle (spa) has been used for determining gender with a high degree of accuracy in various ethnic groups. this measurement can also be helpful in forensic and physical anthropology. the aim of this study was to compare the spa in different adult age groups (males and females) and to use the spa to estimate the demarking point (dp) for the determination of gender. methods: this study included 158 subjects – 59 male and 99 female. the spa was measured electronically using antero-posterior pelvis x-rays. measurements were taken retrospectively using the picture archiving and communication system. spa measurements were compared between the male and female participants in different adult age groups. to determine the gender, the dp was calculated from the means of spa in male and female participants. results: a comparison of the means of spa between males and females showed that females (134.94 ± 15.33°) had wider spa than males (105.88 ± 10.33) with a significant difference (p = 0.012). while a dp > 126.5 is most likely indicative of a female pelvis, a dp < 104.3 is indicative of a male pelvis. the accuracy levels based on the measured dp of participants in this study were 45.8% and 69.7% for males and females, respectively. besides, with regards to age, the mean values for different age groups in males and females were statistically insignificant (p-values were 0.21 and 0.75, respectively). conclusions: according to the obtained results, the variations in the measurements of the spa from pelvic x-rays can be used to determine gender. the calculated spa range and dp were found to predict female gender with higher accuracy. age was not associated with any notable differences in spa measurements. keywords: subpubic angle, pelvis, sudanese, sex differences 1. introduction the accurate determination of sex and race is an important tool in forensic and physical anthropology as well as obstetrics. a variety of simple pelvimetric measurements, including the subpubic angle (spa), can be used before delivery to assess the adequacy of the pelvic outlet. these measurements help in the prediction of obstructed labor, how to cite this article: rabab a. mohammed and khalid a. awad (2020) “association of subpubic angle measurement with age and gender in a group of adult sudanese patients,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 281–289. doi 10.18502/sjms.v15i3.6211 page 281 corresponding author: khalid a. awad; department of anatomy, faculty of medicine, university of khartoum, p.o box 102, khartoum, sudan. email: khalid-alamin@uok.edu khalidalamin77@gmail.com received 3 august 2020 accepted 26 august 2020 published 30 september 2020 production and hosting by knowledge e rabab a. mohammed and khalid a. awad. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:khalid-alamin@uok.edu mailto:khalidalamin77@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences rabab a. mohammed and khalid a. awad which may be complicated by uterine rupture, postpartum hemorrhage, or maternal infection. these complications represent major causes of maternal mortality in the developing world [1, 2]. the size of the spa can be used to assess the suitability of the female pelvis for labor. pelvises with a narrow spa have closer ischial tuberosities and hence smaller outlets. it is believed the spa should be ≥90° if problems during delivery are to be avoided [3]. an spa of <90° significantly increases the chances of damage to the maternal soft tissues and even arrest of the head of the baby [3]. in addition to its importance in obstetrics, measurement of the spa is important in forensic anthropology for identification of sex from skeletal remains. many studies confirm the high accuracy, sensitivity, and specificity of the spa in sex determination [4–6]. measurement of the spa in different ethnic groups at both regional and international levels indicated the occurrence of inter-population variations. studies carried out in egypt [4], uganda [7], nigeria [8], south africa [9], iran [10], united states [11], and england [12] unanimously concluded that the spa was greater in females than males. further evidence of spa variability among ethnic groups can be seen in differences between south africans and americans of white and african descent [9, 11], as well as certain nigerian tribes [8]. table 1 summarizes the measurements of the spa for males and females in selected ethnic groups. table 1 mean spa in males (in °) mean spa in females (in °) type of study egypt [4] 102.3 143.3 radiographic malawi [13] 99.00 129 radiographic nigeria: ikeweri: kalabari [8] 100.3 105 119 125 radiographic uganda [7] 93.9 116.1 radiographic iran [5] 101.5 135.5 radiographic anatolian caucasians [6] 65.9 82.6 computed tomography west australian [14] 69 88 computed tomography america: black white [11] 65.8 63.7 85.2 88.4 skeletal remains england [15] 75.8 93.5 radiographic the measurement of the spa and determining its normal range can be used to predict the occurrence of obstructed labor, hence decreasing maternal mortality. the spa can also be utilized to calculate the demarking point (dp). both of these measurements are doi 10.18502/sjms.v15i3.6211 page 282 sudan journal of medical sciences rabab a. mohammed and khalid a. awad valuable tools in physical anthropology and specifically the determination of gender from bony remains. 2. materials and methods this descriptive cross–sectional study was conducted retrospectively in a hospitalbased setting. antalya medical center, being one of the main radiological centers in khartoum state, was chosen as the study area. the investigation was carried out on sudanese patients attending the center for pelvic x-ray between january 2017 and january 2018. patients with pubic bone fractures, children, and non-sudanese citizens were excluded. data was collected using the center’s picture archiving and communication system (pacs) which enabled the use of patient’s information without breaking confidentiality. demographic data including age and gender of the patients were recorded. the pelvic x-rays used in this study were taken in an antero-posterior view. the patients were placed in the standard supine position with their legs extended and feet approximated while the x-ray tube was angulated vertically. measurements of the angle were obtained electronically from images by computed radiography (allengers-525) (see appendices 1 and 2). data were analyzed using the statistical package for the social sciences (spss. ibm®). statistical tests used were descriptive analyses, and t-test was conducted for comparison of means. the dps for males and females were obtained from the calculated ranges (calculated range = mean ± 2 sd) according to singh and potturi [16]. the dp for males was any angle greater than the minimum calculated range for females and the dp for females was any angle greater than the male calculated maximum range. 3. results in total, 158 subjects were enrolled in this study, 99 of which were females (63%) and the remaining 59 were males (37%). the mean of the spa in females (134.94° ± 15.33) was found to be greater than the mean in males (105.88° ± 10.33). this difference was statistically significant (p-value: 0.012), as shown in table 1. there was no statistical association between gender, age groups, and means of spa (the p-values in males and females were 0.21 and 0.75, respectively), table 2. doi 10.18502/sjms.v15i3.6211 page 283 sudan journal of medical sciences rabab a. mohammed and khalid a. awad the dps obtained showed that any spa <104.3° indicated a male gender, while any angle >126.5° was indicative of a female gender. using these dps, the accuracy level of gender determination was reported as 69.7% and 45.8 % for females and males, respectively (table 3). table 2: descriptive statistics for the spa in males and females. gender number mean ± sd median mode minimum maximum p-value male 59 105.88° ± 10.33 107 109 90 132 0.012* female 99 134.94° ±15.33 135 143 94 167 ∗p-value is significant (p ≤ 0.05 was considered as significant). table 3: association between gender, age group, and means of spa. gender age group n mean ± sd p-value male 18–34 19 103.14 ± 9.23 35–50 22 104.6 ± 8.89 0.21* >50 18 109.6 ± 11.21 female 18–34 28 135.94 ± 14.74 35–50 33 137.53 ± 16.54 0.75* >50 38 133.77 ± 16.68 ∗p-value is insignificant (p ≤ 0.05 was considered as significant). table 4: calculated range for spa in males and females and the demarking points according to singh and potturi. gender minimum spa (mean – 2sd) maximum spa (mean + 2 sd) demarking point accuracy level (%) male 85.2 126.5 <104.3 45.8 female 104.3 165.6 >126.5 69.7 4. discussion pelvic x-ray measurements, including the spa and dp, are significant in the fields of physical anthropology and obstetrics. using the pelvic x-rays from the present study that investigated a select sample of sudanese individuals, it was determined that the spa is generally higher in females than males. furthermore, measurements taken from these images can predict female gender with a higher degree of accuracy. the spa has been measured at regional and international levels in different ethnic groups. in the regional context, a study conducted in egypt by abd-el-hameed et al. using 400 antero-posterior radiographs reported a slightly higher spa in females than those in the present study. the mean value of the spa was found to be approximately doi 10.18502/sjms.v15i3.6211 page 284 sudan journal of medical sciences rabab a. mohammed and khalid a. awad similar in egyptian males and their sudanese counterparts investigated in the current study [4]. overall, the spa is lower in other african countries when compared with the figures found in this investigation. this is evident in data reported from malawi [13], nigeria (conducted among native ethnic groups ikwerre and kalabari) [8], uganda [7], and south africa [9]. despite the different methodologies used in the aforementioned studies (bony remains, radiographs, and computed tomography), the spa values were consistently lower than those in the current study. this difference may be explained by the varying cultural, environmental, and genetic factors that are known to determine the shape of the pelvis [17]. at the international level, results of the present investigation are consistent with those obtained from 200 iranians (males and females) [5]. other investigations were done among anatolian caucasians [6], western australian [14], black and white americans [11], and british [12]. these studies showed even greater differences in the spa measurements where the mean values reported were far lower than the ones reported in this study. this discrepancy may be caused by the ethnic variations as well as the differences in the methods used to measure the spa. findings among the sudanese population, while different from other african nations, are generally similar to egyptians and iranians. the dp method has been used in several surveys to determine the accuracy of the measurements in assigning sex as male and females [4, 16]. in the present study, the dp is more accurate in assigning female gender. when comparing these results to previous studies, they are more accurate than those in ugandan and malawian populations despite the use of the same measurement technique. in contrast, this study’s results are less accurate than in egyptians [4, 7]. the relation between age, gender, and spa was also considered in this study. there was no significant difference in the spa among the different age groups. similar results were reported in the anatolian caucasians by karakas et al. [6]. limitations considering that this study was conducted using data from one center, the population size was limited. future studies may be extended to include multiple centers both inside and outside khartoum. doi 10.18502/sjms.v15i3.6211 page 285 sudan journal of medical sciences rabab a. mohammed and khalid a. awad 5. conclusion the spa is a reliable index to predict the gender with high accuracy. the dps obtained showed that any spa <104.3° indicated male gender while any angle >126.5° was indicative of female gender. dp was more reliable in females than males. spa is not affected by age in prediction of gender. declaration section acknowledgment authors are indebted to dr abdelmonem alattaya for giving the permission to collect data from antalya medical center. they are also grateful to the staff that helped in dealing with (pacs). authors also would like to acknowledge the continued help given by naji m. alfatih, mohammed i. hassan, and mustafa hago for their technical assistance in carrying out this work. they also appreciate sally a. baraka for her help with editing the english language of the paper. ethical approval during this study, privacy and confidentiality were maintained. ethical approval was obtained from the research ethical committee of the faculty of medicine, university of khartoum. permission was obtained from the administration of the antalya medical center to conduct the study. competing interests authors declare that there were no funding or any relationship or activity that interferes with the study. authors’ contributions ram was involved in the study concept and design; acquisition, analysis, and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for the accuracy and integrity of all aspects of the work. doi 10.18502/sjms.v15i3.6211 page 286 sudan journal of medical sciences rabab a. mohammed and khalid a. awad kaa was involved in the study concept and design; analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for the accuracy and integrity of all aspects of the work. appendices appendix 1 antero-posterior pelvic x-ray showing the measurement of spa in a female participant. appendix 2 antero-posterior pelvic x-ray showing the measurement of spa in a male participant. appendix 1 doi 10.18502/sjms.v15i3.6211 page 287 sudan journal of medical sciences rabab a. mohammed and khalid a. awad appendix 2 references [1] kwast, b. e. (1991). postpartum haemorrhage: its contribution to maternal mortality. midwifery, vol. 7, no. 2, pp. 64–70. [2] kassebaum, n. j., bertozzi-villa, a., coggeshall, m. s., et al. (2014). global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the global burden of disease study 2013. the lancet, vol. 384, no. 9947, pp. 980–1004. [3] stansfield, s. (2013). fetal-pelvic disproportion and pelvic asymmetry as a potential cause for high maternal mortality in archaeological populations. msc. thesis. university of central florida. electronic theses and dissertations, 2004-2019. 2695.https://stars.library.ucf.edu/etd/2695 [4] abd-el-hameed, s. y., mohamed, a. a., and thabet, h. z. 2009 (). determination of subpubic angle in egyptian population. journal of forensic medicine and clinical toxicology, vol. 17, no. 1, pp. 41–53. [5] memarian, a., aghakhani, k., mehrpisheh, s., et al. (2017). gender determination from diagnostic factors on anteroposterior pelvic radiographs. journal of the chinese medical association, vol. 80, no. 3, pp. 161–168. doi 10.18502/sjms.v15i3.6211 page 288 https://stars.library.ucf.edu/etd/2695 sudan journal of medical sciences rabab a. mohammed and khalid a. awad [6] karakas, h. m., harma, a., and alicioglu, b. (2013). the subpubic angle in sex determination: anthropometric measurements and analyses on anatolian caucasians using multidetector computed tomography datasets. journal of forensic and legal medicine, vol. 20, no. 8, pp. 1004–1009. [7] igbigbi, p. s. and nanono-igbigbi, a. m. (2003). determination of sex and race from the subpubic angle in ugandan subjects. the american journal of forensic medicine and pathology, vol. 24, no. 2, pp. 168–172. [8] oladipo, g., okoh, p., and hart, j. (2010). comparative study of the sub-pubic angles of adult ikwerres and kalabaris. asian journal of medical sciences, vol. 2, no. 107, p. 10. [9] small, c., brits, d. m., and hemingway, j. (2012). quantification of the subpubic angle in south africans. forensic science international, vol. 222, no. 1–3, pp. 395.e1–.e6. [10] akhlaghi, m., bakhttavar, k., mokhtari, t., et al. (2017). using subpubic angle in sex determination and stature estimation: an anthropometric study on iranian adult population. international journal of medical toxicology and forensic medicine, vol. 7, no. 4: 195–202. [11] tague, r. g. (1989). variation in pelvic size between males and females. american journal of physical anthropology, vol. 80, no. 1, pp. 59–71. [12] young, m. and ince, j. h. (1940). a radiographic comparison of the male and female pelvis. journal of anatomy, vol. 74, no. 3, p. 374. [13] msamati, b., igbigbi, p., and manda, j. (2005). the sub-public angle in adult indigenous malawian subjects. east african medical journal, vol. 82, no. 12, p. 643. [14] franklin, d., cardini, a., flavel, a., et al. (2014). morphometric analysis of pelvic sexual dimorphism in a contemporary western australian population. international journal of legal medicine, vol. 128, no. 5, pp. 861–872. [15] allen, e. p. (1943). the subpubic angle: radiological aspects. the british journal of radiology, vol. 16, no. 189, pp. 279–282. [16] singh, s. and potturi, b. r. (1978). greater sciatic notch in sex determination. journal of anatomy, vol. 125, no. 3, p. 619. [17] abitbol, m. m. (1996). the shapes of the female pelvis. contributing factors. journal of reproductive medicine, vol. 41, no. 4, pp. 242–250. doi 10.18502/sjms.v15i3.6211 page 289 introduction materials and methods results discussion limitations conclusion declaration section acknowledgment ethical approval competing interests authors' contributions appendices appendix 1 appendix 2 appendix 1 appendix 2 references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.6964 production and hosting by knowledge e research article clinical teaching: sixty tips for successful implementation haitham mohamed el bingawi1 and ali hendi alghamdi2 1department of medicine, college of medicine, al baha university, saudi arabia 2department of surgery, college of medicine, al baha university, saudi arabia abstract background: a good planning of clinical teaching which is followed by systematic implementation results in better training outcomes. this paper defines the detailed roles of tutor, students, patients, and the clinical learning environment from the planning phase to what should be done post the session. it relies on the idea of using checklist (tips). our hypothesis is that checklist summarizes all relevant information in a single abstraction. methods: a literature review of various databases such as pubmed, google scholar, and cochrane with different search terms and search strategies were done. qualitative and quantitative studies published in english in the aforementioned databases, discussing both the concepts of clinical teaching as well as the roles of tutor, students, patients, and environment were reviewed. in addition, authors’ experience as clinical educators were further used to define the variables. the term tips are used to refer to the steps in a checklist. results: sixty tips were identified. these tips highlight the roles and characteristics of: clinical tutors (26 tips), students (18 tips), clinical environment (8 tips), and patients (8 tips). conclusions: these tips serve as a mini guide to everyone who conduct clinical teaching to medical students in the ward. keywords: clinical teaching, planning, implementation tips, checklist 1. introduction medical curricula have undergone a major revolution over the last decade – it has moved to more integration between basic and clinical sciences; in addition, new innovative technologies such as high fidelity simulation are also being used in the training [1]. however, despite this remarkable improvement, the overall conduct of the clinical teaching is still suboptimal [2]. the structured schedule of the new curricula is often faced with many challenges; of these, the inconsistency between the theoretical and clinical teaching is the most pertinent one. for example, if the theoretical teaching is centered around diseases of the nervous system, bedside teaching may not cover the how to cite this article: haitham mohamed el bingawi and ali hendi alghamdi (2020) “clinical teaching: sixty tips for successful implementation,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 313–323. doi 10.18502/sjms.v15i3.6964 page 313 corresponding author: haitham mohamed el bingawi; department of medicine, college of medicine, al baha university, saudi arabia email: halbenjawi@bu.edu.sa received 8 june 2020 accepted 14 july 2020 published 30 september 2020 production and hosting by knowledge e haitham mohamed el bingawi and ali hendi alghamdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:halbenjawi@bu.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi same diseases because they may not be available at that time. this gap is further widened by the growing change in patient–doctor relationship, decreased faculty– students’ ratio, busy tutors, the rapid change of training regulations, and the suboptimal preparation of teaching. therefore, it is quite evident that for clinical teaching to succeed and attain its goal, it requires more than scheduling in the timetable. multiple strategies have to be applied. simulation as an adjunct to teaching in the ward seems to have many advantages. in addition to preparing students for the real-life experience, it helps bridging the gap between theory and practice. additionally, one of the important, yet often ignored, strategies to improve clinical teaching, is the good, objective-based, and meticulous planning and implementation [3, 4]. planning is the thinking process that precedes the implementation of teaching. the plan turns in to training program that achieves the predetermined objectives within the limits of the available resources. therefore, the success of teaching is measured by the extent of its ability to achieve the desired objectives. this cannot be achieved without proper and organized planning. critical to the discussion, it is necessary to define and coordinate the role of all parties involved in training, namely, the trainer, the students, the patients, and the training environment for the success of the clinical session. this article defines the detailed roles of tutor, students, patients, and the clinical learning environment (cle). it describes the planning phase, conduction, and finally what should be done post session. it relies on the idea of using checklist (tips). our hypothesis is that checklist summarizes all relevant information in a single abstraction. 2. methods to determine the roles of tutor, students, patients, and the teaching environment in clinical teaching and to develop comprehensive checklist (tips) associated with them; we carried out a review of the literature in databases such as pubmed, google scholar, and cochrane with different search strategies. search terms like “teaching in clinical setting”, “bedside teaching”, “preparation of clinical teaching”, “planning of clinical teaching”, “implementation tips/steps of clinical teaching”, “roles of tutors in clinical teaching”, “students role in clinical teaching”, “patients role in teaching”, and “the role of the clinical environment” were used. in this way, we covered both the literature discussing the concepts of clinical teaching as well as the roles of tutor, students, patients, and environment in its conduction. qualitative and quantitative studies published in english were reviewed. moreover, we used our experience as clinical educators to define the different roles in clinical teaching. doi 10.18502/sjms.v15i3.6964 page 314 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi the term tips are used to refer to the steps in a checklist. checklist is defined as the “list of action items or criteria arranged in a systematic manner, allowing the user to record the presence/absence of the individual items listed to ensure that all are considered or completed” [5]. 3. result sixty tips were identified. these tips are grouped under four headings: tips related to the tutor (26 tips), tips related to students (18 tips), tips related to cle (8 tips), and tips related to patients (8 tips). the clinical session preparation cycle designed by the authors are easy-to-use strategy, as presented in figure 1. successful clinical teaching figure 1: clinical session preparation cycle. 3.1. tips related to the clinical tutor the clinical tutor should handle the session in a way that helps students gain the predetermined clinical competencies. therefore, they should have the necessary skills, knowledge, and attitude [6, 7]. frequently, tutors have other commitments like patients care, research, and administration that affect the planning and conduction of the session. it is therefore pertinent that the tutor plans the sessions in a way not to affect their duties but at the same time help students gain the required skills. the following are the perceived key tasks expected from the clinical tutor during and after the session, they are grouped under three headings: educational roles, organizational roles, and mentoring, as presented in figure 2. doi 10.18502/sjms.v15i3.6964 page 315 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi 3.1.1. educational roles 1. predetermine the time for teaching so that it does not overlap with other activities. 2. leveling: invest some time to know the students, their level and their previous clinical experiences. 3. clearly define the training objectives of the clinical session and plan how to accomplish them. 4. identify their educational strategies for each day. 5. update their own skills before demonstration to students. 6. demonstrate new clinical procedure that students have not seen before. 7. provide students with hands-on opportunities under a direct supervision. 8. during the discussion, allow students to listen, observe, question, demonstrate, and participate. 9. secure some time for students’ reflection and feedback. 10. demonstrate a professional attitude and approach toward both patients and students [7, 8]. 11. at the end of the session, gather the students and summarize the session. 12. reflect on the experience. 3.1.2. organizational role 1. communicate to students the required tasks to achieve their learning objectives. 2. identify patients appropriate for the objectives of the session. 3. seek consent from patients. 4. secure a setting that is suitable for attaining the predetermined objectives. 5. ensure that students have the required equipment. 6. orient the students about wards, patients, and the available resources. 7. brief the ward staff on what the students will do and provide the necessary support. doi 10.18502/sjms.v15i3.6964 page 316 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi 8. remind students to follow safety protocols (e.g., wash their hands carefully before and after examining patients. 9. keep a record of the accomplished objectives. 10. keep records of cases and skills gained by students. 11. thank the hospital staff and patients for their cooperation. 12. thank the students. 3.1.3. monitoring roles 1. be available and play an active role in facilitating students in learning to achieve the intended outcome. 2. during the students’ experience, visit sites of training, observe them while carrying out the assigned tasks, record progress, provide feedback, and solve the arising problems. monitoring roles organization roles educational roles clinical tutor roles figure 2: the triangular roles of the clinical tutor. 3.2. tips related to students students have a major role in the success of the session. good preparation will improve their learning and increase their engagement [8, 9]. however, every too often, their doi 10.18502/sjms.v15i3.6964 page 317 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi preparation is suboptimal. factors that negatively affect their preparation and engagement should be identified and resolved. the following are expected from students during their clinical rotation: 1. they must dress professionally and should wear their identification badges at all time. 2. be punctual and on time. 3. know the code of ethics and adhere to its principles. 4. behave in a manner appropriate for medical students. 5. ensure understanding the overall objectives of the clinical session and work toward achieving them. 6. identify their specific learning objectives and work toward achieving them. 7. ensure that patient consent is obtained. 8. complete the clinical tasks assigned by their tutor. 9. apply what they have previously learned in their clinical sessions. 10. maintain high standards of personal hygiene. 11. maintain patients’ confidentiality. 12. actively participate in the discussion. 13. communicate effectively with colleagues, patients, and tutors. 14. keep up-to-date record of cases seen in their logbooks. 15. give feedback to tutors after the session. 16. thank the tutor, patient, and ward staff. 17. reflect on the day’s experience. 18. develop their next clinical learning objectives. 3.3. tips related to clinical learning environment the cle includes everything that surrounds students and affects their development in the clinical setting [10, 11]. it is where the theoretical parts of the curriculum are integrated with the practical part [11, 12]. adjusting the environment, therefore, is important to doi 10.18502/sjms.v15i3.6964 page 318 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi improve students’ attainment of objectives and should not be left to chance [12, 13]. here are some of the characteristics of a good cle: 1. a health facility which affiliates to a medical school or has a good collaboration and communication with it. 2. has the resources and capacity to deliver safe and relevant learning. 3. has a welcoming, supportive, and invitational staff who assist both students and tutors in achieving their goals. 4. has a diverse patient population. 5. has doctors with all levels of experiences (e.g., interns, residents, specialists, senior specialist, and consultant). 6. is research-rich, wherein students can have the opportunity to be involved in research projects. 7. is equipped to facilitate a hands-on experience under direct supervision. 8. is technology-rich. 3.4. tips related to patients patients are excellent teachers if used properly for the session, they are central to strengthening students’ clinical skills. most patients react positively to being part of student learning. they appreciate the opportunity to interact with the students [14]. moreover, students are more motivated when meeting real patients. however, certain barriers might affect patient’s participation in the session: (1) the nature and severity of the patient’s disease, (2) previous negative experiences with students, (3) concern about confidentiality, (4) patient’s education level, (5) lack of orientation, (6) the students’ genders, and (7) students’ attitudes [15–19]. these factors need consideration when planning the session. furthermore, the patient-centered trend in clinical practice necessitates a different approach to involving patients in students training, precisely, more toward informed consent [20]. the following are to be considered when selecting patients for clinical session: 1. the patient should be clinically stable for history and examination 2. the patient’s clinical problems should fit the learning objectives and the student’s level. doi 10.18502/sjms.v15i3.6964 page 319 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi 3. the patient should agree to take part in the session and be allowed to refuse or end participation. 4. should be briefed about the session’s objectives, number of students, and duration of the interview. 5. patient’s care should be assured throughout the interview time. 6. at the end of the session, students and tutors should give feedback to patients in a way that rewards them for their involvement [18]. 7. if applicable, the patient should participate in students evaluation. 8. the patient should be empowered to provide feedback to students and tutors. 4. discussion its argued that thorough descriptions of educational interventions are helpful for medical educators when translating good practices into their own practice [21]. the authors therefore developed a checklist for thorough description of roles of tutor, students, patients, and the learning environment in clinical teaching. checklists are used frequently in our live, we prepare a shopping list and cross each item off when lifted. we list all important issues to be completed even before the day starts [22]. therefore, checklists are crucial to: (1) describe work routines and (2) guide decisions and tasks within such routines [23]. they are great in assuring that all important tasks are completed [22]. the field of medical education has benefited from using checklist, for example in osce. by doing so, osce is considered to be one of the most robust methods used for clinical assessment across medical education as it reduces examiner bias due to the standardization of items and tasks for each candidate [24, 25, and 26, 27]. not only in the field of medical education, but also in medical practice, checklists can significantly improve patient care and outcomes in term of reducing surgical site infections, postoperative complications and mortality [28, 29]. conversely, in some situations checklists failed to provide some of the expected benefits. a study conducted by heidi concluded that standardized patient osces that are graded with a checklist probably do not effectively measure knowledge, clinical skill, or reasoning [30]. hence, checklists should not be applied in all situations, particularly when unexpected events are frequent [23]. four types of check lists were distinguished; the sequential, flowchart/diagnostic, criteria of merit list and the unstructured laundry list [31]. the developed checklist belongs to the structured laundry list as the purpose of this type of list is to serve as a memory aid doi 10.18502/sjms.v15i3.6964 page 320 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi to insure that required items (or steps to be performed) are present [31]. the next step should be to validate this checklist. 5. conclusion clinical teaching is still the most attractive method of teaching clinical medicine to students. in this environment, students learn what it means to be a doctor [3]. planning is a fundamental component of ward-based teaching. an attempt is made here to develop a checklist (tips) for thorough description of roles of tutor, students, patients, and the learning environment. if applied, it may contribute positively in the quality of the sessions; however, these tips should be designed by experts in the field. references [1] irby, d. m. and wilkerson, l. (2003). educational innovations in academic medicine and environmental trends. journal of general internal medicine, vol. 18, no. 5, p. 370. [2] šimunović, v. j., hozo, i., rakić, m., et al. (2010). new paradigm in training of undergraduate clinical skills (neptune-cs). croatian medical journal, vol. 51, pp. 373–380. [3] ramani, s and leinster, s. (2008). amee guide no. 34: teaching in the clinical environment. medical teacher, vol. 30, pp. 347–364. [4] general medical council. (2009). tomorrow’s doctors: outcomes and standards for undergraduate medical education. london: gmc. available from: http://www.ub. edu/medicina_unitateducaciomedica/documentos/tomorrowsdoctors_2009.pdf [5] hales, b. m. and pronovost, p. j. (2006).the checklist: a tool for error management and performance improvement. journal of critical care, vol. 21, no. 3, pp. 231–235. [6] irby. d. m. (1994). what clinical teachers in medicine need to know? academic medicine, vol. 69, pp. 333–342. [7] ernstzen, d. v., bitzer, e. m., and grimmer-somers, k. (2009). physiotherapy students’ and clinical teachers’ perceptions of clinical learning opportunities: a case study. medical teacher, vol. 31, no. 3, pp. e102–e115. [8] valde, g. a. (1997). promoting student participation and learning through the use of weekly writing assignments. journal on excellent college teaching, vol. 8, no. 3, pp. 67–76. doi 10.18502/sjms.v15i3.6964 page 321 http://www.ub.edu/medicina_unitateducaciomedica/documentos/tomorrowsdoctors_2009.pdf http://www.ub.edu/medicina_unitateducaciomedica/documentos/tomorrowsdoctors_2009.pdf sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi [9] webb, n. m., troper, j. d., and fall, r. (1995). constructive activity and learning in collaborative small groups. journal of educational psychology, vol. 87, no. 3, pp. 406–423. [10] papastavrour, e., dimitriadou, m., tsangari, h., et al. (2016). nursing students’ satisfaction of the clinical learning environment: a research study. bmc nursing, vol. 15, p. 44. doi: 10.1186/s12912-016-0164-4. [11] steven, a., magnusson, c., and smith, p. (2014). patient safety in nursing education: contexts, tensions and feeling safe to learn. nurse education today, vol. 34, pp. 277–284. [12] aalbers, m. w., hommes, j., rethans, j., et al. (2013). why should i prepare? a mixed method study exploring the motives of medical undergraduate students to prepare for clinical skills training sessions. bmc medical education, vol. 13, no. 1, pp. 1–9. [13] mcleod, p. j. and harden, r. m. (1985). clinical teaching strategies for physicians. medical teacher, vol. 7, pp. 173–189. [14] carman, d. and britten, n. (1995). confidentiality of medical records: the patient’s perspective. british journal of general practice, vol. 45, pp. 485–488. [15] shah-khan, m., chowdhry, s., brand, m. i., et al. (2007). patient attitudes toward medical students in an outpatient colorectal surgery clinic. diseases of the colon & rectum, vol. 50, pp. 1255–1258. [16] abdulghani, h. m., al-rukban, m. o., and ahmad, s. s. (2008). patient attitudes towards medical students in riyadh, saudi arabia. education for health, vol. 21, p. 69. [17] howe, a. and anderson, j. (2003). involving patients in medical education. bmj, vol. 327, pp. 326–328. doi: 10.1136/bmj.327.7410.326. [18] al ghobain, a., alghamdi, a., arab, a., et al. (2016). patients’ perceptions towards the participation of medical students in their care. sultan qaboos university medical journal, vol. 16, no. 2, pp. e224–e229. [19] wright, h. j. (1974). patients’ attitudes to medical students in general practice. bmj, vol. i, pp. 372–376. [20] gierk, b. and harendza, s. (2012). patient selection for bedside teaching: inclusion and exclusion criteria used by teachers. medical education, vol. 46, no. 2, pp. 228– 233. doi: 10.1111/j.1365-2923.2011.04054. [21] meinema jg, buwalda n, van etten-jamaludin fs, visser mrm, van dijk n. (2019). intervention descriptions in medical education: what can be improved? a systematic review and checklist. acad med, 94(2):281-290. doi 10.18502/sjms.v15i3.6964 page 322 sudan journal of medical sciences haitham mohamed el bingawi and ali hendi alghamdi [22] explorer surgical. (october 17, 2018). why medical checklists are important. available from: https://explorersurgical.com/blog/medical-checklists-are-important/ [23] reijers, h., leopold, h., and recker, j. (2017). towards a science of checklists. proceedings of the 50th hawaii international conference on system sciences. available from: https://core.ac.uk/download/pdf/301371513.pdf [24] chong l, taylor s, haywood m, adelstein ba, shulruf b. (2017). the sights and insights of examiners in objective structured clinical examinations. j educ eval health prof. 2017 dec 27;14:34. doi: 10.3352/jeehp.14.34. pmid: 29278906; pmcid: pmc5801428. [25] sakurai h, kanada y, sugiura y, motoya i, wada y, yamada m, tomita m, tanabe s, teranishi t, tsujimura t, sawa s, okanishi t. (2014). osce based clinical skill education for physical and occupational therapists. j phys ther sci.;26:1387–1397. [26] brennan pa, croke dt, reed m, smith l, munro e, foulkes j, arnett r. (2016. does changing examiner stations during uk postgraduate surgery objective structured clinical examinations influence examination reliability and candidates’ scores? j surg educ.;73:616 623. [27] hofer re, nikolaus ob, pawlina w. (2011). using checklists in a gross anatomy laboratory improves learning outcomes and dissection quality. anat sci educ 4, 249–255. [28] pronovost, p., needham, d., berenholtz, s., et al. (2006). an intervention to decrease catheter-related bloodstream infections in the icu. new england journal of medicine, vol. 355, pp. 2725–2732. [29] haynes, a. b., weiser, t. g., berry, w. r., et al. (2009). a surgical safety checklist to reduce morbidity and mortality in a global population. new england journal of medicine, vol. 360, pp. 491–499 [30] chumley, heidi. (2008). what does an osce checklist measure? family medicine. 40. 589-91. [31] kramer heidi s. and drews frank a. (2016). checking the lists: a systematic review of electronic checklist use in health care. journal of biomedical informatics. 10.1016/jjbl.09.006 doi 10.18502/sjms.v15i3.6964 page 323 https://explorersurgical.com/blog/medical-checklists-are-important/ https://core.ac.uk/download/pdf/301371513.pdf introduction methods result tips related to the clinical tutor educational roles organizational role monitoring roles tips related to students tips related to clinical learning environment tips related to patients discussion conclusion references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.7271 production and hosting by knowledge e editorial editorial academic referencing practices dr emily paterson-morgan kne publishing https://orcid.org/0000-0002-6681-1709 this is the first of a series of short guidance pieces on international academic standards which the sudan journal of medical sciences will be producing for researchers over the coming year. as the senior editor at kne publishing, i am honoured to have been invited to write the inaugural guest editorial in this series. this editorial will focus on academic referencing practices, providing a brief overview of why accurate referencing is important, what forms it can take, practical considerations and the requirements for the sudan journal of medical sciences. accurate and comprehensive referencing practices are a cornerstone of scientific research and indeed all fields of academic study. references form the foundation of all published studies, not only providing the context for each article, highlighting where each study fits into existing scholarship and what new concepts or techniques it is providing, but also allowing readers to widen their understanding of the field and trace the intellectual heritage of a given publication. there are many reasons why accurate and effective referencing is important. firstly, it ensures authors avoid accusations of plagiarism which can arise if intellectual debts are not adequately signposted. secondly, it helps to showcase the breadth and depth of one’s research to readers and reviewers. thirdly, it defines the uniqueness of a piece of work by contextualizing it within existing scholarship. moreover, references provide supporting evidence for an author’s ideas, making research appear more authoritative and arguments more persuasive. furthermore, referencing allows authors to streamline articles, briefly citing established scholarship before focusing on valuable new material. references should be included whenever an author makes use of an idea derived from someone else’s work, whether it is a complete quotation, a piece of data, a summary, or a paraphrased idea. this information can be drawn from an article or book, newspaper or magazine, website or other electronic resources, conference paper, lecture, or personal correspondence inter alia. references can take various forms and their use is largely determined by a given journal’s style guide. references can be brief in-text citations in parenthesis such as how to cite this article: dr emily paterson-morgan (2020) “editorial academic referencing practices,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 215–217. doi 10.18502/sjms.v15i2.7271 page 215 corresponding author: dr emily paterson-morgan published 30 june 2020 production and hosting by knowledge e dr emily paterson-morgan. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://orcid.org/0000-0002-6681-1709 https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dr emily paterson-morgan (paterson-morgan, 2019). they can also be footnotes or endnotes, comprising simple source statements or more detailed discussions of tangential ideas and literature reviews. depending on the journal, authors might be asked to provide a references list or a bibliography (or both). references are individual works cited within the text, typically in numerical order, whereas a bibliography is a larger list of works which have contributed to the study, usually ordered alphabetically. it is important to always check a journal’s submissions requirements and style guide before submitting an article. there are multiple options to choose from, including the chicago, harvard, apa, mla and vancouver referencing styles. the sudan journal of medical sciences uses the vancouver style. this is a numerical referencing format which includes numbers in parenthesis which relate to numbered references at the end of the document. for example: in the text: the format of sjms complies with the “uniform requirements for manuscripts submitted to biomedical journals” as published by the international committee of medical journal editors in vancouver, british columbia in 1979 [1]. reference: [1] harlem o, huth e j, lock s p, et al. uniform requirements for manuscripts submitted to biomedical journals. ann. intern. med. 1982, jun. 96(6):766-768. however, regardless of which style a journal requires, a researcher can ensure they always have all the necessary information by noting down the following details for every item they read and take notes from: • author surname and first name • the article, chapter, or publication title • publication details (including journal title and volume number, or book publisher and location) • page numbers • website urls and dates accessed (for online resources). this will ensure that an article can easily be prepared in accordance with any journal’s referencing requirements. that is not to say that referencing is not a time-consuming process. however, there are various digital solutions which can help with referencing, such as endnote. in addition, many publishers and research aggregators offer a ‘how to cite’ function for online resources, allowing users to select the appropriate referencing style and download doi 10.18502/sjms.v15i2.7271 page 216 sudan journal of medical sciences dr emily paterson-morgan a correctly formatted reference into their records. meanwhile, some publishers offer editorial solutions (such as kne publishing’s support services) performing the timeconsuming reference formatting processes for a small fee. not conforming to internationally recognized academic referencing standards can raise concerns about the quality of the article and the validity of the underlying research. in addition, if incorrect or inadequate referencing is submitted, this can produce long delays as editors are obliged to send content back to the author requesting additional material. an article will not necessarily get rejected if the wrong referencing style is used but displaying accurate and correct references undoubtedly facilitates acceptance. to conclude, accurate referencing is a mark of academic rigour and high-quality research. it ensures an article will be integrated into wider scholarly discussions and debates, enhancing its potential impact. doi 10.18502/sjms.v15i2.7271 page 217 sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6974 production and hosting by knowledge e research article nurse’s knowledge and practice on the care of preterm infants at khartoum state hospitals hammad ali fadlalmola1 and amal mohamed elhusein2 1nursing college, taibah university, madinah, saudi arabia 2nursing department, bisha university, bisha, saudi arabia abstract background: premature infants can develop a range of problems because their immature organs. a proper nursing care for a premature baby should be established through good nursing performances. this study aimed to assess nurse’s knowledge and practices regarding the care of a premature baby in a neonatal intensive care unit (nicu). methods: this study is a descriptive cross-sectional study, with a systematic collection, analysis, and interpretation of data that reports a clear picture of a particular situation carried out by 72 eligible nurses who were a graduate in bsc., and had at least six months’ experience at the time of the study. result: the study showed that the percentage of nurse’s knowledge regarding care of premature; definition of preterm neonate 44.4%, nurses’ had poor knowledge, umbilical vessels: two arteries & one vein 40.3 %, nurses’ had poor knowledge, and the percentage of nurses’ practices regarding care of premature baby; hand washing o 36.1 %, nurses’ have poor practice, so there were poor nurses’ knowledge and practices regarding care of premature baby. conclusion: based on the results of our study, we concluded that most of the nurses had relatively poor knowledge and practices about the aspects of premature care. keywords: nurses’ performances, preterm neonate, neonate in intensive care unit, nursing care, sudan 1. introduction theworld health organization (who) defines a preterm birth as all births before the completion of 37 weeks of gestation or < 259 days since the last day of a woman’s menstrual period [1]. preterm birth has become a worldwide epidemic that is estimated at a global incidence of 15 million per year [2]. it is a major cause of death and a significant cause of long-term human loss worldwide. the complications of preterm birth are the single largest direct cause of neonatal deaths, responsible for 35% of the world’s 3.1 how to cite this article: hammad ali fadlalmola and amal mohamed elhusein (2020) “nurse’s knowledge and practice on the care of preterm infants at khartoum state hospitals,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 184–194. doi 10.18502/sjms.v15i2.6974 page 184 corresponding author: hammad ali fadlalmola; tel: +966 504900120 email: hazzminno345@gmail.com received 5 may 2020 accepted 24 june 2020 published 30 june 2020 production and hosting by knowledge e hammad ali fadlalmola and amal mohamed elhusein. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hazzminno345@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein million deaths per year and the second most common cause of under-five deaths after pneumonia [3]. an estimated number of 13 million babies are born premature annually. rates are generally highest in lowand middle-income countries, and are on the rise in few middleand high-income countries, particularly the americas. preterm birth is the leading direct cause of neonatal death (27%); more than one million preterm newborns die annually [4]. although, according to the who, more than 60% of the preterm births occur in africa and south asia, it is truly a global problem. in the lower-income countries, on average, 12% of babies are born too early compared with the 9% in the higher-income countries. within these countries, the poorer families are at a higher risk [5]. in a study by lawn et al., it was reported that most premature babies (> 80%) are born between 32 and 37 weeks of gestation, and many die needlessly due to the lack of simple care. the authors outline a series of packages of essential care for every newborn that are includes support for immediate and exclusive breastfeeding, thermal care, and hygienic cord, and skin care. for babies who do not breathe at birth, rapid neonatal resuscitation is crucial [6]. innovative solutions are urgently need to prevent preterm birth worldwide, for example, there is a need of improvement in the antenatal, obstetric, and newborn cares to increase the survival rate [7]. since there were not many studies on the topic of premature infants’ nursing care, particularly focusing on nursing, it encouraged us to address this topic. . two studies were conducted in jordan and iraq, but they were more focused on the respiratory distress syndrome of a newborn in general and not just preterm, they recommended on providing an educational program for nurses for improving the quality of nursing care of neonatal respiratory distress syndrome [8, 9]. in sudan, where the current study was conducted, a good and meticulous search was performed in the literature, and no study matching the subject of the current study was found. yet, there are some studies that dealt with some aspects related to the subject of the study. however, there is a reference to work that assesses the effectiveness of education program on nurses’ knowledge and performance [10]. 1.1. problem statement the investigators observed that the nurses had limited information regarding the care of premature babies. doi 10.18502/sjms.v15i2.6974 page 185 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein 1.2. justification and rationale previous studies about the care of preterm neonates have ignored the important nursing practices, for example the care of umbilical catheter, preterm care on continuous positive airways pressure (cpap), ventilator, and incubator care. a good nursing care of a preterm baby plays an important role in reducing morbidity and mortality and improve the survival for newborns. 1.3. research question what is the level of knowledge and practice of nurses about nursing care of a preterm infant? 1.4. objectives 1.4.1. general objective to assess nurse’s knowledge and practices regarding the care of preterm infants in the neonatal intensive care unit (nicu) in khartoum state hospitals. 1.4.2. specific objectives to assess nurses’ knowledge about preterm care and compare their knowledge with their practices regarding the care of preterm neonates. 2. materials and methods 2.1. study design this is a descriptive cross-sectional hospital-based study, involving a systematic collection, analysis, and interpretation of data to give a clear picture of a particular situation. 2.2. study setting the nicu is distributed in the main two localities, (khartoum and omdurman) this descriptive study was carried out in an nicu at the jaafer ibn ouf pediatrics specialized hospital, which is located in khartoum state on the mak nemir st. north of doi 10.18502/sjms.v15i2.6974 page 186 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein the dermatological hospital and consists of four rooms. the study was also carried out in the omdurman maternity hospital, which is located in omdurman state. the hospital contains one nicu with three rooms. 2.3. study population the focused groups of the study were the nurses working in the nicu. the selected nurses were bsc. graduates and had at least six months’ experience. 2.4. inclusion criteria nurses working in the nicus who accepted to participate in the study, had a bsc. certificate and at least six months’ of experience. 2.5. exclusion criteria nurses who did not agree to participate in the study, were absent at the time of data collection time, and those that had less than six months of experience were excluded from the study. 2.6. sampling 2.6.1. sample size and technique a total of 42 nurses from the omdurman maternity hospital and 30 from the jaafer ibn ouf hospital participated in the study. 2.7. methods of data collection this descriptive cross-sectional study design involves a systematic collection, analysis, and interpretation of data to give a clear picture of a particular situation which was carried out on 72 eligible nurses qualified for the study and who were available during the study period. the study focused mainly on the nursing process such as the care of umbilical catheter, preterm care on cpap, ventilator and incubator care, gavages feeding, oxygen administration, and care of a baby under phototherapy. doi 10.18502/sjms.v15i2.6974 page 187 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein 2.7.1. data collection tools the data was obtained through interview questionnaires. each participating nurse was provided a checklist to cross-assess their practice. therefore, the data collection technique was administrated through written questionnaire and observation. 2.7.2. data analysis data was entered and analyzed using the spss program version 20. it was organized, tabulated, and analyzed based on the objectives of the study using descriptive statistics, that is, the percentage, mean, and standard deviation, represented as figures and tables in the article. 3. results of the 72 nurses participating in the study, about one-fifth (20.8%) stated that they needed training courses on cpap, and a minority (2.8%) of them stated that they needed courses on the care of preterm infants. this indicates that the nurses had poor knowledge about the care of preterm infants as shown in figure 1. moreover, about 68.1% of the study samples stated that a preterm baby is a baby born before 24 weeks of gestation, while only 5.6% knew it refers to a baby born before 40 weeks of gestation, which indicates the nurses’ low level of knowledge about the definition of preterm baby itself (table 1). additionally, about 86.1% of the nurses considered respiratory distress syndrome as a common complication of prematurity, and 61.1% of them stated neonatal septicemia as a common complication of prematurity (table 2). regarding the susceptibility of the preterm infant to infection, 93.1% of the responders stated that low immunity and 19.4% of them stated that anemia increases the susceptibility of preterm infant to infection as shown in figure 2. table 1: distribution of the study samples according to their knowledge regarding the definition of a preterm neonate (n = 72) definition of preterm neonate yes frequency percentage a. baby born before 24 weeks of gestation 49 68.1% b. baby born before 37 weeks of gestation 32 44.4% c. baby born before 40 weeks of gestation 4 5.6% total 72 100% doi 10.18502/sjms.v15i2.6974 page 188 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein figure 1: distribution of the study samples according to their knowledge regarding the training courses. table 2: distribution of the study samples according to their knowledge regarding the common complication of prematurity (n = 72) common complication of prematurity yes frequency percentage a. respiratory distress syndrome 62 86.1% b. anemia and hemorrhage 20 27.8% c. necrotizing enterocolitis 21 29.2% d. neonatal septicemia 44 61.1% total 72 100% 4. discussion the study shows that nurses’ had poor knowledge and practices regarding the care of a premature baby. as per the who scores concerning the knowledge, 0-50% is considered as poor, 50–75% as fair, and (75–100% as[11]. about 43.1% of the study samples had an experience of six months that lead to the poor knowledge of the nurses, as supported by a previous study [12]. of the participants who had at least one year of experience working with newborns, about 98.6% had a bachelor’s degree in nursing sciences. further, about 20.8% of the study samples stated that they needed a training on cpap, and only 2.8% thought they needed a training on the preterm infant care. doi 10.18502/sjms.v15i2.6974 page 189 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein figure 2: distribution of the study samples according to their knowledge regarding the susceptibility of preterm infant to infection. while 68.1% of the study samples stated that a preterm is baby born before 24 weeks of gestation, only 5.6%knew that it refers to a baby born before 40 weeks’ gestation. the current result revealed that 86.1% of the nurses stated respiratory distress syndrome as a common complication of prematurity, which is considered as a good knowledge, and about 61.1% of them stated neonatal septicemia as a common complication, which was termed as a fair knowledge [11, 13]. about 93.1% of the responders stated that low immunity makes a preterm infant susceptible to infection, which was good knowledge in relation to a literature review, and only 19.4% said that anemia makes them susceptible to infection, which shows their poor knowledge on the subject. with respect to complications, 91.7% of the study sample stated that infection is a complication of umbilical vein catheterization, showing nurses’ good knowledge in relation to prof nicholas evans’ study [14] and 51.4% considered thromboembolism as a complication, showing a fair knowledge in relation to the literature review. about 38.9% of the nurses stated that infection can be reduced by attaching three-way taps to the end of each umbilical venous catheters (uvc) lumen, showing their poor knowledge in relation to study which stated the attach 3 way taps to end of each uvc reduce the infection [15]. and a quarter (75.0%) of them they stated that easy manipulation. it was observed that the majority (80.6%) of the study samples stated that the incubator is indicated for all preterm infant < 34 weeks, showing the nurses’ had good doi 10.18502/sjms.v15i2.6974 page 190 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein knowledge in relation to study which stated that an incubator is indicated for all preterm infant < 34 weeks [16]. about 59.7% of the study samples stated that nurse infant supine or in lateral position for 24 hours post-procedure, third-fifth (62.5%) of the study sample they said that doesn’t cover the umbilical stump, the nurses’ fair practice. only 4.2% of the study samples stated that humidification of incubator should be started in all preterm with < 31 weeks’ gestation at 85% humidity, showing that the nurses’ had a poor knowledge with respect to the study of harpin and rutter, which stated that humidification of incubator should be started in all preterm < 31 weeks’ gestation at 85% humidity [17]. about 4.2% of the study samples said that handwashing is important for the preterm care while gavage feeding, showing the nurses’ poor knowledge with respect to abaker’s study [18]. about 97.2% of the responders stated that gavage feeding tube should be checked and fixed with an adhesive tip, and 94.4% of them said that the correct position of the tube in the stomach should also be checked, showing that the nurses had a good practical knowledge of quesenberry and hillyers study, which list handwashing, measuring the placement of the tube from tip of the nose to ear lobe and then up to xiphoid, lubricating the tube with lubrication jelly, checking the correct position of the tube in the stomach, withdrawing injection air from the stomach and aspirating the gastric content, fixing the tube with adhesive tip, disposing waste material as per hospital policy as important factors for preterm care [19]. about 95.8% of the nurses said that the eye and genitalia should be covered during phototherapy, and about 84.7% stated that baby’s temperature should be monitored frequently, showing that the nurses had a good knowledge with respect to murphy et al.’s study. additionally, only about 23.6% of the study sample stated that fluid balance should be monitored carefully, showing nurses’ poor knowledge. about 56.9% of the study samples knew about teaching mothers about breastfeeding, showing their fair knowledge of the who and unicef guidelines. besides, only 13.9% of them explained parent about the environmental hygiene, follow-up plan and immunization, reflecting their poor knowledge on teaching mothers about breastfeeding, explaining about environmental hygiene, and follow-up plan and immunization [20] . 5. conclusion based on the results of the current study, we conclude that most nurses had relatively poor knowledge and practices about the aspects of premature care. they had adequate doi 10.18502/sjms.v15i2.6974 page 191 sudan journal of medical sciences hammad ali fadlalmola and amal mohamed elhusein knowledge about gavages feeding tube and that it must be fixed with adhesive tip, but poor knowledge regarding the humidification of incubator, care of baby on cpap, umbilical vessels, preparation, and procedure of uvc, teaching and supporting the parent. acknowledgements the authors acknowledge the two hospitals in which conduct the research was conducted and thank all nurses that participated in the study. ethical considerations an official letter from the supervisor of the faculty of nursing science, khartoum university was issued to the manager of the omdurman maternity hospital and the jaafer ibn ouf pediatric hospital to carry out this study in their hospitals, ensuring confidentiality and preserving information. all nurses gave a written informed consent prior to the study. competing interests the authors declare that there was no conflict of interest. funding this research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sectors. references [1] linked to “born too soon: the global action report on preterm birth.” country data and rankings for preterm birth embargo until may 2nd 2012. “born too soon glob. action rep. preterm birth,” 2012. retrieved from: http://www.who.int/pmnch/ media/news/2012/201204_borntoosoon_countryranking.pdf [2] purisch, s. e. and gyamfi-bannerman, c. 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(1997). guidelines for the use of phototherapy and photochemotherapy in ireland. irish journal of medical science, vol. 166, no. 2, p. 92. doi 10.18502/sjms.v15i2.6974 page 194 introduction problem statement justification and rationale research question objectives general objective specific objectives materials and methods study design study setting study population inclusion criteria exclusion criteria sampling sample size and technique methods of data collection data collection tools data analysis results discussion conclusion acknowledgements ethical considerations competing interests funding references page 10 research article the relationship between dyslipidemia and lupus nephritis in systemic lupus erythematosus patients attending a saudi rheumatic center, tabuk hyder osman mirghani1*, abdullah abdul khalig alyoussef2, osama salih mohammed3, palanisamy amirthalingam2 1. department of medicine, faculty of medicine, university of tabuk, tabuk, kingdom of saudi arabia 2. department of clinical pharmacy, faculty of pharmacy, university of tabuk, tabuk, kingdom of saudi arabia 3. king fahd specialist hospital, al qadsiyyah, tabuk, saudi arabia abstract background: there is an increasing awareness of the role of dyslipidemia in lupus nephritis patients, no researchers have studied dyslipidemia in systemic lupus erythematosus (sle) in tabuk. in this study, we aimed to investigate the association between dyslipidemia and lupus nephritis in tabuk, saudi arabia. methods: this cross-sectional comparative longitudinal hospital-based study was conducted at a rheumatic clinic in the north west armed force hospital (nwafh) during the period april 2014–june 2015. seventy-three patients diagnosed with sle were invited to participate in the study. all participants were required to sign a written informed consent, following which they were interviewed using a structured questionnaire. data collected include demographic data, clinical characteristics, fasting lipid profile, renal function tests, urine analysis, antinuclear antibody, anti-double-stranded antibodies, complement levels, serum albumin, anticardiolipin, ant bodies, and antiphospholipid antibodies. lupus nephritis was ascertained by renal biopsy. the research was approved by the ethical committees of both the university of tabuk and the nwafh and data were analyzed using the statistical package for social sciences (spss). results: out of 73 patients with sle, 86.3% were females with a mean age of 34 ± 6.4 years. lupus nephritis was evident in 26% of the patients, proteinuria in 44.1%, high total cholesterol in 17.8%, high low-density lipoprotein in 15.1%, high triglycerides in 27.3%, and low high-density lipoproteins in 52.1%. patients with lupus nephritis had high total cholesterol, high ldl, high tg, and low hdl than those without lupus nephritis p < 0.05. conclusion: dyslipidemia was more common among patients with sle nephritis, and an aggressive treatment is recommended to reduce this serious complication. the relatively small size of the study group and the fact that the study was conducted at a single tertiary center are the limitations of this study. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6697 production and hosting by knowledge e how to cite this article: hyder osman mirghani (2019) “the relationship between dyslipidemia and lupus nephritis in systemic lupus erythematosus patients attending a saudi rheumatic center, tabuk”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 10–19. doi 10.18502/sjms.v15i1.6697 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: s.hyder63@hotmail.com. received 09 december 2019 accepted 05 march 2020 published 31 march 2020 production and hosting by knowledge e cc hyder osman mirghani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: dyslipidemia, lupus nephritis, saudi arabia mailto:s.hyder63@hotmail.com sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 11 introduction systemic lupus erythematosus (sle) is a chronic autoimmune disease found in women in their childbearing age; nearly one-fifth of the cases occur in the first two decades of a woman’s life. the disease runs a remitting-relapsing course with breakout difficult to control. cardiovascular disease is the most common cause of death among patients that acquire the disease for more than five years [1]. accelerated atherosclerosis and premature ischemic heart disease are common causes of mortality and morbidity among patients with sle. increasing age is a risk factor for coronary heart disease but unlike the general population, young women with sle are more affected. the potential for cardiovascular disease including myocardial infarction, cerebrovascular and peripheral arterial disease in young women with sle is approximately double than that in the general population [2, 3]. several pathophysiological mechanisms mediate coronary heart disease including atherosclerosis, arteritis, thrombosis, spasm, embolization, and abnormal coronary flow [4]. it is strongly suggested by epidemiological studies that in addition to conventional coronary risk factors, there are non-classical risks in sle patients, in fact, sle is considered an independent risk factor for atherosclerosis [5, 6]. a recently published research concluded that regardless of food intake and nutritional status, preserved kidney function, low disease activity, and low steroid dose, adolescent females with sle have proatherogenic lipid biomarkers that may contribute to atherosclerosis risks [7]. in this regard, dyslipidemia was found to be prevalent in sle patients (55–77%), especially among those with active disease, heavy proteinuria, and concomitant medications. furthermore, cardiovascular complications are the leading cause of death among sle patients with renal failure, and renal impairment was found to be associated with dyslipidemia [8]. no researcher has studied dyslipidemia in sle patients in tabuk, saudi arabia. thus, the present study was conducted to investigate the relationship of dyslipidemia among patients with sle in tabuk. materials and methods this cross-sectional descriptive, longitudinal, hospital-based study was conducted between june 2014 and april 2015 among patients attending the rheumatic outpatients’ sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 12 clinic in the north west armed force hospital. seventy-three patients above the age of 18 years diagnosed with sle based on the american college of rheumatology criteria (acr) [9] signed a written informed consent form before being interviewed and examined by the researcher (a rheumatologist). a structured questionnaire was used to obtain sociodemographic data and clinical characteristics including lupus nephritis based on renal biopsy findings, myocardial infarction, stroke, infections, hypertension, pre-hypertension, and hypotension. all patients were in remission at the time of lipid measurements as indicated by serological markers. patients with active disease were excluded from the study as well as those on steroid dose >10 mg/day, diabetic patients, patients with nephrotic range proteinuria, those with chronic liver disease or active malignancy, patients diagnosed with familial dyslipidemias, active thyroid disorders, and patients on oral contraceptive pills. the following investigations were undertaken: urinalysis for rbcs cast, albumin, and pus cells, full blood count, complement level, erythrocyte sedimentation rate (esr), high sensitive c-reactive protein (crp), and antinuclear antibody profile (ana). total cholesterol and triglycerides were measured using a colorimetric enzyme assay (ningbo ruiyuan biotechnology co., ltd., zhejiang, china). hdl-c and ldl-c were quantified using the gpo–pap method (beckman coulter, miami, fl, usa). the urease method from bun healthcare diagnostics newark de 19714 usa was used for blood urea nitrogen measurement, and serum creatinine was ascertained using crea healthcare diagnostics newark, de 19714 usa based on the idea that in the presence of naoh, pectate reacts with creatinine to form a red chromophore measurable by bichromatic (510e600). for the purpose of this research, the following definitions were adopted: • hypertension: self-reported, on antihypertensive therapy, history of systolic blood pressure >140 mmhg or diastolic blood pressure >90 mmhg. • abnormal lipid profile: total cholesterol [tc] ≥5.18 mmol/l; triglyceride [tg] ≥2.26 mmol/l; high-density lipoprotein cholesterol [hdl-c] <0.91 mmol/l; lowdensity lipoprotein cholesterol [ldl-c] ≥3.37 mmol/l, according to the adult treatment panel iii criteria [10]. the ethical committee of the university of tabuk and the local committee approved the research, and the statistical package for social sciences was used for data analysis. the chi-square test was used to compare categorical data, and data were presented as a mean ± sd and percentages unless otherwise specified with a p < 0.05 considered as significant. sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 13 results female dominance (86.3%) was obvious in the 73 studied patients, their age ranged from 20 to 50 years with a mean age of 34 ± 6.4 years. lupus nephritis was found in 26% of the patients, stroke was evident in 8.2%, while myocardial infarction was concluded in 1.4% of the sle patients. other clinical characteristics are shown in table 1. table 2 illustrates the laboratory investigations among sle patients in which high total cholesterol was found in 17.8%, high ldl in 15.1%, high triglycerides in 27.3%, while low hdl was observed in 52.1%. in the present study, proteinuria was found in 44.1% of the sle patients, rbcs cast was found in 27.5%, raised urea and creatinine were observed in 7.9%, and low serum albumin in 71.45. regarding immunological screening, ana was positive in 98.6%, antidouble stranded antibody was positive in 100%, antismith antibodies were positive in 26%, anticardiolipin was positive in 13.7%, antiphospholipid was positive in 3.9%, while antiribonucleoprotein was positive in 20.5%. table 1: clinical characteristics of systemic lupus erythematosus patients. no. (%)character 19 (26%)lupus nephritis 6 (8.2%)stroke 1 (1.4%)myocardial infarction 4 (5.5%)pulmonary embolism 26 (35.6%)neuropsychiatric manifestations 11 (15.1%)hypertension 19 (26%)prehypertension 25 (34.2%)hypotension 10 (13.7%)infections table 2: laboratory investigations of sle patients. no. (%)investigation 13 (17.8%)high total cholesterol 11 (15.1%)high ldl 20 (27.3%)high tg 38 (52.1%)low hdl 30 (44.1%)proteinuria 19 (27.5%)red blood cells cast 5 (7.9%)raised urea & creatinine 45 (71.4%)low albumin 72 (98.6%)antinuclear antibodies positive 73 (100%)antidoubles stranded antibodies 19 (26%)antismith antibodies positive 10 (13.7%)anticardiolipin positive 3 (3.9%)antiphospholipid positive 15 (20.5%)antiribonucleoprotein positive sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 14 in the current study, the total cholesterol was higher among patients with sle nephropathy 5.40 ± 1.46 mmol/l vs 4.36 ± 0.82 with a significant statistical difference, p value was 0.003, ldl was 3.13 ± 0.82 mmol/l vs 2.66 ± 0.53 in patients with nephropathy and those without nephropathy, respectively, with significant statistical difference, p = 0.028; triglycerides were higher in lupus nephritis 2.31 ± 1.54 mmol/l vs 1.28 ± 0.72 with a p = 0.003, no significant statistical difference was evident regarding high-density lipoproteins levels (see table 3). table 3: the relationship between dyslipidemia and lupus nephritis. lupus nephritis others p value total cholesterol (>5.2 mmol) 5.40 + 1.46 4.36 + 0.82 0.0036 triglycerides (>1.7 mmol) 2.31 + 1.54 1.28 + 0.72 0.0033 ldl (>3.4) 3.13 + 0.82 2.66 + 0.53 0.0285 hdl (male <1 mmol; female <1.5 mmol) 1.11 + 0.32 1.18 + 0.23 0.3901 in the current data, the total cholesterol was higher among patients with proteinuria 5.20 ± 1.31 mmol/liter vs 4.28 ± 0.88 with a significant statistical difference of p value 0.007, ldl was higher among patients with proteinuria 3.06 ± 0.73 vs 2.60 ± 0.52 with a significant statistical difference of p value 0.024. table 4 depicts the relationship between lipid profile and proteinuria among sle patients. table 4: the relationship of dyslipidemia and proteinuria. proteinuria others p value total cholesterol (>5.2 mmol) 5.20 + 1.31 4.28 + 0.88 0.0076 triglycerides (>1.7 mmol) 2.03 + 1.43 1.26 + 0.76 0.0271 ldl (>3.4) 3.06 + 0.73 2.60 + 0.56 0.0248 hdl (male <1 mmol; female <1.5 mmol) 1.12 + 0.29 1.20 + 0.24 0.2736 the triglycerides levels were higher among patients with neuropsychiatric manifestations compared to those without 1.96 ± 1.4 mmol/l vs 1.43 ± 0.92 with a significant statistical difference of p = 0.019; total cholesterol was higher among neuropsychiatric patients 4.88 ± 1.4 vs 4.63 ± 1.02 with no significant statistical difference of p = 0.512. table 5 shows the relationship between lipid profile and neuropsychiatric manifestations. sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 15 table 5: the relationship between neuropsychiatric manifestations and dyslipidemia. neuropsychiatry others p value total cholesterol (>5.2 mmol) 4.88 + 1.4 4.63 + 1.02 0.5121 triglycerides (>1.7 mmol) 1.96 + 1.4 1.43 + 0.92 0.0195 ldl (>3.4) 2.98 + 0.74 2.74 + 0.63 0.2713 hdl (male <1 mmol; female <1.5 mmol) 1.206 + 0.27 1.07 + 0.23 0.0995 the total cholesterol level was 4.65 ± 0.70 mmol/l in patients with low complement level, and 4.71 ± 1.26 in patients with normal complements with no significant statistical difference of p = 0.885; triglycerides were 1.46 ± 1.09 in patients with low complement level vs 1.65 ± 1.17 in patients with normal complement level with no significant statistical difference of p = 0.652. table 6 illustrates the relationship between the complement level and lipid profile. table 6: the relationship between dyslipidemia and complements level. complement cascade (normal) complement cascade (low) p value total cholesterol (>5.2 mmol) 4.71 + 1.26 4.65 + 0.70 0.8851 triglycerides (>1.7 mmol) 1.65 + 1.17 1.46 + 1.09 0.6520 ldl (>3.4) 2.85 + 0.69 2.70 + 0.59 0.5677 hdl (male <1 mmol; female <1.5 mmol) 1.25 + 0.26 1.29 + 0.24 0.0873 the relationship between the serum albumin and lipid profile are shown in table 7 in which the total cholesterol was 4.86 ± 1.38 mmol/l in patients with low serum albumin vs 4.48 ± 0.46 mmol/l in patients with normal serum albumin with no statistically significant difference of p = 0.337; tg was 1.26 ± 0.59 mmol/l vs 1.87 ± 1.30 in patients with low and normal serum albumin, respectively, with p = 0.114; ldl was 2.91 ± 0.71 mmol/l among patients with low albumin vs 2.78 ± 0.48 in normal serum albumin patients with p = 0.583; while hdl level was 1.14 ± 0.27 mmol/l and 1.14 ± 0.23 among patients with low and normal serum albumin, respectively, with p = 0.933. sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 16 table 7: the relationship between dyslipidemia and serum albumin. albumin (<35) albumin (>35) p value total cholesterol (>5.2 mmol) 4.86 + 1.38 4.48 + 0.46 0.3375 triglycerides (>1.7 mmol) 1.26 + 0.59 1.87 + 1.30 0.1141 ldl (>3.4) 2.91 + 0.71 2.78 + 0.48 0.5835 hdl (male <1 mmol; female <1.5 mmol) 1.14 + 0.27 1.14 + 0.23 0.9339 discussion advances in immunosuppressive therapy and supportive care have improved the survival and short-term clinical outcomes of sle patients, with a substantial improvement in the cardiovascular morbidity and mortality, there is an increasing awareness of dyslipidemia as a major vascular risk among these patients [11]. the present data showed high total cholesterol in 17.8%, high ldl in 15.1%, high triglycerides in 27.3%, and low hdl in 52.1% of sle patients, hypercholesterolemia was higher than in an epidemiological study conducted among saudi patients [12] and hypercholesterolemia was found in 8.5%. a study published in jakarta found high total cholesterol, high ldl, high triglycerides, and low hdl in 43%, 26.4%, 44.2%, and 26% of sle patients, respectively [13]. the difference in the percentages of the lipid profile can be attributed to genetic and dietary factors and the level of exercise in the two studies. formiga et al. [14] reported that 55% of young premenopausal sle women with preserved renal function had dyslipoproteinemia, similar to the current study in which 52.1% of sle patients had dyslipidemia; another observational study conducted among children with sle [15] reported dyslipidemia in 63% of the subjects in accordance with the current data. in the present study, patients with lupus nephritis had higher total cholesterol, triglycerides, low-density lipoprotein, and lower high-density lipoprotein than those without lupus nephritis similar to chong et al.’s [8] who reported higher cholesterol and triglycerides and lower hdl in lupus nephritis patients compared to control subjects. in the current research, a positive correlation was evident between dyslipidemias (high total cholesterol, high tg, high ldl, and low hdl) and proteinuria similar to formiga et al.’s [14] and kashef et al.’s [16] studies, who found a positive correlation between dyslipidemias and proteinuria. chong et al. [8] reported no correlation between sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 17 proteinuria and dyslipidemia in contradiction to the present findings, a plausible explanation is the lower level of proteinuria in chong et al.’s study. in the current study the total serum cholesterol in sle patients with lupus nephropathy was 5.4 ± 1.4 mmol/l and was positively correlated with proteinuria and lupus nephritis; similarly, tisseverasinghe et al. found that the serum cholesterol exceeds 5.2 mmol/l in sle patients and was associated with mortality and adverse renal outcomes [17]. previous literature concluded that hyperlipidemia will enhance renal immune complex-mediated complement activation and development of nephritis, in the current study, hyperlipidemia was positively correlated with proteinuria and lupus nephritis confirming the aforementioned observation [18]. in the present study, a correlation was found between hypocomplementemia and dyslipidemia that can be explained by the small size of our study. in the present study, low-density lipoprotein was high in 14.8% and was in positive correlation with proteinuria and sle nephropathy, in accordance with olusi and george who concluded a prevalence of atherogenic ldl in 52% of sle patients [19]. limitations: the study limitation was the small size of the study group, also we could not control for the therapy taken for sle treatment like hydroxychloroquine which can decrease the lipids through various mechanisms. conclusion dyslipidemia was found to be higher among patients with sle compared to the saudi general population and was positively correlated with sle nephropathy and proteinuria. aggressive treatment of dyslipidemia could decrease nephropathy and overall cardiovascular risk. conflict of interest the authors declare no conflict of interest. disclaimer: the views expressed in the submitted article are author’s own and not an official position of the institution or funder. authors contribution • concept and design: dr. hyder mirghani • data collection: dr. hyder mirghani, dr. osama salih sudan journal of medical sciences hyder osman mirghani et al. doi 10.18502/sjms.v15i1.6697 page 18 • data analysis: dr. hyder mirghani • manuscript drafting and critical revision for important intellectual content: dr. hyder mirghani, dr. osama salih, abdullah abdul khalig alyoussef, palanisamy amirthalingam • all authors approved the final version for publication and are accountable for the accuracy and integrity of all aspects of the work. references [1] angélica sinicato n, aparecida da silva cardoso p, appenzeller s (2013). risk factors in cardiovascular disease in systemic lupus erythematosus. current cardiology reviews. 9(1): 15–19. doi:10.2174/157340313805076304 [2] hak ae, karlson ew, feskanich d et al. 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(2012). distinct roles for complement in glomerulonephritis and atherosclerosis revealed in mice with a combination of lupus and hyperlipidemia. arthritis & rheumatology. 64(8): 2707–2718. doi:10.1002/ art.34451 [19] olusi so, george s (2011). prevalence of ldl atherogenic phenotype in patients with systemic lupus erythematosus. vascular health and risk management. 7: 75–80. doi:10.2147/vhrm.s17015 sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7014 production and hosting by knowledge e research article pharmacological therapy for covid-19: where are we now and where are we going? baha eldin hassan juma1, alya salah babiker higazy2, and mohamed h ahmed3 1department of pediatrics-picu section, hamad medical corporation, weill cornell medical collegedoha, qatar 2department of pharmacy-clinical pharmacy section, hamad medical corporation, doha, qatar 3department of medicine and hiv metabolic clinic, milton keynes university hospital nhs foundation trust, eagelstone, milton keynes, buckinghamshire, uk abstract background: up to the point of writing this review, there is no scientific evidence of any effective medical therapy for coronavirus disease 2019 (covid-19). in this review, we attempted to discuss the current summary of evidence of some medication, currently in trial for the treatment of covid-19. material and methods: we have done an electronic literature search using the following database: pubmed, medline, scopus and google scholar. these databases were searched using the keywords covid-19 and pharmacological therapy. results: at present, there are no well randomized controlled studies which can give evidence for most of the therapy used for covid-19. several medications are in trials for covid-19, among them: 1/ chloroquine and hydroxychloroquine; 2/anti-virals oseltamivir, remdesivir, lopinavir/ritonavir and other protease inhibitors; 3/antibiotics macrolide (azithromycin); 4/cytokine therapy interferon; 5/ humanized monoclonal antibody tocilizumab; 6/adjunct therapies vitamins c, d, and herbal medicine; 7/ covid-19 convalescent plasma; 8/systemic steroids; 9/expected covid-19 vaccine. we have also included some of the herbal medicines that are commonly and widely used in the middle east, asia as well in sudan, (black seeds, honey and acacia nilotica). it is worth mentioning that these herbal medicines have shown benefits in treating other diseases, but the evidence of their benefit in covid-19 still needs to be established. conclusion: currently there is no pharmacological therapy for the covid-19. more research and randomized clinical trials are needed to find effective therapy or vaccine against covid-19. keywords: covid-19, pharmacotherapy, herbal medicine, sudan 1. introduction since the declaration of covid-19 as a pandemic in january 2020, the number of cases of infection and mortality continued to rise steadily, as have mortality rates [1–4]. the search for a treatment or vaccine is the main challenge for all scientists across the globe who work in this field. in this short review, we attempted to discuss some of the pharmacological therapies used or have potential benefit in covid-19. how to cite this article: baha eldin hassan juma, alya salah babiker higazy, and mohamed h ahmed (2020) “pharmacological therapy for covid-19: where are we now and where are we going?,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 46–53. doi 10.18502/sjms.v15i5.7014 page 46 corresponding author: mohamed h ahmed; email: mohamed.hassanahmed@mkuh.nhs.uk received 12 may 2020 accepted 19 june 2020 published 6 july 2020 production and hosting by knowledge e baha eldin hassan juma et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mohamed.hassan-ahmed@mkuh.nhs.uk mailto:mohamed.hassan-ahmed@mkuh.nhs.uk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences baha eldin hassan juma et al 2. material and methods we have performed an electronic literature search using the following database: pub med, medline, scopus and google scholar. these databases were searched using the keywords covid-19 and pharmacological therapy. the authors searched also using a combination of the following terms [(covid-19) and (therapy) and (treatment)] or the name of different medication with covid19]. the search based on studies published in the english language without restriction for the publication date. however, most of the published materials were found to be published in 2020. 3. results and discussion 3.1. chloroquine and hydroxychloroquine chloroquine and hydroxychloroquine were shown to inhibit the replication of covid-19 cells in vitro through increasing ph of lysosomes [1, 2] and other intracellular acidic organelles and preventing fusion of the virus to the host cell [4–7]. also, chloroquine and hydroxychloroquine have an immunomodulatory effect that theoretically could contribute to an anti-inflammatory response in patients with viral infections. these agents were synthesized for the treatment of malaria and have been used for the treatment of other illnesses such as systemic lupus erythematosus and other rheumatic conditions [3]. they are generally well tolerated with commonly reported adverse effects like nausea, vomiting, itching and headache. other serious adverse effects include qtc prolongation, hematologic toxicities, and hypoglycemia. these side effects are uncommon but require appropriate monitoring and patient selection [4]. hydroxychloroquine and chloroquine can have significant drug interactions, especially with drugs with potential for qtc prolongation. due to uncertainty in benefits and harms, infectious diseases society of america (idsa) guidelines on the treatment and management of patients with covid-19 recommends the use of hydroxychloroquine in the context of the clinical trial [5, 8]. the guideline on the management of critically ill adults with covid19 by the surviving sepsis campaign (ssc) and the national institute of health (nih) did not make a recommendation for or against its use, however, nih recommended against the use of high dose hydroxychloroquine [6, 11]. 3.2. azithromycin azithromycin (c38h72n2o12) is a macrolide antibiotic that acts by inhibiting protein synthesis through binding to 50s ribosomal subunit [9]. macrolides are some of the most commonly prescribed antibiotics. they are used for a wide range of acute and chronic infections. adverse events profile includes gastrointestinal symptoms, taste disturbance and hearing loss [10]. azithromycin has been studied for the treatment of covid-19 in combination with hydroxychloroquine. although azithromycin itself is not usually associated with qtc prolongation, its use with hydroxychloroquine may increase the risk of torsades de pointes. due to safety concerns and limited poor-quality evidence, doi 10.18502/sjms.v15i5.7014 page 47 sudan journal of medical sciences baha eldin hassan juma et al infectious diseases society of america (idsa) and national institutes of health (nih) recommend the use of hydroxychloroquine and azithromycin combination to be limited to clinical trials [5, 11]. 3.2.1. remdesivir remdesivir (c27h35n6o8p) is an investigational broad-spectrum antiviral [5]. it causes premature termination of rna transcription after conversion to an adenosine analogue. although remdesivir is considered the most promising drug, idsa, and ssc did not make recommendations regarding its use due to insufficient evidence. more recently, nih recommended the use of remdesivir for patients hospitalized for severe covid-19. it also recommended that its use for mild to moderate disease be limited to the setting of clinical trials [11]. it can cause gastrointestinal side effects, elevated liver enzymes and elevated prothrombin time [5, 6, 12]. first randomized, double-blind, placebo-controlled, multicenter trial of use remdesivir in adults with severe covid-19 published in lancet last april 2020 included 237 patients were enrolled (158 to remdesivir and 79 to placebo). this study concluded that remdesivir use was not associated with a difference in time to clinical improvement (95% ci 0·87–1·75) which is not statistically significant, however, patients receiving remdesivir had fast clinical improvement with symptom duration of 10 days or less [12]. 3.2.2. oseltamivir oseltamivir (c16h28n2o4) is an antiviral drug used for treatment and prophylaxis of influenza a and b. it exerts its action by inhibiting neuraminidases enzyme and preventing the release of the virus from the host cell [11]. neuraminidases is not known to be found in sars-cov-2, thereby the mechanism is unclear. there the use of oseltamivir was already reported during the covid-19 epidemic in china, either with or without antibiotics and corticosteroids [14], however, some trials studying oseltamivir as a part of a combination with chloroquine and favipiravir are underway [15]. 3.2.3. lopinavir/ritonavir and other protease inhibitors lopinavir (c37h48n4o5) is an antiretroviral drug used in combination with the pharmacokinetic enhancer ritonavir for the treatment of human immunodeficiency virus (hiv) [10]. lopinavir inhibits 3-chymotrypsin-like protease of sars-cov-2 in vitro. gastrointestinal adverse effects are commonly observed, in addition to possible qtc prolongation and elevated transaminases [11]. the surviving sepsis campaign (ssc) guideline suggests against the use of lopinavir/ritonavir for treatment of covid-19 in critically ill adults, while idsa and nih recommend limiting to clinical trials [5, 6, 13]. these recommendations are derived from the results of a small randomized controlled trial which failed to show the benefit of this intervention [13]. nih also recommends limiting the use of other protease inhibitors to clinical trials, however ssc makes no recommendation on their use due to insufficient evidence [6, 10]. several trials involve lopinavir-ritonavir treatment doi 10.18502/sjms.v15i5.7014 page 48 sudan journal of medical sciences baha eldin hassan juma et al in comparison with the use of other drugs for covid-19 are going on, however the combination of lopinavir-ritonavir was associated with clinical improvement comparing with standard care procedures [13]. 3.3. interferons used for their antiviral activity, interferons are a group of cytokines that are being considered as a potential therapy for covid-19. many interferons have in vitro effect against sars-cov and mers-cov. they are usually used for the treatment of viral hepatitis and some types of malignancies. for the treatment of covid-19, they are used in combination with ribavirin or lopinavir/ritonavir. flu-like symptoms, hematologic toxicity and depression are amongst the most common adverse effects of interferons. the nih recommends limiting the use of interferons to clinical trials while surviving sepsis campaign was not able to issue a recommendation due to insufficient evidence [6, 10]. during the writing of this review, in hong kong, a multicenter, prospective, openlabel, randomized, phase 2 trial was conducted using triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of adult covid 19 patients. more clinical trials are needed to evaluate the efficacy and safety of recombinant human interferon in treating patients with new coronavirus infection. 3.3.1. tocilizumab tocilizumab is a humanized monoclonal antibody that inhibits interleukin-6. it is expected to suppress the possible high immune response in covid-19 patients. it is used for the treatment of conditions like cytokine release syndrome and rheumatoid arthritis, but it is associated with an increased risk of infections [6]. nih and scc made no recommendation regarding the use of tocilizumab because of insufficient data, while idsa recommends limiting its use to clinical trials settings [5, 6, 11]. adequately powered randomized controlled trials are in need to determine the efficacy of tocilizumab with consideration of the toxicity of this medicine. 3.3.2. covid-19 convalescent plasma this is theoretically done by taking plasma which contains neutral antibodies from those who recovered from covid-19 and transfused to patients with covid-19. the rationale behind this therapy it could provide short-term passive immunity against covid-19, decrease viral load and improves the outcome [17]. as reported at sars pan epidemic 2003 use of convalescent plasma obtained from patients provide some benefits (shorter duration of hospitalization, decreased mortality). moreover, those who received the plasma within less than 14 days from the start of symptoms have a better outcome [18]. efficacy data are not available from controlled clinical studies to date. multiple registered clinical trials initiated in the us and other countries to evaluate the use of covid-19 convalescent plasma. idsa and nih did not make recommendations regarding the use of convalescent plasma outside of the clinical trial setting, however, scc suggests doi 10.18502/sjms.v15i5.7014 page 49 sudan journal of medical sciences baha eldin hassan juma et al against its routine use in critically ill adults. this recommendation is driven by previous studies for other viral infections like ebola and influenza which showed no benefit. in addition to uncertainty regarding its preparation [5, 6, 11]. 3.3.3. systemic corticosteroids the rationale of the use of systemic steroids to maintain a systemic anti-inflammatory that will minimize the symptoms of covid-19 especially on those patients complicated with severe respiratory sequences (ards). however, who does not recommend the liberal use of systemic steroids unless patients are recruited in clinical studies or there is another medical indication [19]. importantly, the use of steroid during the mers epidemic was associated with increase in use of invasive ventilation and raised mortality rate at 90 days [20]. nih (strong recommendation) and idsa (conditional recommendation) do not support the routine use of corticosteroid. on the other hand, scc (weak recommendation) and nih (moderate recommendation) support the use of low dose corticosteroid in covid-19 patients in refractory shock. for patients on mechanical ventilation without acute respiratory distress syndrome (ards), scc (weak recommendation) and nih (strong recommendation) do not recommend the use of corticosteroids, however, scc suggests using corticosteroids for patients with ards [5, 6, 11]. 3.3.4. vitamins c and d the use of vitamins c and d was associated with many benefits in term of increasing the effectiveness of the immune system and increase wound healing with vitamin c. interestingly, vitamin c infusion was associated with improvement in the prognosis of severe acute respiratory tract infections in covid-19 patients and this could be attributed to the improvement of alveolar epithelization in severe respiratory distress syndrome patients [21, 22]. furthermore, vitamin d has a role in mitigating the scope of acquired immunity and endothelial lining regeneration, hence this may minimize alveolar damage caused in ards. vitamin d supplementation has a 12% overall protective effect against bacterial and viral acute respiratory tract infection [23]. indeed, there is no harm from using these vitamins during the covid-19. 3.3.5. vaccine there is currently no vaccine available to protect against covid-19. multiple registered clinical trials are ongoing worldwide in europe and usa as well as asia. one of the leading candidates is the mrna-1273 vaccine which was developed by the national institute of allergy and infectious diseases (niaid) scientists. this vaccine is currently in phase i trial. the estimated completion time is june 2021 [24]. once a safe and effective vaccine becomes available it will be vital that it is accessible to everyone who needs it (who reports). doi 10.18502/sjms.v15i5.7014 page 50 sudan journal of medical sciences baha eldin hassan juma et al table 1: summary of current data on selected covid-19 therapies. drug preclinical data safety considerations recommendations (outside the context of clinical trials) hydroxy-chloroquine inhibits the replication of covid-19 cells in vitro through increasing ph of endosomes. also has immunomodulatory effects qtc prolongation, hematologic toxicities, and hypoglycemia nih recommends against the use of high dose hydroxychloroquine remdesivir causes premature termination of rna transcription after conversion to an adenosine analogue gastrointestinal side effects, elevated liver enzymes and elevated prothrombin time recommended by nih for patients hospitalized for severe covid-19 lopinavir/ritonavir inhibits 3-chymotrypsin-like protease of sars-cov-2 in vitro gastrointestinal adverse effects, qtc prolongation and elevated transaminases ssc suggests against the use of lopinavir/ritonavir for treatment of covid-19 in critically ill adults interferon many interferons have in vitro effect against sars-cov and mers-cov flu like symptoms, hematologic toxicity and depression nih recommends against the use of interferons tocilizumab suppress the possible high immune response in covid-19 increased risk of infections idsa recommends limiting its use to clinical trials settings convalescent plasma short-term passive immunity against covid-19 transfusion related adverse events including risk of infection and overload of blood circulation scc suggests against routine use of convalescent plasma in critically ill adults with covid-19 corticosteroids systemic anti-inflammatory that will minimize the symptoms of covid-19 possible increased need for mechanical ventilation, increased risk of mortality 1. nih (strong recommendation) and idsa (conditional recommendation) do not support routine use of corticosteroid. 2. scc (weak recommendation) and nih (moderate recommendation) support the use of low dose corticosteroid in covid-19 patients in refractory shock. 3. for patients on mechanical ventilation without acute respiratory distress syndrome (ards), scc (weak recommendation) and nih (strong recommendation) do not recommend the use of corticosteroids. 4. for mechanically ventilated patients with ards, scc suggests using corticosteroid doi 10.18502/sjms.v15i5.7014 page 51 sudan journal of medical sciences baha eldin hassan juma et al 3.3.6. traditional and herbal medicine many reports and news from cultural and religious background reported some herbal traditional medicine have been used with no scientific background or pharmacological evidence. reports from china that chinese herbal formula might be associated with blocking of the proliferation and replication of the virus particles, therefore, can minimize viral load sequences. natural honey was also widely used during covid-19 in these countries, either alone or in combination with nigellla sativa. certain herbs, if misused, could boost the immune system even more and lead to “a cytokine storm,” or a fatal overactive immune response, according to gersh [25]. hence, efforts from health authorities to restrict use are highly appreciated as these are not well scientifically studied. despite the popularity of herbal medicine in sudan, no clinical studies or randomized clinical trials have yet assessed the use of these herbal medicines. 4. conclusion the world is in a race to find effective treatment and vaccine against covid-19. this will continue to be challenging disease, as we have not yet developed a full understanding of the pathogenesis of covid-19. summary of possible potential therapy of covid-19 was provided in table 1. drug discovery and clinical trials will need time, and many peoples may suffer or die as a result of this long wait. the discovery of vaccine or pharmacological therapy against covid-19 will be the main success in getting out of the lockdown of covid-19. references [1] browning d.j. 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(2018) beneficial effects of ascorbic acid to treat lung fibrosis induced by paraquat. plos /one 13(11): e0205535. https://doi.org/10.1371/journal.pone.0205535. [23] martineau adrian r, jolliffe david a, hooper richard l, greenberg lauren, aloia john f, bergman peter et al. vitamin d supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data bmj 2017; 356: i6583 [24] national institute of allergy and infectious diseases (niaid),author. nih clinical trial of investigational vaccine for covid-19 begins study enrolling seattle-based healthy adult volunteers. https://corona. kpwashingtonresearch.org/ [25] ries, j. (2020). herbal remedies and covid-19: what to know. cassellhttps://www.healthline.com/ health-news/herbal-remedies-covid-19-what-to-know doi 10.18502/sjms.v15i5.7014 page 53 https://www.covid19treatmentguidelines.nih.gov/ https://clinicaltrials.gov/ct2/show/nct04303299 https://apps.who.int/iris/handle/10665/331446 https://clinicaltrials.gov/ct2/hom https://clinicaltrials.gov/ct2/hom https://doi.org/10.1371/journal. pone.0205535 https://corona.kpwashingtonresearch.org/ https://corona.kpwashingtonresearch.org/ https://www.healthline.com/health-news/herbal-remedies-covid-19-what-to-know https://www.healthline.com/health-news/herbal-remedies-covid-19-what-to-know introduction material and methods results and discussion chloroquine and hydroxychloroquine azithromycin remdesivir oseltamivir lopinavir/ritonavir and other protease inhibitors interferons tocilizumab covid-19 convalescent plasma systemic corticosteroids vitamins c and d vaccine traditional and herbal medicine conclusion references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7130 production and hosting by knowledge e research article covid-19 in sudan: will the mitigation efforts win against the virus? amel a. sulaiman1,2, wadie m. y. elmadhoun3, nassma mohy eldeen altayeb4,5, heitham awadalla6, and mohamed h. ahmed7 1department of community medicine, faculty of medicine, nile valley university, sudan 2family medicine academy, qassim health cluster, al qassim region, saudi arabia 3department of pathology, faculty of medicine, sudan international university, sudan 4health emergency and epidemics control directorate, federal ministry of health, sudan 5department of community medicine, sudan international university, sudan 6department of community medicine, faculty of medicine, university of khartoum & federal ministry of health, sudan 7department of medicine and hiv metabolic clinic, milton keynes university hospital, nhs foundation trust, eaglestone, milton keynes, buckinghamshire, uk abstract background: the covid-19 pandemic has hit hard both the affluent and poor countries. the objective of this article is to highlight the efforts of the ministry of health in sudan in mitigating the pandemic and reflecting on counteracting factors. methods: we traced the reports and plans of the federal ministry of health and looked at the models projecting the pandemic in sudan. results: the fundamental plan of the government of sudan to cope up with the pandemic included the control of the source of infection, blocking transmission, and preventing the spread. the response mechanism had a multi-sector approach with involvement of government, civil society organizations, and non-governmental organizations (ngos). the action plans involved protocols for covid-19 diagnosis and treatment, surveillance, epidemiological investigation, and management of case contacts. however, several factors continued to jeopardize the mitigation efforts of these plans. at the time of writing this article (at the end of the may 2020), there were about 4,000 confirmed cases, 300 recoveries, and 170 deaths. although these numbers are below the projected numbers in many proposed models, in the light of the limited testing capacity, case identification and contact tracing, the exact situation might not be ascertained. conclusion: sudan has prepared a national plan to prevent and contain covid19 pandemic. however, tremendous challenges are opposing these efforts. the poor health infrastructure, fragility of the health system, and the economic crisis are the major obstructions. keywords: covid-19, sudan, preventions how to cite this article: amel a. sulaiman, wadie m. y. elmadhoun, nassma mohy eldeen altayeb, heitham awadalla, and mohamed h. ahmed (2020) “covid-19 in sudan: will the mitigation efforts win against the virus?,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 259–269. doi 10.18502/sjms.v15i3.7130 page 259 corresponding author: wadie m. y. elmadhoun; email: wadie2222@yahoo.com received 20 august 2020 accepted 15 september 2020 published 30 september 2020 production and hosting by knowledge e amel a. sulaiman et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:wadie2222@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences amel a. sulaiman et al 1. introduction coronaviruses are important pathogens in humans that can also be transmitted from animals and cause disease ranging from common cold to severe or even fatal respiratory infections [1]. in december 2019, a new strain of coronavirus, named severe acute respiratory syndrome coronavirus-2 (sars-cov-2), was first isolated from three patients with unusual pneumonia; this was later given the name of coronavirus disease 2019 (covid-19) by the chinese center for disease control and prevention [2, 3]. epidemiological reports soon proved person-to-person transmission of the disease [4, 5]. however, it was not until january 30, 2020 that the world health organization (who) declared the covid-19 outbreak a “public health emergency of international concern” (pheic). as of february 28, 2020, a steady rise was seen in the number of patients infected with covid19 globally, with an increase in mortality rate [6]. subsequently, on march 11, 2020, who declared covid-19 a “pandemic” and urged all nations to take global steps in containing the infection [7]. at the time of writing this article (i.e., may 26, 2020), there were more than 5.6 million confirmed cases of infection in 213 countries, about 2.4 million recoveries, and about 348,241 deaths with an overall estimated case fatality rate of around 6% [8]. the case fatality rate of covid-19 varies widely between countries, ranging from 0.2% to 7.7% [9]. while the first confirmed case of covid-19 in sudan was reported on march 13, 2020, there are currently 3,976 confirmed cases with 503 recoveries and 170 deaths with an estimated case fatality rate of 4.3% [10]. due to the limited testing capacity and the location of test centers in few major cities only, these numbers may not reflect the exact situation. 2. country settings sudan is a developing country with a population of 43 million and a gross national income per capita of about usd 2,370 and the total health expenditure of the country is 7.2% of the general government expenditure. while more than 60% of the population is below the age of 25 years, 2.5% are above 65 and the average life expectancy is 65 years [11]. the country is standing amidst a storm of a political transitional period following a revolution that ended a 30-year dictatorship rule a year ago. sudan is facing a lot of challenges including, but not limited to, severe economic crisis, multiple foci doi 10.18502/sjms.v15i3.7130 page 260 sudan journal of medical sciences amel a. sulaiman et al of civil war, sociocultural conflicts, and widespread corruption inherited from the exgovernment. in addition, there are several existence-threatening issues facing sudan such as the economic sanctions imposed by the united states for more than 20 years, the continuous immigration of health professionals, and the limited budget allocated for health for the last three decades. all these factors have led to a very fragile health system, characterized by chaotic governance, poor infrastructure, irrational utilization, and scarce human and material resources. having these facts in mind, a lot of questions are posed about the country’s capacity to cope with the current covid-19 pandemic. 3. the health system in sudan the political and administrative governance of the country has been based on a presidential republic and a federal system. the health system can be categorized into three levels: federal, state, and local governments, and there are 18 states and 184 localities/districts in total [12]. while the federal government is typically responsible for the provision of nationwide health policies, plans, strategies, overall monitoring and evaluation, coordination, training, and external relations, the state government is concerned with the state’s plans, strategies, and funding and implementation of plans based on federal guidelines. the localities on the other hand are responsible for the implementation of plans [12]. the health services provided in sudan follow the classical three basic arrangements: primary, secondary, and tertiary healthcare. primary healthcare (phc) is the first point of contact for patients and includes, dressing stations, dispensaries, phc units, and health centers located in urban and rural areas[13]. the importance of phc is that it provides essential care to the population at large. the secondary and tertiary levels are responsible for providing more specialized medical services. however, in practice, much overlap exists between the three levels of service [14]. the coverage of the phc units and centers is 1.5 per 10,000 population [14]. as in most lowand middle-income countries (lmic), the healthcare system in sudan is overwhelmed by a double burden of both communicable and non-communicable diseases [15]. sudan is frequently hit by different types of disasters that require national response and sometimes international support, most of which are related to infectious diseases such as malaria and cholera outbreaks [15]. doi 10.18502/sjms.v15i3.7130 page 261 sudan journal of medical sciences amel a. sulaiman et al 4. sudan’s response to covid-19 the first confirmed case of covid-19 was reported on march 13, 2020. the patient was a male in his 50s, who had arrived from abroad less than a week ago. despite being tested upon clinical suspicion, the diagnosis was not confirmed until a post-mortem sample was obtained [10]. on march 29, five more cases tested positive for the virus, all of whom were male adults and had arrived from high-risk countries. case number 6, however, succumbed to the disease on the same day the disease was confirmed. subsequently, the cases continued to be reported sporadically with some evidence of community transmission. the number of suspected cases and contacts of confirmed cases was in hundreds, many were unknown, not all of them were being tested, and therefore it was difficult to trace. according to the situational report released by fmoh on may 18, 2020, there were 4,258 suspected cases, 2,592 confirmed cases, 108 deaths (case fatality rate, cfr: 4.2%), and 222 recoveries. moreover, about 81.4% of the sudanese confirmed cases were reportedly from khartoum state. of the confirmed cases, 59% were male, and the age of those infected ranged from 1 to 70 years and above. few cases were reportedly imported (n=27), while most were attributed to local transmission (2,565) [16]. according to the who critical preparedness, readiness and response actions for covid-19 and based on the transmission scenarios for covid-19, sudan is one of the countries experiencing larger outbreaks of local transmission [17]. the main purpose of the response plan for covid-19 pandemic is to support the national capacity system so quick detection of new cases can be achieved and this may help in preventing a further spread of covid-19 in sudan. the higher task force committee (htfc) on covid-19 pandemic in sudan was established in january 2020 as a joint multi-sectors committee to assess the situation and coordinate the country’s response. the htfc proposed the national strategic plan to contain covid-19 upon the following functional sections: surveillance, rapid response and case investigation teams, portals of entry, national laboratories, case management, infection prevention and control, operations support and logistics, risk communication and community engagement, coordination with other sectors, and legislations and laws. the main objectives were controlling the source of infection, blocking transmission, and preventing wide spread. the response mechanism has a multi-sector approach with involvement of government, civil society organizations, and non-governmental organizations (ngos). the action plans involved: protocols for covid-19 diagnosis and treatment, surveillance, epidemiological investigation, management of case contacts, doi 10.18502/sjms.v15i3.7130 page 262 sudan journal of medical sciences amel a. sulaiman et al laboratory testing was formulated, and relevant surveillance activities and epidemiological investigations were conducted. and allocation of medical supplies was coordinated [18]. the epidemiology and emergency department at the federal ministry of health (fmoh) issues daily updates about the global and local situation of the pandemic including the number of confirmed cases, suspected cases, deaths, besides the imposed regulations, plans, and procedures. the fmoh provided hotline call numbers working over the hour to respond to public notifications or any queries from the sentinel sites and set into action rapid response teams. the surveillance system focuses on the rapid detection of cases and comprehensive and rapid contact tracing. health quarantine was prepared for all arrivals from high-risk countries through airports and land-entry points. at the time of reporting, a few hundred suspected cases were tested and scheduled for isolation (either facility-based quarantine or self-isolation at home) for a minimum of two weeks. the national public health laboratory, in khartoum, is the only diagnostic facility for testing specimens. a few public hospitals in khartoum and other states are prepared to receive cases that need critical care, however, in worse-case scenarios, the capacity of these hospitals will not cope with the expected cases. currently, there are much less ventilators in the country than needed in case of widespread infection, most of them are located in khartoum state, and in private health sector. the situation might have improved had aid been received from other countries and international organizations. based on clinical presentation, covid-19 cases can be categorized as mild, severe, or critical. about 5% may be categorized as critical cases in which patients are likely to suffer respiratory failure and/or multiple organ dysfunction and need mechanical ventilation [19]. if covid-19 cases followed the projected models in sudan, the available beds with ventilators will not be sufficient for the expected number of patients, as projected in figure 2. the who has set an excel-based tool [the essential supplies forecasting tool (esft)] to help member states manage essential supplies and forecast the estimated number of covid-19 cases [19] (figure 1). the fmoh in sudan predicts the modelling and estimating the numbers of expected cases, those who require hospital care, and intensive services. three assumptions were put ahead during the preparation phase. first, this outbreak is expected to spread in urban areas rather than rural areas and blocked communities, therefore, the population at risk is estimated to be 34% of the population (>60% in rural areas). second, as there is a lack of data regarding this pandemic, the assumption was calculated using the wuhan incidence (0.21%) and doubling it for sudan (i.e., 0.42%) – due to less doi 10.18502/sjms.v15i3.7130 page 263 sudan journal of medical sciences amel a. sulaiman et al figure 1: crude estimation of covid-19 cases in sudan if mitigation efforts are put in place*. 1: asymptomatic or mild symptoms, but not tested; 2: estimated patients tested positive for covid-19; 3: cases need hospitalization; 4: patients who need icu care; 5: *projected number of mortality. *these estimated numbers are based on the who covid-19 essential supplies forecasting tool [20]. *the estimated mortality rate depends on the case fatality rate (cfr = 4.0%). figure 2: confirmed number of covid-19 cases in sudan as of may 14, 2020 and mitigation measures. source: federal ministry of health – sudan (http://www.fmoh.gov.sd) doi 10.18502/sjms.v15i3.7130 page 264 http://www.fmoh.gov.sd sudan journal of medical sciences amel a. sulaiman et al community response to social distancing and prevention measures. thirdly, based on the population pyramid and prevalence of comorbidities, the high-risk groups and those expected to need hospitalization were calculated. therefore, the projected numbers were round 60,000 expected positive cases, of which 11,000 were expected to require hospitalization and 3,000 intensive care. of note, there are other models projecting higher number of cases. so, in this phase, the sudanese government emphasized the preventive measures to break the disease transmission chain, mainly by calling for social distancing, raising public awareness, and promoting hand washing. new laws and legislations have been set in place to restrict movement and prohibit mass gathering. partial and complete lockdown has been imposed in certain cities. 4.1. sociocultural factors favoring the worst-case scenario • poverty: the vast majority of the population (about 70%) is below the poverty line. furthermore, the economic crisis is going to worsen as a result of lockdown. at a certain point of time, compliance with lockdown would not stand in front of the hunger revolution. • misbelieves about life, disease, and self are wide-spread, for example, the covid19 is fake news, blacks have more potent immune response than other races, being in malaria zone would give them protection, and many more unrealistic tales [20]. • the high number of refugees, homeless, and internally displaced people (idps) in sudan who live either in crowded camps or have no shelter at all. • the open and poorly controlled borders of sudan with neighboring countries can facilitate the transmission of virus. • the high illiteracy rate among the population that exceeds 25% can jeopardize control measures. • the social and religious festivals, overcrowding in public places and around the common community services can increase covid-19 transmission. • stigma and denial associated with covid-19 is increasing in sudan. • the poor control of quarantine facilities, despite the hard efforts exerted by authorities. self-isolation in most of our housing settings is not as it should be. • the scarce personal protective equipment (ppes) and lack of infection control measures can increase the risk for healthcare providers. doi 10.18502/sjms.v15i3.7130 page 265 sudan journal of medical sciences amel a. sulaiman et al • the perceived concept that “all is well,” as evidenced by the low impact of previous viral outbreaks such as influenza, mers-cov-1, and sars on the population health. • there is a chance for a second wave in case of easing preventive measures such as social distancing, gathering, and wearing of masks. 5. conclusion sudan has prepared a national plan to prevent and contain covid19 pandemic. however, tremendous challenges are opposing these efforts. the poor healthcare infrastructure, fragility of the health system, and the economic crisis are the major obstructions. therefore, the numbers of affected patients may exceed those of the initial wave, and sudan may witness an unprecedented crisis in worst-case scenario. it has been stated that “in times of uncertainty, facts bring clarity,” however, in this covid-19 pandemic neither facts nor clarity are foreseeable. declaration section acknowledgements the authors are grateful for their families for their support during the time of writing this manuscript competing interests no competing interest for all authors availability of data and material none funding none doi 10.18502/sjms.v15i3.7130 page 266 sudan journal of medical sciences amel a. sulaiman et al abbreviations and symbols non-governmental organizations (ngos) world health organization (who) public health emergency of international concern (pheic) personal protective equipment (ppes) the essential supplies forecasting tool (esft internally displaced people (idps) primary healthcare (phc) lowand middle-income countries (lmic) federal ministry of health (fmoh) references [1] chen, t., wu, d., chen, h., et al. 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[20] ahmed mh. black and minority ethnic (bame) alliance against covid-19: one step forward. j racial ethn health disparities. 2020 oct;7(5):822-828 doi 10.18502/sjms.v15i3.7130 page 269 https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/covid-19-critical-items https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/covid-19-critical-items introduction country settings the health system in sudan sudan's response to covid-19 sociocultural factors favoring the worst-case scenario conclusion declaration section acknowledgements competing interests availability of data and material funding abbreviations and symbols references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7161 production and hosting by knowledge e short communications sars-cov-2: current perspective on control, prevention, and therapeutic promise david chibuike ikwuka1, ed nwobodo1, ugochukwu bond anyaehie2, george uchenna eleje3,4, adaeze c. ayuk5, chukwuanugo nkemakonam ogbuagu6, and princewill ugwu2 1department of human physiology, nnamdi azikiwe university nnewi campus, nigeria. 2department of physiology, university of nigeria enugu campus, enugu state, nigeria. 3department of obstetrics and gynecology, nnamdi azikiwe university teaching hospital, nnewi, nigeria. 4effective care research unit, department of obstetrics and gynecology, nnamdi azikiwe university, nnewi campus, nigeria. 5department of paediatrics, college of medicine, university of nigeria, enugu campus & university of nigeria teaching hospital, enugu state, nigeria. 6department of medical microbiology and parasitology, nnamdi azikiwe university teaching hospital nnewi, nnewi, nigeria. abstract background: the novel coronavirus disease (covid-19) outbreak has halted activities throughout the globe because of its rapid spread. covid-19 is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) a β-coronavirus first detected in china. sars-cov-2 has been implicated to be transmitted via direct contact, fomite, respiratory droplets, and possibly aerosol. the spread of the disease is complicated due to the slow onset of symptoms and asymptomatic infected patients. methods: this narrative communication summarizes the recent researches sourced using sensitive search strategies to identify covid-19 current perspectives on the control, prevention, and therapeutic promise. result: several strategies and multiple control measures have been implemented around the globe to contain covid-19. considering the exponential spread of the pandemic, several scientists and physicians have been racing to discover possible therapeutics and vaccines for covid-19. there are clinical trials to investigate the vaccine designed to protect against the infection and also to substantiate the claim made for bcg protection against covid-19. although, there is currently no universally approved medication to treat sars-cov-2, there have been random reports of existing medications ameliorating the infection, and these regimens are still under clinical trial. there is also the potential therapeutic prospect of rhinothermy to fight sars-cov-2 judging from its success in fighting upper respiratory tract viral infection. conclusion: the information provided in this communication gives a reliable intellectual grounding regarding the current perspective on covid-19 control, progress made in the development of vaccines and therapeutic regimen, and where future research in this area should be focused. keywords: covid-19; sars-cov-2; control; who; respiratory; cases; tract how to cite this article: david chibuike ikwuka, ed nwobodo, ugochukwu bond anyaehie, george uchenna eleje, adaeze c. ayuk, chukwuanugo nkemakonam ogbuagu, and princewill ugwu (2020) “sars-cov-2: current perspective on control, prevention, and therapeutic promise,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 80–84. doi 10.18502/sjms.v15i5.7161 page 80 corresponding author: david c ikwuka; department of human physiology, nnamdi azikiwe university nnewi campus, nnewi, nigeria. phone numbers: +2348037147603 email: davidikwuka@gmail.com received 12 may 2020 accepted 4 july 2020 published 19 july 2020 production and hosting by knowledge e david chibuike ikwuka et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:davidikwuka@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences david chibuike ikwuka et al 1. introduction 1.1. sars-cov-2 coronavirus disease 2019 (covid-19) is a novel strain of coronaviruses (cov) and was first identified amidst an investigation that lead into an outbreak in wuhan city, hubei province, china in late december 2019. covid-19 was initially called 2019-ncov, however, it was renamed as sars-cov-2 by the world health organization (who) on february 12, 2020. due to its exponential spread, sars-cov-2 was labelled as a public health emergency of international concern by the international health regulations committee of the who on january 30, 2020. sars-cov-2 is a β-coronavirus which is a single-stranded positive-sense rna virus belonging to a group within the subgenus s arbecovirus, orthocoronavirinae subfamily [1, 2]. the symptoms of sars-cov-2 infection may include: fever, shortness of breath, tiredness, dry cough, aches and pain, sore throat, and few may experience diarrhea, nausea, or a runny nose [3]. people with underlying medical conditions and the elderly have a higher risk of developing severe disease and death [3]. while some carriers could be asymptomatic, they are contagious as the onset of symptoms ranges between one and 14 days, or even more [4]. sars-cov-2 is thought to be transmitted through direct contact, fomite, fecal, and respiratory droplets [5]. recently, there have been emerging suggestions that sars-cov-2 can exist as an aerosol under very limited conditions as the virus particles on droplets of mucus or saliva could be suspended in the air for a few seconds, and that anyone passing through that pathogenic cloud could be vulnerable to the infection. the result of experimental procedure evaluating sars-cov2 and sars-cov-1 stability in aerosols and other surfaces indicates that fomite and aerosol transmission of sars-cov-2 are possible, as sars-cov-2 could remain viable and virulent in aerosols for hours and on surfaces for days, and this is comparable to the transmission of sars-cov-1 [5]. as of june 10, 2020, according to the who covid-19 situation report-141, a total of 7,039,918 cases were confirmed and a total of 404,396 deaths had resulted from the covid-19 pandemic globally [6]. africa accounts for about 2.8% (198,553) of the total confirmed cases (7,039,918) and 1.3% (5,372) of the total confirmed deaths (404,396) [6]. based on the analysis of gilbert et al. [7], algeria, egypt, and south africa were identified to have the highest importation risk and moderate to high capacity in outbreak responsiveness; and nations like nigeria, sudan, ethiopia, ghana, angola, tanzania, and kenya to have the variable capacity in outbreak responsiveness and high vulnerability. congruent to this analysis [6] is also a high prevalence of covid-19 cases recorded in countries with highest importation risk like south africa (50,879), egypt (35,444), morocco (8,302), and algeria (10,265); and not a corresponding high vulnerability in countries like nigeria (12,801), ethiopia (2,156), sudan (6,244), angola (92), tanzania (509), ghana (9,910), and kenya (2,862) [6]. however, a nation’s vulnerability is not dependent on certain indicators but it is a function of its willingness to observe and apply stringent control measures key to containing the spread of this pandemic. doi 10.18502/sjms.v15i5.7161 page 81 sudan journal of medical sciences david chibuike ikwuka et al 2. control and prevention the fight against covid-19 has to be a concerted effort by all. covid-19 spreads rapidly and there is sustained local transmission making it impossible to isolate all cases; this calls for the use of mitigation measures to be put in place with the objective of slowing down the spread of the virus within a country or a region. these measures include: the banning of mass gathering events such as sporting, political, social, and large religious gatherings, and closure of schools, targeted at avoiding the multiplication of cases that will overburden healthcare systems. the who therefore recommends: frequent washing of hands with soap for 20 sec; maintaining physical distancing of at least 1 m or 3 ft ; avoidance of touching eyes, nose, and mouth; regular practice of respiratory hygiene of using a handkerchief or tissue paper when sneezing or coughing or otherwise a flexing or bending the elbow; seeking medical care early in the event of symptom manifestation; and staying informed and following advice given by the healthcare professionals [8]. in the who recommendation, there is, therefore, an emphasis on hygiene as a major means of breaking transmission of covid-19. covid19 outbreak is overwhelming nations, hence, the need for the application of stringent multiple control measures by other countries struggling to contain the pandemic as was implemented by china [8]. xifeng, xiaolin, and xuchu [9] outlined six key lessons the international community could learn from china in halting the spread of sars-cov2; they include: speed and accuracy in the identification and detection of covid-19 carriers; making the right decisions for the right people at the right time and at the right place; big data and information technology are important to avoid a rebound; appraising medical resources and response systems; enforcement of precautionary measures in schools, businesses, government offices, homes, and communities can control the trajectory of this epidemic; and keeping the public well-informed. preparedness is key to mitigating the effect of covid-19 at national and local levels. a human clinical trial to evaluate an investigational vaccine mrna-1273 designed to protect against sars-cov-2 is ongoing at the kaiser permanente washington health research institute (kpwhri) [10]. recently, a body of evidence has emerged about the possibility of using bcg (bacillus calmette-guerin) vaccine given to counter tb as protection against covid-19. a correlation study of 178 countries has shown that nations with bcg vaccination program have fewer covid-19 cases in comparison to where bcg programs are no longer deployed [11]. moorlag et al. (2019) reported that bcg vaccine induces heterologous immunity against other infections including viral infections [12], and previous research had also provided evidence that bcg vaccine reduced respiratory tract infections in adolescents [13]. however, the who does not yet recommend bcg vaccination for the prevention of covid-19 and is presently testing the theory with human clinical trials on selected cohorts concerning the success theory of bcg vaccination to forestall covid-19 [14]. also, randomized controlled clinical trials are currently ongoing in the netherlands and australia to substantiate the use of bcg for covid-19 prevention (nct04327206, nct04328441). indeed, a safe and potent vaccine to protect against sars-cov-2 infection will be a very important step toward fighting the spread of this contagion. doi 10.18502/sjms.v15i5.7161 page 82 sudan journal of medical sciences david chibuike ikwuka et al 3. therapeutic prospects of note, the covid-19 broke out in china and spread in iran, italy, and the rest of europe during the winter season. viruses have a temperature range in which they can survive for some time, and this range is dependent on their outer layer envelope. wang et al. [15] investigated how air temperature and humidity influence covid19 transmission, and their findings suggest that high temperature and high humidity remarkably reduces the transmission of covid-19 influenza. park et al. [16] stressed that experiences from sars and mers epidemics and treatment of other endemic and epidemic respiratory viruses could provide some guidance on the treatment strategies that may be helpful to covid-19 patients. the who laboratory work shows that heat at 56ºc kills the sars coronavirus at around 10,000 units per 15 min. this could pave way for a potential therapeutic prospect of warm steam inhalation/heated humidified air delivery/rhinothermy, which has been traditionally and clinically proven to be potent against viral upper respiratory tract infections [17–19]. moreover, there is currently no universally approved medication by any regulatory agency for the treatment of covid-19. the prevention of covid-19 infection remains the mainstay of containment of the pandemic. infected people may need supportive care to help them survive the illness. several companies and research groups are currently developing or testing certain drugs against the virus that causes covid-19. clinical trials are currently ongoing for existing drugs like remdesivir, hydroxychloroquine or chloroquine, and favipiravir [20, 21]. who instituted solidarity trial to help find potent therapy for covid-19 and will compare four therapeutic alternatives against the standard of care to determine their relative effectiveness against covid-19 [22]. the human clinical trial aims to rapidly ascertain whether any of the prescriptions slow disease progression or improve survival and will enroll patients in multiple countries. the treatment options selected for the study are remdesivir; lopinavir/ritonavir; lopinavir/ritonavir with interferon beta-1a; and hydroxychloroquine [22]. as of june 3, 2020, over 3,500 patients have been recruited in over 400 hospitals in 35 countries for human clinical trials [22]. 4. conclusion in over six months that covid-19 has ravaged the world, over seven million people have been affected with more than 404,396 deaths and still counting. global economy, government ,and business activities have been seriously affected by this pandemic as various countries have implemented stringent control measures to contain its spread. however, there is hope as there are potential therapeutic promises, and real commitment globally to control its spread, identify and design efficacious vaccine and therapeutics that will enable us to win sars-cov-2 infection war. doi 10.18502/sjms.v15i5.7161 page 83 sudan journal of medical sciences david chibuike ikwuka et al references [1] zhu, n., zhang, d., wang, w., et al. (2020). a novel coronavirus from patients with pneumonia in china, 2019. the new england journal of medicine, vol. 382, no. 8, pp. 727–733. [2] huang, c., wang, y., li, x., et al. (2020). clinical features of patients infected with 2019 novel coronavirus in wuhan, china. lancet, vol. 395, pp. 497–506. [3] world health organization. coronavirus. retrieved from: https://www.who.int/health-topics/ coronavirus#tab=tab_3 [4] bai, y., yao, l., wei, t., et al. (2020). presumed asymptomatic carrier transmission of covid-19. jama. doi: 10.1001/jama.2020.1490. [5] doremalen, n. v., bushmaker, t., morris, d. h., et al. (2020). aerosol and surface stability of sars-cov-2 as compared with sars-cov-1. the new england journal of medicine, vol. 382, no. 16, pp. 1564–1567. [6] world health organization. (2020). coronavirus disease (covid-19) situation reports-141. retrieved from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports [7] gilbert, m., pullano, g., pinotti, g., et al. (2020). preparedness and vulnerability of african countries against importations of covid-19: a modelling study. lancet vol. 395, pp. 871–877. [8] world health organization. (2020). coronavirus disease (covid-19) advice for the public. retrieved from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public [9] xifeng, w., xiaolin, x., and xuchu, w. (2020). 6 lessons from china’s zhejiang province and hangzhou on how countries can prevent and rebound from an epidemic like covid-19. world economic forum covid action platform. retrieved from: https://www.weforum.org/agenda/2020/03/coronavirus-covid19-hangzhou-zhejiang-government-response/ [10] national institute of health. (2020). nih clinical trial of investigational vaccine for covid-19 begins. retrieved from: https://www.nih.gov/news-events/news-releases/nih-clinical-trialinvestigational-vaccine-covid-19-begins [11] miller, a., reandelar, m. j., fasciglione, k., et al. (2020). correlation between universal bcg vaccination policy and reduced morbidity and mortality for covid-19 an epidemiological study. medrxiv pre-print. [12] moorlag, s. j. c. f. m., arts, r. j. w., van crevel, r., et al. (2019). non-specific effects of bcg vaccine on viral infections. clinical microbiology and infection, vol. 25, pp. 1473–1478. [13] nemes, e., geldenhuys, h., rozot, v. (2018). prevention of m. tuberculosis infection with h4:ic31 vaccine or bcg revaccination. the new england journal of medicine, vol. 379, no. 2, pp. 138–149. [14] rajarshi, k., chatterjee, a., and ray, s. (2020). bcg vaccination strategy for prevention against covid19: hype or hop? preprints, 2020040351. doi: 10.20944/preprints202004.0351.v1. [15] wang, j., tang, k., feng, k., et al. (2020 ). high temperature and high humidity reduce the transmission of covid-19. ssrn. retrieved from: https://ssrn.com/abstract=3551767 [16] park, m., thwaites, r. s., and openshaw, p. j. m. (2020). covid-19: lessons from sars and mers. european journal of immunology, vol. 50, pp. 308–316. [17] chen, d. y., zee, e. d., gildengorin, g., et al. (2019). a pilot study of heated and humidified low flow oxygen therapy: an assessment in infants with mild and moderate bronchiolitis (hhot air study). pediatric pulmonology, vol. 54, pp. 620–627. [18] hei, sv., mckinstry, s., bardsley, g., et al. (2018). randomized controlled trial of rhinothermy for treatment of the common cold: a feasibility study. bmj open, vol. 8, e019350. doi: 10.1136/bmjopen-2017-019350 [19] bibby, s., reddy, s., cripps, t., et al. (2016). tolerability of nasal delivery of humidified and warmed air at different temperatures: a randomized double-blind pilot study. pulmonary medicine, 7951272. retrieved from: http://dx.doi.org/10.1155/2016/7951272 [20] national institute of health. (2020). nih clinical trial of remdesivir to treat covid-19 begins. retrieved from: https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdisivirtreat-covid-19-begins [21] national institute of health. (2020). nih clinical trial of hydroxychloroquine, a potential therapy for covid-19 begins. retrieved from: https://www.nih.gov/news-events/news-releases/nih-clinical-trialhydroxychloroquine-potential-therapy-covid-19-begins [22] world health organization. (2020). “solidarity” clinical trial for covid-19 treatments. retrieved from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novelcoronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments doi 10.18502/sjms.v15i5.7161 page 84 https://www.who.int/health-topics/coronavirus#tab=tab_3 https://www.who.int/health-topics/coronavirus#tab=tab_3 https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public https://www.weforum.org/agenda/2020/03/coronavirus-covid-19-hangzhou-zhejiang-government-response/ https://www.weforum.org/agenda/2020/03/coronavirus-covid-19-hangzhou-zhejiang-government-response/ https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins https://ssrn.com/abstract=3551767 http://dx.doi.org/10.1155/2016/7951272 https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdisivir-treat-covid-19-begins https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdisivir-treat-covid-19-begins https://www.nih.gov/news-events/news-releases/nih-clinical-trial-hydroxychloroquine-potential-therapy-covid-19-begins https://www.nih.gov/news-events/news-releases/nih-clinical-trial-hydroxychloroquine-potential-therapy-covid-19-begins https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments introduction sars-cov-2 control and prevention therapeutic prospects conclusion references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7230 production and hosting by knowledge e short communication burnout syndrome among healthcare workers is associated with violence against them. what needs to be done? elhadi m. awooda consultant in restorative dentistry and health management abstract background: patients have seemingly become more aggressive against healthcare workers when seeking their demands during the sars-cov2 pandemic. violence against healthcare workers is multifactorial and one that strongly associates with the burnout syndrome. objectives: the aim of this study was to draw a conclusion from the previously published literature about the association of violence against health care workers (hcws) and their burnout syndrome. and also, to find out other associated factors and possible solutions for this phenomenon. results: hcws are subject to stressful situations and high pressure, alongside highly infectious diseases (sars-cov2), shortage of ppe, working for more than 24 hr, without payment or reward, difficulties at the workplace, and a poor workplace administration , which can all lead to what is known as a “burnout syndrome.” on the other hand, patients have high expectations of their needs. their attendants’ (co-patients) are generally anxious about their patients’ medical fate. also, patients or co-patients perceive a doctor as their only savior, and so any unexpected or unpleasant behavior from the burnt-out hcws can be counteracted by aggressiveness and violence. conclusion: violence against hcws is associated with burnout syndrome and vice versa. a real attempt should be made focusing on the radical solution for the problem of burnout syndrome rather than enacting laws to punish the aggressors against hcws. keywords: dehumanization, doctors’ abuse, maslach theory, mental fatigue, sarscov2, workplace aggressiveness 1. introduction violence against hcws has been frequently raised recently and represents an uprising bending problem. it jeopardizes the quality of healthcare services and can affect the self-satisfaction of both patients and healthcare providers. stakeholders, policymakers, healthcare authorities, and even the communities are all keeping distance and watching the repeated aggressions against hcws without any action to find out a radical solution to the problem. the career success and competency of healthcare personnel how to cite this article: elhadi m. awooda (2020) “burnout syndrome among healthcare workers is associated with violence against them. what needs to be done?,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 128–135. doi 10.18502/sjms.v15i5.7230 page 128 corresponding author: elhadi mohieldin awooda; mobile phone: 00 249 9 121 44 969 email: dr.alhadi@yahoo.com received 14 may 2020 accepted 2 july 2020 published 1 october 2020 production and hosting by knowledge e elhadi m. awooda. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr.alhadi@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences elhadi m. awooda relies on learning and training on vulnerable groups of peoples, that is, the patients. healthcare profession is one of the demanding professions that besides skill in human communication, interaction, and expression of human sympathy to others, also requires mental, physical, and emotional fitness. prolonged personal contact with patients can lead to a condition known as burnout. hcws who experience burnout are unable to continue working and find the interaction with patients unbearable [1]. burnout syndrome is regarded as one of the relevant consequences of violence against hcws [2] and vice versa. sudan, like all countries in the world, is combatting sars-cov2 – the millennium pandemic of this century. the measures that are being practiced to stop the disease from spreading are: “staying at home,” “avoiding crowds,” and social distancing,” besides the cessation of almost all working activities. unfortunately, the cessation has involved private clinics and included a recommendation stating that any nonemergency treatments be deferred for the coming weeks until the pandemic recedes. an increasing numbers of patients attending different (private and governmental) hospitals for emergencies, including known or unknown cases of sars-cov2 were allowed to be attended, which led to a knockout of many hospitals that went out of the services and also the quarantining of contacted hcws. this critical situation puts a burden on the hcws and healthcare facilities to meet the standards when only emergencies are being managed through limited resources. another issue is the shortage of personal protective equipment (ppe) in the country, making the hcws extremely vulnerable to the sars-cov2 infection. on the contrary, refusal to treating the patients will affect their ethical obligation toward their duties. the result will be a burnout syndrome among hcws, while patient reaction and response will be violent against them. this short communication highlights the possible association of burnout syndrome among hcws with the violence against them, and what needs to be done? 1.1. burnout syndrome burnout is a syndrome of being burned or nervous breakdown. it is characterized by three key aspects: emotional exhaustion (mental fatigue), depersonalization or dehumanization (psychological distancing from others), and reduced personal accomplishment. [3] burnout is an accumulative and gradual process that occurs over an extended period of time. the syndrome can affect anyone with a job that requires being in contact with the public. working with humans is not like working with animals or machines, it requires doi 10.18502/sjms.v15i5.7230 page 129 sudan journal of medical sciences elhadi m. awooda some sort of interaction. for example, police officers, cashiers, bankers, governmental employees, etc. in a country like sudan, doctors and nurses are more affected by this syndrome because of the stressful nature of their profession, besides not being wellsalaried, long duties ranging from 24 to 32 hr, poor work facilities, poor nutrition, no vacations, and bad rest houses. also, the lack of appreciation and acknowledgement to the sudanese hcws is a puzzling matter, indicating that there is a misunderstanding in patients and communities with respect to the great role played by the hcws, especially during this pandemic. the appreciation and gratitude of the hcws have become a general trend and tradition in many countries around the world, which leaves a positive impact on their morale. it also reflects positively on the way they would deal with patients, despite the bad conditions surrounding the work environment. in sudan, the most critical factor is the poor administrative quality in the healthcare sector, which comprises 80% of the health services process while the doctors comprise only 20%. unfortunately, doctors and nurses are performing at most all the duties supposed to be done by others. a burned-out doctor or nurse will dehumanize patients, that is, perceive the patient as an object rather than a human, and this might result in detrimental negligence in the treatment procedures and disregard of the psychological aspect of treating the patients [4]. the resultant will be how the patient will react? and that the reaction may be violence against them. burnout syndrome can affect all hcws during their career – from undergraduates to consultancy level. globally, burnout had been reported by 54.4% of physicians in the united states [5], 50% in brazil [6], 72% of psychiatrists in japan [7], and 60.6% of physicians in china [8]. it can therefore be concluded from these studies that more than 50% of hcws worldwide are affected by the burnout syndrome. i think the situation in sudan may be more worst, but to figure out the situation and associated factors and to determine the undermined causes, further descriptive cross-sectional studies are needed. burnout syndrome can also affect students, interims, registrars, and specialists or nurses more than consultants because they are in direct contact with patients for a long time while performing their duties. it could hurt their future career, reflecting them as a condescending person over others. on the other hand, the shortage of doctors in governmental hospitals and specifically in emergency departments during the sars-cov2 pandemic can lead to stressful clinical work and can progress to burnout syndrome. doi 10.18502/sjms.v15i5.7230 page 130 sudan journal of medical sciences elhadi m. awooda 1.2. violence against hcws violence against hcws has been reported in many places including europe [9], asia [10], the united states [11], africa, and the middle east [12], with a prevalence range of approximately 19–87% [13–17]. hcws worldwide have been experiencing violence in various forms including verbal, physical, cultural, or sexual, that possess a risk to them [18, 19]. female hcws are more prone to verbal violence, while males are to physical violence [20]. a recent systematic review from spain concluded that in most cases, the aggressors are men, whereas the victim hcws are mostly women [21]. it could be concluded that violence against hcws is a worldwide phenomenon a high prevalence rate of > 87% in some countries [22]. violence against hcws can affect their job satisfaction, insecure regarding the patients’ unexpected behavior, their life, work environment, and the results could be finally be burnout syndrome. this will affect the process and quality of healthcare services provided to the patients, and as a consequence, there will be more violence against the hcws [22]. 1.3. factors associated with violence against hcws healthcare system factors: health services, hospital workplace environments, and health service provider’s competency, availability, and readiness to manage patients have a heavy impact on patients and co-patients. poor quality of medical healthcare services during this pandemic in most countries and increased awareness of ethical issues among patients have increased medical disputes and at times violence against hcws. patients factor: unsatisfied co-patients or an unexpected tragedy of a patient can lead to an aggressive behavior against hcws. importantly, the patient and co-patients are in the most vulnerable situation, facing a temporary or permanent disability, or even death. they perceive a doctor as their only savior and require empathy and support from all hcws rather than unintentional negligence or disputes [23]. hcws factor: doctors’ approach of un-humanizing others leads to poor communication with patients or co-patients, and the result is generally violence against them. moreover, violence against hcws can leads to burnout syndrome [2]. other causes perceived are delayed medical provision, visiting-hours violation, and dissatisfaction with the nursing staff. the doctors feel that “patients come late to hospitals when complications have set in and then get impatient and violent in the hospital” [24]. they also think that they are overworking even though they face aggressiveness. doi 10.18502/sjms.v15i5.7230 page 131 sudan journal of medical sciences elhadi m. awooda unfortunately, hcws lack training and education on how to cope up with workplace stress, breaking bad news, communication skills, working at different times of the day: morning, afternoon, or night, and even 24 hours’ duties [25]. 1.4. what needs to be done? role of law and hospital administration: the way to abet this violence is not to hit back but rather prevent it. often the problem is not the law, which does exist, but the implementation of it [23]. legislating deterrent laws and assigning national protective rules that criminalize assaulting medical personnel, [19] regardless of verbal or physical nature, can reduce the number of attacks and make the aggressor think a lot before doing it. restrictive entry of co-patients to the clinical workplace, strengthening of security, and displaying information and also the laws governing the safety of doctors up-front should be done to make patient and co-patients aware of the consequences of violence against hcws [23]. unfortunately, facts are rarely reported or recorded [21], so, assaulting hcws on duty should be documented, investigated, and archived, even if the problem is resolved amicably. prolonged duty and work for more than 24 hr, lead to a risk hcws health and life. indeed, it is much better for the sake of the hcws to restrict duty to 8 hr only, while in case of their need to stay, a suitable rest zone with healthy food supplement should be provided. role of hcws: hcws must take a step toward solving this emerging critical issue by sharpening their communication skills and taking time to clearly explain patient prognosis to co-patients to avoid any unreasonable expectations [24]. the hcws have to understand that patients and co-patients are going through extraordinary fear, anxiety, and doubt and may not thus behave rationally. further, the hcws have to understand that patients come from a variety of backgrounds in terms of class, education, and economic status [23]. they should provide a sense of security to the patient and relatives, in the sense that everything is going as per plan, which will convince them and decrease their worries and tensions. in case of a sign of patient/doctor dispute arising (conversation with loud voices) or if breaking bad news is needed, a senior doctor with experience in such situations should take the action. role of the academic institutions: early teaching and training of communication skills, professionalism, and breaking bad news is crucial and should be part of the undergraduate medical sciences curriculum. students should show their competency in performing doi 10.18502/sjms.v15i5.7230 page 132 sudan journal of medical sciences elhadi m. awooda communication skills and should be assessed during formative and summative exams. also, a specialized counseling office should be founded in each healthcare service premise or university to provide consolatory, treatment, and prevention of burnout syndrome. regular follow-up and any sign or symptoms of burnout should be managed early and the undermined causes should be solved officially through the administrative system and work laws [4]. finally, unless doctors regain their most-favored status, and undermined causes are solved, such violence will not be ebbed [24]. 2. conclusion burnout syndrome is a real problem facing hcws worldwide, while burned hcws are more prone to aggressiveness from patients or co-patients. to improve the quality of healthcare services, by satisfying both patient and healthcare providers, a real attempt should be made focusing on the radical solution of the violence rather than enacting laws to punish the aggressors. competing interests the author declare that there are no competing interests. author’s contribution this work was carried out by ema who designed the study, reviewed the literature, wrote the protocol, and revised the manuscript critically for important intellectual content. ema read and approved the final manuscript references [1] murtomaa, h., haavio-mannila, e., and kandolin, i. 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(2019). manifestations of verbal and physical violence towards doctors: a comparison between hospital and community doctors. bmc health services research, vol. 19, p. 888. doi 10.18502/sjms.v15i5.7230 page 135 introduction burnout syndrome violence against hcws factors associated with violence against hcws what needs to be done? conclusion competing interests author's contribution references sudan journal of medical sciences sjms special issue 2020: competing with covid-19 in sudan, doi 10.18502/sjms.v15i5.7146 production and hosting by knowledge e research article the association of lymphocyte count, crp, d-dimer, and ldh with severe coronavirus disease 2019 (covid-19): a meta-analysis almigdad h. m. ali, sagad omer obeid mohamed, ibrahim h. e. elkhidir, mohamed elata hassan elbathani, abazr a. h. ibrahim, almutasim b. e. elhassan, mohammed suliman tawer salman, mazin a.m. elhassan, mahmoud elnil, and abdelhamid ibrahim hassan abuzied faculty of medicine, university of khartoum, sudan abstract background: the rapid progression of coronavirus disease 2019 (covid-19) and its increasing burden on health systems necessitate the identification of parameters of severe infection to help in monitoring, prognoses and development of treatment algorithms. objectives: this review aims to investigate the association of lymphocyte count, crp, ldh, and d-dimer with the severity of covid-19. methods: this review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. the databases of medline/pubmed, who-virtual health library (vhl), and sciencedirect were used for the systematic search. random effects model was used to estimate the pooled standardized mean differences (smd) with the corresponding 95% confidence interval (ci), using openmeta analyst software. results: a total of 11 studies, with 2437 covid-19 patients, which fulfilled the eligibility criteria were included in the meta-analysis. the analysis revealed that lymphocyte count was significantly lower in patients with the severe form of covid-19 (smd = 1.025, p value <.001). also, the analysis of smd showed that patients with severe covid-19 have a significantly higher serum levels of crp (smd = 3.363, p value <.001), d-dimer (smd = 1.073, p value <.001), and ldh (smd = 3.345, p value <.001). conclusion: low lymphocyte count and high levels of crp, ldh, and d-dimer are associated with severe covid-19. these laboratory markers could be used as clinical indicators of worsening illness and poor prognosis of covid-19. keywords: covid-19, lymphocyte count, crp, d-dimer, ldh, meta-analysis 1. introduction in december 2019, wuhan – the capital of central china’s hubei province – witnessed the emergence of a new virus of the coronaviridae family that caused several cases of severe respiratory disease [1, 2]. the virus was named by the world health organization how to cite this article: almigdad h. m. ali, sagad omer obeid mohamed, ibrahim h. e. elkhidir, mohamed elata hassan elbathani, abazr a. h. ibrahim, almutasim b. e. elhassan, mohammed suliman tawer salman, mazin a.m. elhassan, mahmoud elnil, and abdelhamid ibrahim hassan abuzied (2020) “the association of lymphocyte count, crp, d-dimer, and ldh with severe coronavirus disease 2019 (covid-19): a meta-analysis,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 9–23. doi 10.18502/sjms.v15i5.7146 page 9 corresponding author: almigdad h. m. ali; faculty of medicine, university of khartoum, qasr street. p.o. box 11111 khartoum, sudan tel: 00249910174057 email: almigdad.h.m@gmail.com received 22 april 2020 accepted 15 may 2020 published 1 june 2020 production and hosting by knowledge e almigdad h. m. ali et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:almigdad.h.m@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences almigdad h. m. ali et al (who) as a severe acute respiratory syndrome novel coronavirus 2 (sars-cov-2) and the disease caused by this virus as coronavirus disease 2019 (covid19) [1, 2]. the disease spread dramatically and reached other provinces in china and many other countries around the world, forcing the who to declare it as a global pandemic on march 11, 2020 [3]. despite all the efforts made to contain the disease, it has spread to over 200 countries around the world, causing a significant burden to healthcare facilities, as well as economic burdens on international systems [4]. the sars-cov-2 is transmitted by infective respiratory droplets from infected patients, fomites, and surfaces reaching conjunctiva or respiratory mucosa. the incubation period usually ranges from 2 to 14 days after exposure, during which the patient may be infectious [4, 5]. animal-to-human transmission is still being investigated, knowing that similar coronaviruses are found in bats, rodents, and birds [5, 6]. most people infected with covid-19 experienced a mild-to-moderate respiratory illness, with cough and shortness of breath being the most common symptoms [6, 7]. approximately 14% of the patients developed a severe disease with complications like acute respiratory distress syndrome and respiratory failure, acute liver injury, acute kidney injury, cardiovascular complications, septic shock, and multi-organ failure [6, 7]. older people and those with underlying co-morbidities like diabetes, chronic respiratory diseases, cardiovascular diseases, and immune-compromised patients had a higher risk of developing severe disease [8]. patients with severe disease or complications require special care such as admission to intensive care units (icu) with mechanical ventilation [9]. however, there is a wide gap between the total population and the number of intensive care beds available [9]. further adding to the burden, icu services cost the hospitals around 39% of the total drug costs, 25% of the equipment, and 13% of the lab investigations [10]. researchers are still working to find a definitive treatment of covid-19, and there are ongoing trials on some antiviral, anti-inflammatories, and anti-malarial drugs such as hydroxychloroquine sulfate and chloroquine phosphate products to be used for certain hospitalized patients with covd-19 [5, 11]. diagnosis is dependent on the evaluation of the risk of contact with an infected patient, clinical signs and symptoms, and polymerase chain reaction testing of viral rna on respiratory samples [1, 4, 5]. other investigations have been used to evaluate the patient’s condition and to predict severe outcomes of the disease such as complete blood count, d-dimer, procalcitonin, c-reactive protein (crp), and lactate dehydrogenase (ldh) [4, 5]. two recent meta-analyses showed that increased procalcitonin values and thrombocytopenia are associated with a higher risk of severe covid-19 [12, 13]. doi 10.18502/sjms.v15i5.7146 page 10 sudan journal of medical sciences almigdad h. m. ali et al other studies suggested that lymphocytes count, d-dimer, crp, and ldh have a role in the prognosis of covid-19 [30, 31]. however, and to the best of our knowledge, there is no meta-analysis on these biomarkers. therefore, the objective of this review is to assess the association between severe covid-19 and these laboratory markers. taking into consideration the disease burden and the limited resources and capacities of health facilities, it is very crucial to find parameters that support the clinical condition’s risk assessment to aid the anticipation of severe complications. 2. materials and methods 2.1. search strategy and inclusion criteria in this meta-analysis, we followed the preferred reporting items for systematic reviews and meta-analyses (prisma) statement [14]. the systematic literature search was performed using the electronic databases of medline/pubmed, who-virtual health library (vhl), and sciencedirect, without date or language restriction. the search terms used were “novel coronavirus,” “2019 ncov,” “covid-19,” “sars-cov-2,” “lymphopenia,” “lymphocytopenia,” “leukopenia,” “leukocytopenia,” “d-dimer,” “c-reactive protein,” “crp,” “lactate dehydrogenase,” and “ldh” to ensure no possible relevant articles were missed. also, we reviewed the articles referenced by the identified articles in this search. all observational studies reporting sufficient information on lymphocyte count, crp, ldh, and d-dimer levels in both severe and non-severe covid-19 patients, with a clear definition of severe illness, were included in the analysis for calculating the standardized mean difference (smd) estimates. the exclusion criteria for the study were: case reports, editorials, letters, abstracts, and studies without sufficient data of interest. if two or more studies had the same patient population, the study with more data was included to avoid duplication. the included studies determined severe covid-19 based on the composite of respiratory distress with hypoxia and/or hypoxemia [15–17], the american thoracic society guidelines for community-acquired pneumonia [18], youden’s index [19], guidelines of expert chinese group [20], non-survival [21], disease progression [22], oxygen saturation < 90% [23], the requirement of icu admission [24], and the requirement of supplemental oxygen [25]. the titles and abstracts of all articles retrieved from this search were screened for potential inclusion in this review. then, potentially relevant studies were reviewed (full doi 10.18502/sjms.v15i5.7146 page 11 sudan journal of medical sciences almigdad h. m. ali et al text) for inclusion according to the defined eligibility criteria, and data were extracted by independent reviewers using a data extraction form. the quality of the studies was assessed using the newcastle – ottawa scale. any disparity among the reviewers at any step was resolved by discussion and consensus. 2.2. data analysis the statistical analyses were carried out using r language. the pooled smd was calculated from the random-effects model due to the notable heterogeneity in this metaanalysis. statistical heterogeneity was assessed with the i2 statistics and publication bias was determined through egger’s test and visual examination of the funnel plot [26]. 3. results 3.1. characteristics of the studies the schematic flow of the studies’ identification and selection process is presented in figure 1, and the summary of data from the included studies is shown in supplementary table 1. our search retrieved records for 285 published articles, of which, full texts of 34 potentially relevant studies were retrieved for full-text screening and 23 studies were subsequently omitted because of duplication of the study populations and insufficient data to estimate the outcomes of interest. last, a total of 11 studies with 2,437 patients, published from december 2019 to march 2020 were included for the analysis. all of them were from mainland china [16–25], while one study was based in singapore [26]. 3.2. analysis of smd of the lymphocyte count between the two groups of patients the pooled effect size showed that the lymphocyte count was significantly lower in patients with severe covid-19 than patients with non-severe covid-19 and the smd = –1.02 (95% ci, –1.33 – –0.74: p< 0.001; figure 2). no evidence of publication bias was detected based on visual examination of the funnel plot and from the results of egger’s test (p = 0.59; figure 6a). doi 10.18502/sjms.v15i5.7146 page 12 sudan journal of medical sciences almigdad h. m. ali et al figure 1: the flow diagram for the process of study selection and systematic review of literature. figure 2: pooled smd of lymphocyte count estimates between the two groups of patients (severe and non-severe covid-19). 3.3. analysis of smd of the crp between the two groups of patients the pooled effect size showed that crp level was significantly higher in patients with severe covid-19 than patients with non-severe covid-19 with an smd = 3.34 (95% ci, 2.19 – 4.49: p < 0.001; figure 3). a slight publication bias was detected based on visual examination of the funnel plot and from the results of egger’s test (p = 0.03; figure 6b). the duvall and tweedie trim and fill method indicated that potential missing studies were three. doi 10.18502/sjms.v15i5.7146 page 13 sudan journal of medical sciences almigdad h. m. ali et al figure 3: pooled smd of crp estimates between the two groups of patients (severe and non-severe covid-19). 3.4. analysis of smd of the d-dimer between the two groups of patients the pooled effect size showed that d-dimer level was significantly higher in patients with severe covid-19 than patients with non-severe covid-19, with an smd = 1.79 (95% ci, 1.38 – 2.19: p < 0.001; figure 4). no evidence of publication bias was detected based on visual examination of the funnel plot and from the results of egger’s test (p = 0.97; figure 6c). figure 4: pooled smd of d-dimer estimates between the two groups of patients (severe and non-severe covid-19). 3.5. analysis of smd of the ldh between the two groups of patients the pooled effect size showed that ldh level was significantly higher in patients with severe covid-19 than patients with non-severe covid-19, with an smd = 3.34 (95% ci, doi 10.18502/sjms.v15i5.7146 page 14 sudan journal of medical sciences almigdad h. m. ali et al 1.92 – 4.77: p < 0.001; figure 5). no evidence of publication bias was detected based on visual examination of the funnel plot and from the results of the egger’s test (p = 0.83; figure 6d). the leave-one-out sensitivity analyses indicated that our results were robust and were not driven by any single study. figure 5: pooled smd of ldh estimates between the two groups of patients (severe and non-severe covid-19). figure 6: (a–d) funnel plots for assessment of the publication bias. 4. discussion in addition to the clinical criteria, it is of great benefit to have laboratory markers for severe infection that will help in monitoring and prognosis and will be used to develop workup and treatment algorithms. this meta-analysis investigated the association between severe covid-19 and several biomarkers. the analysis showed that doi 10.18502/sjms.v15i5.7146 page 15 sudan journal of medical sciences almigdad h. m. ali et al patients with poor outcomes of covid-19 are likely to have lymphopenia, as shown in figure 2. based on several studies, it has been suggested that the immune system is impaired during the disease and covid-19 might damage t lymphocytes [6, 8, 27]. these studies showed a particular decrease in the cd4+ subset of lymphocytes and higher naive cd4+ cells than memory cells in severe cases [6, 8, 27]. the higher naive to memory cells ratio indicates that the immune system was impaired more severely [6, 8]. the baseline lymphocyte count for these patients was not provided in these studies to determine if the lymphopenia was disease-related or was it present prior to the infection. if it was provided, these suggestions would have been more conclusive. the changes in peripheral white blood cells were presumed to be caused by a cytokine storm in the body that generates a series of immune responses [27]. the levels of crp and other inflammatory markers, such as il-6, il-8, il-2r, and il-10, were noticed to be higher in severe cases than non-severe cases [21]. increased levels of cytokines, chemokines, and neutrophils to lymphocyte ratio (nlr) in severe cases suggest a possible hyper-inflammatory response role in the pathogenesis of covid-19 [20]. it is perplexing how elderly persons are more prone to severe covid-19 despite their impaired immunity. this incongruence can be partially explained by the fact that elderly people have impaired innate and adaptive immunity. innate immunity in healthy individuals manages to neutralize the virus early in the disease, keeping it from reaching the alveoli. the situation differs in elderly patients, where the innate immunity fails to do so, and the virus manages to reach the alveoli and replicate in high numbers. this triggers macrophages and lymphocytes to mount a vigorous response to eradicate virally infected cells. this response is associated with elevated levels of cytokines [28]. the d-dimer level elevation in patients with severe disease may raise the suspicion of underlying abnormal blood coagulation function [20]. the effect of d-dimer widens to include not only the correlation with the severity of the disease but also with mortality percentage, as shown by zhou f. et al.’s study in wuhan, china, who found that a ddimer level of > 1 mg/ml is associated with fatal outcome [21]. gao y. et al. showed that the clinical benefit of d-dimer level prediction of the severity of the disease will increase if it is combined along with il6 level [20]. also, the level of ldh, which is an inflammatory marker, shows a similar correlation with mortality percentages as that of d-dimer [19, 21]. ldh enzyme is found in the cytoplasm of all cells, thus any tissue damage would cause an increase in the serum level of the enzyme. different tissues display different isoenzymes, but the isoenzymes were not specified in any of the reviewed studies. therefore, the origin of the ldh couldn’t be specifically identified [29]. doi 10.18502/sjms.v15i5.7146 page 16 sudan journal of medical sciences almigdad h. m. ali et al the findings of this study need to be considered in the context of some limitations. all studies we found were conducted in asia, whereas nowadays the majority of cases are in the united states and europe. due to the limitedness of the available data and variable definition of disease severity among the studies, there is a need for further studies to explore and clarify the prognostic role as well as the precise mechanisms underlying the changes in these biomarkers in patients with severe covid-19. 5. conclusion lymphopenia and high levels of crp, ldh, and d-dimer are associated with severe covid-19. these laboratory markers could be used as clinical indicators of worsening illness and poor prognosis of covid-19. this will help in developing different algorithms for managing covid-19 patients according to the anticipated severity of the disease. 6. declarations ethical approval and consent to participate not applicable consent for publication not applicable availability of data and material the dataset generated during this study are available from the corresponding author on reasonable request. competing interests none declared funding no funding doi 10.18502/sjms.v15i5.7146 page 17 sudan journal of medical sciences almigdad h. m. ali et al acknowledgment none to acknowledge supplementary materials table 1 (summary of the included studies in the review) abbreviations • covid-19: coronavirus disease 19 • sars-cov-2: severe acute respiratory syndrome novel coronavirus 2 • crp: c-reactive protein • ldh: lactate dehydrogenase authors contribution aa conceptualized the research idea; aa, sm, and ie designed the study; aa, sm, me, ms, ai, and ae undertook articles searching, articles assessment, and data extraction; sm and ie undertook data analysis. all authors interpreted the results and drafted the manuscript. all authors revised and approved the final manuscript and all of them agree to be accounted for the accuracy and integrity of all aspects of the work. references [1] singhal, t. 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[30] harenberg j, favaloro e. covid-19: progression of disease and intravascular coagulation – present status and future perspectives. clinical chemistry and laboratory medicine (cclm). 2020;0(0). retrieved from: https://www.degruyter. com/view/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0502/article-10. 1515-cclm-2020-0502.xml [31] sun y, dong y, wang l, xie h, li b, chang c, wang fs. characteristics and prognostic factors of disease severity in patients with covid-19: the beijing experience. journal of autoimmunity. 2020 apr 24:102473. retrieved from: https://www.ncbi.nlm.nih.gov/ pmc/articles/pmc7180376/ doi 10.18502/sjms.v15i5.7146 page 21 https://doi.org/10.1016/j.tmaid.2020.101623 https://www.degruyter.com/view/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0502/article-10.1515-cclm-2020-0502.xml https://www.degruyter.com/view/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0502/article-10.1515-cclm-2020-0502.xml https://www.degruyter.com/view/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0502/article-10.1515-cclm-2020-0502.xml https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7180376/ https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7180376/ introduction materials and methods search strategy and inclusion criteria data analysis results characteristics of the studies analysis of smd of the lymphocyte count between the two groups of patients analysis of smd of the crp between the two groupsof patients analysis of smd of the d-dimer between the two groups of patients analysis of smd of the ldh between the two groupsof patients discussion conclusion declarations ethical approval and consent to participate consent for publication availability of data and material competing interests funding acknowledgment supplementary materials abbreviations authors contribution references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8160 production and hosting by knowledge e research article the controversy on the role of ace2 receptor in covid-19 infection: the protective shift toward the ace2 axis sarah i y ahmed independent researcher, khartoum, sudan abstract background: angiotensin-converting enzyme 2 (ace2) is recognized as the main cellular receptor for the new coronavirus, sars-cov-2, that facilitates its entry into the host target cell, leading to the fatal viral infection, coronavirus disease 2019 (covid-19). thus, it is considered as a main therapeutic target in the sars-cov-2 infection. the dual role of ace2 as a gate for sars-cov-2 virus and as a part of lung and multi-organ protection has built a scientific debate that affects the choice of treatments used against covid-19 patient. ace2 inhibitors like anti-ace2 antibodies were first introduced as therapeutic solutions that, theoretically, would decrease the availability of target molecules for sars-cov-2 by downregulating ace2 expression. however, animal studies showed that ace2 upregulation acts as a counterbalance to the hypertensive pro-inflammatory angiotensin i-converting enzyme (ace) in the renin–angiotensin system (ras) and results in a protective role against acute lung injury – a fatal consequence of the disease. the current study tests the effect of ace2activating treatments against the outcome of genetic variations in the population that have ace2-upregulatory effects. conclusion despite its role as a receptor for the sars-cov-2 virus, experimental studies and the genetic polymorphisms in populations that have ace2 upregulation revealed a protective role against covid-19 infection. keywords: ace2 ace covid-19 treatments genetic variations 1. introduction the mechanism for sars-cov-2 infection necessitates the binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ace2) receptor, followed by the internalization of the complex by the infected host cell [1]. the main function of ace2 is to regulate the blood pressure by opposing the action of angiotensin ii (ang ii), the active peptide of the classical renin–angiotensin system (ras). the ras can be classified into two main axes that counteract each other to maintain vascular homeostasis: the classical vasoconstrictive axis including angiotensinogen, renin, angiotensin-converting enzyme, ang i, ang ii, angiotensin ii receptor type 1 (at1r), and the vasorelaxant axis including ace2, angiotensin-(1-7), and mas receptor how to cite this article: sarah i y ahmed (2020) “the controversy on the role of ace2 receptor in covid-19 infection: the protective shift toward the ace2 axis,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 378–382. doi 10.18502/sjms.v15i4.8160 page 378 corresponding author: sarah i y ahmed; independent researcher, khartoum, sudan received 3 october 2020 accepted 18 december 2020 published 31 december 2020 production and hosting by knowledge e sarah i y ahmed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sarah i y ahmed (masr) [2]. ace2 acts primarily to counterbalance the effect of ace. as ace generates ang ii from angiotensin i, which has hypertensive pro-inflammatory effects, ace2 generates angiotensin (1-7) from ang ii, which has potentially beneficial vasodilatory and anti-inflammatory properties [35], see figure 1. some researchers believed that the increased expression of the ace2 receptor may elevate the rate of sars-cov-2 infection via increasing viral load, morbidity, and mortality. accordingly, they assumed that ace2 inhibitors like anti-ace-2 antibodies could be used to block sars-cov-2 binding to the receptor [6, 7]. however, preclinical studies showed that the combination of the coronavirus spike protein and ace2 reduces ace2 expression, leading to acute lung injury and pulmonary edema symptoms, which are the main symptoms of the disease [8]. recently, recombinant soluble ace2 has been introduced to neutralize sars-cov-2 by binding to the viral spike protein, and at the same time minimizing injury to multiple organs, including lungs, kidneys, and heart [9, 10]. the current study believes that the shift from ace to the ace2 axis has a beneficial effect against covid19. in this study, the effect of ace2-activating treatment is discussed and compared to the protective effect of ace2 upregulating genetic polymorphisms in populations. figure 1: the possible therapeutic targets in the renin–angiotensin system (ras) and protective genetic polymorphisms. the red lines represent the ace axis and the green lines represent the ace2 axis that counteracts the ace action. at1r, ace2, and mas receptor represent the membrane-bound receptors. the possible therapeutics in ace and ace2 axes are coupled with genetic polymorphisms that have comparable upregulatory or downregulatory actions. doi 10.18502/sjms.v15i4.8160 page 379 sudan journal of medical sciences sarah i y ahmed 1.1. covid-19 treatment and ace2 the use of medications that have ace2-activating effects as a treatment for covid-19 was questioned. theoretically, it was assumed that increasing the levels of ace2 would increase the availability of target molecules for sars-cov-2 [11]. an example of ace2activating treatments is anti-hypertensive treatments – angiotensin-converting enzyme inhibitor (acei) and angiotensin-receptor blocker (arb) that elevate the expression of ace2. despite the argument, a retrospective study by zhang et al. found that covid-19 patients, who were taking aceis and arbs as a hypertension treatment, have a low mortality rate. this is in line with the animal studies that showed a potential protective effect with high ace2 levels as a result of the increasing production of the vasodilator angiotensin 1–7, which ameliorates the severity of acute lung injury in sars-covinfected mice [12]. on the other hand, the deficiency ace2 gene in animal studies showed comparable pathological changes found in human lung failure, including sars and avian influenza a [12, 13]. the drop in the levels of ace2 in infective cells due to the interaction of the spike protein of the coronavirus with ace2 is also found to be responsible for the lung damage in covid-19. this led to the idea of introducing soluble ace2 that can neutralize sars-cov-2 by binding the viral spike protein, and at the same time minimizing injury to lungs and other organs [10]. 1.2. genetic variations and covid-19 infection the genetic polymorphisms of the ace axis that decrease the activity of the ras system along with the polymorphisms that upregulate the ace2 axis are hypothesized to be protective by shifting the balance toward the ace2 axis, see figure 1. the i allele of ace i/d polymorphism has lower tissue and plasma activity than the d allele. individuals with the i allele are prone to be at lower risk of having hypertension than those with the d allele. it was found that the occurrence of acute respiratory distress syndrome (ards) and the mortality rate are higher in patients with dd genotype compared with the i allele, and the ace i/d polymorphism was an independent prognostic factor for ards for 30-day survival [14, 15]. a recent study that investigated the geographic distribution of i and d alleles and the prevalence of covid-19 infection found that with an increase in the i/d allele ratio (i allele increases or d allele decreases), the recovery rate also increases. this explains the higher recovery rate observed among the populations with a high i/d allele ratio such as the east asian countries of china, japan, and south korea, while european countries like spain, italy, and the uk with a low i/d allele ratio took the worst-hit of the disease [16]. this is in agreement with another ecological study on highincome countries that found an association between the high frequency of the d-allele and the increased covid-19 incidence and mortality rate [17]. the point is that genetic polymorphism of the ace gene that has ace-downregulating effect increases ace2 and are found to have low infection and mortality rates in different populations, thus it is comparable to ace inhibitors. on the other hand, ace2 genetic polymorphisms that directly increase its expression level are also found to be associated with the course of infection. a wide genetic association study in india revealed that the alternate allele doi 10.18502/sjms.v15i4.8160 page 380 sudan journal of medical sciences sarah i y ahmed (tt-plus strand or aa-minus strand) of ace2 rs2285666 elevate the expression level by up to 50%, and are found to have a strong correlation with low infection rate and low mortality rate among indian populations [18]. other witnesses are the vulnerable conditions like aging, copd, smoking, hypertension, diabetes, and other cardiovascular disorders that have low ace2 levels and are known to be at high risk of infection, while healthy individuals like healthy athletes and children have high levels of expression that render them to be more protected [19–22]. 2. conclusion genetic association studies revealed that genetic polymorphisms that result in high ace2 levels are associated with low infection and low rates [16-18]. this can be taken as evidence for the protective shift toward the ace2 axis. thus, the use of “shift toward ace2 axis” treatments, including both ace2-activating and ace downregulatory drugs, can be applied to covid-19 and comorbidities like the safe use of metformin, the antidiabetic drug that has ace2-activating effect, for covid-19 patients with diabetes. of note, the relative risk of a particular genetic polymorphism or a combination of genetic polymorphisms in populations with a low rate of infection can reflect the better choice for therapeutic targets. for example, the high relative risk of acei/d reflects the importance of ace inhibitors. the same for other genetic variations like the relative risk of ace2 rs2285666 and the effect of ace2 activators, at1r a1166c and at1r blockers. conflicts of interest the author has no conflicts of interest to disclose. funding none. references [1] zhang, h., penninger, j. m., li, y., et al. (2020). angiotensin-converting enzyme 2 (ace2) as a sarscov-2 receptor: molecular mechanisms and potential therapeutic target. intensive care medicine, vol. 46, no. 4, pp. 586–590. retrieved from https://pubmed.ncbi.nlm.nih.gov/32125455/ [2] povlsen, a., grimm, d., wehland, m., et al. (2020). the vasoactive mas receptor in essential hypertension. journal of clinical medicine, vol. 9, no. 1, p. 267. retrieved from https://pubmed.ncbi.nlm.nih.gov/ 31963731/ [3] santos, r. a. s., sampaio, w. o., alzamora, a. c., et al. (2018). the ace2/angiotensin-(1–7)/mas axis of the renin-angiotensin system: focus on angiotensin-(1–7). physiological reviews, vol. 98, no. 1, pp. 505–553. retrieved from https://pubmed.ncbi.nlm.nih.gov/29351514/ [4] dandona, p., dhindsa, s., ghanim, h., et al. 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(2016). pulmonary angiotensin-converting enzyme 2 (ace2) and inflammatory lung disease. shock, vol. 46, no. 3, pp. 239–248. retrieved from https://pubmed.ncbi.nlm.nih.gov/27082314/ [14] marshall, r. p., webb, s., bellingan, g. j., et al. (2002). angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. american journal of respiratory and critical care medicine, vol. 166, no. 5, pp. 646–650. retreived from https://pubmed.ncbi.nlm.nih.gov/12204859/ [15] adamzik, m., frey, u., sixt, s., et al. (2007). ace i/d but not agt (-6)a/g polymorphism is a risk factor for mortality in ards. european respiratory journal, vol. 29, no. 3, pp. 482–488. retrieved from https://pubmed.ncbi.nlm.nih.gov/17107992/ [16] hatami, n., ahi, s., sadeghinikoo, a., et al. (2020). worldwide ace (i/d) polymorphism may affect covid19 recovery rate: an ecological meta-regression. endocrine, vol. 68, no. 3, pp. 479–484. retrieved from https://pubmed.ncbi.nlm.nih.gov/32542429/ [17] kenyon, c. (2020). ace-1 i/d polymorphism associated with covid-19 incidence and mortality: an ecological study. preprint, 2020040262. retrieved from https://www.preprints.org/manuscript/202004. 0262/v1 [18] srivastava, a., bandopadhyay, a., das, d., et al. (2020). genetic association of ace2 rs2285666 polymorphism with covid-19 spatial distribution in india. frontiers in genetics, vol. 11, 564741. retrievd from https://pubmed.ncbi.nlm.nih.gov/33101387/ [19] xudong, x., junzhu, c., xingxiang, w., et al. (2006). ageand gender-related difference of ace2 expression in rat lung. life sciences, vol. 78, no. 19, pp. 2166–2171. retrieved from https://pubmed.ncbi. nlm.nih.gov/16303146/ [20] leung, j. m., yang, c. x., tam, a., et al. (2020). ace-2 expression in the small airway epithelia of smokers and copd patients: implications for covid-19. european respiratory journal, vol. 55, no. 5, p. 2000688. retrieved from https://pubmed.ncbi.nlm.nih.gov/32269089/ [21] rockx, b., baas, t., zornetzer, g. a., et al. (2009). early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. journal of virology, vol. 83, no. 14, pp. 7062–7074. retrieved from https://pubmed.ncbi.nlm.nih.gov/19420084/ [22] prata, l. o., rodrigues, c. r., martins, j. m., et al. (2017). original research: ace2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis. experimental biology and medicine, vol. 242, no. 1, pp. 8–21. retrieved from https://pubmed.ncbi.nlm.nih.gov/27550926/ doi 10.18502/sjms.v15i4.8160 page 382 https://pubmed.ncbi.nlm.nih.gov/32142651/ https://pubmed.ncbi.nlm.nih.gov/32753842/ https://pubmed.ncbi.nlm.nih.gov/16007097/ https://pubmed.ncbi.nlm.nih.gov/16001071/ https://pubmed.ncbi.nlm.nih.gov/16001071/ https://pubmed.ncbi.nlm.nih.gov/33131609/ https://pubmed.ncbi.nlm.nih.gov/33131609/ https://pubmed.ncbi.nlm.nih.gov/32339534/ https://pubmed.ncbi.nlm.nih.gov/32339534/ https://pubmed.ncbi.nlm.nih.gov/18448662/ https://pubmed.ncbi.nlm.nih.gov/27082314/ https://pubmed.ncbi.nlm.nih.gov/12204859/ https://pubmed.ncbi.nlm.nih.gov/17107992/ https://pubmed.ncbi.nlm.nih.gov/32542429/ https://www.preprints.org/manuscript/202004.0262/v1 https://www.preprints.org/manuscript/202004.0262/v1 https://pubmed.ncbi.nlm.nih.gov/33101387/ https://pubmed.ncbi.nlm.nih.gov/16303146/ https://pubmed.ncbi.nlm.nih.gov/16303146/ https://pubmed.ncbi.nlm.nih.gov/32269089/ https://pubmed.ncbi.nlm.nih.gov/19420084/ https://pubmed.ncbi.nlm.nih.gov/27550926/ introduction covid-19 treatment and ace2 genetic variations and covid-19 infection conclusion conflicts of interest funding references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7275 production and hosting by knowledge e research article profile of abdominal surgical complications of enteric fever in children in a developing country kevin emeka chukwubuike pediatric surgery unit, department of surgery, enugu state university teaching hospital, enugu, nigeria abstract background: surgical complications of enteric fever has been associated with significant morbidity and mortality. the aim of this study was to determine the pattern and outcome of the treatment of abdominal surgical complications of enteric fever in children in a teaching hospital in enugu, nigeria. methods: this retrospective study included children who had undergone a surgery for abdominal complications of enteric fever at the pediatric surgery unit of enugu state university teaching hospital (esuth), enugu, nigeria. the medical records of the pediatric patients over a five-year period were evaluated for the patients’ demographics, presenting symptoms, investigations, intraoperative findings, procedures performed, and postoperative complications and outcome. results: during the study period, there were 44 cases of abdominal surgical complications of enteric fever with an age range of 6–14 years (mean 9.5 years) and the male to female ratio of 2.7:1. the mean duration of symptoms prior to presentation was five days. all the patients had fever and abdominal pain. while 95% of the patient had typhoid intestinal perforation, 5% had typhoid hemorrhage. primary closure of intestinal perforation and right hemicolectomy with ileotransverse anastomosis were performed for typhoid intestinal perforation and typhoid intestinal hemorrhage, respectively. surgical site infection was the most common postoperative complication. the mortality rate was 6.8%. conclusion: abdominal surgical complications of enteric fever are still obtainable in developing countries. typhoid intestinal perforation was the most common complication recorded in the present study. keywords: abdominal, children, enteric fever, surgical complications 1. introduction enteric fever, also known as typhoid fever, is a common multisystem infection caused by the bacteria salmonella enterica serovar typhi and salmonella enterica serovar paratyphi a and b which are transmitted through feco-oral route [1]. it is a public health problem particularly in low-income countries due to poor sanitation, lack of potable how to cite this article: kevin emeka chukwubuike (2020) “profile of abdominal surgical complications of enteric fever in children in a developing country,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 270–280. doi 10.18502/sjms.v15i3.7275 page 270 corresponding author: kevin emeka chukwubuike; department of surgery, enugu state university teaching hospital, enugu, nigeria. email: chukwubuikeonline@yahoo.com received 11 august 2020 accepted 15 september 2020 published 30 september 2020 production and hosting by knowledge e kevin emeka chukwubuike. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:chukwubuikeonline@yahoo.com mailto:chukwubuikeonline@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences kevin emeka chukwubuike water, and improper waste disposal [2]. generally, complications of enteric fever of surgical importance could be associated with significant morbidity and mortality. these complications include typhoid intestinal perforation, intestinal bleeding, gall bladder diseases, and osteomyelitis. other complications, though rare, include pancreatitis, pleural effusion, orchitis, hepatic, and splenic abscesses. among all the complications, typhoid intestinal bleeding is the most common. however, several authors have reported typhoid intestinal perforation as the most dreaded and feared complication [3–6]. this study focuses on the surgical complications of typhoid fever that occur in the abdomen. the objective of this study was to determine the pattern and outcome of the treatment of abdominal surgical complications of enteric fever in children in a teaching hospital in enugu, nigeria. 2. materials and methods this retrospective study included children aged 15 years and below who had undergone a treatment for abdominal complications of typhoid fever between january 2014 and december 2018 at the pediatric surgery unit of the enugu state university teaching hospital (esuth) enugu, nigeria. esuth serves the whole of the enugu state, which according to the 2016 estimates of the national population commission and nigerian national bureau of statistics has a population of about 4 million people and a population density of 616.0/km2. the hospital also receives referrals from its neighboring states. ethical approval was obtained from the ethics and research committee of the hospital. informed consent was obtained from the patients’ caregivers. however, patients who have had surgery for typhoid complication and those who are above the age of 15 years were excluded from this study. in addition, patients with incomplete case records were also excluded. 2.1. preoperative protocol all the consecutive children who presented during the study period were recruited into the study. the diagnosis of typhoid complication was made based on clinical features, investigations, intraoperative findings and histological examination. investigations such as ultrasound and x-rays were performed depending on the clinical presentation of the patients. all patients had taken widal tests which were strongly positive. on presentation at the hospital, all patients were resuscitated using intravenous fluids and placed on intravenous ceftriaxone. doi 10.18502/sjms.v15i3.7275 page 271 sudan journal of medical sciences kevin emeka chukwubuike 2.2. intraoperative protocol the intraoperative procedure depended on the type of typhoid complication. for instance, in typhoid intestinal perforation following adequate resuscitation, laparotomy was performed through a transverse infraumbilical incision under general anesthesia with endotracheal intubation. the bowel perforation was identified and the surgeon closed the perforation in two layers. the peritoneal cavity was mopped dry and abdomen closed in layers. in recalcitrant typhoid hemorrhage that has failed to stop following nonoperative treatment, right hemicolectomy with ileotransverse anastomosis was performed. 2.3. postoperative protocol and follow-up postoperatively, graded oral intake was commenced when bowel function returned. the surgical site was examined on the fourth day and the patient discharged on the fifth day if there are no problems. the follow-up period was for 12 months. 2.4. data collection the following data were collected: age and gender of the patient, duration of symptoms before presentation, time interval between presentation and surgery, type of typhoid complication, complications of treatment, duration of hospital stay, and the outcome of the treatment. 2.5. data analysis data were analyzed using the statistical package for social science (spss) version 23 (manufactured by ibm cooperation, chicago illinois) were expressed as percentages, means, and standard deviation. 3. results 3.1. patients’ demographics in total, 47 cases of abdominal surgical complications of typhoid fever were treated during the five-year study period. however, only 44 of them had complete case records doi 10.18502/sjms.v15i3.7275 page 272 sudan journal of medical sciences kevin emeka chukwubuike and thereby formed the basis of this report. there were 32 (72.7%) male and 12 (27.3%) female participants, which corresponded to a male-to-female ratio of 2.7:1. details are depicted in table 1. 3.2. clinical presentation the patients presented with a constellation of symptoms that included abdominal pain, bleeding per rectum, fever, abdominal swelling, diarrhea, vomiting, and constipation in various combinations. all patients had fever and abdominal pain. the frequency of the symptoms is shown in table 2. 3.3. investigations performed all patients had undergone an abdominopelvic ultrasound and the presence of echorich peritoneal fluid was negative in 10 (22.7%) patients. plain x-ray showed air under the diaphragm in 25 (56.8%) patients, while air-fluid level was seen in 35 (79.5%) patients. 3.4. intraoperative finding a single ileal perforation was observed in 35 (79.5%) patients. nine (20.5%) patients had more than one perforation. all perforations occurred within a proximity of 30 cm to the ileocaecal valve. the perforations were round or ovoid in shape, each measuring about 1.5 cm and located at the anti-mesenteric border of the ileum. there was no colonic perforation. additionally, no intestinal perforation was observed in two (4.5%) patients who had bleeding per rectum. 3.5. definitive diagnosis and procedure performed while 42 (95.5%) patients had typhoid intestinal perforation, two (4.5%) patients had typhoid intestinal hemorrhage. no typhoid gall bladder disease was recorded during the study period. the typhoid perforations were closed primarily after excising the edges and tissue specimen sent for histology. for patients with typhoid hemorrhage, a right hemicolectomy was performed, which excises the peyer’s patches from the terminal ileum, and specimen sent for histology. the specimen sent for histology showed cryptic changes with evidence of acute and chronic inflammation on the peyer’s patches. this histopathological finding is consistent with typhoid intestinal pathology. doi 10.18502/sjms.v15i3.7275 page 273 sudan journal of medical sciences kevin emeka chukwubuike 3.6. postoperative complications postoperative complication is shown in figure 1. figure 1: post-operative complications. 3.7. outcome thirty nine (88.6%) patients did well and were discharged home. two (4.5%) patients signed out, in the postoperative period, against medical advice. mortality was recorded in three (6.8%) patients. 4. discussion salmonella typhi is a gram-negative, motile, aerobic, non-spore-forming intracellular bacillus that causes the systemic infection, typhoid fever [7]. despite awareness that has been created, typhoid fever is still hovering around in developing countries. surgical complications of typhoid fever have been documented to occur in 10–15% of typhoid fever patients, and these complications are more likely to occur if the typhoid fever has lasted for more than two weeks [8]. doi 10.18502/sjms.v15i3.7275 page 274 sudan journal of medical sciences kevin emeka chukwubuike table 1: patients’ demography. variables values gender male 32 (72.7%) female 12 (27.3%) mean age of the patients 9.5 years (6–14) mean duration of symptoms prior to presentation 5 days (2–8) presented within 24 hr 4 (9.1%) presented between 24 and 72 hr 8 (18.2%) presented after 72 hr 32 (72.7%) mean duration from presentation to surgery 2 days (1–5) mean duration of hospital stay 12.9 days (7–21) table 2: symptomatology of the patients. symptoms number of patients percentage (%) abdominal pain 44 100 fever 44 100 abdominal distension 30 68.2 vomiting 25 56.8 constipation 13 29.5 diarrhea 11 25.0 bleeding per rectum 2 4.5 moreover, this study found that the male patients were more affected than the female; which is consistent with other series on typhoid complications [9, 10]. however, there are also few reports of female predominance [11, 12]. the reason for this difference in sex is unclear. there is a postulation of hormonal factors as being responsible [13]. the mean ages of the patients who have complications of typhoid fever vary from one study to another [9, 10, 14]. typhoid fever complications rarely occur in children under the age of five years. ekenze et al. reported typhoid complication in children less than five years of age [5]. however, the world health organization recommends the administration of the live attenuated oral typhoid vaccine to persons above five years of age [15]. moreover, typhoid complications in children less than five years of age present in unusual manner [5]. majority of our patients presented after 72 hr of the onset of their symptoms. poverty and ignorance that is common in low-income countries may explain the late arrival in hospital. the clinical presentation of the patients depends on the type of typhoid complication. for patients who had intestinal perforation, fever and abdominal pain were reported in most patients. the finding is in alignment with reports of other researchers [16, 17]. for typhoid intestinal hemorrhage, a consistent finding was gastrointestinal bleeding doi 10.18502/sjms.v15i3.7275 page 275 sudan journal of medical sciences kevin emeka chukwubuike which could be mild or massive. in very minimal bleeding, typhoid intestinal hemorrhage may manifest as altered blood in stool [18]. colonoscopy is the gold standard for the evaluation of lower intestinal bleeding [19]. however, none of the studied patients had colonoscopy due to absence of the facility. typhoid was suggested as the cause of the intestinal bleeding by the patients’ clinical features and confirmed by histopathological examination of the resected specimen. ultrasound is non-invasive, available, affordable, and fairly sensitive test in the assessment of abdominal problems. abdominal ultrasound for typhoid perforation may show free peritoneal fluid due to leakage of intestinal contents. a significant number of our patients had free peritoneal fluid. this finding has also been reported by other series on typhoid intestinal perforation [20, 21]. the ability to detect leakage of intestinal content may depend on the quantity of peritoneal fluid and experience of the radiologist. about half of the studied patients had pneumoperitoneum. pneumoperitoneum was also documented by ugochukwu et al. and chalya et al. [20, 21]. in typhoid intestinal hemorrhage, nothing may be found on abdominal ultrasound because the bleeding is intraluminal. however, non-specific features of enteric fever such as hepatomegaly, splenomegaly, ileal and cecal thickening may be noticed during ultrasound [22]. one perforation on the ileum was the predominant finding in typhoid perforation patients. this is in line with the findings of other workers [12, 20]. the severity of symptoms does not depend on the number of intestinal perforations [23]. colonic involvement in typhoid fever has been documented [24]. for the two patients who had bleeding per rectum, there was no intestinal perforation. typhoid intestinal bleeding results from erosion of a necrotic peyer’s patch through the wall of an enteric vessel [8]. in most cases, the hemorrhage is mild and stops spontaneously. however, the bleeding can be fatal if a large vessel is involved [8]. in the index study, there were far more typhoid intestinal perforation than typhoid intestinal bleeding. this is consistent with the reports of other studies [9, 25]. however, other researchers reported typhoid intestinal bleeding as the most common [8, 24]. the reason for the differences in the report is not known but might be explained by the fact that most bleeding are mild and only present as melana stool. vagholkar et al. reported that patients give a history of melena preceding onset of abdominal pain in typhoid perforation [26]. treatment of abdominal surgical complication depends on the type of complication. in the present study, typhoid perforation was treated by simple primary closure in two layers. other modalities of treatment include segmental bowel resection or creation of ileostomy. the choice of option may be based on the available facilities and the degree of the peritoneal contamination. in typhoid hemorrhage, a right hemicolectomy excises most doi 10.18502/sjms.v15i3.7275 page 276 sudan journal of medical sciences kevin emeka chukwubuike of the terminal ileum where the peyer’s patches are located. this was the modality of treatment offered to the studied patients. in developed countries where all the facilities are available, endotherapy and angiographic coil embolization of the bleeding vessel are the current modalities of the treatment [27]. surgical site infection was the most common complication in the index study. this finding is supported by the report of uba et al. [10]. abdominal wounds following laparotomy for typhoid complications is considered as dirty wound with an infection rate of over 40% [17]. mortality following the treatment of typhoid complication may be multifactorial. in developing countries like nigeria, delayed presentation is a significant factor that affects mortality. limitations of this study this study was limited by the small number of cases. a larger number of cases would have availed better analysis. culture and isolation of the organism, salmonella, was not possible due to the retrospective nature of the study. 5. conclusion abdominal surgical complications of enteric fever are still obtainable in developing countries. in this study, typhoid intestinal perforation was more common than typhoid hemorrhage. the outcome of the treatment can be improved by early presentation. there is a need for increased awareness both among the public and the clinicians. declarations acknowledgements none ethical considerations this study was approved by the ethics and research committee of the hospital. doi 10.18502/sjms.v15i3.7275 page 277 sudan journal of medical sciences kevin emeka chukwubuike competing interests none availability of data data is available with the corresponding author and can be provided on reasonable request. funding none authors’ contributions the author was solely involved in the study concept, design, data acquisition, analysis, etc. the author bears the responsibility for the accuracy and integrity of all aspects of this work. references [1] archampong, e. q., tandoh, j. f., nwako, f. a., et al. (1994). surgical problems of enteric fever. in: e. a. badoe, e. q. archampong, m. o. jaja, (eds.), principles and practice of surgery including pathology in the tropics (2𝑛𝑑 ed.). ghana: ghana publishing corporation, pp. 602–604. [2] ochiai, r. l., acosta, c. j., danovaro-holliday, m. c., et al. (2008). a study of typhoid fever in five asian countries: disease burden and implications for controls. bulletin of the world health organization, vol. 86, pp. 260–268. [3] atamanalp, s. s., aydinli, b., ozturk, g., et al. (2007). typhoid intestinal perforations: twenty-six year experience. world journal of surgery, vol. 31, pp. 1883–1888. [4] santillana, m. (1991). surgical complications of typhoid fever: enteric perforation. world journal of surgery, vol. 15, pp. 170–175. [5] pujar, k. a., ashok, a. c., rudresh, h. k., et al. 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(2006). ultrasound in the diagnosis of typhoid fever. indian journal of pediatrics, vol. 73, no. 8, pp. 681–685. doi: 10.1007/bf02898444. [23] contini, s. (2017). typhoid intestinal perforation in developing countries: still unavoidable deaths? world journal of gastroenterology, vol. 23, pp. 1925–1931. doi: 10.3748/wjg.v23.i11.1925. [24] sharma, a. k., sharma, r. k., sharma, s. k., et al. (2013). typhoid intestinal perforation: 24 perforations in one patient. annals of medical and health science research, vol. 3, no. 1, pp. s41–s43. doi: 10.4103/2141-9248.121220. [25] chaudhary, p., kumar, r., munjewar, c., et al. (2015). typhoid ileal perforation: a 13-year experience. healthcare in low-resource settings, vol. 3, p. 4677. doi: 10.4081/hls.2015.4677. [26] vagholkar, k., mirani, j., jain, u., et al. (2015). abdominal complications of typhoid fever. journal of surgery, vol. 10, no. 4, pp. 227–338. doi: 10.7438/1584-9341-10-4-9. [27] goel, a. and bansal, r. (2017). massive lower gastrointestinal bleed caused by typhoid ulcer: conservative management. euroasian journal of hepatogastroenterology, vol. 7, no. 2, pp. 176–177. doi: 10.5005/jp-journals-10018-1242. doi 10.18502/sjms.v15i3.7275 page 280 introduction materials and methods preoperative protocol intraoperative protocol postoperative protocol and follow-up data collection data analysis results patients' demographics clinical presentation investigations performed intraoperative finding definitive diagnosis and procedure performed postoperative complications outcome discussion limitations of this study conclusion declarations acknowledgements ethical considerations competing interests availability of data funding authors' contributions references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8165 production and hosting by knowledge e research article the cross-talk relationship between metformin and gut microbiota hyder o. mirghani. md, m.sc. associate professor of internal medicine and endocrine, medical department, faculty of medicine, university of tabuk, ksa abstract background: metformin is the first-line oral therapy for type 2 diabetes mellitus. however, its mode of action is poorly defined. there is an increasing awareness regarding the cross talk of gut microbiota and metformin. the current review aimed to assess the bidirectional relationship between metformin and gut microbiota. methods: electronic search was conducted in pub med and the first 100 articles in google scholar published until november 2019. however, only randomized controlled trials on humans published in the english language were included. the terms “gut microbiota,” “gut flora ”and “ metformin” were as keywords to perform the search. although 124 articles were retrieved, only six met the inclusion criteria of the study. results: of the six full texts of randomized controlled trials included in the study, two-thirds were published in europe, one in the usa, and one in china. six hundredthirty five patients were included and the duration of the studies ranged from seven days to six months. the studies concluded that microbiota modulates some metformin actions on plasma glucose; while metformin enhances the abundance of microbiota that positively affect insulin resistance and plasma glucose. conclusion: the current review showed that microbiota dysbiosis may mediate metformin antidiabetic effects. whereas metformin shifted the gut microbiota toward the beneficial species ameliorating insulin resistance. the present study might provide insights into a novel therapeutic approach to treat type 2 diabetes mellitus. keywords: gut microbiota, metformin, type 2 diabetes 1. introduction over decades of clinical use as the first-line drug for the treatment of diabetes mellitus, metformin has proved to be safe and well tolerated. metformin enhances insulin action in the liver and skeletal muscles to decrease insulin production and increase nonoxidative disposal of glucose. when taken together, these actions reduce insulin in the hyperglycemic state with little potential for hypoglycemia [1]. however, the mechanism of action of metformin is not completely understood. there is an increasing awareness about the role of the gastrointestinal tract in the regulation of plasma glucose, mainly through microbiota effects on incretins, bile acids, and glucagon-like peptide [2]. how to cite this article: hyder o. mirghani. md, m.sc. (2020) “the cross-talk relationship between metformin and gut microbiota,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 425–430. doi 10.18502/sjms.v15i4.8165 page 425 corresponding author: hyder o. mirghani; faculty of medicine, university of tabuk, po box 3378 tabuk 51941, saudi arabia email: s.hyder63@hotmail.com received 3 november 2020 accepted 18 december 2020 published 31 december 2020 production and hosting by knowledge e hyder o. mirghani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:s.hyder63@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hyder o. mirghani the inhibition of the mitochondrial respiratory chain mediated by activation of adenosine monophosphate-activated protein kinase (ampk) thought as the center of metformin action has been challenged and it may account for indirect changes in insulin sensitivity [3]; blocking this pathway is not followed by loss of metformin effects on glucose. in addition, oral metformin is more effective than intravenous, raising the possibility of an important gut role. the gut microbiota is the first protection system of the gastrointestinal tract; it is composed of thousands of species and more than 15,000 kinds of bacteria in weight equal to 1 kg [4]. recent studies showed that the gut microbiota might play an important role in the pharmacodynamics and pharmacokinetics of metformin, while the drug metformin alters the functional capacity of gut microbiota [5, 6]. the gut microbiota is an area of extensive research due to its associations with various diseases including diabetes mellitus. an interesting recent study conducted among patients with type 2 diabetes mellitus (50%), overweight/obesity (78%), co-morbid psychiatric (65%), and opioid use (45%) disorders in the usa concluded the interaction between metformin, gut microbiota, and opioid use [7]. the current review assessed the role of metformin on the gut microbiota, and whether the gut microbiota mediates the actions of metformin. 2. methods an electronic search was conducted in pub med database and the first 100 articles in google scholar for relevant articles in the english language; the search was limited to randomized controlled trial on humans from the first published article to november 2019. the terms “gut flora” “metformin,” and “gut microbiota were used as keywords with protean and/or or. articles published in languages other than english and studies on animals were not included. one hundred twenty-four articles were retrieved. the titles and abstracts of the articles were screened for the removal of duplications and irrelevant articles. only six articles fulfilled the inclusion criteria. figure 1 illustrates the different phases of the search process. 3. results the six selected randomized controlled trials (four from europe, one from the usa, and one from asia) included 635 patients who received metformin for a duration ranging from seven days to six months, the dose ranged from 1 gr/day to 1.7 gr/day. all studies showed that metformin altered microbiota and improved glucose tolerance. in addition, metformin increased the gut microbiota species with positive effects on insulin resistance and plasma glucose, some studies reported a favorable effect on lipids as well (table 1). doi 10.18502/sjms.v15i4.8165 page 426 sudan journal of medical sciences hyder o. mirghani records iden!fied through database searching (n = 124) s c r e e n in g in c lu d e d e li g ib il it y id e n ti fi c a ti o n addi!onal records iden!fied through other sources (n = 0); no other sources records a#er duplicates removed (n = 111) records screened (n = 46) records excluded (n = 55) full-text ar!cles assessed for eligibility (n = 46 ) full-text ar!cles excluded (n = 40) studies included in the qualita!ve synthesis (n = 6) figure 1: flow diagram of the different phases of the systematic review (prisma flowchart). 4. discussion in the present review of randomized controlled studies, napolitano et al. [8] assessed 14 patients on metformin 1000 mg/day and followed them up for three months. the study assessed gut microbiota, gut hormones including glucagon-like peptide-1 (glp-1), peptide tyrosine-tyrosine, glucose-dependent insulinotropic peptide), and blood and fecal bile acids at four points (baseline, after metformin withdrawal, when the fasting plasma glucose was 25% above normal, and after the drugs were reintroduced. the researcher observed an increased level of glp-1 and reduction in bile acids with doi 10.18502/sjms.v15i4.8165 page 427 sudan journal of medical sciences hyder o. mirghani table 1: the relationship between metformin and gut microbiota. author year country number of patients study duration results napolitano et al. 2014 uk 14 three months on metformin 1000 mg/day metformin changed gut microbes ( phylum firmicutes and bacteroidetes abundance) in patients with type 2 diabetes burton et al. 2015 usa 14 two weeks on 1500 mg/day with microbiome modulator microbiome modulator (nm504) in addition to metformin increased efficacy and tolerability of the drug pendersen et al. 2016 uk 29 patients prebiotics for 21 weeks no effect of prebiotics on microbiota proposed that metformin may play a role wu et al. 2017 sweden 120 days on metformin or placebo with a washout period microbiota mediates some metformin antidiabetic effects; moreover, fecal transplantation from metformin-treated patients improved glycemia among mice albere et al. 2018 latvia 18 metformin 850 twice daily for seven days metformin had an immediate effect on gut microbiota tong et al. 2018 china 400 12 weeks metformin shifted the gut microbiota (the abundance of the blautia spp. that improved insulin resistance), ameliorated hyperlipidemia, and improved glycemic control metformin, while the reverse happened with metformin withdrawal. furthermore, the researchers observed that the abundance of bacteroidetes was negatively correlated with changes in cholic acid and conjugates, while phylum firmicutes abundance was positively correlated. these results imply that metformin exerts gut-based pharmacology. a study published in the united states [9] found that the addition of microbiome modulator to metformin increased both efficacy and tolerability in the form of glucose profile improvement and lesser gastrointestinal manifestations (the most common side effects of metformin). the aforementioned findings supported the previous observations regarding the role of gut microbiota on metformin. also, it may pave the way for more use of this essential first-line antidiabetic medication. pendersen et al. [10] assessed the effects of prebiotics on gut microbiota and found no positive results. however, the authors proposed that metformin might play a role. a study [11] with a long period of follow-up (120 days) observed that microbiota mediates some metformin antidiabetic effects; moreover, fecal transplantation from metformin-treated patients improved glycemia among mice. this observation suggested that metformin may play a major role in fecal transplantation, and supporting the previous finding, fecal transplantation was an effective measure including diabetes mellitus, autism, and inflammatory bowel disease among various diseases [12–14]. it is interesting to note that metformin had an immediate effect on the gut microbiota starting from the first 24 hr [15], a study with a relatively large sample size [16] showed that metformin shifted the gut microbiota, ameliorated hyperlipidemia, and improved glycemic control. doi 10.18502/sjms.v15i4.8165 page 428 sudan journal of medical sciences hyder o. mirghani 5. conclusion the current review showed that microbiota dysbiosis might mediate the antidiabetic effects of metformin. while metformin shifted the gut microbiota toward the beneficial species, the current review showed that gut microbiota might serve as a promising target for diabetes control, which has become a worldwide public health threat. acknowledgements the author would like to acknowledge dr. abdullah hammad el-temani, associate professor of family medicine, department of family medicine, faculty of medicine, university of tabuk, saudi arabia for revising this manuscript ethical considerations the study has been approved by the university of tabuk, saudi arabia. competing interests the author declares that there are no conflicts of interest. availability of data and material the data included in the study is available upon reasonable request funding none references [1] hostalek, u., gwilt, m., and hildemann, s. 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(2017). metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. nature medicine, vol. 23, no. 7, pp. 850–858. doi:10.1038/nm.4345 [12] bordalo tonucci, l., dos santos, k. m., de luces fortes ferreira, c. l., et al. (2017). gut microbiota and probiotics: focus on diabetes mellitus. critical reviews in food science and nutrition, vol. 57, no. 11, pp. 2296–2309. doi:10.1080/10408398.2014.934438 [13] sanctuary, m. r., kain, j. n., chen, s. y., et al. (2019). pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. plos one, vol. 14, no. 1, p. e0210064. doi:10.1371/journal.pone.0210064 [14] paramsothy, s., nielsen, s., kamm, m. a., et al. (2019). specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis. gastroenterology, vol. 156, no. 5, pp. 1440–1454.e2. doi:10.1053/j.gastro.2018.12.001 [15] elbere, i., kalnina, i., silamikelis, i., et al. (2018). association of metformin administration with gut microbiome dysbiosis in healthy volunteers. plos one, vol. 13, no. 9, p. e0204317. doi:10.1371/journal.pone.0204317 [16] tong, x., xu, j., lian, f., et al. (2018). structural alteration of gut microbiota during the amelioration of human type 2 diabetes with hyperlipidemia by metformin and a traditional chinese herbal formula: a multicenter, randomized, open label clinical trial. mbio, vol. 9, no. 3, pii: e02392-17. doi:10.1128/mbio.02392-17 doi 10.18502/sjms.v15i4.8165 page 430 introduction methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8167 production and hosting by knowledge e research article errors and near-miss errors encountered by nursing students in clinical settings in governmental universities, khartoum state (2018) sahar ahmed1, mohamed toum2, samah abdalla3, and montahaa mohammed4 1assistant professor of medical nursing, faculty of nursing sciences, university of khartoum 2professor of surgery, faculty of medicine, university of khartoum 3assistant professor of medical nursing, faculty of nursing sciences, university of khartoum 4assistant professor of medical nursing, faculty of nursing sciences, university of khartoum abstract background: identifying and analyzing the occurrence and sort of student clinical errors which will allow for early detection of problems and offer chance for system evaluation and improvement. this study intended to explain the types of errors along with near-miss errors encountered by nursing students in clinical settings. methods: this descriptive cross-sectional study was conducted at five recognized governmental universities in khartoum state and included 470 nursing students in their fourth year (2017–2018)who met the selection criteria of the study. a full-converge sampling method was used and data were first collected by the researcher using published self-administered survey and then analyzed. results: initially, the study included 519 nursing students but only 470 of them responded(at a rate of 90.5%).the responses showed that while one-third of them, that is, 162(34.5%) students, had never encountered an error, 99(21.1%), 79 (16.8%), 71 (15.1%), 46(9.8%), and 13(2.8%) of them encountered errors with respect to needle stick, medical administration, omission of treatment, and wrong treatment, respectively. regarding the near-miss errors encountered by the respondents, almost half, that is, 202(43%)of them had never encountered a near-miss errors, while 112(23.8%), 106(22.6%), 18(3.8%),17(3.6%), and 15(3.2%) of them encountered near-miss errors with respect to medication administration, omission of treatment, wrong patient, providing wrong treatment and others such as improper bedrail used, did not follow sterile precautions respectively. conclusion: this study concluded that errors and near-miss errors exist and that awareness on clinical errors and near-misses need to be raised and strategies be developed for error management. keywords: errors, near-miss errors, nursing students, clinical setting, nursing errors how to cite this article: sahar ahmed, mohamed toum, samah abdalla, and montahaa mohammed (2020) “errors and near-miss errors encountered by nursing students in clinical settings in governmental universities, khartoum state (2018),” sudan journal of medical sciences, vol. 15, issue no. 4, pages 440–446. doi 10.18502/sjms.v15i4.8167 page 440 corresponding author: sahar ahmed; email: sahar88@uofk.edu sa262697@gmail.com received 2 november 2020 accepted 16 december 2020 published 31 december 2020 production and hosting by knowledge e sahar ahmed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:sahar88@uofk.edu mailto:sa262697@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sahar ahmed et al 1. introduction a near-miss error is defined as “an error that has the potential to cause an adverse event (patient harm) but fails to do so because of chance or because it is intercepted.”the institute of medicine(iom) also defines a near-miss as “an act of commission or omission that could have harmed the patient but did not cause harm as a result of chance, prevention or mitigation” [1]. many factors that contribute to the development of a near-miss have been identified; these include individual factors, system factors, and chaotic environments [2]. adverse events are defined as the harm, whether transient or permanent, caused by medical interventions relatively to the core situation of the patient[3]. moreover, the cost of preventable medication errors in the united states(us) is on average $20 million. it has been reported that 672,000 patients are injured and98,000 die due to preventable medication errors each year. in addition, the european medicines agency has reported that the estimated annual cost of preventable medication errors in european countries varies between 4.5 and21.8 billion euro. in developed countries, the world health organization (who) has emphasized that one in every ten patients is injured because of errors or adverse events during their hospital process[4]. concerning nursing, the common reply to student error has been some type of punishment, vary from a verbal warning to abrupt release or dismiss. this environment of shame and blame remains widespread. also, several faculty members accept that individual self-vigilance is what matters most and that if an error or a near-miss occurs, the student is at a mistake; if the fact of student errors becomes open knowledge, clinical organization may be unwilling to have students in their facilities [5]. education in nursing schools is expected to be up-to-date and of high quality, which should be done by ensuring that the new novice nurses are able to offer safe patient care in a variety of clinical settings[6]. nursing students are one of the primarily responsible bodies for their effective implementation of skills and perception of students is an significant factor in determining types of errors in clinical settings. in sudan, due to the lack of awareness about errors and near-miss errors and the absence of patient safety reporting systems, no published statistics on the topic were available. upon checking with hospital faculties, the researchers found that no tool was available for the nurse students to repot errors or near-miss errors. therefore, this study was carried out to clarify the types of errors and near-miss errors encountered by nursing students in clinical settings. 2. materials and methods to find out the types of errors and near-miss errors encountered by nursing students in clinical settings, an exploratory cross-sectional study was conducted using a published self-administered survey[6]and including470 nursing students in their fourth year (2017– 2018)who met the selection criteria of the study. it is a full-coverage sample. doi 10.18502/sjms.v15i4.8167 page 441 sudan journal of medical sciences sahar ahmed et al 3. results in this descriptive survey, a total of 519 of nursing students were included from five governmental universities located in khartoum state. of these, 49 did not take part in the survey by either refusing to participation or submitting largely incomplete questionnaires. this resulted in a final sample size of 470 students with a response rate of 90.5%. figure 1: types of clinical settings in which students are taught (n=470). as shown in figure 1, among the 470 respondents, inpatients’ setting was the most frequently ticked response for the clinical teaching site at 93.2%. regarding the errors encountered by the respondents,162(34.5%) of them had never encountered an error, while 99(21.1%), 79 (16.8%), 71 (15.1%), 46(9.8%), and 13(2.8%) encountered others errors such as did dressing inappropriately, wrong procedure in order to remove urinary catheter, used tap water for oxygen humidification, shared oxygen mask and suction catheters, followed by medication administration by79 (16.8%), needle stick by 71 (15.1%)„ omission of treatment by 46(9.8%), and wrong treatment 13(2.8%),as presented in figure 2. with regards to the near-miss errors encountered by the respondents,202(43%) of them had never encountered a near-miss errors, while 112(23.8%), 106(22.6) , 18(3.8),17(3.6), and 15(3.2) encountered others near-miss errors such as improper bedrail used, did not follow sterile precautions, used some equipment inappropriately, chemotherapy spilled, gave the patient wrong information about nutrition, followed by medication administration by 112(23.8%), omitted a treatment by106(22.6), wrong patient by18(3.8), and a wrong treatment given by15(3.2) ,as shown in figure 3. doi 10.18502/sjms.v15i4.8167 page 442 sudan journal of medical sciences sahar ahmed et al figure 2: types of errors encountered by respondents (n=470). figure 3: near-miss events encountered by respondents (n=470). doi 10.18502/sjms.v15i4.8167 page 443 sudan journal of medical sciences sahar ahmed et al 4. discussion the code of ethics in nursing obligate nurses to provide safe, competent, and ethical care. this study describes the types of errors and near-miss errors encountered by fourth-year nursing students in clinical settings. the results of this study demonstrated that of the 470 students included, 162(34.5%) had never encountered errors, while 99(21.1%) of them encountered errors such as did dressing inappropriately, tried to remove the urinary catheter without aspirating the amount of water used for fixation, used tap water for oxygen humidification, shared oxygen mask and suction catheters were, followed by medication administration by79 (16.8%). this is comparable with the study conducted in san franciscoincluding121 prelicensure nursing students, in which the greater part of the subjects replied not at all encountering an error. however, for the students who had been exposed to an error, medication administration was the most frequent type followed by wrong treatment provided to the patient, omission of treatment, and needle stick[6].the annual cost of preventable medication errors is staggering, with a reported $10.3 billion price tag for avoidable healthcare spending [10]. interestingly, 38 systematic reviews focused on the barriers to reporting medication errors and near-misses in nursing revealed that organizational barriers such as culture, the reporting system, and management behavior in addition to personal and professional barriers such as fear, accountability, and characteristics of nurses are the most common barriers to reporting medication errors [11]. nursing students often meet strangers while in their clinical site, having to organize and handle patient care in a complex environment. indeed, developing an innovative pharmacology and medication administration will better prepare the nursing students for practice and to enter the workforce, capable of offering quality care, as well as acquiring critical thinking skills related to pharmacology and safe medication administration[8]. the present study also confirmed needle stick injuries (nsis) in71 (15.1%) participants. this is in line with a study conducted in jordan including162 students from different levels which reported that the two-thirds of the student nurses practiced nsis. nursing students must be well-informed to distinguish the severity of such incidences and thus be qualified to avoid unintentional exposure while performing their nursing duties. also, continuous in-service training must be integrated into the curriculum and workplace on a regular basis, particularly when there are innovations and changes made on the prickly instruments [9]. besides, regarding the near-miss errors encountered by the respondents,202(43%) of them had never encountered a near-miss error, while 112(23.8%) reported near-miss errors such as improper bedrail used, did not follow sterile precautions, inappropriate use of some equipment, chemotherapy spilled, gave the patient wrong information about nutrition, followed by medication administration most of the time. this is in-line with a study conducted in san francisco that reported that a greater part of nursing students did not encounter a near-miss event, and those who did, a near-miss or medication error event led the list[6]. doi 10.18502/sjms.v15i4.8167 page 444 sudan journal of medical sciences sahar ahmed et al it is important that the clinical nurse and instructors focus on safe medication administration practice in order to build a culture of safe and quality patient care. also, we need to incorporate tools to report near-miss errors in order to put forward a process to identify potential adverse events before they occur. in addition to voluntary disclosure of near-misses, it may also help improve students’ outcome and increase transparency. however, it is necessary to develop a non-blaming, non-punitive, and non-fearful learning culture at unit and organizational level [11]. 5. limitations the main limitation of this study is that it included only upper-level students (fourth year). it would be more interesting to compare the different levels of nursing students. moreover the lack of literature in national settings for comparing the results of the study should be considered and this study is hoped to be an input to this regard. 6. conclusion this study concluded that errors and near-miss errors exist in clinical settings and explains the importance of a classroom and clinical instructions regarding safe, appropriate care, and strategies for error management, the main challenge associated with nursing education is developing an educational framework with an emphasis on innovation and the encouragement of an open safe culture in which students can learn from their mistakes. also, awareness on clinical errors and near-misses need to be raised and strategies for error management be developed. acknowledgements the authors are very indebted to the dean of faculties of nursing sciences for the nice cooperation and to the nursing students participated in this study. ethical considerations the study was approved by the dean of faculties of nursing sciences. prior to starting the study, subjects were clearly informed about the goal of the study and a written consent was obtained from them. also, permission was sought through email for the use of published questionnaire from the author. competing interests the authors declare that there is no conflict of interests regarding the publication of this paper. doi 10.18502/sjms.v15i4.8167 page 445 sudan journal of medical sciences sahar ahmed et al availability of data and material the data used in the study are available upon reasonable request. funding there was no fund . references [1] sheikhtaheri, a. (2014). near misses and their importance for improving patient safety. iranian journal of public health, vol. 43, no. 6, pp. 853–854. [2] linnard-palmer, l. and ngo, t. (2015). near misses: nurses’ experiences with medication errors, power distance and error recover. clinical nursing studies, vol. 4, no. 1, p. 40. [3] martinez, w., lehmann, l. s., hu, y.-y., et al. (2017). processes for identifying and reviewing adverse events and near misses at an academic medical center. joint commission journal on quality and patient safety, vol. 43, no. 1, pp. 5–15. [4] gök, d. and sar𝚤, h. y. (2017). reporting of medication errors by pediatric nurses. journal of nursing education and practice, vol. 7, no. 9, p. 25. [5] disch, j., barnsteiner, j., connor, s., et al. (2017). ce: original research exploring how nursing schools handle student errors and near misses. american journal of nursing, vol. 117, no. 10, pp. 24–31. [6] cooper, e. e. (2017). nursing students’ perception of safety in clinical settings: from the quality and safety officer. nursing education and practice, vol. 7, no. 10, pp. 91–96. [7] who. (2017).patient safety: making health care safer, pp. 20–24. geneva: who. available from: https://creativecommons.org/licenses/by-nc-sa/3.0/igo [8] johnson, k. f. (2016). us nursing students’ perceptions of safe medication administration[phd thesis], pp. 192–16.usa:walden university.available from: http://scholarworks.waldenu.edu/dissertations [accessed december 8, 2017]. [9] nawafleh, h. a., el abozead, s., al momani, m. m., et al. (2017). investigating needle stick injuries: incidence, knowledge and perception among south jordanian nursing students. journal of nursing education and practice, vol. 8, no. 4, p. 59. [10] claffey, c. (2018). near-miss medication errors provide a wake-up call. nursing, vol. 48, no. 1, pp. 53–55. [11] vrbnjak, d., denieffe, s., o’gorman, c., et al. (2016). barriers to reporting medication errors and near misses among nurses: a systematic review. international journal of nursing studies, vol. 63, pp. 162– 178. doi 10.18502/sjms.v15i4.8167 page 446 https://creativecommons.org/licenses/by-nc-sa/3.0/igo http://scholarworks.waldenu.edu/dissertations introduction materials and methods results discussion limitations conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8172 production and hosting by knowledge e short communication diagnosis of viral diseases in sudan: coronaviruses unveil the concealed venues wadie m y elmadhoun1, nadir abuzeid2, shahinaz bedri3, and m h ahmed4 11department of pathology, faculty of medicine, sudan international university, khartoum, sudan 2department of microbiology, faculty of medical laboratory sciences, omdurman islamic university, khartoum, sudan 3department of pathology, faculty of medicine, ahfad university for women, the national public health laboratory, sudan 4department of medicine, milton keynes university hospital nhs foundation trust, milton keynes, buckinghamshire, uk abstract establishing the diagnosis of viral diseases often needs sophisticated settings, equipment, expertise, and strict laboratory methods. in sudan, as in most developing countries, viral diseases are mostly diagnosed by clinical presentation. as most viral infections are self-limiting and there is no specific treatment for most of them, laboratory diagnosis has not been a focus for improvement, particularly in public sector until the current pandemic of covid-19. during this pandemic, the vital need for well-equipped clinical virology laboratories is urged. the aim of this work is to highlight the various diagnostic methods and to describe the current situation of clinical virology diagnostics in sudan. 1. introduction sudan is a developing country, having only one reference public health laboratory and four regional laboratories, with a limited diagnostic capacity and personnel [1]. historically, many local viral outbreaks have been reported in sudan. these include measles, polio, yellow fever, dengue fever, west nile, rift valley fever, chikungunya, crimean–congo hemorrhagic fever, ebola, influenza poliomyelitis, and lately the pandemic of covid-19 [2]. there are over 4,000 known viruses in plants, animals, and bacteria. these viruses are generally distributed in 71 families, 9 subfamilies, and 164 genera [3]. clinical features of viral diseases are, to some extent, similar and therefore need laboratory assays to identify the causative agent. however, viral disease diagnosis is sophisticated and needs specific equipment and strict settings. in sudan, as in most developing countries, the diagnosis of viral diseases has not been up to the level of the challenges faced. the aim of this paper is to highlight the various diagnostic modalities of viral diseases and to describe the current situation of clinical virology diagnostics in sudan. how to cite this article: wadie m y elmadhoun, nadir abuzeid, shahinaz bedri, and m h ahmed (2020) “diagnosis of viral diseases in sudan: coronaviruses unveil the concealed venues,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 455–460. doi 10.18502/sjms.v15i4.8172 page 455 corresponding author: wadie m y elmadhoun; email: wadie2222@yahoo.com received 2 december 2020 accepted 27 december 2020 published 31 december 2020 production and hosting by knowledge e wadie m y elmadhoun et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:wadie2222@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences wadie m y elmadhoun et al 2. methods of viral disease diagnosis many laboratory methods are used for diagnosing viral diseases. these include electron microscopy, virus culture (also referred to as cell or tissue culture), immunological tests such as counter immunoelectrophoresis, latex agglutination, co-agglutination, immunochromtography test, enzyme linked-immunosorbent assays (elisa), precipitation tests, complement fixation, immunofluorescence tests, neutralization tests, western blot and line immunoassays, and antibody avidity assays. furthermore, antigen detection, viral genome detections, and gene sequencing by molecular techniques are increasingly used in the virology laboratory. table 1 summarizes the details about the advantages and limitations of the most common laboratory methods [4–8]. 3. diagnostic virology in sudan public health laboratories in sudan conduct the most common tests for commonly encountered viral diseases, such as hepatitis b and c, hiv, and few screening tests for congenitally acquired viral diseases. some tests are available only during epidemics or disease outbreaks. however, private sector laboratories may conduct some of the most uncommon tests, upon request. table 2 summarizes the most commonly conducted laboratory tests for viral syndromes in sudan. it is obvious that many tests for viral diseases are not available in public health laboratories in sudan. 4. discussion oftentimes in large countries such as sudan, viral infections are missed. it is difficult to establish a confident diagnosis based on clinical findings, as many viruses have similar clinical features. for example, the symptoms and signs of hepatitis can be caused by many viruses. on the other hand, a specific virus may have many different clinical presentations [9]. it is therefore essential to seek specific laboratory diagnosis to enable correct management of patient. specific viral diagnosis is also important from an epidemiological perspective. it has been shown that even experienced clinicians are not able to clinically diagnose cases of rubella or measles correctly. a specific diagnosis of a viral infection is important, not only for the clinical management of the patient but also for the control of infection, outbreak control, and the public health perspective of continuing to ensure the efficacy of vaccination programs [10]. diagnostic microbiology in sudan is at a critical juncture and needs drastic improvement to cope with the growing healthcare complexities. recent and emerging trends such as changing demographics, exponential growth in medical discoveries, appearance of superbugs are some examples. the diagnostic microbiology has to improve in better direction with best practices. there is a need for additional laboratory tests for the agents of the priority healthcare infections. currently, there is an urgent need than ever for better viral diagnostics in the light of increased immunosuppressed individuals as a result of non-communicable diseases, chemotherapy, and the widespread use of other immunomodulant medications. doi 10.18502/sjms.v15i4.8172 page 456 sudan journal of medical sciences wadie m y elmadhoun et al table 1: overview of viral diagnostic methods: advantages and limitations. laboratory method technique assay time advantages limitations viral isolation conventional culture 1–21 days allows isolation of many viruses; can detect unexpected or novel viruses; more sensitive than antigen detection requires expertise to interpret cpe and maintain cell cultures; some viruses do not grow in routine cultures; biosafety concerns for zoonotic and emerging viruses antibody detection elisa, eia, clia,if, ic, ib, iggavidity testing <30 min–24 hr can document primary, recent, and past infections, and carrier states; can be automated; some tests can be done at point of care; fourth generation hiv tests combine antibody and antigen detection in one reaction cross-reactivity between similar viruses is common (e.g., arboviruses); diagnosis often retrospective; igm assays have moderately high false-positive rates; immunocompromised hosts may not make antibody antigen detection if elisa/clia ic 1–2 hr < 2 hr < 30 min can be done “on demand” as samples arrive in the laboratory; reagents available for eight respiratory and four herpesviruses; can assess sample quality can be automated; requires less skill than if requires no equipment and little expertise; simply add sample and set timer; approved for use at “point of care requires substantial expertise for accurate results; manual and labor-intensive; requires an adequate number of target cells for valid results limited test menu less sensitive than other methods; limited test menu naat conventional pcr real-time pcr 5–9 hr 1–5 hr uses inexpensive conventional thermocyclers; less affected by genome variability and more amenable to multiplex testing than real-time assays faster, less prone to cross-contamination, readily quantified; lab-developed assays can be readily updated; more commercial kits becoming available, including walk-away tests prone to carryover contamination from amplified products since tube is opened after amplification; slower than real-time methods; ethidium bromide used for amplicon detection is toxic more prone to falsely negative or low values due to genetic variations in viral strains; lack of standardization; values obtained in different laboratories can vary by 3 log10; limited capacity to multiplex clia, chemiluminescent immunoassay; cpe, cytopathic effect; csf, cerebrospinal fluid; eia, enzyme immunoassay; elisa, enzyme-linked immunosorbent assay; hiv, human immunodeficiency virus; ib, immunoblot; ic, immunochromatography; if, immunofluorescent assay; igm, immunoglobulin m; naat, nucleic acid amplification test; pcr, polymerase chain reaction. doi 10.18502/sjms.v15i4.8172 page 457 sudan journal of medical sciences wadie m y elmadhoun et al table 2: common viral syndromes and availability of their diagnostic tests in sudan. clinical syndrome viruses tests available in public health laboratories in sudan tests not available in public health laboratories in sudan respiratory infections influenza naat antigen, culture parainfluenza antigen, culture, naat rsv antigen, culture, naat coronaviruses serology, naat for sars-cov-2, antigen serology for other coronaviruses adenoviruses naat, dfa, culture rhinoviruses naat enteroviruses naat, culture gastro-intestinal syndromes rotavirus antigen, naat, em norovirus antigen, naat, em enteric adenoviruses serology, naat nervous system syndromes hsv-1 serology, naat rabies antigen detection, naat, culture, serology; histopathology poliovirus naat. culture systemic infections hiv serology, naat measles serology culture, naat ebv serology naat cmv serology culture, naat chikungunya serology naat coxsackie serology, naat hepatitis hav serology hbv serology, antigen, naat hcv serology serology, naat hdv serology, naat hev serology, naat hemorrhagic and febrile conditions dengue serology naat, culture yellow fever serology naat ebola serology, naat rift valley fever serology, naat, isolation mucocutaneous, genital, congenital and other syndromes hsv-1, hsv-2 culture, dfa, or naat vzv dfa or naat rubella serology, naat mumps serology, culture, naat cmv, cytomegalovirus; dfa, direct fluorescent assay; ebv, epstein–barr virus; em, electron microscopy; hbv, hepatitis b virus; hsv, herpes simplex virus; naat, nucleic acid amplification technique; vzv, varicella-zoster virus. doi 10.18502/sjms.v15i4.8172 page 458 sudan journal of medical sciences wadie m y elmadhoun et al factors jeopardizing virology diagnostics include: sophisticated machines and technical difficulties, reagent and supply chain issues, maintenance and training needs, biosafety and ethical dilemmas, and hazardous waste disposal. the outbreak of covid-19 pandemic brought to attention the importance for investing in diagnostics of emerging pathogens. in this regard, the need for infrastructure, expertise, and diagnostic tools are the most important. in addition to logistics such as guidelines for handling specimens, personal protective equipment and legislations to deal with highly hazardous pathogens are also required. noteworthy points of paramount importance that hamper health sector improvement are: economic constraints, political instability, rapid staff turnover, and brain drain that constitute constant challenges. the collaboration between the public and private sectors to import the test needs has made it possible for any individual who seeks the diagnostic service for covid-19 to find it available at hand, whether due to the suspicion of the disease or for travel purposes. the same approach may prove successful for other viral conditions. 5. conclusion the diagnosis of viral diseases in public health laboratories in sudan is beyond the challenges. many viral diseases cannot be accurately diagnosed due to lack of the diagnostic technology and expertise. efforts to upgrade the laboratory capacity are urgently needed. these include health policies, human and material resources, in addition to better infrastructure, protocols, and quality control measures. ethical considerations not applicable. competing interests none. references [1] el-sony, a. i., khamis, a. h., enarson, d. a., et al. (2002).treatment results of dots in 1797 sudanese tuberculosis patients withor without hiv co-infection. international journal of tuberculosis and lung disease, vol. 6, no. 12, pp. 1058–1066. [2] abuagla, a. and badr, e. (2016). challenges to implementation of the who global code of practice on international recruitment of health personnel: the case of sudan. human resources for health, vol. 14, no. 1, p. 26. [3] valero, n. and maldonado, m. (2006). [importance of the confirmatory diagnosis in viral exanthematic diseases in zulia state, venezuela: a review of the problem]. investigación clínica, vol. 47, no. 3, pp. 301–310. [4] dusheiko, g. m. (1994). rolling review–the pathogenesis, diagnosis and management of viral hepatitis. alimentary pharmacology & therapeutics, vol. 8, no. 2, pp. 229–253. doi 10.18502/sjms.v15i4.8172 page 459 sudan journal of medical sciences wadie m y elmadhoun et al [5] schramlova, j., arientova, s., and hulinska, d. (2010). the role of electron microscopy in the rapid diagnosis of viral infections–review. folia microbiologica, vol. 55, no. 1, pp. 88–101. [6] shingu, m. (1989). laboratory diagnosis of viral myocarditis. a review. japanese circulation journal, vol. 53, no. 1, pp. 87–93. [7] gershon, a. a. (1983). rapid viral diagnosis: a review. israel medical association journal, vol. 19, no. 10, pp. 874–875. [8] belak, s. (2005). the molecular diagnosis of porcine viral diseases: a review. acta veterinaria hungarica, vol. 53, no. 1, pp. 113–124. [9] browne, l. b., menkir, z., kahi, v., et al. (2015). notes from the field: hepatitis e outbreak among refugees from south sudan gambella, ethiopia, april 2014-january 2015. morbidity and mortality weekly report, vol. 64, no. 19, p. 537. [10] rull, m., masson, s., peyraud, n., et al. (2018). the new who decision-making framework on vaccine use in acute humanitarian emergencies: msf experience in minkaman, south sudan. conflict and health, vol. 12, article no. 11. [11] peaper, d. r. and landry, m. l. (2014). laboratory diagnosis of viral infection. in a. c. tselis and j. booss (eds.), handbook of clinical neurology (vol. 123, 3rd series). elsevier. doi 10.18502/sjms.v15i4.8172 page 460 introduction methods of viral disease diagnosis diagnostic virology in sudan discussion conclusion ethical considerations competing interests references page 65 research article profile of prenatally diagnosed major congenital malformations in a teaching hospital in nigeria olufemi oloyede*, mustafa lamina, peter olubunmi adefuye department of obstetrics and gynaecology, olabisi onabanjo university teaching hospital, ogun state, nigeria abstract background: prenatal diagnosis of major congenital abnormality is one of the main goals of antenatal care, because of its contribution to perinatal morbidity and mortality. awareness of the profile in terms of rates and spectrum could aid management and prevention strategies. this study aims to determine the profile of congenital malformations, and the relationship between the rates and some maternal sociodemographic and obstetric variables. methods: a retrospective cross-sectional study of prenatally diagnosed congenital malformations in singleton pregnancies over a four-year period. the ultrasound scan findings and the findings of fetal ultrasonography, together with maternal sociodemographic and obstetric variables, were collected from the ultrasound scan reports or medical records of each pregnancy. data were analyzed using microsoft excel 2010. results: among the 968 singleton pregnancies, 78 had major congenital malformation, giving an antenatal rate of 8.04/1000 (0.8%). the first trimester prevalence was comparable with other trimesters. malformation mostly involved single systems (93.6%), which are mainly central nervous (48.7%) and gastrointestinal/ abdominal systems (21.8%). the rate was statistically significant (<0.0018) in women aged >35 years. the mean maternal age and parity were 31.4 + 4.7 and 2.8 + 0.4, respectively. the rates of congenital malformation in spontaneously or assisted conceptions were not statistically significant (p = 0.073 and p = 0.085). conclusion: maternal age >35 years and multiparity are important risk factors for congenital malformation. the commonly involved systems are the central nervous and gastrointestinal systems. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6706 production and hosting by knowledge e how to cite this article: olufemi oloyede (2019) “profile of prenatally diagnosed major congenital malformations in a teaching hospital in nigeria”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 65–72. doi 10.18502/sjms.v15i1.6706 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: oloyedeoao@gmail.com received 11 december 2019 accepted 09 february 2020 published 31 march 2020 production and hosting by knowledge e cc olufemi oloyede. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: congenital malformations; prevalence; spectrum; antenatal ultrasound scan; nigeria introduction congenital malformations (cm) are structural or functional anomalies that occur during intrauterine life and can be diagnosed in the prenatal period, at birth or later in life [1]. sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 66 it is an important cause of perinatal morbidity and mortality, with an estimated 303,000 neonatal deaths occurring within four weeks of birth every year, worldwide [1–3]. cm are commonly diagnosed in late pregnancy, during the neonatal period, or during infancy [2, 4–6]. however, the rise in the rate of diagnosis in the first trimester can be attributed to the widespread availability and utilization of prenatal ultrasound scan [5]. studies on the prevalence and the spectrum of major cm are mainly from developed countries, leaving only few published studies from developing countries, especially in nigeria. good epidemiological data on the rate and pattern of cm in a specific region provides the opportunity to identify possible etiological factors and can be useful for their prevention in this country and across the wider region [7]. the preventive measures include vaccination, folic acid and iodine supplementation, and reduction in alcohol intake can also be adopted against common malformation in an environment [1]. the primary aim of the study was to evaluate the spectrum of major cm, while the secondary aim was to determine the relationship between cm and some maternal sociodemographic and obstetric variables. methods this is a retrospective cross-sectional study of the ultrasound scan or medical records of pregnant women, who had ultrasound scan over a four-year period (july 1st, 2014– june 31st, 2018), in the fetal medicine or radiology unit of the olabisi onabanjo university, sagamu, ogun state nigeria. ultrasound scans were performed by a fetal-maternal medicine specialist certified by fetal medicine london to perform anomaly scan and a consultant radiologist with experience in ultrasound diagnosis of fetal anomalies. the scan machines used were the voluson p8, bt 2005 (ge kretz, austria) or phillips hdi 1500. maternal socio-demographic and obstetrics parameters were extracted from ultrasound scan reports and medical records. only major cm in singleton pregnancies were included for analysis, while minor cm were excluded. major structural anomalies are defined as structural changes that have significant medical, social, or cosmetic consequences for the affected individual, and typically require medical intervention. major cm is defined according to the standard anatomical nomenclature of the system(s) involved. they are classified as single or isolated if only one body system is involved sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 67 and complex or multiple, if >2 systems are involved. the overall antenatal rate of cm was calculated from the ratio of number of fetuses to the cm and the total number of pregnancies scanned. data was analyzed using 2010 microsoft excel. descriptive data are expressed in percentages and presented in simple frequency tables. mean and standard deviations were used as where appropriate. the statistical significance of the data relationship was defined using p < 0.05. results a total of 9,698 women had prenatal ultrasound scans during the study period, of which 853 (8.8%) were in the first trimester, 5,394 (55.6%) in the second trimester, and 3,453 (35.6%) in the third trimester; 78 out of the 9,698 fetuses (0.8%) had congenital abnormalities. the malformed fetuses constitute the primary subjects of this study (table 1). most of the malformations were diagnosed in the second (55.6%) and third (35.6%) trimesters, while only 8.8% were diagnosed in the first trimester. table 1: frequencies of major congenital malformations during pregnancy. gestational period (trimester) number of pregnancies frequencies (%) number of congenital malformations frequencies (%) first trimester 853 8.8 6 0.7 second trimester 5,394 55.6 41 0.8 third trimester 3,451 35.6 26 0.8 total 9,698 100.0 78 0.8 the spectrum of diagnosed congenital abnormalities is shown in table 2. central nervous system malformations were diagnosed in 38 (48.7%) fetuses, with the commonest being hydrocephalus or ventriculomegaly in 22 (57.9%) fetuses and acrania or anencephaly in 13 (34.2%) fetuses. holoprosencephaly was diagnosed in 2 (5.3%) fetuses and dandy-walker malformation in only 1 (2.6%) fetus. gastrointestinal system malformations were found in 17 (21.8%) fetuses, with 7 (41.2%) presenting with polyhydramnious. polycystic kidney was the commonest (57.1%) urogenital system malformation, followed by lower urethra tract obstruction (luto) in 28.6% and hydropelvis in 14.3%, respectively. malformations of the musculoskeletal system sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 68 table 2: spectrum of major congenital malformations. systems congenital malformations number (%) central nervous system 38 (48.7%) hydrocephalus/ventriculomegaly 22 (57.9) acrania/anencephaly 13 (34.2) holoprosencephaly 2 (5.3) dandy walker malformation 1 (2.6) gastrointestinal system 17 (21.8%) duodenal atresia 7 (70.0) jejunal atresia 1 (30.0) gastroschisis 3 (30.0) omphalocele 6 (60.0) urogenital system 14 (17.9%) lower urethral tract obstruction 3 (21.4) hydropelvis 2 (21.4) polycystic kidney 8 (57.1) musculoskeletal system 13 (16.7%) thanatophoric dwarfism 5 (38.5) skeletal dysplasia 8 (61.5) cardiovascular system 2 (2.6%) tetralogy of fallot 1 (50.0) ventricular septal defect 1 (50.0) respiratory system 1 (1.3%) congenital cystic adenomatoid malformation 1 (100.0) systems involved multiple (>2 systems) 73 (93.6%) – 5 (6.4%) single (1 system) 5 (6.4%) – 73 (93.6) were found in 13 fetuses (16.7%) cases. two fetuses (2.6%) displayed cardiovascular malformations: tetralogy of fallot (tof) and ventricular septal defect (vsd) were diagnosed. the vsd was postnatally confirmed, while the tof ended in miscarriage. respiratory system abnormality was the least prevalent malformation diagnosed in the study (1.3%). the malformation involved one system in 73 (93.6%) fetuses and multiple systems in 5 (6.4%) fetuses the maternal age in the study ranged between 21 and 52 years, with a mean of 31.5 ± 4.7 years. the mothers above the age of 35 years were 3,446 (35.5%); 47 (53.8%) out of the 78 fetuses with cm were in this category (p ≤ 0.0018). the mean and range of parity were 2.8 + 0.4 and 0–8, respectively; 52 (66.7%) fetuses with cm were diagnosed in mothers who were para ≥3. pregnancy was spontaneously conceived in 8,139 (83.9%) women, among whom were 74 (94.5%) fetuses out of all malformed fetuses (p = 0.073). conception was achieved by assisted reproductive technology in 1,559 (16.1%) women, and 5.1% (p = 0.085) of all the fetuses with cm were in this group (table 3). sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 69 table 3: relationship of major congenital malformations with maternal sociodemographic and obstetric variables. maternal sociodemographic and obstetric variables range number frequencies (%) p value no (n = 9,698) no cm (n = 78) maternal age 20–25 1,130 4 0.4 0.076 26–30 2,007 5 0.7 31–35 3,115 22 0.7 36–40 1,284 39 3.1 0.0018 41–45 2,028 6 0.3 >46 134 2 1.5 parity 0–2 5,237 26 0.4 0.0056 3–4 3,992 44 1.1 >5 429 8 1.7 mode of conception spontaneous/ natural 813,974 0.9 0.073 assisted 15,594 0.3 0.085 discussion prenatal diagnosis of cm is one of the key goals of antenatal care. in the study, 0.8% of fetuses had cm. the prevalence of major cms range between 0.6% in barbados [7] and 2.8% in saudi arabia [4], and 23.9 per 1,000 births for 2003–2007 in europe [8]. in nigeria, the prevalence reported is between 2.7 and 6.2% [9, 10]. the prevalence from our study is strikingly lower than rates reported from other local studies. the variations could be due to differences in study population characteristics, presence of environmental teratogens, local sociocultural factors that encourage concealment of information about birth defect and study design among others. the highest rate of 6.2% was reported in a teaching hospital study where the environment was affected by oil spillage and its consequent environmental degradation effects. crude oil spillage is believed to have teratogenicity effects on the fetus, which could explain the higher rates of occurrence of cm in the pregnant population. in contrast, a lower rate was reported in other areas that are not affected by oil-induced environmental degradation. consanguinity and culture of concealment of disease data may explain the difference between our study finding from some other environments in the middle east and europe. in omani population, about 2.5% of the babies at birth were affected by cm compared with the 1.5% in non-omani births (p < 0.05) [11]. sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 70 the profile of first-trimester prenatally diagnosed cm is relatively scarce in scientific literature. the practice should however be encouraged because it provides opportunity for early counseling and fetal therapy [4]. late pregnancy booking and scarcity of experts in first trimester diagnostic scans could contribute the present situation. it is however instructive to observe that while the lowest proportion of all antenatal ultrasound scans was in the first trimester, the proportion of cm cases diagnosed in this first trimester to number of ultrasound scans was similar to other trimesters. these findings show that the first trimester is an equally important period to diagnose fetal anomalies, which could have resulted in abortion before the time of second trimester scan. the predominance of cns abnormality over abnormalities of other systems was also confirmed in our study [9, 10, 12]. the relatively larger size of the fetal head is believed to explain the relative ease of diagnosis due to easy visualization of its structures. the cardiovascular system anomaly was in the lowest data range, similar to the reports from other studies [4, 13]. the relationship between cm and maternal age was shown to be unimodal, contrary to the bimodal distribution [14]. the risk for cm in women aged >35 years can be explained by factors such as the high risk of maternal age-induced aneuploidy, and increased incidence of medical complications such as diabetes mellitus could be responsible for the unimodal distribution [14]. multiple systems abnormality is commoner in regions with higher risk of consanguineous marriage [14]. conclusion this study shows that profiling cm is similar to many other hospital-based studies. the first trimester ultrasound data should encourage a policy for routine first trimester scanning in women that present in early pregnancy, while routine second trimester scanning should be routinely done in all other pregnancies. furthermore, postnatal confirmation of all antenatal diagnosis should be done as an important component of auditing. a multicenter study that would give a better representative population rate is recommended to be done by expert sonographers. acknowledgement the author acknowledges the support of medical record staff in all participating units. sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 71 conflict of interest the authors declare that there is no conflict of interest. references [1] world health organization (2015). congenital anomalies, fact sheet no. 370. available at who.int/mediacentre/factsheet/fs370/en [2] ekwunife oh, okoli cc, ugwu jo et al. (2017). congenital anomalies: prospective study of pattern and associated risk factors in infants presenting to a tertiary hospital in anambra state, south east nigeria. nigeria journal of pediatrics. 44(20): 76–80. [3] irvine b, luo w, león ja (2015). congenital anomalies in canada 2013: a perinatal health surveillance report by the public health agency of canada’s canadian perinatal surveillance system. health promotion and chronic disease prevention in canada. 35(1): 21–22. [4] bahauddin is, manal sa, reham aa et al. (2008). antenatal diagnosis, prevalence and outcome of major congenital anomalies in saudi arabia: a hospital-based study. annals of saudi medical. 28(4): 272–276. [5] lamina ma, oloyede oao, adefuye po (2004). should ultrasonography be done routinely for all pregnant women? tropical journal of obstetrics and gynaecology. 21(1): 11–14. [6] al-dalla ali fj, mahmood ns, al-obaidi bk (2013). incidence of birth defects at birth among babies delivered at maternity and children teaching hospital in ramadi. al-anbar medical journal. 11(1): 1–10. [7] singh k, krishnamurthy k, greaves c et al. (2014). major congenital malformations in barbados: the prevalence, the pattern, and the resulting morbidity and mortality. isrn obstetrics and gynecology. doi: 10.1155/2014/65178 [8] dolk h, loane m, garne e (2010). the prevalence of congenital anomalies in europe. advances in experimental medicine & biology. 686: 349–364. [9] akinmoladun ja, ogbole gi, oluwasola tao (2018). pattern and outcome of prenatally diagnosed major congenital anomalies at a nigerian tertiary hospital. nigerian journal of clinical practice. 21(5): 560–565. [10] abbey m, oloyede oa, bassey g et al. (2017). prevalence and pattern of birth defects in a tertiary health facility in the niger delta area of nigeria. international journal of women’s health. 9: 115–121. https://www.ncbi.nlm.nih.gov/pubmed/?term=irvine%20b%5bauthor%5d&cauthor=true&cauthor_uid=25811402 https://www.ncbi.nlm.nih.gov/pubmed/?term=luo%20w%5bauthor%5d&cauthor=true&cauthor_uid=25811402 https://www.ncbi.nlm.nih.gov/pubmed/?term=le%26%23x000f3%3bn%20ja%5bauthor%5d&cauthor=true&cauthor_uid=25811402 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4939458/ https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4939458/ https://www.ncbi.nlm.nih.gov/pubmed/?term=singh%20k%5bauthor%5d&cauthor=true&cauthor_uid=25006483 https://www.ncbi.nlm.nih.gov/pubmed/?term=krishnamurthy%20k%5bauthor%5d&cauthor=true&cauthor_uid=25006483 https://www.ncbi.nlm.nih.gov/pubmed/?term=greaves%20c%5bauthor%5d&cauthor=true&cauthor_uid=25006483 https://www.ncbi.nlm.nih.gov/pubmed/?term=dolk%20h%5bauthor%5d&cauthor=true&cauthor_uid=20824455 https://www.ncbi.nlm.nih.gov/pubmed/?term=loane%20m%5bauthor%5d&cauthor=true&cauthor_uid=20824455 sudan journal of medical sciences olufemi oloyede et al. doi 10.18502/sjms.v15i1.6706 page 72 [11] kiran ps (2005). profile of major congenital malformations at nizwa hospital, oman: 10-year review. journal of paediatrics and child health. 41(7): 323–330. [12] abouel-ella ss, tawfik ma, aboel-fotoh wm et al. (2018). study of congenital malformations in infants and children in menoufia governorate, egypt. egyptian journal of medical human genetics. 19(4): 359–365. [13] benavides-lara a, faerron angel je, umanasolis l et al. (2011). epidemiology and registry of congenital heart disease in costa rica. revista panamericana de salud pública. 30: 31–38. [14] goetzinger kr, shanks al, odibo ao et al. (2017) advanced maternal age and the risk of major congenital anomalies. american journal of perinatology. 34(3): 217–222. sudan journal of medical sciences volume 12, issue no. 1, doi 10.18502/sjms.v12i1.858 production and hosting by knowledge e letter to the editor teaching procedures and skills in medical schools: gaps, weakness, and challenges mohamed d. awadalla gismalla department of surgery, faculty of medicine, gezira university, sudan abstract there is deficiency and gaps among medical graduates in performing certain procedures and skills. till recent years, some school used an apprenticeship model for teaching procedures. the way of teaching skills should be revised and reinforced. medical schools showed adopt formal curricula based training for teaching procedure. in this letter, we would like to highlight the challenges and weakness in teaching procedure for undergraduates medical students. هناك نقص وثغرات بين خريجي الطب يف أداء وإجراء بعض المهارات. وحتى ىف السنوات األخيرة، أستخدمت بعض الكليات النماذج والدمى للتدريب المهني يف تدريس وإجراء هذه المهارات. وينبغي تنقيح وتعزيز مهارات التدريس. ويجب أن تعتمد كليات الطب مناهج معتمدة تؤسس للتدريب على إجراء المهارات. يف هذه الرسالة، نود أن نسلط الضوء على التحديات وضعف التدريس ألداء وإجراء المهارات بين طالب الطب. 1. gaps in procedure skills among graduates promes et. al. talked about the gaps in procedural and skills training and experiences among medical school graduates. they found that, first-year residents had the most experience in suturing and foley catheter placement. there is some procedure which done less than five. they had the least experience in central venous access. most had not performed basic life support, and more than one-third had not performed cardiopulmonary resuscitation (cpr). they found the residents who had procedure course during undergraduates are significantly more likely to report competency in performing basic medical procedures [1]. other study done among graduate’s students showed that more than two-thirds of the participant were capable of doing venipuncture, intravenous placement, arterial puncture, placement of the nasogastric tube, placement of foley catheter, suturing lacerations, and cpr [2]. in a survey of basic practical skills in one of uk medical school, it was found that not all skills had been mastered to the same degree as venous blood sampling and how to cite this article: mohamed d. awadalla gismalla, (2017) “teaching procedures and skills in medical schools: gaps, weakness, and challenges,” sudan journal of medical sciences, vol. 12 (2017), issue no. 1, 46–51. doi 10.18502/sjms.v12i1.858 page 46 corresponding author: mohamed d. awadalla gismalla; email: mohadaff22@gmail.com received: 15 december 2016 accepted: 20 february 2017 published: 28 may 2017 production and hosting by knowledge e mohamed d. awadalla gismalla. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mohadaff22@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e intravenous cannula insertion [3]. the proportions reported in another study for intravenous cannula insertion are higher than those in previous studies; for example, an audit of clinical skills conducted among final-year medical students in nigeria reported that only 4.8% of final-year students had never inserted an intravenous cannula [4]. other studies have reported a number of final year medical students or newly graduated doctors not attempting common procedural skills such as basic life support, nasogastric tube insertion, simple wound suturing, lumbar puncture, endotracheal intubation and thoracentesis [5]. a significant number, 38 (45.2%) had never inserted a urinary catheter nor had any experience with bag/mask skills [4]. all these mention studies showed the concern of educators about skill competences among medical students and graduates. it demonstrates the weakness and gaps in some skills and procedure competence. also, it state that not all procedure done with the same competence and it differ from school to another. 2. teaching medical procedure most of medical schools depend on an apprenticeship model as teaching methods for skills and procedures through observation, trial, and demonstration; see one, do one, teach one. but it does not offer to students and graduates adequate experience for future prepare to specialized residency. also, apprenticeship model can be affected by patient sitting, teaching environments, and another surrounding learner (cosmetician), and the educator himself (teacher) [6]. studies have shown that observation of procedures does not give the students self-confidence and competence to perform in patients’ real life [7–9]. so nowadays, medical schools have started formal procedural skills training curricula. this will help students to get formal procedural training maintained skills performance superiority over subsequent years of medical school [10]. several studies showed that clinical skills curricula have demonstrated significant improvements in medical student confidence after implementation of formal procedural skills courses [9, 11, 12]. 3. how to teach and learn procedure it is important to provide students an opportunity for the student to be prepared to learn that procedure. this preparation session showed to be in very structured format before the laboratory or bedside session. the aim of this session is to prepare the students with more information about indications and contraindications of specific procedure, the instruments and the tools used to perform the procedure, and the expected outcome of the procedure [13]. in addition, learners should take the time to review the risks of any procedure they perform, including the possible complications doi 10.18502/sjms.v12i1.858 page 47 sudan journal of medical sciences production and hosting by knowledge e and how to manage them if they occur. apart from this preparation should focus on the process of obtaining informed consent as well as documentation of the procedure [14, 15]. before starting skill laboratory or bedside session, the students should recall information regarding the procedure before its performance. students can be prepared to the procedure by several methods assigned chapters, computer programs, or videos containing the information, they would like the learner to have mastered before the teaching experience. the problem of this preparation session, it cannot go beyond theory and it is not active sessions [13]. 4. the process of learning steps in the process of learning a procedure: 1. conceptualization — understanding the reasons for performing a procedure, the overall process, the tools involved, and the risks/benefits 2. visualization — observing a demonstration of the procedure, performed in a fluid and competent manner by the master teacher 3. verbalization — reviewing a verbal deconstruction of the procedure while it is performed by the expert, with opportunity for interruptions and clarifications 4. guided practice — performing the sequential steps of the procedure under thesupervision of an expert physician [13]. therefore, it is important to be cognizant of the basics of a procedure, as some instructors may have to alter their “usual” method for performing a procedure to deliver a more standardized educational experience. once the standard method is mastered by the learner, particular variations and shortcuts may be taught, but if taught prematurely, these will only confuse the novice learner and lengthen the time required for motor learning of the procedure [16]. as the learner becomes more comfortable with the procedure, demonstrating increased skill competence, the instructor’s involvement in the procedure should decrease until the learner is essentially performing it without assistance. practice without guidance can precipitate errors and result in imprinting of inappropriate actions, which is dangerous to patients and a disservice to the learner. immediate feedback, both positive and negative, is invaluable throughout the learning process. more specifically, effective feedback is performance based, highlighting portions of the procedure that were done well and pointing out areas for improvement, with specific tips on how to improve the skill attempted [17]. once a basic procedure is mastered by a learner, the next step in skill acquisition is to present variations on that procedure. it is in this final step that learners can be introduced to the shortcuts or varied methods that instructors use in their daily doi 10.18502/sjms.v12i1.858 page 48 sudan journal of medical sciences production and hosting by knowledge e practice. they should be challenged to apply the procedure in difficult situations and learn alternative techniques to accomplish the desired outcome [18]. 5. creating a procedural education elective for preclinical medical students many educators and clinicians have commented that medical school is the optimal time in physician training to teach basic procedural skills. because medical students have less direct patient care responsibilities and more time to spend practicing acquired skills, many emergency medicine clerkships have designated space within their curricula for procedural education. beyond the basic skills learned at the bedside, specific procedural skills sessions using cadavers and simulators are now an increasingly popular way to provide exposure to clinical procedures for the new learners within a safe, well-supervised environment [13]. overall, this course presents a successful example of procedural education for early learners that takes into account the educational theory of motor skills acquisition and uses multiple models for guided practice and learning with feedback. it provides a venue for students to learn basic procedures in a prescribed sequence from master teachers, rather than in the unstructured and often inexperienced hands of residents during their clinical rotations [19]. 6. conclusion apprenticeship model only for teaching procedures has a lot of drawback and weakness. medical schools should adopt well structure curriculum for teaching procedures. during medical school the students has very good chance to learn procedures and skills before their residency program and future career. references [1] s. b. promes, s. m. chudgar, c. o. grochowski et al., “gaps in procedural experience and competency in medical school graduates,” academic emergency medicine, vol. 16, no. 2, pp. s58–s62, 2009. [2] c. w. sanders, j. c. edwards, and t. k. burdenski, “a survey of basic technical skills of medical students,” academic medicine, vol. 79, no. 9, pp. 873–875, 2004. [3] p. board and m. mercer, “a survey of the basic practical skills of final-year medical students in one uk medical school,” medical teacher, vol. 20, no. 2, pp. 104–108, 1998. [4] n. j. jebbin and j. m. adotey, “an audit of basic practical skills acquisition of final year medical students in a nigerian medical school,” annals of african medicine, vol. 11, no. 1, pp. 42–45, 2012. doi 10.18502/sjms.v12i1.858 page 49 sudan journal of medical sciences production and hosting by knowledge e [5] l. coberly and l. m. goldenhar, “ready or not, here they come: acting interns’ experience and perceived competency performing basic medical procedures,” journal of general internal medicine, vol. 22, no. 4, pp. 491–494, 2007. [6] d. nutter and m. whitcomb, the aamc project on the clinical education of medical students: clinical skills education, association of american medical colleges, washington, dc, 2005. [7] j. j. dehmer, k. d. amos, t. m. farrell, a. a. meyer, w. p. newton, and m. o. meyers, “competence and confidence with basic procedural skills: the experience and opinions of fourth-year medical students at a single institution,” academic medicine, vol. 88, no. 5, pp. 682–687, 2013. [8] e. h. wu, d. m. elnicki, e. j. alper et al., “procedural and interpretive skills of medical students: experiences and attitudes of third-year students,” academic medicine, vol. 81, no. 10, pp. s48–s51, 2006. [9] r. a. stewart, l. s. hauge, r. d. stewart, r. l. rosen, a. charnot-katsikas, and r. a. prinz, “a crash course in procedural skills improves medical students’ selfassessment of proficiency, confidence, and anxiety,” american journal of surgery, vol. 193, no. 6, pp. 771–773, 2007. [10] r. remmen, a. scherpbier, c. van der vleuten et al., “effectiveness of basic clinical skills training programmes: a cross-sectional comparison of four medical schools,” medical education, vol. 35, no. 2, pp. 121–128, 2001. [11] k. shanmugarajah, j. shalhoub, s. mastoridis, and p. a. paraskeva, “a course in basic surgical techniques improves medical student confidence in key skills.,” medical teacher, vol. 32, no. 9, pp. 789–790, 2010. [12] m. panahkhahi, “station-based deconstructed training model for teaching procedural skills to medical students: a quasi-experimental study,” advances in medical education and practice, vol. volume 1, pp. 17–23, 2010. [13] s. moayedi and m. torres, “teaching invasive medical procedures,” practical teaching in emergency medicine, second edition, pp. 72–84, 2012. [14] j. h. george and f. x. doto, “a simple five-step method for teaching clinical skills. fam med,” in doto fx. a simple five-step method for teaching clinical skills. fam med, vol. 33, pp. 577–578, 577–578, 33, 2001. [15] m. e. gallery, “teaching clinical skills,” in the emergency medicine teaching fellowship manual, american college of emergency physicians, m. f. whiteside and m. a. geist, eds., p. 11, tx, dallas, 2001. [16] t. s. wang, j. l. schwartz, d. j. karimipour, j. s. orringer, t. hamilton, and t. m. johnson, “an education theory-based method to teach a procedural skill,” archives of dermatology, vol. 140, no. 11, pp. 1357–1361, 2004. [17] p. j. mcleod, y. steinert, j. trudel, and r. gottesman, “seven principles for teaching procedural and technical skills,” academic medicine, vol. 76, no. 10, p. 1080, 2001. doi 10.18502/sjms.v12i1.858 page 50 sudan journal of medical sciences production and hosting by knowledge e [18] t. m. van der vlugt and p. m. harter, “teaching procedural skills to medical students: one institution’s experience with an emergency procedures course,” annals of emergency medicine, vol. 40, no. 1, pp. 41–49, 2002. doi 10.18502/sjms.v12i1.858 page 51 gaps in procedure skills among graduates teaching medical procedure how to teach and learn procedure the process of learning creating a procedural education elective for preclinical medical students conclusion references page 35 research article a cross-sectional study on hepatitis b immune status among vaccinated healthcare workers in khartoum, sudan abdullahi elsheikh mahgoub1*, yassir hamadalnil2, osama mohammed3, rasha nakhleh4,5, and musa mohamed khair6 1. geriatric fellow, hurley medical center, flint, michigan, usa 2. department of clinical microbiology, faculty of medicine, nile university, khartoum, sudan 3. central laboratory, khartoum, sudan 4. geriatric fellowship program/hurley medical center 5. college of human medicine, michigan state university 6. medicine, university of khartoum, khartoum, sudan abstract background: hepatitis b virus (hbv) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (hcc). vaccination against the virus plays an important role in its prevention. health personnel at risk of infection are recommended to receive the vaccine and to check their immune status thereafter. objective: to determine hepatitis b immune status among vaccinated health personnel in khartoum state, sudan. a total of 106 health personnel from different hospitals and doctors’ mess in khartoum and from different jobs were surveyed and their hbv surface antibodies levels were determined by hbsab (quantitative) elisa kits. methods: of the 106 participants in this study, the majority were females 72.6%. the mean age of those involved was 27.69 years, and nurses made for more than 50% of those surveyed. about 56.6% (60) of the health personnel involved took three or more doses of hbv vaccine while the rest received one or two doses. the results of the participants who received three or more doses of the vaccine represented immunity by 70%. in general, about 47.2% (50) of the participants in this study did show excellent immune response (>100 miu/ml) and 18.9% (20) had weak protective levels (between 10 and 100 miu/ml) so, we concluded that hbv post-vaccination immunity status of health personnel in khartoum state is lower than post-vaccination hbv immunity in other parts of the world. there is an urgent need for a national protocol of hbv vaccination to improve the immunization status of health personnel with a regular checkup of hbv immunity and easy access to a good-quality vaccine. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6700 production and hosting by knowledge e how to cite this article: abdullahi elsheikh mahgoub (2019) “a cross-sectional study on hepatitis b immune status among vaccinated healthcare workers in khartoum, sudan”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 35–42. doi 10.18502/sjms.v15i1.6700 corresponding author: abdullahimahgoub@hotmail.com. received 18 january 2020 accepted 07 march 2020 published 31 march 2020 production and hosting by knowledge e cc abdullahi elsheikh mahgoub. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: hepatitis b vaccines; healthcare workers; immune response sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 36 introduction hepatitis b virus (hbv) is a member of the hepadnaviridae family with a small dna virus and unusual features of replication similar to retroviruses, in which hbv can replicate through an rna intermediate and forming a stable minichromosome (cccdna) in the nucleus. these features of the hbv replication cycle give it the ability to persist in infected cells [1]. hbv can cause acute hepatitis and can also lead to other more serious complications like chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (hcc) [2]. hbv can survive outside the body for up to seven days; the virus incubation period is around two and a half months. the virus can be transmitted perinatally from a mother to her baby, horizontally by exposure to infected blood or blood products, or through direct spread percutaneously or to mucosal membranes [3]. hbv infects more than 300 million people worldwide; sudan is classified among the countries with high hbv seroprevalence. exposure to the virus varied from 47 to 78%, with a hepatitis b surface antigen prevalence ranging from 6.8% in central sudan to 26% in southern sudan [4]. hbv vaccine is a recombinant dna vaccine that contains hbsag genetically engineered from the yeast saccharomyces cerevisiae. it provides a seroprotection rate of 85–100% that was seen one month after the last dose of vaccine and it confers immunity for at least 10 years [5]. hepatitis b vaccine is recommended for unvaccinated adults who are at risk for hbv infection like people whose sex partners have hepatitis b, sexually active persons who are not in a long-term monogamous relationship, persons seeking evaluation or treatment for a sexually transmitted disease, men who have sex with men, people who share needles, syringes, or other drug-injection equipment, household contacts of hbv-infected persons, health personnel and public safety workers at risk for exposure to blood or body fluids, residents and staff of facilities for developmentally disabled persons, persons in correctional facilities, victims of sexual assault or abuse, travelers to regions with increased rates of hepatitis b, people with chronic liver disease, patients on hemodialysis, hiv infection, or diabetes, and anyone who wants to be protected from hbv. the vaccine is usually given as three shots over a period of a six-month period [6]. serum antibody to the hepatitis b surface antigen (anti-hbs) has long been established as a marker of vaccine-induced protection against hepatitis b. an anti-hbs level of ≥10 iu/ml has been suggested to indicate protection against hepatitis b disease [7]. old age in adults, male gender, increased body mass index, smoking, and concomitant disease are some of the factors that may decrease the immunologic response to hbv vaccine [8]. this study was conducted to determine hepatitis b immune status among vaccinated health personnel in khartoum, sudan. sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 37 materials and methods this is a descriptive cross-sectional study conducted at public hospitals of khartoum including the ibn sina specialized hospital, the alshaab teaching hospital, and the academic hospital from 30th july to 30th september 2017. the study included healthcare providers working in all departments, including trained nurses, medical attendants, and clinicians – both surgical and medical-related specialties and laboratory technicians. the investigator approached healthcare workers through the hospital administration and the heads of the departments. a self-administered questionnaire that covered age, gender, job description, total doses of vaccine and the date of the last dose plus other data such as duration since the last dose and a history of immunosuppressive treatment and blood transfusion was used to obtain information from the participants. the questionnaires were collected from the healthcare workers upon completion by appointment with the participant; 5 ml venous blood sample was collected from the cubital vein under complete possible aseptic conditions in edta containers, centrifuged at 3000 rounds per min for 10 min to be separated and stored at –20ºc till it was used. the elisa procedure was followed according to the manufacturer’s instructions. in brief, 50 μl of the serum were incubated at 37ºc for 60 min in 118-well microplate coated with hbsag reactive to hbsab (anti-hbs). subsequently, the wells were washed (three times) to remove residual serum. 50 μl of anti-hbs conjugated ab was added and incubated at 37ºc for 60 min. the wells were washed (three times) to eliminate unbound conjugate, 50 μl of enzyme-substrate and chromogen were added and incubated at 37ºc for 60 min; 50 μl diluted stop solution (sulphuric acid) was added and the plate was read at 450 nm as indicated by the manufacturer. interpretation of the result the cut-off value was estimated by calculating the mean (m) absorbance value of negative control x 2.1. cut-off = mean of the negative control x 2.1 for the validity of the accomplishment, the following is required: (a) negative control means: absorbance of individual negative control values must be <0.9 (b) positive control means: it must be >1.1 (c) equivocal means: absorbance of individual equivocal values must be between 0.9 and 1.1. all statistical calculations were done using spss for windows, version 24. sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 38 results a total of 106 health personnel participated in this study, of those, 77 (72.6 %) were females and 29 (27.4%) males with a female:male ratio of 2.65:1. the mean age of the participants was 27.69 years, the minimum age was 20 years, and the maximum age was 55 years. furthermore, 56 (52.8%) participants were nurses by profession, 35 (33%) were doctors, 4 (3.7%) lab technicians, and 11 (10.4%) others. about 97 (91.5%) participants took the last dose of vaccine within the past 10 years and 12 (11.3%) took their vaccine during childhood. the number of subjects who completed the all three doses of vaccine or more were 60 (56.6%), those who took two doses were 23 (21.7%), and those with only one dose were 23 (21.7%), see table 1. table 1: total number of hbv vaccine doses received vs immunity acquired after each dose. number of hbv vaccine doses received frequency percent valid percent 1 dose 5.20 + 1.31 4.28 + 0.88 0.0076 2 doses 2.03 + 1.43 1.26 + 0.76 0.0271 3 doses 3.06 + 0.73 2.60 + 0.56 0.0248 >3 doses 1.12 + 0.29 1.20 + 0.24 0.2736 total 106 100% 100% sixty participants completed the three or more doses of vaccine, about forty two (66%) had hbsabs titer ≥10 miu/ml and eighteen (30%) had titer <10 miu/ml. of those who took two doses of the vaccine, 17 (73.9%) had hbsabs titer >10 miu/l and 6 (26.1%) <10 miu/ml. and of those who received one dose, 12 (52.1%) had titer <10 miu/ml and 11 (47.8%) ≥10 miu/ml (figure 1). about 34 (32%) participants were exposed to needle stick injury during their work but didn’t received treatment, 3 (8.8%) had undergone blood transfusion, and 1 had received hepatitis b immunoglobulin after accidental needle injury from hepatitis b-infected patient and her hbsab result was excellent at 191.0 miu/ml (figure 2). discussion hcws are at a higher risk of blood-borne infections, especially hbv. vaccination is effective in protecting 90–95% of adults [9]. according to the world health organization (who) estimate, hepatitis b vaccination coverage among healthcare workers varies from 18% being lowest in africa to the highest 77% in australia and new zealand [10]. sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 39 figure 1: distribution of subjects participating in this study according to specialty in which nurses (56) were more than all the other groups. figure 2: correlation between hbsab titer and number of participants receiving different doses of hbv vaccine (p = 0.035). in this study, we examined the level of anti-hbsab in healthcare personnel in three public hospitals in khartoum state besides khartoum doctors’ mess; the hospitals were the ibn sina specialized hospital, the alshaab teaching hospital, and the academic teaching hospital. they were chosen mainly because of their easy accessibility. in this study, 60 (56.6%) participants completed all three doses of vaccine, which is higher sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 40 compared to the lower vaccination rates found in the other two studies conducted in ethiopia, one in the gondar university hospital (28.7%) [11] and the other at the adama general hospital and medical college (25.6%) [12] while nearly similar results as ours was seen in a study conducted in the makueni county of kenya (48%) [13]. another study reveals a higher percentage of full vaccination (72%) in libya [14]. from our results, we notice that there is a direct relationship between the numbers of doses the participants received and their immune status against hbv (p = 0.035), so those who received three or more doses of the vaccine, their results represented immunity by 70%. on the other hand, just 47.8% of those who took one dose of hbv vaccine in their lifetime are immune to the virus (table 1). in our study about 70% of the subjects were immuned after receiving at least three doses of the vaccine which is lower than the study done in west pomeranian region of poland (94.5%) [15]. another finding in this study was that there is no big difference in hbv immunity between those who took their last dose of the vaccine <10 years ago (64.95% are immune) and the participants who took their last vaccine dose ≥10 years ago (77.8% are immune). in general, about 47.2% (50) of the participants in this study did show excellent immune response (>100 miu/ml), 18.9% (20) had weak protective levels (between 10 and 100 miu/ml) which in comparison to the lasemi, eshagh et al’s study, were a little bit higher as in their study, 54% of the students had an excellent protective immune response and 24.2% had a positive but weak immune response [16]. some suggest that the weak immune response among health personnel in sudan may be due to the type of vaccine that is used, which is an imported vaccine from outside the country. no official data about the type of vaccine are available from the national medical supplies fund (nmsf). only 56.6% of the involved health personnel finished the recommended three doses that reflects the gap in the health education and awareness about hbv vaccination among health personnel. this may be due to the high cost and lack of a public protocol for health personnel hbv vaccination, we found only two previous researches close to this topic in sudan [17]. it is worth mentioning that most participants 56 (52.8%) were nurses, who were more willing to get involved and check their hbsab levels than doctors. about 70 (66.0%) participants were surveyed at the ibn sina hospital; they were eager to get involved because they wanted to know their immune status against hbv as the hospital is the main referral hospital for gastroenterology and hepatology in sudan. they have better awareness about the importance of vaccination against the hbv and their increased risk of acquiring the disease if they don’t have immunity against the virus especially with the high numbers of hepatitis b patients in their hospital. sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 41 conclusion from this research, we can conclude that hbv post-vaccination immunity status of health personnel in khartoum state is lower than the post-vaccination hbv immunity in other parts of the world. so, there is an urgent need for a national protocol of hbv vaccination to improve the immunization status of healthcare workers that includes regular checkups of hbv immunity and easy access to a good-quality vaccine. to get more accurate results of the response to the hepatitis b vaccine among healthcare workers in sudan, more large-scale studies should be conducted. references [1] liang, tj (2009). hepatitis b: the virus and disease. hepatology. 49(5): s13–s21. [2] ganem d, prince am (2004). hepatitis b virus infection–natural history and clinical consequences. n engl j med. 350(11): 1118–1129. [3] who (2016). hepatitis b. fact sheet. [4] mudawi hm (2008). epidemiology of viral hepatitis in sudan. clin exp gastroenterol. 1: 9–13. [5] hamadalnil y, bakheit s (2017). hepatitis b virus_surface gene mutations and their clinical implications. sudan j med sci. 12(2): 101–13. [6] nelson np, easterbrook pj, mcmahon bj (2016). epidemiology of hepatitis b virus infection and impact of vaccination on disease. clin liver dis. 20(4): 607–628. [7] bagheri-jamebozorgi m, keshavarz j, nemati m, mohammadi-hossainabad s, rezayati mt, nejad-ghaderi m et al. (2014). the persistence of anti-hbs antibody and anamnestic response 20 years after primary vaccination with recombinant hepatitis b vaccine at infancy. hum vaccin immunother. 10(12): 3731–3736. [8] yang s, tian g, cui y et al. (2016). factors influencing immunologic response to hepatitis b vaccine in adults. sci rep. 6: 27251. [9] coppola n, onorato l, minichini c et al. (2015). clinical significance of hepatitis b surface antigen mutants. world j hepatol. 7(27): 2729–2739. [10] pruss-ustun a, rapiti e, hutin y (2005). estimation of the global burden of disease attributable to contaminated sharps injuries among health-care workers. the am j ind med. 48(6): 482–490. [11] ayalew mb, horsa ba (2017). hepatitis b vaccination status among health care workers in a tertiary hospital in ethiopia. hepat res treat. 2017: 6470658. sudan journal of medical sciences abdullahi elsheikh mahgoub et al. doi 10.18502/sjms.v15i1.6700 page 42 [12] akibu m, nurgi s, tadese m et al. (2018). attitude and vaccination status of healthcare workers against hepatitis b infection in a teaching hospital, ethiopia. scientifica. 2018: 6705305. [13] kisangau en, awour a, juma b et al. (2018). prevalence of hepatitis b virus infection and uptake of hepatitis b vaccine among healthcare workers. j public health (oxf). 41(4): 765–771. [14] ziglam h, el-hattab m, shingheer n et al. (2013). hepatitis b vaccination status among healthcare workers in a tertiary care hospital in tripoli, libya. j infect public health. 6(4): 246–251. [15] ganczak m (2012). a cross-sectional study on anti-hepatitis b immune status in vaccinated healthcare workers in the west pomeranian region of poland. hepat mon. 12(3): 185–189. [16] lasemi e, haddadpour n, navi f et al. (2011). rate of acquired immunity in dental students after hepatitis b vaccination. dent res j. 8(3): 128–131. [17] abdel a, khamis g, jacoub ao et al. (2014). knowledge, attitudes and practices of surgical staff at khartoum state hospitals towards hepatitis b infection. khartoum med j. 7(1): 932–940. sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.7272 production and hosting by knowledge e research article spinal myoclonus as a rare presentation of neurological disease in sudan etedal ahmed a. ibrahim1,2 and asmhan m. osman2,3 1alneelain university, khartoum, sudan 2the national center for neurological science, khartoum, sudan 3nile valley university, atbara, sudan abstract background: spinal myoclonus is a very rare movement disorder characterized by myoclonic involvement of the whole body. structural lesions are usually the cause, however, in primary spinal myoclonus, the etiology remains unknown. case description: we report a case of 50 year-old farmer from the eastern part of sudan presented with jerky movement affecting his entire body, and diagnosed clinically with a spinal myoclonus. laboratory study was normal and the mri of brain and cervical and dorsal spines were also normal. the patient received clonazepam with marked improvement. conclusion: in any case of spinal myoclonus, eeg, emg, and mri of brain and spinal cord must be done to exclude structural lesions. clonazepam is the drug of choice with significant improvement. in segmental spinal myoclonus, botulinum toxin is the best treatment. keywords: spinal myoclonus, sudan 1. introduction myoclonusis a movement disorder presented with sudden, brief, shock-like jerks. most myoclonic jerks are due to a brief burst of muscular activity, resulting in positive myoclonus [1]. jerks resulting from brief cessation of ongoing muscular activity are called negative myoclonus (nm). while positive myoclonus is generally more common, nm frequently occurs in hospital settings as a result of toxic metabolic causes. a combination of both forms may be present in one disease, as in post-hypoxic myoclonus or progressive myoclonic epilepsies (pmes). 2. spinal myoclonus spinal myoclonus may be segmental or propriospinal, reflecting spinal segmental organization and the presence of propriospinal pathways that connect different spinal segments [2]. it is generally resistant to supra spinal influences such as sleep (therefore it how to cite this article: etedal ahmed a. ibrahim and asmhan m. osman (2020) “spinal myoclonus as a rare presentation of neurological disease in sudan,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 218–222. doi 10.18502/sjms.v15i2.7272 page 218 corresponding author: etedal ahmed a. ibrahim; the national center for neurological science ,al neelain university, khartoum, sudan. postal code: 11111 email: eetedalibrahim@yahoo.com received 22 january 2020 accepted 24 may 2020 published 30 june 2020 production and hosting by knowledge e etedal ahmed a. ibrahim and asmhan m. osman. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:eetedalibrahim@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences etedal ahmed a. ibrahim and asmhan m. osman may persist in sleep) or voluntary action (therefore it is present at rest, without activation), and may or may not be stimulus-sensitive [3]. spinal segmental myoclonus is usually symptomatic of an underlying structural lesion such as syringomyelia, myelitis, spinal cord trauma, vascular lesion, or malignancy [2]. it is confined to one or few contiguous myotomes and may occur irregularly or quasi-rhythmically, with a frequency as low as 12/min or as high as 100/min. emg myoclonic bursts are prolonged up to 1000 ms. propriospinal myoclonus is a form of spinal myoclonus where the spinal generator recruits axial muscles up and down the spinal cord via long propriospinal pathways [2]. typically, there are axial flexion jerks involving the neck, trunk, and hips with a frequency of hz. emg bursts are long, lasting several 100 ms. clinically, it can be distinguished from brainstem myoclonus, which is also axial in distribution, by sparing of the face and insensitivity to auditory stimuli. it typically occurs spontaneously, especially in recumbent position, or may be provoked by tapping of the abdomen or by eliciting tendon reflexes. as opposed to segmental myoclonus, most patients with propriospinal myoclonus have no clear etiology. symptomatic forms are reported in cervical trauma, tumor, or viral myelitis (brown, psychogenic forms of propriospinal myoclonus are now increasingly recognized) [4]. one recent study on a large cohort of patient with idiopathic spinal myoclonus showed that at least 30% of patients had a definite premovement potential, indicating that the etiology was psychogenic [5]. in another large series, a psychogenic cause was suggested in 34 out of 35 patients with axial jerks, who were initially thought to have propriospinal myoclonus [6]. to approach a patient with spinal myoclonus, we need a detailed history and examination of the exact cause and other associated diseases. investigation needed eeg, emg showed specific myoclonic burst. brain and spinal mri to exclude structural lesion. 3. treatment of spinal myoclonus in spinal myoclonus, pharmacological treatment is unsatisfactory. clonazepam is the first choice of drug for both types of spinal myoclonus, and dosages up to 6 mg are needed to diminish spinal segmental myoclonus. levetiracetam was reported to be effective in a series of three patients with spinal segmental myoclonus [7]. 4. case description a 50-year-old man from the eastern part of sudan presented with an abnormal movement that suddenly started affecting his entire body—a sudden jerky, rhythmic movement, similar to an electric shock, unaffected by light or noise. it was neither associated with convulsion nor with the loss of consciousness or headache, not even weakness or doi 10.18502/sjms.v15i2.7272 page 219 sudan journal of medical sciences etedal ahmed a. ibrahim and asmhan m. osman figure 1: cervical mri and dorsal mri. sensory disturbance, the patient could not walk because of abnormal movement. the sphincter was controlled and a systemic review was non-significant; he had suffered two attacks in 2012–2015 with the same abnormal movement that were aborted by medication. there was no record of patient’s family and drug history. o/e exam the patient not pale fully conscious oriented. cvs, chest and abdomen were normal. neurologically, he was fully conscious, with normal mini-mental score test, normal tone and power. reflexes in the upper and lower limbs, planter were flexor, with mildly impaired pass pointing and normal sensation. the jerky movement of head, trunk, upper doi 10.18502/sjms.v15i2.7272 page 220 sudan journal of medical sciences etedal ahmed a. ibrahim and asmhan m. osman figure 2: brain mri. and lower limbs increased when changing posture, was unaffected by noise or light, no opsoclonus was seen, and the movement could not be suppressed by patient’s will. he could not walk because the movement interfered with his normal walking. general investigations were normal, brain and spinal cord mri, eeg, and emg were normal (figures 1 and 2). the patient received clonazepam 4 mg with remarkable improvement, he started to walk without aid and the movement was totally aborted. he was discharged and sent home in a good condition. 5. discussion the current case is presented with unusual and distinct form of jerks, clinically compatible with manifestation of spinal myoclonus. normal brain and spinal mri exclude structural lesions. there was no ataxia or certain history of toxin, nor a significant family history of spinal myoclonus. we noticed that myoclonic jerk in the current case were doi 10.18502/sjms.v15i2.7272 page 221 sudan journal of medical sciences etedal ahmed a. ibrahim and asmhan m. osman spontaneous and not sensitive to external stimuli; this feature basically excludes the possibility of reticular reflex myoclonus that is usually stimulus-sensitive. the significant exacerbation of myoclonic symptoms before sleep in the current case was noticeable in 1997; matagna et al. first described that spinal myoclonus can arise when a patient is mentally and physically relaxed, particularly close to the onset of sleep. they further discovered that jerks occurred when alpha activities on eeg were recorded. 6. conclusion in any case of spinal myoclonus, eeg, emg, and brain and spinal cord mri must be done to exclude structural lesions. the best treatment is clonazepam with significant improvement. in segmental spinal myoclonus, botulinum toxin is the best treatment. references [1] shibasaki, h. and hallett, m. (2005). electrophysiological studies of myoclonus. muscle nerve, vol. 31, no. 2, pp. 157–174. [2] brown, p., rothwell, j. c., thompson, p. d., et al. (1994). propriospinal myoclonus: evidence for spinal “pattern” generators in humans. movement disorders, vol. 9, no. 5, pp. 571–576. [3] caviness, j. n. and brown, p. (2004). myoclonus: current concepts and recent advances. the lancet neurology, vol. 3, no.10, pp. 598–607. [4] williams, d. r., cowey, m., tuck, k., et al. (2008). psychogenic propriospinal myoclonus. movement disorders, vol. 23, no. 9, pp. 1312–1313. [5] esposito, m., edwards, m. j., bhatia, k. p., et al. (2009). idiopathic spinal myoclonus: a clinical and neurophysiological assessment of a movement disorder of uncertain origin. movement disorders, vol. 24, no. 16, pp. 2344–2349. [6] van der salm, s. m., koelman, j. h., henneke, s., et al. (2010). axial jerks: a clinical spectrum ranging from propriospinal to psychogenic myoclonus. journal of neurology, vol. 257, no. 8, pp. 1349–1355. [7] keswani, s. c., kossoff, e. h., krauss, g. l., et al. (2002). amelioration of spinal myoclonus with levetiracetam. journal of neurology, neurosurgery, and psychiatry, vol. 73, no. 5, pp. 457–458. doi 10.18502/sjms.v15i2.7272 page 222 introduction spinal myoclonus treatment of spinal myoclonus case description discussion conclusion references sudan journal of medical sciences sjms special issue 2020: competing with covid-19 in sudan, doi 10.18502/sjms.v15i5.6983 production and hosting by knowledge e letter to the editor gamal abdalla ejaimi (md),1 zakaria hassan elrosassy (md),1 and sittelnissa saeed ahmed (da, bahs)2 1department of anesthesia and intensive care, taiba hospital, kuwait 2department of anaesthesia and intensive care, aseer central hospital, abha, ksa dear sir, one of the most serious complications of the coronavirus disease 2019 (covid-19) is acute severe respiratory syndrome mandating intensive care admission and assisted ventilation [1]. pneumonia, hypoxemic respiratory failure and acute respiratory distress (ards), shock, and multi-organ failure, are the most common complications of severe covid-19, along with the complications associated with prolonged hospitalization – including secondary nosocomial infection, thromboembolism, gastrointestinal bleeding, and critical illness polyneuropathy and myopathy [2]. endotracheal intubation (eti) is a particularly challenging element of covid-19 for staff performing these procedures owing to the high risk of transmission of the infection. therefore, anesthesiologists, intensive care staff, and emergency physicians are the most exposed groups, and guidance on the therapeutic management of patients with covid-19 is vitally important to ensure the safety of key healthcare staff [3]. a videoassisted laryngoscope is recommended for intubation of covid-19 patients. however, it was shown that intubation utilizing video-assisted laryngoscope required extra time compared to a regular laryngoscope. in this letter, we want to suggest the adoption of a modified technique for video-assisted laryngoscope intubation which could be used successfully in covid-19 patients. at present, the therapeutic strategies to deal with covid-19 are focusing on supportive treatment for affected patients. in some communities, preventive measures have been applied aggressively in order to reduce the transmission rate. across the world, health experts and scientists are working hard to control and treat the disease [2, 3]. at the time of writing, the accepted science is that the disease is transmitted via droplets from direct contact or indirect through waste and fluid secretions. the minimal protective personal equipment (ppe) required during the managing of suspected or confirmed cases of covid-19 include: a ffp2 or ffp3 respirators (for respiratory protection); goggles or face shields (for eye protection); long-sleeved water-resistant gowns for body protection); and gloves (for hand protection) [4]. airway manipulation is considered an aerosol-generating condition. so, the association of anesthetists have recommended precautions and guidelines during high-risk procedures, including intubation to protect the staff and decrease the transmission of the disease. the association also advices the avoidance of high flow devices during intubation, the use of video-assisted laryngoscopy, the sheathing of all equipment where possible, and the use of ultra-rapid sequence intubation or small tidal volumes with manual ventilation [4]. how to cite this article: gamal abdalla ejaimi (md), zakaria hassan elrosassy (md), and sittelnissa saeed ahmed (da, bahs) (2020), sudan journal of medical sciences, vol. 15, issue no. 2, pages 5–8. doi 10.18502/sjms.v15i5.6983 page 5 corresponding author: gamal abdalla ejaimi; email: gamalejaimi@hotmail.com received 20 april 2020 accepted 4 may 2020 published 10 may 2020 production and hosting by knowledge e gamal abdalla ejaimi et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:gamalejaimi@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences gamal abdalla ejaimi et al eti in covid-19 patients is a particular concern for health care providers. in a critically ill patient, the eti is especially difficult as a proper airway assessment is not possible and may therefore increase intubation time. during intubation with a regular laryngoscope, the health practitioner needs to be extremely close to the patient’s airway to see the opening of the glottis. this heightens the risk of contracting covid-19 from the infected patient (figure 1a). a video-assisted laryngoscope is recommended by the association of anesthetists because it increases the distance from the patient’s airway. however, studies performed in emergency departments have shown that intubation using this method requires significantly more time in comparison with the regular laryngoscope [5]. we suggest that shortening the glidescope video-assisted laryngoscope intubation time could help in decreasing the risk of cross-infection [4]. during traditional intubation with a glidescope, the blade is inserted first, followed by optimization of the glottis opening, and finally the insertion of endotracheal tube (ett) via the mouth for tracheal intubation (figure 1b). using the combined glidescope technique, both the glidescope blade and ett were inserted at the same time, and the glottis opening will be optimized for tracheal intubation (figure 2). the combined glidescope technique was evaluated by ejaimi et al. and they found that the exposure time to contaminated airway will be shortened while maintaining the distance from it [6]. using this technique, they achieved successful intubation in all difficult airway patients in less than 15 seconds from the beginning of the blade insertion. adding a disposable, transparent plastic sheet covering the patient’s upper chest and head could also facilitate this technique as the insertion of the blade and ett will be carried in one step and so no double movement (figure 3). using this alternative technique for video-assisted laryngoscope for endotracheal intubation in covid-19 patients could shorten the exposure time during the procedure while ensuring a larger distance from the patient’s airway. figure 1: (a) endotracheal intubation with a regular laryngoscope. left: insertion of the laryngoscope blade to see the glottis opening. right: insertion of the ett under vision (practitioner is closed to patient airway). (b) traditional intubation with glidescope. left (step one): insertion of the glidescope blade. right (step two): insertion of the ett following optimization of glottis view. doi 10.18502/sjms.v15i5.6983 page 6 sudan journal of medical sciences gamal abdalla ejaimi et al figure 2: combined intubation with glidescope. both the glidescope blade and ett are inserted together. figure 3: combined intubation with glidescope and covering the patient chest and head with transparent plastic sheet for double protection. references [1] guan, w.j., et al. (2020). clinical characteristics of coronavirus disease 2019 in china. n. engl. j. med. [2] coronavirus disease 2019 (covid-19). centers for disease control and prevention. 2020 [cited 1 april 2020]. available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidancemanagement-patients.html [3] greenland, j., michelow, m., wang, l. and london, m. (2020). covid-19 infection: implications for perioperative and critical care physicians. anesthesiology. [epub ahead of print]. doi: https://doi.org/ 10.1097/aln.0000000000003303 [4] association of anesthetists. (2020).anesthetic management of patients during a covid19 outbreak. available from: https://anaesthetists.org/home/resources-publications/anaesthetic-management-ofpatients-during-a-covid-19-outbreak. doi 10.18502/sjms.v15i5.6983 page 7 https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html https://doi.org/10.1097/aln.0000000000003303 https://doi.org/10.1097/aln.0000000000003303 https://anaesthetists.org/home/resources-publications/anaesthetic-management-of-patients-during-a-covid-19-outbreak https://anaesthetists.org/home/resources-publications/anaesthetic-management-of-patients-during-a-covid-19-outbreak sudan journal of medical sciences gamal abdalla ejaimi et al [5] platts-mills, t.f.et al. (2009). a comparison of glidescope video laryngoscopy versus directlaryngoscopy intubation in the emergency department. acad. emerg. med., vol. 16, issue 9, pp. 866-871. [6] ejaimi, g., et al. (2020). a step ahead for difficult airway management using glidescope®: a prospective, randomised, comparative study. euro. med. j. innov., vol. 4, issue 1, pp. 57-62. doi 10.18502/sjms.v15i5.6983 page 8 references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7749 production and hosting by knowledge e research article the role of pet-ct in gastric cancer — a narrative review raluca-ioana dascălu1, dan nicolae păduraru1,2, alexandra bolocan1,2, daniel ion1,2, and octavian andronic1,2 1the university of medicine and pharmacy carol davila, bucharest, romania 2university emergency hospital of bucharest, romania abstract background: gastric cancer is one of the most common and leading causes of cancer death worldwide, with an increasing risk and prevalence. although the usage of 18-fdg pet-ct in gastric cancer evaluation remains a matter of debate and is not consistently recommended by international guidelines, our descriptive review aims to highlight its actual role in the diagnostic accuracy, staging, therapeutic management, and relapse monitoring of this malignancy. methods: the current research was conducted using scholarly databases including pubmed, scopus, and google scholar by searching useful science journals, references, and abstracts on the topic. the keywords used were “gastric cancer” and “pet-ct”. results: 18-fdg pet-ct remains a promising method with increasing clinical utility not only across a wide variety of malignancies, but also among gastric cancer patients. conclusions: we are certain that with further improvements, this technique could improve the diagnosis and evaluation of gastric cancer, and make it more approachable and accurate. keywords: gastric cancer (gc), pet-ct, 18-fdg pet-ct, 18f-fdg uptake, cect (contrast-enhanced ct) 1. introduction gastric cancer is one of the most common and leading causes of cancer death worldwide, with an increasing risk and prevalence. when talking about gastric cancer, we usually refer to adenocarcinomas, whereas this histopathological type represents about 90% of the cases. there are also other less-common gastric malignancies, such as lymphomas, gastrointestinal stromal tumors (gist), neuroendocrine tumors, or metastases located at this level. geographical variations seem to be marked in the incidence of this malignancy, with the highest rates reported in east asia, south america, and eastern europe and how to cite this article: raluca-ioana dascălu, dan nicolae păduraru, alexandra bolocan, daniel ion, and octavian andronic (2020) “the role of petct in gastric cancer — a narrative review,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 332–344. doi 10.18502/sjms.v15i3.7749 page 332 corresponding author: raluca-ioana dascălu received 22 june 2020 accepted 3 september 2020 published 30 september 2020 production and hosting by knowledge e raluca-ioana dascălu et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences raluca-ioana dascălu et al the lowest rates in the united states and western europe [1]. moreover, studies have shown that the incidence has increased among elderly patients with peaks in the seventh decade, especially in men, who are more commonly affected than women, with the male incidence rates being twice as that of females. also, there is an inverse proportional link between gastric cancer incidence and social class, with lower rates in professional groups and higher rates in unskilled laborers [2]. however, in western countries, survival rates seem to increase progressively, and in japan, due to the routine screening programs and the focused management of prognosis-related factors, it seems to be the highest [3]. it is well-known that there are plenty of factors involved in the etiology of gastric cancer, such as helicobacter pylori infection, smoking and alcohol, dietary factors, atrophic gastritis, partial gastrectomy, epstein–barr virus, or genetic predisposition. based on the anatomical location, tumors can either be proximal (cardiac and esogastric junction) or distal (basal, bodily or antral); the incidence of the proximal tumors seems to be increasing. microscopically, there are several histological classifications for gastric adenocarcinoma, and the most widely used classification was proposed by lauren, dividing gastric cancer into diffuse and intestinal types [2]. when it comes to 18-fdg pet uptake, it might be difficult to differentiate the normal uptake from pathological. many benign lesions like polyps, gastritis, or even normal gastric mucosa could show moderate-to-intense 18f-fdg uptake, hence 18f-fdg might not be a cancer-specific agent [5]. in the nondistended stomach, 18-fdg pet may normally present diffusely increased uptake, as well as in the gastroesophageal junction. in this case, it is also likely to be physiological due to normal muscular contraction of the lower esophageal sphincter, when there are no ct abnormalities. a similar situation can be found in gastroesophageal reflux disease [6]. moreover, several studies have shown that there is a considerable interdependence between 18-fdg pet uptake and patient survival and that standardized uptake values (suvs) are important in follow-up of patients and estimating the prognosis. so, it seems that unlike patients with low suvs, those with high tumor suvs had lower prognosis with lower rates of survival [7]. also, a strong connection can be noticed between suv and the primary size of tumors [7], whereas, if tumors exceed more than 3.5 cm and have a deeper invasion, detection rates also increase. additionally, it looks like that the intestinal type of gastric adenocarcinoma is associated with a higher mean suv (7.7), while in mucinous and signet ring cell tumors, there is a modest fdg activity (suv mean, 4.2). the explanation for this could be the lower expression of glut-1 transporters on doi 10.18502/sjms.v15i3.7749 page 333 sudan journal of medical sciences raluca-ioana dascălu et al the cell membrane surface, an increased amount of intracellular mucin in mucinous and signet ring cell tumors, or the decreased cellularity [6]. an accurate evaluation and early diagnosis are important in deciding not only regarding the prognosis, but also the treatment. for the patients who present with advanced gastric cancer (agc), some efficient techniques are in demand for the accuracy of staging and quantitative evaluation, so as to enhance an appropriate selection of treatments. it is of great importance for patient management and surgical planning of the lymph node involvement, distant metastasis and an accurate staging, including the full disclosure of the local invasion extent [4]. moreover, the results of pet imaging proved to have a powerful impact on patient management, either by avoiding previously planned therapeutic procedures or by using previously unexpected therapeutic procedures [30]. considering the great importance of the therapy outcomes in the management of the patients, with personalized treatment and guiding future therapy improvements, it appears that pet-ct technology could be effective in monitoring tumor response to treatments and might show prognostic value with the potential to change therapeutic strategies [3]. it seems that over the years, the clinical evaluation of gastric cancer has strongly improved with the conventional tools like computed tomography (ct), magnetic resonance imaging (mri), endoscopic ultrasound (eus), pet-ct and laparoscopic staging, although they all have some technical limitations [3]. using 18f-fluorodeoxyglucose (fdg), positron emission tomography (pet) turned out to have significant advantages in therapeutic evaluation, staging, metastases, and recurrence in plenty of malignancies by providing metabolic information about tumors [4]. basically, in contrast with other imaging tools, such as ct and mri, which reflect primarily anatomical structure, pet reflects biological functions in tissue and allows noninvasive imaging of physiological parameters within the body, such as metabolic activity and perfusion, using tracers labeled with positron-emitting radioisotopes. in pet, the spatial distribution and concentration of administered positron-emitting compounds are used to generate cross-sectional images through the body that reflect pathological states or elucidate physiological processes, leading to applications in clinical practice as well as in research. the principal clinical uses of pet in gastroenterology are in the area of oncology [2]. 2. materials and methods in order to approach and maybe give a better understanding of how gastric malignancies could be present and recognized on 18-fdg pet-ct, we analyzed the studies of patients doi 10.18502/sjms.v15i3.7749 page 334 sudan journal of medical sciences raluca-ioana dascălu et al performed and described in literature articles. our research was conducted on pubmed, scopus, and google scholar databases comprising useful science journals, references, and abstracts on the topic of our interest, and using the following keywords: “gastric cancer” and “pet-ct”. the results were filtered by year (published in the last 10 years), language (english), and article type (original article and review). 3. results due to the unclear impact of 18-fdg pet-ct on gastric cancer staging, the primary lesion (t) staging, the lymph node staging (n), and the distant metastases (m) staging, also the involvement of 18-fdg pet-ct in response evaluation and relapse monitoring, we followed the results and discussions described in the different studies. it is commonly believed that 18-fdg pet-ct improves tnm staging. taking into consideration the primary lesion staging, different factors may influence the diagnostic accuracy, such as the histological type of the tumor, its size or location, as well as the physiological fdg uptake by the gastric wall [4]. it looks like, among studies, when using 18f-fdg-pet alone for the detection of primary lesion, the sensitivity rate ranges between 58 and 94% (median 81.5%) and the specificity, however, ranges between 78 and 100% (median 100%). also, when it comes to early gastric cancer (egc), it has been noticed that the detection rate might be even lower: in egc, only the intestinal type could be detected with 18f-fdg-pet [8]. although there is no agreement on its benefit, the national comprehensive cancer network (nccn) recommends the use of 18f-fdg petct in the preoperative staging of gastric cancer. besides, several studies investigated its role in the primary staging of gastric cancer in comparison with cect (contrastenhanced ct) as routine staging method. for instance, in a study which investigated a group of 31 patients (24 m; 7 f; mean age: 58.9 ± 12.6 years) for primary staging of gastric cancer during one year (between june 2011 and june 2012), primary tumor was detected in 20 patients by 18f-fdg pet-ct and in 23 patients with cect [9]. also, while in the first clinical studies, the accuracy, sensitivity, and specificity of 18f-fdg pet-ct for detecting primary tumor has been reported as 93%, 100%, and 95%, respectively [10], further studies showed a sensitivity as low as 60%. on the other hand, in advancedstage gastric cancer (agc), regarding the detection of primary tumor, a sensitivity of pet-ct as 93% and cect as 90% was reported by young ke et al. [11]; also, shimizu k et al. discovered that mucosal cancers have a lower detection rate than submucosal ones (16.6 vs 68.8%) [12]. it appears that, even though recent studies suggest that there might be an evolving role for the diagnosis of primary gastric tumors, literature suggests doi 10.18502/sjms.v15i3.7749 page 335 sudan journal of medical sciences raluca-ioana dascălu et al the potential utility of performing later time-point images to improve the detectability of gastric cancer [13]. therefore, fdg-pet provides little information concerning the layer of the gastric wall involved and the invasion of adjacent organs. when it comes to gastric lymph nodes, an effective classification belongs to the japanese association for gastric cancer, according to which there are 16 perigastric ganglion groups, divided in four drainage stations from n1 to n4, within the location of the primary tumor. this grouping system is the result of studies of lymphatic flow in different tumor locations, along with survival associated with metastases at each nodal station. thus, the first station (”proximal” ganglion station – n1) consists of the first six groups (left and right paracardial ln, ln along the left, the right and the short gastric vessels, ln along the left and the right gastroepiploic vessels, suprapyloric ln and infrapyloric ln); the second station (“distal” ganglion station – n2) consists of: group 7 – ln along the left gastric artery, group 8 – ln along the common hepatic artery, group 9 – ln along the celiac artery, group 10 – ln along the splenic hilum, and group 11 – ln along the splenic artery. the rest of the groups (12–16) constitutes the metastatic n3 and n4 stations: group 12 – ln in the hepatoduodenal ligament, group 13 – retropancreatic ln, group 14 – ln along the mesenteric artery, group 15 – ln along the middle colic artery, and group 16 – satellite ln of the aorta and inferior vena cava. depending on the gastrectomy performed being partial or total, d1 dissection is defined as a dissection of all the first group nodes and some of the station 7 nodes. d2 dissection is defined as dissection of all the first and the second group nodes, while d3 is defined as dissection of all the groups. since in agc, all patients undergo d1 dissection anyway, it seems that detecting n1 disease status might not influence the surgical management of patients with gastric adenocarcinoma [14]. so that, a greater clinical impact could determine the n2 or n3 disease status, considering that the presence of n2 disease might increase the extent of lymph node dissection from d1 to d2 or greater [15]. it is considered necessary to lift a minimum of 15 nodes together with the resection piece. comparing with eus, mri, or ct, no significant diagnostic difference was reported for n staging in gastric malignancies. literature has pointed out major limitations of ct in detecting cancerous involvement of normal-sized lymph nodes; also, it cannot differentiate between reactive hyperplasia and metastatic enlargement. however, other individual studies claimed that fdg-pet or pet-ct was less sensitive, but more specific, contrasting with commonly used ct and mri [17, 18]. furthermore, in a series of 59 patients confirmed with regional lymph node metastases, while the accuracy and sensitivity of pet-ct was found to be inferior to cect, the specificity and positive predictive value for pet-ct seemed to be considerably higher than for ct [11]. both doi 10.18502/sjms.v15i3.7749 page 336 sudan journal of medical sciences raluca-ioana dascălu et al the 18f-fdg-pet and ct have reduced sensitivity in detecting n2 and n3 lymph node stations, but even so, the specificity of 18f-fdg-pet ranges from 91 to 100% (median: 96%) for n1 and n2 stations [7]. there are plenty of factors influencing or compromising the sensitivity of fdg-pet for n staging, such as the histological type of the primary tumor, the size of metastatic lymph nodes, or the high physiological uptake background from the normal gastric wall. for instance, while some cell types might be detected with moderate sensitivity (30–71%), others, like signet ring cell carcinoma, reveal the lowest sensitivity (15%) [7]. while the current 18f-fdg-pet scanners have 4–10 mm spatial resolution, perigastric n1 lymph nodes or metastatic lymph nodes smaller than 3-4 mm are beyond the detection capacity of most pet scanners. in order to represent local metastasis, regional lymph nodes should meet certain criteria: round shape, exhibiting central necrosis with marked or heterogeneous enhancement, should be solitary or separate nodes of 8 mm or greater in the long axis diameter. however, literature suggests that 55% of the metastatic lymph nodes usually have a diameter of 5 mm or less [16]. additionally, the nearby primary tumor could generate a radioactive volume effect, so that the discrimination of some small lymph nodes could be even more difficult [4]. besides, a link has been shown between the suvmax of the lymph nodes and the suvmax of the primary tumor and one report pointed out that in patients without fdg-avid primary tumors, 60–70% of lymph node metastases could not be detected [11]. another study revealed that a poor prognosis in this malignancy is significantly associated with a high nodal suvmax and, so as to predict survival in gastric cancer, metabolic information of metastatic lymph nodes represented by nodal suvmax could be more important than primary tumor [5]. taking all the discussions into account, we can affirm that fdgpet or pet-ct usually proves a higher specificity than other commonly used imaging techniques in the n staging of gastric cancer. furthermore, owing to this high specificity, pet-ct has valuable potential for determining lymphadenectomy or reducing futile laparotomies [6]. it is commonly known that the most frequently targeted sites of distant metastases from gastric adenocarcinomas are within the abdominal cavity (including the peritoneal surfaces, liver, adrenals, kidneys, ovaries, and spleen), in the left supraclavicular lymph nodes, and in the bones. frequently, distant metastases are detected by using contrast ct, however, pet-ct might be more useful in detecting distant sites of solid organ metastases because it seems an excellent adjunct modality to detect these anatomically small but potentially metabolically active focuses of metastatic disease [19]. thus, recent studies showed that fdg-pet-ct imaging was able to detect solid organ metastasis (lungs, liver, bone, or adrenal gland) with high sensitivity (95.2%) and specificity (100%) doi 10.18502/sjms.v15i3.7749 page 337 sudan journal of medical sciences raluca-ioana dascălu et al [20]. regarding bone metastases, whole-body bone scanning is the most preferred way to evaluate the status, so as, one study revealed the comparison between the value of fdg-pet and whole-body bone scintigraphy for the determination of bone metastasis in gastric cancer patients. the authors of the study concluded that fdg-pet was superior for the detection of synchronous bone metastasis, even if the two modalities had a similar sensitivity and accuracy [21]. when compared with ct, fdg-pet usually shows a lower sensitivity especially for determining peritoneal seeding, maybe because of the small and diffuse growing patterns or the diffuse histological type of gastric cancer. therefore, many studies propose ct for diagnosing peritoneal metastasis because of its high quality [22]. however, even if for identifying peritoneal metastases of gastric cancer it might not increase benefit to high-quality contrast ct, using fdg-pet-ct in addition to ct, eus or laparoscopy prove to have some advantages both therapeutically and economically speaking; hence, unecessary gastrectomy could be avoided in almost 10% of patients and more than $10,000 could be saved per patient [23]. despite its limitations, the literature has proven that preoperative 18f-fdg-pet-ct could provide meaningful information and emerge as an effective instrument not only for therapeutic evaluation, but also for prognosis and recurrence after surgical resection in patients with gastric cancer. although collective data does not appear to fully agree, preoperative fdg uptake has been established as an autonomous and considerable prognostic factor after curative gastrectomy [24]. conventional imaging techniques might be noninvasive and the cheapest of the available methods, but they present limitations regarding the accuracy of recurrence assessment and they have limited role in differentiating post-surgical changes from local tumor recurrence [25]. in one study evaluating 130 patients, 91 of them had recurrent disease, while the remaining 39 were negative for recurrence. when comparing the final diagnosis with pet-ct findings, among 91 patients with true recurrence, 83 showed positive and 8 showed negative fdg uptakes. the remaining 39 patients who did not have true recurrence showed positive fdg uptakes in 15 and negative in 24 patients. therefore, the sensitivity turned out to be 91.2%, specificity 61.5%, and accuracy of pet-ct 82.3%. taking the results into account, the study suggests that pet-ct might be greatly effective in detecting or confirming recurrence once a patient with gastric cancer is clinically or radiologically suspicious of recurrence during follow-up [25]. another study evaluated the correlation between suvmax and cancer recurrence: lee and colleagues [26] noticed that on 18f-fdg-pet, a suvmax equal or higher than 8.2, represents a poor prognostic factor associated with an increasing risk of doi 10.18502/sjms.v15i3.7749 page 338 sudan journal of medical sciences raluca-ioana dascălu et al cancer recurrence after curative surgical resection for gastric cancer patients who did not receive any neoadjuvant therapy. in addition, a significantly lower incidence of recurrence and better recurrence-free survival was seen after the surgery in patients with lower preoperative fdg uptake in the gc [4, 24]. also, there are debates focused on the comparison between cect, the most frequently used imaging technique for gastric cancer, and fdg pet-ct, concerning aftersurgery surveillance. while some studies suggest that these two might share a similar performance in detecting post-surgery recurrence [27], others reveal that fdg pet-ct might be superior. hence, analyzing both the sensitivity and specificity of fdg pet-ct in determining gastric cancer recurrence after surgical removal, two recent meta-analyses discovered they were 78–86%, 82–88%, respectively [28, 29]. further, with regards to the treatment planning and response to therapy, a majority of patients still relapse following resection; surgical removal with lymph node dissection is currently the only treatment modality that is potentially curative, multidisciplinary treatment planning being mandatory. even so, in addition to the surgical removal for gastric cancer patients, preoperative chemotherapy or radiotherapy have been gaining a great interest and recently has been used in order to improve the relapse-free and overall survival [4]. even if conflicting reports claimed that the survival rate did not reveal a considerable difference between patients with tumor fdg uptakes and those without, evidence has shown that fdg-pet-ct could be an efficient and non-invasive tool concerning therapeutic evaluation. for instance, lower preoperative fdg uptake could predict the curability of the tumor. on the contrary, a positive fdg uptake in local lymph nodes with a higher fdg uptake in the primary tumor have been strongly correlated with noncurative resection, suggesting that these patients should volunteer for neoadjuvant cht [24]. furthermore, after beginning the treatment, changes in fdg uptake related to final outcome were observed. therefore, literature revealed that while metabolic responders proved better prognosis, neoadjuvant therapies might be ineffective in metabolic nonresponders and in patients with reduced fdg uptake [4]. 4. discussions taking everything into account, the main limitations of fdg-pet and pet-ct in diagnosing and evaluating this malignancy arise from the spatial resolution of pet, the histological diversity in gastric cancer and, from the physiological properties of the stomach. when talking about spatial resolution, in the future, it could be improved by doi 10.18502/sjms.v15i3.7749 page 339 sudan journal of medical sciences raluca-ioana dascălu et al optimizing the design of the camera [4]. depending on the tumor being intestinal or non-intestinal, considering that many fdg non-avid histological types strongly reduce the sensitivity of fdg-pet and pet-ct to detect gastric cancer, there are currently under evaluation new tracers such as flt-pet and some metabolic agents as alternatives [4, 7]. as for the physiological properties of the stomach, pharmaceutical interventions, which include muscle relaxants, proton pump inhibitors, and gastric distention by different kind of methods are under debate [4]. furthermore, studies have reported a limited significance of pet in the detection of peritoneal carcinomatosis with a low sensitivity (range: 9–50%; median: 32.5%), but relatively higher specificity (63–99%; median: 88.5%) [7]. this reduced sensitivity could be justified by a small number of tumor cells in pleural, ascites, and bone metastases, the small size of peritoneal lesions (<5 mm), or the fibrosis associated [31]. n staging in gastric cancer is yet not adequate under current circumstances. nevertheless, despite the limitations, 18f-fdg-pet provides useful information on estimating the prognosis and the aggressiveness of tumor. overall, combining the higher sensitivity of ct with higher specificity of pet could be even more beneficial for improving the accuracy of many diseases, including gastric cancer, rather than the use of imaging alone [7]. as future prospects, the clinical usefulness of pet-ct could further increase with application of more effectively techniques. hopefully, the new generation of multimodality imaging equipment, such as pet-mr or pet-ct-mr, will ensure considerable benefits in the diagnosis and evaluation of gastric cancer and many different malignancies [4]. 5. conclusion in the light of the aforementioned discussion, although it seems to be a matter of controversy, the value of 18f-fdg pet-ct remains promising. over the years literature revealed its lower sensitivity due to physical fdg-uptake or involuntary movements of the gastric wall, when compared with other malignancies or other imaging techniques like cect. the limitations of 18f-fdg pet-ct have been proven not only in the early stage and signet ring cell carcinomas, but also in the detection of lymph node metastasis. on the other hand, data suggest that pet-ct could be used in demonstrating occult metastatic disease or for patients in whom metastatic cancer is not evident. furthermore, other studies support the utility of pet-ct in gastric cancer staging, particularly in describing distant or lymphatic metastases beyond compartment i or ii. additionally, some data supports its potential to change therapeutic strategies by higher doi 10.18502/sjms.v15i3.7749 page 340 sudan journal of medical sciences raluca-ioana dascălu et al precision in preoperative staging preventing worthless surgery and higher sensitivity in detecting recurrence in postoperative follow-up of patients; also, needless prolonged chemotherapy and the related toxicity could be prevented with the anticipation of early response to therapy for 18f-fdg-avid tumors. thus, 18-fdg pet-ct remains a promising method with increasing clinical utility not only across a wide variety of malignancies, but also in gastric cancer patients. therefore, with further improvements, this technique could enhance the diagnosis and evaluation of gastric cancer and make it more approachable. declaration section acknowledgements none competing interests none availability of data and material open data funding none references [1] waddell, t., verheij, m., allum, w., et al. (2013). gastric cancer+: esmo-essoestro clinical practice guidelines for diagnosis, treatment and follow-up. annals of oncology, vol. 24, no. 6. [2] yamada, t., alpers, d. h., kalloo, a. n., et al. (2009). textbook of gastroenterology (5th ed.), vol. 1–2, blackwell publishing ltd, usa [3] de raffele, e., mirarchi, m., cuicchi, d., et al. (2017). evolving role of fdgpet/ct in prognostic evaluation of resectable gastric cancer. world journal of doi 10.18502/sjms.v15i3.7749 page 341 sudan journal of medical sciences raluca-ioana dascălu et al gastroenterology, vol. 23, no. 38, pp. 6923–6926. [4] wu, c. x. and zhu, z. h. (2014). diagnosis and evaluation of gastric cancer by positron emission tomography. world journal of gastroenterology, vol. 20, no. 16, pp. 4574–4585. [5] song, b. i., kim, h. w., won, k. s., et al. (2015). preoperative standardized uptake value of metastatic lymph nodes measured by 18f-fdg pet/ct improves the prediction of prognosis in gastric cancer. medicine, vol. 94, no. 26., pp 1-8 [6] malibari, n., hickeson, m., and lisbona r. (2015). pet/computed tomography in the diagnosis and staging of gastric cancers. pet clinics, vol. 10, no. 3, pp. 311–326. [7] atay-rosenthal s., wahl, r. l., and fishman, e. k. (2012). pet/ct findings in gastric cancer: potential advantages and current limitations. imaging in medicine, vol. 4, no. 2. retrieved from: https://www.openaccessjournals.com/articles/petct-findingsin-gastric-cancer-potential-advantages-and-current-limitations.html?fbclid= iwar1fmjh5ytslzly2pplkcckmvzn0splu4za9zelj866aghgzvrlvspmfj5i [accessed on december 16, 2019]. [8] mukai, k., ishida, y., okajima, k., et al. (2006). usefulness of preoperative fdg-pet for detection of gastric cancer. gastric cancer, vol. 9, no. 3, pp. 192–196. [9] filik, m., kir, k. m., aksel, b., et al. (2015). the role of 18f-fdg pet/ct in the primary staging of gastric cancer. molecular imaging and radionuclide therapy, vol. 24, no. 1, pp. 15–20. [10] yeung, h. w. d., macapinlac, h., karpeh, m., et al. accuracy of fdg-pet in gastric cancer. preliminary experience. molecular imaging and biology, vol. 1, no. 4, pp. 213–221. [11] kim, e. y., lee, w. j., choi, d., et al. (2011). the value of pet/ct for preoperative staging of advanced gastric cancer: comparison with contrast-enhanced ct. european journal of radiology, vol. 79, no. 2, pp. 183–188. [12] shimizu, k., ito, k., matsunaga, n., et al. (2005). diagnosis of gastric cancer with mdct using the water-filling method and multiplanar reconstruction: ct-histologic correlation. american journal of roentgenology, vol. 185, no. 5, pp. 1152–1158. [13] perlaza, p., ortín, j., pagès, m., et al. (2018). should 18f-fdg pet/ct be routinely performed in the clinical staging of locally advanced gastric adenocarcinoma? clinical nuclear medicine, vol. 43, no. 6, pp. 402–410. [14] yun, m., lim, j. s., noh, s. h., et al. (2005). lymph node staging of gastric cancer using 18f-fdg pet: a comparison study with ct. journal of nuclear medicine, vol. 46, no. 10, pp. 1582–1588. doi 10.18502/sjms.v15i3.7749 page 342 https://www.openaccessjournals.com/articles/petct-findings-in-gastric-cancer-potential-advantages-and-current-limitations.html?fbclid=iwar1fmjh5ytslzly2pplkcckmvzn0splu4za9zelj866aghgzvrlvspmfj5i https://www.openaccessjournals.com/articles/petct-findings-in-gastric-cancer-potential-advantages-and-current-limitations.html?fbclid=iwar1fmjh5ytslzly2pplkcckmvzn0splu4za9zelj866aghgzvrlvspmfj5i https://www.openaccessjournals.com/articles/petct-findings-in-gastric-cancer-potential-advantages-and-current-limitations.html?fbclid=iwar1fmjh5ytslzly2pplkcckmvzn0splu4za9zelj866aghgzvrlvspmfj5i sudan journal of medical sciences raluca-ioana dascălu et al [15] tamura, s., takeno, a., and miki, h. (2011). lymph node dissection in curative gastrectomy for advanced gastric cancer. international journal of surgical oncology, vol. 2011, no. 1 pp. 1–8. [16] kwee, r. m. and kwee, t. c. (2009). imaging in assessing lymph node status in gastric cancer. gastric cancer, vol. 12, no. 1. pp. 6–22. [17] seevaratnam, r., cardoso, r., mcgregor, c., et al. (2012). how useful is preoperative imaging for tumor, node, metastasis (tnm) staging of gastric cancer? a metaanalysis. gastric cancer, vol. 15, no.1, pp. s3–s18. [18] ha, t. k., choi, y. y., song, s. y., et al. (2011). f18-fluorodeoxyglucose-positron emission tomography and computed tomography is not accurate in preoperative staging of gastric cancer. journal of korean surgical society, vol. 81, no. 2, pp. 104–110. [19] hopkins, s. and yang, g. y. (2011). fdg pet imaging in the staging and management of gastric cancer. journal of gastrointestinal oncology, vol. 2, no. 1, pp. 39–44. [20] chung, h. w., lee, e. j., cho, y.-h., et al. (2010). high fdg uptake in pet/ct predicts worse prognosis in patients with metastatic gastric adenocarcinoma. journal of cancer research and clinical oncology, vol. 136, no. 12, pp. 1929–1935. [21] ma, d. w., kim, j.-h., jeon, t. j., et al. (2013). 18f-fluorodeoxyglucose positron emission tomography-computed tomography for the evaluation of bone metastasis in patients with gastric cancer. digestive and liver disease, vol. 45, no. 9, pp. 769– 775. [22] wang, z. and chen, j. q. (2011). imaging in assessing hepatic and peritoneal metastases of gastric cancer: a systematic review. bmc gastroenterology, vol. 11, no,1 , p. 19. [23] smyth, e., schöder, h., strong, v. e., et al. (2012). a prospective evaluation of the utility of 2-deoxy-2-[18f] fluoro-d-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. cancer, vol. 118, no. 22. pp. 5481–5488. [24] yun, m. (2014). imaging of gastric cancer metabolism using 18 f-fdg pet/ct. journal of gastric cancer, vol. 14, no. 1, pp. 1–6. [25] cayvarl𝚤, h., bekiş, r., akman, t., et al. (2014). the role of 18f-fdg pet/ct in the evaluation of gastric cancer recurrence. molecular imaging and radionuclide therapy, vol. 23, no. 3, pp. 76–83. [26] lee, j. w., lee, s. m., lee, m. s., et al. (2012). role of 18f-fdg pet/ct in the prediction of gastric cancer recurrence after curative surgical resection. european journal of nuclear medicine and molecular imaging, vol. 39, no. 9, pp. 1425–1434. doi 10.18502/sjms.v15i3.7749 page 343 sudan journal of medical sciences raluca-ioana dascălu et al [27] sim, s. h., yu, j. k., oh d.-y., et al. (2009). the role of pet/ct in detection of gastric cancer recurrence. bmc cancer, vol. 9, p. 73. [28] wu, l. m., hu, j. n., hua, j., et al. (2012). 18f-fluorodeoxyglucose positron emission tomography to evaluate recurrent gastric cancer: a systematic review and metaanalysis. european journal of gastroenterology & hepatology, vol. 27, no. 3, pp. 472–480. [29] zou, h. and zhao, y. (2013). 18fdg pet-ct for detecting gastric cancer recurrence after surgical resection: a meta-analysis. surgical oncology, vol. 22, no. 3, pp. 162– 166. [30] bilici, a., et al. (2011). the role of 18f-fdg pet/ct in the assessment of suspected recurrent gastric cancer after initial surgical resection: can the results of fdg pet/ct influence patients’ treatment decision making? european journal of nuclear medicine and molecular imaging, vol. 38, no. 1, pp. 64–73. [31] dassen, a. e., lips, d. j., hoekstra, c. j., et al. (2009). fdg-pet has no definite role in preoperative imaging in gastric cancer. european journal of surgical oncology, vol. 35, no. 5, pp. 449–455. doi 10.18502/sjms.v15i3.7749 page 344 introduction materials and methods results discussions conclusion declaration section acknowledgements competing interests availability of data and material funding references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7013 production and hosting by knowledge e research article distribution of blood groups in patients with angiographically defined coronary artery disease in iranian community yousef rasmi1,2, fatemeh kheradmand1,2, mohadeseh nemati2, leila mollazadeh2, mir-hossein seyyed-mohammadzad3, alireza shirpoor4, and naser khalaji4 1cellular and molecular research center, urmia university of medical sciences, urmia, iran 2department of biochemistry, faculty of medicine, urmia university of medical sciences, urmia, iran 3department of cardiology, faculty of medicine, urmia university of medical sciences, urmia, iran 4department of physiology, faculty of medicine, urmia university of medical sciences, urmia, iran abstract background: in the past, the relationship between coronary artery disease (cad) and blood group type has been studied extensively. the abo blood group has a significant effect on homeostasis and is therefore associated with adverse cardiovascular events. this study aimed to determine the distribution of abo blood group and rhesus (rh) status (abo/rh) in patients with different severity of cad in iranian community. material and methods: a total of 1,236 cad patients undergoing angiography were evaluated and their abo/rh blood type was determined in a study center between february 2005 and december 2010. of the 1,236 records, only 1,046 medical documents recorded the number of involved vessels. the patients were classified according to the number of significantly affected stenotic vessels into single vessel (1vd), two vessels (2vd), and three vessels (3vd) disease subgroups. results: a substantially different abo/rh blood groups distribution was seen in the examined samples (o: 29.7%, a: 39.7%, b: 22.2%, ab: 8.3%, rh positivity: 89.2%). the abo/rh blood group phenotype distribution in cad patients with 1vd, 2vd, and 3vd was as follows: 37.5%, 41.3%, and 41.5%, respectively, for group a; 24.1%, 20.5%, and 20.6%, respectively, for group b; 31.2%, 26.8%, and 30.2%, respectively, for group o; 7.1%, 11.4% and 7.7%, respectively, for group ab (p = 0.26), and 88.7%, 90.5%, and 87.6%, respectively, for rh positivity, (p = 0.47). conclusions: no significant correlation was not found among the abo/rh blood group distribution and the number of vessels involved, however, according to the different distribution of abo/rh blood group in cad patients and healthy population, abo/rh might have an unknown role in cad patients. keywords: coronary artery disease, blood group, stenosis, vessel, rhesus. how to cite this article: yousef rasmi, fatemeh kheradmand, mohadeseh nemati, leila mollazadeh, mir-hossein seyyed-mohammadzad, alireza shirpoor, and naser khalaji (2020) “distribution of blood groups in patients with angiographically defined coronary artery disease in iranian community,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 217–224. doi 10.18502/sjms.v15i3.7013 page 217 corresponding author: fatemeh kheradmand; tel: +984432770698 email: fkheradmand@umsu.ac.ir received 2 june 2020 accepted 17 july 2020 published 30 september 2020 production and hosting by knowledge e yousef rasmi et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:fkheradmand@umsu.ac.ir https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences yousef rasmi et al 1. introduction the abo blood group system was first described by karl landsteiner in 1901 [1]. it consists of three alleles: a and b (co-dominant) and o (recessive) [2, 3]. each a and b allele encodes glycosyltransferases that add the n-acetylgalactosamine and dgalactose to precursor h antigen and convert it to a and b antigen. while o does not encode any transferase enzyme, the h antigen is expressed unchanged in this group [4]. the abo antigens [3] are not only present at the surface of red blood cells (rbcs) but are also widely expressed in a number of human tissues and cells, including sensory neurons, the epithelium, the vascular endothelium and platelets [3]. a number of experimental and clinical studies have evaluated whether the abo blood group could affect the traditional risk factors of arterial or venous thrombotic events [5]. several reports have indicated a specified relationship among non-o blood groups, and the risk of progressing severe manifestations of atherosclerosis [6–8]. atherosclerosis is one of the major causes of adults’ death in numerus countries. atherosclerotic developmental risk factors provide useful ways to prevent coronary artery disease (cad) [9]. gender, obesity, smoking, age, hypertension, diabetes mellitus, and family history are considered as main cardiovascular risk factors [10]. one of the recently published cohort articles of bmc medicine evaluated over 50,000 subjects and demonstrated that almost 6% of total death and 9% of cardiovascular death have non-o blood groups [11]. in addition, some studies have suggested that in a blood group subjects, the incidence of ischemic heart disease may be higher than other blood groups [7, 12]. on the other hand, amirzadegan et al. reported that there is not association between different abo blood types and the development of cad in iranian population [13]. so, the present study aimed to determine the distribution of abo blood group and rhesus (rh) status (abo/rh) in patients with different severity of cad in iranian community. 2. methods 2.1. study design and population in this retrospective study, medical documents of 1,236 cad patients (with documents that showed cardiac disease or suspected for poss it) hospitalized at the department of cardiology, urmia university of medical sciences (umsu), urmia, iran between february 2005 and december 2010 were reviewed. coronary angiography and determination of abo/rh blood group were performed for all patients. subjects were classified into four groups according to the different blood types and two groups according to the rh doi 10.18502/sjms.v15i3.7013 page 218 sudan journal of medical sciences yousef rasmi et al types, respectively: ab-type group, a-type group, b-type group, and o-type blood group and rh-positive and rh-negative groups. further analysis was performed between o type and non-o type. all clinical and demographic data were prepared in the dedicated cardiovascular database. smoking habits, hypertension, diabetes mellitus, hypercholesterolemia, and renal disorders were recorded. however, of the 1,236 cad records, only 1,046 medical documents recorded severity of stenosis. next, according to the results of the angiography, the subjects with stenosis in at least one major coronary artery were classified into three subgroups depending on the number of diseased vessels: patients with single-vessel (1vd), two-vessels (2vd), and three-vessels (3vd) disease subgroups. this research agrees with current ethical considerations and was approved by the medical ethics committee of umsu. 2.2. statistical analysis data were analyzed using the spss version 18. fisher’s exact test, chi-square test, and one way-anova were used to analyze the data from different disease groups. p-value < 0.05 was considered to be statistically significant. 3. results a total of 1,236 medical documents of cad patients were reviewed. table 1 presents the gender, smoking habit, history of diabetes mellitus, hypertension, hyperlipidemia, table 1: the relation of abo/rh blood group distribution with demographics and characteristics of coronary artery disease patients. blood groups rh status a b ab o non-o blood p‡ p¶ rh+ rh– p-value female/male* 187/304 106/169 42/61 139/228 335/534 0.95 0.43 416/686 57/76 0.09 age (mean ± sd) 58.6 ± 11.2 57.7 ± 10.7 58.2 ± 11.5 59.4 ± 11.1 58.3 ± 11.1 0.28 0.28 59.4 ± 11.2 58.7 ± 10.3 0.58 smoking (+/–)* 161/266 99/140 37/58 104/224 298/463 0.09 0.11 359/610 42/77 0.39 diabetes (+/–)* 85/345 41/191 16/76 73/236 (30.9%) 142/612 (23.2%) 0.30 0.04 195/757 19/91 0.25 hypertension (+/–)* 183/248 106/133 36/51 139/161 325/432 0.72 0.17 416/534 48/59 0.49 hyperlipidemia (+/–)* 41/109 23/60 7/19 32/72 71/188 0.93 0.30 89/230 14/30 0.31 renal disorders (+/–)* 13/450 8/255 0/96 11/334 21/802 0.38 0.33 29/1009 3/125 0.52 *different number between groups in table 1 is related to impaired medical documents records. p‡: between different blood groups; p¶: between o and non-o blood groups doi 10.18502/sjms.v15i3.7013 page 219 sudan journal of medical sciences yousef rasmi et al and renal disorders based on the blood group distribution of these persons (p > 0.05). patients included 474 women (38.3%) and 762 (61.7%) men, with a mean age of 58.5 ± 11.4 years, of which 61.9% (401/648) were smokers. the mean age of all types of abo blood group in patients is demonstrated in table 1. the age distribution among different blood groups were alike in patient subgroups (p = 0.28). only the prevalence of diabetes was significantly different in 23.2% (142/612) patients with non-o blood group versus 30.9% (73/236) of patients with group o; table 1 (p = 0.04). as mentioned earlier, of the 1,236 cad patient records, only in 1,046 medical documents had records of number of vessels involved with stenosis. further, of the 1,046 cad patients, 365 (34.9%) patients had 1vd, 317 (30.3%) had 2vd, and 364 (34.8%) had stenosis in 3vd. table 2 shows the abo and rh blood group distribution in 1vd, 2vd, and 3vd patients (p = 0.26 and p = 0.47, respectively). of note, no significant difference was observed in the distribution of 1vd, 2vd, and 3vd stenosis when the patients were divided according to the presence of o and non-o blood groups; table 2 (p = 0.42). table 2: distribution of abo/rh blood group in the number of vessels involved in coronary artery disease patients. blood groups n (%) rh status a b ab o non-o blood type p‡ p¶ 1046 rh+ rh– p-value 1vd 137 88 26 114 251 365 (34.9%) 324 41 2vd 131 65 36 85 232 0.26 0.42 317 (30.3%) 287 30 0.47 3vd 151 75 28 110 253 364 (34.8%) 318 45 1vd = single vessel disease; 2vd = 2 vessels disease; 3vd = 3 vessels disease p‡: between different blood groups; p¶: between o and non-o blood groups 4. discussion abo blood groups are the most studied antigenic system of red blood cells and their phenotypes are easily identified; they have been used as genetic markers in researches of relationship with different diseases [14]. unsurprisingly, the clinical significance of the abo blood group now develops beyond the traditional boundaries of immunohematology and blood transfusion medicine, in which the antigen system appears to play a role in the pathophysiology of most human diseases including cardiovascular disorders [15, 16]. however, the association among abo blood group and cad in clinical practice is unclear. briancari et al. reported that abo blood groups had a very similar distribution between patients undergoing coronary artery bypass graft compared to the general doi 10.18502/sjms.v15i3.7013 page 220 sudan journal of medical sciences yousef rasmi et al population. the study also found that blood type b was associated with higher angiographic scores, but postoperative complications did not differ between groups (17). moreover, the data from the official report of the local blood transfusion center showed the distribution of abo/rh groups in the iranian people as follows: o: 34.7%, a: 33.7%, b: 20.7%, ab: 8.4%. also, positive rh was seen in 89.6% of the healthy population [18]. the result of this study showed a diverse distribution in our evaluated population (o: 29.7%, a: 39.7%, b: 22.2%, ab: 8.3%, and rh+: 89.2%), which may be related to the lower susceptibility of o blood group to cad as presented in table 3. table 3: comparison of the abo/rh groups distribution between iranian healthy population and cad patients a b ab o rh+ iranian healthy population 33.7% 20.7% 8.4% 34.7% 89.6% cad patients 39.7% 22.2% 8.3% 29.7% 89.2% stakisaitis et al. found a relation between b blood group and coronary atherosclerosis in lithuanian women [19], which is not compliant with our study. chen et al. [20] reported that non-o group is associated with the presence of significant cad indicated by > 50% stenosis in ≥ 1 coronary artery in angiography, however, we did not observe any significant association between the o and non-o groups with cad. perhaps, this contradiction is because the study type of these two investigations was different. also, they reported that there was no association between the abo group and the number (1 or 2 or 3) of coronary arteries with > 50% stenosis. omidi et al. [21] in iran investigated the relationship between o and non-o groups with severity of cad and found that there is severe involvement among them. a database of 1,236 patients undergoing coronary angiography were evaluated to better understand the relation among cad severity and abo blood type. the authors of this study analyzed the possible relationship between cad severity and abo blood type, as well as its association with traditional atherosclerosis risk factors. our data do not support the major contribution of abo blood system in severe cad stenosis, and no clinical outcome can be deduced from this data. for many years, the abo blood group has been related with a tendency to venous and arterial disorders including peripheral vascular disease, cad, and venous thromboembolism [7, 12, 22]. non-o individuals have a higher susceptibility to these conditions, which can be due to high levels of plasma viii factors and von-willebrand factor [23]. in the majority of previous studies, patients under study were known case of cad, and this study could not find enough information about abo blood groups and severity of cad. therefore, this study’s investigators designed a study on the abo/rh blood groups distribution in a series of patients who doi 10.18502/sjms.v15i3.7013 page 221 sudan journal of medical sciences yousef rasmi et al were diagnosed angiographically as cad in order to evaluate whether abo/rh blood groups are associated with the number of vessels involved as a risk of cad severity. according to the best of author’s knowledge, there is no other research in iranian society about the evaluation of abo blood type and cad severity. 5. conclusion in this study, no association was observed between the type of abo blood groups and the rate of coronary artery atherosclerotic lesions in iranian patients with chronic cad. also, no significant relationship between o-type blood and the number of vessels involved as a risk of cad severity was observed. funding this paper was extracted from a research grant financially supported by the urmia university of medical sciences, urmia, iran. acknowledgment we would like to thank all the patients who kindly participated in the study. references [1] landsteiner, k. (1961). on agglutination of normal human blood. transfusion, vol. 1, no. 1, pp. 5–8. [2] yamamoto, f.-i., clausen, h., white, t., et al. (1990). molecular genetic basis of the histo-blood group abo system. nature, vol. 345, no. 6272, pp. 229–233. [3] storry, j. and olsson, m. l. (2009). the abo blood group system revisited: a review and update. immunohematology, vol. 25, no. 2, p. 48. [4] lowe, j. b. (1993). the blood group-specific human glycosyltransferases. bailliere’s clinical haematology, vol. 6, no. 2, pp. 465–492. [5] franchini, m., favaloro, e. j., targher, g., et al. (2012). abo blood group, hypercoagulability, and cardiovascular and cancer risk. critical reviews in clinical laboratory sciences, vol. 49, no. 4, pp. 137–149. doi 10.18502/sjms.v15i3.7013 page 222 sudan journal of medical sciences yousef rasmi et al [6] nydegger, u. e., wuillemin, w. a., julmy, f., et al. (2003). association of abo histo-blood group b allele with myocardial infarction. european journal of immunogenetics, vol. 30, no. 3, pp. 201–206. [7] whincup, p. h., cook, d. g., phillips, a. n., et al. (1990). abo blood group and ischaemic heart disease in british men. bmj, vol. 300, no. 6741, pp. 1679–1682. [8] meade, t. w., cooper, j. a., stirling, y., et al. (1994). factor viii, abo blood group and the incidence of ischaemic heart disease. british journal of haematology, vol. 88, no. 3, pp. 601–607. [9] amirzadegan, a., salarifar, m., sadeghian, s., et al. (2006). correlation between abo blood groups, major risk factors, and coronary artery disease. international journal of cardiology, vol. 110, no. 2, pp. 256–258. [10] 27th bethesda conference. (1996). matching the intensity of risk factor management with the hazard for coronary disease events. september 14-15, 1995. journal of the american college of cardiology, vol. 27, no. 5, pp. 957–1047. [11] etemadi, a., kamangar, f., islami, f., et al. (2015). mortality and cancer in relation to abo blood group phenotypes in the golestan cohort study. bmc medicine, vol. 13, p. 8. [12] garrison, r. j., havlik, r. j., harris, r. b., et al. (1976). abo blood group and cardiovacular disease: the framingham study. atherosclerosis, vol. 25, no. 2–3, pp. 311–318. [13] amirzadegan, a., salarifar, m., sadeghian, s., et al. (2006). correlation between abo blood groups, major risk factors, and coronary artery disease. international journal of cardiology, vol. 110, no. 2, pp. 256–258. [14] kanbay, m., gur, g., arslan, h., et al. (2005). the relationship of abo blood group, age, gender, smoking, and helicobacter pylori infection. digestive diseases and sciences, vol. 50, no. 7, pp. 1214–1217. [15] franchini, m., favaloro, e. j., targher, g., et al. (2012). abo blood group, hypercoagulability, and cardiovascular and cancer risk. critical reviews in clinical laboratory sciences, vol. 49, no. 4, pp. 137–149. [16] anstee, d. j. (2010). the relationship between blood groups and disease. blood, vol. 115, no. 23, pp. 4635–4643. [17] biancari, f., satta, j., pokela, r., et al. (2003). abo blood group distribution and severity of coronary artery disease among patients undergoing coronary artery bypass surgery in northern finland. thrombosis research, vol. 108, pp. 195–196. doi 10.18502/sjms.v15i3.7013 page 223 sudan journal of medical sciences yousef rasmi et al [18] pour fathollah, a. a., oodi, a., and honarkaran, n. (2004). geographical distribution of abo and rh (d) blood groups among iranian blood donors in the year 1361 (1982) as compared with that of the year 1380 (2001). blood, vol. 1, pp. 11–17. [19] stakisaitis, d., maksvytis, a., benetis, r., et al. (2002). [coronary atherosclerosis and blood groups of abo system in women (own data and review)]. medicina, vol. 38, no. 2, pp. 230–235. [20] chen, y., chen, c., ke, x., et al. (2014). analysis of circulating cholesterol levels as a mediator of an association between abo blood group and coronary heart disease. circulation: cardiovascular genetics, vol. 7, no. 1, pp. 43–48. [21] omidi, n., khorgami, m. r., effatpanah, m., et al. (2017). association between abo blood group and severity of coronary artery disease in unstable angina. arya atherosclerosis, vol. 13, no. 4, p. 172. [22] koster, t., blann, a. d., briet, e., et al. (1995). role of clotting factor viii in effect of von willebrand factor on occurrence of deep-vein thrombosis. lancet, vol. 345, no. 8943, pp. 152–155. [23] o’donnell, j. and laffan, m. a. (2001). the relationship between abo histo-blood group, factor viii and von willebrand factor. transfusion medicine, vol. 11, no. 4, pp. 343–351. doi 10.18502/sjms.v15i3.7013 page 224 introduction methods study design and population statistical analysis results discussion conclusion funding acknowledgment references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7748 production and hosting by knowledge e research article the best time for completion thyroidectomy on differentiated thyroid carcinoma: a literature review hyder o. mirghani, md, msc department of internal medicine, faculty of medicine, university of tabuk, saudi arabia abstract background: completion thyroidectomy is performed for high-risk differentiated thyroid carcinoma; however, the timing of the completion thyroidectomy is a matter of controversy. the current review aimed to assess the best time for completion thyroidectomy in patients with differentiated thyroid carcinoma. methods: an electronic search was conducted in various databases, such as pub med, google scholar, scopus, and medline, for relevant articles assessing the timing of completion thyroidectomy from the first published article to october 2019. keywords, “completion thyroidectomy” and “timing” were used. the search was limited to articles published in the english language. among the 190 articles retrieved, only 11 fulfilled the inclusion criteria. results: of the 11 articles included, two were from europe, one from africa, one from australia, and seven from asia, and all were retrospective studies with the mean duration of studies being 12.71 ± 12.31 years. five studies (45.5%) showed no effect of timing on the outcomes, two (18.2%) recommended both early and late operation, another two (18.2%) concluded that late operation is better, one (9.1%) found that early surgery is better, while one study (9.1%) stated that the timing of operation should be based on the category of the patient. conclusions: the results were mixed with some studies recommending late completion thyroidectomy, some observing that both early and late thyroidectomy are safe, while some finding no effect of time on the completion thyroidectomy. welldesigned controlled trials will resolve the issue. keywords: early completion thyroidectomy, late thyroidectomy, timing 1. introduction the type of surgery in differentiated thyroid carcinoma is controversial; many authors recommend total thyroidectomy due to the rare metastatic potential, recurrence, morbidity of the second operation, and the effectiveness of radioactive iodine. on the other hand, a conservative approach is recommended based on the observations that the clinical course is not affected by the multifocal disease, anaplastic transformation is how to cite this article: hyder o. mirghani, md, msc (2020) “the best time for completion thyroidectomy on differentiated thyroid carcinoma: a literature review,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 324–331. doi 10.18502/sjms.v15i3.7748 page 324 corresponding author: hyder osman mirghani; associate professor of internal medicine and endocrine, faculty of medicine, university of tabuk, saudi arabia po box 3378 tabuk 51941, saudi arabia. email: s.hyder63@hotmail.com received 22 june 2020 accepted 15 august 2020 published 30 september 2020 production and hosting by knowledge e hyder o. mirghani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:s.hyder63@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hyder o. mirghani very low (<1%), and radioactive iodine therapy is possible with low morbidity [1]. while there is a debate on what needs to be done in patients with lobectomy (conservative approach) during the first operation, a completion thyroidectomy is often suggested in high-risk patients [2] to remove the remaining thyroid tissue after the first surgery when malignancy is found. due to inflammation, edema, and scarring after the first operation, the completion of thyroidectomy is thought to carry a high risk of complications including recurrent laryngeal nerve palsy and hypoparathyroidism due to loss of landmarks [3, 4]. an early completion thyroidectomy is typically the operation conducted within seven days post lobectomy, while a late operation is the one conducted after three months [5]. although the timing of the second operation is critical, the best time remains uncertain. thus, we conducted the current review to assess the timing of completion thyroidectomy in patients with differentiated thyroid carcinoma. 2. materials and methods 2.1. eligibility criteria according to picos we included all articles investigating the timing of completion thyroidectomy, the participants were adult patients with differentiated thyroid carcinoma who underwent completion thyroidectomy. with regards to the outcome measures, all manuscripts that compare early and late completion thyroidectomy in terms of operation complications, recurrence rate, and mortality between the two groups were included. manuscripts published on surgery other than completion thyroidectomy timing were excluded from the review. 2.2. information source and search methods databases such as pub med, scopus, medline, and google scholar were searched for relevant articles including those in press starting from the first published articles to those published until october 2019. the terms used for the search were: “completion thyroidectomy” or “thyroid reoperation” and “timing”. in the current review, the filter was set to english language publications among adults. doi 10.18502/sjms.v15i3.7748 page 325 sudan journal of medical sciences hyder o. mirghani 2.3. data extraction and study selection the abstracts and full articles were screened manually for relevant articles; clearly, irrelevant manuscripts were excluded according to the inclusion and exclusion criteria. the authors’ name, year of publication, country, type of study, number of patients, and the duration of the study were reported (table 2). for the purpose of the current review, an early completion thyroidectomy is defined as an operation within the first seven days post the first operation, while a late thyroidectomy is the one conducted after three months. 2.4. assessment of risk of bias in the included articles the newcastle–ottawa scale for cross-sectional studies was used to assess the quality of the selected studies (table 1). figure 1 shows the different phases of the systematic review. 3. results a total of 190 studies were identified through the database search. next, the duplicate manuscripts were removed and 20 papers were shortlisted, finally, only 11 full-text articles meeting the inclusion criteria of the review were included: (two [18.2%] papers were from europe, one [9.1%] from africa, one [9.1%] from australia, and seven [63.6%] from asia). all studies were retrospective (1616 patients included). the mean duration was 12.71 ± 12.31 years. five studies (45.5%) showed no effect of timing on the outcomes, two (18.2%) recommended both early and late operation, another two (18.2%) concluded that late operation is better, one (9.1%) found that early surgery is better, while one study (9.1%) stated that the timing of operation should be based on the category of the patient. table 2 depicts the details of the studied articles. 4. discussion in the present review, the first published article retrieved [6] concluded that completion thyroidectomy should be performed as early as possible (<7 days) to prevent any permanent damage to the recurrent laryngeal nerve; a study published in germany assessed the papillary and follicular thyroid cancer for disease-free and long-term survival, whereby a completion thyroidectomy was conducted within an interval ranging doi 10.18502/sjms.v15i3.7748 page 326 sudan journal of medical sciences hyder o. mirghani records iden!fied through database searching (n = 190) s c r e e n in g in c lu d e d e li g ib il it y id e n ti fi c a ti o n addi!onal records iden!fied through other sources (n = 0); no other sources records a#er duplicates removed (n = 20) records screened (n = 20) records excluded (n = 9) full-text ar!cles assessed for eligibility (n =11 ) full-text ar!cles excluded (n =0) because they are not randomized trials studies included in the qualita!ve synthesis (n = 11) figure 1: flow diagram of the different phases of the systematic review (prisma flowchart). from three days to four months [7]. the authors suggest that completion thyroidectomy is better performed within seven days or after three months. tan et al. [8] assessed 63 patients (operation time within ten days and after three months) and concluded that the timing of thyroidectomy has no impact on complications; similar findings were observed by makay and colleagues [9] who observed 150 patients (the operation time ranged from five days to six months, followed for recurrent laryngeal nerve injury, transient, and permanent hypothyroidism). balock et al., kepenekçi et al., and erbil et al. [10–12] found that the best time is after three months. cho et al. [13] studied 522 patients with papillary thyroid carcinoma in south korea, the american thyroid association [14], and doi 10.18502/sjms.v15i3.7748 page 327 sudan journal of medical sciences hyder o. mirghani table 1: the quality of the selected studies determined using the newcastle–ottawa scale. author selection compatibility and outcome total score rau et al. 4 2 6 walgenbach et al. 4 3 7 tan et al. 4 3 7 makay et al. 4 3 7 balock et al. 4 1 5 erbil et al. 4 2 6 kepenekçi et al. 4 2 6 cho et al. 4 3 7 glockzin et al. 4 3 7 k𝚤saoğlu et al. 4 2 6 salem et al. 4 3 7 the national comprehensive cancer network (nccn) [15] were followed for the extent of surgery the authors compared early surgery (within three months) and follow-up groups without immediate surgery, the patients were observed for central and lateral recurrences. based on the observation that no differences were found between groups, the authors concluded that the timing of completion thyroidectomy should be based on the patient’s risk category. cho and colleagues’ [13] study was limited due to the short period of follow-up (3.5 years) that may not be enough for metastasis evaluation, and also the fact that four surgeons conducted the operations should be considered, since it is well-known that the access to an experienced surgeons is among the predictive factors of the outcome [16]. moreover, while glockzin et al. [17] concluded that the best time is within three days or after three months, k𝚤saoğlu et al. [1] found no effect of timing on morbidity. on the contrary, a relatively recent study conducted in egypt [18] concluded that the best timing is at least six months after the first surgery. 5. conclusion the time of completion thyroidectomy is better within seven days or after three months. however, some studies found no effect of timing on the outcome. declaration section doi 10.18502/sjms.v15i3.7748 page 328 sudan journal of medical sciences hyder o. mirghani table 2: the timing of completion thyroidectomy and complications. author year country type patients study period result rau et al. 1998 germany retrospective 60 10 years time > 7 days is associated with permanent damage to the recurrent laryngeal nerve walgenbach et al. 2002 germany retrospective 81 16.25 years within seven days or after three months tan et al. 2002 australia retrospective 63 45 years timing has no impact on complications makay et al. 2006 turkey retrospective 150 6.5 years timing has no impact on complications balock et al. 2007 pakistan prospective 141 6.75 years timing does not influence the complications rate erbil et al. 2008 turkey retrospective 60 – 90 days after kepenekçi et al. 2009 turkey retrospective 241 5.67 years can be undertaken at any time cho et al. 2012 south korea retrospective 522 4 years should be based on the patient’s risk category glockzin et al. 2012 germany retrospective 128 17 years within three days or after three months k𝚤saoğlu et al. 2014 turkey retrospective 52 8 years timing of surgery does not affect morbidity salem et al. 2017 egypt retrospective 118 8 the operation should be performed at least six months after the primary surgery acknowledgements the author would like to acknowledge ibrahin eltedlawi, professor of oncology surgery, university of tabuk, saudi arabia for revising this manuscript. ethical considerations the current study has been approved by the ethical committee of the medical college, university of tabuk, saudi arabia. doi 10.18502/sjms.v15i3.7748 page 329 sudan journal of medical sciences hyder o. mirghani competing interests the author declares that there are no conflicts of interest availability of data and material the data included in this manuscript are available upon request funding the manuscript is self-funded and not supported by any institute or organization references [1] k𝚤saoğlu, a., özoğul, b., akçay, m.n., et al. (2014). completion thyroidectomy in differentiated thyroid cancer: when to perform? turkish journal of surgery, vol. 30, pp. 18–21. [2] akcan, a., sözüer, e., aky𝚤ld𝚤z, h., et al. (2008). completion thyroidectomy in well-differentiated thyroid cancers-retrospective clinical study. turkish journal of surgery, vol. 24, no. 83, pp. 88. [3] pironi, d., pontone, s., vendettuoli, m., et al. (2014). prevention of complications during reoperative thyroid surgery. clinical therapeutics, vol. 165, pp. 285–290. [4] li, y. j., wang, y. z., yi, z. b., et al. (2015). comparison of completion thyroidectomy and primary total surgery for differentiated thyroid cancer: a meta-analysis. oncology research and treatment, vol. 38, pp. 528-31. doi: 10.1159/000440690. [5] bin saleem, r., bin saleem, m., bin saleem, n. (2018). impact of completion thyroidectomy timing on postoperative complications: a systematic review and meta-analysis. gland surgery, vol. 7, no. 5, pp. 458–465. doi: 10.21037/gs.2018.09.03. [6] rau, h. m., fass, j., schumpelick, v. (1998). [results of two-stage thyroidectomy in differentiated thyroid gland carcinoma]. langenbecks arch chir suppl kongressbd, vol. 115, pp. 1061–1062. [7] walgenbach, s. and junginger, t. (2002). [is the timing of completion thyroidectomy for differentiated thyroid carcinoma prognostic significant?]. zentralblatt fur chirurgie, vol. 127, no. 5, pp. 435–438. doi 10.18502/sjms.v15i3.7748 page 330 sudan journal of medical sciences hyder o. mirghani [8] tan, m. p., agarwal, g., reeve, t. s., et al. (2002). impact of timing on completion thyroidectomy for thyroid cancer. british journal of surgery, vol. 89, no. 6, pp. 802–804. [9] makay, o., unalp, o., icoz, g., et al. (2006). completion thyroidectomy for thyroid cancer. acta chirurgica belgica, vol. 106, no. 5, pp. 528–531. [10] baloch, m. n., aslam, t., and maher, m. (2007). completion thyroidectomy: relation of timing with complications. pakistan journal of surgery, vol. 23, pp. 245–247. [11] kepenekçi, i., demirer, s., koçak, s., et al. (2009). timing of the reoperation in completion thyroidectomy. turk klin tip etigi hukuku tarihi, vol. 29, pp. 1212–1216. [12] erbil, y., bozbora, a., ademoglu, e., et al. (2008). is timing important in thyroid reoperation? journal of otolaryngology – head & neck surgery, vol. 37, no. 1, pp. 56–64. [13] cho, j. s., yoon, j. h., park, m. h., et al. (2012). observational study of central metastases following thyroid lobectomy without a completion thyroidectomy for papillary carcinoma. journal of korean surgical society, vol. 83, no. 4, pp. 196– 202. doi: 10.4174/jkss.2012.83.4.196. [14] american thyroid association (ata) guidelines taskforce on thyroid nodules and differentiated thyroid cancer; cooper, d. s., doherty, g. m., et al. (2009). revised american thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. thyroid, vol. 19, pp. 1167–1214. [15] sherman, s. i., angelos, p., ball, d. w., et al. (2007). thyroid carcinoma. journal of the national comprehensive cancer network, vol. 5, pp. 568–621. [16] sherman, s. i. (1998). the risks of thyroidectomy: words of caution for referring physicians. journal of general internal medicine, vol. 13, pp. 60–61. [17] glockzin, g., hornung, m., kienle, k., et al. (2012). completion thyroidectomy: effect of timing on clinical complications and oncologic outcome in patients with differentiated thyroid cancer. world journal of surgery, vol. 3, no. 5, pp. 1168–1173. doi: 10.1007/s00268-012-1484-5. [18] salem, m. a., ahmed, b. m., and elshoieby, m. h. (2017). optimum timing and complication of completion thyroidectomy for differentiated thyroid cancer. journal of cancer therapy, vol. 8, pp. 518–526. doi: 10.4236/jct.2017.85044. doi 10.18502/sjms.v15i3.7748 page 331 introduction materials and methods eligibility criteria according to picos information source and search methods data extraction and study selection assessment of risk of bias in the included articles results discussion conclusion declaration section acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8163 production and hosting by knowledge e research article prevalence and risk factors of depression among adult type 2 diabetic patients at al-jemaih diabetic center, dongola, northern state, sudan, 2019 mohamed osman abdelaziz1, mohamed ali alzain2, and mohammed abdalmageed abdalkhaleg3 1associate prof. of internal medicine.department of medicine, faculty of medicine & health sciences, university of dongola, dongola, po box 47 dongola 41111, sudan 2assistant prof. department of community medicine, faculty of medicine & health sciences, university of dongola, dongola, po box 47 dongola 41111, sudan. department of public health, college of public health and health informatics, university of hail, ksa. +966 (54) 8398414 3teaching assistant, department of medicine, faculty of medicine & health sciences, university of dongola, dongola, po box 47 dongola 41111, sudan abstract background: type 2 diabetes and depression are common diseases with bidirectional associations. depression in diabetics leads to poor adherence to diet and medication, poor glycemic control, reduced quality of life, and increased diabetes-related healthcare expenditure. this study aimed at evaluating diabetic patients with depression to improve the quality of care delivered. materials and methods: an institution-based cross-sectional study was conducted among adult type 2 diabetics at al-jemaih diabetic center, dongola, in july– december 2019a standardized pretested questionnaire was used to collect data, and the depression subscale of the patient health questionnaire was used to diagnose depression. chi-square test and logistic regression were used to analyze the data using the statistical package for social sciences version 25.0. results: out of the 407 participants, 282 (69.3%) were females, and more than half were aged between 40 and 59 years. the prevalence of depression among type 2 diabetic patients was 35.6%, ranging from mild (24.3%) to moderate (7.4%), moderately severe (2.2%), and severe depression (1.7%). the risk factors associated with depression in type 2 diabetes were: combining antidiabetic therapy, long duration of diabetes, family history of psychiatric illness, diabetes-related complications, poor glycemic control, and lack of regular exercise. conclusion: more than a third of type 2 diabetics have depression. screening diabetic patients for depression, establishing a psychiatric unit at the diabetic center, and community-based studies are recommended. keywords: diabetes mellitus, depression, dongola, northern state how to cite this article: mohamed osman abdelaziz, mohamed ali alzain, and mohammed abdalmageed abdalkhaleg (2020) “prevalence and risk factors of depression among adult type 2 diabetic patients at al-jemaih diabetic center, dongola, northern state, sudan, 2019,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 408–417. doi 10.18502/sjms.v15i4.8163 page 408 corresponding author: mohamed osman abdelaziz; department of medicine, faculty of medicine & health sciences, university of dongola, po box 47, dongola 41111, northern state, sudan mobile: +249912634357, +24912316669. email: dralomda34@gmail.com received 7 october 2020 accepted 17 december 2020 published 31 december 2020 production and hosting by knowledge e mohamed osman abdelaziz et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dralomda34@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed osman abdelaziz et al 1. introduction the worldwide number of diabetic patients is rising to pandemic levels [1]. the estimated total number of diabetics was 463 million in 2019 and is expected to increase by 51% to 700 million cases in 2045 [1]. the global rise of the diabetic population is more likely to affect low-and middle-income countries than the high-income ones. in the middle east and north african (mena) region, diabetic estimates will rise by 96% from 55 million in 2019 to 108 million in 2045 [2]. sudan was included among the top five countries with the highest prevalence of diabetics in the mena region in 2019; with a prevalence of 17.9%, a total of 3.7 million cases, and one in every six adults with diabetes [3]. previous studies demonstrated high prevalence rates of diabetes in north sudan compared to the other parts of the country [4, 5]. moreover, a strong association has been observed between diabetes mellitus (dm) and mental disorders like depression. depression is a common mental problem, with a global prevalence of 2–6% in 2017, affecting more than 264 million people and tends to increase with age [6, 7]. the overall prevalence of depression in sudan was 3.78% in 2017 [7]. depression is common among diabetic patients and is considered a modifiable risk factor for type 2 diabetes mellitus (t2dm) as well as for the progression of diabetes-related complications [8]. having t2dm more than doubles the risk of depression, and concurrent depression with diabetes is associated with poor adherence to diet and medication, poor glycemic control, reduced quality of life, and increased diabetes-related healthcare expenditure [9]. therefore, it is important to evaluate diabetic patients for depression to improve the quality of care delivered. in different studies, two types of validated questionnaires were used to screen diabetic patients for depression: the patient health questionnaire (phq-9) and the depression subscale of the hospital anxiety and depression scale (hads-d). both questionnaires have been effectively used in different studies among diabetic patients [8, 10, 11]. phq is a self-administered version of the primary care evaluation of mental disorders (prime-md®) instrument used for primary care diagnosis of mental disorders, while the phq-9 subscale is used for depression [12]. literature review revealed one study about the prevalence of depression among t2dm patients in central sudan (omdurman) using the hads questionnaire [13]. thus far, no study has explored depression among diabetics in the northern state, sudan, despite the high prevalence rate of diabetes. therefore, this study aimed to determine the prevalence and associated factors of depression among adult t2dm patients attending regular follow-up at al-jemaih diabetic center in dongola, northern state, sudan. 2. materials and methods 2.1. study design, area, and population an analytical cross-sectional study was carried out among adults with t2dm attending regular follow-up at the al-jemaih diabetic center in dongola, the capital city of the doi 10.18502/sjms.v15i4.8163 page 409 sudan journal of medical sciences mohamed osman abdelaziz et al northern state, sudan, during the period from july 1 to december 30, 2019. the center was initially established in 2003 and then inaugurated after the development as well as renewal by the al-jemaih charity organization (kingdom of saudi arabia) in april 2018. the center offers medical services at primary, secondary, and tertiary levels to diabetic patients from the whole state. to date, 10,163 diabetic patients including 119 diabetic children have been registered and about 150–250 patients are seen daily. 2.2. sample size determination the study population included all adult t2dm patients registered at the center and attending routine follow-up during the study period. the minimum sample size was 379, calculated using the following formula: 𝑧2𝑃 (1 − 𝑃) 𝑑2 , when the prevalence of depression among dm in sudan was considered as 44% [13] with 95% confidence interval and 5% precision. 2.3. ethical considerations ethical approval was obtained from the research ethics committee at the state ministry of health. informed consent was taken from each participant. participants with moderate-to-severe depression were recommended to be seen by a psychiatrist for further assessment and management. 2.4. data collection all adult t2dm patients attending the clinic during the study period were invited to participate. a convenient sampling method was used to select the participants. those who did not agree to participate, children aged <18 years, type 1 diabetic patients, and those who had a recent psychiatric illness or suffered from recent (within one month) loss of a first-degree relative or spouse were excluded from the study. a standardized pretested questionnaire was used to collect data. the questionnaire included personal data, duration, treatment, compliance, follow-up and complications of dm, history of chronic illness or long-term medication, history of tobacco or alcohol use or drug abuse, and family history of psychiatric disease. the participant was considered as having controlled dm if a recent (within three months) glycosylated hemoglobin (hba1c) level was <7 and uncontrolled if the hba1c level was ≥7. the phq-9 was used as a validated screening tool for detecting depression among diabetic patients [12, 14] after it was translated in arabic and the translation was reviewed by an expert. a pilot sample of 30 respondents was used to measure the reliability of the arabic-translated phq-9 (0.778; 95%ci: 0.744–0.809) using cronbach’s alpha test. two general medical practitioners were trained in data collection to explain to the patients in a simple local language, especially those who were not fluent in arabic. phq-9 scores range from 0 (not at all) to 3 (nearly every day) for the nine diagnostic criteria of depression encountered within doi 10.18502/sjms.v15i4.8163 page 410 sudan journal of medical sciences mohamed osman abdelaziz et al the last two weeks [15]. while the total score ranges from 0 to 27 [15], the total phq-9 score of participants is categorized as following: 0–4 = no or minimal depression, 5–9 = mild depression, 10–14 = moderate depression, 15–19 = moderately severe depression, and 20–27 = severe depression [15]. the participants with score ≥5 were classified as having depression in the further analysis. 2.5. data analysis frequency percentage was used to determine the depression prevalence of various degrees of depression, which has been displayed in a histogram. to determine risk factors for depression among diabetic patients, both chi-square and binary logistic regression were used. odds ratios (or) with a confidence interval (ci) were used to present the logistic regression results. p-value < 0.05 was considered statistically significant. all analyses were done using the statistical package for social sciences (spss), version 25.0. (armonk, new york: ibm corp, usa). 3. results a total of 407 diabetic patients were included in the study, of which 282 (69.3%) were females and 125 (30.7%) males. the study observed that more than half of the respondents were aged between 40 and 59 years, belonged to the danaglah tribe, and had an education level below the university degree. in addition, more than twothirds (69.8%) of the diabetic patients in our study were treated by oral hypoglycemic, and almost one-third (33.2%) of them had diabetes-related complications. the majority (82.6%) of the participants had poor glycemic control, and 11.8% of the respondents had a family history of psychiatric illness, while more than half (54%) of the study population did not practice regular excise. chi-square test found that the prevalence of depression among diabetics was significantly increased with long diabetic duration, type of diabetes treatment, presence of complications, family history of psychiatric disease, glycemic control, and exercise status, as shown in table 1. the overall prevalence of depression among diabetic patients was 35.6%, ranging from mild to severe forms of depression, whereas the prevalence of major depression (moderate to severe or phq-9 score of ≥10) was 11.3%, as shown in figure 1. binary logistic regression indicates a positive association between the duration of diabetes and prevalence of depression; whereas diabetic patients with the longer duration (≥20 years) were more than three times (or = 3.55; 95%ci: 1.76–7.13) more likely to have depression compared to those with shorter duration (<5 years). patients treated with a combination of oral hypoglycemic drugs and insulin were more than four times (or = 4.26; 95%ci: 1.02–17.86) more likely to have depression than those treated only through dietary control. furthermore, uncontrolled diabetics and those with diabetesrelated complications, family history of psychiatric disease, and those who had never performed physical exercise were almost twice (or = 1.80; 95%ci: 1.00–3.19), (or = 1.97; 95%ci: 1.07–3.61), and (or = 1.98; 95%ci: 1.07–3.61) more likely to have depression compared to other groups, as shown in table 2. doi 10.18502/sjms.v15i4.8163 page 411 sudan journal of medical sciences mohamed osman abdelaziz et al table 1: baseline characteristics of adult type 2 diabetic patients and the prevalence of depression in al-jemaih diabetic center, dongola, northern state, sudan, 2019. variables total n (%) with depression n (%) without depression n (%) p-value total 407 (100) 145 (35.6) 262 (64.4) – age <40 years 49 (12) 18 (36.7) 31 (63.3) 0.260 40–59 years 228 (56) 88 (38.6) 140 (61.4) ≥60 years 130 (31.9) 39 (30.0) 91 (70.0) gender male 125 (30.7) 44 (35.2) 81 (64.8) 0.905 female 282 (69.3) 101 (35.8) 181 (64.2) tribes danaglah 223 (54.8) 75 (33.6) 148 (66.4) 0.140 mahass 50 (12.3) 21 (42.0) 29 (58.0) halab 43 (10.6) 21 (48.8) 22 (51.2) others 91 (22.4) 28 (30.8) 63 (69.2) education illiterate 171 (42) 58 (33.9) 113 (66.1) 0.670 pre-university 205 (50.4) 76 (37.1) 129 (62.9) university & above 31 (7.6) 11 (35.5) 20 (64.5) dm duration <5 years 124 (30.5) 31 (25.0) 93 (75.0) 0.008 5–10 years 125 (30.7) 46 (36.8) 79 (63.2) 10–15 years 66 (16.2) 25 (37.9) 41 (62.1) 15–20 years 44 (10.8) 17 (38.6) 27 (61.4) ≥20 years 48 (11.8) 26 (54.2) 22 (45.8) type of treatment diet only 12 (2.9) 3 (25.0) 9 (75.0) oral hypoglycemic 284 (69.8) 87 (30.6) 197 (69.4) 0.001 insulin 65 (16) 28 (43.1) 37 (56.9) combined (insulin & tablets) 46 (11.3) 27 (58.7) 19 (41.3) dm complications yes 135 (33.2) 59 (43.7) 76 (56.3) 0.017 no 272 (66.8) 86 (31.6) 186 (68.4) family history of psychiatric yes 48 (11.8) 24 (50.0) 24 (50.0) 0.027 no 359 (88.2) 121 (33.7) 238 (66.3) glycemic control (hba1c) controlled 71 (17.4) 18 (25.4) 53 (74.6) 0.047 uncontrolled 336 (82.6) 127 (37.8) 209 (62.2) exercise yes 187 (49.9) 54 (28.9) 133 (71.1) 0.009 no 220 (54.1) 91 (41.4) 129 (58.6) doi 10.18502/sjms.v15i4.8163 page 412 sudan journal of medical sciences mohamed osman abdelaziz et al figure 1: prevalence of different levels of depression among adult type 2 diabetic patients at the al-jemaih diabetic center in dongola, northern state, sudan, 2019. table 2: factors associated with the prevalence of depression among adult type 2 diabetic patients at the al-jemaih diabetic center in dongola, northern state, sudan, 2019. variable or (95%ci) p-value duration of dm <5 years reference 5–10 years 1.75 (1.01–3.01) 0.045 10–15 years 1.83 (0.96–3.47) 0.065 15–20 years 1.89 (0.91–3.92) 0.088 ≥20 years 3.55 (1.76–7.13) <0.001 type of treatment diet only reference oral hypoglycemic 1.32 (0.35–5.01) 0.679 insulin 2.27 (0.56–9.17) 0.250 combined (insulin & tablets) 4.26 (1.02–17.86) 0.047 glycemic control yes reference no 1.80 (1.00–3.19) 0.049 dm complication no reference yes 1.97 (1.07–3.61) 0.029 family history of psychiatric no reference yes 1.98 (1.07–3.61) 0.029 exercise yes reference no 1.74 (1.15–2.63) 0.009 doi 10.18502/sjms.v15i4.8163 page 413 sudan journal of medical sciences mohamed osman abdelaziz et al 4. discussion depression is common among diabetic patients and affects diabetics in terms of morbidity and mortality. our study showed a lower prevalence rate of depression compared to a previous study among t2dm in omdurman locality, khartoum state, with a prevalence rate of depression of 44% [13]. the difference may be partially explained by the different scoring systems; while the study in khartoum state used the hads questionnaire, this study used the phq-9 score. besides, our prevalence was also lower than most of the international studies assessing depression in t2dm using phq-9 score. a study from suez canal university hospital in egypt revealed a rate of depression of 69% in patients with t2dm [16], while a study conducted in ethiopia showed a depression rate of 54.2% [17]. two studies from india showed that the prevalence rates of depression were 41% and 62% among t2dm [18, 19]. the rate of depression in t2dm varies greatly among different sub-saharan african and middle eastern countries, ranging from as low as 15% in nigeria and 20% in jordan and oman to as high as 70% in iran [20]. the prevalence of major depression was 11.3%, slightly low compared to that of the study from ethiopia with 13% [17]. the relatively low prevalence of depression among t2dm in the northern states compared to the national and international studies might be explained by the good family support of diabetic patients and good community awareness about dm as it is a common disease. this study revealed that the risk factors associated with depression in t2dm were: combined antidiabetic therapy (or = 4.26), long duration of diabetes (or = 3.55), family history of psychiatric illness (or = 1.98), diabetes-related complications (or = 1.97), poor glycemic control (or = 1.80), and lack of regular exercise (or = 1.74). the rates of depression showed no significant difference regarding age, gender, tribe, and educational level. the observed association between combined antidiabetic therapy and depression concurs with an earlier meta-analysis that explored the association between insulin treatment and depression in t2dm; it revealed that insulin therapy was associated with a higher risk of depression [21]. this might be explained by the reluctance of t2dm patients to take insulin as a last option for uncontrolled dm as well as taking multiple medications with increased cost. other reasons include the long duration of t2dm as most patients start insulin late as well as the presence of diabetesrelated complications and comorbidities. regarding the duration of t2dm, symptoms of depression tend to increase early after diagnosis and decrease over a few years and then rise with the longer duration of dm, making a j-shaped curve; the rise with the duration of dm may be related to frailty associated with old age and longer duration [22]. many studies have demonstrated the significant association between depression in t2dm and diabetes-related complications, poor glycemic control, and lack of exercise [23–27]. the family history as a risk factor may be explained by a potential common genetic susceptibility to both t2dm and depression [28], but no study has mentioned a family history of psychiatric illness as a risk factor for depression in t2dm. interestingly, the depression rate was more common in females than males, but the association was not statistically significant. most studies considered female gender a significant risk factor for depression in t2dm [22, 25–27]. doi 10.18502/sjms.v15i4.8163 page 414 sudan journal of medical sciences mohamed osman abdelaziz et al limitations: the current study had the following limitations: first, it was a crosssectional study, which could not determine the causal factors of depression in t2dm patients; second, it was conducted at an institutional but not at the community level as more depressed diabetics might be seen at the diabetic center indicating possible selection bias. however, this is the first study conducted in the northern state, a state with high prevalence rates of dm in sudan, and most likely the second study in sudan, thus adding new insight to a common problem among diabetics. the study also enrolled a reasonable sample size with a high response rate. moreover, the cross-sectional study design would give a quick snapshot of the depression rate among diabetic patients in the state for future interventions. 5. conclusion our study shows that more than a third of t2dm have depression. risk factors for depression in t2dm include combined insulin and oral hypoglycemic drug therapy, long duration of t2dm, family history of psychiatric disease, diabetes-related complications, poor glycemic control, and lack of exercise. screening for depression as well as other psychiatric disorders in all diabetics at the center is necessary and healthcare staff providing diabetic care should be able to diagnose, manage, or refer diabetic patients with depression. the establishment of a psychiatric unit at the center is recommended. further longitudinal large-scale studies and qualitative studies are recommended for in-depth assessment of depression, anxiety, and other psychiatric disorders among diabetic as well as nondiabetic populations. acknowledgements the authors would like to express their gratitude to the staff of al-jemaih diabetic center for their great help in carrying out the study at the center. they are also thankful to the patients who agreed to participate in the study. ethical considerations ethical approval was obtained from the ethics committee of the state ministry of health, northern state, sudan. competing interests the authors declare hereby that there are no conflicts of interest. availability of data and materials all data are available upon reasonable request. doi 10.18502/sjms.v15i4.8163 page 415 sudan journal of medical sciences mohamed osman abdelaziz et al funding no funding was received from any governmental or nongovernmental institution. authors’ contributions abdelaziz mo and alzain ma participated in developing the research concept and design as well as in the training and supervision of the data collectors. abdakhaleg ma performed data collection. abdelaziz mo carried out data entry and alzain ma carried out data analysis using spss. all authors participated in writing, editing, and approving the final manuscript. disclosure: this article or the abstract was not presented in any conference nor it was submitted to any other journal for publication references [1] huizinga, m. m. and rothman, r. l. 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https://www.euro.who.int/en/publications/abstracts/addressing-comorbidity-between-mental-disorders-and-major-noncommunicable-diseases-2017 https://www.euro.who.int/en/publications/abstracts/addressing-comorbidity-between-mental-disorders-and-major-noncommunicable-diseases-2017 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3738724/pdf/hippokratia-16-205.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3738724/pdf/hippokratia-16-205.pdf introduction materials and methods study design, area, and population sample size determination ethical considerations data collection data analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and materials funding authors' contributions disclosure: references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8158 production and hosting by knowledge e research article prevalence of post-partum depression among sudanese women using edinburgh postnatal depression scale (epds) in two major delivery hospitals in khartoum state maram osman elawad mabyoue faculty of medicine, university of khartoum, qasr street. p.o. box 11111, khartoum, sudan abstract background: postpartum depression is a mood disorder that can affect women after childbirth; it can occur at any time during the first year after delivery. mothers experience depressive symptoms that may make it difficult for them to complete daily care activities. the aim of this study was to find out the prevalence of postpartum depression among sudanese women as well as determining the association between postpartum depression (ppd), socio-demographic, and obstetric characteristics. method: in this cross-sectional study, 129 women selected through convenient sampling technique were interviewed; the participants were recruited from the postnatal and child welfare clinics at the saad abueleella and the dream international hospitals. to assess any possible depression, information was collected at six weeks postpartum using a structured questionnaire in addition to a screening tool. results: at a cutoff score of ≥12, the prevalence of ppd was found to be 10.9% (confidence interval 6.5–17.3%); while 79.1% of mothers revealed no signs of ppd and scored <9 points, 10.1% scored 9–11, indicating a need for extra visits. interestingly, 59.7% of the respondents were aged between 25 and 35 years, 76% were university graduates, 64.3% housewives, 20.9% had obstetric complications, 3.1% reported a history of ppd, and almost 97.7% breastfed their babies. moreover, ppd was found to be associated with occupational status (p = 0.01) and a previous history of ppd (p = 0.01). conclusion: the prevalence of postpartum depression was 10.9% among the studied sample. interventions to address its risk factors should be implemented, physicians and health personnel should be qualified on screening and referring depressed mothers for further clinical assessment. keywords: postpartum depression, prevalence, screening, sudanese 1. introduction 1.1. background depression is a serious public health problem that occurs more commonly in women than men during their childbearing years [1]; depressive disorders are believed to be the leading cause of global disability burden worldwide in 2020 [2]. how to cite this article: maram osman elawad mabyoue (2020) “prevalence of post-partum depression among sudanese women using edinburgh postnatal depression scale (epds) in two major delivery hospitals in khartoum state,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 355–370. doi 10.18502/sjms.v15i4.8158 page 355 corresponding author: maram osman elawad mabyoue; faculty of medicine, university of khartoum, qasr street. p.o. box 11111, khartoum, sudan email: maramalawad1@gmail.com received 10 october 2020 accepted 15 december 2020 published 31 december 2020 production and hosting by knowledge e maram osman elawad mabyoue. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:maramalawad1@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences maram osman elawad mabyoue since the risk of developing mental disorders during pregnancy and postpartum period is higher for a large number of women, motherhood tends to bring serious emotional disturbances and sad times rather than happiness and joy [3]. postpartum depression (ppd) includes feeling of sadness, exhaustion, fear, and mood instability. although it usually occurs within four weeks after delivery, it has also been reported to occur in the month prior to delivery, which is known as ”depression with peripartum onset” [4]. the possible risk factors for ppd may include: a past history of anxiety and depression “vulnerability,” poor social support, adverse life events, unplanned pregnancy, low income, and immediate hormonal changes following the birth [5]. in addition, several studies have demonstrated a decreased prevalence of breastfeeding among depressed mothers compared to non-depressed ones [6]. the interaction of these factors is likely to play a role in causing ppd, and addressing these modifiable risk factors may prevent its development. a collaborative-care approach between mental health professionals and obstetricians would be appropriate to identify the mothers who are at high risk for developing ppd. settlement of marital and family conflicts before conception, helping the mothers to set up a support plan, to have a realistic expectation of birth and parenting, resolving self-esteem issues, and encouraging them to quit smoking might help to decrease their chances of acquiring ppd [7]. this should illustrate the need for raising awareness among women, their families and their communities about the symptoms, causes, treatment, and consequences of maternal depression. support programs and group classes may help women to form social connections, build a social network to make them feel supported and to promote their comfort with care services. the clinician should also pay attention to those women at risk to provide help as early as possible and to discuss treatment options in a sensitive and culturally appropriate way to insure cooperation [8]. 1.2. problem statement the prevalence of non-psychotic post-partum depression in western countries is approximately 10–15% [9], while in the developing countries, it varies between 4.9 and 59%; in sudan, it was estimated to be 9.2% in 2015 [10]. maternal mental health studies aim to increase the availability of information needed to take evidence-based policy decisions concerning the mother and child development, as well as improving services for both. although important, it isn’t readily available in sudan [1]. ppd not only affects mothers but also their babies and families which makes it a social and community concern as a whole rather than an individual one. moreover, it could be an indirect cause of maternal morbidity and mortality if untreated [1], and the presence of high prevalence of ppd may interrupt the attainment of the millennium developmental goal 4 concerning the reduction in child mortality and the millennium developmental goal 5 related to maternal reproductive health improvement; therefore, planning interventions are needed to be carried out [9]. doi 10.18502/sjms.v15i4.8158 page 356 sudan journal of medical sciences maram osman elawad mabyoue 1.3. justification maternal mental health has not been well-studied in sudan, the numbers and information available on ppd is not enough to reflect the actual picture. more studies need to be conducted to fill the knowledge gap and reach accurate statistics and to know the exact risk factors and the psychosocial effects of ppd in sudan. moreover, ppd is becoming a serious under-diagnosed condition, mostly because of the lack of screening tests for it in the primary health care units and also due to the feeling of embarrassment in women due to which they do not voluntarily admit this kind of emotional distress or seek help. the reasons behind the inadequate treatment may include failure to recognize the symptoms or underestimating their severity. some women experience major depression and persistent depressive symptoms that can cause life impairment, so it is important to get those mothers identified and treated without delay to avoid developing long-term impairments in both mother and child. women should know that several treatments such as supporting groups, counseling, and medications actually exist for the disorders, and that they need not suffer in silence anymore. 1.4. objectives 1.4.1. general objective to determine the prevalence of ppd among sudanese women attending two major delivery hospitals in khartoum state – saad abueleella and dream international hospitals – using the edinburgh postnatal depression scale (epds) for a duration of six weeks. 1.4.2. specific objective to determine if there is a significant association between ppd and age, educational level, occupational status, obstetric complications, breastfeeding, and a previous history of similar condition. 1.5. hypothesis there is a significant association between ppd and age, educational level, occupational status, obstetric complications, breastfeeding, and a previous history of similar condition. 2. materials and methods 2.1. study design this study was a descriptive hospital-based cross-sectional research. doi 10.18502/sjms.v15i4.8158 page 357 sudan journal of medical sciences maram osman elawad mabyoue 2.2. study area this study was conducted at two major delivery hospitals in khartoum state, sudan. 1. the dream international hospital in the al-manshiya neighborhood, khartoum locality. it is a private hospital specialized in obstetrics and childbirth. 2. the saad abueleella hospital in the al-sahafa neighborhood, khartoum locality. it is a teaching hospital of the university of khartoum, established in 2013 and specialized in obstetrics and childbirth. it also provides services such as in vitro fertilization. the dream hospital was selected in the current study because the women attending private hospitals were not included in the only research conducted in sudan regarding ppd in 2015 and also because it has a high patient flow. the saad abueleella hospital on the other hand was selected conveniently for its high patient flow. mothers were recruited from postnatal and child welfare clinics. 2.3. study population all sudanese ladies included in the study were present at the selected hospitals, at six weeks following the delivery, and were aged between 18 and 45 years old. because the prevalence of ppd among women aged 14–18 years has been found to be high, indicating that they will be confounded by many factors [1], they were excluded from the current study. 2.4. inclusion criteria a female, aged between 18 and 45 years and at six weeks after the delivery. 2.5. exclusion criteria those who refused to participate in the study and mothers with a language barrier. 2.6. variables 1. independent variables: the age, educational level, occupational status, obstetric complications, breastfeeding, and previous history of ppd 2. dependent variable: ppd 2.7. sampling to determine the sample size, the following equation was used: 𝑛 = 𝑍 2𝑃(1 − 𝑃) 𝑑2 , doi 10.18502/sjms.v15i4.8158 page 358 sudan journal of medical sciences maram osman elawad mabyoue where n = sample size, z = standard deviation = 1.96 at 95% confidence level, p = prevalence, and d = maximum tolerable error for the prevalence estimate (0.05). *the prevalence in sudan was found to be 9.2%(10), so p = 0.092 𝑛 = (1.96) 2 × 0.092 × (1 − 0.092) (0.05)2 𝑛 = 128.3 so, the sample size was 129. a convenient sampling technique was used, due to the difficulty in finding women at six weeks postpartum at postnatal clinics. 2.8. data collection the participants were asked to fill a questionnaire by the principal investigator at the time of the interview. because direct interviews are considered to yield the best information and result in a higher response rate from patients, it was selected as the appropriate methodology. the questionnaire was composed of two sections: section a: socio-demographic and reproductive profile this was developed by the researcher to record personal information, past obstetric history, past history of similar psychological condition, and status of breastfeeding. section b: edinburgh postnatal depression scale (epds) this is a standard scale of 10 items scored from 0 to 3, as the score goes higher, the higher the score, the more depressive the are symptoms [11]. the scale has been validated in many languages [12], and is widely used in screening ppd for epidemiological concerns. it was validated in sudan in 2015, where the cronbach’s coefficient of the epds was 0.83 [10]. scoring the questionnaire takes only a few minutes with experience. a cut-off score of 12.5 has been shown to detect major depression, and a woman who scores this threshold needs further evaluation. 2.9. data analysis data were analyzed using the spss software, version 20. the data analysis plan included: master sheet, data cleaning, descriptive statistics like percentages and frequency tables, summary measures, data display in tables and figures, calculating the prevalence, odd ratios, and determining the associations using the chi-square test and multiple linear regression test. a p-value < 0.05 was considered as significant. doi 10.18502/sjms.v15i4.8158 page 359 sudan journal of medical sciences maram osman elawad mabyoue 3. results 3.1. socio-demographic characteristics table 1: socio-demographic characteristics of mothers screened for ppd at the saad abueleella and dream international hospitals; n = 129. characteristic frequency percentage age <25 18 14.0 25–35 77 59.7 >35 34 26.3 level of education not educated 5 3.9 primary 6 6.4 secondary 20 15.5 university and above 98 76.0 occupational status housewife 83 64.3 employed 42 32.6 worker 4 3.1 of the total 129 mothers included in the study, 59.7% were aged between 25 and 35 , 14% were <25, and 26.4% were >35 years. additionally, 76% of them were university graduates and some had post-graduate degrees. thus, a majority of them has completed their university education. of the remaining, 64.3% of mothers were found to be housewives, while 31.8% were employed, as shown in table 1. 3.2. obstetric data as shown in figure 1, 20.9% of the mothers confirmed having complications during or after the delivery, while 79.1% didn’t mention any complications for them or their babies. four mothers reported having a previous history of ppd and mentioned that they were on medications. almost all mothers (97.7%) reported breastfeeding their babies. as presented in figure 2, while 79% of the mothers revealed no signs of ppd and scored <9 points in epds, 10.1% scored 9–11, indicating a need for extra visits and 10.9% scored 12 or more (confidence interval 6.6–17.3%) indicating a possible ppd. 3.3. association between ppd and mother’s characteristics this study aimed at determining the association between the socio-demographic, economic, and obstetric characteristics and ppd, which included the age, level of education, doi 10.18502/sjms.v15i4.8158 page 360 sudan journal of medical sciences maram osman elawad mabyoue figure 1: percentages of mothers’ obstetric complications, history of ppd, and breastfeeding status, who were screened for ppd at the saad abueleella and dream international hospitals; n = 129. figure 2: percentages of mothers’ epds points screened for ppd, at the saad abueleella and dream international hospitals; n = 129. occupational status, complications during or after delivery, breastfeeding, and a previous history of ppd. associations were done using the chi-square test and multiple linear regression results were considered significant if p-value < 0.05. the chi-square test analysis showed a significant association between the epds scores and occupational status (p = 0.01), it was higher in housewives compared to working mothers. it was also found to be associated with a previous history of ppd (p = 0.01), indicating the possibility of further episodes of the disease in affected mothers, as shown in table 2. multiple linear regression analysis found that the history of ppd was significantly associated with epds scores (p = 0.045), as shown in table 3. doi 10.18502/sjms.v15i4.8158 page 361 sudan journal of medical sciences maram osman elawad mabyoue table 2: results of the chi-square test on factors associated with epds scores; n = 129. variable test positive epds score ≥≥≥ 12 test negative epds score <<< 12 crude or (95% ci) p-value mean occupational status housewife 10 73 2.67 0.01 1.36 employed 2 39 (0.55–12.80) 1.21 history of ppd yes 2 2 9.42 0.01 2.00 no 12 113 (1.21–73.03) 1.30 ci: confidence interval; or: odd ratio; and p-value from the chi-square test. table 3: results of the multiple linear regression on factors associated with epds scores; n = 129. variable coefficient standard error t p-value history of ppd –0.179 0.335 –2.028 0.045 yes no obstetric complications –0.155 0.147 –1.706 0.091 yes no 4. discussion the prevalence of ppd in the study area based on epds scores was found to be 10.9%, this indicates that ppd is a common problem in developing countries like sudan and that epds can be used as a screening tool. there is a notable resemblance in the prevalence of ppd based on the epds across different societies, the fact that epds is highly dependent on the timing makes the comparison of the studies more difficult. the advantage of using it is that it measures symptoms of anxiety in addition to symptoms of depression. this is critical because of the key symptoms as excessive worry, lack of concentration, and restlessness [13]. although in this study, the ppd was observed only at six weeks postpartum, according to the literature, the peak time for ppd is four–six weeks following the birth [6] but the onset can happen anytime earlier, which could be as early as the first trimester of pregnancy. knowing that a lot of mothers conceal or deny their depression symptoms during childbearing or the postpartum period, the possibility of a past history of depression cannot be eliminated [14]. the prevalence of ppd in this study was in close proximity to the prevalence in nigeria (10.6%), uganda (6.1%), and several other african and arabic countries [15]. the figures do vary slightly between our study and those similar regional studies, but this could be due to the methodological differences, timing, and socioeconomic conditions in those countries compared to sudan. doi 10.18502/sjms.v15i4.8158 page 362 sudan journal of medical sciences maram osman elawad mabyoue the total number of respondents was 129. women aged <25 (14% in this study) are the most affected age group according to the literature [16]. although our study has shown no significant association between ppd and maternal age, many previous studies in sudan have reported ppd to be associated with maternal age, that is, younger mothers, aged “<30,” carry more depression probability than older ones [13]. some studies have stated that socioeconomic variables such as low level of education and unemployment are evident to play a small role in developing ppd [13]. in our sample, 76% of the screened mothers were university graduates and 64.3% were housewives. moreover, ppd was found to be associated with occupational status (p = 0.01, or = 2.67) and was higher among the housewives than the working mothers, which is consistent with the previous study conducted in sudan [16]. moreover, no significant association was found between educational status and ppd. it is likely that the sudanese mothers are vulnerable to ppd because even after being well-educated and having a university degree, they have stay at home as housewives and raise their children, which may have contributed to their mental health. about 20.9% of mothers had obstetric complications such as pre-eclampsia, postpartum hemorrhage, and some had an emergency caesarian section. in our study, and similar to other studies, obstetric complications were not found to be significantly associated with ppd [17]. some studies have shown that insufficient pain treatment and emergency cs largely anticipate dissatisfaction with labor, but does not increase the risk of ppd, although the emergency cs mothers were younger and their children were more likely managed at the neonatal intensive care unit compared to other children [13]. moreover, 3.1% of the mothers reported a past history of ppd which was evident to be strongly associated with ppd and found to increase the probability of ppd in our sample (p = 0.01, or = 9.42), this is in consistent with the literature and with the previous study in sudan. in addition, 97.7% of mothers breastfed their babies and no association was found between ppd and breastfeeding status, which is also in line with the literature [17]. this is expected because in sudanese culture, breastfeeding is a favorable attitude and mothers tend to exclusively breastfeed their babies up to four months. the sample in this study was taken from two major delivery hospitals in khartoum state, the dream international hospital (60% of the sample) and the saad abueleella hospital (40% of the sample). initially, we had planned to include samples from the st. mary’s maternity hospital and bashayir teaching hospital as well, but due to the lack of family planning utilization in these hospitals, our target mothers were unavailable there. depressed mothers are insufficiently recognized in primary health care. there are numerous reasons for poor recognition. ppd may be thought as insignificant and a normal part of postpartum time. this is not surprising specially when we think of our mothers, because they deal with these feelings silently, discreetly, smiling at it. they try hard to protect their infants from these negative emotions, perhaps by denial and expressing optimistic affections (reaction formation). this makes it difficult to investigate because mothers with mental health problems are often stigmatized in our society and are less likely to participate in any preventive healthcare. we have to change this and start by implementing screening programs in primary healthcare units for early detection and treatment of such mothers. doi 10.18502/sjms.v15i4.8158 page 363 sudan journal of medical sciences maram osman elawad mabyoue facilitating questionnaire and interview measures are not used adequately and the mother and the nurse at the well-baby clinic may not be able to detect depressive symptoms [13]. many self-rated questionnaires are available now, of which epds is the most often used. the easiest way to detect ppd would be a more frequent use of such questionnaires to detect mothers who need to be referred for more precise clinical evaluation [18], as who states, “no health without mental health” [15]. 5. study limitations the study was limited by exclusion of mothers below 18 years, selection bias caused by the use of convenient sampling, ppd women were more likely not to attend a sixweek follow up, so the 10.9% figure is less likely to accurately estimate the true ppd prevalence. the sample was selected conveniently due to the difficulty in finding sixweeks postpartum women at postnatal clinics, as the utilization of family planning in sudan is very weak. they were captured while visiting child welfare clinics for the vaccination purpose. 6. conclusions ppd is a fairly common healthcare problem in the studied area, that was addressed by using the epds as a screening tool. several risk factors of ppd were studied, including the age, educational level, occupational status, obstetric complications, a previous history of ppd, and breastfeeding status. of these, the occupational status and the previous history of ppd were significant determinants in depressed mothers in comparison with non-depressed ones. 7. recommendations 1. the researcher recommends routine admiration of epds to all mothers at the time of discharge and six-weeks’ follow-up. 2. it is important to recognize mothers with symptoms of depression, as there are many successful studies on the treatment of ppd suitable for use in the primary healthcare. 3. it is crucial to provide sufficient knowledge and resources at the well-baby clinics to enhance maternal mental health. 4. encouraging the parents to start family planning with their doctors, this will support the parents in both aspects – psychologically and socially – to prevent ppd as well as improving the parent–infant relationship. 5. future researches including mothers below 18 years and exploring potential link between ppd and female genital mutilation (fgm) doi 10.18502/sjms.v15i4.8158 page 364 sudan journal of medical sciences maram osman elawad mabyoue 6. to conduct a qualitative exploration of mothers with ppd and to use a longitudinal study design. acknowledgements the author is grateful to the supervisors who were always helpful. she is also thankful to the medical directors of the hospitals they visited for never hesitating in allowing the study and willingly supporting the whole process. finally, a special thanks to the mothers for their cooperation in the study. ethical consideration 1. the current research has been approved by the research committee of the khartoum university. 2. permission was taken from the administrations of the selected delivery hospitals in khartoum state. 3. participation was voluntary and confidentiality was assured to all respondents. women were informed about the study’s objectives and procedures and that the data collected would be used only for the stated research purposes. 4. women who showed symptoms of ppd were advised to follow-up with either social workers, psychologists, or psychiatrists, as appropriate. availability of data and material the study materials are available with the author upon request. competing interests none to declare. funding the author received no funding for this research. doi 10.18502/sjms.v15i4.8158 page 365 sudan journal of medical sciences maram osman elawad mabyoue appendices edinburg postnatal depression scale (epds) j.l.cox, j.m. holden, r. sagovsky department of psychiatry, university of edinburgh name: address: baby’s age: as you have recently had a baby, we would like to know how you are feeling. please underline which comes closest to how you have felt in the past 7 days, not just how you feel today. here is an example, already completed. i have felt happy: yes, all the time. yes, most of the time. no, not very often. no, not at all. this would mean, “i have felt happy most of the time” during the past week. please complete the other questions in the same way. in the past 7 days: 1. i have been able to laugh and see the funny side of things as much as i always could. 0 – as much as i always could 1 – not quite so much now. 2 – definitely not so much now 3 – not at all 2. i have looked forward with enjoyment to things. 0 – as much as i ever did 1 – rather less than i used to 2 – definitely less than i used to 3– hardly at all 3. i have blamed myself unnecessarily when things went wrong. 3 – yes, most of the time. 2 – yes, some of the time 1 – not very often 0 – no, never doi 10.18502/sjms.v15i4.8158 page 366 sudan journal of medical sciences maram osman elawad mabyoue 4. i have been anxious or worried for no good reasons. 0 – no, not at all. 1 hardly, ever 2 – yes, sometimes 3 yes, very often 5. i have felt scared or panicky for no very good reason. 3– yes, quite a lot 2 – yes, sometimes 1 – no, not much 0 – no, not at all 6. things have been getting on top of me. 3– yes, most of the time i haven’t been able to cope at all 2 yes, sometimes i haven’t been coping as well as usual 1 – no, most of the time i have coped quite will 0 – no, i have been coping as well as ever 7. i have been so unhappy that i have had difficulty sleeping 3– yes, most of the time 2 – yes, sometimes 1 – not very often 0 – no, not at all 8. i have felt sad or miserable 3-yes, most of the time 2yes, quite often 1-not very often 0-no, not at all 9. i have been so unhappy that i have been crying 3-yes, most of the time 2yes, quite often 1 -only occasionally 0 – no, not at all 10. the thought of harming myself has occurred to me. 3-yes, quite often 2-sometimes 1-hardly ever 0-never doi 10.18502/sjms.v15i4.8158 page 367 sudan journal of medical sciences maram osman elawad mabyoue رطوم ا جامعة الطب ية تمع طبا ق رطوم ا ية و الرئيسية دة مستشفياتالو ة مقياسإدں ستخدام السوداںيات النساء ب دة الو بعد اكتئابما اںتشار ثبعںوان: ت. للبيا التامة ية ال ع افظة ا وست بغرضالبحثالع ستبيان ا هذا أعد ��� رة: س ا ر �� العمر: -١ : التعل -٢ � فوق ا جام ںوي٤) أساس٣) (٢ ة متع غ (١ هںة: ا -٣ � الحرة أ (٤ موظفة (٣ عام (٢ ل م ربة (١ دة: الو ة ف هلحدثتأيمضاعفاتأثںاء -٤ � (٢ ںعم (١ سابقة: تںفسية عاںيتمنحا هل -٥ � (٢ ںعم (١ طبيعية: أرضعتطفلكرضاعة هل -٦ � (٢ ںعم (١ السابق: سبوع ا ل خ � شياء: ا واںبالطريفة ا أرى كوأن أ أن استطاع ن -٧ ا كںتدا بںفسالقدر (٠ ن ا بںفسالقدر اما ليس (٢ ن ا ليسبںفسالقدر لتأكيد (١ استطاع يكن قا إط (٣ � اح: وان تعة مور ل كںتأںظر -٨ السابق كںت بںفسالقدر (٠ ما ںوعا السابق من أقل بدرجة (٢ السابق أقلمن بدرجة لتأكيد (١ اح وان تعة أشعر د أ (٣ � مور: ا تسوء عںدما ر م دون ںف كںتألوم -٩ الوقت معظم ںعم، (٣ حيان بعضا ںعم، (١ حيان أغلبا ليس ، (٢ قا دثإط ، (٠ � : دونسببوا ذر وا لقلق كںتأشعر -١٠ قا دثإط ، (٠ أجزم د أ ، (٢ حيان بعضا ںعم، (١ حيان أغلبا ںعم، (٣ � : دونسببوا وفوالفزع كںتأشعر -١١ doi 10.18502/sjms.v15i4.8158 page 368 sudan journal of medical sciences maram osman elawad mabyoue جدا ا كث ںعم، (٣ أحيا ںعم، (١ ا ليسكث ، (٢ قا إط ، (٠ � : للحي وفاقدة أمري ع أصبحتمغلوبة -١٢ قا حداثإط ا مع التعامل أستطع حيان ا معظم ںعم، (٣ السابق كںتأفعل حداث ا مع التعامل أستطع أحيا ںعم، (١ جيدة بصورة حيان ا معظم حداث ا تعاملتمع ، (٢ السابق كںت حداثبںفسالقدر ا مع كںتأتعامل ، (٠ � الںوم: وجدتصعوبة أں لدرجة سعيدة كںتغ -١٣ حيان ا معظم ںعم، (٣ أحيا ںعم، (١ ا ليسكث ، (٢ قا إط ، (٠ � بة: وال زن كںتأشعر -١٤ حيان ا معظم ںعم، (٣ جدا ا كث ںعم، (١ فقط أحيا (٢ قا إط ، (٠ � : كںتأب أں لدرجة سعيدة كںتغ -١٥ حيان ا معظم ںعم، (٣ أحيا ںعم، (١ دثذلك أجزم، د أ (٢ دثذلك قا إط (٠ � : ںف إيذاء فكرة اطري مر لقد -١٦ جدا ا كث ںعم، (٣ أحيا ںعم، (١ دثذلك أجزم، د أ (٢ دثذلك قا إط (٠ references [1] stewart, d. e., robertson, e., phil, m., et al. (2003). postpartum depression: literature review of risk factors and interventions. who. retrieved from: http://www.who.int/mental_health/prevention/suicide/ lit_review_postpartum_depression.pdf [2] biratu, a. and haile, d. (2015). prevalence of antenatal depression and associated factors among pregnant women in addis ababa, ethiopia: a cross-sectional study. reproductive health, vol. 12, no. 1, pp. 1–8. [3] shanthi, r. and girja, m. (2014). prevalence of postnatal depression among arab women : a narrative review. international journal of nursing and midwifery, vol. 3, no. 1, pp. 1–13. [4] hilt, r. j. (2015). postpartum depression screening. pediatric annals, vol. 44, no. 9, pp. 344–347. [5] shakeel, n., eberhard-gran, m., sletner, l., et al. (2015). a prospective cohort study of depression in pregnancy, prevalence and risk factors in a multi-ethnic population. bmc pregnancy childbirth, vol. 15, no. 1, p. 5. doi 10.18502/sjms.v15i4.8158 page 369 http://www.who.int/mental_health/prevention/suicide/lit_review_postpartum_depression.pdf http://www.who.int/mental_health/prevention/suicide/lit_review_postpartum_depression.pdf sudan journal of medical sciences maram osman elawad mabyoue [6] motzfeldt, i., andreasen, s., pedersen, a. l., et al. (2013). prevalence of postpartum depression in nuuk, greenland – a cross-sectional study using edinburgh postnatal depression scale. international journal of circumpolar health, vol. 72, no. 1, pp. 1–6. [7] mehta, s. and mehta, n. (2014). an overview of risk factors associated to post-partum depression in asia. mental illness, vol. 6, no. 1, p. 5370. [8] ahmed, a., bowen, a., and feng, c. x. (2017). maternal depression in syrian refugee women recently moved to canada: a preliminary study. bmc pregnancy childbirth, vol. 17, no. 1, pp. 1–11. [9] thompson, o. and ajayi, i. (2016). prevalence of antenatal depression and associated risk factors among pregnant women attending antenatal clinics in abeokuta north local government area, nigeria. depression research and treatment, vol. 2016, no. 12, pp. 1–15. [10] khalifa, d. s., glavin, k., bjertness, e., et al. (2015). postnatal depression among sudanese women: prevalence and validation of the edinburgh postnatal depression scale at 3 months postpartum. international journal of women’s health, vol. 2015, no. 7, pp. 677–684. [11] cox, j. l., holden, j. m., and sagovsky, r. (1987). detection of postnatal depression: development of the 10-item edinburgh postnatal depression scale. british journal of psychiatry, vol. 150, no. 3, pp. 782–786. [12] matijasevich, a., munhoz, t. n., tavares, b. f., et al. (2014). validation of the edinburgh postnatal depression scale (epds) for screening of major depressive episode among adults from the general population. bmc psychiatry, vol. 14, no. 1, pp. 1–9. [13] hiltunen, p. (2003). maternal postnatal depression: causes and consequences. international journal of circumpolar health, vol. 62, no. 3, pp. 308–309. [14] wissart, j., parshad, o., and kulkarni, s. (2005). prevalence of preand postpartum depression in jamaican women. bmc pregnancy childbirth, vol. 5, no. 15, pp. 2–6. [15] fisher, j., de mello, m. c., patel, v., et al. (2012). prevalence and determinants of common perinatal mental disorders in women in low-and lower-middle-income countries: a systematic review. bulletin of the world health organization, vol. 90, no. 2, pp. 139–49. [16] caparros-gonzalez, r. a., romero-gonzalez, b., strivens-vilchez, h., et al. (2017). hair cortisol levels, psychological stress and psychopathological symptoms as predictors of postpartum depression. plos one, vol. 12, no. 8, pp. 1–17. [17] khalifa, d. s., glavin, k., bjertness, e., et al. (2016). determinants of postnatal depression in sudanese women at 3 months postpartum: a cross-sectional study. bmj open, vol. 6, no. 3, e009443. [18] prenoveau, j. m., craske, m. g., west, v., et al. (2017). maternal postnatal depression and anxiety and their association with child emotional negativity and behavior problems at two years. developmental psychology, vol. 53, no. 1, pp. 50–62. doi 10.18502/sjms.v15i4.8158 page 370 introduction background problem statement justification objectives general objective specific objective hypothesis materials and methods study design study area study population inclusion criteria exclusion criteria variables sampling data collection the questionnaire was composed of two sections: section a: socio-demographic and reproductive profile section b: edinburgh postnatal depression scale (epds) data analysis results socio-demographic characteristics obstetric data association between ppd and mother's characteristics discussion study limitations conclusions recommendations acknowledgements ethical consideration availability of data and material competing interests funding appendices edinburg postnatal depression scale (epds)j.l.cox, j.m. holden, r. sagovskydepartment of psychiatry, university of edinburgh references page 85 editorial improvement of the medical education situation in sudan: collegectomy is not the only management option mohamed elhassan abdalla*, mohamed hassan taha medical education centre and college of medicine, university of sharjah, united arab emirates abstract sudan witnessed an increase in the number of colleges of medicine after the higher education revolution in the early 1990s. many authors writing about medical education, both in sudan and across the world, have described a negative correlation between the increased number of medical colleges and the quality of education provided by those colleges. many educational leaders in sudan are calling for action to deal with the issues arising from this great expansion of medical colleges, with opinions varying from collegectomies (closure of the colleges) to merging colleges. several strategies have been implemented in canada, iran, the philippines and south africa to deal with similar situations. these have included college support such as funding or technical support, changing the colleges’ educational strategies, modifying the curriculum, integrating (rather than merging) colleges, and collegectomies. this paper outlines possible actions to be taken in response to the expansion of medical colleges in the sudanese context. it explores the international experience with the situation in an attempt to augment the discussion with options that may help to improve medical education. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6708 production and hosting by knowledge e how to cite this article: mohamed elhassan abdalla (2019) “improvement of the medical education situation in sudan: collegectomy is not the only management option”, sudan journal of medical sciences, vol. 15, issue no. 1, pages 85–90. doi 10.18502/sjms.v15i1.6708 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: melsayed@sharjah.ac.ae received 25 february 2020 accepted 20 march 2020 published 31 march 2020 production and hosting by knowledge e cc mohamed elhassan abdalla. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: collegectomy; medical education; sudan; social accountability introduction sudan witnessed an increase in the number of colleges of medicine after the higher education revolution in the early 1990s. the total number rose from three to 66, an increase equally split between public and private colleges [1, 2]. many researchers in the field of medical education have described a negative correlation between this increased number and the quality of the education at these colleges [3, 4]. the situation in the united states that lead to the flexner report in 1910 is still shaping our thinking about medical education [5], although some authors have argued that there is no evidence of this correlation [6]. sudan journal of medical sciences mohamed elhassan abdalla and mohamed hassan taha doi 10.18502/sjms.v15i1.6708 page 86 those who are concerned by the negative impact on quality call for actions against colleges that do not meet educational standards [7], such as the immediate closure of these colleges (i.e., a collegectomy). this paper outlines the possible actions to be taken to address the expansion of medical colleges in sudan, expanding the discussion via the provision of a range of options that may help to improve medical education while avoiding ‘collegectomies’. colleges of medicine and the society in general, medical colleges hold a distinguished position within society and higher education systems because their mandate is to serve that society [8]. according to the definition of social accountability for medical colleges, ‘society’ includes the local society, the country, the region and the nation – provided the colleges’ graduates engage in research and health services that serve any of these levels [9]. based on this mandate, medical colleges are engaged in a highly dynamic relationship with society, using it and its institutions to teach and train students, provide direct and indirect health services, and draw on resources for research. based on the above, medical colleges have a social contract with the society they serve. this contract has an explicit duty to graduate safe doctors to practice in the society, especially if the students are recruited from the same area where the college is located. incidentally, research has indicated that attracting students from or training of medical students in less developed regions leads to retention of a large number of graduates in those areas as part of the working health force in the future [10, 11]. colleges also participate in the development of health systems and the healthcare environment in general, as medical education is defined as ‘the art and science of training doctors who can practice safely in the society and work with partners to create a suitable environment for the work of those graduates’ [12]. another part of the contract is implicit, and relates to fostering the development of the society through different activities, such as students’ extracurricular activities, the public service activities of faculty members, and the creation of job opportunities for members of the society. what is mentioned above does not mean that the establishment of medical colleges is the only solution to a society’s development, as establishment in itself requires preparation and adequate resources [7, 13, 14]. these can include: sudan journal of medical sciences mohamed elhassan abdalla and mohamed hassan taha doi 10.18502/sjms.v15i1.6708 page 87 .1 the presence of hospitals and health centers that provide the minimum level of clinical training with a plan to provide advanced training if needed (the goal here is not only buildings but also the number and appropriateness of cases for training, taking into consideration that some practical training may need to be conducted in other social institutions, like social affairs institutions, depending on the type of curriculum being used). .2 the presence of a working and living environment that facilitates the recruitment of the minimum number of permanent faculty members to create an acceptable ratio of faculty members to students (not everyone who teaches at a college is considered as a permanent faculty member, as there are also adjunct faculty members and visiting faculty members who affect the ratio of teachers to students). .3 administration, governance (including the nature of the relationship with the university administration) and a faculty development plan. .4 a curriculum that is appropriate to the nature and purpose of establishing the college (one of the most dangerous things a medical college can do is adopt another college’s curriculum as it is). .5 support staff and services. .6 other educational resources (laboratories, libraries, dissection rooms, clinical skills/simulation laboratories, etc.) .7 student recruitment plan: being aware of the faculty–student ratio, learning resources and places of residence. some colleges in sudan were established without a complete study plan. however, these colleges have students, faculty, employees and workers, and the society in which they operate has benefited from the presence of the college in many ways, including new job opportunities and the provision of health and medical services. the most important thing to consider is that these colleges may produce much-needed new doctors, after all the doctor to population ration in sudan remains small, especially with regards to the general health coverage goal of 2030 [15]. however, it is crucial that a high level of quality in all the colleges is ensured so that their outputs satisfy society’s health needs. collegectomy or not? this paper proposes a balance between quality and society’s needs by asking that each college be taken as a separate case instead of making a collective decision. it is necessary to consider all the educational and social aspects related to the college to avoid doubly penalizing the societies in which these colleges operate: both by opening sudan journal of medical sciences mohamed elhassan abdalla and mohamed hassan taha doi 10.18502/sjms.v15i1.6708 page 88 the college in the first place without the necessary study plans, and then by making a decision regarding its closure without carrying out the appropriate studies. based on successful practices in medical education worldwide, some of the decisions may be made using the following list: .1 college support. here, support is not limited to financial but to any other form of support including that pertaining to the faculty and the curriculum. 2. changing the college strategy. this can be done by adopting social accountability, a solution that several other countries such as south africa, canada, the philippines and australia have used to increase the effectiveness of their medical colleges [16–19]. 3. modifying the curriculum. this can be done by following the step-ladder curriculum, which is one of the solutions which the philippines has used to establish medical colleges in remote places [20, 21]. society-based clinical training could also be implemented – it is currently practiced in certain canadian colleges [22]. finally, adopting inter-professional education to maximize the effectiveness of graduates should be considered [23]. 4. integrating medical colleges. colleges could be encouraged to work together and share experiences and learning resources using a schedule to work toward independence; canada and iran have implemented this [17, 24]. 5. collegectomy. if no other option can be applied, a flexnerian-era collegectomy becomes a viable option [25]. 6. any other solution that fits the sudanese context. a common but discouraged practice is to transfer students from one college to another college; this has adverse effects on the host college’s students by increasing the proportion of students to faculty and heightening the academic burden on the faculty members and the hosting college’s students. it also has future adverse effects on the guest students, as it reduces their association with their college and the society of that college. in short, it may negatively impact and even undermine the goal of establishing the college in the first place. many stakeholders, especially those on social media platforms, are calling for the closure of the so-called ‘new’ medical colleges (‘collegectomies’). however, this paper argues that what should drive the decision-making regarding collegectomy is sudan’s medical council (smc), which has a well-structured process and standards for accrediting medical schools. it is important to support smc in this regard, which can be done with political empowerment and the necessary financial resources as part of a national plan to improve the quality of medical education in sudan featuring collaboration between all stakeholders. sudan journal of medical sciences mohamed elhassan abdalla and mohamed hassan taha doi 10.18502/sjms.v15i1.6708 page 89 conclusion this communication suggests a balance between quality in medical education in sudan and the society’s health and health-related needs; it explores international experiences that can be adapted to the sudanese medical education sector, allowing for the consideration of each college as a separate case. closing colleagues (collegectomy) is not the only solution. references [1] fahal ah (2007). medical education in the sudan: 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[2] al sadig al mahdi t (2019). overview of the course of undergraduate medical education in the sudan. sudan journal of medical sciences. 14(4): 188–201. [3] ahmed am (2012). medical education in sudan: emerging issues and acute needs. sudanese journal of public health. 7: 2. [4] tekian a, almazrooa aa (2011). does saudi arabia need an abraham flexner? medical teacher. 33(1): 72–73. [5] benor de (2014). a new paradigm is needed for medical education in the midtwenty-first century and beyond: are we ready? rambam maimonides medical journal. 5(3): e0018. [6] abdulrahman k. bin (2011). saudi arabia does not need an abraham flexner. medical teacher. 33(1): 74–75. [7] sjöström h, christensen l, nystrup j et al. (2019). quality assurance of medical education: lessons learned from use and analysis of the wfme global standards. medical teacher. 14(6): 1–6. [8] hays r (2007). community-oriented medical education. teaching and teacher education. 23(3): 286–293. 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(2008). effective interprofessional education: argument, assumption and evidence (promoting partnership for health). john wiley & sons. [24] tresilian f (1997). the reform of medical education in iran. the bmj. 1(3032): 172. [25] cooke m, irby dm, sullivan w et al. (2006). american medical education 100 years after the flexner report. the new england journal of medicine. 355(13): 1339–1344. sudan journal of medical sciences volume 12, issue no. 1, doi 10.18502/sjms.v12i1.856 production and hosting by knowledge e research article the initial experience of trans-rectal ultrasound and biopsy in diagnosis of carcinoma prostate in gezira hospital for renal disease and surgery (ghrds) walaa eldin ibraheem1, sami mahjoub taha2, mustafa omran mansour2, and mohammed el imam mohamed ahmed2 1department of surgery, faculty of medicine, assistant professor, university of west kordofan 2department of surgery, faculty of medicine, university of gezira & department of urology, gezira hospital for renal disease and surgery, medani, sudan abstract background: prostate cancer prevalent cancer in males above sixty-five worldwide, this lead to the introduction of screening of the psa and using of the transrectal ultrasound scanning, and sextant biopsy of the prostate. objectives: to compare the accuracy of the transrectal ultrasound guided biopsy (trus/bx) in the diagnosis of prostate cancer in gezira hospital for renal diseases and surgery (ghrds), with specific considerations to the digital rectal examination (dre) findings and prostate specific antigen (psa) level. materials and methods: this is a prospective, descriptive small-scale hospital based study. a total of 297 patients with clinically symptomatic enlarged prostate underwent transrectal ultrasound guided true cut needle biopsy of the prostate were studied in (ghrds) in the period from june2006 to june2009. results: the majority 188 (63.3%) of patients were between 50-70 years of age. abnormal digital rectal examination (dre) like obliteration of the median sulcus, and fixed mucosa revealed higher incidence of carcinoma prostate (cap) with a significant value (p = 0.0000). psa level showed significant relation (p = 0.0001) with the diagnosis of carcinoma prostate. transrectal u/s findings well correlated to the histopathological results, where abnormal findings (like hypo-echoic lesions or calcifications and cysts) showed higher incidence of malignancy in 46 patients constitute 52.8% of the abnormal u/s findings. conclusions and recommendations: psa level is highly sensitive but less specific in detection of prostate cancer. normal dre doesn’t exclude prostate cancer, fixed mucosa and obliterated median sulcus has the highest predictors of cancer prostate in dre. presence of calcifications and cyst on trans-rectal ultrasound has the highest liability for cancer prostate in compare to the other ultrasonic findings. keywords: prostate cancer, dre, psa level, trus/ bx (transrectal ultra sound biopsy), sextant biopsy how to cite this article: walaa eldin ibraheem, sami mahjoub taha, mustafa omran mansour, mohammed el imam mohamed ahmed, (2017) “the initial experience of trans-rectal ultrasound and biopsy in diagnosis of carcinoma prostate in gezira hospital for renal disease and surgery (ghrds),” sudan journal of medical sciences, vol. 12 (2017), issue no. 1, 25–32. doi 10.18502/sjms.v12i1.856 page 25 corresponding author: sami mahjoub taha; email: samimahj@gmail.com received: 15 december 2016 accepted: 20 february 2017 published: 28 may 2017 production and hosting by knowledge e walaa eldin ibraheem et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:samimahj@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e الخلفية: سرطان البروستات هو سرطان منتشر يف الذكور فوق سن الخامسة والستين يف جميع أنحاء العالم، ولهذا السبب تم إدخال فحص ىب أس أىي وإستخدام المسح بالموجات فوق الصوتية عبر المستقيم، وخزعة سيكسانت من البروستات. عبر الموجهة الصوتية فوق بالموجات المأخوذة الخزعة دقة مقارنة هى األهداف: المستقيم يف تشخيص سرطان البروستات يف مستشفى الجزيرة ألمراض وجراحة الكلى، مع إعتبارات محددة لنتائج فحص المستقيم األصبعى ومستويات فحص ىب أس أىي. ما درس وقد بالمستشفى قائمة صغير نطاق على وصفية إستباقية دراسة ىف الطرق: مجموعه ٢٩٧ مريضاً مع أعراض سريرية وتضخم للبروستات الموجات فوق الصوتية عبر المستقيم موجهة خياطة إبرة قطع حقيقية من البروستاتا يف (غردز) يف الفترة من يونيو ٢٠٠٦ إىل يونيو ٢٠٠٩. فحص العمر. من سنة ٥٠-٧٠ بين المرضى من (٪٦٣٫٣) ١٨٨ األغلبية كانت النتائج: المخاطي والغشاء األوسط، التلم من طمس مثل طبيعي غير األصبعى المستقيم .(٠٫٠٠٠٠ = p) الماتصق كشفت عن حدوث أعلى من سرطان البروستات مع قيمة كبيرة البروستات. سرطان تشخيص مع (٠٫٠٠٠١ = p) كبيرة عالقة أىي أس ىب مستوى أظهر النتائج مع جيد بشكل المستقيم عبر الموجهة الصوتية فوق الموجات نتائج وترتبط النسيجية، حيث أظهرت نتائج غير الطبيعية (مثل األورام أو التكلسات واألكياس) ارتفاع الصوتية فوق الموجات نتائج من (٪٥٢٫٨) شكلت حيث مريضا ٤٦ يف الخباثة نسبة الموجهة عبر المستقيم الغير طبيعية. عن الكشف يف تحديداً أقل ولكن للغاية حساس أىي أس البى مستوى اإلستنتاجات: سرطان وجود يستبعد ال الطبيعى األصبعى المستقيم فحص البروستات. سرطان من تنبؤات أعلى لديهما التلم وسط وطمس المثبت المخاطي والغشاء البروستات، سرطان البروستات يف نتائج فحص المستقيم األصبعى . وجود التكلسات والكيسات على الموجات فوق الصوتية عبر المستقيم لديه أعلى مسؤولية عن سرطان البروستات مقارنة للنتائج األخرى من الموجات فوق الصوتية. 1. introduction prostate cancer is more common in countries with higher proportions of elderly men in their population, and so accounts for around 15% of cancers in men in developed countries, but only 4% in developing countries [1]. in sudan prostate cancer was not considered among the top 10 commonest cancer in sudan in the period (1967-1984), but in the period (1984-2004), it was listed at the bottom of the top 10 common male cancers [2]. prostate cancer in gezira state, sudan, was studied in patients diagnosed and treated in the national cancer institute & ghrds in wad medani in the period 2002-2007, comprised 8% of all cancer in the period before trus introduction. it jumped to 14% in the first year after introduction of trus/bx. the prostate cancer became number one doi 10.18502/sjms.v12i1.856 page 26 sudan journal of medical sciences production and hosting by knowledge e male cancer compared to number three cancers before trus was introduced. however, no other study was reported in sudan regarding trus/bx [2]. before trus improvements and serum psa testing became widespread, clinicians relied mainly on digital rectal examination to establish a diagnosis of prostate cancer and performed digitally directed lesion biopsies. the presence of focal nodules on digital rectal examination still will prompt a biopsy using the trus technique regardless of psa levels. trus-directed prostate needle biopsy remains the gold standard for diagnosis of prostate cancer [3]. the risk of a positive dre turning out to be cancer is dependent greatly on the psa value. this was shown by the nomogram, which showed an increase in the positive predictive value as the psa level increase from 0 to 10 ng/ml [4]. psa-based screening programs have markedly improved early prostate cancer detection. these initiatives were significantly increase the rate of organ-confined and potentially curable disease [6]. currently, most clinicians recommend biopsy once a patient’s serum psa rises above 4.0 ng/ml [4]. evidence for lowering the psa threshold from work by catalona’s group showed higher rates of organ-confined disease at the time of radical retropubic prostatectomy in men sampled with psas in the 2.6to 4.0-ng/ml range [7]. these findings have led many urologists to recommend prostate biopsy to men younger than 60 years of age once their psa level rises above 2.5 ng/ml [4]. there is a general trend toward allowing older men (70 years or older) to have slightly higher “normal” psas, in the range of 5.5 to 6.5 ng/ml, although this is not universally accepted [8, 9]. patients with a serum psa value between 4.0 and 10.0 ng/ml, using a percentage of free psa thresholds of less than 25% detected 95% of cancers while eliminating 20% unnecessary biopsies, and within this group, the risk of prostate cancer increased dramatically as the percentage of free psa level declined [10]. regardless of initial psa value, a psa velocity greater than 0.75 to 1.0 ng/ml per year is frequently associated with prostate cancer and warrants biopsy [9], whereas an elevated psa density and psa density-transitional zone have both been shown to increase the likelihood of diagnosing prostate cancer on repeat biopsy [11]. the original sextant biopsy scheme, (one core from the base, mid, and apex bilaterally) significantly improved cancer detection over digitally directed biopsy of palpable nodules and ultrasound-guided biopsy of specific hypoechoic lesions) [12, 13]. taken in the parasagittal plane these cores sampled a portion of the peripheral zone but also included a significant amount of tissue from the transitional zone, with subsequent studies of radical prostatectomy specimens demonstrating that the vast majority of adenocarcinomas arise in the posterolateral peripheral zone [14], thus explaining some of the false-negative results of standard sextant biopsy [15]. doi 10.18502/sjms.v12i1.856 page 27 sudan journal of medical sciences production and hosting by knowledge e 2. materials and methods this is a prospective, descriptive, hospital based study-carried out in (ghrds) in wad medani, gezira state, sudan. gezira hospital for renal disease and surgery it serves patients from gezira state which is the second popular state in sudan with population of 4 million capita, also serves patients coming from nearby states . all patients, were above fifty, presenting with lower urinary tract symptoms suggestive of prostatic problems, were seen in the referred clinic. history, clinical examination including digital rectal examination (dre) was done, investigations including, prostate specific antigen, and abdominal ultrasound were done. patients indicated for trus/bx are selected, prepared through clinical work up, including history and examination to exclude contra-indications like bleeding tendency, painful anorectal conditions, and urinary sepsis. written consent for the procedure and the study were obtained. patients used to come early in the morning fasting, enema were routine, followed by an intravenous injection of gentamycin. in left lateral position with flexed right hip and kneerectal probe, covered with sterile condom was introduced lubricated with xylocaine jelly. sextant biopsy was taken according to the sudanese guidelines policy. more biopsies were taken in the presence of when palpable nodules, or suspicious hypoechoic, hyper-echoic, calcifications or cyst formation. the procedure of trus/bx was done by the urologist. biopsies were preserved in formalin (10%) containers sent for histopathology. data were statistically analyzed using spss packages, the chi square test was used for categorical variables .variable was considered to be significant if the p value was 0.05 or less. the sensitivity and specificity and positive predictive value were calculated by using the formula: sensitivity = tp/tp+fn specificity = tn/fp+tn positive predictive value = tp/tp+fp tp = true positive fn = false negative tn = true negative fp = false positive 3. results the study included 297 patients who underwent transrectal ultrasound and biopsy at gezira hospital for renal diseases and surgery, during the period from june 2006 to june 2009. the ages of the patients ranged between 50 – 70 years. dre was found in 145 (48.8%) to be normal, 135 (93.1%) of them had histopathology results but 10 (6.9%) revealed cancer of the prostate . doi 10.18502/sjms.v12i1.856 page 28 sudan journal of medical sciences production and hosting by knowledge e dre histopathology total benign adenocarcinoma inflammatory normal 135 (93.1%)* 10 (6.9%) 0 145 hard nodular 81 (87.1%)* 9 (9.7%) 3 93 obliteration median sulcus 17 (53.1.1%) 15 (46.9%) 0 32 fixed mucosa +pelvic extension 6 (23.1%) 21 (76.9%)* 0 27 239 55 3 297 t 1: the relation between the dre findings and the histopathology of 297 patients had trus/bx. dre sensitivity = 78.6%, dre specificity = 56.3%, *p value=0 .000. psa ng/ml histopathology total benign adenocarcinoma inflammatory < 4 16 (84.2%)* 3 (15.8%) 0 19 4 to 10 115 (90.6%)* 12 (9.4%) 0 127 11 to 100 106 (70.7%)* 41 (27.3%) 3 150 > 100 1 (100%) 0 0 1 238 56 3 297 t 2: the histopathological distribution of 297 trus/bx biopsies according to the psa level. psa sensitivity = 94.5%, psa specificity = 76.0%, *p value=0.001. patients with abnormal dre findings comprise 151 (50.8%), of them 107 (70.9%) had benign and 44 (29.1%) had malignant, as shown in table (1), the sensitivity of dre was 78.6 and the specificity was 56.3. psa less than 4 ng/dl was found in 19 (6.4%) case, 3 (15.8%) had cancer prostate on histopathology, psa level 4-10 ng/dl was found in 127 (42.8%) case, 12(9.4%) of them had cancer prostate. psa level 11-100 ng/dl was found in 150 (50.5%) case, 41(27.3%) of them had cancer prostate, and 3 cases showed inflammatory changes. one case (0.3%) has reported more than 100 ng/dl of psa, but his histopathology result was benign. the relation between stocktickerpsa and histopathology results was significant (p= 0.001) as shown in table 2, the psa sensitivity and specificity were 94.5% and 76.0 % respectively. ultrasound was reported 210 cases as normal echo texture of the prostate,10 (4.8%) of them had cancer prostate. the abnormal ultrasound findings was in 87patient ultrasound finding histopathology total benign adenocarcinoma inflammatory large normal texture 199 10 (4.8%) 1 210 hypo-echoic lesion 37 17 (19.5%)* 2 56 calcification + cyst 2 29 (33.3%)* 0 31 238 29+17=46 (52.8%)* 3 297 t 3: trus findings correlated to the histopathology of 297 trus/bx. trus sensitivity = 91.1%, trus specificity = 83.1%, p value = 0.000. doi 10.18502/sjms.v12i1.856 page 29 sudan journal of medical sciences production and hosting by knowledge e 46(52.2%) of them were adenocarcinoma .hypo-echoic lesions were found to be in 56case, 17 of them had cancer prostate , and only two cases were inflammatory. calcifications and cysts were seen in 31-case, 29 (33.3%) of them had cancer prostate. the relation between trus and histopathology results was significant (p value 0.000). the sensitivity and specificity of trus in this study were 91.1 and 83.1 respectively as shown in table 3. 4. discussion introduction of psa screening, and trus/bx in ghrds changed the picture in detecting cancer prostate patients in an earlier stage, together with the ability to increase the number of patients who are candidates for prostatic biopsy i.e. to include patients with abnormal digital rectal examination findings, patients with stocktickerpsa level more than 4ng/ml, and patients with abnormal transrectal ultrasound echo texture. this practice consisted with the european guidelines of urology. dre is the most important part in assessing patients with prostate enlargement, and remained an essential predictor of cancer prostate. this is well documented in this study, which showed significant correlation between abnormal dre findings and cancer prostate (cap) (pvalue 0.000). psa is an important predictor of prostate cancer, since the introduction of psa as an screening tool, the incidence of cancer prostate jumped to be the leading cancer in males above 65 years old [1]. we consider the level 4ng/ml as a cut off value, but as shown in many studies [7] levels between (2 to 4 ng/ml) in younger ages i.e. less than 60 years old have significant number of cancer prostate. therefore, we should reduce the cutoff value for younger patients, and at the same time take higher levels for old patients [4]. to increase the sensitivity of psa as a predictor for cancer prostate, we can use more sensitive predictors like free psa level/total psa ratio, psa density, and psa density of the transitional zone. this will reduce about 20% unnecessary biopsies [9, 10]. transrectal ultrasound screening of the prostate improved the biopsy technique very much, where you can direct the needle targeting specific areas like the para sagittal zone to take the sextant biopsies , also you can direct the needle towards suspicious areas detected by the ultrasound screen i.e. hypoechoic, hyper-echoic regions, and cysts or calcification zones. transitional zone can be included with sextant biopsy, this explain the high negative biopsies in the classical sextant biopsies [15]. the combination of dre, psa, and trus as diagnostic procedures used to screen population for cancer prostate, showed that the positive predictive value increases as the number of abnormal modalities increases i.e. if one of the modalities is abnormal the positive biopsy rate is 6-25%, with two abnormalities it is 18-60%, and if all three modalities are positive, it is 56-72%. this shows that combination of the three diagnostic modalities give the highest chance for detecting early cases of cancer prostate, and this what was done in our study [16, 17]. doi 10.18502/sjms.v12i1.856 page 30 sudan journal of medical sciences production and hosting by knowledge e 5. conclusions psa level is highly sensitive but less specific in detection of prostate cancer. normal dre doesn’t exclude prostate cancer, fixed mucosa and obliterated median sulucus has the highest predictors of cancer prostate in dre. presence of calcifications and cyst on trans-rectal ultrasound has the highest liability for cancer prostate in compare to the other ultrasonic findings. 6. the author contributions i. study concept and design: 1. walaa eldin ibraheem 2. prof. mustafa omran 3. dr.sami mahjoub taha ii. collection of data: 1. walaa eldin ibraheem 2. dr.sami mahjoub taha iii. analysis and interpretation of data: 1. walaa eldin ibraheem 2. dr.sami mahjoub taha references [1] d. m. parkin, f. i. bray, and s. s. devesa, “cancer burden in the year 2000 the global picture,” eur j cancer, vol. 37, 8, pp. 4–66, 2001. [2] d. abuidris, e. mohammed imam, and o. e. mustafa, “elgaylani ahmed elhag, the impact of trus in detection of prostate cancer in gezira, sudan,” gjhs, vol. 6, no. 1, pp. 35–42, 2010. [3] r. r. john, j. h. elhan, and g. g. leonard, “ultrasonagraphic and biopsy of the prostate,” in in: wein: campbell, walsh, urology, 2007, 9th ed, 2007, saunders. [4] j. a. eastham, r. may, j. l. robertson, o. sartor, and m. w. kattan, “development of a nomogram that predicts the probability of a positive prostate biopsy in men with an abnormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/ml,” urology, vol. 54, no. 4, pp. 709–713, 1999. 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[13] j. e. mcneal, e. a. redwine, f. s. freiha, and t. a. stamey, “zonal distribution of prostatic adenocarcinoma. correlation with histologic pattern and direction of spread,” the american journal of surgical pathology, vol. 12, no. 12, pp. 897–906, 1988. [14] l. a. eskew, r. l. bare, d. l. mccullough, and t. a. stamey, “systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate,” journal of urology, vol. 157, no. 1, pp. 199–203, 1997. [15] w. j. ellis, m. p. chetner, s. d. preston, and m. k. brawer, “diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography,” journal of urology, vol. 152, no. 5 i, pp. 1520–1525, 1994. [16] c. mettlin, g. p. murphy, r. j. babaian et al., “the results of a five-year early prostate cancer detection intervention,” cancer, vol. 77, no. 1, pp. 150–159, 1996. [17] w. t. jones and m. i. resnick, “prostate ultrasound in screening, diagnosis and staging of prostate cancer,” probl urol, vol. 4, pp. 343–357, 1990. doi 10.18502/sjms.v12i1.856 page 32 introduction materials and methods results discussion conclusions the author contributions references page 43 research article clinical staging and flowcytometric cd38 and zap-70 prognostic indicators in sudanese patients with chronic lymphocytic leukemia enaam abdelrhman abdelgader*1,2, nada hassan eltayeb3, tasniem ahmed eltahir2, osama ali altayeb4, eman abbass fadul4, soaad fadlallah ali5, eldirdiri m. abdelrhman2 1. department of pathology, faculty of medicine, alneelain university, sudan 2. khartoum oncology hospital, sudan 3. department of physiology, faculty of medicine, alneelain university, sudan 4. flow cytometry laboratory for leukemia & lymphoma diagnosis, sudan 5. department of pathology, faculty of medicine, gezira university, sudan abstract background: the clinical course of chronic lymphocytic leukemia is highly variable. the determination of zap70 and cd38 is increasingly utilized as prognostic factor for chronic lymphocytic leukemia. the aim of conducting this study was to investigate the frequency of cd38 and zap70 expression among sudanese chronic lymphocytic leukemia (cll) patients and to relate them to the binet and rai clinical staging systems. method: a total of 93 patients (mean age; 62.29 ± 11.68, sd) were enrolled in this crosssectional study. cd38 and zap70 expression levels were measured with four color flowcytometry using the cut-off values of 20% for zap70 and 30% for cd38 expression. staging was assessed by using clinical examination and cbc for all patients. data were analyzed using the statistical package for social science for windows (spss), version 22. results: there were 93 cll patients and the median age of the group was 63 years (36–95 years). about 71% of the patients presented with lymphadenopathy, 53.8% with splenomegaly, 73.1% with anemia, and 45.2% with thrombocytopenia. there was higher frequency of binet stage c and rai stage iv (62 [66.6%] patients and 34 [36.5%] patients, respectively). in addition, cd38 and zap70 showed higher frequency among binet and rai advance stages. zap70 and cd38 positivity were detected in 21 patients (22.6%) and 31 patients (33.3%), respectively. there was no statistically significant association between zap70 and cd38 and clinical staging systems (p > 0.05). conclusion: no significant association was observed between flowcytometric (cd38 and zap70) prognostic indicators and clinical staging systems. sudan journal of medical sciences volume 15, issue no. 1, doi 10.18502/sjms.v15i1.6704 production and hosting by knowledge e how to cite this article: enaam abdelrhman abdelgader (2019) “clinical staging and flowcytometric cd38 and zap-70 prognostic indicators in sudanese patients with chronic lymphocytic leukemia,” sudan journal of medical sciences, vol. 15, issue no. 1, pages 43–55. doi 10.18502/sjms.v15i1.6704 sudan journal of medical sciences volume 14, issue no. 4, doi 10.18502/sjms.v14i4.5899 production and hosting by knowledge e research article overview of the course of undergraduate medical education in the sudan tahra al sadig al mahdi medical education, school of medicine, ahfad university for women, omdurman, khartoum, sudan abstract background: sudan’s experience with medical education (me) is one of the oldest regionally. it started with one school and has currently reached 66. this number is among the highest and sudan is one of the largest physicians-exporting countries. thus, sudanese me has great regional influence. objective: to review the history of sudanese me and determine factors contributing to its transformation. methods: internet and desk search was conducted, relevant articles and websites were accessed, hard documents were reviewed, and eminent sudanese figures in the field were consulted. results: sudanese me is meagerly documented. the path of me was described in four phases including some of the significant local and global factors. phase one (1924–1970) started by establishing the first medical school and characterized by steady growth and stability. influences were the flexner’s era and the sudanese independence atmosphere. during phase two (1978–1990), provincial public schools were opened in addition to the first private school. influences were the sudan’s commitment to al ma ata recommendations and the revolutionary changes following constructivist views on learning. phase three (1990–2005) was formed by the revolution in higher education leading to mushrooming of public and private schools across the country and influenced by local sociopolitical turbulence. in phase four (2006–2018), authorities launched formal me regulatory efforts. it is still being transformed by contradicting local factors and strong international directions. conclusion: sudanese experience with me is noteworthy; it offers important lessons and gives the needed wisdom for dealing with me challenges in sudan and beyond. 1. introduction sudan is the third largest country in africa with a total population of around 40 million people [1]. it borders seven countries and its capital is khartoum. sudan is a miniature representation of the diversity found in most african countries [2, 3]. the country is composed of 18 states; approximately 66% of the population lives in rural areas [4], and the percentage of poverty is around 46.5% [5]. the country suffers from a marked shortage in health workforce worsened by poor distribution over the how to cite this article: tahra al sadig al mahdi (2019) “overview of the course of undergraduate medical education in the sudan,” sudan journal of medical sciences, vol. 14, issue no. 4, pages 188–201. doi 10.18502/sjms.v14i4.5899 page 188 corresponding author: tahra al sadig al mahdi received 23 august 2019 accepted 14 december 2019 published 30 december 2019 production and hosting by knowledge e tahra al sadig al mahdi. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf corresponding author: enaamresearch@gmail.com. received 15 january 2020 accepted 02 september 2019 published 31 march 2020 production and hosting by knowledge e cc enaam abdelrhman abdelgader. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf key words: chronic lymphocytic leukemia; flowcytometry; zap70; cd38; clinical staging systems introduction chronic lymphocytic leukemia (cll) follows a remarkably heterogeneous course ranging  from mild disease without ever requiring treatment to aggressive and mailto:enaamresearch@gmail.com sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 44 drug-resistant disease [1]. the rai and binet [2, 3] clinical staging systems are valuable in classifying cll patients into broad prognostic subgroups. clinical stages, however, have some limitations and this has led to a search for novel parameters with improved predictive power. prognostic predictions in b-cll at early clinical stage are based on biological disease parameters, such as zap-70 and cd38 protein levels, genomic aberrations as well as immunoglobulin variable heavy chain gene (igvh) mutation status [4]. dna microarray studies have shown that b-cll cells with unmutated igvh genes can be distinguished from those with mutated igvh genes by the differential expression of a small number of genes, one of which encodes the 70-kda zeta associated protein (zap-70) [5, 6]. zap-70, a member of the syk-zap-70 protein tyrosine kinase family, is a key signaling molecule for t lymphocytes and natural killer cells. while zap-70 is not expressed in normal b lymphocytes, it is associated with increased intracellular signaling via the immunoglobulin receptor in b-cll cells [7, 8]. considering three recently published studies [9–11], zap-70 is the most promising surrogate marker for the igvh mutation status. in contrast to the technically demanding igvh analysis, zap-70 protein expression is conveniently measured by flow cytometry [9, 12, 13]. cd38 is a type ii transmembrane glycoprotein that acts as a complex ecto-enzyme and receptor molecule with signaling functions in b-cll cells [14]. detection of cd38 cell surface expression can be conveniently performed by flowcytometry, and, together with zap-70 [11], cd38 analysis may prove a valuable adjunct in the diagnostic workup of b-cll patients. cd38 expression also has been suggested as a surrogate marker for the two important igvh mutated and unmutated subgroups of b-cll [15]. at present, both zap-70 and cd38 are regarded as independent prognostic variables in b-cll [9, 16]. the main objective of this study is to determine the frequency of cd38 and zap-70 expression and the relationship between clinical staging system and flowcytomtery prognostic markers (cd38 and zap-70) in sudanese patients with cll. material and methods patients this observational cross-sectional (hospital based) study was conducted in khartoun oncology hospital during the period from september 2016 to februray 2017. this study was approved by the ethical committee, sudan medical specialty board (smsb). informed consent was obtained from all participants in accordance to the requirements and guidelines of the ethical committee. a total of 93 untreated sudanese patients with cll were included in this study. the patients were diagnosed according to the international sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 45 cll workshop criteria [18] and the guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [19]. demographic and clinical data were collected from the study population using a well structured questionnaire. 5 ml of venous blood were collected from each patient in ethylene diamine tetra acetic acid (edta) vacuum tubes under adequate precautions and according to the standard protocol. then the samples were transported to the flow cytometry laboratory for leukemia & lymphoma diagnosis (khartoum2, sudan), preserved at room temperature (22–24ºc) and processed within 6–24 h of collection. methods routine investigations physical examination was done to evaluate bidimensional diameters of the largest palpable lymph nodes in each of the following sites: cervical, axillaries, supraclavicular, inguinal, and femoral. the size of the liver and spleen, were assessed by using chest radiography and abdominal ultrasound. cbc was carried out using automated cell counter (sysmex xe-2100™). physical examination and complete blood count were used for assigning both rai and binet clinical staging systems. flowcytometry four color flowcytometer (coulter epics xl-mcltm flowcytometer miami, florida usa) with system ii software was used to determine the immunophenotyping, surface cd38 expression and intracellular zap-70 expression for the study population. the instrument set up was checked daily using qc check beads flowcytometry (beckman coulter, usa). immunophenotyping of lymphocytes from lysed whole peripheral blood was carried out to confirm the diagnosis of cll using the following monoclonal antibodies (beckman coulter, usa); cd45, cd5, cd19, cd20, cd22, cd23, kappa and lambda light chains, fmc7, cd79b. a marker was considered positive at a cutoff level of  20%. the matutes scoring system allocates one point each for the expression of weak smig, cd5, cd23, and absent or low expression of cd79b and fmc7 [20, 21]. surface cd38 expression surface cd38 was analyzed in peripheral blood using io test cd38-pc5 kit (beckman coulter, usa) according to the manufacturer protocol. cd38 is measured by flowcytometry and plotted against b-cell marker cd19 expression. the cd38 expression was considered positive at cutoff level of 30%. sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 46 intracellular zap-70 expression intracellular zap70 expression in pb samples was measured using perfix-nc a fixation  and permeabilization kit and io test zap-70-pe (pn b57658) kit (beckman coulter,  usa) according to the manufacturer protocol. the zap-70 expression was considered positive at a cutoff level of 20%. data management data were sorted, categorized, coded and summarized on master sheet. the collected data were analyzed using the software program of the statistical package for social science for windows (spss), version 22. frequencies were determined using descriptive statistic. chi square test was used to investigate the relationship between age, gender, clinical stages, cd38 and zap70 at p = 0.05. results demographic data the 93 patients enrolled in this study include 63 (67.7%) male and 30 (32.3%) female  with a median age of 63 (36-95 years). at the time of diagnosis, mean of patient  ages  was  62.29  ± 11.68, sd. most of the patients 55 (59.1%) were in the age group 56 – 75. (table 1). lymph nodes and organomegaly the majority of patients presented with lymphadenopathy in 66 patients (70.9%). on the other hand clinical examination showed presence of splenomegaly in 50 patients (53.8%), hepatomegaly in 23 patients (24.7%) and hepatosplenomegaly in 22 patients (23.7%) (table 1). cbc cbc results showed white blood cell count more than 50 x 109 in 62 (66.7%) patients, anaemia in 68 (73.1%) patients and thrombocytopenia in 42 (45.2%) patients, (table 1). sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 47 table 1: chracteristics of the study population. parameter frequency no (%) parameter frequency no (%) age leukocyte count (x 103/µl) 36–55 29 (31.2%) ≤50 31 (33.3%) 56–75 55 (59.1%) >50 62 (66.7%) 76–95 9 (9.7%) scoring system sex score 3 5 (5.4%) male 63 (67.7%) score 3.5 5 (5.4%) female 30 (32.3%) score 4 27 (29.0%) ln (no of sites involved) score 4.5 4 (4.3%) absent 27 (29.0%) score 5 52 (55.9) 1 site 4 (4.3%) rai staging system 2 sites 7 (7.5%) stage 0 4 (4.3%) 3 sites 4 (4.3%) stage i 8 (8.6%) >3 sites 51 (54.8%) stage ii 18 (19.4%) splenomegaly stage iii 29 (31.2%) present 50 (53.8%) stage iv 34 (36.5%) absent 43 (46.2%) binet staging system hepatomegaly stage a 10 (10.8%) present 23 (24.7%) stage b 21 (22.6%) absent 70 (75.3%) stage c 62 (66.6%) haemoglobin (g/dl)* cd38 and zap-70 expression severe 13 (14.0) cd38 + 31 (33.3) moderate 31 (33.3%) cd38 − 62 (66.7) mild 24 (25.8) zap-70 + 21 (22.6) non anaemia 25 (26.9) zap-70 − 72 (77.4) platelets count (×103/µl) cd38 + / zap-70 + 10 (10.8) <150 42 (45.2) cd38 − / zap-70 − 51 (54.8) 150–450 50 (53.7) cd38 + / zap-70 − 21 (22.6) >450 1 (1.1) cd38 − / zap-70 + 11 (11.8) staging systems the study results showed that, there was higher frequency of binet stage c and rai stage iv (62 (66.6%) patients, 34 (36.5%) patients respectively) followed by bient stage b and rai stage iii (21 (22.6%) patients, 29 (31.2%) patients respectively), binet stage a and rai stage ii 10 (10.8%) patients, 18 (19.4%) patients respectively) and rai stage 1 and rai stage 0 (8 (8.6%) patients, 8 (8.6%) patients respectively), (table 1). cd38 expression the b-cll cells were considered cd38 positive when ≥30% expressed the membrane antigen. based on this cutoff value, 31 patients (33.3%) were cd38 positive and 62 patients (66.7) were cd38 negative (table 1). sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 48 zap-70 expression a cll population was considered zap-70-positive when at least 20% of the gated cells (cd19 positive b cells) expressed it. the leukemic cells were zap-70 positive in 21 patients (22.6%) and zap-70 negative in 72 patients (77.4), (table 1). association of clinical staging systems with lymph nodes, organomegaly and cbc rai and binet staging system showed highly significant association with lymphadenopathy  (p = 0.01, 0.00 respectively), haemoglobin concentration (p = 0.00 for both) and platelet count (p =0.00 for both). splenomegaly showed highly significant association with rai staging system (p =0.00) while no significant association was observed with binet staging system (p = 0.20). no significant association was observed of binet and rai clinical staging systems with age, sex, hepatomegaly and twbcs count (p > 0.05), table 2. table 2: association between clinical staging systems and the study variables. variables rai staging system (%) binet staging system (%) 0 i ii iii iv p value a b c p value age 36–55 1 (1.1%) 2 (2.2%) 5 (5.4%) 10 (10.7%) 11 (11.7%) 0.91 2 (2.2%) 6 (6.5%) 21 (22.5%) 0.61 56–75 3 (3.2%) 6 (6.5%) 11 (11.7%) 17 (18.3%) 18 (19.4%) 8 (8.6%) 13 (14.0%) 34 (36.5%) 76–95 0 (0.0%) 0 (0.0%) 2 (2.2%) 2 (2.2%) 5 (5.4%) 0 (0.0%) 2 (2.2%) 7 (7.5%) sex (%) male 3 (3.2%) 4 (4.3%) 11 (11.8%) 17 (18.3%) 28 (30.1%) 0.20 5 (5.4%) 14 (15.0%) 44 (47.3%) 0.42 female 1 (1.1%) 4 (4.3%) 7 (7.5%) 12 (12.9%) 6 (6.5%) 5 (5.4%) 7 (7.5%) 18 (19.4%) lymphadenopathy not found 4 (4.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0.01 6 (6.4%) 2 (2.2%) 19 (20.4%) 0.00 one site 0 (0.0%) 1 (1.1%) 3 (3.2%) 0 (0.0%) 4 (4.3%) 1 (1.1%) 0 (0.0%) 3 (3.2%) two sites 4 (4.3%) 0 (0.0%) 2 (2.2%) 2 (2.2%) 10 (10.7%) 3 (3.2%) 2 (2.2%) 2 (2.2%) three sites 10 (10.7%) 1 (1.1%) 0 (0.0%) 2 (2.2%) 16 (17.2%) 0 (0.0%) 2 (2.2%) 2 (2.2%) more than three sites 9 (9.6%) 2 (2.2%) 2 (2.2%) 0 (0.0%) 21 (22.5%) 0 (0.0%) 15 (16.1%) 36 (38.6%) (continued) sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 49 splenomegaly present 0 (0.0%) 0 (0.0%) 5 (5.3%) 9 (9.7%) 9 (9.7%) 0.00 2 (2.2%) 13 (14.0%) 35 (37.6%) 0.20 absent 4 (4.3%) 8 (8.6%) 13 (13.9%) 20 (21.5%) 25 (26.9%) 8 (8.6%) 8 (8.6%) 27 (29.0%) hapatomegaly present 0 (0.0%) 0 (0.0%) 5 (5.4%) 9 (9.7%) 9 (9.7%) 0.52 1 (1.1%) 4 (4.3%) 18 (19.3%) 0.60 absent 4 (4.3%) 8 (8.6%) 13 (14.0%) 20 (21.5%) 25 (26.8%) 9 (9.7%) 17 (18.3%) 44 (47.3%) haemoglobin concentration (g/dl) severe 0 (0.0%) 0 (0.0%) 0 (0.0%) 6 (6.5%) 7 (7.5%) 0.00 0 (0.0%) 0 (0.0%) 13 (13.9%) 0.00 moderate 0 (0.0%) 0 (0.0%) 0 (0.0%) 19 (20.4%) 12 (12.9%) 0 (0.0%) 1 (1.1%) 30 (32.2%) mild 2 (2.2%) 3 (3.2%) 9 (9.6%) 4 (4.3%) 6 (6.5%) 4 (4.3%) 10 (10.8%) 10 (10.8%) no anaemia 2 (2.2%) 5 (5.4%) 9 (9.6%) 0 (0.0%) 9 (9.7%) 6 (6.5%) 10 (10.8%) 9 (9.6%) twbcs count x 109 ≤50 2 (2.2%) 4 (4.3%) 8 (8.6%) 4 (4.3%) 13 (13.9%) 0.10 4 (4.3%) 10 (10.8%) 17 (18.2%) 0.21 >50 2 (2.2%) 4 (4.3%) 10 (10.8%) 25 (26.8%) 21 (22.6%) 6 (6.5%) 11 (11.8%) 45 (48.4%) platelet count x 109 <150 0 (0.0%) 2 (2.2%) 3 (3.2%) 3 (3.2%) 34 (36.6%) 0.00 2 (2.2%) 3 (3.2%) 37 (39.8%) 0.00 150–450 3 (3.2%) 6 (6.5%) 15 (16.1%) 26 (27.9) 0 (0.0%) 7 (7.5%) 18 (19.4%) 25 (26.8%) >450 1 (1.1%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (1.1%) 0 (0.0%) 0 (0.0%) association of zap-70 and cd38 expression with lymph nodes, organomegaly, cbc and clinical staging systems cd38 and zap70 showed higher frequency among bient and rai advance stages. the frequency of cd38 in rai stage iii and iv was equal (11 patients (11.8%). zap70 frequency in rai stage iii and iv was (8 (8.6%), 7 (7.5%), respectively), (table 4). the results showed no significant association of flowcytometric (cd38 and zap-70) prognostic indicators with lymphadenopathy, organomegaly, twbcs, haemoglobin concentration, platelet count and clinical staging systems (p > 0.05), (table 3). table 2: (continued) sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 50 table 3: association of flowcytometer prognostic indicators with the study variables. variables cd38 no (%) zap-70 no (%) cd38 + cd38 − p value zap-70 + zap-70 − p value age 36–55 7 (7.5%) 22 (23.7%) 0.40 9 (9.7%) 20 (21.5%) 0.35 56–75 20 (21.5%) 35 (37.6%) 11 (11.8%) 44 (47.3%) 76–95 4 (4.3%) 5 (5.4%) 1 (1.1%) 8 (8.6%) sex male 22 (23.7%) 41 (44.08%) 0.64 14 (15.1%) 49 (52.7%) 0.36 female 9 (9.7%) 21 (22.6%) 7 (7.5%) 23 (24.7%) lymphadenopathy not found 9 (9.7%) 18 (19.4%) 0.64 6 (6.5%) 21 (22.6%) 0.42 one site 0 (0.0%) 4 (4.3%) 1 (1.1%) 3 (3.2%) two sites 2 (2.2%) 5 (5.3%) 0 (0.0%) 7 (7.5%) three sites 1 (1.1%) 3 (3.2%) 0 (0.0%) 4 (4.3%) more than three sites 19 (20.4%) 32 (34.4%) 14 (15.0%) 37 (39.8%) splenomegaly present 19 (20.4%) 31 (33.3%) 0.49 12 (12.9%) 38 (40.9%) 0.83 absent 12 (13.0%) 31 (33.3%) 9 (9.7%) 34 (36.5%) hepatomegaly present 10 (10.8%) 13 (13.9%) 0.40 5 (5.4%) 18 (19.4%) 0.85 absent 21 (22.6%) 49(52.7%) 16 (17.2%) 54 (58.0%) haemoglobin concentration (g/dl) severe 6 (6.5%) 7 (7.5%) 0.68 3 (3.2%) 10 (10.8%) 0.99 moderate 11 (11.8%) 20 (21.5%) 7 (7.5%) 24 (25.8%) mild 7 (7.5%) 17 (18.3%) 5 (5.4%) 19 (20.4%) no anaemia 7 (7.5%) 18 (19.4%) 6 (6.5%) 19 (20.4%) twbcs count x 109 ≤50 10 (10.8%) 21 (22.6%) 0.88 5 (5.4%) 26 (27.9%) 0.29 >50 21 (22.6%) 41 (44.0%) 16 (17.2%) 46 (49.5%) platelet count x 109 <150 16 (17.2%) 26 (28.0%) 0.56 9 (9.7%) 33 (35.5%) 0.83 150–450 15 (16.1%) 35 (37.6%) 12 (12.9%) 38 (40.8%) >450 0 (0.0%) 1 (1.1%) 0 (0.0%) 1 (1.1%) table 4: association between flowcytometer prognostic indicators and clinical staging systems. parameter cd38 no (%) zap-70 no (%) positive negative p value positive negative p value rai staging system stage 0 1 (1.1%) 3 (3.2%) 0.69 1 (1.1%) 3 (3.2%) 0.91 stage i 1 (1.1%) 7 (7.5%) 1 (1.1%) 7 (7.5%) stage ii 7 (7.5%) 11 (11.8%) 4 (4.3%) 14 (15.1%) stage iii 11 (11.8%) 18 (19.4%) 8 (8.6%) 21 (22.6%) stage iv 11 (11.8%) 23 (24.7%) 7 (7.5%) 27 (29.0%) (continued) sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 51 binet staging system stage a 4 (4.3%) 6 (6.5%) 0.81 2 (2.2%) 8 (8.6%) 0.97 stage b 6 (6.5%) 15 (16.1%) 5 (5.4%) 16 (17.2%) stage c 21 (22.6%) 41 (44.0%) 14 (15.0%) 48 (51.6%) association between zap-70 and cd38 expression the study results showed that, there was higher frequency of cd38 (31 patients, (33.3)) than zap-70 (21 patients, (22.6)) among patients. ten of 93 patients (10.8%) were concordant zap-70 positive cd38 positive and 51 patients (54.8%) were concordant zap-70 negative cd38 negative (table 1). no significant statistical association was  observed between zap-70 and cd38 expression among sudanese cll patients (p = 0.05). discussion in order to investigate the frequency of zap-70 and cd38 and their relationship with clinical staging systems we performed a cross sectional study in 93 cases of cll. to our knowledge this is the first study to examine the frequency of zap-70 and cd38 and their relationship with clinical staging systems in sudan. clinical staging systems are the most robust and established prognostic factors in cll. recent studies have pointed out some of the limitation in these traditional staging systems [9]. not all early-stage patients fall into the same prognostic category. a study from vroblová et al [22] showed that the classic staging systems by rai and binet are not able to determine an individual patient’s ongoing clinical course at the time of diagnosis, particularly in early stages. most of our patients presented in advance stages (bient stage c and rai stage iv (71.2%, 40.4% respectively)). this may be explained by; poor health services distribution and lack of screening program and awareness. rai and binet staging system showed highly significant association with lymphadenopathy (p = 0.01, 0.00 respectively), haemoglobin concentration (p = 0.00 for both) and platelet count (p = 0.00 for both). splenomegaly showed highly significant association with rai staging system (p = 0.00) while no significant association was observed with binet staging system (p = 0.20). no significant association was observed between both rai and binet staging systems and age, sex, hepatomegaly and twbcs count (p > 0.05), (table 2). various studies have reported zap-70 positivity ranging from 25% to 57% and cd38 positivity in cll ranging from 29% to 60% as given in (table 5). table 4: (continued) http://www.indianjcancer.com/viewimage.asp?img=indianjournalofcancer_2013_50_4_333_123620_t4.jpg sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 52 table 5: comparison of zap-70 and cd38 frequency with literature. study no. of patients zap-70% cd38% crespo et al. [23] 56 57 60 gogia et al. [24] 80 25 36 hus et al. [24] 156 36 33 schoroer et al. [4] 252 46 29 d’arena et al. [26] 157 36 29 present study 93 22.6 33.3 our study results showed that, there was higher frequency of cd38 than zap-70, among 93 patients who were tested 33.3% (31 patients) were cd38 positive and 22.6% (21 patients) were zap-70 positive. crespo et al, investigated zap-70 and cd38 among 56 patients with cll. 57% of patients were positive for zap-70 and 60% positive for cd38 [23]. this in agreement with our study. also our findings are in accordance with a study by gogia et al which examined zap-70 and cd38 expression among 80 cll patients, they found that zap-70 was positive in 25% and cd38 was positive in 36% [24]. in contrast a study by hus et al reported positive expression for zap-70 in 36% of 156 patients and cd38 in 33% [4]. this is inconsistent with our findings. our results are incompatible with a study carried out by schoroer et al among 252 patients. their results revealed that 46% of patients were zap-70 positive and 29% were cd 38 positive [25]. one hundred and fifty seven patients were enrolled in a study by d’arena et al, their results reported that zap-70 was positively expressed among 36% of patients and cd38 among 29%.this in disagreement with our results [26]. flowcytometric (cd38 and zap-70) prognostic indicators show no significant association with age, sex, lymph nodes, organomegaly, cbc and clinical staging systems (p > 0.05). a study by del poeta et al., and hus et al. indicated significant correlation between high zap-70 levels and advanced rai stage and splenomegaly [4, 27]. this in disagreement with our results. our findings goes in line with a study done by gogia et al from india, reported no associationof zap-70 and cd38 positivity with age, sex, lymphadenopathy, organomegaly, and rai staging [24]. the contrast in our results may be contributed to biological factors, ethnic heterogeneity and environmental factors. conclusion in conclusion, cd38 (31 patients, (33.3)) show higher frequency than zap-70 (21  patients, (22.6)) among patients. there was no significant association of zap-70 and cd38 positivity with age, sex, lymphadenopathy, organomegaly, bient and rai staging http://www.indianjcancer.com/searchresult.asp?search=&author=a+gogia&journal=y&but_search=search&entries=10&pg=1&s=0 http://www.indianjcancer.com/searchresult.asp?search=&author=a+gogia&journal=y&but_search=search&entries=10&pg=1&s=0 http://www.indianjcancer.com/searchresult.asp?search=&author=a+gogia&journal=y&but_search=search&entries=10&pg=1&s=0 sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 53 systems. further studies are recommended to develop a standardized flowcytometry protocol that will allow comparison of zap-70 and cd38 measurements between different laboratories. acknowledgement i would like to thank those who have contributed so much to this work; dr. osama ali, director of the flow cytometry laboratory for leukemia & lymphoma diagnosis, who allowed me to work in his laboratory where i also received much help from his technical staff especially; mis. eman abass , dr. asma mukhtar and many of their colleagues. conflict of interest the authors have no conflict of interest to declare. references [1] rozman c, montserrat e (1995). chronic lymphocytic leukaemia. n engl j med. 333: 1052–1057. 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(2003). zap-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. blood. 101(12): 4944–4951. sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 54 [7] chen l, widhopf g, huynh l et al. (2002). expression of zap-70 is associated with increased b-cell receptor signaling in chronic lymphocytic leukemia. blood. 100(13): 4609–4614. [8] chen l, apgar j, huynh l et al. (2005). zap-70 directly enhances igm signaling in chronic lymphocytic leukemia. blood. 105(5): 2036–2041. [9] crespo m, bosch f, villamor n et al. (2003). zap-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. n engl j med. 348(18): 1764–1775. [10] orchard ja, ibbotson re, davis z et al. (2004). zap-70 expression and prognosis in chronic lymphocytic leukaemia. lancet. 363(9403): 105–111. [11] rassenti lz, huynh l, toy tl et al. (2004). zap-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. n engl j med. 351(19): 893–901. [12] dürig j, nückel h, cremer m et al. (2003). zap-70 expression is a prognostic factor in chronic lymphocytic leukemia. leukemia. 17(12): 2426–2434. [13] schroers r, pukrop t, dürig j et al. (2004). b-cell chronic lymphocytic leukemia with  aberrant cd8 expression: genetic and immunophenotypic analysis of prognostic factors. leukemia & lymphoma. 45(8): 1677–1681. [14] deaglio s, capobianco a, bergui l et al. (2003). cd38 is a signaling molecule in b-cell chronic lymphocytic leukemia cells. blood. 102(6): 2146–2155. [15] damle rn, wasil t, fais f et al. (1999). ig v gene mutation status and cd38 expression as novel prognostic indicators in chronic lymphocytic leukemia. blood. 94(6): 1840–1847. [16] hamblin tj, orchard ja, ibbotson re et al. (2002). cd38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but cd38 expression may vary during the course of the disease. blood. 99(3): 1023–1029. [17] cheson bd, bennett jm, grever m et al. (1996). national cancer institute-sponsored working group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. blood. 87(12): 4990–4997. [18] hallek m, cheson bd, catovsky d et al. (2008). guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the international workshop on chronic lymphocytic leukemia updating the national cancer institute – working group 1996 guidelines. blood. 111(12): 5446–5456. sudan journal of medical sciences enaam abdelrhman abdelgader et al. doi 10.18502/sjms.v15i1.6704 page 55 [19] matutes e, owusu-ankomah k, morilla r et al. (1994). the immunological profile of b-cell disorders and proposal of a scoring system for the diagnosis of cll. leukemia. 8(10): 1640–1645. [20] moreau ej, matutes ea, ‘hern rp et al. (1997). improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody sn8 (cd79b). am j clin pathol. 108(4): 378–382. [21] vroblová v, smolej l, vrbacky f et al. (2009). biological prognostic markers in chronic lymphocytic leukemia. acta medica. 52(1): 3–8. [22] del poeta g, maurillo l, venditti a et al. (2001). clinical significance of cd38 expression in chronic lymphocytic leukemia. blood. 98(9): 2633–2639. [23] gogia a, sharma a, raina v et al. (2013). prevalence of zap-70 and cd38 in indian chronic lymphocytic leukemia patients. indian journal of cancer. 50(4): 333–336. [24] hus i, podhorecka m, bojarska-junak a et al. (2006). the clinical significance of zap70 and cd38 expression in b cell chronic lymphocytic leukemia. ann oncol. 17(4): 683–690.  [25] d’arena g, tarnani m, rumi c et al. (2007). prognositc significance of combined analysis of zap-70 and cd38 in chronic lymphocytic leukemia. am j haematol. 82(9): 787–791.   [26] zenz t, frohling s, mertens d et al. (2010). moving from prognostic to predictive factors in chronic lymphocytic leukaemia (cll). best pract res clin haematol. 23(1): 71–84. sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7175 production and hosting by knowledge e rapid review convalescent plasma a potential therapy in covid-19 patients in low resource setting abdelrahman h. abdelmoneim1,9, mujahed i. mustafa2, raghda hatim abdalhaleem adlan3, noun eltayeb ahmed abdulgader4,5, hiba awadelkareem osman fadl6, nosaiba kamal alhassan7, and sahar g. elbager8 1faculty of medicine, al-neelain university, khartoum, sudan. 2department of biotechnology, university of bahri, khartoum, sudan. 3faculty of medicine, khartoum university, sudan. 4human clinical anatomy department-national university, khartoum, sudan. 5alraqi university hospital, khartoum, sudan. 6faculty of medical laboratory sciences, al-neelain university, khartoum-sudan. 7faculty of medical laboratory sciences, national ribat university, khartoum, sudan. 8faculty of medical laboratory sciences, university of medical sciences and technology (umst), sudan. 9m.d. clinical immunology resident, sudan medical specialization board, khartoum, sudan. abstract background: the covid-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). at the time of writing, neither a cure nor a vaccine has been approved by the world health organization (who) for this disease. given the fact that the severe acute respiratory syndrome coronavirus (sars) and middle east respiratory syndrome (mers) viruses have a genetic sequencing similar to sars-cov2, and since the use of convalescent plasma therapy (cp) has proved its efficacy in sars and mers virus infections, researchers are starting to focus more on it as a possible therapy for the covid-19 disease. the main objective of this rapid review is to report and summarize the published evidence on the role of convalescent plasma therapy in the current covid-19 pandemic. method: the pico method was used to establish the review question. moreover, papers were gathered from pubmed and google scholar, critically appraised for the best evidence. piersons 5-component scheme was used to check the quality of the review papers. results: after website screening: 10 papers in pubmed and 6 papers from google scholars were retrieved. there were encouraging reports regarding the uses of cp in the previous viral outbreaks likes sars and ebola, yet there is still a doubt on the efficacy of this mode of therapy in the current covid-19 pandemic. conclusion: cp is a very promising treatment approach for covid-19 patients; however, more clinical trials are required to validate the effectiveness of this therapy. keywords: covid-19, convalescent plasma therapy, sars-cov-2, therapy. how to cite this article: abdelrahman h. abdelmoneim, mujahed i. mustafa, raghda hatim abdalhaleem adlan, noun eltayeb ahmed abdulgader, hiba awadelkareem osman fadl, nosaiba kamal alhassan, and sahar g. elbager (2020) “convalescent plasma a potential therapy in covid-19 patients in low resource setting,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 20–31. doi 10.18502/sjms.v15i5.7175 page 20 corresponding author: abdelrahman h. abdelmoneim; email: abduhamza009@gmail.com tel:024914173555 mujahed i. mustafa received 22 april 2020 accepted 25 may 2020 published 10 june 2020 production and hosting by knowledge e abdelrahman h. abdelmoneim et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abduhamza009@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdelrahman h. abdelmoneim et al 1. introduction severe acute respiratory syndrome coronavirus 2 (sars-cov-2), originating from wuhan in china, has rapidly enveloped the world becoming a pandemic [1]. as of the 13th of april,2020, there were 1,773,084 worldwide confirmed cases with 111,652 deaths as reported by the world health organization (who) [2]. the virus sequencing revealed a high similarity to sars, making it the seventh virus discovered of this family. on the 11th of february, 2020, the who officially named the disease caused by this virus, covid-19. many trials have assessed possible therapeutics and prevention methods for the disease. nonetheless, to date, there are no drugs or vaccines specifically approved for the disease by the who [3]. options of treatment such as antiviral drugs and corticosteroids are still under review by many agencies and are yet to be officially approved by the who [3, 4]. serology testing of covid-19 patients has revealed a notable rise in igm antibodies in the acute setting, followed by rise in igg antibodies as the patient entered the recovery phase. therefore, many researchers have suggested using convalescent plasma from the recovered patient, and applying it as a passive antibody therapy for severe covid19 patients [5, 6]. specific application of plasma therapy was similarly used during the ebola virus pandemic in 2014, when the who officially authorized the use of convalescent plasma as an empirical treatment therapy and published guidelines that specify the steps for donor selection, specimen collection and administration of this therapy to the ebola infected patients [7]. convalescent plasma therapy was also used successfully in managing diseases, caused by influenza virus and other pathogens [8, 9]. closely related to the use of convalescent plasma therapy, is the use of monoclonal antibodies. the therapeutic potential of this mode of treatment has proved effective in the past in the treatment of many diseases. some studies tested the effectiveness of monoclonal antibodies in vitro and in vivo against viral infections like sars and mers and they were found to yield positive results, yet like other types of treatment modalities, more clinical trials are needed to confirm the effectiveness of this method in the context of covid-19 patients [10, 11]. when the patient is infected with a virus, his immune system starts to produce antibodies against the virus, which can later be harnessed in the form of convalescent plasma and transfused into a patient with a current infection, where it can neutralize and even induce antibody-dependent cellular cytotoxicity against the invading virus. this approach is usually used in conjunction with other antiviral and maintenance therapy [5, 12–16]. mechanisms of convalescent plasma therapy illustrated in fig 1. cp therapy has been applied in clinical practice for a long time but its efficacy remains a point of debate between health professionals. previous research proved this technique useful in the case of sars1 and mers infections, and since sars-cov2 and sarscov1 and mers viruses share clinical and genetic similarities, it is predicted that this type of therapy will have a good result in covid-19 patients. yet, some reports doubted the efficiency of this maneuver as the plasma will not be pure, and it may even contain other viral particles, which may cause patients to contact other diseases [17–19]. doi 10.18502/sjms.v15i5.7175 page 21 sudan journal of medical sciences abdelrahman h. abdelmoneim et al figure 1: mechanisms of convalescent plasma therapy (this image was created by author mujahed i. mustafa) however, using antivirals may not be a cost-e ffective method for treatment in low income countries like sudan, whereas plasma therapy extraction and preparation are more readily available and achievable in these countries making it a more reasonable choice of therapy [20]. the main objective of this rapid review is to clarify the conflicting evidence regarding the use of convalescent plasma therapy in covid-19 patients, and to summarize the best evidence available. 2. method on the 10th of april 2020 the research databases pubmed, google scholar were screened for articles providing information on the use of convalescent plasma for the treatment of covid-19 patients, (fig.2). the inclusion criteria were any published (full text) articles written in english and all clinical study designs including case series. furthermore, any articles published before 2019, and articles with no significant or duplicated information were excluded. subsequently, reference lists of identified articles were searched to extract further relevant articles. two reviewers conducted a detailed screening of the titles and abstracts. all authors independently performed full-text screening of identified articles and participated in the steps of manuscript preparation, writing and final revision. the pico method was used to establish the review question in a standardized form (table 1). the quality of each clinical report study was evaluated doi 10.18502/sjms.v15i5.7175 page 22 sudan journal of medical sciences abdelrahman h. abdelmoneim et al using piersons 5-component scheme, which composes of the following five components each with a score of zero to one (uniqueness, documentation, interpretation, objectivity, and educational value) with scores of 5 or less indicate of insufficient quality [21] 2.1. data synthesis the results were presented in a narrative format as the heterogeneity of outcomes and study designs made quantitative synthesis inappropriate. table 1: picos items: formation of the review question. picos item description population patients with laboratory-confirmed sars-cov-2 infection. intervention convalescent plasma therapy comparisons patients with covid-19 disease who did not receive cp transfusion. outcome clinical outcomes of sars-cov-2 infection including but not limited to death, intensive care admission, ventilation, and sars-cov-2 viral shedding. 3. results a total of 16 articles were found after preliminary screening of the pubmed and google scholars databases. after title and abstract screening, a total of 9 articles were excluded. full-text screening of the remaining 7 articles was conducted. among these studies, after critical appraisal full-text screening, a total of 4 articles were included in the final review, all were published in respected journals. three articles were excluded after full-text screen (1 review article, 1 letter to the editor, and 1one commentary) fig 2. details of studies included in this review are summarized in table 2. pierson’s assessment showed that the article produced by duan et al [5] was the highest quality report with a score of 9 in comparison to only 8 in the other three reports (shen et al [22],jy ahn et al [23],and zhang et al [24]). 4. discussion currently antiviral medication remdesivir along with other antiviral drugs hold promising results in the fight against covid-19. however, factors such as the high price and the unavailability of these medications in low resource setting countries coupled with the long time period needed to develop and test a vaccine (12 to 18 moths) [17], these factors make these medications inappropriate choices in low resource settings like sudan and other similar countries. therefore, searching for more reasonable treatment choices like convalesce plasma therapy [13], is appropriate since most countries already have the infrastructure, needed to prepare and perform this type of therapy. doi 10.18502/sjms.v15i5.7175 page 23 sudan journal of medical sciences abdelrahman h. abdelmoneim et al ta bl e 2: su m m ar y of fo ur cl in ic al re po rt s on th e ef fe ct iv en es s of co nv al es ce nt pl as m a th er ap y in c o v id -1 9 pa tie nt s. r e fe re n ce d ua n et al 20 20 [5 ] sh en et al 20 20 [2 2] jy a hn et al 20 20 [2 3] zh an g et al 20 20 [2 4] n o .o f p a ti e n ts 10 pa tie nt s 5 pa tie nt s 2 pa tie nt s 4 pa tie nt s a m o u n t o f p la sm a re ce iv e d 20 0 m l 40 0 m l 50 0 m l 90 0 m l, 20 0 m l, 24 0 0 m l an d 30 0 m l c lin ic a li m p ro ve m e n t -f ev er an d re sp ira to ry si gn s la rg el y im pr ov ed w ith in 1 to 3 da ys up on tr an sf us io n. -t w o ou to ft hr ee pa tie nt s w er e w ea ne d fro m m ec ha ni ca lv en til at io n to hi gh -fl ow na sa l ca nn ul a, an d on e ou to ft hr ee pa tie nt s di sc on tin ue d hi gh -fl ow na sa lc an nu la . -in on e pa tie nt tr ea te d w ith co nv en tio na ln as al ca nn ul a ox yg en at io n, co nt in uo us ox yg en at io n w as sh ift ed to in te rm itt en to xy ge na tio n. -b od y te m pe ra tu re no rm al iz ed w ith in 3 da ys in 4 of 5 pa tie nt s. -a r d s re so lv ed in 4 pa tie nt s at 12 da ys af te r tr an sf us io n. -3 pa tie nt s w er e w ea ne d fro m m ec ha ni ca lv en til at io n w ith in 2 w ee ks of tr ea tm en t -t he so fa sc or e de cr ea se d -p ao 2 /f io 2 in cr ea se d w ith in 12 da ys -b ot h pa tie nt s sh ow ed im pr ov em en ti n th e pa o 2 /f io 2 ra tio -b ot h pa tie nt s w ea ne d fro m th e m ec ha ni ca lv en til at or th e cl in ic al co nd iti on im pr ov ed in th e 4 ca se s an d th ey w er e di sc ha rg ed fro m th e ic u at (1 4, 7, 10 ,2 7 ) da ys of pl as m a tr an sf us io n la b o ra to ry im p ro ve m e n t -7 ou to f1 0 pa tie nt s sh ow in g an in cr ea se of ly m ph oc yt e co un ts . -c -r ea ct iv e pr ot ei n le ve lr ed uc ed -a la ni ne a m in ot ra ns fe ra se an d a sp ar ta te am in ot ra ns fe ra se re du ce d. -t he to ta lb ili ru bi n re m ai ne d un ch an ge d, ex ce pt fo r an ob vi ou s in cr em en ti n on e pa tie nt . -t he ne ut ra liz in g an tib od y tit er s of fiv e pa tie nt s in cr ea se d an d fo ur pa tie nt s re m ai ne d at th e sa m e le ve l. -s a r sc ov -2 –s pe ci fic el is a an d ne ut ra liz in g an tib od y tit er s in cr ea se d. -c r p, pr oc al ci to ni n, de cr ea se d in al lp at ie nt s -il 6 de cr ea se d in 4 ou to f5 pa tie nt s. -t he le ve lo fc r p an d il -6 re du ce d in bo th pa tie nt s. -l eu ko cy to si s an d ly m ph op en ia re co ve re d in on e pa tie nt . tw o ou to ff ou r ca se s pr od uc ed an tisa r sc ov -2 ig g ab ou t1 4 da ys af te r co nv al es ce nt pl as m a tr an sf us io n r a d io lo g ic a li m a g e im p ro ve m e n t a ll pa tie nt s sh ow ed di ffe re nt de gr ee s of ab so rp tio n of pu lm on ar y le si on s af te r tr an sf us io n c t sc an sh ow ed im pr ov em en to f th e pu lm on ar y le si on on on e pa tie nt on th e th ird da y af te r th e pl as m a tr an sf us io n an d gr ad ua l re so lu tio n of pu lm on ar y le si on s of ot he r pa tie nt s at 3d ay s af te r th e pl as m a tr ea tm en t th e de ns ity of bi la te ra l in fil tr at io n on ch es tx -r ay im pr ov ed in bo th pa tie nt s th e fo ur pa tie nt s sh ow ed re so lu tio n of th e ch es t ra di og ra ph le si on s t im e to v ?. ,m n b ir u s cl e a ra n ce sa r sc ov -2 r n a de cr ea se d to an un de te ct ab le le ve li n th re e pa tie nt s on da y 2 , th re e pa tie nt s on da y 3, an d on e pa tie nt on da y 6 (t he re m ai ni ng 3 pa tie nt s w er e ne ga tiv e be fo re tr an sf us io n) v ira ll oa ds be ca m e ne ga tiv e w ith in 12 da ys af te r th e tr an sf us io n sa r sc ov -2 w as ne ga tiv e af te r da y 20 in on e pa tie nt an d da y 26 in th e se co nd pa tie nt th e rt pc r be ca m e ne ga tiv e w ith in 4 da ys of pl as m a in fu si on in 3 pa tie nt s an d w ith in 3 w ee ks in th e fo ur th pa tie nt p ie rs o n s sc o re 9 8 8 8 doi 10.18502/sjms.v15i5.7175 page 24 sudan journal of medical sciences abdelrahman h. abdelmoneim et al figure 2: flow-gram of search and selection of articles 4.1. the use of convalescent plasma against sars-cov-2 plasma treatment is an old method of therapy that can be traced back for more than a century ago [14]. furthermore, there are several examples where convalescent plasma has been used successfully as a treatment of infectious diseases like sars, mers, h1n1, h5n1 and ebola. during sars outbreak, patients who were treated with plasma had more favorable prognosis and fewer side effects than those treated with antiviral drugs [25-32]. the largest study enrolled 80 patients in hong kong with sars1. the patients who received treatment before day 14 had better outcomes as defined by the release from hospital before day 22 [28]. in comparison fewer studies were done in mers outbreak possibly due to the limited numbers of donors [17]. in this current pandemic of sars-cov-2, several studies with limited data suggested that convalescent plasma is beneficial in extremely severe covid-19 patients [5, 22-24]. duan et al [5] in wuhan performed a pilot study to explore the feasibility of cp treatment in 10 severe covid-19 patients. 200 ml of convalescent plasma derived from recovered donors was transfused to the patients with neutralizing antibody titers more than 1:640. the patients were receiving maximal supportive treatment and antiviral therapy. after the transfusion, the neutralizing antibody titer was raised to 1:640 in five cases and maintained at a high level (1:640) in four cases. the clinical outcome showed dramatic improvement of symptoms within 1 to 3 days, and improved oxygen saturation within 3 days. laboratory parameters also improved, the mean lymphocyte counts were raised from (0.65 × 109/l) to (0.76 × 109/l) and the mean c-reactive protein declined from (55.98 mg/l) to (18.13 mg/l). radiological imaging showed varying degrees of reduction of pulmonary lesions within 7 days. the viral load was undetectable in seven patients after transfusion who had previous viremia. no severe adverse effects were detected. the dose mention here is close to the therapeutic dose of 250 ml, recommended doi 10.18502/sjms.v15i5.7175 page 25 sudan journal of medical sciences abdelrahman h. abdelmoneim et al in a review by evan m. bloch and colleagues [7]. nevertheless, the optimal dose and treatment duration, as well as the clinical benefit of cp therapy need further investigation in larger well-controlled trials. in addition, shen et al [22] in shenzhen, china, assessed the initial clinical experience with convalescent plasma transfusion administered to critically ill patients with covid19. the study involved five critically ill patients on mechanical. the patients were receiving antiviral treatment and methylprednisolone. following convalescent plasma transfusion, the patients’ body temperature improved in 4 out of 5 patients within three days. the sofa (sequential organ failure assessment score) declined from (2-10) before transfusion to (14) 12 days after the transfusion. the pao2/fio2 ratio was raised from (172-276) to (284-366) after 12 days, and the viral load became undetectable within the same period. the neutralizing antibody titers were raised from (40-60) to (80-320) on the seventh day after the transfusion. within 2 weeks, four patients recovered from ards (acute respiratory distress syndrome), and three patients were weaned from mechanical ventilators. two out of five patients were stable at 37 days, and three have been discharged within 2 months. these preliminary outcomes raise the probability that convalescent plasma transfusion may be supportive in the treatment of critically ill patients with covid-19. in korea, jy ahn et al [23] reported two cases of severe covid-19 patients presenting acute respiratory distress syndrome (ards), who showed a favorable clinical course after the convalescent plasma infusion. in the first patient the fever normalized and oxygen demand declined one day after the transfusion. the patient’s condition was much improved with decreased crp and il-6 to normal levels. after 8 days pao2/fio2 ratio became normal. chest x-ray revealed disappearance of lung lesions after 3 days. the virus was undetectable after day 26. the patient had tracheostomy and was successfully weaned from mechanical ventilation. in the second case, leukocytosis and lymphopenia recovered immediately after plasma transfusion. the density of pulmonary infiltrates on chest x-ray much improved 3 days after transfusion with increase in the pao2/fio2 ratio to 230. the level of crp and il-6 also normalized. sars-cov-2 was undetectable after day 20, and the patient was discharged on day 24. this rapid improvement was witnessed again in a study done by zhang et al [24]. they report the disease course on four critically ill patients infected with sars-cov-2 and treated with supportive care and convalescent plasma. they were confirmed positive by reverse transcriptase pcr. all of them received antiviral therapy and other supportive measures. the four patients developed ards during the first week of admission, and 3 of them received invasive ventilation. three out of four developed septic shock, and 2 of them deteriorated to multi organ failure who received continuous renal replacement therapy (crrt) and veno-venous extracorporeal membrane oxygenation (ecmo). the 4 patients received different doses of plasma therapy (900ml, 200 ml, 2400ml and 300 ml) respectively. the four patients showed resolution of the chest radiograph lesions. the rt pcr became negative within 4 days of plasma infusion in 3 patients and within 3 weeks in the fourth patient. the 4 patients were discharged from the icu at (14, 7, 10, 27) days of plasma transfusion. the difference in the time of recovery between these groups of patients could be attributed to the difference in the doses and duration of doi 10.18502/sjms.v15i5.7175 page 26 sudan journal of medical sciences abdelrahman h. abdelmoneim et al convalescent plasma used in these studies among other possible reasons. furthermore, the absence of severe side effects in these reports supports the safety profile of this mode of therapy, although amore prolonged clinical trials are needed to confirm these results. this improvement in patient condition and decrease in hospital stays are equivalent to what was noticed in the use of convalescent plasma therapy in sars patients in 2004 in a retrospective study done by soo yo et al. where they compare the clinical outcomes between two groups of sars patients, one group on methyl prednisolone and the other on convalescent plasma, in which they reported a shorter hospital stay (p 0.001) and lower mortality (p 0.049) in the group receiving the plasma therapy [28]. the common factors in these four studies are the clinical benefit of convalescent plasma therapy and the very limited number of participants, which necessitates further investigation in larger well-controlled trials. despite the rapid improvement witnessed in these patients, animal studies in sars cov virus, sometimes show an aggravation of clinical symptoms despite the reduction in viral load, possibly due to the role of passive plasma antibodies in shifting the burden of infections to macrophage which potentiates the dysregulated immune response against the virus [33]. 4.2. donor eligibility zhang dingyu, the director of wuhan jinyintan hospital, has stated that to be a donor you have to be between 18 and 55 years old, and to have recovered for at least 14 days before blood donation. if the person is in good health, the age range cloud is extended to up 60 years old. before donation, the donor has to screen for relevant transfusion-transmitted infections such as hiv, syphilis, hepatitis b and c [34, 35]. 4.3. patient eligibility • laboratory confirmed the covid-19 status of the patient by rt-pcr. • severe or immediately life-threatening covid-19. severe disease is defined as showing one or more of the following: shortness of breath, respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, the partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, lung infiltrates > 50% within 24 to 48 hours. the life-threatening disease is defined by the occurrence of one or more of the following: respiratory failure, septic shock and multiple organ failure. • informed consent provided by the patient who will receive the therapy [35]. doi 10.18502/sjms.v15i5.7175 page 27 sudan journal of medical sciences abdelrahman h. abdelmoneim et al 4.4. preparation of convalescent plasma in low resource setting the protocol for plasma preparation differs between countries but usually it contains two major parts: the first is the donor selection, which was previously mentioned; and the second is plasma preparations. the plasma preparations start by separation the plasma from the blood by plasma apheresis device or any other simple extraction methods (well within the remit of most blood banks) and then checking the antibodies level in the plasma by the enzymelinked immunosorbent assay (elisa). (in addition, checking and inactivation of the viral load will be undertaken to decrease the possibility of transmitting infection). and finally, freezing the plasma and storing it in aliquots of around 300ml [36]. these steps are summarized in figure 3. 4.5. convalescent plasma therapy limitations although being a relatively available method of treatment yet, the recovered patients have to wait at least 14 days before they can donate their blood. furthermore, the dose has to be high enough to be effective, as it was noticed in the clinical trials of convalescence plasma in mers-cov infection, saudi arabia [17]. other practical concerns in plasma donation may include difficulties in reaching the recovered patients by phone and the refusal of voluntary involvement in the donation [37]. figure 3: flow chart of convalescent plasma preparation in covid-19 patients showing the major steps from donor selection to the administration of screened plasma units. pcr: polymerase chain reaction. elisa: enzyme-linked immunosorbent assay doi 10.18502/sjms.v15i5.7175 page 28 sudan journal of medical sciences abdelrahman h. abdelmoneim et al 5. conclusion in summary, this rapid review shows a potential therapeutic effect of convalescent plasma in the treatment of covid-19 patients. this is due to the fact that all the laboratory investigations come back to normal, as well as the clinical outcome, showed a dramatic improvement of symptoms within 1 to 3 days following convalescent plasma transfusion. though convalescent plasma therapy has not yet been approved as a treatment for covid-19 disease, there is growing evidence of its effectiveness in the previous sars and mers infection. hence, we recommend plasma therapy to be used as treatment in the current covid-19 pandemic in the form of clinical trials, especially in areas with low resource setting such as sudan. 6. limitations of the reviewed evidence several clinical trials reported enrolling small number of patients, which will be poorly representative of the general population, and hence it will be difficult to generalize the results of these studies. another problem is the lack of long follow-up, which means that we are lacking the knowledge of the possible long side effects of this therapy [15, 16]. 7. strength and limitations of the current paper to our knowledge, this is the first rapid review, reporting the available evidence regarding the effectiveness and safety of convalescent plasma therapy in covid-19 patients in low resource setting countries. in our attempt to spread the knowledge in a timely manner, we rapidly conducted this review in a duration of 14 days without strict adherence to systemic reviews guideline. yet, we made sure that all reports used are published in well-respected journals and hence we believe this review will provide an invaluable asset in the fight against covid-19 pandemic. conflict of interest the authors wish to declare that they have no conflict of interest regarding the publication of this study. ethical clearance ethical clearance was not required for this paper. funding the authors received no financial support for the research, authorship, or publication of this paper. doi 10.18502/sjms.v15i5.7175 page 29 sudan journal of medical sciences abdelrahman h. abdelmoneim et al references [1] ren l.l., et al. 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(2017). use of convalescent plasma in ebola virus infection. transfusion and apheresis science vol. 56, issue 1, pp. 31-4. [32] fleming a.b., et al. (2004). retrospective comparison of convalescent plasma with continuing highdose methylprednisolone treatment in sars patients. clinical microbiology and infection, vol. 10, issue 7, pp. 676-8. [33] tiberghien p., de lambalerie x., morel p., gallian p., lacombe k. and yazdanpanah y. (2020). collecting and evaluating convalescent plasma for covid-19 treatment: why and how. vox sanguinis. [34] chang l., yan y. and wang l.. (2020). coronavirus disease 2019: coronaviruses and blood safety. transfusion medicine reviews. pubmed pmid: 32107119. https://doi.org/10.1016/j.tmrv.2020.02.003]. [35] li x.y., et al. (2020). the keypoints in treatment of the critical coronavirus disease 2019 patient. zhonghua jie he he hu xi za zhi / chinese journal of tuberculosis and respiratory diseases, vol. 43, p. 26. [36] who. (2014). use of convalescent whole blood or plasma collected from patients recovered from ebola virus disease for transfusion, as an empirical treatment during outbreaks: interim guidance for national health authorities and blood transfusion services. geneva: world health organization. [37] wong h.k., et al. (2010). practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza a (h1n1) infection. transfusion, vol. 50, issue 9, pp. 1967-71. doi 10.18502/sjms.v15i5.7175 page 31 https://doi.org/10.1016/j.tmrv.2020.02.003 introduction method data synthesis results discussion the use of convalescent plasma against sars-cov-2 donor eligibility patient eligibility preparation of convalescent plasma in low resource setting convalescent plasma therapy limitations conclusion limitations of the reviewed evidence strength and limitations of the current paper conflict of interest ethical clearance funding references sudan journal of medical sciences volume 12, issue no. 1, doi 10.18502/sjms.v12i1.854 production and hosting by knowledge e research article knowledge, practice, and willingness to participate in community health insurance scheme among households in nigerian capital city aderibigbe s. adedeji, aganaba doyin, osagbemi g. kayode, and aderibigbe a. ayodele department of epidemiology & community health, faculty of clinical sciences, university of ilorin abstract background: health insurance is a social security system that guarantees the provision of needed health services to persons on the payment of token contributions at regular intervals. the objective of the survey was to determine knowledge, practice, and willingness of households in nigerian capital city to pay and participate in community health insurance scheme. materials and methods: this descriptive and analytical cross-sectional study was carried out using the multistage cluster sampling technique to obtain data from 300 selected household heads or main financial decision makers. the data was analyzed using epi-info software package. statistical significance of p < 0.05 and confidence limit of 95% was used. results: the major findings showed that the level of awareness (13%) concerning community health insurance (chi) was found to be very low among the respondents. the general principles of chi were also poorly understood by the respondents. attitude to the programme was positive as many showed interest in participating and enrolling themselves (97.0%), some family members (96.3%) and entire family members (90.3%). borrowing money to settle medical bills in this study has occurred in 30% of instances. majority of respondents were willing to pay premiums ranging from n450 (96.6%) to n1200 (72.5%) for simple packages that do not include surgery and hospitalization. conclusions: the community members were willing to participate and enrol if the programme is brought to them. there is a need to adequately subsidize the premiums that respondents were willing to pay in order to meet up with the cost of treatment. keywords: willingness, participate, community health insurance how to cite this article: aderibigbe s. adedeji, aganaba doyin, osagbemi g. kayode, and aderibigbe a. ayodele, (2017) “knowledge, practice, and willingness to participate in community health insurance scheme among households in nigerian capital city,” sudan journal of medical sciences, vol. 12 (2017), issue no. 1, 9–18. doi 10.18502/sjms.v12i1.854 page 9 corresponding author: aderibigbe s. adedeji; email: tayonov23@yahoo.com received: 15 december 2016 accepted: 20 february 2017 published: 28 may 2017 production and hosting by knowledge e aderibigbe s. adedeji et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:tayonov23@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e الخدمات توفير يضمن الذي اإلجتماعي الضمان نظام هو الصحي التأمين الخلفية: الصحية الالزمة لألشخاص مقابل دفع مساهمات رمزية على فترات منتظمة. وكان الهدف العاصمة يف األسر ورغبة والممارسة المعرفة تحديد هو اإلستقصائية الدراسة هذه من النيجيرية للدفع والمشاركة يف نظام التأمين الصحي المجتمعي. المواد والطرق: أجريت هذه الدراسة المقطعية التحليلية الوصفية بإستخدام تقنية أخذ األسر أرباب من ٣٠٠ من بيانات على للحصول المراحل متعددة العنقودية العينات المختارة أو صناع القرار الماليين الرئيسيين. تم تحليل البيانات بإستخدام حزمة البرنامج إيبي-إنفو. وتم استخدام الداللة اإلحصائية p <٠٫٠٥ و حد الثقة ٩٥٪. النتائج: أظهرت النتائج الرئيسية أن مستوى الوعي بشأن التأمين الصحي المجتمعي كان الصحي للتأمين العامة المبادىء أن كما .(٪١٣) المستجيبين بين جداً منخفضاً المجتمعي كانت غير مفهومة أيضاً من قبل المجيبين. وكان الموقف من البرنامج إيجابيا حيث أبدى الكثيرون اهتمامهم بالمشاركة وتسجيل أنفسهم (٩٧٫٠٪) وبعض أفراد األسرة هذه يف الطبية الفواتير لتسوية المال إقتراض .(٪٩٠٫٣) بأكملهم العائلة وأفراد (٪٩٦٫٣) لدفع إستعداد على المستجيبين غالبية وكانت الحاالت. من ٪٣٠ يف حدث قد الدراسة تشمل ال التي البسيطة للحزم (٪٧٢٫٥) n١٢٠٠ إىل (٪٩٦٫٦) n٤٥٠ بين تتراوح أقساط الجراحة واإلستشفاء. اإلستنتاجات: كان أفراد المجتمع على إستعداد للمشاركة والتسجيل إذا تم جلب البرنامج لهم. وهناك حاجة إىل تقديم الدعم الكايف لألقساط التي كان المستجيبون على إستعداد كبة تكاليف العالج. يجب إختيار طرق اإلسترجاع المناسبة والمناسبة لدفعها من أجل موا بشكل فردي لكل مستقبل. 1. introduction healthcare delivery remains one of the most important basic social services any government or organisation can render to its people. public health system in nigeria is characterised by low funding, poor motivation of health workers and inequitable access to health [1]. although the federal government of nigeria has estimated that public funding of health is 1-2 % of national gross domestic product (gdp), this figure falls very much below the world bank’s estimate of 0.3 % of gdp for the period 19901996 [2, 3]. these estimates are even much lower than the 2.6 % average observed for sub-saharan africa, and the 15 % recommended by the world health organization [4]. in nigeria, about 70% of the population reside in the rural areas [5]. similarly, only about 60% of rural dwellers have access to health care, which is mainly of a poorer quality of care than what obtains at the urban centres [6]. access to health care has been greatly reduced for the poor households due to their low purchasing power evidenced by their earning and expenditure patterns. this is because the predominant health care financing mechanism in nigeria has been the out of pocket option. to get doi 10.18502/sjms.v12i1.854 page 10 sudan journal of medical sciences production and hosting by knowledge e round this problem and safeguard the rural poor from the catastrophic nature of health financing, prepayment schemes and community-based insurance schemes have been advocated [5, 7, 8]. community-based health insurance (cbhi) schemes attempt to bridge the gap between increasing health needs and scarce resources in poor communities as well as providing protection for the most vulnerable groups through cross-subsidization. however, these schemes are often initiated without strong empirical information that can help to benchmark cost-sharing potentials and other forms of participation of households in the community. previous studies have reported varying levels of willingness to pay (wtp) for a cbhi; onwujekwe et al. reported a wtp of between 3.6% 38% among their respondents in the south eastern part of nigeria [9], bamidele et al. in the south western part of nigeria reported a wtp of 82.4% among artisans [10]. in ethiopia, haile et al. reported a wtp of 78% among their respondents [11] while ahmed et al. in bangladesh reported a wtp of 86.7% [12]. age, gender, socioeconomic status and place of residence have been identified in previous studies as determinants of wtp, [9, 10]. this descriptive and analytical cross-sectional study was therefore carried out to assess the knowledge and practice of household heads in federal capital territory (fct) communities on community health insurance schemes, determine willingness to pay; and identify the major factors that can influence willingness of households in fct communities to pay and participate in a community health insurance scheme. 2. materials and methods the study area consists of the 6 area councils of the fct. the area councils are similar in population sizes but different with regards to socio-demographic characteristics. using fischer’s formula, a sample size of 223 was calculated using a previous study with prevalence of willingness to participate in a community health insurance scheme of 82.4% [10]. the sample size was adjusted to 300 household heads to cater for nonresponse and to increase the power of the study. multistage sampling technique was adopted for the study. one community was selected from each of the area councils using simple random sampling by balloting, making a total of 6 communities used for the study. cluster sampling technique was adopted to select 50 households in each of the selected communities. at the household level, any person recognised by other residents as the household head or the major financial decision-maker and who gives consent to participate was interviewed. a pre-tested interviewer-administered semi-structured questionnaire was used in this survey. the questionnaire was designed to elicit information on the knowledge, attitude, and willingness to pay and participate in a community health insurance scheme from the household heads in the study area. questionnaires with inconsistencies were returned to the communities for revalidation by supervisors. the data obtained were doi 10.18502/sjms.v12i1.854 page 11 sudan journal of medical sciences production and hosting by knowledge e variables freq (%) aware of chi no 261 (87.0) yes source of information 39 (13.0) radio friends television 18 (46.2) community members school 8 (20.5) family members 7 (17.9) knowledge of chi 3 (7.7) principles 2 (5.1) pooling of pre-paid funds 1 (2.6) dynamic mutual aid targets the informal sector 8 (20.5) not-for profit 3 (7.7) community participation 8 (20.5) 7 (17.9) 13 (33.4) t 1: knowledge of chi among respondents. sorted out, edited and coded before being fed into the computer for statistical analysis using the epi-info 2000 software package version 3.5.2. data analysis was done using both descriptive and inferential statistics. the data was analyzed using epi-info software package. statistical significance of p < 0.05 and confidence limit of 95% was used. descriptive statistics such as mean, frequency and percentages were used in the presentation of results. 3. results most (30.5%) respondents had at least primary education while 18.0% had no formal education. almost all (95%) respondents earned a living one way or the other while 5% did not have any income. the monthly income of respondents ranged between 10000 and 167000 naira with a mean of 33600 naira. majority (61.5%) of the respondents without income survived mainly on their spouses, 23.1% on parents while 7.7% equally depended on friends and the government. most (87%) of the respondents were not aware of community health insurance while 13% of them had heard of community health insurance before. the main sources of information were the radio (46.2%), friends (20.5%), television (17.9%), community members (7.7%), the school (6.0%) and family members (3.0%). the percentage level of awareness for the principles known as a characteristic of chi by respondents doi 10.18502/sjms.v12i1.854 page 12 sudan journal of medical sciences production and hosting by knowledge e includes pooling of pre-paid funds (20.5%), dynamic mutual aid (7.7%), targets the informal sector (20.5%), not-for-profit (17.9%) and community participation (33.4%) (table 1). the household health expenses (including hospital bills, drugs, chemists, and traditional healers) in the preceding year ranged between 0 to n350000 with a mean of n35536 and mode of n10000. the main methods of paying health bills were out of pocket (97.6%), nhis (1.0%) while other sources accounted for 1.4% (table 2). ever borrowing money to pay health bills occurred among 30% of respondents with the mean amount borrowed ranging from n500 to n135000 and a mean of n19583. money was mostly (93.7%) borrowed from friends with relatives and cooperatives accounting for 3.0% and 3.3% respectively. ever sold personal items to pay hospital bills occurred among 26.7% of respondents (table 2) with 23.2% of them having done so in the preceding one year. close to half (44.2%) of respondents’ household members had been ill but did not seek medical attention from modern health facilities at one time or the other in the previous year. the main reasons for not seeking care were that the illness was not perceived as serious (98.5%) and lack of money (90.0%). few (6.7%) of the respondents’ household members currently had any form of health insurance as at the time of the study. almost all (97.0) of respondents were willing to enrol themselves and most (90.3%) were willing to enrol their entire household members if offered community health insurance. for those not willing to enrol, the main reasons were lack of awareness (51.7%) and general lack of interest (27.7%). (table 3). majority of respondents were willing to pay premiums ranging from n450 (96.6%) to n1200 (72.5%) for simple packages that do not include surgery and hospitalization. educational level and gender were significant factors influencing the knowledge and awareness of the respondents. (p<0.05) (table 4). 4. discussion the level of awareness (13%) concerning community health insurance (chi) was found to be very low among the respondents. this is expected considering the fact that the programme was just at its initial stages in the fct at the time of this study. the general principles of chi were also poorly understood by the respondents as none of the principles was known by more than 33.4% of respondents. this finding is comparable to a study in uganda where majority (64.5%) of insured persons had poor knowledge of community health insurance [13]. among those that were aware, radio was reported as the main source of information compared to television and community members. thus the radio would be animportant strategy for subsequent population-based iec in the area. there is thus a need for large scale information, education and communication (iec) programme through social marketing in the area prior to and during commencement of chi. doi 10.18502/sjms.v12i1.854 page 13 sudan journal of medical sciences production and hosting by knowledge e respondent has a source of income (freq, %) yes 285 (95.0) no 15 (5.0) monthly income (range; mean) 10000 – 167000; 33600 household health expenses in preceding year (range; mean) 0 – 350000; 35536 method of paying health bills (freq, %) out of pocket 293 (97.6) nhis 3 (1.0) others 4 (1.4) ever borrowed money to pay health bills (freq, %) yes 90 (30.0) no 210 (70.0) amount borrowed (range; mean) 500 – 135000; 19583 money borrowed from (freq, %) friends 281 (93.7) relatives 9 (3.0) cooperative 10 (3.3) ever sold personal items to pay hospital bills (freq, %) yes 80 (26.7) no 220 (73.3) premium respondents are willing to pay (range; mean) 450 – 1200 t 2: household health expenses pattern. variables freq (%) has any form of health insurance yes 20 (6.7) no 280 (93.3) willing to enrol self in chi scheme yes 291 (97.0) no 9 (3.0) willing to enrol some family members in chi scheme yes 289 (96.3) no 11 (3.7) willing to enrol entire household in chi scheme yes 271 (90.3) no 29 (9.7) reason for not willing to enrol in chi scheme don’t know health insurance 15 (51.7) just not interested 8 (27.7) no trust in insurance 3 (10.3) money is lost if not sick 3 (10.3) t 3: distribution of respondents by willingness to enrol in chi scheme. doi 10.18502/sjms.v12i1.854 page 14 sudan journal of medical sciences production and hosting by knowledge e variables compared p values earning a living and level of interest in insurance 0.97 educational level and awareness 0.00 earning a living and selling of household items to pay health bills 0.19 having a member of the household with insurance and level of awareness 0.11 gender and level of awareness 0.00 marital status and the level of interest 0.95 rural urban differential and awareness 0.10 area councils and level of awareness 0.44 area councils and level of interest 0.03 t 4: factors influencing knowledge and practice of respondents about chi. after the interviewers explained the chi and its principles, the general attitude to the programme was positive as many showed interest in participating and enrolling themselves (97.0%) and entire family members (90.3%). the positive disposition of most respondents is a good finding that would enhance programme success in the area. whether these translate to actual enrollment would be demonstrated during subsequent intervention and enrollment programmes. for those not showing interest, the main reason was given to be the fact that they did not yet know about chi and just lack of general interest. in a study carried out in south east nigeria, less than 40 percent of urban and 7 percent of rural households were willing to pay for communitybased health insurance membership both for themselves and other members of the households [9]. the need to increase the level of iec is therefore further supported by these findings. selling of household assets is one of the cushioning effects to offset medical bills [13]. this practice has ever occurred in 26.7% of respondents in this study with 23.2% having done so in the preceding one year. in a ugandan study, about 55% of respondents ever sold household assets to pay medical bills [13]. chi is expected to reduce the practice of having to sell household assets to pay medical bills. it is also common in the nigerian environment to have to borrow money to settle medical bills which has occurred in 30% of instances in this study with the amount borrowed ranging from n500 to n135000 and a mean of almost n20000 mainly (93.7%) borrowed from friends. these practices are likely to reduce if chi is effectively imbibed and provided in the various communities. majority of respondents were willing to participate in the chi and willing to pay premiums ranging from n450 (96.6%) to n1200 (72.5%) for simple packages that do not include surgery and hospitalization. for packages that include surgery and hospitalization, the premium the respondents were willing to pay ranged between n50 to n4000 with a mean of n1200. the most frequently acceptable amount for nonsurgical package was n1000 and for surgery, it was n1500. the implication of this for the programme is the need to find a way to subsidise these amounts and based on the doi 10.18502/sjms.v12i1.854 page 15 sudan journal of medical sciences production and hosting by knowledge e principle of pooling of financial resources, this should be workable. the final premium to be paid would, however, be subject to the policy of the fct administration but these figures are useful guidelines. the community members were willing to participate and enrol if the programme is brought to them, with most of them willing to make financial contributions in favor of themselves and family members. the respondents health expenditure were being mainly met from out of pocket means and are most likely to benefit from subsequent chi programmes that will conserve household funds for other socio-economic ventures. there is a need to adequately subsidize the premiums that respondents were willing to pay in order to meet up with the cost of treatment through relevant collaborations and government allocations. education and gender were the variables found to exert significant effects on the respondents’ knowledge and practice towards chis. onwujekwe et al. also reported similar factors as predictors of wtp among respondents in their study in south eastern region of nigeria [9]. bamidele et al. also elicited that educational status of respondents was a key predictor of their practice towards cbhi scheme in the south western region of nigeria [10]. angel-urdinola et al. concluded in their study that most household decisions in most african settings are usually affected by gender to the advantage of men and that men are usually the de facto head of household [14]. it was also reported that educated decision makers are more likely to take favorable decisions concerning the household than non-educated ones [14]. it is therefore not surprising that this present study which is also in an african setting seems to agree with the results from these other studies [9, 10, 14]. the implication of these findings is that socio-demographic variables influence the knowledge and practice of respondents with regards to chi and should, therefore, play a role in the implementation of chi in the fct. 5. conclusion it is therefore concluded that the level of awareness to chi in fct is low with a need to implement subsequent community-based iec using available social marketing strategies to stimulate community level awareness and knowledge of chi in the fct. the respondents demonstrated positive attitude and acceptance towards chi and were committed to subsequent implementation of the programme. there is thus a need to enhance this trend by subsequently implementing the programme in the fct. 6. conflict of interest none of the authors has any conflict of interest to disclose. doi 10.18502/sjms.v12i1.854 page 16 sudan journal of medical sciences production and hosting by knowledge e 7. ethical consideration we confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. 8. authors contribution • aderibigbe sa analysis and interpretation of data, drafting and revision of final manuscript for publication and funding. • aganaba d study concept and design, collection of data and funding. • osagbemi gk study concept and design, collection of data, drafting and revision of final manuscript for publication and funding. • aderibigbe aa collection of data, drafting and revision of final manuscript for publication and funding. references [1] t. hodges, nnp commission, and unc office, childrens and womens rights in nigeria: a wake-up call?: situation assessment and analysis, national planning commission, 2001. [2] consultative group on nigeria, federal government of nigeria. nigeria economic policy and strategy: the way forward. 2000. [3] v. verbeek-demiraydin, “african development indicators, 2000,” the world bank, 1999. [4] d. k. zschock, “general review of problems of medical care delivery under social security in developing countries,” international social security review, vol. 35, no. 1, pp. 3–16, 1982. [5] f. godlee, “the world health organisation: who at country level – a little impact, no strategy,” bmj, vol. 309, no. 6969, pp. 1636–1639, 1994. [6] c. atim, f. diop, j. ette, d. evrard, and p. marcadent, the contribution of mutual health organizations to financing, delivery, and access in health care in ... | popline.org. popline. 2001. http://www.popline.org/node/531502 (accessed jan 6, 2017). [7] i. ogunbekun, health insurance: a viable approach to financing health care in nigeria? john snow inc, arlington, va, 1996. [8] h. dong, b. kouyate, j. cairns, f. mugisha, and r. sauerborn, “willingness-to-pay for community-based insurance in burkina faso,” health economics, vol. 12, no. 10, pp. 849–862, 2003. [9] o. onwujekwe, e. okereke, c. onoka, b. uzochukwu, j. kirigia, and a. petu, “willingness to pay for community-based health insurance in nigeria: do economic doi 10.18502/sjms.v12i1.854 page 17 sudan journal of medical sciences production and hosting by knowledge e status and place of residence matter?” health policy and planning, vol. 25, no. 2, pp. 155–161, 2010. [10] jo bamidele and wo adebimpe, “attitude and willingness of artisans in osun state southwestern nigeria to participate in community based health insurance,” j community med prim health care, no. participate, p. 24, 2012. [11] m. haile, s. ololo, and b. megersa, “willingness to join community-based health insurance among rural households of debub bench district, bench maji zone, southwest ethiopia,” bmc public health, vol. 14, no. 1, 2014, article no. 591. [12] s. ahmed, m. e. hoque, a. r. sarker et al., “willingness-to-pay for communitybased health insurance among informal workers in urban bangladesh,” plos one, vol. 11, no. 2, article id e0148211, 2016. [13] l. manje, client satisfaction with health insurance in uganda. 2007; published online jan. http://www.microfinancegateway.org/library/client-satisfactionhealth-insurance-uganda. [14] d. angel-urdinola and q. wodon, “income generation and intra-household decision making: a gender analysis for nigeria,” in in. gender disparities in africas labor market, illustrated. world bank publications, p. 420, 420, 2010. doi 10.18502/sjms.v12i1.854 page 18 introduction materials and methods results discussion conclusion conflict of interest ethical consideration authors contribution references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6750 production and hosting by knowledge e research article the risk factors of developing diabetic foot ulcers among diabetic patients in mukalla city-hadhramout/yemen eidha a. bin hameed and maryam hamed baras department of biology, faculty of sciences, hadhramout university, yemen abstract background: diabetes is on the rise worldwide and is already considered as an epidemic by some experts. so, there is a need to raise awareness on the important factors that can help prevent bacterial infection in wounds of patients with diabetes. objective: to study the risk factors of developing diabetic foot ulcer (dfu) in patients with diabetes. the study is the first in yemen to investigate the prevalence of bacterial infection in wounds of diabetic patients. materials and methods: this is a case-control study carried out from november 2018 to may 2019. twenty diabetic patients with foot ulcer and twenty without foot ulcer were examined. risk factors and clinical profile of patients were studied by using a standardized questionnaire that included gender, age groups, past history of diabetes, duration of the disease, type of diabetes, dfu, type of ulcer, smoking, glucose level, and control of blood glucose level. results: the risk factors that affected significantly the occurrence of dfu were gender (0.038), age groups (0.010), and duration of diabetes mellitus (dm) while hyperglycemic control, smoking, and family history were not. there was no significant difference (0.977) in mean fasting blood glucose (mbg) between the dm and dfu patients. conclusions: male diabetic patients aged more than 55 years and suffering from dm for more than 10 years were most likely to have dfu. keywords: diabetic foot ulcer, diabetes mellitus, risk factors, yemen 1. introduction foot ulcers remain one of the most significant and devastating complications of diabetes and an extremely distressing problem among diabetic patients [1]. every year, more than 1 million people lose a leg as a consequence of this disease worldwide [2]. patients with diabetes may present to the hospital with different levels of foot lesions [3]. several studies have specifically assessed factors associated with the occurrence of a dfu. characteristics that have been shown to confer a risk of foot ulceration in persons with diabetes include gender, longer duration of diabetes, previous ulceration or amputation, how to cite this article: eidha a. bin hameed and maryam hamed baras (2020) “the risk factors of developing diabetic foot ulcers among diabetic patients in mukalla city-hadhramout/yemen,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 153–162. doi 10.18502/sjms.v15i2.6750 page 153 corresponding author: maryam hamed baras; department of biology, faculty of science, hadhramout university. tel: 0096770418669 email: yaam8y@gmail.com received 6 may 2020 accepted 23 june 2020 published 30 june 2020 production and hosting by knowledge e eidha a. bin hameed and maryam hamed baras. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:yaam8y@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences eidha a. bin hameed and maryam hamed baras fasting blood glucose (fbg), high hba1c levels, smoking and inappropriate foot selfcare habits [4]. in dfu patients, long-term glycemic control is desirable. the standard of care in diabetes management is self-monitoring of blood glucose at any time.. blood glucose monitoring frequency should be individualized and adapted to address the goals of diabetes care [5]. also, a longer duration of diabetes and smoking increases the risk of foot ulcer [6]. 2. materials and methods twenty diabetic patients with foot ulcer (dfu) and twenty without dfu were obtained and diagnosed by the doctors in mukalla city’s hospitals during the period from november 2018 to may 2019. data related to risk factors of dfu was collected using a standardized questionnaire consisting of systematic questions about study variables, which was used to interview the participants. the variables included in the questionnaire were gender, age groups, past history of diabetic, duration of diabetic disease, type of diabetes, dfu, type of ulcer, smoking, glucose level, and control of blood glucose level. the blood samples were taken from the volunteers after 8–10 hr of fasting. the blood glucose test was done according to the instructions of kit manufactured by spectrum company using stat fax spectrophotometer instrument. and cbc test was done according to the instructions of full automated hematology analyzer instrument. data analysis was conducted using the software of statistical package for social sciences (spss) version 25. the graphs were presented using the software program (excel for windows microsoft) version 10. descriptive statistics (frequencies, percentages, mean, and standard deviation) for the study variables were obtained and compared using t-test. the association between different categories of the explanatory variables was measured and compared using pearson chi-square (χ2) test. the level of significance was set at p-value < 0.05. 3. ethical considerations ethical approval for this study was obtained from the hadhramout university before commencing the study. the information were taken from the participants after they agreed gave verbal consent according to the informed consent with confidentiality of each participant as well as the results. doi 10.18502/sjms.v15i2.6750 page 154 sudan journal of medical sciences eidha a. bin hameed and maryam hamed baras 4. availability of data and material this work was supported by different hospitals in mukalla city – hadhramout includes ibn-sina teaching hospital, hadhramout modern hospital, university hospital for gynobst and pediatrics, al-riyan specialized hospital, al-borj consultant hospital and al-madina polyclinic, as well as the medical microbiology department at the national center for public health laboratories, hadhramout branch, yemen. 5. results of the 20 diabetes mellitus (dm) patients, 11 (55%) were male and 9 (45%) were female, and their age group distribution were as follows: two (10%) were < 18 years, six (30%) were 18–25 years, three (15%) were 26–35 years, one (5%) was 36–55 years, eight (40%) were more than 55 years; 45% of them were suffering from dm for < 5 years, 35% for 5–10 years, and 20% for > 10 years. on the other hand, in the dfu patients group, 17 (85%) were male and 3 (15%) were female. their age group distribution was as follows: zero (0%) were < 18 years, zero (0%) were 18–25 years, one (5%) was 26–35 years, five (25%) were 36–55 years, and fourteen (70%) were > 55 years. table 1 shows the relationship of diabetes and dfu with demographic characteristics (gender and age groups). males were infected more than females. the age groups 18– 25 and > 55 years were infected more with diabetes and age groups 36–55 and > 55 years were infected more with dfu. a statistically significant association (p < 0.05) was observed in the study. according to the studied data of clinical characteristics, the duration of dm was highly significant in relation to the occurrence of dfu (p-value 0.001). other factors such as hyperglycemic control, smoking, and family history showed insignificant relation to dfu. table 2 shows the relationship of diabetes and dfu with clinical characteristics. as shown in table 3, the mean of fbg levels in dfu patients was higher than the dm patients, but there was no significant difference between the means of dm and dfu patients. 6. discussion the complication of foot ulcer in dm patients is one of the significant medical problems and an economic burden, therefore identifying the risk factors might help to develop doi 10.18502/sjms.v15i2.6750 page 155 sudan journal of medical sciences eidha a. bin hameed and maryam hamed baras table 1: frequencies and percentages of diabetic and dfu patients in relation to demographic characteristics demographic characteristics diabetes mellitus diabetic foot ulcer total (%) 𝜒2 test value p-value no. (%) no. (%) gender male 11 (27.5%) 17 (42.5%) 28 (70%) female 9 (22.5%) 3 (7.5%) 12 (30%) total 20 (50%) 20 (50%) 40 (100%) 4.286 0.038* age groups (years) < 18 2 (5%) 0 (0%) 2 (5%) 18–25 6 (15%) 0 (0%) 6 (15%) 26–35 3 (7.5%) 1 (2.5%) 4 (10%) 36–55 1 (2.5%) 5 (12.5%) 6 (15%) > 55 8 (20%) 14 (35%) 22 (55%) total 20 (50%) 20 (50%) 40 (100%) 13.303 0.010* *statistical significance at p-value < 0.05 table 2: frequencies and percentages of diabetic and dfus patients in relation to clinical characteristics clinical characteristics diabetes mellitus diabetic foot ulcer total (%) 𝜒2 test value p-value no. (%) no. (%) hyperglycemic control yes 9 (22.5%) 9 (22.5%) 18 (45%) no 11 (27.5%) 11 (27.5%) 22 (55%) total 20 (50%) 20 (50%) 40 (100%) 0.000 1 duration of diabetes mellitus < 5 years 9 (22.5%) 1 (2.5%) 10 (25%) 5–10 years 7 (17.5%) 3 (7.5%) 10 (25%) > 10 years 4 (10%) 16 (40%) 20 (50%) total 20 (50%) 20 (50%) 40 (100%) 15.2 0.001* smoking yes 6 (15%) 7 (17.5%) 13 (32.5%) no 14 (35%) 13 (32.5%) 27 (67.5%) total 20 (50%) 20 (50%) 40 (100%) 0.114 0.736 family history yes 10 (25%) 12 (30%) 22 (55%) no 10 (25%) 8 (20%) 18 (45%) total 20 (50%) 20 (50%) 40 (100%) 0.404 0.525 *statistical significance at p-value < 0.05 better prevention strategies in diabetic patients. this study focused on the risk factors that lead to the incidence of dfu in diabetic patients. in this study, males had a higher incidence of dfu than females with 70%. similar results were observed in many studies globally, in australia 66.2% [7], china 63.8% doi 10.18502/sjms.v15i2.6750 page 156 sudan journal of medical sciences eidha a. bin hameed and maryam hamed baras table 3: the difference between fasting blood glucose level in diabetic and diabetic foot ulcers patients category fasting blood glucose levels (mg/dl) t-test p-value mean standard deviation diabetes mellitus 197.7 89.1 diabetic foot ulcer 198.5 83.1 –0.029 0.977 [8], india 71.7% [9], pakistan 59% [10], iran 70% [11], egypt 65% [12], iraq 72% [13], and united arab emirates 76.3% [14], whereas the findings were completely different with nigerian study that reported females were more affected with dfu 62.0% [15]. and there was un significant associated with gender as the findings reported with [16, 17]. our results showed a significant effect of gender among dfu patients, which is similar to a jordanian study [18]. males are more affected by dfu, possibly due to the burden of life and their exercise habits since male population is more exposed to harder work with higher risk of trauma in work zone [9]. in our study, the age group > 55 years was the most frequent with dfu, followed by the age group of 36–55 years and 26–35 years. this is similar to some other studies carried out in different countries, where the elderly population (> 50 years) was more likely to get diabetic foot complications in india [19] and egypt [20]. another study revealed that the most common age groups of diabetic patients with foot involvement were at the fourth and fifth decades [21]. other studies showed that the foot diseases were more common in diabetic individuals aged > 60 years in the united states of america [22] and india [23, 24]; this might be because older age poses the risk of diminished ability for self-care due of poor vision and impaired mobility. the absence of these factors in younger patients may make them less susceptible to foot trauma [25]. also, we found that diabetic patients aged < 25 years do not grow dfu. shanmugam et al. indicated that the age range of dfu is 35–80 years [24], so this is a little different from our study results. in this study, a direct and statistically significant (p = 0.001) relationship was found between the duration of dm and the presence of dfu in diabetic patients, similar to the study reported in [18]. also, the study found that the patients with dm for > 10 years were most likely to have dfu with a rate of 50%, followed by those with dm for 5–10 years and < 5 years with a rate of 25% of each; these results were in agreement with an iraqi study results [17]. other studies revealed that the duration of diabetes was > 10 years in 58%, 94%, and 61.41% in india [21], egypt [16], and pakistan [25], respectively. this is most likely because of other risk factors such as peripheral neuropathy and peripheral vascular disease developing with time [16]. in contrast, different findings were seen doi 10.18502/sjms.v15i2.6750 page 157 sudan journal of medical sciences eidha a. bin hameed and maryam hamed baras in some studies. a study showed that patients with a duration of dm between 5 and 10 years of were more likely to have dfu [9]. however, bhaktavatsalam and chavan showed that the patient with dm for < 5 years were most likely to be affected with dfu [26]. this variance in the results might be because the complications are not only dependent on duration but also on the level of chronic glycemia [5]. most dfu patients in this study had poor glycemic control (55%) with no statistically significant relationship between the incidence of dfu and hyperglycemic control as previously reported by other studies carried out in india (70%) [21], pakistan (69%) [27], and saudi arabia (66%) [28]. in our study, 60% of the diabetic patients had a family history of diabetes. but historical family wasn’t considered as a risk factor in (p-value ≥ 0.05). similar findings were reported by other studies where family history of diabetes was not associated with dfu [3–26]. in this study, 32.5% of diabetic patients had a history of smoking with no significant association with development of diabetic foot complications; this is similar to the study that reported smoker’s rate in dm patients as 30% [29]. however, higher rates, that is, 44% [6], 61.3% [9], and 70% [30], were also seen in other studies, as well as lower rates were reported in studies carried out in western sydney, australia 14.5% [7], pakistan 9% [27], india 14.8% [23], and iran 8.1% [31]. besides, several other studies [16, 26, 28, 30] reported statistically significant association between smoking and dfu. our findings showed that the mean fbg levels were higher in patients with dfu (198.4mg/dl) than patients without foot ulcers (197.7mg/dl) with no significant association with the incidence of dfu. these findings correlated with some studies carried out in iraq, in [32], the mean fbg was 222.35 mg/dl and 258.5 mg/dl for dm and dfu patients, respectively, [33] reported 190.1 mg/dl and 223.2 mg/dl for dm and dfu patients, respectively, , and [34] shows 215mg/dl and 128mg/dl for dfu and dm patients, respectively, with highly significant association. similar results were reported in iran [31], egypt [12], and united arab emirates [14], and other study that adopted hba1c to evaluate the blood sugar levels [30]. these differences in the results may be due to the techniques used to measure the blood glucose levels. a1c is probably a better measure of the relationship between blood glucose levels and developing diabetic foot complications than an fbg measurement. doi 10.18502/sjms.v15i2.6750 page 158 sudan journal of medical sciences eidha a. bin hameed and maryam hamed baras 7. conclusion gender, age groups, and duration of dm were the risk factors that contributed most to the development of dfu. hence, diabetic patients should be wary of their lifestyle and follow-up regularly on their health to avoid development in their case with age advancement. also, glucose control should be advised by doctors to their diabetic patients. acknowledgements the authors are thankful to the department of biology, faculty of science, hadhramout university, yemen, for its efforts in developing scientific research. funding the study did not receive any fundings. conflict of interest the authors declare that they there is no conflict of interest. references [1] rosyid, f. n. 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(2014). can procalcitonin be an accurate diagnostic marker for the classification of diabetic foot ulcers? international journal of endocrinology and metabolism, vol. 12, no. 1, pp. 1–6. doi 10.18502/sjms.v15i2.6750 page 162 introduction materials and methods ethical considerations availability of data and material results discussion conclusion acknowledgements funding conflict of interest references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.6885 production and hosting by knowledge e research article evaluation of the adherence of obstetricians to the international guidelines for dispensing misoprostol and oxytocin in saad abu ella maternity hospital: a retrospective study mona hashim elbashir1, safaa badi2, muhammad abdou abdulraheem2, and bashir alsiddig yousef3 1department of clinical pharmacy, faculty of pharmacy, university of khartoum, al-qasr ave., khartoum 11111, sudan 2department of clinical pharmacy, faculty of pharmacy, omdurman islamic university, aboseid street, khartoum 11111, sudan 3department of pharmacology, faculty of pharmacy, university of khartoum, al-qasr ave., khartoum 11111, sudan abstract background: misoprostol and oxytocin are commonly prescribed drugs by obstetricians to induce labor and prevent postpartum hemorrhage. in sudan, there is no national guideline for prescribing these drugs. thus, the prescribers follow the international guidelines. hence, our study aimed to evaluate the adherence of sudanese obstetricians to the international guidelines for dispensing misoprostol and oxytocin. methods: a retrospective descriptive hospital-based study was performed at saad abu ella hospital through their medical files archived in 2018 using a checklist designed by the researcher. collected data were analyzed and presented in frequency tables using the statistical package for social sciences (spss). results: a total of 357 medical files were evaluated, about 50% of cases examined was in the 25–35 years age range, multigravida pregnant ladies were 62%. general indications of oxytocin and/or misoprostol were induction of labor (17%), postpartum hemorrhage prevention (pph) after normal vaginal delivery (nvd) (30%) and cesarean sections (32%), evacuation of incomplete miscarriage (20%), and termination of pregnancy (1%). compared to the guidelines, only 14% were given the recommended regimens for labor induction; 9.4% of women who had undergone nvd were given the recommended regimen to prevent pph. while, 57% and 43% of the cases with incomplete miscarriage and termination of pregnancy were given the recommended regimens, respectively. based on the correct indication, total adherence was estimated to be 17%. conclusions: higher percentages of cases with incomplete miscarriage and intrauterine fetal death were given the recommended regimens to manage them. while, lower percentages of the participants were given the recommended regimens for labor induction and to prevent pph. keywords: misoprostol, oxytocin, obstetricians, adherence, international guidelines how to cite this article: mona hashim elbashir, safaa badi, muhammad abdou abdulraheem, and bashir alsiddig yousef (2020) “evaluation of the adherence of obstetricians to the international guidelines for dispensing misoprostol and oxytocin in saad abu ella maternity hospital: a retrospective study,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 171–183. doi 10.18502/sjms.v15i2.6885 page 171 corresponding author: bashir alsiddig yousef; department of pharmacology, faculty of pharmacy, university of khartoum, al-qasr ave., khartoum 11111, sudan. phone: +249155662037 fax: +249183780696 mobile: +249912932418 email: bashiralsiddiq@gmail.com received 10 june 2020 accepted 19 june 2020 published 30 june 2020 production and hosting by knowledge e mona hashim elbashir et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bashiralsiddiq@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mona hashim elbashir et al 1. introduction labor is a rhythmic process of contraction and relaxation of the uterine muscles with progressive effacement and dilation of the cervix, leading to the expulsion of the fetus, placenta, and membranes through the birth canal [1, 2]. this process can be natural or induced by stimulating the uterine contraction before the spontaneous onset of labor, with no complication [3]. in a life-threatening situation like severe antepartum hemorrhage and major cephalopelvic disproportion, the surgical cesarean section should be performed [4]. one of the major complications that may occur during labor is postpartum hemorrhage prevention (pph) [2]. a pregnancy of up to 23 weeks can be terminated and an embryo weighing up to 500 grams is expelled, this is called an incomplete miscarriage, whereas, termination after 24 weeks of pregnancy and delivery with no signs of life is called intrauterine fetal death (iufd) [5, 6]. due to these complications, maternal mortalities continue to be one of the most serious and intractable health problems for women of reproductive age in low-income countries [7, 8]. misoprostol and oxytocin are the most common drugs used to treat or prevent different complications related to pregnancy. moreover, the ideal use of these drugs by following the guidelines has great value in managing the complication and reducing maternal mortality. in 2000, the world health organization (who) recommended the prophylactic use of a uterotonic immediately after delivery for all women, as part of the active management of the third stage of labor; oxytocin is recommended as a first-line drug [9]. for women without risk factors for postpartum hemorrhage delivering vaginally, oxytocin 10 iu by intramuscular injection is the agent of choice for prophylaxis in the third stage of labor, a higher dose of oxytocin is unlikely to be beneficial. while, for cesarean section, oxytocin 5 iu by slow intravenous injection should be used [10]. in settings where the use of oxytocin is not feasible, 800 mcg sublingual misoprostol might be a suitable first-line treatment of pph (7). for induction of labor, oral misoprostol appears to be less effective than vaginal misoprostol, regimen includes 50 mg of misoprostol every 4 hr pv to 200 mg tablets every 6 hr orally [11]. medical management of incomplete abortion and miscarriage include the use of misoprostol 600 mcg orally, which was included in the who 16th model list of essential medicines in 2009 and who priority medicines for mothers and children issued in 2011 [12]. the recommended dose of misoprostol for the treatment of incomplete abortion is 600 mcg orally or 400 mcg sublingually or 400–800 mcg vaginal insert [13]. for the use of misoprostol for late iufd, the dose should be adjusted according to gestational age; 200 mcg vaginal pessaries, sublingual, buccal every 4–6 doi 10.18502/sjms.v15i2.6885 page 172 sudan journal of medical sciences mona hashim elbashir et al hr before 26 weeks of gestation, 100 mcg vaginal pessaries sublingual, buccal every 4 hr at 27 weeks or more up to 24 hr [13]. oxytocin is superior to misoprostol in the prevention of postpartum hemorrhage (evidence level 1++), appraisal of evidence from the cochrane reviews together with consideration of standard practice in the uk suggests that for a woman delivering vaginally, oxytocin 10 iu by intramuscular injection is the regimen of choice for prophylaxis in the third stage of labor (evidence level 1+) [10]. misoprostol is not preferred to injectable uterotonic (oxytocin and ergometrine) for the management of third stage of labor [10]. there is no added benefit of offering misoprostol as an adjunct treatment for pph in women who have received oxytocin during the third stage of labor. where oxytocin is available and is used in the management of the third stage of labor, oxytocin alone should be used in preference to adjunct misoprostol for the management of pph [14]. since there is no national protocol for the use of oxytocin and misoprostol in sudan, and in order to assess the prescribing behavior of obstetricians, the adherence of prescribers for international guidelines, royal college of obstetrics and gynecology (rcog) in saad abu ella specialist hospital during 2018 was assessed. 2. methods and materials 2.1. study setting this study was a retrospective descriptive cross-sectional hospital-based study. the study was conducted at the saad abu ella’s maternity hospital. the data were collected from the records of the patients who attended the hospital with normal vaginal deliveries (nvds), emergency and elective cesarean sections c/s, missed miscarriage, and iufd, between january and december 2018. 2.2. inclusion criteria the target population was pregnant women with nvds, emergency and elective cesarean sections c/s, missed miscarriage, and iufd attending the hospital from january to december 2018. doi 10.18502/sjms.v15i2.6885 page 173 sudan journal of medical sciences mona hashim elbashir et al 2.3. exclusion criteria participants with incomplete records, pregnancy termination and evacuations done during the study period were excluded from the study. 2.4. study sample data were collected from the records of the patients by using a simple random sampling technique. the total number of pregnant women with nvds, emergency (em-cs) and elective cesarean sections (el-cs), missed miscarriage, and iufd who attended to the hospital during the study period was 3,320. sample size was calculated by using slovin’s equation [15]: 𝑛 = 𝑁 1+𝑁(𝑒)2 = 𝑛 = 3320 1+3320(0.05)2 , n = 356.9 = 357 where n = total target population attending the center during the study period; n = sample size, and e = margin of error (0.05) at 95% confidence level. 2.5. data collection tool the data was collected using a predesigned standardized and structured checklist, which was developed by the researcher. the data collection tool included patients’ information such as the drugs used, indication, dose, and the outcomes, which were documented in medical records. in order to measure the adherence of sudanese obstetricians, all collected information about used drugs were compared with the recommendations of the royal college of obstetrics and gynecology (rcog) guidelines. 2.6. statistical analysis data were analyzed using the ibm statistical package for social sciences [spss] for windows, version 23.0 software [armonk, ny: ibm corp]. data are demonstrated as tables for the descriptive statistics (frequency tables). 3. results doi 10.18502/sjms.v15i2.6885 page 174 sudan journal of medical sciences mona hashim elbashir et al 3.1. socio-demographic and clinical data of the participants out of the 357 included cases, 49% were aged 25–35 years; 32% were pregnant women with cesarean sections; 30% were women who underwent normal vaginal deliveries, of which 17% received drugs to facilitate the labor; 20% of the participants were pregnant women suffering from an incomplete miscarriage; and only 7% had intrauterine, vaginal deaths that needed termination. in all deliveries, the primigravida was 38% of all deliveries, while multigravida was found in 62% of all deliveries (table 1). by classifying the types of delivery for primigravida pregnant ladies, about 58% of all cases were normally delivered, 29% were delivered by em-cs, and finally, only 13% were delivered by el-cs. as per the multigravida pregnant ladies’ files, 49% had a normal delivery, 34% delivered by el-cs, and only 17% underwent em-cs. the different indications that led to surgical intervention (n = 123), either an el-sc or an em-cs were evaluated, in which, 32.5% of them was due to a previous cesarean scar, 16.2% was due to fetal distress, 13.8% was due to failure of the fetus progression, and 12.1% was due to the breech presentation (table 2). 3.2. regimens used for the induction of labor of all nvd cases (n = 117 cases), about 53 (45.2%) cases did not use any drug(s) to facilitate the labor and had nvd, while the other 64 (54.7%) cases used different regimen(s) to facilitate the vaginal labor, 47 (73.4%) of them successfully ended in nvd and 17(26.6%) cases failed to progress to nvd and underwent em-sc. in all 64 cases, only in 9 (14%), the recommended regimen of adding oxytocin 5 iu to an isotonic solution was used, while in the 41 (64%) oxytocin 2 iu was used, 30 (73%) of them succeeded to undergo nvd while others failed. on the other hand, for misoprostol, no case received the recommended induction dose (50–100 mcg vaginal pessary, 200 mcg oral) (table 3) 3.3. regimens used after nvd and after cs as pph prophylaxis post nvd, different regimens were given as pph prophylaxis agent, as shown in table 4; the most used regimen for pph prophylaxis was oxytocin 20 iu given as 10 iu by intramuscular and 10 iu by intravenous routes of administrations. the recommended doses after cs is oxytocin 5 iu, which was not seen in all files surveyed. on the contrary, the most used regimen was the combination therapy of misoprostol four tablets (given doi 10.18502/sjms.v15i2.6885 page 175 sudan journal of medical sciences mona hashim elbashir et al as one tablet sublingual and three tablets per rectum) in 75 (61%) participants and oxytocin 30 iu (given as 10 iu intravenous injection and 20 iu given via intravenous infusion) in 20 (16.2%) participants (table 4). 3.4. adherence of prescribers to guidelines the adherence of prescribers to each uterotonic indication was evaluated compared to the recommended rcog guidelines. we found that only 14% of the cases were given the recommended regimens for labor induction. of the participants who delivered through nvd, only 9.4% were given the recommended regimen and doses to prevent pph, while, on the other hand, no one among those who delivered through caesarian section was given the recommended regimens to prevent pph regarding. however, 57% and 43% of the cases with incomplete miscarriage and iufd were given the recommended regimens, respectively (table 5). the total adherence was calculated by dividing the total correct indications by the total indications, and it was estimated to be 17%. table 1: socio-demographic and clinical characteristics of the participants (n = 357) number (%) variable age of the participants 15–25 years 95 (27%) 25–35 years 175 (49%) 35–45 years 87 (24%) indications for misoprostol and oxytocin induction of labor 64 (17%) normal vaginal delivery (nvd) 117 (30%) cesarean section 123 (32%) incomplete miscarriage 76 (20%) intra uterine fetal death 7 (1%) gravida (𝑛 = 240) primigravida 90 (38%) multigravida 150 (62%) type of delivery (primigravida) (𝑛 = 90) nvd 52 (58%) emergency caesarian section (em-sc) 26 (29%) elective caesarian section (el-sc) 12 (13%) type of delivery (multigravida) (𝑛 = 150) nvd 74 (49%) em-sc 25 (17%) el-sc) 51 (34%) doi 10.18502/sjms.v15i2.6885 page 176 sudan journal of medical sciences mona hashim elbashir et al table 2: different indications for emergency (em-cs) and elective cesarean section (el-cs) (n = 123) indication number (%) em-cs el-cs breech presentation 15 (12.2%) 6 8 uterine fibroid 1 (0.8%) – 1 previous cesarean scar 49 (39.8%) – 49 refusal of vbac 5 (4.1%) – 5 fetal distress 20 (16.3%) 20 – failure to progress 17 (13.8%) 17 – sizeable baby 2 (1.6%) – 2 severe preeclampsia 3 (2.5%) 3 – pregnancy induced hypertension 2 (1.6%) 2 – abruptio placentae 2 (1.6%) 2 – oligohydramnios 1 (0.8%) – 1 polyhydramnios 1 (0.8%) – 1 chorioamnionitis 1 (0.8%) – 1 precious baby 1 (0.8%) – 1 fetal bradycardia 1 (0.8%) 1 – twin baby 2 (1.6%) – 2 total 123 (100%) 51 (41.5%) 72 (58.5%) table 3: different regimen(s) used to induce labor among participants (n = 64) regimen number of cases (%) number of successful cases number of failure* oxytocin 2 iu 41 (64%) 30 11 oxytocin 4 iu 1 (1.6%) 0 1 oxytocin 5 iu 9 (14%) 7 2 oxytocin 10 iu 1 (1.6%) 1 0 oxytocin 20 iu 3 (4.7%) 3 0 misoprostol 1 tab vaginally 3 (4.7%) 3 0 misoprostol 4 tabs orally 3 (4.7%) 0 3 misoprostol 3 tabs oral + oxytocin 2 iu 2 (3.1%) 2 0 misoprostol 4 tabs oral +oxytocin 4 iu 1 (1.6%) 1 0 total 64 (100%) 47 (73.4%) 17 (26.6%) *those for whom the treatment failed were directly indicated to emergency caesarian section 4. discussion maternal mortality remains a major concern, particularly in developing countries, as there are around 450 maternal deaths per 100,000 live births versus only 9 in developed countries [16]. therefore, proper management of the complications has great importance in reducing the mortality rate. the current study was conducted to evaluate the adherence of sudanese obstetricians to international guidelines for dispensing doi 10.18502/sjms.v15i2.6885 page 177 sudan journal of medical sciences mona hashim elbashir et al table 4: different regimens used after normal vaginal delivery (nvd) and after caesarian section (cs) as postpartum hemorrhage prophylaxis (pph) regimen number (%) regimens used for pph prophylaxis in nvd no drug 9 (7.7%) misoprostol 4 tabs 5 (4.2%) misoprostol 4 tabs + oxytocin 20 iu 3 (2.6%) misoprostol 4 tabs + oxytocin 30 iu 3 (2.6%) misoprostol 3 tabs + oxytocin 20 iu 2 (1.7%) misoprostol 3 tabs + oxytocin 30 iu 1 (0.9%) misoprostol 4 tabs + oxytocin 20 iu+ ergometrine 1 (0.9%) oxytocin 10 iu 11 (9.4%) oxytocin 20 iu 76 (64.9%) oxytocin 30 iu 6 (5.1%) total 117 (100%) regimens used in pph prophylaxis in cs delivery oxytocin 10 iu 2 (1.6%) oxytocin 20 iu 4 (3.2%) oxytocin 30 iu 20 (16.2%) misoprostol 4 tabs 7 (5.7%) misoprostol 3 tabs + oxytocin 30 iu 1 (0.8%) misoprostol 4 tabs + oxytocin 20 iu 8 (6.5%) misoprostol 4 tabs + oxytocin 30 iu 75 (61%) misoprostol 4 tabs + oxytocin 40 iu 4 (3.2%) misoprostol 4 tabs + oxytocin 50 iu 2 (1.6%) total 123 (100%) the most commonly used drug for these complications at a specialized hospital. half of the studied women were aged between 25 and 35 years and 62% of them were multigravida. these drugs were mainly indicated for cesarean section, normal vaginal delivery, incomplete miscarriage, induction of labor, or intrauterine death. for the induction of labor, 55% of nvds used these drugs to facilitate labor; of them, about 73% resulted in successful-nvd, while 27% suffered a failure to progress the labor resulting in em-cs. the most used dose of oxytocin was 2 iu (64%), usually added to 500 ml normal saline drip given at different rates of 15, 16, or 20 drop/min, the recommended dose is 5 iu added to 500ml of isotonic solution. most of the files lack information on the infusion rate to detect the actual drug received. besides that, the facility has no pump to adjust the dose of oxytocin, which leads to fluctuation in the dose given. side effects of oxytocin are dose-related, including fetal heart rate changes and uterine tachysystole, which may result in abruptio placentae and uterine rupture [17]. rest of doi 10.18502/sjms.v15i2.6885 page 178 sudan journal of medical sciences mona hashim elbashir et al table 5: different regimens used for incomplete miscarriage evacuation and intra uterine fetal death. regimen number (%) regimens used for incomplete miscarriage evacuation misoprostol 2 tabs vaginally 4 (5.3%) misoprostol 3 tabs vaginally 2 (2.6%) misoprostol 4 tabs vaginally 7 (9.2%) misoprostol 2 tabs orally 4 (5.3%) misoprostol 3 tabs orally 30 (39.5%) misoprostol 4 tabs orally 29 (38.1%) total 76 (100%) regimens used for intra uterine fetal death misoprostol ½ tab vaginally/4 h 1 (14.2%) misoprostol 1 tab vaginally/6 h 2 (28.6%) misoprostol 4 tabs orally 2 (28.6%) misoprostol 4tabs + oxytocin 40 iu 2 (28.6%) total 7 (100%) the regimen used exceeded the suggested doses by rcog, and the increase in uterus contraction may lead to fetal distress due to a decrease in blood supply and oxygen ending the delivery to an em-cs in about 27% of all cases. many obstetricians used unnecessarily high doses of oxytocin, causing excessive uterine activity and believed that intervention was not needed unless there were unnecessary changes in fetal heart rate [18]. oxytocin administered as an intravenous bolus of 10 iu was reported to induce chest pain, transient profound tachycardia, and hypotension, and ecg changes suggestive of myocardial ischemia [19, 20]. also, oxytocin misuse increases the risk of ruptured uterus, fetal asphyxia, and fetal death [21]. oxytocin augmentation had been associated with neonatal sepsis, fetal distress, postpartum hemorrhage, uterine rupture, and a higher incidence of cesarean section [13]. misoprostol is used to induce labor in different doses alone or in combination with oxytocin, the most effective route of administration is through vagina [22, 23], yet different regimens include oral route as well. also, the dose of misoprostol in 9% of the cases were above the recommended dose. when used in combination with oxytocin, oxytocin should not be commenced until 4 hr of misoprostol last dose [24], which is not observed in doctor’s orders in files. the doses used to induce labor were way above the recommended dose; 50 mcg pv [25 mcg pv by rcog], 3–4 tabs orally [200 mcg po,17]. in nigeria, a study revealed that the mean induction to the vaginal delivery interval was significantly shorter in the misoprostol user compared to the oxytocin users; in addition, misoprostol is more effective in reducing the complications such as pph when compared to the oxytocin. doi 10.18502/sjms.v15i2.6885 page 179 sudan journal of medical sciences mona hashim elbashir et al the most used pph prophylactic dose post-normal vaginal delivery was 20 iu of oxytocin (65%) given as 10 iu intravenously and 10 iu intramuscularly, the recommended dose of oxytocin by rcog is 10 iu given by i.m route [22, 23], which was achieved only by 9.4% of all cases. as results shows, there none of the cases used the recommended dose of oxytocin post-cesarean delivery (5 iu) [22, 23]. six regimens used a different combination of both misoprostol and oxytocin, which does not exist in any protocol unless actual hemorrhage occurs. the most used regimen (61% of all cases) is a combination of misoprostol 4 tablets and oxytocin 30 iu given as 1 tablet sublingually, 3 tablets rectally beside 10 iu oxytocin intravenously and 20 iu through infusion postoperatively which is considered as an overdose because the use of misoprostol is not associated with any significant reduction in the incidence of pph; of all uterotonic, ergometrine is the drug of choice in pph prevention followed by oxytocin [26, 27]. only one case used ergometrine with other uterotonic as pph prevention agent, and that case was considered to be of high pph risk (twin baby). the use of misoprostol as pph prevention agent is not preferred to conventional injectable uterotonic [10]. regarding doses of missed miscarriage, the guideline has many options for misoprostol ranging from 400 mcg to 800 mcg as a vaginal insert to 600 mcg orally, so adherence of prescribers to the guideline was about 56.6%. the success of medical treatment was 39.5% of all cases, and the rest needed surgical intervention. use of misoprostol for second-trimester termination of pregnancy has been associated with uterine rupture, particularly when combined with oxytocin infusion. in a report of 803 women admitted to hospital with abortion complications in rio de janeiro, 458 reported using misoprostol. there were three deaths (two from sepsis and one from the uterine rupture at 16 weeks of gestation) following self-medication with misoprostol. therefore, the misoprostol dosage used in the second trimester needs to be limited, and oxytocin infusion should not commence within 6 hr of administering misoprostol [28]. regarding iufd, 57% of cases used an overdose regardless of the guideline’s recommendation. the concurrent use of misoprostol with oxytocin was reported to potentiate misoprostol effect; only two cases used this regimen [22, 23]. generally, the prescriber’s adherence to guidelines in the current study was achieved only in 17% of all cases. a study conducted in seven countries in 2005–2006 reported that the active management of the third stage of labor was only implemented correctly in 0.5–32% of deliveries observed [29], hence, adherence to guidelines is a major problem facing many countries. this study is not without limitations; first, the study was conducted at only one center. therefore, we cannot generalize the finding of this study to the whole of sudan. doi 10.18502/sjms.v15i2.6885 page 180 sudan journal of medical sciences mona hashim elbashir et al second, upon data collection, many missed data were observed, such as infusion rate and adverse effects, which also affect the measurement of the adherence. however, even with these limitations, our findings are valuable, as it highlights the importance of following the guidelines. thus, further multi-central studies are highly recommended to evaluate adherence nationally. the study concludes that higher percentages of cases with incomplete miscarriage and iufd were given the recommended regimens of misoprostol or oxytocin to manage them, while lower percentages of the participants were given the recommended regimens for labor induction and to prevent postpartum hemorrhage. furthermore, the overall calculated adherence for the obstetricians was found to be low. ethical consideration the study was approved by the ethical committee of the faculty of pharmacy, university of khartoum. the additional official agreement was obtained from saad abul-ella teaching hospital to check the medical record; all medical records were coded ensuring confidentiality throughout the study. acknowledgement the authors would like to appreciate all members of saad abu ella hospital for their collaboration. conflicts of interest there are no conflicts of interest. author contribution concept, design, and literature search were done by mona hashim elbashir and dr. bashir alsiddig yousef. data were collected by mona hashim elbashir and analyzed by safaa badi and muhammad abdou abdulraheem. dr. bashir alsiddig yousef drafted the manuscript and critically revised the important intellectual content. all authors gave their approval to publish the final version of the manuscript. doi 10.18502/sjms.v15i2.6885 page 181 sudan journal of medical sciences mona hashim elbashir et al references [1] spinner, m. r. 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(2011). induction of labour of intrauterine fetal death 24/40: audit of a uk teaching hospital’s practice over 1 year, prior to introduction of recent rcog green-top guideline no. 55. archives of disease in childhood fetal and neonatal edition, vol. 96, fa89. [7] tsu vd, shane b. new and underutilized technologies to reduce maternal mortality: call to action from a bellagio workshop. int j gynaecol obstet. 2004;85(suppl 1):s83s93. [8] hill s, yang a, bero l. priority medicines for maternal and child health: a global survey of national essential medicines lists. plos one. 2012;7:e38055. [9] who. (2003). pregnancy, childbirth, postpartum, and newborn care: a guide for essential practice. who. [10] no g-tg. (2016). prevention and management of postpartum haemorrhage. bjog, vol. 124, pp. e106–e149. [11] national collaborating centre for women’s and children’s health (uk). (2008). induction of labour. london: rcog press. 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[17] olefile km, khondowe o, m’rithaa d. misoprostol for prevention and treatment of postpartum haemorrhage: a systematic review. curationis. 2013;36(1):1-10. [18] simpson kr, james dc. effects of oxytocin-induced uterine hyperstimulation during labor on fetal oxygen status and fetal heart rate patterns. am j obstet gynecol. 2008;199(1):34.e1–5. [19] weeks ad, fiala c, safar p. misoprostol and the debate over off-label drug use. bjog. 2005;112(3):269-72. [20] allen r, o’brien bm. uses of misoprostol in obstetrics and gynecology. rev obstet gynecol. 2009;2(3):159-68. [21] tang os, gemzell-danielsson k, ho pc. misoprostol: pharmacokinetic profiles, effects on the uterus and side-effects. int j gynaecol obstet. 2007;99(suppl 2):s160– s167. [22] rcog. (2008). induction of labour (nice clinical guidelines, no. 70). london: rcog press. [23] mccarthy fp, kenny lc. induction of labour. obstetrics, gynaecology & reproductive medicine. 2014;24(1):9-15. [24] stanton c, armbruster d, knight r, ariawan i, gbangbade s, getachew a, et al. use of active management of the third stage of labour in seven developing countries. bulletin of the world health organization. 2009;87(3):207-15. [25] ezechi oc, loto om, ezeobi pm, okogbo fo, gbajabiamila t, nwokoro ca. safety and efficacy of misoprostol in induction of labour in prelabour rupture of fetal membrane in nigerian women: a multicenter study. international journal of reproductive biomedicine. 2008;6(3):83-0. [26] güngördük k, olgaç y, gülseren v, kocaer m. active management of the third stage of labor: a brief overview of key issues. turk j obstet gynecol. 2018;15(3):188-92. [27] maughan kl, heim sw, galazka ss. preventing postpartum hemorrhage: managing the third stage of labor. am fam physician. 2006;73(6):1025-8. [28] costa, s. h. and vessey, m. p. (1993). misoprostol and illegal abortion in rio de janeiro, brazil. lancet, vol. 341, pp. 1258–1261. [29] stanton, c., armbruster, d., knight, r., et al. (2009). use of active management of the third stage of labour in seven developing countries. scielo public health. doi 10.18502/sjms.v15i2.6885 page 183 introduction methods and materials study setting inclusion criteria exclusion criteria study sample data collection tool statistical analysis results socio-demographic and clinical data of the participants regimens used for the induction of labor regimens used after nvd and after cs as pph prophylaxis adherence of prescribers to guidelines discussion ethical consideration acknowledgement conflicts of interest author contribution references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.6823 production and hosting by knowledge e research article post-chikungunya joint pain sequelae: a sudanese single-center study bashir a. bashir1 and abubaker el-dirdiri2 1hematology department, faculty of medical laboratory sciences, port sudan ahlia college, port sudan, sudan 2orthopaedic department, port sudan teaching hospital, port sudan, sudan abstract background: chikungunya has recently been reported by the who to account for many cases in sudan. the infection is extremely symptomatic, with fever, skin rash, and incapacitating arthralgia, which can promote chronic arthritis and rheumatism in older patients. a few studies on chronic pain owing to the chikungunya virus (chikv) infection have been issued. the aim of this study was to outline the laboratory findings and the physical symptom frequency of joint pain of the current sudanese chikv outbreak, and evaluate its impact on the individual. methods: this cross–sectional study included 23 chikv-confirmed patients attending a sudanese single private medical center between march and september 2019. the included patients were checked for rheumatoid factor (rf) value, c-reactive protein (crp) titer, erythrocyte sedimentation rate (esr) value, and uric acid (ua) level. physical scrutiny was conducted and persistent symptoms were registered. results: the significant rheumatologic conditions were polyarthralgia 39.1%, polyarthritis 21.7%, arthralgia 17.4%, arthritis 13%, and osteoarthritis 8.8%. swelling signs were noted in 21.9% of the patients. joints implicated were knees 59.4%, wrists 56.3%, fingers 50%, shoulders 37.5%, feet 34.4%, ankles 31.3%, spine 18.8%, and elbow 9.4%. crp, rf, and esr were significantly increased in patients with persistent joints pain versus non-persistent joint pain patients (p = 0.000, 0.002, 0.008, respectively). whereas the ua was insignificant (p = 0.920). conclusion: knee joint pain remarks a significant dilemma post-chikv. it is noted that these remarks were linked with the risk of subsequently creating chronic sequelae. polyarthralgia was the dominant inflammatory sequel post-chikungunya infection. keywords: chikv, arthritis, arthralgia, polyarthralgia, polyarthritis, sudan 1. introduction chikungunya virus (chikv) infection is a mosquito-borne disease that can cause prompt chronic articulations pain and arthritis [1]. chikv is an arbovirus transmitted by the bite of the casualty female of mosquitoes, aedes aegypti, and aedes albopictus. patients with how to cite this article: bashir a. bashir and abubaker el-dirdiri (2020) “post-chikungunya joint pain sequelae: a sudanese single-center study,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 300–312. doi 10.18502/sjms.v15i3.6823 page 300 corresponding author: dr. bashir abdrhman bashir mohammed; associate professor of hematology, chairman of hematology department, faculty medical laboratory sciences, port sudan ahlia college, port sudan, sudan tel: 00249912358772 fax: 00249 3118 26537 email: bashirbashir17@hotmail.com received 2 july 2020 accepted 26 august 2020 published 30 september 2020 production and hosting by knowledge e bashir a. bashir and abubaker el-dirdiri. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bashirbashir17@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri severe contagion present with fever, headache, myalgia, rash, and joint pain. previous outbreaks have been documented in africa, asia, europe, and the indian and pacific ocean islands and even sudan [2]. chikv can cause extreme morbidity and, since 2005, scanty fatal cases were quantified [3]. sudan is an african nation that fringes the red sea and seven nations. the atmosphere in sudan is hot and dry. in the year 2018, 15 of sudan’s 18 states have been influenced by overwhelming downpours and floods among june and early november [2]. the circumstance made great ground for mosquitoes’ reproduction. the distribution of chikv in the overall public is obscure in sudan. sporadic instances of chikv having co-infection with dengue fever have been accounted for from sudan [2]. nonetheless, high densities of aedes aegypti have been recognized in all states of sudan excluding khartoum and northern states [3]. chikv causes both acute and chronic disabling trouble. beginning weeklong prostrated fevers are predominantly followed by musculoskeletal and joint pain, frank arthritis, and, more infrequently eye inflammation, vision loss, guillain-barre syndrome, paralysis, vasculitis, encephalitis, hepatitis, and/or myopericarditis [4]. the term “chikungunya” signifies “that which bends up” about the extreme arthralgia related to the intense period of infection and the subsequent posture of those afflicted. to date, the exact mechanism for chikv’s incapacitating sequelae stay to be completely obscure. underlying comorbidities, for example, cardiovascular disease, hypertension, concomitant osteoarthritis, obesity, and diabetes have been distinguished as conceivably expanding the seriousness of chikv disease. likewise, age at the time of extreme infection has been accounted for by many examiners to be predictive of persistent arthralgia or arthritis after chikv infection [5]. research conducted in the american outbreak explored that 30–70% of chikv infected patients experience persistent joint pain months or years after their severe sickness. there have been a few statements of the recurrence of chronic joint pain in american [6]. in this study, we examined the laboratory findings and the physical symptom frequency of joint pain of the current sudanese chikv outbreak and its effect on the individual. 2. patients and methods thirty-two patients with clinically and laboratory-confirmed chikv infection were recorded as a portion of a prospective cross-sectional study in the period from march to september 2019. this study was started six months after the end of the current sudanese outbreak. the diagnosis of chikv was immunologically verified by enzymelinked immunosorbent assay (elisa). a baseline survey was documented to ascertain exposure history, rheumatologic symptoms, duration of symptoms, number of joints doi 10.18502/sjms.v15i3.6823 page 301 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri affected, and comorbidities. patients defined as suffering from joint pain were taken to complete the arthritis disease activity score questionnaire [7]. individuals who already have features or confirmed for arthritis, systemic lupus erythematosus (sle), sjogren’s syndrome, sarcoidosis, chronic infection, and cancer were excluded from this study. all enrolled chikv patients were screened for rheumatoid factor (rf) titer, c-reactive protein (crp) titer, erythrocyte sedimentation rate (esr), and serum uric acid level. 2.1. arthritis severity score the disease activity sequelae in patients were estimated using the internationally validated disease activity score recommended by the american college of rheumatology [7]. 2.2. quality control standard operational procedures (sops) were carefully pursued, and quality control materials were applied for all serological tests. moreover, the research facility quality was guaranteed by well-prepared experts and supervision during sample processing. 2.3. sample size calculation the gauging of sample size was calculated using a cross-sectional statistic formula at 95% ci, 18% marginal errors with 50% of chikv distributed in a similar study [8]. a 10% unresponsive rate was likewise used to turn away any errors and expand the dependability of the findings. the sample size was adjusted to 32. 2.4. laboratory analysis for each patient, 3 ml venous blood samples were gathered under an aseptic condition in sterile plain containers for performing uric acid level, rf and crp titers. 2 ml venous blood samples added to 3.2% tri-sodium citrate containers in a proportion of 1: 4 forwarded to carried out esr (westergren technique). doi 10.18502/sjms.v15i3.6823 page 302 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri 2.5. data analysis data are summarized as mean ± standard deviation for continuous variables and as the number (percentage) for categorical variables. the kolmogorov-smirnov test was employed to assess the distributions of continuous variables and it exhibited that the variables were normally distributed for each group. nonparametric tests, mann-whitney test and wilcoxon signed rank test were used to compare crp, rf, esr, and ua between patients with persistent joint pain and non-persistent joint pain. the chi-squared test or fisher’s exact test was conducted for rheumatological symptoms and diagnosis. linear regression was applied to explore the provoke of crp and rf with the duration of the disease. the correlation between variables was measured by spearman’s rank-order correlation analysis. p< 0.05 was taken statistically significant. data were analyzed employing statistical package for social science (spss 24.0 version, ibn, chicago, usa). 3. results a total of 32 participants were enrolled and fulfilled the criteria of the study. of 32 patients, 16 (50%) were males and 16 (50%) were females. the baseline categories of the confirmed cases were highlighted in (table 1). the most frequent baseline comorbidity was diabetes (13%). the most commonly influenced joints were knees joint, wrists joint, fingers joint, and shoulders joint (table 2). the underlying joint pain during the intense infection lasted a median of 3 months, and numerous patients had sporadic and persistent joint pain after the initial infection. at the point when patients were arranged by sex, it was noted that both genders were equally prone to have chikv infection symptoms. during follow-up, the median duration of joint pain was documented as 3 months. 23 out of 32 patients (71.9%) had persistent joint pain. about 48% of patients with persistent joint pain were female (table 1). this study reported up to 6 joint involvements, including the number of joints implicated and the span of joint symptoms. the elementary infection was observed the overwhelmed majority of chikv infection among the studied 25 (78.1%), whereas recurrent infection was seen only in 7 (21.9%) of the patients. according to the disease activity score, most of the cases in this study are polyarthralgia (39.1%) followed by polyarthritis (21.7%), arthralgia (17.4%), and arthritis (13.0%) (table 1). the difference between the chikv infected patients with persistent joint pain and non-persistent joint pain was found to be significant in crp, rf, and esr (p= 0.000, 0.002, and 0.008, respectively). while uric acid was insignificant between the two doi 10.18502/sjms.v15i3.6823 page 303 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri groups (p=0.920) (table 1). esr was significantly increased in persistent joint pain (ranged 25 50) in 50% of patients. esr. crp and rf titer values were ranging between 3 and 60 (median 14.3 mg/liter) and from 4.7 24 (median 11.2 iu/ml), respectively. 34.4% of patients with persistent joint pain had a significant increase in rf value which indicates inflammatory arthritis. 59.4% of persistent joint pain was concerned with high crp titer levels. 8 (25%) of patients had high rf and crp titer values. moreover, crp was not affected by the duration of the disease (p= 0.152), unlike rf which was statistically increased with the increasing duration of the illness (p= 0. 013). this was highlighted by regression analysis (figure 1, 2). among the participants in the present report, the most frequent joint pain symptoms recorded were knee joint pain which was experienced by 59.4% of the patients followed by wrist joint pain 56.3%, fingers joint pain 50%, shoulder joint pain 37.5%, feet joint pain 34.4%, ankle joint pain 31.3%, swelling 21.9%, spine joint pain 18.8%, and elbow joint pain 9.4%. interestingly, the knee joint pain symptom represented the signature symptom post-chikv infection (p = 0.000) as well as wrist joint pain (p= 0.001), fingers joint pain (p= 0.002) (table 2). however, it is great to note that these remarks were linked with the risk of subsequently creating chronic sequelae. the statistical elaboration of findings with the rheumatologic conditions is illustrated in table 3. in this report, age was found to be significantly correlated with the number of joint affected (r = 0.442/ p < 0.011), underlying disease (r = 0.482/ p < 0.005), and shoulder joint pain (r = 0.361/ p = 0.042), and negatively correlated with rf level, crp level, and esr level (r = 0.125/ p < 0.494, r = 0.032/ p = 0.862, r = 0.176/ p = 0.336, respectively). a positive correlation was seen in the number of joint affected by esr level, shoulder joint pain, and swelling (r = 0.603/ p < 0.000, r = 0.501/ p = 0.003, r = 0.471/ p = 0.007, respectively). furthermore, a significant correlation was also noted in crp level with the number of joint affected, esr level, knee joint pain, and shoulder joint pain (r = 0.720/ p = 0.000, r = 0.700/ p = 0.000, r = 0.352/ p = 0.048, r = 0.378/ p = 0.033, respectively), and negatively correlated with the number of joint affected, underlying disease, rf level, and swelling (r = 0.004/ p = 0.985, r = 0.129/ p = 0.483, r = 0.197/ p = 0.280, r = 0.249/ p = 0.115, respectively). on the other hand, the esr was positively correlated with crp (r = 0.545/ p = 0.001) and negatively correlated with rf (r = 0.249/ p = 0.169). doi 10.18502/sjms.v15i3.6823 page 304 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri table 1: baseline characteristics of the patients serologically confirmed chikv classified according to joint pain status categories subcategory persist joint pains n= 23 no persist joint pain n= 9 p age mean±sd year 43.56±16.97 33.22±9.61 0.097 sex male female 12 (52.2%) 11 (47.8%) 4 (44.4%) 5 (55.6%) 0.705 prior comorbidity hypertension (htn) diabetes (dm) htn + dm gout none 1 (4.35%) 3 (13.04%) 1 (4.35%) 1 (4.35%) 17 (73.91%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 9 (100%) 0.162 relapse repeated infection frist infection 7 (30.4%) 16 (69.6%) 0 (0%) 9 (100%) 0.064 rheumatologic findings crp titer, mg/l rf titer, iu/ml uric acid, mg/dl esr, mm/hr 22.18±14.4 11.21±5.56 5.13±1.42 48.74±29.27 6.72±1.86 5.79±1.38 4.70±1.19 21.89±7.49 0.000 0.002 0.920 0.008 rheumatologic diagnosis arthralgia arthritis polyarthralgia polyarthritis osteoarthritis normal 4 (17.4%) 3 (13.0%) 9 (39.1%) 5 (21.7%) 2 (8.8%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 9 (100%) 0.000 4. discussion there are three discerned common genotypes of chikv: asia, east/central/south africa, and west africa. these genotypes are presented invasively throughout the indian ocean region [8]. extreme chikv infection may cause significant physical impotency [9]. therefore, this study was taken to elucidate the rheumatologic sequel of postchikungunya infection. arthritis/arthralgia is a flagship feature of chikv. many patients were improved within a few weeks, but somewhat up to 50% reveal chronic joint pain and/or swelling. once rheumatic symptoms persist for ≥ 3 months, this indicates a feature of chronic chikungunya arthritis [10]. in acute chikv infection, many cytokines get abundant such as interleukin families (1ra, 1β, 6, 7, 8, 12) as well as interferon-alpha (ifn-α). therefore, t cells and the chemokine c-c ligand 5/regulated on activation, normal t cell expressed and secreted (rantes) decreased in severe infection. chronic chikungunya arthritis doi 10.18502/sjms.v15i3.6823 page 305 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri table 2: symptoms of patients serologically confirmed chikv classified according to joint pain status categories all confirmed cases n=32 persist joint pains n= 23 no persist joint pain n= 9 p rheumatologic symptoms wrist pain ankle pain fingers pain elbow pain knee pain spine pain shoulder pain feet pain swelling 18 (56.3%) 10 (31.3%) 16 (50.0%) 3 (9.4%) 19 (59.4%) 6 (18.8%) 12 (37.5%) 11 (34.4%) 7 (21.9%) 14 (60.9%) 8 (34.8%) 13 (56.5%) 3 (13.0%) 16 (69.6%) 6 (26.1%) 11 (47.8%) 8 (34.8%) 7 (30.4%) 4 (44.4%) 2 (22.2%) 3 (33.3%) 0 (0.0%) 3 (33.3%) 0 (0.0%) 1 (11.1%) 3 (33.3%) 0 (0.0%) 0.001* 0.042* 0.002* 0.270 0.000* 0.095 0.009* 0.042* 0.064 duration of joint pain, months mean±sd median range 3.10±1.83 3.0 1 – 9 3.08±2.0 3.0 1 – 9 1.78 ± 0.44 2.0 1 – 2 0.950 number of joints affected mean±sd median range 2.63±1.89 3.0 0 – 6 3.65±1.07 4.0 2 – 6 – – – 0.000 *p< 0.050 table 3: laboratory findings with rheumatologic conditions in the study parameters arthritis n = 3 arthralgia n = 4 polyarthralgia n = 9 polyarthritis n = 5 osteoarthritis n = 2 crp, mg/l abnormal normal 3 (9.4%) 0 1 (3.1%) 3 (9.4%) 8 (25%) 1 (3.1%) 5 (15.6%) 0 2 (6.3%) 0 rf, iu/ml abnormal normal 0 3 (9.4%) 4 (12.5%) 0 0 9 (28.1%) 5 (15.6%) 0 2 (6.3%) 0 esr, mm/hr abnormal normal 2 (6.3%) 1 (3.1%) 2 (6.3%) 2 (6.3%) 5 (15.6%) 4 (12.5%) 5 (15.6%) 0 2 (6.3%) 0 uric acid, mg/dl abnormal normal 0 3 (9.4%) 0 4 (12.5%) 0 9 (28.1%) 1 (3.1%) 4 (12.5%) 0 2 (6.3%) may elevate the levels of il-6, il-17, and granulocyte-macrophage-colony stimulating factor (gm-csf) [11]. il-17 specifically, may drive chronic joint pain, triggering the upregulation of the other pro-inflammatory cytokines (il-1, il-6, tumor necrosis factor (tnf-α), and matrix metalloproteinase) prompting osteoclastogenesis and bone disintegrations [12]. this study explored that both sexes are more likely to prone the risk of persistent arthralgia/arthritis. this result is not a concordance with other previous studies that have demonstrated females to be at increased risk for persistent arthralgia/arthritis doi 10.18502/sjms.v15i3.6823 page 306 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri figure 1: relationship between c-reactive protein and the duration of chikv disease figure 2: relationship between rheumatoid factor and the duration of chikv disease [13-15]. however, this unconformity may be excused due to a shortage of sample size. 79.1% of our studied members have been fulfilled the definition of persistent doi 10.18502/sjms.v15i3.6823 page 307 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri arthralgia/arthritis, which emphatically consented with an ongoing meta-analysis on the occurrence of persistent arthralgia officiated by rodriquez-morale et al [16]. their investigations indicated that in studies with more than 200 members, 34% of chikv infected patients would go on to develop persistent arthritis/arthralgia. this extent is likewise comparable to that as of the detailed by feldstein et al [17] and is also considerable with our findings. the intensity of chikv infection has recently been answered to be predictive of recovery and long-haul arthritis and arthralgia remarks [18, 19]. similarly, in our work, a few severe symptoms, including knee pain, wrist pain, shoulder pain, finger pain, which are revealed more serious illness were examined as linked to expanded chronic disease risk. this work highlighted that knee joint pain is a countersign symptom of the disease. a finding also similar to chang et al [20]. thus, shoulder joint pain, wrist joint pain, finger joint pain, foot joint pain, and ankle joint pain were found significant in association with chikv infection. the prevalence of these symptoms was also explored in rodriquez-morale et al and van anlst et al [16, 21]. the disease intensity and the following risk of arthralgia/arthritis have been interlinked with viral burden [22]. remarkably, post-chikv infection sequel depends on the duration of the disease onset [23], this surveillance was accentuated to our study. concerning rheumatologic conditions associated with the present study, polyarthralgia, polyarthritis, arthralgia, and arthritis were represented the most rheumatologic problems. these findings are similar to heath et al and ganu et al [23, 24]. laboratory findings such as rf, crp, and esr were found to be significant in association with chikungunya infection, this may support the evidence that the presence of increased value of these parameters is a factor implicated in the progression of chikungunya complications [23]. besides, this study revealed that age and the number of joint affected were also considered factors that enhance in augments of chikungunya sequel. a significant increase in crp results was noted in 59.4% of the study. these findings concur with ganu et al [24]. esr was elevated in 50% of patients as a screening marker of inflammation. rf was significantly positive in 34.4%. a determination was also likewise detected previously [20, 24]. the high titer of rf could be falsely positive or its output could have been activated by chikv disease [24]. this study was subject to some limitations summarized as, this is a short communication survey with very limited sample size, in addition to that, we have neglected other physical symptoms of individuals who did not seek consultation. recall bias could not be ruled out. a prospective study with considerable expansion should be planned to monitor the structural joint damage, the therapeutic drugs used, doi 10.18502/sjms.v15i3.6823 page 308 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri combined molecular and serological characterization of chikv, and more laboratory sophisticated analyses. 5. conclusion polyarthralgia was characterized as the dominant inflammatory sequel in this study, followed by polyarthritis, and arthralgia for at least 3 months. knee joint pain represented a significant dilemma post-chikv infection. effective cure post-chikv symptoms sequel could improve the health of an individual. acknowledgement we wish to convey our profound gratitude to all patients who availed themselves voluntary to participate in this survey. competing interest the author declares that they have no competing interests. availability of data and material the data which are published are always reproducible by investigators funding none ethics approval this study was ratified by a regional ethical review committee. informed consent was taken from each participant of the study. doi 10.18502/sjms.v15i3.6823 page 309 sudan journal of medical sciences bashir a. bashir and abubaker el-dirdiri references [1] manimunda, s. p., vijayachari, p., uppoor, r., et al. 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(2010). persistent chronic inflammation and infection by chikungunya arthritogenic alphavirus in spite of a robust host immune response. journal of immunology, vol. 184, pp. 5914–5927. [24] heath, c. j., lowther, j., noël, t. p., et al. (2018). the identification of risk factors for chronic chikungunya arthralgia in grenada, west indies: a cross-sectional cohort study. open forum infectious diseases, vol. 5, no. 1, pp. 1–10. doi 10.18502/sjms.v15i3.6823 page 312 introduction patients and methods arthritis severity score quality control sample size calculation laboratory analysis data analysis results discussion conclusion acknowledgement competing interest availability of data and material funding ethics approval references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8935 production and hosting by knowledge e research article determination of normal and variant hemoglobin using capillary electrophoresis among voluntary blood donors in north central nigeria: implications on blood transfusion services idayat adenike durotoye1, adekunle ganiyu salaudeen2, emmanuel oladipo sanni3, abiola samuel babatunde1, adekunle kabir durowade4, hannah oluwayemisi olawumi1, tanimola makanjuola akande2, and omotosho ibrahim musa2 1fmcpath. department of haematology, university of ilorin, nigeria 2dr adekunle ganiyu salaudeen fwcp. department of epidemiology and community health, university of ilorin, nigeria 3dr emmanuel oladipo sanni, fmcpath. department of haematology, faculty of basic clinical sciences, nile university of nigeria, nigeria 4dr adekunle kabir durowade, fmcph. department of community medicine, afe-babalola university, ado ekiti, nigeria orcid: idayat adenike durotoye: http://orcid.org/0000-0001-5274-1829 abstract background: voluntary non-remunerated blood donation is a strategy adopted by world health organization aimed at ensuring safety and adequacy of blood supply. sub-saharan africa has a high prevalence of hemoglobin disorders and therefore needs to adopt stringent measures in donor selection to ensure safety for the recipient of blood transfusion. this study aimed to analyze normal and variant hemoglobin among voluntary blood donors. methods: in this descriptive cross-sectional study, 100 prospective blood donors including 55 (55%) males and 45 (45%) females, aged 18–34 years were recruited. capillary electrophoresis using the minicap system was used for determining the hemoglobin variants in alkaline buffer (ph 9.4). data analysis was done using spss version 20 and p-value < 0.05 was considered as the level of significance results: the mean age of the participants was 22.23 ± 3.3 sd years. the proportion of participants with genotype aa was 67 (67%), those with as were 17 (22 %), while those with ac were 11 (11 %). while hb a ≥ 90% was noted in 67 (67%) blood donors, hb s was seen in 22 (22%) and hb a2 > 3.5% in 57 (57%). hb f > 2% was observed in 3% of the studied participants conclusion: variant hemoglobin is common among blood donors and this should be taken into consideration whenever blood is being crossmatched for recipients of blood transfusion. data from this study will be useful in raising awareness and genetic counseling. keywords: prevalence, hemoglobin variants, capillary electrophoresis how to cite this article: idayat adenike durotoye, adekunle ganiyu salaudeen, emmanuel oladipo sanni, abiola samuel babatunde, adekunle kabir durowade, hannah oluwayemisi olawumi, tanimola makanjuola akande, and omotosho ibrahim musa (2021) “determination of normal and variant hemoglobin using capillary electrophoresis among voluntary blood donors in north central nigeria: implications on blood transfusion services,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 33–42. doi 10.18502/sjms.v16i1.8935 page 33 corresponding author: idayat adenike durotoye; department of haematology, faculty of basic medical sciences, college of health sciences, university of ilorin, ilorin, nigeria. email: idayat2007@yahoo.co.uk received 2 january 2021 accepted 16 march 2021 published 31 march 2021 production and hosting by knowledge e idayat adenike durotoye et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:idayat2007@yahoo.co.uk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences idayat adenike durotoye et al 1. introduction structural abnormalities affecting the polypeptide chain of the globin molecule are disorders inherited genetically as occurs in hemoglobin (hb) c, hb s, hb e. hemoglobin disorder is one of the most common inherited genetic disorder worldwide and accounts for about 7% of the world population (approximately 269 million people) said to be carriers [1, 2]. the emotional and economic burden of managing hemoglobin disorders is quite enormous especially in africa with limited resources. the sub-saharan part of africa has a prevalence of 10–45% for carriers of sickle cell [3, 4] and about 20–30% of the nigerian population is reported to be carriers of the mutant s gene [5, 6]. a previous study done among people living in the south western part of nigeria reported the prevalence of hb ac (hb c trait) to be 6% [7]. about 270 million people all over the world are carriers of abnormal hemoglobin [8]. hemoglobin electrophoretic analysis of hemoglobin variants in previous studies in nigeria and other part of sub-saharan africa was largely carried out with the use of cellulose acetate method at alkaline ph [7, 9]. analyzing hb with the use of capillary electrophoresis has been identified with increased accuracy. of note, for the numerical and qualitative analysis of hemoglobin, superlative similarity between use of capillary electrophoresis and high-performance cation-exchange chromatography (hplc) has been established and reported in several previous studies [10–12]. the task of ensuring safe, continuous, and adequate supply of blood as instructed by world health organisation (who) will remain sacrosanct. blood transfusion safety entails blood collection from voluntary, non-remunerated, risk-free donors with strict adherence to procedures for selecting donors [13]. the suitability of blood donated by donors with sickle cell trait has limitations for use in some clinical situations, although present blood donation criteria allow them to donate blood [13, 14]. in neonatal exchange transfusion as well as intrauterine transfusion, donated blood from sickle cell carriers may not be appropriate due to possible worsening of hypoxia especially when this blood has been stored for couples of days. transfusing patients with sickle cell anemia who had acute chest syndrome and those with stroke who are on chronic transfusion with blood donated by hb s carrier may worsen patient’s outcome since such blood are not tagged or separated from other blood units [15]. blood transfusion in patient with sickle cell anemia who had stroke is intended to lower the proportion of hb s to value <30%, thus blood donated by sct will not be appropriate for this category of patients [15, 16]. doi 10.18502/sjms.v16i1.8935 page 34 sudan journal of medical sciences idayat adenike durotoye et al this study intends to determine hemoglobin variants among blood donors using capillary electrophoresis method. 2. materials and methods 2.1. study design this study is a descriptive cross-sectional study. it assesses the hb variants among voluntary blood donors. 2.2. study participants the recruited participants included 100 prospective blood donors who met the required criteria for blood donor selection. the participants were male and female students of kwara state polytechnic, ilorin who were aged between 18 and 34 years. only those that granted consent were included in the study. 2.3. materials and tools materials and tools used included the h6500cap analyser, tri-potassium ethylene diamine tetra-acetic acid (k3edta) tubes, reagents cups and filters, centrifuge, and capiclean. the prepared solutions and reagents used included wash solution, hemolyzing reagent, the kit containing use stock reagents, distilled water, b2 buffer solution, a2 control, and afsc control. 2.4. sampling method convenient sampling method was adopted for the recruitment of blood donors. the studied participants were enrolled via a non-probability method of sampling. they were recruited based on their readiness to donate blood. 2.5. sample collection four milliliters of blood were collected via venipuncture from the ante-cubital vein and was subsequently put into labelled k3edta tubes. the collected samples were kept doi 10.18502/sjms.v16i1.8935 page 35 sudan journal of medical sciences idayat adenike durotoye et al at 2–8°c. sample analysis was carried out in the laboratory within a period of 24 hr of blood collection. 2.6. principle and procedure in capillary electrophoresis, normal hemoglobin was separated via electrophoretic mobility of the charged molecules into hemoglobin a, a2, and f. the common hemoglobin variants including s, c, e, or d were detected via electrophoresis in alkaline buffer at ph 9.4. the surface charge of the hemoglobin variants are different and thus their electrophoretic mobility in free solution is also different. the electro osmotic flow and ph of the electrolytes also determine the separation of the charged molecules. capillary electrophoresis using the minicap system was used to analyze the variants of hemoglobin. the analyzer directly detected the hb variants s, c, e, and d while the normal hb were separated into a, f, and a2. the minicap system with its silica capillaries works efficiently in parallel allowing two concurrent analysis of hb. at 415-nm wavelength of the absorbance, specific and direct detection of the separated hb were done. the procedure was carried out according to the company’s manual. 4 ml of the collected donor blood sample in edta bottle was put in a plastic tube (labeled). with the use of a centrifuge, the blood in the plastic tube was then spinned at a rated of 5000 per minute for a total of 7 mins. with a micropipette, 200 hundred microliters of packed red cell were subsequently introduced into a nesting cup. the open analyzer (h6500cap) was started and a 10ml solution of the hemolyzing reagent was put inside the tube placed in position 27. the door was closed, and the ok button was clicked. the analyzer then requested for the control in position 28. 200-µl of the control reagent was subsequently placed in a nesting cup and placed into the labeled hemoglobin a2 control tube at position number 28. the door was then closed, and the ok button was clicked. an indicator appeared requesting to input the lot # and analysis was done after selecting 1 run button. the assembled test samples were then put inside the rotating wheel (carousel) of the analyzer from locations numbered 1–26 and the door was closed. the instrument was now left to run the samples. analysis of the results was done as stated in the company’s manual. doi 10.18502/sjms.v16i1.8935 page 36 sudan journal of medical sciences idayat adenike durotoye et al 2.7. data analysis and ethical consideration relevant information was collected using structured questionnaires and data generated from the study was subsequently analyzed using spss version 20. the proportion and percentages of hemoglobin variant of blood donors were determined. the means and standard deviation of the age, gender, and each of the normal hemoglobin analyzed were established using the independent t-test while comparison of proportion was done using chi-square. test of significance was put at values of p < 0.05. 3. results in this study of 100 donors, 55 (55%) were males and 45 (45 %) females. the mean age of the participants was 22.23 ± 3.3 sd years. fifty-seven (57%) participants were aged 20–24 years and were found to have the highest donation (table 1). the proportion of participants with phenotype aa was 67 (67%), those with as was 17 (22 %), while those with ac was 11 (11 %). among participants with phenotype aa, the proportions of males was 38 (38 %) while that of females was 29 (29%). for participants with phenotype as, the proportions of males was 10 (10%) and that of females 12 (12%). seven (7%) and four (4%) females were of phenotype ac (table 2). hb a ≥ 90% was noted in 67 (67%) blood donors, hb s was seen in 22 (22%), while hb a2 > 3.5% was seen in 57 (57%). hb f > 2% was observed in 3% of the studied participants (table 3). table 1: gender and age group distribution among voluntary blood donors. variables frequency percentage (%) gender male 55 55 female 45 45 total 100 100 age group (yrs) 15–19 22 22 20–24 57 57 25–29 19 19 30–34 2 2 total 100 100 doi 10.18502/sjms.v16i1.8935 page 37 sudan journal of medical sciences idayat adenike durotoye et al table 2: prevalence of hemoglobin phenotypes among voluntary blood donors. hb variants gender proportion percentage male female aa 38 (38%) 29 (29%) 67 67% ac 7 (7%) 4 (4%) 11 11% as 10 (10%) 12 (12%) 22 22% total 55 (55%) 45 (45%) table 3: proportion of donors with normal and specific hemoglobin variants. hemoglobin frequency percentage (%) hb a 100 100.0 hb a ≥≥≥ 90.0% yes 67 67.0 no 33 33.0 hb a2 100 100.0 hb a2 >>> 3.5% yes 53 53.0 no 47 47.0 hb s 22 22.0 hb f 16 16.0 hb f >>> 2.0% (n = 16) yes 3 18.8 no 13 81.3 hb f with hb s 3 3.0 hb f >>> 2.0% and hb s (n = 3) yes 1 33.3 no 2 66.7 hb c 11 2 hb a2 >>> 3.9% and hb f >>> 1% 2 11 on the hemoglobin variants among the donors, about a quarter had hbs. only 3% had both hbs and hbf. 4. discussion blood transfusion is a clinical procedure aimed at correcting anemia, replacing losses from hemorrhages, supporting patients on chemotherapy, and so on. it is thus a lifesaving procedure. careful and selective processes are undertaken by blood bank service providers to ensure that donated blood is safe for the recipients of this blood. safe blood donation practice must be given very important consideration to ensure availability of safe blood without risk to the recipient. despite stringent measures adopted in blood donor selection criteria, quite a number of blood donors who did not know their carrier doi 10.18502/sjms.v16i1.8935 page 38 sudan journal of medical sciences idayat adenike durotoye et al status still find their way into blood donor population and this poses a risk to some category of blood transfusion recipients. our study reported a prevalence of hbaa to be 67%, hbas was found to be 22%, while hb ac was 11%. these findings were consistent with the results of previous works by garba et al. and omisakin et al., in which the prevalence rates for hb aa were reported as 66.9% and 72.4%, respectively [17, 18]. the frequency of hb aa in our study falls within the normal range of 55–75%, earlier reported among blacks [19]. the prevalence of hb as in our study was 22% and is consistent with the results of akhigbe et al. who reported 22.19% as prevalence of hb as in blood donors among students and zaccheaus et al. with a finding of 19.68% [20, 21]. omisakin et al. reported 26.1% for hb s [18]. high prevalence rate of sct was noted in children of african descent with up to 10-40% being carriers of the s gene, as reported by who in 2006 [17]. the prevalence of carriers of mutant s gene among blood donors as revealed in our study is similar to findings from other parts of nigeria [17]. thus, the prevalence rate of hb s trait is high in nigeria. the prevalence of hb c trait in our study was 11%, which was higher than the prevalence of 6% reported in a previous study [7]. further studies with a larger cohort will be needed to determine the prevalence rate of hb c trait in our environment. our study showed hb a2 > 3.5% in 57 (57%) blood donors which raises the suspicion of a possibility of β-thalassemia among blood donors in our environment. 5. conclusion although blood donors with hb s trait are allowed to donate their blood if they satisfy the donor selection criteria and screening test for ttis, the use of blood containing hb s trait is subject to limitations. the prevalence of hb s trait is high in nigeria. blood banking service providers must ensure screening of donated blood for hemoglobin variants determination before crossmatching blood for recipients who have sickle cell crisis or stroke whenever blood transfusion is indicated. findings in research studies on hb s carriers in blood donors can be used for raising awareness and genetic counseling since most voluntary blood donors fall within premarital age group. thus, blood donation can help prospective blood donors to know their carrier status early and can help them make informed future decisions. acknowledgement the authors want to appreciate all voluntary blood donors that participated in this study. doi 10.18502/sjms.v16i1.8935 page 39 sudan journal of medical sciences idayat adenike durotoye et al ethical considerations ethical approval from the ethical 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(2006). abnormal haemoglobin variants, abo and rh blood groups among students of african descent in port harcourt, nigeria. journal of african health sciences, vol. 6, no. 3, pp. 177–181. doi 10.18502/sjms.v16i1.8935 page 42 introduction materials and methods study design study participants materials and tools sampling method sample collection principle and procedure data analysis and ethical consideration results discussion conclusion acknowledgement ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8933 production and hosting by knowledge e research article prevalence of blactx-m, blatem, and blashv genes among extended-spectrum 𝛽-lactamases-producing clinical isolates of enterobacteriaceae in different regions of sudan hisham n altayb1, mohamed a m siddig3, nagwa m el amin4, and maowia m. mukhtar5 1biochemistry department, faculty of sciences, king abdulaziz university, jeddah, 21452, saudi arabia 3botany department, faculty of science, university of khartoum, sudan 4department of microbiology, faculty of medicine, qassim university, ksa 5bioscience research institute, ibn sina university, p.o. box 11463, khartoum, sudan orcid: mohamed a m siddig: http://orcid.org/0000-0002-8884-5336 abstract background: this study aimed to characterize blactx-m, blatem, and blashv genes among extended-spectrum beta-lactamases (esbls)-producing enterobacteriaceae species in different regions of sudan. methods: in this cross-sectional study, different clinical samples (n = 985) were collected randomly from symptomatic patients from four geographical regions of sudan and cultured on chromogenic media. following bacterial identification, phenotypic screening of esbls was done according to clsi guidelines using cefotaxime (30 μg), ceftazidime (30 μg), and cefepime (30 μg) discs with and without clavulanic acid. the dna was extracted by guanidine hydrochloride protocol, and then conventional pcr was used to detect blactx-m, blatem, and blashv genes. the presence of genes’ subtypes was characterized by dna sanger sequencing for selected samples. results: enterobacteriaceae represented 31% (305/985) of all isolates, 42 (128/305) of which were esbls producer, confirmed by phenotypic confirmatory test (75% [96/128] of them were positive for blactx-m genes, 61% [78/128] for blatem genes, and 38% [48/128] for blashv genes). fourteen isolates (11%) were negative for all genes. forty-eight percent (63/75) of escherichia coli isolates were positive for blactx-m, while in klebsiella pneumoniae, the dominant gene was blatem (82%) and had a low amount of blashv (59%). there was a significant association (p-value = 0.001 for all except for chloramphenicol, p = 0.014, and amikacin, p = 0.017) between resistance to third-generation cephalosporins and ciprofloxacin, nalidixic acid, meropenem, chloramphenicol, and amikacin. forty-two percent (40/96) of ctx-m-positive isolates were in gizera state, 33% (32.96) in sinnar, 24% (23/96) in khartoum, and 1% (1/96) in white nile. conclusion: we conclude that blactx-m genes are the most dominant genes in esblsproducing isolates and are more prevalent in big cities than in rural areas. keywords: phenotypic, blactx-m, blatem, and blashv esbls genes, enterobacteriaceae, sudan how to cite this article: hisham n altayb, mohamed a m siddig, nagwa m el amin, and maowia m. mukhtar (2021) “prevalence of blactx-m, blatem, and blashv genes among extended-spectrum 𝛽-lactamases-producing clinical isolates of enterobacteriaceae in different regions of sudan,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 5–16. doi 10.18502/sjms.v16i1.8933 page 5 corresponding author: hisham n altayb; biochemistry department, faculty of sciences, king abdulaziz university, jeddah, 21452, saudi arabia email: hdemmahom@kau.edu.sa received 7 february 2021 accepted 20 march 2021 published 31 march 2021 production and hosting by knowledge e hisham n altayb et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hdemmahom@kau.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hisham n altayb et al 1. introduction extended-spectrum beta-lactamases (esbls) are the types of enzymes that cause resistance to most beta-lactam ring containing antibiotics [1]. enterobacteriaceae sp. can resist a wide range of antibiotics, including cephalosporin and carbapenems, used as last-line antibiotics [2]. infections caused by esbls-producing enterobacteriaceae are increasingly being reported worldwide, causing high mortality rates, prolonged hospital stay, and rising medical costs [3]. escherichia coli and klebsiella pneumoniae species are considered among species associated with the high spread of esbls genes globally, especially the blactx-m genes, which have become more common in the last 20 years. recently, a dramatic increase has been reported in the frequency of blactx-m types β-lactamases-producing bacteria, which replaced the predominant types in the past, such as blatem and blashv [4]. blactx-m carrier, e. coli, can disseminate these genes in the community and hospitals from intestinal flora and cause infection [5]. sudan is one of the many developing countries suffering from irrational use of antibiotics, where 63% of prescriptions contain antibiotics, and various forms of irrational cephalosporins usage are noticed [6, 7]. in sudan, there is no regulation or system to govern antimicrobial use in humans or animals [8]. resistance to cephalosporins and production of esbls genes in hospitals and environment have been reported in previous studies [9–11]. for the first time, this study aimed to detect blactx-m, blashv, and blatem genes and their subtypes among esbls-producing enterobacteriaceae in different regions of sudan. 2. materials and methods a total of 975 clinical samples (n = 985; urine = 951, wound swab = 17, high vaginal swab = 12, pus = 3, sputum = 2) were collected from four different regions of sudan – the haj alsafi teaching hospital in khartoum (the capital of sudan); wad madani teaching hospital in wad madani city (the second city in sudan); wad alabass hospital in sennar state, southern sudan; and abu rugba village (remote village) in white nile state. all samples were collected randomly from symptomatic patients (hospitalized or outpatients) during the study period and cultured on chromogenic agar media (liofilchem co. italy). biochemical tests were applied for bacterial identification [12]. escherichia coli (atcc 25922), staphylococcus aureus (atcc 29213), and k. pneumonia (atcc 700603) were used as quality-control strains. doi 10.18502/sjms.v16i1.8933 page 6 sudan journal of medical sciences hisham n altayb et al 2.1. antimicrobial susceptibility testing the antimicrobial susceptibility of the selected bacteria was done by the disc-diffusion technique [13]. the following antibiotic discs were used: amikacin (30 μg), ceftazidime (30 μg), cefotaxime (30 μg), cefepime (30 μg), chloramphenicol (30 μg), meropenem (10 μg), and nalidixic acid (30 μg) (liofilchem co. italy). 2.2. phenotypic detection of esbls phenotypic screening of esbls was done according to clsi guidelines, the following discs were used: cefotaxime (30 μg), ceftazidime (30 μg), and cefepime (30 μg) discs with and without clavulanic acid. phenotypically, esbls-positive isolates showed an increase of ≥5 mm in the zone around discs with clavulanic acid discs compared to the area around the disc without clavulanic acid [13]. 2.3. identification of extended-spectrum 𝛽-lactamase genes all positive isolates with phenotypic confirmatory tests were subjected to molecular screening to detect β-lactamases genes using a conventional pcr machine. dna isolation was done by the guanidine hydrochloride method, according to sabeel et al. [14]. pcr was carried out using primer sequences presented in table 1 (metabion, germany) for blactx-m, blatem, and blashv genes [15, 16]. a reaction volume of 25 μl containing 5 µl master mix (intron biotechnology, seongnam, korea), 2 µl dna, 0.6 μl of each primer, and 16.8 µl dw was used. the pcr steps were firstly subjected to 94°c for 5 min, then 30 cycles (94°c for 45 sec, 57°c for 45 sec, 72°c for 60 sec), and final elongation at 72°c for 5 min. pcr products were run at 2% agarose gel for bands detection by uv transilluminator. control positive (obtained from previously sequenced blactx-m, blatem, and blashv genes) and control negative (containing dw, primers, and master mix) were used. sanger sequencing was achieved for both directions of dna products by macrogen company (seoul, korea). dna sequencing was performed for 25 blactx-m (7 from sinnar, 5 from khartoum, 1 from white nile, and 12 from gizera), 3 blashv, and 4 blatem genes. doi 10.18502/sjms.v16i1.8933 page 7 sudan journal of medical sciences hisham n altayb et al 2.4. statistical analysis data were analyzed by the statistical package for social science (spss) version 16, using the chi-square test. a p-value < 0.05 was considered significant. 3. results while 68% (671/985) of the cultured samples showed a significant growth, 32% (314/985) showed no growth. of the 671 isolates, 305 (45.4%) were enterobacteriaceae isolates (e. coli = 177, k. pneumoniae = 81, c. freundii complex = 11, enterobacter species = 19, p. mirabilis = 11, p. vulgaris = 6); 133 (19.7%) were enterococcus species; 177 (26.3%) were s. aureus; 19 (2.8%) were pseudomonas aeruginosa; and 37 (5.5%) were yeast cells. more than 45% (139/305) of all enterobacteriaceae isolates were resistant to cefotaxime, 39.3% (120/305) to ceftazidime, and 13.4% (41/305) to cefepime. in addition, 92 (30.2%) isolates were resistant to ciprofloxacin, 79 (25.9%) to the nalidixic acid, 21 (6.9%) to meropenem, 99 (32.5%) to chloramphenicol, and 54 (17.7%) to amikacin. there was a statistically significant (p-value < 0.05) association between resistance to thirdgeneration cephalosporins and resistance to other antibiotics used in this study (p-value = 0.001 for all except for chloramphenicol [p = 0.014] and amikacin [p = 0.017]) (table 2). 3.1. phenotypic confirmatory test of esbls the occurrence of esbls genes was confirmed phenotypically in >41% (128/305) of the isolates; 54% (54/100) were in gizera state (madani), 63.8% (23/36) in khartoum state (haj alsafi hospital), 52.1% (48/92) in sinnar state (wad alabas), and 1.3% (1/77) in white nile state (abu rugba village) (table 3). there was a statistically significant (p-value < 0.05) association between esbls genes and the different regions of sudan. 3.2. genotyping of genes of the 128 isolates that showed esbls phenotype, 89% (114/128) were positive for esbls genes by pcr; 75% (96/128) were positive for blactx-m genes (figure 1), 42% (40/96) of which were in gizera, 33% (32.96) in sinnar, 24% (23/96) in khartoum, and 1% (1/96) in white nile; 61% (78/128) were positive for blatem genes (figure 2), and 38% (48/128) were positive for blashv genes (figure 3; table 4). twenty-four isolates possessed only doi 10.18502/sjms.v16i1.8933 page 8 sudan journal of medical sciences hisham n altayb et al blactx-m genes, seven only blatem genes, and one only blashv gene. twenty-six isolates possessed the three genes together, seven harbored blatem and blashv genes, twentynine possessed both blactx-m and blatem genes, and ten harbored blactx-m and blashv genes. moreover, 14 isolates (11%) gave negative results for the three genes. 3.3. dna sequencing blactx-m−15 represented 78.3% (18/23) of blactx-m genes, blactx-m−14 13.1% (3/23), blactx-m−27 4.3% (1/23), and blactx-m−98 4.3% (1/23). out of the five blatem genes (971 bp), three isolates showed 100% identity with blatem−1 (km598665), while one isolate (isolate-29) showed 99% identity with blatem−1 of e. coli from china (afi61435). dna sequencing was also done for three blashv genes (797 bp); two isolates showed 100% identity (one with blashv−28 [acz97629] and the other with blashv−1 [acz97625.1]). the third isolate showed 98% identity with blashv−1 (acz97624). table 1: primer sequences used in the detection of genes. target primer name sequence product size (bp) annealing temp. ctx-m ma-1 f ma-2 r scsatgtgcagyacc agtaa ccgcratatgrt tggtggtg 550 57°c tem c-f d-r tcggggaaatgtgcgcg tgcttaatcagtgaggca cc 971 55°c shv os-5-f os-6-r ttatctccctgttagccacc gatttgctgatttcgctcgg 797 55°c table 2: the association between antibiotic resistance and esbls-producing and non-esbls-producing bacteria. anti-microbial agent esbl producers resistant isolates non-esbl producers resistant isolates p-value ciprofloxacin 66 (72%) 26 (28.2%) 0.001 nalidixic acid 61 (77%) 18 (22.7%) 0.001 meropenem 17 (81%) 4 (19%) 0.001 chloramphenicol 70 (71%) 29 (29.2%) 0.014 amikacin 43 (80%) 11 (20%) 0.017 doi 10.18502/sjms.v16i1.8933 page 9 sudan journal of medical sciences hisham n altayb et al table 3: phenotypic confirmatory test of esbls-producing isolates in different regions of sudan. region confirmatory test p-value ctx/cla caz/cla cpm/cla khartoum (n = 36) 66 (72%) 19 (52.7%) 21 (58.3) 0.001 gizera (n = 100) 61 (77%) 45 (45%) 44 (44) 0.001 sinnar (n = 92) 17 (81%) 43 (46.7%) 44 (47.8) 0.0001 white nile (n = 77) 70 (71%) 1 (1.3%) 1 (1.3) 0.0001 total (n = 305) 43 (80%) 108 (35.4%) 110 (36) 0.0001 caz: ceftazidime; ctx: cefotaxime; cpm: cefepime; cla: clavulanic acid; esbls: extended spectrum beta-lactamases table 4: frequency of ctx-m tem and shv genes among esbls-producing enterobacteriaceae isolates. isolate ctx-m tem shv e. coli (n = 75) 63 (84%) 42 (56%) 24 (32%) k. pneumoniae (n = 34) 21 (62%) 28 (82%) 20 (59%) enterobacter sp. (n = 7) 5 (71%) 4 (57%) 1 (14%) p. mirabilis (8) 4 (50%) 3 (38%) 2 (25%) p. vulgaris (1) 1 (100%) 0 (0%) 1 (100%) c. freundii complex (n = 3) 2 (66%) 1 (33%) 0 (0%) total (n = 128) 96 (75%) 78 (61%) 48 (38%) figure 1: pcr amplification of ctx-m genes. lane 1 dna marker (100–1500 bp), lane 2 positive control, lane 3 negative control, lanes 4–10 were positive for ctx-m genes (550 bp). 4. discussion several studies exhibited that the prevalence of esbl-producing bacteria is a serious problem of global public health, and their distribution can be varied according to geographic region, country, and studied institution [17, 18]. doi 10.18502/sjms.v16i1.8933 page 10 sudan journal of medical sciences hisham n altayb et al figure 2: amplification of tem genes. lane 1 dna marker (100–1500bp), lane 2 positive control, lanes 3–5 were positive for tem (971 bp), lanes 6–10 are negative samples. figure 3: pcr amplification of shv genes separated. lane 1 dna marker: mw 100–1500 bp, lane 2 positive control, lanes 3–9 were positive for shv genes (797 bp), lane 10 is negative control. in this study, we report the increasing rates of esbls-producing enterobacteriaceae compared to other previous study conducted in khartoum state by mekki et al. [19], we recorded esbls production among klebsiella sp. and e. coli isolated as 53% in 2010. moreover, ahmed et al. [20] had recorded esbls production among enterobacteriaceae sp. as 59.6% in 2013. this finding in the sinnar state is higher than that previously reported in 2012 by hamedelnil and eltayeb [21], who reported that 36% of 133 isolates were esbls producers. in the current study, we report that resistance to cefotaxime (45%) is higher than that to ceftazidime (39.3%) and cefepime (13.4%). we also observed a high ceftazidimeresistant rate (39.3%) within ctx-m-positive isolates, which may be because we report high frequencies of blactx-m genes in our isolates. previous reports indicated several types of blactx-m genes exhibiting an increased enzymatic activity against ceftazidime doi 10.18502/sjms.v16i1.8933 page 11 sudan journal of medical sciences hisham n altayb et al [22, 23]. a high resistance rate was observed in this study to ciprofloxacin, nalidixic acid, meropenem, chloramphenicol, and amikacin within esbls-producing isolates. there was statistically significant (p-value < 0.05) association between resistance to thirdgeneration cephalosporins and these antibiotics (p-value = 0.001, 0.001, 0.001, 0.014, and 0.017, respectively). the possible cause for this phenomenon may be that esbls are encoded on mobile plasmids, facilitating its transmission from one organism to another [24]. furthermore, 89% (114/128) of esbls-positive isolates by phenotypic detection were also positive by pcr; blactx-m genes were positive in 75% (96/128), blatem genes in 61% (78/128), and blashv genes in 38% (48/128). this finding agrees with hamedelnil and eltayeb [21] and omar et al. [20], who reported that blactx-m genes were the most dominant genes followed by blatem and blashv genes. high frequencies of blashv genes (67.4%) were reported in other studies; feizabadi et al. [25] reported genes encoding the esbls, including blashv and blactx-m among 89 k. pneumonia isolates by pcr. there were 14 isolates (11%) that gave negative results by pcr but positive by phenotypic test for esbls; this may be due to other esbls genes that were not covered by our primers sets. many studies have confirmed the presence of other esbls genes in enterobacteriaceae like blaveb-1, blaoxa, and blaper or may be due to the presence of another mechanism of resistance [26, 27]. furthermore, 19 esbls-positive isolates harbored only blatem and blashv genes; some of these genes were blatem-1, and blashv-1 and esbls phenomenon may arise from another mechanism of resistance. in the present study, we observed that the cephalosporin-resistance rate and production of esbls genes were higher in urban cities compared to rural areas. in khartoum, 64% (23/36) of the isolates were resistant to cephalosporin, 54% (54/100) in madani (gizera state), and 51% (48/94) in wad alabass locality (sinnar state), while in rural areas such as abu rugba village, they were much lower (2.6 % [2/76]). this difference may be because cities are more crowded than rural areas, which facilitates esbls spread. also, antibiotic consumption is higher in cities than in rural areas due to easy access to hospitals and pharmacies, and this is observed in the result of abu rugba village, where there is no pharmacy or hospital. unfortunately, in sudan, cephalosporins and other antibiotics are sold as over-the-counter medication, explaining the overuse of antibiotics [6, 7]. doi 10.18502/sjms.v16i1.8933 page 12 sudan journal of medical sciences hisham n altayb et al limitations limited resources prevented us from sequencing all amplified genes, and we selected some samples from different regions to be used as control strains to give us a general idea about the common gene subtypes. 5. conclusions this study has shown a high prevalence of esbls-producing bacteria in different regions of sudan, especially in big cities than in rural areas. blactx-m genes are the most dominant genes in esbls-producing isolates. this alarming situation of explosive spreading of esbls genes, especially blactx−𝑀-producing isolates, highlights the need for their epidemiological monitoring. integrated and regular management of antibiotic consumption needs to be monitored in our society to limit their spread. acknowledgments the authors are thankful to hassuna eltayeb from abu dhabi media co. for the language editing of the manuscript. they also acknowledge dr. hiba salah-eldin and dr. saher m bakhiet for their support. ethical considerations the study protocol was approved by the ethical research committee of sudan university of science and technology (sust/dsr/1ec/ea2/2014), sudan. because we collected the remaining medical samples with limited data, participant consent was waived. competing interests none. availability of data and material all sequencing data were uploaded on genbank and assigned accession numbers found in the supplementary file. doi 10.18502/sjms.v16i1.8933 page 13 sudan journal of medical sciences hisham n altayb et al funding none. authors’ contributions hna, mam, nme, and mmm contributed to the study design; hna did the experiments; hna and nme contributed to data analysis; hna, mam, nme, and mmm contributed to manuscript writing; all approved the final version of this article. references [1] kapoor, d., kalia, s., and kalia, a. 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(1996). characterization of betalactamase gene blaper-2, which encodes an extended-spectrum class a betalactamase. antimicrobial agents and chemotherapy, vol. 40, no. 3, pp. 616–620. doi 10.18502/sjms.v16i1.8933 page 16 introduction materials and methods antimicrobial susceptibility testing phenotypic detection of esbls identification of extended-spectrum -lactamase genes statistical analysis results phenotypic confirmatory test of esbls genotyping of genes dna sequencing discussion limitations conclusions acknowledgments ethical considerations competing interests availability of data and material funding authors' contributions references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.6969 production and hosting by knowledge e research article sensitivity and specificity of gold chromatography immunoassays igm/igg antibody test for covid-19: review of the current literature ehab mohammed elmadenah mohammed1,2, sahar elderdiri gafar osman3, and nazik elmaliaka hussain4 1department of hematology, faculty of medical laboratory science, dongola university, aldabbah, sudan 2department of hematology, medical laboratory science program, alfajr college of science and technology, khartoum, sudan 3department of histopathology and cytology, medical laboratory science program, alfajr college of science and technology, khartoum, sudan 4department of pathology, faculty of medicine, omdurman islamic university, khartoum, sudan abstract background: the world health organization recommends molecular tests polymerase chain reaction (pcr) to the diagnosis of coronavirus disease of 2019 (covid-19), which detect the severe acute respiratory syndrome (sars-coronavirus 2) virus rna. however, these tests are expensive and give a high negative result. there were urgent medical and public health needs for early diagnosis and treatment to minimize the spread of covid-19. this review aimed to summarize known to date information about the latest research progress of the sensitivity and specificity of rapid combined igm/igg antibody test to diagnose the pandemic novel coronavirus disease of 2019 (covid-19). methods: databases such as pubmed, google scholar, science direct, web of science electronic databases were search related articles published between january 23, 2020 and april 29, 2020, using the following search terms: “covid19 or covid-19,” “novel coronavirus,” “sars cov-2 or sars cov2,” “rapid antibody test,” “igm/igg,” “sensitivity,” “specificity.” results: the review included eight clinical studies for a total of 782 patients with covid-19 and 631 healthy controls. the sensitivity and specificity of gold chromatography immuno-assays (gcias) igm/igg rapid test vary greatly among published studies. of the eight shortlisted studies, the igm/igg sensitivity ranged from 73.9% to 89.3% in six (75%) and the igm/igg specificity ranged from 88.9% to 100% in the eight (100%) reviewed studies. the pooled data revealed that the average sensitivity and specificity was 70% and 94.5%, respectively. they agreed on its simplicity, fastness, and fewer requirements. conclusion: the gcias igm/igg rapid tests are simply fast and safe. besides their short turnaround time, no specific equipment or skilled technicians’ requirements, they can serve as a rapid diagnostic test of rt–pcr-negative highly suspected patients and screening of sars cov-2 carriers. it cannot take the place of pcr, but the huge lab diagnosis pressure can be greatly relieved and more research is needed to detect its reliability and clinical utility in limited-resource settings. how to cite this article: ehab mohammed elmadenah mohammed, sahar elderdiri gafar osman, and nazik elmaliaka hussain (2020) “sensitivity and specificity of gold chromatography immunoassays igm/igg antibody test for covid-19: review of the current literature,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 71–79. doi 10.18502/sjms.v15i5.6969 page 71 corresponding author: sahar elderdiri gafar osman; mobile: 00249111487548 email: sahardirdery@yahoo.com received 5 may 2020 accepted 19 june 2020 published 9 july 2020 production and hosting by knowledge e ehab mohammed elmadenah mohammed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:sahardirdery@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ehab mohammed elmadenah mohammed et al keywords: covid-19, rapid test, igm/igg, sensitivity, specificity, limited-resource 1. introduction coronavirusesare a large group of viruses that belong to coronaviridae family. these viruses are enveloped rna viruses, surrounded by a club-like projection (spikes) on the outer surface, which give the virus a crown-shaped appearance [1]. they were known to cause acute respiratory diseases such as middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars) [2]. the world health organization officially named the novel coronavirus 2019-ncov as sars cov-2 and the disease as coronavirus disease 19 (covid-19) [3]. on december 12, 2019, patients with pneumonia of unknown origin were identified, which was followed by an outbreak in wuhan city, china on december 31, 2019. the chinese center for disease control and prevention (china cdc) detected the novel coronavirus in samples of the lower respiratory tract from patients with pneumonia and discovered the genomic sequence on january 11, 2020. on march 11, 2020, the who declared covid19 outbreak a global pandemic [4]. as of april 29, 2020, who had reported 2,954,222 confirmed cases and 202,597 death worldwide [5]. bats have been suspected as the natural host origin of the virus by several studies, and is transmitted to humans through unknown intermediate host[6]. the disease is highly infectious, and human-to-human transmission occurs due to close contact with a person with respiratory symptoms such as sneezing and coughing. the aerosols and droplets reach the lungs through inhalation via the mouth and nose [2] . also, fecal-oral transmission and transmission via vomits have been reported [7, 8]. the clinical features of covid-19 are highly nonspecific and varied, ranging from asymptomatic to severe pneumonia, respiratory failure, and even death in certain cases [4, 9]. the main symptoms reported were sore throat, dry cough, fever, chills, headache, fatigue, muscle and joint pain, sputum production, shortness of breath, conjunctival and nasal congestion [4, 10]. the digestive symptoms such as diarrhea, nausea, or vomiting cab be an early sign of infection [11]. approximately 80% of the people infected with sars cov-2 had mild to moderate disease and recovered, which includes pneumonia and non-pneumonia cases. the evere disease was reported to have occurred in about 13.8% and the symptoms included dyspnea or high respiratory rate (≥ 30 breath/min), low pulse oxygen saturation (≤ 93%), and low pao2/fio2 ratio (< 300). about 6.1% represent the critical cases that include respiratory failure, septic shock, and multiple organ dysfunction [12]. the high-risk factors for severe disease and death include cancer, people aged > 60 years, and chronic diseases such as cardiovascular disease, diabetes, hypertension, and chronic respiratory disease [4, 15]. the disease in children aged < 19 years was rare and mild, and a very small proportion of them developed severe or critical condition [4, 12, 14]. the diagnosis of covid-19 is based on clinical symptoms, epidemiological history, and auxiliary examination such as real time-pcr (rt-pcr) for virus nucleic acid, ct doi 10.18502/sjms.v15i5.6969 page 72 sudan journal of medical sciences ehab mohammed elmadenah mohammed et al imaging, liver enzymes, serological tests, blood culture, and some hematological parameters [16]. however, since the clinical manifestations were highly atypical, auxiliary examinations were necessary as primary tools for the diagnosis [17]. currently, rt-pcr for virus nucleic acid (rna) is considered as the gold standard for detecting sars cov-2 [18]. the rna virus is detected using lower and upper respiratory samples. the upper respiratory samples such as nasopharyngeal swabs, oropharyngeal swabs, nasopharyngeal washes, and nasal aspirates were recommended in the reviewed studies. however, the lower respiratory samples such as sputum, endotracheal aspirates, and broncho alveolar lavage were recommended for patients with productive cough (19). in severe cases, the virus nucleic acid (rna) may also be detected in the stool (9). although rt-pcr is considered as a standard method for the diagnosis because they identify the specific sequence of the pathogen, it also has a high false-negative rate [19, 20]. as an alternative to rt-pcr, computed tomography (ct scan) can also be used for the clinical diagnosis of covid-19, as a ct scan is more sensitive and specific, and can therefore be used to diagnose asymptomatic and suspect patients with negative molecular diagnosis [9]. overall, ct imaging revealed infiltrates, ground glass appearance, and consolidation with or without vascular enlargement [21], as well as interlobular septal thickening, in comparison to images of healthy lungs [22]. generally, the laboratory examination results are highly non-specific. the white blood cell counts (wbcs) and the platelet count were usually normal or decreased with lymphopenia [6]. the level of c-reactive protein (crp) and erythrocyte sedimentation rate (esr) were generally elevated [23]. however, in severe cases, neutrophils counts were high whereas lymphocyte counts were low [6]. the level of alanine aminotransferase (alt), aspartate aminotransferase (ast), procalcitonin, prothrombin time, creatinine, ddimer, creatine phosphokinase (cpk), and lactate dehydrogenase (ldh) were increased [24, 25]. several serological tests for the measurement of specific igm/igg antibody in sera of covid-19 patients developed and were pre-tested by some companies, such as enzyme-linked immunosorbent assay (elisa), chemiluminescence immunoassay (maglumi 2000 plus clia), and point of care testing (poct), but very few articles were published. while immunoglobulin igg indicates recent and past infection, igm indicates current infection [26]. the serological test may help in the diagnosis of a patient suspected with covid-19 with a negative rt-pcr result and in the documentation of asymptomatic infection [23]. the sensitivity of the assay is the ability to correctly detect positive cases, whereas specificity is the ability to correctly detect negative cases. so, highly sensitive test means there were few false-negative results and a highly specific test mean there were few false-positive results [27]. there are urgent medical and public health needs of a sensitive and specific test for the early diagnosis and treatment to minimize the spread of covid-19. doi 10.18502/sjms.v15i5.6969 page 73 sudan journal of medical sciences ehab mohammed elmadenah mohammed et al 2. materials and methods a search was run for articles on covid-19 by using electronic databases such as pubmed, google scholar, science direct, supplemented by web of science electronic databases, using the following search terms: “covid19 or covid-19,” or “novel coronavirus,” “sars cov-2,” “sars cov2,” “rapid antibody test,” “igm/igg,” “sensitivity,” and “specificity.” the full-text articles were identified and screened for original data. the reference lists were retrieved and checked manually for further relevant studies. studies were included when the article was published in the english language and referred to humans. 3. results the studies were retrieved between january 23, 2020 and april 29, 2020. a total of 142 titles were retrieved, and after removing duplication and excluding articles that did not meet the inclusion criteria, eight studies were included in the review and considered as eligible. in the eight included studies, a total of 782 cases were reported, of which, 707 were confirmed cases for covid-19 by pcr, 75 were negative pcr but with signs of covid19, and 631 were healthy controls (see table 1). the study populations of the three studies were grouped according to the time of disease onset. six studies detected sars cov-2 igm/igg antibody in serum, whereas two studies detected it in whole blood. all studies considered pcr as the gold standard. only one study imported from denmark aimed to evaluate the sensitivity and specificity of six commercially available points of care igm/igg rapid tests and the rest of the studies were imported from china aimed to evaluate commercially available point of care igm/igg rapid test, see table 2. table 1: sensitivity and specificity of combined igm/igg rapid tests no. author study population sensitivity% specificity% pcr+ve pcr–ve healthy igm/igg igm/igg 1 (li et al., 2020) [27] 397 128 88.7 90.3 2 (hoffman et al., 2020) [28] 29 124 81.1 99.6 3 (cassaniti et al., 2020) [29] 38 12 30 18.4 91.7 4 (dohla et al., 2020) [30] 39 10 36.4 88.9 5 (ying et al., 2020) [31] 90 89 85.6 91 6 (xiang et al., 2020) [32] 29 124 82.4 100 7 (perez et al., 2020) [33] 55 63 45 73.9 100 8 (lassauniere et al., 2020) [34] 30 81 89.3 94.5 4. discussion although, currently, rt pcr is considered as a gold standard test for covid-19, this technique is expensive, requires high-quality and well-equipped laboratory facilities, doi 10.18502/sjms.v15i5.6969 page 74 sudan journal of medical sciences ehab mohammed elmadenah mohammed et al table 2: manufacturer information of igm/igg rapid test no. reference no. product name 1 [27] sars cov-2 rapid igg/igm combined antibody test kit/jiangsu medomics medical technologies, nanjing, china. 2 [28] covid19 igg/igm rapid test cassette/zhejiang orient gene biotech co. ltd, huzhou, zhejiang, china. 3 [29] vivadiag covid19 igm/igg rapid test/vivacheck biotech co. ltd, china. 4 [30] not mentioned 5 [31] sars cov-2 igg/igm antibody test kit/chinese biotechnology company, china. 6 [32] novel coronavirus igg/igm antibody gica kit/zhu hai liv zon diagnostic inc., china. 7 [33] covid19 igg/igm/all test biotech, hangzhou, china. 8 [34] 2019 n cov igg/igm rapid test/dynamiker biotechnology, tianjin, china. anti-sarscov-2 rapid test/auto bio diagnostics, zhengzhou, china. 2019 n cov igg/igm rapid test cassette/hangzhou all test biotech, hangzhou, china. on-site tm covid19 igg/igm rapid test/ctk biotech, poway, ca, usa. 2019 n cov igg/igm rapid test cassette/acro biotech, rancho cucamonga, ca, usa. coronavirus diseases 2019 (covid19) igg/igm antibody test/artorn laboratories, burnaby, canada. trained staff, and has a high false-negative results rate [19, 20, 25]. the possible explanation for the high false-negative results is that sars cov2 infection mainly occurs in the lungs (lower respiratory tract), whereas the samples are taken mostly from the upper respiratory tract. wang et al. reported that the rt-pcr of nasal and pharyngeal swab detected virus only in two-third and one-third of cases, respectively, and the rates of the positive result were 63% and 32%, respectively, when compared to bronchoalveolar lavage fluid and sputum, 93% and 72%, respectively [36]. however, according to ren et al., the sensitivity and specificity of rt-pcr for pharyngeal swab were 98.8% and 78.2%, respectively [37]. the gcia, on the other hand, is a rapid serological test for the detection of igm/igg combined antibody of sars cov2, and can give the result in less than 15 min without the requirement of high-quality and well-equipped laboratory facilities, trained staff, or specimen transportation as compared to pcr [32]. it remains a good choice in developing countries such as sudan. igm antibody can be detected in the blood specimen after three–six days, while igg is detected after eight days of disease onset (38). the current review showed that eight studies used the gcia for the igm/igg antibody. the gcia is simple and provides a rapid diagnosis for covid19. however, when the specimen is collected in the early stage of the disease onset, the falsenegative result rate was high [15]. further, li et al. reported the sensitivity and specificity of igm/igg as 88.7% and 90.6%, respectively. they explained that the false-negative was due to low antibody concentration, the differences in immune response between individuals, decrease and disappeared igm antibody after two weeks, and difficulties in knowing the exact time of infection [28]. likewise, xiang et al. reported a sensitivity and specificity of igm/igg as doi 10.18502/sjms.v15i5.6969 page 75 sudan journal of medical sciences ehab mohammed elmadenah mohammed et al 82.4%, and 100%, respectively [33]. hoffman et al., in their study, found the sensitivity of igm and igg to be 69% and 93.1% and the specificity to be 100% and 99.2%, respectively. they observed one false-positive result for igg from healthy control group sample collected in 2018; this result indicates cross-reaction between sars-cov and sarscov2 or another human coronavirus [29]. further, hoffman et al. grouped the patients into two categories according to the time of disease onset and found no significant difference in the igm and igg between the two groups. they concluded that the performance of igm/igg rapid test was satisfactory [29]. also, perez et al. and ying et al. found that the sensitivity and of igm/igg were 73.9% and 82.4% and the specificity were 100% and 100%, respectively. perez et al. and ying et al. categorized the cases into three groups according to the time of disease onset and found an increase in the positivity rate for igm/igg from 7–13 days to ≥ 14 days [32, 34]. although lassauniere et al. used the same kit as perez et al., the sensitivity and specificity was, however, 100% and 87%, respectively. these differences may probably be due to the differences in the setting or the study population [34, 35]. perez et al. concluded that the immune-chromatography test is considered as a reliable diagnostic test for sars cov2 infection from 14 days of disease onset [34], and ying et al. concluded that the sensitivity and specificity of the gcia for igg/igm combined test were good [32]. on the other hand, cassaniti et al. and dohla et al. found that the sensitivity and specificity of igm/igg were 18.4% and 36.4%, and 91.7% and 88.9%, respectively, and additionally due to poor sensitivity, they concluded that covid19 igm/igg rapid diagnostic test is not recommended for a patient with suspected covid-19 [30, 31]. perhaps, the low sensitivity may be due to samples taken in the early onset of the disease. dohla et al. recommend the acceleration of improvement and assessment of the effective point of the care test system [31]. currently, the available serological tests use antibodies against either nucleocapsid protein (n) or spike protein (s) on the surface of sars cov2 [39]. previous studies reported that the sensitivity and specificity of assays that used antibodies against s protein were high because the s protein is highly immunogenic and its affinity to angiotensin-converting enzyme receptor2 (ace2) correlated with infectivity [40, 41]. hence, igm/igg tests may be of help for the diagnosis when there is a positive test result accompanied with repeated negative rt-pcr in a highly suspected patient and for rapid screening of sars cov-2 carriers in limited-resource countries like sudan where people are used to present late. also, it can be used to screen health workers following isolation and for management using convalescence plasma. additionally, the huge laboratory diagnosis pressure can be greatly relieved; also giving value to the diagnosis and treatment. 5. limitations the main limitation of the current study was that seven studies were from the same country (china) and only one from denmark. not all studies grouped the population according to disease onset. there were differences in sample size and the type of sars doi 10.18502/sjms.v15i5.6969 page 76 sudan journal of medical sciences ehab mohammed elmadenah mohammed et al cov-2 antigen targeted in assay between the studies. the cross-reactivity between sars-cov and another human coronavirus might have happened. 6. conclusion the sensitivity and specificity of the gcia for igm/igg vary greatly among published studies. of the eight reviewed studies, the igm/igg sensitivity ranged from 73.9% to 89.3% in six (75%) and from 88.9% to 100% in all the reviewed studies (100%). they agreed that igm/igg rapid test are good, as besides being rapid, they do not need any special equipment or skilled staff. although it cannot replace pcr, it can serve as a rapid diagnostic 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[40] lou b, li t, zheng s, su y, li z, liu w, et al. serology characteristics of sars-cov-2 infection since the exposure and post symptoms onset. medrxiv. 2020;(3):1-26. doi: 10.1101/2020.03.23.20041707. doi 10.18502/sjms.v15i5.6969 page 79 introduction materials and methods results discussion limitations conclusion conflicting interest funding references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8938 production and hosting by knowledge e case report unexpected diagnosis of complete androgen insensitivity syndrome (cais) during inguinal hernia repair in 11-year-old-girl rayan khalid1, 2, alaa m. siddig1, 3, abdelrahman a. abudoam1, 4, abdel bagi alzain1, 5, and imad fadl-elmula1, 2, 6 1sudanese intersex working group, sudan, khartoum, sudan 2department of clinical genetics, assafa college, khartoum, sudan 3department of pediatric surgery, khartoum teaching hospital, khartoum, sudan 4department of psychiatry, international university of africa, khartoum, sudan 5department of obstetrics and gynecology, assafa college, khartoum, sudan 6department of surgery, assafa college, khartoum, sudan orcid: rayan khalid: http://orcid.org/0000-0002-2829-9871 abstract complete androgen insensitivity syndrome (cais) is an x-link recessive genetic mutation of androgen receptor (ar) gene leading to complete inability of cell to respond to the androgens. cais occurs in 1 out of 20,400 xy live-birth babies, and affects about 1–2% of prepubertal girls that present with an inguinal hernia. although individuals with cais have xy, those with grades 6 and 7 on the quigley scale are born phenotypically female, without any signs of genital masculinization. thus, individuals affected by cais develop a normal external female phenotype with normal female external genitalia, well-developed breast, absent uterus, and bilateral undescended testicles. the question of cais diagnosis does not come forward until the absent menses at the puberty is noted or accidentally during an inguinal hernia repair in a premenarchal girl. the present study reports a case of inguinal hernia repair on 11year-old girl, which led to unexpected intraoperative notion of cais. the diagnostic work-up, genetic counseling, sex assignment, and the need for preoperative cais screening in girls with bilateral inguinal hernia are described and discussed. keywords: dsd, cais, bilateral inguinal hernia, gonadectomy 1. introduction complete androgen insensitivity syndrome (cais) is a rare disorder of sex development (dsd). it is manifested due to mutation in androgen receptor (ar) gene which has been mapped to xq11-12 [1]. ar gene mutation is maternally inherited in 70% of the cases, whereas the remaining 30% are de novo mutations. the disease is characterized by how to cite this article: rayan khalid, alaa m. siddig, abdelrahman a. abudoam, abdel bagi alzain, and imad fadl-elmula (2021) “unexpected diagnosis of complete androgen insensitivity syndrome (cais) during inguinal hernia repair in 11-year-old-girl,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 70–75. doi 10.18502/sjms.v16i1.8938 page 70 corresponding author: rayan khalid; department of clinical genetics, al neelain stem cells center, al neelain university, khartoum, sudan phone: +249912883686 email: rynkhalid@yahoo.com received 26 january 2021 accepted 7 march 2021 published 31 march 2021 production and hosting by knowledge e rayan khalid et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:rynkhalid@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences rayan khalid et al feminization of external genitalia and bilateral undescended testes in a 46,xy individual [2]. although, cais is easily diagnosed after puberty, it can be seen accidentally during surgical repair in girls with bilateral inguinal hernia. however, controversy exists about the need to screen premenstrual girls with bilateral inguinal hernia, the best methods of the screening, and the suitable time for gonadectomy. this report describes unexpected intraoperative findings (testis) during a repair of inguinal hernia in 11-year-old girl, which was later diagnosed as cais. 2. case presentation an 11-year-old phonotypical female child presented to kassala hospital in eastern sudan with bilateral inguinal swellings. her family history with special probing on her maternal side revealed no previous similar condition. on examination, her height was 128 cm and weight 30 kg. the examination revealed normal female external genitalia and bilateral inguinal swellings, which became prominent on coughing and/or straining. the rest of the physical examination was unremarkable. the diagnosis of bilateral indirect inguinal hernia was made with strong recommendation for surgical repair. during the surgical session, a macroscopic testicular-like structure was found lying inside the rt. hernial sac. the suspicion of cais was evident so the operation was withheld and sutured back without taking tissue biopsy. later, the patient was referred to the care of sudanese intersex working group at elite clinic, khartoum, where abdominal/pelvic ultrasound revealed bilateral well-formed testicles (rt 17 x 7 mm, lt 16 x 8 mm) located in the mid inguinal canals and no uterine shadow was detected. hormonal analysis showed normal male testosterone level and chromosomal analysis showed normal male karyotype (46,xy) (figure 1). subsequent pcr for sry gene showed presence of sex-determining region (figure 2). the final diagnosis of xy, confirmed dsd (cais) and thus patient and parents were referred for genetic, psychological counseling and social support. the counseling mainly focused on parents since they were anxious, worried, rather clinically depressed, and highly preoccupied about the future of their daughter’s gender assignment. they were enlightened about the cais and the future hormonal and surgical management. due to cultural factors, they demanded to preserve the female sex of their daughter and requested urgent gonadectomy. according to the parents will, the young girl’s insight about her sex was kept discrete to avoid an unwanted conflict doi 10.18502/sjms.v16i1.8938 page 71 sudan journal of medical sciences rayan khalid et al figure 1: normal male karyotype 46,xy. figure 2: pcr amplification of the sry gene. from left to right: (lane 1) 100 bp ladder; (lane 2) –ve control (fertile female); (lane 3) +ve control (fertile male), (lane 4) patient. at the age of early adolescence. however, her expected removal of gonads will be explained on the lines of hernial repair. she should be taken in confidence when she is over 18 years old with the help of her parents and a religious leader. professional news breaking should be exercised to her and further to whoever would marry her that she will not bear children. doi 10.18502/sjms.v16i1.8938 page 72 sudan journal of medical sciences rayan khalid et al 3. discussion the aforementioned case represents the dramatic scenario of intraoperative finding (testicular-like structure in a hernial sac) in a girl with cais. the unexpected findings are weird for the operating surgeon and traumatizing for the parents and their 11-year-old girl let alone the surprise of the limited experience of the surgeon to provide proper counseling and management of such cases. it has been suggested that all premenstrual girls with inguinal hernias should undergo chromosomal study to rule out the possibility of an early diagnosis of cais [3]. this idea originates from the increased prevalence (0.8–2.4%) of cais in phenotypic females presenting with inguinal hernias [4]. contrastingly, other authors argue that the 2.4% prevalence does not justify chromosomal screening since the vast majority (>97%) of phenotypic female cases presenting with inguinal hernia are less likely to have cais. moreover, in areas with limited health resources such as africa, screening methods such as sonography and/or chromosomal analysis are not available or otherwise are very costly. in fact, the reported incidence of cais has not been convincing enough to support the routine use of such investigations even if they are available [5]. this view is supported by hurme et al.’s study in which they diagnosed cais in only one case following karyotype analyses of 109 premenstrual females who had undergone inguinal hernia repair [6]. in fact, most authors agree on the unnecessity for chromosome analysis in girls with inguinal hernia and instead consider ultrasonography capable of revealing the uterus and/or the ovaries in most cases [7]. considering sudanese culture on sex assignment and orientation in rural community, parents easily accepted the decision not to reassign an opposite sex to the patient.this was evident in the unusual management in this reported case, where both parents were adamantly demanding early gonadectomy. the fear of social stigma may justify the concern of the parents stressing the surgeon to comply and perform early gonadectomy. according to the statistics, most of the patients with cais present late with primary amenorrhea leading to delayed diagnosis, in some cases, post marriage. in fact, early diagnosis may help appropriate scheduling of gonadectomy as well as systematic parental counseling regarding several long-term issues of hormone-replacement therapy and fertility [8, 9]. early diagnosis of cais is equally essential for better management of psychosocial comorbidities and genetic counseling including carrier detection and pre-implantation genetic test with 100% chance for carrier females to bear healthy children; putting end to the transmission of the mutated x chromosome to the coming generations. doi 10.18502/sjms.v16i1.8938 page 73 sudan journal of medical sciences rayan khalid et al ethical considerations the study protocol was approved by the institutional ethical committee of assafa college. data were collected anonymously, and verbal consent were obtained from both parents. competing interests the authors hereby declare that they have no competing interest. availability of data and material all the data included in the present study is available and can be provided upon request. funding the study was self-funded by the authors as part of ongoing project of the sudanese intersex working group authors’ contributions data presented in the case report is original data of the authors and has not been published previously. the manuscript has been reviewed and approved by all authors. all authors equally contributed to this paper. references [1] lubahn, d. b., joseph, d. r., sullivan, p. m., et al. (1988). cloning of human androgen receptor complementary dna and localization to the x chromosome. science, vol. 240, no. 4850, pp. 327–330. [2] sharma, s., balwan, w. k., kumar, p., et al. (2012). androgen insensitivity syndrome (testicular feminization). journal of obstetrics and gynecology of india, vol. 62, no. 2, pp. 199–201. [3] konar, s., dasgupta, d., patra, d. k., et al. (2015). chromosomal study is must for prepubertal girl with inguinal hernia: opportunity to diagnose complete androgen doi 10.18502/sjms.v16i1.8938 page 74 sudan journal of medical sciences rayan khalid et al insensitivity syndrome. journal of clinical and diagnostic research, vol. 9, no. 4, p. gd01. [4] oakes, m. b., eyvazzadeh, a. d., quint, e., et al. (2008). complete androgen insensitivity syndrome—a review. journal of pediatric and adolescent gynecology, vol. 21, no. 6, pp. 305–310. [5] sarpel, u., palmer, s. k., and dolgin, s. e. (2005). the incidence of complete androgen insensitivity in girls with inguinal hernias and assessment of screening by vaginal length measurement. journal of pediatric surgery, vol. 40, no. 1, pp. 133–137. [6] hurme, t., lahdes-vasama, t., mäkelä, e., et al. (2009). clinical findings in prepubertal girls with inguinal hernia with special reference to the diagnosis of androgen insensitivity syndrome. scandinavian journal of urology and nephrology, vol. 43, no. 1, pp. 42–46. [7] okada, t., sasaki, s., honda, s., et al. (2012). irreducible indirect inguinal hernia containing uterus, ovaries, and fallopian tubes. hernia, vol. 16, no. 4, pp. 471–473. [8] dejager, s., bry-gauillard, h., bruckert, e., et al. (2002). a comprehensive endocrine description of kennedy’s disease revealing androgen insensitivity linked to cag repeat length. journal of clinical endocrinology and metabolism, vol. 87, no. 8, pp. 3893–3901. [9] aschim, e. l., nordenskjöld, a., giwercman, a., et al. (2004). linkage between cryptorchidism, hypospadias, and ggn repeat length in the androgen receptor gene. journal of clinical endocrinology and metabolism, vol. 89, no. 10, pp. 5105–5109. doi 10.18502/sjms.v16i1.8938 page 75 introduction case presentation discussion ethical considerations competing interests availability of data and material funding authors' contributions references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7005 production and hosting by knowledge e a narrative review immunological and neurological manifestations of covid-19: an intimate relationship m. elsayed1,2, r. ahmed3,4, a. alkhedir2, m. saeed5,6, and s. el-sadig7,8 1department of neurology, omdurman islamic university khartoum, sudan 2sharjah university hospital, sharjah, uae 3ahfad university for women khartoum sudan 4university of sharjah, sharjah, uae 5department of neurology, altagana university, khartoum, sudan 6national center for neurological sciences, khartoum, sudan 7department of neurology, khartoum university, khartoum, sudan 8soba university hospital, khartoum, sudan abstract background: covid-19 has superseded all medical scientific challenges in 2020. it presented with a range of respiratory involvement from the mild upper respiratory tract to severe pneumonia with ards. a percentage of these patients manifested variable neurological presentations expanding the challenges of patients’ assessment, care, and management. objective: to discuss the neurological manifestations and the possible immunopathology of covid-19. methods: a literature search was performed in the pubmed database for the relevant articles published in english language between april 9th , 2020 and june 1, 2020. few papers were extracted from google scholar and pre-print material as well. the keywords used to perform search included “covid-19,” “sars cov2,” “neurological manifestations,” and “immunology and pathology of covid-19”. however, animal studies were excluded in the neurological manifestations, and the final number of literature search outcome was 27 articles. results: the immunopathology involves angiotensin-converting enzyme (ace) receptor 2 and spike protein s1. covid-19 has a tremendous affinity to the ace2 receptor. the status of secondary hemophagocytic lymphohistiocytosis (shlh) and the cytokine storm lead to different organ damage and the corresponding clinical manifestations. the documented neurological manifestations mainly include acute ischemic stroke, hemorrhagic stroke, temporal lobe, thalamic encephalitis, and one case of guillain-barre syndrome, in addition to agitation, headache, and seizures. conclusion: although the intimate relationship between the neurons and the immune activation is the basic concept of covid-19 immunopathology, the definite routes of entry to the neuronal cells are yet to be disclosed. acute stroke, myositis, headache, and meningoencephalitis are the most common types of complications of covid-19 so far. keywords: covid-19, neurological manifestations, ace2 how to cite this article: m. elsayed, r. ahmed, a. alkhedir, m. saeed, and s. el-sadig (2020) “immunological and neurological manifestations of covid-19: an intimate relationship,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 111–122. doi 10.18502/sjms.v15i5.7005 page 111 corresponding author: m. elsayed email: muaz.elsayed@uhs.ae received 12 may 2020 accepted 24 july 2020 published 29 july 2020 production and hosting by knowledge e m. elsayed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:muaz.elsayed@uhs.ae https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences m. elsayed et al 1. introduction covid-19, which caused a global lockdown in 2020, exerts a major health and economic challenge. starting at the molecular level, the genome of corona virus disease 2019 (covid-19) has many similarities with the severe acute respiratory syndrome coronavirus (sars-cov) that caused the epidemic of 2003. hence, the who initially named it as sars-cov-2, which was later changed to covid-19. both viruses share the same receptors to enter the cells that are the angiotensin-converting enzyme 2 receptor [1]. the major organs affected by covid-19 are the lungs with rapidly fatal pneumonia, occasionally requiring ventilatory support. the brain expresses a metallopeptidase, ace2 receptors in the glial cells and neurons. this can make the neurons a possible goal for covid-19 virus [2, 3]. the objective of this review was to discuss the neurological manifestations and the possible related immunopathology of covid-19. 2. methodology for this narrative review, articles published in english language between april 9th , 2020 and june 1, 2020 were searched in pubmed database. a review of the bibliographies from google scholar was performed to identify the supplementary papers that were not originally found in the initial search. the terms “covid-19” and “sars cov2” were used and searched for the last five years. only human studies for all ages and countries were included in this study. next, a search for immunology and pathology of covid19 was done using the same inclusion criteria. further, a cross-search using the term “covid-19” and “neurological manifestations” revealed some retrospective descriptive studies from wuhan, china and a few case reports. two review articles were included, in addition to few pre-print articles that met our search criteria. moreover, the literature with negative serology of covid-19 and literature in other languages were excluded. animal studies were also excluded in the neurological manifestations. the final number of literature search outcome was 27 articles. 3. results 3.1. immunopathology the process involves activation of both innate and adaptive immunity. the ace2 receptor affinity for sars-cov2 is mediated by the spike protein s1 which facilitates the virus attachment to the cell wall. this receptor is expressed in the human airway epithelia, lung parenchyma, vascular endothelial cells, kidneys, cardiac, testicular, and small intestine. another coronavirus, the middle east respiratory syndrome (mers-cov) enters human cells through di-peptidyl peptidase 4 (dpp4) in the lower respiratory tract and other tissues. covid-19 has an average of 15-fold higher affinity for the spike protein s1 than in sars-cov [1]. hence, covid-19 virus makes use of the ace 2 receptors to facilitate its cell entry to various target organs. the aforementioned proteins are not the only mechanisms of virus cellular entry as some tissues failed to demonstrate the doi 10.18502/sjms.v15i5.7005 page 112 sudan journal of medical sciences m. elsayed et al presence of ace2 receptors but still got the virus documented such as some endothelial and intestinal cells [2]. the immune system response in infectious conditions may differ from one human to another depending on various genetic, racial, or environmental factors. however, some will develop a secondary hemophagocytic lymphohistiocytosis (shlh). during this hyperinflammatory immune syndrome, there is a fatal and fulminant hypercytokinemia. this is usually triggered by viruses in adults [4] and complicates around 4% of sepsis cases [5]. moreover, major cytokines may be involved in this process like il-6, il-1beta, il-2, il-8, il-17, g-csf, gm/csf, ip-10, mcp1, mip1 alpha (ccl3), and tnf [6]. the mode of entry of the virus to the central nervous system (cns) harbors many theories such as the direct invasion, hematogenous/lymphatic spread, peripheral nerve invasion, and trans-synaptic transmission [2]. moreover, the ards patients are critically ill patients and during their illness, they were noticed to have confounding metabolic and toxic factors adding or creating an encephalopathic state. other coronaviruses may cause generalized motor seizures or subclinical epileptic activity in a less common fashion [7, 8]. the inflammatory process may induce a thrombotic cascade leading to a stroke. this is mediated by multiple factors which may include increased d-dimers, accelerated atherosclerosis, and dehydration [9]. the elevated d-dimers are recognized as a characteristic laboratory finding in covid-19 infection. the c-reactive protein is also elevated. around 5% of covid-19 patients develop ards, septic shock, and/or multiple organ failure [6, 10]. they show a status of exhausted lymphocytes and lymphopenia with a reduced number of cd4 t cells, cd8 t cells, b cells, and natural killer (nk) cells. also, the number of basophils, eosinophils, and monocytes are reduced [11]. both innate and adaptive immunities are activated with uncontrolled responses contributing to tissue damage [12]. the condition exerts an increased igg response and higher titers of all antibodies; this status of antibody immune incontinence is associated with the worst outcome [13]. hence, this suggests an antibody-dependent enhancement (ade) of covid-19 infection. besides, trans-nasal inoculation of sars-cov or mers-cov caused brain involvement in transgenic mice mainly in the thalamus and brainstem. this caused high mortality in infected mice without demonstration of lung involvement. in contrast to avian influenza virus inoculation intranasally, sars-cov2 caused both brainstem and pneumonia. the affected nuclei included the nucleus ambiguous and nucleus of the solitary tract. the human body breathing reflex includes the action of the mechanoreceptors and chemoreceptors in the lungs which sends their afferent impulses to the solitary tract nucleus. the efferent fibers emerge from the solitary tract nucleus and nucleus ambiguous to the airway smooth muscles, glands, and vascular bed [2]. this reflex is interrupted during the viral infection by coronaviruses due to nuclei infection which echoes the neuroinvasive tendency of the coronaviruses. while in mice, the sars-cov managed to cause neuron death in the brain cells through entry by the nose, cribriform plate, and olfactory bulb, in humans, the exact route of entry to the neural cells by the sars-cov and mers-cov is not yet confirmed. it is unlikely that it is through hematogenous or lymphatics because no virus was detected in the non-neuronal tissues. however, there is some evidence that coronaviruses may doi 10.18502/sjms.v15i5.7005 page 113 sudan journal of medical sciences m. elsayed et al enter through the peripheral nerves and travel to the cns through synapses. due to similarities in the genomic structure, receptor vulnerability, respiratory involvement, the sars-cov model can be used to suggest possible routes of entry to the neuronal cells in covid-19. 3.2. neurological manifestations the neurological manifestations in the brain for covid-19 patients are still emerging as the case fatality rises in europe and usa. coronaviruses can cause multiple systematic involvements in various animals including humans. along with the multiple factors which add to the cns involvement stand the elevated d-dimers. the risk of a cerebrovascular event is high during these changes, especially in the microcirculation which will be liable to thrombosis or bleeding. the poor outcome in covid-19 infection may be related to age < 40 or > 60 years, high pyrexia, crp, neutrophil counts, elevated liver enzymes, high serum creatinine, and low platelets [14]. a pioneer pre-print work in wuhan gave an overall view of neurology and covid-19 as it described the neurological involvement in 214 covid-19 patients through a review of the electronic medical records. these were categorized into cns, peripheral nervous system (pns), and muscle involvement [15]. the most common symptoms included dizziness (16.8%) and headache (13.1%). the diagnoses of cns involvement depend on the ct findings, while muscle injury was determined by myalgia and creatinine kinase ck level > 200 u/l. the latter may be attributed to the skeletal muscles vasculitic process in covid-19 as in sars [16]. while the pns involvement included the symptomatology of hypogeusia (poor/loss of taste) without congestion and early hyposmia (reduced sense of smell) [17, 18], in the same retrospective study, 24.8% had cns involvement, 8.9% had pns, and 10.7% had skeletal muscle involvement [15]. of all the patients, neurological manifestations were reported in 36.4% and were more common in patients with severe infection, multiple co-morbidities (47%), mainly hypertension (ht) and atypical symptoms (p-value < 0.05). almost 45% of the patients with severe infections developed neurological symptoms. specific disorders in these patients with severe infection included acute cerebrovascular disease in 5.7% (80% of whom had an ischemic stroke), impaired consciousness in 14.8%, and muscle injury in 19.3%. all had significant p-values [15]. it is worth noticing that the ischemic brain injury seems to follow the usual expected vascular pathology in stroke patients being more ischemic than hemorrhagic. we expect this retrospective study to be the cornerstone in the clinical context of covid-19 neurology. this is because it occurred in the early days of the virulent virus and when potential drugs were unknown compared to a few months later. therefore, immune system of those patients’ was left to defend the virus only with the supportive measures. the initial stroke percentage reported from wuhan was 5.7% in which the majority was ischemic in nature in severe cases. one percent of non-severe covid-19 patients developed a stroke. older people with co-morbidities were more prone to develop a cerebrovascular event than younger patients with covid-19 infection [9]. one case report of a middle-aged female presenting with the classical symptoms and positive doi 10.18502/sjms.v15i5.7005 page 114 sudan journal of medical sciences m. elsayed et al covid-19 serology had associated confusion. the ct brain showed bilateral hypoattenuation signals on the thalami. the mri showed “evidence of hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and sub insular regions” [19]. the albacovid registry which was recently published included a larger group of patients (841) in spain and stroke occurred in 1.7% of patients. these were severe cases [20]. in one report of large vessel acute stroke in five young (below 50 years of age) covid19 patients, the national institute of health and stroke scale (nihss) mean score was 17, indicating severe disability. four patients had reduced consciousness level and one had hemiplegia. only one patient was discharged home and the others were in icu or rehabilitation units [21]. hence, both large and small vessels are liable to vascular insults (vasculitis) reflecting their tendency to be caught in the severe inflammatory storm caused by covid-19 infection. the radiological changes have proved involvement of different anatomical/vascular brain structures. this may suggest direct virus invasion of brain tissues as reported in mers-cov/ sars-cov. as the covid-19 puzzle is unfolding slowly, emerging neurological recommendations are coming through on the same speed. in the acute ischemic stroke setting, after the activation of the stroke code in case of the available stroke team, or if not, one doctor or resident with full ppe (personal protective equipment) should be exposed to the suspected case till the patient returns from radiology. this will reduce the risk during donning and doffing of ppe. if thrombolysis was indicated, the same doctor will remain inside the room while the patient is in radiology and during the first hour of tissue plasminogen activator (tpa) infusion. monitoring the patient requires filling of the q15 minute neuro-check; this can be performed by the doctor/resident/nurse inside the room. the clinical (including nihss) and imaging results should be discussed over the phone with the neurologist. in high-risk patients presenting with impaired gcs or large hemispheric infarctions, remote clinical assessment through video techniques (ipad/phone) should be performed. however, in highor low-risk groups, concerns of bedside assessment can be revealed by the bedside neurologist assessment with ppe [22]. it is important to add here that there are no concerns about the inter-rater reliability in nihss assessment between different persons as it was appraised previously [23]. in the post-thrombectomy patients via catheter intervention, remote checks of the groin complications may be performed according to the recommendations and to avoid the risk of covid-19 infection [24]. imaging repetition is not generally recommended [22]. the other workup package includes all other relevant tests like trans esophageal echo (tee), carotid doppler, and brain mri should be delayed unless there is an endocarditis. it is also worth knowing that in general for acute stroke patients, the mri is unlikely to exert major management changes [25]. a recent french study reported a bilateral frontotemporal hypoperfusion in 18%, asymptomatic lacunar strokes in 3%, and an established stroke in 1.7% of covid-19 patients [26]. in cases of intracranial hemorrhage, the same initial steps apply here. the follow-up ct, in general, may be done 3–6 hr later as up to 40% of stroke patients may develop doi 10.18502/sjms.v15i5.7005 page 115 sudan journal of medical sciences m. elsayed et al a clinically significant expansion of hematoma [27]. the prognosis will be worsened in case of covid-19 positive patients due to the involvement of other organs. severe neurological involvement in the brain has been documented before in mers cov [28]. hence, in our expectations, few covid-19 cases may develop subarachnoid hemorrhage (sah) due to accelerated atherosclerosis and the effect of the inflammation on the stability of intracranial aneurysms [29]. the management of these patients should consider, in addition to the aforementioned points, the maintenance of euvolemia to prevent overload in ards, early intubation for large sah, shorten icu stay/early external ventricular drainage (evd) clamp (avoid vasospasm), and the use of prophylaxis against dvt as covid-19 patients have higher coagulability state [22]. the conclusion for acute stroke patients in the setting of covid-19 infection is that it is more encountered in severe covid-19 infection and they are mainly ischemic in nature with high disability. specific management largely depends on the consultation of the stroke team. then, the benefit–risk ratio should be assessed in the scope of infection control. the protocol recommends using teleneurology to minimize exposure, decide on the frequency of assessments, and relevant radiology for stroke in these highly infectious patients [22]. the severe inflammatory response causes ards in half of the patients. hence, it can result in hemorrhagic encephalitis affecting various areas in the brain [30]. in a newer study observing neurological manifestations of sars2 in an icu in strasbourg france, agitation was reported in 69% of patients enrolled. before the icu admission, 14% had neurological manifestations, while 67% were observed to have it after cessation of neuromuscular block and sedation. this is not easy to be solely due to the virus effect on the brain as many metabolic, pharmacological, and inflammatory factors are involved. a high percentage (67%) developed diffuse pyramidal signs with hyperreflexia and clonus. at the time of discharge, 34% had executive disturbances, inattention, disorientation, and disorganized movements. the encephalopathic features necessitated mri imaging which showed leptomeningeal enhancement in 13%. the leptomeningeal signs and the frontotemporal signs may support the neuroinvasive character of the virus. however, the final pcr results did not support this. the electroencephalogram (eeg) showed nonspecific changes in 14%. cerebrospinal fluid (csf) was acellular in 12%, while matched oligoclonal bands (ocb) were reported in 3.4%. only one patient had high protein and igg levels in the csf. in 12% of the patients, the csf pcr tested negative for covid19 [26]. it seems that the variation of csf immune and cytology findings reflects the variable immune mechanisms by which the virus may affect the neural tissues. the first case to be reported as associated with encephalitis was described in a 24-year old man. his symptoms started with headache, fever, and malaise. on the second day, the patient was reviewed and treated as influenza by laninamivir plus antipyretics. however, on day five, the patient deteriorated with a sore throat and worsening headache. the blood tests and cxr were reassuring. on the ninth day, he was found collapsed with surrounding vomitus. in the er he presented with low gcs and developed a generalized motor seizure which recurred later multiple times. the patient had neck stiffness indicating meningio-encephalitis. there was evidence of neutrophil leukocytosis with leukopenia and high crp. his nasopharyngeal swab doi 10.18502/sjms.v15i5.7005 page 116 sudan journal of medical sciences m. elsayed et al for covid-19 was negative but the ct chest was suggestive. lumber puncture (lp) showed a clear csf with high opening pressure > 320 mmh2o, with cells of 12/µl (10 mononuclear and 2 polymorphonuclear). no antibodies against herpes were detected, however, the rna of covid-19 was detected in the csf. on day one, the brain mri diffusion-weighted images showed hyperintensities along with the inferior horn of the lateral ventricle on the right side. the fluid attenuation inversion recovery (flair), on the other hand, showed hyperintense signals on the medial temporal lobe and hippocampus with slight hippocampal atrophy. this also documents the meningeal component besides the encephalitis process. this represents the first documented case of covid-19 encephalitis with negative nasopharyngeal swab testing by pcr [31]. it seems that there is a predilection for the temporal lobes as herpes simplex virus but this is too early to be generalized. a single case of encephalitis was also reported in the albacovid registry. currently, there are no clear guidelines for the treatment of the encephalopathic state in covid-19 patients. the general measures apply and further steps depend on the outcome of relevant neuro-medical tests and the decision of the neurologist. the pioneering study of 214 patients in wuhan reported headache to be a symptom in 13.1%. this is quite similar to 14.1% of the albacovid registry. on the other hand, a study enrolled 62 patients and although headache as a symptom was higher (34%), the later study targeted patients with human-to-human transmission only [32]. in a retrospective study in wuhan which enrolled 41 positive patients for covid-19, 8% had a headache [6]. however, in the largest study with 262 patients, headache was reported in 6.2%, and it was the lowest among all studies [33]. in a smaller group of 30 medical workers, headache was reported in 53.3% [34]. the headache symptom was also reported in the first case of encephalitis with covid-19. the variation reported in headache reflects that headache is a common presenting symptom of covid-19 infection and the average percentage may be around 25%. the management of chronic headache types with acute exacerbation in this setting is by using a combination of iv paracetamol, triptans, and different antiemetics. the use of opioids should be avoided so as not to degrade the respiratory effort. the symptomatic treatment by nsaids is not carrying a sufficient risk to worsen the infection depending on the available literature evidence [35]. further evaluation of headache is needed if there are changes in the neurological examination or gcs or if it is a thunderclap headache. in these situations, the boston medical center recommends proceeding for brain ct and lp if sah is suspected. we think that the primary cause of headache in covid-19 infection is not easy to separate as being a manifestation of the systemic immune changes or the direct involvement of the brain as proved in few cases either by imaging or csf analysis. the accumulation of more headache-related literature in the setting of covid-19 patients may reveal the final result. muscles constitute a large bulk of human body and are expected to be involved in the severe inflammatory process of covid-19. while most of the literature has reported myalgia as a common feature of the infection that may occur in many viruses, where in one study, it was found in 44% of the patients [6], a lower percentage of 17.2% was reported from the albacovid registry [20]. another case report on an elderly female doi 10.18502/sjms.v15i5.7005 page 117 sudan journal of medical sciences m. elsayed et al with multiple co-morbidities reported myalgia starting early in her deadly covid-19 infection. myalgia was also reported in middle-aged female air workers as a common symptom. in most of them, the creatinine kinase (ck) levels were > 200 iu plus high inflammatory markers. this suggests a degree of muscle damage (myositis). it may not be severe enough to cause primary muscle weakness but the common occurrence and the persistence and associated elevation of muscle enzyme makes it a genuine immune characteristic of the virus and extends its target cells from neurons to muscle fibers. the real epidemiological statistics of seizures in covid-19 are still to be determined. however, in other coronaviruses’ infections, seizures were estimated to range between 6% and 50% [7]. the recent report which reviewed 841 patients in spain reported rarity of seizures in covid positive patients as the percentage was only 0.7% [20]. it is expected that some will manifest clinical motor or other subclinical seizures. the underlying pathophysiology will range between the direct invasion in areas like temporal lobes, the disturbed hemostasis, and metabolic state. the former structure is well-known for its association with focal to bilateral sensory-motor seizures, and the stressful immune activation associated with covid-19 may easily affect the electrical stabilization of this area. moreover, the relevant imaging showed involvement of temporal lobes in some cases either on one or both sides. the boston medical center recommendations in the management of the acute motor seizures in covid19 follows the standard protocol with caution in cases with liver or kidney injuries. in liver disturbances, brivaracetam, lacosamide, levetiracetam, or zonisamide may be preferred. the eeg recording should be discussed with the technician and the neurologist first to meet the fundamental goal of risk reduction. patients with impaired consciousness may need continuous eeg monitoring to detect subclinical seizures, and this needs to be tailored according to the risk–benefit ratio [22]. the loss of taste and smell proved common neurological presentation in even mild disease. the albacovid reported anosmia in 4.9% and dysgeusia in 6.2% [20]. for patients with suspected guillain-barre syndrome (gbs) with covid-19 infection, the initial assessment follows the standard neurological assessment with special focus on the signs of respiratory failure and pulmonary function testing. the point of care is preferred to be the icu especially if we considered the risk of dysautonomia. the relevant investigations like nerve conduction studies (ncs) and lp may be delayed if the clinical diagnosis is obvious as these tests are equivocal in up to 50% of cases in the first week. moreover, the high risk in contracting the infection from these patients may have affected the detailed electrophysiological classification of myoneuropathy in them [36]. the standard gbs therapeutic measures apply in covid-19 situation [22]. the options include the intravenous immune globulins infusions or the plasma exchange. till april 12, 2020, only one case assumed to have an acute gbs associated with covid-19 infection was reported. the case scenario mentioned that four days after returning from the index city of wuhan, a 61-year-old lady developed remarkable fatigue and acute lower limbs weakness. this was not accompanied by the cardinal symptoms of covid-19 infection or respiratory failure. her signs included power 4/5 muscle weakness, absent reflexes, and abnormal light touch and pin prick sensations. the ncs confirmed a form of demyelinating neuropathy while the blood counts showed doi 10.18502/sjms.v15i5.7005 page 118 sudan journal of medical sciences m. elsayed et al lymphopenia and thrombocytopenia. after receiving the intravenous immune-globulins (ivig), on day 8 she started to develop fever, dry cough, typical radiological features on ct scan as ground-glass appearance, and tested positive for covid-19. in the third week, her blood counts normalized, and by the fourth week, she recovered completely including the tendon reflexes in the four limbs. the authors discussed the casual association in this case between gbs and covid-19 in detail as the parainfectious rather than post-infectious neuropathy in this setting. however, they did not explain the sensory signs which are recognized in a small percentage of gbs subtype and the ncs which is expected to be normal in the first week in a significant percentage of patients. hence, we believe that this may represent other para-infectious sensory-motor neuropathy which seems to be mild with good recovery. since gbs is an autoimmune disease and molecular mimicry is the main immunopathological mechanism in its etiology, we find it difficult to confirm this case given the lack of csf and autoantibodies result. the recruitment of other similar cases may reveal the ambiguity of the association [37]. however, in june, one case of gbs was described in the albacovid registry [20]. the same study reported myopathy in 3.1% and dysautonomia in 2.5%. in conclusion to gbs and covid-19 the association seems to be a rare one. despite that the prevention may lay out of the scope of this narrative review, covid-19 exerted strict health and economical prevention methods. neurology is not an exception in this worldwide trend. the prevention protocol is essential for patients with known pns disorders as they can contract the infection from the community or their caregivers. the adherence to the international/national guidelines of movement restriction, use of ppe, and restriction of hospital follow-up are of paramount importance. in the case of seropositive test, any pre-existing neurological disease will exert its negative effect on the outcome and the intensive care measures. this can be hypothetically generalized for other similar conditions especially hereditary and congenital muscle diseases. a target group here may include patients with myasthenia gravis, motor neuron disease, neurologic respiratory involvement, and kyphoscoliosis, all of which tend to have a poor respiratory reserve escalating morbidity and mortality profile. patients with < 60% predicted fvc (forced vital capacity) are unlikely to wean from ventilation and patients with < 40% fvc are likely to be on nippv (noninvasive positive-pressure ventilation) already [38]. the septic status and prolonged stay in the icu will increase the likelihood of critical illness neuromyopathy which adds to the negative outcome and functional disabilities [39]. neurological complications may emerge due to non-virus causes like hypoxia, secondary hypercoagulable state, disseminated intravascular coagulopathy, and drug toxicities. another emerging puzzle is the use of immunosuppressive during covid-19 infections in patients with multiple sclerosis (ms), autoimmune neuropathy, and autoimmune encephalitis that are susceptible to immune-related complications. these diseases represent the peak of neuronal immune activation with many questions pending solution and made worse by covid mystery. medications like high-dose steroids, natalizumab (tysabri), other monoclonal antibodies are yet to be investigated for their role in adding to the immune disturbance/mortality in concomitant covid-19 infection. the association doi 10.18502/sjms.v15i5.7005 page 119 sudan journal of medical sciences m. elsayed et al of british neurologist released their recommendations about the safe use of natalizumab, dimethyl fumarate (tecfidera), interferon beta 1a & 1b, teriflunomide, and glatiramer acetate. while the fingolimod (gilenya) carried a moderate risk, a significant risk was suggested with the alemtuzumab, cladribine (mavenclad), ocrelizumab, rituximab, siponimod, and ofatumumab. this may not match the recommendations for individual drugs in other publications [40]. a conservative recommendation indorses cautious use of highly efficient medications. this may be paralleled by rebound activation of the disease, making the balance difficult [41]. many strategies were recommended to treat different categories of neurological patients during the pandemic of covid-19. this included the hereditary ataxia patients especially during the prevention and control period of covid-19 fatal pneumonia. elderly with late-stage dementia, and young syndromic patients are also at high risk of complications. other minor neurological symptoms encountered by the authors and related to the covid-19 situation rather than the virus itself included self-limiting sensory ulnar neuropathy due to remote overworking from home, postauricular pain due to n95 straps, and mask-induced headaches. all the navigated neurological manifestations during this infection may reflect the diversity of the symptomatology or the complications of the pre-existing diseases in such group of patients which constitutes a high risk for covid-19. 4. conclusion the extreme immunological storm caused by the virus results in a secondary hemophagocytic lymphohistiocytosis (shlh) ending with serious pathological damage to the lungs, brain, muscles, and kidneys. the virus has a huge affinity to the ace 2 receptor placing the brain as a target organ. headache is a common symptom of covid-19 infections and affects around one-quarter of cases while myalgia affects almost half of them. stroke in the setting of covid-19 infection can affect both large vessels in < 50 years and small vessels in older patients with severe infection. intracerebral hemorrhage is less common. the primary pathology for stroke seems to be vasculitic as well as for the muscles. the encephalopathic features may be multifactorial but at least in part are strongly related to the neuroinvasion by the virus as previously documented in mers-cov and sars-cov. this is supported by abnormal csf findings in some of these patients and positive pcr for covid-19. seizures may be caused by affection of the temporal lobes as shown in some cases. pns involvement is uncommon in covid-19 infection, while the loss of smell and taste are common symptoms even in patients with mild infection. the later symptoms may support the route of entry of the virus being near to the cranial neural structures. the final epidemiological pattern for the neurological manifestations of covid-19 is yet to be revealed after the pandemic fades away. doi 10.18502/sjms.v15i5.7005 page 120 sudan journal of medical sciences m. elsayed et al disclaimer the views mentioned in the conclusion represent the professional authors’ opinions and not their corresponding institutions. references [1] baig am, khaleeq a, ali u, syeda h. evidence of the covid-19 virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. acs chemical 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[41] barzegar m, mirmosayyeb o, nehzat n, sarrafi r, khorvash f, maghzi ah, et al. covid-19 infection in a patient with multiple sclerosis treated with fingolimod. neurology(r) neuroimmunology & neuroinflammation. 2020;7(4). doi 10.18502/sjms.v15i5.7005 page 122 introduction methodology results immunopathology neurological manifestations conclusion disclaimer references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7170 production and hosting by knowledge e research article medical research perspective of the undergraduate medical students of university of khartoum: a cross–sectional study abubaker emadeldin adlan koko, almegdad sharafaldin mohamed ahmed, almustafa siddig mohammed mustafa, and mohamed nasr mohamed ahmed elsheikh faculty of medicine, university of khartoum, khartoum, sudan abstract background: research is one of the crucial factors in the advancement of health. undergraduate medical research training is a cornerstone in medical students’ education. this study aimed to evaluate the knowledge and attitude of medical students toward medical research. methods: this cross-sectional analytical study included 200 medical students in their fifth and sixth years at the faculty of medicine, university of khartoum. data was collected using a self-administered questionnaire, assessing students’ knowledge and attitudes toward medical research, which were scored out of 100. data were analyzed using the spss software. results: of the 200 students, 69% were females and 31% males; 81% of them held a sudanese secondary school diploma and reported future clinical career choice. their mean academic score was 16 out of 32 ± 6.6 points. students’ mean knowledge score was 36 out of 100, which was considered low. their mean attitude score toward medical research was 48.2 out of 100, which was considered moderate. conclusions: this study concluded that the knowledge of fifthand sixth-year medical students about medical research was low. however, moderately positive attitude was reported among them. it is recommended that students’ engagement in active research ought to be started early in their medical school. additionally, more engaging and interactive methods of teaching research are endorsed to be implemented. keywords: attitude; knowledge; medical research; medical students; university of khartoum 1. introduction research is one of the prominent cornerstones in the advancement of health [1]. it is believed that health research has immense economic value as it contributes to the economic gain from good health of workforce, financial savings originally expended on how to cite this article: abubaker emadeldin adlan koko, almegdad sharafaldin mohamed ahmed, almustafa siddig mohammed mustafa, and mohamed nasr mohamed ahmed elsheikh (2020) “medical research perspective of the undergraduate medical students of university of khartoum: a cross–sectional study,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 237–248. doi 10.18502/sjms.v15i3.7170 page 237 corresponding author: abubaker emadeldin adlan koko; elqasr avenue, 11111, khartoum, sudan. email: bakri.imad.adlan@gmail.com received 5 july 2020 accepted 19 august 2020 published 30 september 2020 production and hosting by knowledge e abubaker emadeldin adlan koko et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bakri.imad.adlan@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abubaker emadeldin adlan koko et al healthcare, and its influence on commercial development [2]. undergraduate medical research training is one of the important pillars of medical education [3]. evidence suggests that medical students with research experience in medical school would have a positive postgraduate academic output and are more likely to pursue an academic career after graduation [4–7]. the undergraduate medical research education not only benefits those who pursue academic careers but also students’ research experience can help in sharpening their skills of searching and critically appraising the literature [8, 9]. besides, linking research and clinical practice is crucial for improving the knowledge base, generating evidencebased medicine, and enhancing patient care through making systematic scientifically based clinical decisions [10, 11]. teaching research methodology as part of the medical school curriculum is very crucial and has been linked with better attitude toward research [12]. furthermore, negative attitude toward research has been associated with poor performance in research among medical students [13]. serving this purpose, several strategies have been developed and introduced into medical schools’ curricula including lectures, tutorials, students’ scientific conferences, and mandatory and elective research projects assignments [14]. undergraduate medical research in developing countries is hindered due to several factors; a study reported that medical schools in many developing countries were not considering research as part of their curriculum [14]. other barriers reported include lack of funding, time, and professional supervision [3]. in sudan, medical research is included in the curriculum of many medical schools, including the faculty of medicine at the university of khartoum [15]. however, the evidence about medical students’ awareness concerning medical research is relatively scarce. the aim of this study was to assess the knowledge and attitude of the fifthand sixth-year medical students toward medical research. 2. methods 2.1. study design and participants this cross-sectional analytical study was conducted at the faculty of medicine, university of khartoum. this faculty is the oldest and number one-ranked medical school in the country. the school admits a class of more than 300 students each year and offers the degree of bachelor of medicine and bachelor of surgery (mbbs) upon graduation. the school’s curriculum was updated in the last five years. community medicine became doi 10.18502/sjms.v15i3.7170 page 238 sudan journal of medical sciences abubaker emadeldin adlan koko et al a longitudinal course after this update which is now spread throughout different study years. this study included fifthand sixth-year students, because a research methodology course is administered in the fourth year as part of the curriculum. a list of all students enrolled in the fifthand sixth year was obtained from the faculty’s register office; a systematic random sample of 200 students was selected from this list using students’ identification numbers. 2.2. data collection tools data were collected using a self-administered questionnaire with a previously pretested and validated scale to assess knowledge and attitudes toward medical research [16]. while the first part of the questionnaire assessed demographic data of the students, their academic performance, and type of career choice whether academic or clinical, the second part assessed knowledge about medical research and comprised of 10 questions and the third part assessed attitudes toward medical research and comprised of six questions. each question on the knowledge and attitude scales was scored as 1 if the student answered correctly and as 0 if the answer was incorrect. each scale was reported as a percentage to facilitate comparison with previous studies using the same scales. in addition, academic performance was assessed in the basic sciences (physiology, anatomy, biochemistry, microbiology, neuroscience, pharmacology, immunology, and behavioral sciences). for each subject, a score of 0, 1, 2, 3, and 4 were given for fail, pass, good, very good, and distinction degrees, respectively. individual scores for each student were summed up to generate an academic performance scale with a total of 32. data were collected between february and march 2018. 2.3. statistical analysis data entry and analysis were done using the statistical package for social sciences (spss) version 21.0. while the continuous variables were analyzed and presented as medians and means ± standard deviations (sd), the categorical variables were reported as frequencies and percentages. besides, mann–whitney u and kruskal– wallis tests were used to assess the differences in knowledge and attitude between groups since the data was not normally distributed. we used a multiple linear regression model to evaluate the association between continuous variables and knowledge and doi 10.18502/sjms.v15i3.7170 page 239 sudan journal of medical sciences abubaker emadeldin adlan koko et al attitude. results were presented as means and medians ± sd; frequencies; regression coefficients; and p-values, considering values < 0.05 as significant for all tests. 2.4. ethical considerations ethical approval was obtained from the institutional review board of the community medicine department, faculty of medicine, university of khartoum. additionally, an informed consent was obtained for each student before collecting the data, and the methods were carried out in accordance with the relevant guidelines and regulations [17]. 3. results 3.1. participants’ information the study included 200 students distributed evenly between the fifthand sixth year, with a mean age of 21.8 years, ranging from 19 to 25 years. females constituted the majority of the respondents (69%). most of the students (81%) received sudanese secondary school’s diploma, while arabic and international graduates constituted 12% and 7%, respectively. a large proportion of students (81%) reported a clinical career choice, while students favoring an academic career choice represented 14%. also, 55.5% of students had at least one family member who studied medicine. the mean academic performance score was 16 out of 32 with an sd of 6.6. 3.2. participants’ knowledge the mean knowledge score of students was 36 out of 100 (sd = 14.8). while multiple linear regression model showed a statistically significant influence of academic score on the knowledge scores of students (beta = 0.263, p < 0.001), the age of students did not have a statistically significant effect (beta = 0.007, p = 0.916). in addition, no significant difference was found in the knowledge scores of medical students across their academic levels (p = 0.076), types of high school certificate (p = 0.69), or their future career choices (p = 0.12). seventy-six (38%) participants differentiated the ordinal scale from other types of scale, 99 (49.5%), 88 (44.0%), and 13 (6.5%) students knew the definitions of scientific theory, scientific hypothesis, and scientific truth, respectively. moreover, 69 (34.5%) doi 10.18502/sjms.v15i3.7170 page 240 sudan journal of medical sciences abubaker emadeldin adlan koko et al participants said that the best way to check the number of citations for a published paper is the citation index of the science citation index database; 96 (48.0%) said that medline is a medical database; 138 (69.0%) thought that representativeness is the key characteristic of a sample, and 54 (27.0%) said that the essential characteristic of science is that all conclusions are temporary. table 1 shows the students’ responses to knowledge questions . table 1: responses of fifthand sixth-year medical students to knowledge questions. i. a scale from 1 to 5 (like grades on an examination) is called: frequency percentage 1. interval 16 8% 2. it is not a scale 14 7% 3. nominal 44 22% 4. ordinal* 76 38% 5. ratio scale 50 25% ii. all listed rules apply to the process of writing an introduction 1. clearly define the question to which your research aims to provide an answer 18 9% 2. clearly state why the research has been started 17 8.5% 3. do not explain textbook facts 35 17.5% 4. do not explain words from the title of the paper 43 21.5% 5. make it longer rather than shorter* 87 43.50% iii. how would you define scientific theory? 1. scientific hypotheses that may be proven, but lacking evidence for verification 72 36% 2. set of scientific knowledge on a given topic or area 18 9% 3. speculation or assumption with no or insufficient evidence 11 5.5% 4. system of hypotheses logically connected to one another, with common background, some of which have been verified* 99 49.5% iv. how would you define the scientific hypothesis? 1. a proposed idea or thought 52 26% 2. an answer or solution to a question 9 4.5% 3. an answer or solution to a question which has a capacity of verification or empirical demonstration* 88 44% 4. logical deduction of the premises that may or may not be verified empirically 51 25.5% v. how would you define the scientific truth? 1. absolute truth 11 5.5% 2. consensus of competent experts* 13 6.5% 3. fact that can be found in the textbooks 22 11% 4. facts that your professors teach you 1 0.5% 5. the truth that will be reached through scientific research 153 76% doi 10.18502/sjms.v15i3.7170 page 241 sudan journal of medical sciences abubaker emadeldin adlan koko et al vi. in the previous year you have published a paper in a prestigious journal – journal of immunology. now you want to check the number of citations your paper has received. the best way to do it would be to search the: 1. author index of the current contents database 27 13.5% 2. author index of the medline database 44 22% 3. author index of the science citation index database 41 20.5% 4. citation index of the science citation index database* 69 34.5% 5. corporate index of the science citation index database 19 9.5% vii. medline is 1. abbreviation (acronym) that lists the parts of the research article 26 13% 2. international association of medical informaticians 37 18.5 3. medical database* 96 48% 4. printed form of the excerpta medica 6 3% 5. the first and best known ”on-line” medical journal 35 17.5% viii. representativeness is a key characteristic of a 1. population 6 3% 2. professional paper 15 7.5% 3. sample* 138 69% 4. scientific paper 22 11% 5. scientific research 19 9.5% ix. the essential characteristic of science is 1. all scientific conclusions are temporary* 54 27% 2. an experiment is not an objective model of the nature but serves as an introduction into real research of natural phenomena 80 40% 3. rather obvious scientific conclusion does not have to be testable 11 5.5% 4. scientific theory cannot merely explain natural phenomena, but must somehow also exert influence upon them 55 27.5% x. the part of a scientific paper is 1. acknowledgment to persons who assisted you during the research* 91 45.5% 2. author’s curriculum vitae 34 17% 3. description of the timeline 45 22.5% 4. letter to the editor enclosed with the paper 30 15% *mark the correct answer. 3.3. participants’ attitude the mean attitude score was 48.2% with an sd of 18.9. although the age of the students was found to influence their attitude scores (beta = 0.144, p = 0.048), their academic score had no significant influence (beta = 0.013, p = 0.86), as indicated by multiple regression. in addition, the attitude scores differed significantly between students with doi 10.18502/sjms.v15i3.7170 page 242 sudan journal of medical sciences abubaker emadeldin adlan koko et al different career choices (academic: m (mean) = 55.95, md (median) = 50; clinical: m = 47.4, md = 50; others: m = 29.1, md = 25), p = 0.022. moreover, the attitude scores differed significantly between students’ academic levels (fifth: m = 43, md = 33.3; sixth: m = 53.5, md = 50; p < 0.001) and types of high school certificate (sudanese: m = 46.2, md = 50; arabic: m = 52.7, md = 50; international: m = 63, md = 58.3; p = 0.004). table 2 shows the students’ responses to attitude questions. table 2: responses of the fifthand sixth-year medical students to attitude questions. i. do you feel confident in interpreting and writing a research paper? frequency percentage 1. no 69 34.50% 2. undecided 60 30.00% 3. yes 71 35.50% ii. do you think undergraduate students can plan and conduct a research project and write a scientific paper? 1. no 6 3.00% 2. undecided 12 6.00% 3. yes 182 91.00% iii. do you think undergraduate students should participate in research? 1. no 6 3.00% 2. undecided 8 4.00% 3. yes 186 93.00% iv. have you ever participated in a research project (apart from mandatory academic projects)? 1. yes 67 33.50% 2. no 133 66.50% v. have you ever written a scientific paper? 1. yes 29 14.50% 2. no 171 85.50% vi. medical students can plan and conduct research project without supervision 1. no 128 64.00% 2. undecided 28 14.00% 3. yes 44 22.00% total 200 100.00% 4. discussion this study assessed the knowledge and attitude of fifthand sixth-year medical students in the university of khartoum, faculty of medicine toward medical research. usually, the formal research methodology course delivered by the department of community doi 10.18502/sjms.v15i3.7170 page 243 sudan journal of medical sciences abubaker emadeldin adlan koko et al medicine starts in the fourth year; this course is preceded by small courses in epidemiology and biostatistics during the first two years in medical school, and the students are obligated to do a research project and submit their final report by the end of the fifth year. medical students’ knowledge in this study was considered low, with a mean score of 36%; however, it is worth mentioning that their score was not associated with their gender nor with their type of high schooling and academic performance. a similar study was conducted among pakistani medical students which revealed a moderate level of knowledge with a higher mean score of 49% [16]. similarly, another croatian study concluded that medical students’ level of knowledge was moderate with a mean score of 44% [18]. this low level of knowledge might be attributed to many factors including limited research activities in the faculty that include journal clubs, evidencebased medicine sessions, and medical students research conferences. furthermore, it might be due to the theoretical methods of teaching relying fundamentally on lectures and ignoring other types of engaging ways of teaching like workshops and seminars; however, new methods of teaching have been implied [19]. in addition, relative lack of research opportunities and mentorship might all be contributing factors. regarding the mentorship and supervision, it’s worth mentioning that 22% of study participants thought that medical students are capable of planning and conducting research on their own and without supervision, this might be a serious indicator about a huge gap between medical students and their supervisors in the faculty. conversely, the level of attitude of medical students toward medical research was considered moderate with a mean score of 48%, students from international high schools and those who had academic career choice had better attitude than their colleagues, and so did the sixth-year students over fifth-year ones, this might be due to the fact that sixth-year students engage more in research and have better experience [4]. in comparison to other studies, students in this study had a better attitude than contemporaries from pakistan, however, a lower attitude than the croatians [16, 18]. although 93% of students in this study thought that medical students should participate in research, only 34% reported voluntary participation in research compared to 55% among saudi medical students and 43% among the canadians [3, 12]. this might be credited to the deficiency of initiatives that encourage medical students and facilitate their participation in active research. furthermore, in this study, only 15% of the participants said that they had ever written a scientific paper, while in contrast, a study reported that german medical students had contributed with more than a quarter of publications in one institution [20]. the low level of knowledge might have doi 10.18502/sjms.v15i3.7170 page 244 sudan journal of medical sciences abubaker emadeldin adlan koko et al affected students’ confidence on writing and interpreting scientific papers since only 36% claimed that they have the ability to do that, on the contrary, 90% of pakistani medical students confidently claimed that they can do that [16]. this study deduced that the level of knowledge about medical research among fifthand sixth-year medical students at the faculty of medicine, university of khartoum was low. however, moderately positive attitude was reported among the students, which may open the door for positive improvements in the faculty research environment in the future. it is recommended that students’ engagement in active research ought to be started early in their medical school. additionally, more engaging and interactive methods of teaching research should be implemented in the curriculum. it is also recommended that extracurricular research activities in forms of seminars, workshops, research awards, and scientific conferences be encouraged. limitations this study explored the medical students’ perspective of research on a small subset of medical students population in a single institution, so studies on a much wider scale are recommended. in addition, the study did not delve into students’ practices regarding medical research due to lack of a valid and reliable assessment tool. declarations acknowledgements none. ethical considerations ethical approval was obtained from the institutional review board of the community medicine department, faculty of medicine, university of khartoum. competing interests no potential conflict of interest relevant to this article was reported. doi 10.18502/sjms.v15i3.7170 page 245 sudan journal of medical sciences abubaker emadeldin adlan koko et al availability of data and materials the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. funding none. abbreviations m: mean; mbbs: bachelor of medicine, bachelor of surgery; md: median; sd: standard deviation; spss: statistical package for social sciences. authors’ contribution conceptualization: ak; study design: ak, aa, am, me; data acquisition: ak, aa, am; data analysis: me; writing initial draft: ak, aa, am; and writing and revising final version: ak, aa, me. references [1] paho/who. 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(2005). extracurricular research experience of medical students and their scientific output after graduation. doi 10.18502/sjms.v15i3.7170 page 246 https://www.who.int/phi/who_strategy_on_research_for_health.pdf https://www.who.int/phi/who_strategy_on_research_for_health.pdf sudan journal of medical sciences abubaker emadeldin adlan koko et al medical education, vol. 39, no. 2, p. 237. [6] hren, d., lukić, i. k., marušić, a., et al. (2004). teaching research methodology in medical schools: students’ attitudes towards and knowledge about science. medical education, vol. 38, no. 1, pp. 81–86. [7] houlden, r. l., raja, j. b., collier, c. p., et al. (2004). medical students’ perceptions of an undergraduate research elective. medical teacher, vol. 26, no. 7, pp. 659–661. [8] frishman, w. h. (2001). student research projects and theses: should they be a requirement for medical school graduation? heart diseases, vol. 3, no. 3, pp. 140– 144. 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(1998). contribution of medical student research to the medlinetm-indexed publications of a german medical faculty. medical education, vol. 32, no. 4, pp. 439–440. doi 10.18502/sjms.v15i3.7170 page 248 introduction methods study design and participants data collection tools statistical analysis ethical considerations results participants' information participants' knowledge participants' attitude discussion limitations declarations acknowledgements ethical considerations competing interests availability of data and materials funding abbreviations authors' contribution references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7746 production and hosting by knowledge e research article evaluation of the efficiency of n-terminal pro-b-type natriuretic peptide for diagnosis of acute myocardial infarction abuagla m. dafalla1, leena a. dafalla1, shamseldein m. ahmed1, yousif a. mohammed2, adam d. abakar3, wed elbahar h.aballah4, elhadi a. ahmed5, and gadallah modawe6 1department of clinical chemistry, faculty of medical laboratory sciences, university of gezira, sudan 2national cancer institute, university of gezira, sudan 3department of medical parasitology, faculty of medical laboratory sciences, university of gezira, sudan 4department of hematology and immunohematology faculty of medical laboratory sciences, managil university of science and technology sudan 5department of medical microbiology, faculty of medical laboratory sciences, university of gezira, sudan 6department of biochemistry, faculty of medicine and health sciences, omdurman islamic university, omdurman, sudan abstract background: cardiac diseases are one of the major causes of death worldwide with increasing incidence rate per year, particularly in developing countries such as sudan owing to urbanization and changing lifestyle. myocardial infarction is a consequence of the imbalance between the heart blood supply and the required heart cell; this disorder leads to necrosis of myocardium and may cause death. it could be diagnosed by at least two of the following criteria: chest pain, electrocardiography (ecg) elevation, and levels on cardiac biomarkers. this study aimed to evaluate the efficiency of n-terminal prob-type natriuretic peptide (ntprobnp) for the diagnosis of acute myocardial infarction (ami). methods: this analytical case–control hospital-based study was conducted on total of 70 individuals, of which 40 participants were suspected of or diagnosed with ami,while30 healthy subjects were included as a control group. three ml of venous blood were collected in lithium heparin containers. troponin i (tni) as a cardiac biomarker was measured by tosoh aia-360,while thentprobnp level was detected using i-chroma ii. personal and clinical data were collected directly from each participant usinga predesigned questionnaire. results: a significant increase in the tni level (mean: 13.13 ± 18.9ng/ml) and ntprobnp (mean: 5756.5 ± 8378.2pg/ml) in ami patients were detected when compared with control mean (0.02 ± 0.00ng/ml and 57.8 ± 42.32pg/ml, respectively). conclusions: ntprobnp gave a high sensitivity (87.5%), specificity (100%), positive predictive value (100%), and negative predictive value (85.7%) in the diagnosis of ami when compared with another cardiac biomarker such as tni. keywords: acute myocardial infarction, ntprobnp, troponin i, medani heart center, sudan how to cite this article: abuagla m. dafalla, leena a. dafalla, shamseldein m. ahmed, yousif a. mohammed, adam d. abakar, wed elbahar h.aballah, elhadi a. ahmed, and gadallah modawe (2020) “evaluation of the efficiency of n-terminal pro-b-type natriuretic peptide for diagnosis of acute myocardial infarction,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 249–258. doi 10.18502/sjms.v15i3.7746 page 249 corresponding author: gadallah modawe; email: gadobio77@hotmail.com received 20 june 2020 accepted 15 august 2020 published 30 september 2020 production and hosting by knowledge e abuagla m. dafalla et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:gadobio77@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abuagla m. dafalla et al 1. introduction a cardiac disease refers to any disorder that affects the heart function by either minimizing or eliminating the heart output [1]. cardiac diseases are caused either by structural heart disorder or myocardium abnormalities such as myocardial infarction (mi) [2]. an acute myocardial infarction (ami) is a consequence of the imbalance between the heart blood supply and the required heart cell. this disorder leads to necrosis of the myocardium and may even cause death [1].mi is the most common cause of death worldwide [3, 4]. the frequency of mi has increased over the last few decades throughout several states of sudan, which may be due to the increase in the prevalence of risk factors such as underlying diseases and habits [5]. the symptoms of a cardiac disease include chest pain and dyspnea due to the reduction of oxygen in myocardial cells, whichis considered as a cardinal indication of ami [6], and palpitations due to the increase in oxygen demand. other symptoms include headache and limb weakness [7]. the diagnosis of cardiac diseases depends on the history, risk factor, clinical examination, symptoms, laboratory investigation, chest radiology, electrocardiography (ecg), and echocardiography (echo) [8]. moreover, ami can be diagnosed by at least two of the following three criteria; first, typical symptoms such as a history of chest pain; second, changes on the ecg, and third, elevation on cardiac biomarkers [9]. the latter are specific elements produced by the cardiac cells and increase in cardiac disorders. cardiac biomarkers include troponin, creatine kinase (ck), myoglobin [10, 11], and brain natriuretic peptides (bnps) [12].cardiac troponin is a muscle-regulatory protein produced by a muscular cell present in skeletal and heart muscles. troponins are generally categorized into three types; troponin t, troponin i (tni), and troponin c [13]. for cardiac biomarkers, tni is more sensitive and specific than others troponins [14]. in ami, the tni rises in plasma after 4–8 hr of the onset of the symptoms, reaches the peak at 12–24 hr, and then returns to normal within 7–10 days of ami [15]. ck, on the other hand, is an enzyme consisting of two protein subunits:muscle protein (m) and brain protein (b), and depending on the constituent, ck has three isoenzymes; ckbb, ckmm, and ckmb [16].while ckbb is more abundant in the brain cells, ckmm is more abundant in the muscular cells and ckmb in the cardiac muscles [17]. ckmb is more sensitive and specific for the diagnosis of cardiac disease than ckmm and ckbb [15].ckmb level in plasma increases after 4-8 hours of mi and reaches the peak at 12 – 24 hours then return to the normal level within 2 – 3 days (16). bnps are polypeptides produced by myocardium in response to the increased wall stress due to an increase in volume or pressure of blood, to reduce intravascular volume doi 10.18502/sjms.v15i3.7746 page 250 sudan journal of medical sciences abuagla m. dafalla et al by diuretics, vasopressin, and suppuration the sense of thirst (16). bnps are secreted as pro-hormone then activated by reacting with protease enzyme to cleave it into active form bnp and inactive form ntprobnp(18). in the case of cardiac disease, both bnps are elevated, thus, measurement of plasma bnp and /or ntprobnp is a useful indicator for cardiac diseases (16). the objective of the present study was to evaluate the efficiency of n-terminal pro-b-type natriuretic peptide (ntprobnp) for the diagnosis of ami. 2. materials and methods this analytical case-control hospital-based study aimed to evaluate the efficiency of ntprobnp for the diagnosis of ami. the study was conducted in medani heart center, sudan. a purposive sample was collected from patients with ami attending medani heart center from april 2018 to june 2019. a total of 70 individuals participated in this study, 40 were ami cases and 30 were healthy individual as a control group. ami cases were included according to the final diagnoses by medani heart center physicians. ami patients with renal failure or biotin treatment were excluded. the control group was non-smokers, nonobese, normotensive, non-diabetic and have no history of renal or cardiac diseases. the demographic data were collected from each participant after final diagnosis using a questionnaire included clinical remarks such as ami symptoms, ecg, echo and risk factors. 2.1. ethical consderion permission to carry out the study was obtained from the college of graduate studies, faculty of medical laboratory sciences, university of gezira and ministry of health, sudan. all enrolled patients were informed about the purpose of the study before collection of specimens and consents for participation were taken. 2.2. data variable, collection and criteria sex, age (year) tni (ng/ml) ntprobnp (pg/ml) – risk factors clinical diagnosis echocardiogram – electrocardiogram were the variables used and also the data were collected using laboratory analysis, doctor’s report, other findings and data collection form. restricted criteria for eligibility of case and control (inclusion and exclusion criteria) doi 10.18502/sjms.v15i3.7746 page 251 sudan journal of medical sciences abuagla m. dafalla et al was followed to reduce sources of bias.a purposive sample was used to determine the sample size because there is no previous prevalence for ami in sudan. 2.3. measurement of cardiac biomarkers three ml of blood specimen from each participant were collected in lithium heparin anticoagulant tubes for laboratory analysis; plasma was separated into two new plain containers and examined within 2 hrs. the laboratory work was done in medani heart center and department of clinical chemistry, faculty of medical laboratory sciences, university of gezira. tosoh aia-360 automated machine (germany) was used to measure tni levels while i-chroma ii immunofluorescence system (korea) was used to measure ntprobnp levels. 3. data analysis collected data were analyzed by using suitable statistic software including spss computer version 22 and medical calculator program version 16. calculation of sensitivity, specificity, positive predictive value and the negative predictive value was done by these equations: sensitivity = tp/tp+fn*100. specificity = tn/tnfp*100. positive predictive value = tp/tp+fp*100. negative predictive value = tn/tn+fn*100. tp: true positive fp: false positive tn: true negative -fn: false negative. 4. results 4.1. demographics of ami subjects this study enrolled 40 patients with ami, among whom 62.5% were male, 45% diabetic, 40% hypertensive, 25% smokers, 25% obese,97.5% has no history of cardiac diseases. patients with age group above 59 years constituted 50% as shown in table (1). doi 10.18502/sjms.v15i3.7746 page 252 sudan journal of medical sciences abuagla m. dafalla et al 4.2. performance of ntprobnp and tni total positive results of ntprobnp and tni were 35/40 and 32/40, respectively. sensitivity, specificity, positive and negative predictive values of ntprobnp and tni of ami patients and control were shown in table 2. 4.3. biomarkers levels plasma levels of ntprobnp and tni were significantly detected among ami patients; the level of ntprobnp ranged from15 to 30000 with mean of 5756.5 pg/ml while tni recorded from 0.015 to 50 with mean of 13.1 ng/ml(table 3). 4.4. biomarkers results related to ecg and echo positive ecg was recorded with 26 patients of 32 tni positive and with 27 patients of 35 ntprobnp positive. while, less sensitively positive echo were obtained with 20 patients of 32 tni positive, and with 21 patients of 35 ntprobnp positive table 4.measuring of ntprobnp and tni results using area under the curve auc according to ecg as the gold standard method shown in table 5, figure (1). table 1: characteristics of acute myocardial infarction patients. n % sex male 25 62.5 female 15 37.5 age/year <59 20 50 <59 20 50 diabetes diabetic 18 45 non-diabetic 22 55 chest pain yes 40 100 no 0 0 hypertension yes 16 40 no 24 60 smoking yes 10 25 no 30 75 history of cardiac disease yes 1 2.5 no 39 97.5 ecg stemi 32 80 non-stemi 8 20 obesity obese 10 25 non-obese 30 75 doi 10.18502/sjms.v15i3.7746 page 253 sudan journal of medical sciences abuagla m. dafalla et al table 2: performances of ntprobnp and troponiniamong cases and control. biomarker case control sensitivity % specificity % positive predictive value% negative predictive value% ntprobnp positive 35 0 87.5 100 100 85.7 negative 5 30 tni positive 32 0 80 100 100 78.9 negative 8 30 table 3: levels of ntprobnp (pg/ml)and troponin i (ng/ml) among40 cases of ami patients and 30 control subjects no mean sd p.value ntprobnp case 40 5756.5 8378.2 0.00 control 30 57.8 42.3 tni case 40 13.1 18.9 0.00 control 30 0.02 0.000 table 4: relationship between the results of troponin i and ntprobnp with ecg and echo tni /ntprobnp ecg total positive negative ntprobnp positive 27 8 35 negative 5 0 5 tni positive 26 6 32 negative 6 2 8 echo positive negative ntprobnp positive 21 14 35 negative 3 2 5 tni positive 20 12 32 negative 4 4 8 table 5: therea under roc curve for ntprobnp and tni according to ecg as a gold standard method. variable 1 tni variable 2 ntprobnp classification variable ecg sample size 70 positive group 𝑎 32 (45.71%) negative group 𝑏 38 (54.29%) area under the roc curve for tni 0.827 area under the roc curve for ntprobnp 0.817 doi 10.18502/sjms.v15i3.7746 page 254 sudan journal of medical sciences abuagla m. dafalla et al 5. discussion mi is a consequence of the imbalance between heart blood supply and the heart cell needs; this disorder leads to necrosis of the myocardium and may cause death (1). it is diagnosed by at least two of three of the following criteria; firstly, chest pain, secondly changes on the ecg, and thirdly elevation on cardiac biomarkers (9). from this study, chest pain was recorded with all ami patients, male patients more frequently than females with a percentage of 62%.on the other hand, the age group above and below 59 years were equally stated, these findings were in agreement with a study done by ahmed in sudan(19).diabetes mellitus and hypertension as risk factors in the current study were observed in 45 % and 40% from ami cases, this threat could be decreased by routine follow up of patients and establishment of specialized centers for care. from the results, smokers were less than non-smokers; this was in concord with a similar study(20) and in contrast with elkhader et al(21).according to the clinical diagnosis, 80% of ami patients were st-elevation myocardial infarction (stemi), this result was near to the percentage concluded byabdallah in sudan(22).in the current study, each of tni and ntprobnp had significant values in the diagnosis of ami in studied patients, same findings were reported in the uk(23) and usa(24), however, in our study 12.5% (5/40) and 20% (8//40) of suspected cases gave insignificant concentrations for ntprobnp and tni,respectively.ntprobnp values were highly sensitive when compared withtni according to ecg and echo, this result differs with those done bydimiati et al. in indonesia who foundtni was more sensitive(25).the rea under roc curve for ntprobnp was (0.817) and for tni equal (0.827) according to ecg as a gold standard method, this indicates that each of the studied biomarkers had a good performance in the diagnosis of ami. 6. conclusions the ntprobnp had high sensitivity, specificity, positive predictive value and negative predictive value when compared with tni in the diagnosis of ami. funding this research has been fully financed by the german academic exchange service (daad) in-country scholarship program sudan, 2016 (57298697). doi 10.18502/sjms.v15i3.7746 page 255 sudan journal of medical sciences abuagla m. dafalla et al acknowledgments i am grateful to the help and support offered by the staff of wad medani cardiac center for helping me in my practical (lab and archive department) and staff of laboratory of professor bakryyousif. especial thanks to laboratory specialist mohamed snhory.i owe a deep debt of gratitude to dr. mohamed hamzaand laboratory specialist (sidig said and omer eltigani) for helping me to obtain ntprobnp reagents. i am very grateful to the patients and healthy peoples who participated in the study from gezira state. references [1] danish, m. i. (2012).short textbook of medical diagnosis and management. medtech; pakistan. 11𝑡ℎ edition. [2] gary, a. t. and kevin, t. p. (2015).anatomy and physiology (9th ed.). netherlands: elsevier health sciences. [3] ambrose, j. a. and singh, m. (2015). pathophysiology of coronary artery disease leading to acute coronary syndromes. f1000prime reports, vol. 14, no. 7, p. 08. doi: 10.12703/p7-08. [4] yang, z. and zhou, d. (2006). cardiac marker and their point of care testing for diagnosis of acute myocardial infarction clinical biochemistry, vol. 39, no. 8, pp. 771–780. [5] omer, a., mohemed, e., abdulrahman, a., et al. (2016) studying of heart disease prevalence, distribution and co-factors in sudanese population. international journal of research in medical sciences, vol. 4, no. 1, p. 206. doi: http://dx.doi.org/10.18203/ 2320-6012.ijrms20160032. [6] lee, g. and andrew, s. (2012).goldman’s cecil medicine (24th ed.). philadelphia, pa: elsevier saunders. [7] chatzizisis, y. s., saravakos, p., boufidou, a., et al (2010). acute myocardial infarction manifested with headache. open cardiovascular medicine journal, vol. 16, no. 4, pp. 148–150. doi: 10.2174/1874192401004010148. [8] skelly, a. c., hashimoto, r., buckley, d. i., et al. (2016). non-invasive testing for coronary artery disease [internet](comparative effectiveness reviews, no. 171.) . rockville (md): agency for healthcare research and quality (us). retrieved from: https://www.ncbi.nlm.nih.gov/books/nbk361148 doi 10.18502/sjms.v15i3.7746 page 256 http://dx.doi.org/10.18203/2320-6012.ijrms20160032 http://dx.doi.org/10.18203/2320-6012.ijrms20160032 https://www.ncbi.nlm.nih.gov/books/nbk361148 sudan journal of medical sciences abuagla m. dafalla et al [9] christenson, e. and christenson, r. h. (2013). the role of cardiac biomarkers in the diagnosis and management of patients presenting with suspected acute coronary syndrome. annals of laboratory medicine, vol. 33, no. 5, pp. 309–318. doi:10.3343/alm.2013.33.5.309. [10] mythili, s. and malathi, n. (2015). diagnostic markers of acute myocardial infarction. biomedical reports, vol. 3, no. 6, pp. 743–748. doi: 10.3892/br.2015.500. [11] korff, s., katus, h. a., and giannitsis, e. (2006). differential diagnosis of elevated troponins. heart, vol. 92, no. 7, pp. 987–993. doi: 10.1136/hrt.2005.071282. [12] expert group on biomarkers.(2015). biomarkers in cardiology part 2: in coronary heart disease, valve disease and special situations. arquivos brasileiros de cardiologia, vol. 104, no. 5, pp. 337–346. doi: 10.5935/abc.20150061. [13] scott, w. d. and meg, s. (2008). cardiac troponins. journal of veterinary emergency and critical care, vol. 18, no. 3, pp. 235–245. doi: 10.1111/j.1476-4431.2008.00307.x. [14] regan, b., o’kennedy, r., and collins, d. (2018). point-of-care compatibility of ultrasensitive detection techniques for the cardiac biomarker troponin i – challenges and potential value. biosensors, vol. 8, no. 4, p. 114. doi: 10.3390/bios8040114. [15] korff, s., katus, h. a., and giannitsis, e. (2006). differential diagnosis of elevated troponins. heart, vol. 92, no. 7, pp. 987–993. doi: 10.1136/hrt.2005.071282. [16] michael, l. b., edwart, p. f., and larry, e. s. (2013).clinical chemistry principles, techniques, and correlations (7𝑡ℎ ed.).burlington, ma: jones & bartlett learning. [17] wendy, a. and jean, b. (2007).clinical chemistry a laboratory perspective (1sted.). philadelphia, pa: f. a. davis company. [18] ichiki, t., huntley, b. k., and burnett, j. c., jr. (2013). bnp molecular forms and processing by the cardiac serine protease corin. advances in clinical chemistry, vol. 61, pp. 1–31. doi: 10.1016/b978-0-12-407680-8.00001-4. [19] ahmed, y. m. m. (2017). estimation of serum ferritin level among myocardial infarction patients attending wadmadani heart center, gezira state, sudan (2016– 2017) (master dissertation,university of gezira, sudan). [20] ahmed, m. h., awadalla, h., elmadhoun, w. m., et al. (2017) prevalence and risk factors for acute coronary syndrome among sudanese individuals with diabetes: a population-based study. cardiology research, vol. 8, no. 5, p. 184. [21] bahaaeldin, a. e., alsafi, a. a., and mohammed, a. a. (2016). correlation of smoking and myocardial infarction among sudanese male patients above 40 years of age. polish journal of radiology, 81: no.1, p.138-140. doi: 10.12659/pjr.894068. doi 10.18502/sjms.v15i3.7746 page 257 sudan journal of medical sciences abuagla m. dafalla et al [22] abdallah, m.a.a. (2018). red cell distribution width as a prognostic marker for patients with myocardial infarction, wadmadani heart centre, gezira state, sudan (master dissertation, university of gezir, sudan). [23] kristensen, s. l., mogensen, u. m., jhund,p. s.,et al. (2019). n-terminal pro-btype natriuretic peptide levels for risk prediction in patients with heart failure and preserved ejection fraction according to atrial fibrillation status. circulation: heart failure, vol. 12, no. 3, e005766. doi:10.1161/circheartfailure.118.005766. [24] navaid, i., wentworth, b., choudhary, r.,et al. (2012). cardiac biomarkers: new tools for heart failure management. cardiovascular diagnosis and therapy, vol. 2, no. 2, pp. 147–164. doi:10.3978/j.issn.2223-3652.2012.6.03. [25] dimiati, h., wahab, a. s., juffrie, m., et al. (2019) study of ntprobnp and hstroponin i biomarkers for early detection of children’s heart function of proteinenergy malnutrition. pediatric reports, vol. 11, no. 2, p. 7997. doi:10.4081/pr.2019.7997. doi 10.18502/sjms.v15i3.7746 page 258 introduction materials and methods ethical consderion data variable, collection and criteria measurement of cardiac biomarkers data analysis results demographics of ami subjects performance of ntprobnp and tni biomarkers levels biomarkers results related to ecg and echo discussion conclusions funding acknowledgments references sudan journal of medical sciences volume 12, issue no. 1, doi 10.18502/sjms.v12i1.853 production and hosting by knowledge e research article the effect of pt link and waterbath antigenic retrieval procedures on the expression of common receptors in breast cancer cases ahmed abdelbadie1, elsadig ahmed adam1, and manar abdelrahman2 1department of pathology, faculty of medicine, the national ribat university, sudan 2faculty of medical laboratory sciences, umst, sudan abstract background: antigen retrieval (ar) techniques play a major role in determining the quality and functional state of tissue proteins recovered from formalin fixed paraffin embedded blocks (ffpeb). different techniques are used each with its merits and drawbacks. materials and method: ffpeb from cases diagnosed as breast cancer were examined for the expression of estrogenreceptor (er), progesterone receptor (pr) and her2 by immunohistochemical techniques using two different ar methods. results: fifty cases, 49 were from females, the age ranged from 28–85 years were examined. the expression of er using water bath and pt link (pretreatment system) as antigen retrieval methods was equal, both methods showed 20(40%) positive cases and 30(60%) negative cases, whereas, the expression of pr was found positive in 18 cases (36%) and negative in 32 (64%) when water bath was used, in comparison to10 positive (20%) and 40 negative (80%) when pt link was used (p value 0.312).the expression of her2 was as follows; water bath her2 weak positive 20 cases (40%), moderate expression 10 cases (20%), overexpression 2 cases (4%). pt link weak expression 13 cases (26%), moderate expression 15 cases (30%), overexpression 4cases (8%); yet, the total number of negative cases and positive cases was equal for both methods (p-value 0.035). conclusion: antigen retrieval methods were found to affect the expression of common receptors in breast cancer. the magnitude of this effect was found to be significant in pr and her2 receptors, however, the different methods of antigen retrieval did not affect the expression of er. the appropriate and suitable retrieval methods have to be chosen individually for each receptor. keywords: antigen retrieval, er, pr, her2 expression, pt link, waterbath how to cite this article: ahmed abdelbadie, elsadig ahmed adam, and manar abdelrahman, (2017) “the effect of pt link and waterbath antigenic retrieval procedures on the expression of common receptors in breast cancer cases,” sudan journal of medical sciences, vol. 12 (2017), issue no. 1, 1–8. doi 10.18502/sjms.v12i1.853 page 1 corresponding author: ahmed abdelbadie; email: ahmedbadie60@yahoo.co.uk received: 15 december 2016 accepted: 20 february 2017 published: 28 may 2017 production and hosting by knowledge e ahmed abdelbadie et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ahmedbadie60@yahoo.co.uk mailto:ahmedbadie60@yahoo.co.uk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e والوظيفية النوعية تحديد في رئيسيا دورا المستضد إسترجاع تقنيات تلعب الخلفية: البارافين. فى والمطمورة بالفورمالين المثبتة الكتل من المستردة ا-نسجة لبروتينات وتستخدم تقنيات مختلفة لكل منها مزاياها وعيوبها. المواد والطريقة: تم فحص بروتينات ا-نسجة المستردة من الكتل المثبتة بالفورمالين والمطمورة فى البارافين من الحاالت التي تم تشخيصها على أنها سرطان الثدي للكتشف عن مستقبالت هرمون اaستروجين، مستقبالت هرمون البروجسترون ومستقبل عامل مختلفتين طريقتين بإستخدام المناعية التقنيات بواسطة اaنسان فى ٢ للبشرة النمو aسترداد المستضدات. النتائج: خمسون حالة، ٤٩ من اaناث، تراوحت أعمارهم بين ٢٨-٨٥ سنة. كان الكشف عن المعالجة (نظام تى البى ووصلة المتعرج الماء حمام بإستخدام المستضد إسترداد من (٪٦٠) ٣٠ و اaيجابية الحاالت من (٪٤٠) ٢٠ الطريقتين كال وأظهرت متساويا، المسبق) الحاالت السلبية، في حين تم الكشف عن إسترداد للمستضد إيجابيا في ١٨ (٣٦٪) و سالبا في ٣٢ (٦٤٪) عند إستخدام حمام الماء، بالمقارنة مع ١٠ موجب (٢٠٪) و ٤٠ سلبي (٨٠٪) عند إستخدام وصلة البى تى (p ٠٫٣١٢). وكان كشف مستقبل عامل النمو للبشرة ٢ فى اaنسان على النحو التالي؛ فى حمام الماء ضعيفة إيجابية ٢٠ حالة (٤٠٪)، توضيح معتدل ١٠ حاالت (٢٠٪)، توضيح ،(٪٢٦) حالة ١٣ التوضيح ضعيفة تى البى وصلة .(٪٤) الحاالت من ٢ فى زائد توضيح معتدل ١٥ حاالت (٣٠٪)، توضيح زائد فى ٤ حاالت (٨٪)؛ ومع ذلك، كان العدد اaجمالي للحاالت .(٠٫٠٣٥ p قيمة) يجابية متساويًا لكال الطريقتينaالسلبية والحاالت ا مستقبالت عن الكشف على المستضد إسترجاع طرق تأثير على العثور تم ا0ستنتاج: مستقبالت في بوضوح التأثير هذا حجم على العثور تم الثدي. سرطان في مشتركة الطرق فإن ذلك، ومع اaنسان، فى ٢ للبشرة النمو عامل ومستقبل الشائعة العالقات اaستروجين. هرمون مستقبالت عن الكشف على تؤثر ال المستضد aسترجاع المختلفة يجب إختيار طرق اaسترجاع المناسبة والمناسبة بشكل فردي لكل مستقبل. 1. introduction breast cancer is an ideal paradigm to study hormone-dependent tumors. immunohistochemical testing revealed that around 70% of breast cancer cells are positive for estrogen (er) and/or progesterone (pr) receptors. stepping of breast lesions towards cancer is mainly influenced by estrogen. thus, targeting er using serms (selective estrogen-receptor modulators) is an effective therapeutic regimen for all stages of this disease [1]. as the most effective serm, tamoxifen has been used as a major adjuvant treatment for primary breast cancer. but, efficiency wise over 50% of er-positive tumors that initially respond to tamoxifen therapy will eventually develop resistance, resulting in recurrence and stepping forward of the cancer and the subsequent death of patients [1, 2]. doi 10.18502/sjms.v12i1.853 page 2 sudan journal of medical sciences production and hosting by knowledge e recently molecular classifications of breast cancer draw much attention [3–6]. however, guidance of targeted therapy as tamoxifen and trastuzumab on immunohistochemical basis for tumors positive for estrogen / progesterone (er/pr) receptors and her2 (human epidermal growth factor receptor 2 is not far little specific compared to genetic and molecular-based guidance. estrogen receptors are a group of proteins found inside cells. they are receptors that are activated by the hormone estrogen (17𝛽estradiol) [7]. two classes of estrogen receptors exist er, which is a member of the nuclear hormone family of intracellular receptors, and gper, which is a member of the rhodopsin-like family of g protein-coupled receptors. this article refers to the former (er) [8]. while er𝛼 is obviously associated with more differentiated tumors, the involvement of er𝛽 is questionable. different versions of the esr1 gene have been identified (with single-nucleotide polymorphisms) and are associated with different risks of developing breast cancer [9]. progesterone is a product of a single gene located on chromosome 11q22. whereas, progesterone receptor pr (nr3c3) is a protein existed inside cells [10]. progesterone has 2 variants a and b having different molecular weights [11]. binding of hormone to receptor prompted changes that cancel the inhibitory effect due to lack of hormone. these changes are prevented by progesterone antagonists. human epidermal growth factor receptor 2(her2) also known as neu, erbb-2, cd340 (cluster of differentiation 340) or p185 is a protein that in humans is encoded by the erbb2 gene. her2 is a member of the epidermal growth factor receptor (egfr/erbb) family. amplification or over-expression of this gene has been shown to play an important role in the pathogenesis and progression of certain aggressive types of breast cancer and in recent years it has evolved to become an important biomarker and target of therapy for approximately 30% of breast cancer patients. erbb2 gene is overexpressed in nearly 30% of breast cancers and accompanied with increased disease recurrence and a poor prognosis [12]. antigen retrieval is applied to unmask proteins as an initial step prior to immunohistochemical staining of formalin fixed paraffin embedded blocks [13]. in fact, different heating methods are in use for this purpose. this raised a lot of queries regarding how much and how heating methods are applied and their possible effects on staining intensity. antigen retrieval affects the expression of er / pr,her2 receptor so it will finally affect the categorization of the disease and treatment policy. this study aimed at the evaluation of the effect of antigen retrieval methods on the expression of er and pr and her2 receptors in patient suffering from breast cancer. 2. materials and methods a retrospective descriptive cross-sectional study was conducted at histopathology department, university of medical sciences and technology. doi 10.18502/sjms.v12i1.853 page 3 sudan journal of medical sciences production and hosting by knowledge e fifty formalin-fixed, paraffin-embedded blocks (ffpe) were collected from histology laboratory at ribat university hospital, alzuitona hospital, and total lab care center. all blocks were from cases diagnosed as breast cancer. sections of 5 micron thickness were obtained using rotary microtome. from each paraffin embedded block 6 sections were taken, in 3 sections antigen retrieval was done by ptlink antigenic retrieval and other 3 sections antigen retrieval was done by waterpath method. each section has been stained for er and pr and her2/neu . tests for immunohistochemistry were performed using the procedure provided by dako with kits, temperature-controlled waterbath, dako autostainer slide rack (code s3704), incubation container and cover, retrieval solution, tris-buffered saline (code s3001) were used. ptlink device automatically retrieves antigens in a way similar to the manually set waterbath antigen retrieval, which incorporate preheat temperature, antigen retrieval temperature, and time as well as cool down settings. typically, antigen retrieval is performed for 50 minutes at 97∘c. dako ptlink (code pt100/pt101). slides were reviewed by an experienced pathologist. nuclear staining in more than 10% of tumor cells was considered positive for er and pr. her2 neu scoring was done according to asco/cap guidelines (college of american pathologists/american society of clinical oncology)as follows: strong circumferential membranous staining in > 30% of invasive carcinoma cells = 3+; moderate, circumferential membranous staining in ≥ 10% of invasive tumor cells or 3+ in ≤ 30% of cells = 2+; weak and incomplete membranous staining in invasive tumor cells = 1+, no staining = 0. tumors with 0 and 1+ staining were considered negative and cases scored as 2+ equivocal, and 3+ were considered positive, evaluated on 4× and 10× magnifications. 2.1. data analysis data was analyzed by calculating the means and frequencies of receptors expression. chi-square and p value were calculated to determine differences if any in receptors expression according to ar method. data was analyzed by spss version 16. 3. results fifty patients were enrolled in the study, 1male and 49 females, with age range of 28– 85 years. in this study the expression of estrogen-er receptor using water bath and pt link as antigen retrieval methods was equal with 20(40%) positive cases and 30(60%) cases were negative, methods of antigen retrieval did not affect the expression of er. whereas, the expression of pr receptor was found 18(36%). positive and 32 negative cases (64%) when water bath was used, and 10 positive (20%),40 negative(80%)when pt link was used. therefore, there was a difference in doi 10.18502/sjms.v12i1.853 page 4 sudan journal of medical sciences production and hosting by knowledge e type of carcinoma frequency percent invasive ductal carcinoma 44 88.0 lobuler carcinoma 5 10.0 phylloides 1 2.0 total 50 100.0 t 1: the distribution of study group according to the type of cancer. retrieval method er positive er negative pr positive pr negative total waterbath 20 30 18 32 50 pt link 20 30 p value = 0.018 10 40 p value = 0.312 50 total 40 60 28 72 100 t 2: the expression of estrogen receptors (er) and progesterone receptors (pr) using waterbath and pt link as antigen retrieval methods. the expression of pr by using water bath and pt link, this difference was not statistically significant (p value 0.312).the expression of her2 was as follows: water bath her2 weak positive 20 cases (40%), moderate expression 10 cases (20%), overexpression 2 cases (4%). pt link weak expression 13 cases (26%), moderate expression 15 cases (30%), over expression 4cases (8%). the total number of negative cases and positive cases was equal. the difference was statistically significant (p-value 0.035). positivity and negativity of her2 was not affected by the method of antigen retrieval. but, the degree of expression of her 2 was significantly affected by the different methods of antigen retrieval.pt link showed better expression of her2. 4. discussion antigen retrieval has improved the diagnostic accuracy through reducing the false negative results and also making results more reproducible. so expression of receptors and treatment protocols will be affected very much, i.e. the use of anti-hormonal drugs like tamoxifen and herceptin. in this study, the expression of er was found to be equal by using waterbath and pt link and er-positive 40% and er-negative was found to be 60%. these figures were in agreement with (elgaili et al., 2010) [14] who found er negativity 68.3% and the findings are different from study in nigeria that estimated ernegative cases by 72% of the cases which was higher than the figures recorded in sudan. in the present study, the expression of progesterone was found to be higher when waterbath was used as antigen retrieval method compared to pt link, 36% versus20%, doi 10.18502/sjms.v12i1.853 page 5 sudan journal of medical sciences production and hosting by knowledge e retrieval method her-2expression her2positive+ her2positive++ her2positive+++ her-2 negative total p value waterbath 20 10 2 18 50 0.035 pt link 13 15 4 18 50 total 33 25 6 36 100 t 3: the expression of her-2 using water bath and pt link as antigen retrieval methods. so pr negativity would be 64% and 80%. in the study done by elgaili et al. progesterone negative was found to be 69.5% [14].this percentage is in agreement with that scored by using waterbath as compared to negativity of 80% found with the use of pt link. therefore, waterbath improved antigen expression when compared to pt link regarding progesterone receptors. waterbath results were similar to previous studies. that is to say, waterbath is more superior for antigen retrieval when compared to ptlink for progesterone receptors. in our study, the expression of her2 as positive and negative was equal, and negativity her2 was found to be 36%. in the present study the expression of her2 was found 20 cases weak expression,10 cases moderate and 2 cases overexpression by using pt link, and were found 13 cases weak,15 cases moderate and 4 cases overexpression by using pt link, the difference in expression was found to be statistically significant. this finding indicates that pt link use improves the expression of her2 in comparison to waterbath . one study compared the staining intensity of her2 by using waterbath and microwave as methods of antigen retrieval and it was documented that staining intensity was found to be better by using waterbath than microwave. since both pt link and waterbath are heat-induced epitope retrieval methods, other methods should be assessed separately. standardization of fixation as well as antigen retrieval methods for each antigen to attain best result in ihc. 5. conclusion waterbath and ptlink methods showed similar results regarding the expression of er estrogen receptors. there was a difference in expression of pr progesterone receptors by changing method of retrieval. waterbath demonstrated better expression of pr progesterone compared to pt link. positivity and negativity of her2 was not affected by the method of antigen retrieval. but, the intensity of expression of her 2 was significantly affected by methods of antigen retrieval. pt link showed better expression of her2. doi 10.18502/sjms.v12i1.853 page 6 sudan journal of medical sciences production and hosting by knowledge e 6. conflict of interest none of the authors has any conflict of interest to disclose. 7. ethical clearance this work was approved by the ethical committee at university of medical sciences and technology, faculty of medical laboratory sciences. references [1] h. yamashita, y. yando, m. nishio et al., “immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer,” breast cancer (tokyo, japan), vol. 13, no. 1, pp. 74–83, 2006. [2] h. yamashita, “current research topics in endocrine therapy for breast cancer,” international journal of clinical oncology, vol. 13, no. 5, pp. 380–383, 2008. [3] l. a. carey, c. m. perou, c. a. livasy et al., “race, breast cancer subtypes, and survival in the carolina breast cancer study,” the journal of the american medical association, vol. 295, no. 21, pp. 2492–2502, 2006. [4] h. y. chang, d. s. a. nuyten, j. b. sneddon et al., “robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival,” proceedings of the national academy of sciences of the united states of america, vol. 102, no. 10, pp. 3738–3743, 2005. [5] m. dolled-filhart, l. rydén, m. cregger et al., “classification of breast cancer using genetic algorithms and tissue microarrays,” clinical cancer research, vol. 12, no. 21, pp. 6459–6468, 2006. [6] t. sørlie, r. tibshirani, and j. parker, “repeated observation of breast tumor subtypes in independent gene expression data sets,” proceedings of the national academy of sciences of the united states of america, vol. 100, pp. 8418–8423, 2003. [7] k. dahlman-wright, v. cavailles, s. a. fuqua et al., “international union of pharmacology. lxiv. estrogen receptors,” pharmacological reviews, vol. 58, no. 4, pp. 773–781, 2006. [8] e. r. levin, “integration of the extranuclear and nuclear actions of estrogen,” molecular endocrinology, vol. 19, no. 8, pp. 1951–1959, 2005. [9] b. j. deroo and k. s. korach, “estrogen receptors and human disease,” journal of clinical investigation, vol. 116, no. 3, pp. 561–570, 2006. [10] m. misrahi, m. atger, l. d’auriol et al., “complete amino acid sequence of the human progesterone receptor deduced from cloned cdna,” biochemical and biophysical research communications, vol. 143, no. 2, pp. 740–748, 1987. doi 10.18502/sjms.v12i1.853 page 7 sudan journal of medical sciences production and hosting by knowledge e [11] g. kase nathan, leon;. glass, and l. robert, “clinical gynecologic endocrinology and infertility,” in hagerstown, md: lippincott, williams & wilkins, hagerstown, 1999, isbn 0-683-30379-1. [12] m. tan and d. yu, “molecular mechanisms of erbb2-mediated breast cancer chemoresistance,” advances in experimental medicine and biology, vol. 608, pp. 119–129, 2007. [13] k. emoto, s. yamashita, and y. okada, “mechanisms of heat-induced antigen retrieval: does ph or ionic strength of the solution play a role for refolding antigens?” journal of histochemistry and cytochemistry, vol. 53, no. 11, pp. 1311– 1321, 2005. [14] e. m. elgaili, d. o. abuidris, m. rahman, a. m. michalek, and s. i. mohammed, “breast cancer burden in central sudan,” international journal of women’s health, vol. 2, no. 1, pp. 77–82, 2010. doi 10.18502/sjms.v12i1.853 page 8 introduction materials and methods data analysis results discussion conclusion conflict of interest ethical clearance references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8162 production and hosting by knowledge e research article il1 𝛽 exon5 3954 c/t polymorphism: a potential genetic risk factor of heart diseases’ predisposition in sudanese patients manal a. fadl and sahar s. noor algalil dept of biochemistry and molecular biology-faculty of science and technology-alneelain university abstract background: il-1β was known to cause an inflammation in heart tissue leading to progressive loss of contractile tissues. the aim of this study was to evaluate “for the first time” the relationship between il-1β polymorphism (rs1143634) and the risk of heart diseases (hds) in sudanese patients. methods: fifty patients with hd and 65 healthy controls were enrolled in this crosssectional study. the il-1β (rs1143634) polymorphism was detected by pcr-rflp using taqi restriction enzyme. results: about 82% of the hd cases were aged >40 years. no gender difference was reported between the two groups (p = 0.28). 24% of the cases had a previous history of heart attack. family history of hd was associated with a six-fold increased risk of hd. the analysis provides evidence that the mutant genotype (ct + tt) of the il1β polymorphism is significantly associated with hd, with up to four-fold increased risk of the disease (p = 0.015, or = 3.8). the mutant allele t was significantly higher in hd patients as compared to the controls (p = 0.023). the frequency of the ct genotype among patient who have family history, previous attack of hd, hypertension, and diabetes was 79%, 33%, 81%, and 90% respectively. conclusion: the il1β (rs1143634) polymorphism was associated with the increased risk of hd in our samples. the carriage of the mutant allele among those who have family history of hd, previous attack, hypertension, and diabetes might be a predictive factor for the onset of clinical manifestation of hd in sudanese patients. keywords: heart diseases’ risk factors, gene polymorphisms, interleukin (il)-1 β 1. introduction heart diseases (hds) are the number one cause of death worldwide. the magnitude of hds continues to accelerate globally and it is expected to rise more rapidly in developing countries [1] not only because many people in these countries have been exposed to unhealthy life habits, high prevalence of hypertension, dyslipidemia and diabetes, but also because this situation is coupled with the lack of prevention and control regimes [1]. hds are multifactorial, where both environmental and genetic factors contribute to how to cite this article: manal a. fadl and sahar s. noor algalil (2020) “il1 𝛽 exon5 3954 c/t polymorphism: a potential genetic risk factor of heart diseases’ predisposition in sudanese patients,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 399–407. doi 10.18502/sjms.v15i4.8162 page 399 corresponding author: manal a. fadl; dept of biochemistry and molecular biology-faculty of science and technology-alneelain university email: manalfadl1@hotmail.com received 10 october 2020 accepted 8 december 2020 published 31 december 2020 production and hosting by knowledge e manal a. fadl and sahar s. noor algalil. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:manalfadl1@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences manal a. fadl and sahar s. noor algalil the disease. to date, many genes are thought to contribute to the risk of hd, however, the results have been inconclusive [2–10]. the role of the cytokines in the alterations of vascular endothelial cells functions has been documented [11]. such alterations occur as a result of the exposure of the vascular endothelial cells to cytokines which involve the downregulation of the endothelial nitric oxide synthase, production of new proteins, and induction of endothelial cell apoptosis [11]. based on this, a series of studies have been conducted to investigate the contribution of different cytokines in the development and progress in cardiovascular diseases; however, the results have been contradictory [12–16]. l-1 is one of the inflammatory cytokines with pleotropic effects consisting of two distinct ligands – il-1α and il-1β. the release of il-1β results in widespread inflammation, leading to further death of cardiomyocytes, progressive loss of viable contractile tissue, and development of cardiomyopathy and heart failure [17]. the contribution of il-1 gene to developing the risk of hds have been studied among different ethnic groups with contradictory outcomes [18–23]. il1β polymorphism is not only being presented as a risk factor for susceptibility to hd [24, 25], but it also associated with the severity and worse prognosis of the disease [26, 27]. in sudan, while several studies have focused on the pathophysiology and progression of chronic heart failure [28–30], relatively little attention has been paid to unravel the genetic association with hd. based on the above, this study aimed to investigate a possible association of the 3954c/t il-1β polymorphism (rs1143634) with hd susceptibility in our patients. 2. materials and methods this case–control retrospective study included 50 heart patients and 65 controls. the samples were collected from the alshorta hospitals and modern medical center in khartoum state. the demographic data of all subjects were obtained using a welldesigned questionnaire. dna quantification and purity were assayed using a uv spectrophotometer at 260 and 280 nm. in this study, we conducted a polymerase chain reaction–restriction fragment length polymorphism (pcr-rflp) analysis of il-1β exon 5. as describe in table 1, the polymorphism (rs1143634) was done using the intron biotechnology, inc. pre-mix, followed by incubation in taq1 restriction enzyme. the homozygous wild type genotype (cc) of the 3954c/t polymorphism (rs1143634) in exon 5 of il-1β was indicated by the presence of 249 bp band. the homozygous mutant genotype was cleaved giving a band of 136 and 113 bp. the heterozygous genotype was indicated by the presence of three fragments, 249 bp, 136 bp, and 113 bp. doi 10.18502/sjms.v15i4.8162 page 400 sudan journal of medical sciences manal a. fadl and sahar s. noor algalil table 1: the rflp–pcr method used. primer sequence forward primer 5’gttgtcatcagactttgacc 3’ reverse primer 5’ttcagttcatatggaccaga3‘ pcr mix contains (i) intron biotechnology, inc. pre-mix (ii) 1 μl of 10 pmol/μl of each primer (iii) 3–5 μl of 50 ng/μl of template dna (iv) volume completed to 12.5 μl pcr program (i) 95°c for 5 min for initial denaturing (ii) 30 cycles of denaturing at 95°c for 30 sec, annealing at 55°c for 1 min, and extension at 72°c for 30 sec (iii) final extension at 72°c for 10 min rflp: restriction mix containing (i) 2 μl of the pcr product (ii) 0.5 u of taq1 restriction enzyme (new england biolabs) (iii) 1 μl tango buffer (iv) the mix was completed to 10 μl (v) the restriction mixture was incubated for 3 hr 2.1. statistical analysis the spss, version 21, was used to count the genotype, chi square, p-value, odds ratio (or). p < 0.05 was considered as statistically significant. in addition, ors were used to assess the strength of the association of the tested variables with the risk of hds in sudanese patients. 3. result no significant gender difference was observed between the cases and the controls (p = 0.28). about 82% of the hd patients were aged >40 years with a significant difference when compared with the controls (p = 0.001). atherosclerosis was observed in 42% of the hd cases. in addition. low frequency of other types of hds including the dilated cardiomyopathy (dcm) and hypertrophic cardiomyopathy (hcm) was observed (4% and 2%, respectively). previous attack of hd had been encountered in 24% of the patients (table 2). although not all patients and controls were able to answer with certainty whether they have family history of hd or not, among those who answered, a six-fold increased risk of hds were reported. also, of the total hd patients, 42% and 38% had hypertension and diabetes mellitus, respectively, of which 48% and 21%, respectively, developed hd within less than five years of disease onset (table 2). the genotype analysis of the il1β c > t (rs1143634) polymorphism (figure 1) considering the mutant genotype versus the wild genotype (ct + tt vs cc) showed a significantly higher frequency in hd patients compared to the controls and was associated with about four-fold increased risk of hd (p = 0.015, or = 3.8). carriage of the mutant il-1 β (+3954) allele t was higher (62%) in hd patients as compared to the controls, with a significantly high difference between the two groups (p = 0.023) (table 3). doi 10.18502/sjms.v15i4.8162 page 401 sudan journal of medical sciences manal a. fadl and sahar s. noor algalil the mutant tt and ct genotypes were reported in atherosclerotic patients with frequencies of 38% and 48%, respectively (table 4). moreover, 33% and 42% frequencies of the ct and tt genotypes were observed in hd patients who encountered previous attack of the disease. considering the cofounding factors, the family history of hd, hypertension, and diabetes mellitus, the mutant heterozygote ct genotype was observed with frequencies of 79%, 81%, and 90% in hd, respectively (table 4), and the frequency of the mutant t allele ranged 40–58%, as shown in table 4. table 2: the demographic data of the hd cases and healthy controls. case n = 50 control n = 65 n p-value sex male 27 (57.4%) 32 (49.2%) p = 0.28 female 20 (42.6%) 33 (50.8%) age <40 years 9 (18%) 30 (46.2%) p = 0.001 40–60 years 41 (82%) 35 (53.8%) type of hds atherosclerosis 21 (42%) 0% dcm 4 (8%) hcm 2 (4%) other 23 (46%) previous attack yes 12 (24%) no 38 (76%) family history of hds yes 19 (40.4%) 3 (9.7%) p = 0.003 no 28 (59.6%) 28 (90.3) or = 6.3 missing data 3 34 hypertension yes 21 (42%) 0% no 29 (58%) diabetes mellitus yes 19 (38%) no 31 (62%) hypertension for <5 years 10/21 (47.6%) diabetes mellitus for <5 years 4/19 (21.1%) 4. discussion hds are the number one leading causes of death and a serious public health problem worldwide [31]. hds are multi-factorial and polygenic where not more than one gene contributes to the disease outcomes. to the best of our knowledge, the current research is the first genetic study aimed to investigate the association of gene polymorphism with the risk of hds in sudanese patients. doi 10.18502/sjms.v15i4.8162 page 402 sudan journal of medical sciences manal a. fadl and sahar s. noor algalil table 3: comparison of the genotypes and allele frequency of il1β c > t (rs1143634) polymorphism between hd cases and controls. genotypes cases (hds) n=50 controls n=65 p value odd ratio cc 7 (14.0%) 25 (38.5%) p=0.015, or=3.8 tc 24 (48.0%) 22 (33.8%) tt 19 (38%) 18 (27.7%) allele frequency c t 0.38 0.62 0.55 0.45 p=0.023 table 4: frequencies of genotypes and the mutant allele of il1β c > t (rs1143634) polymorphism and the confounding factors in hd patients. cc ct tt mutant t atherosclerosis (n = 21) 3 (14.3%) 10 (47.6%) 8 (38.1%) 61.9% previous attack (n = 12) 3 (25%) 4 (33.3%) 5 (41.7%) 58.3% family history of hd (n = 19) 4 (21.1%) 15 (78.9%) 0% 39.5% hypertension (n = 21) 4 (19.0%) 17 (81%) 0% 40.5% diabetes mellitus (n = 19) 2 (10.5%) 17 (89.5%) 0% 44.7% figure 1: lanes 1–4 and 7–9 are uncleaved wild-type homozygous cc (249 bp), lanes 5, 6, and 10–12 are heterozygous ct mutant (249, 136, 113 bp), lane 13 is negative control, and lane 14 represents the 25 bp dna ladder. the statistical genotype analysis provided evidence for the association of the il1β c > t (rs1143634) polymorphism with hds’ susceptibility (p = 0.015) with a four-fold increased risk of hds. although, this result is in line with several previous studies [25, 26, 32], it disagree with some [33–35], which can be explained by the differences in the genetic makeup of the varied ethnic groups enrolled in these studies. the significantly higher frequency of the mutant t allele among cases (p = 0.023), the 42% frequencies of tt genotypes in hd patients who encountered previous attack of the disease, and the ≥40% frequency of the mutant t allele in hd patients who had a family history of hd, doi 10.18502/sjms.v15i4.8162 page 403 sudan journal of medical sciences manal a. fadl and sahar s. noor algalil hypertension, and diabetes mellitus, supports the important role of polymorphism in hd predisposition in these patients. the analysis of the other demographic data showed that the previous attack of hd had been encountered in 24% of the patients and 82% of the hd patients aged 40–60 years with a significant difference when compared with the controls (p = 0.001). this reflects the adverse effect of hds on the quality of life of a large scale of the patients at the reproductive age. although not all patients and controls are able to answer with certainty whether they had a family history or not, a six-fold increased risk of hds was reported among patients with a family history of hd, indicating a lack of awareness about the disease and off course about the disease risks among the general population. hypertension and diabetes mellitus were considered as risks for hd [36, 37]. this study revealed that 42% and 38% of the hd patients had hypertension and diabetes mellitus, respectively, of which 48% and 21%, respectively, develop hd within less than five years of the disease onset. this study also showed that the mutant heterozygote ct genotype was reported with high frequencies among hypertensive and diabetics – 81% and 90%, respectively. all these not only suggest an important role of the il1β c > t (rs1143634) polymorphism with hd susceptibility, but also indicate a possible role in hypertension and diabetes outcomes. 5. conclusion the results of this study demonstrate that il1β c > t (rs1143634) polymorphism was associated with an increased risk of hd in our samples. the carriage of the mutant allele and/or the heterozygote ct genotype among those who had a family history of hd, previous attack, hypertension, and diabetes might be a predictive factor for the onset of clinical manifestation of hd in sudanese patients. recommendation further genetic studies targeted more polymorphisms in il1 and in other candidate genes are needed. such studies enable the identification of people at risk of developing the disease and also enables a provision of targeted therapy. in addition, a cost-effective public awareness and early detection programs are desperately needed to decrease the burden of the hds in the general population. acknowledgements the authors would like to thank the hd patients and the control individuals who willingly participated in this study. also, the help of the physician at the hospital is greatly appreciated. doi 10.18502/sjms.v15i4.8162 page 404 sudan journal of medical sciences manal a. fadl and sahar s. noor algalil ethical approval this study has been approved by the ethical committee at the alneelain university, faculty of medical laboratory science. a verbal consent was obtained from all participants after explaining the purpose of the study. competing interest the authors declare that there is no conflict of interest. availability of data and material data will be available from the authors upon reasonable request. 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(2005). polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro. arteriosclerosis and thrombosis and vascular biology, vol. 25, issue1, pp. 222–227. [33] vohnout, b., di castelnuovo, a., trotta, r., et al. (2003). interleukin-1 gene cluster polymorphisms and risk of coronary artery disease. haematologica, vol. 88, no.1, pp. 54–60. [34] liang, z., cai, j., liu, g., et al. (2012). associations between interleukin-1 gene polymorphisms and coronary heart disease risk: a meta-analysis. plos one, vol. 7, no. 9, p. e45641. [35] wang, s., dai, y. x., chen, l. l., et al. (2015). effect of il-1β, il-8, and il-10 polymorphisms on the development of myocardial infarction. genetic molecular research, vol. 14, no. 4, pp. 12016–12021. doi 10.18502/sjms.v15i4.8162 page 406 https://www.who.int/cardiovascular_diseases/publications/atlas_cvd/en/ sudan journal of medical sciences manal a. fadl and sahar s. noor algalil [36] world health organization. (2009). global health risks: mortality and burden of disease attributable to selected major risks. geneva: who. [37] allen, l., cobiac, l., and townsend, n. (2017). quantifying the global distribution of premature mortality from non-communicable diseases. journal of public health, vol. 39, no. 4, pp. 698–703. doi 10.18502/sjms.v15i4.8162 page 407 introduction materials and methods statistical analysis result discussion conclusion recommendation acknowledgements ethical approval competing interest availability of data and material funding references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8171 production and hosting by knowledge e research article treatment of acute bronchiolitis in a resource-limited setting in port sudan city: a simple effective regimen suhair abdelrahim osman hassan associate professor, consultant paediatrician and neonatologist, port sudan paediatric teaching hospital, red sea university, sudan abstract background: bronchiolitis is an acute lower respiratory viral infection, caused by the respiratory syncytial virus (rsv) in 60–85% of cases and other respiratory viruses in remaining ones. it is the leading cause of hospitalization for infants and toddlers during the winter and early spring months. at the moment, there is no consensus on its treatment worldwide. the prevalence is increasing in port sudan eastern sudan, while we have no admission policy or a unified management protocol. therefore, the aim of this study is: (1) to formulate an admission policy and a new simple management protocol; (2) to determine the factor(s) that increased the prevalence in port sudan as a secondary objective; and (3) to compare the outcome in the study (119 infants) and historical (135 infants) groups concerning the hospitalization length and death rate as a primary objectives. method: this is a hospital-based, controlled clinical trial (cct) study, demographic data were collected by a questionnaire, and data were analyzed manually. severity criteria for acute bronchiolitis are defined. a management guideline was defined and applied to bronchiolitis cases (119 case) with intention to treat, from october to april each year (2013–2015). all infants aged between 1 and 23 months with only acute bronchiolitis were included, while cases with bronchiolitis and associated dysmorphic features, heart disease, tracheo-oesophageal fistula, other respiratory diseases, other morbidities, infants below one month or above two years were excluded from this study. the outcome was compared to a group of matched infants with bronchiolitis (135 cases) who received antibiotics, b2 agonist, and steroids, between october and april of years 2011–2012. results: while several new lifestyle factors increased the prevalence, the new guidelines decreased the admission rate (9.6 vs 5.7 mo), is simple and effective, less expensive, and the duration of hospitalization also reduced (p = 0.04). keywords: acute bronchiolitis, resource-limited settings, advanced respiratory intervention, simple effective intervention,s-7pro3no regimen how to cite this article: suhair abdelrahim osman hassan (2020) “treatment of acute bronchiolitis in a resource-limited setting in port sudan city: a simple effective regimen,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 447–454. doi 10.18502/sjms.v15i4.8171 page 447 corresponding author: suhair abdelrahim osman hassan; email: othman_suhair@outlook.com received 12 november 2020 accepted 25 december 2020 published 31 december 2020 production and hosting by knowledge e suhair abdelrahim osman hassan. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:othman_suhair@outlook.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences suhair abdelrahim osman hassan 1. introduction bronchiolitis is the leading cause of hospital visits and admission among infants and toddlers during the winter and early spring months [1], causing small airways obstruction and air trapping [2–4], especially among urban population living in flats or apartments, due to limited space, closer contact, and decreased house ventilation rather than those living in large houses with compounds or villas. some cultural factors also play a role in the prevalence and severity of the disease, such as avoiding bathing infants in winter months in order to prevent them from cold or the lack of knowledge on the importance of hand washing. many viruses like metapneumovirus, adenovirus, influenza and para influenza, rhinovirus and human bocavirus are accused, but the most common one is the respiratory syncytial virus (rsv) [1, 2]. although the peak age for bronchiolitis is three–six months, it mostly occurs in infants less than four months old, who may need advanced respiratory support with cpap and mechanical ventilation [2–6], which is not always attainable in developing countries and form an obstacle to manage such cases. severity is variable – from a mild disease that needs simple intervention and follow-up (happy wheezers) to a severe one that necessitates intensive care. fortunately, in sudan, severe cases are less common and most cases are mild to moderate. this is attributed to the wide, well-ventilated houses, and the abundant sun. there is no specific treatment. antibiotics, bronchodilators, and corticosteroids are controversial [2, 4]. though there is no consensus between different institutes and even between consultants in the same hospital, concentrated saline (≥3%) nebulization gained the consensus [5–12]. most units use o2, short β2agonists (salbutamol), antibiotics, and hydrocortisone, resulting in prolonged hospitalization, morbidity, staff work burden, and parents’ dissatisfaction. moreover, in a resource-constrained settings where intensive care facilities are limited, ways to save lives of infants with severe bronchiolitis should be obtained and implemented. so, the aim of this study is to (1) formulate an admission policy depending on the disease severity; (2) create a simple management protocol as there is no known management protocol for bronchiolitis in sudan; (3) determine the factor(s) that increased the prevalence in port sudan as a secondary objective; and (4) compare the outcome in the study (119 infants) and historical (135 infants) groups concerning the hospitalization length and death rate as a primary objectives. 2. methods this is an observational, longitudinal study comparing the outcome in the cases of moderate and severe bronchiolitis, in patients aged 1–23 months, admitted to the sea ports corporation hospital (spch) in port sudan, sudan, during the winter months (october–april) of the years 2013–2015 (a total of 119 infant – 9 severe and 110 moderate cases). hospital records of all admitted bronchiolitis cases in the years 2011–2012 were revised, 137 cases were found, 2 were excluded due to associated bacterial pneumonia in one and dysmorphic features in the other. the remaining 135 infants (7 severe, 128 moderate) in the same age range were compared to the study group. data were collected and spread on an excel sheet and analyzed manually. doi 10.18502/sjms.v15i4.8171 page 448 sudan journal of medical sciences suhair abdelrahim osman hassan to unify the severity and admission criteria and classification of cases, the following definitions are made (see table 1): 1. severe case is defined by the author as an infant who is sick with spasmodic cough, tachypnoea (rr 60 bpm or more), severe retractions of the sub-costal area and tracheal tug, nasal flaring, lethargic or irritable, unable to feed and has typetwo respiratory failure on blood gases or clinical cyanosis while breathing room air or hypoxic (spo2 ≤ 90 in room air), with inspiratory and expiratory rhonchi on lung auscultation. 2. moderate case is defined by the author as an infant who is unwell, has a spasmodic cough, tachypnoea (rr 50 –< 60 bpm), with retractions, decreased feeding and type-1 respiratory failure on blood gases or hypoxia (spo2 90–94% while breathing room air), with inspiratory and expiratory rhonchi on lung auscultation. 3. mild case is defined by the author as an infant who is well with spasmodic cough but no tachypnoea ( rr ≤ 50 bpm), has mild or no retractions, pink (spo2 ≥ 96 %) while breathing room air and feeding well with rhonchi on lung auscultation. table 1: definition of the severity phenotype. criterion severe moderate mild general condition lethargic/irritable unwell well rr (bpm) ≥60 50 –< 60 < 50 retractions severe present mild/no spo2% in room air ≤90 90–94 ≥ 96 cyanosis ++ +/– – blood gases type 11 rf type 1 rf normal ability to feed unable decreased normal a new simple, supportive regimen is defined and implemented by the author, and applied to all admitted cases (total = 119 case) with intension to treat. reg-1 (for severe cases) composed of: 1. provide vital signs assessment every 2 hr or as needed; 2. provide nebulized 3% saline or n/s through a high flow o2 ≥ 8 l/min, continuously or every 1 hr till stabilization; 3. provide l-epinephrine nebulizer 2.5 ml diluted in 5 ml n/s, every 2–4 hr; 4. provide oxygen as needed to maintain spo2 ≥ 96%; 5. provide i.v. fluids, 2/3rd of the maintenance, and keep npo; 6. provide ngt mucolytic syrup 1.5–2.5 ml every 8 hr, depending on age; 7. provide nasal care (congestion/obstruction relievers like sea water nasal spray ± nasal drops containing ephedrine, plus nasal suctioning when needed); doi 10.18502/sjms.v15i4.8171 page 449 sudan journal of medical sciences suhair abdelrahim osman hassan 8. no antibiotics; 9. no steroids; and 10. no β2 agonist. reg-2 (for moderate cases) composed of: 1. provide vital signs assessment every 2 hr; 2. provide 10 ml nebulized 3% saline or n/s through a nebulizer, every 2–4 hr; 3. provide l-epinephrine nebulizer 2.5 ml diluted in 5 ml n/s, every 4–6 hr if needed; 4. provide oxygen as needed to maintain spo2 ≥ 96%; 5. provide ngt feeds or i.v. fluids if needed or allow direct sucking if possible; 6. provide oral mucolytic syrup 1.5–2.5 ml every 8 hr, depending on age; 7. provide nasal care (congestion/obstruction relievers [sea water sprays] ± nasal drops containing ephedrine, plus nasal suctioning when needed); 8. no antibiotics; 9. no steroids; and 10. no β2 agonist. control group received salbutamol nebulizer, o2, antibiotics, steroids, and fluids or ngt feeds plus saline nasal drops. the first group (study group) received reg-1 regimen (for severe cases), and reg-2 regimen (for moderate cases). 2.1. study group all patients (1–23 months old) to were admitted to the pediatric wards of the sea ports corporation hospital (spch) in port sudan, sudan with bronchiolitis in the winter months (october–april) of the years 2013–2015 and received the new regimen without antibiotics, steroids, or salbutamol nebulizer. the exclusion criteria of the study were any congenital abnormalities including heart, syndromic infants, and other associated medical problems or evidence of respiratory bacterial infection. mild bronchiolitis cases were followed at the outpatient clinic. severe cases were admitted directly to icu and received continuous, either 3% saline or n/s (if 3% is not available) nebulization, that is, we put 20 cc ns or 3% saline in the nebulizer cub and attach it to a humidifier (bubbler) that attached to an oxygen cylinder, set at 8l o2 or more/min, and the amount of saline was replaced immediately whenever finished. adrenaline (l-epinephrine) 2.5 cc (two and half ampoules of 1 mg/1 ml ) diluted in 5 ml n/s was given as nebulizer every 2 hr, through a face mask, with continuous monitoring of vital signs. all infants were kept nothing per mouth (npo), given two-thirds of their maintenance fluid, plus nasal care with sea water spray (hypertonic saline) as doi 10.18502/sjms.v15i4.8171 page 450 sudan journal of medical sciences suhair abdelrahim osman hassan needed, ephedrine containing nasal drops for children every 8 hr, plus nasal suctioning as needed (reg-1. infants from this group who improved to moderate state were shifted to the pediatric ward to continue their treatment of reg-2). moderate cases were admitted to the pediatric ward and received intermittent n/s or 3% saline (every 1–2 hr) nebulization, plus diluted adrenaline nebulization same dose as above but at a 3–4 hr interval, plus i.v. fluid or ngt feeds, plus same nasal care and monitoring. those who improved and reclassified as mild were discharged home with follow-up. 2.2. historical control group this group comprised of 135 patients (7 severe, 128 moderate cases), all of them received the same treatment regimen of: antibiotic ceftriaxone plus β2 agonist nebulization every 4–6 hr plus injectable steroid (hydrocortisone) and other supportive care (i.v. fluids or ngt feeds, o2/nasal cannula, and ns nasal drops ± nasal suctioning). 3. results with the application of the new regimen, the admission rate decreased significantly (39.7/season vs 67.5/season, p < 0.5). in the study group of 119 infants with bronchiolitis, 9 cases (7.6%) were severe, 110 (92.4%) were moderate and no deaths were encountered (table 2) . table 2: severity phenotype and outcome in the study group. type discharged died total severe 09 (100%) 0 9 moderate 110 (100%) 0 110 total 119 0 119 table 3: severity phenotype and outcome in the control group. type discharged (%) died (%) total severe 03 (42.9) 0 4 (57.1) 7 moderate 125 (97.7) 01 (0.8) 128 total 128 (94.8) 05 (3.7) 135 in the historical control group of 135 infants, 7 were severe and 128 moderate. the death rate was 3.7% (table 3) with statistically significant difference from the study group (p < .04) the mean hospitalization time in the study group was 6.4 days in severe cases and 4.7 days in the moderate group, while it was 11.1 days in severe cases and 8 days in moderate cases in the control group, which is again, statistically significant (p < 0.5 ) (see table 4). table 5 summarizes the major differences between the two groups. doi 10.18502/sjms.v15i4.8171 page 451 sudan journal of medical sciences suhair abdelrahim osman hassan table 4: the mean hospital stay. mhs∗ (days) study (1𝑠𝑡 ) group control (2𝑛𝑑) group p-value severe cases 6.4 11.1 <0.5 moderate cases 4.7 8 <0.5 *mean hospital stay table 5: comparison between the outcomes in the two groups. observation study group control group total no. of cases 119 135 severe cases 09 (7.6%) 07 (5.2%) moderate cases 110 (92.4%) 128 (94.8%) discharged (100%) 119 128 (94.8%) deaths 0 (0%) 5 (3.7% ) many factors are found to contribute to the increasing prevalence of bronchiolitis in sudan (table 6 ). interestingly, 100% of the carers believed that bath in the winter will subject/increase the flu illness, while more than 98% were not aware of the importance of hand washing. about 71% of the cases were residing in flats or unventilated houses, while 90% were unaware of the importance of opening widows to allow sun and air exchange. in 88% of the cases, the families were large, and 73% of the mothers were either illiterate or had received low-grade education, while in 53% there was a smoking person in the house (see table 6) table 6: contributory factors to bronchiolitis contributory factor % avoiding bathing infants during the winter months 100% unawareness of the importance of hand washing 98.55 contact with a household common cold/flu case 97% unaware of the importance of allowing sun rays and air exchange (opening the widows) in the house 90% large families and overcrowding 88% illiterate/low-grade educated mothers/parents 73% residence in flats/apartment or a small house 71% a smoking person inside the house 53% the application of the stated definitions for the disease severity decreased the admission rate (39.7/season vs 67.5/season, p < 0.5), thereby decreasing the burden on the staff and doctors. the protocol was found to be simple, satisfying, easily kept by the resident doctors as a treatment package for bronchiolitis, and easily carried out by the nursing staff. the treatment expenses are found to be much less when antibiotics, β2 agonist, and steroids are omitted. doi 10.18502/sjms.v15i4.8171 page 452 sudan journal of medical sciences suhair abdelrahim osman hassan 4. discussion of note, there is no similar study on contributory factors to acute bronchiolitis, the prevalence of acute bronchiolitis is increasing in port sudan city than what we used to see previously, primarily due to the changing lifestyle and living in flats with decreased ventilation, and many other contributory factors, the most prominent being the avoidance of bathing infants during the winter months (due to the widely spread believe in the arabic world that bathing increases respiratory diseases, in addition to the unawareness of the mothers and carers of the importance of hand washing). residing in flats which lack good ventilation and sun is an important factor that encourages viruses to live and persist in the place. the previous sudanese housing models of large houses with compounds and good ventilation allowed sun exposure and were therefore unsuitable for viruses to live or persist. this style has now changed to apartments and flats. other factors like poor self-hygiene due to illiteracy, the presence of a smoking person in the household, and over-extending families living in the same place or the crowding of the sudanese social activity play major roles in increasing acute bronchiolitis prevalence in port sudan city. though the incidence is large in the underdeveloped countries despite the incomplete data according to who [13], fortunately, the prevalence of severe cases in sudan is much less compared to other countries like egypt and ksa (unpublished observational study). the new protocol showed simplicity and acceptance and effectiveness. no encountered complications nor death, and expenses including length of hospital stay were significantly less, that is because bronchiolitis is a viral disease and the use of antibiotics and steroids will decrease the immunity (killing the normal commensals and suppressing the immune system) subjecting the recipient to more spread of the virus and hence more prolonged and severe disease. the use of β2 agonist is controversial, as there is no element of bronchospasm in the pathogenesis of bronchiolitis, but it may help thinning the mucus to ease its excretion. using the stated clinical classifying criteria allows diagnosis acute bronchiolitis on clinical basis only, suits poor-resourced places, and is in agreement of discouraging unnecessary investigation and unneeded treatment [14]. 5. conclusion acute bronchiolitis prevalence is increasing in our city, the reg1 and 2 regimens should be adopted as a hospital policy in treating bronchiolitis as it proved its efficacy, safety, and cheapness. acknowledgements the author is greatly indebted to all doctors and nursing staff in the pediatric ward of our hospital who helped with the current study, as well as to all parents and carers who gave their trust and acknowledged the way of treatment. doi 10.18502/sjms.v15i4.8171 page 453 sudan journal of medical sciences suhair abdelrahim osman hassan ethical considerations this study was approved by the spch ethical committee on september 8, 2013. references [1] medline plus. (2020). medline plus medical encyclopedia: bronchiolitis. retrieved from http://www.nlm. nih.gov/medlineplus/ency/000975.htm [2] nsw. (2018). management of acute bronchiolitis. retrieved from http://www.eih.health.nsw.gov.au/ __data/assets/pdf_file/0010/458884/clinical-practice-guideline-acute-management-of-bronchiolitis. pdf [3] piedra, p. a. and stark, a. r. (2013). bronchiolitis (and rsv) in infants and children (beyond the basics) in uptodate. [4] the royal children’s hospital melbourne. clinical guidelines: bronchiolitis. retrieved from http://www. rch.org.au?rchcpg/hospital_clinical_guidelines [5] fujiogi, m., goto, t., yasunaga, h., et al. (2013). trends in bronchiolitis hospitalizations in the united states, 2000–2009. pediatrics, vol. 132, no. 1, pp. 28–36. [6] hall, c. b., weinberg, g. a., blumkin, a. k., et al. (2013). respiratory syncytial virus–associated hospitalizations among children less than 24 months of age. pediatrics, vol. 132, no. 2, pp. e341–e348. [7] basco, w. t., jr. (august 23, 2013). infants with bronchiolitis: what treatment is best? medscape pediatrics. [8] shay, d. k., holman, r. c., newman, r. d., et al. (1999). bronchiolitis-associated hospitalizations among us children, 1980–1996. jama, vol. 282, pp. 1440–1446. [9] nagakumar, p. and doull, i. (2012). current therapy for bronchiolitis. archives of disease in childhood, vol. 97, no. 9, pp. 827–830. [10] midulla, f. (2010). respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. archives of disease in childhood, vol. 95, pp. 35–41. [11] brandenburg, a. h. (1997). local variability in respiratory syncytial virus disease severity. archives of disease in childhood, vol. 77, no. 5, pp. 410–414. [12] kneyber, m. c., brandenburg, a. h., rothbarth, p. h., et al. (1996). relationship between clinical severity of respiratory syncytial virus infection and subtype. archives of disease in childhood, vol. 75, no. 2, pp. 137–140. [13] rudan, i., tomaskovic, l., boschi-pinto, c., et al. (2004). global estimate of the incidence of clinical pneumonia among children under five years of age. bulletin of the world health organization, vol. 82, no. 12, pp. 895–903. [14] schroeder, a. r. and mansbach, j. m. (2014). recent evidence of management of bronchiolitis. current opinion in pediatrics, vol. 26, no. 3, pp. 328–333. doi 10.18502/sjms.v15i4.8171 page 454 http://www.nlm.nih.gov/medlineplus/ency/000975.htm http://www.nlm.nih.gov/medlineplus/ency/000975.htm http://www.eih.health.nsw.gov.au/__data/assets/pdf_file/0010/458884/clinical-practice-guideline-acute-management-of-bronchiolitis.pdf http://www.eih.health.nsw.gov.au/__data/assets/pdf_file/0010/458884/clinical-practice-guideline-acute-management-of-bronchiolitis.pdf http://www.eih.health.nsw.gov.au/__data/assets/pdf_file/0010/458884/clinical-practice-guideline-acute-management-of-bronchiolitis.pdf http://www.rch.org.au?rchcpg/hospital_clinical_guidelines http://www.rch.org.au?rchcpg/hospital_clinical_guidelines introduction methods study group historical control group results discussion conclusion acknowledgements ethical considerations references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8166 production and hosting by knowledge e research article enhancing the knowledge of cervical cancer screening among female nursing students: an interventional educational program dr: hayam fathey a. eittah, dr: khalid abdullah s. aljohani, and dr: mohammed saeed e. aljohani 1assist. prof. of maternal and newborn health nursing, faculty of nursing, menoufia university, egypt associate prof. of maternal and newborn health nursing, nursing college, taibah university madinah, ksa 2assist. professor, community health nursing, nursing college, taibah university, madinah, ksa 3assistant professor, medical and surgical nursing, nursing college, taibah university, madinah, ksa abstract background: cervical cancer is a growing health risk facing women worldwide with the human papillomavirus (hpv) as the primary underlying cause. pap smear is a simple screening test that can detect early changes in cervical cells, which might develop into cancer cells. raising awareness of cervical cancer prevention has a significant impact on decreasing the burden of the disease. the aim of the study is to assess female nursing students’ knowledge on early detection and screening of cervical cancer, and to determine the effectiveness of an educational program. methods: a quasi-experimental research design (one group for preand post-tests) was utilized with a convenience sample of 130 female nursing students in one of the nursing colleges in saudi arabia. the study’s educational intervention included information about anatomy of genital tract and the importance of regular check-ups. the preand post-tests were applied to identify changes after intervention measures. results: the mean age of the participants were 21.32 years (sd: 1.34). the findings revealed a significant improvement of post-test students’ knowledge in all items related to risk factors, signs and symptoms, occurrence, identification of hpv as causative agent, vaccination against hpv, and finally pap smear for early detection and screening of cervical cancer. conclusion: the study results support implementing educational intervention to improve nursing students’ knowledge and awareness about cervical cancer prevention. furthermore, it is imperative that cervical cancer awareness education modules should be developed and integrated within the nursing curriculum. further studies with large sample size are recommended to increase generalization of the results. keywords: cervical cancer, education program, primary prevention, nursing students, saudi arabia how to cite this article: dr: hayam fathey a. eittah, dr: khalid abdullah s. aljohani, and dr: mohammed saeed e. aljohani (2020) “enhancing the knowledge of cervical cancer screening among female nursing students: an interventional educational program,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 431–439. doi 10.18502/sjms.v15i4.8166 page 431 corresponding author: khalid abdullah s. aljohani; assist. professor, community health nursing, nursing college, taibah university, madinah, ksa email: kajohani@taibahu.edu.sa received 9 october 2020 accepted 19 december 2020 published 31 december 2020 production and hosting by knowledge e hayam fathey a. eittah et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:kajohani@taibahu.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hayam fathey a. eittah et al 1. introduction cervical cancer is one of the diseases that could be avoided by encouraging people who are at risk to have a regular screening. increasing people’s awareness about the importance of disease screening may encourage them to be actively engaged in disease prevention initiatives. according to the world health organization (who), cervical cancer is the fourth most common cancer among women, with an estimated 570,000 new cases representing 6.6% of all female cancers around the world in 2018. death from cervical cancer in lowand middle-income countries is about 90% [1]. factors increasing death in developing countries include lack of awareness and high vaccine costs [2]. from saudi arabian context, cervical cancer is not a major contributor to women’s health problems in the country. more than 90% of cervical cancer cases are related to human papillomavirus (hpv) infection [3]. the pathogenesis can develop through precancerous lesions to invasive cancer over a period of 10–20 years and ultimately lead to death [4]. cancer of the cervix is preventable and can be easily managed if identified at early stages through pap smear [5]. unfortunately, about 90% of deaths did not have regular pap smear. a recent report mentioned that about 316 new cases of cervical cancer were diagnosed annually in saudi arabia. cervical cancer is the ninth most common cancer among females aged 15–44 years [6]. henceforth, studies exploring cervical cancer educational interventions are warranted [7]. effective health education programs targeting cervical cancer awareness need sophisticated and comprehensive planning and needs assessment of the target groups such as the level of knowledge, beliefs, attitudes, and behavior [8, 9]. comprehensive health education programs are more likely to promote screening, so it is important for health providers including nursing students to provide information about risk factors, early signs of cervical cancer, and encourage women to screen for cervical cancer on a regular basis [3, 10]. raising awareness of cervical cancer prevention has a significant impact on decreasing the burden of the disease. specifically, evidence has shown that education interventions to raise awareness improve accessibility to services, increase individuals’ efficacy, and inspire future choices, which in turn enhance the efficiency of preventive health services [11]. the aim of this study was to assess and enhance female nursing students’ knowledge and early detection and screening of cervical cancer utilizing an education program as an intervention. the study hypothesis assumes that educational programs will raise the knowledge and awareness of nursing students about cervical cancer, screening, and early detection. 2. methods a quasi-experimental design (pre-test–post-test design) was utilized to explore a convenient sample of 130 female nursing students the nursing college at taibah university in saudi arabia. the study included students who were 18 years or older. those who doi 10.18502/sjms.v15i4.8166 page 432 sudan journal of medical sciences hayam fathey a. eittah et al were younger than 18 years were excluded. potential candidates were approached and invited to participate in the study. 2.1. instrument the study instrument consisted of two sections: the first section consisted of the sociodemographic data including age, education level, age of menarche, family history, smoking, and attending an educational session about cervical cancer; while the second section was the pre–post intervention test. as academics, the researchers constructed this section of simple questions recalling knowledge about the importance of genital tract check-ups, diseases that affect the genital tract, definition of cervical cancer, causes and screening, vaccination, hpv, pap smear definition, importance of test, and the use, technique, periodicity, and precautions before having a pap smear. this section tested for content validity by five academic nursing experts. modifications were made according to the experts’ assessment. although the instrument was administered to the same population for more than one session under similar conditions, a pilot study involving 13 participants were undertaken. the final version of the instrument was attained following the pilot study outcome. further, the scoring system was adapted from a previous study [12]. in detail, the scoring system classified participants’ answers into three categories (wrong answer = 0, incomplete answer = 1, and complete answer = 3). the student with a score below 50% was considered to have poor knowledge. the overall score was classified as follows: low = <50%; accepted knowledge level = 50–75%; and good knowledge = >75%. data were analyzed using the statistical package for social sciences software package (spss inc., chicago, il, usa) version 20.0. frequencies, percentages, mean, and median were calculated for the knowledge score. student t-test and chi-square test were utilized to analyze the results. statistical significance was identified at p < 0.05. 2.2. procedure the aim of the study was explained to the participants followed by assessing the pretest knowledge level (estimated time 10–13 min). the intervention was an educational session delivered for 120 min including the following: 1. anatomy of genital tract and importance of genital tract screening 2. cervical cancer definition, risk factors, causes, signs, and symptoms 3. the relation between sexual activity and cervical cancer 4. hpv, its vaccine, screening of cervical cancer, pap smear technique, timing, periodicity, and precautions before pap smear the researchers used audio–visual aid such as microsoft powerpoint presentation, videos, and pictures for explanations. the final stage of post-test followed the education intervention (estimated time 10–13 min). doi 10.18502/sjms.v15i4.8166 page 433 sudan journal of medical sciences hayam fathey a. eittah et al 3. results the mean age of the study participants was 21.32 years (sd = 1.34), while the mean age of menarche was 12.93 years (sd = 1.39). other sociodemographic characteristics (table 1) showed that 90% of study samples were not married. neither of the participants smoked nor had a family history of cervical cancer. the majority knew about cervical cancer but did not attend any educational session in this regard. sources of information about cervical cancer were tv, social media, friends, academic study, and reading newspapers (16.1%, 63.1%, 2.3%, 2.3%, and 16.2%, respectively). table 1: sociodemographic characteristics (n = 130). characteristics no. % marital status single 117 90.0 married 13 10.0 smoking status yes 0 0 no 130 100.0 cervical cancer family history yes 0 0 no 130 100.0 attended previous educational activity yes 01 0.80 no 129 99.2 prior knowledge of cervical cancer yes 99 76.2 no 31 23.8 preferred source of information tv 21 16.1 social media 82 63.1 friends 03 02.3 academic study 03 02.3 newspapers 21 16.2 as shown in table 2, high statistically significant improvements were observed in the results of the post-test knowledge of students in the sample regarding the importance of check-up of genital tract, diseases that affect the cervix, risk factors, signs and symptoms of cervical cancer, and the relationship between sexual activity and cervical cancer when compared with the pre-test results, at p < 0.001. it is evident that the complete and correct answers were 22.3%, 27.7%, 6.9%, 3.1%, 2.3%, and 42.3%, respectively in pre-test, while at the post-test, the percentage of complete and correct responses rose, respectively, to 79.2% ,89.2%, 88.5%, 90.0%, and 96.9%. regarding the students’ knowledge about causative organism of cervical cancer (hpv) and its vaccination, there doi 10.18502/sjms.v15i4.8166 page 434 sudan journal of medical sciences hayam fathey a. eittah et al table 2: comparison of the results of pre–post knowledge tests related to cervical cancer, hpv (n = 130). knowledge statements answer group test x2 p-value pre post the importance of check-up of genital tract? complete 29 22.3% 103 79.2% 94.8 0.001** incomplete 83 63.8% 12 9.2% wrong 18 13.8% 15 11.5% diseases affecting the cervix complete 36 27.7% 116 89.2% 101.5 0.001** incomplete 56 43.1% 7 5.4% wrong 38 29.2% 7 5.4% knowledge about cervical cancer complete 9 06.9% 115 88.5% 176.9 0.001** incomplete 63 48.5% 14 10.8% wrong 58 44.6% 1 0.8% cervical cancer risk factors complete 04 03.1% 115 88.5% 200.1 0.000 incomplete 43 33.1% 15 11.5% wrong 83 63.8% 0 0.0% signs and symptoms of cervical cancer complete 3 2.3% 117 90.0% 210.7 0.000 incomplete 34 26.2% 13 10.0% wrong 93 71.5% 0 0.0% relationship between sexual activity and cervical cancer yes 55 42.3% 126 96.9% 91.7 0.000 no 75 57.7% 4 3.1% knowledge about hpv complete 16 12.3% 126 96.9% 188.6 0.000 incomplete 11 8.5% 2 1.5% wrong 103 79.2% 2 1.5% hpv vaccine complete 4 3.1% 122 93.8% 218.5 0.000 incomplete 26 20.0% 7 5.4% wrong 100 76.9% 1 0.8% was a high statistically significant improvement in post-test results as compared to pretest, the complete and correct answers were 96.9%, 93.8% in post-test compared to 12.3% and 3.1% in pre-test at p-value = 0.000. table 3 shows the comparison of preand post-tests knowledge assessment of female students regarding pap smear definition, associated pain, timing, periodicity, and prior precautions, and statistically significant improvements were observed in all these items, p = 0.000. at the pre-test, the majority of the students had incorrect and wrong answers but this result was reversed to complete and correct at post-test. doi 10.18502/sjms.v15i4.8166 page 435 sudan journal of medical sciences hayam fathey a. eittah et al table 3: pre–post knowledge of the students regarding pap smear (screening of cervical cancer) (n =130). answers group x2 p-value pre post do you know what a papanicolaou/pap smear is? yes 5 3.8% 125 96.2% 221.5 0.000 no 125 96.2% 5 3.8% knowledge about pap smear complete 7 5.4% 110 84.6% 181.1 0.000 incomplete 19 14.6% 15 11.5% wrong 104 80.0% 5 3.8% is there pain during pap smear? yes 94 72.3% 119 91.5% 23.8 0.000 no 36 27.7% 11 8.5% recommended age and frequency for performing of pap smear complete 3 2.3% 123 94.6% 222.7 0.000 incomplete 27 20.8% 4 3.1% wrong 100 76.9% 3 2.3% precautions before performing pap smear complete 2 1.5% 117 90.0% 222.1 0.000 incomplete 11 8.5% 11 8.5% wrong 117 90.0% 2 1.5% table 4: comparison of total pre–post knowledge test among student in the study sample (n = 130). knowledge assessment statistical test p-value pre post no. % no. % poor (<50) 126 96.9% 1 0.8% x2 = 242.8 0.001** fair (50–<75%) 4 3.1% 23 17.7% good (75%+) 0 0.0% 106 81.5% range 1–14 11–22 t = 46.8 0.001** mean (sd) 6.44 (2.7) 19.9 (1.9) the results of pre–post total knowledge scores of female students in the study sample are presented in table 4. it indicates statistically significant improvement in the total students’ knowledge scores in the post-test compared to the pre-test, p = 0.001. as seen in the table, the great majority of students (96.9%) had poor knowledge pre-test, which was greatly improved post-test, where 81.5% had good knowledge. 4. discussion working on preventing cervical cancer through screening is a valuable strategy to combat the increasing rate of the disease. despite the provision of medical services doi 10.18502/sjms.v15i4.8166 page 436 sudan journal of medical sciences hayam fathey a. eittah et al and availability of screening tests, increasing people’s risk awareness and supporting them to be actively engaged in disease prevention could be the best approach to increase screening rate. the current study showed that the majority of the participants despite having a prior knowledge of cervical cancer had not attended any educational programs. while social media was the main source of cervical cancer information, tv and newspapers were the second. these results are in line with a previous study conducted in egypt that found 95.1% of the participant nurses did not attend any program about cervical cancer, but about two-third of them took their information from work experience followed by academic study and doctors [13]. in addition, similar results were found in india where 20% of the participants identified that reading newspapers is their source of cervical cancer information [10]. the finding of the present study supports previous studies where a significant improvement of post-test students’ knowledge in all items of cervical cancer has been reported, which supports the implementation of educational programs especially in mass gathering locations such as universities and schools [13]. educational programs were a crucial factor in applying cervical cancer awareness campaigns [14]. furthermore, these programs enhance women’s health beliefs, thereby helping in cervical cancer prevention and detection [3, 15]. according to the american cancer association guideline, pap smear and the hpv dna test are significant diagnostic tools [16]. improvement in participants’ awareness about hpv and its vaccine was evident taking into account the difference in the scores of the preand post-tests. similar trend was found in previous studies conducted outside saudi arabia [17]. at pre-test, majority of the participants had poor knowledge about pap smear, importance, procedures, timing, periodicity, and prior precautions. however, the post-test showed great improvement in the students’ knowledge regarding all of these items. in the same line of findings, previous studies of similar intervention made significant positive enhancement in participants’ knowledge noticing the difference between the preand post-tests [18]. in general, the study supports the findings of previous international studies proving overall cervical cancer knowledge improvements [9, 11, 13]. therefore, it is imperative to recommend educational programs to attain cervical cancer awareness among target groups [1]. the study results recommend further similar initiatives within the university to raise the general awareness of all students. furthermore, enhanced educational programs for cervical cancer awareness should be included in the nursing curriculum. from a community stand, community campaigns are warranted to raise public awareness on cervical cancer and pap smear screening become a routine test for all women in childbearing age. 5. conclusion in this study, the majority of the participants had poor knowledge about cervical cancer pre-test. after delivering the educational intervention, the post-test indicated significant improvements in the participants’ level of knowledge for almost all items. therefore, doi 10.18502/sjms.v15i4.8166 page 437 sudan journal of medical sciences hayam fathey a. eittah et al the study results conclude that educational interventions about cervical cancer were successful in increasing awareness and knowledge among the study participants. acknowledgments none. ethical considerations the college of nursing research ethics committee (rec-tucn) approved the study proposal. potential participants received an invitation including explanation of the study aim and procedures. study data were treated confidentially and not utilized for academic purposes. competing interests none. availability of data and material the data used in this study is available upon reasonable request. funding none. references [1] who. (2020). who technical guidance and specifications of medical devices for screening and treatment of precancerous lesions in the prevention of cervical cancer 2020. geneva, switzerland: who. [2] marek, e., dergez, t., rebek-nagy, g., et al. (2012). effect of an educational intervention on hungarian adolescents’ awareness, beliefs and attitudes on the prevention of cervical cancer. vaccine, vol. 30, no. 48, pp. 6824–6832. [3] ahmed, s. r. h., esa, a. s. m., and mohamed el-zayat, o. s. (2018). health belief model-based educational program about cervical cancer prevention on women knowledge and beliefs. egyptian nursing journal, vol. 15, no. 1, pp. 39–49. [4] ombech, e. a., muigai, a., and wanzala, p. (2012). awareness of cervical cancer risk factors and practice of pap smear testing among female primary school teachers in kasarani division, nairobi kenya. african journal of health sciences, vol. 21, no. 21, pp. 121–132. [5] pimple, s. a. and mishra, g. a. (2019). global strategies for cervical cancer prevention and screening. minerva ginecologica, vol. 71, no. 4, pp. 313–320. [6] hpv information centre. (2019). saudi arabia human papillomavirus and related diseases report. hpv information centre. [7] alsbeih, g. (2014). hpv infection in cervical and other cancers in saudi arabia: implication for prevention and vaccination. frontiers in oncology, vol. 4, p. 65. [8] who. (2012). health education: theoretical concepts, effective strategies and core competencies—a foundation document t guide capacity development of health educators. geneva: who. doi 10.18502/sjms.v15i4.8166 page 438 sudan journal of medical sciences hayam fathey a. eittah et al [9] mary, b. and d’sa, j. l. (2014). evaluation of an educational program on cervical cancer for rural women in mangalore, southern india. asian pacific journal of cancer prevention, vol. 15, no. 16, pp. 6603– 6608. [10] naik, p. r., nagaraj, k., and nirgude, a. s. (2012). awareness of cervical cancer and effectiveness of educational intervention programme among nursing students in a rural area of andhra pradesh. healthline, vol. 3, pp. 41–45. [11] naz, m. s. g., kariman, n., ebadi, a., et al. (2018). educational interventions for cervical cancer screening behavior of women: a systematic review. asian pacific journal of cancer prevention, vol. 19, no. 4, pp. 875–884. [12] siddiqui, a. f., al qahtani, s. q., al qahtani, a. m., et al. (2018). knowledge, attitudes and practice of burns prevention and first aid among medical students of king khalid university, saudi arabia. bangladesh journal of medical science, vol. 17, no. 4, pp. 537–544. [13] abo-lela, h., mansour, s. e., rafik ibrahem barakat, r. i., et al. (2017). effect of applying educational sessions on the nurses’ knowledge regarding cervical cancer. iosr journal of nursing and health science, vol. 6, pp. 29–36. [14] pirzadeh, a. and mazaheri, m. a. (2012). the effect of education on women’s practice based on the health belief model about pap smear test. international journal of preventive medicine, vol. 3, no. 8, pp. 585–590. [15] atwa, a. m. e., hassan, h. e., and ahmed, s. i. (2019). the impact of a hospital-based awareness program on the knowledge of patients about breast cancer and cancer cervix. international journal of nursing studies, vol. 4, no. 1, p. 20. [16] tsikouras, p., zervoudis, s., manav, b., et al. (2016). cervical cancer: screening, diagnosis and staging. journal of the balkan union of oncology, vol. 21, no. 2, pp. 320–325. [17] kessler, t. a. (2017). cervical cancer: prevention and early detection. seminars in oncology nursing, vol. 33, no. 2, pp. 172–83. [18] devi, a. m. (2019). to assess the effectiveness of planned teaching program (ptp) on knowledge regarding early detection and prevention of cervical cancer among women: pre-experimental study. international journal of nursing education, vol. 11, no. 2, pp. 1–6. doi 10.18502/sjms.v15i4.8166 page 439 introduction methods instrument procedure results discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 15, issue no. 3, doi 10.18502/sjms.v15i3.7253 production and hosting by knowledge e research article antioxidant vitamins are correlated with different aspects of phagocytic processes in healthy nigerians: benefits as supplements during antimicrobial treatment ganiyu olatunbosun arinola and fabian victory edem department of immunology, university of ibadan, nigeria abstract background: antioxidant vitamins are important for the immune system to function efficiently through several mechanisms. however, according to several previous studies, individual step of leucocyte phagocytosis is not correlated with different antioxidant vitamins. methods: this study included 50 healthy nigerians whosecellular phagocytic mechanism such as percentage leucocyte migration (%lm) and intracellular killing (%nitroblue tetrazolium test) were determined by microscopy, neutrophil chemokines [plasma interleukin 8 (il-8)] was determined using elisa,and respiratory burst indices [plasma catalase (cat), superoxide dismutase (sod), myeloperoxidase (mpo), hydrogen peroxide (h2o2), and nitric oxide (no)] were determined by spectrophotometry. while the plasma antioxidant vitamins (vitamins a, c, and e) were determined using hplc, the phagocytic indices, chemokines, and respiratory burst indices were correlated with plasma antioxidant vitamins using spearman’s correlation analysis at α0.05. results: the results show that although among the healthy nigerian adults, vitamin c was significantly and positively correlated with %nbt,it was negatively correlated with cat activity. vitamin a showed a significantly positive correlation with sod while vitamin e showed a significantly negative correlation with mpo. conclusions: these findings suggest that antioxidant vitamins affect different stages of phagocytosis. it is advisable to use a combination of antioxidant vitamins as supplements with recommended treatment strategies against intracellular microorganisms or inflammatory diseases. keywords: antioxidants, intracellular microbial killing, vitamins 1. introduction inadequate intake of antioxidant vitamins suppresses immunity and predisposes to microbial infections that increase morbidity and mortality. it has since been established that the immune system needs vitamins a, d, c, e, b6, b12, and folate in both innate how to cite this article: ganiyu olatunbosun arinola and fabian victory edem (2020) “antioxidant vitamins are correlated with different aspects of phagocytic processes in healthy nigerians: benefits as supplements during antimicrobial treatment,” sudan journal of medical sciences, vol. 15, issue no. 3, pages 225–236. doi 10.18502/sjms.v15i3.7253 page 225 corresponding author: o.g.arinola; department of immunology, university of ibadan, nigeria +234 80 2345 1520 email: drarinolaog64@yahoo.com received 15 june 2020 accepted 12 august 2020 published 30 september 2020 production and hosting by knowledge e ganiyu olatunbosun arinola and fabian victory edem. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:drarinolaog64@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem immunity and adaptive immune response to micro-organisms [1]. phagocytosis constitutes an important innate defense mechanism. during phagocytosis, the appropriate immune cell internalizes micro-organisms through interaction with specific receptors on phagocytic cells. ultimately, engulfed micro-organisms are digested in phagosomes by hydrolyzing enzymes of the polymorphonuclear leukocytes (pmnl) and macrophages [2]. the sod enzyme converts superoxide to hydrogen peroxide (h2o2), which is used to produce an oxidant (hypochlorous acid) via myeloperoxidase (mpo). hypochlorous acid further combines with amines to produce other oxidants chloramines [3]. phagocytic stages include adherence, movement, engulfment, and reactive oxygen production. a study reported that the entire steps of phagocytosis were increased after the addition of vitamin e and ascorbic acid in the medium containing peritoneal macrophages [4]. both phagocytosis and superoxide anion production were enhanced in kupffer cells treated in vivo with all-trans-retinol [5]. moreover, while vitamin e deficiency decreased the activity of nk cells, vitamins c and e reduced the superoxide production by neutrophils [6]. in another study, supplementation with vitamins c and e in healthy humans also demonstrated to suppress neutrophil production of free oxygen radicals [7]. in addition, supplementation of vitamin c also improved antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity [6].alvarado et al.[8]reported that patients with recurrent infections had impaired leukocyte chemotaxis, which was restored with vitamin c. a report provided evidence that a single dose of vitamin c improved primary abnormalities in neutrophil motility and antimicrobial activity in humans [9]. many aspects of innate immunity are modulated by vitamin a and its metabolites. for instance, vitamin a controls neutrophil maturation, and during vitamin a deficiency, neutrophil numbers were increased but with impaired phagocytic function [10]. vitamin a also supports phagocytic activity, oxidative burst of macrophages, and bacterial killing [11]. additionally, itcontrols dendritic cell and cd4+ t lymphocyte maturation,while vitamin a deficiency diminishes natural killer cell activity and alters the balance between t helper 1 and t helper 2 lymphocytes [12]. wu et al. [13] demonstrated apositive association between plasma vitamin e and cell-mediated immune responses, and a negative association between plasma vitamin e and the risk of infections in healthy adults. supplementing adults with vitamin e improved chemotaxis and phagocytosis of neutrophils, natural killer cell activity, and mitogen-induced lymphocyte proliferation [14]. as elucidated earlier, several investigators have suggested that antioxidant vitamins are immunologically beneficial and protective against microbial infections. however, to doi 10.18502/sjms.v15i3.7253 page 226 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem provide additional mechanisms for these earlier observations, the present study determined and correlated separate steps of phagocytosis such as adherence, chemotaxis, digestion, and intracellular killing with antioxidants vitamins. 2. methods 2.1. subject population this study comprised of 50 healthy subjects who are staff and students in the university college hospital, ibadan, nigeria. while the study included subjects with no communicable and non-communicable disease, those who drink alcoholic beverages, smoke cigarette,and were on compulsory medications or supplements were excluded from the study. all participants gave their consent prior to the studyand the research was conducted in compliance with the declaration of helsinki. 2.2. plasma isolation blood was collected in a covered test-tube with lithium heparin anticoagulant and carefully mixed. plasma was removed after centrifuging at 1500g for 10 min in a centrifuge;the liquid component (plasma) was transferred into a clean polypropylene tube using a pasteur pipette in a freezer (–20°c). 2.3. percentage leucocyte migration percentage leucocyte migration (%lm) was determined as previously described out in our laboratory by one of the authors [15]. dextran (6%) was properly but gently mixed with the whole blood (1:1) and incubated for 45 min at 37°c. supernatant containing the leucocytes was obtained and washed thrice in kreb–ringers solution. washed leucocytes were then filled into capillary tubes and anchored into a migration chamber filled with either kreb–ringers solution or antigen (bcg) and kreb–ringers solution (1:50) and incubated for 18 hr at 37°c. the area of lm in the chamber containing antigen was compared with the area of migration in the chamber without antigen. the %lm was calculated as follows: %lm = (area of migration in antigen solution/area of migration in medium alone) x 100. doi 10.18502/sjms.v15i3.7253 page 227 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem 2.4. percentage nitroblue tetrazolium dye reduction percentage nitroblue tetrazolium (%nbt) dye reduction was based on a previously described methodcarried out in our laboratory [15]. for stimulated nbt procedure, nbt solution (50 μl of 0.2% nbt), heparinized blood (25 μl), and 25 μl of stimulant solution (nonviable bacterial extract) were mixed gently and incubated at 37°c for 10 min. a thick smear of the mixture was prepared which was allowed to air-dry, treated with wright stain for 15 sec, and flooded with distilled water for 30 sec before air-dried. two hundred leukocytes were counted under oil immersion objective and leukocytes showing dark formazan deposit were recorded as positive. the percentage of bacterially stimulated nbt was calculated as: %nbt = [leucocyte with dark formazan deposit (positive)/total leukocytes counted] x 100. 2.5. superoxide dismutase activity determination the superoxide dismutase (sod) activity was determined as previously carried out in our laboratory by us [44]. this method is based on the principle that sod inhibits autoxidation of epinephrine at ph 10.2. 2.6. catalase activity determination catalase (cat) activity was determined as previously carried outin our laboratory [44] based on the principle that dichromate in acetic acid is reduced to chromic acetate when heated in the presence of h2o2, with the formation of perchromic acid as an unstable intermediate. the chromic acetate then produced is measured at 570 nm. 2.7. myeloperoxidase activity determination myeloperoxidase (mpo) activity was determined as previously described in our laboratory [44]. the rate of decomposition of h2o2 by peroxidase, with guaiacol as hydrogen donor, produced tetraguaiacol which was measured at 436 nm. doi 10.18502/sjms.v15i3.7253 page 228 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem 2.8. hydrogen peroxide determination hydrogen peroxide (h2o2) concentration was determined as previously carried outin our laboratory [44] based on peroxide-mediated oxidation of fe2+, followed by the reaction of fe3+ with xylenol orange to form fe3+-xylenol orange complex with an absorbance maximum of 560 nm. plasma h2o2 was determined by comparing absorbance with standard solutions of h2o2. 2.9. nitric oxide determination plasma nitric oxide (no) concentration was determined using griess reagent [sulfanilamide and n-1-napthyethylene-diamine dihydrochloride (ned)] as previously described by us [44]. the assay is based on a reaction that utilizes sulfanilamide and ned under acidic (phosphoric acid) conditions. nitrite forms colored chromophore with reagent, with an absorbance maximum at 540nm. 2.10. estimation of chemokine il-8 the serum level of il-8 was determined through enzyme-linked immunosorbent assay (elisa) using different kits (abcam, ma, usa, assaypro, mo, usa and calbiotech, usa). the elisa was performed as previously carried out in our laboratory [16]. all the reagents, sample, and standards were allowed to attain working room temperature prior tocommencement of the assay. stock standard solution was diluted to varying concentration used for the standard curve. standards, samples, reagents, and immunoplate wereallowed to attain room temperature before being used.after the procedure as described by the manufacturer and as previously carried out, the absorbance of each well was read at 450nm with the aid of a microplate reader [spectramax 384 plus (molecular devices, usa)]. using a four-parameter logistic curvefit, the unknown sample concentration was extrapolated from the standard curve. 2.11. estimation of serum concentrations of vitamins a, c and e using high-performance liquid chromatography serum vitamins a and c concentrations were determined using high-performance liquid chromatography (hplc) [18]. hplc is a chromatographic technique used in separating, identifying, and quantifying components in a mixture. it involves passing doi 10.18502/sjms.v15i3.7253 page 229 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem liquid sample oversolid adsorbent material that is packed into a column using a flow of liquid solvent. analytes in samples interact in a slightly different manner with the adsorbent material, and therebyslowsdown the flow of the analytes differently. a volume of 250μl of standard, controls, and sample were added to 50μl internal standard and 250μl of precipitating reagent in a 1.5ml precipitation tube. the mixture was briefly mixed using vortex mixer and leftfor 30 min between 2°c and 8°c, and then centrifuged at 10,000g for 2 min (for vitamin a) or 10 min (for vitamin c). supernatant (100μl)was picked and injected into the hplc-system and the chromatograms weredetected through the uv detector. 2.12. statistical analysis spearman’s rank correlation was used to establish the correlation between %nbt, %lm, il 8, sod, mpo, cat, no, and h2o2 with antioxidant vitamin levels (vitamins a, c, and e). values were considered significant at p<0.05. 3. results table 1 shows that although vitamin c was significantly and positively correlated with %nbt, it was negatively correlated with catactivity. in addition, while vitamin a showed a significantly positive correlation with sod, vitamin e showed a significantly negative correlation with mpo. 4. discussion there are several reports on the role of vitamins in hostingimmunity and susceptibility to infection [6–14]. however, the mechanism is not yet exhausted because it is difficult or rather impossible in humans to study one immune response, single immune cell, or a particular vitamin in isolation due to the synergism of all components of humans. more so, it is difficult to specifically point out if the infection started before vitamin deficiencies orvitamin deficienciescame before the infection. global threats of infectious diseases [18] coupled with the ongoing global covid-19 pandemic calls for use of immune boosters, antioxidant, and anti-inflammatory supplements with recommended management regimens. in children, a close correlation between the deficiency of vitamin a and infectious diseases of respiratory and digestive systems was reported [17, 19]. to some extent, doi 10.18502/sjms.v15i3.7253 page 230 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem table 1: spearman’s correlation analysis of %nbt, %lm, il-8, sod, mpo, cat, no, and h2o2 with antioxidant vitamin levels (vitamins a, c, and e). vit a vit c vit e %nbt r p –0.081 0.202 0.278 0.000* 0.060 0.349 %lm r p –0.066 0.290 0.075 0.232 0.111 0.076 il-8 r p –0.117 0.062 –0.004 0.955 –0.061 0.332 sod r p 0.136 0.028* 0.068 0.272 0.104 0.095 mpo r p –0.080 0.196 –0.044 0.482 –0.194 0.002* cat r p –0.011 0.862 –0.168 0.007* –0.006 0.929 h2o2 r p 0.068 0.276 0.068 0.272 –0.007 0.908 no r p 0.150 0.016* 0.022 0.724 0.108 0.083 *significantly correlated vitamin a demonstrated a therapeutic effect in diseases transmitted through the respiratory system such as pneumonia and measles in children [20]. in rodents, deficiency of vitamin a reduced the adhesion and phagocytosis of pseudomonas aeruginosa and the production of reactive oxidative molecules [21]. epidemiological studies showed that the healthy population had a significantly higher serum level of vitamin a than pulmonary tuberculosis patients [22, 23]. the suggested immunological effect was based on the fact that vitamin a is a micronutrient that protects epithelium integrity [18–20] and plays a crucial role in mucus production, epithelial-formation, -keratinization, -stratification, -differentiation, and functional maturation [24]. antioxidant enzymes such as sod and cat act as a defense against oxidative stress [25]. sod catalyzes the conversion of a highly reactive superoxide anion (o−−2 ) into a less reactive species h2o2 and molecular oxygen (o2). h2o2formed by sod activity is decomposed to water and molecular oxygen (o2), a reaction catalyzed by the enzyme cat [26]. in the present study, vitamin a had a positive correlation with sod, thus increasingthe levels of vitamin a and thereby increasing the sod activities and production of antimicrobial h2o2. this might be one of the bases for the protective uses of vitamin a. vitamin c deficiency increases susceptibility to a variety of infections [27] and humansdeficient in vitamin c are susceptible to pneumonia [28]. vitamin c supplementation decreased the duration and severity of common cold [29]. pulmonary tuberculosis patients have decreased plasma vitamin c concentrations compared doi 10.18502/sjms.v15i3.7253 page 231 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem withuninfectedsubjects [30]. based on chest x-ray results, acute lung infections have shown rapid clearance following an administration of intravenous vitamin c [31, 32]. in addition, pre -clinical studies of animals with sepsis-induced lung injury have indicated that vitamin c administration increased alveolar fluid clearance, enhanced bronchoalveolar epithelial barrier function, attenuated sequestration of neutrophils [33]. immunomodulatory function of vitamin c was based on its requirement for the biosynthesis of collagen, maintenance of epithelial integrity, leucocyte chemotaxisin response to inflammatory mediators, phagocytosis and killing of microbes, apoptosis, and clearance by macrophages [34]. vitamin c has effective antioxidant capacitybecause of its ability to donate electrons, thus protecting important biomolecules (such as proteins, lipids, carbohydrates, and nucleic acids) from damage by oxidants generated during normal cellular activities [35]. in addition to these previously suggestedmechanisms, the present study added that positive correlation of nbt (ability to generate reactive oxygen species) or negative correlation of cat (another antioxidant enzyme) with vitamin c levels might also contribute to the usefulness of vitamin c in immune function. our findings are in support of earlier reports that state leukocytes actively accumulate vitamin c [36], which increases following oxidative burst [37] and that vitamin c is a water-soluble antioxidant that scavenges numerous oxidants and can also regenerate important cellular and membrane antioxidants such as glutathione and vitamin e [38]. another study by bozonet and carr [39] also demonstrated that supplementation with vitamins c and e in healthy humans suppressed neutrophil production of free oxygen radicals.moreover, the supplementation of elderly women with a combination of 1 g/day vitamin c with vitamin e enhanced neutrophil functions, including chemotaxis [40]. this observation therefore supports the use of combination of antioxidant vitamins. further, vitamin e was shown toreduce susceptibility to infections by enhancingproliferation of lymphocytes, production of t helper 1-type cytokines, activities of natural killer cells, and phagocytosis of macrophages/neutrophils [41]. it was shown thatthe positive association existed between plasma vitamin e and cell-mediated immune responses, and a negative association has been demonstrated between plasma vitamin e and the risk of infections in healthy adults over 60 years of age [42, 43]. during the respiratory burst, leucocytes consume a large amount of o2 to generate h2o2 through dismutation reaction catalyzed by sod [25]. this h2o2 combines with halide ions (i−, cl−, br−) to produce hypohalous acid (hocl/hobr) in the presence of mpo. hocl/hobr may react with o2· −− or fe2+ to form another strong oxidant, probably the hydroxyl radical (·oh). if not controlled and due to high concentrations, the reactive oxygen species (o2· −, ·oh), hocl/hobr, and h2o2 may leak into surrounding doi 10.18502/sjms.v15i3.7253 page 232 sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem cells resulting in increased quantities of free radicals [26]. this study shows a negative correlation between vitamin e and mpo supporting that vitamin e is an antioxidant vitamin. it is thus likely that vitamin e is consumed as mpo activity increases so as to reduce the excessive production of hocl/hobr and subsequent stronger oxidants like o2· − and ·oh. therefore, according to this study, antioxidant vitamins a, c, and e 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[31] bharara, a., grossman, c., grinnan, d., et al. (2016). intravenous vitamin c administered as adjunctive therapy for recurrent acute respiratory distress syndrome. case reports in critical care, 8560871. [32] fowler, a.a., kim, c., lepler, l., et al. (2017). intravenous vitamin c as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. world journal of critical care medicine, vol. 6, pp. 85–90. doi 10.18502/sjms.v15i3.7253 page 235 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd005532.pub3/full https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd005532.pub3/full https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd000980.pub4/full https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd000980.pub4/full sudan journal of medical sciences ganiyu olatunbosun arinola and fabian victory edem [33] fisher, b.j., kraskauskas, d., martin, e.j., et al. (2012). mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. american journal of physiology-lung cellular and molecular physiology, vol. 303, pp. l20–l32. [34] wilgus, t.a., roy, s., and mcdaniel, j.c. (2013). neutrophils and wound repair: positive actions and negative reactions. advances in wound care, vol. 2, pp. 379–388. [35] carr, a. and frei, b. (1999). does vitamin c act as a pro-oxidant under physiological conditions? faseb journal, vol. 13, pp. 1007–1024. [36] bergsten, p., amitai, g., kehrl, j., et al. (1990). millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. depletion and reaccumulation. journal of biological chemistry, vol. 265, pp. 2584–2587. [37] corpe, c.p., lee, j.h., kwon, o., et al. (2005). 6-bromo-6-deoxy-l-ascorbic acid: an ascorbate analog specific for na+-dependent vitamin c transporter but not glucose transporter pathways. journal of biological chemistry, vol. 280, pp. 5211–5220. [38] buettner, g.r. (1993). the pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. archives of biochemistry and biophysics, vol. 300, pp. 535–543. [39] bozonet, s. m. and carr, a. c. (2019). the role of physiological vitamin concentrations on key functions of neutrophils isolated from healthy individuals. nutrients, vol. 11, no. 6, p. 1363. [40] nusgens, b.v., humbert, p., rougier, a., et al. (2001). topically applied vitamin c enhances the mrna level of collagens i and iii, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. journal of investigative dermatology,vol. 116, pp. 853–859. [41] wu, d. and meydani, s. n. (2004). age-associated changes in immune function: impact of vitamin e intervention and the underlying mechanisms. endocrine, metabolic & immune disorders drug targets, vol. 14, pp. 283–289. [42] lee, g. andhan, s. (2018). the role of vitamin e in immunity. nutrients, vol.10, p. 614 [43] meydani, s. n., han, s. n., and wu, d. (2005). vitamin e and immune response in the aged: molecular mechanisms and clinical implications. immunological reviews, vol. 205, pp. 269–284. [44] akinyoola, s. b., edem, v. f., arinola, o. g., et al.(2012). vitamin e or red palm oil increases the level of nitric oxide in wister rats chronically exposed to dichlorvos. tropical journal of health sciences, vol. 19, p. 8e11. doi 10.18502/sjms.v15i3.7253 page 236 introduction methods subject population plasma isolation percentage leucocyte migration percentage nitroblue tetrazolium dye reduction superoxide dismutase activity determination catalase activity determination myeloperoxidase activity determination hydrogen peroxide determination nitric oxide determination estimation of chemokine il-8 estimation of serum concentrations of vitamins a, c and e using high-performance liquid chromatography statistical analysis results discussion references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8932 production and hosting by knowledge e editorial university staff and student protection from covid-19: strategic measures for teaching and learning in resource-limited setting mohamed a. m. ibnouf, frcsed, phd publons web of science researcher id: c-4902-2009 orcid: mohamed a. m. ibnouf: https://orcid.org/0000-0001-8231-9899 so far, covid-19 has claimed millions of lives [1, 2]. this editorial in sudan journal of medical science reflects the strategic measures designed for teaching and learning in omdurman islamic university (oiu) as an example of a high educational institute in a low-income country to protect the staff and students during the pandemic. however, the published protocols and guidelines may prove inadequate for combating the disastrous effects of the fast-spreading new strains of the virus [3]. in addition to high mortalities during the first wave of covid-19 in sudan, in march– june 2020, government universities faced extraordinary challenges in introducing elearning in their curricula. this situation was worsened by the unprecedented inflation in economy, repeated electricity cut-offs, and low-frequency internet flow. several published studies have explored the impact of covid-19 on university education, as well as experiences in e-learning during the pandemic. we searched databases such as pubmed, medline, google, as well as the local social media for relevant data published between december 1, 2019 and march 12, 2021. according to the published reports, covid-19 mortalities rose faster among college communities than in the rest of the population. moreover, since the onset of the pandemic, a times’s survey has identified 397,000 infections at more than 1,800 colleges and universities in the us. the cases included >90 deaths of college employees and students [4]. also, 20 staff members and 2 students from universities across south africa were reported to have died of coronavirus [5]. about 109 deaths occurred among sudanese medical doctors and 7 university staff members between january 14, 2020 and march 12, 2021. we noticed that adherence to covid-19 prevention measures among the staff and students were not optimal, despite the fact that transmission is lower with physical distancing ≥1 m than <1 m and face mask (particularly n95) reduces significantly the infection rate [6]. how to cite this article: mohamed a. m. ibnouf, frcsed, phd (2021) “university staff and student protection from covid-19: strategic measures for teaching and learning in resource-limited setting,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 1–4. doi 10.18502/sjms.v16i1.8932 page 1 corresponding author: mohamed a. m. ibnouf; email: maibnouf@gmail.com received 20 march 2021 accepted 26 march 2021 published 31 march 2021 production and hosting by knowledge e mohamed a. m. ibnouf. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:maibnouf@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed a. m. ibnouf during the pandemic, transition to e-learning was considered the best alternative. during the short advocacy period, the voice of the opponents and the resistant staff was rather high. challengers spoke about the unfamiliarity with elearning, poor facilities for staff and students, instability of electricity, etc. hence, to evaluate the training needs of the oiu staff, a validated, pretested self-administered questionnaire was sent as a google form to 1,500 oiu staff members. separately, two other validated, pretested self-administered questionnaires were sent as google forms to the teaching staff members of the faculty of medicine and to the medical students. data were analyzed automatically by google. the retrieval rate of the questionnaire sent to the members of the university teaching staff was 740 (49.3%). of these responders, 358 (48.4%) were capable of using computer for preparing their lectures. also, 713 (96.8%) had access to smart phones and computers with internet facilities and 643 (86.9%) used e-mails and social media programs. however, only 295 (39.8%) responders used electronic media to send assignments and receive responses from their students. about 510 (69%) oiu staff members had variable experiences in using computers such as preparing a pdf file, but only 9.9% had experience with a learning management program, particularly moodle. the university information technology (it) center added a bandwidth of 158 mbps to broaden and fasten the university internet speed. the university website was upgraded to upload all timetables and archives of the educational modules. training in utilizing moodle to ensure an effective e-learning delivery was given. moodle was chosen because it is a free learning management system (lms) source to augment and move the existing learning environment online. at the time of writing this editorial, several courses in 5 of the 21 university faculties were started as blended modules. the students show up for face-to-face training only at the end of the semester. the exam results revealed good student attainments. however, in the remaining 16 faculties, routine classical teaching has been resumed. the compliance of the students and adherence to the preventive measures was rather low. the anticipated fast-spreading strains of the virus dictated enhancing training for the rest of the faculties. however, one of the major obstacles is the financial constraints and resistance of few senior teaching staff members. the resistant staff and those who have technophobia [7–9] will be assigned for face-to-face training of the students and to take the responsibility of some administrative jobs. because this was a preliminary exploratory survey to assess the training needs of university students and staff, we accepted the small sample size to fasten the e-learning program. face-to-face interaction during teaching and learning is the classical method doi 10.18502/sjms.v16i1.8932 page 2 sudan journal of medical sciences mohamed a. m. ibnouf that builds confidence between the educator and students. however, in the covid-19 pandemic, universities are working hard to endure the change in a new norm. the fast-developing technologies have improved distance communication, teleconferencing, and virtual classrooms to access teaching and training from worldwide sources. as the pandemic has hit hard the global economy and claimed millions of lives, transnational collaboration and nongovernmental support spark to give hope to overcome the challenges. however, with the donors’ fatigue, oiu struggles hard to train the staff and students to adopt a distant-learning strategy as an alternative to faceto-face teaching in crowded classrooms in a low-resource setting. all the given reasons along with the electricity cut-offs and unstable internet bandwidth slowed the change and forced the oiu staff and students to incline toward asynchronous e-learning. university staff and students were reported to develop high psychological distress that influences their presence and absence [10]. nevertheless, e-learning is a great opportunity to enhance the university’s effectiveness and efficiency, however, the needed infrastructure for e-learning might not be readily found in lowand middleincome countries (lmic) [11]. in order to prevent further loss of precious lives, oiu is moving toward blended learning. this strategy safeguards asynchronous teaching in the theoretical part of the curricula augmented by social media and telecommunication between students and staff. also, it guarantees physical distancing in small student groups during training at the end of each semester. references [1] ramani, v. k., shinduja, r., suresh, k. p., et al. (2020). a study on the global scenario of covid-19 related case fatality rate, recovery rate, and prevalence rate and its implications for india -a record-bases retrospective cohort study. advances in infectious diseases journal, vol. 10, pp. 233–248. [2] katherine, l. (2020). the link between humidity and covid-19 caused death. journal of biosciences and medicines, vol. 8, no. 6, pp. 50–55. [3] tomezuka, t., kanatani, y., and kawahara, k. (2013). insufficient preparedness of primary care practices for pandemic influenza and the effect of a preparedness plan in japan: a prefecture-wide plan cross-sectional study. bmc family practice, vol. 14, p. 174. [4] ivory, d., gebeloff, r., and mervosh, s. young people have less covid-19 risk, but in college towns deaths rose fast. the new york times. march 2, 2021. doi 10.18502/sjms.v16i1.8932 page 3 sudan journal of medical sciences mohamed a. m. ibnouf [5] macupe, b. south african universities record 22 deaths from covid-19. the mail & guardian. 2020, july 23. [6] chu, d. k., aki, e. a., duda, s., et al. (2020). physical distancing, face mask and eye protection to prevent person-to-person transmission of sars-cov-2 and covid-19: a systematic review and meta-analysis. lancet, vol. 395, no. 10242, pp. 1973–1987. [7] rajab, n. h., gazal, a. m., and alkattan, k. (2020). challenges to online medical education during the covid-10 pandemic. cureus, vol. 12, no. 7, e8966. [8] estrada-munoz, c., castillo, d., vega-munoz, a., et al. (2020). teacher technostress in the chilean school system. international journal of environmental research and public health, vol. 17, no. 15, p. 5280. [9] pietrocola, m., rodrigues, e., bercot, f., et al. (2020). risk society and science education: lessons from covid-19 pandemic. science education, pp. 1–25. retrieved from: https://rdcu.be/cgp7g [10] van der heltz-cornelis, c. m., varley, d., aligar, v. l., et al. (2020). workplace stress, presenteeism, absenteeism and resilience amongst university staff and students in covid-19 lockdown. frontiers in psychiatry, vol. 11, 588803. [11] frehywot, s., vovides, y., talib, z., et al. (2013). e-learning in medical education in resource constrained lowand middle-income countries. health, vol. 4, no. 11, p. 4. doi 10.18502/sjms.v16i1.8932 page 4 references sudan journal of medical sciences volume 15, issue no. 2, doi 10.18502/sjms.v15i2.7067 production and hosting by knowledge e research article menstrual disorders among nursing students at al neelain university, khartoum state aisha mohammed adam1, hammad ali fadlalmola2, and huda khalafala mosaad3 1department of obstetrics and gynecological nursing, faculty of nursing sciences, al neelain university, sudan 2department of community health nursing, nursing college, taibah university, saudi arabia 3faculty of applied medical sciences, department nursing, hafar albatin university, saudi arabia abstract background: menstrual disorders can severely affect the daily life of young females, particularly the student population, which generates a massive tension that extends to families, but they seldom affect the quality and standard of life. objectives: the aim of this study was to determine the morbidity nature of menstrual disorders among nursing students and their effect on students’ life activities. methods: this study was a descriptive cross-sectional institutional-based study conducted at the al neelain university, faculty of nursing. of the 200 students recruited, 149 completed the questionnaire with the responding rate of (74.5%). data were collected using a self-administered structured questionnaire. results: of the 149 participants, most were young and in the age range of 18–24 years with a mean age of 21 years. most students (74%) started their menarche at a normal age range of 12–15 years. a relatively high dysmenorrhea (94.0 %) was observed among the participants. more than half of the respondents (55.0%) had irregular menstruation. conclusion: the authors concluded that the prevalence and morbidity of dysmenorrhea and menstrual irregularity were high but broadly comparable to those observed in similar developing countries. therefore, national health policies need to consider the health and educational impact of menstrual disorders on nursing students and develop the plan through a change in students’ lifestyle; moreover, school authorities and teachers need to be aware of the problems to provide psychological and academic support. keywords: morbidities, dysmenorrhea prevalence, menstrual disorders, nursing students, irregular menstruation 1. introduction menstrual disorders are an acute class of problem that young women face during their reproductive years, the most prominent gynecology sickness occurring between 20 and 25 years of age [1]. this not only affects their family life but also the day-to-day activities, how to cite this article: aisha mohammed adam, hammad ali fadlalmola, and huda khalafala mosaad (2020) “menstrual disorders among nursing students at al neelain university, khartoum state,” sudan journal of medical sciences, vol. 15, issue no. 2, pages 199–214. doi 10.18502/sjms.v15i2.7067 page 199 corresponding author: dr. hammad ali fadlelmola; nursing college, taibah university, saudi arabia email: hazzminno345@gmail.com received 12 march 2020 accepted 7 june 2020 published 30 june 2020 production and hosting by knowledge e aisha mohammed adam et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hazzminno345@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences aisha mohammed adam et al seldom affecting the quality and standard of life, as well the social and national economy [2]. menstruation is an episodic and repeated peeling of endometrium accompanied by loss of blood, it is a regular biological process in females of reproductive age that starts during puberty and may be accompanied by numerous symptoms [3]. it started as assessment means for normal development and the exclusion of irrational situations. the normal menstruation starts at the age of menarche which is ranged between 9 and 15 years [4]. the length of menstrual cycle is 28 to 32 days, duration of flow is 3 to 7 days, and the amount of blood flow per period is ≤ 80 ml [5]. menstrual disorders are one of the main difficulties facing women worldwide [6], greatly affecting the daily life activities of young women [7], and represents 1% of women’s gynecological appointment [6]. the common types of menstrual disorders are premenstrual syndrome (pms), dysmenorrheal (painful menstruation), amenorrhea (absence of menstruation), hypomenorrhea (light menstruation), menorrhagia (heavy flow)), metrorrhagia (intermenstrual bleeding), menometrorrhagia (prolonged excessive irregular and more frequent menstruation), polymenorrhea (frequent menstruation), and oligomenorrhea (infrequent menstruation) [8]. while most women experience menstrual discomfort or disruption during their reproductive life, more than 10% of young women are affected for up to three days due to monthly menstrual disorder and nearly 50% of them go through painful menstruation frequently. besides that, abnormal uterine bleeding, which is one of dangerous menstrual disorders, affects about 5–15% of women of reproductive age [9]. menstrual disorders are common health problems but with greater burden than any other gynecological complaints [10]. that stated, there is a very scant data on its effects on the health status and quality of life of young females and very little or no attention is given to it in developing countries [5, 11]. in spite of that, the global burden of disease (gbd) approach integrates valuation of morbidity and quality of life in identifying priorities a moment ago [6]. menstrual disorders, like other parts of sexual and reproductive health are not involved in the gbd estimations [12, 13]. nevertheless, these morbidities are reported as an important unmet area of reproductive health services for women worldwide including in developing countries [6]. researches in morbidity and risk factors of menstrual disorders are recommended and anxiously warranted and awaited by many researchers [6, 14]. students are the future of a country, so they must be qualified to become good future leaders and be responsible for improving the health and social and economic status of the country [15]. menstrual disorders are the common cause of anxiety morbidity in female life and can possibly have significant physical and emotional consequences among students [7, 16]; moreover the stress of education causes emotional and physical doi 10.18502/sjms.v15i2.7067 page 200 sudan journal of medical sciences aisha mohammed adam et al discomfort during menstruation and leads to absenteeism from school or college [7], affecting the educational performance and attendance of students and hindering their practical growth [17, 18]. khadir and colleagues studied menstrual disorders among nursing students and reported that they affected students’ academic performance in forms of lectures absence, loss of concentration and understanding, sleeping desire during lectures in addition to affecting their practical performance [17]. various risk factors have been suggested to be associated with dysmenorrhea such as hormonal imbalance, failure to cope with stress, greater bmi, younger age of menarche, nutritional deficiencies, smoking or exposure to passive smoking, and lack of physical activity. dysmenorrhea has negative physical and psychological consequences at school, university, leading to absence, academic underachievement, and undermining quality of life [19]. several studies have been published on the prevalence of dysmenorrhea among female students and especially among female medical students since they are under a lot of academic pressure and have to attend hospitals at difficult times. most of these studies reported high prevalence of dysmenorrhea among this category, it was found to be more than three quarters among technical secondary schools’ girls, and medical college students [20–25]. although menstrual disorders among students have been studied in various countries [26, 27], to the best of our knowledge, very little information on the topic is available in sudan [28]. 2. materials and methods 2.1. study design this descriptive cross-sectional institutional-based study was conducted at the al neelain university, faculty of nursing to determine the nature of morbidity for menstrual disorders among nursing students and their effect on students’ educational activities. about 420 female nursing students from different class levels (from level one to level four) registered in the academic year 2018–2019 were included in the study; 25% of them had menstrual disorders with 5% error and 95% confidence interval calculated using internet sample size; 200 sample size was estimated and recruited in clusters to participate according to their proportional representation in the class levels. doi 10.18502/sjms.v15i2.7067 page 201 sudan journal of medical sciences aisha mohammed adam et al 2.2. data collection a self-administered, structured, questionnaire in english was designed for the study. it was translated to arabic to ensure the harmony in understanding; then, a pilot study was conducted with 12 students, three students randomly selected from each of the four class levels and were analyzed to determine the tool-reliability. self-administered questionnaires were distributed to be filled by the nursing students in their break which took them about 15 min to respond. 2.3. data analysis data were clean coded and interred in spss, version 20, and analyzed using frequencies and percentages. bivariate analysis of data with a chi-squared test of significance was done where appropriate, p < 0.05 was considered statistically significant. 2.4. ethical considerations the study was approved by the ethical committeeobtained and all participants gave their consent before participating in the study. 3. results all students included in this study are young, aged between 18 and 24 years with a mean age of 21 years. most of them were prepared for menarche (the first onset of menstruation) period by their mothers and teachers as shown in table 1. menarche varies between the populations due to diverse factors such as nutritional, geographical, and environmental conditions. in this study, most of the respondents (74%) began their menarche at the normal age range of 12–15 years, with a mean age of 13.5 years as shown in table 2. with regard to the number of days of the menstrual cycle, we found that in the current study, most respondents had normal menstrual duration of 4 to 7 days. in the present study, more than half of our respondents (55.0%) had irregular menstruation, while dysmenorrhea was relatively very high (94.0%) as shown in table 2. in this study most respondents reported absence from study for a one to three days due to menstrual problems. concerning reasons of absentees from the study, the third (32.89%) of the respondents confirmed very painful period and 13.16% suffered painful doi 10.18502/sjms.v15i2.7067 page 202 sudan journal of medical sciences aisha mohammed adam et al table 1: background characteristics (n = 149) frequency percentage valid percentage cumulative percentage age group < 18 years 5 3.9 3.9 3.9 18–20 years 82 64.1 64.1 68.0 21–24 years 37 28.9 28.9 96.9 > 24 years 4 3.1 3.1 100.0 total 128 85.0 85.0 missing value 21 15.0 15.0 total 149 100.0 100.0 student educational level level one 27 21.1 21.1 21.1 level two 24 18.8 18.8 39.8 level three 42 32.8 32.8 72.7 level four 35 27.3 27.3 100.0 total 128 85.0 85.0 missing value 21 15.0 15.0 total 149 100.0 100.0 preparation for the menarche (first menstruation) yes 119 79.9 79.9 79.9 no 30 20.1 20.1 100.0 total 149 100.0 100.0 menstruation information source mother and grand mother 54 36.2 45.4 45.4 older sisters 16 10.7 13.4 58.8 books and magazines 5 3.4 4.2 63.0 mass media 6 4.0 5.0 68.1 teachers 38 25.5 31.9 100.0 total 119 79.9 100.0 heavy period with vomiting that hindered them from attending their study as shown in figure 1. in the present study, correlations between absentness from study and different menstrual problems were presented as shown in table 3. 4. discussion while much data concerning menstrual problems are available in the other countries [26, 27, 29], very scant such data among nursing students are available in sudan [30]. doi 10.18502/sjms.v15i2.7067 page 203 sudan journal of medical sciences aisha mohammed adam et al table 2: menstrual history (n = 149) frequency percentage valid percentage cumulative percentage first menses < 9 years old 0 0 0 0 9–11 years old 4 2.7 2.7 2.7 12–15 years old 107 71.8 72.2 74.9 > 15 years old 38 25.5 26.1 100.0 total 149 100.0 100.0 menstrual duration < 3 days 11 7.4 7.4 7.4 4–7 days 133 89.3 89.3 97.3 > 7 days 4 2.7 2.7 100.0 total 148 99.3 100.0 missing system 1 0.7 total 149 100.0 the length of the cycle 28–32 days 76 51.0 51.0 51.0 < 28 or > 32 days 73 49.0 49.0 100.0 total 149 100.0 100.0 regularity during the last 12 months regular 67 45.0 45.0 45.0 irregular 82 55.0 55.0 100.0 total 149 100.0 100.0 presence of dysmenorrhea there is dysmenorrhea 140 94.0 94.0 94.0 no dysmenorrhea 9 6.0 6.0 100.0 total 149 100.0 100.0 figure 1: reasons of absentees from study in faculty doi 10.18502/sjms.v15i2.7067 page 204 sudan journal of medical sciences aisha mohammed adam et al table 3: correlations between absentness from study and different menstrual problems (n=149) absentees from study age of menarche menstrual duration length of the cycle regularity presence of dysmenorrhea absentees from study pearson correlation 1 –0.032 –0.087 –0.185∗ 0.090 0.282∗∗ sig. (2-tailed) 0.697 0.293 0.024 0.274 0.001 n 149 149 149 149 149 149 age of menarche pearson correlation –0.032 1 –0-.136 0.020 –0.022 0.021 sig. (2-tailed) 0.697 0.098 0.809 0.785 0.800 n 149 149 149 149 149 149 menstrual duration pearson correlation –0.087 –0.136 1 0.110 0.070 –0.175∗ sig. (2-tailed) 0.293 0.098 0.182 0.398 0.033 n 149 149 149 149 149 149 length of the cycle pearson correlation –0.185∗ 0.020 0.110 1 0.075 –0.129 sig. (2-tailed) 0.024 0.809 0.182 0.366 0.118 n 149 149 149 149 149 149 regularity pearson correlation 0.090 –0.022 0.070 0.075 1 –0.058 sig. (2-tailed) 0.274 0.785 0.398 0.366 0.486 n 149 149 149 149 149 149 presence of dysmenorrhea pearson correlation 0.282∗∗ 0.021 –0.175∗ –0.129 –0.058 1 sig. (2-tailed) 0.001 0.800 0.033 0.118 0.486 n 149 149 149 149 149 149 *correlation is significant at 0.05 level (2-tailed) **correlation is significant at 0.05 level (2-tailed) so, our study aimed to determine the morbidities of menstrual disorders on nursing students. the finding of this study is in accordance with that of many other studies that revealed mothers are the main source of information on menarche period for young females aged [31, 32, 34]. this is partially in accordance with others who found that 75% received this information from their relatives such as mother and sister [35, 36],and differs from many studies that reported school nurse were the first source of information [37], friends were the most important source of information [38]. a study by singh et al. revealed that the major source of information was media (television, radio) [31]. menarche is the key of women’s physical development during adolescence when they become capable to reproduce; menarche varies between populations according to various factors such as nutritional, geographical, and environmental conditions [39, 40]. doi 10.18502/sjms.v15i2.7067 page 205 sudan journal of medical sciences aisha mohammed adam et al most females experience at an age of 9 to 15 year [4]. however, age at menarche has generally declined in most industrialized nations and is reported at 13 years with 0.5 year deviations between countries, the decreased age of menarche is important because of its potential impact on early matureness in girls’ behaviors [41]. in our study, most of our respondents (74%) started their menarche at a normal age range of 12–15 years, with a mean age of 13.5 years, which is comparable with other reports in khartoum schools girls in sudan [30], 13.85 year in egypt [42, 43], 13.40 years in nigeria [29], and in 13.91 years in mozambique [26]. however, 25.5% of our studied students had delayed menarche at age more than 15 years in consistent with the study conducted in kassala, eastern sudan that reported a delayed menarche age [44] contradicting most industrialized nations [41]. this delay in menarche may be due to nutritional, geographical, and environmental conditions [39, 40], particularly in sudan . in the current study, most participants had normal menstrual duration (4–7 days), supported by the study of menoufiya university, egypt [45]. about half of them had cycle with abnormal length either oligo or polymenorrhea, this finding is supported by a study in lebanon [46], egypt [45], and saudi arabia [46] and disagrees with the study carried out by neamat et al. in which the majority of respondents had normal menstrual cycle. (31) polymenorrhea is stated as the top reason for gynecologic visits [5] and may put women at risk of anemia [27, 47, 48]. moreover, it can result in poor menstrual hygiene and increased risk of infection since many young girls may not be able to afford costly sanitary pads to take care of the extra days especially when they are on campus [21, 49]. in sudan, especially in the capital of khartoum, most nursing students came from various districts. more than half of the respondents (55.0%) in this study had irregular menstruation, indeed the prevalence of irregular menstrual cycle is varying within different students’ studies. our finding is observed to be consistent to the finding of the indian college students the prevalence rate of 57.1% [50] , relatively higher than the findings of the study of school girls in kassala, eastern sudan, turkey university students, and saudi nursing students with the prevalence rates of 25.1%, 31.2%, and 36.4%, respectively [44, 51, 52]. in contrast, it is relatively lower than the recent finding of the palestinian study that reached 74.1% [53]. irregular menstruation is a factor that increases the rate of emotional and psychological stresses for the female and over prolonged periods can lead to development of infertility, endometrial hyperplasia, and problems due to prolonged anovulation, besides the deterioration in the quality of life and being the leading cause for clinical visits [54, 55]. doi 10.18502/sjms.v15i2.7067 page 206 sudan journal of medical sciences aisha mohammed adam et al dysmenorrhea was relatively high (94.0%) in our respondents; this finding is in line and fits within the published reported values from developing and developed countries as in saudi, egypt, and oman nursing students which is about 94.0% [31, 43, 52, 56– 58].however, it is relatively higher than found in the studies in india, kassal eastern sudan, palestine, ethiopia, australia, and nigeria that reached 87.87%, 85.1%, 80%, and (76%), respectively [44, 53, 59–62]. the literature has suggested various risk factors for dysmenorrhea hormonal imbalance, namely, failure to cope with stress, greater bmi, younger age of menarche, nutritional deficiencies, smoking or exposure to passive smoking, and lack of physical activity [47, 63, 64]. since our respondents were under a lot of academic pressure and had to attend the clinical training and practice in the hospital which is more stressful for them; in addition to that most of them are living away from their families that can expose them to nutritional deficiencies and possible lack of activities. our finding is answerable and supported by many studies that reported high prevalence of dysmenorrhea among medical students [20–22]. in this study, most respondents reported absence from the study for a period ranging between one and three days due to menstrual problems; this is similar to the findings of the studies of kassala, eastern sudan, kingdom of saudi arabia, amharaethiopia, nigeria, and india [5, 44, 52, 60, 65–68]. in contrasts, our finding is relatively higher compared to the egyptian and australian findings [31, 69]. our respondents’ absenteeism seems to be due to the high prevalence of dysmenorrhea which is declared as having negative physical and psychological consequences leading to school/university absence, academic underachievement, and undermined quality of life [47, 63, 70].the respondents’ absence from study in the current research is significantly associated with the presence of dysmenorrhea and the length of the cycle, similar to the finding of a study in nigeria [67]. concerning reasons of absentees from the study, one-third (32.89%) of the respondents confirmed very painful period, and 14.47% suffered painful heavy period accompanied with vomiting, hindering them from attending their study. this finding is supported by the literature that evident painful menses is an important health problem in university female students and has a negative effect on their academic performance [66]. 5. conclusion the authors conclude that the prevalence and morbidity of dysmenorrhea and menstrual irregularity were high but broadly comparable to those observed in similar developing doi 10.18502/sjms.v15i2.7067 page 207 sudan journal of medical sciences aisha mohammed adam et al countries. therefore, national health policies need to consider the health and educational impact of menstrual disorders on nursing students and develop the plan through a change in students’ lifestyle. moreover, school authorities and teachers need to be aware of the problems to provide psychological and academic support. besides, health authorities who are working in the university’s student clinic should design a health education program to organize the college community to adjust students’ behaviors. further research into risk factors for menstrual disorders and their morbidity is recommended. acknowledgments the authors are thankful to all nursing students who participated in this research and convey great thanks to the faculty of nursing, al neelain university. funding authors declared that no funding was provided for this study. conflict of interest authors declare that there is no conflict of interest. availability of data and material the study materials are available with the corresponding author on request. references [1] burnett, m. a., antao, v., black, a. 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(2017). prevalence of dysmenorrhea and its effects on school performance: a cross-sectional study. journal of women’s health care, vol. 6, no. 2, p. 361. doi 10.18502/sjms.v15i2.7067 page 213 sudan journal of medical sciences aisha mohammed adam et al [67] titilayo, a., agunbiade, o. m., banjo, o., et al. (2009). menstrual discomfort and its influence on daily academic activities and psychosocial relationship among undergraduate female students in nigeria. tanzania journal of health research, vol. 11, no. 4, pp. 181–188. [68] dambhare, d. g., wagh, s. v., and dudhe, j. y. (2012). age at menarche and menstrual cycle pattern among school adolescent girls in central india. global journal of health science, vol. 4, no. 1, pp. 105–111. [69] parker, m. a., sneddon, a. e., and arbon, p. (2010). the menstrual disorder of teenagers (mdot) study: determining typical menstrual patterns and menstrual disturbance in a large population-based study of australian teenagers. bjog, vol. 117, no. 2, pp. 185–192. [70] ballagh, s. a. and heyl, a. (2008). communicating with women about menstrual cycle symptoms. the journal of reproductive medicine, vol. 53, no. 11, pp. 837–846. doi 10.18502/sjms.v15i2.7067 page 214 introduction materials and methods study design data collection data analysis ethical considerations results discussion conclusion acknowledgments funding conflict of interest availability of data and material references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9284 production and hosting by knowledge e editorial diagnosis of covid-19 in countries with limited health resources – blood markers versus rrt–pcr imad fadl-elmula and rayan khalid department of clinical genetics, assafa college, khartoum, sudan orcid: imad fadl-elmula: https://orcid.org/0000-0003-3191-9485 since the outbreak of coronavirus disease 2019 (covid-19) in china in december 2019 and its rapid worldwide spread, the real-time reverse transcription–polymerase chain reaction (rrt–pcr) test has become the gold standard for the etiological diagnosis of covid-19 infection [1]. however, for countries with limited health resources, rrt–pcr test is relatively expensive and requires specialized laboratories and highly trained personnel [2]. recent studies have shown that some routine blood test markers might help in the diagnosis of covid-19 infection in suspected patients with a very high predictive value (>95%) [3]. this editorial aims to assess the role of blood markers in diagnosing covid19 infection as an alternative for rrt–pcr in countries with limited health resources by performing online search in electronic databases such as medline, scopus, and web of science, using keywords such as “blood markers’ role in diagnosis of covid 19.” additionally, the references of identified documents were cross-checked for detecting additional studies. overall, 203 articles were found using the aforementioned search criteria, of which 200 were excluded after scrutinization by the authors. only three studies were finally selected and used in the present editorial based on the comparison of the final diagnosis reached by rrt–pcr and the high predictive value of blood markers. another reason for excluding most studies was that they focused on the disease outcome rather than the diagnostic value. santotoribio et al. (2019) evaluated the role of six routine blood tests (blood lymphocyte, eosinophil count, ferritin serum level, lactate dehydrogenase (ldh), c-reactive protein (crp), and d-dimer) in diagnosing cases of suspected covid-19 [4. the study showed that 91% of patients infected with covid-19 met one or more of these biomarker criteria. thus, it is possible to rule out coronavirus infection with a high degree of probability in patients who meet none of these criteria. they concluded that these how to cite this article: imad fadl-elmula and rayan khalid (2021) “diagnosis of covid-19 in countries with limited health resources – blood markers versus rrt–pcr,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 143–144. doi 10.18502/sjms.v16i2.9284 page 143 corresponding author: imad fadl-elmula; department of clinical genetics, assafa college, khartoum, sudan email: imad@fadl-elmula.com received 2 may 2021 accepted 22 june 2021 published 30 june 2021 production and hosting by knowledge e imad fadl-elmula and rayan khalid. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:imad@fadl-elmula.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences imad fadl-elmula and rayan khalid markers could very well be used as a tool for diagnosing and screening suspected covid-19 in adult patients at hospital admission. another study by ferrari et al. compared the routine blood analysis of the plasma levels of white blood cells (wbcs), platelets, crp, aspartate aminotransferase (ast), alanine aminotransferase (alt), γ-glutamyl transpeptidase (ggt), alkaline phosphatase (alp), and ldh of 207 patients who had tested positive for covid-19 using the rrt–pcr test [5]. the results showed statistically significant differences in the plasma levels of wbc, crp, ast, alt, and ldh between those who were positive and those who were negative at the genetic testing. using rrt–pcr as the gold standard, almost 70% of the patients could be classified as covid-19-positive or -negative on the basis of their hematological parameters. the last study was conducted in sudan under the supervision of the authors of this editorial [6]. the study included 56 patients who had all tested positive for covid19 using rrt–pcr. for all patients, the complete blood count (cbc), crp, erythrocyte sedimentation rate (esr), total protein, albumin, total and direct bilirubin, ast, alt, alp, urea, creatinine, and electrolytes were measured upon admission. in this study, intense statistical analyses were done using the spss program. with a significance level of p ≤ 0.05 and confidence limits (cls) of 95%, group comparison was tested using mann– whitney test for quantitative variables while qualitative variables were tested using chisquare (fisher exact) test. the receiver operating characteristic/area under the curve (roc/auc) was used to obtain the true positive, and false positive predictive values were calculated using the best cutoff values. the roc/auc ensured the appellant result of lymphocytes (%) as a predictor with 92% auc, 90% neutrophils, 95.8% esr, 89% crp, and 86.8% wbcs. about 98% of the suspected individuals diagnosed with covid-19 using roc showed a cutoff of <=21.8 for lymphocytes (%), >=67.7 for neutrophils, >=37.5 for esr, >=6.2 for crp, and >=7.15 for wbcs. the applicable value of these studies based on the fact that hospitals in developing countries, including the ones with limited health resource, have the facilities of automated analyzers that can test for these inexpensive highly sensitive and specific blood markers in <60 min. if physicians combine the blood markers with the medical history and imaging tests, they can very well diagnose and/or screen patients suspected of covid-19. in addition to that, using blood markers in diagnosis may be crucial in detecting a new genetic variant of coronavirus, that is, the indian strain in which molecular testing encounters a high percentage of false-positive/negative cases. doi 10.18502/sjms.v16i2.9284 page 144 sudan journal of medical sciences imad fadl-elmula and rayan khalid references [1] lippi, g., mattiuzzi, c., bovo, c., et al. (2020). current laboratory diagnostics of coronavirus disease 2019 (covid-19). acta biomedica, vol. 91, no. 2, pp. 137–145. [2] cohen, j. and kupferschmidt, k. (2020). countries test tactics in ‘war’ against covid19. science, vol. 367, no. 6484, pp. 1287–1288. [3] velavan, t. p. and meyer, c. g. (2020). mild versus severe covid-19: laboratory markers. international journal of infectious diseases, vol 95, pp. 304–307. [4] santotoribio, j. d., nuñez-jurado, d., and lepe-balsalobre. e. (2020). evaluation of routine blood tests for diagnosis of suspected coronavirus disease 2019. clinical laboratory, vol. 66, no. 9. [5] ferrari, d., sabetta, e., ceriotti, d., et al. (2020). routine blood analysis greatly reduces the false-negative rate of rt-pcr testing for covid-19. acta bio medica, vol. 91, no. 3, e2020003. [6] ibnouf, a.-a. o., khalil, m. h., khalid, r., et al. (2020). blood markers (lymphocyte percentages, neutrophils, crp and esr) can help in prioritizing rrt-pcr test for suspected covid-19 patients in countries with limited health resources. pan african medical journal, vol. 37, p. 331. doi 10.18502/sjms.v16i2.9284 page 145 references sudan journal of medical sciences volume 12, issue no. 1, doi 10.18502/sjms.v12i1.855 production and hosting by knowledge e research article aetiology of vertigo as seen at the federal medical center lokoja, north central nigeria stephen agbomhekhe ogah consultant otolaryngologist, head, and neck surgeon department of surgery, federal medical centre lokoja, kogi state, nigeria. p.o. box 1256 abstract background: human beings are able to maintain their balance from a combination of proprioceptive, graviceptive, visual and the vestibular inputs integrated by the central nervous system. hence, symptoms of imbalance can arise whenever there is a defect either in these peripheral sensors or the modulating central nervous system. the prevalence of vertigo is 20-30% and it is a major health issue all over the world. objectives: to determine the prevalence and causes of vertigo in federal medical center lokoja, north central nigeria. materials and methods: this is a 3-year retrospective hospital based study undertaken in the ent unit of the department of surgery federal medical centre, lokoja. from the hospital medical records, patients’ files were retrieved. data about their age, sex, occupation, presentation, treatment modality and outcome were extracted, studied and analyzed. results: three thousand two hundred and fourteen patients were seen and 65 of them had vertigo with a prevalence of 2.0%. fifteen files had incomplete information and were not include in the study. the remaining 50 patients’ files that were reviewed, consisted of 32 males (64%) and 18 females (36%). male to female ratio was 1.8:1 and a mean age of 24.8 years. bengin paroxysmal positional vertigo (bppv) 22(44%) was the commonest aetiology found followed by meniere’s disease 8(16%), trauma 7(14%) and vestibular neuronitis 5(10%) respectively. keywords: aetiology, vertigo, bppv, meniere’s disease how to cite this article: stephen agbomhekhe ogah, (2017) “aetiology of vertigo as seen at the federal medical center lokoja, north central nigeria,” sudan journal of medical sciences, vol. 12 (2017), issue no. 1, 19–24. doi 10.18502/sjms.v12i1.855 page 19 corresponding author: stephen agbomhekhe ogah; email: stephenogah@yahoo.com received: 15 december 2016 accepted: 20 february 2017 published: 28 may 2017 production and hosting by knowledge e stephen agbomhekhe ogah. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:stephenogah@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e مستقبالت تكامل من مزيج من توازنهم على الحفاظ على قادرون البشر الخلفية: الجهاز قبل من والدهليزية البصرية والمدخالت الحسية الجاذبية الحسية، الوضعية العصبي المركزي. وبالتايل، يمكن أن تنشأ أعراض عدم التوازن كلما كان هناك خلل إما يف وهي ٪٢٠-٣٠ هو الدوار إنتشار المركزي. العصبي الجهاز أو الطرفية اإلستشعار أجهزة قضية صحية شائعة يف جميع أنحاء العالم. وسط شمال لوكوجا، االتحادي الطبي المركز يف الدوار وأسباب إنتشار لتحديد األهداف: نيجيريا. المواد والطرق: هى دراسة إستطالعية بأثر رجعي لثالث سنوات أجريت يف وحدة األنف واألذن والحنجرة من قسم الجراحة بالمركز الطبي اإلتحادي، لوكوجا. تم إسترجاع ملفات وتحليل ودراسة إستخراج تم بالمستشفى. الطبية السجالت من الدراسة قيد المرضى البيانات المتعلقة بعمرهم وجنسهم ومهنهم وعرضهم وطريقة عالجهم ونتائجه. دوار لديهم منهم ٦٥ كان مريضاً عشر وأربعة ومائتان آالف ثالثة مجموع من النتائج: بنسبة إنتشار ٢٫٠٪. وكان خمسة عشر ملفاً غير مكتملة المعلومات ولم تدرج يف الدراسة. أما ملفات المرضى الخمسين المتبقية التي تمت مراجعتها، فتتألف من ٣٢ ذكر (٦٤٪) و ١٨ أنثى (٣٦٪). وكانت نسبة الذكور إىل اإلناث ١٫٨: ١ ومتوسط عمر ٢٤٫٨ سنة. كان الدوار النوىب الموضعى الحميد المسبب األكثر شيوعاً ىف ٢٢ (٤٤٪) من الحاالت ثم مرض منير ٨ (١٦٪)، والصدمة ٧ (١٤٪) وإلتهاب العصب الدهليزي ٥ (١٠٪) على التوايل. 1. introduction vertigo is an illusion of rotatory movement of either the patient or his/her environment [1]. the causes can be summarized using the word ’vertigo’ itself as a mnemonic, where ’v’ stands for vestibular diseases like vestibular neuronitis, ’e’ stands for endocrine diseases like hypergycaemia in diabetes. ’r’ stands for receiving drugs, such as ototoxic drugs like the aminoglycosides, antimalarias like quinine and chloroquinine, anticancers like cisplatin etc. ’t’ stands for trauma of any kind affecting the vital areas. ’i’ stands for infections like labyrinthinitis, vestibular neuronitis, petrositis and otitis media. ’g’ stands for growth (neoplasm) such as acoustic neuromas, glomus tumours and ’o’ stands for ocular diseases, other diseases like demyelinating diseases like multiple sclerosis and the non-specific cochleovestibulopathies. at clinic presentation, other symptoms may be necessary in making the diagnosis of the aetiology [2]. for example, cochlear symptoms like tinnitus and hearing loss may suggest that doi 10.18502/sjms.v12i1.855 page 20 sudan journal of medical sciences production and hosting by knowledge e the pathology is in the labyrinthine or viii cranial nerve [3]. symptoms like diplopia, dysarthria and facial weakness may suggest brain stem causes. drug history, duration, co-morbidities and previous surgeries are also very important in making the diagnosis [3]. in benign paroxysmal positional vertigo, there is usually a latent phase and the vertigo only last for a few seconds (5-10secs), in the migraine type, it usually can last from some minutes to a few hours. whereas in meniere’s disease, it may last for hours and in vestibular neuronitis it usually lasts for days [4]. the prevalence of vertigo ranges from 20-30% in the usa [5], 4.9-21% in uk [6], 5% in germany [7], 18.6% and 24.6% in two separate studies involving elderly patients in south western nigeria [8, 9]. 2. materials and methods this is a 3-year retrospective hospital based study undertaken in the ent unit of the department of surgery federal medical centre, lokoja. from the hospital medical records, patients’ files were retrieved. data about their age, sex, occupation, presentation, period of illness treatment modality and outcome were extracted, studied and analyzed. 3. results three thousand two hundred and fourteen patients were seen and 65 of them had vertigo with a prevalence of 2.0%. fifteen files had incomplete information and were not include in the study. the remaining 50 patients’ files that were reviewed, consisted of 32 males (64%) and 18 females (36%). male to female ratio was 1.8:1 and a mean of 24.8 years. twenty five patients had their vertigo occurring within seconds consisting 50% of the study population, 12(24%) were in minutes, 10(20%) occurring in hours and 3(6%) in days (table 2). majority of the patients (44%) suffered from bppv followed by meniere’s disease (16%), trauma (14%), vestibular neuronitis (10%) and (8%) of unknown etiology. migraine, ototoxicity, diabetes and vertebrobasillar insufficiency were the least aetiologies found in this study (table 3). 4. discussion vertigo is a symptom associated with so many ear diseases but usually subsides when the causative disease is given the proper treatment. one should not be surprised to find it in association with diseases as simple as impacted wax, otitis media, otitis externa et cetera [10]. male preponderance was notice in this study which is probably due to the increase trauma cases in our hospital located along okene/abuja high way. vertigo was noticed to be more common in males in their fifth decade of life although a study doi 10.18502/sjms.v12i1.855 page 21 sudan journal of medical sciences production and hosting by knowledge e age group male female total (%) 0-10 0(0.0%) 0(0.0%) 0(0.0%) 11-20 2(4.0%) 1(2.0%) 3(6.0%) 21-30 5(10.0%) 3(6.0%) 8(16.0%) 31-40 3(6.0%) 2(4.0%) 5(10.0%) 41-50 11(22.0%) 6(12.0%) 17(34.0%) 51-60 6(12.0%) 3(6.0%) 9(18.0%) 61-70 3(6.0%) 2(4.0%) 5(10.0%) 71-80 2(4.0%) 1(2.0%) 3(6.0%) total 32(64.0%) 18(36.0%) 50(100%) t 1: age and gender distribution of patient with vertigo. duration of vertigo number of patients % seconds 25 50.0 minutes 12 24.0 hours 10 20.0 days 3 6.0 total 50 100.0 t 2: duration of the vertigo. by adegbiji et al [9] who found it more in females with a bimodal age distribution. however, the lower modal age is similar to that found in this study. vertigo prevalence found in this study is 2.0% and this is low when compared to other studies done in time past [11–13]. this low prevalence may be due to lack of awareness by the communities where the hospital is located or patients perhaps deciding to use alternative traditional medication due to the level of growing poverty amongst our people. the duration of most vertigo lasted for a few seconds and only few of them lasted for some days which further support the diagnosis of bppv. these findings are in agreement with what has been reported by other researchers [13–15]. aetiology of vertigo number % bppv 22 44.0 meniere’s disease 8 16.0 trauma 7 14.0 vestibular neuronitis 5 10.0 unknown causes 4 8.0 migraine 1 2.0 diabetes 1 2.0 ototoxicity 1 2.0 cervical vertigo 1 2.0 total 50 100.0 t 3: aetiologies of the vertigo. doi 10.18502/sjms.v12i1.855 page 22 sudan journal of medical sciences production and hosting by knowledge e 5. conclusions benign paroxysmal positional vertigo was found to be the commonest aetiology of vertigo in this study and that early referral of patients to the ent specialist is advised for cost effective treatment. 6. ethical consideration i confirm that i have read the journal’s position on ethical issues concerning this publication and i wish to declare that this manuscript is consistent with those guidelines. 7. conflict of interest none to be declare. 8. funding and support this work was done as part of scientific programs of the department of surgery federal medical center, lokoja, kogi state, nigeria and that there was no financial support to be acknowledge. references [1] j. p. pattern, “balance disorders and vertigo,” in scott-browns otolaryngology & head-neck surgery, vol. 3, pp. 3932–3933, hodder arnold, 3, 7th edition, 2008. [2] m. yin, k. ishikawa, w. h. wong, and y. shibata, “a clinical epidemiological study in 2169 patients with vertigo,” auris nasus larynx, vol. 36, no. 1, pp. 30–35, 2009. [3] j.-m. guilemany, p. martínez, e. prades, i. sañudo, r. de españa, and a. cuchi, “clinical and epidemiological study of vertigo at an outpatient clinic,” acta otolaryngologica, vol. 124, no. 1, pp. 49–52, 2004. [4] n. chawla and j. s. olshaker, “diagnosis and management of dizziness and vertigo,” medical clinics of north america, vol. 90, no. 2, pp. 291–304, 2006. [5] h. k. neuhauser, “epidemiology of vertigo,” current opinion in neurology, vol. 20, no. 1, pp. 40–46, 2007. [6] b. gopinath, c. m. mcmahon, e. rochtchina, and p. mitchell, “dizziness and vertigo in an older population: the blue mountains prospective cross-sectional study,” clinical otolaryngology, vol. 34, no. 6, pp. 552–556, 2009. [7] o. a. sogebi, a. j. ariba, t. o. otulana, and b. s. osalusi, “vestibular disorders in elderly patients: characteristics, causes and consequences,” pan african medical journal, vol. 19, 2014, article no. 146. doi 10.18502/sjms.v12i1.855 page 23 sudan journal of medical sciences production and hosting by knowledge e [8] o. l. akeem, “prevalence, clinical and life-style correlate of dizziness among the community elderly from the ibadan study of ageing,” ear nose throat j, vol. 93, pp. e37–e44, 2014. [9] w. a. adegbiji, s. k. aremu, b. s. alabi, c. c. nwawolo, and o. a. olajuyin, “vertigo presentation in developing country, nigeria,” american journal of research communication, vol. 2, no. 5, pp. 258–271, 2014. [10] s. a. ogah, “the prevalence of ear wax among the elderly in lokoja, nigeria,” international journal of academic research part a, vol. 6, no. 6, pp. 49–50, 2014. [11] m. karatas, “central vertigo and dizziness: epidemiology, differential diagnosis, and common causes,” neurologist, vol. 14, no. 6, pp. 355–364, 2008. [12] s. isaradisaikul, n. navacharoen, c. hanprasertpong, j. kangsanarak, and r. panyathong, “causes and time-course of vertigo in an ear, nose, and throat clinic,” european archives of oto-rhino-laryngology, vol. 267, no. 12, pp. 1837–1841, 2010. [13] i. shami and a. al sanosi, “causes of vertigo in saudi patients seen at tertiary teaching hospital,” journal of taibah university medical sciences, vol. 6, no. 1, pp. 26–32, 2011. [14] t. o. adedeji, j. e. tobih, and a. o. olaosun, “peripheral vestibular disorders and its management in a nigerian teaching hospital,” world journal of medicine and medical science, vol. 2, no. 2, pp. 1–11, 2014. [15] o. g. b. nwaorgu, p. a. onakoya, and m. a. usman, “cervical vertigo and cervical spondylosis-a need for adequate evaluation,” nig journal of medicine, vol. 12, no. 3, pp. 140–144, 2003. doi 10.18502/sjms.v12i1.855 page 24 introduction materials and methods results discussion conclusions ethical consideration conflict of interest funding and support references sudan journal of medical sciences volume 12, issue no. 2, doi 10.18502/sjms.v12i2.921 production and hosting by knowledge e case report breast cancer case using tamoxifen during pregnancy: a case report and literature review kamal eldein h. mohamed1 and sarah mirghani2 1associate professor of clinical oncology, faculty of medicine, university of khartoum 2clinical oncologist abstract this is a case of 32 years old nulliparous female who was diagnosed in november 2004 as a case of carcinoma of the right breast , luminal a , (estrogen receptor positive progesterone receptor negative, her 2 negative, ki67 10 %), poorly differentiated invasive ductal cancer, tnm stage,t2 n0 mo. she had a wide local excision and axillary clearance. as she is a case of low risk early stage luminal a breast cancer; she was not given chemotherapy, instead she had a course of external irradiation and was put on tamoxifen (astra zeneca, 20 mg daily), and was advised not to get pregnant during this treatment, but she got pregnant and delivered normally a healthy infant, although tamoxifen is potentially teratogenic. keywords: breast cancer, tamoxifen, teratogenic effects هذه هى حالة دراسة المراة تبلغ ٣٢ عاما لم تحمل من قبل تم تشخيصها يف نوفمبر ٢٠٠٤ مستقبالت سلبية االستروجين، مستقبالت (إيجابية ،a اللمعية األيمن، الثدي بسرطان التمييز،تمرحل فقير الغازى القنوات سرطان (٪١٠ ki٦٧ ، her٢ سلبية ، البروجسترون mnt ، t٢ ٠m n٠. اجرى لها استئصال موضعى واسع وتنظيف لإلبطين. وبما انها حالة منخفضة المخاطر يف وقت مبكر مرحلة اللمعية من سرطان الثدي. لم تحصل على العالج (أسترا تاموكسيفين على ووضعت الخارجي التشعيع من دورة اعطيت بل الكيميايئ، زينيكا، ٢٠ ملغ يوميا)، ونصحت بعدم الحمل أثناء هذا العالج، لكنها حصلت على الحمل يكون أن يحتمل التاموكسيفين أن من الرغم على صحيحا، طفل طبيعيا وووضعت مسخيا. 1. introduction breast cancer is the commonest cancer among females worldwide. in sudan it’s the leading cancer in females. it forms (30–34%) of all female cancers, 40% are below the how to cite this article: kamal eldein h. mohamed and sarah mirghani, (2017) “breast cancer case using tamoxifen during pregnancy: a case report and literature review,” sudan journal of medical sciences, vol. 12 (2017), issue no. 2, 108–118. doi 10.18502/sjms.v12i2.921 page 114 corresponding author: kamal eldein h. mohamed; email: kamaleldein4@yahoo.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e kamal eldein h. mohamed and sarah mirghani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:kamaleldein4@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e age of 45years, i.e. within the reproductive age, this reflects our population pyramid [1]. carcinoma of the breast is the most common malignancy occurring during pregnancy [2]. tamoxifen is a non-steroidal drug which has estrogenic and an anti-estrogenic effect. it stimulates ovulation and has a teratogenic effect when used during pregnancy that has been established in animals and humans [3]. 2. case report a thirty two years old married patient with good performance status, and no co morbidities presented to us in november 2004 with a right breast central 3x3cm ,firm lump, and no other abnormality on clinical examination. she has no family history of breast cancer, her cbc, ue and lft and ct chest and ct abdomen and pelvis were normal. she had a truecut needle biopsy, positive for a poorly differentiated invasive ductal carcinoma, grade three. breast conservative surgery and a xillary clearance were performed, and the histopathology report showed (2.5 x 2 cm) mass, with 12 out of 12 reactive lymph nodes, grade iii invasive ductal cancer, negative margins, more than 1.5 cm in all directions, with negative skin, nipple, and no lymph vascular invasion. er positive (6/8), pr positive (5/8), her2 negative, ki 67% = 10 % as she has a luminal a, low risk stage (t2 n0 m0) breast cancer. she was given a course of external irradiation (40 gy/15 fractions) by co60 excluding the axilla, and (tamoxifen 10 mg twice per day, astra zeneca). she and her husband were counseled, and she was advised not to get pregnant during this treatment and to use an intrauterine contraceptive device (iucd). the risks of getting pregnant during this treatment were well explained. she was advised to come for regular follow up, and in case she gets pregnant to stop tamoxifen and come immediately for follow up. she remained well, until september 2011, when she was seen at an antenatal clinic, where a four months pregnancy was confirmed and was therefore referred to us. abdominal ultrasound showed 17weeks gestation with no abnormality, (edd = 10th feb 2012), and no evidence of metastases. clinically there was no evidence of local recurrence or metastases. her laboratory investigations were normal. after counseling the couple, they were very keen to keep the pregnancy and accepted the consequences, as she is a nulliparous and they were married for 4 years. so the pregnancy was maintained, and she was followed with regular ultrasound of the abdomen. amniocentesis testing was not a available, she delivered normally a healthy infant on the 15th feb 2012. she was then followed regularly; she remained well with no evidence of disease when she was last seen at the follow up clinic in march 2017. doi 10.18502/sjms.v12i2.921 page 115 sudan journal of medical sciences production and hosting by knowledge e 3. discussion breast cancer is the commonest cancer in sudanese women [1]. during pregnancy tamoxifen and its metabolites affects the rapidly growing fetal tissue. it leads to birth defects in 20% of exposures [2–9]. astra zeneca data base records of patients exposed to tamoxifen during pregnancy, showed 16 live births with congenital abnormalities and 122 live births without malformations. in addition there were 12 spontaneous abortions, 17 terminations of pregnancy without fetal defects, six terminations of pregnancy with fetal defects, two still births without malformations, two still births with malformation and another 57 unknown outcomes [10]. tamoxifen induced abnormalities include goldenhar’s syndrome; ambiguous genitalia, vaginal bleeding and abortions, yet several reports described exposure to tamoxifen with healthy neonates [5]. clark et.al studied 85 healthy women with high risk of developing breast cancer who were given tamoxifen prophylactially. they became pregnant while on tamoxifen, with no fetal abnormalities observed after deliveries [11]. a case reported by tewari et.al described a case of an infant borne with ambiguous genitalia, and three other case reports described four live births with congenital anomalies, no specific abnormality is identified to be associated with exposure to tamoxifen during pregnancy [4]. the relatively high frequency of congenital abnormalities means that reliable birth control during tamoxifen treatment is essential during its use and a washout period of two months should be observed based on the known half-life of tamoxifen. so, there is a general agreement to postpone tamoxifen treatment until after delivery [10]. there are no prospective studies assessing the effect of termination of pregnancy on survival. our patient got pregnant while on tamoxifen, in spite of the fact that she and her husband were counseled, the risks were explained, and was advised not to get pregnant while on tamoxifen and to have an intrauterine contraceptive device, but she didn’t use any form of contraception as she was very keen to get pregnant due to the social pressures from the husband and the family and the fear that her husband may divorce her or remarry. but fortunately she delivered a normal infant, similar cases were reported by isaacs et al. [7], oksuzogolo et al. [9], and emra koca et al. [12]. 4. conclusion using tamoxifen during pregnancy is contraindicated because it causes birth defects in 20% of the cases, so good counseling of breast cancer premenopausal women treated with tamoxifen is important. they should be advised not to get pregnant and to stop doi 10.18502/sjms.v12i2.921 page 116 sudan journal of medical sciences production and hosting by knowledge e tamoxifen immediately if they get pregnant. we reported a case where tamoxifen was used during pregnancy and luckily there were no birth defects. references [1] a. elamin, m. e. ibrahim, d. abuidris, k. e. h. mohamed, and s. i. mohammed, “part i: cancer in sudan-burden, distribution, and trends breast, gynecological, and prostate cancers,” cancer medicine, vol. 4, no. 3, pp. 447–456, 2015. [2] t. t. white, “carcinoma of the breast and pregnancy,” annals of surgery, vol. 139, no. 1, pp. 9–18, 1954. [3] t. iguchi, m. hirokawa, and n. takasugi, “occurence of genital tract abnormalities and bladder hernia in female mice exposed neonatally to tamoxifen,” toxicology, vol. 42, no. 1, pp. 1–11, 1986. [4] k. tewari, r. g. bonebrake, t. asrat, and a. m. shanberg, “ambiguous genitalia in infant exposed to tamoxifen in utero,” lancet, vol. 350, no. 9072, p. 183, 1997. [5] s. l. cullins, g. pridjian, and c. m. sutherland, “goldenhar’s syndrome associated with tamoxifen given to the mother during gestation,” jama: the journal of the american medical association, vol. 271, no. 24, pp. 1905–1906, 1994. [6] j. c. berger and c. l. clericuzio, “pierre robin sequence associated with first trimester fetal tamoxifen exposure,” american journal of medical genetics, part a, vol. 146, no. 16, pp. 2141–2144, 2008. [7] b. geert, h. denys, o. de wever, v. cocquyt, and r. van den broeck, “use of tamoxifen before and during pregnancy,” oncologist, vol. 16, no. 11, pp. 1547–1551, 2011. [8] k. koizumi and t. aono, “pregnancy after combined treatment with bromocriptine and tamoxifen in two patients with pituitary prolactinomas,” fertility and sterility, vol. 46, no. 2, pp. 312–314, 1986. [9] r. j. isaacs, w. hunter, and k. clark, “tamoxifen as systemic treatment of advanced breast cancer during pregnancy case report and literature review,” gynecologic oncology, vol. 80, no. 3, pp. 405–408, 2001. [10] b. geert, h. denys, o. de wever, v. cocquyt, and r. van den broeck, “use of tamoxifen before and during pregnancy,” oncologist, vol. 16, no. 11, pp. 1547–1551, 2011. [11] s. clark, “prophylactic tamoxifen,” the lancet, vol. 342, no. 8864, p. 168, 1993. doi 10.18502/sjms.v12i2.921 page 117 sudan journal of medical sciences production and hosting by knowledge e [12] e. koca, t. y. kuzan, t. babacan, i. h. turkbeyler, f. sarici, and k. altundag, “safety of tamoxifen during pregnancy: 3 case reports and review of the literature,” breast care, vol. 8, no. 6, pp. 453–454, 2013. doi 10.18502/sjms.v12i2.921 page 118 introduction case report discussion conclusion references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8164 production and hosting by knowledge e research article thorax gunshot and sharp cutting tool injuries: for 5 months nyala experiences hüseyin fatih sezer1 and hakan dayanir2 1kocaeli university, kocaeli/turkey 2university of health sciences gülhane health vocational school, ankara/turkey abstract background: the two most common causes of penetrating thoracic trauma are firearm injuries and injuries by sharpened cutting tool. penetrating thoracic injuries are risk factors for high mortality and morbidity, so they need to be diagnosed correctly and timely in order to perform an effective intervention. in this study, patients with penetrating thoracic trauma were treated through surgical intervention accompanying minimal morbidity–mortality compared to literature, even though they were admitted relatively late. methods: in this retrospective study, 29 gunshot and stab wounds penetrating thoracic trauma patients were admitted to the emergency department of nyala sudan turkey education and research hospital between april and september 2018. results: of the 29 patients, 7 (24.13%) were gunshot injuries and 22 (75.86%) were injured with a sharp cutting tool. while 13 of the cases (44.82%) were admitted on the day the incident took place, 5 of them (17.24%) were post-traumatic first day of the admission, 9 of them (31.03%) were post-traumatic day 2, whereas 1 of them (3.44%) was post-traumatic the third day of admission. finally, 14 patients (48.28%) were followed-up conservatively without tube thoracostomy, while 15 patients (51.72%) underwent tube thoracostomy in follow-up. no patient was operated for penetrant trauma. mortality was not seen. conclusion: patients with penetrating thoracic trauma were treated by surgical interventions accompanying minimal morbidity–mortality even though they were admitted relatively late to healthcare facilities. keywords: penetrating thoracic injuries, sharp cutting tool, gunshot 1. introduction thorax traumas are the third most common type of trauma after cranial and extremity traumas considering the frequencies and are responsible for about 25% of traumatic deaths [1, 2]. the vast majority of thorax traumas are blunt traumas, with approximately 30% of them being penetrant in origin (3, 4). the two most common causes of penetrating thoracic trauma are as a consequence of firearm or by a the sharp cutting tool (2). penetrating thoracic injuries are risk factors for high mortality and morbidity, so they need to be diagnosed correctly and timely in order to perform an effective intervention. how to cite this article: hüseyin fatih sezer and hakan dayanir (2020) “thorax gunshot and sharp cutting tool injuries: for 5 months nyala experiences,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 418–424. doi 10.18502/sjms.v15i4.8164 page 418 corresponding author: hüseyin fatih sezer; kocaeli university medical faculty hospital, kocaeli/turkey. email: hfs.hfs@gmail.com received 12 november 2020 accepted 26 december 2020 published 31 december 2020 production and hosting by knowledge e hüseyin fatih sezer and hakan dayanir. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hfs.hfs@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hüseyin fatih sezer and hakan dayanir if the thoracic injury is accompanied by multi-organ lacerations, the risk of mortality and morbidity tends to be higher (1). in this study, patients with penetrating thoracic trauma were treated with surgical interventions accompanying minimal morbidity–mortality compared to literature, even though they were admitted relatively late to a healthcare facility. 2. materials and methods in this retrospective study, 29 gunshot and stab wounds penetrating isolated thoracic trauma patients were admitted to the emergency department of nyala sudan turkey education and research hospital between april and september 2018. patients were evaluated in terms of age, gender, trauma cause, duration of application, thoracic pathologies resulting from trauma, accompanying non-thoracic pathologies, treatment and their application period, intensive care unit stay, complications, hospital stay, mortality and follow-ups after discharge. 2.1. statistical analysis statistical evaluation was performed using ibm spss 20.0 (spss inc., chicago, il, usa). the normal distribution fitness test was assessed using the kolmogorov–smirnov test, categorical variables were expressed as a percentage (%). relationships between categorical variables were evaluated by chi-square analysis. 3. results of note, 27 (93.10%) of the 29 patients were male and 2 (6.89%) were female, aged 14–68 years. the mean age of the patients was 26.59 years, with the mean age of the men being 26.56 years and that of the women being 27 years (table 1). of the included patients, 7 (24.13%) were gunshot injuries and 22 (75.86%) were injured with a sharp cutting tool. besides, 13 of the cases (44.82%) were admitted on the day the incident took place while 5 of them (17.24%) were post-traumatic first day of admission, 9 of them (31.03%) were post-traumatic day 2, and 1 of them (3.44%) was post-traumatic third-day admission (figure 1). the average duration of application was 1.92 days. interestingly, in 17 (58.62%) patients, the injury was in the right hemithorax, in 10 (34.48%) patients, it was in the left hemithorax, and 2 (6.89%) patients had bilateral injuries. all patients underwent a pa or ap chest x-ray, in addition to which 10 (34.48%) patients underwent lateral chest x-ray, 13 (44.82%) had thoracic ct, and 1 (3.44%) underwent abdomen ct. while 21 (72.41%) patients experienced thoracic pathologies secondary to trauma, no such condition was seen in the remaining 8 (27.58%) of them. pneumothorax was present in all patients with this pathology. hemothorax was found in 11 (37.93%) patients, rib doi 10.18502/sjms.v15i4.8164 page 419 sudan journal of medical sciences hüseyin fatih sezer and hakan dayanir figure 1: patient application times. fracture was evident in 3 (10.34%), lung contusion in 3 (10.34%), mediastinal emphysema in 5 (35.71%), and subcutaneous emphysema in 8 (27.58%) patients with this pathology (figure 2). in addition, one (3.44%) patient had an injury with sharp cutting tool related to the retroperitoneus except for this injury, such a condition associated with thorax trauma were not encountered. figure 2: thoracic pathologies due to penetrant injury seen in patients. in total, 14 (48.28%) patients were followed-up conservatively without tube thoracostomy, while 15 (51.72%) patients underwent tube thoracostomy in follow-up. one (3.44%) patient had to undergo a second tube thoracostomy with expansion defect. continuous oxygen therapy was given to 10 (34.48%) patients and 5 (50%) of them received this doi 10.18502/sjms.v15i4.8164 page 420 sudan journal of medical sciences hüseyin fatih sezer and hakan dayanir treatment for mediastinal emphysema when oxygen therapy was given to these five patients (50%) with partial pneumothorax. no patient was operated for penetrant trauma. during the follow-up and treatment, intensive care was needed for 11 (37.93%) patients and the mean intensive care unit admission period was 2.36 days (table 1). the mean follow-up chest drain was 6.67 days in patients followed-up with tube thoracostomy (table 1). in addition, six patients (20.68%) had complications during follow-up and three (50%) of these complications were expansion defect, three (50%) were atelectasis and one (16.66%) was a wound infection. no other complications were observed. one (1.66%) patient underwent perioperative blood transfusion. mortality was not seen. the mean duration of hospitalization was 4.5 days (table 1). table 1: mean periods. age 26.59 (year) male 26.56 (year) female 27 (year) application time to hospital 1.92 (day) tube thoracostomy time 6.67 (day) intensive care time 2.36 (day) total hospital stay 4.5 (day) following the discharge, no complication was reported by any of the patients; all of them were followed-up in a healthy manner. in three cases, after the trauma, there were bullet cores in various parts of thorax but it was not clinically important and no attempt for removal was performed. 4. discussion considering the trauma frequencies, thoracic trauma ranks third after the cranial and extremity traumas [1]. trauma is the most common cause of deaths before the age of 40 in the community and one in four of the traumatic deaths are related to thoracic trauma [3]. approximately 30% of thoracic traumas are penetrant traumas [3, 4]. the two most common causes of penetrating thoracic trauma are firearm injuries and injuries by sharp cutting tool [2]. the other major causes of penetrant thoracic trauma are traffic accidents, falls, and assaults. in a large study conducted by demetriades et al. with a long duration of nine years and 34,120 trauma patients, 35% of the thoracic traumas were observed to be penetrating, mortality was observed in 7.8% of the patients, and 4% of them were due to penetrating thoracic trauma [5]. they also reported that the most common critical injuries were cranial and the second most frequent were thoracic injuries [3, 5]. moreover, in the same study, penetrant trauma had a mortality rate of 11.5% in itself [5]. according to our concept of study, all of our patients were a penetrating thoracic trauma. seven (24.13%) patients were gunshot injuries while 22 (75.86%) were injured with a sharp cutting tool [3, 5]. unlike the literature, there was no mortality in our cases. doi 10.18502/sjms.v15i4.8164 page 421 sudan journal of medical sciences hüseyin fatih sezer and hakan dayanir penetrating thorax traumas are often seen in patients between 20 and 40 years of age [6]. men are more frequently exposed to penetrating traumas [1, 2, 4]. in our study, the mean age of the patients was 26.59 years and the male ratio was 93.10%, which was in line with the literature. penetrating thoracic injuries are most often caused by cutter drill and less frequent firearm injuries, even if different ratios are given in the wider series [2, 4, 7, 8]. in our study, 24.139% of the penetrating thoracic trauma was caused by firearms and 75.86% by cutting piercing tools which is also in line with the literature. in our study, the referral period of patients was often after the first day because of the location of our hospital, transportation difficulties, material concerns, sociocultural beliefs and indifference. we did not find any satisfactory result with regards to finding a relevant english and native literature over the last 25 years on the post-penetrating thoracic trauma admission time to the health center. perhaps the most useful diagnostic technique for penetrating thorax trauma is radiological imaging after the physical examination. generally, pa, lateral, and ap lung chest x-ray are used, however, chest ct is frequently applied. chest x-ray was used for all of our patients and thoracic ct was used in 13 (44.82%) patients. the most common thoracic pathologies in penetrating thoracic trauma are: hemothorax and pneumothorax [1–3, 7, 8]. less frequent occasions are subcutaneous and mediastinal emphysema, contusion, laceration, tracheoesophageal injury, chylothorax, and cardiac injury. in our study, pneumothorax (72.41%) and hemothorax (37.93%) were the most common complications. one of our patients had extrathoracic penetrating injury and all of the other patients had penetrant trauma specific to thorax. we think that this situation depends on the sociocultural structure and habits. in general, tube thoracostomy-closed drainage system can be applied, and conservative approach is also possible [3]. if tubal thoracostomy is followed by 1500 cc hemorrhagic drainage or a drainage <1500 cc with an hourly 200 cc drainage lasting for 4 hr or if 100 cc hemorrhagic drainage continues for 6–8 hr and in case of hypovolemic shock, cardiac injury, major vascular injury, trachea-bronch-large lung parenchymal laceration or prolonged air leak, thoracotomy-sternotomy-vats (video assisted thoracic surgery) can be performed. usually follow-up with tube thoracostomy is sufficient, thoracotomystereotomy rates due to penetrating thoracic trauma in national wide-ranging studies ranged from 2.9 to 14.3% [1, 9, 10]. moreover, many international publications have reported high thoracotomy rates [1]. continuous oxygen therapy, respiratory exercises, postural drainage, pain control can be used in conservative treatment. in our study, 14 (48.28%) patients without tube thoracostomy were followed-up conservatively, while 15 (51.72%) who underwent tube thoracostomy and were also followed-up. continuous oxygen therapy was given to 10 patients (34.48%); 5 (50%) of them received it for mediastinal emphysema treatment, while the other 5 (50%) received it for partial pneumothorax treatment. contrary to the literature, no patient required thoracotomy. in national publications, the most common cause of morbidity in penetrating thoracic traumas was found to be atelectasis [8, 9]. in our study, six (20.68%) patients had complications during follow-up when three (50%) of them were atelectasis, three (50%) of expansion defect, and one (16.66%) of wound infection; no other complications were doi 10.18502/sjms.v15i4.8164 page 422 sudan journal of medical sciences hüseyin fatih sezer and hakan dayanir encountered. additionally, one (1.66%) patient underwent blood transfusion. although our patients had relatively late admission, mortality was not seen; the lack of other systemic injuries associated with appropriate surgical management and follow-up, the absence of pulmonary–thoracic wall vascular injuries that required major thoracic vascular injury or thoracotomy may be the reason for this condition. 5. conclusion thoracic penetrant trauma is a risk factor for mortality and morbidity. diagnosis and necessary intervention should be done, as soon as possible for this reason. tube thoracostomy is often adequate for follow-up and treatment, but conservative treatment may be available in some cases. successful results can be obtained by appropriate surgical intervention even in penetrating thoracic trauma that does not apply in time. although of late presentation, our patients had good outcome in our facility. acknowledgements we would like to thank at first, dr. i̇smayil y𝚤lmaz and nyala, sudan, turkey education and research hospital employees. and we would like to thank all the patients who kindly participated in the study ethical considerations the study protocol was approved by the kocaeli university ethics committee (19.6.2019/ 2019-179). competing interests no potential conflict of interest relevant to this article was reported. availability of data and material the raw data used and/or analyzed during the current study are available from the corresponding author on reasonable request. funding none doi 10.18502/sjms.v15i4.8164 page 423 sudan journal of medical sciences hüseyin fatih sezer and hakan dayanir references [1] leblebici, h. i̇., kaya, y., 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(1998). toraks travmalar𝚤: 6 y𝚤ll𝚤k deneyimlerimiz. ulusal travma ve acil cerrahi dergisi, vol. 4, pp. 248–252. doi 10.18502/sjms.v15i4.8164 page 424 introduction materials and methods statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7136 production and hosting by knowledge e research article the psychological impact of the covid-19 pandemic on health professionals in sudan 2020 muna mohamed elamin1, salih boushra hamza2, yassin abdelrahim abdalla2, ahmed alsayed mohammed mustafa2, mosab abbas altayeb2, maria adam mohammed2, radi tofaha alhusseini3, and mohamed fathelrahman mohammed abass4 1community department, faculty of medicine, omdurman islamic university, khartoum, sudan 2medical student, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 3medical student, faculty of medicine and health sciences, alzaiem alazhari university, khartoum, sudan 4department of pediatrics, omdurman islamic university, khartoum, sudan abstract background: the 2019 novel coronavirus (covid-19) is highly contagious with pandemic transmission, and is therefore associated with severe health problems and high public anxiety, with healthcare community speculation to be the most distressed because they are at the highest risk of infection. this study aimed to investigate the psychological impact on frontline medical staff in khartoum state, sudan, during the covid-19 pandemic between january and march 2020. materials and methods: patient health questionnaire-9 (phq-9) scale, generalized anxiety disorders (gad-7) scale, and the revised impact of event scale (ies-r) were used to assess depression, anxiety, and post-traumatic stress disorders (ptsd) on the participants, respectively, through an online questionnaire. the data were analyzed using the statistical package for social science (spss) version 24. results: phq-9 depression scale showed that 285 (82%) staff members had some degree of depression, with mild depression being the most frequent, seen in 96 (24.2%), whereas, severe depression was found to be more common among the age group between 45 and 65 years and was associated with working in the emergency room (er) (p = 0.03). the ptsd among our participants was assessed by the ies-r that showed that 116 (29.3%) had subclinical ptsd, 124 (31.3%) had mild ptsd symptoms, 98 (24.7%) had moderate ptsd symptoms, and 58 (14.6%) had severe ptsd symptoms. also, a statistical association was seen between the ies-r mean score and the age group between 25 and 34 years (p < 0.0001), having a friend or family member infected with the disease (p < 0.0001), and having a history of contact with a positive case of covid-19 (p < 0.0001). we used gad-7 anxiety score that showed mild anxiety in 32 (23.2%) participants, moderate anxiety in 53 (13.4%), and severe anxiety 66 (16.7%). conclusion: this study aimed to explore the psychological impact of covid-19 pandemic on medical staff’s perception and its determinants. most of our participants were found to be suffering from anxiety and depression with combining personal variables and working conditions as predictors. how to cite this article: muna mohamed elamin, salih boushra hamza, yassin abdelrahim abdalla, ahmed alsayed mohammed mustafa, mosab abbas altayeb, maria adam mohammed, radi tofaha alhusseini, and mohamed fathelrahman mohammed abass (2020) “the psychological impact of the covid-19 pandemic on health professionals in sudan 2020,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 54–70. doi 10.18502/sjms.v15i5.7136 page 54 corresponding author: muna mohamed elamin ahmed, md community medicine, md dermatology, msc medical education, assistant professor and head department of community medicine, acting faculty dean; tel: 0924555942 email: monalameen2@gmail.com received 12 may 2020 accepted 19 june 2020 published 9 july 2020 production and hosting by knowledge e muna mohamed elamin et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:monalameen2@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences muna mohamed elamin et al keywords: covid-19, psychological impact, health workers, sudan, gad-7, phq-9, ies-r 1. introduction overthe last century, the world has witnessed great pandemics with potentially destructive effects. starting from the “spanish” influenza that swept through the world between 1918 and 1919 and to the severe acute respiratory syndrome (sars) crisis in november 2003, caused by a novel corona virus that resulted in the death of 349 out of 5327 patients [1]. since december 2019, an outbreak of severe acute respiratory infection of unknown etiology had emerged in wuhan city, the capital of hubei province, china. later, a third generation of corona virus was suspected and the name covid-19 was given to this novel disease; it gained extreme awareness nationwide and internationally, and was declared as a public health emergency of international concern by the world health organization (who) on january 30, 2020. a strict range of preventive measures were urgently adopted, including complete social distancing, contact tracing, early identification using regional and national diagnostic criteria besides isolation of suspected and diagnosed cases. all these scientific and valid measures have resulted in a remarkable and striking decline in the virus transmission rate [2, 3]. pandemic infectious diseases not only are life-threatening to human beings, but greatly impose psychosocial trauma to people because most people usually lack sufficient knowledge about newly emerging diseases, which brings about massive panic in people and leads to an illogical response to the disease [4]. medical personnel, including paramedics, ambulance personnel, and healthcare workers (hcws) have been found to be more psychologically traumatized and experience higher levels of stress, depression, and anxiety [5]. this can be explained by the expected anxiety and fear of getting infected due to their risk of exposure and worse is their worry of infection transmission to their families, friends, or colleagues. this puts them at a great challenge of how to balance between professional duty, humanity, and personal fear for oneself and others, a situation that can often cause conflict and dissonance in many hcws [6]. the sars epidemic, with high transmission and mortality rates, caused significant terror and apprehension around the world [7–10]. the literature has revealed that hcws are not at equal risk for developing an adverse psychological sequence; healthcare providers who are in proximal contact with patients and are directly exposed to infection are found to be more vulnerable to developing adverse psychiatric problems. these include healthcare providers in emergency departments, intensive care units, and isolation wards [11]. apart from the exposure, health workers may suffer from panic and worry of getting sick or dying, feel helpless, or face blame from others who are ill, all precipitating a state of mental collapse [12]. doi 10.18502/sjms.v15i5.7136 page 55 sudan journal of medical sciences muna mohamed elamin et al different presentations of psychiatric illnesses have been found, ranging from depression, anxiety, panic attacks, somatic symptoms, and post-traumatic stress disorder symptoms to delirium, psychosis, and even suicide [13]. these symptoms have been associated with a younger age and increased feelings of self-guilt [13–15]; stigmatization, and social avoidance had also been reported by bai et al. and robertson et al. 2004. in a survey conducted during the initial outbreak of covid-19 in china to assess the psychological effect, the result showed that 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe [16]. the effect of infectious pandemics extends beyond the healthcare providers to reach the whole healthcare system [12]. as during the outbreak, some hospitals were closed with cancellation of all hospital-based outpatient clinics, severe staff shortages resulted from quarantined health workers [17–22]. during the sars outbreak, marital status was also found to be associated with stress level, where an elevated fear was reported to be more in married hospital employees compared to those who were divorced or unmarried [23]. quarantine is an essential and effective preventive measure during an epidemic, although it is often an unpleasant experience for those who go through it [24]. to minimize the adverse effects of quarantine, officials need to ensure that quarantined households have enough supplies for their basic needs [25]. this study was designed to examine the long-term psychological impact of covid-19 outbreak on healthcare workers in khartoum state, and aimed to identify personal and environmental variables that increase vulnerability to distress during an epidemic. 2. materials and methods 2.1. participants this is a cross-sectional study that targeted medical staffs in khartoum state, sudan, during the covid-9 pandemic. the sample consisted of 396 healthcare providers; the questionnaire was restricted to respondents who had to authenticate their membership to their specialty through their social media groups. the sample was stratified by profession, including different groups of healthcare workers, doctors, nurses, dentists, pharmacists, and laboratory workers. disproportionate stratified random sample was used for recruitment into the study because our sample size is not proportional to the relative size of the strata and to compensate for the small number of certain groups. sample size was calculated using the sample size of the unknown population (cochran’s formula): n0 = 𝑧2𝑝(1−𝑝) 𝑒2 . z = z value (1.96 for 95% confidence interval) p = degree of variability (0.5) e = 95 % confidence interval doi 10.18502/sjms.v15i5.7136 page 56 sudan journal of medical sciences muna mohamed elamin et al n = (1.96)2 x 0.5(1–0.5) ÷ (0.05)2 = 384 2.2. measures a validated questionnaire containing sociodemographic characteristics, patient health questionnaire-9 (phq-9), generalized anxiety disorders-7 (gad-7) scale, and the revised impact of event scale (ies-r) were used to assess depression, anxiety, and post-traumatic stress disorder on the participants, respectively. the ies-r is a short, easy, and self-report measure designed to assess current subjective distress resulting from a traumatic life event for both healthy as well as frail individuals and is composed of 22 items, each one of which is rated using a likert scale from 0 to 4. the maximum score is 88. the results consist of a total raw score and raw score for three subscales: the avoidance scale, intrusion scale, and the hyperarousal scale [26]. the event used for this questionnaire was the exposure to or infection by covid-19. the total scores were categorized as follows: subclinical (0–8), mild distress (9–25), moderate distress (26–43), and severe distress (44–88) [27]. phq-9 scale contains nine questions to measure depressive symptoms, each question contains four options ranging from (not at all) given zero points to (nearly every day) given three points and the result is interpreted as (0–4) having minimal or no depression, (5–9) having mild depression, (10–14) having moderate, (15–19) having moderately severe, and (20–27) having severe depression [28]. the gad scale contains seven questions and is used to measure the anxiety symptoms in the participants, each question contains four options ranging from (not at all) to (nearly every day) given a three point result and interpreted as (5–9) for mild anxiety, (10–14) moderate anxiety, and (> 15) for severe anxiety [29]. as arabic or sudanese versions are not available, the english version of ies-r and gad scales was translated into arabic language by two bilingual persons whose native language is arabic and english. the arabic version was translated back into english by two independent bilingual persons and both the new and original english versions were compared. the arabic version of phq-9 is available [30] and was used after the consent was taken from the developer. a pilot study was conducted in 10% of the sample (∼ 38 participants) with a cronbach’s alpha of (0.925), (0.944), and (0.946) for phq-9, ies-r, and gad-7 respectively. 2.3. procedure as our study was conducted in unusual circumstances, in which there were restrictions on most activities and movements, and person-to-person contacts were maximally reduced due to the fear of the spread of covid-19 infection, the data were collected using an internet-mediated questionnaire. doi 10.18502/sjms.v15i5.7136 page 57 sudan journal of medical sciences muna mohamed elamin et al 2.4. data analysis the data were analyzed using the statistical package for social science (spss) version 24, after being primarily analyzed by google form. descriptive analysis was used to describe the demographic data and the covid-19 exposure and perception and included the mean and standard deviation (sd). as the wilk–shapiro test showed a significant deviation from the normal distribution (p-value < 0.0001), the demographic data and the covid-19 exposure and perception were compared to ies-r scores using the independent samples kruskal–wallis and the mann–whitney tests. the demographic data and covid-19 exposure and perception were also compared to gad-7 and phq-9 scores using chi-square (χ2) test. a p-value < 0.05 was considered statistically significant. 3. results 3.1. demographic characteristics in our study, we enrolled 396 healthcare providers, the majority, that is, 203 (51.3%) of them were between 25 and 34 years of age, and among them 262 (66.2%) were females and 124 (33.8%) were males. the majority, that is, 258 (65.2%) were single, while 110 (27.8%) were married. bachelor holders were 243 (61.4%) and 202 (51.01) of our participants worked in governmental hospitals. about 171 (43.2%) stated that they worked in the emergency room (er) (table1). 3.2. covid 19 exposure and perception regarding the covid 19 exposure and perception, we found that 76 (19.2%) of our participants responded that they handled covid 19 cases, while 65 (16.4%) had a friend or family member diagnosed with covid 19. the majority, that is, 317 (80.1%) of our participants stated that their families are worried and afraid that they will transmit the disease to them. about 140 (35.4%) of our participants thought that people started to avoid them because of the nature of their job, and 249 (62.9%) of them stated that their income got lowered during the covid 19 pandemic, while 256 (65.6%) thought that their working hours were increased during this time. when asked about the availability of enough personal protective equipment in their workplace, 289 (73%) responded with the answer ”no,” and only 57 (14.4%) pointed to the availability of mechanical ventilators in their workplace (table 2). about 108 (27.3%) of our participants went through home isolation during the covid 19 pandemic. on asking them about the reason for their home isolation, 33 (8.3%) reported a confirmed case after contact with another confirmed case, and 20 (5.1%) were positive cases. also, 25 (6.3%) of them reported contact with a suspected case, 9 (2.3%) reported contact with confirmed case, 1 participant (0.3%) reported developing symptoms as a cause of isolation, and 4 (1%) reported other causes (table 3). about 187 (47.2%) of them stated that they get information from tv, radio, and doi 10.18502/sjms.v15i5.7136 page 58 sudan journal of medical sciences muna mohamed elamin et al social media, while 114 (25.8%) reported getting their information from social media and official websites (table 4). 3.3. depression among participants upon evaluating depression among our participants using the phq9 scale, we found that 285 (82%) of them perceived some degree of depression, with mild depression being the most common in 96 participants (24.2%), followed by moderate depression in 80 (20.2%), while moderately severe and severe depression were among 47 (11.9%) and 62 (15.7%) participants, respectively (figure 1). figure 1: phq-9 depression score among participants. we explored the association between depressive level and participant’s demographic characteristics and found that those of the age group 45–54 years were having severe depression, but this association was statistically insignificant (p = 0.2). on the other hand, we found that working in an er is associated with both a high prevalence of depression and a higher percentage of severe depression (p = 0.03). there are no significant associations with covid-19 exposure and perception of depression. doi 10.18502/sjms.v15i5.7136 page 59 sudan journal of medical sciences muna mohamed elamin et al figure 2: gad-7 score among participants. 3.4. post-traumatic stress disorder among participants the ies-r scale and its subscales were used to evaluate the post-traumatic stress disorder among our participants, and the result showed that 116 (29.3%) had subclinical ptsd, 124 (31.3%) had mild ptsd symptoms, 98 (24.7%) had moderate ptsd symptoms, and 58 (14.6%) had severe ptsd symptoms. on the other hand, on reviewing the subscales, we found that the participants in our study had a mean of 0.99 in the avoidance scale, 1.05 for the intrusion scale, and 1.026 for the hyperarousal scale (table 5). we further evaluated the association between the age groups and the educational level of the participants. a higher mean ies-r score was found in the age group between 25 and 34 years and in master degree holders (p-value < 0.0001) (table 6). health workers who had no history of contact with an infected patient or no friend or family member infected with the disease had a significantly higher mean ies-r score compared to those who did (p-value < 0.0001). when we explored the effect of working conditions, result showed that participants who did not had enough ppe in their workplace had significantly lower mean ies-r compared to those who did (p-value < 0.0001). no significant difference was found between the person who had been quarantined and the person who had not (table 6). doi 10.18502/sjms.v15i5.7136 page 60 sudan journal of medical sciences muna mohamed elamin et al table 1: demographic characteristics variables number percentage (%) age 18–24 years 104 26.3 25–34 years 203 51.3 35–44 years 40 10.1 45–54 years 10 2.5 55–64 years 16 4 above 65 years 23 5.8 gender male 124 33.8 female 262 66.2 marital status single 258 65.2 married 110 27.8 widows 13 3.3 divorced 15 3.8 current occupational position house officers 122 30.8 medical officers 93 23.5 registrars 53 13.4 specialists 21 5.3 consultants 19 4.8 consultants 19 4.8 nurses 21 5.3 lab technicians 35 8.8 pharmacists 17 4.3 dentists 12 3.0 physiotherapist 1 0.3 radiology technician 1 0.3 health officer 1 0.3 educational qualification bachelor 255 64.4 master 58 14.6 md\phd 80 20.2 diploma 3 0.8 current workplace governmental hospital 202 51.01 private hospital 48 12.12 both private and governmental hospitals 79 19.94 private clinics 39 9.84 primary health care center 19 3.03 pharmacies 9 2.3 private labs 6 1.51 blood bank 1 0.25 direct contact with the emergencies emergency room 171 43.2 respiratory area 59 12.9 isolation room 9 2.3 x-ray room 6 1.5 not working in any of them 151 38.1 doi 10.18502/sjms.v15i5.7136 page 61 sudan journal of medical sciences muna mohamed elamin et al table 2: covid 19 exposure and perception yes no n % n % handling a positive patient 76 19.2 320 80.8 any friend or family member positive for covid 19 65 16.4 331 83.6 fear of friends/family members of transmitting the disease 317 80.1 79 19.9 avoidance of community member from participants 195 49.2 201 50.8 income reduction during covid 19 pandemic among participants 249 62.9 147 37.1 increase in working hours during covid 19 pandemic among participants 140 35.4 256 65.6 ppe availability in enough amounts in workplace 107 27 289 73 ventilator availability in workplace 57 14.4 339 85.6 home isolation among participants 108 27.3 288 72.7 table 3: cause of home isolation of the participants cause of home isolation frequency percentage didn’t have home isolation 288 72.7 diagnosed with the disease 20 5.1 exciting in place with confirmed case 1 .3 direct contact with confirmed case 9 2.3 direct contact with suspected case 25 6.3 been suspected case 11 2.8 direct contact with person who had direct contact with confirmed 3 .8 diagnosed with the disease; direct contact with confirmed case 33 8.3 come from infected country 1 .3 other 4 1.0 feeling symptoms 1 .3 total 396 100.0 table 4: source of participants’ information about covid 19 source of information frequency percentage tv and radio 8 2.0 social media 25 6.3 official health website 114 28.8 tv and radio; social media 187 47.2 social media and official health website 37 9.3 tv and radio and official health website 21 5.3 tv and radio; social media and official health website 4 1.0 total 396 100.0 doi 10.18502/sjms.v15i5.7136 page 62 sudan journal of medical sciences muna mohamed elamin et al table 5: ies-r subscales among participants ies-r subscales n range minimum maximum mean std. deviation avoidance score 396 3.13 0.00 3.13 0.9953 0.85860 intrusion score 396 3.13 0.00 3.13 1.0581 0.91304 hyperarousal score 396 3.17 0.00 3.17 1.0261 0.94058 valid n (listwise) 396 table 6: comparison of demographic characteristics and covid-19 exposure and perception with ies-r scale variable frequency ies-r mean sd p-value age 18–24 104 22.1 19.3 < 0.0001 25–34 203 24.6 16.9 35–44 40 22.4 16.8 45–54 10 21.0 23.4 55–64 16 18.9 26.7 +65 23 9.9 23.2 educational level master 58 25.4 18.3 < 0.0001 phd/md 80 15.6 22.3 bachelor 255 24.1 17.2 diploma 3 18.3 18.9 dealing with infected person yes 76 11.8 16.9 < 0.0001 no 320 25.1 18.3 infected friend or family member yes 65 8.0 14.9 < 0.0001 no 331 25.4 18.1 availability of ppe in enough amounts in workplace yes 107 29.7 21.5 < 0.0001 no 289 19.9 17.0 3.5. anxiety among participants we used gad-7 score to evaluate anxiety among our participants, we found that most of our participants had scored different levels of anxiety ranging from mild anxiety in 32 (23.2%), moderate anxiety in 53 (13.4%), and severe anxiety in 66 (16.7%) (figure 2). when we evaluated the association of the gad-7 score with our participant’s personal characteristics, we found that those aged 24–35 years had the lowest gad-7 score compared to other age groups (p = 0.001); those who worked in the er had a significantly higher gad-7 scores than those who were working in other departments (p = 0.034); and those who hold bachelor degree had lower gad-7 score (p < 0.0001) (table 7). we also explored that those who did not contact a positive case of covid-19 had lower gad-7 scores than those who did (p < 0.0001), also those who did not have a doi 10.18502/sjms.v15i5.7136 page 63 sudan journal of medical sciences muna mohamed elamin et al table 7: comparison of demographic characteristics, covid-19 exposure, and perception with gad-7 scale variable none mild moderate severe total p-value age 18–24 53(28.3) 23(25.0) 9(17.0) 19(28.8) 103(26.1) 0.001 25–34 73(39.7) 58(63.0) 37(69.8) 34(51.5) 202(51.1) 35–44 20(10.9) 10(10.9) 6(11.3) 4(6.1) 40(10.1) 45–54 6(3.3) 1(1.1) 1(1.9) 2(3.0) 10(2.5) 55–64 12(6.5) 0(0.0) 0(0.0) 4(6.1) 16(4.1) 65+ 20(10.9) 0(0.0) 0(0.0) 3(4.5) 23(5.8) occupation health officer 0(0.0) 0(0.0) 1(1.9) 0(0.0) 0(0.3) 0.034 house officer 59(32.1) 25(27.2) 12(22.6) 26(39.1) 122(30.9) radiology technician 0(0.0) 0(0.0) 1(1.9) 0(0.0) 1(0.3) general practitioner 43(23.4) 18(19.6) 15(28.3) 17(25.8) 93(23.5) registrar 13(7.1) 18(19.6) 11(20.8) 10(15.2) 52(13.2) specialist 14(7.6) 3(3.3) 2(3.8) 2(3.0) 21(5.3) consultant 10(5.4) 5(5.4) 0(.0) 4(6.1) 19(4.8) nurse 12(6.5) 6(6.5) 2(3.8) 1(1.5) 21(5.3) lab worker 19(10.3) 10(10.9) 3(5.7) 3(4.5) 35(8.9) pharmacist 8(4.3) 4(4.3) 4(7.5) 1(1.5) 17(4.3) dentist 6(3.3) 3(3.3) 1(1.9) 2(3.0) 12(3.0) physiotherapy 0(0.0) 0(0.0) 1(1.9) 0(0.0) 1(0.3) education diploma 2(0.5) 0(0.0) 0(0.0) 1(1.5) 3(0.5) < 0.0001 mbbs 4(2.2) 5(5.4) 3(5.7) 0(.0) 12(3.0) master 23(15.5) 13(14.1) 13(24.5) 9(13.6) 58(14.7) phd/md 57(31.0) 8(8.7) 2(3.8) 13(19.7) 80(20.3) bachelor 98(53.3) 66(71.7) 35(66.0) 43(65.2) 242(61.3) handling a positive patient yes 53(28.8) 11(12.0) 7(13.2) 5(7.6) 76(19.2) < 0.0001 no 131(71.2) 81(88.0) 46(86.8) 61(92.4) 319(80.8) any friend or family member positive for covid 19 yes 52(28.3) 3(3.3) 5(9.4) 5(7.6) 65(16.5) < 0.0001 no 132(71.7) 89(96.7) 48(90.6) 61(92.4) 330(83.5) fear of friends or family members of transmitting the disease yes 146(79.3) 81(88.0) 46(86.8) 44(66.7) 317(80.3) 0.005 no 38(20.7) 11(12.0) 7(13.2) 22(33.3) 78(19.7) increase working hours during covid19 pandemic among participants yes 84(45.7) 24(26.1) 14(26.4) 17(25.8) 139(35.2) 0.001 no 100(54.3) 68(73.9) 39(73.6) 49(74.2) 256(64.8) availability of enough ppe in work place yes 43(23.4) 29(31.5) 9(17.0) 25(37.9) 106(26.8) 0.031 no 141(46.6) 63(68.5) 44(83.0) 41(62.1) 289(73.2) doi 10.18502/sjms.v15i5.7136 page 64 sudan journal of medical sciences muna mohamed elamin et al friend or a family member diagnosed with covid 19 had a lower score of gad-7 and thus less anxiety than those who did (p < 0.0001). while the fear of friends and family members of transmitting the disease was found to be statistically associated with low scores (p = 0.005), no increase in working hours during the covid-19 pandemic among participants (p = 0.001) and unavailability of enough personal protective equipment in the workplace (p = 0.031) were associated with low gad-7 score (table 7). 4. discussion covid-19 pandemic crisis is probably one of the most challenging threats to national and international public health in the last few decades. the epidemic had a significant impact on healthcare communities. initially, the hcws were placed in a stressful condition due to the uncertainty about the mode of transmission of the disease, tremendous fear, and implementation of rigorous infection control protocols. therefore, the purpose of this investigation was to examine the psychological impact of covid-19 pandemic crisis on hospital health workers in khartoum state, sudan and to explore the relationship between personal variables and working conditions on stress responses using three validated standard scales that measure depression, anxiety, and post-traumatic stress disorder. to the best of our knowledge, this was the first research on the mental health of sudanese medical staffs conducted during pandemic times, where there were restrictions on most activities and significantly reduced person-to-person contact. we chose to rely on the network platform for the questionnaire survey, considering that it is difficult to directly investigate the respondents. regarding depression, among the participants, 82% perceived some degree of depression, with mild depression being the most common in 24.2% participants, and severe depression seen only in 15.7% of the participants; this result is consistence with another study conducted in china during the sars outbreak, where 63.33% of the participants showed symptoms of depression with 89% of them having mild depression [31]. this finding is also similar to the result of another study conducted to measure the psychological impact and mental disturbance among medical staff in wuhan during the covid-19 epidemic, where most participants experienced mild disturbance, and severe disturbance was found in only about 16% [32]. severe depression was found to be associated with those working in er and in isolation wards; this correlates with a result obtained from a comparable study conducted in china, which showed that the healthcare providers who were caring for covid-19 cases showed severe depression [33], this can be explained by the higher risk of infection due to the close proximity with patients. our study showed that 29.3% of the participants had subclinical ptsd. these results are in contrast with those of tan et al.’s, which was done in singapore on 500 health workers and which reported that only 7.7% of clinical concern of ptsd [34], whereas another study done by lee et al. for health workers who worked during mers outbreak found higher ies-r scores [35]. doi 10.18502/sjms.v15i5.7136 page 65 sudan journal of medical sciences muna mohamed elamin et al one interesting finding is that there is a significant association between the age and educational level of participants with ies-r score (p < 0.0001). a higher ies-r score was found in people who had not dealt with infected people compared to the ones who had. moreover, the person who did not have an infected friend or family member had a higher ies-r score. perhaps, the most interesting finding was that participants who did not have enough ppe in their workplace had a lower ies-r score compared to who did; this finding is at par with the findings of wang et al. that reported a lower ies-r score for participants using ppe [36]. no significant difference was found between a person who had been quarantined and those who had not, which is consistent with the finding of lee et al. who found no difference in ies-r scores between people who were quarantined and those who were not [35]. a possible explanation to this is that covid-19 is a novel virus and that we have little information about it and how to handle it, and it is possible that there are immeasurable variables that could account for some aspects of the results. gad-7 was applied to evaluate the participant’s anxiety symptoms in the last two weeks. we found that most of our participants had scored different levels of anxiety ranging from mild anxiety in 32 (23.2%), moderate anxiety in 53 (13.4%), and severe anxiety in 66 (16.7%). when the demographic data and covid-19 exposure and perception were compared with gad-7 score using chi-square (χ2) test, the data showed that those who did not have a friend or family member diagnosed with covid-19 had a lower score of gad-7 and thus less anxiety than those who did (p = 0.0001); this finding is similar to a study done in wuhan city, china, during this covid-19 pandemic that found increase in anxiety among those with infected family member (p = 0.006) [37]. we also found that medical staff who did not deal with a positive case on covid-19 had a lower gad-7 score than those who did (p = 0.0001). during the sars outbreak, all hospital workers are exposed to some risk of infection; however, the extent of this risk is not distributed equally. some specialties, like ers and critical care staff, are likely to be at higher risk than those in unrelated or non-acute specialties [38]. our study showed that health workers who work in er had higher gad-7 scores than those who are working in other departments (p = 0.034). previous studies had shown that nursing staff felt more nervous and anxious when compared with other groups (p=0.02) (34), this is conflicting to our situation where nurses were found to be less anxious. no increase in working hours during the covid-19 pandemic was associated with low gad-7 score (p = 0.001. while other study reports that doctors were more unhappy about working overtime during the covid-19 outbreak than other hcws (p =0.02) [9], the unavailability of enough personal protective equipment in working places was associated with a low gad-7 score (p = 0.031); this contradicts another study which found that the availability of strict infection control guidelines, specialized equipment, recognition of their efforts by hospital management and the government, and reduction in reported cases of covid-19 provided psychological benefit [39]. doi 10.18502/sjms.v15i5.7136 page 66 sudan journal of medical sciences muna mohamed elamin et al 5. conclusion this study is the first to explore the impact of covid-19 pandemic on medical staff’s perception and determinants of their psychological distress during this outbreak. most of our participants were found to be suffering from anxiety and depression with multiple independent factors. this highlights that more attention should be paid to the mental health of frontline medical personnel at the outbreak of covid-19 in sudan for healthcare administrators; this means that a likely strategy for appeasing the negative outcomes of stress should be addressed besides the working conditions that they face during novel times of crisis. future research directions researchers should conduct further studies on the long-term psychological impact of covid-19 pandemic on healthcare providers, as also a similar study can address samples from the general population and from recovered patients who experienced the unpleasant and traumatizing experience of quarantine. limitations an online questionnaire was used to collect data in this study. the internet is a flexible and cost-effective medium for collecting data from large and specialized samples, with research-approved reliability and internal validity characteristics that are in proportion to traditional paper-and-pencil questionnaire formats [40–41]. however, it has low acceptance as a data collection tool and due to a lack of interactivity between the respondent and researcher affects the researcher’s ability to authenticate an individual’s responses [40]. in this study, we addressed these issues in the following ways. first, the questionnaire was posted on the personal website or social media groups of the participants, this encouraged their participation. second, access to the questionnaire was restricted to particular professionals. lastly, the confidentiality of the participant’s responses was guaranteed on the pre-questionnaire informed consent web page. this was done to motivate the participants to respond more frankly to the questionnaire, which in turn would have increased the validity of our findings. the online questionnaire also affects the interpretation of our results because of the disproportional selection of the strata. another limitation of this study was our use of cross-sectional self-report data which prohibited attribution of causality. however, the inferences we have made regarding the impact of covid-19 on healthcare providers are consistent with longitudinal data in the area. it reflects that the important associations among the variables we studied are the strong corroboration between these findings and similar relationships found in the burnout and existing sars and covid-19 literature. it can also affect the interpretation of our results because it cannot be used to analyze the psychological impact of the participants overtime, so that the online survey was distributed on 11th of april when there were only 19 reported cases and two deaths according to the report of the official doi 10.18502/sjms.v15i5.7136 page 67 sudan journal of medical sciences muna mohamed elamin et al website of federal ministry of health on the same day [42]. the number of total cases was increased to 5499 cases on the 2nd of june, so that the results of the survey reflect the early stage of local pandemic and there might be an increase in the psychiatric burden of the pandemic. also, it cannot be used to determine the onset of the psychological impact, whether before or after the onset of the pandemic. ethical consideration ethical clearance was obtained from the research ethical committee (rec), faculty of medicine, omdurman islamic university. written consent was taken from all participants through the questionnaire. acknowledgment the authors express their sincere thanks to all medical staff who participated in this study and to the faculty of medicine, omdurman islamic university, for their valuable support. completing interests none declared. authors’ contribution all authors participated in the literature search, manuscript editing, and preparation. mme and sbh were responsible for draft writing, conceiving the idea for the article, and wrote the final manuscript. am analyzed the data of this study and participated in draft writing. all authors contributed to and approved the final report. references [1] who. 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[42] federal ministry of health, sudan. committee for health emergency response april 11 2020. retrieved from: http://fmoh.gov.sd/index.php/files/index/116 doi 10.18502/sjms.v15i5.7136 page 70 http://www.sciencedirect.com/science/article/pii/s0889159120303482 http://www.sciencedirect.com/science/article/pii/s0889159120303482 https://doi.org/10.7326/m20-1083 https://doi.org/10.7326/m20-1083 https://doi.org/10.1016/j.comppsych.2018.10.003 https://doi.org/10.1016/j.bbi.2020.04.028 https://doi.org/10.1016/j.bbi.2020.04.028 https://www.medrxiv.org/content/10.1101/2020.02.20.20025338v2 http://fmoh.gov.sd/index.php/files/index/116 introduction materials and methods participants measures procedure data analysis results demographic characteristics covid 19 exposure and perception depression among participants post-traumatic stress disorder among participants anxiety among participants discussion conclusion future research directions limitations ethical consideration acknowledgment completing interests authors' contribution references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8159 production and hosting by knowledge e short communication tele screening, triaging of dental patients, and reopening of dental services during sar-cov2 pandemic elhadi m. awooda1 and reem e. siddig2 1consultant in restorative dentistry and health management 2researcher at sudanese medical sciences research association (smra) abstract background: the nature of dental profession requires a dentist to be in a close proximity to the patient’s mouth to perform various operative treatments including procedures such as generating aerosols. as such, dentistry is considered as one of the riskiest profession for the cross-transmission of sars-cov2. although the prevalence and incidence of sars-cov2 continue to increase worldwide; the dental services and treatment of non-emergency cases have resumed in many countries including sudan. moreover, the use of smartphone technology in communication with patients can play an important role in controlling the spread of sars-cov2. therefore, the aim of this short review was to draw a summary on using smartphone technology for telescreening dental patients prior to their visit to the clinics and to set guidelines and rules for dental treatment during sars-cov2 pandemic. methods: for the purpose of this study, telescreening is referred as a virtual contact between patients and healthcare personnel used to provide health services during the highly contiguous sars-cov2 pandemic. using a smartphone, dental patients can be screened and questioned about their medical history and particularly for sars-cov2 (for symptoms such as fever, headache, coughing, breath shortness, loss of smell or taste). they should also be asked about their travel history to epidemic area, visiting hospital or coming in contact with a confirmed sars-cov2 patient during the last 14 days. on arrival to a dental clinic, the patient’s temperature should be measured, instruction for wearing masks, hand hygiene, and keeping distances from others inside the waiting zone. conclusion: telescreening and triaging will minimize the time of patients’ exposure to dental clinic environments, hence decreasing the risk of getting sars-cov2 infection for both patients and dental healthcare workers. keywords: covid-19, dentistry, procedure generating aerosols, smartphone, social distance, surgical masks. 1. introduction the global sars-cov2 pandemic continues to challenge scientists around the world on discovering its mode of transmission, treatments, and vaccination. as it continues spreading worldwide, health services resources, healthcare professions, economies, how to cite this article: elhadi m. awooda and reem e. siddig (2020) “tele screening, triaging of dental patients, and reopening of dental services during sar-cov2 pandemic,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 371–377. doi 10.18502/sjms.v15i4.8159 page 371 corresponding author: elhadi m.awooda; consultant in restorative dentistry and health management email: dr.alhadi@yahoo.com received 12 november 2020 accepted 9 december 2020 published 31 december 2020 production and hosting by knowledge e elhadi m. awooda and reem e. siddig. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr.alhadi@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences elhadi m. awooda and reem e. siddig and social life around world remain under the immense pressure of depletion, depression, and constraints on the future of earth’s planet life [1]. the rapid spread of the sars-cov2 highlights the possibility of airborne transmission through aerosols and droplets [2]. a contradictory result has been questioned on the risk of getting crossinfection to healthcare workers (hcws) during their routine duties, as an early chinese study reported increased infection rates among hcws, while a retrospective study from switzerland [3] was inconsistent to others and revealed that cross-infection of sarscov2 clusters occurred within the same household or after an enclosed, extended close contact [4, 5]. dentistry is one of the medical professions that involves “procedures generating aerosols” (pga) and represents one of the high-risk professions in crosstransmission of sars-cov2 [6], to both patients and hcws [7]. dentistry has been recommended as a non-emergency treatment until the pandemic is controlled. however, at the same time, dental and oral diseases are chronic in nature; if not managed early, the consequences may cost time, resources, efforts, and finances. likewise, many other non-emergency treatments examples: early dental caries of the enamel and dentin, gingivitis or replacement of a missing tooth or teeth) are of paramount importance to the patient’s psychological, physiological, physical, and mental well-being. many countries have recently implemented strategies for the reopening of dental services [8]. in sudan, however, the clinics were re-opened on june 10, 2020. certain guidelines are required to be followed to avoid risking the dental health care workers’ (dhcps), patients’, or community cross-infection of the sars-cov2. the objective of this short communication was to discuss the implementation of telescreening and triage in dental clinics to prevent and control the spread sars-cov2 and to set guidelines and regulations inside the clinics for patients seeking dental treatment during this pandemic. 2. methods this report represents a summary of the experiences and recommendations of other studies from the literature reviewed for using tele-screening and triage during the sarscov2 pandemic and reopening of dental services. tele-screening: announcements through different social media and communication systems to advise patients; to use the tele-communication for consultation and arranging an appointment. one of the most practical and easily available option is using a smartphone, and when calling, the patient should answer the following questions: 1. have you traveled to any area with a high incidence of sars-cov2, abroad or inside the country [6, 9]? 2. have you visited or met anyone who within the last two months has traveled to any area with the sars-cov2 epidemic? 3. have you come in contact with a known case of sars-cov2 or a suspicious one, at home, markets, neighborhood, social events, etc.? doi 10.18502/sjms.v15i4.8159 page 372 sudan journal of medical sciences elhadi m. awooda and reem e. siddig 4. have you taken any healthcare services (primary, secondary, or tertiary) during the last two weeks for whatever reason (sick, accompanied, visitor, taxi driver or hcw)? 5. have you experienced a fever or headache in the past days? 6. have you experienced dry cough or shortness of breath during the past few days? [6, 9] 7. have you contacted people in public, work, meetings, social events during the past few days? [10] 8. have you lost your sense of smell or taste during the last two weeks? [11] 9. have you heard or seen two or more people with fever and/or respiratory symptoms at home, office, school classrooms, etc. within the last two weeks? 2.1. triaging on arrival to the dental clinic 1. the entrance doors should be kept open in case of non-sliding doors. 2. assigned trained nurse or junior dentist should act as an infection control officer, to be responsible for infection control and prevention measures, for patients and for other dental personals. 3. post signs at entrances reminding patients that the disease has not gone yet and labeled instructions to wear masks, keeping a distance from others inside the waiting zone, no handshaking, hand hygiene, and using disposable tissues while coughing or sneezing [12, 13]. 4. inform patients verbally or through a written brochure about the protocol the clinic follows to prevent and control the sars-cov2, including instructions about compulsory temperature measurement, wearing masks, hand hygiene, and keeping a distance from others. 5. the patient has the right to refuse following the guidelines and rules set by the clinic/hospital, but they should have the clinic/hospital compound and not be allowed to enter. in case they accept the rules and guidelines, a verbal or signed written consent is mandatory. 6. before starting any procedure, the patient’s temperature should be measured [6, 9] and the presence of any respiratory tract symptoms be assessed [14]. 7. an alcoholic disinfectant and masks should be available to all individuals inside the waiting room and should be used all the time [14, 15]. 8. instructions should be given to the patient and/or co-patients about hand hygiene, either by the use of hand sensitizer or hand washing [14]. 9. no-touch receptacles should be provided for the disposal of tissues [11, 13, 15]. doi 10.18502/sjms.v15i4.8159 page 373 sudan journal of medical sciences elhadi m. awooda and reem e. siddig 10. the clinic should have enough space to maintain a physical distance of minimum 1.5 mm between two people [13, 16]. 11. questions about patient’s medical history that was previously asked through telephone should be asked again. 12. a history of the chief complaint should be carried out in a triage area near the entrance. 13. for suspected/confirmed cases of sars-cov2 that are medically stable, authorities responsible for further investigation and management should be consulted [14]. 14. to prevent cross-infection of sars-cov2 within the dental clinics, for cases in (xiii) the treatment should be rescheduled for after a minimum of two weeks, and the patient should be encouraged to self-quarantine [10, 13, 16]. 15. cases with clear acute symptoms and signs of sars-cov2 should be referred to a nearby hospital for further investigations and management. 16. if emergency treatment is needed for those patients with suspicion/confirmed sars-cov2, appropriate personal protective equipment should be used and the protocols of infection control prevention for highly contagious airborne viruses be followed [13]. 3. discussion although, in sudan, the lockdown strategy was implemented for more than three months, the sars-cov2 continues to spread her and all over the world, with no near-future resolution of this pandemic. diseases of dental and oral cavity origins are most likely chronic in nature and early intervention gives better treatment outcomes and prevent unwanted consequences. during the lockdown period, many dental and oral diseases may have been developed, including the highly prevalent dental caries, gingivitis, and periodontitis. the reopening is an inevitable decision for the prevention and treatment of oral and dental diseases. before the reopening, employers and dhcps must understand the following key points: dental settings have unique characteristics that warrant specific infection control consideration; prioritizing the most critical dental services and providing care in an important way that minimizes harm to patients from delaying care and harm to personnel from potential exposure to sars-cov2. appropriate training should be given to all dhcws on infection prevention control measures. also, clinic attendees should have enough knowledge and awareness about sars-cov2 symptoms and its mode of transmission and prevention. audiovisuals, verbal, and written instructions (on coughing and sneezing etiquette, proper hand hygiene, wearing mask all the time, and keeping distances from other while waiting) should be provided to remind and encourage patients to prevent the cross-transmission of the disease. tele-screening can be used as the first step in providing dental consultation and treatments. one of the recommendations is to communicate with patients via smartphones. this minimizes patients’ attendance to the clinic. it also reduces the waiting doi 10.18502/sjms.v15i4.8159 page 374 sudan journal of medical sciences elhadi m. awooda and reem e. siddig time, eventually preventing unwanted crowding. also, patients can be advised to defer the treatment for the coming weeks or even be referred for further medical consultation in case of any suspicious of sars-cov2 infection. recent advances in communication technology (e.g., webinars, video calling, skype, etc.) paired with high internet speed and easy-to-use and highly capable smartphones make it easy for patient and healthcare provider to communicate virtually and to draw treatment planning [7]. american dental association (ada) recommends tele-dentistry as a mean for patient care through the following modalities: 1) synchronous (live video); means direct interaction between patient and dhcw using audiovisual communication. 2) asynchronous (store and forward); for example, radiographs, photographs, video, digital impressions and photomicrographs of patients, to evaluate their dental conditions and arrangement for the suitable alternative way of management. 3) remote patient monitoring (rpm); it means collecting personal health data of an individual in one location through electronic communication to a dental practitioner who use the information outside the real time or live interaction to set plan for management. 4) mobile health (mhealth); through uses of smart phones to provide dental health care and information. [17] worldwide, many hospitals and clinics including the different branches and specialties in medicine and dentistry have recently implemented tele-screening. however, barriers to broad implementation of such services continue to exist in many countries including sudan. where the tele-communication infrastructures still lack and majority of the people reside in rural areas, with electricity deficiency, inability to afford smart phones, and incapability to use it. still with the limited facilities of smart technology in sudan, it can provide a minimal of dental consultation to avoid risking patients cross-infection from health care facilities. recent policy changes promote the use of tele-screening as a way to deliver acute, chronic, primary, and specialty care [18]. in addition, the cost of protective equipment and dental equipment, provider training, and payment regulatory services must be taken into account [19]. tele-screening in dentistry may have some potential limitations, because dental treatment is an interventional operative procedure that necessitates the presence of operator, instruments, and artificial biomaterials. another issue is the level of comfort with technology for dhcps and patients because some patients may have privacy concerns, so the issue of consent should be considered [8]. moreover, the cultural acceptance of conducting virtual visits instead of in-person visits may need time. another guideline is patients’ triaging on arrival to the clinic, which assists in determining the acuity of concerns necessitating early intervention as well as a decrease in overutilization of healthcare resources and particularly for the prevention of crossinfection of sars-cov2. 4. conclusion many countries have recently implemented strategies for the reopening of dental services, it is state of a new normal which cannot be as normal as practiced in the past before the sars-cov2 pandemic. there is a need to avoid crowding, social distancing, doi 10.18502/sjms.v15i4.8159 page 375 sudan journal of medical sciences elhadi m. awooda and reem e. siddig hand hygiene, minimizing the waiting time of patients inside clinics, and appropriate ppe. providing dental treatment services effectively and safely for both patients and dhcws can be guaranteed through tele-screening and triage implementation. authors’ contributions this work was carried out by elhadi mohieldin awooda (ema) & reem isam siddig (ris), where ema who designed the study, reviewed the literature, wrote the protocol, and revised the manuscript critically for important intellectual content. ris, wrote the draft, discussion, and literature searched. both authors, read and approved the final manuscript. competing interests both authors have declared that no competing interests exist. ethics approval: the information provided in this manuscript is of the author’s and coauthor own opinion. the recommendations and summary discussed were extracted from peer review journals and pertinent literatures, were cited accordingly. consent for publication: not applicable. availability of data and materials: all relevant data were within the manuscript, in case of any queries, contact the correspondence author, ema. references [1] zou, l., ruan, f., huang, m., et al. (2020). sars-cov-2 viral load in upper respiratory specimens of infected patients. the new england journal of medicine, vol. 382, no. 12, pp. 1177–1179. [2] chan, j. f., yuan, s., kok, k. h., et al. (2020). a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. lancet, vol. 395, no. 10223, pp. 514–523. [3] veraa, c., heidia, l., janb, p., et al. (2020). transmission risk of sars-cov-2 to healthcare workers – observational results of a primary care hospital contact tracing. swiss medical weekly, vol. 150, p. w20257. doi:10.4414/smw.2020.20257 [4] rothe, c., schunk, m., sothmann, p., et al. (2020). transmission of 2019-ncov infection from an asymptomatic contact in germany. the new england journal of medicine, vol. 382, no. 10, pp. 970–971. retrieved from: http://dx.doi.org/10.1056/nejmc2001468 doi 10.18502/sjms.v15i4.8159 page 376 http://dx.doi.org/10.1056/nejmc2001468 sudan journal of medical sciences elhadi m. awooda and reem e. siddig [5] liu, y., eggo, r. m., and kucharski, a. j. (2020). secondary attack rate and super spreading events for sars-cov-2. lancet, vol. 395, no. 10227, p. e47: doi: http://dx.doi.org/10.1016/s0140-6736(20)30462-1 [6] peng, x., xu, x., li, y., et al. (2020). transmission routes of 2019-ncov and controls in dental practice. international journal of oral science, vol. 12, no. 9, pp.1-6. retrieved from: https://doi.org/ 10.1038/s41368-020-0075-9. [7] tom, s. and jessyka, g. (2020). telemedicine in the era of the covid-19 pandemic: implications in facial plastic surgery. facial plastic surgery & aesthetic medicine, vol. 22, no. 3, pp. 155–156. doi:10.1089/fpsam.2020.0163 [8] centers for disease control and prevention. usa (2020). cdc releases interim reopening guidance for dental settings. division of oral health, national center for chronic disease prevention and health promotion. retrieved from: https://www.cdc.gov/oralhealth/infectioncontrol/statement-covid.html [9] cantore, s. and ballini, a. (2020). coronavirus disease 2019 (covid-19) pandemic burst and its relevant consequences in dental practice. the open dentistry journal, vol. 14, pp. 111–112. retrieved from: https://doi.org/10.2174/1874210602014010111 [10] ather, a., patel, b., ruparel, n., et al. (2020). corona virus disease 19 (covid-19): implication for clinical dental care. journal of endodontics, vol. 46, no. 5, pp. 584–595. [11] spinato, g., fabbris, c., polesel, j., et al. (2020). alterations in smell or taste in mildly symptomatic outpatients with sars-cov-2 infection. jama, vol. 323, no. 20, pp. 2089–2090. doi:10.1001/jama.2020.6771 [12] centers for disease control and prevention (cdc). usa (2020). strategies to prevent the spread of covid-19 in long term care facilities (ltcf) 2020. retrieved from: https://www.cdc.gov/coronavirus/ 2019-ncov/healthcare-facilities/prevent-spread-in-long-term-carefacilities.html [13] fallahi, h., kehyan, s., zandian, d., et al. (2020). being a front line dentist during the covid-19 pandemic: a literature review. maxillofacial plastic and reconstructive surgery, vol. 42, no. 1, p. 12. doi:10.1186/s40902-020-00256-5 [14] ge, z., yang, l., xia, j., et al. (2020). possible aerosol transmission of covid-19 and special precautions in dentistry. journal of zhejiang university science b, vol. 21, no. 5, pp. 361– 368. doi:10.1631/jzus.b2010010. [15] spagnuolo, g., de vito, d., rengo, s., et al. (2020 ). covid-19 outbreak: an overview on dentistry. international journal of environmental research and public health, vol. 17, no. 6, p. 2094. doi:10.3390/ijerph17062094 [16] klyn, s. l., cummings, d. e., richardson, b. w., et al. (2001). reduction of bacteria-containing spray produced during ultrasonic scaling. general dentistry, vol. 49, no. 6, pp. 648–652. [17] american dental association (ada) policy on teledentistry. https://www.ada.org/en/about-the-ada/ ada-positions-policies-and-statements/statement-on-teledentistry. (accessed december 2020). [18] bashushur, r., doarn, c. r., frenk, j. m., et al. (2020). telemedicine and the covid19 pandemic, lessons for the future. telemedicine journal and e-health, vol. 26, no. 5, pp. 571–573. [19] hollander, j. e. and carr, b. g. (2020). virtually perfect? telemedicine for covid-19. the new england journal of medicine, vol. 382, pp. 1679–1681. doi:10.1056/nejmp2003539 doi 10.18502/sjms.v15i4.8159 page 377 http://dx.doi.org/10.1016/s0140-6736(20)30462-1 https://doi.org/10.1038/s41368-020-0075-9. https://doi.org/10.1038/s41368-020-0075-9. https://www.cdc.gov/oralhealth/infectioncontrol/statement-covid.html https://doi.org/10.2174/1874210602014010111 https://www.cdc.gov/coronavirus/2019-ncov/healthcare-facilities/prevent-spread-in-long-term-carefacilities.html https://www.cdc.gov/coronavirus/2019-ncov/healthcare-facilities/prevent-spread-in-long-term-carefacilities.html https://www.ada.org/en/about-the-ada/ada-positions-policies-and-statements/statement-on-teledentistry. https://www.ada.org/en/about-the-ada/ada-positions-policies-and-statements/statement-on-teledentistry. introduction methods triaging on arrival to the dental clinic discussion conclusion authors' contributions competing interests ethics approval: consent for publication: availability of data and materials: references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8941 production and hosting by knowledge e research article the perception of physiologists toward implementing team-based learning in sudan: a national-scale cross-sectional study mohamed elnajid tahir1,2, daffalla mohammed elamean alam /elhuda3, and hosam eldeen elsadig gasmalla4,5 1department of physiology, sudan international university, khartoum, sudan 2department of physiology, university of medical science and technology (umst), khartoum, sudan 3department of community medicine, university of khartoum, khartoum, sudan 4department of anatomy, al-neelain university, khartoum, sudan 5dean, deanship of quality and research, sudan international university, khartoum, sudan orcid: mohamed elnajid tahir: https://orcid.org/0000-0002-3057-6612 hosam eldeen elsadig gasmalla: https://orcid.org/0000-0003-2590-8587 abstract background: team-based learning (tbl) is a teaching approach that fosters active learning and promotes the application of knowledge; its implementation remains sporadic and on a volunteering basis in sudan. the aim of this study was to investigate the perception of sudanese physiologist concerning the implementation of tbl. methods: this descriptive cross-sectional study included all physiologists in sudan during 2018. data were collected using qualitative and quantitative methods, namely, questionnaire and nominal group technique (ngt), respectively. results: this study was the first national-scale study on tbl in sudan, the study adds to the evidence of the benefits of tbl: improving the engagement of students, enhancing deep learning, and providing better instructor–student interaction. furthermore, tbl was perceived to be of good use in tutorials. however, although tbl is perceived well by instructors, its implementation revealed two main challenges: first, the attendance of the students (and therefore their engagement) is a place of concern mostly because tbl is not well-allocated in the curricula of most medical schools and second, the substantial effort of preparation of tbl material and sessions will put a burden on the staff, rendering them less enthusiastic. conclusion: fostering tbl requires administrative support and training to the staff, as well as proper incorporation of tbl in the curriculum. keywords: education, team-based learning, deep learning, physiology 1. introduction team-based learning (tbl) is a teaching approach that fosters active learning. it was introduced in the 1970s for business education (1). tbl includes both individual and team how to cite this article: mohamed elnajid tahir, daffalla mohammed elamean alam /elhuda, and hosam eldeen elsadig gasmalla (2021) “the perception of physiologists toward implementing team-based learning in sudan: a national-scale cross-sectional study,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 101–110. doi 10.18502/sjms.v16i1.8941 page 101 corresponding author: hosam eldeen elsadig gasmalla; department of anatomy, faculty of medicine, al-neelain university-sudan. dean, deanship of quality and research„ sudan international university-sudan. email: hosamalwakeel@hotmail.com received 10 december 2020 accepted 8 march 2021 published 31 march 2021 production and hosting by knowledge e mohamed elnajid tahir et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hosamalwakeel@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed elnajid tahir et al works with feedbacks provided instantly (2-5). it engages participants with the kinds of problems they will encounter in real practice in the future (6). tbl is a teaching approach that is made of units of teaching, each one is known as “module,” those modules are arranged to be taught in a series of three steps: step one is “readiness assurance process,” or rap, which is conducted before the session; step two is the “individual readiness assurance test” or irat; and step three is the “group/team readiness assurance test,” or trat . the students’ grades are assembled from combining the individual’s and groups’ scores . the objectives of tbl are achieved through the interaction between group members, number of the members in the group, well-designed objectives, and good preparation. therefore, the instructor in tbl is considered a leader. the traditional approach of lectures and practical sessions has become inadequate for the students to build an excellent base to depend on in the following clinical years . not many works of literature discuss this, however, tbl can be used as a method to teach physiology revisions and tutorials . the physiology course in sudanese medical schools is taught in two years (four semesters) in the form of lectures and practical sessions. although, since 2004, tbl has been applied globally, it was not implemented in sudanese medical schools as a learning method until recently. the aim of this study was to understand the perception of sudanese physiologists about implementing tbl. 2. materials and methods 2.1. study design this descriptive cross-sectional mixed-method study included all physiologists in sudan during 2018 (n = 60). data were collected using qualitative and quantitative methods, namely, questionnaire and nominal group technique (ngt), respectively. a five-point likert’s scale questionnaire was adopted from a similar study . sociodemographic and academic background variables were added to the questionnaire. the final form of the questionnaire was validated by two experts in health professions education; the confirmatory factor analysis showed an adequate validity, which was then piloted in a group of 33 sudanese physiologists (outside sudan) in which cronbach’s alpha was >0.7. cronbach’s alpha is a tool for measuring the reliability of a given set of data, it was developed by lee cronbach in 1951 (7) and it is widely used to measure doi 10.18502/sjms.v16i1.8941 page 102 sudan journal of medical sciences mohamed elnajid tahir et al the internal consistency. the result is given as a correlation in which the higher the correlation, the higher the reliability. the questionnaire comprised of the following 10 items: 1. tbl prompts students in the learning process. 2. with tbl, i do not have to worry about the classroom attendance of the students. 3. i spend much time listening and observing than making formal presentations. 4. compared to the traditional curriculum, tbl enables weaker students to successfully complete and stay on track in their coursework. 5. tbl prompts the acquisition of knowledge. 6. tbl prompts a depth of understanding. 7. with tbl, i have developed personally rewarding relationships with students. 8. tbl can be successfully employed in large classes. 9. when it comes to tutorials, tbl is the best option. 10. i spend much time preparing for the tbl session. ngt is a procedure used to facilitate effective group decision. it is a tool for qualitative data collection. ngt is easy in application and effective in terms of efficiency and cost. this technique aims to create items and reach a consensus about those discussiongenerated items. it includes a face-to-face meeting based on a predesigned structure and can take up to 2 hr. the group can be composed of five to nine participants. the participants were sat in a comfortable private room, each of them was given a paper containing the questions and was asked to write the answers in the space provided in the paper individually. the facilitator gave them time to answer and then wrote the questions and the answers provided by each participant on a provided board. after that, the discussion started, and the facilitator asked them to select the most suitable answers from the answers provided on the board. the answers were then ranked first, second, and third according to the participants’ votes. ordinal data obtained from the participants’ responses to the questionnaire were converted to quantitative data. the collected data were analyzed using the statistical package of social sciences (spss); they were summarized and presented as mean, median, and standard deviation, the significance level was set at the 95% confidence interval (ci). doi 10.18502/sjms.v16i1.8941 page 103 sudan journal of medical sciences mohamed elnajid tahir et al 3. results a total of 60 people participated in this study. their responses were collected in structured questionnaires and ngt. the participants’ age were aged 25–65 years (mean 34.6 ± 7.71). the years of teaching experience ranged between 1 and 35 years; while most of them were lecturers with a master’s degree (>60%), the experience in tbl implementation ranged between 1 and 10 years. 4. discussion the results showed that a third of the participants are not uncertain about the classroom attendance when using tbl, which is inconsistent with a similar study conducted in a biochemistry course which reported that the majority of teachers agree with tbl and that they don’t have to worry about student’s attendance (8). the authors have utilized ngt to explore this matter (question 1 in table 2), the participants agreed that the main reason is the attendance (most of the semester’s attendances are taken from lectures), this will not motivate the students to attend other activities. it also indicates that the current hidden curricula relay on the lectures as the primary instructional method, and as physiologists implement tbl, the curricula (and the general context as well) imply to the student that any activity other than lectures are “just an accessory,” effective implementation of tbl requires fostering the culture of active learning among students as well as their instructors. in other words, tbl needs to be integrated and rooted in both the course design and context of teaching (9). compared to traditional methods, participants agreed that tbl elevates the level of the weaker students (10) other studies have replaced some of the anatomy lectures with tbl sessions; it showed improvement in students’ performance in the final exam scores compared to the previous years. comparing with the traditional methods of teaching physiology, adam m. persky noted that using more tbl within a physiology course had a favorable impact on student’s retention of material and attitudes toward the course . another interesting study suggested that tbl can be a good option that carries the advantages of both traditional and small group learning (5, 9, 11). tbl established a higher body of knowledge according to the majority (88%) of the participants, and more than half of them (56.7%) felt that tbl promotes deep levels of understanding, this input supports the body of the evidence that suggests the higher performance of medical students in examinations is related to tbl (9, 12, 13). furthermore, tbl allows students to increasingly resolve more complex scenarios and doi 10.18502/sjms.v16i1.8941 page 104 sudan journal of medical sciences mohamed elnajid tahir et al table 1: perception and attitude of participants toward team-based learning. questions strongly agree n (%) agree n (%) uncertain n (%) disagree n (%) strongly disagree n (%) mean rating total no. of responses cronbach’s alpha q1. tbl prompts students in the learning process 31 (51.7) 26 (43.3) 3 (5) 0 (0) 0 (0) 3.47 60 0.712 q2. with tbl, i don’t have to worry about the classroom attendance of the students. 11 (18.3) 16 (26.7) 20 (33.3) 10 (16.7) 3 (5) 2.37 60 0.755 q3. i spend much time listening and observing than making formal presentations. 15 (25) 33 (55) 6 (10) 6 (10) 0 (0) 2.95 60 0.748 q4. compared to the traditional curriculum, tbl enables weaker students to successfully complete and stay on track in their coursework. 21 (35) 28 (46.7) 9 (15) 2 (3.3) 0 (0) 3.13 60 0.707 q5. tbl prompts the acquisition of knowledge. 26 (43.3) 27 (45) 7 (11.7) 0 (0) 0 (0) 3.32 60 0.708 q6. tbl prompts a depth of understanding. 34 (56.7) 20 (33.3) 4 (6.7) 2 (3.3) 0 (0) 3.43 60 0.712 q7. with tbl, i have developed personally rewarding relationships with students. 27 (45) 22 (36.7) 9 (15) 2 (3.3) 0 (0) 3.23 60 0.700 q8. tbl can be successfully employed in large classes. 10 (16.7) 29 (48.3) 13 (21.7) 6 (10) 2 (3.3) 2.65 60 0.725 q9. when it comes to tutorials, tbl is the best option. 28 (46.7) 26 (43.3) 5 (8.3) 1 (1.7) 0 (0) 3.35 60 0.716 q10. i spend much time preparing for the tbl session. 12 (20) 35 (58.3) 8 (13.3) 5 (8.3) 0 (0) 2.90 60 0.745 problems, it also fosters higher levels of understanding (14, 15). in physiology, with tbl, there is a high level of information retention by the students . according to mcinerney doi 10.18502/sjms.v16i1.8941 page 105 sudan journal of medical sciences mohamed elnajid tahir et al table 2: perception of participants using nominal group technique (ngt). questions participants’ opinions final answers voting score rank 1why are you uncertain about student’s attendance when using tbl? participant 1: students think perhaps these are the exam questions, they don’t have to come, and they can take the questions with the answers later from their colleagues who attended. participant 2: most of the students believe that the tutorials are unhelpful. most of the semester’s attendances are taken from lectures. participant 3: unsuitable time (at the end of the day) no strict rules for attendance in tutorials. 1. most of the semester’s attendances are taken from lectures. unsuitable time (at the end of the day) most of the students believe that the tutorials are unhelpful. 1, 1, 1 = 3 1, 1 = 2 1 = 1 1st 2nd 3rd 2when it comes to tutorials, tbl is the best option. (why?) participant 1 because the students can learn from the discussion that happens during the sessions even if they are not prepared in advanced, unlike problem-based learning (pbl). it is cost-effective. participant 2 not the best option for a tutorial because it is difficult to assess each student separately, especially when the number is large. unlike pbl, it does not contain open-ended questions. participant 3 good option because students can be evaluated using i-rat. encourages students to study. because students can learn from the discussion between the members and the final discussion with the teacher. encourages students to come prepared for the tutorial. 1, 1, 1 = 3 1, 1 = 2 1st 2nd 3why do you spend much time preparing for the tbl session? participant 1 finding suitable questions for discussion. student’s survey to find weak and high academic students to mix them together. participant 2 -same ideas as the first participant. participant 3 just initially but with experience is going to be easy and fast. unlike pbl, lack of standard questions bank. finding suitable questions for discussion (lack of standard questions bank). just initially but with experience is going to be easy and fast. student’s survey to find weak and high academic students to mix them together. 1, 1, 1 = 3 1, 1 = 2 1 = 1 1st 2nd 3rd doi 10.18502/sjms.v16i1.8941 page 106 sudan journal of medical sciences mohamed elnajid tahir et al and fink, tbl motivates learners, and provides them with skills for resolving complex problems (16). according to the participants in this study, tbl helps in developing a positive teacher– student relationship. similar results were reported by [13] persky and pollack, and chhabra et al. (8, 17). our study showed that participants perceive tbl as a process that can be applied to a large group. almost 50% of the participants agreed that tbl could be done with large number of students; results from studies in physiology courses reflect the same conclusions (11). most of the participants (90%) felt that the best option for tutorials is tbl. after discussion with the participants using the ngt, the most voted answer was tbl is the best option for tutorials because students can learn from the discussion between the members and the final discussion with the teacher. this result is consistent with a study conducted by amalladinna et al. (18) which compared traditional ways of teaching with the tbl technique in tutorial teaching in physiology education. facilitation in tbl differs from facilitation of other modalities of the small group settings (19). more than half of the participants agreed that they spend much time preparing for the tbl than other teaching methods. putting this question for discussion in ngt, the participants agreed that there should be a questions bank for tbl just like pbl. they also suggested that much time is spent only at the beginning of the semester, the initial tbl sessions (i.e., preparing the cards, the classroom, and mixing the students according to their academic performances), after which the process will go smoothly. the substantial effort of preparation of tbl material and sessions will put a burden on the staff, rendering them less enthusiastic , this requires administrative support as well as proper incorporation of tbl in the curriculum. 5. conclusion this is the first national-scale study on tbl in sudan, the study adds to the evidence of the benefits of tbl: improving the engagement of students, enhancing deep learning, and providing better instructor–student interaction. furthermore, tbl was perceived to be of good use in tutorials. however, although tbl is perceived well by instructors, its implementation remains sporadic, and on a volunteering basis, this raised two concerns. first, the attendance of the students (and therefore their engagement) is a point of concern mostly because tbl is not well-allocated in the curricula of most medical schools and second, the substantial effort of preparation of tbl material and sessions will put a burden on the staff, rendering them less enthusiastic. doi 10.18502/sjms.v16i1.8941 page 107 sudan journal of medical sciences mohamed elnajid tahir et al recommendation fostering tbl requires administrative support and training to the staff, as well as proper incorporation of tbl in the curriculum; development of a questions bank for tbl is also recommended. limitations all physiologists in sudan at the time of the study were included, they all had a reasonable experience in tbl; however, their experiences are variable and range from all -year implementation to frequent implementation, therefore, the variation between their experiences must be considered. acknowledgements the authors would like to thank dr hamdan zaki hamdan for his help, support, and encouragement and mr. omer elsadig for all the technical support. ethical considerations the study protocol was approved by the institutional review board, al-neelain university (irb). competing interests the authors report no conflict of interest. availability of data and material data are stored in a local electronic store and will be available upon reasonable request. funding none. doi 10.18502/sjms.v16i1.8941 page 108 sudan journal of medical sciences mohamed elnajid tahir et al authors’ contributions met worked on the study concept and literature search. the study methodology was finalized by met and heeg. data acquisition, data analysis, and statistical analysis were performed by met and dmea. manuscript preparation, editing, and review were done by dmea and heeg. the final version of the manuscript was approved by heeg. currently he is the dean of quality and research, sudan international university. references [1] hrynchak p, batty h. the educational theory basis of team-based learning. med teach. 2012;34(10):796-801. 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[19] gullo c, ha tc, cook s. twelve tips for facilitating team-based learning. med teach. 2015;37(9):819-24. doi 10.18502/sjms.v16i1.8941 page 110 introduction materials and methods study design results discussion conclusion recommendation limitations acknowledgements ethical considerations competing interests availability of data and material funding authors' contributions references sudan journal of medical sciences volume 15, issue no. 4, doi 10.18502/sjms.v15i4.8157 production and hosting by knowledge e research article effects of nurse’s work environment and practice on patient’s safety montaha mohammed ibrahim1 and hammad ali fadlalmola2 1university of king khalid, saudi arabia 2nursing college, taibah university, saudi arabia abstract background: when a patient with an acute medical illness is admitted to a hospital, their safety is a prime concern for healthcare professionals. ongoing nursing assessment is a type of nursing assessment that commences at the beginning of every shift. and **is completed on every patient. this information is used to develop a plan of care. the aim of this study is to assess the application of ongoing nursing assessment approaches in intensive care units. methods: this cross-sectional hospital-based study included a total of 135 nurses, of which 23 (17%) were from khartoum hospital, 62 (46%) from alshaab hospital, 15 (11%) from soba university hospital, and 35 (26%) from national center for neurological science. results: the ongoing nursing assessment approaches were available in most intensive care units of the study area with the domination of abcde approach. factors that can impact the thoroughness of the ongoing nursing assessment performance suggested by the studied participants were nurses’ knowledge and competency, followed by insufficient time and resources to carry out the assessment. conclusions: most participants did not complete the assessment suggesting a poor performance. the knowledge base of the participants was not reflected in their practice with a wide difference between them. keywords: nursing assessment approach, intensive care unit, assessment performance, sudan 1. introduction nurses comprise the largest group of professionals within the healthcare workforce and provide for 75% of the care received by patients in hospital settings. there is an increasing demand for healthcare and nursing services due to population growth, while the supply of nurses is diminishing [1]. improvement in nurses’ practice environment in acute care hospitals has been the focus, challenge, and recommendation of many studies, commissions, and committees; lack of a productive, healthy work environment has been related to nursing shortage, poor quality of nurses’ work lives, their job dissatisfaction, low productivity, and poor-quality and unsafe patient care. the first how to cite this article: montaha mohammed ibrahim and hammad ali fadlalmola (2020) “effects of nurse’s work environment and practice on patient’s safety,” sudan journal of medical sciences, vol. 15, issue no. 4, pages 345–354. doi 10.18502/sjms.v15i4.8157 page 345 corresponding author: hammad ali fadlalmola; nursing college, taibah university, saudi arabia email: hazzminno345@gmail.com received 15 october 2020 accepted 18 november 2020 published 31 december 2020 production and hosting by knowledge e montaha mohammed ibrahim and hammad ali fadlalmola. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hazzminno345@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola attempt to measure the attributes of an excellent staff nurse work environment began with 1984 [2]. the conditions in which nurses work can influence the likelihood of errors and the quality of care afforded to patients [3]. the link between nurse staffing and adverse outcomes has been noted in the field and has led to some action, the american nurses association began its nursing safety and quality initiative in 1994 to develop hospital quality indicators [4]. the study conducted by vincent et al.in british hospitals, to examine the feasibility of detecting adverse events through record and to make preliminary estimates of the incidence and costs of adverse events, concluded that about half of these events were judged preventable with ordinary standards of care, when a third of adverse events led to moderate or greater disability or death, also suggesting that adverse events are a serious source of harm to patients and a large drain on nhs resources [5]. over the last two decades, substantial changes have been made in the organization and delivery of healthcare; these fast-paced changes have resulted from multiple, concurrent events, including major modifications in which government and private health insurance programs reimburse healthcare providers (including hospitals, nursing homes, home healthcare agencies, and individual practitioners), cost containment efforts of healthcare organizations (hcos) in response to these changes in reimbursement growth in, and increased demand for new healthcare technologies and changes in the healthcare workforce. hcos have responded in a variety of ways that in turn have affected the work and environment of nurses [6]. while the world health organization (who) defines patient safety as the absence of preventable harm to a patient during the process of healthcare [7], others have similarly defined it as the freedom from accidental injury caused by medical care, which further translates to medical error [8]. for nurses, patient safety is not just part of what they do, they are committed through their code of ethics to provide “safe, competent and ethical care” [9]. in 2015, the hospital national patient safety goals were developed to improve patient’s safety, focusing on problems in healthcare safety and how to solve them; these include: • identifying patients correctly • improving the effectiveness of communication among caregivers • improving the safety of using medications • reducing the risk of healthcare-associated infections [10] • accurately and completely reconcile medications across the continuum of care • reducing the risk of patient harm resulting from falls • reducing the risk of influenza and pneumococcal disease in institutionalized older adults • reducing the risk of surgical fires • encouraging patient’s active involvement in their care as a patient safety strategy • preventing healthcare associated with pressure ulcers • improving recognition and responses to changes in a patient’s condition [11] doi 10.18502/sjms.v15i4.8157 page 346 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola a 2016 study by waleed et al. in sudan revealed that almost half of the nurses (46.2%) had low levels of job satisfaction which may negatively affect nurse’s work environment and practice on patients [23]. 1.1. justifications generally, there is a lack of effort to assess the effect of nurse’s work environment and practice on patient safety. hospitals with a positive work environment are characterized by open communication among their staff, nurses magnifying the importance of patient safety, continuous training for patient safety practice, and encouragement to freely report nurse’s errors. 1.2. objectives of the study 1.2.1. general objective to assess the effect of nurse’s work environment and practice on patient safety in selected khartoum state hospitals. 1.2.2. specific objectives 1. to identify nurses’ work environments that can affect patient safety 2. to assess the effect of nurses’ practice on patient safety 3. to elicit nurses’ opinion that will promote an effective work environment for patient safety 2. materials and methods 2.1. study design this is a descriptive cross-sectional hospital-based study design. 2.2. study area and sitting khartoum state is one of the 18 states of sudan. although it is the smallest state in area (22,142 km2), it is the most populated (5,274,321 according to the 2008 census). it contains the country’s largest city by population – omdurman, khartoum north and the city of khartoum –which is the capital of the state and contains federal ministry of government as well as the national capital of sudan. the study was conducted in three hospitals representing the three areas (khartoum, bahri, and omdurman), these hospitals are as follows. doi 10.18502/sjms.v15i4.8157 page 347 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola 1. academy hospital: the academy hospital lies in the sprawl of grade three. the hospital has many departments including icu, medical, surgical, hemodialysis, pediatric, and emergency departments. a total of 148 nurses work in this hospital. 2. khartoum north hospital (bahri teaching hospital): this hospital lies at the center of bahri city. the hospital has several departments including medicine, surgery, obstetric, and pediatrics in addition to an outpatient for emergency cases. a total of 230 nurses work in this hospital. 3. omdurman teaching hospital: this is a big hospital located in the old city of omdurman. the hospital has several departments including an outpatient. a total of 200 nurses work in this hospital. 2.3. study population the study included all graduate staff nurses who have been working in the different departments of the aforementioned three hospitals. a total of 230 nurses from the bahri, 200 from the omdurman, and 148 from the academy hospitals were included, of which 234 were finally selected. 2.4. inclusion criteria nurses working at the selected hospitals during the study period and willing to participate in the study and graduate nurses. 2.5. exclusion criteria nurses who were unavailable during the study period due to sick leave, yearly leave, and certified nurses. 2.6. data collection instruments data were collected by standard closed-ended filled questionnaire as a tool for data collection. the tool was extracted and designed after careful review of the literature and previous studies, and a checklist was taken from the national center for patient safety goal, which were modified and adapted according to the khartoum state hospitals. after the tool was designed, a pilot study was done. this study included a total of 15 nurses. the questionnaire comprised of 20 questions and the questions were found to be understandable by the participants, therefore the questionnaire was adopted. the self-administered questionnaire and checklist consisted of the following three parts: 1. part 1: demographics and personal data, composed of four questions. 2. part 2: identifying nurse’s work environment that effects patient’s safety, composed of 13 questions. doi 10.18502/sjms.v15i4.8157 page 348 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola 3. part 3: reflecting opinions and intention of nurses regarding effective work environment and patient safety, composed of two questions. 4. part 4: checklist to assess nurse’s practice, composed of 11 questions. 2.6.1. effects scale: effect = yes = 3 not sure about effect = not sure = 2 no effect = no = 1 2.6.2. practice scale: high practice = done by all steps = 3 fair practice = done inappropriately by half steps = 2 low practice = not done by steps = 1 2.6.3. attitude scale: high attitude = strongly agree = 3 fair attitude = agree = 2 low attitude = disagree = 1 2.7. data analysis and management data were analyzed using the statistical package for social science (spss), version 21 with a reference p-value 0.05 and confidence degree 0.95. descriptive statistics measures (frequency and percentage) were done for qualitative data, and the relationship was tested using chi-square and fisher exact tests for independence. 2.8. ethical consideration 1. ethical clearance for the study was obtained from the university of medical sciences and technology – faculty of nursing sciences (irb number: 00008867). 2. an approval to carry out the study was taken from the ministry of health, khartoum state. 3. permission was also sort from the khartoum north teaching hospital, academy hospital, and omdurman teaching hospitals. 4. a brief consent form to be filled by the respondents regarding the confidentiality of information was given along with the questionnaire. 5. no personal identification was registered, and confidentiality was maintained. doi 10.18502/sjms.v15i4.8157 page 349 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola 3. results regarding the overall answer of nurses in three hospitals, 80.3% agreed that work environment can affect patient safety, 11.5% did not agree, and 8.1% were unsure. figure 1: shows the participants response regarding work environment can effect on patient’s safety or not. regarding the knowledge about the effect of work environment on patient safety, most nurses stated that all factors mentioned affect patient safety as follows: volume of work assigned to individuals from 67.1–78.3%, 76.1–78% for professional skills required for specific job assignments, when the duration of experience in a particular job category accounted by 74.4% to 86.7%, 69.6% to 72% for work schedules. interactions among workers accounted 64.1% to 80%, 75.8% to 85% nature and scope of the work, were the staff level of education take one of the highest percent 78.5% to 84.1%. the majority agree with effect of nursing staffing level 82.8% to 94.9%, 73.1% to 81.7% for number of patients that care, the number of staff leave the job take the lowest percent 60.2% to 64.2%. the study result also showed that the nurse’s knowledge and experience were adequate to help them determine that their work environment affects patient safety. the effect of work environment on patient safety represented that more than half of the nurses knew ways to assess the effect of their work environment and practices on patient safety and that they need to be committed to following it because the goal is to deliver the best care to every patient every day. moreover, the current study found that 74.2– 91.7% of the nurse’s work environment affects patient outcomes that are related to patient safety (by means of readmission, failure to rescue cardiac arrest, hospitalacquired pneumonia, and other adverse events). one of the biggest problems currently facing the nursing profession is the complexity of the plan of care and the effect thereof on nurses to execute the plan, which can thereby affect patient safety. accordingly, 70% of the nurses at the academy, 58.1% at the bahri, and 77.8% at the omdurman doi 10.18502/sjms.v15i4.8157 page 350 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola hospitals agree that the effect of the complexity of the plan of care on the nurses while implementing it can affect patient safety, as shown in table 1. table (1) shows the participants response regarding the effect of work environment on patient safety outcome and error recognition. table 1 assess the effect of work environment on patient safety academy bahri omdurman pvalue frequency % frequency % frequency % do nurses work environment affect patient outcomes that are related to patient safety? no 1 1.7 13 14.0 6 7.3 .013 not sure 4 6.7 11 11.8 3 3.7 yes 55 91.7 69 74.2 73 89.0 do nurses work force environment affect the rate of medical errors? no 9 15.0 26 28.0 11 13.6 .094 not sure 8 13.3 12 12.9 8 9.9 yes 43 71.7 55 59.1 62 76.5 do nurses work environment affect the rate of recognition of medical errors after they occur? no 9 15.3 11 11.8 8 9.8 .779 not sure 11 18.6 17 18.3 12 14.6 yes 39 66.1 65 69.9 62 75.6 do nurses work environment affect the probability that adverse events will occur following detected or undetected medical errors? no 7 11.7 6 6.5 9 11.0 .402 not sure 6 10.0 19 20.4 14 17.1 yes 47 78.3 68 73.1 59 72.0 does the complexity of the plan of care affect the nurses to implement it which can lead to effect on patient safety no 10 16.7 20 21.5 6 7.4 .048 not sure 8 13.3 19 20.4 12 14.8 yes 42 70.0 54 58.1 63 77.8 doi 10.18502/sjms.v15i4.8157 page 351 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola in relation to safety training, only 69% of the nurses reported that they had attended mandatory medication, hand hygiene, and medical error safety training in the last year. therefore, as shown in table 2. table (2) show the participants response regarding whether they received training on patient safety or not. table 2 training in patient safety academy bahri omdurman total no frequency 20 31 15 66 % 33.9 33.3 18.8 28.4 not sure frequency 2 1 3 6 % 3.4 1.1 3.8 2.6 yes frequency 37 61 62 160 % 62.7 65.6 77.5 69.0 total frequency 59 93 80 232 % 100 100 100 100 one of the pertinent issues to be recommended in the research is to provide training in patient safety to the nurses. 4. discussion the work environment of nurses has been linked to patient safety outcomes through previous research studies; evidence suggest that when nurses improved their work environment to support patient safety, the outcomes were enhanced [12]. nursing staff plays a key role in ensuring the safety of patients because it provides direct assistance and care to the patients and their family, composing the largest group of professionals in the field of healthcare worldwide; because these professionals have direct participation in the safety of patients, it is essential to understand the conditions and complexities of their work environment that may compromise the quality of care delivery, especially in regard to interruptions of the activities performed by nurses [13]. the study conducted indicates that nurse staffing has a definite and measurable impact on patient outcomes, medical errors, length of stay, nurse turnover, and patient mortality [14]. also, similar to our study, liang’s study found that the work environment of nurses has a critical impact on patient safety [14]. many studies agree with the results of our research results; a study conducted by the national human resources for health strategic plan for sudan 2012–2016 revealed that sudan has been pursuing the attainment of its millennium development goals (mdgs) despite confronting a range of complex public health challenges including the shortages and misdistribution of the human resources for health [15]. three statistically significant relationships were found between nurse staffing and adverse events readmission, failure to rescue cardiac arrest, and hospitalacquired pneumonia [16]. a study published in october 2014 by yakusheva et al. from the university of michigan found that a 10% increase in the proportion of baccalaureate prepared nurses on hospital units was associated with lowering of patient mortality doi 10.18502/sjms.v15i4.8157 page 352 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola by 10.9%. authors also found that increasing the amount of care provided by nurses have a bachelor of science in nursing (bsns) to 80% would result in significantly lower readmission rates and shorter lengths of stay [17]. the current study revealed that work schedule affects patient safety, being in line with a previous study that concluded that both errors and near errors are more likely to occur when hospital staff nurses work for 12 or more hours at a stretch, the use of extended work shifts, and overtime has escalated as hospital cope with a shortage of registered nurses. the risks of making an error were significantly increased when work shifts were longer than 12 hr, when nurses worked overtime, or when they worked more than 40 hr/week [18]. in january 2003, the school of government bipartisan congressional health policy conference reported that recent evidence suggests that more nurses lead to better patient outcomes [19]. a study conducted among a canadian-hospital nurses to assess the impact of nursing work environments on patient safety outcomes and the mediating role of burnout/engagement suggest that patient safety outcomes are related to the quality of the nursing practice work environment and nursing leadership role in changing the work environment to decrease nurse burnout. [20]. in a study published in september 2003 in the online journal of issues in nursing synthesizing much of the research done on nurse staffing and patient outcomes, the impact of organizational characteristics on nurse staffing patterns, patient outcomes, costs, and the impact of nurses’ experience on patient outcomes, the author concluded that nurse staffing has a definite and measurable impact on patient outcomes [21]. moreover, literature indicates that appropriate staffing ratios are important, however, ratios must be modified by the nurses’ level of experience, the organization’s characteristics, and the quality of clinical interaction between and among physicians, nurses, and administrators [21]; 72.8% of the participants in the selected hospitals agree that the work environment factor affects patient safety. so, changes in healthcare work environments are needed to realize quality and safety improvements. in order to assess the effect of work environment on patient safety, 66.7% of the academy, 82.2% of the bahri, and 86.4 % of the omdurman nurses use patient outcome. moreover, the current study found that 74.2–91.7% of the nurse’s work environment affects patient outcomes that are related to patient safety (by means of readmission, failure to rescue, cardiac arrest, hospital-acquired pneumonia, and other adverse events). this is in agreement with a study published in march 2007 that concluded that improving the work environment of nurses reduces the effect related to patient outcome and was associated with less hospital-related mortality, failure to rescue, cardiac arrest, hospital-acquired pneumonia, and other adverse events [22]. 5. conclusion the study concludes that the nurses’ work environment does have an effect on patient safety and improving it by treating the different factors (i.e., the volume of work assigned to individuals, professional skills required for specific job assignments, duration of experience in particular job category, work schedules, etc.) that affect patient safety will optimize patient safety. doi 10.18502/sjms.v15i4.8157 page 353 sudan journal of medical sciences montaha mohammed ibrahim and hammad ali fadlalmola references [1] marie, p. n. 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(2015). interruptions of nurses’ activities and patient safety: an integrative literature review. revista latino-americana de enfermagem, vol. 23, no. 1, pp. 169–179. [14] lin, l. and liang, b. a. (2007). addressing the nursing work environment to promote patient safety. nursing forum, vol. 42, no. 1, pp. 20–23. [15] hubbard, i. j., harris, d., kilkenny, m. f., et al. (2012). adherence to clinical guidelines improves patient outcomes in australian audit of stroke rehabilitation practice. archives of physical medicine and rehabilitation, vol. 93, no. 6, pp. 965–971. [16] ann, r. e., wei-ting, h., linda, s. d., et al. (2004). the working hours of hospital staff nurses and patient safety. health affairs, vol. 23, no. 4, pp. 202–212. [17] yakusheva, o., lindrooth, r., and weiss, m. (2014). economic evaluation of the 80% baccalaureate nurse workforce recommendation: a patient-level analysis. medical care, vol. 52, no. 10, pp. 864–869. [18] mchugh, m. d., kelly, l. a., smith, h. l., et al. (2013). lower mortality in magnet hospitals. the journal of nursing administration, vol. 43, no. 10 0, pp. s4–s10. [19] keenan, p. (2003). the nursing workforce shortage: causes, consequences, proposed solutions (commonwealth fund issue brief no. 619), pp. 1–8. [20] laschinger, h. k. s. and leiter, m. p. (2006). the impact of nursing work environments on patient safety outcomes: the mediating role of burnout engagement. the journal of nursing administration, vol. 36, no. 5, pp. 259–267. [21] curtin, l. l. (2003). an integrated analysis of nurse staffing and related variables: effects on patient outcomes. online journal of issues in nursing, vol. 8, no. 3, p. 118. [22] kane, r. l., shamliyan, t., mueller, c., et al. (2007). nurse staffing and quality of patient care. evidence report/technology assessment, vol. 151, no. 1, p. 115. [23] abduelazeez, a. e. and tahir, m. m. (2016). job satisfaction and related factors among intensive care nurses in governmental hospitals at khartoum state–sudan. journal of community & public health nursing; vol. 2, no. 2, p. 114. doi 10.18502/sjms.v15i4.8157 page 354 http://www.who.int/patientsafety/about/en/ http://www.who.int/patientsafety/about/en/ www.ivyleaguenurse.com introduction justifications objectives of the study general objective specific objectives materials and methods study design study area and sitting study population inclusion criteria exclusion criteria data collection instruments effects scale: practice scale: attitude scale: data analysis and management ethical consideration results discussion conclusion references sudan journal of medical sciences volume 12, issue no. 2, doi 10.18502/sjms.v12i2.919 production and hosting by knowledge e research article awareness of diabetic retinopathy among patients with diabetes mellitus in ilorin, nigeria olokoba l. b.1, mahmud o. a.1, adepoju f. g.1, and olokoba a. b.2 1department of ophthalmology, university of ilorin teaching hospital, ilorin, nigeria 2department of medicine, university of ilorin teaching hospital, ilorin, nigeria abstract background: diabetic retinopathy is a major cause of blindness worldwide. the associated loss of productivity and quality of life of the patients with diabetic retinopathy will lead to additional socioeconomic burden. this study aims to determine the level of awareness of diabetic retinopathy among diabetic patients. materials and methods: this hospital-based cross sectional study, was carried out at the diabetic and ophthalmology clinics of university of ilorin teaching hospital, nigeria from november 2011 to july 2012. a total of 365 patients had validated, semi-structured, and interviewer-administered questionnaires to obtain information on socio-demographic characteristics, clinical information and awareness of diabetic retinopathy. results: a total of 365 patients were enrolled, with age between 19 and 90 years, and a mean of 45.8 ± 16.3 years. the male to female ratio was 1: 2.2. ninety-nine respondents (27.1%) had no education. the majority (30.4%) had only primary education; 21.1% had tertiary; 14.5% had secondary while 6.8% had quranic education. the mean duration of diabetes mellitus was 14.1 ± 13.09 years. of the 365 patients with diabetes mellitus, 279(76.4%) had heard that diabetes mellitus affects the eyes, while 86(23.6%) had not. of those who had heard, 221(79.2%) heard it from health personnel, 45(16.1%) from radio/television, 25(9.0%) from internet, 23(8.2%) from books/newspapers, while 16(5.7%) heard from other sources. conclusion: there was a high level of awareness of diabetic retinopathy amongst the patients. however, the high level of awareness of the blinding complication of diabetes mellitus did not translate to a correspondingly high level of ocular examination for diabetic retinopathy. keywords: awareness, diabetic retinopathy, diabetes mellitus, eye examination how to cite this article: olokoba l. b., mahmud o. a., adepoju f. g., and olokoba a. b., (2017) “awareness of diabetic retinopathy among patients with diabetes mellitus in ilorin, nigeria,” sudan journal of medical sciences, vol. 12 (2017), issue no. 2, 89–100. doi 10.18502/sjms.v12i2.919 page 89 corresponding author: olokoba l. b.; email: drlbolokoba@gmail.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e olokoba l. b. et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:drlbolokoba@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e الخلفية: اعتالل الشبكية السكري هو أحد األسباب الرئيسية للعمى يف جميع أنحاء العالم. الشبكية باعتالل المصابين للمرضى الحياة ونوعية باإلنتاجية المرتبطة الخسارة إن تحديد إىل الدراسة هذه تهدف إضايف. اقتصادي اجتماعي عبء إىل ستؤدي السكري مستوى الوعي باعتالل الشبكية السكري بين مرضى السكري. عيادات يف المستشفى، إىل المستندة المقطعية الدراسة هذه أجريت والطرق: المواد نوفمبر من نيجيريا التعليمي، إيلورين جامعة مستشفى يف العيون وأمراض السكري االجتماعية الخصائص عن معلومات على للحصول و .٢٠١٢ يوليو إىل ٢٠١١ ٣٦٥ من السكري الشبكية اعتالل بمرض والوعي السريرية والمعلومات والديموغرافية مريضا، تم استخدام استبيانات مدروسة ومعدة لهذا الغرض مع اجراء المقابالت. سنة، ٩٠ و ١٩ بين أعمارهم تراوحت مريضا، ٣٦٥ مجموعه ما تسجيل تم النتائج: ومتوسط عمر ٤٥٫٨ ± ١٦٫٣ سنة. وكانت نسبة الذكور إىل اإلناث ١: ٢٫٢. ولم يتلق ٩٩ (٢٧٫١ ٪) مشاركا أي تعليم. أما األغلبية (٣٠٫٤ ٪) فلم يحصلوا إال على التعليم االبتدايئ؛ و ٢١٫١٪ لديهم التعليم العايل. ١٤٫٥٪ منهم ثانويون و ٦٫٨٪ لديهم تعليم قرآين. كان متوسط مدة داء (٪٧٦٫٤) ٢٧٩ السكري، بداء مصاب مريض ٣٦٥ بين من سنة. ١٣٫٠٩ ± ١٤٫١ السكري سمعوا أن داء السكري يؤثر على العينين، يف حين أن ٨٦ (٢٣٫٦٪) لم يسمعوا بذلك. من بين الذين سمعوا، ٢٢١ (٧٩٫٢٪) سمعوا من العاملين يف المجال الصحي، و ٤٥ (١٦٫١٪) من اإلذاعة والتلفزيون، و ٢٥ (٩٫٠٪) من اإلنترنت، و ٢٣ (٨٫٢٪) من الكتب / الصحف، يف حين أن ١٦ (٥٫٧٪ ) سمعت من مصادر أخرى. اإلستنتاج: كان هناك مستوى عال من الوعي عن اعتالل الشبكية السكري بين المرضى. مرض من للعمى المسببة بالمضاعفات الوعي من العاىل المستوى فإن ذلك، ومع السكري لم تترجم إىل مستوى عال للمقابلة من فحص العين السريرى العتالل الشبكية السكري. 1. introduction diabetes mellitus (dm) is a chronic metabolic disorder of multiple aetiologies [1] it is associated with various forms of both acute and chronic complications, which often lead to premature death [2]. dm increases the risk of a range of eye diseases including cataract, but the main cause of blindness associated with dm is diabetic retinopathy (dr) [3]. vision threatening dr is treated most commonly with laser to prevent visual impairment and blindness [3]. studies have shown that the incidence of blindness from dr is significantly reduced by early treatment with laser photocoagulation [4, 5]. dr has few symptoms until vision loss develops. early treatment can only be instituted if retinopathy is detected early by regular ocular examination through a screening programme for patients with dm. doi 10.18502/sjms.v12i2.919 page 90 sudan journal of medical sciences production and hosting by knowledge e in the united states of america (usa), dr accounts for 12,000 – 14,000 new cases of blindness yearly. it also accounts for 11.9% of all blind registration in those aged 16– 64 years in the united kingdom (uk) [6]. in the recently concluded nigerian blindness survey, dr accounted for 0.02% of the total blindness in nigeria in adults 40 years and above [7]. sadly, there is no treatment that can restore vision that has already been lost from dr. fortunately, dr has a ten to twenty-year delay before onset allowing a small window of opportunity for early detection through regular and routine screening and treatment [3]. in our institution, university of ilorin teaching hospital (uith), nigeria with the availability of laser equipment and the human resources to deliver laser photocoagulation, the goal is to reduce blindness from dr by providing prompt treatment (laser photocoagulation). there is a paucity of information on patient’s level of awareness of dr, and screening protocols for dr. this study was therefore designed to determine the level of awareness of dr with a view to developing a protocol for screening of dm patients in order to achieve this goal. 2. patients and methods this was a hospital-based cross sectional study, carried out at the diabetic and the ophthalmology clinics of uith, nigeria from november 2011 to july 2012. 2.1. sample size determination the minimum sample size was calculated using the fisher’s formula [8] n = z2 pq/d2, where n = required sample size. z = standard normal distribution corresponding to specified confidence level = 1.96 with a confidence level of 95%. p = 15.1% [9] q = 1-p = 0.849 d = degree of accuracy=0.05 n = 1.96 x 1.96 x 0.151 x 0.849/0.05 x 0.05 = 197 patients. correcting for 10% attrition rate, 10/100 x 197 = 19.7. 197 patients plus 20 (for attrition) = 217 patients as the minimum sample size. a total of 365 patients were eventually recruited for the study. validated, semistructured, interviewer-administered questionnaires were administered to obtain information on socio-demographic characteristics, and clinical information on dm. laboratory investigations such as fasting blood glucose, and urinalysis were carried doi 10.18502/sjms.v12i2.919 page 91 sudan journal of medical sciences production and hosting by knowledge e out. patients with confirmed diagnosis of dm, and those on treatment for dm were enrolled. patients who decline consent were excluded. 2.2. subject selection on each clinic day, an average of 60 dm patients were seen. the list and case notes of all patients booked to be seen at the clinic were retrieved from the medical records department a day before the clinic. using a systematic random sampling technique, 20 dm patients were selected and screened on each clinic day. the case notes of the selected patients were marked to prevent them from being recruited again at their next clinic visit. the first patient to be recruited each clinic day was chosen by balloting in a simple random fashion. thereafter, with a sampling interval of 3, every 3rd patient was selected using a systematic random sampling technique. patients with confirmed diagnosis of dm, and those on treatment for dm were included in the study. 2.3. laboratory tests about 2 ml of venous blood was drawn from the antecubital vein using a vacutainer needle into fluoride oxalate for fasting blood glucose. the blood samples were analysed in the general laboratory of the hospital on the day of collection according to standard protocol. about 2ml of urine sample was also collected (into a sterile universal sample bottle) from the patients for urinalysis using a reagent strip. approval for the study was obtained from the ethics and research committee of the uith. verbal and informed consent was obtained from all the participants. 2.4. statistical analysis data collation and editing were done manually to detect omission and ensure uniform coding. the data was entered into a computer and statistical analysis was carried out with epi-info version 6.1 statistical software. frequency tables were generated for all the variables. quantitative variables were expressed as mean and standard deviation. 3. results a total of 365 patients were enrolled, with age ranging from 19 and 90 years, and a mean age of 45.8 ± 16.3 years. the male to female ratio was 1: 2.2 (table 1). mean ± sd = 45.83 ± 16.28. doi 10.18502/sjms.v12i2.919 page 92 sudan journal of medical sciences production and hosting by knowledge e age distribution frequency percentage (%) ≤20 2 (0.5) 21-30 7 (1.9) 31-40 20 (5.5) 41-50 50 (13.7) 51-60 108 (29.6) 61-70 119 (32.6) 71-80 49 (13.4) 81-90 10 (2.7) total 365 (100.0) t 1: age distribution of respondents. education level frequency percentage (%) no formal education 99 (27.1) quranic only 25 (6.8) primary 111 (30.4) secondary 53 (14.5) tertiary 77 (21.1) total 365 (100.0) t 2: frequency distribution of educational status of respondents. ninety-nine respondents (27.1%) did not have any form of formal education. one hundred and eleven respondents (30.4%) had only primary education; 77 (21.1%) had tertiary education; 53(14.5%) had secondary education; while 25(6.8%) had quranic education (table 2). out of the 365 patients, 141 (38.6%) were traders; 87 (23.8%) were retired civil servants; 56 (15.3%) were serving civil servants; 43(11.8%) were unemployed; 23 (6.3%) were artisans; 11(3.0%) were farmers; while 4(1.1%) were students (table 3). type 2 dm was the main type of dm 352(96.4%) respondents had type 2 dm, 12(3.3%) respondents had type 1 dm. while 1 respondent (0.3%) had gestational dm. the mean duration of dm was 14.1 ± 13.09 years. majority of the patients 203 (55.6%) had dm for 1-10 years, 66 patients (18.1%) had dm for 11-20 years, 49 patients doi 10.18502/sjms.v12i2.919 page 93 sudan journal of medical sciences production and hosting by knowledge e occupational status frequency percentage (%) trading 141 (38.6) retired 87 (23.8) civil servant 56 (15.3) none 43 (11.8) artisan 23 (6.3) farmer 11 (3.0) student 4 (1.1) total 365 (100.0) t 3: frequency distribution of respondents’ occupation. (13.4%) had dm for 21-30 years, while 47 patients (12.9%) had dm for longer than 30 years. 3.1. awareness of diabetic retinopathy out of the 365 patients with dm, 279(76.4%) had heard that dm affects the back of the eyes, while 86(23.6%) had not. out of those who had heard, 221(79.2%) heard it from health personnel, 45(16.1%) from radio/television, 25(9.0%) from internet, 23(8.2%) from books/newspapers, while 16(5.7%) heard from other sources. two hundred and thirty-one (63.3%) respondents knew dm can cause blindness, 34(9.3%) said dm cannot cause blindness, while 100(27.4%) said they don’t know if dm can cause blindness. majority 297(81.4%) believed eye examination for dr was necessary, 18(4.9%) believed eye examination for dr was not necessary, while 50(13.7%) said they don’t know. out of those who believed eye examination for dr was necessary, 65(21.9%) think it should be carried out every 6 months, 31(10.4%) think is should be every one year, 16(5.4%) think it should be when there are problems with the eyes, while 185(62.3%) said they don’t know (table 4). 3.2. previous eye examination for dr only 83(22.7%) respondents have had eye examination on account of dm, while 282(77.3%) had not. out of those who have had eye examination, 46(55.4%) were referred by their doctor, 34(41.0%) was because of eye complains, while 3(3.6%) went on their own for routine check. out of those who have had eye examination, 53 doi 10.18502/sjms.v12i2.919 page 94 sudan journal of medical sciences production and hosting by knowledge e response frequency percentage (%) ever heard that diabetes can affect the back of the eyes yes 279 (76.4) no 86 (23.6) total 365 (100.0) *if yes, source of information (n = 279) health personnel 221 (79.2) radio/tv 45 (16.1) internet books/newspaper 25 23 (9.0) (8.2) other 16 (5.7) can diabetes cause blindness? yes 231 (63.3) no 34 (9.3) don’t know 100 (27.4) total 365 (100.0) do you belief that eye examination for diabetes is necessary? yes 297 (81.4) no 18 (4.9) don’t know 50 (13.7) total 365 (100.0) if yes, how often? every six months 65 (21.9) every one year 31 (10.4) only when the person have problem with his/her vision 16 (5.4) don’t know 185 (62.3) total 297 (100.0) t 4: awareness of diabetic retinopathy in respondents. (63.9%) had eye examination once, 17(20.5%) had it twice, 7(8.4%) had it thrice, and 6(7.2%) had more than thrice in the last one year (table 5). doi 10.18502/sjms.v12i2.919 page 95 sudan journal of medical sciences production and hosting by knowledge e response frequency percentage (%) ever had eye examination for dm before yes 83 (22.7) no 282 (77.3) total 365 (100.0) why did you go for the eye examination my doctor reffered me 46 (55.4) have eye complaints 34 (41.0) routine check 3 (3.6) total 83 (100.0) number of times had an eye examination because of diabetes in the last one year 1 53 (63.9) 2 17 (20.5) 3 7 (8.4) >3 6 (7.2) t 5: previous eye examination for diabetes mellitus. 4. discussion our hospital is an urban teaching hospital, with a specialist dm clinic and a wellsupported eye department. this provides an ideal set-up for dm patients to get regular eye examinations and treatment when necessary. this study took a cross-sectional look at the patients attending the dm clinic of uith, and determined the patients’ awareness and knowledge on eye examination for dr. the age of the subjects who participated in this study ranged from 19-90 years with a mean of 45.8 ± 16.3 years. the mean age in the study population is lower than in other nigerian studies. ashaye et al [10] and omolase et al. [11] in south west nigeria found the mean age of their dm patients to be 57.5 and 57.6 years respectively. lawan and mohammed [12] in kano, north west nigeria found the mean age of their dm patients to be 54.0 years. nwosu in nnewi [13] south east nigeria found a mean age of 57.2 years. in this study, majority of the patients were in their seventh decade of life. this is different from that of lawan and mohammed [12] who found that majority of their dm patients were in their sixth decade (50-59 years). it is also different from that of osunbokun in ibadan, south west nigeria who found that majority of their dm patients were in their fifth decade [14]. doi 10.18502/sjms.v12i2.919 page 96 sudan journal of medical sciences production and hosting by knowledge e in this study, most of the respondents were females compared to males (68.5% vs. 31.5%). this is similar to the findings by erasmus et al. [9] in ilorin, north central nigeria of nearly three decades earlier (54.6% vs. 45.4%), and onokpoya et al. [15] in ile-ife, south west, nigeria (61.4% vs. 38.6%). similarly, lawan and mohammed [12] and mumba et al. [16] in tanzania found more females than males in their studies (58.9% vs. 41.1%) and (53.5% vs. 46.5%) respectively. however, other authors in this environment (ashaye et al, omolase et al, and nwosu) reported more males than females in their studies [10, 11, 13]. the higher number of female respondents is probably because the health seeking behaviour of females tends to be better than males, and this may explain the larger population of females in this study. also, it may be related to the fact that dm manifest in some female patients during pregnancy which is an additional risk factor for dm that is absent in males [1]. majority of the respondents (72.9%) had some form of formal education with 21.1% of them having up to tertiary level of education. more than a quarter (27.1%) of the respondents had no formal education. this was similar to the findings of omolase et al. [11] where 26.0% of their study population had no formal education. this is different from what was reported by muhammed and waziri [17] where majority of their patients (78.4%) had no formal western education. the high level of education in this study may be due to the urban setting of the study site (the hospital is sited in ilorin, the state capital). also, it may be due to the generally higher literacy level of the south west geo-political zone that constitutes the neighbouring states (ekiti, osun, and oyo) which are also served by the hospital. out of the 365 patients, 141 (38.6%) were traders; 87 (23.8%) were retired civil servants; 56 (15.3%) were serving civil servants; 43(11.8%) were unemployed; 23 (6.3%) were artisans; 11(3.0%) were farmers; while 4(1.1%) were students. this pattern of occupation of respondents in our study may be a reflection of the quality of education of the respondents, and may also influence their awareness of dr. quite a large number of respondents (76.4%) in this study were aware that dm can affect the eye. this was similar to the high percentage of awareness reported by mohammed and waziri who reported an awareness rate of 84.3% [17]. in this study, most of the patients (79.2%) attributed their source of information to the hospital personnel. other sources were the mass media (16.1%), the internet (9.0%), and books/newspapers (8.3%) which did not play significant roles compared to health talk from hospital personnel. this may be due to challenges of poor electricity supply, low computer literacy rate, and language barrier. majority of respondents (63.3%) knew dm could result into blindness, and a larger percentage (81.4%) believed eye examination on account of dm was necessary. despite their belief on the necessity of eye examination, more than two-thirds (62.3%) doi 10.18502/sjms.v12i2.919 page 97 sudan journal of medical sciences production and hosting by knowledge e did not know how often they needed to have their eyes examined with a small percentage (5.4%) of them reporting that eye examination should be carried out only when there are complaints with the eye. this may be a reflection of the depth of information provided by the health personnel to the patients. the information provided may lack necessary details such as frequency of eye examinations. the lack of depth of the information provided by the health personnel may also account for the poor rate of eye examination as only 22.7% of the respondents had eye examination on account of dm in the past. this low level of eye examination among dm patients was also reported by mohammed and waziri [17], and onokpoya [15] et al. who reported rates of 15.7% and 28.9% respectively. a high level of awareness of dr was found among the dm patients in this study; however this did not translate to a higher level of eye examination. majority (55.4%) of those who had examination in the past were referred by their doctor followed by those that went on account of eye complaints (41.0%) with only a small percentage (3.6%) having eye examination for routine checkup. possibly, the reason why eye examination rates were low in this study was because of the low level of referral by managing physicians or lack of adequate knowledge. a qualitative study will have to be carried out in the future to identify the barriers to eye examinations in dm patients in this centre. 5. conclusion there was a high level of awareness of dr amongst the diabetic patients. however, the high level of awareness of the blinding complication of dm did not translate to a correspondingly high level of ocular examination for dr. there was a gap in the dm patients’ knowledge on how often to have eye examination. this gap needs to be filled by health personnel involved in the care of these patients as the patients’ main source of information was from the health workers. 6. source of funding none 7. conflict of interest nil doi 10.18502/sjms.v12i2.919 page 98 sudan journal of medical sciences production and hosting by knowledge e references [1] “report of the expert committee on the diagnosis and classification of diabetes mellitus,” diabetes care, vol. 20, no. 7, pp. 1183–1197, 1997. [2] a. b. olokoba, o. a. obateru, and l. b. olokoba, “type 2 diabetes mellitus: a review of current trends,” oman medical journal, vol. 27, no. 4, pp. 269–273, 2012. [3] w. iris and y. david, “diabetic retinopathy: everybody’s business,” community eye health, vol. 24, no. 75, pp. 1–3, 2011. [4] early treatment diabetic retinopathy study research group, “early photocoagulation for diabetic retinopathy. etdrs report no. 9,” ophthalomology, vol. 98, no. 5, supplement, pp. 766–785, 1991. [5] f. ferris, “early photocoagulation in patients with either type 1 or type 2 diabetes,” trans am ophthalmol soc, vol. 94, pp. 505–537, 1996. [6] report of who consultation, prevention of blindness from diabetes mellitus. 2005; november. geneva, switzerland. [7] the nigeria national blindness and visual impairment survey, 2005-2007. [8] m. o. araoye, research methodology with statistics for health and social sciences. 1st ed. nathadex publishers. ilorin. 2003, chapter six, pp. 115-130. [9] r. t. erasmus, r. a. alanamu, b. bojuwoye, p. oluboyo, and a. arije, “diabetic retinopathy in nigerians: relation to duration of diabetes, type of treatment and degree of control.,” east african medical journal, vol. 66, no. 4, pp. 248–254, 1989. [10] a. ashaye, a. arije, m. kuti, b. olusanya, e. ayeni, and a. fasanmade, “retinopathy among type 2 diabetic patients seen at a tertiary hospital in nigeria: a preliminary report,” clin ophthalmol, vol. 2, no. 1, pp. 103–108, 2008. [11] c. o. omolase, o. adekanle, j. f. a. owoeye, and b. o. omolase, “diabetic retinopathy in a nigerian community,” singapore medical journal, vol. 51, no. 1, pp. 56–59, 2010. [12] a. lawan and t. b. mohammed, “pattern of diabetic retinopathy in kano, nigeria,” annals of african medicine, vol. 11, no. 2, pp. 75–79, 2012. [13] s. n. nwosu, “diabetic retinopathy in nnewi, nigeria,” nigerian journal of ophthalmology, vol. 8, no. 1, pp. 7–10, 2000. [14] b. o. osuntokun, “diabetic retinopathy in nigerians: a study of 758 patients,” british journal of ophthalmology, vol. 53, no. 10, pp. 652–663, 1969. [15] o. h. onakpoya, a. o. adeoye, and b. a. kolawole, “determinants of previous dilated eye examination among type ii diabetics in southwestern nigeria,” european journal of internal medicine, vol. 21, no. 3, pp. 176–179, 2010. doi 10.18502/sjms.v12i2.919 page 99 sudan journal of medical sciences production and hosting by knowledge e [16] m. mumba, a. hall, and s. lewallen, “compliance with eye screening examinations among diabetic patients at a tanzanian referral hospital,” ophthalmic epidemiology, vol. 14, no. 5, pp. 306–310, 2007. [17] i. mohammed and a. m. waziri, “awareness of diabetic retinopathy among diabetic patients at the murtala mohammed hospital, kano, nigeria,” niger med j , vol. 50, no. 2, pp. 38–41, 2009. doi 10.18502/sjms.v12i2.919 page 100 introduction patients and methods sample size determination subject selection laboratory tests statistical analysis results awareness of diabetic retinopathy previous eye examination for dr discussion conclusion source of funding conflict of interest references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8943 production and hosting by knowledge e research article the effect of innovative teach-back tool kit session on the postgraduate nursing students’ knowledge about injectable artesunate sahar ahmed1, eiman eisa2, montaha mohammed1, and samah abdalla1 1department of medical nursing, faculty of nursing sciences, university of khartoum, khartoum, sudan 2medical surgical nursing, faculty of nursing sciences, university of khartoum, khartoum, sudan orcid: sahar ahmed mohamed: https://orcid.org/0000-0001-7607-0679 abstract background: injectable artesunate (inj as) is a new anti-malarial treatment recently introduced in sudan for the treatment of severe malaria . inj as has demonstrated its superiority over injectable quinine in african and asian patients. this study aimed to evaluate the outcome of innovative teach-back tool kit session on the knowledge of inj as among the postgraduate nursing students at the university of khartoum, sudan. methods: this interventional pre–posttest studyincluded30postgraduatenursing students selected though a full-coverage sampling method and meeting the selection criteria. data were collected using standardized self-administered questionnaire after taking a written approval from the participants. the pretest included an initial assessment followed by implementation of interactive session about new anti-malaria treatment using an innovative teach-back toolkit, and the final assessment was conducted after two weeks (posttest). the collected data were then analyzed and interpreted using descriptive and inferential statistics based on the objective and hypothesis of the study. a two-tailed p-value at 0.05 was considered as the level of significance using spss version 20. results: majority of the participants were aged between 20 and 30years; of them, 26 (87%) were female and 4(13%) male, and all of them had >1year of experience. the findings of the study showed that half of the participants (15[50%]) had a good knowledge score, 12 (40%) had a poor knowledge, and 3(10%) had a very poor knowledge score in the pretest. however, the knowledge scores increased significantly to 86.7% posttest, which is very good. the overall mean of pretest knowledge scores regarding inj as was7.4 with a statically significant difference (p=0.000). the mean score was increased to 12 with a statically significant difference posttest (p=0.000). conclusion: there was a statistically significant improvement in the knowledge scores of the postgraduate nursing students about inj as after the implementation of interactive teaching session using innovative teach-back tool kit. keywords: inj artesunate, teach back-toolkit, nursing students, session how to cite this article: sahar ahmed, eiman eisa, montaha mohammed, and samah abdalla (2021) “the effect of innovative teach-back tool kit session on the postgraduate nursing students’ knowledge about injectable artesunate,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 122–134. doi 10.18502/sjms.v16i1.8943 page 122 corresponding author: sahar ahmed mohamed; email: sa262697@gmail.com received 14 january 2021 accepted 10 march 2021 published 31 march 2021 production and hosting by knowledge e sahar ahmed et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:sa262697@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sahar ahmed et al 1. introduction the world health organization (who) guidelines have recommended inj artesunate (inj as) as the preferred medicine for treating life-threatening conditions. teach-back is a communication strategy in which the patients are asked to reiterate information provided to them using their own words, to confirm their understanding of the information.teach-back isalso used as an educational approach to educate both the care givers and the patients about a new medication.the method is aproven teaching and learning strategy that improves the quality of care and ensures that healthcare professionals are educating patients and caregivers in an effective way to improve the efficacy with new medications [1]. teach-back is a practical technique to ensure that the health professional has clearly explained a particular information to the patient and that the patient has understood what they have been told. this technique goes beyond using questions such as “is that clear?” and “have you understood everything?” instead, the health professional asks the patient to explain or demonstrate, using their own words, what has just been discussed with them. teach-back does not assess patient’s knowledge but it is an effective technique to check how well the patient has understood the information provided to them by a health professional [2]. a tool kit is a special set of tools that are kept together and are often used for a particular purpose. a tool kit is the set of skills, abilities, knowledge, or other things needed in order to do a particular task or job [3]. a study conducted in the united states of america, aimed to improve patient outcomes using a tailored, evidence-based intervention to develop, encourage, and support rns’ abilities to educate and monitor patient and caregiver’s knowledge of new medications early in and throughout the patient’s hospitalization, used teach-back method. results of the study showed an increase in hospital consumer assessment of healthcare provider and system (hcahps)scores and confirmed that teach-back is an effective method to educate patients and caregivers about new medications. of note, since caregivers can recall the purpose and side effects of medications more often than patients, caregivers or family members should be included in patient education. as shown through this project, teach-back has been approved as a teaching and learning strategy that improves the quality of care. malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female anopheles’ mosquitoes. it is preventable and curable [4]. with an ongoing transmission of malaria in 95 countries and territories, in 2018,who reported that 219 million cases of malaria occurred worldwide, which was doi 10.18502/sjms.v16i1.8943 page 123 sudan journal of medical sciences sahar ahmed et al significantly lower than the 239 million cases in 2010.malaria occurred most frequently in the who african region (92%), followed by the who south-east asian region (5%) and the eastern mediterranean region (2%) [5]. approximately 300 cases of severe malaria are reported in the us each year, most of them are acquired from travel to malaria-endemic countries; cases of severe malaria should be treated with intravenous (iv)antimalarial medication. however, in the us, the food and drug administration(fda)approved iv antimalarial and iv quinine have now been discontinued, and inj as is the first-line drug for the treatment of severe malaria [6]. inj as is a medication used to treat malaria and the intravenous form is preferred to quinine for severe malaria. it is often used as a part of combination therapy, such as artesunate + mefloquine, but it is not used for the prevention of malaria [7, 8]. artesunate is a water-soluble hemisuccinate derivative of artemisinin indicated for the treatment of severe falciparum malaria and initiated treatment of uncomplicated falciparum malaria, when persistent vomiting precludes oral therapy. it comes in the form of powder for injection in 20,60,120, and 160-mgvial with one 1-ml ampoule of 5% sodium bicarbonate and one 5-ml ampoule of 0.9%sodium chloride for slow iv injection (3–5 min) or slow im injection. nurse must dissolve the powder in the entire volume of 5% sodium bicarbonate and shake the vial until the solution becomesclear. to add the 0.9%sodium chloride into the vial, 5ml of the 0.9%sodium chloride is added to obtain 6mlof artesunate solution containing 10mg/ml for iv injection and 2ml of 0.9%sodium chloride is added to obtain 3ml of artesunate containing 20mg/ml. the dosage and duration are as follows: childrenweighing <20 kg:3mg/kg/dose; children weighing≥20kg and adult:2.4mg/kg/dose. the first dose is given on admission (h0), the second 12 hr after the admission (h12), the third 24 hr after the admission (h24), and then once daily. at least three doses should be administered parenterally;if the patient can tolerate the oral route, change to an artemisinin-based combination. of note, inj as may cause gastrointestinal disturbances, dizziness, headache, fever, muscle and joint pain, pruritus,rashes in rare cases, qt interval prolongation, and post-treatment hemolytic anemia (especially in cases of hyperparasitemia and in young children). however, there is no contraindication for pregnancy and breast feeding [9]. in the past few years, many efficacy studies have been carried out in different regions of sudan and the findings have shown a decreasing efficacy to artesunate + sulphadoxine–pyrimethamine (as+sp), particularly in gadarif state (>10%), anda high efficacy (>95%) of artemether–lumefantrine (al) and dihydroartemisinin–piperaquine (dhap).moreover, sudan’s malaria indicators survey) mis) 2016 showed irrational use of artemether intramuscular for treatment of uncomplicated malaria. some published doi 10.18502/sjms.v16i1.8943 page 124 sudan journal of medical sciences sahar ahmed et al studies showed higher rate of non-adherence of healthcare providers to the treatment guidelines and self-treatment. in response to this situation, the malaria technical advisory committee (formed from national experts and partners) recommended the use of al as a first-line and dhap as a second-line treatment for malaria in sudan. the committee also recommended the use of quinine or intravenous artesunate for the treatment of severe malaria at hospital level [10]. a 2019 study in tanzania showed the level of knowledge among healthcare providers on the preparation of inj as in public health facilities was low [11]. hence, this study was done to evaluate the effect of an innovative teach-back tool kit session on the postgraduate nursing students’ knowledge about inj as. 1.1. research questions 1. what is the baseline knowledge of the postgraduate nursing students aboutinjectable artesunate (inj as)? 2. what is the impact of an innovative teach-back tool kit session on postgraduate nursing students’ knowledge about injectable artesunate (inj as)? 1.2. research hypotheses h0:there will be no difference between preand posttest mean knowledge scores toward injectable artesunate (inj as) using an innovative teach-back tool kit after implementation of the interactive teaching session. h1: there will be a significant difference between preand posttest mean knowledge scores toward injectable artesunate (inj as) using an innovative teach-back tool kit after implementation of the interactive teaching session. 2. materials and methods 2.1. design and setting an interventional pre–posttest study was conducted in the faculty of nursing sciencesat university of khartoum, sudan. doi 10.18502/sjms.v16i1.8943 page 125 sudan journal of medical sciences sahar ahmed et al 2.2. study population the target population of the study was students pursuing master’s degree in nursing sciences in all specialties. because the students are attached to different hospitals, they can easily transfer knowledge to their colleagues when they go back to their respective hospitals. 2.3. inclusion criteria all students pursuing the master’sdegree of nursing sciences with all specialties in batch12 in the faculty of nursing sciences, university of khartoum, sudan. 2.4. exclusion criteria master’s students attending workshop or training on new inj as. 2.5. sample size and technique a total of 30 students participated in the study. they were selected through a fullcoverage sampling method. 2.6. data collection methods data were collected by the researcher using a self-administered questionnaire after conducting a pilot study to ensure the validity and reliability of the questionnaire. the questionnaire consisted of two parts: part 1 included socio demographic data and consisted of three variables (age, sex ,and practical experience ), part 2 consisted of knowledge regarding inj as and included 14 close-ended questions(yes or no). each correct answer was given a score of “1” and a wrong answer was given a score of “0.” after that, the sum and the percentage of the total score was calculated. 11–14 very good 7–10 good <6 poor doi 10.18502/sjms.v16i1.8943 page 126 sudan journal of medical sciences sahar ahmed et al 2.6.1. structured interactive session contents of the session: 1. definition of teach-back. 2. use the tool kit. 3. definition of malaria. 4. information about artesunate injection. 5. therapeutic action, indications, route of administrations, dosage and duration, and contraindications of injas. objective of the session by the end of this presentation, every student will be able to: 1. identify to the teach-back toolkit as a teaching strategy. 2. recognize an overview about malaria and new antimalarial treatment (inj as). 3. should be able to calculate dose, indications, contraindications, and drug interactions. interactive session was conducted in 60 min and comprised of a brief talk using innovative teach-back tool kit and small group discussions. 2.7. data analysis data were collected, coded, entered, and then analyzed using the statistical package for social sciences (spss) using mean, standard deviation, paired t-test, and p-value. 3. results in this interventional pre–posttest study,30 nurses were included and the collected data were tabulated, analyzed, and interpreted using description and inferential statistics based on the objective of the study. analysis was done based on the objective and hypothesis of the study. a two-tailed p-value at 0.05 was considered as the level of significance. doi 10.18502/sjms.v16i1.8943 page 127 sudan journal of medical sciences sahar ahmed et al table 1: distribution of the study subjects according to their demographic background (n=30). characteristics frequency % age (yr) 20–30 >30 28 2 93 7 gender male female 4 26 13 87 experience (yr) <1 >1 0 30 0 100 total 30 100 table 1 shows that the mean age of the participants was 25 years (age group 20– 30),most of the participants were female (26 [87%]), and all participants had a nursing experience of >1 year. table 2: students’ knowledge about injectable artesunate (injas) (n=30). no. knowledge aspects pretest posttest pretest1 and posttest1 paired t-test p-value mean sd mean sd mean sd 1 which form of these drugs isbetter used to treat severe malaria? 1.5667 0.62606 1.2000 0.40684 0.36667 0.80872 0.019 2 can artesunate injection be given iv& im? 0.4333 0.50401 0.9333 0.25371 –0.50000 0.57235 0.000 3 can artesunate injection be given rapidly? 0.0667 0.25371 0.1333 0.34575 –0.06667 0.44978 0.423 4 do you know how to prepare artesunate injection? 0.6000 0.49827 1.0000 0.00000 –0.40000 0.49827 0.000 5 do you know how to calculate the dose? 0.4000 0.49827 0.9333 0.25371 –0.53333 0.50742 0.000 6 do you know different formulas available? 0.5667 0.50401 0.9333 0.25371 –0.36667 0.49013 0.000 7 do you know the administration protocol in the first 24hr? 0.5000 0.50855 0.9000 –0.40000 0.30513 0.56324 0.001 doi 10.18502/sjms.v16i1.8943 page 128 sudan journal of medical sciences sahar ahmed et al no. knowledge aspects pretest posttest pretest1 and posttest1 paired t-test p-value mean sd mean sd mean sd 8 do you knowthe administration protocol after 24 hr? 0.4667 0.50742 0.9000 0.30513 –0.43333 0.56832 0.000 9 do you record the dose, route, ml, and time given for each administration of artesunate? 0.6667 0.47946 0.9667 0.18257 –0.30000 0.53498 0.005 10 do you prepare a fresh solution for each administrationand discardthe unused solution? 0.5333 0.50742 1.0000 0.00000 –0.46667 0.50742 0.000 11 is iv artesunate safe in pregnancy and breast feeding? 0.3333 0.47946 1.0000 0.00000 –0.66667 0.47946 0.000 12 can artesunateinjectioncause gastrointestinal disturbance,headache, pruritus, qt interval prolongation, and post hemolytic anemia? 0.6000 0.49827 0.8333 0.37905 –0.23333 0.62606 0.050 13 doesartesunatereact withmefloquineand pyrimethamine? 0.3000 0.46609 0.7000 0.46609 –0.40000 0.77013 0.008 14 is artesunateinjectionsafe for liver and kidney diseases? 0.3333 0.47946 0.7000 0.46609 –0.36667 0.55605 0.001 15 association betweenpreand posttest 7.3667 2.79758 12.1333 1.59164 –4.76667 2.73777 .000 doi 10.18502/sjms.v16i1.8943 page 129 sudan journal of medical sciences sahar ahmed et al table 2 shows that the knowledge of the students about inj as was poor and that there was a considerable improvement after the implementation of the interactive teaching session. table 3: pre–posttest association between students’ demographic data and knowledge (n=30). f mean standarddeviation p-value male female 4 26 12.0000 12.1538 0.00000 1.71330 0.056 table 3 shows that there was no difference in the knowledge between male and female participants. table 4: improvement in knowledge among participants(n=30). score pretest posttest frequency percentage frequency percentage 11–14: very good 3 10 26 86.,7 6–10:good 15 50 4 13.3 <5:poor 12 40 0 0 table 3 shows the total preand posttest knowledge of the respondents about inj as and the significant improvement in their knowledge after the implementation of interactive session. 4. discussion inj as is a new anti-malarial treatment recently introduced in sudan. it is used to treat severe malaria. this study aimed to evaluate the effect of an innovative teach-back tool kit session on the knowledge of the students pursuing master’s degree in nursing sciences about inj as and included 30 nurses. in the pretest, an initial assessment done followed by implementation of interactive session about inj as using an innovative teachback toolkit. a final assessment was conducted after two weeks (posttest) to evaluate the effectiveness of the interactive session. the mean pretest knowledge regarding the question about better treatment of severe malaria was 1.6 and that of posttest was 1.2. the association between the preand posttest was p = 0.4, which was not significant (0.019>0.05) and the participants thought that quinine was better than artesunate as artesunate injections are unavailable in sudan and are also expensive, as shown in table 1. however, contrary to our results, previous studies reveled that inj as gains advantage over other anti-malarial injections in treating severe malaria due to its tolerable side effects and high parasitic clearance. doi 10.18502/sjms.v16i1.8943 page 130 sudan journal of medical sciences sahar ahmed et al it is also associated with low mortality in both children and adults with fewer side effects compared to quinine [11]. however, in tanzania mainland, inj as is the first drug of choice while artemether injection is the alternative for treating severe malaria in the general population and quinine injection is the first-line treatment of severe malaria in pregnant women ([12]. the mean pretest knowledge about question regarding injectable artesunate given rapidly was 0.1 and that that of posttest was 0.1. the association between preand posttest was p = 0.1, which was not significant (423>0.05), as shown in table 1. the present study confirmed that there was a considerably low level of knowledge concerning different formulas, preparation, calculation, and administration following the protocol in pretest. this is in line with a turkish study that found a low level of knowledge among nurses in administering im medicines at ventrogluteal site [13]. however, the nurses’ knowledge improved significantly after implementing the teaching session. in general, the total preand posttest knowledge regarding inj as is significant with the mean total of pretest 7.4 and posttest12 and the association between the total preand posttest was –4.8 which is significant (p=0.000). in addition, half of the participants, that is 15, (50%) had a a good knowledge score and12 (40%) had a poor knowledge in pretest which increased significantly to 86.7% posttest. in comparison with the study done in tanzania which showed that the level of knowledge on the preparation of inj as for the treatment of severe malaria among public healthcare providers in all municipalities of dar-al-salaam region, the majority of hcp had low knowledge (82.5%) on how inj as was prepared and only few had moderate (11.9%)-to-high knowledge (5.6%) despite its high availability in healthcare facilities and preference by hcp [11]. the present study revealed that knowledge scores of participants increased significantly after the implementation of interactive teaching session using innovative teachback tool kit. therefore ,nurses in clinical practice need to adopt teach-back tool kit as a teaching strategy for any new treatment. in addition, hospital policy-makers must put informational posters for any new treatment around the hospital compound which could aid in recalling the treatment protocols. in the same direction, an italian study showed the efficacy of posters, protocols, and brochures in reducing medication errors for iv drugs administration [14]. the study reveals that even with the utility of these orientation resources, there is a high likelihood of errors due to negligence of some vital issues that might be emphasized during training. this will possibly be reflected by the fact that almost half of the hcp knew the flow pattern to follow when preparing artesunate injection and the doi 10.18502/sjms.v16i1.8943 page 131 sudan journal of medical sciences sahar ahmed et al difference between the im and iv artesunate preparation but could not respond correctly as what to do when the mixture does not mix up, when to discard the prepared solution, or the correct dose by body weight [11]. 4.1. hypothesis testing h0: there will be no difference between preand posttest mean knowledge scores regarding the new anti malarial treatment injectable artesunate (inj as) using an innovative teach-back tool kit. the aforementionednull hypothesis is rejected, and the alternative hypothesis h0 is accepted, since there was a significant differencebetween the preand posttest mean knowledge scores,p < 0.000, as shown in table 1. h1: there will be a significant difference between preand posttest mean knowledge scores toward injectable artesunate (inj as) using an innovative teach-back tool kit after implementation of the interactive teaching session. hypothesis h1 is accepted as there was a significant improvement in the knowledge scores of post graduate students after the administration of the interactive teaching session. 5. conclusion there was statistically significant improvement in the knowledge scores of the postgraduate nursing students about inj as after the implementation of interactive teaching session using the innovative teach-back tool kit. limitations 1. the study was limited to students pursuing master’s degree in nursing sciences in the faculty of nursing, university of khartoum, sudan. 2. the sample for the study was limited to 30 students only .future studies must be conducted in hospital settings. 3. inadequate literature and studies to make comparisons with. doi 10.18502/sjms.v16i1.8943 page 132 sudan journal of medical sciences sahar ahmed et al strengths to the best of our knowledge, no previous study has been conducted on the current topic in sudan. acknowledgements the authors are thankful to the dean of the faculty of nursing sciences and the coordinator of the master’s degree of nursing sciences at the faculty of nursing sciences, university of khartoum, sudan for their support and to the students for participating in this study. ethical considerations the study protocol was approved by both the dean and the coordinator of the master’s degree of nursing sciences at the faculty of nursing sciences, university of khartoum, sudan. also, a written agreement was signed by the participants prior to the study. competing interests the authors declare that there is no conflict of interests regarding the publication of this paper. availability of data and material the data used in the study are available upon reasonable request. funding none. references [1] prochnow, j. a., meiers, s. j., and scheckel, m. m. (2019). improving patient and caregiver new medication education using an innovative teach-back toolkit. journal of nursing care quality, vol. 34, no. 2, pp. 101–106. doi 10.18502/sjms.v16i1.8943 page 133 sudan journal of medical sciences sahar ahmed et al [2] scottish health council. (2014). the participation toolkit: supporting patient focus and public involvement in nhs scotland. better evaluation. [3] cobuild, c. (2008). collins cobuild advanced learner’s english dictionary, new digital edition 2008©. harpercollins publishers. [4] world health organization. (2020). malaria: fact sheet. world health organization: regional office for the eastern mediterranean. [5] whitethorn, c.,bremen, j., daily, j., et al. (2010). epidemiology, prevention and control of malaria in endemic areas.uptodate. [6] centers fordisease control and prevention. (2019). global health-division of parasitic diseases and malaria. [7] centers for disease control and prevention. (2016). malaria diagnosis & treatment (united states). retrieved from: www.cdc.gov. [8] world health organization. (2013). artesunate. who. [9] drugs, e. (2013). practical guidelines intended for physicians, pharmacists, nurses and medical auxiliaries. in essential drugs. médecins sans frontières. [10] federal ministry of health, khartoum, sudan. (2017).sudan malaria treatment protocol. [11] mikomangwa, w. p., kaaya, c., kilonzi, m., et al. (2019). level of knowledge among health care providers on preparation of injectable artesunate for treatment of severe malaria in public health facilities in tanzania. bmc research notes, vol. 12, no. 1, p. 224. [12] national environment management council (nemc).(). the national environmental research agenda for tanzania. [13] kadam, p. and bhalerao, s. (2010). sample size calculation. international journal of ayurveda research, vol. 1, no. 1, p. 55. [14] khan, a. n., khan, m. u., shoaib, m. h., et al. (2014). practice nurses and pharmacists: a perspective on the expectation and experience of nurses for future collaboration. oman medical journal, vol. 29, no. 4, p. 271. doi 10.18502/sjms.v16i1.8943 page 134 www.cdc.gov. introduction research questions research hypotheses materials and methods design and setting study population inclusion criteria exclusion criteria sample size and technique data collection methods structured interactive session data analysis results discussion hypothesis testing conclusion limitations strengths acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8939 production and hosting by knowledge e case report ruptured rudimentary uterine horn pregnancy: a case report dr. mohmmed eltayeb abdelkhalig mustafa md, mrcog1 and dr. eltayeb abdelkhalig mustafa md2 1assistant professor ahfad university for women, department of obstetrics and gynaecology. senior specialist at elsaudi hospital, omdurman, sudan. 2assistant professor elbaha university, department of obstetric and gynaecology, ksa senior consultant obstetrician and gynaecologist. orcid: mohmmed eltayeb abdelkhalig mustafa: https://orcid.org/0000-0003-4576-2036 abstract pregnancy in rudimentary uterine horn has been reported to be very rare in literature, and is associated with adverse complications. furthermore, it is also difficult to diagnose, and in most cases, is diagnosed after being ruptured. a case of ruptured rudimentary uterine horn pregnancy presented at elsaudi maternity hospital (sudan). despite her recurrent presentation for persistent suprapubic pain and frequent ultrasound scans, the uterine horn pregnancy was not detected, and the diagnosis was made during laparotomy as her condition started to deteriorate progressively due to massive internal bleeding from the ruptured uterine horn. keywords: rudimentary uterine horn pregnancy, ectopic pregnancy, mullerian anomalies, early pregnancy complication 1. introduction mullerian anomalies have been reported to affect about 5–8% of women [1, 2], diagnosed mainly through imaging techniques, such as a 2d/3d ultrasound scan, ct scan, mri, and combined laparoscopy and hysteroscopy. however, it is difficult to diagnose and is sometimes diagnosed intraoperatively. recently, there has been an increase in the diagnosis of mullerian anomalies due to the availability of advanced imaging methods that aid in proper planning of pregnancies and therefore decreasing the unexpected and missed complications. live birth rate with mullerian anomalies depends on the type and its classification, with increased risk of recurrent miscarriage in septate and arcuate uterus. however, better outcome has been reported after hysteroscopic removal of uterine septum. according to the eshre classification, there are two types of rudimentary uterine horn, communicating and non-communicating. pregnancy is how to cite this article: dr. mohmmed eltayeb abdelkhalig mustafa md, mrcog and dr. eltayeb abdelkhalig mustafa md (2021) “ruptured rudimentary uterine horn pregnancy: a case report,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 76–80. doi 10.18502/sjms.v16i1.8939 page 76 corresponding author: mohmmed eltayeb abdelkhalig mustafa received 16 february 2021 accepted 10 march 2021 published 31 march 2021 production and hosting by knowledge e mohmmed eltayeb abdelkhalig mustafa and eltayeb abdelkhalig mustafa. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohmmed eltayeb abdelkhalig mustafa and eltayeb abdelkhalig mustafa impossible in the non-communicating type. however, pregnancy in communicating rudimentary uterine horn poses a risk of catastrophic complications, including rupture which increases the risk of maternal morbidity and mortality as reported in both case reports [3, 4]. 2. case presentation a 22-year-old sudanese pregnant women in her first pregnancy at 25 weeks gestational age presented with generalized abdominal pain for one day. one week prior, she had presented with a history of liquor drainage and longstanding suprapubic pain, pprom, and preterm labor was one of the differential diagnosis; therefore, she was admitted, her vital signs were checked which were all normal, speculum examination was negative for liquor drainage or vaginal discharge, and her cervix was closed. her investigation including full blood count and crp was normal, and her ultrasound scan revealed normal intrauterine pregnancy corresponding to 25 weeks of gestation. she was given antibiotic and steroid and was then discharged. a follow-up plan was made. the second time, the patient presented with generalized abdominal pain with shoulder tip pain along with nausea and vomiting. on examination, she was pale, tachycardic, tachypneic, and had low blood pressure (bp). her abdominal examination showed generalized tenderness, rigid abdomen, and a fundal level of 28 weeks. vaginal examination revealed closed cervix, no vaginal bleeding; however, cervical excitation test was positive. abruptio placenta was suspected; thus, resuscitation was initiated, the patient cannulated, and blood sample was taken for blood group, cross-matching, rft, lft, and coagulation profile. she received up to 3 liters of fluid, two binds of blood, and four binds of fresh frozen plasma. her investigation showed an hb of 7 gm/dl, a platelet count of 110, normal rft and lft, and prolonged aptt. fetal heart could not be detected using a handheld fetal doppler, and bedside ultrasound scan showed no fetal heart, with transverse lie. therefore, decision was made to go for laparotomy. intraoperatively, a ruptured right-side communicating uterine horn with intact right ovary and tube was seen, along with intact uterus. the fetus was floating inside abdominal cavity, the ruptured horn was partially connected to the uterus near fundus and at the lateral site, and the concept of removal was conundrum, as there was a large area to be repaired at the lateral site of the uterus which would affect her future fertility and even early uterine rupture. however, attempts to repair the ruptured horn with continuous/locking suture failed as her vitals continued to deteriorate; thus, the decision was made to remove the ruptured uterine horn and the uterus was repaired carefully doi 10.18502/sjms.v16i1.8939 page 77 sudan journal of medical sciences mohmmed eltayeb abdelkhalig mustafa and eltayeb abdelkhalig mustafa in three layers at the site of communicating horn near the fundus, with preservation of right ovary, after which the patient’s vitals started to improve. postoperatively, the patient was admitted to icu; she received four binds of blood along with ffp, cryoprecipitate, and two binds of platelet. her vitals and her mewos chart were improving. she was discharged on day 5 in good condition and appointment was made to discuss the result of histopathology after two weeks. 3. discussion unicornuate uterus is a type-2 classification with unilateral hypoplasia or agenesis that can be further classified into communicating, non-communicating and with cavity or no cavity. unicornuate uterus with rudimentary uterine horn is associated with wide range of obstetric and gynecological complications such as infertility and dysmenorrhea. pregnancy in the rudimentary horn is rare, it occurs in 1:100,000 to 1:140,000 cases [5]. the diagnosis of rudimentary uterine horn pregnancy is lifesaving, despite its difficulty due to the scarcity of the condition. rupture of the horn due to underdeveloped myometrium, and that the uterine muscle will not extend with growing fetus which lead to rupture [3]. all mullerian anomalies can be diagnosed through ultrasound with varying degrees of sensitivity; the sensitivity of diagnosing rudimentary horn is 26% [5]. however, the eshre recommends mri for the diagnosis. placenta previa and placenta accrete spectrum can be associated with rudimentary horn pregnancy, which further increase maternal morbidity and mortality, in terms of massive blood transfusion and maternal death. renal anomalies are commonly associated with mullerian anomalies [6]; therefore, the follow-up should include careful assessment of kidneys and renal tract with appropriate involvement of other disciplines. the key in diagnosing such condition lay behind strong suspicion and careful obstetrics and gynecological history. in this case, unfortunately, despite more than three ultrasound scans that were done during her follow-ups, the condition could not be diagnosed timely, and the patient had to eventually undergo laparotomy. this of course was associated with increased morbidity and later litigations. if condition diagnosed antenatally, the main strategy is excision of the rudimentary horn [6, 7], whether laparoscopically, if the patient’s condition is stable and the condition is diagnosed early, or via laparotomy, if the patient is unstable. in our case, although we tried to suture the ruptured horn, there was bleeding and the patient’s hemodynamical status was deteriorating, which lead us to proceed for excision, after which the patient’s condition was improved. doi 10.18502/sjms.v16i1.8939 page 78 sudan journal of medical sciences mohmmed eltayeb abdelkhalig mustafa and eltayeb abdelkhalig mustafa 4. conclusion delayed diagnosis of pregnancy occurring in rudimentary horn is associated with increased maternal morbidity and mortality. however, early diagnosis and detection of the condition will reduce the risk, allowing the healthcare professional to plan an appropriate noninvasive intervention. acknowledgements the authors are thankful to their colleagues at the elsaudi hospital. ethical considerations ethical clearance was obtained from the hospital and the patient gave consent for taking picture and for publication. competing interests none declared availability of data and material funding none. references [1] buntugu. k., ntumy, m., ameh, e., et al. (2008). rudimentary horn pregnancy: prerupture diagnosis and management. ghana medical journal, vol. 42, no. 2, pp. 92–94. [2] chan, y. y., jayaprakasan, k., zamora, j., et al. (2011). the prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review. human reproduction update, vol. 17, no. 6, pp. 761–771. [3] dhar, h. (2012). ruptured rudimentary horn at 22 weeks. nigerian medical journal, vol. 53, no. 3, pp. 175–177. doi 10.18502/sjms.v16i1.8939 page 79 sudan journal of medical sciences mohmmed eltayeb abdelkhalig mustafa and eltayeb abdelkhalig mustafa [4] ambusaidi, q. and jha, c. (2014). pregnancy in the rudimentary uterine horn: case report of an unusual presentation. sultan qaboos university medical journal, vol. 14, no. 1, pp. e134–e138. [5] jain, r., gami, n., puri, m., et al. (2010). a rare case of intact rudimentary horn pregnancy presenting as hemoperitoneum. journal of human reproductive sciences, vol. 3, no. 2, pp. 113–115. [6] park, j. k. and dominguez, c. e. (2007). combined medical and surgical management of rudimentary uterine horn pregnancy. jsls, vol. 11, no. 1, pp. 119–122. [7] li, x., peng, p., liu, x., et al. (2019). the pregnancy outcomes of patients with rudimentary uterine horn: a 30-year experience. plos one, vol. 14, no. 1, p. e0210788. doi 10.18502/sjms.v16i1.8939 page 80 introduction case presentation discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 12, issue no. 2, doi 10.18502/sjms.v12i2.917 production and hosting by knowledge e research article social meaning and consequences of infertility in ogbomoso, nigeria fehintola a. o.1, fehintola f. o.2, ogunlaja o. a.1, awotunde t. o.1, ogunlaja i. p.3, and onwudiegwu u.4 1obstetrics and gynaecology department, bowen university teaching hospital, ogbomoso, oyo state, nigeria 2community medicine department, bowen university teaching hospital, ogbomoso, oyo state, nigeria 3obstetrics and gynaecology department, general hospital, ilorin, kwara state, nigeria 4department of obstetrics, gynaecology,and perinatology, obafemi awolowo university, ile-ife, osun state, nigeria abstract background: this study examined the meaning of infertility from layman’s perspective, and experiences of women suffering from infertility among reproductive age women seeking care at the gynaecology unit of the bowen university teaching hospital, ogbomoso, nigeria. materials and methods: it was a cross-sectional study. quantitative and qualitative data collection methods were employed. quantitative data collection was by the aid of a structured interviewer-administered questionnaire among 200 women seeking care for infertility at the hospital. qualitative data collection was by focus group discussions (fgds) and key informant interviews (kiis). result: approximately 40% and 60% of the respondents seeking care for infertility were suffering from primary and secondary infertility respectively. perceived meaning and etiologies of childlessness were multidimensional, but 33% of the respondents not sure of the causal factor. seventy-nine percent were under pressure to become pregnant. the high premium placed on fertility within marriage has placed a larger proportion of them under pressure from their husbands (25%), their mother-in-laws (40%), and the community (14%). conclusion: this study concluded that women regard infertility to be caused by multiplicity of factors. most of these etiologies were unscientific and unverifiable. fruitful expectations also put enormous burden on those women suffering from infertility including adverse psychosexual effects. the unceasing pressure due to infertility in this group of patients calls for urgent intervention as most of these women become susceptible to high risk sexual behavior, depression and other severe consequences. keywords: social meaning, consequences, infertility how to cite this article: fehintola a. o., fehintola f. o., ogunlaja o. a., awotunde t. o., ogunlaja i. p., and onwudiegwu u., (2017) “social meaning and consequences of infertility in ogbomoso, nigeria,” sudan journal of medical sciences, vol. 12 (2017), issue no. 2, 63–77. doi 10.18502/sjms.v12i2.917 page 63 corresponding author: fehintola a. o.; email: akintunds@yahoo.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e fehintola a. o. et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:akintunds@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e الخلفية: بحثت هذه الدراسة معنى العقم من وجهة نظر الشخص العادي، وتجارب النساء اللوايت يعانين من العقم بين النساء يف سن اإلنجاب الالىئ حضرنا للحصول على الرعاية يف وحدة أمراض النساء يف مستشفى بوين الجامعى التعليمى اوقبوموسو، نيجيريا. الكمية البيانات جمع أساليب توظيف فيها تم مستعرضة دراسة ىف والطرق: المواد والنوعية. تم جمع البيانات الكمية بمساعدة من مقدمى استبيان المقابلة المعد من ٢٠٠ البيانات جمع تم المستشفى. يف بالعقم الخاصة الرعاية على للحصول حضرن امرأة النوعية من المناقشات البؤرية والمقابالت المفتاحية. النتيجة: حوايل ٤٠٪ و ٦٠٪ من المستطلعات اللواىت يلتمسن العالج من العقم يعانين من العقم االبتدايئ والثانوي على التوايل. وكان معنى ومسببات عدم اإلنجاب من وجهة النظر متعددة األبعاد، ولكن ٣٣٪ من المستطلعات لم تكن متأكدة من عامل السببية. وكانت ٩٩ ٪ تحت الضغط لتصبح حامال. وقد وضعت أهمية كبيرة على الخصوبة يف إطار الزواج نسبة كبيرة منهن تحت ضغط من أزواجهن (٢٥٪)، امهات أزواجهن (٤٠٪) والمجتمع (١٤٪). الخالصة: خلصت هذه الدراسة إىل أن النساء يعتبرن أن يكون سبب العقم هى عوامل عديدة. وكانت معظم هذه المسببات غير علمية وال يمكن التحقق منها. وضعت التوقعات والطموحات أيضا عبء هائل على تلك النساء اللوايت يعانين من العقم بما يف ذلك آثار يدعو المرضى من المجموعة هذه يف العقم بسبب المتواصل الضغط سلبية. نفسية للتدخل العاجل ألن معظم هؤالء النساء تصبح عرضة للسلوك الجنسي عالية المخاطر، واالكتئاب وعواقب وخيمة أخرى. 1. introduction infertility can be defined as the inability of a couple to achieve conception over a twelve months’ period despite regular unprotected sexual intercourse [1]. recent global evidence shows infertility as a major public health problem. it is a problem of global proportion affecting between 8 and 12 percent of couples worldwide [2]. in developing countries, about 25% of couples are infertile due to primary or secondary infertility [3]. in nigeria, overall prevalence of infertility is 22% with primary infertility at 5% and secondary at18% [4]. infertility possess socio-cultural attributes and challenges at both etiological and experiential levels. etiological explanation differs to an extent between health care providers, patients, and the society [5]. from the western medical tradition, explanations on the causes of infertility centered on biological and empirical factors which could readily be subjected to clinical investigations [6]. to the traditional medical practitioners, the factors responsible for infertility would range from explainable such as biological factors to unexplainable factors such as supernatural factors. doi 10.18502/sjms.v12i2.917 page 64 sudan journal of medical sciences production and hosting by knowledge e cultural beliefs are major determinants in the prevailing explanation of infertility from the lay perspectives. the divergence in the etiological explanation of infertility between the patient and the professional health care provider has implications for care provision and compliance of the patient to treatment. infertility has psychosocial impacts on couples especially the women [7]. this is more obvious in high fertility settings where children are highly desired and parenthood is culturally mandatory [8]. in african settings, infertility is a socially unacceptable condition; leading most infertile couples on a relentless “quest for conception” [9]. studies have shown that women not only are harassed by the family members but face various forms of marital instabilities [10–17]. on the above backdrop, this study investigated the perceived causes and impacts of infertility in the context of patient seeking care at bowen university teaching hospital ogbomoso in oyo state. understanding patient’s perception on the etiology and experiences of infertility will go a long way in furthering patient centered care and scaling up compliance to treatment. 2. material and methods 2.1. location of the study the study was carried out at the bowen university teaching hospital (buth) ogbomoso. the teaching hospital has gynaecology unit. ogbomoso is a semi-urban town with a projected population of 861,300 according to the 2004 national census. this study was based in the gynaecology unit of the hospital. 2.2. study design this study was cross-sectional in nature. 2.3. study population the study was carried out among women of reproductive age (15 49 years) who are currently married with infertility challenge and currently seeking care at the gynaecology unit of the hospital. another group of currently married women (15-49) having at least two living children who brought their children for care at the well infant clinic of the hospital during the period of the study were included in the qualitative aspect of the study. women outside the age group stated above and those who refused to participate were excluded. doi 10.18502/sjms.v12i2.917 page 65 sudan journal of medical sciences production and hosting by knowledge e 2.4. sampling method a purposive sampling methodology was used to select eligible patients for the study while sample size was determined using fishers’ formular11. this gave a total of 200 women. every patient with infertility that fulfilled the inclusion criteria for the study was enrolled at every gynaecology clinic visit until the expected sample size of 200 was achieved. forty women who are currently married (between 15 and 49 years) having at least two living children were recruited for the four fgds i.e. ten participants per group. from the women suffering from infertility, eight were chosen by balloting for the 8 kiis. 2.5. data collection techniques and instruments data collection was by quantitative and qualitative research techniques. t semistructured interviewer administered questionnaires, key informants interviews and focus group discussions were the instruments used in the study 2.6. quantitative data a semi-structured interviewer administered questionnaire was used in quantitative data collection. this tool was designed based on findings from the literatures. information on the educational status of the patient and the job description of the husband was also collected and used for socio economic stratification into class 1 to 5.12 in this study, class 1 and 2 were grouped as upper social class, class 3 as middle social class while class 4 and 5 were grouped as lower social class to aid data analysis. the instrument was translated from english to yoruba and was administered in yoruba. interviews were conducted by appropriately trained interviewers. 2.7. qualitative data a total of 4 fgds and 8 key informants interviews (kiis) were conducted throughout the period of the study. separate guideline for fgds and kiis were developed in english and translated into yoruba language, and pretested. kiis conducted for women with infertility to delve into their perceptions and experiences regarding infertility. 2.8. method of data analysis quantitative data entry was done using statistical package for social science (spss) version 20. descriptive analysis was used, among others, for the socio-demographic doi 10.18502/sjms.v12i2.917 page 66 sudan journal of medical sciences production and hosting by knowledge e characterization of the respondents and other relevant variables (age, education, social status etc. audio recordings of fgds and kiis were transcribed within 48 hours of the interview to ensure data credibility, and content analysis was done. 2.9. ethical consideration ethical clearance was obtained from the ethics and research committee of bowen university teaching hospital, ogbomoso. during data collection individuals were informed about the purpose of the study, confidentiality, and the right not to participate or withdraw at any time without any effect on their health or other services. 3. results 3.1. quantitative data majority of the respondents (50%) were between 30 and 39 years of age. more than two-third (68%) of the respondents were christians. majority (82.5%) were within the first ten years of their marriage. sixty-five percent of the respondents had less than secondary school education. fifty percent of the respondents belonged to lower social class as shown in table 1 above. table 2 showed that 60% of the respondents had at least a pregnancy before now. within the category of women who had been pregnant before, majority (33.4%) had a living child. more than three fourth (79%) of the respondents were under pressure to become pregnant at the time of the survey. a relatively high proportion (40%) attributed the source to their mother-in-laws, while (25.3%) perceived their husbands as the source. society in general contributed (19%) as the source of pressure. a number of the respondents perceived infertility aetiology from multiple sources. a high proportion of the respondents were disoriented on this as (33%) could not provide concrete response on etiology. the view that lifestyle and risky behaviors could have implications on fertility was shared by (25%) of the respondents as they attributed the cause to induced abortion and stis. sixteen percent of the respondents attributed aetiology of infertility to spiritual forces such as the devils, witches, and ancestral spirits while 22% in-correctly highlighted use of ocps and iucd as causes of infertility. according to table 4 above, all the respondents had sought orthodox care at one time or the other for infertility. multiple health seeking behavior was observed among the respondents. about (56%) sought for help from the church while (50%) visited doi 10.18502/sjms.v12i2.917 page 67 sudan journal of medical sciences production and hosting by knowledge e variables frequency percentage age of women (years) 20 – 29yrs 85 42.5 30 – 39yrs 100 50 40 – 49yrs 15 7.5 total 200 100 religion christianity 136 68 islam 64 32 traditional none 0 total 200 100 no. of years married 5-jan 80 40 10-jun 85 42.5 15-nov 25 12.5 >15 10 5 total 200 100 level of education no formal education primary 40 20 secondary tertiary 90 45 total 50 25 20 10 200 100 social class upper 40 20 middle 60 30 lower 100 50 total 200 100 t 1: socio-demographic characteristics of the respondents. doi 10.18502/sjms.v12i2.917 page 68 sudan journal of medical sciences production and hosting by knowledge e variable frequency percent yes 120 60 no 80 40 total 200 100 pregnancy outcome voluntary termination 43 35.8 spontaneous abortion 37 30.8 delivered 40 33.4 total 120 100 current pressure to become pregnant yes 158 79 no 42 21 total 200 100 source of the pressure to become pregnant husband 40 25.3 mother-in-law 60 40 father – in-law 5 3 parents 2 1.2 friends 13 8.2 society in general 30 19 self 8 3.3 total 158 100 t 2: pregnancy history and pressure to become pregnant among the respondents. the herbalists. fifty six percent had prayers and spiritual cleansing while (19%) had to offer sacrifices to appease the gods apart from seeking medical care. doi 10.18502/sjms.v12i2.917 page 69 sudan journal of medical sciences production and hosting by knowledge e variables frequency percent induced abortion 28* 14 stis 21* 11 devil 15* 7.5 sinful lifestyle 11* 5.5 ancestral spirit 9* 4.5 witches 8* 4 abnormal menses 22* 11 watery sperm 18* 9 use of iucd and ocps 22* 11 i don’t know 66 33 t 3: respondents’ perception on factors responsible for infertility and consequences of infertility on marital relationship. *multiple responses were recorded. variable frequency percent source of care sought apart from the hospital church 112* 56 herbalist 100* 50 treatment received apart from orthodox medicine prayers spiritual cleansing 60* 30 herbal concoction 52* 26 sacrifice to appease gods 70* 35 38* 19 t 4: sources of health seeking and treatment given among survey respondents with infertility. *multiple responses were recorded. 4. qualitative data 4.1. key findings from focus group discussion doi 10.18502/sjms.v12i2.917 page 70 sudan journal of medical sciences production and hosting by knowledge e 4.1.1. perception of participants about infertility and its etiologies in this environment: majority of the participants perceived infertility as inability to achieve pregnancy in a couple some other participants perceived infertility as not having more than a child or having no male child irrespective of number of children. this was corroborated by a statement made by one of the participants “ a couple with only one child is not better than those with none”……………a 38 year old farmer. 4.2. socially acceptable limit of infertility majority of the participants perceived that a fertile couple should achieve conception within the first 3 to 6 months of marriage, while for others it may take up to a year or longer. this is because of the pressure that may be exerted if the waiting time until pregnancy goes beyond a socially acceptable limit. “if a woman marries this month, we start counting the months, one, two, and three; still if nothing happens the elders will tell the husband to seek help “…………a 32 years old pepper seller majority of the participants felt that infertility etiologies were more spiritual, and traditional than medical. in explaining the spiritual causes, a 26 years old tailor said,“it is the devil that causes infertility since it is the will of god that marriage be fruitful.” “it runs in some families as a result of ancestral curses; as such the couple needs to go for deliverance” …………a 30 years old hospital maid. some participants perceived infertility as a result of punishment from god. a 29 years old food vendor said that a woman may be punished as a result of previous termination of pregnancy. majority of the participants perceived infertility as women’s problem. only 8% of the participants said that it could be caused by men. other causes mentioned include dark menses, and egress of semen from the vagina after intercourse. 4.2.1. attitudes of people towards women with infertility majority of the participants said they empathize with women who have challenges of infertility some of them however believed that they are suffering from their sins and should be dealt with carefully in order to prevent transfer of curses to others. “such couple can never wish you well. they usually maltreat other people’s children. it is better to doi 10.18502/sjms.v12i2.917 page 71 sudan journal of medical sciences production and hosting by knowledge e avoid them” ……. a 33 years old civil servant. “i can never allow them to carry or play with my children because they can poison them” ………. a 36 years old teacher. some of the participants said that infertile women are sometimes called “witches” and usually not invited to naming ceremonies and children’s birthday parties. 4.2.2. findings from key informants interviews (kiis) the kiis explored the perceptions of the women with infertility on the subject matter and their experiences so far. informants were chosen at random over 8 clinic visits. one of the informants has a living child who is a ten-year-old boy. three of the informants are presently in their second marriage. their first marriage ended in divorce due to infertility. in two out the remaining five informants, their husbands married a second wife. majority of the informants perceived infertility as inability to achieve pregnancy in a woman living with a man for at least a year. however, some of the informants said that pressure to become pregnant became enormous barely six months into their marriage. all the informants believed that a woman with a living child is not infertile irrespective of the sex. 4.3. causes of infertility most of the informants perceived aetiology of infertility as more spiritual than physical. a 42 years old food vendor said “my mother was married for 15years before she was able to conceive. i am presently experiencing the same. there is a curse upon us”. very few informants agreed that infertility may be caused by men. “my husband has a low sperm count and we were told that it was the cause of our childlessness. he is presently on medication” ……. a 34 years old banker. other etiologies mentioned were stis, and uterine fibroids 4.4. treatment of infertility most of the informants had sought care from many hospitals, churches and some have visited herbalists before coming to our facility. “i was given concoction mixed with my urine. my husband started beating me when i refuse to take it. i carried a sacrifice to one of the junctions in our neighborhood naked in the middle of the night two years ago” ………...a 45 years old hospital maid. none of the informants accepted child adoption as an option for management of infertility. “i will rather remain childless than to take another woman’s child as mine. the child will eventually know. our relatives will laugh at me “………….a 37 years old banker. doi 10.18502/sjms.v12i2.917 page 72 sudan journal of medical sciences production and hosting by knowledge e majority of the informants said that they were left to source for funds for the treatment of infertility. “my husband believes that i am the one having problem since the second wife is presently pregnant. he is not ready to waste money on me” …………..a 29 years old tailor. “my husband does not believe in orthodox medicine. he sees hospital treatment as a waste of money” ……………a 43 years old banker. 4.5. consequences of infertility four of the eight informants reported history physical assault in their marriage as a result of infertility. “my husband usually comes home late and drunk. he occasionally beats me calling me different names. he once said that i was the source of his sorrow” …………a 39 years old food vendor. psycho-social effects of infertility gathered from the kiis ranged from depression, low self-esteem, to attempted suicide. “i felt tired of living on the day of the naming ceremony of my husband’s second wife. my husband did not allow me to carry the baby. they started calling me a witch. i left the venue of the ceremony disgraced. i felt so bad that i drank a bottle of kerosene when i got home. it was a neighbor that god used to save me by taking me to the hospital” ………..a 49 years old trader. 5. discussion the findings of this study provided an insight into the dynamics of infertility from the perspectives of women attending infertility clinics. majority of the respondents in this study were between ages 30 and 39 years, and had spent more than five years in marriage. most of them also had secondary infertility and were in the lower social class. these findings were similar to that of sule et al. [13] where higher proportion of the women had secondary infertility and have spent more than five years in their marriages. as shown in the kiis, the acceptable waiting time until pregnancy was less than six months from day of wedding. pressure starts mounting up after 6 months of marriage and it became intense after the first 3 years of infertility. this finding was similar to that of okonofua et al. [9]. majority of the respondents seek help through modern medicine and other sources. this may be a pointer to the perceptions of the women and community in general about the etiology of infertility. this was similar to the findings from other local studies [10, 14]. more than two thirds of the respondents were under pressure to achieve conception in the study with higher proportion of the pressure from their husbands and in-laws. this emphasized the need for adequate doi 10.18502/sjms.v12i2.917 page 73 sudan journal of medical sciences production and hosting by knowledge e and quality counseling which may be difficult to achieve considering the high work load and inadequate staffing in the modern health system in nigeria. issues relating to infertility are often negotiated within communal context rather than between the husband and wife alone [18–21]. the interference of significant others in marital relations and challenges is common among nigerians. earlier studies have confirmed the likely pressure from these significant others [2, 8, 10]. infertility related pressure could cause marital strains. this was confirmed by most of the respondents as they established the existence of threats from husbands and relatives to secure other wives for their husbands as a way of overcoming their infertility. some marriages ended in divorce as some of the women who participated in the kiis were in their second marriages because of infertility. this was similar to the findings of previous studies [9, 10, 22–24]. while it is easier for husbands and in-laws to consider marrying a second wife as an alternative to infertility, the same attitude is not displayed towards child adoption. a negative disposition towards child adoption is not only common among husbands and relatives, but even among infertile women. this was confirmed by reactions of participants in the fgds and kiis on the subject of child adoption. this negative disposition has been well documented in previous studies [15, 16, 25]. the practice of plural health seeking is common in nigerian communities [17, 18]. this practice was also confirmed among respondents as they sought help through the orthodox and non-orthodox medical systems. similar to the health seeking patterns, a number of the respondents perceived aetiology of infertility from multiple sources. this pattern has also been reported in previous studies [17–20]. most participants in this study correctly identified some of the causes of infertility but some also incorrectly highlighted factors that do not cause infertility such as use of iucd and ocps. the in-correct fear that the method will cause infertility can lead to under-utilization and worsening of the un-met need for contraception in the developing countries. most of the respondents in this study were blamed for their infertility and were made to source for funds for their treatments leading to financial constraints and economic deprivation. women with secondary infertility especially those with a living child enjoy some support from their husbands, and are less likely to be under intense pressure compared to those with primary infertility. orthodox treatment, even the low technology ones is beyond the reach of most of the respondents. physical violence was reported by some of the respondents in this study while others reported threats of violence. psycho-social effects of infertility recorded in this study ranged from depression, low self-esteem to actual suicide attempt. this was similar to findings from previous studies [30-33]. doi 10.18502/sjms.v12i2.917 page 74 sudan journal of medical sciences production and hosting by knowledge e the limitation of this study includes the fact that it is hospital based. this would have excluded other women within the same category and similar challenges seeking help through alternative sources. in spite of these limitations, the study was able to make minimal contributions on the effects of infertility on reproductive age women in the yoruba community. 6. conclusion cultural beliefs are major determinants in the prevailing explanation of infertility from the lay perspectives in nigeria. these create divergence in the etiological explanation of infertility between the patient and the professional health care provider which has implications for care provision and compliance of the patient to treatment. with the continued pressure, due to infertility in the absence of quality support from the hospital system in form of adequate counseling and from the significant others, a number of the women under pressure could become susceptible to high risk sexual behavior, depression and other psychological problems. 7. competing interests the authors declare that they have no competing interests. 8. acknowledgements i am using this opportunity to acknowledge useful contributions from dr. olorunfemi ogundele of the community health department, obafemi awolowo university teaching hospitals complex, ile 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[17] a. s. jegede, “the yoruba cultural construction of health and illness,” nordic journal of african studies, vol. 11, no. 3, pp. 322–335, 2002. [18] b. j. feyisetan, s. asa, and j. a. ebigbola, “mothers’ management of childhood diseases in yorubaland: the influence of cultural beliefs,” health transition review: the cultural, social, and behavioural determinants of health, vol. 7, no. 2, pp. 221– 234, 1997. [19] b. datta and f. okonofua, “what about us? bringing infertility into reproductive care,” quality/calidad/qualite, vol. 13, pp. 1–31, 2002. [20] l. leonard, (2001). problematizing fertility: scientific accounts and chadian women’s narratives. in m.c inhorn, and f. van balen (eds.). infertility around the globe: new thinking on childlessness, gender, and reproductive technologies (pp.193-213). berkeley: university of califonia press. [21] e. vayena, p. rowe, d. griffin, p. van look, and t. turmen, current practices and controversaries in assisted reproduction. in: vayena e., rowe p., griffin d., editors. report of a meeting on ”medical, ethical, and social aspects of assisted reproduction; 2001, 17-21 sept; geneva, switzerland: who; 2002. p. xv-xxi. [22] p. butler, “assisted reproduction in developing countries-facing up to the issues,” progress in reproductive health research, vol. 63, pp. 1–8, 2003. [23] b. datta and f. okonofua, “what about us? bringing infertility into reproductive care,” quality/calidad/qualite, vol. 13, 2002. [24] l. leonard, (2001). problematizing fertility: scientific accounts and chadian women’s narratives. in m. c. inhorn, and f. van balen (eds.). infertility around the globe: new thinking on childlessness, gender, and reproductive technologies (pp.193-213). berkeley: university of califonia press. [25] s. carr, n. unwin, and t. pless-mulloli, an introduction to public health and epidemiology. bershire, open university press, mcgrawhill education, england, 2007. doi 10.18502/sjms.v12i2.917 page 77 introduction material and methods location of the study study design study population sampling method data collection techniques and instruments quantitative data qualitative data method of data analysis ethical consideration results quantitative data qualitative data key findings from focus group discussion perception of participants about infertility and its etiologies in this environment: socially acceptable limit of infertility attitudes of people towards women with infertility findings from key informants interviews (kiis) causes of infertility treatment of infertility consequences of infertility discussion conclusion competing interests acknowledgements disclosure statement references sudan journal of medical sciences volume 12, issue no. 3, doi 10.18502/sjms.v12i3.915 production and hosting by knowledge e research article changes in serum iron, total iron binding capacity and transferrin saturation percent in sudanese females newly diagnosed with breast cancer at khartoum oncology hospital: a case control study rufaida mustafa ahmed mustafa1 and nazik elmalaika obaid seid ahmed husain2 1b.sc, m.sc, hematology and immunohematology, sudan university of science and technology, sudan 2mbbs, msc, md clinical pathology, department of pathology, faculty of medicine and health sciences, omdurman islamic university and medical laboratory department, khartoum oncology hospital, sudan abstract background: iron is a vital constituent of cells but in excess may be harmful and is associated with a raised risk for some malignant diseases including breast cancer. we aimed to study changes in iron profile in sudanese females newly diagnosed with breast cancer. methods: a casecontrol study in which serum iron, total iron binding capacity (tibc), and transferrin saturation percent were measured for fifty females with breast cancer referred to khartoum oncology hospital and seventy apparently healthy females, using manual method (iron-ferrozine). results: mean age was 47 years and 42 years in cases and control, respectively and the mean of parity was 4 in both groups. mean of serum iron ±sd in case group was 244.30 ± 151.598(𝜇g/dl) and in control group was 57.59 ± 43.191(𝜇g/dl) (p. value = 0.000). mean of tibc ±sd in cases was 412.98 ± 177.460(𝜇g/dl) and in controls it was 403.71 ± 168.765(𝜇g/dl) (p. value = 0.838). the mean of transferrin saturation percent ± sd in cases was 61.08 % ±41.523 and in controls was 223.23 % ±149.195 (p. value=0.000). the mean of tibc in grade i 343.00(𝜇g/dl), 467.10(𝜇g/dl) in grade ii and 321.25(𝜇g/dl) in grade iii (p. value 0.019) according to modified bloom richardson’s grading system. conclusion: there is a statistically significant increase in the mean of serum iron and decrease in transferrin saturation percent in women with breast cancer. tibc vary significantly according to histopathological grade. serum iron and transferrin saturation percent may be helpful as biochemical risk markers for breast cancer and tibc may act as a predictor of disease grade. keywords: iron profile, serum iron, tibc, transferrin saturation percent, breast cancer, modified bloom richardson’s grading system, sudan how to cite this article: rufaida mustafa ahmed mustafa and nazik elmalaika obaid seid ahmed husain, (2017) “changes in serum iron, total iron binding capacity and transferrin saturation percent in sudanese females newly diagnosed with breast cancer at khartoum oncology hospital: a case control study,” sudan journal of medical sciences, vol. 12 (2017), issue no. 3, 119–132. doi 10.18502/sjms.v12i3.915 page 119 corresponding author: nazik elmalaika obaid seid ahmed husain; email: nazikhusain@gmail.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e rufaida mustafa ahmed mustafa and nazik elmalaika obaid seid ahmed husain. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:nazikhusain@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e 1. introduction breast cancer is the most common malignancy in females worldwide with estimated incidence of 252.710 invasive breast cancer and 41.070 deaths expected in 2017 in the united states alone [1]. in sudan, breast cancer incidence is increasing. its frequency was 610 (10.01% of registered cancer cases) in 2003 and 1015 (16.7% of registered cancer cases) in 2010 as referred to statistic department at khartoum oncology hospital. moreover, breast cancer showed high incidence in young and middle age group (27% at 41-50 years old and 26% at group 31-40 years old) [2]. iron is necessary for human life. most functional iron is in the form of haemoglobin and myoglobin, but a small, significant portion of iron is used to bind with cofactors essential to basic metabolic oxidative and reduction reactions. the regulation of body iron is complex and exquisitely done so as to preserve iron needed but not to allow highly toxic excess [3]. although iron is a crucial element for cells but in excess may be dangerous. iron overload is linked with an elevated risk for some malignant diseases, including breast cancer [4]. iron is necessary for cell proliferation and iron metabolism is influenced by oestrogen hormones. interactions between iron and oestrogen may synergistically promote breast cancer [5]. cancer patient suffers from many abnormalities. females with breast cancer suffer from anaemia which is related directly to cancer, such those patients when given therapeutic iron to treat anaemia may impact with a prognosis of breast cancer. a few published studies showed a relationship between serum iron, tibc and transferrin saturation percent and breast cancer and they pointed to the need for more studies. this study is expected to raise the attention to the consideration of serum iron status at the diagnosis and as a prognostic marker of breast cancer. whether high or low levels were encountered, a balance should be taken for the best outcome of the patient. 2. materials and methods this is a case-control study that measured serum iron, tibc and transferrin saturation percent in newly diagnosed breast cancer at khartoum oncology hospital (koh) and apparently healthy sudanese females in khartoum state, in the period from february to august 2015. females confirmed histopathologically to have breast cancer within one month of the date of histopathology report regardless of the menopausal status, with no other chronic condition or not under treatment with iron supplements which affect the result doi 10.18502/sjms.v12i3.915 page 120 sudan journal of medical sciences production and hosting by knowledge e were included in this study. breast cancer patients diagnosed histologically more than one month, breast cancer patients underradiation or hormonal or chemotherapy and patients receiving therapeutic iron were excluded from this study. the control group included apparently healthy females matched to patients in age group and parity. women not known to have any cancer, chronic illness, anaemia or taking iron supplements were selected. the samples size was set by using the formula: 𝑛 = 𝑁 𝑁 + (𝑑2) (1) 𝑛 = sample size 𝑁 = total number of females newly diagnosed with breast cancer per year 𝑑 = degree of precision (0.05) [6]. according to the formula, sample size is 100 samples and was set to be 120 (50 as cases and 70 as controls). cases were selected using simple random sampling technique. the control group was selected using stratified sampling technique from the 41 primary health centers (phcs) distributed among the seven localities of khartoum state. data concerning population size and phcs were collected from the website of ministry of health – khartoum state. data were collected through an interview using a questionnaire which contains the following variables: age, marital status, parity, menopausal status, chronic illness, the presence of cancer, treatment, use of iron supplements. the date, type of breast cancer, and histopathological grade were reported from the patients’ clinical records. five ml of the blood were collected from the superficial vein in the antecubital fossa from the study population under the sterile condition and collected in a plain container, centrifuged to get serum and kept at -20 till the samples were analysed. 2.1. the method of serum iron measurement estimation of serum iron was performed using a manual method (iron-ferrozine) [7] based on the fact that transferrin-bound ferric ions in the sample are released by guanidinium and reduced to ferrous by means of an ascorbic acid. ferrous ions react with ferrozine forming a coloured complex that can be measured by a spectrophotometer (cecil instrument, cambridge england 1000 series) [7]. the procedure was briefly as follows: three test tubes were labelled (sample-sample blank-standard). 1.0 ml from working reagent was placed in a tube labelled with the sample and the standard. 1.0 ml from reagent a was placed in the tube labelled with sample blank. 200𝜇l from the sample doi 10.18502/sjms.v12i3.915 page 121 sudan journal of medical sciences production and hosting by knowledge e was added to the tube labelled with sample and sample blank. 200𝜇l from standard was added to the tube labelled with the standard. all tubes were mixed thoroughly and let stand for 5 minutes at room temperature. absorbance (a) for all tubes was read at 560 nm against distilled water. serum iron concentration was calculated using the following general formula: 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑠𝑒𝑟𝑢𝑚 𝑖𝑟𝑜𝑛 𝑖𝑛 𝑠𝑎𝑚𝑝𝑙𝑒 = 𝐴𝑏𝑠𝑜𝑟𝑏𝑎𝑛𝑐𝑒 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 − 𝐴𝑏𝑠𝑜𝑟𝑏𝑎𝑛𝑐𝑒 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 𝑏𝑙𝑎𝑛𝑘 𝐴 𝑜𝑓 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 (2) the reference value in women is 50-170 𝜇g/dl [7]. 2.2. the method of total iron binding capacity measurement estimation of total iron binding capacity (tibc) was performed by using a manual method (iron-ferrozine) with the following principle: excess of 𝐹𝑒+3 is added to the sample to saturate serum transferrin. uncomplexed 𝐹𝑒+3 is precipitated with magnesium hydroxide carbonate and the iron bonded to protein in the supernatant is then spectrophotometrically measured [7]. the procedure was briefly as follows: 1.0 ml from reagent a was placed in a clean dry test tube. 0.5 ml from the sample was added. the test tube was mixed thoroughly and let stand for 5-30 minutes at room temperature. one spoonful of reagent b was added. the test tube was mixed thoroughly and let stand for 30-60 minutes at room temperature. the test tube was centrifuged at a minimum 3000 round per minute for 10 minutes. the supernatant was carefully collected [7]. the serum iron concentration in the supernatant was measured using the kit of iron from biosystems company, barcelona (spain). 𝑇𝑜𝑡𝑎𝑙 𝑖𝑟𝑜𝑛 𝑏𝑖𝑛𝑑𝑖𝑛𝑔 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 (𝑇𝐼𝐵𝐶) = 𝑆𝑒𝑟𝑢𝑚 𝑖𝑟𝑜𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝑠𝑢𝑝𝑒𝑟𝑛𝑎𝑡𝑎𝑛𝑡 × 3 (3) 3 = dilution factor. the reference value is 250-425 𝜇g/dl in adults [7]. 2.3. calculation of transferrin saturation percent 𝑇𝑟𝑎𝑛𝑠𝑓𝑒𝑟𝑟𝑖𝑛 𝑠𝑎𝑡𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑝𝑒𝑟𝑐𝑒𝑛𝑡 = 𝑠𝑒𝑟𝑢𝑚 𝑖𝑟𝑜𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑇𝐼𝐵𝐶 × 100 (4) the reference value in women is 15-50% [7]. doi 10.18502/sjms.v12i3.915 page 122 sudan journal of medical sciences production and hosting by knowledge e 2.4. data analysis data were computed and analysed using statistical package for social science (ibm spss version 22.0) computer software. pearson chi-squire, student t-test and oneway anova were used. p. value at 0.05 was considered statistically significant. 3. results the study was conducted on 120 samples, 50 breast cancer cases and 70 non-cancer controls. the mean age of the studied case group was 47years and 42 years in the control group with the most common age group 45-54 years and 35-44 years, respectively, while the mean of parity number was 4 in both groups. there were 49.0(98.0%) married females and 1.0 (2.0%) was single in the case group, 43.0(61.4%) married, 11.0 (15.7%) single, 8.0(11.4%) divorced and 8.0(11.4%) widow in the control group. the mean of serum iron in the study group is shown in table1. the mean of serum iron in invasive ductal carcinoma 247.76 (𝜇g/dl), 188.00(𝜇g/dl) in stromal sarcoma and 254.00(𝜇g/dl) in non-invasive ductal carcinoma. table (2) showed the mean of serum iron, mean of tibc and mean of transferrin saturation percent in different histopathological grades of breast carcinoma according to modified bloom richardson’s grading system. table (3) stated the mean of serum iron, mean of tibc and mean of transferring saturation percent in menopausal and non-menopausal breast cancer patients. 4. discussion it is known that iron is present throughout the body. most physiologically active, but some are stored for future use. the intracellular space of the liver and bone marrow contains the majority of the stored iron. iron is stored for the most part in the form of ferritin, which is composed of iron and a protein called apoferritin, when apoferritin is unavailable, iron is stored as hemosiderin [8]. iron is an essential metal vital for living cells and may be the main culprit in tumour immunosuppression. it plays a role in the different mechanisms and functions of tumorigenesis [9]. it is required by a large number of heme and non-heme enzymes and proteins, which have essential functions in oxygen transport and oxidative phosphorylation [10]. preclinical and clinical models proved that iron metabolism is deregulated in breast cancer [11]. iron is a cofactor for ribonucleotide reductase, an enzyme that converts ribonucleotides to deoxyribonucleotides for the synthesis and repair of dna. thus it is doi 10.18502/sjms.v12i3.915 page 123 sudan journal of medical sciences production and hosting by knowledge e parameters status n mean sd. deviation p. value serum iron (𝜇g/dl) case 50.0 244.30 151.598 0.000 control 70.0 57.59 43.191 tibc* (𝜇g/dl) case 50.0 412.98 177.460 0.838 control 70.0 403.71 168.765 transferrin saturation percent (%) case 50.0 61.08 41.523 0.000 control 70.0 223.23 149.195 t 1: serum iron concentration, tibc, and transferrin saturation percent among the study population. n = number, *tibc = total iron binding capacity. a crucial element in dna synthesis, and a constant supply of iron is required to maintain dna activity [12]. being highly proliferative, tumour cells need more iron and they usually show high intracellular iron concentration [13, 14]. the growth of mammary adenocarcinoma cell xenografts in rats was inhibited by low iron diet [15]. moreover, exposing the dividing tumour cells to different iron chelators inhibited proliferation and lead to cell cycle arrest in in vitro as well as in vivo models [16–18]. the status of systemic iron is normally regulated by hepcidin, which is a liver peptide hormone. it blocks iron release from enterocytes into plasma [19]. in cultured breast cancer cells, the expression of ferroportin proved to be negatively regulated by hepcidin through a post-transcriptional mechanism. moreover, since the concentration of hepcidin is higher in tumour cells than in normal cells, the higher hepcidin/ferroportin ratio increases the expressionof ferritin and subsequently, raises the iron labile pool in cancer cells [20]. though the mechanisms of miss-regulated expression of iron-related genes are not clearly known, the fundamental signalling of iron homoeostasis, the hepcidinferroportin axis was found to promote the growth of breast cancer when disordered [21]. zhang et al found high levels of serum hepcidin in patients with breast cancer and greatly reduced concentration of tumour ferroportin in breast tumours, especially in malignant tumours, compared to adjacent tissues [19]. further, they verified that high levels of ferroportin inhibited cell proliferation in vitro and in vivo by knocking down the expression of tumour hepcidin. so, to lock up breast cancer growth, targeting the hepcidin-ferroportin signalling pathway would signify a talented therapeutics [19]. furthermore, high ferritin level in some solid tumours, including breast cancer, has been reported by several studies [22]. pusatcioglu et al reported the significantly higher level of iron accumulation in colonic tissue of colorectal cancer patients compared to controls [21]. moreover, an independent relationship between the level of serum ferritin and hepatocellular carcinoma was found in patients with chronic liver doi 10.18502/sjms.v12i3.915 page 124 sudan journal of medical sciences production and hosting by knowledge e parameter histopathological grade* n mean sd deviation p. value serum iron (𝜇g/dl) i 3.0 248.67 147.873 0.883 ii 31.0 252.06 168.055 iii 16.0 228.44 123.601 tibc (𝜇g/dl) i 3.0 343.00 104.446 0.019 ii 31.0 467.10 185.205 iii 16.0 321.25 129.657 transferrin saturation percent (%) i 3.0 71.00 28.844 0.531 ii 31.0 55.85 37.209 iii 16.0 69.38 51.015 t 2: serum iron concentration, tibc and transferrin saturation percent in different histopathological grades of breast cancer among respondents. n = number, tibc = total iron binding capacity, *modified bloom richardson’s grading system. parameters menopausal status n mean sd deviation p. value serum iron (𝜇g/dl) yes 23.0 423.0 150.40 0.691 no 27.0 403.0 200.03 tibc (𝜇g/dl) yes 23.0 272.0 178.48 0.224 no 27.0 220.0 122.70 transferrin saturation percent (%) yes 23.0 62.0 34.88 0.691 no 27.0 60.0 47.09 t 3: correlation of menopausal status and concentration of serum iron, tibc and transferrin saturation percent in breast cancer patients. n = number, tibc = total iron binding capacity. disease due to viruses [23]. a relative risk (rr) of1.03; 95% ci, 0.97-1.09 for breast cancer for an increase of 1 mg/day of heme iron consumption was reported. the greater consumption of heme iron, but not serum ferritin has shown a tendency toward a positive association with cancer risk [24]. on the other hand, there are reliable publications linking the mutations of c282y and h63d in the high iron fe (hfe) which is encoded by the hemochromatosis gene that causes iron overload (heterozygous mutations) and hereditary hemochromatosis of type i (homozygous mutations) to the risk of developing breast cancer (odds ratios ranging between 2.05 and 4.4) [25, 26]. however, a study on pre-menopausal women did not demonstrate any association between hfe single nucleotide polymorphysm snps and risk of breast cancer [27]. doi 10.18502/sjms.v12i3.915 page 125 sudan journal of medical sciences production and hosting by knowledge e during the early steps of carcinogenesis the gene encoding human ferritin (fth) is found to be up-regulated [28]. interestingly, the ectopic expression of microrna 200b that negatively regulates fth in breast cancer cells has shown a better response to doxorubicin in vitro [29]. the iron labile the pool is increased through inhibition of ferroportin expression and stimulation of ferritin expression through iron regulatory protein 2 (irp2), which is overexpressed in breast cancer, hence playing an early role in cancer-related iron overload [30]. in spite of its importance for cell respiration, iron can cause oxidative stress and dna damage [11]. fe2+ catalyses the production of very active hydroxyl radicals, through the fenton and haber–weiss reactions, that can form dna adducts and initiate carcinogenesis [11]. furthermore, breast carcinogenesis is promoted by stimulating tumour growth through activation of oestrogen receptors by oestrogens and also by the production of genotoxic metabolites of estradiol. dna adducts can further be formed by catechols and their quinoline derivatives and they can favour the occurrence of mutations. the growth of breast tumours is stimulated by oxidised derivatives of oestrogens [31]. the oxidative stress produced by iron could favour the production of these genotoxic metabolites [11]. physiologically, hepcidin expression is negatively regulated by increased erythropoiesis [32] or hypoxia and contrariwise, it is inspired by the high level of circulating iron and by inflammation. the expression of hepcidin is induced by lipopolysaccharides (lps) and interleukin 6 (il-6) during inflammation, which activates hepcidin synthesis through the signal transducer and activator of transcription 3 (stat3) pathway [32]. thus, iron overload is incriminated in carcinogenesis via different mechanisms including the assembly of free radicals, development of oxidative stress, the interaction with other carcinogens and genetic mutations in addition to immunomodulation [11]. in this study 120 females, 50 as cases with breast cancer and 70 as non-breast cancer controls were involved; for all those women serum iron, tibc and transferrin saturation percent were measured or calculated. it revealed a statistically significant increase in the mean of serum iron and decrease in transferrin saturation percent in women with breast cancer while no significant variation in the mean of tibc between case and control groups. the finding of pavithra et al in their study is similar to this study in serum iron level; they found significantly high levels of serum iron in 54 female patients with breast cancer when compared to 54 female controls [33]. in the study conducted by dhankha et al, it was found that the serum iron level, tibc and transferrin saturation percent were significantly elevated in sixty breast cancer patients as compared to thirty healthy controls [34] . though agree with results concerning serum iron but disagree in the level of tibc and transferrin saturation percent in the current study. this could be attributed to the methods used. doi 10.18502/sjms.v12i3.915 page 126 sudan journal of medical sciences production and hosting by knowledge e transferrin (tf), a bi-lobed glycoprotein is the chief iron transport protein in the mammalian blood [35]. there is no significant variation in the mean of serum iron and transferrin saturation percent according to the type of breast cancer and histopathological grade in this study, but there is a significant increase in the mean of tibc in females with grade ii. that is disagreeing with dhankhar et al study in which they reported that patients with advanced disease showed greater values as compared to an early stage, as patients in the current study were in the early stage of the disease because all patients were taken in this study within one month of histopathology report. nevertheless, there is an agreement regarding tibc [34]. interestingly, dhankhar et al analysed iron, ferritin and tibc in thirty patients with early stage, thirty with advanced stage breast carcinoma before and after treatment and the results were related to thirty healthy controls. breast cancer patients showed significantly higher levels of all the three parameters as related to healthy controls and patients with advanced disease showed greater values as when matched to early stage disease. additionally, there is a decrease in these levels following treatment significantly in patients with complete response [34]. therefore, serum analyses of iron, ferritin and tibc may be of prognostic help in assessing the severity of breast cancer. furthermore, a cohort study done by wen et al in 309,443 adults in taiwan in women who had no history of cancer had serum iron levels tested at the time of recruitment. the authors associated the firstly measured iron levels with subsequent cancer risk by connecting individuals with the national cancer registry and national death file. the relationship between serum iron and cancer risk was a j-shaped one, with higher cancer risk at both ends, either at lower than 60 mg/dl or higher than 120 mg/dl [36]. high serum iron could be either a common disorder or/and a biochemical marker of increased risk for breast cancer [36]. on the other hand, there is no significant variation in the mean of transferrin saturation percent, tibc and serum iron in menopausal and nonmenopausal female in this study. nevertheless, another study reported that serum iron is a weak risk factor in menopausal women (hazard ratio of standardized si 1.09 (95% ci 1.02-1.015) [37]. high levels of stored iron may act as a risk factor for mortality due to cancer in postmenopausal women and may be attributed by a buildup of stored iron among women after menopause [37]. the limitation of this study includes small sample size besides the use of the manual methods. more studies should be undertaken with adequate sample size and more advanced method for measurement of serum iron and tibc must be used. doi 10.18502/sjms.v12i3.915 page 127 sudan journal of medical sciences production and hosting by knowledge e 5. conclusion in spite of its limitations, this study concluded that there is a statistically significant difference in serum iron (increased) and transferrin saturation percent (decreased) between sudanese females newly diagnosed with breast cancer and apparently healthy females. while there is no significant difference in tibc between sudanese females newly diagnosed with breast cancer and apparently healthy females. serum iron, tibc and transferrin saturation percent did not vary in regard to the type of breast cancer and menopausal status. tibc but not serum iron and transferrin saturation percent vary significantly according to histopathological grade. the results of this study affirm the previous studies that serum iron and transferrin saturation percent may be helpful as biochemical risk markers for breast cancer and that tibc may act as a predictor of disease grade. 6. acknowledgements we would like to thank the staff of the research laboratory at sudan university of science and technology for their availability at any time and their help in doing this work very easily. 7. ethical consideration informed consent was written and signed by each participant following explanation of the study and sample collection procedure. the participants’ information was kept confidential. ethical approval was obtained from the ministry of health, khartoum state. a permission of study conduction was taken from the head administrative of koh. 8. competing interests authors declare that they have no competing interests. 9. availability of data and material data are available upon request. doi 10.18502/sjms.v12i3.915 page 128 sudan journal of medical sciences production and hosting by knowledge e 10. funding none. 11. abbreviations and symbols koh: khartoum oncology hospital phcs: primary health centers tibc=total iron binding capacity 12. author contributions both authors participated in: 1. the study concept and design, analysis, and interpretation of data. 2. drafting the article, revising it critically for important intellectual content. 3. final approval of the version to be published. 4. agreement to be accountable for accuracy and 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[37] a. gaur, h. collins, w. wulaningsih, l. holmberg, h. garmo, and n. hammar, “iron metabolism and risk of cancer in the swedish amoris study,” cancer causes & control : ccc, vol. 24, pp. 1393–1402, 2013. doi 10.18502/sjms.v12i3.915 page 132 introduction materials and methods the method of serum iron measurement the method of total iron binding capacity measurement calculation of transferrin saturation percent data analysis results discussion conclusion acknowledgements ethical consideration competing interests availability of data and material funding abbreviations and symbols author contributions references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7176 production and hosting by knowledge e research article knowledge, attitudes, and practices surrounding covid-19 among sudan citizens during the pandemic: an online cross-sectional study khawla nasr aldeen altayb mousa, malaz malik yousif saad, and mohammed tayseer bashir abdelghafor medical student, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan. abstract background: a number of protective and cautionary protocols have been adopted to control the rapid spread of covid-19 in sudan. people’s commitment to these protocols is affected by their knowledge, attitudes, and practices (kap). objective: to measure the sudanese population’s kap in relation to covid-19 during the pandemic. method: a web sample was enrolled with success via the authors’ relations with citizens and standard media in khartoum, sudan. a self-administered online kap questionnaire was completed by the respondents. results: among the study sample (n=2336),66.4% between 18 and 29 years old, 60.7% were ladies, 75.9% had a high school education, and 76.1% were khartoum citizens. the general correct rate of the knowledge questionnaire was 84.7%. the majority of the participants (94.8%) were ready to commit to the decision of staying at home. a large proportion of the participants (92%) frequently washed their hands or using antiseptic. conclusion: health teaching programs geared to enhancing covid-19 knowledge are useful for sudan citizens fostering positive attitudes and disseminating knowledge relating to helpful practices. due to the limited sample representativeness, we must be cautious when generalizing these findings. keywords: knowledge, attitude, practice, covid-19, sudan. 1. introduction coronaviruses are a big family of viruses which can cause health problems in animals and humans. in humans, many coronaviruses are known to cause respiratory illnesses starting from the common cold to more severe diseases like middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars) [1]. a continuing pandemic of pneumonia related to a novel coronavirus, called severe respiratory syndrome coronavirus 2 (sars-co-2), was reported in wuhan, hubei how to cite this article: khawla nasr aldeen altayb mousa, malaz malik yousif saad, and mohammed tayseer bashir abdelghafor (2020) “knowledge, attitudes, and practices surrounding covid-19 among sudan citizens during the pandemic: an online cross-sectional study,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 32–45. doi 10.18502/sjms.v15i5.7176 page 32 corresponding author: khawla nasr aldeen altayb mousa received 27 april 2020 accepted 19 may 2020 published 10 june 2020 production and hosting by knowledge e khawla nasr aldeen altayb mousa et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences khawla nasr aldeen altayb mousa et al province china in december 2019. in the following weeks, infections spread across china and other countries around the world. the chinese public health, clinical, and scientific communities took prompt action and shared the infective agent gene sequence to the world. on january 30, 2020, the world health organization (who) declared the natural event a public health emergency of global concern [2]. the ongoing covid-19 pandemic has spread rapidly and by april 29, 2020, the virus had reached 213 countries, leading to 2,995,758 laboratory-confirmed cases and 204,987 confirmed deaths since december 2019. in reaction to the current circumstances, the who announced a public health emergency of global attention on january 30 and called for cooperative efforts of all countries to inhibit the speedy spread of covid-19 [3, 4]. at the time of writing, the source of sars-cov-2, the coronavirus (cov) leading to covid-19, remains uncertain. all available proofs suggest that sars-cov-2 has a natural animal origin and is not a constructed virus. the sars-cov-2 virus most likely has its ecological reservoir in bats. sars-cov-2 belongs to a group of genetically connected viruses, which also include sars-cov and several different covs isolated from bats populations [1]. people may get covid-19 from individuals who have the virus. the disease can transmit from person to person through small droplets from the nose or mouth which are spread once someone with covid-19 coughs or exhales. these droplets land on objects and surfaces around the person. other people then get covid-19 by touching these objects or surfaces, then touching their eyes, nose or mouth. people can also get covid-19 if they breathe in droplets from someone with covid-19 who coughs out or exhales droplets. this is why it is necessary to stay more than one meter away from anyone who is ill [1]. while sars-cov-2 rna has been detected in stool and blood, neither fecal-oral nor bloodborne transmission seems to be important sources of infection. the sars-cov-2 infection has been described in animals, however, there is no proof to recommend that animals are a significant source of transmission [5]. there is an instant necessity to know the public’s awareness of covid-19 at this alarming period to promote outbreak management of covid-19 in sudan. in this study, we were measuring the kap towards covid-19 of sudan citizens throughout the speedy rise interval of the covid-19 outbreak. 2. methods 2.1. participants we conducted this cross-sectional study from march 25 to april 4, 2020. throughout this period it was not possible to achieve a community-based sampling study so, we decided to gather the data online leveraging the authors’ relations with people who live in sudan posting the survey link on whatsapp, telegram groups, facebook, and twitter applications. doi 10.18502/sjms.v15i5.7176 page 33 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al this online post included a short introduction about our study’s aims, the free choice for participation, and statement of confidentiality. persons who live in sudan, of any age group, who had read and understood the post, and accepted to participate in the study were directed to fill the questionnaire via clicking the link. 2.2. measures the self-administered online questionnaire contained two parts: demographics variables which are: gender, age, marital status, education, occupation, and place of current residence. and questions about knowledge, attitude, and practices towards covid-19. knowledge part had 17 questions: 9 regarding clinical presentations, 3 regarding transmission routes, and 5 regarding prevention and control of covid-19 (table 1). attitudes towards covid-19 were measured by 3 questions: about the thinking on the control of covid-19 successfully, the belief in winning against covid-19 and adherence to the decision of staying at home. the practices of participants were evaluated by 4 actions: going to a crowded area, wearing a mask when going out in last few days, using tissues when coughing or sneezing, and washing hands with soap and water or using antiseptic. all questions were answered on a yes/no basis. 2.3. data analysis data analyses were conducted with spss. frequencies of correct knowledge answers and different attitudes and practices were described. multivariable linear regression analysis using all of the demographic variables as independent variables and knowledge score as the outcome variable was conducted to determine factors related to knowledge. similarly, binary logistic regression analyses were used to determine factors related to attitudes and practices. 3. results a total of 2,336 participants completed the study questionnaire. within this population, 1,552 (66.4%) were between 18 and 29 years old, 1,418 (60.7%) were ladies, 1,773 (75.9%) have a high school education, and 1,778 (76.1%) were khartoum citizens. other demographic features are including in table 2. the mean covid-19 knowledge score was 14.41 (sd: 1.54, range: 0-17), indicating a general 84.7% (14.41/17*100) correct rate on this knowledge test. knowledge scores considerably varied‘ ‘ among genders, age-groups, classes of marital status, education levels, occupation, and residence places (table 2). according to demographic features: male gender, age of 17 or less, marital status of others, education of primary school or lower, occupation of free work, and residence of outside khartoum were related to lower knowledge score. doi 10.18502/sjms.v15i5.7176 page 34 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 1: questionnaire of knowledge, attitudes, and practice towards covid-19. questions options k1. is fever one of the main clinical symptoms of covid-19? () yes, no k2. is fatigue one of the main clinical symptoms of covid-19? yes, no k3. is dry cough one of the main clinical symptoms of covid-19? yes, no k4. is myalgia one of the main clinical symptoms of covid-19? yes, no k5. is diarrhea one of the main clinical symptoms of covid-19? yes, no k6. is eyes congestion one of the main clinical symptoms of covid-19? yes, no k7. unlike the common cold, stuffy nose, runny nose, and sneezing are less common in persons infected with the covid-19 virus. yes, no k8. till now there is no definite treatment for covid-2019, but early symptomatic and supportive management may assist most patients to recover from the infection. yes, no k9. not all people with covid-2019 will reach to severe stages. only old persons, those who have chronic diseases, and obese are highly susceptible to severe stages. yes, no k10. eating or handling wild animals would lead to infection by the covid-19 virus. yes, no k11. people with covid-2019 cannot transmit the infection to others if they had no fever. yes, no k12. the covid-19 virus transmits via respiratory droplets from sick persons. yes, no k13. normal people can wear general medical masks to prevent the infection by the covid-19 virus. yes, no k14. children and youths do not have to take actions to inhibit the infection by the covid-19 virus. yes, no k15. to inhibit the infection by covid-19, peoples must avoid going to crowded places such as train stations and avoid using public transportations. yes, no k16. isolation and treatment of sick people with the covid-19 virus are useful ways to decrease the expansion of the virus. yes, no k17. persons who have contact with individual infected with the covid-19 virus must be isolated in a suitable area immediately. generally, the observation period is 14 days. yes, no attitudes a1. do you think that covid-19 will be successfully controlled? yes, no a2. do you believe that sudan can win against the covid-19 virus? yes, no a3. are you ready to commit (adhere) to the decision of staying at home? yes, no practices p1. in the last few days, have you gone to any crowded area? yes, no p2. in the last few days, have you worn a mask when leaving home? yes, no p3. when coughing or sneezing do you use the tissue? yes, no p4. do you wash your hands frequently or using the antiseptic before touching your face? yes, no doi 10.18502/sjms.v15i5.7176 page 35 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al most of the respondents thought that covid-19 will be successfully controlled (85.1%). the attitude towards the success in controlling covid-19 considerably varied among genders and residence places. (or 1.381 (1.098, 1.737) 1.568 (1.168, 2.105)) sequentially (table 3). the percentage of those who had to believe that sudan will successfully cope with covid-19 is 60.9%. (or 1.296 (1.151, 1.459) 1.118 (1.049, 1.192)) sequentially (table 4). nearly all the participants (94.8%) were ready to commit to the decision of staying at home. the attitude towards this question considerably varied among genders (or 3.206 (2.179, 4.717) (table 5). 60.9% of respondents had not visited any crowded area however 49.3% wore masks when going outside in the days immediately prior to their taking the survey. there was still a significant portion of the respondents who had visited crowded areas (30.1%) and had not worn masks when leaving home (50.7%), (tables 6 and 7). result analysis showed that gender, marital status, occupation, and residence (0.570 (0.477,0.682), 1.202 (1.011,1.430), 1.129 (1.056,1.206), 0.777 (0.627,0.962)) sequentially had a significant impact on the tendency to go to a crowded area. occupation and education (or 1.115 (1.001, 1.241), 1.087 (1.022, 1.156)) sequentially appear to be less of a factor in the decision to not wear a mask outside. also, a large portion of participants (86.6%) used tissues when coughing or sneezing, and (92%) frequently washed their hands or used antiseptic. the rates of these two practices considerably varied among demographic classes (tables 8 and 9). 4. discussion according to our information this is the first study in sudan measuring the kap towards covid-19 among sudan citizens. in this preponderantly female, young, unmarried and moderately educated population, we found a general correct rate of 84.7% on the knowledge test, indicating that majority of participants have good knowledge about covid-19. almost all the participants also display a positive attitude towards the covid-19 epidemic: 85.1% thought that covid-19 will be successfully controlled; 60.9% consider sudan will defeat the virus; 94.8% were ready to commit to the decision of staying at home. despite this, the practices of sudan citizens were different, we found that 69.9% avoided crowded areas, only 49.3% wore masks when leaving the home, 86.6% used tissues when coughing or sneezing, 92% frequently washed their hands or used antiseptic throughout the interval of the covid-19 pandemic. we additionally analyzed the features of kap towards covid-19 and identified some demographic factors related to kap; these findings are helpful for public health policymakers and health workers to identify target populations for covid-19 prevention and health education [2]. a high correct rate of covid-19 knowledge in sudan citizens was predictable as we conducted this study some time after the pandemic started, giving time for knowledge doi 10.18502/sjms.v15i5.7176 page 36 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 2: demographic features of participants and the knowledge score of covid-19 by demographic variables. (n= 2336). characteristics number of participants knowledge score(mean±sd) t/f p gender male 918 (39.3%) 14.19±1.63 -5.54 0.00* female 1418 (60.7%) 14.55±1.46 age <=17 64 (2.7) 13.44±2.14 8.66 0.00* 18-29 1525 (66.4) 14.40±1.49 30-40 530 (22.7) 14.54±1.51 41-50 137 (5.9) 14.62±1.40 >=51 53 (2.3) 14.08±2.12 marital status married 713 (30.5) 14.53±1.54 3.12 0.04* unmarried 1547 (66.2) 14.37±1.50 others** 76 (3.3) 14.24±2.12 education primary school or lower 14 (0.6) 12.71±2.52 26.69 0.00* secondary school 1773 (75.9) 14.44±1.46 bachelor 171 (7.3) 13.61±1.85 master or higher 378 (16.2) 14.71±1.56 occupation student 880 (37.7) 14.30±1.47 3.62 0.01* employee 214 (9.2) 14.39±1.84 housewife 801 (34.3) 14.56±1.48 unemployed 226 (9.7) 14.46±1.65 free work 215 (9.2) 14.29±1.53 current residence khartoum 1778 (76.1) 14.46±1.50 2.79 0.01* outside khartoum 558 (23.9) 14.25±1.63 total 2336 (100) 14.41±1.54 *significant association **others include: divorced, engaged, and suttee. about the virus and countermeasures to be disseminated amongst the population. the seriousness of the situation ensured widespread tv coverage in addition to guidance made publicly available on the who website and the national campaigns for public education. comparing our findings with a cross-sectional kap study towards covid-19 among chinese residents [2], we found most chinese respondents were knowledgeable about covid-19 (90% correct rate), slightly higher than the 84.7% rate in the respondents to our study. they had an optimistic attitude towards the covid-19 pandemic: 90.8% doi 10.18502/sjms.v15i5.7176 page 37 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 3: attitudes towards covid-19 by demographic variables, (do you think that covid-19 will be successfully controlled?) (n=2336). characteristics yes no or (95% ci) gender male 758 (32.4) 160 (6.8) 1.381(1.098,1.737)* female 1230 (52.7) 188 (8.0) age <=17 53 (2.3) 11 (0.5) 1.171 (0.993,1.380) 18-29 1310 (56.1) 242 (10.4) 30-40 457 (19.6) 73 (3.1) 41-50 119 (5.1) 18 (0.8) >=51 29 (2.4) 4 (0.2) marital status married 616 (26.4) 97 (4.2) 0.951 (0.761,1.188) unmarried 1302 (55.7) 245 (10.5) others** 70 (3.0) 6 (0.3) education primary school or lower 10 (0.4) 4 (0.2) 1.012 (0.870,1.177) secondary school 1511 (64.7) 262 (11.2) bachelor 145 (6.2) 26 (1.1) master or higher 322 (13.8) 56 (2.4) occupation student 738 (31.6) 142 (6.1) 1.041 (0.954,1.136) employee 185 (7.9) 29 (1.2) housewife 686 (29.4) 115 (4.9) unemployed 198 (8.5) 28 (1.2) free work 181 (7.7) 34 (1.5) current residence khartoum 1491 (63.8) 287 (12.3) 1.568 (1.168,2.105)* outside khartoum 497 (21.3) 61 (2.6) 1988 (85.1) 348 (14.9) *significant association **others include: divorced, engaged, and suttee. believed that covid-19 will finally be successfully controlled, and 97.1% had confidence that china could defeat the virus. chinese respondents were very cautious: nearly all avoided crowded areas (96.4%) and wore masks when leaving the home (98.0%) much higher figures than we found in the sudanese survey. although the sudan government has made worthy efforts to control the virus outbreak, an unprepared country such as sudan cannot mobilize an efficient national response. this is also true of neighboring countries in africa, further facilitating the spread of the disease. matters are complicated in sudan by the grinding poverty, lack of household savings to offset lost income, lack of access to clean water, proper sanitation, and health supplies and the millions who are living in displaced person doi 10.18502/sjms.v15i5.7176 page 38 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 4: attitudes towards covid-19 by demographic variables, (do you have to believe that sudan can win against the covid-19 virus?) (n=2336). characteristics yes no or (95% ci) gender male 561 (24.0) 357 (15.3) 0.990 (0.835,1.173) female 863 (36.9) 555 (23.8) age <=17 34 (1.5) 30 (1.3) 1.296 (1.151,1.459)* 18-29 912 (39.0) 640 (27.4) 30-40 341 (14.6) 189 (8.1) 41-50 95 (4.1) 42 (1.8) >=51 42 (1.8) 11 (0.5) marital status married 455 (19.5) 258 (11.0) 0.850(0.722,1.000) unmarried 926 (39.6) 621 (26.6) others** 43 (1.8) 33 (1.4) education primary school or lower 7 (0.3) 7 (0.3) 1.087(0.973,1.215) secondary school 1071 (45.8) 702 (30.1) bachelor 102 (4.4) 69 (3.0) master or higher 244 (10.4) 134 (5.7) occupation student 502 (21.5) 378 (16.2) 1.118 (1.049,1.192)* employee 136 (5.8) 78 (3.3) housewife 493 (21.1) 308 (13.2) unemployed 142 (6.1) 84 (3.6) free work 151 (6.5) 64 (2.7) current residence khartoum 1077 (46.1) 701 (30.0) 1.070 (0.880,1.302) outside khartoum 347 (14.9) 211 (9.0) 1424 (61) 912 (39) *significant association **others include: divorced, engaged, and suttee. camps across darfur where covid-19 might spread rapidly with devastating results. additionally, the unprecedented demand on an inadequate health care system (with only eighty ventilators and two hundred intensive care hospital beds) could well presage its collapse. even government-run containment facilities cannot look after the sick for the required fourteen-day quarantines [6]. these factors contribute to the results of our survey. in particular, we draw attention to increasingly popular conviction that sudan’s high daily temperatures and young population will ensure the country avoids the worst effects of the disease. the young are displaying a tendency to perceive themselves as impervious to the disease. while this is not an uncommon response (the same conviction doi 10.18502/sjms.v15i5.7176 page 39 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 5: attitudes towards covid-19 by demographic variables, (are you ready to commit to the decision of staying at home?) (n=2336). characteristics yes no or (95% ci) gender male 838 (35.9) 80 (3.4) 3.206 (2.179,4.717)* female 1377 (58.9) 41 (1.8) age <=17 59 (2.5) 5 (0.2) 1.098 (0.847,1.423) 18-29 1474 (63.1) 78 (3.3) 30-40 499 (21.4) 31 (1.3) 41-50 131 (5.6) 6 (0.3) >=51 52 (2.2) 1 (0.0) marital status married 687 (29.4) 26 (1.1) 0.641 (0.443,0.928)* unmarried 1458 (62.4) 89 (3.8) others** 70 (3.0) 6 (0.3) education primary school or lower 12 (0.5) 2 (0.10 1.280 (0.971,1.687) secondary school 1675 (71.7) 98 (4.20 bachelor 164 (7.0) 7 (0.3) master or higher 364 (15.6) 14 (0.6) occupation student 837 (35.8) 43 (1.8) 0.905 (0.790,1.037) employee 208 (8.9) 6 (0.3) housewife 757 (32.4) 44 (1.9) unemployed 214 (9.2) 12 (0.5) free work 199 (8.5) 16 (0.7) current residence khartoum 1689 (72.3) 89 (3.8) 0.866 (0.572,1.313) outside khartoum 526 (22.5) 32 (1.4) 2215 (94.8) 121 (5.2) *significant association **others include: divorced, engaged, and suttee. is visible in other countries) it is a potentially devastating one in a country like sudan where different ages of people live under one roof [6]. the present study showed that 30.1% of citizens went to crowded areas and 50.7% did not wear masks when leaving homes in the days immediately prior to taking the survey, 13.3% did not use tissues and 8% did not wash their hands frequently. these potentially risky behaviors were most likely to be displayed by unmarried male gender of 29 years or less, with secondary school education or less, and poor covid-19 knowledge. this correlates with findings from previous studies regarding age and gender patterns of risk-taking behaviors [2]. the considerably higher risk of practices among males could be ascribed to the need for working daily for the sake of living. doi 10.18502/sjms.v15i5.7176 page 40 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 6: practices towards covid-19 by demographic variables, (in the last few days, have you gone to any crowded area?) (n=2336). characteristics yes no or (95% ci) gender male 343 (14.7) 575 (24.6) 0.570 (0.477,0.682)* female 360 (15.4) 1058 (45.3) age <=17 15 (0.6) 49 (2.1) 0.939 (0.832,1.061) 18-29 481 (20.6) 1071 (45.8) 30-40 161 (6.9) 369 (15.8) 41-50 30 (1.3) 107 (4.6) >=51 16 (0.7) 37 (1.6) marital status married 188 (8.0) 525 (22.5) 1.202 (1.011,1.430)* unmarried 495 (21.2) 1052 (45.0) others** 20 (0.9) 65 (2.4) education primary school or lower 3 (0.1) 11 (0.5) 0.935 (0.830,1.052) secondary school 546 (23.4) 1227 (52.5) bachelor 49 (2.1) 122 (5.2) master or higher 105 (4.5) 273 (11.7) occupation student 238 (10.2) 642 (27.5) 1.129 (1.056,1.206)* employee 38 (1.6) 176 (7.5) housewife 280 (12.0) 521 (22.3) unemployed 72 (3.1) 154 (6.6) free work 75 (3.2) 140 (6.0) current residence khartoum 557 (23.8) 1221 (52.3) 0.777 (0.627,0.962)* outside khartoum 146 (6.3) 412 (17.6) 703 (30.1) 1633 (69.9) *significant association **others include: divorced, engaged, and suttee. we noticed that higher covid-19 knowledge scores were found to be considerably associated with a lower likelihood of potentially dangerous practices towards the covid-19 pandemic in our study. this indicates the importance of enhancing citizens’ covid-19 knowledge via health education, which can also result in improved practices relating to covid-19. we recommend that the health education intervention targets certain demographic groups such as males, young aged and people with a low level of education. we considered that poor knowledge, defeatist attitudes, and unacceptable practices relating to covid-19 prevention are strongly associated with limited access to the internet and online health information resources, vulnerable populations such as doi 10.18502/sjms.v15i5.7176 page 41 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 7: practices towards covid-19 by demographic variables, (in the last few days, have you worn a mask when leaving home?) (n=2336). characteristics yes no or (95% ci) gender male 437 (18.7) 481 (20.6) 1.123 (0.951, 1.326) female 716 (30.7) 702 (30.1) age <=17 31 (1.3) 33 (1.4) 1.052 (0.943, 1.175) 18-29 755 (32.3) 797 (34.1) 30-40 271 (11.6) 259 (11.1) 41-50 68 (2.9) 69 (2.9) >=51 28 (1.2) 28 (1.2) marital status married 359 (15.4) 354 (15.2) 0.977 (0.834 ,1.144) unmarried 753 (32.2) 794 (34.0) others** 41 (1.8) 35 (1.5) education primary school or lower 4 (0.2) 10 (0.4) 1.115 (1.001, 1.241)* secondary school 853 (36.5) 920 (39.4) bachelor 101 (4.3) 70 (3.0) master or higher 195 (8.3) 183 (7.8) occupation student 399 (17.1) 481 (20.6) 1.087 (1.022, 1.156)* employee 82 (3.5) 132 (5.7) housewife 468 (20.0) 333 (14.3) unemployed 94 (4.0) 132 (5.7) free work 110 (4.7) 105 (4.5) current residence khartoum 865 (37.0) 913 (39.1) 1.126 (0.931, 1.362) outside khartoum 288 (12.3) 270 (11.6) 1153(49.3) 1183(50.7) *significant association **others include: divorced, engaged, and suttee. older adults and rural people. therefore, kap towards covid-19 among vulnerable populations needs special research attention. in summary, our findings suggest that sudan citizens of a relatively young age, in particular ladies, have had good knowledge, hopeful attitudes, and acceptable practices towards covid-19 throughout the interval of the covid-19 pandemic. also, good covid-19 knowledge is associated with acceptable practices towards covid-19, suggesting that health education programs aimed at enhancing covid-19 knowledge help encourage and keep safe practices. finally, with additional national efforts toward public doi 10.18502/sjms.v15i5.7176 page 42 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 8: practices towards covid-19 by demographic variables, (when coughing or sneezing do you use the tissue?) (n=2336). characteristics yes no or (95% ci) gender male 737 (31.5) 181 (7.7) 2.413 (1.893,3.075)* female 1287 (55.1) 131 (5.6) age <=17 52 (2.2) 12 (0.5) 1.635 (1.338,1.998)* 18-29 1309 (56.0) 243 (10.4) 30-40 486 (20.8) 44 (1.9) 41-50 127 (5.4) 10 (0.4) >=51 50 (2.1) 3 (0.1) marital status married 663 (28.4) 50 (2.1) 0.538 (0.421,0.688)* unmarried 1292 (55.3) 255 (10.9) others** 69 (3.0) 7 (0.3) education primary school or lower 13 (0.6) 1 (0.0) 1.340 (1.119,1.605)* secondary school 1514 (64.8) 259 (11.1) bachelor 150 (6.4) 21 (0.9) master or higher 347 (14.9) 31 (1.3) occupation student 723 (31.0) 157 (6.7) 1.124 (1.025,1.234)* employee 196 (8.4) 18 (0.8) housewife 734 (31.4) 67 (2.9) unemployed 188 (8.0) 38 (1.6) free work 183 (7.8) 32 (1.4) current residence khartoum 1551 (66.4) 227 (9.7) 0.814 (0.622,1.067) outside khartoum 473 (20.2) 85 (3.6) 2024(86.6) 312(13.3) *significant association **others include: divorced, engaged, and suttee. education and researches about covid-19 sudan will successfully control and prevent covid-19. acknowledgement we thank all the participants involved in this study for their cooperation and support. also, we appreciate the efforts of our great supervisor dr. mazen almobasher alnoor and we would like to thank our university and our doctors for their time and support. doi 10.18502/sjms.v15i5.7176 page 43 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al table 9: practices towards covid-19 by demographic variables, (do you wash your hands frequently or using the antiseptic before touching your face?) (n=2336). characteristics yes no or (95% ci) gender male 809 (34.6) 109 (4.7) 2.346 (1.730,3.182)* female 1341 (57.4) 77 (3.3) age <=17 56 (2.4) 8 (0.3) 1.480 (1.159,1.888)* 18-29 1412 (60.4) 140 (6.0) 30-40 501 (21.4) 29 (1.2) 41-50 130 (5.6) 7 (0.3) >=51 51 (2.2) 2 (0.1) marital status married 674 (28.9) 39 (1.7) 0.667 (0.494,0.902)* unmarried 1406 (60.2) 141 (6.0) others** 70 (3.0) 6 (0.3) education primary school or lower 12 (0.5) 2 (0.1) 1.301 (1.037,1.631)* secondary school 1621 (69.4) 152 (6.5) bachelor 159 (6.8) 12 (0.5) master or higher 358 (15.3) 20 (0.9) occupation student 799 (34.2) 81 (3.5) 0.942 (0.842,1.054) employee 206 (8.8) 8 (0.3) housewife 760 (32.5) 41 (1.8) unemployed 197 (8.4) 29 (1.2) free work 188 (8.0) 27 (1.2) current residence khartoum 1643 (70.3) 135 (5.8) 0.817 (0.583,1.144) outside khartoum 507 (21.7) 51 (2.2) 2150(92) 186(8) *significant association **others include: divorced, engaged, and suttee. references [1] q&a on coronaviruses (covid-19) [internet]. who.int.2020[cited 25 april 2020]. available from: https: //www.who.int/news-room/q-a-detail/q-a-coronaviruses [2] zu z.y. et al. coronavirus disease 2019 (covid-19): a perspective from china. radiology. 200490. (2020). available from: https://www.researchgate.net/publication/ 339418733_coronavirus_disease_2019_covid-19_a_perspective_from_china [3] coronavirus [internet]. who.int. 2020 [cited 29 april 2020]. available from: https://www.who.int/ emergencies/diseases/novel-coronavirus-2019. [4] zhong b., et al. knowledge, attitudes, and practices towards covid-19 among chinese residents during the rapid rise period of the covid-19 outbreak: a quick online cross-sectional survey. int j bio sci. 2020; 16 (10):1745-1752. pubmed pmid:32226294. [5] uptodate [internet]. uptodate.com. [cited 25 april 2020]. available from: https://www.uptodate. com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus% doi 10.18502/sjms.v15i5.7176 page 44 https://www.who.int/news-room/q-a-detail/q-a-coronaviruses https://www.who.int/news-room/q-a-detail/q-a-coronaviruses https://www.researchgate.net/publication/339418733_coronavirus_disease_2019_covid-19_a_perspective_from_china https://www.researchgate.net/publication/339418733_coronavirus_disease_2019_covid-19_a_perspective_from_china https://www.who.int/emergencies/diseases/novel-coronavirus-2019. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus%20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type=default&display_rank=12#h1988437058 https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus%20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type=default&display_rank=12#h1988437058 https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus%20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type=default&display_rank=12#h1988437058 sudan journal of medical sciences khawla nasr aldeen altayb mousa et al 20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type= default&display_rank=12#h1988437058 [6] hudson c. (2020, april). coronavirus comes to sudan-atlantic council. atlantic council. available from: https://www.atlanticcouncil.org/blogs/africasource/coronavirus-comes-to-sudan/ doi 10.18502/sjms.v15i5.7176 page 45 https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus%20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type=default&display_rank=12#h1988437058 https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus%20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type=default&display_rank=12#h1988437058 https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-questions-and-answers?search=coronavirus%20patient%20education%20beyond&source=search_result&selectedtitle=12~150&usage_type=default&display_rank=12#h1988437058 https://www.atlanticcouncil.org/blogs/africasource/coronavirus-comes-to-sudan/ introduction methods participants measures data analysis results discussion acknowledgement references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9291 production and hosting by knowledge e research article the relationship between serum vitamin d level and psychosomatic symptoms in females in mosul city janan a. alrefaee1, ban k. rushdi2, and ghada k. adeeb3 1department of medical physiology, college of medicine, university of mosul, mosul, iraq 2department of physiology, senior chief general practitioners, mosul, iraq 3ibn sina teaching hospital mosul, iraq orcid: janan a. alrefaee: https://orcid.org/0000-0002-4609-9005 abstract background: a widespread severe deficiency of vitamin d (vit d) exists in iraq, especially among women of reproductive age. depression or anxiety is related to deficiency of vit d. these patients may present with psychosomatic symptoms which are symptoms with no sufficient organic cause in the body but from psychological causality. the study aimed to investigate the serum level of vit d in females with psychosomatic symptoms residing in mosul city, iraq and explore the effect of vitamin d3 (vit d3) supplements for treating psychosomatic symptoms. methods: a total of 73 female patients aged 15–45 years presented with several symptoms. all patients underwent physical examination and psychiatric interviews. patients with minimal to mild depression were selected. all included patients underwent investigation of first serum vit d level. the supplementation with vitamin d3 was started. the second serum vit d level was investigated at first post-improvement visit. results: in the improved group, the post-supplementation serum vit d level was higher than that before the supplementation (p = 0.00). in addition, the vit d serum difference before and after its supplementation was greater in the improved group than the nonimproved one (p = 0.00). patients not only experienced improvement in their mood swings, but also recovered from other recorded symptoms such as headache, fatigue, tiredness, and joint pain. conclusion: this study revealed a noticeable association concerning serum levels of 25-oh d and mild depression in addition to psychosomatic symptoms in females living in mosul city. supplementation with suitable loading vit d3 dosages improved these symptoms showing a probable causal relationship. keywords: psychosomatic symptom, vit d, depression, vit d3 supplementation how to cite this article: janan a. alrefaee, ban k. rushdi, and ghada k. adeeb (2021) “the relationship between serum vitamin d level and psychosomatic symptoms in females in mosul city,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 233–244. doi 10.18502/sjms.v16i2.9291 page 233 corresponding author: janan a. alrefaee; phd, department of medical physiology, college of medicine, university of mosul, mosul, iraq. email: janan.alnoman@uomosul.edu.iq janan1969@yahoo.com received 23 april 2021 accepted 9 june 2021 published 30 june 2021 production and hosting by knowledge e janan a. alrefaee et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://orcid.org/0000-0002-4609-9005 mailto:janan.alnoman@uomosul.edu.iq mailto:janan1969@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences janan a. alrefaee et al 1. introduction the two major forms of vitamin d (vit d) are d2 gained from plants and d3 cholecalciferol acquired from fatty fish and eggs. however, about 80–90% of vitamin d3 (vit d3) storage is acquired by ultraviolet irradiation to the skin from 7-dehydrocholesterol [1]. nowadays, low vit d level is an epidemic worldwide, unrelated to race, sex, and age [2–4]. in iraq, most women of reproductive age suffer from a severe deficiency of vit d [5]. the incidence of vit d3 deficiency is related to a combination of inadequate intake of vit d-rich food and inadequate sunlight exposure [6] as well as obesity due to vit d3 sequestration in adipose tissue [7]. the greatest status assessment of vit d is the measurement of serum 25-hydroxy vitamin d. the 25-oh d is described as vit d deficiency when it is <20 ng/ml, while a vit d insufficiency is diagnosed when it is 21–29 ng/ml, the normal level being 30– 100 ng/ml. levels >100 ng/ml is considered toxic [8–10]. vit d plays a principal role in maintaining normal concentration of extracellular fluid calcium. although the deficiency of vit d is well-known to play a role in bone disease, it has increasingly been linked to respiratory, gastrointestinal, musculoskeletal, cardiovascular, metabolic, neurological, breast cancer, and skin diseases [11]. vit d is essential for the health of both the brain and nervous system, which has been sufficiently proved in the past [12]. moreover, vit d deficiency has been reported to be related to depression of major level [13] or symptoms that are linked with depression [14] or anxiety disorders [15]. somatization (psychosomatic symptoms) occurs when a patient presents with symptoms of no or insufficient organic cause but mainly psychological causality [16]. it has been suggested as well that the somatization is a protection mechanism to overcome expression or awareness of psychogenic problems [17]. a variety of presentations of somatization have been observed. somatization could be presented as an atypical chest pain, fibromyalgia, hyperventilation, chronic fatigue syndrome, irritable bowel syndrome, tension headache, unexplained abdominal pain, chronic pelvic pain, and atypical facial pain [16]. these symptoms are considered misleading for the diagnosis which may result in the wrong treatment which thereby affects the health and economic status of the patients and community as well. therefore, this study aimed to investigate the serum vit d svd level in patients with physical symptoms associated with affective complains of psychosomatic symptoms and demonstrate the relationship between them. doi 10.18502/sjms.v16i2.9291 page 234 sudan journal of medical sciences janan a. alrefaee et al it has been suggested recently that intakes of vit d more than recommended dosage may lead to a better health [18]. clearly, it is an important cause to investigate the supplementation role of vit d3 in the improvement of psychosomatic symptoms. 2. materials and methods a study with a clinical case series was conducted between july 2019 and end of december 2019. a total of 73 female participants aged 15–45 years (in reproductive age) were recruited from a private clinic in mosul city. all patients had a sub-sufficient level of vit d – about 66% of them had vit d deficiency and 34% had vit d insufficiency. about 48% of the patients lived in urban areas, while 52% lived in rural parts. all patients included in this study presented with mood swings, headache, fatigue and tiredness, joint pain, bone and back pain, muscle pain, and weak immunity (repeated viral and bacterial infections). the patients with less and more symptoms were excluded from this study. additionally, pregnant women and male patients were also excluded. all patients underwent complete physical examination to eliminate any organic disease and psychiatric interviews were conducted for assessing their mental state. psychiatric interviews were done by a psychiatrist, the affective symptoms were diagnosed clinically according to the dsm5 criteria (diagnostic and statistical manual of mental disorders dsm-5) in addition to the phq-9 questionnaire [19]. arabic version of the test was used to assess the patients. the phq-9 is a self-rating tool used for diagnosing depression. it was developed in 1999 by spitzer et al. the tool monitors the presence and severity of depression, depending on the criteria of the ”diagnostic and statistical manual of mental disorders dsm-iv.” in total, nine symptoms are defined, and the patient is asked to indicate how much she has been affected by these symptoms over the last two weeks. patients with a phq-9 score of 0–9 were considered as having minimal to mild depression. these patients were included in the study while those with higher scores were excluded and referred to receive psychiatric services. all patients were referred to the private laboratory under qualified pathologist’s supervision. at baseline, prior to any intervention, all participants provided first blood samples to investigate circulating serum vit d level (25-oh d). reassessment for the affective symptoms (low mood) was done after the patient started their therapeutic dose in about two–three months from the first assessment (depending on the compliance of the patient to follow-up). doi 10.18502/sjms.v16i2.9291 page 235 sudan journal of medical sciences janan a. alrefaee et al vit d assay was done by using mini-vidas instrument (french company). minividas is an immunoassay system with compact automated characters and relies on the principles of enzyme-linked fluorescent assay (elfa). the system needs patient id acquisition and the sample size is 200 micron of serum. the spr and strip are then placed into the machine and the start key is pressed [20]. 2.1. intervention method it has been proved that vit d supplementation as an intramuscular together with oral is safe and effective [21]. in this study, the total dose was calculated relying on the basal reading of serum vit d [22]. a starting supplementation dose of 300,000 iu vit d per ampule was decided, which was received by patients either as intramuscular injection or orally at morning. this dose was given at an interval of two weeks. it was repeated up to three times, however, few cases who had very low basal serum vit d level received it four times [21, 23–26]. eventually, all patients were advised to take a maintenance dose of 5,000 iu per week [27]. none of the patients had received any treatment for the affective symptoms at the time of the study or shortly before it. regular follow-up of patients was done to assess clinical improvement and continuation of treatment. despite that, the patients were instructed to make an urgent visit once they had an improvement of any symptom or some of their symptoms. in this study, the first visit of the recruited patients post improvement was registered at the end of or after the second month post vit d intervention (depending on patient compliance in followup visits). then, those patients were instructed to make post-improvement second or third visit once other symptoms started to subside. the affective symptoms started to subside on follow-up visits in patients with both clinical and phq-9 scores of 4 and below. patients who had no improvements in symptoms for up to three months or more after the intervention made their final visit that was referred as a no-improvement visit [24]. all participants provided second blood samples exactly at first post-improvement visit equally if they had improvements in some or all of their symptoms. the participants who had no improvement provided the second blood sample at three or more months post vit d intervention. second blood sample was collected to investigate circulating vit d level in serum. the patients were grouped into two groups based on the improvement in their symptoms. doi 10.18502/sjms.v16i2.9291 page 236 sudan journal of medical sciences janan a. alrefaee et al either all or some symptoms improved or in some cases, none. these groups were called as improved and non-improved groups, respectively. 2.2. analysis of statistical data data in this study were obtained as numbers in addition to percentage or mean and ranges. comparison of patient groups was carried out using non-parametric wilcoxon and parametric; t-test sig. 2-tailed, a mann–whitney, and one-way anova as appropriate using the spss software ibm, version 19.0. p ≤ 0.05 was considered as significant. 3. results overall, the number of patients included in this study was 73. all patients were females with low mood and multiple physical symptoms underwent serum vit d test before and after vit d supplementation. the patients were aged between 15 and 45 years. about 66% of them had a deficiency, while 34% had insufficient vit d level before starting the vit d supplementation. the patients were 52% rural and 48% urban. the sample was divided into two groups: 53 improved and 20 non-improved depending on the improvement in patients’ symptoms after vit d supplementation. table 1 shows the relationship between the serum level of vit d in improved and non-improved groups after vit d supplementation. the mean of both vit d levels before and after vit d supplementation was less than normal in both improved as well as non-improved groups. however, the association between the serum level of vit d before and after vit d supplementation in improved group was significant (p = 0.00). the serum vit d mean after vit d supplementation in improved group was higher than that before vit d supplementation. table 2 presents the relationship between the difference in the serum level of vit d in improved and non-improved groups before and after vit d supplementation. a significant association was seen between improved and non-improved groups in the difference in the serum vit d before and after vit d supplementation (p = 0.00). the mean difference in the serum vit d level was greater in the improved than in the non-improved group. table 3 shows the difference in the serum vit d level between urban and rural patient groups before and after vit d supplementation. a non-significant result was noted with doi 10.18502/sjms.v16i2.9291 page 237 sudan journal of medical sciences janan a. alrefaee et al respect to the association between urban and rural patient groups in the difference in serum vit d level before and after vit d supplementation (p = 0.55). the percentages of patients’ improvement in mood swings and other somatic symptoms depending on the recurrent visits to the doctor are shown in table 4. table 1: the relationship between the serum level of vit d in improved and non-improved group. after vit d supplementation total no. (73) age (yr) normal range of serum vit d serum vit d before vit d supplementation (mean ±±± sd) serum vit d after vit d supplementation (mean ±±± sd) p-value improved 53 30 (15–45) 30–100 ng/ml 16.9 ± 5.5 29.5 ± 5.2 0.000 non-improved 20 30 (18–45) 18.8 ± 3.5 18.8 ± 3.5 0.309 table 2: the relationship between the difference in the serum level of vit d in improved and non-improved groups before and after vit d supplementation. patients’ groups after vit d supplementation (mean ± sd) p-value improved (n = 53) non-improved (n = 20) difference in serum vit d level before and after vit d supplementation 12.6 ± 3.3 0.1 ± 0.3 0.000 table 3: vit d level among urban and rural patients. difference in vit d level before and after vit d supplementation urban patients n = 35 (48%) (mean ± sd) rural patients n = 38 (52%) (mean ± sd) pvalue 9.0 ± 5.9 9.3 ± 6.7 0.55 table 4: the percentage of patients’ improvement in mood swings and other somatic symptoms depending on the recurrent visits to the doctor post improvement. symptoms post-improvement visits recurrences 1st visit∗ 2nd visit 3rd visit no improvement∗∗ mood swings 100% (53) nil nil nil headache 100% (53) nil nil nil fatigue and tiredness 100% (53) nil nil nil joint pain 100% (53) nil nil nil decrease immunity 13% (7) 59% (31) 28% (15) nil muscle pain 45% (24) 43% (23) 4% (2) 8% (4) bone and back pain 57% (30) 43% (23) nil nil data expressed as % number. *first visit once some or all psychosomatic symptoms subsided. ∗∗no improvement at last visit after completion of three months. doi 10.18502/sjms.v16i2.9291 page 238 sudan journal of medical sciences janan a. alrefaee et al 4. discussion the present study conducted in mosul city of iraq found that all patients who participated in the study complained of mood swings and multiple somatic symptoms such as headache, fatigue and tiredness, joint pain, weak immunity, muscle pain, as well as bone and back pain. all patients were diagnosed as having a mild depression and their levels of serum vit d were less than sufficient values. this finding is consistent with other studies that demonstrated that low levels of vit d is related with depression symptoms or low mood [28–30]. this finding may be explained by the presence vit d receptors in the brain which increase the possibility of a role of vit d deficiency or insufficiency in mood and depressive disorders [31]. this study revealed that vit d supplementation has an important effect in mild depression. there was a dramatic improvement in depressive clinical symptoms adjacent with significant increases in vit d level after vit d treatment. this finding is supported by previous works which have revealed that there is an improvement in the state of depression after vit d deficiency correction [22, 32]. however, this finding is inconsistent with the findings of other studies that revealed no effect of supplementation of vit d on reducing the severity of symptoms of depression [24, 33]. the difference in the study population and locality in addition to severity of depression may explain these discrepancies. while those studies have included patients of both sex, from different localities, and with mild to severe symptoms of depression, our study included only female patients residing in mosul city suffering from mild depression. this study reports that vit d3 supplementation may have a role in improvement of psychosomatic symptoms. it was found that once the patients improved from mild depression, all of them also improved completely from some other recorded symptoms such as headache, fatigue and tiredness, as well as joint pain. although this improvement was noted, the mean of both vit d levels before and after vit d supplementation was lower than normal range in both improved and non-improved groups. consequently, these symptoms (which subsided once mild depression subsided) are considered as psychosomatic symptoms but other symptoms which did not subside in all patients with mild depression improvement need further study to prove its causative. this finding is supported by another study which demonstrated that fatigue, headache, and muscular pain are all related to numerous and frequently non-specific causations [34]. this finding is consistent with the study which revealed a significant improvement in patients with doi 10.18502/sjms.v16i2.9291 page 239 sudan journal of medical sciences janan a. alrefaee et al chronic tension headaches when they received daily cholecalciferol d3 in addition to calcium. this improvement occurs within four to six weeks after treatment [35]. another study found that vit d treatment led to decrease or disappearance of musculoskeletal pain in 90% of hypovitaminosis d patients with indo-pakistani and arabic nationality. this finding also supports our study because muscle and back pain did not improved in all patients with significant increases in vit d level after vit d supplementation [36]. finally, this study found that there was no difference among patients from urban and rural regions with respect to the increase in the level of vit d after vit d3 supplementation. this may be due to the difficult circumstances which faced all population in mosul city for the last six years. this study recommends that vit d3 supplementation would probably be vulnerable in dealing with mild severity depression and psychosomatic complaining associated with it. a therapeutic action for supplementation with vit d in mild depression treatment and its related psychosomatic symptoms can possibly offer a safe with low-cost intervention in addition to its role in bone and general health well-being. 5. conclusion this study revealed a noticeable association between the serum level of 25-oh d and mild depression as well as psychosomatic symptoms in the females of mosul city. supplementation with loading suitable dosage of vit d3 may improve these symptoms showing a potential underlying cause relationship. acknowledgements the authors acknowledge their families for their support and patience. ethical considerations the study protocol was approved by the college of medicine/university of mosul ethics committee. a written informed consent was provided prior to any study intervention by all participants. those patients with moderate and severe mood disturbances were excluded from this study and referred to be managed under supervision of a psychiatrist with advice to complete their treatment and follow-up regarding vit d. doi 10.18502/sjms.v16i2.9291 page 240 sudan journal of medical sciences janan a. alrefaee et al competing interests none. availability of data and material data used in this study are collected from private clinic. funding references [1] zerwekh, j. e. 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(2010). effect of a single ‘megadose’ intramuscular vitamin d 600,000 iu injection on vitamin d concentrations and bone mineral density following biliopancreatic diversion surgery. obesity surgery, vol. 20, no. 6, pp. 732–737. [22] amrein, k., sourij, h., wagner, g., et al. (2011). short-term effects of high-dose oral vitamin d3 in critically ill vitamin d deficient patients: a randomized, double-blind, placebo-controlled pilot study. critical care, vol. 15, no. 2, p. r104. doi 10.18502/sjms.v16i2.9291 page 242 http://www.annulab.com/annonces_classees/v_occasions.shtml http://www.annulab.com/annonces_classees/v_occasions.shtml sudan journal of medical sciences janan a. alrefaee et al [23] cipriani, c., romagnoli, e., scillitani, a., et al. 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[31] parker, g. and brotchie, h. (2011). ‘d’ for depression: any role for vitamin d? ’food for thought’ ii. acta psychiatrica scandinavica, vol. 124, no. 4, pp. 243–249. [32] gloth 3rd, f. m., alam, w., and hollis, b. (1999). vitamin d vs broad spectrum phototherapy in the treatment of seasonal affective disorder. journal of nutrition, health and aging, vol. 3, no. 1, pp. 5–7. [33] gowda, u., mutowo, m. p., smith, b. j., et al. (2015). vitamin d supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. nutrition, vol. 31, no. 3, pp. 421–429. [34] knutsen, k. v., brekke, m., gjelstad, s., et al. (2010). vitamin d status in patients with musculoskeletal pain, fatigue and headache: a cross-sectional descriptive study in doi 10.18502/sjms.v16i2.9291 page 243 sudan journal of medical sciences janan a. alrefaee et al a multi-ethnic general practice in norway. scandinavian journal of primary health care, vol. 28, no. 3, pp. 166–171. [35] prakash, s. and shah, n. d. (2009). chronic tension-type headache with vitamin d deficiency: casual or causal association? headache, vol. 49, no. 8, pp. 1214–1222. [36] badsha, h., daher, m., and ooi, k. k. (2009). myalgias or non-specific muscle pain in arab or indo-pakistani patients may indicate vitamin d deficiency. clinical rheumatology, vol. 28, no. 8, pp. 971–973. doi 10.18502/sjms.v16i2.9291 page 244 introduction materials and methods intervention method analysis of statistical data results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 12, issue no. 1, doi 10.18502/sjms.v12i1.857 production and hosting by knowledge e research article assessment of the primary and intermediate school staffs’ knowledge, attitude and practice on care of children with type 1 diabetes at school, al-jouf, saudi arabia al duraywish a. a. and abdelsalam m. nail diabetes research center, college of medicine, aljouf university, sakaka, saudi arabia abstract background: children with diabetes type 1 (t1dm) need close monitoring for their blood glucose, food intake, insulin therapy and physical activity during school hours in order to guard against the development of acute and long-term complications. objectives: to evaluate the current situation of management of t1dm in primary and intermediate schools children through assessment of the working staffs’ attitude, knowledge and practice at al-jouf, saudi arabia. materials and methods: this descriptive cross-sectional study enrolled consented voluntarily participating working staffs from primary and intermediate schools in al-jouf region, saudia arabia. a questionnaire (included 23 questions) testing knowledge, attitudes and practice regarding t1dm and care of diabetic children was used. results: 744 teachers were studied (62.1% females) where58.1%of them were working in primary schools. of all, 69% were class teachers, 20.4% administrators, 8.6% school counselors, and 2% physical education teachers. 75.4% of the participants had adequate general knowledge about diabetes. only 43.78% of the respondents had specific knowledge about diabetes in the school and teachers with a family diabetic patient showed higher knowledge about diabetes vs. their counterparts. only 16.0%of the participants reported that their schools have trained personnel in diabetes. large proportion of study teachers’ (94%) was willing to join a training program for care of diabetic students. of the total group of teachers, 665 support recruitment of a school nurse. conclusion: diabetes care training programs for school teachers and staffs, availability of school nurses and instigating collaboration between the diabetic center and the school is essential for safety of such diabetes student patients in the schools. keywords: type 1 diabetes mellitus, school teachers, training programs, diabetes care, knowledge about diabetes, school nurse, diabetes care at the school how to cite this article: al duraywish a. a. and abdelsalam m. nail, (2017) “assessment of the primary and intermediate school staffs’ knowledge, attitude and practice on care of children with type 1 diabetes at school, al-jouf, saudi arabia,” sudan journal of medical sciences, vol. 12 (2017), issue no. 1, 33–45. doi 10.18502/sjms.v12i1.857 page 33 corresponding author: al duraywish a. a.; email: dr-aaad@hotmail.com received: 15 december 2016 accepted: 20 february 2017 published: 28 may 2017 production and hosting by knowledge e al duraywish a. a. and abdelsalam m. nail. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr-aaad@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e دقيقة مراقبة إىل األول النوع من السكري بمرض المصابين األطفال يحتاج الخلفية: ساعات خالل البدين والنشاط باألنسولين، والعالج الطعام، وتناول الدم، سكر لمستوى الدوام المدرسي من أجل الحيلولة دون حدوث مضاعفات حادة أوطويلة األجل. األهداف: تقييم الوضع الحايل إلدارة مرض السكري من النوع األول يف المدارس اإلبتدائية والمتوسطة من خالل تقييم المعرفة والسلوك والتصرف لدى العاملين بمنطقة الجوف، المملكة العربية السعودية. المواد والطرق: شملت هذه الدراسة الوصفية المقطعية الموافق عليها طوعاً الموظفين المملكة الجوف، منطقة يف والمتوسطة اإلبتدائية المدارس من المشاركين العاملين والسلوك المعرفة الختبار سؤاالً) ٢٣ (شمل إستبيان وإستخدم السعودية. العربية والممارسة المتعلقة بمرض السكري من النوع األول ورعاية األطفال المصابين بالسكري. يف يعملون منهم ٪٥٨٫١ كان حيث اإلناث) من ٪٦٢٫١) معلماً ٧٤٤ دراسة تم النتائج: المدارس اإلبتدائية. وكان ٦٩ يف المائة منهم من معلمي الصفوف و ٢٠٫٤ يف المائة من المدراء و ٨٫٦ يف المائة من المرشدين يف المدارس و ٢ يف المائة من معلمي التربية البدنية. وكان لدى المشاركين معرفة كافية حول مرضى السكري. فقط ٤٣٫٧٨٪ من المستطلعين مريض لديهم الذين والمعلمين المدرسة يف السكري مرض عن دقيقة معرفة لديهم بالسكري ىف األسرة أظهروا معرفة أعلى عن مرض السكري مقابل نظرائهم. وأفاد ١٦٫٠٪ نسبة وكانت السكري. مرض يف العاملين دربت قد مدارسهم أن المشاركين من فقط كبيرة من المعلمين ىف الدراسة (٩٤٪) على استعداد لالنضمام إىل برنامج تدريبي لرعاية يدعمون مشاركا ٦٦٥ هناك كان الدراسة، ىف المشاركين مجموع ومن السكري. طالب وجود الممرضة المدرسية. والموظفين، المدارس لمعلمي السكري مرضى رعاية على التدريب برامج اإلستنتاج: أمر والمدرسة السكري مركز بين التعاون على والتشجيع المدارس ممرضات وتوافر ضروري لسالمة مرضى السكري من هؤالء الطالب يف المدارس. 1. introduction diabetes mellitus is one of the most prevailing non-communicable diseases in children [1]. in saudi arabia, the annual incidence rate of type 1diabetes (t1dm) is 31.4 new children per 100,000 total population. 16,100 children in kingdom of saudi arabia have t1dm which represent 25% of the total population of children with t1dm in the middle east region’s totaling to 60,700 [2]. these statistics demonstrate the rising incidence of the disease among children and the increased need for diabetes knowledge, care and management. diabetes is a chronic, currently incurable disease that needs effective management in order to avoid the risk of emergence of its long-term complications such as blindness, vascular diseases, renal failure and neuropathy [3–5]. doi 10.18502/sjms.v12i1.857 page 34 sudan journal of medical sciences production and hosting by knowledge e the implementation of intensive insulin therapy and such rising prevalence of t1dm highlight the role played by diabetes educators and school staffs. compliance of the majority of children to the intensive diabetes treatment at school is deficient due mainly to lack of appropriate school staff support [6]. all children including those with diabetes mellitus have the right to learn and continue their education [7]. in order to ensure that such student diabetic patients at school achieve their full capabilities while participating in academic and various school activities, partnership between health and education services is mandatory. moreover, to assure the immediate safety, long-term well-being, and optimal academic performance of student diabetic patients, such proper diabetes care at school should be reinforced. this care should include blood glucose testing, caloric calculation, administration of insulin, activity and exercise within the school environment, awareness of the impact of stresses within the school environment, assistance if unwell, and emergency management of severe hypoglycemia and ketoacidosis [8]. since t1dm prevails amongst young school children, basic knowledge about the disease should be indemnified within the schools environment – staffs, administrators, teachers and/or dedicated nurse. among such young children, to control blood glucose to an optimum level, it is essential to balance carefully food intake, physical activity and insulin [9]. children with diabetes may require multiple doses of insulin while in school [10]. some children may require someone to supervise or deliver insulin. children with t1dm need to be active. teaching the importance of physical activity is an essential healthy habit to enable the child well into adulthood. however, physical activity also impacts blood glucose levels, and teachers need to know how to respond to these changes [11]. having trained personnel on care of diabetes, which know how to check blood glucose, inject insulin, and choose an appropriate snack when blood glucose levels are low, provides an enormous preventive measure. the potential cognitive vulnerability associated with hypoglycemic seizures and chronic hyperglycemia among such group of students should be considered by the school teachers. early detection of minor difficulties should be considered a priority employing assessment of the cognitive skills as a reflection of day-to-day control of the disease [12]. youth fail to meet hba1c goals despite advances in diabetes management and their health and safety are at risk when medication, food, and physical activity are not balanced [13]. the responsibility of the school administrators and educators is very critical in the monitoring and management of t1dm among diabetic school children, given the fact that school-age children spend the greater part of their day time in school. at present in saudi arabia, responsibility for the management of the disease among diabetic children of school age is often undertaken by the children and their parents. to expand the umbrella of this management, school teacher should be equipped by satisfactory knowledge and get training to change their attitude and practical capacities to share actively in the management of disease. doi 10.18502/sjms.v12i1.857 page 35 sudan journal of medical sciences production and hosting by knowledge e to date, there are no reported studies investigating the awareness of school staffs, administrators, and educators about diabetes in school children in saudi arabia. therefore, this study aimed to assess the knowledge, attitudes and practice of school staffs, administrators, and teachers towards participating in the efforts for managing t1dm and its complications amongst children while at school utilizing the primary and intermediate schools at sakaka city, al-jouf, saudi arabia as our sample. 2. materials and methods this descriptive cross-sectional study was conducted in the period from january 2016 to march 2016 among school staffs, administrators, and educators working in primary and intermediate schools of four sectors (sakaka, domataljandal, tabarjal and sowair) in al-jouf region. the study included the respondent 744 participants out of the 1000 teachers targeted. their socio-demographic data (age, gender, working place, and type of school, job description, academic status and years of experience) were collected. the main study questionnaire included 23 questions testing knowledge, attitudes and practice regarding t1dm and care of diabetic children. the knowledge domain included 7 questions about manifestations of t1dm and hypoglycemia and preparation of diabetic children before physical activity sessions. the attitude domain included 5 questions about management of hypoglycemia, willingness to have diabetic children in their classes, need for specialized nurse children, and for a training program to increase awareness of diabetes care at school. the practice domain included 11 questions regarding general affection of students with t1dm particularly attendance, academic performance, support of diabetic children, preparedness of diabetic children before their physical activity sessions and availability of special meals. additionally, the sources of the participants’ information about the disease were recorded. the questionnaire was in arabic language and all were closed-ended with three answers (yes, no, or unsure). a pilot study was done before conducting the survey that included 30 individuals not included in the study to assure validity of the questionnaire and essential modifications were done. ethical approval was obtained from the ethics and research committees of the college of medicine, aljouf university and directorate of education of al-jouf region. data analysis utilized the computerized statistical packages for the social sciences (spss; version 16). the demographic variables of participants were presented as numbers and percentages. for calculation of knowledge score of diabetes, incorrect and unsure answers were given zero, whereas, the correct answer was given one point. the mean score for each section (general knowledge on diabetes, knowledge about diabetes at the school and doi 10.18502/sjms.v12i1.857 page 36 sudan journal of medical sciences production and hosting by knowledge e situation about diabetes at the school) was calculated as the summation of the total possible score in each, and then it was expressed as percentage of total score in each. the diabetes knowledge score was calculated based on the total marks of the three sections. win episcope (version 2.0) was used to assess the chi squire to explore the association between the demographic variables (gender, type of school and family with diabetic children, level of education, years of experience and professional task) and good knowledge on t1dm. we expressed out data as frequency (n and %) and mean ± sdm as appropriate. 3. results in this study, 744 participants completed the submitted questionnaires (74.4% response rate). demographics, work description and education background of participants is depicted in table 1. general knowledge on diabetes: the results show that the overall general knowledge on diabetes of the participating teachersis75.4%.good level of awareness of the symptoms of dm prevailed among majority of participants (73.4 96.8%), while awareness about symptoms of hypoglycemia was 87.9%. awareness was low regarding negative effect of t1dm on school children (48.8%), insulin as a replacement therapy (48.5%) and t1dm effect on attendance (47.7%). it was worth noting that awareness for management of hypoglycemia was high (84.3%; table 2). regarding their sources of information, 35.5% reported that they had this information as a part of their general knowledge. teachers with a family diabetic child, with the higher level of education and longer career experience had enhanced knowledge of diabetes vs. their counterparts. knowledge about diabetes in the school setting: with respect to the presence of diabetic children among the class students, 263 (35.3%) of participants reported presence of diabetic children in the class, 404 (54.3%) stated that they encounter diabetic children in their class, while 16 (2.2%) were unsure about the presence of diabetic children in the class. 617 (82.9%) of participants were welcoming the presence of diabetic children in their class, while 86 (11.6%) stated that they would be worried having diabetic children in their classes, and 63 (5.9%) were unsure about accepting diabetic children in their classes. 561 (75.4%) of the participants answered that diabetic children could attend the physical education sessions. 125 (16.8%) of the teachers declared that they were unsure about this question, while 58 (7.8%) stated that diabetic children are not eligible to attend physical education classes. only 460 (61.8%) of the participants believed that the diabetic child should take sweets or juices before physical activities. regarding diabetic emergencies, 558 (75.0%) of the participants reported absence of trained person who could deal with doi 10.18502/sjms.v12i1.857 page 37 sudan journal of medical sciences production and hosting by knowledge e characteristics range (mean ± sdm) or n (%) age (range and mean ± sdm), years 23 – 60 (39.2 ± 10.2) gender, male/female 282/462 residence location: sakaka 415 (55.8) domat al jandal 212 (28.5) sowair 64 (07.1) tarbajal 53 (08.7) education level: bachelor’s degree 603 (81) diploma 118 (15.9) master’s degree 20 (2.7) doctorate degree 3 (0.4) years of experience: <10/≥10 years 262 (35.2)/482 (64.8) education sector: primary/intermediate 432 (58.1)/312 (41.9) professional title: teachers 513 (69) administrators 152 (20.4) counselors 64 (8.6) physical educators 15 (2) t 1: demographic and work information of the study participants. questions answers yes no unsure n (%) n (%) dm leads to polyuria in diabetic student 720 (96.8) 8 (1.1) 16 (2.2) dm leads to polydepsia in diabetic student 686 (92.2) 19 (2.6) 39 (5.2) dm leads to fatigue and lack of concentration in diabetic student 569 (76.5) 78 (10.5) 97 (13.0) dm leads to loss of weight in diabetic student 545 (73.3) 85 (11.4) 114 (15.3) type 1 dm is treated with insulin 361 (48.5) 154 (20.7) 229 (30.8) tremors and sweating means hypoglycaemia in diabetic student 587 (78.9) 34 (4.6) 123 (16.5) the diabetic student should take sweets or juices before physical activities class 460 (61.8) 110 (14.8) 174 (23.4) t 2: knowledge indicators about diabetes mellitus (dm) in the school setting among the studied population of teachers. diabetic emergencies in their schools. 178 (23.9%) of teachers knew about presence of a trained personnel for checking blood sugar and giving insulin in the school. regarding snacks and school lunches for diabetic children, 656 (88.2%) mentioned no snacks or special school lunches presented to diabetic children and 44 (5.9%) were not sure about that. only 302 (40.6%) of the participants knew that their school have a training program in how to deal with diabetic children in their schools (table3). doi 10.18502/sjms.v12i1.857 page 38 sudan journal of medical sciences production and hosting by knowledge e questions answers yes no unsure n (%) n (%) school children are usually affected by type 1 dm 363 (48.8) 68 (9.1) 313 (42.1) dm affects the student’ academic performance 248 (33.3) 340 (45.7) 156 (21.0) dm increases absence rate of diabetic student 355 (47.7) 253 (34.0) 136 (18.3) do you have any diabetic student in your class? 263 (35.3) 404 (54.3) 77 (10.3) do you give support to the diabetic children in your class? 672 (90.3) 34 (4.6) 38 (5.1) are diabetic children eligible to attend the physical education session? 561 (75.4) 58 (7.8) 125 (16.8) does your school present special meals for diabetic student? 44(5.9) 656 (88.2) 44 (5.9) does your school appoint somebody to look after the diabetic students? 154 (20.7) 518 (69.6) 72 (9.7) is there any trained person to check blood sugar and inject insulin in your school? 178 (23.9) 506 (68.0) 60 (8.1) is there any trained person in dealing with diabetic emergencies in your school? 119 (16.0) 558 (75.0) 67 (9.0) does your school have a training program for dealing with diabetic students? 302 (40.6) 398 (53.5) 44 (5.9) t 3: diabetes mellitus (dm) practice indictors among the studied population of teachers concerning children diabetes at the school setting. attitude indicators about diabetes at the school setting (table 4): 587 (78.9%) of the teachers knew that tremors and sweating means hypoglycemia in diabetic student and 627 (84.3%) mentioned that the diabetic child with hypoglycemia should take sweet juice. only 475 (63.8%) answered that in case of coma, small amount of jam or honey should be put on the mouth of the diabetic child. 154 (20.7%) of the respondents agreed that somebody should be appointed to look after the diabetic childrenincluding the presence of a dedicated school nurse (665; 89.4%). effect of gender on the study outcomes: the gender effect on different domains of our study was significantly different comparing male scores vs. females regarding knowledge and training indicators only. the scores regarding general and specific knowledge, symptoms of the disease, emergency responses, practice and training needs was equally distributed between male and female (table 5). effect of type of school on the study outcome: cross-tabulating the effect of nature of school (primary vs. intermediate) on different domains of our study, scores regarding general and specific knowledge, symptoms of the disease, emergency responses, practice and training needs showed significant gender differences. scores regarding knowledge and training indicators were equally distributed in both primary and intermediate schools (table 6). doi 10.18502/sjms.v12i1.857 page 39 sudan journal of medical sciences production and hosting by knowledge e questions answers yes no unsure n (%) n (%) are you willing to have diabetic children in your class? 617 (82.9) 86 (11.6) 41 (5.5) in case of hypoglycaemia, should the diabetic student take sweet juice? 627 (84.3) 41 (5.5) 76 (10.2) in case of coma, can small amount of jam or honey be put into the mouth of the diabetic student? 475 (63.8) 90 (12.1) 79 (24.1) would you like to join training program for dealing with diabetic students? 693 (93.1) 41 (5.5) 10 (1.3) do you support presence of school nurse? 665 (89.4) 67 (9.0) 12 (1.6) t 4: diabetes mellitus attitude indictors among the studied population of teachers concerning children diabetes at the school setting. variable gender n mean ± sdm p< general knowledge male 282 2.28 ± 0.304 0.535 female 462 2.27 ± 0.315 symptomatology male 282 2.57 ± 0.360 0.009* female 462 2.50 ± 0.360 emergency response male 282 2.62 ± 0.398 0.484 female 462 2.64 ± 0.378 practice guidelines male 282 1.42 ± 0.591 0.800 female 462 1.41 ± 0.559 training needs male 282 2.44 ± 0.413 female 462 2.56 ± 0.411 0.000** t 5: effect of gender on the scores in different domains of study regarding diabetes. *significant using independent samples ”t”-test and assuming equal variance. **significant using independent samples ”t”-test but not assuming equal variance. 4. discussion the mission of the college of medicine, aljouf university is community serving and citizenship development. this is why the college adopted the community-oriented education system. the college plan for the establishment of the diabetes research center was to promote diabetes research and improve preventive and clinical community services. to guarantee the safety and well-being of the child with diabetes at the school setting, partnership between health and education services is indispensable. assessing the level of school staffs, administrators and teachers’ awareness of diabetes is supportive for health educators to plan for future enhancement programs. students with diabetes and their parents report inadequate knowledge, preparation, or support from the school teachers and a lack of education for substitute teachers, bus drivers, coaches, and other ancillary school personnel [14]. doi 10.18502/sjms.v12i1.857 page 40 sudan journal of medical sciences production and hosting by knowledge e variable school n mean p< general knowledge primary 432 2.25 ± 0.323 0.005* middle 312 2.31 ± 0.290 symptomatology primary 432 2.54 ± 0.349 0.284* middle 312 2.51 ± 0.378 emergency response primary 432 2.65 ± 0.353 middle 312 2.60 ± 0.425 0.061 practice guidelines primary 432 1.33 ± 0.496 middle 312 1.53 ± 0.643 0.001** training needs primary 432 2.47 ± 0.385 middle 312 2.59 ± 0.445 0.001** t 6: effect of the type of schools on the scores in different domains of study regarding diabetes. **significant using independent samples ”t”-test but not assuming equal variance. *significant using independent samples ”t”-test and assuming equal variance. poor diabetic control for young people is linked to increased heart complications, peripheral nerve function, and other serious complications [15, 16]. providing training to the school personnels significantly improves the diabetic child’s glycemic control, and furnishes a more supportive school environment [17–19]. upon proper support of the students witht1dm not only their academic and social but also their medical outcomes improve [20]. we planned the present 3-steps investigation to help establishing guidelines for managing diabetes at school in al-jouf region. firstly, questionnaires assessed the extent to which primary and intermediate school teachers are knowledgeable about children diabetes mellitus at school setting. secondly, we tested how school staffs, administrators and teachers reacted to diabetes needs. thirdly, we highlighted deficiencies in information and training programs that could improve health care for diabetic children at school setting. we observed adequate general knowledge about diabetes among school personnels in al-jouf regions. this is attributable to the level of education of participants and the high prevalence of the disease in saudi arabia [21].however, the study also noticed the lack of enthusiasm of teachers to have diabetic child in their class and unawareness about the management of diabetic emergencies among school personnels in al-jouf region. in fact, a diabetic emergency as hypoglycemia is life threatening and occurring more frequently in children with dm. awareness about complications of dm was found to be similarly low in countries of the region like bahrain and turkey [22, 23]. t1dm treatment with insulin needs help from school nurses and teachers. however, the study recorded that only a few schools have school nurses and trained personnels. consequently, the responsibility of children’s health is shouldered by parents. regarding the information sources about dm among the participants, 40.6% of them reported acquiring their information as a part of their general education. school nurses were reported to be the major source of information for chronic diseases, and are required to obtain concise disease-specific doi 10.18502/sjms.v12i1.857 page 41 sudan journal of medical sciences production and hosting by knowledge e information [24]. regarding activity and exercise within the school environment, most of the participants answered that diabetic children could attend the physical activity sessions. however, they were not aware about the measures that should be taken before, during or after any activity such as blood glucose monitoring before and after any activity, consuming additional carbohydrates, and if using an insulin pump, decisions related to whether the pump should be disconnected or temporary basal rates set [25]. only one fifth of the participants of our study knew that their schools appoint somebody to look after the diabetic students and/or was trained for checking blood sugar and giving insulin. less than one fifth of school personnels received training on how to recognize and respond to diabetic emergencies. the study showed that there is deficiency in training programs regarding diabetes at school and the overwhelming majority liked to join such training program. 76.5% of the participating personnels showed willingness to pay the required support to diabetic children at school. this means that majority of personnels would attend and gets benefit from such training programs. therefore, a positive impact on academic and health performance of diabetic children would be the gain. a comprehensive review of the published literature that examined publications concerned with care of children with diabetes at school and ways of improving it showed areas of deficiencies to be; communication, after-school support, education of staff and peers, school nurse availability, and lunch choices [26]. 5. conclusion this is the first report to check the knowledge about diabetes at school among saudi teachers in al-jouf region. our data shows that primary and intermediate school teachers in al-jouf region have enough general knowledge on diabetes regarding symptoms. however, they were deficient regarding diabetes complications and management. furthermore, the majority of teachers did not receive training programs on diabetes at school, although majority of them expressed willingness to pay the required support to diabetic children and attend such programs. therefore, our study suggests that more efforts should be paid to improve knowledge, practice and attitude of diabetes at school setting and its associated complications among primary and intermediate school teachers. we suggest three stages of training as following: 1) basic understanding targeting all school staffs through training on how to recognize and respond to the signs and symptoms diabetic emergencies and who to make urgent contacts in case of an emergency, 2) specific personnels with the responsibility of taking care of diabetic students should receive additional training on managing diabetes, its complications and emergencies, and, 3) advanced training for a few school staffs should be an in-depth training about diabetes, its routine care and emergencies in support for each student with diabetes. doi 10.18502/sjms.v12i1.857 page 42 sudan journal of medical sciences production and hosting by knowledge e 6. ethical clearance ethical approval was obtained from the ethics and research committees of the college of medicine, aljouf university and directorate of education of al-jouf region. 7. competing interests the authors declare that they have no competing interests. 8. funding none. 9. authors’ contributions both authors contributed in planning the study, collecting data and wrote and read the final version of the manuscript. 10. acknowledgments we wish to thank all study participants and the schools where this research was undertaken. references [1] international society of pediatric and adolescent diabetes (ispad 2000), consensus guidelines for the management of type 1 diabetes mellitus in children and adolescents. [2] m. e. craig, a. hattersley, and k. donaghue, “epidemiology and classification. global idf/ispad guideline for diabetes in childhood and adolescence,” ispad, pp. 8–16, 2011. [3] t. m. nguyen, k. j. mason, c. g. sanders, p. yazdani, and r. a. heptulla, “targeting blood glucose management in school improves glycemic control in children with poorly controlled type 1 diabetes mellitus,” journal of pediatrics, vol. 153, no. 4, pp. 575–578, 2008. [4] c. c. jackson, a. albanese-o’neill, k. l. butler et al., “diabetes care in the school setting: a position statement of the american diabetes association,” diabetes care, vol. 38, no. 10, pp. 1958–1963, 2015. [5] american diabetes association, “diabetes care in the school and day care setting,” diabetes care, vol. 33, pp. s70–s74, 2009, suppl. 1. doi 10.18502/sjms.v12i1.857 page 43 sudan journal of medical sciences production and hosting by knowledge e [6] a. marks, v. wilson, and j. crisp, “the management of type 1 diabetes in primary school: review of the literature,” comprehensive child and adolescent nursing, vol. 36, no. 1-2, pp. 98–119, 2013. [7] e. akesen, s. turan, t. güran, z. atay, d. save, and a. bereket, “prevalence of type 1 diabetes mellitus in 6-18-yr-old school children living in istanbul, turkey,” pediatric diabetes, vol. 12, no. 6, pp. 567–571, 2011. [8] g. klingensmith, f. kaufman, d. schatz, and w. clarke, “care of children with diabetes in the school and day care setting,” diabetes care, vol. 26, no. 1, pp. s131– s135, 2003. 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[14] r. hayes-bohn, d. neumark-sztainer, a. mellin, and j. patterson, “adolescent and parent assessments of diabetes mellitus management at school,” journal of school health, vol. 74, no. 5, pp. 166–169, 2004. [15] centers for disease control and prevention, national diabetes fact sheet: general information and national estimates on diabetes in the united states, 2011. atlanta, ga. us department of health and human services, available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf, (last accessed on october 1, 2016). [16] l. m. siminerio, a. albanese-o’neill, j. l. chiang et al., “care of young children with diabetes in the child care setting: a position statement of the american diabetes association,” diabetes care, vol. 37, no. 10, pp. 2834–2842, 2014. [17] l. m. siminerio and g. koerbel, “a diabetic education program for school personnel,” practical diabetes international, vol. 17, no. 6, pp. 174–177, 2000. [18] j. wagner and a. james, “a pilot study of school counselor’s preparedness to serve students with diabetes: relationship to self-reported diabetes training,” journal of school health, vol. 76, no. 7, pp. 387–392, 2006. [19] s. l. mandali and t. a. gordon, “management of type 1 diabetes in schools: whose responsibility?” journal of school health, vol. 79, no. 12, pp. 599–601, 2009. doi 10.18502/sjms.v12i1.857 page 44 http://www.uptodate.com/home sudan journal of medical sciences production and hosting by knowledge e [20] k. lange, c. jackson, and l. deeb, “diabetes care in schools–the disturbing facts,” pediatric diabetes, vol. 10, pp. 28–36, 2009. [21] a. l. wakeel js, a. al-suwaida, a. c. isnani, a. al-harbi, and a. alam, “concomitant macro and micro-vascular complications in diabetic nephropathy,” saudi j. kidney dis. transpl, vol. 20, pp. 402–409, 2009. [22] f. a. latif alnasir, “assessment of knowledge of diabetes mellitus among bahraini school teachers,” bahrain medical bulletin, vol. 25, no. 4, pp. 172–176, 2003. [23] a. önder, z. aycan, s. çetinkaya et al., “assessment of the knowledge of diabetes mellitus among school teachers within the scope of the managing diabetes at school program,” jcrpe journal of clinical research in pediatric endocrinology, vol. 4, no. 4, pp. 199–203, 2012. [24] a. husband, d. pacaud, k. grebenc, and e. mckiel, “the effectiveness of a cd-rom in educating teachers who have a student with diabetes,” diabetes research and clinical practice, vol. 25, no. 4, pp. 286–290, 2001. [25] f. macmillan, a. kirk, n. mutrie, l. matthews, k. robertson, and d. h. saunders, “a systematic review of physical activity and sedentary behavior intervention studies in youth with type 1 diabetes: study characteristics, intervention design, and efficacy,” pediatric diabetes, vol. 15, no. 3, pp. 175–189, 2014. [26] r. tolbert, “managing type 1 diabetes at school: an integrative review,” journal of school nursing, vol. 25, no. 1, pp. 55–61, 2009. doi 10.18502/sjms.v12i1.857 page 45 introduction materials and methods results discussion conclusion ethical clearance competing interests funding authors' contributions acknowledgments references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9696 production and hosting by knowledge e research article assessment of self-medication practices during covid-19 pandemic in hyderabad and karachi, pakistan mudassar iqbal arain1, saira shahnaz2, ramesha anwar3, and khurram anwar4 1department of pharmacy practice, faculty of pharmacy, university of sindh, jamshoro, pakistan 2department of pharmacy practice, faculty of pharmacy, nazeer hussain university, karachi, pakistan 3department of pharmacy practice, faculty of pharmacy, university of karachi, karachi, pakistan 4isra dental college, hyderabad, pakistan orcid: mudassar iqbal arain: https://orcid.org/0000-0002-1797-9927 abstract background: lack of appropriate treatment for covid-19 infection led the general population of pakistan toward self-medication and symptomatic treatment; almost 80% of the population collected medications for future use during pandemic. thus, the current study aimed to assess the use of medication as symptomatic treatment preventive strategy. methods: this descriptive cross–sectional study was conducted on a local population of hyderabad and karachi, sindh, pakistan. the study duration was six months (april– september 2020). a total of 698 responders were selected via random sampling method. the number of participants were recruited based on 95% confidence interval with 5% margin error. data were transferred into analysis sheet descriptively. results: most participants responded to the use of different over-the-counter (otc) products for headache. the use of antibiotics with prescription due to allergic conditions, cough, respiratory tract infections including sore throat, and urinary tract infections was also found among the majority. few respondents had self-medication practice with sedatives due to difficulty in falling asleep, and 9.5% had self-medication practice due to pain. about 20.8% of the population agreed that lockdown was a contributing factor in the self-medication practice. conclusion: pharmacists and healthcare professionals are advised to counsel the general public regarding the use of medication. a close collaboration is required at this stage to fight against covid-19 and preventing the situation from worsening. keywords: self-medication, covid-19, hyderabad, karachi, pakistan how to cite this article: mudassar iqbal arain, saira shahnaz, ramesha anwar, and khurram anwar (2021) “assessment of self-medication practices during covid-19 pandemic in hyderabad and karachi, pakistan,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 347–354. doi 10.18502/sjms.v16i3.9696 page 347 corresponding author: mudassar iqbal arain; email: mudassarpk@live.com received 23 july 2021 accepted 05 september 2021 published 30 september 2021 production and hosting by knowledge e mudassar iqbal arain et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mudassarpk@live.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mudassar iqbal arain et al. 1. introduction the world health organization (who) defines self-medication (sm) as utilization of a medication without being prescribed by a healthcare professional to target symptoms that are self-recognized [1]. sm includes usage of medication through direct purchase from pharmacies, reusing previously prescribed medicines, or buying overthe-counter (otc) medications from medical stores/pharmacies [2]. the most commonly self-prescribed medications are analgesics, antipyretics, sedative drugs, certain common antibiotics, supplements, herbal medicines, and homeopathic remedies. covid-19 broke in as an infection in the late 2019, since then 30,905,162 confirmed cases were reported till the mid of 2020 [3, 4]. the who declared this situation as pandemic in the beginning of 2020. the pandemic and the fear of getting infected increased with the number of cases. covid-19 has influenced the entire world with the confusion to preventive measures and no available treatment [5]. cases of sm increased due to lack of appropriate guidelines to establish safety and treatment [6]. more number of people started sm practice to treat symptoms of infections such as cold, flu, and to strengthen their immunity in 2020 regardless of their knowledge, level of education, and socioeconomic status [7]. the literature supports high levels of sms among underdeveloped countries where the healthcare systems are costly and difficult to approach. despite the fact that who stresses on rational prescribing practices and avoiding otc medication among general population, this practice is constantly rising. sm may cause resistance to microorganisms and serious health risks with adverse drugs reactions, prolonging the morbidities [8]. compared to other developed countries, the doctors-to-patients ratio in pakistan was low. researchers and healthcare professionals are continuously searching for solution to combat the symptoms of covid-19 [9]. most countries in the world went into a lockdown, confining general public to their homes, so people could rely only on social media for updates and information related to the pandemic [10– 12]. according to a recent report in march 2020, a 10-fold increase in the number of cases was noted only in the span of three months. the total deaths reported were six times more than the previous record [12]. the lack of a recognized treatment for the infection led people toward sm and symptomatic treatment, almost 80% of the population collected medication for future use during the pandemic. thus, the current study aimed to assess the use of medication as symptomatic treatment preventive strategy. doi 10.18502/sjms.v16i3.9696 page 348 sudan journal of medical sciences mudassar iqbal arain et al. 2. materials and methods a descriptive cross–sectional study was conducted among the local population of hyderabad and karachi, sindh, pakistan. the duration of study was six months (april– september 2020). a total of 698 responders were selected from various retail pharmacies via random sampling method. retail pharmacies were selected based on patients’ flow. the number of participants were recruited based on 95% confidence interval with 5% margin error. patients aged >18 years and visiting one of the selected retail pharmacy were included. verbal consent was also taken from the responders before filling the questionnaire. the questionnaire was divided into three parts: sociodemographic information; sm practices; and knowledge regarding covid-19. the questionnaire was validated among 50 participants and necessary changes were made. data were transferred descriptively into the analysis sheet. 3. results of the 698 respondents, 56.2% were male while 43.8% were female. based on their age, patients were divided into three categories: 19.3% were in the group of 18–38 years, 43.4% in 39–59 years, and 37.3% in >60 years. moreover, about 43.7% of the responders were illiterate while 56.3% were educated (table 1). the responders were also questioned about their current jobs – 28.2% were unemployed, 53.5% had a private job, and 18.3% had a government job. table 1: demographic information. variable frequency percentage gender male 393 56.2% female 305 43.8% age (yr) 18–38 134 19.3% 39–59 302 43.4% ≥60 260 37.3% education illiterate 304 43.6% literate 394 56.3% job status unemployed 197 28.2% private job 373 53.5% government job 127 18.3% doi 10.18502/sjms.v16i3.9696 page 349 sudan journal of medical sciences mudassar iqbal arain et al. the main objective of the study was to assess the prevalence of sm practice and the reason thereof. majority of the participants responded to the use of different otc products – 23.3% for the headache and seasonal cough and cold symptoms. however, the use of antibiotics with prescription due to allergic conditions, cough and respiratory tract infections including sore throat, and urinary tract infections was also found among the majority. few respondents practiced sm with sedatives due to difficulty in falling asleep, while 9.5% had it due to pain (table 2). table 2: reasons of self-medication. reason frequency percentage p-value otc products for common illness headache 163 23.3% 0.004 cold 135 19.4% 0.005 fever 107 15.4% 0.034 use of antibiotics for infective symptoms allergy 25 3.7% 0.013 cough 45 6.5% 0.001 respiratory infection 93 13.4% 0.005 urinary tract infection 42 6.1% 0.001 others sleeping problem 18 2.6% 0.021 body ache/ muscular pain 66 9.5% <0.001 factors involved in the use of sm during the pandemic were assessed and respondents were asked about the basic reasons behind the off-prescription use of medication: majority of them were afraid of getting infected in case of going out and seeking medical advice, 30.5% were afraid of getting the covid-19 infection. during the peak of pandemic, a large number of countries observed lockdown confining people to their homes for months, this is considered as one of the contributing factors in the rising sm practice; about 20.8% of the respondents agreed to this, 5.5% stated the long waiting hours at the clinics as their reason for practicing sm, while 12.6% practiced sm based on their previous knowledge and experience with the disease (table 3). table 3: factors of self-medication in context of covid-19. factors frequency percentage due to minor problem 88 12.6% lockdown 145 20.8% busy schedules of doctors 68 9.7% fear to get covid-19 213 30.5% previous knowledge regarding the problem 88 12.6% high fees 58 8.4% time wastage 38 5.5% doi 10.18502/sjms.v16i3.9696 page 350 sudan journal of medical sciences mudassar iqbal arain et al. 4. discussion sm practice is a major issue that worsens scenarios of health-related problems. the prevalence of sm has been increasing continuously in the past decades [13]. according to a study, sm practice with different otc products and antibiotics has increased from 36.2% in 2019 to 60.4% in 2020 [14]. moreover, the use of sms for symptomatic treatment and based on the past experience of a patient is not a new phenomenon, this finding of ours is in line with the results of another study [15]. the majority of people were afraid to go out in the pandemic and more number of males were observed using medication with medical advice [16, 17]. after the pandemic broke, a vast majority of population was left jobless. bamgboye et al. determine self-education practice and factors affecting them, and had similar results as that of our study [18]. while sm due to common symptoms, respiratory tract infection, and due to fear was practiced only after the onset of pandemic, those practicing sm based on their past experience were doing so even before the lockdown and pandemic [19]. the who recommends the use of precautionary measures during the pandemic, however, it does not recommend sm for the symptoms of covid-19 and related factors [20]. despite this, frequent use of antibiotics was found among the studied population [21–22]. the use of medication for different symptoms were in accordance with the study. 5. conclusion the study aimed to find the prevalence of sm during covid-19. pharmacists and healthcare professionals are advised to counsel the population regarding the use of medication. a close collaboration is required at this stage to fight against covid-19 and preventing the situation from worsening. acknowledgements the authors acknowledge all supporting staff and faculty members who guided them throughout the research work. ethical considerations verbal consent was taken from all responders prior to extracting data. doi 10.18502/sjms.v16i3.9696 page 351 sudan journal of medical sciences mudassar iqbal arain et al. competing interests none. availability of data and materials all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding none. references [1] malik, m., tahir, m. j., jabbar, r., et al. (2020). self-medication during covid-19 pandemic: challenges and opportunities. drugs & therapy perspectives, vol. 36, no. 12, pp. 565–567. [2] quispe-cañari, j. f., fidel-rosales, e., manrique, d., et al. (2021). self-medication practices during the covid-19 pandemic among the adult population in peru: a cross-sectional survey. saudi pharmaceutical journal, vol. 29, no. 1, pp. 1–11. [3] daniel, j. (2020). education and the covid-19 pandemic. prospects, vol. 49, no. 1, pp. 91–96. [4] onchonga, d. (2020). a google trends study on the interest in self-medication during the 2019 novel coronavirus (covid-19) disease pandemic. saudi pharmaceutical journal: spj, vol. 28, no. 7, p. 903. [5] molento, m. b. (2020). covid-19 and the rush for self-medication and self-dosing with ivermectin: a word of caution. one health, vol. 10, 100148. [6] sadio, a. j., gbeasor-komlanvi, f. a., konu, r. y., et al. (2021). assessment of selfmedication practices in the context of the covid-19 outbreak in togo. bmc public health, vol. 21, no. 1, pp. 1–9. [7] sahanic, s., boehm, a., pizzini, a., et al. (2020). assessing self-medication for obstructive airway disease during covid-19 using google trends. european respiratory journal, vol. 56, no. 5, 2002851. [8] watkins, j. (2020). preventing a covid-19 pandemic. bmj, vol. 368, m810. doi 10.18502/sjms.v16i3.9696 page 352 sudan journal of medical sciences mudassar iqbal arain et al. [9] nicola, m., alsafi, z., sohrabi, c., et al. (2020). the socio-economic implications of the coronavirus and covid-19 pandemic: a review. international journal of surgery, vol. 78, pp. 185–193. [10] van bavel, j. j., baicker, k., boggio, p. s., et al. (2020). using social and behavioural science to support covid-19 pandemic response. nature human behaviour, 4(5), 460-471. [11] omer, s. b., malani, p., and del rio, c. (2020). the covid-19 pandemic in the us: a clinical update. jama, vol. 323, no. 18, pp. 1767–1768. [12] karbownik, m. s., dobielska, m., paul, e., et al. (2020). health-, medication-and dietary supplement-related behaviors and beliefs relatively unchanged during the covid-19 pandemic lockdown. research in social and administrative pharmacy. [13] ruiz, m. e. (2010). risks of self-medication practices. current drug safety, vol. 5, no. 4, pp. 315–323. [14] figueiras, a., caamano, f., and gestal-otero, j. j. (2000). sociodemographic factors related to self-medication in spain. european journal of epidemiology, vol. 16, no. 1, pp. 19–26. [15] awad, a., eltayeb, i., matowe, l., et al. (2005). self-medication with antibiotics and antimalarials in the community of khartoum state, sudan. journal of pharmacy and pharmaceutical sciences, vol. 8, no. 2, pp. 326–331. [16] afolabi, a. o. (2008). factors influencing the pattern of self-medication in an adult nigerian population. annals of african medicine, vol. 7, no. 3, pp. 120–127. [17] mainous, a. g., diaz, v. a., & carnemolla, m. (2008). factors affecting latino adults’ use of antibiotics for self-medication. the journal of the american board of family medicine, vol. 21, no. 2, pp. 128–134. [18] selvaraj, k., kumar, s. g., and ramalingam, a. (2014). prevalence of self-medication practices and its associated factors in urban puducherry, india. perspectives in clinical research, vol. 5, no. 1, p. 32. [19] abasaeed, a., vlcek, j., abuelkhair, m., et al. (2009). self-medication with antibiotics by the community of abu dhabi emirate, united arab emirates. the journal of infection in developing countries, vol. 3, no. 7, pp. 491–497. [20] karimy, m., rezaee-momtaz, m., tavousi, m., et al. (2019). risk factors associated with self-medication among women in iran. bmc public health, vol. 19, no. 1, pp. 1–7. [21] lukovic, j. a., miletic, v., pekmezovic, t., et al. (2014). self-medication practices and risk factors for self-medication among medical students in belgrade, serbia. plos one, vol. 9, no. 12, e114644. doi 10.18502/sjms.v16i3.9696 page 353 sudan journal of medical sciences mudassar iqbal arain et al. [22] mansuri, f. m., zalat, m. m., khan, a. a., et al. (2020). estimating the public response to mitigation measures and self-perceived behaviours towards the covid19 pandemic. journal of taibah university medical sciences, vol. 15, no. 4, pp. 278– 283. doi 10.18502/sjms.v16i3.9696 page 354 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8936 production and hosting by knowledge e research article communication patterns and related factors among iranian couples: a cross-sectional study sedigheh hasanimoghadam1, jila ganji2, hamid sharif nia3, mohsen aarabi4, and soghra khani5, 6 1student research committee, nasibeh school of nursing and midwifery, mazandaran university of medical sciences, sari, iran. 2department of reproductive health and midwifery, sexual and reproductive health research center, mazandaran university of medical science, sari, iran. 3department of medical-surgical nursing, amol faculty of nursing, mazandaran university of medical sciences, sari, iran. 4cardiovascular research center, mazandaran university of medical sciences, sari, iran. 5department of reproductive health and midwifery, sexual and reproductive health research center, mazandaran university of medical sciences, sari, iran. 6department of reproductive health and midwifery, diabetes research center, mazandaran university of medical sciences, sari, iran. orcid: soghra khani: http://orcid.org/0000-0001-6958-8234 abstract background: given the effect of various factors on the use of communication patterns by couples, this study aimed to determine the most common communication pattern among couples and related factors in sari, northern iran. methods: this cross-sectional study was performed on 520 people (260 couples) in sari. data were collected using a demographic–fertility factors questionnaire, enrich couple scale, communication patterns questionnaire, general health questionnaire (ghq-28), and neo personality inventory. data analysis was performed in spss version 25 using descriptive and inferential statistics (multiple regression model). results: while the mean (standard deviation) age of women included in the study was 34.08 (7.71) years, the mean age of men was 39.13 (9.18) years. the most common communication patterns in both women and men was the mutual constructive communication, whereas the lowest frequent communication pattern was the demand/withdraw communication in both men and women. marital satisfaction had a significant positive correlation with mutual constructive communication pattern in women and men (p = 0.001). in addition, a significant inverse correlation was observed between the number of marriage to date, women’s age, and spouses’ demand/withdraw communication pattern with mutual constructive communication pattern in women. also, a significant inverse correlation was observed between flexibility (p = 0.047), number of marriages (p = 0.013), and the wives’ age (p = 0.005) with mutual constructive communication pattern in men. conclusion: according to the results of the study, it is necessary to recognize the factors related to couples’ communication patterns in order to improve the communication patterns so that marital conflicts could be avoided while a more effective communication is established. keywords: communication patterns, couples, personality characteristics, marital satisfaction, public health how to cite this article: sedigheh hasanimoghadam, jila ganji, hamid sharif nia, mohsen aarabi, and soghra khani (2021) “communication patterns and related factors among iranian couples: a cross-sectional study,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 43–55. doi 10.18502/sjms.v16i1.8936 page 43 corresponding author: dr. soghra khani; associate professor; sexual and reproductive health research center, nasibeh nursing and midwifery school, vesal street, amir mazandarani boulevard, sari, iran tel: +981133368918 email: khanisog343@gmail.com received 26 january 2021 accepted 17 march 2021 published 31 march 2021 production and hosting by knowledge e sedigheh hasanimoghadam et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:khanisog343@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences sedigheh hasanimoghadam et al 1. introduction couple communication patterns play an important role in families. in fact, communication patterns are recognized as a set of communication networks occurring frequently in a family [1–4]. there are three types of couple communication patterns. in mutual constructive communication pattern, couples can easily talk about their issues and solve them without any aggressive behavior. demand–withdraw pattern, which encompasses two parts including demander husband/withdrawer wife and vice versa. this pattern is in the form of a cycle, where the increase of one leads to the exacerbation of the other, and intensification of the pattern results in more marital issues. in this pattern, a demander spouse is a dependent person while the withdrawer spouse has the fear of becoming dependent. another pattern is mutual avoidance communication. in this pattern, communication is avoided, minimal, or non-existent [5–9]. communication patterns can determine the level of marital satisfaction so that >90% of disturbed couples consider this problem as their main issue in their relationship [5, 10–12]. defective communication patterns decrease couples’ proper understanding of each other, leading to their failure to support each other, making efforts to meet the needs of each other, and understanding each other’s views on conflicting issues. these issues ultimately result in marital issues and dissatisfaction. in contrast, healthy and productive communication patterns are one of the most important factors of marital satisfaction [13–15]. therefore, modification of couples’ communication patterns is a method used in couple therapy to solve marital problems since changing communication patterns is more important, compared to other factors affecting marital conflicts, such as personality traits and socioeconomic status [5, 10, 16–18]. several studies have been conducted to evaluate the relationship between couples’ communication patterns and various factors such as marital satisfaction and emotional intelligence [19, 20]. many studies found that mutual constructive communication pattern was positively correlated with marital satisfaction [20], but some other studies did not support such a link [21, 22]. the need to conduct more research in this area to identify the most common pattern that can lead couples to more emotional and orderly relationships is felt in every society. in the present study, the basis of the work is couples’ communication pattern, which is followed to determine the factors positively and negatively affecting this issue so that the necessary suggestions could be made for consolidating the family foundation. to the best of our knowledge, there is no comprehensive study evaluating couples’ communication patterns and related factors in iran, especially in mazandaran province. doi 10.18502/sjms.v16i1.8936 page 44 sudan journal of medical sciences sedigheh hasanimoghadam et al moreover, most studies have focused on the evaluation of patterns of family communication [23]. considering the aforementioned issue, this study aimed to determine the most common couples’ communication pattern and related factors in sari, iran. it is hoped that effective steps could be taken toward solving couples’ marital conflicts by recognizing these patterns. 2. materials and methods this cross-sectional research was performed on couples in sari, north of iran in 2018. the inclusion criteria of the study were being a couple residing in sari, educational level of elementary fifth and above, living with the spouse, and being married for a minimum of one year. the exclusion criterion was the unwillingness of one or both spouses to participate in the study. in total, 27 households were randomly determined as cluster heads by the health center statistics unit using the random number table. the sample size was determined by selecting 10 samples for each factor, which led to the selection of 350 people (175 couples). since subjects were selected by cluster sampling and the impact factor was 1.5, a total of 524 people (262 couples) were selected. however, two couples were removed from the research due to incomplete questionnaires, which led to the entrance of 10 families in each cluster (260 couples). notably, 27 students were trained in a 3-hr educational session to conduct the research inquiry. the inquiry sessions took 30-45 min. after receiving the address of cluster heads, the interviewers referred to the addresses as two-member teams every day. in case of the absence of households or their unwillingness to participate in the study, inquiries were conducted with other households. interviews were conducted in an apartment. of note, interviewers verbally explained the questionnaire to each couple. in addition, research objectives were explained prior to the study and the subjects were ensured of the confidentiality terms regarding their personal information. in addition, they were allowed to withdraw from the research at any time. data were collected using the following tools: 1. demographic-fertility factors questionnaire this questionnaire comprised of two sections of demographic characteristics and fertility-related information such as type of contraceptive method; history, type, and cause of infertility; children from a previous marriage; menstrual cycle regularity; duration of menstrual cycle; current pregnancy; number of children; currently living with the spouse; and children’s gender. doi 10.18502/sjms.v16i1.8936 page 45 sudan journal of medical sciences sedigheh hasanimoghadam et al 2. enrich couple scale (ecs) the 35-item version of the ecs scale was used. the validity and reliability of this questionnaire have previously been confirmed in iran [24, 25]. 3. the communication patterns questionnaire (christensen and salavi) this was a 35-item questionnaire, validity and reliability of which have been confirmed in iran [26]. 4. general health questionnaire (ghq-28) the ghq-28 is a 28-item questionnaire, the validity and reliability of which have previously been confirmed in iran [27]. 5. neo personality inventory this was a 60-item questionnaire. the validity and reliability of this questionnaire have been confirmed in iran [28]. 2.1. statistical analysis data were analyzed by spss version 25 using a skewness-kurtosis test (to assess the normal distribution of the data), as well as descriptive (frequency, mean, and standard deviation [sd]) and inferential (linear and multiple regressions) statistics. first, the relationship between factors related to the communication patterns was evaluated applying the univariate regression. ultimately, the significant factors that had linear relations were entered into the multiple regression model to determine the predictive variables of couples’ communication patterns. moreover, the cutoff point of the patterns was obtained based on the estimation of half the difference between maximum and minimum scores in order to determine the frequency of couples’ communication patterns, followed by developing a dichotomous variable. in this context, the scores obtained from the minimum possible score of the questionnaire to the cut-off point were coded 0 while the scores above that level were scored 1. in the end, the frequency and related factors of these dichotomous variables were estimated. 3. results according to the results of the study, the mean (sd) age of women was 34.08 (7.71) years and that of men was 39.13 (9.18) years. the majority of women were housewives (69.6%) while the majority of men were employees (43.8%). in terms of the level of education, doi 10.18502/sjms.v16i1.8936 page 46 sudan journal of medical sciences sedigheh hasanimoghadam et al most men and women had a degree between diploma and bsc (68.5% and 72.3%, respectively) (table 1). table 1: demographic characteristics of subjects. variables category male female level of education n* (%) below diploma 40 (15.4) 69 (26.6) diploma to bsc 188 (72.3) 178 (68.5) above bsc 32 (12.8) 13 (5) level of occupation n (%) unemployed/ housewife 7 (2.7) 181 (69.6) employee 114 (43.8) 79 (30.4) worker 38 (14.6) – other 101 (38.9) – age (yr) 39.13 minimum 17 34.08 (7.71) minimum 22 m** (sd***) (9.18) maximum 55 maximum 65 age at marriage in female (yr) 22.02 (4.58) minimum 13 m (sd) maximum 38 duration of marriage (yr) 11.86 (8.54) minimum 1 m (sd) maximum 36 duration of relationship with the spouse before marriage (month); m (sd) 22.74 (31.53) minimum 1 maximum 24 *number; **mean; ***standard deviation frequency of communication patterns and the related factors are presented in tables 2 to 4. table 2: frequency distribution of couples’ communication patterns. communication pattern sex n (%) minimum maximum cut-off point demand/withdraw communication female 89 (34.2) 6 47 20.5 male 101 (38.8) mutual constructive communication female 230 (88.5) -23 23 23 male 227 (87.3) mutual avoidance communication female 130 (50) 3 27 12 male 105 (40.4) doi 10.18502/sjms.v16i1.8936 page 47 sudan journal of medical sciences sedigheh hasanimoghadam et al table 3: regression of factors related to mutual constructive communication pattern in women type of communication predictive variable non-modified (simple) modified (multiple) b β p-value ci95% b β p-value ci95% mutual constructive communication pattern marital satisfaction 0.22 0.384 0.001 0.174, 0.265 0.223 0.387 0.001 0.156, 0.291 number of marriages to date -6.197 -0.146 0.019 -11.357, -1.038 -7.18 -0.123 0.013 -12.844, -1.515 women’s age -0.154 -0.143 0.021 -0.284, -0.024 -0.166 -0.134 0.036 -0.331, 0.00 male demand/ withdraw communication pattern -0.126 0.159 0.001 -0.194, 0.059 -0.101 -0.122 0.019 -0.185, -0.017 table 4: regression of factors related to mutual constructive communication pattern in men. type of communication pattern predictive variable non-modified (simple) modified (multiple) b β 𝑃-value ci95% b β 𝑃-value ci95% mutual constructive communication pattern marital satisfaction 0.22 0.384 0.001 0.174, 0.265 0.234 0.406 0.001 –0.167, 0.301 flexibility –0.103 –0.050 0.257 –0.280, 0.075 –0.214 –0.098 0.047 –0.486, –0.002 number of marriages to date –1.292 –0.027 0.664 –7.136, 4.552 –7.275 –0.124 0.013 –12.978, –1.572 women’s age –0.198 –0.174 0.005 –0.336, –0.061 –0.166 –0.134 0.005 –0.331, 0.00 4. discussion the couples’ communication pattern is a process during which the wife and husband interact with each other verbally and non-verbally. researchers believe that over 90% of dissatisfied couples report an inability to communicate as a major issue in their lives. suitable communication patterns significantly affect couples’ current life, whereas improper communication can result in the separation of couples. changing communication patterns are the most prominent ways to deal with marital maladjustments and doi 10.18502/sjms.v16i1.8936 page 48 sudan journal of medical sciences sedigheh hasanimoghadam et al couple therapies [29]. according to the results of the present research, the highest and lowest frequencies were related to mutual constructive and demand/withdraw communication patterns, respectively. a review of the literature revealed a lack of a research to evaluate the distribution of couples’ communication patterns. in this context, it could be expressed that spouses who use the mutual constructive pattern more in their marital relationship avoid destructive behaviors more and make efforts to establish a healthy relationship. in addition, they feel that they understand each other, express their feelings appropriately, suggest a solution to the communication problem, and negotiate with each other, which ultimately results in more satisfaction with their marital life [29, 30]. furthermore, using the demand/withdraw communication pattern by couples could lead to decreased marital satisfaction (especially when there is a demander wife and a withdrawer husband) and might predict divorce. in this respect, the more the use of demand/withdraw communication pattern, the lower the level of marital compatibility [10]. our findings revealed a significant, negative relationship between women’s age and mutual constructive communication pattern (in men and women), which is consistent with the results of khodakarami et al. [31] and bakhshi et al. [32]. on the other hand, our findings were inconsistent with the results of vaijayanthimala et al. [33] and karny et al. [34]. the results obtained by bakhshi et al. [32] and khodakarami et al. [31] demonstrated that the level of marital satisfaction decreased by the increase in women’s age. this finding can be justified by the fact that as a woman gets older, she becomes more mature and aware of her marital status, which in turn reduces marital conflicts and problems. in contrast, marriage at a young age can lead to numerous problems and consequently reduced marital satisfaction due to a lack of physical, mental, and emotional preparedness. it may be argued that since individuals have not yet attained the mental, emotional, cultural, social, economic growth, they have not gained many of the skills required to lead a successful life and lack the necessary skills to play the role of spouse, which often leads to many conflicts and incompatibilities. the necessity of achieving economic growth and job stability for men with regard to their responsibilities in providing family finances and housing in marriage and finishing the military service results in the preparedness of men for marriage at an age higher than women, which itself could decrease problems and increase marital satisfaction. according to the results of the present study, there was an inverse correlation between the number of marriages and mutual constructive communication patterns (in men and women). based on these findings, more marriages can lead to more marital strife. other studies have shown that the duration of marriage could have a different doi 10.18502/sjms.v16i1.8936 page 49 sudan journal of medical sciences sedigheh hasanimoghadam et al effect on marital intimacy. furthermore, kardan-souraki et al. marked a negative and significant correlation between marital intimacy and the duration of the marriage. in other words, the couple’s intimacy level decreased by the increased duration of marriage [35]. our findings also demonstrated a negative association between flexibility personality traits and mutual constructive communication patterns only in men. this could be justified by the fact that due to inherent traits and variety-driven personality, as well as issues related to financial and social problems, financial costs, inflation in today’s society of iran in the past few years, and tolerating additional financial pressure and mental tensions, men might practice inappropriate behaviors that could lead to marital conflicts and decrease flexibility in the relationship with the spouse and dealing with family problems [36, 37]. our study indicate an inverse correlation between demand/withdraw communication pattern in men and mutual constructive communication pattern in women. in a research by gottman et al., it was reported that the demand/withdraw communication pattern (especially when there is a demander wife and a withdrawer husband) led to decreased marital satisfaction and increased possibility of divorce [30]. in a study aimed to evaluate the relationship between the demand/withdraw communication pattern and marital compatibility, it was concluded that the more the use of the demand/withdraw communication pattern by couples, the lower the level of marital compatibility [38]. while previous studies have shown a relationship between this pattern and marital satisfaction and compatibility, most of them have suggested that the nature of this model is complex and how it is affected is not yet fully understood. this complexity and lack of certainty of the type of relationship can be justified by the fact that the association between marital communication patterns and marital satisfaction might depend on the couples’ beliefs about marriage. therefore, given the role of this pattern in the prediction of important marriage consequences (e.g., marital satisfaction and divorce) [30], it is recommended that efforts be dedicated to a better and more accurate understanding of the relationship in future studies. according to the results of the current study, there was a positive relationship between marital satisfaction and mutual constructive communication pattern in men and women, which is in line with the results of other studies [39, 40]. in this regard, it could be pointed out that couples who use mutual constructive communication patterns more in their marital relation avoid destructive behaviors and make efforts to maintain a healthy relationship. in addition, they feel that they understand each other, can properly express their feelings, find solutions for communication problems and negotiate, which ultimately increases their marital satisfaction. doi 10.18502/sjms.v16i1.8936 page 50 sudan journal of medical sciences sedigheh hasanimoghadam et al the lack of the presence of men at the time of interviews, which was controlled by visiting the home of the participants by prior appointment is a limitation of our study. all questionnaires were checked for completeness at the time of delivery and the parts left incomplete were explained to the couples again. in case of the presence of spouse, the questionnaires would be completed at the same time; otherwise, interviewers would refer to the participants to complete the questionnaires at another time. some of the strengths of the present study included cluster sampling, referral of interviewers to the house of the participants in the presence of the man of the house, and the completeness of the questionnaires used. 5. conclusion according to the results of the study, the most common communication pattern in both women and men was the mutual constructive communication pattern. therefore, it is necessary to recognize the factors related to mutual constructive communication patterns in couples so that marital conflicts could be avoided while a more effective communication is established. acknowledgments the authors acknowledge the financial support of the deputy of research and technology of mazandaran university of medical sciences, sari, iran. ethical considerations subjects were selected by cluster sampling after approval from the vice-chancellor for research and the ethics committee of the mazandaran university of medical sciences. an introduction letter was obtained from the vice-chancellor for research and presented to the relevant centers. all subjects gave a written informed consent prior to participating in the study. competing interests the authors have no conflicts of interest to declare for this study. doi 10.18502/sjms.v16i1.8936 page 51 sudan journal of medical sciences sedigheh hasanimoghadam et al availability of data and material all relevant data and methodological detail pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding this study has been financially supported by the deputy of research and technology, mazandaran university of medical sciences, sari, iran. authors’ contributions shm and sk conceived and designed the study, conducted research, provided research materials, and collected and organized data. sk supervised the research process. hsn and ma 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(2018). effective interactions: communication and high levels of marital satisfaction. journal of psychology in africa, vol. 28, no. 2, pp. 161–167. doi 10.18502/sjms.v16i1.8936 page 55 introduction materials and methods statistical analysis results discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding authors' contributions references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9700 production and hosting by knowledge e research article evaluation of serum gonadotropin and prolactin level among sudanese patients with chronic renal failure maha fathalla1, abdelkarim a. abdrabo1, and gadallah modawe2 1department of clinical chemistry, faculty of medical laboratory sciences, alneelain university, khartoum, sudan 2department of biochemistry, faculty of medicine and health sciences, omdurman islamic university, omdurman, sudan orcid: gad allah modawe: https://orcid.org/0000-0003-0536-0614 abstract background: generally, patients on hemodialysis for chronic renal failure also have endocrine defects and sexual function disorders. in this study, we aimed to assess the serum prolactin (prl), luteinizing hormone (lh) and follicle-stimulating hormone (fsh) in patients with chronic renal failure. methods: this hospital-based case–control study was conducted at jabal aulia teaching hospital, khartoum, sudan. the study was carried out between august 2019 and february 2020. a total of 100 subjects were enrolled – 50 chronic renal failure patients and 50 as controls. the serum hormones were estimated using tosoh 360. spss version 25 was used to analyze the results. results: the serum prl, lh, and fsh were significantly increased among chronic renal failure patients than their healthy counterparts (p-value = 0.000). the age of patients was positive correlated with plasma hormones, prl (r = 0.332, p = 0.001), lh (r = 0.387, p = 0.000), and fsh (r = 0.320, p = 0.001). no correlation was found between the duration of the disease and serum hormones. conclusion: patients with chronic renal failure had a highly significant increase of serum prl, lh, and fsh and also the age of the patients was positively correlated with serum hormones. keywords: chronic renal failure, prolactin, gonadotropin, hemodialysis 1. introduction patients with chronic kidney disease sometimes experience sexual and gonadal dysfunction, as well as infertility [1]. reduced libido, erectile dysfunction, premature or delayed ejaculation, and difficulty achieving orgasm are all signs of male sexual dysfunction in renal failure. whereas reduced libido, trouble achieving orgasm, lack of vaginal lubrication, discomfort during sex, and infertility are all signs of female renal failure how to cite this article: maha fathalla, abdelkarim a. abdrabo, and gadallah modawe (2021) “evaluation of serum gonadotropin and prolactin level among sudanese patients with chronic renal failure,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 399–408. doi 10.18502/sjms.v16i3.9700 page 399 corresponding author: gadallah modawe; email: gadobio77@hotmail.com received 26 june 2021 accepted 03 september 2021 published 30 september 2021 production and hosting by knowledge e maha fathalla et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:gadobio77@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences maha fathalla et al. [2]. with the development of end-stage renal disease, gonad dysfunction worsens. on hemodialysis, up to 40% of male and 55% of female patients have trouble achieving orgasm [2]. in patients with chronic renal failure, serum prolactin (prl) levels and biological activity are both elevated [3]. the increase in serum prl is related to a decrease in glomerular filtration rate. the primary cause of increased serum prl levels is decreased dopaminergic inhibition of prl release from the pituitary gland, followed by decreased luteinizing hormone (lh)-rh release. prl is a uremic toxin that causes libido loss, erection problems, and infertility. in males, it can cause gynecomastia and galactorrhea, and in females, it can cause menstrual disorders (amenorrhea and oligomenorrhea) and galactorrhea (0–40% of chronic renal failure – 5d patients). thyrotrophic-releasing hormone stimulation decreases prl production in both men and women [4]. uremia affects the release of gnrh and thus gonadotropin production and secretion in both males and females by disrupting local amino acid neurotransmitter outflow in the hypothalamus [5, 6]. hemodialysis patients have higher follicle-stimulating hormone (fsh) and lh levels in their blood than healthy people. this rise is due to a longer half-life for immune-reactive and -bioactive lh, as well as increased immunoreactive lh secretion [7]. male and female chronic renal failure patients also suffer from gonadal dysfunction. the purpose of this study was to assess serum prl, lh, and fsh levels in patients with chronic renal failure. 2. materials and methods 2.1. study population this hospital-based case–control study was conducted at jabal aulia teaching hospital, khartoum, sudan. the study was carried out between august 2019 and february 2020. a total of 100 subjects were enrolled – 50 chronic renal failure patients (male 30 [60%], female 20 [40%]) with an average age ranging from 18 to 55 years (40.46 ± 9.611 years) and 50 as controls (male 25 [50%], female 25 [50%]) with an average age ranging from 18 to 52 years (32.24 ± 10.024 years). 2.2. inclusion and exclusion criteria patients on hemodialysis for chronic renal failure were included. there were no significant medical complications associated with hemodialysis patients; patients using prl drugs and those taking anabolizing androgen were excluded. doi 10.18502/sjms.v16i3.9700 page 400 sudan journal of medical sciences maha fathalla et al. 2.3. data collection and blood sampling data were collected through questionnaire. blood samples were the serum collected through centrifugation that was drawn from all subjects between 8 and 10 am after an overnight fast and was held at –20ºc until assayed. serum hormones were estimated using tosoh 360. 2.4. statistical analysis the statistical package for sciences (spss, version 25) was used to perform statistical analysis. data were expressed as (mean ± sd) and compared first with controls and then with the provided reference values of the reagents and the data published in the literature. means of continuous variables were compared between the two groups. pvalue was computed for hormone levels in the obtained study results. besides, pearson’s correlation test was applied to predict the correlation of serum hormone with age, duration of disease/years in patients. 2.5. ethical consideration the study was approved from the alneelain university, faculty of medical laboratory sciences. 3. results table 1: the (mean ± sd) of serum prl, lh, fsh and age in the study population. parameters patients (n = 50) control (n = 50) p-value prl (ng/ml) 45.0 ± 9.7 (33.00–68.00) 15.1 ± 5.1 (6.00–25.00) 0.000 lh (mlu/ml) 84.9 ± 9.2 (70.0–102.0) 29.0 ± 15.6 (6.00–64.00) 0.000 fsh (mlu/ml) 28.2 ± 3.2 (24.00–38.00) 11.9 ± 4.05 (5.00–19.00) 0.000 age (yr) 40.4 ± 9.6 (18–55) 32.2 ± 10.0 (18–52) —– n: number; p: significant difference; lh: luteinizing hormone; prl: prolactin; fsh: follicle-stimulating hormone; ng: nongame; ml: milliliter; sd: standard deviation. 4. discussion our study revealed that the serum hormones were increased dramatically in chronic renal failure patients. on the other hand, serum hormones had strong correlation with doi 10.18502/sjms.v16i3.9700 page 401 sudan journal of medical sciences maha fathalla et al. table 2: the (mean ±sd) of serum prl, lh and fsh among gender in chronic renal failure. variables male (n = 30) female (n = 20) p-value prl 43.3 ± 9.1 (33.00–61.00) 47.5 ± 10.2 (33.00–68.00) 0.144 lh 85.03 ± 8.84 (72.00–102.00) 84.7 ± 10.05 (70.00–100.00) 0.917 fsh 28.3 ± 3.4 (24.00–38.00) 28.05 ± 3.01 (24.00–35.00) 0.757 n: number; p: significant difference; lh: luteinizing hormone; prl: prolactin; fsh: follicle-stimulating hormone; ng: nongame; ml: milliliter; sd: standard deviation. table 3: correlations of age and duration with prl, lh and fsh in chronic renal failure. prl lh fsh age (yr) r 0.332 0.387 0.320 p-value 0.001 0.000 0.001 duration r 0.079 0.172 0.100 p-value 0.587 0.232 0.491 lh: luteinizing hormone; prl: prolactin; fsh: follicle-stimulating hormone; r: correlation. figure 1: means of serum prl, lh, and fsh in study population. elderly patients. the association between renal failure disease with sex hormones has been examined in several previous studies [8, 9]. hyperprolactinemia is likely a contributing to factor in chronic renal failure due to its atherosclerotic process [10]. increased expression of prl receptors has been found in human atherosclerotic plaques and may be a contributing factor to vascular derangements per sec [10, 11]. the age group of study population was supported by highlander and lehtihet’s study [12]. our study agrees with the finding of nihal et al. [13] and report the elevation of serum, prl, lh. the hypothalamic-pituitary axis in chronic renal failure is reset in such a way that it is more susceptible to the negative feedback inhibition of testosterone, and the regulation of gonadotropin secretion is impaired [14]. the significant reduction (70%) in renal filtration and whole body clearance rate of lh could also be due to a factor in doi 10.18502/sjms.v16i3.9700 page 402 sudan journal of medical sciences maha fathalla et al. figure 2: means of serum prl, lh, and fsh among gender in chronic renal failure. figure 3: correlation of age with prolactin in case group (r = 0.332, p = 0.001). uremic serum capable of blocking the lh receptor [15]. our results similar to that found by mohammed and amar (2019) registered that hyperprolactinemia exists in renal failure patients. sobki et al. (2004) reported that the levels of fsh and lh were significantly increased in saudi male patients on hemodialysis. early renal insufficiency is associated with elevated lh levels, which increase with declining renal function [18]. moreover, levels of inhibin and gonadal hormone reflect to, are interested in the input of pituitary gonadal hormone levels and the functional state of the seminiferous epithelium [19]. our findings contradict a sudanese study conducted in khartoum state, which found no substantial differences in patient key prl levels when compared to the control doi 10.18502/sjms.v16i3.9700 page 403 sudan journal of medical sciences maha fathalla et al. figure 4: correlation of age with lh in case group (r = 0.387, p = 0.000). figure 5: correlation of age with fsh in case group (r = 0.320, p = 0.001). group, implying that hyperprolactinemia exists in renal failure patients [20]. another research found that ckd is linked to higher levels of the hormone prl in the blood (hyperprolactinemia) [21]. doi 10.18502/sjms.v16i3.9700 page 404 sudan journal of medical sciences maha fathalla et al. figure 6: correlation of duration with prl in case group (r = 0.079, p = 0.587). figure 7: correlation of duration with lh in case group (r = 0.172, p = 0.232). 5. conclusion patients with chronic renal failure had a highly significantly increase of serum prl, lh, and fsh. also, the age of patients had a positive correlation with serum hormones. doi 10.18502/sjms.v16i3.9700 page 405 sudan journal of medical sciences maha fathalla et al. figure 8: correlation of duration with fsh in case group (r = 0.100, p = 0.491). acknowledgements the authors would like to thank the members of the department of clinical chemistry, their colleagues, and the staff workers at the medical laboratory of alneelain university for their contribution and support. ethical considerations this study has been approved by the faculty of medical laboratory sciences review board, alneelain university. competing interests none declared. availability of data and material all data and materials associated with this paper were available through the corresponding author upon reasonable request. doi 10.18502/sjms.v16i3.9700 page 406 sudan journal of medical sciences maha fathalla et al. funding none. references [1] rathi, m. and ramachandran, r. 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(2016). evaluation of serum prolactin level in chronic renal failure. asian journal of pharmaceutical and clinical research, vol 9, no. 4, pp. 201–203. doi 10.18502/sjms.v16i3.9700 page 408 introduction materials and methods study population inclusion and exclusion criteria data collection and blood sampling statistical analysis ethical consideration results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9694 production and hosting by knowledge e research article interventional study on adherence to pharmacotherapy and drug pattern in elderly patients at civil hospital of badin, pakistan muhammad shehnshah1, mudassar iqbal arain2, muhammad ali ghoto2, abdullah dayo1, saira shahnaz3, and ramesha anwar4 1department of pharmaceutics, faculty of pharmacy, university of sindh, jamshoro, pakistan 2department of pharmacy practice, faculty of pharmacy, university of sindh, jamshoro, pakistan 3faculty of pharmacy, nazeer hussain university, karachi, pakistan 4department of pharmacy practice, faculty of pharmacy, university of karachi, karachi, pakistan orcid: mudassar iqbal arain: https://orcid.org/0000-0002-1797-9927 abstract background: to assess the contributing factors to adherence of pharmacotherapy and perception of elderly patients. methods: this prospective cross-sectional study was conducted in the outpatient clinic of civil hospital badin, pakistan from january to june 2019. a total of 300 samples were selected to analyze the results. a self-designed proforma (prescribing indicator form) was used for collecting data including patient demographics, diagnosis, and the current medications prescribed for each patient. results: of the 300 selected participants, 221(73.7%) were male, while 79 (26.3%) were female. majority of the subjects in the age group of 60–69 (52%) and 70–79 years (27%) followed by those aged >79 (21%). antibiotics were prescribed to 17.2% and vitamins to 14.7%. patients’ responses related to nonadherence factor were 92.7% for the cost, 32.7% for the long treatment duration, and 24% for the lack of knowledge. out of the total patients, 28% were forgetful, 26.7% complained about complex therapy, 26.3% blamed financial problems, 19.7% patients had side effects, and 14.3% were negligent in taking the medication. conclusion: patient conformity can be enhanced by dropping polypharmacy and simplifying complex management, use of extended formulations, rate of medications, and by creating awareness among elderly patients. keywords: elderly, polypharmacy, pharmacotherapy, adherence 1. introduction in geriatric patients, irrational prescription of medicines has been found to be the most frequent reason of morbidity and mortality. irrational medication is defined as: “a medicine in which the risk of an undesirable event is more, its clinical benefit, mainly when there is a safer or more useful alternate treatment for the same situation how to cite this article: muhammad shehnshah, mudassar iqbal arain, muhammad ali ghoto, abdullah dayo, saira shahnaz, and ramesha anwar (2021) “interventional study on adherence to pharmacotherapy and drug pattern in elderly patients at civil hospital of badin, pakistan,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 325–333. doi 10.18502/sjms.v16i3.9694 page 325 corresponding author: mudassar iqbal arain; email: mudassar.arain@usindh.edu.pk received 05 july 2021 accepted 09 september 2021 published 30 september 2021 production and hosting by knowledge e muhammad shehnshah et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:mudassar.arain@usindh.edu.pk mailto:mudassar.arain@usindh.edu.pk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences muhammad shehnshah et al. is available.” previous studies have shown the incidence of adverse reactions of drug are due to irrational prescription of medications [1, 2]. it is pertinent to recognize the irrational medications use in this group of population to curtail pharmacotherapy-related problems [3]. it is an important prompt factor for the conception of criteria for the harmless medicines usage in the elderly people, specifically, the beers criteria, released in 1997 and updated in 2012 and 2015 [4]. the beers criteria in geriatric, usually known as the beers list, sets out the parameters for healthcare providers to assist in the safe prescription of medicines for older adults. it emphasizes on medication prescribing which is redundant [5]. it was observed that 10–31% of geriatrics admissions in hospital emergency department were related to greater use of unnecessary medications [5, 6]. medications adherence generally refers to whether a patient is taking their medications as prescribed, as well as whether they continue to obtain the prescribed medicine [7]. adherence can be defined as: “the extent to which an individual behavior corresponds with agreed recommendations from a health care provider” [8]. it is also considered that whether patients take medications according to prescribed instructions and recommendations [9, 10]. various factors such as patients’ age and gender, socioeconomic status, severity of illness, difficulty in prescribing medication, public approval, poor patientrelated relationships, high cost, poor memory, and presence of emotional problem have been shown to influence the adherence in various populations [2]. there are five adherence-related dimensions that are considered most important in healthcare system. societal, healthcare system-related, circumstance-related, physiotherapy-related, and patients-related. nonadherence is a complicated problem that not only affects patients but also healthcare providers. medication nonadherence occurs when patient fails to take medicines according to the prescribed instructions [11]. 2. materials and methods a prospective cross-sectional study was conducted in the outpatient clinic of civil hospital badin, pakistan from january to june 2019. a total of 300 samples were selected to analyze the results. a self-designed proforma (prescribing indicator form) was used for collecting data which including patient demographics, diagnosis, and current medications prescribed for each patient. both male and female elderly patients who were taking two or more medications for any medical illness were included. patients receiving care at home were excluded. patients’ demographic information, previous treatment history, and existing medications were distinguished in a self-predesigned proforma. patients’ relevant information were obtained from hospital records and through direct interviews doi 10.18502/sjms.v16i3.9694 page 326 sudan journal of medical sciences muhammad shehnshah et al. with patients. the patients’ demographic information, diagnosis, previous medical and current diagnosis with prescribed medication was arranged in patient proforma. at the end of the research, results were analyzed using the ms excel and descriptive statistics. 3. results out of the 300 selected participants, 221 (73.7%) were male while 79 (26.3%) were female. majority of the subjects were in the age group of 60–69 (52%) and 70–79 years (27%), followed by those aged >79 (21%), as shown in table 1. table 1: demographic details of the patients (age distribution). age distribution of patients frequency (n) percentage (%) valid (yr) 60–69 156 52% 70–79 81 27% >79 63 21% total 300 100% moreover, majority of patients were diagnosed with arthritis and diabetics (36%) and heart problems, as shown in table 2. table 2: comorbidities among patients. comorbidities frequency (n) percentage (%) arthritis and diabetes 108 36.0% heart problems and hypertension 41 13.7% respiratory diseases and diabetes 54 18.0% gastro-intestinal problem 34 11.3% psychological and hypertension 25 8.3% eye diseases 15 5.0% skin infections 11 3.7% seasonal allergy 9 3.0% cholecystitis 3 1.0% total 300 100.0 further, majority of the patients were prescribed multiple-drug therapy. most prescriptions had either seven (27.7%) or six (21%) drugs prescribed in them (table 3). results showed that antibiotics were prescribed to 17.2% patients, followed by vitamins and nutritional supplement to 14.7%, as shown in table 4. patient’s response related to nonadherence factor were 92.7% for cost, 32.7% for long duration of treatment period, and 24% for lack of knowledge about the disease (table 5). doi 10.18502/sjms.v16i3.9694 page 327 sudan journal of medical sciences muhammad shehnshah et al. table 3: drugs prescribed per prescription. number of drugs frequency (n) percentage (%) p-value valid 2 drugs 7 2.3 3drug 17 5.7 4drugs 52 17.3 5 drugs 41 13.7 6 drugs 63 21.0 7 drugs 83 27.7 >7 drugs 37 12.33 total 300 100.0 0.005 table 4: drug utilization pattern. prescribed drugs in prescription no. of drugs (n) percentage (%) antibiotics 295 17.2% vitamins and nutritional supplements 255 14.7% antiprotozoal 134 7.7% antacid 182 10.5% laxatives 112 6.4% diuretics 101 5.8% analgesics 121 7% anti-hypertensive 163 9.4% cholagogues 59 3.4% antidiabetics 158 9.1% others 150 8.7% total 1733 100% table 5: factors of nonadherence. factors no. of patient (300) percentage (%) p-value social and economic cost of medication too expensive 278 92.7% illiterate 105 35% 0.23 therapy-related complexity of medication regimen 121 40.3% long duration of treatment period 98 32.7% no. of medications/too many medications 101 33.7% 0.0034 patient-related lack of knowledge about the disease 72 24% failure to remember to take all the pills 69 23% when felt worse/bad 41 13.7% decision to omit 48 16% 0.0013 patients related to bmq (access screen) response showed that 66% of the patients had difficulty in obtaining medications on time but after interventions it was 59.4%. doi 10.18502/sjms.v16i3.9694 page 328 sudan journal of medical sciences muhammad shehnshah et al. table 6: frequency of patient’s responses to bmq (access screen). bmq (access screen) no. of patients pre-interventions (300) no. of patients post-interventions (244) reported difficulties in reading what was written on the packet 153 (51%)* 150 (61.5%)* reported difficulty in obtaining the medications on time 198 (66%)** 145 (59.4%)** reported difficulties in taking various medicine at the same time 166 (55.3%)* 146 (59.8%)** *p =< 0.005, **p =< 0.001. 4. discussion medication nonadherence is a complex problem, and a major public health issue. adherence to pharmacotherapy is a primary determinant of successful therapy and considers a multi-factorial response. clinical practitioners apply principles and adherences methods in daily practice in a similar manner for the effectual supervision of healthcare system shown in the study [9, 10]. majority of elderly patients in this study was male (73.7%). gender distribution of elderly patients has been addressed in various previous studies that have reported findings similar to ours. although adherence to treatment involves multiple factors, age can be considered as one of the leading cause for forgetfulness and polypharmacy in relation to the comorbidities. majority of our patients were in the age group of 60–69 (52%) and 70–79 years (27%), followed by those aged >79 years (21%), similar to the study of fernandez et al. [28]. the noncompliance and nonadherence are influenced by the increasing age of the patients. the standard for adherence evaluation is more competent use of restricted resources for maximization of healthcare benefit at lower cost. the results of the current study showed that the majority of the patients were on multiple-drug therapy which indicates polypharmacy since 27.7% of them were prescribed six or more medicines and 21% were given more than five. clearly, polypharmacy is the major factor contributing to the noncompliance as reported by payne and esmonde-white [29]. according to schuz et al., nonadherence as difficulty in reading, in remembering time and comorbidities with multiple disease requires multiple drugs [12]. clearly, studies on elderly people have shown that there is a need to address adherence-related problems among elderly patients [12–14]. kharicha et al. showed that elderly people generally resist to taking medications [15–17]. different studies support age factor as the chief reason for nonadherence [18]. the cost of the medication cannot be ignored in assessing the compliance since our study showed that it was a significant cause for the noncompliance (92.7%; p = 0.23). therapy-related reasons were also part of our assessment since complex regimen was found among 40.3% (p = 0.0034) as doi 10.18502/sjms.v16i3.9694 page 329 sudan journal of medical sciences muhammad shehnshah et al. studied by many researchers and in line with the findings of navaratnam et al. [26]. moreover, our study showed patients-related factors among 24%, which is similar to the findings of nikolaus et al. [19]. polytherapy involves a multiple-drug treatment, which is quite difficult to follow. for elderly patients, the polypharmacy plays a major role as a contributing factor to nonadherence, as the results of the current study showed that 59% of the patients failed to take medication on time, which is also supported by some previous studies [20–23]. the interventions were performed to assess the response; post-intervention results showed significant changes in the reading of details about medications which was altered from 51% of the patients to 61.5% (p =< 0.005). similarly, previous interventional studies have also shown a positive response [24–26]. various comorbidities have an express association with obedience of medication in elderly patients as patients with numerous diseases obviously require a higher complex dosing regimen, polypharmacy, and amplified medication costs [27–29]. 5. conclusion the study of elderly patient for nonadherence and utilization of medicine therapies showed an association with the intensity of compliance. the patients who show regularity in follow-up sessions and attend interventional guideline generally showed better medication compliance. standard follow-up and patient education is recommended for generating appropriate knowledge about their treatments. acknowledgements the authors acknowledge all supporting staff and faculty members who guided them throughout the research work. ethical considerations the study was approved by the advance studies and research board, university of sindh jamshoro, pakistan. all patients filled a consent form after receiving all information by the patients and their hcps. competing interests the authors have no conflicts of interest to declare for this study. doi 10.18502/sjms.v16i3.9694 page 330 sudan journal of medical sciences muhammad shehnshah et al. availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding none. references [1] kocurek, b. 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(2000). observational studies of antihypertensive medication use and compliance: is drug choice a factor in treatment adherence? current hypertension reports, vol. 2, no. 6, pp. 515–524. doi 10.18502/sjms.v16i3.9694 page 333 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9289 production and hosting by knowledge e research article the polymorphisms of epidermal growth factor-driven signaling and cancer pathogenesis monica dugăeșescu1, florentina mușat2, and octavian andronic2,3 1fundeni clinical institute, carol davila university of medicine and pharmacy, bucharest, romania 2university emergency hospital of bucharest, romania 3carol davila university of medicine and pharmacy, bucharest, romania orcid: monica dugăeșescu: http://orcid.org/0000-0002-7672-086x florentina mușat: http://orcid.org/0000-0003-2575-8646 octavian andronic: http://orcid.org/0000-0002-9053-0018 abstract background: epidermal growth factor (egf) is a stimulating protein for cell proliferation and differentiation. an amplification of its signaling pathway has been frequently reported in numerous malignant tumors. specific polymorphisms of the genes encoding proteins involved in this cellular pathway may constitute risk factors for carcinogenesis. the aim of this study was to identify the most relevant polymorphisms of egf and their signaling pathways and their relation to carcinogenesis. methods: the study included 40 full-text articles published between january 2010 and may 2020, extracted from pubmed, scopus, web of science, and science direct databases in may 2020, using the following keywords: egf or epidermal growth factor and polymorphism and cancer or neoplasia or tumor. results: we identified relevant polymorphisms of the egf signaling pathway that were involved in the development and progression of hepatocellular carcinoma, esophageal cancer, gastric cancer, colorectal cancer, glioma, lung cancer, breast cancer, cervical cancer, and head and neck cancer. rs4444903 variants have been widely studied and the association with numerous tumors has been confirmed by multiple studies. other frequently investigated polymorphisms are –191c/a and –216g>t. conclusion: the polymorphisms of egf signaling pathway have been widely studied in connection to various malignancies. some predisposing variants are common in different forms of cancer. these polymorphisms might be general risk factors for carcinogenesis. keywords: epidermal growth factor, cancer, polymorphism, signaling pathway how to cite this article: monica dugăeșescu, florentina mușat, and octavian andronic (2021) “the polymorphisms of epidermal growth factordriven signaling and cancer pathogenesis,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 207–222. doi 10.18502/sjms.v16i2.9289 page 207 corresponding author: monica dugăeșescu; fundeni clinical institute, carol davila university of medicine and pharmacy, bucharest, romania. email: monicadugaesescu@yahoo.com received 23 april 2021 accepted 1 june 2021 published 30 june 2021 production and hosting by knowledge e monica dugăeșescu et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0002-7672-086x http://orcid.org/0000-0003-2575-8646 http://orcid.org/0000-0002-9053-0018 mailto:monicadugaesescu@yahoo.com mailto:monicadugaesescu@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences monica dugăeșescu et al 1. introduction representing >1% of the whole allele frequency, single-nucleotide polymorphisms (snps) are the most frequent dna variation. an snp is the result of point mutations, it involves a single base pair and, usually, has no effect. the sequencing of the entire human genome was the start of a new research direction: genome-wide association studies (gwas) [1, 2]. their purpose is to identify a genetic susceptibility by testing the association with a disease for hundreds of thousands of snps in a gwas. one of the many medical fields which can benefit from the identification of such genetic risk factors is oncology [3]. in 1985, sporn and roberts explained that malignant cells produce elevated levels of growth factors to maintain their proliferation rate. this observation was followed by an enormous number of research projects which confirmed the importance of growth factors for cancer pathogenesis and described the mechanisms and molecular interactions involved in this process [4]. discovered in 1962, epidermal growth factor (egf) is encoded by prepro-egf gene, on chromosome 4 (4q25-q27) [5]. in 1986, cohen and levi-montalcini won the nobel prize for medicine for the description of the peptide structure of egf [6]. it is the member of a family of growth factors which can bind to the same receptor: egf receptor (egfr, erbb1). egfr is a type i transmembrane protein with intrinsic tyrosine kinase activity. when a ligand binds to egfr, the receptor forms homodimers (dimerization with an identical egfr) or heterodimers with other members of its family. the dimerization activates the intrinsic tyrosine kinase and the autophosphorylation of the c-terminal tyrosine residue, facilitating the recruitment of signaling molecules. signaling pathways involved in cell proliferation, differentiation, apoptosis, such as ras/raf/mek/erk, jak/stat, pi3k/akt/mtor, and plc/pkc, are activated. a series of malignant tumors were associated with an amplification of egf/egfr pathway, caused by increased egf synthesis, egfr overexpression, and egfr mutations. progression of cancer and metastasis are correlated with the level of egf/egfr. considering the role it plays in cancer pathogenesis, egfr inhibition is used as a target in oncologic therapies [5]. considering that the connection of egf/egfr signaling pathway with malignant tumors is well established [5], it is expected to identify the presence of predisposing snps in the encoding regions for various forms of cancer. in the era of gwass, the quantity of information about susceptibility and genetic factors, such as snps, is abundant [3] and reviews are mandatory, as a way to organize all this knowledge and highlight the issues that can be addressed in the clinic. therefore, the aim of this study was doi 10.18502/sjms.v16i2.9289 page 208 sudan journal of medical sciences monica dugăeșescu et al to analyze the data extracted from genomic studies regarding cancer and egf/egfr pathways and present it. 2. materials and methods we conducted a search on pubmed, scopus, web of science, and science direct in may 2020, using the following search keywords: egf or epidermal growth factor and polymorphism and cancer or neoplasia or tumor. after a thorough investigation of database interrogation results, we included in our study the most relevant 40 full-text articles published in the last 10 years. 3. results we identified relevant polymorphisms of the egf signaling pathway that were involved in the development and progression of hepatocellular carcinoma (hcc), esophageal cancer, gastric cancer, colorectal cancer, glioma, lung cancer, breast cancer, cervical cancer, and head and neck cancer. the snps, their connection to these malignancies, and the studies that identified the relevant variants are presented below, starting with a presentation of each cancer and its predisposing polymorphisms and ending with the discussion of these findings. 3.1. epidermal growth factor (egf) signaling pathway and liver cancer egf was identified as a factor which induces malignant transformation among hepatocytes, and it has an important impact on the progression of tumor too, as a hepatocytic mitogen factor. a polymorphism of egf gene, position 61 a>g, snp rs4444903, results in an increased egf production in liver [7]. several studies investigated the risk of developing hcc and the presence of rs4444903 snps. an association between a/g and g/g genotypes and increased risk of hcc was identified [8–10]. two case–control studies were conducted in parallel, one of them on non-asian population from los angeles (region having one of the lowest incidences of hcc in the world), and the other on natives from guangxi, china (population having one of the highest incidences of hcc in the world). among the non-asian los angeles population, there was a 78% increased risk of developing liver cancer in patients who doi 10.18502/sjms.v16i2.9289 page 209 sudan journal of medical sciences monica dugăeșescu et al had at least one 61*g allele (rs4444903 snp), which is associated with high activity and egf production, in comparison to egf a/a genotype. the results were, however, not statistically significant. among the chinese population, no association was identified between this polymorphism and hcc risk [7]. based on the findings resulted from the numerous case–control studies regarding rs4444903 snp and hcc, various meta-analyses were conducted. we identified six meta-analyses that revealed an association between g allele and an elevated risk of developing hcc. the a allele is considered a protective factor [11–16]. 3.2. epidermal growth factor (egf) signaling pathway and esophageal cancer a genome-wide association study conducted on 1,942 patients with esophageal squamous cell carcinoma, 1,758 patients with gastric cancer, and 2,111 controls investigated 127 genes of the egf pathway. gnai3, chrne, pak4, wasl, itch genes were associated with esophageal squamous cell carcinoma, but there was no significant association with the pathway [17]. 3.3. epidermal growth factor (egf) signaling pathway and gastric cancer the genome-wide association study investigating 127 genes of the egf pathway also concluded that fyn, mapk8, map2k4, gnai3, map2k1, tln1, prlr, plcg2, rps6kb2, pik3r genes, and the egfr pathway were associated with gastric cancer [17]. a case–control study conducted on high-risk chinese population from jiangxi investigated seven egfr exon snps. the study identified only one variant, rs2072454, t allele and tt genotype, significantly associated with elevated risk of developing gastric cancer [18]. ag/gg rs2237051 (non-synonymous exon region) and ag/gg rs3733625 (3‘ untranslated region) variants of egf gene were identified as susceptibility factors in a study conducted on chinese population [19]. a study based on mexican population suggested the association of –216g>t, 191c>a polymorphisms of egfr and the risk of developing gastric cancer [20]. rs4444903 was also investigated regarding gastric cancer [21]. a study conducted in portugal on caucasian subjects identified different risk profile associated with +61 a/g polymorphism, depending on the patient’s sex. female carriers of a variant had a low risk of developing gastric cancer. a possible explanation for this phenomenon is doi 10.18502/sjms.v16i2.9289 page 210 sudan journal of medical sciences monica dugăeșescu et al the lower secretion of gastric acid than men. male carriers of a polymorphism had an elevated risk of developing this neoplasia [22]. a meta-analysis conducted in 2014 on six case–control studies strongly suggested that this polymorphism leads to elevated gastric cancer risk, especially in asian population [21]. 3.4. epidermal growth factor (egf) signaling pathway and colorectal cancer a study conducted on iranian population investigated the association of rs2298979 polymorphism, located in a noncoding region – intron 1 of egf gene, with colorectal cancer. a/g genotype carriers were identified as less susceptible than the carriers of a/a genotype [23]. the association between colorectal cancer and snp rs4444903 was also researched. a study based on syrian subjects demonstrated that a/a variant of r521k is a protective factor for colorectal cancer [24], while another study based on chinese population indicated an association of egf a61g polymorphism with elevated risk for developing colorectal cancer [25]. two studies failed to highlight an association between +61a>g polymorphism and elevated colorectal cancer risk [26, 27]. a meta-analysis based on nine studies concluded that egf a61g polymorphism might be a risk factor for colorectal cancer development (g allele in the caucasian group and gg genotype in both caucasian and asian populations) [28]. 3.5. epidermal growth factor (egf) signaling pathway and glioma a higher risk of developing glioma was associated with –191 c/a snp of egfr. this polymorphism was also identified as a prognostic factor in patients with glioblastoma. short (ca)n repeats (<17) were associated with elevated risk, especially for glioblastoma and oligodendroglioma [29]. a study conducted in 2012 on han chinese population identified two polymorphisms (rs1468727 and rs730437) in the egfr gene which are associated with increased risk of glioma. aatt haplotype had a protective effect, while cgtc haplotype was associated with an increased risk of developing glioma. the findings of this study including han chinese subjects were not consistent with the results of previous studies on european populations, therefore ethnic differences are strongly suggested [30]. numerous studies have identified an association between +61g allele of egf and high risk for developing glioma. a study conducted on chinese population from eastern doi 10.18502/sjms.v16i2.9289 page 211 sudan journal of medical sciences monica dugăeșescu et al china concluded that genotypes +61 g/a and +61 a/a were associated with higher risk of glioma, in comparison to g/g, considered wild type [31]. a meta-analysis including nine studies concluded that egf +61g/a polymorphism is a risk factor for glioma [32]. a meta-analysis including six case–control studies concluded that this polymorphism is a risk factor for european population, but a protective factor regarding chinese population [33]. another meta-analysis based on seven studies concluded that egf +61g/a polymorphism is associated with a higher risk of developing glioma in asian population, but not in caucasians [34]. 3.6. epidermal growth factor (egf) signaling pathway and breast cancer a study investigating egfr snps and breast cancer risk identified associations among snps in egfr gene and the risk for development of breast cancer. after multiple comparisons, none of the results remained statistically significant [35]. rs11543848 (egfr r497k) and rs1136201 (her2 i655v) were associated with the risk of developing breast cancer [36]. rs1136201 (ile 655 val) genetic polymorphism of human epidermal growth factor receptor-2 (her2) was identified as a possible risk factor for developing breast cancer in brazilian population [37]. 3.7. epidermal growth factor (egf) signaling pathway and lung cancer a study based on jordan population identified rs2233947 egfr polymorphism as a risk factor for lung cancer development. this snp is located in the exon 25 and does not produce an amino acid modification. the a allele is protective for the development of lung cancer [38]. rs712829 egfr polymorphism (gg+gt), rs2072454, –191c/a (rs712830), rs6965469, rs763317, and tccg haplotype of rs712829, rs712830, rs2072454, rs11543848 were associated with lung cancer [39–41]. a study conducted on indian population identified +61 ag and gg genotypes as risk factors for developing non-small cell lung adenocarcinoma [42], while a recently published meta-analysis based on six case–control studies failed to identify an association between 61a/g egf polymorphism and the development of lung cancer [43]. doi 10.18502/sjms.v16i2.9289 page 212 sudan journal of medical sciences monica dugăeșescu et al 3.8. epidermal growth factor receptor (egfr) family and osteosarcoma rs1136201 and rs1058808 polymorphisms of her2 (erbb2) and ctgg haplotype were associated with an elevated risk of developing osteosarcoma in han chinese population [44]. 3.9. epidermal growth factor (egf) signaling pathway and cervical cancer a study investigating snps in members of erbb family (egfr, erbb2, erbb3, erbb4) identified 14 polymorphisms that were significantly over transmitted (from parents to their offspring) in women who developed cervical cancer. four snps were inside intron 1 of egfr and two other were located in intron 24 of erbb4. the snps identified in egfr were in the proximity of enhancers, silencers, and important functional regions [45]. 3.10. epidermal growth factor (egf) signaling pathway and head and neck squamous cell carcinoma rs12535536, rs2075110, rs1253871, rs845561, rs6970262 snps located inside egfr introns and synonymous rs2072454 egfr snp were significantly associated with elevated risk of developing head and neck squamous cell carcinoma, while rs12538371, rs845561, rs6970262 were associated with elevated risk among patients who never used tobacco [46]. 4. discussion we identified numerous studies investigating the presence of single nucleotide polymorphisms of genes encoding proteins involved in egf signaling pathway and the risk of developing different forms of malignant tumors. some of these polymorphisms, such as rs4444903, were widely studied and meta-analyses were conducted to increase the strength of the results. the findings can be explained by the functional importance of these snps, many of them leading to an increase in the pathway activity, and, in the end, promoting the progression of the malignancy [21, 39, 40]. genetic variants of the egf signaling pathway and egfr family were identified as risk factors for various tumors, such as: hcc [8–16], esophageal cancer [17], gastric cancer [17–22], colorectal cancer doi 10.18502/sjms.v16i2.9289 page 213 sudan journal of medical sciences monica dugăeșescu et al [23–28], glioma [29–34], lung cancer [38–42], breast cancer [36, 37], cervical cancer [45], and head and neck cancer [46]. egf is important for tumor survival, progression, metastasis, and angiogenesis [19]. egf signaling pathway might be relevant not only for the risk of developing different forms of cancer, but also for prognosis. for example, a study conducted on indian population also identified an association between +61ag and gg genotypes and overall reduced survival in lung cancer patients [42]. the finding of the studies investigating the same snps and the development of a particular form of cancer were different. some studies suggest an association between a malignant tumor and these variants, while others fail to identify a statistically significant result [26, 27, 43]. we identified numerous sources that might lead to inconsistent results: the sample size – from tens of subjects to thousand, study population and its different genetic and specific environmental risk factors that can modify susceptibility, data analysis tools and thresholds for significance, and inclusion and exclusion criteria for study population. however, most studies had similar conclusions regarding the most relevant polymorphisms. one of the most relevant polymorphisms, according to the studies we identified, is rs4444903 snp. this polymorphism is located in 5‘ – untranslated region of egf gene and +61 gg and +61 ag variants lead to an increased protein expression compared to +61 aa genotype [21]. this polymorphism has been widely studied regarding various forms of cancer and an association of the risk of developing tumors has been identified by most studies: liver cancer [8–16], gastric cancer [21, 22], colorectal cancer [25], glioma [31–34], and lung cancer [42]. few studies failed to identify this association [26, 27, 43]. the results from case–control studies were different, depending on study population. it was suggested that rs4444903 snp is a low-penetrance susceptibility biomarker [33]. considering the functional relevance and the known association with an increased activity of egfr signaling pathway of this variant, the positive results of the studies are supported by evidence provided by fundamental studies [21]. aa genotype was identified as a protective factor [12, 15], which is consistent with its functional importance: the protein production is not very high, while ag and gg genotypes were suggested to be risk factors, which is explained by the higher production of the protein and an increased activity of the pathway, leading in the end to an increased proliferation and survival of the malignant cell [8–16, 21, 22, 25, 31–34, 42]. the promoter region is essential to produce protein and polymorphisms of this sequence might lead to important functional alterations. –216g/t and –191c/a snps, both located inside the promoter region of egfr gene, and polymorphic (ca)n doi 10.18502/sjms.v16i2.9289 page 214 sudan journal of medical sciences monica dugăeșescu et al microsatellite sequence in the first intron have regulatory functions regarding transcription [29]. –191c/a snp results in an increased production of egfr and it occurs at the binding site of the promoter region with a transcription factor [39, 40]. while –216 g/t genotype was not significantly associated with glioma, –191 c/a snp was associated with higher risk of developing glioma. also, short (ca)n repeats (<17) were associated with elevated risk, especially for glioblastoma and oligodendroglioma [29]. both –216g>t and 191 c>a were associated with the risk of developing gastric cancer [20]. –191c/a (rs712830) was also associated with lung cancer [39, 40]. considering the location inside egfr gene, functional importance and the results of previous studies, these polymorphisms and association with cancer should be further investigated. egf receptor or erb family members are her1 (egfr, erbb1), her2 (erbb2, neu), her3 (erbb3), and her4 (erbb4) [36]. polymorphisms of her2 were also identified as risk factors in both breast cancer and osteosarcoma [37, 44]. overall, erb family might be relevant for malignancy pathogenesis and further studies should be conducted to determine its importance for cancer development. to the best of our knowledge, this narrative review is the first article that synthesizes and analyses the information regarding different types of tumors and polymorphisms as risk factors. all studies we identified were based on a specific tumor and associated polymorphisms. we consider it is important to summarize all this information together, because, as mentioned earlier, some snps are relevant for various forms of malignancy and polymorphisms of egf signaling pathway might be relevant for cancer pathogenesis in general, not only for a specific malignant cell and it can be important to identify such variants for most tumors. the results of our study were affected by several factors: limited access to research conducted in this area and the studies we included had wide differences regarding sample size, study population, environmental risk factors. genetic and molecular screening can have a major role in improving the diagnostic efficiency and treatment response in patients with cancer [47]. identifying genetic variants of egf signaling pathway as risk factors is important to determine if a subject is at risk of developing a malignancy and to use this information to take preventive steps and to start periodic screening. furthermore, the proteins involved in this cellular pathway can be used as future targets in patients who have an increased activity of egf signaling. future research is required to investigate the association between egf signaling pathway and malignancies. these studies need larger sample size, and they should doi 10.18502/sjms.v16i2.9289 page 215 sudan journal of medical sciences monica dugăeșescu et al take into consideration sex differences together with the genetic and environmental factors of the study population. 5. conclusion our narrative review confirms the presence of predisposing polymorphisms of the genes related to egf signaling pathway, which are relevant for the development of various forms of cancer, such as hcc, esophageal cancer, gastric cancer, colorectal cancer, glioma, lung cancer, breast cancer, cervical cancer, and head and neck cancer. rs4444903 egf gene variants have been widely studied and the association with different tumors has been confirmed by numerous meta-analyses. functionally important snps of egfr gene are –191c/a and –216g>t. other relevant snps might be identified by studies on larger samples and further investigation should be conducted to use these variants as risk evaluation and prognosis tools or as therapeutic targets. acknowledgements none ethical considerations not applicable. competing interests none. availability of data and material none. 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(2015). identification of epidermal growth factor receptor (egfr) genetic variants that modify risk for head and neck squamous cell carcinoma. cancer letters, vol. 357, no. 2, pp. 549–556. retrieved from: https:// linkinghub.elsevier.com/retrieve/pii/s0304383514007514 [47] bolocan, a., stoian, r. v., ion, d., et al. (2012). peculiarities of diagnosis and treatment in the polyp-cancer sequence. chirurgia, vol. 107, no. 1, pp. 66–70. retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/22480119 doi 10.18502/sjms.v16i2.9289 page 222 https://linkinghub.elsevier.com/retrieve/pii/s0304383514007514 https://linkinghub.elsevier.com/retrieve/pii/s0304383514007514 http://www.ncbi.nlm.nih.gov/pubmed/22480119 introduction materials and methods results epidermal growth factor (egf) signaling pathway andliver cancer epidermal growth factor (egf) signaling pathway andesophageal cancer epidermal growth factor (egf) signaling pathway and gastric cancer epidermal growth factor (egf) signaling pathway and colorectal cancer epidermal growth factor (egf) signaling pathway and glioma epidermal growth factor (egf) signaling pathway and breast cancer epidermal growth factor (egf) signaling pathway and lung cancer epidermal growth factor receptor (egfr) family andosteosarcoma epidermal growth factor (egf) signaling pathway and cervical cancer epidermal growth factor (egf) signaling pathway and head and neck squamous cell carcinoma discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 12, issue no. 3, doi 10.18502/sjms.v12i3.931 production and hosting by knowledge e research article molecular diagnosis of shigella, salmonella and campylobacter by multiplex real-time pcr in stool culture samples in ouagadougou (burkina faso) salfo sawadogo, msc, engineer1,2, birama diarra, pharmd, msc, phd student1, cyrille bisseye, phd, assistant professor1,3, tegwindé rebeca compaore, phd, assistant researcher1,4, florencia w. djigma, phd, assistant professor1,4, djénéba ouermi, phd, assistant professor1,3, aboubakar s. ouattara, phd, full professor5, and jacques simporé, phd, full professor1,4 1pietro annigoni biomolecular research centre, cerba/labiogene, university of ouaga i pr joseph ki-zerbo, 01 bp 364 ouagadougou 01, burkina faso 2el fateh suka clinic, 04 bp 8297 ouagadougou 04, burkina faso 3laboratory of molecular and cellular biology (labmc), university of sciences and techniques of masuku (ustm), bp 943 franceville, gabon 4saint camille medical centre, 01 bp 364 ouagadougou 01, burkina faso 5crsban, university of ouaga i pr joseph ki-zerbo, 03 bp 7131 ouagadougou 03, burkina faso abstract background: bacteriological diagnosis of campylobacter spp, salmonella spp and shigella spp could be necessary in case of infectious gastroenteritis syndrome. the objective of this study was to diagnose concomitantly the three enteropathogenic bacteria by multiplex real-time pcr in stool culture samples in ouagadougou (burkina faso). materials and methods: the study was conducted from february 5th to march 9th, 2013. two hundred stool samples were received during the study period. the bacteria were identified by bacterial culture following by multiplex real-time pcr. results: shigella spp and campylobacter spp were sought by culture in all 200 samples. enteropathogenic e. coli was sought only in 37 samples from all children under 2 years old. the bacterial culture was positive in 12 stool samples. shigella spp and salmonella spp. were isolated respectively in 5 (2.5%) and 3 samples (1.5%). enteropathogenic e. coli was isolated in 10.8% (4/37) of the samples tested. the multiplex real-time pcr identified bacteria in 20 patients, including 17 cases of shigella spp., 1 case of salmonella spp. and 2 cases of campylobacter spp. conclusions: this study has highlighted the low frequency of 3 sought bacterial genera in stool samples. it has also demonstrated a significant difference between the culture and the multiplex real-time pcr method in the diagnosis of shigella. keywords: stool culture; real-time pcr; shigella spp.; salmonella. spp. ; campylobacter spp. burkina faso how to cite this article: salfo sawadogo, birama diarra, cyrille bisseye, tegwindé rebeca compaore, florencia w. djigma, djénéba ouermi, aboubakar s. ouattara, and jacques simporé, (2017) “molecular diagnosis of shigella, salmonella and campylobacter by multiplex real-time pcr in stool culture samples in ouagadougou (burkina faso),” sudan journal of medical sciences, vol. 12 (2017), issue no. 3, 163–173. doi 10.18502/sjms.v12i3.931 page 163 corresponding author: cyrille bisseye; email: cbisseye@gmail.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e salfo sawadogo et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:cbisseye@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e 1. authors’ contribution study concept and design: dr cyrille bisseye and prof jacques simpore collection of data: salfo sawadogo and dr birama diarra analysis and interpretation of data; salfo sawadogo, dr birama diarra, dr cyrille bisseye and dr tegwindé rebeca compaoré drafting the article and revision: salfo sawadogo, dr cyrille bisseye, dr birama diarra, dr djeneba ouermi, dr florencia w. djigma, dr tegwindé rebeca compaoré, final approval of the version to be published: prof aboubakar s. ouattara and prof jacques simpore funding: prof jacques simpore from: dr. cyrille bisseye pietro annigoni biomolecular research centre cerba/labiogene university of ouaga i pr joseph ki-zerbo, 01 bp 364 ouagadougou 01, burkina faso burkina faso, west africa fax: +226 50 30 23 28 email: cbisseye@gmail.com 2. introduction each year, there are about two billion cases of diarrheal diseases worldwide causing the death of more than 2 million people, including 1.9 million children under the age of 5 mainly in developing countries [1]. in burkina faso, diarrhea is responsible for 12% of deaths in children under 5 years old [2]. among the pathogens involved in these infections, enteric bacteria such as campylobacter, salmonella and shigella are important because of the frequency and severity of the symptoms they could cause. thus, campylobacter is currently considered the leading cause of intestinal bacterial infections in humans worldwide with an increasing incidence in developed countries [3–5]. although, campylobacter infection is usually mild, the increase in cases of campylobacteriosis, the existence of rare but serious complications such as abortions, peritonitis, meningitis, guillain-barre syndrome and the alarming increase of campylobacter antibiotic resistance explain the renewed interest in this bacterial genus [3]. regarding salmonella, the world health organization (who) estimates about 17 million cases of typhoid fever in the world with more than 500,000 deaths and 1.3 billion annual cases of gastroenteritis due to non-typhoid salmonella with 3 million deaths annually [6]. doi 10.18502/sjms.v12i3.931 page 164 sudan journal of medical sciences production and hosting by knowledge e as for shigella, it is the leading cause of malnutrition in developing countries where shigellosis remains endemic [7]. the cases of antibiotics’ multi-resistant bacteria at high levels are also reported for salmonella and shigella [8–11]. the direct diagnosis of these three bacteria can be done by stool culture. campylobacter diagnosis is generally not performed in bacteriology laboratories in burkina faso. in this country, no study has yet reported the molecular diagnosis of shigella, salmonella and campylobacter in human stool samples. the objective of this study was to diagnose by multiplex realtime pcr, shigella, salmonella and campylobacterin routine stool culture samples in ouagadougou. 3. materials and methods 3.1. sample collection a total of 200 stool culture samples were collected, including 101 samples from el fateh suka clinic and 99 at saint camille medical centre in ouagadougou between february 5th and march 9th, 2013. for each stool sample, a portion of the sample was transferred into a sterile tube and stored at -80∘c for molecular diagnostics. the rest was used for stool culture process within 2 h of receipt. patients or parents and/or guardians of under-age children answered a questionnaire including their socio-demographic and clinical characteristics. 3.2. stool culture salmonella, shigella and enteropathogenic e. coli (epec) were sought on the basis of existing repositories [12]. for all samples, the hektoen agar petri dish and salmonella enrichment broth (selenite broth) were inoculated and incubated in an oven at 37∘c. after 5 to 6 hours, selenite broth was sub-cultured on a second hektoen agar plate. both hektoen boxes were then incubated in an oven at 37∘c for 18 to 24 hours.the suspected colonies were biochemically identified by api 20e (biomérieux®, marcyetoile, france) and also sub-cultured on kligler-hajna medium. salmonella and shigella colonies identified on kligler-hajna medium were agglutinated with salmonella and shigella antisera (bio-rad®, marnes-la-coquette, france) for confirmation and species or serotype identification. the detection of epec (enteropathogenic e. coli) was carried out on the samples of the children under 2 years old. its identification was performed on emb agar. typical colonies were agglutinated with an enteropathogenic e. coli antisera (bio-rad®, marnes-la-coquette, france). doi 10.18502/sjms.v12i3.931 page 165 sudan journal of medical sciences production and hosting by knowledge e 3.3. sample preparation, extraction and amplification of bacterial genomes after thawing the samples, 1 ml (for liquid stool) or 1 gram (for solid faeces) was used for the extraction of bacterial dna using the dna-sorb-b extraction kit (sacace biotechnologies®, como, italy) according to the manufacturer’s instructions. the bacterial genomes were amplified by multiplex real-time pcr using the kit ”shigella/salmonella/campylobacter real-tm” (sacace biotechnologies®, como, italy). the amplification reaction was performed in a sacycler-96 real-time pcr (sacace biotechnologies®, como, italy) according to the manufacturer’s recommendations. the target genes were respectively ipah, ttrb, and 23srrna for shigella, salmonella and campylobacter. 3.4. statistical analysis the results were analyzed using spss 17.0 software and epi info version 3.5.1. the chisquare test was used for comparisons and the difference was considered significant for p-value < 0.05. 4. results 4.1. epidemiological and clinical characteristics of patients the stools were predominantly from female patients (60.5%), outpatients (94.5%) and subjects over 15 years (57.5%). the major clinical features of patients were respectively, fever (44.5%), diarrhea (21%) and vomiting (13%). the presence of blood and leucocytes in stool was observed in 2.5% and 5% of patients, respectively. some of the patients (14.5%) had started antibiotic therapy before sample collection. the epidemiological and clinical characteristics of the patients are shown in table 1. 4.2. identification of bacteria from stool specimens by culture and multiplex real time pcr the number and percentage of germs diagnosed by the two diagnostic methods are shown in table 2. enteropathogenic escherichia coli was sought only in samples of children aged less than 2 years was isolated 4 times by culture (4/37, 10.8%) the prevalence of the three bacteria detected by multiplex real-time pcr was higher than that detected by stool culture; but the observed difference was not statistically doi 10.18502/sjms.v12i3.931 page 166 sudan journal of medical sciences production and hosting by knowledge e significant (10% vs 6%, p = 0.140). bacteria prevalence detected by multiplex real time pcr and by stool culture were respectively, 8.5% vs 2.5% for shigella and 0.5% vs 1.5% for salmonella. shigella prevalence detected by pcr was significantly higher compared to that detected by culture (p = 0.006). the distribution of shigella species identified in the 5 patients was as follows: 3 cases of s. flexneri, 1 case of s. boydii and 1 case of s. dysenteriae. the 3 cases of salmonella identified were represented by three different serotypes: salmonella typhi, salmonella paratyphi b and salmonella sp. of the 3 positive samples by culture, two were negative by pcr. campylobacter spp. was identified by pcr only in 1% of patients (table 2). the distribution of positive samples for the three bacteria by pcr based on epidemiological and clinical features of the patients is summarized in table 3. the distribution of shigella spp. among patients was not associated with age, neither with sex or fever. the prevalence of shigella was higher among patients with diarrheal compared to non-diarrheal patients (23.8% vs 4.4%; p < 0.001). 5. discussion this study aimed the concomitant search for shigella, salmonella, and campylobacterby multiplex real-time pcr in stool samples from patients in ouagadougou. to our knowledge, this is the first study on the molecular diagnosis of these three bacteria in burkina faso. however, the diagnosis of these pathogens by traditional methods has been reported in previous studies in children with diarrhea [13–17]. the prevalence of shigella, salmonella and campylobacter by multiplex real-time pcr was 8.5%; 0.5% and 1%, respectively. this reduced prevalence of enteropathogenic bacteria could be explained the weak frequency of diarrhoeal patients among the stool specimens tested. diarrhea is the major cause of stool specimens’ culture [12, 18]. this suggests that in burkina faso, stool culture is done as well as parasites stool examination in the systematic search for certain gastrointestinal disorders in primary care. diarrheas were more common in infants than adults (68.6% vs 12.2%). similar results have been reported in burkina faso [13, 14] and brazil [20]. despite this high rate of diarrhea, bacteria were isolated only in 28.6% of infants. this could be explained by the fact that, viruses are the leading cause of diarrhea in children [12, 20]. in addition, the period of the study coincided with the cold dry season where the frequency of virus is highest among children with diarrhea in burkina faso [16, 17]. bloody stool samples having a positive leukocyte microscopy examination, were all positive by culture and by pcr, which is in agreement with the entero-invasive nature of these bacteria [12]. doi 10.18502/sjms.v12i3.931 page 167 sudan journal of medical sciences production and hosting by knowledge e characteristics number percentage (%) age group (years) <2 37 18.5 2-15 48 24.0 >15 115 57.5 sex male 79 39.5 female 121 60.5 type of patient in-patient 11 5.5 out-patient 189 94.5 diarrhea yes 42 21.0 no 158 79.0 fever yes 89 44.5 no 111 55.5 vomitting yes 26 13.0 no 174 87.0 on antibiotherapy * yes 29 14.5 no 155 85.5 stoolconsistency liquid 12 6.0 semi-liquid 23 11.5 hard 165 82.5 bloody stools yes 5 2.5 no 195 97.5 leucocytesin stools yes 10 5.0 no 190 95.0 t 1: patients’ epidemio-clinic characteristics. *: total number of answers = 184. real-time pcr n = 200 bacterial culture n = 200 germs n % n % salmonella 1 0.5 3 1.5 shigella 17 8.5 5 2.5 campylobacter 2 1.0 nd nd total 20 10 t 2: bacterial culture and pcr results summary. nd = not done. doi 10.18502/sjms.v12i3.931 page 168 sudan journal of medical sciences production and hosting by knowledge e number of bacteria detected by pcr characteristics shigella salmonella campylobacter age group (years) n n (%) n (%) n (%) <2 37 5 (13.5) 0 0 2-15 48 3 (6.3) 0 2 (4.2) >15 115 9 (7.8) 1 (0.9) 0 sex male 79 8 (10.1) 0 2 (2.5) female 121 9 (7.4) 1 (0.8) 0 in-patient no 11 2 (18.2) 0 0 yes 189 15 (7.9) 1 (0.5) 2 (1.1) on anti-biotherapy no 155 13 (8.4) 1 (0.6) 2 (1.3) yes 29 4 (13.8) 0 0 diarrhea no 158 7 (4.4) 1 (0.6) 1 (0.6) yes 42 10 (23.8) 0 1 (2.4) fever no 111 8 (7.2) 1 (0.9) 1 (0.9) yes 89 9 (10.1) 0 1 (1.1) stool consistency liquid 12 5 (41.7) 0 0 semi-liquid 23 5 (21.7) 0 2 (8.7) hard 165 7 (4.2) 1 (0.6) 0 bloody stool no 196 14 (7.1) 0 0 yes 4 3 (75.0) 0 0 leucocytes in stools no 190 8 (4.2) 1 (0.5) 1 (0.5) yes 10 9 (90.0) 0 1 (10.0) t 3: distribution of positive cases by pcr according to the patients’ epidemio-clinic criterea. shigella was the most identified bacteria by stool culture as well as multiplex realtime pcr. culture has identified 5 cases of shigellosis. shigella flexneri was the most frequently isolated (3 of 5 cases), which is consistent with previous studies which have shown that it is the most common species in developing countries [16, 17, 21, 22]. the frequency of shigella spp. was higher by pcr than stool culture. this difference should be interpreted with caution. indeed, the pcr target gene ipah which allowed the detection of shigella is also present in the entero-invasive e. coli (eiec).thus, the highest frequency of shigella by pcr could be due to the presence of eiec in stool of doi 10.18502/sjms.v12i3.931 page 169 sudan journal of medical sciences production and hosting by knowledge e patients. to our knowledge, there is no molecular technique to differentiate shigella from eiec [23]. thus, 5 samples were found positive for shigella in culture and by the pcr technique. for 12 samples negative in culture but positive by pcr, the presence of the eiec could not be excluded; although a recent study in burkina faso showed a very low frequency of eiec (0.3%) compared to enteroaggregative e. coli (12%) and enteropathogenic e. coli (8%) [17]. the prevalence of shigella spp. showing a discrepancy between the results of pcr and culture have been reported in vietnam [24]. the present report and previous studies in vietnam [24], india [25] and thailand [26] suggest that stool culture has a lower sensitivity than pcr in the diagnosis of shigella spp. regarding salmonella, of the 3 positive samples in stool culture, two were pcr negative. the absence of salmonella in negative pcr samples suggests either a lower specificity of culture (biochemical and antigenic similarity to other bacteria) or a lower sensitivity of pcr in the diagnosis of salmonella compared to stool culture. a low sensitivity of pcr compared to culture in the detection of salmonella was reported by cunningham et al, [27]. however, because of the reduced size of our sample, additional data are needed to confirm one or the other of the two hypotheses. the frequency of campylobacter (1%) found in this study is similar to those reported in burkina faso [17] and france [28]. a study combining enzyme immunoassay methods, molecular and culture had reported a 9.5% rate in hospitalized patients with gastrointestinal problems [29]. the detection of campylobacter by stool culture has been recommended by some studies [3, 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[19] p. p. orlandi, g. f. magalhães, n. b. matos et al., “etiology of diarrheal infections in children of porto velho (rondonia, western amazon region, brazil),” brazilian journal of medical and biological research, vol. 39, no. 4, pp. 507–517, 2006. [20] p. mariani-kurkdjian and bingen e., analyse bactériologique des selles. in: bactériologie médicale, techniques usuelles. masson ed. paris: masson; 2011. [21] f. yang, j. yang, x. zhang et al., “genome dynamics and diversity of shigella species, the etiologic agents of bacillary dysentery,” nucleic acids research, vol. 33, no. 19, pp. 6445–6458, 2005. [22] m. qu, x. zhang, g. liu et al., “an eight-year study of shigella species in beijing, china: serodiversity, virulence genes, and antimicrobial resistance,” journal of infection in developing countries, vol. 8, no. 7, pp. 904–908, 2014. 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[26] o. sethabutr, p. echeverria, c. w. hoge, l. bodhidatta, and c. pitarangsi, “detection of shigella and enteroinvasive escherichia coli by pcr in the stools of patients with dysentery in thailand,” journal of diarrhoeal diseases research, vol. 12, no. 4, pp. 265–269, 1994. [27] s. a. cunningham, l. m. sloan, l. m. nyre, e. a. vetter, j. mandrekar, and r. patel, “three-hour molecular detection of campylobacter, salmonella, yersinia, and doi 10.18502/sjms.v12i3.931 page 172 sudan journal of medical sciences production and hosting by knowledge e shigella species in feces with accuracy as high as that of culture,” journal of clinical microbiology, vol. 48, no. 8, pp. 2929–2933, 2010. [28] p. weber, p. laudat, and r. epiville, “bactéries entéropathogènes isolées des coprocultures en médecine de ville: enquête «epicop» 1999-2000 bulletin epidémiologique hebdomadaire,” 2003;8:45–46. [29] e. bessède, a. delcamp, e. sifré, a. buissonnière, and f. mégraud, “new methods for detection of campylobacters in stool samples in comparison to culture,” journal of clinical microbiology, vol. 49, no. 3, pp. 941–944, 2011. doi 10.18502/sjms.v12i3.931 page 173 authors' contribution introduction materials and methods sample collection stool culture sample preparation, extraction and amplification of bacterial genomes statistical analysis results epidemiological and clinical characteristics of patients identification of bacteria from stool specimens by culture and multiplex real time pcr discussion conclusion references sudan journal of medical sciences volume 12, issue no. 3, doi 10.18502/sjms.v12i3.937 production and hosting by knowledge e research article deranged liver among sudanese patients with dengue virus infection in port sudan teaching hospital bashir abdrhman bashir mohammed 1assistant professor of hematology, chairman of hematology department, medical laboratory sciences division, port sudan ahlia college, port sudan, sudan abstract background: deranged liver is a well-recognized feature of dengue infection, often demonstrated by coagulopathy and mild to moderate increase in transaminase levels although jaundice and fulminant hepatic failure are generally uncommon. objective: this study aimed to evaluate the hepatic effect of dengue fever amongst sudanese patients. materials and methods: a cross-sectional descriptive study recruited in port sudan teaching hospital in the period from february 2013 to june 2014. 334 cases of dengue along with 101 cases of control were enrolled. the rapid immune chromatographies test was used to confirm positive dengue cases and who criteria were used for classifying the dengue severity. prothrombin time (pt), partial thromboplastin time (ptt), fibrinogen level (fb), platelet count (plt), aspartate aminotransferase (ast), alanine aminotransferase (alt) and c-reactive protein (crp) were all measured. results: pt, ptt, and fb were found to be significantly higher in the infected cohort when compared to the controls (p < 0.0001). pt was prolonged in 9%, ptt was prolonged in 12.6% and shortened by 5.4% of the patients, whereas hypofibrinogenemia in 18.3% and hyperfibrinogenemia in 67.4% of the patients. bleeding was seen in 10.5% of patients and thrombocytopenia was detected in 83.5% of patients. out of 334 patients, 101 (30.2%) had abnormal coagulation results. of 101 patients, 72 were subjected mixing studies for pt and ptt that revealed deficiencies in factors viii (35%), ix (10%), v (10%), x (19%), and xii (14%). 43.6% patients had elevated ast and 21.8% had elevated alt. conclusion: this study demonstrated that hepatic dysfunction may be attributed to dengue virus infection which evident by prolongation in pt and ptt as well as hypofibrinogenemia and factor deficiencies. keywords: deranged liver, dengue, dhf, coagulation factors, sudan how to cite this article: bashir abdrhman bashir mohammed, (2017) “deranged liver among sudanese patients with dengue virus infection in port sudan teaching hospital,” sudan journal of medical sciences, vol. 12 (2017), issue no. 3, 187–197. doi 10.18502/sjms.v12i3.937 page 187 corresponding author: bashir abdrhman bashir mohammed; email: bashirbashir17@hotmail.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e bashir abdrhman bashir mohammed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bashirbashir17@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e 1. introduction dengue virus has recently become a major public health concern, particularly in tropical and subtropical countries, predominantly in urban and periurban areas [1]. the incidence of dengue has grown dramatically over the world in recent decades. over 2.5 billion people of the world’s population are now at risk from dengue [2]. who currently estimated there may be 50-100 million dengue infections worldwide every year [2]. the resurgence of dengue has been observed in port sudan, red sea state, sudan and dengue outbreak have been frequently reported from different part of the state in both urban and rural populations [3, 4]. dengue virus (denv) is a mosquito-borne flavivirus that is transmitted by mosquitoes such as aedes aegypti or aedes albopictus. based on the antigenic difference, denv can be divided into five different serotypes, denv 1 – 5. the most serious manifestations of the infection are dengue hemorrhagic fever (dhf) and dengue shock syndrome (dss) [5, 6]. the degree of liver dysfunction varies from mild injury with an elevation of aminotransferase to even fulminant hepatic failure [7, 8]. hepatic dysfunction in dengue infection may be attributed to direct viral effect on liver cells or as a consequence of dysregulation host immune responses against the virus [7]. jaundice in dengue infection has been associated with fulminant liver failure and by itself is a poor prognostic factor [9]. however, there is still not much work was done in the studied area regarding the liver changes of dengue infection. this study was conducted to evaluate the variations of liver dysfunction by measuring the level of the liver enzymes, prothrombin time (pt), partial thromboplastin time (ptt), fibrinogen (fb) level and coagulation mixing studies. the significance of this study is the importance of measuring the liver enzymes in the patients with dengue virus infection. 2. materials and methods a cross-sectional descriptive study was conducted in the period from february 2013 to june 2014 at port sudan teaching hospital, red sea state, sudan. three hundred thirtyfour patients who were positive for dengue infection attending the hospital and 101 healthy controls were enrolled in the study. doi 10.18502/sjms.v12i3.937 page 188 sudan journal of medical sciences production and hosting by knowledge e 2.1. inclusion and exclusion criteria all patients with clinical features and serologically positive dengue infection were included. the sample taken before hemostatic agents and blood transfusion administrated to the patients. the exclusion criteria include patients with serologically negative dengue or any other disease. 2.2. study sample the blood samples were collected from all of the studied population. 3 ml of blood was transferred to trisodium citrate buffer tube, 3 ml in plain containers and 3 ml treated with tri-potassium ethylene diamine tetra acetic acid (k3edta). the samples under standard laboratory temperature were processed to obtain serum and platelet poor plasma by using a centrifugation. the analysis was performed by expert technologists. chemical tests: aspartate aminotransferase (ast), alanine aminotransferase (alt), and c-reactive protein (crp) were examined within 2 hours of collection and determined by nycocard® method using nycocard® reader ii (sn 67498, axisshield poc as, oslo, norway). chemical tests were determined by (biosystems chemicals s. a costa brava, barcelona (spain), expiry at 8/2015). hematological tests: platelet counts were done using an automated hematology analyzer (sysmex kx-21n, b 7151, and mf 9/2008 japan). coagulation tests: pt, ptt and fb were examined within 4 hours of collection using a semi-automated blood coagulation analyzer (bio bas-1 manufactured by ral for spinreact, sn 536, spain-european community). coagulation tests were determined by (biomed diagnostic reagent, germany). 2.3. definition of dengue dengue is a disease caused by any one of five closely related dengue viruses (denv-1, -2, -3, -4, and -5) [6]. the clinical spectrum of dengue classified to df and dhf (dhf i, dhf ii, dhf iii and dhf iv) [10]. 2.4. criteria for dengue severity patients were classified as dengue fever, dengue hemorrhagic fever or dengue shock syndrome according to who guidelines. the laboratory diagnosis of dengue was established by the demonstration of igm and igg immune chromatography rapid doi 10.18502/sjms.v12i3.937 page 189 sudan journal of medical sciences production and hosting by knowledge e diagnostic test (rdt) (biotracer/biofocus, ref: 17112, exp.12/2015, korea), sensitivity 95.6 and specificity 96. 2.5. statistical analysis laboratory data of plt, coagulation tests, and chemical investigations of patients with df, dhf were statistically tested by independent-sample t test, correlation, and pearson chi-square test, whichever was appropriate. a p. value less than 0.05 were considered statistically significant. the statistical package for social sciences (spss 20.0 version, ibn. chicago, usa) was used for data analysis. 2.6. ethical considerations this study was approved by the regional ethical review committee (erc), written informed consent was obtained from all of the patients. 3. results the total number of the confirmed dengue patients was 334. of the 334 patients, (217) 65% were males and (117) 35% were female. in the control group, (64) 63.4% were males and (37) 36.6% were females. minimum age of the patient was 3 years and maximum age was 80 years with the mean age being 30±15. minimum age of control was 6 years and maximum age was 76 years with mean age 22±6. the clinical findings have been summarized in table 1. the clinical demographic manifestations of the studied group were fever (334,100%), headache (282, 84.4%), joint pain (262, 78.2%), backache (198, 59.3%), myalgia (156, 46.7%), retro-orbital pain (69, 20.7%), and rash (28, 8.4%). according to the who classification system most cases of the current study were dengue fever; followed by dengue hemorrhagic fever i (table 1). all of the patients (334) presented were screened for pt, ptt and fb. the difference between the patient group and the control group was found to be significant in prothrombin time, partial thromboplastin time, and fibrinogen level (p < 0.0001). prothrombin time, partial thromboplastin time, and fibrinogen levels were higher in the patient group than in the control (table 2). thrombocytopenia was observed in (279/334; 83.5%) of the patients. 234 (81%) presented in df cases and 45 (100%) presented in dhf cases. bleeding manifestations were observed higher in dhf than in df patients (p < 0.0001). bleeding was recorded in 35 (10.5%) cases of all dengue patients (table 3). bleeding manifestations included hematuria in 19 (54.3%) cases, doi 10.18502/sjms.v12i3.937 page 190 sudan journal of medical sciences production and hosting by knowledge e hematemesis in 1 (2.9%), hemoptysis in 1 (2.9%), epistaxis in 5 (14.2%) cases, and gum bleeds in 9 (25.7%) cases. pt was prolonged in 30 (9.0%) of the patients and normal in 304 (91%). ptt was prolonged in 42 (12.6%) of patients, shortened in 18 (5.4%) of patients, and normal in 274 (82%) of the patients. 8 (2.4%) patients had prolonged pt and ptt together. the reduced fibrinogen level was noted in 61 (18.3%), 48 (14.4%) patients had high fibrinogen level, and 225 (67.4%) was normal fibrinogen level (table 3). out of 61 patients with reduced fibrinogen 29 patients were associated with prolonged pt and ptt. there was a positive correlation between short ptt and high fibrinogen (p < 0.0003); this relationship could be interpreted as an acute phase response situation. out of 334 patients’ positive dengue infection, 101 (30.2%) had abnormal coagulation results. 81 (80.2%) patients with df and 20 (19.8%) patients with dhf were screened for special parameters such as ast, alt, and crp (table 4). the transaminase liver enzymes were relatively higher in dhf than df. 44 (43.6%) patients had an elevated level ast, while 22 (21.8%) patients had an elevated level alt. c-reactive protein was significantly higher in dhf 20 (100%) patients than the df 65 (80.3%) patients (table 5). of 101 patients 72 correction tests for pt and ptt were performed. the corrected results indicate a deficient factor. 72 mixing experimental studies for pt and ptt revealed deficiencies in factors viii 25 (35%), ix, 7 (10%), v 7 (10%), x 14 (19%), ii 9 (12%), and xii 10 (14%). this suggests the dysfunction of liver cells in respect to the decreased synthesis of these factors. 4. discussion deranged liver function in dengue infection can be a result of the direct effect of the virus on liver cells or the unregulated host immune response against the virus. hepatic dysfunction in dengue infection is often demonstrated by mild to moderate raising in transaminase enzyme levels [11]. abnormal liver tests are generally present in the first days of clinical infection and peak during the second week of illness [12]. aminotransferase levels are useful in predicting the occurrence of hepatic dysfunction and spontaneous bleeding. liver enzyme elevation is a common feature in dengue infection [13]. wang and shyn reported that ast abnormality was predominantly high as compared to alt; 91% and 72% respectively [14]. however, in this study, ast levels were equal to or greater than those of alt levels in most infected patients, a finding that has also been reported earlier [5, 15]. abnormal liver enzymes in dengue infection have been reported also by various authors and the levels varies from 36.4% 96% [16]. our study observed elevated ast in 43.2% of df, 45% of dhf and elevated alt in 21% of df, 25% of dhf. the liver enzymes were significantly more common in dhf/dss doi 10.18502/sjms.v12i3.937 page 191 sudan journal of medical sciences production and hosting by knowledge e characteristics patients (n = 334) control (n = 101) p. value age (mean ± sd) 30 ± 15 22 ± 6 0.0001 (range) 3 – 80 y 6 – 76 y sex male 217 (65%) 64 (63.4%) 0.7262 female 117 (35%) 37 (36.6%) clinical diagnosis dengue fever 289 (86.5%) dhf grade i 31 (9.3%) dhf grade ii 12 (3.6%) dhf grade iii 2 (0.6%) clinical manifestations rash (purpura) 28 (8.4%) 0.0030 fever 334 (100%) 0.0001 joint pain 262 (78.4%) 0.0001 backache 198 (59.3%) 0.0001 headache 282 (84.4%) 0.0001 myalgia 156 (46.7%) 0.0001 retro-orbital pain 69 (20.7%) 0.0001 bleeding manifestations 35 (10.5%) 0.0001 epistaxis 5 (1.5%) hematemesis 1 (0.3%) hemoptysis 1 (0.3%) hematuria 19 (5.7%) bleeding gums 9 (2.7%) t 1: the epidemiological and clinical feature of the studied population. when compared to df, a finding similar to other studies[17, 18]. souza et al reported in large studies in brazil, out of 1585 dengue cases, raised ast and alt in 63.4% and 45% of patients respectively [19]. jagadishkumar et al suggested that the higher incidence of more than 10-fold rise in liver enzymes was observed in children in comparison to adult. this may be due to that children are at higher risk of hepatic involvement [11]. ast levels rise more than alt in case of dengue and this may be due to myositis, doi 10.18502/sjms.v12i3.937 page 192 sudan journal of medical sciences production and hosting by knowledge e parameters test group mean ± sd control group mean ± sd median test median control range test range control p.value pt second 14.1± 2.1 13.3 ± 1.6 13.8 13.5 10–20.4 10-16.5 0.0001 ptt second 33.5 ± 9.7 29.6 ± 4.5 32.4 28.9 15–80.7 20-39 0.0001 fb g/dl 4.15 ± 6.99 3.26 ± 1.44 2.60 2.90 0.5 – 63.96 1.3710.23 0.0001 t 2: the difference between test and control in studied parameters. parameter dfn = 289 dhf n = 45 p. value thrombocytopenia 234 (81%) 45 (100%) 0.0001 bleeding manifest 10 (3.5%) 25 (55.6%) 0.0001 prolong pt 27 (9.3%) 3 (6.7%) 0.0001 prolong ptt 32 (11.1%) 10 (22.2%) 0.0001 hypofibrinogenemia 48 (16.6%) 13 (28.9%) 0.0001 hyperfibrinogenemia 40 (13.8%) 8 (17.8%) 0.1902 t 3: general parameters among df and dhf patients. possibly related to coexisting myositis and released of ast from the injured muscle cells [12]. in the current study the prolonged pt values presented in 9% of the all cases and it was significantly more in df (9.3%). wong et al and itha et al reported that the derangement in pt and ptt in 42.5% and 7% respectively of his cases [13, 20]. while the deranged pt and ptt in this study was 21.6%. this because that most of our cases are df 86.5% unlike the above mentioned studies most of their cases are dhf and dss. a correlation between the levels of ast and ptt shows a strong association between ast elevation and ptt prolonged time in dengue infection in our patients (p< 0.0003), this might seem to relate to the process of hepatic parenchymal damage than the biliary tract obstruction. parameters median mean ± sd range of test normal range crp 136 mg/l 125 ± 49 4 – 230 5 – 120 mg/l ast 34 u/l 54 ± 69 5 – 480 up to 40 u/l alt 22 u/l 34 ± 43 2 – 279 up to 41 u/l t 4: laboratory findings of specific parameters among the studied dengue patients. doi 10.18502/sjms.v12i3.937 page 193 sudan journal of medical sciences production and hosting by knowledge e parameters df n = 81 dhf n = 20 p. value high crp 70 (86.4%) 17 (85%) 0.2873 high ast 35 (43.2%) 9 (45%) 0.9785 high alt 17 (21%) 5 (25%) 0.6171 t 5: special parameters among df and dhf patients. fulminant hepatic failure may occur because of acute hepatitis and massive necrosis of the liver, causing hepatic encephalopathy and even death [21]; this finding was not diagnosed in our patients. with regard to crp, the level was high in dhf patients. nevertheless, this high circulating level of crp is not correlated with the severity of illness and the occurrence of complications (p< 0.0966). a study by shiann et al [22] in taiwan showed that patients with dengue infection were more likely to have low crp, which is different from our results, this difference may be due to the environmental factor and sample size numbered. in contrast, juffrie et al [23] reported a high level of crp in their study and kutsuna et al [24] who reported that crp is useful to indicate the dengue fever; our findings are consistent with them. the advantage of this study is that it is prospective and only serological confirmed positive dengue infected patients were enrolled. the limitation of this study is that liver biopsy was not performed in any patients to confirm the diagnosis. this study could be considered a base for the future studies regarding the liver damage. 5. conclusion in summary, this study demonstrated that hepatic dysfunction may be attributed to dengue virus infection which evident by prolongation in pt and ptt as well as hypofibrinogenemia and factor deficiencies. the presence of bleeding may be useful in predicting the extent of liver involvement. 6. acknowledgement the author would like to knowledge the support of port sudan teaching hospital of this project. 7. competing interest the author declares that they have no competing interests. doi 10.18502/sjms.v12i3.937 page 194 sudan journal of 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[20] m. wong and e. shen, “the utility of liver function tests in dengue,” ann acad med, vol. 37, no. 1, p. 82, 2008. [21] r. karoli, j. fatima, z. siddiqi, k. i. kazmi, and a. r. sultania, “clinical profile of dengue infection at a teaching hospital in north india,” the journal of infection in developing countries, vol. 6, no. 07, 2012. [22] t.-s. ho, s.-m. wang, y.-s. lin, and c.-c. liu, “clinical and laboratory predictive markers for acute dengue infection,” journal of biomedical science, vol. 20, no. 1, article 75, 2013. [23] m. juffrie, g. m. vo meer, c. e. hack et al., “inflammatory mediators in dengue virus infection in children: interleukin-6 and its relation to c-reactive protein and secretory phospholipase a2,” american journal of tropical medicine and hygiene, vol. 65, no. 1, pp. 70–75, 2001. doi 10.18502/sjms.v12i3.937 page 196 sudan journal of medical sciences production and hosting by knowledge e [24] s. kutsuna, k. hayakawa, y. kato et al., “the usefulness of serum c-reactive protein and total bilirubin levels for distinguishing between dengue fever and malaria in returned travelers,” american journal of tropical medicine and hygiene, vol. 90, no. 3, pp. 444–448, 2014. doi 10.18502/sjms.v12i3.937 page 197 introduction materials and methods inclusion and exclusion criteria study sample definition of dengue criteria for dengue severity statistical analysis ethical considerations results discussion conclusion acknowledgement competing interest availability of data and material ethics approval references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9287 production and hosting by knowledge e research article knowledge and practice regarding coronavirus disease prevention (covid-19) among internally displaced persons in camps in central darfur region, sudan mohammed abdelkrim adam abdelmalik1,2, abdalbasit adam mariod3,4, mohamed adam beraima5, hammad ali fadlalmola6, eltagi elsadeg sulliman rahama7, huda khalafallah masaad8, mohammed ibrahim osman ahmed9,10, ibrahim abbakr ibrahim abbakr11, eyas gaffar abdelraheem osman12, and ibrahim musa ibrahim hassan13 1department of medical–surgical nursing, college of applied medical sciences, shaqra university, saudi arabia 2faculty of nursing, university of elimam el mhadai, kosti city, sudan 3department of food chemistry. a-college of sciences and arts-alkamil, university of jeddah, saudi arabia 4indigenous knowledge and heritage center, ghibaish college of science and technology, ghibaish, sudan 5department of medical–surgical nursing, alghad international colleges for applied medical sciences, dammam, saudi arabia 6department of community health nursing, taibah university, almadenah, saudi arabia 7department of medical–surgical nursing, faculty of nursing sciences, university of el imam el mhadai, aba island, sudan 8department of medical–surgical nursing, applied medical science college, hafr albatin university, saudi arabia 9department of medical–surgical nursing, erada complex for mental health, riyadh, ksa 10faculty of nursing, university of el imam el mhadai, kosti city, sudan 11department of nursing practice, college of nursing, umm alqura university, ksa 12department of econometric and statistical data analysis, college of community, shaqra university, saudi arabia 13department of community health nursing, faculty of health sciences, university of zalingei, central darfur, sudan orcid: mohammed abdelkrim adam abdelmalik: https://orcid.org/0000-0002-3161-8351 abdalbasit adam mariod: https://orcid.org/0000-0003-3237-7948 hammad ali fadlalmola: https://orcid.org/0000-0002-5065-9626 mohammed ibrahim osman ahmed: https://orcid.org/0000-0002-1894-5446 ibrahim abbakr ibrahim abbakr: https://orcid.org/0000-0002-8505-7449 eyas gaffar abdelraheem osman: https://orcid.org/0000-0001-8384-3705 abstract background: the lacking healthcare system services in conflict areas and the emergence of infection with a pandemic of coronavirus disease may exacerbate the humanitarian crisis among the camp residents in the central dafur region of sudan. adequate knowledge and practices are vital to prevent coronavirus disease 2019 (covid-19). therefore, this study aimed to investigate the knowledge and practice regarding covid-19 among internally displaced persons in sudan. how to cite this article: mohammed abdelkrim adam abdelmalik, abdalbasit adam mariod, mohamed adam beraima, hammad ali fadlalmola, eltagi elsadeg sulliman rahama, huda khalafallah masaad, mohammed ibrahim osman ahmed, ibrahim abbakr ibrahim abbakr, eyas gaffar abdelraheem osman, and ibrahim musa ibrahim hassan (2021) “knowledge and practice regarding coronavirus disease prevention (covid-19) among internally displaced persons in camps in central darfur region, sudan,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 178–195. doi 10.18502/sjms.v16i2.9287 page 178 corresponding author: mohammed abdelkrim adam abdelmalik, assistant professor of medical-surgical nursing; college of applied medical sciences, shaqra university, saudi arabia. faculty of nursing, university of elimam el mhadai, kosti city, sudan. phone number: +966504543043 email: mohammedabdelkrim9@gmail.com received 11 april 2021 accepted 3 may 2021 published 30 june 2021 production and hosting by knowledge e mohammed abdelkrim adam abdelmalik et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://orcid.org/0000-0002-3161-8351 https://orcid.org/0000-0003-3237-7948 https://orcid.org/0000-0002-5065-9626 https://orcid.org/0000-0002-1894-5446 https://orcid.org/0000-0002-8505-7449 https://orcid.org/0000-0001-8384-3705 mailto:mohammedabdelkrim9@gmail.com mailto:mohammedabdelkrim9@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al methods: in this cross-sectional study, data were collected through an online survey using a self-administered questionnaire. convenience sampling method was used for the internally displaced persons in two camps of zalingei town, central darfur region, sudan. results: in total, 143 participants responded; 75 (52.4%) of them were female, while 68 (47.6%) were male; 49 (34.3%) were between the age of 50 and 60 years; 78 (54.5%) were formally uneducated; 126 (88.1%) did not have a chronic disease; and 56 (39.2%) knew about covid-19 from their relatives and friends. the overall mean of participants’ knowledge toward covid-19 was 3.68 (sd ± 0.60(, denoting good with a rate of 73.6% and that of the practice was 2.65 (sd ±1.08), denoting moderate with a rate of 53%. a positive correlation was seen between knowledge and practice (r = 0.700, p < 0.000). statistically significant differences were observed between the mean score of knowledge and practice with age, education, and information sources (p < 0.0001). while graduates showed a higher knowledge (116.29, p = 0.000), secondary respondents showed a higher practice (115.04, p = 0.000) than others. conclusion: this study suggests educational intervention and awareness programs for uneducated and older people. keywords: darfur, camp residents, knowledge, practical measures, covid-19 1. introduction the coronavirus disease 2019 (covid-19) is continuously introducing change in our lifestyle. recently, it has had considerable effects on global health, economic, and social aspects [1]. the pandemic has led to the cause of morbidity and mortality worldwide [2]. coronaviruses are a large family of viruses and exist in both animals and humans. the viruses could cause illnesses ranging from the common cold to severe diseases such as severe acute respiratory syndrome (sars) observed in november 2002 and the middle east respiratory disorder (mers) that emerged in september 2012 and transmitted from camels [3, 4]. in december 2019, wuhan city of china reported a new strain of coronavirus disease, recognized as the covid-19 virus. on march 11, 2020, who confirmed it as a global pandemic [5]. to date, many coronaviruses have appeared from animal reservoirs. the symptoms of covid-19 include fever, dry cough, tiredness, muscle pain, and difficulty in breathing. some patients complain of aches, runny nose, sore throat, and diarrhea, usually gradually. however, some individuals could also be asymptomatic. approximately 80% of cases recover from the illness without needing specific treatment [6–8]. people with doi 10.18502/sjms.v16i2.9287 page 179 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al diabetes, heart disease, respiratory disease, hypertension, or those aged >60 years are at greater risk of developing severe disease. the incubation period for the novel coronavirus is about 1–14 days, with an average of 5–6 days [4, 9, 10]. the covid-19 virus is mainly transmitted through respiratory droplets. an infected person can transmit the disease by coughing, sneezing, or talking closely (within a distance of six feet) to another. also, individuals may become infected by touching contaminated surfaces or objects and then touching their eyes, nose, or mouth. however, there is no evidence that the covid-19 virus is transmitted through houseflies. the preventive measures from infection frequently include handwashing with soap and water for least 20 sec or using an alcohol-based handrub, staying home/indoors, avoiding crowded places, avoiding touching mouth, eyes, or nose with dirty hands, covering mouth and nose with a disposable tissue when coughing or sneezing or using elbow if no tissue is available [11, 12]. knowledge of the covid-19 pathway and relevant precautions is essential in controlling the pandemic. knowledge such as washing hands frequently or using alcohol-based handrub, wearing face masks, covering nose and mouth when coughing or sneezing, maintaining social distancing, and self-isolation when sick is crucial to reducing the widespread infection. also, adequate knowledge motivates people to make quick decisions that may prevent and control epidemics [13]. prompt preventive measures are necessary at the early stages of prevalence to protect against the disease spread. knowledge and perceptions of people affect their behavior [14]. determining public’s opinion may prove crucial in determining the outcome of covid-19 [15] some pieces of evidence have shown a deficit of knowledge, attitudes, and a lack of community practices regarding covid-19 [16, 17]. in sudan, authorities and health ministries are striving to reduce its widespread in all country borders. according to the federal ministry of health of sudan, the recent cases have continued to speed up in sudan after the first covid-19 case was confirmed on march 13, 2020, for a 50-year-old man who traveled from an arabic country (18). most people affected by the war live in the bare region; they have difficulty accessing health information. also, there is little information about the new disease’s knowledge and practical measures among internally displaced persons. besides, it shows limited studies in sudan to explore internally displaced persons’ knowledge and practice (kp) regarding covid19. therefore, our current study aimed to first investigate the kp regarding covid19 prevention among internally displaced persons in sudan. second, to check the correlation between kps of the study variable. and third, to find out any differences within demographic variables and kps of the study population. doi 10.18502/sjms.v16i2.9287 page 180 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al 2. materials and methods 2.1. study design, setting, and population this cross-sectional and community-based study was conducted to investigate the kp regarding covid-19 prevention among internally displaced persons in two camps (hamadiya and el hassahissa camps) of central darfur around zalingei city, sudan between april 4, 2020 and may 1, 2020. darfur region lies in western sudan, which is approximately 493,180 km2 in area and has a population of nearly six million. it comprises of the states of north, west, south, east, and central darfur. however, since the breaking out of the conflict in 2003, around 1.9 million people have been internally displaced people (idp), and nearly 60% of them are children living in camps as a result of the war conflict [19]. the internal conflicts affected the healthcare system’s services reported by the united nations, which left a vast humanitarian crisis around over one million internally displaced people in the darfur region. in addition, there is a shortage of primary, secondary, and tertiary healthcare for pregnant women, children aged <5 years, those who lost their families, breastfeeding women, and elderly people [21]. zalingei city is in the central darfur region and is one of the urban areas surrounded by three camps of idp: the hesahesa, the al hamedia plus the teyba, as a result of the war conflict [20]. the hesahesa and the al hamedia camps are bigger than others and close to zalingei city. 2.2. sample size and technique we used both manual and online google forms for data collection through convenience sampling and snowball sampling. we trained two data collectors who were nurses with a diploma. in the manual method of data collection, we maintained protective measures of covid-19, such as social distancing and wearing a face mask during data collection. in the online method, we distributed google forms link through social networking platforms such as whatsapp groups in the camps. initially, data for 159 people were collected through nonprobability sampling, but only 143 eligible participants meeting the inclusion criteria were included in the survey. doi 10.18502/sjms.v16i2.9287 page 181 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al 2.3. inclusion and exclusion criteria those participants who were willing to join the survey were included, while those who were unwilling to participate, were a non-resident of the camps, and those who pretested in the pilot test were excluded. 2.4. data collection instrument the researchers developed a questionnaire in the english language from a literature review based on guidelines [22–24]. we created an arabic version of the original questionnaire and back-translated it into english for validity by three experts in the english language to match the original questionnaire. the researchers administered the final arabic questionnaire to participants because the arabic language is the primary language in sudan. the researchers conducted a pilot study on 10 participants. according to pretest findings, the researchers made corrections for the feasibility, content applicability, and duration before starting the actual data collection phase—the participants of the pilot study were excluded from the actual study. we conducted the reliability test for internal consistency, and it was good. the cronbach’s alpha coefficient of the tool assessing kps regarding covid-19 was 0.879 and 0.924, respectively. as a thumb rule, values <0.6 are considered poor, 0.6–0.7 are acceptable, and >0.7 are good. the questionnaire comprised of three parts. part one included seven demographic variables: gender, age, education level, previous disease, tobacco use, the camp resident’s name, and information sources. the second part comprised of 10 questions assessing the respondent’s knowledge related to covid-19 based on a five-point likerttype scale to measure the level of knowledge as follows: always true (5 points), usually true (4 points), neutral (3 points), rarely true (2 points), and never true (1 point). part three comprised of 10 items of practice toward preventive measures against covid-19. every question was rated on a 5-point likert scale to measure the level of practice ranging from never do (1 point), rarely do (2 points), sometimes do (3 points), often do (4 points), and always do (5 points). the total mean scores of all answers in kp were computed. while scores above the mean score indicated high kp, scores lower than mean scores indicated low kp. the total scores of kps were converted into percentages by dividing the total obtained score of each part by the same part’s maximum score and multiplied by a 100. doi 10.18502/sjms.v16i2.9287 page 182 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al we used a five-point likert scale with intervals created with the majority of the differences being constant (0.79) except for the last one that is wider and has a slighter difference of (0.1) among the rest [25]. the likert scale is explained as follows: 1 = 1.00–1.79 = never 2 = 1.80–2.59 = rare 3 = 2.60–3.39 = sometimes 4 = 3.40–4.19 = often 5 = 4.20–5.00 = always 2.5. statistical analysis we used a statistical package of social sciences (spss) version 25 to analyze this study, including descriptive statistics and inferential statistics. the non-parametric tests (mann– whitney u-test, kruskal–wallis, and spearman correlation coefficient) were conducted to analyze the data because the kolmogorov–smirnov test abnormally distributed the data preliminarily. the significance level was at < 0.05. 3. results 3.1. demographic characteristics in this study, 143 participants responded to the survey. the majority, that is, 75 (52.4%) of them were female, while 68 (47.6%) were male; 49 (34.3%) of them were ages between 50 and 60 years; 78 (54.5%) were formally uneducated; 126 (88.1%) of them did not have a chronic disease; and 56 (39.2%) knew about covid-19 from their relatives and friends, as shown in table 1. 3.2. assessment of knowledge toward covid-19 the current results showed that more than half (51.7%) of the participants neutrally responded that coronaviruses are a large group of viruses and may cause disease in animals and humans. however, less than half of the participants answered correctly about the type and origin of the infection (43.4%) and its signs and symptoms (42.7%). also, nearly half of them responded neutrally about the transmission (42.7%), the incubation period of covid-19 (47.6%), no definite treatment (49.0%). besides, about half of the participants answered correctly about the effective ways to reduce the spread of doi 10.18502/sjms.v16i2.9287 page 183 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al table 1: distribution of demographic characteristics of the participants (n = 143). variable frequency percentage gender male 68 47.6 female 75 52.4 age (yr) <20 6 4.2 20–30 24 16.8 30–40 22 15.4 50–60 49 34.3 >60 42 29.4 education level formally uneducated 78 54.5 primary 34 23.8 secondary 14 9.8 graduate 17 11.9 do you have asthma, diabetes, or heart disease? yes 17 11.9 no 126 88.1 do you smoke? yes 11 7.7 no 132 92.3 source of information radio 25 17.5 television 11 7.7 health workers 14 9.8 workers in humanitarian aid organizations 7 4.9 relatives and friends 56 39.2 mosque 20 14.0 social media, facebook, whatsapp 10 7.0 the virus (42.7%), agreed that avoiding crowded places is an effective way to reduce the spread of the disease (40.6%), and that the new coronavirus disease may lead to death (48.3%). the overall mean score of respondents’ knowledge was 3.69 (sd = 0.60, range: 1–5) denoting good with a rate of 73.8% (3.69/5*100) about covid-19, as shown in table 2. 3.3. assessment of practice toward prevention of covid-19 answers related to practice toward preventing covid-19 showed that 52 (36.4%) participants did not practice frequent handwashing, 39 (27.3%) did not refrain from touching doi 10.18502/sjms.v16i2.9287 page 184 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al table 2: distribution of participants’ knowledge regarding covid-19 (n = 143).* questions frequency (%)* always true usually true neutral rarely true never true coronaviruses are a large group of viruses that may cause disease in animals and humans? 21 (14.7%) 45 (31.5%) 74 (51.7%) 2 (1.4%) 1 (0.7%) the new corona disease is an infectious disease discovered in the chinese city of wuhan? 30 (21.0%) 62 (43.4%) 46 (32.2%) 0 (0.0%) 5 (3.5%) the symptoms of coronavirus disease are fatigue, dry cough, and fever? 36 (25.2%) 61 (42.7%) 41 (28.7%) 4 (2.8%) 1 (0.7%) coronavirus transmission occurs through direct contact with droplets dispersed from an infected person, touching contaminated surfaces, and then touching the eyes, nose, and mouth? 23 (16.1%) 49 (34.3%) 61 (42.7%) 7 (4.9%) 3 (2.1%) the incubation period of coronavirus disease ranges from one to fourteen days? 23 (16.6%) 44 (30.8%) 68 (47.6%) 5 (3.5%) 3 (2.1%) the elderly and people with high blood pressure, heart disease, lung disease, cancer, or diabetes are more likely to develop severe complications? 30 (21.0%) 56 (39.2%) 51 (35.7%) 0 (0.0%) 6 (4.2%) there is currently no definite treatment that can prevent or treat the new coronavirus disease? 23 (16.1%) 35 (24.5%) 70 (49.0%) 14 (9.8) 1(0.7%) isolating infected people is one of the effective ways to reduce the spread of the virus? 24 (16.8%) 61 (42.7%) 49 (34.3%) 6 (4.2%) 3 (2.1%) avoiding going to crowded places is an effective way to reduce the spread of the disease? 31 (21.7%) 58 (40.6%) 46 (32.2%) 5 (3.5%) 3 (2.1%) the new coronavirus disease may lead to death? 33 (23.1%) 69 (48.3%) 34 (23.8%) 5 (3.5%) 2 (1.4%) overall mean score 3.69 (sd =±±± 0.60) 73.8% note: *the frequency and percentages are based on n =143. sd: standard deviation. 5-point likert scale (range 1–5), mean score 1–2.59 denotes low, 2.60–3.39 denotes moderate, and 3.40–5 denotes high knowledge. their eyes or nose, and 47 (32.9%) never covered their mouth and nose with an elbow or tissue when coughing or sneezing. additionally, 52 (36.4%) of them answered that they never maintained a distance of 3 feet, 51 (35.7%) did not follow the “staying at home doi 10.18502/sjms.v16i2.9287 page 185 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al table 3: frequency of practice responses regarding covid-19 (n = 143).* n (%) questions always often sometimes seldom never do you frequently clean hands using alcohol-based hand rub or soap and water; after contact or doing anything? 13 (9.1) 29 (20.3) 43 (30.1) 6 (4.2) 52 (36.4) do you try to avoid touching your eyes, nose with your unclean hand? 14 (9.8) 36 (25.2) 38 (26.6) 16 (11.2) 39 (27.3) do you try to cover your mouth and nose with a flexed elbow or a tissue when coughing and sneezing? 13 (9.1) 23 (23.1) 32 (22.4) 18 (12.6) 47 (32.9) do you maintain at least 3 feet distance between yourself and anyone who is coughing or sneezing? 15 (10.5) 26 (18.2) 24 (16.8) 26 (18.2) 52 (36.4) do you stay at home and limit going out as necessary? 11 (7.7) 30 (21.0) 26 (18.2) 25 (17.5) 51 (35.7) do you try to avoid shaking hands when you meet your relatives? 12 (8.4) 22 (15.4) 29 (20.3) 19 (13.3) 61 (42.7) do you attempt to avoid sharing objects that touch your mouths, such as cups, dishes, and bottles? 10 (7.0) 37 (25.9) 23 (16.1) 17 (11.9) 56 (39.2) do you wear a mask all time if you have symptoms of fever, cough, and difficulty breathing? 21 (14.7) 17 (11.9) 15 (10.5) 15 (10.5) 75 (52.4) do you try to avoid the consumption of undercooked animal products such as raw meat, milk, or animal organs? 65 (45.5) 40 (28.0) 13 (9.1) 8 (5.6) 17 (11.9) do you isolate yourself in the room from family if you have a headache and runny nose until you recover? 13 (9.1) 35 (24.5) 24 (16.8) 18 (12.6) 53 (37.1) overall mean score of practice 2.65 (sd =± 1.08) 53.0% note: *the frequency and percentages are based on n = 143. sd: standard deviation. 5-point likert scale (range 1–5), mean score 1–2.59 denotes low, 2.60–3.39 denotes moderate, and 3.40–5 denotes good practice. and limiting going out” protocol, 61 (42.7%) participants answered that they did not avoid shaking hands, and 56 (39.2%) practiced no measures to avoid sharing objects such as cups, dishes, and bottles. also, 75 (52.4%) participants never wore a mask all time even if they had symptoms of fever, cough, and difficulty breathing and 53 doi 10.18502/sjms.v16i2.9287 page 186 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al table 4: normality test in the study sample (143). normal parameter overall mean score of knowledge overall mean score of practice asymp. sig. (2-tailed) mean 3.6916 2.6538 0.002* standard deviation 0.60041 1.08041 0.000* note: we used one-sample kolmogorov–smirnov test. *statically significant at p-value < 0.05. table 5: correlation between knowledge and practice of the study variable. variable rho p-value knowledge and practice 0.700** 0.000** note: spearman’s rho test was used. *statically significant at p-values < 0.05. (37.1%) participants never isolated themselves until recovery. however, nearly half of them responded always to avoid consuming undercooked animal products that is, 65 (45.5%). the overall mean score of respondents’ practice was 2. 65 (sd =1. 08, range: 1–5), denoting moderate practice toward preventive measures against covid-19 with a rate of 53% (2. 65 /5*100) regarding covid-19 as shown in table 3. 3.4. normality test in this, we used the kolmogorov-smirnov test to examine the normality of the data for the knowledge, practice (kp) of participants in the study sample. the current results revealed not normally distributed data in mean scores of kpm (p< 0.000) in table 4. therefore, we adopted non-parametric tests to analyze the rest of the data. 3.5. correlation between knowledge and practice (kp) of study variables 3.5.1. testing correlation hypothesis h0: there is no significant correlation between knowledge and practice of study variables. h1: there is a significant correlation between knowledge and practice of study variables. we tested the hypothesis of a correlation between knowledge and practice by spearman’s rho non-parametric test. we observed a strong correlation between knowledge and practice (r = 0.70**, p < 0.000). therefore, the test that supported the alternative hypothesis is mentioned in table 5. doi 10.18502/sjms.v16i2.9287 page 187 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al table 6: comparison of mean scores of knowledge and practice with demographic characteristics (n = 143). variable n k-average 3.69 ±±± 0.60 mean rank p-value n paverage 2.65 ±±± 1.08 mean rank p-value gender male 68 70.88 0.758 68 69.90 0.564 female 75 73.01 75 73.90 age (yr) <20 6 117.83 0.000* 6 105.17 0.000* 20–30 24 107.69 24 98.79 30–40 22 86.41 22 74.30 50–60 49 63.31 49 67.29 >60 42 47.65 42 56.25 education level uneducated 78 45.78 0.000* 78 47.25 0.000* primary 34 92.85 34 94.82 secondary 14 113.68 14 115.04 graduate 17 116.29 17 104.47 do you have asthma, diabetes, heart disease? yes 17 40.88 0.001 17 45.97 0.006 no 126 76.20 126 75.51 do you smoke? yes 11 98.05 0.029 11 88.68 0.164 no 132 69.83 132 70.61 source of information radio 25 85.52 0.000* 25 93.08 0.000* television 11 108.09 11 116.41 health workers 14 110.68 14 113.89 workers in humanitarian aid organizations 7 105.93 7 100.00 relatives and friends 56 45.91 56 41.50 mosque 20 48.88 20 59.95 social media, facebook, whatsapp 10 112.95 10 87.10 note: *statically significant at –p-values < 0.05. we used non-parametric tests, mann–whitney u-test, kruskal–wallis test. k-average: knowledge mean score; paverage: practice mean score. 3.6. compare mean scores of kp and demographic characteristics. 3.6.1. testing differences hypothesis h0: there are no significant differences between the knowledge and practice of idps with demographic characteristics. doi 10.18502/sjms.v16i2.9287 page 188 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al h1: there are significant differences between the knowledge and practice of idps with demographic characteristics. we compared the mean scores of knowledge and practice with each demographic characteristic to determine any differences within them. we used inferential statistics tests such as mann–whitney u-test for two independent groups and the kruskal–wallis test for more than two independent groups to compare mean scores of knowledge and practice variables with their demographic characteristics. we found significant differences between the mean scores of knowledge, practice, and all age groups. the participants that were aged <20 years (117.83) showed higher knowledge and practice than other age groups. also, we observed a significant difference in educational level. graduates (116.29) showed a statistically significantly higher average score of knowledge than other levels. similarly, those with secondary education (115.04) showed a statistically significantly higher average score of practice. and accordingly, uneducated people exhibited significantly less knowledge (45.78) and practice (47.25), respectively. there was a significant difference between the mean score of knowledge with people who did not have medical disease and smokers and information source. respondents who received their information from social media, facebook, whatsapp (112.95) showed higher knowledge than others, while respondents who received their information from television (116.41) showed significantly higher practice. however, we did not notice any statistically significant difference in the mean scores of the knowledge and practice with gender (p > 0.05) (table 6). 4. discussion this study aimed to investigate the knowledge and practice of covid-19 among idps in sudan. the current study revealed that most respondents gained information about covid-19 from their relatives and friends; this could be the limitation of social media sources and internet services in conflict regions. conversely, a study conducted in india reported that the primary sources of information about the disease were television and social media [26]. our research found that the respondent’s overall mean score of knowledge regarding covid-19 was good with the rate was 73.8% (3.69/5*100), and they responded correctly about the type, origin, signs, and symptoms of the infection, complications, and ways to reduce the spread of the virus. this high knowledge among the internally displaced populations may be from their relatives and friends. however, a study conducted among idps in somalia found that most participants did not know about basic coronavirus prevention measures [27]. the researchers tested the correlation doi 10.18502/sjms.v16i2.9287 page 189 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al between the study variable of kps; the spearman’s rho test demonstrated a significant positive, strong correlation between knowledge and practice regarding covid-19 prevention. this result explains that participants with high knowledge regarding covid19 disease can adopt reasonable and positive practical measures toward preventing covid-19. in contrast, a previously community-based study in addis ababa, ethiopia revealed a weak correlation between knowledge and practice, but only a moderate positive correlation between respondents’ knowledge and attitude [28]. we tested the hypothesis to compare overall mean scores of knowledge and practice variables with demographic characteristics to determine the differences. we found that the participants aged <20 years revealed significantly higher knowledge than other age groups. the graduates showed a statistically significantly higher average score of knowledge than other educational levels. however, uneducated people exhibited significantly less knowledge and practice. there is no formal education program campaign to increase their awareness and adherence to practical measures against covid-19. besides, there is limited access to online social-medical services in rural areas like the darfur region. the studies are in line with those conducted in pakistan and india that reported that older people had poor knowledge compared to students and graduates [22, 23]. however, a study conducted in malaysia reported that knowledge scores were higher among females, higher income group, and those aged >50 [29]. thus, we suggest focusing on continuous educational intervention and awareness programs for illiterates, less educated, and older people in future. in the current study, the respondents’ overall mean score was 2.65+1.08 with a rate of 53%, denoting moderate practice toward preventive measures against covid-19. respondents belonging to the younger ages and secondary education level showed significantly higher practice. however, those aged >60 years, uneducated respondents, and those who received their source of information from relatives and friends showed significantly low practice. there is no formal education program among older people to increase their adherence to practicing preventive measures against covid-19. in contrast, young people and graduates gained the information of covid-19 from social media, facebook, and whatsapp. the result of our study is similar to a study conducted in pakistan that reported that preventive practices toward covid-19 were far from satisfactory. the study attributed poor behavior of practice because the study participants were older, formally uneducated, lived in the countryside, and had limited access to online health information resources [30]. therefore, we suggest an urgent focus on the campaign to increase awareness of practical measures by demonstrating correct handwashing, wearing a mask, maintaining social distances, and avoiding doi 10.18502/sjms.v16i2.9287 page 190 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al crowded areas. since primary preventive measures from infection were frequently handwashing with soap and water for least 20 sec or using an alcohol-based handrub, staying at home, avoiding crowded places, avoiding touching eyes, nose, or mouth with unwashed hands, covering the mouth and the nose with a disposable tissue when coughing or sneezing or using elbow if no tissue is available. it is also essential to avoid close contact with anyone who has had a respiratory infection and maintaining at least a 1 m distance socially (11,12). 5. conclusion most respondents had adequate knowledge and moderate practice toward covid-19. participants with a high level of education, namely secondary education and graduates, showed higher knowledge and practice toward covid-19 than others. our findings suggest an urgent need for educational intervention and awareness programs to focus on uneducated and older people. limitations this current study has some limitations. first, the study was conducted among sudanese idp population in the central darfur region, namely in zalingei city. second, we used a convenience sampling technique of a non-probability sampling method. we used both manual and online google forms for data collection through convenience sampling and snowball sampling. thus, the results do not represent the entire idp population of sudan. implications our findings from this study may contribute to the existing literature. it may help the health policymakers plan awareness programs to raise consciousness and improve practical infection control measures against covid-19 among the idp population that may thereby reduce the spreading of the new coronavirus disease pandemic in the darfur region. doi 10.18502/sjms.v16i2.9287 page 191 sudan journal of medical sciences mohammed abdelkrim adam abdelmalik et al acknowledgements the authors express gratitude to all participants who voluntarily agreed to take part in this study. ethical considerations the study was approved by the faculty of nursing sciences’ ethical committee, university of el imam el mahdi (approval no/fns/2020/02). researchers explained the study’s purpose to all study participants and achieved informed consent before proceeding with the questionnaire, and respondents were free to withdraw. all their responses were kept anonymous and strictly confidential and were used for research only; the results did not recognize the participants personally. competing interests the authors declare that there is no competing or conflict of interest. availability of data and material all materials of this study are available from the corresponding author upon reasonable request. funding nil. references [1] oldekop, j. a., horner, r., hulme, d., et al. 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(2019). some biases in likert scaling usage and its correction. international journal of sciences: basic and applied research. retrieved from: http://gssrr.org/index.php?journal=journalofbasicandapplied [26] goruntla, n., bhupalam, p., jinka, d. r., et al. (2020). knowledge, perception, and practices towards covid-19 pandemic among general public of india: a crosssectional online survey. current medicine research and practice, vol. 10, no. 4, pp. 153–159. [27] alawa, j., al-ali, s., walz, l., et al. (). knowledge and perception of covid-19, prevalence of pre-existing conditions, and access to essential resources and health services in somali idp camps. medrxiv. retrieved from: https://doi.org/10.1101/2020. 08.17.20176271 [28] desalegn, z., deyessa, n., teka, b., et al. (2021). covid-19 and the public response: knowledge, attitude and practice of the public in mitigating the pandemic in addis ababa, ethiopia. plos one, vol. 16, no. 1, p. e0244780. [29] azlan, a. a., hamzah, m. r., sern, t. j., et al. (2020). public knowledge, attitudes and practices towards covid-19: a cross-sectional study in malaysia. plos one, vol. 15, no. 5, p. e0233668. [30] salman, m., mustafa, z. u., asif, n., et al. (2020). knowledge, attitude and preventive practices related to covid-19: a cross-sectional study in two pakistani university populations. drugs & therapy perspectives. retrieved from: https://www.ncbi.nlm. nih.gov/pmc/articles/pmc7210795/ doi 10.18502/sjms.v16i2.9287 page 195 https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters http://gssrr.org/index.php?journal=journalofbasicandapplied https://doi.org/10.1101/2020.08.17.20176271 https://doi.org/10.1101/2020.08.17.20176271 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7210795/ https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7210795/ introduction materials and methods study design, setting, and population sample size and technique inclusion and exclusion criteria data collection instrument statistical analysis results demographic characteristics assessment of knowledge toward covid-19 assessment of practice toward prevention of covid-19 normality test correlation between knowledge and practice (kp) of study variables testing correlation hypothesis compare mean scores of kp and demographic characteristics. testing differences hypothesis discussion conclusion limitations implications acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9705 production and hosting by knowledge e research article prevalence and severity of dental fluorosis among primary school children aged 12–14 years in abosied and alfetehab localities, omdurman, sudan hagir abd rahman mahmoud ali1 and moneer mohammed alhassn algdal2 1faculty of dental and oral medicine, kararay university, omdurman, sudan 2omdurman military hospital, omdurman, sudan orcid: hagir abd rahman mahmoud ali: https://orcid.org/0000-0002-4969-6614 abstract background: dental fluorosis is a disease of dental hard tissues resulting from excess fluoride intake during the developmental stages of teeth causing hypomineralization of the enamel. this study aimed to assess the prevalence of dental fluorosis among school children in omdurman locality. methods: students in the sixth grade of school were examined to determine the prevalence of dental fluorosis using dean’s index. results: the prevalence of dental fluorosis was 68.3%. the majority of students were diagnosed with very mild (23.2%) and mild (26.5%) forms. there was no difference in the grade of fluorosis between children who were born outside and in omdurman. conclusion: prevalence of dental fluoride was found to be very high among school children with no difference between males and females. keywords: fluorosis, sudan, school children 1. introduction fluoride is a natural element found in drinking water. consumption of fluoride is essential because of its impact on dental health. fluoride ions replace the hydroxyl in the hydroxyapatite crystals resulting in fluorapatite crystals which decreases the solubility of tooth structures [1]. the optimal fluoride concentration in drinking water which promotes dental health is 0.5–1.5 mg/l [2, 3]. however, there are areas with low fluoride levels, so these individual communities added fluoride to their drinking water in a procedure called fluoridation [4]. this was done to increase the concentration of fluoride in drinking water to prevent dental caries and protect tooth development in young children. on the other hand, fluoride content of 1.5–4 mg/l in drinking water leads to dental fluorosis, and concentrations >4 mg/l lead to dental, skeletal, and crippling fluorosis how to cite this article: hagir abd rahman mahmoud ali and moneer mohammed alhassn algdal (2021) “prevalence and severity of dental fluorosis among primary school children aged 12–14 years in abosied and alfetehab localities, omdurman, sudan,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 475–483. doi 10.18502/sjms.v16i3.9705 page 475 corresponding author: hagir abd rahman mahmoud ali; email: hagir3@hotmail.com received 26 july 2021 accepted 09 july 2021 published 30 september 2021 production and hosting by knowledge e . this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hagir3@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences [2, 3]. dental fluorosis is a developmental disease caused by excessive intake of fluoride during the periods of tooth development leading to hypomineralization of the enamel [5, 6]. in most areas of sudan, water from wells is used for domestic and livestock consumption, and as high concentration of fluoride in water are generally found in groundwater, this study therefore aims to assess the prevalence of dental fluorosis. 2. materials and methods this school-based, cross-sectional study was conducted during the school health program held by the faculty of dentistry, karary university. the program targeted 13 public schools in abosied and alfetehab localities in omdurman city. the target group was students studying in the sixth grade of school excluding children with orthodontic brackets, crowns, or fractured anterior teeth. the clinical examination was carried out in the school premises by the researcher. children were seated on ordinary chair under natural day light, the examinations were carried out without prior cleaning or drying of the teeth and the instruments used were sterilized mouth mirror, probe, and dental tweezer. the severity of the fluorosis was assessed using dean’s index which is a six-point ordinal scale [7] (table 1). table 1: dean’s index for dental fluorosis [7]. classification criteria normal (0) the enamel represents the usual translucency with smooth and glossy surface with a pale, creamy color. questionable (0.5) a definitive diagnosis of the mildest form of fluorosis is not warranted and a classification of ”normal” not justified. very mild (1) small opaque, white areas that are scattered or streaked over the tooth, but not involving as much as approximately 25% of the tooth surface. mild (2) the white opaque areas in the enamel of the teeth are more extensive, but do not involve as much as 50% of the tooth surface. moderate (3) all enamel surfaces of the teeth are affected, and surfaces subject to attrition show wear. brown stain is frequently a disfiguring feature. severe (4) all enamel surfaces are affected and hypoplasia is marked that the general form of the tooth may be affected. discrete or confluent pits are extensive and brown stains are widespread. doi 10.18502/sjms.v16i3.9705 page 476 sudan journal of medical sciences 3. results the study was performed on 578 students of which 411 (71.1%) were girls and 167 (28.9%) were boys. the mean age of subjects surveyed was 11.6 ± 1 years ranging from 10 to 16 years. 401 (69.4%) children were born in omdurman locality. dental fluorosis was detected in approximately 68.3% of the students examined (n = 395), and the community fluorosis index was 1.10 ± 1.02. the majority of students were diagnosed as having very mild (23.2%) and mild (26.5%) forms of fluorosis (figure 1). it was observed that students having severe fluorosis status were 80% boys and 20% girls. there was no difference in the grade of dental fluorosis between children who were born outside and in omdurman (table 2). figure 1: prevalence of dental fluorosis among school students. table 2: comparison of the dean’s index with respect to the students’ gender and place of birth. fluorosis level pvalue normal questionable very mild mild moderate severe gender male 51 (27.9%) 13 (23.6%) 36 (26.9%) 45 (29.4%) 14 (32.6%) 8 (80.0%) 0.015 female 132 (72.1%) 42 (76.4%) 98 (73.1%) 108 (70.6%) 29 (67.4%) 2 (20.0%) birthplace omdurman 130 (71.0%) 40 (72.7%) 95 (70.9%) 102 (66.7%) 28 (65.1%) 6 (60.0%) 0.851 outside omdurman 53 (29.0%) 15 (27.3%) 39 (29.1%) 51 (33.3%) 15 (34.9%) 4 (40.0%) *chi-square test. doi 10.18502/sjms.v16i3.9705 page 477 sudan journal of medical sciences table 3: summary of previous studies on the prevalence of dental fluorosis. country fluoride level study population number prevalence of fluorosis gender butana sudan [10] 1.1–4.0 mg/l students 7–14 years 134 60.6% not mentioned treitel biga sudan [11] 0.25 ppm students 6–12 years 55 91% males abu groon sudan [11] 2.56 ppm students 6–12 years 58 100% equal tiraat el-bijah sudan [12] 0.24–1.31 mg/l all ages 400 42.5% equal umduwanban sudan [12] 1.29–1.43 mg/l all ages 400 70% equal india [13] ≤1.5 mg/l students 12 & 15 years 1875 29.8% equal india [14] ≤1.5 mg/l all ages 6093 39.2% males india [15] 2.42 mg/dl students 6–12 years 1008 69.84% not mentioned india [16] not mentioned students 12–15 years 840 82.04% equal india [17] 0.53–5 ppm students 6–14 year 178 78% females india [18] <0.2–6.5 ppm students 5–12 years 1800 4.1% females india [19] <0.1 ppm students 5–12 years 525 31.4% equal ghana [20] 1.50 ppm children 7–18 years 200 63% equal saudi arabia [21] not mentioned all ages 253 73.5% equal mexico [22] 1.41 mg/l students 12–15 years 101 85% equal mexico [23] 1.95 ppm students 12 & 15 years 1024 83.8% equal mexico [24] not mentioned students 10–12 years 239 59% equal brazil [25] not mentioned students 12 & 15–19 years 535 25% females brazil [26] 0.9 mg/l students 7 & 15 years 52 33% not mentioned 4. discussion this study was conducted in aboseid and alftihab localities which covers an area of 49 km2. there were a total of 50 governmental primary schools. the water sources in this area are wells and the nile. the average fluoride concentration in the water wells was 0.675 ppm, while the fluoride concentration in the nile was 0.35 ppm. this fluoride level was below the level recommended by the who [8]. doi 10.18502/sjms.v16i3.9705 page 478 sudan journal of medical sciences 4.1. fluorosis several studies have been conducted across the world regarding the degree of dental fluorosis compared to the fluoride levels in drinking water, these studies are summarized in table 3. in the present study, nearly two-thirds (68.3%) of children experienced dental fluorosis, this showed a high prevalence despite the fluoride level being �1 mg-f/l. other studies from sudan also showed high fluorosis incidence, however, they were conducted in areas with high fluoride level like butana [9, 10]. many areas in al-butana region had a high concentration of fluoride; a study aimed at measuring fluoride level in different wells in al-butana region showed that in the northern part, the levels ranged from 0.5 to 1.5 mg/l, while in the southern part, the level was <0.5 mg/l, and the levels of 1.5 mg/l were limited and scattered throughout the area [9]. a study in butana showed that the prevalence of fluorosis was about 60.6%, with a fluoride level in drinking water ranging from 1.1 to 4.0 mg-f/l [10]. ibrahim et al. studied the fluoride levels of drinking water and assessed the prevalence of dental fluorosis among children in treitel biga and abu groon areas. the level of fluoride in treitel biga was 0.25 ppm, while in abu groon it was 2.56 ppm. the study reported a 91% and 100% prevalence of dental fluorosis in treitel biga and abu groon areas, respectively [11]. another study from tiraat el-bijah and umduwanban reported a prevalence of about 42.5% and 70% dental fluorosis with a fluoride level of 0.45 mg/l and 1.36 mg/l, respectively [12]. the high dental fluorosis in this study could be explained by the fact that in hot areas, the amount of consumed water is increased, thus increasing the amount of fluoride ingested leading to dental fluorosis. this was supported by another study from sudan which calculated the higher allowed fluoride level in drinkable water as 0.35 ppm [27]. similar results from an indian studies which were conducted in low fluoride areas (≤1.5 mg/l) showed a dental fluorosis prevalence of 29.8% [13] and 39.2% [14]. studies from different parts of the world showed diverse fluorosis prevalence, high prevalence was reported by many studies; indian studies reported a prevalence of 69.8–82.04% [13, 15–17]. a study was carried in bongo community of ghana reported a 63% prevalence [20]. moreover, a 73.5% prevalence was recorded from hail, saudi arabia [21], two studies from mexico reported a prevalence of 85% [22] and 83.8%, respectively [23], and a study of students living in mexico city reported a prevalence 58.6% [24]. however, many studies showed lower rates for fluorosis; a brazilian study reported a prevalence doi 10.18502/sjms.v16i3.9705 page 479 sudan journal of medical sciences of 25% [25] and two studies from india showed dental fluorosis to be 4.1% [18] and 31.4% [19]. of note, females and males have the similar likelihood of developing dental fluorosis [22]. similar results were found in this study with no significant difference between genders, this is consistent with other studies conducted in sudan [12], and among bongo community of ghana [20], saudi arabia [21], mexico city [24], and india [13, 16, 19]. however, some studies have concluded that gender was associated with dental fluorosis, with some studies showing fluorosis to be more prevalent in females [17, 18, 25]. one study of children from omdurman reported a 64% and 50% prevalence of dental fluorosis among boys and girls, respectively [28], another study showed that in treitel biga, the prevalence and severity of fluorosis was higher among boys than girls [11]; in addition, another study from india reported that the overall percentage of dental fluorosis was more in males than in females [14]. the predominant categories of fluorosis were very mild and mild (49.7%), and only 9.1% were in the moderate and severe types, respectively; those few children with increased severity may have had an overexposure to fluoride from other sources like toothpastes. these results are consistent with the results of a sudanese study that found that the predominant categories in their study were very mild and mild [12] and a study from mexico city that reported very mild and mild fluorosis in 51.9% of their students and moderate or severe levels in only 6.69% [24]. similarly, an indian study didn’t report severe fluorosis and the prevalence of moderate fluorosis was 0.2% [18]. however, another indian study showed a more severe results with 29.8% students showing moderate and 6.7% severe fluorosis [17]. 5. conclusion prevalence of dental fluoride was found to be very high among school children with no difference between males and females. although the majority of dental fluorosis were in the categories of very mild and mild, concerns regarding its growing prevalence underscores the need for careful observation. acknowledgements the authors would like to thank the faculty of dental and oral medicine, karary university for facilitation of the school health program. doi 10.18502/sjms.v16i3.9705 page 480 sudan journal of medical sciences ethical considerations ethical approval was obtained from the ethical committee at the faculty of oral and dental medicine. agreement to examine the children was abstained from the school’s principals as this examination was part of a school health program carried out by the ministry of health. competing interests there is no competing interest. availability of data and material all data used in this study are available upon reasonable request with the corresponding author. funding none received. references [1] ten cate, j. and featherstone, j. (1991). mechanistic aspects of the interactions between fluoride and dental enamel. critical reviews in oral biology & medicine, vol. 2, no. 3, pp. 283–296. [2] who. (1994). drinking water quality control in small community supplies (vol. ii). geneva: who. [3] bailey, j., chilton, j., dahi, e., et al. (2006). fluoride in drinking-water. geneva: world health organization.. [4] who. (2017). guidelines for drinking-water quality: fourth edition incorporating the first addendum. geneva: who. [5] denbesten, p. and li, w. (2011). chronic fluoride toxicity: dental fluorosis. fluoride and the oral environment, vol. 22, pp. 81–96. [6] burt, b. a. and eklund, s. a. (2005). dentistry, dental practice, and the community. elsevier health sciences. doi 10.18502/sjms.v16i3.9705 page 481 sudan journal of medical sciences [7] dean, h. t. (1934). classification of mottled enamel diagnosis. the journal of the american dental association, vol. 21, no. 8, pp. 1421–1426. [8] fawell, j. k. and bailey, k. (2006). fluoride in drinking-water. geneva: who. [9] abdel-magid, h. m., abdellah, a. m., and yahia, n. a. (2011). well drinking water fluoride content and dental fluorosis in al-butana region of central sudan. asian journal of water, environment and pollution, vol. 8, no. 4, pp. 37–46. [10] smith, d., harris, h., and kirk, r. (1953). fluorosis in the butana, sudan. journal of tropical medicine and hygiene, vol. 56, pp. 57–58. [11] ibrahim, y., affan, a., and bjorvatn, k. (1995). prevalence of dental fluorosis in sudanese children from two villages with 0.25 and 2.56 ppm fluoride in the drinking water. international journal of paediatric dentistry, vol. 5, no. 4, pp. 223–229. [12] ramadan, a. and ghandourb, i. (2016). dental fluorosis in two communities in khartoum state, sudan, with potable water fluoride levels of 1.36 and 0.45 mg/l. fluoride, vol. 49, no. 4, pp. 509–520. [13] sukhabogi, j. r., parthasarathi, p., anjum, s., et al. (2015). dental fluorosis and dental caries prevalence among 12 and 15 year old school children in nalgonda district, andhra pradesh, india. annals of medical and health sciences research, vol. 4, no. 3, pp. 245–252. [14] kotecha, p. v., patel, s. v., bhalani, k. d., et al. (2012). prevalence of dental fluorosis & dental caries in association with high levels of drinking water fluoride content in a district of gujarat, india. indian journal of medical research, vol. 135, no. 6, pp. 873–877. [15] sarvaiya, b., bhayya, d., arora, r., et al. (2012). prevalence of dental fluorosis in relation with different fluoride levels in drinking water among school going children in sarada tehsil of udaipur district, rajasthan. journal of indian society of pedodontics and preventive dentistry, vol. 30, no. 4, p. 317. [16] naidu, g. m., rahamthullah, s. u., kopuri, r. k. c., et al. (2013). prevalence and self perception of dental fluorosis among 15 year old school children in prakasham district of south india. journal of international oral health, vol. 5, no. 6, p. 67. [17] varsha, d. and ragini, m. (2013). prevalence and severity of dental fluorosis among school students in dongargaon of chandrapur district, maharashtra, india. journal of environmental research and development, vol. 8, no. 2, p. 309. [18] chauhan, d., chauhan, t., sachdev, v., et al. (2012). a study of prevalence and severity of dental fluorosis among school children in a northern hilly state of india. srm journal of research in dental sciences, vol. 3, no. 3, p. 170. doi 10.18502/sjms.v16i3.9705 page 482 sudan journal of medical sciences [19] saravanan, s., kalyani, c., vijayarani, m., et al. (2008). prevalence of dental fluorosis among primary school children in rural areas of chidambaram taluk, cuddalore district, tamil nadu, india. indian journal of community medicine, vol. 33, no. 3, p. 146. [20] firempong, c., nsiah, k., awunyo-vitor, d., et al. (2013). soluble fluoride levels in drinking water-a major risk factor of dental fluorosis among children in bongo community of ghana. ghana medical journal, vol. 47, no. 1, pp. 16–23. [21] alhobeira, h. a., siddiqui, a. a., and mian, r. i. (2015). prevalence and severity of dental fluorosis in hail, saudi arabia. journal of international oral health, vol. 7, no. 12. [22] vazquez-alvarado, p., prieto-garcía, f., coronel-olivares, c., et al. (2010). fluorides and dental fluorosis in students from tula de allende hidalgo, mexico. journal of toxicology and environmental health sciences, vol. 2, no. 3, pp. 24–31. [23] pontigo-loyola, a. p., islas-márquez, a., loyola-rodríguez, j. p., et al. (2008). dental fluorosis in 12-and 15-year-olds at high altitudes in above-optimal fluoridated communities in mexico. journal of public health dentistry, vol. 68, no. 3, pp. 163–166. [24] molina-frechero, n., gaona, e., angulo, m., et al. (2015). fluoride exposure effects and dental fluorosis in children in mexico city. medical science monitor, vol. 21, pp. 3664–3670. [25] rigo, l., caldas junior a. df., souza, e. h. ad. (2010). factors associated with dental fluorosis. revista odonto ciência, vol. 25, no. 1, pp. 8–14. [26] ramires, i., olympio, k. p. k., maria, a. g., et al. (2006). fluoridation of the public water supply and prevalence of dental fluorosis in a peripheral district of the municipality of bauru, sp. journal of applied oral science, vol. 14, no. 2, pp. 136–141. [27] ramadan, a. and hilmi, y. (2014). the influence of climate on the determination of the upper permissible fluoride level in potable water in sudan. fluoride, vol. 47, pp. 123–133. [28] aziz ghandour, i. a., ibrahim, f. a., and shehata, a. h. (1988). the prevalence of dental caries, fluorosis, and dental attitudes among primary schoolchildren in omdurman– sudan. odonto-stomatologie tropicale, vol. 11, no. 3, pp. 103–106. doi 10.18502/sjms.v16i3.9705 page 483 introduction materials and methods results discussion fluorosis conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi:10.11131/2017/sjms.v16i4.9948 production and hosting by knowledge e research article comparison of pocket pulse oximeter and standard pulse oximeter with abg analysis in critically ill patients jeswanth reddy n.1, kiran h. s.2*, b. j. subhash chandra2, basavana gowdappa h.2 1department of general medicine, melmaruvathur adhiparasakthi institute of medical sciences & research, melmaruvathur, kancheepuram district, tamil nadu, india 2department of general medicine, jss medical college and hospital, jssaher, mysore, karnataka, india orcid: kiran h. s.: https://orcid.org/0000-0002-6070-6529 abstract background: pulse oximetry (spo2) is a standard monitoring device in patients presenting to emds and intensive care units (icus). pocket pulse oximeters (ppos) are used widely in wards, emds, and small hospitals/clinics. these inexpensive ppos also guide therapeutic interventions. few studies have evaluated the accuracy of spo2 in patients presenting to critical care areas vis-à-vis devices like ppo and standard pulse oximeter (spo). this study becomes extremely relevant in view of the ongoing crisis of the covid-19 pandemic wherein spo2 monitoring is very important in hospitals, quarantine centers, small clinics, or even at home. methods: patients presenting to critical areas who underwent arterial blood gases (abg) analysis on the recommendation of the treating physician between november 2016 and october 2018 were included in this study. along with the abg analysis, a simultaneous assessment of spo2 was done with a single ppo and spo and all values were noted. statistical analysis was done using the spss v.21.0 for windows. results: the study included 300 patients. we compared the o2 saturations of abg, spo, and ppo with respect to sex, different age groups, and at different levels of abg pco2, hco3, and ph in all patients. all parameters were compared using the pearson’s correlation test; the results showed that abg o2 saturations were closer to the spo than the ppo but the differences were not statistically significant as the pearson’s correlation values for all parameters were >0.8. we also compared the parameters by bland altman plot and all observations were outside 95% ci (confidence interval), which means that there was a good agreement between o2 saturations by all three methods, that is, abg, spo, and ppo; however, abg o2 saturations were closer to spo than ppo but this difference was not statistically significant. hence, we conclude that the ppo is a useful tool for reliable monitoring of o2 saturations. conclusion: this study highlights that inexpensive and noninvasive ppo can be used as a standard monitoring device with reliability in critically ill patients presenting to emds, icus, and small hospitals/clinics, quarantine centers, and even at home. keywords: pulse oximeter, standard pulse oximeter, pocket pulse oximeter, arterial blood gas analysis, oxygen saturation how to cite this article: jeswanth reddy n., kiran h. s., b. j. subhash chandra, basavana gowdappa h. (2021) “comparison of pocket pulse oximeter and standard pulse oximeter with abg analysis in critically ill patients,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 509–518. doi 10.18502/sjms.v16i4.9948 page 509 corresponding author: kiran h. s.; email: drhskiran@gmail.com received 12 october 2021 accepted 01 december 2021 published 31 december 2021 production and hosting by knowledge e jeswanth reddy n. et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:drhskiran@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences jeswanth reddy n. et al. 1. introduction pulse oximeter is a device for noninvasive measurement of spo2 (oxygen saturation) in blood [1].sending specific wavelengths of light through nail bed based on differential absorption of the wavelengths of the light by deoxygenated and oxygenated hemoglobin, the pulse oximeter calculates and shows an spo2 value [1]. nowadays, pulse oximeter spo2 is considered as a “fifth vital sign” (in addition to temperature, blood pressure, pulse, and respiratory rate) in clinical assessment [2].ever since its inception in 1970s, it is being used in various clinical settings [3].pocket pulse oximeters (ppos) are increasingly being used in wards, critical care areas, peripheral clinics, etc. their small size, handy nature, and affordable cost have established their role in modern clinical care just like thermometers in the management of patients with fever [3]. however, these commercially available pocket devices have not been adequately evaluated [2]. hence, we wanted to find out the reliability of pocket pulse oximeter (ppo) vis-à-vis standard pulse oximeter (spo – which comes with a finger probe connected to a standard monitor), and abg (arterial blood gases) analysis. although this study was done in pre-covid era, it becomes extremely relevant in view of the ongoing crisis of covid-19 pandemic wherein spo2 monitoring is very important in hospitals, quarantine centers, small clinics, or even at home [4, 5]. 2. materials and methods this observational prospective and comparative study was undertaken at a medical college teaching hospital. the study included 300 patients admitted to critical care areas between november 2016 and october 2018. consecutive patients presented to critical areas who underwent abg analysis as per the decision of the treating physician were included by convenience sampling. patients with shock in whom pulse oximetry does not record the saturation (spo2) and patients with anemia and abnormal hemoglobin were excluded. along with the abg analysis, a simultaneous assessment of spo2 was done with a single ppo and spo, and all values were noted. spo2 obtained by ppo, spo were compared with each other and with various parameters of abg analysis. to ensure the accuracy of the measurement, the values were recorded only after the ppo sensor showed a steady pulse and/or pulse waveform. doi:10.11131/2017/sjms.v16i4.9948 page 510 sudan journal of medical sciences jeswanth reddy n. et al. table 1: descriptive statistics comparing spo vs abg o2 saturation. n minimum maximum mean std. deviation difference between abg and spo spo2% 300 –10.00 5.9 –0.2262 1.65147 table 2: descriptive statistics comparing ppo vs abg o2 saturation. n minimum maximum mean std. deviation difference between abg and ppo spo2% 300 –13 6.9 0.46 1.727 3. results out of the 300 patients included in the study, 69% were male and 31% female. pearson’s correlation showed that abg o2 saturation was closer to spo than ppo in both males and females; however, these differences were within the acceptable limits. hence, there was no statistically significant difference between males and females for monitoring o2 saturation by ppo. furthermore, 5% of the patients were <20 years old, 27% between 20 and 40, 34% between 40 and 60, 29% between 60 and 80, and 5% >80. across all age groups, abg o2 saturations were closer to spo than ppo but this difference was not significant as the pearson’s correlation values were >0.8, which is considered to have excellent correlation. hence, age does not have any statistically significant influence on ppo saturation monitoring. according to the pearson’s correlation, there was an excellent correlation between the saturation recorded by ppo and spo with abg o2 saturation. spo values were closer to abg o2 saturation than ppo but this difference was not significant. linear regression showed standardized coefficient error of 0.868 and 0.878 with ppo and spo, respectively, when compared with the saturations of abg which is insignificant as the standardized coefficient error is <0.1 (standardized coefficient error <0.1 is insignificant). only 10/300 (3.3%) patients were beyond 95% ci (confidence interval) which means there is a good agreement between the two methods (abg sao2 and spo). overall, 13/300 (4.3%) observations were outside 95% ci, which means there is still a good agreement between the two methods (abg sao2 and ppo). only 6/300 (2%) had >95% ci, which means there is a good agreement between the two methods. doi:10.11131/2017/sjms.v16i4.9948 page 511 sudan journal of medical sciences jeswanth reddy n. et al. figure 1: bland altman plot comparing spo vs abg o2 saturation. figure 2: bland altman plot comparing ppo vs abg o2 saturation. finally, to conclude, based on the bland altman plot, while abg is in better agreement with spo than ppo, both were within the acceptable limits. doi:10.11131/2017/sjms.v16i4.9948 page 512 sudan journal of medical sciences jeswanth reddy n. et al. figure 3: bland altman plot of agreement between ppo vs spo. table 3: descriptive statistics showing agreement between ppo and abg o2 saturation. mean median standard deviation minimum maximum percentile 25 percentile 75 difference between spo and ppo 0.69 1.00 0.73 –1 2.00 0.00 1.00 hence, based on the bland altman plot, ppo can be a reliable tool for monitoring saturation. we also compared the saturations of all three, that is, abg, ppo, and spo at different levels of abg pco2 values to determine whether pco2 levels have any influence. results showed that there was a better correlation between abg and spo o2 saturations than ppo but the difference was within the acceptable limit. so, abg pco2 does not influence the saturation monitoring by ppo. we also compared the saturations of all three, that is, abg, ppo, and spo at different levels of abg hco3 values to determine whether hco3 level has any influence. results showed that there was a better correlation between abg and spo than between abg and ppo but the difference was within the acceptable limit. so, hco3 level does not influence the saturation monitoring by ppo. in addition, neither respiratory acidosis/alkalosis nor metabolic acidosis/alkalosis affect the ppo saturation monitoring. both in metabolic acidosis and alkalosis abg, values of o2 saturation are closer doi:10.11131/2017/sjms.v16i4.9948 page 513 sudan journal of medical sciences jeswanth reddy n. et al. to spo than ppo but within acceptable limits. similarly, in respiratory acidosis or alkalosis, abg values of o2 saturation are closer to spo than ppo but within acceptable limits. 4. discussion ppo is nowadays a ubiquitous, disseminated technology used for monitoring o2 saturation in patients presenting to critical care units such as emds, icus, small hospitals/clinics owing to their ease of use and the ability to provide continuous and immediate oxygen saturation values [1–3]. furthermore, ppo is a noninvasive method for monitoring oxygen saturation (so2), so knowing its precision and accuracy is of great importance in clinical practice [1, 2]. hence, this study was carried out to compare the o2 saturation of ppo with that of spo and abg o2 saturations and to examine the effect of several factors on this relationship. our study showed that spo o2 saturation was more closely related to abg values than ppo across all parameters, that is, sex, different age groups, and at different levels of abg pco2, hco3, and ph. similarly, abg o2 saturation was more closely related to spo than ppo across all parameters. there was a better correlation between abg and spo than ppo, however, as per the statistical analysis, those differences were within acceptable limits and statistically insignificant. hence, inexpensive ppo can be used as a standard monitoring device with reliability in critically ill patients. van de louw a et al. noted large differences between saturation measured by ppo and abg in critically ill patients with poor reproducibility of spo2 [6], however, our study showed that there was an excellent correlation between the saturations recorded by ppo, spo, and abg (as the pearson’s correlation values >0.8 are considered to have excellent correlation; linear regression showed a standardized coefficient error of 0.868 which occurred between ppo and abg saturation which is insignificant as the standardized coefficient error is <0.1 which is considered insignificant; bland altman plot also showed an excellent correlation between the two as 13/300 (4.3%) observations were outside 95% ci, which means that there is a good agreement between the two methods). da costa jc et al. showed that ppo was less precise than spo but had agreement limits that were comparable [7]. our study also showed the same results. moreover, van de louw et al. [6] compared only abg and ppo and da costa jc et al. [7] compared only between spo and ppo, but in this study, we compared all three methods of monitoring doi:10.11131/2017/sjms.v16i4.9948 page 514 sudan journal of medical sciences jeswanth reddy n. et al. o2 saturation, that is, abg, spo, and ppo, which showed a good correlation between all three methods. wilson et al. showed that ppo overestimates abg-determined sao2 by a mean of 2.75% in patients with sepsis and septic shock [8]. this overestimation is exacerbated by the presence of hypoxemia. when sao2needs to be determined with a high degree of accuracy, abg is recommended. in our study, we have excluded patients with shock, hence the issue does not arise at all. moreover, seguin et al. demonstrated that neither anemia nor acidosis alters the precision of measurements, thus ppo remains a valuable tool in the care of icu patients [9]. in this study, we excluded patients with anemia. in our study also, acidosis, either respiratory or metabolic, does not alter the precision of measurement as the pearson’s correlation values were >0.8, which means that there exists a good correlation. in our study, we also compared o2 saturations at different levels of abg alkalosis, that is, both respiratory and metabolic alkalosis and results showed that alkalosis also do not alter the precision of measurement as the pearson’s correlation values obtained were >0.8. munoz et al. reported that carbon dioxide arterial tension status can impair the agreement between arterial oxygen saturation and arterial oxygen saturation measured by pulse oximetry, particularly in patients with hypercapnia [10]. therefore, it is likely that arterial oxygen saturation measured by oximetry may not be sufficiently accurate when assessing patients for long-term home oxygen therapy and should not substitute the gold standard arterial oxygen tension measured in arterial blood. our study also showed that there exists differences between the saturations recorded by ppo and abg at different levels of abg pco2, but these differences were within agreeable limits by pearson’s correlation. one of the most important part of covid-19 patient management is ppo more so because of “silent hypoxia” [3, 11, 12]. many countries have adopted ppo at primary healthcare/home settings [3].in a recent study done to assess the correlation between ppo (spo2) and abg analysis (sao2) in patients with covid-19, who were fit to be shifted from an icu to a ward, it was found that ppo correlated with sao2 measurement; although suboptimal, it was within the acceptable levels for food and drug authority approval [13]. doi:10.11131/2017/sjms.v16i4.9948 page 515 sudan journal of medical sciences jeswanth reddy n. et al. 5. limitations and highlights in this study, we excluded patients with shock, anemia, and abnormal hemoglobin levels [14]. hence, we could not estimate the correlation between abg, ppo, and spo in the above situations. this is the first ever study of its kind in our country since we compared, simultaneously, saturations recorded by ppo and spo with abg which, to the best of our knowledge, none of the other studies have done so far. 6. conclusion this study highlights that inexpensive ppo can be used as a standard monitoring device with reliability in critically ill patients presenting to emds, icus, and small hospitals/clinics in the periphery; more so, during the current covid-19 pandemic. acknowledgements the authors dedicate this article to dr takuo aoyagi (who passed away last year) – “the father of the pulse oximeter” – for his contributions in its development [15]. the authors are also thankful to their laboratory department for its support. ethical considerations institutional ethics committee approval and informed consent of patients were obtained. competing interests none. availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to the corresponding author. doi:10.11131/2017/sjms.v16i4.9948 page 516 sudan journal of medical sciences jeswanth reddy n. et al. funding none. references [1] torp, k. d., modi, p., and simon, l. v. (2021). pulse oximetry. treasure island, fl: statpearls publishing. [2] hafen, b. b. and sharma, s. (2021). oxygen saturation. treasure island, fl: statpearls publishing. [3] singh, a., kataria, s., das, p., et al. (2020). a proposal to make the pulse oximetry as omnipresent as thermometry in public health care systems. journal of global health, vol. 10, no. 2, p. 0203102. [4] michard, f., shelley, k., and l’her, e. (2021). covid-19: pulse oximeters in the spotlight. journal of clinical monitoring and computing, vol. 35, no. 1, pp. 11–14. [5] quaresima, v. and ferrari, m. (2020). more on pulse oximetry for monitoring patients with covid-19 at home. annals of the american thoracic society, vol. 17, no. 11, p. 1496. [6] van de louw, a., cracco, c., cerf, c., et al. (2001). accuracy of pulse oximetry in the intensive care unit. intensive care medicine, vol. 27, no. 10, pp. 1606–1613. [7] da costa, j. c., faustino, p., lima, r., et al. (2016). comparison of the accuracy of a pocket versus standard pulse oximeter. biomedical instrumentation & technology, vol. 50, no. 3, pp. 190–193. [8] wilson, b. j., cowan, h. j., lord, j. a., et al. (2010). the accuracy of pulse oximetry in emergency department patients with severe sepsis and septic shock: a retrospective cohort study. bmc emergency medicine, vol. 10, no. 9. [9] seguin, p., le rouzo, a., tanguy, m., et al. (2000). evidence for the need of bedside accuracy of pulse oximetry in an intensive care unit. critical care medicine, vol. 28, no. 3, pp. 703–706. [10] muñoz, x., torres, f., sampol, g., et al. (2008). accuracy and reliability of pulse oximetry at different arterial carbon dioxide pressure levels. european respiratory journal, vol. 32, no. 4, pp. 1053–1059. [11] wilkerson, r. g., adler, j. d., shah, n. g., et al. (2020). silent hypoxia: a harbinger of clinical deterioration in patients with covid-19. american journal of emergency medicine, vol. 38, no. 10, pp. 2243.e5–2243.e6. doi:10.11131/2017/sjms.v16i4.9948 page 517 sudan journal of medical sciences jeswanth reddy n. et al. [12] brouqui, p., amrane, s., million, m., et al. (2021). asymptomatic hypoxia in covid-19 is associated with poor outcome. international journal of infectious diseases, vol. 102, pp. 233–238. [13] philip, k. e. j., bennett, b., fuller, s., et al. (2020). working accuracy of pulse oximetry in covid-19 patients stepping down from intensive care: a clinical evaluation. bmj open respiratory research, vol. 7, no. 1, p. e000778. [14] moyle, j. (2021). pulse oximetry gives artificially high readings in presence of carboxyhaemoglobin. bmj, vol. 373, p. n1103. [15] yamakage, m. (2021). pulse oximetry: the outstanding achievements of dr. takuo aoyagi. journal of anesthesia, vol. 35, article 605. doi:10.11131/2017/sjms.v16i4.9948 page 518 introduction materials and methods results discussion limitations and highlights conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9293 production and hosting by knowledge e research article trends of tuberculosis treatment outcomes of notified cases in three refugee camps in sudan: a four-year retrospective analysis, 2014–2017 tsegay legesse1, mohammed hussein elduma1, nagi masoud awad2, mousab siddig elhag3, israa abushama2, hamdan mustafa2, kabashi hashim3, hassan mahmoed4, yassen mohamed5, ahmed e.dafalla6, fathia alwan1, and desta kassa1 1inter-governmental authority on development, djibouti 2national tb program, federal ministry of health, sudan 3communicable and non-communicable disease department (dcd), federal ministry of health, sudan 4tb programme, white nile, sudan 5tb programme, kassala, sudan 6unhcr office, sudan orcid: desta kassa: http://orcid.org/0000-0003-0624-8122 abstract background: refugees are vulnerable to tuberculosis (tb) infection. tracking of program performance is needed to improve tb care and prevention. the objective of this study was to assess the trends of tb treatment outcomes of notified cases in three refugee camps in sudan from 2014 to 2017. methods: this study was a historical cohort study. sex, age, type of tb, tb patient category, and treatment outcome of all tb cases registered in three refugee camps (al kashafa, shagarab, wadsherify) from january 1, 2014 to december 31, 2017 were collected from the tb register. multivariable logistic regression was performed to explore factors for unsuccessful tb treatment. results: a total of 710 tb cases of which 53.4% were men, 22.1% children (<15 years), and 36.2% extrapulmonary tb (eptb) were registered. overall, the tb treatment success rate was 75.7% with a declining trend from 86.2% in 2015 to 63.5% in 2017. on average, 11.4% were lost to follow-up (ltfu), 6.6% died, 5.9% were not evaluated, and in 0.3% the treatment failed. being 15–24 years old and having eptb were significantly associated with unsuccessful treatment outcome. conclusion: the treatment success rate in the refugee camp in 2017 (63.5%) was far lower than the national treatment success rate (78%) and the end tb global target (≥90%) that needs to be improved. ltfu, died, and not evaluated outcomes were high which indicated the necessity to improve the tb treatment program. keywords: refugees, sudan, treatment outcome, tuberculosis how to cite this article: tsegay legesse, mohammed hussein elduma, nagi masoud awad, mousab siddig elhag, israa abushama, hamdan mustafa, kabashi hashim, hassan mahmoed, yassen mohamed, ahmed e.dafalla, fathia alwan, and desta kassa (2021) “trends of tuberculosis treatment outcomes of notified cases in three refugee camps in sudan: a four-year retrospective analysis, 2014–2017,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 259–275. doi 10.18502/sjms.v16i2.9293 page 259 corresponding author: desta kassa; intergovernmental authority on development, djibouti mobile: +251 9114 792 12 email: dkassa2003@gmail.com received 2 april 2021 accepted 7 may 2021 published 30 june 2021 production and hosting by knowledge e tsegay legesse et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0003-0624-8122 mailto:dkassa2003@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences tsegay legesse et al 1. introduction tuberculosis (tb) is a major public health challenge around the globe. according to the world health organization (who) report, in 2017, 10 million tb cases and 1.6 million tb deaths (hiv-negative) were recorded worldwide. in sudan, the estimated tb incidence and mortality rate (hiv-negative) per 100,000 population in 2017 were 77 and 12, respectively [1]. although, tb burden has been falling in the past 20 years worldwide [1], it still remains a primary cause of death from a single infectious agent since 2011 [1, 2]. tb is more severe among refugees and internally displaced populations (idps) who are at risk to acquire and develop active tb infection [3–6], multi-drug-resistant tb (mdr-tb) [7], as well as low tb treatment success [8, 9]. the reasons for higher tb burden in refugees and other key populations are poor shelter, poor nutritional status, and inadequate tb care and prevention [3–6, 10]. by the end of 2018, nearly 71 million refugees and asylum seekers were registered globally [11]. majority (>86%) of refugees are from and stay within developing countries where the tb burden is higher [12]. studies have shown an increase in the prevalence of tb [13, 14] and tb case notification [14, 15] when the number of refugee population increases. thus, key populations such as refugees have been given special focus in the stop tb [16] and end tb [2] who strategic documents so as to achieve the global targets by 2035. sudan (with a population size of 41 million in 2017) is among the countries with high tb incidence rates (≥20/100,000 population) in the world [1]. sudan has a long history of hosting refugees. by the end of 2019, the country had hosted >1.1 million refugees living in camps and out of camps (70%) in over 130 localities across the country’s 18 states [17]; 74, 11, and 8.5% of the refugees in sudan originate from south sudan, eritrea, and syria, respectively, and the remaining are from ethiopia, democratic republic of congo (drc), chad, somalia, and yemen. the number of refugees and asylum seekers in sudan increased continuously during the study period, from 437,518 in 2014 to 924,810 in 2017 [17]. the aforementioned pieces of evidence [13–17] indicate that tb is one of the main health problems in the refugee camps of sudan. hence, periodic review of tb program performance in the refugee camps is needed to address the gaps and improve the implementation of tb care and prevention program. tb treatment outcome is the most important global indicator to assess the overall quality of tb program and the effectiveness of tb treatment program in particular [18, 19]. doi 10.18502/sjms.v16i2.9293 page 260 sudan journal of medical sciences tsegay legesse et al as defined in the end tb strategy, the 2020 tb treatment success rate target is at least 90% [2]. generally, tb treatment success in the refugee population can be affected by factors including less adherence to treatment, death, noncompletion due to lost to follow-up (ltfu), malnutrition, and other coexisting illnesses such as hiv coinfection [8, 20, 21]. studies showed lower treatment success rate among refugees in ethiopia (75.1%) [22] and in refugees hosted in different countries (ranging from 63.6 to 77.5%) [23–28]. the tb program in sudan including in the refugee camps is guided by the national tb program (ntp), under the communicable and non-communicable disease department, in the ministry of health (moh) [22]. the ntp in sudan has a surveillance system but it largely focuses on the government-owned health facilities run by federal and state minsters of health. however, there is no specific study on the trends of treatment outcome and factors associated with unsuccessful treatment outcome in the refugee camps. hence, this study aimed to investigate trends of tb treatment outcomes of notified tb cases and assess factors for unsuccessful treatment outcomes in three refugee camps in sudan from 2014 to 2017. 2. materials and methods 2.1. study settings and participants in sudan, tb program in the refugee camps is led and coordinated by the ntp and is implemented according to the national tb guideline [22]. the data collection for the tb surveillance system occurs at tb management units (tbmus) that utilize patient cards and registers [22]. this study was a refugee health facility based which used unit tb registers in the refugee camps as data source. according to the inclusion criteria, all refugee health facilities which provided tb diagnosis and treatment at least since january 2017 were included. thus, three health facilities which fulfilled the inclusion criteria in three refugee camps (al kashafa, shagarab, wadsherify) located in white nile and kassala states were included. the study participants were all tb cases registered in these three refugee camps from january 1, 2014 to december 31, 2017. doi 10.18502/sjms.v16i2.9293 page 261 sudan journal of medical sciences tsegay legesse et al 2.2. study design and data collection this study was a historical cohort study. variables included in the unit tb register such as sex, age, type of tb, tb patient category, and treatment outcome of all tb cases registered in three refugee camps (al kashafa, shagarab, wadsherify) were collected. data collection tool was developed and pretested. nurses and program officers were recruited as data collectors and supervisors, respectively, and received training on data collection tools including practical exercise. data were collected from january to april 2019. data quality was assured through provision of training to data collectors and supervisors and undertaking daily field supervision by the field supervisors. in addition, 10% of the data collected were randomly selected and recollected by the field supervisors and checked page by page. 2.3. data analysis epi-info statistical software version 7 was used for data entry, and data were exported to stata version 13 (stata corp, college station, tx, usa) for analysis. frequencies, proportions, and ratios were calculated to describe treatment outcome variables. bivariate and multivariable logistic regression analysis were done to assess factors associated with unsuccessful treatment outcome. the independent variables used were age, sex, baseline weight, type of tb, category of tb patient, refugee camps, year of treatment, and hiv infection. odds ratios (or) with 95% confidence interval was used to assess the strength of association between variables. statistical significance level was considered at a p-value < 0.05. 2.4. operational definitions the operational definitions of tb cases and tb treatment outcome categories in this study are based on the national tb management guideline in sudan [29] and the who document [30] included in supplement 1. doi 10.18502/sjms.v16i2.9293 page 262 sudan journal of medical sciences tsegay legesse et al 3. results 3.1. general characteristics table 1 shows the general characteristics of the study participants. during the study period, 710 tb cases of all forms were notified in al kashafa, wadsherify, and shagarab refugee camps. more specifically, the notified tb cases in al kashafa, shagarab, and wadsherify refugee camps were 334, 206, and 170, respectively. of these tb cases, 377 (53.4%) were males and 329 (46.6%) females. the male-tofemale ratio (m: f) of the notified cases increased from 1:1 in 2014 to 1.7:1 in 2016 and then declined to 1.1:1 in 2017. the mean (standard deviation, sd) age was 34.1 (21.4) years. among the notified cases, children aged <15 years and adults aged ≥15 years constituted 22.1 and 77.9%, respectively. by refugee camp, majority, 334 (47.0%), of the tb cases were from al kashafa, 206 (29.0%) were from shagarab, and 170 (23.9%) were from wadsherify. 3.2. tb cases by diagnostic and age categories overall, the number of notified tb cases in the camps increased from 143 in 2014 to 341 cases in 2017. we further analyzed the notified cases disaggregated by diagnostic category and gender (table 1). from 2014 to 2017, the proportion of extrapulmonary tb (eptb) increased from 29.3 to 39.3%. among the notified tb cases, the proportion of smear-positive ptb remained lower and decreased from 37.8% in 2014 to 24.9% in 2017 (table 1; figure 1). similarly, the proportion of bacteriologically confirmed cases among new and relapse ptb patients decreased from 52.6% in 2014 to 40.2% in 2017 (table 1). over the study period, the difference in the proportion of notified cases by age was observed (table 1). from 2014 to 2017, the percentage of tb accounted by children (<15 years) increased from 8.4 to 34.3%, while the share of the younger age group (15–34 years) decreased from 39.9 to 27.3%. 3.3. notified tb cases by hiv status among the 710 notified tb cases in the four-year period, hiv testing was done for 42.7%. the proportion of notified tb cases who did not receive hiv test and results increased from 30% in 2015 to 62.5% in 2017. the tb–hiv coinfection rate decreased doi 10.18502/sjms.v16i2.9293 page 263 sudan journal of medical sciences tsegay legesse et al figure 1: trends of notified tb cases (bar) by diagnostic category (line) in al kashafa, wadsherify, and shagarab refugee camps, sudan, 2014–2017. from 7.1% (4/56) in 2015 to 4.7% (6/128) in 2017 (table 1). all identified hiv-positive tb cases in each year were put on art. 3.4. tb treatment outcomes from 2014 to 2017 treatment outcome was determined for 143, 80, 146, and 341 tb cases of all forms that were notified in 2014, 2015, 2016, and 2017, respectively (table 2). the treatment success rate remained lower at a range 63.5–82.9% (increasing gradually from 78.3% in 2014 to 82.9% in 2016 then decreasing to 63.5% in 2017). on average, 18.7% were cured, 57.0% treatment completed, 0.3% treatment failed, 11.4% ltfu, 6.6% died, and 5.9% not evaluated. from 2015 to 2017, there was an increase in the percentage of ltfu (from 3.8 to 15.8%) and dead (3.8 to 8.5%) patients, but a decrease in the percentage of cured patients (from 26.6 to 10.6%). doi 10.18502/sjms.v16i2.9293 page 264 sudan journal of medical sciences tsegay legesse et al 3.5. demographic and clinical characteristics associated with unsuccessful tb treatment outcomes in sudan refugee camps (2014–2017) using a simple bivariate logistic regression analysis, age group and type of tb were seen to be associated with unsuccessful treatment outcomes. more specifically, age 15–24 years [or = 0.4, 95% ci: 0.2–0.8, p = 0.01], 25–34 years [or = 0.5, 95% ci: 0.3–0.9, p = 0.02], 45–54 years [or = 0.5, 95% ci: 0.2–0.96, p = 0.04], smear-positive pulmonary tb (ptb+) [or = 0.5, 95% ci: 0.3–0.8, p = 0.01], and eptb [or = 0.5, 95% ci: 0.3–0.8, p = 0.006] were associated with unsuccessful treatment outcomes. after adjusting for potential confounders by multivariable modelling, only age groups 15–24 years [adjusted odds ratio (aor) = 0.4, 95% ci: 0.2–0.9, p = 0.02] and being an eptb case [aor = 0.5, 95% ci: 0.3–0.9), p= 0.009] were associated with unsuccessful treatment outcome (table 3). 4. discussion the findings of this study generate evidence on trends of treatment outcomes of notified case during the study period (2014–2017), which is relevant to improve the quality of tb program in al kashafa, wadsherify, and shagarab refugee camps in sudan. 4.1. notified tb cases in countries with good tb diagnoses and reporting system, case notifications can be used as a proxy for tb incidence estimates [19]. moreover, bacteriologic diagnosis of tb allows patients to be correctly diagnosed and started on the most effective treatment regimen. in this study, the absolute number of notified new and relapse cases showed an increment during the study period which could be due to the increment of refugees or new influxes following the conflicts in south sudan. similarly, an increase in notified tb cases (from 138 cases in 2014 to 588 in 2017) was reported in refugee population hosted in refugee camps in ethiopia [22]. in contrast, notified incident tb cases among syrian refugees in jordan has declined from 79 cases in 2013 to 58 cases in 2015 [28]. in this study, 45.3% of the new and relapse ptb cases in the refugee camps in 2017 were bacteriologically confirmed, which is lower than the 2018 who report for sudan (49%), african region (66%), and for the globe (56%) [1], and the end tb global target where 80% of the new and relapse tb patients need to be bacteriologically confirmed doi 10.18502/sjms.v16i2.9293 page 265 sudan journal of medical sciences tsegay legesse et al by 2020 [2]. the low proportion of bacteriologically confirmed cases may reflect gaps in capacity for accurate diagnosis. analyzing the notified tb cases by type of tb is important for targeted interventions. in this study, proportion of eptb increased from 29.4% in 2014 and reached 39.3% by 2017. this is higher than the proportion of eptb among new cases in darfur conflict zone in sudan (2004–2014) (35%) [31], in the globe (14%), and in sudan (26%) in 2017 [1]. the higher proportion of eptb in the refugee settlements can be due to demographic factors (age, sex), origin of refugee population, host factors (immune status due to comorbidities such as hiv coinfection) [32, 33], or due to pathogen factor (phenotypes of the tubercle bacilli) [34]. thus, operation research aimed to investigate the factors attributed to the higher and increased trend in eptb in the refugee settlements is recommended. tb largely affects productive age groups. similar to 2018 who tb report [1] and studies done in other developing countries [35, 36], our study findings also showed that the highest notified cases were in the age groups 15–34 (30.4%) and 35–54 (26.0%) years (table 1). thus, tb programs should strengthen case-finding efforts focusing on these age groups. high childhood tb is an indication of high missed cases among adults and continuity of tb transmission [23]. according to the 2018 who report, 14.1% of tb cases notified in sudan were of children (<15 years) [1]. in the refugee camps the contribution of children to total notified tb cases increased from 8.4% in 2014 to 34.3% in 2017. the remarkable increment in childhood tb in 2017 in the refugee camps was largely due to the availability of gene xpert in al kashafa. it is expected that childhood tb is misdiagnosed, overestimated, and/or underreported [2]. 4.2. treatment outcomes tb treatment outcome is a good indicator for the overall quality of tb program and in particular the tb treatment program [19]. according to the who end tb global plan, at least 90% of all tb cases on treatment need to achieve treatment success rate by 2020 [2]. in the refugee camps, on average 75.7% (range 63.5–86.2%) of the tb cases achieved treatment success during the study period. by 2017, the treatment success rate in the refugee camps (63.5%) was lower than that of the national/sudan achievement in 2017 (78%) [1] and the who global target (≥90%) [1]. overall, the treatment success rate in the three refugee camps (range 63.5–86.2%) was comparable to the findings among smear positive pulmonary tb (65–66%) in darfur doi 10.18502/sjms.v16i2.9293 page 266 sudan journal of medical sciences tsegay legesse et al conflict zones in sudan over 10 years (2004–2014) [24], and to treatment success rate among refugees in different parts of the world (63.6 to 77.5%) [23–28]. the declining trend in treatment success rate in the refugee camps started in 2016, and this was probably due to the increase in influx of new refugees in 2016 and 2017 and high mobility of the refugees. this was due to high ltfu, mortality, and unevaluated treatment outcomes, which called for action by the refugee health and ntp. overall, the mean treatment failure (0.3%), ltfu (11.4%), and died (6.6%) in the refugee camps (table 3) were comparable to the reports from other refugee camps in different countries which showed 4.6–10.9% death rate, 7.1–27.3% ltfu, and 1.3–2.0% treatment failure [8, 26, 27]. in summary, the low tb treatment success rate in the refugee health facilities indicated the need to improve the tb treatment program, which includes improving documentation, provision of training to healthcare workers, supportive supervision, follow-up sputum smear and culture examination, supplementary nutritional support, and racing of ltfu cases through the engagement of community health workers. 5. conclusion the proportion of eptb (from 29.4 to 39.3%) and tb <15 years (from 8.4 to 34.3%) increased over the study period. tb treatment success rate was at a range 63.5–86.2%. the 2017 treatment success rate in the refugee camps (63.5%) was lower than the report for sudan (78%) and the end tb target for 2020 (≥90%), which needs to be addressed. there was a high ltfu, mortality, and non-evaluation, which showed that there was a gap in the tb treatment program in the refugee heath facilities. future research is recommended to investigate the increase in eptb. the study has generated useful evidence of treatment outcomes of notified tb case from 2014 to 2017 that will support to plan effective tb care and prevention programs in the refugee camps in sudan. however, as this study was conducted retrospectively based on secondary data, it had some limitations. although, socioeconomic factors (occupation, education, and income level), health system factors, and patient-related factors were reported to be associated with unsuccessful treatment outcome in other studies, we were not able to include these variables in our analysis as we used secondary data. we used only independent variables available in the unit tb register to assess factors associated with unsuccessful treatment outcomes. doi 10.18502/sjms.v16i2.9293 page 267 sudan journal of medical sciences tsegay legesse et al acknowledgements none. ethical considerations individual consent was not required as the data used were secondary, collected from the tb register in the refugee camps. ethical approval and permission were obtained from the national research ethics review committee, health research council, ministry of health, republic of sudan (proposal no 1-1-19). competing interests the authors declare that they have no competing interests. availability of data and materials all analyzed data were included in this manuscript. however, patient-level data, which were analyzed, can be received with permission of ntp, communicable and noncommunicable disease department, in the ministry of health (moh), sudan. funding this study was financially supported by the global fund to fight aids, tb and malaria, the global health campus chemin du pommier 40, 1218, le grand-saconnex, switzerland. supplement 1 operational definitions tb case notification: tb is diagnosed in a patient and is reported within the national tb surveillance system. tb cases: a patient in whom tb has been diagnosed. a tb case is defined as: doi 10.18502/sjms.v16i2.9293 page 268 sudan journal of medical sciences tsegay legesse et al (i) a bacteriologically confirmed tb case: is one from whom a biological specimen is positive by smear microscopy, culture, or who-approved rapid diagnostics (such as xpert mtb/rif). (ii) a clinically diagnosed tb case: is one who does not fulfil the criteria for bacteriological confirmation but has been diagnosed with active tb by a clinician or other medical practitioner who has decided to give the patient a full course of tb treatment. bacteriologically confirmed or clinically diagnosed cases of tb are also classified according to anatomical site of disease, history of previous treatment, drug resistance, and hiv status. classification based on anatomical sites: (i) pulmonary tuberculosis (ptb): any bacteriologically confirmed or clinically diagnosed case of tb involving the lung parenchyma or the tracheobronchial tree. (a) pulmonary tb positive (ptb+): bacteriologically confirmed ptb cases using available confirmatory diagnostic. (b) pulmonary tb negative (ptb–): clinically diagnosed ptb cases. (ii) extrapulmonary tuberculosis (eptb): any bacteriologically confirmed or clinically diagnosed case of tb involving organs other than the lungs classification based on history of previous tb treatment (patient registration group): (i) new tb patients: are those who have never been treated for tb or have taken anti-tb drugs for less than one month. (ii) previously treated tb patients: are those who have received one month or more of anti-tb drugs in the past. they are further classified by the outcome of their most recent course of treatment as follows: (a) relapse patients: are those who have previously been treated for tb, were declared cured, or the treatment was completed at the end of their most recent course of treatment but and are now diagnosed with a recurrent episode of tb (either a true relapse or a new tb caused by reinfection). (b) treatment after failure patients: are those who have previously been treated for tb and whose treatment failed at the end of their most recent course of treatment. doi 10.18502/sjms.v16i2.9293 page 269 sudan journal of medical sciences tsegay legesse et al (c) treatment after loss to follow-up patients: are those who have previously been treated for tb and were declared ltfu at the end of their most recent course of treatment. (these were previously known as treatment after default patients.) (d) other previously treated patients: are those who have previously been treated for tb but whose outcome after their most recent course of treatment is unknown or undocumented. (e) transfer in: a patient who started treatment in one health facility (reporting unit) and was then transferred to another health facility (reporting unit) to continue treatment. classification based on tb treatment outcomes for drug sensitive-tb: (i) cured: a pulmonary tb patient with bacteriologically confirmed tb at the beginning of treatment who was smearor culture-negative in the last month of treatment and on at least one previous occasion. (ii) treatment completed: a tb patient who completed treatment without evidence of failure but with no record to show that sputum smear or culture results in the last month of treatment and on at least one previous occasion were negative either because tests were not done or because results are unavailable. (iii) treatment failed: a tb patient whose sputum smear or culture is positive at month 5 or later during treatment. (iv) lost to follow-up (ltfu): a tb patient who did not start treatment or whose treatment was interrupted for two consecutive months or more. (v) died: a tb patient who dies for any reason before starting or during the course of treatment. (vi) not evaluated: a tb patient for whom no treatment outcome is assigned. this includes cases “transferred out” to another treatment unit as well as cases for whom the treatment outcome is unknown to the reporting unit. (a) successful treatment: sum of cured and treatment completed outcomes. (b) unsuccessful treatment: sum of died, treatment failed, and ltfu outcomes. doi 10.18502/sjms.v16i2.9293 page 270 sudan journal of medical sciences tsegay legesse et al table 1: characteristics of notified tb cases in al kashafa, wadsherify, and shagarab refugee camps, sudan, 2014–2017 (n = 710). characteristic 2014, n (%) 2015, n (%) 2016, n (%) 2017, n (%) total (2014–2017) total tb cases (row, %) 143 (20.1) 80 (11.3) 146 (20.6) 341 (48.0) 710 (100) mean age (sd), yr 38.2 (19.1) 42.0 (21.6) 39.5 (19.0) 28.2 (21.4) 34.1 (21.4) by age groups <15 12 (8.4) 8 (10.0) 20 (13.7) 117 (34.3) 157 (22.1) 15–24 30 (21.0) 8 (10.0) 10 (6.9) 50 (14.7) 98 (13.8) 25–34 27 (18.9) 17 (21.3) 30 (20.1) 44 (12.9) 118 (16.6) 35–44 19 (13.3) 12 (15.0) 25 (17.1) 36 (10.6) 92 (13.0) 45–54 20 (14.0) 13 (16.3) 19 (13.0) 40 (11.7) 92 (13.0) 55–64 11(7.7) 5 (6.3) 26 (17.8) 31 (9.1) 73 (10.3) >=65 24 (16.8) 17 (21.3) 16 (11.0) 21 (6.2) 78 (11.0) not recorded 0 0 0 2 (0.6) 2 (0.3) by gender male 72 (50.4) 46 (57.5) 81 (55.9) 178 (52.7) 377 (53.4) female 71 (49.6) 34 (42.5) 64 (44.1) 160 (47.3) 329 (46.6) male to female ratio 1 1.4 1.7 1.1 1.1 by type of tb ptb 101 (70.6) 51 (63.8) 94 (64.4) 207 (60.7) 453 (63.8) eptb 42 (29.4) 29 (36.2) 52 (35.6) 134 (39.3) 257 (36.2) by diagnostic category ptb+ 54 (37.8) 30 (37.5) 37 (25.3) 85 (24.9) 206 (29.0) ptb– 47 (32.9) 21 (26.3) 57 (39.1) 122 (35.8) 247 (34.8) eptb 42 (29.4) 29 (36.2) 52 (35.6) 134 (39.3) 257 (36.2) by type of tb patients new and relapse 138 (96.5) 80 (100) 141 (96.6) 321 (94.1) 680 (95.8) treatment after failure 4 (2.8) 0 0 1 (0.3) 5 (0.7) lost to follow-up to treatment 1 (0.7) 0 5 (3.4) 15 (4.4) 21 (3.0) others 0 0 0 4 (1.2) 4 (0.6) new and relapse –ptb patients 97 (70.3) 51 (63.8) 89 (63.1) 189 (58.9) 426 (62.6) bacteriologically confirmed 51 (52.6) 30 (58.8) 36 (40.4) 76 (40.2) 193 (45.3) clinically diagnosed 46 (47.4) 21 (41.2) 53 (59.6) 113 (59.8) 233 (54.7) by hiv status positive 1 (2.0) 4 (7.1) 3 (4.2) 6 (4.7) 14 (4.6) negative 47 (98.0) 52 (92.9) 68 (95.8) 122 (95.3) 289 (95.4) not documented 95 (66.4) 24 (30) 75 (52.4) 213 (62.5) 407 (1.6) by refugee camps al kashafa 0 0 60 274 334 (47.0%) shagarab 98 41 47 20 206 (29.0%) wadsherify 45 39 39 47 170 (23.9%) ptb+: smear-positive pulmonary tb; ptb–: clinically diagnosed ptb, which includes smear-negative pulmonary tb and smear not done/unknown. doi 10.18502/sjms.v16i2.9293 page 271 sudan journal of medical sciences tsegay legesse et al table 2: tb treatment outcome of all tb cases registered in al kashafa, wadsherify, and shagarab refugee camps, sudan, 2014–2017 (n = 710). years total treatment outcome 2014 (n = 143) n (%) 2015 (n = 80) n (%) 2016, (n = 146) n (%) 2017 (n = 341) n (%) total (n = 710) n (%) cured 38 (26.6) 28 (35.0) 25 (17.1) 42 (10.6) 133 (18.7) treatment completed 74 (51.7) 41 (51.2) 96 (65.8) 194 (56.9) 405 (57.0) treatment failed 0 0 1 (0.7) 1 (0.3) 2 (0.3) ltfu 12 (8.4) 3 (3.8) 12 (8.2) 54 (15.8) 81 (11.4) died 6 (4.2) 3 (3.8) 9 (6.2) 29 (8.5) 47 (6.6) not evaluated 13 (9.1) 5 (6.2) 3 (2.0) 21 (6.2) 42 (5.9) success rate 112 (78.3) 69 (86.2) 121 (82.9) 252 (63.5) 538 (75.7) table 3: demographic and clinical characteristics associated with unsuccessful tb treatment outcomes among all tb cases in al kashafa, wadsherify, and shagarab refugee camps, sudan, 2014–2017. characteristics successful outcomes unsuccessful outcomes x2, p-value bivariate analysis multivariable analysis or (95%ci) p-value adjusted or (95%ci) p-value gender female 250 (80.7) 60 (19.3) 0.002 1 male 285 (80.5) 69 (19.5) 0.9 1.02 (0.7–1.5) 0.9 age group <15 110 (71.9) 43 (28.1) 1 15–24 80 (86.0) 13 (14.0) 15.2 0.4 (0.2–0.8) 0.01 0.4 (0.2–0.9) 0.02 25–34 91 (84.3) 17 (15.7) 0.03 0.5 (0.3–0.9) 0.02 0.5 (0.3–1.0) 0.06 35–44 70 (81.4) 16 (18.6) 0.6 (0.3–1.1) 0.1 0.6 (0.3–1.2) 0.2 45–54 69 (84.1) 13 (15.9) 0.5 (0.2–0.96) 0.04 0.5 (0.3–1.0) 0.06 55–64 59 (83.1) 12 (16.9) 0.5 (0.3–1.1) 0.07 0.6 (0.3–1.2) 0.1 >=65 59 (79.7) 15 (20.3) 0.7 (0.3–1.3) 0.2 0.7 (0.3–1.3) 0.2 pretreatment weight, kg* >40 188 (81.0) 44 (19.0) 1.2 1 <40 78 (75.7) 25 (24.3) 0.2 1.4 (0.7–2.4) 0.2 type of tb ptb– 169 (73.8) 60 (26.2) 1 1 ptb+ 162 (83.9) 31 (16.1) 10.1 0.5 (0.3–0.8) 0.01 0.6 (0.4–1.1) 0.07 eptb 207 (84.1) 39 (15.9) 0.006 0.5 (0.3–0.8) 0.006 0.5 (0.3–0.9) 0.009 hiv status negative 238 (88.5) 31 (11.5) 1.5 1 0.2 positive 10 (76.9) 3 (23.1) 0.2 2.3 (0.6–8.8) ptb+: smear-positive pulmonary tb; ptb–: clinically diagnosed ptb, which includes smear-negative pulmonary tb and smear not done/unknown; or: odds ratio; ci: confidence interval; 1:00, reference; x2: chi-square. *analysis done for adults aged ≥15 years. doi 10.18502/sjms.v16i2.9293 page 272 sudan journal of medical sciences tsegay legesse et al references [1] who. 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(2007). clinical and demographic characteristics of patients hospitalized with tuberculosis in brazil between 1994 and 2004. jornal brasileiro de pneumologia, vol. 33, no. 5, pp. 565–571. doi 10.18502/sjms.v16i2.9293 page 275 introduction materials and methods study settings and participants study design and data collection data analysis operational definitions results general characteristics tb cases by diagnostic and age categories notified tb cases by hiv status tb treatment outcomes from 2014 to 2017 demographic and clinical characteristics associated withunsuccessful tb treatment outcomes in sudan refugee camps (2014–2017) discussion notified tb cases treatment outcomes conclusion acknowledgements ethical considerations competing interests availability of data and materials funding supplement 1 operational definitions references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9295 production and hosting by knowledge e research article feelings, stress, and coping of nurses amidst covid-19 outbreak in saudi arabia natividad, maria jocelyn b.1, aljohani, khalid a.2, roque, mark y.3, and gamboa, helen m.3 1medical surgical nursing department, college of nursing, taibah university, madinah, saudi arabia 2community health nursing department, college of nursing, taibah university, madinah, saudi arabia 3maternity & child nursing department, college of nursing, taibah university, madinah, saudi arabia orcid: natividad, maria jocelyn b.: http://orcid.org/0000-0003-2701-6144 aljohani, khalid a.: http://orcid.org/0000-0003-3242-0820 roque, mark y.: http://orcid.org/0000-0003-3401-3152 abstract background: a year after the covid-19 pandemic spread around the world, the pandemic is still affecting healthcare systems with an increasing number of infected healthcare workers. such a unique situation may often result in emotional turmoil, anxiety, depression, and fear, which could lead to resignation and burnout. the study intended to assess the feelings of nurses toward the covid-19 outbreak; ascertain the factors that cause stress; and determine their coping strategies and factors contributing to coping. methods: a descriptive cross-sectional design was utilized to recruit 313 nurses working in the ministry of health (saudi arabia) hospitals that accommodate covid-19 patients. the study instrument was adapted and modified from the ”mers-cov staff questionnaire” and the brief cope. results: the results showed that female, married, those with a bachelor’s degree, and aged 25–34 years had higher significant coping strategies. on the other hand, filipino nurses assigned in the outpatient department and covid-19 isolation ward had more negative feelings and encountered several factors causing stress but were coping in a better way than others. conclusion: nurses’ commitment to their profession appears to be an intrinsic motivation to continue caring for covid-19 patients despite the risk of infection. comfort with religion, spiritual beliefs, and the presence of a support system were the coping strategies used by nurses to ameliorate the stress and negative feelings during the covid-19 outbreak. keywords: covid-19, saudi arabia, nurses, feelings, factors causing stress, coping strategies how to cite this article: natividad, maria jocelyn b., aljohani, khalid a., roque, mark y., and gamboa, helen m. (2021) “feelings, stress, and coping of nurses amidst covid-19 outbreak in saudi arabia,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 285–300. doi 10.18502/sjms.v16i2.9295 page 285 corresponding author: maria jocelyn b. natividad; medical-surgical department college of nursing, taibah university, madinah, saudi arabia. email: mjnatividad@taibahu.edu.sa received 25 march 2021 accepted 8 june 2021 published 30 june 2021 production and hosting by knowledge e maria jocelyn b. natividad et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0003-2701-6144 http://orcid.org/0000-0003-3242-0820 http://orcid.org/0000-0003-3401-3152 mailto:mjnatividad@taibahu.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences maria jocelyn b. natividad et al 1. introduction the world was alarmed when the who declared a public health emergency of international concern on january 30, 2020, about the outbreak of novel coronavirus disease 2019 (covid-19) [1]. this virus is identical to the coronavirus family that caused severe acute respiratory syndrome (sars-cov), which was reportedly originated from china in 2003 and the middle east respiratory syndrome (mers-cov) in saudi arabia in 2012 [2, 3]. a year later, the pandemic spread across the world and had a great impact on the healthcare system. in particular, healthcare providers (hcps) were under great pressure to deal with the pandemic, including technical procedures to prevent the transmission such as prolonged use of personal protective devices [4, 5]. moreover, hcps are the ones who spearheaded the outbreak response in health institutions [6]. consequently, they struggle with psychological agony and mental distress [7, 8], in addition to the risk of exposure to the virus, long working hours, and fatigue [9, 10]. from a nursing stand, nurses as front liners experienced dilemmas because they thought of safety not only for themselves but also their families [11, 12]. as they are exposed to covid-19 patients, fear escalates, emotion intensifies, and anxiety increases, thereby coping is more utilized [13]. previous studies conducted during the mers-cov outbreak in saudi arabia and south korea, found that nurses caring for positive clients were worried about transmitting the infection to others, leading them to stress, but they could not refuse to attend their clinical duties due to their professional responsibility during the pandemic [14, 15]. during the height of covid-19 infection in wuhan, china, nurses assigned to isolation units did not receive mental health coaching, which increased nurses’ susceptibility to suffer from psychological distress [16]. during crises, mental health counseling matters [17], therefore, the hospital designated an area to isolate nurses from others, wherein food and daily living supplies were provided, leisure activities to reduce stress were offered, and psychological counseling was conducted [18]. in saudi arabia, expatriate nurses form the majority. their feelings of being away from family during difficult times may bring mixed feelings and emotions in which they need to utilize coping strategies to reduce stress and remain committed to their oath being in the frontline. interestingly, the international nursing workforce operates the saudi healthcare system. henceforth, there is a need for a study to investigate nurses’ feelings, stress, and coping during a year of covid-19 pandemic. this may contribute doi 10.18502/sjms.v16i2.9295 page 286 sudan journal of medical sciences maria jocelyn b. natividad et al to enhancing the guidelines on staffing, workforce, management of resources, protocol compliance, and debriefing approaches among nurses. 1.1. objectives of the study the study intended to assess the feelings of nurses toward the covid-19 outbreak; ascertain the factors that cause stress; and determine their coping strategies and factors contributing to coping. 2. materials and methods 2.1. study design a descriptive cross-sectional design was used to assess the feelings, factors that cause stress, and coping strategies of nurses caring for covid-19 clients at the ministry of health (moh) hospitals and other health agencies in madinah, saudi arabia. using raosoft sample calculator with a 5% margin of error at 95% confidence level [19], a total of 275 (n = 275) samples were taken as participants from the total population (n = 964). the adopted method of determining sample size for descriptive design has been widely used in recent studies [20, 21]. however, 313 nurses participated in the study, which is more than the sample size, thus, ensuring accuracy for missing data and nonresponse from other participants. it applied the following inclusion criteria: male and female nurses assigned in the emergency & triage department (ed), outpatient department (opd), critical care unit (ccu), covid isolation ward, and medical surgical ward. nurses who did not have direct contact with covid-19 patients were excluded. 2.2. instrument the instruments were adapted and modified from khalid et al.’s (2016) “mers-cov staff questionnaire” for the feelings and factors that cause stress [14] and “brief cope” for coping strategies [22]. the study instrument consisted of 9 question items exploring feelings, 12 items exploring factors causing stress, and 20 items were lifted from the original 28 brief cope to assess coping strategies that best fit with the current situation and culture in saudi arabia. the instrument underwent face and content validity through the help of research experts, as well as a pilot tested with 30 staff nurses in which cronbach’s alpha showed scores of 0.700 for feelings, 0.850 for factors causing stress, doi 10.18502/sjms.v16i2.9295 page 287 sudan journal of medical sciences maria jocelyn b. natividad et al and 0.831 for coping strategies. these scores supported the instrument’s ability to measure the variables being tested. the likert scale used for feelings and factors causing stress ranged from most of the time, some of the time, seldom, and never; while for coping strategies were always used, often used, sometimes used, and never used. 2.3. data collection the instrument was uploaded to surveymonkey.com and the link was sent to the participants via whatsapp. however, in other hospitals, questionnaires were distributed with the help of the nursing education and training departments. a period of two months including follow-up were allotted to data collection. data were collected, summarized, tallied, and reviewed for analysis and interpretation. 2.4. data analysis data were analyzed using spss version 23. descriptive statistics like weighted mean and standard deviation were utilized to determine the variability of responses and identify the highest and the lowest value. independent sample t-test and two-way anova were utilized to measure significant differences within the groups. furthermore, the significant difference was also tested using the post-hoc test known as bonferroni. 3. results three hundred thirteen (313) nurses answered the questionnaires. the majority of the nurses caring for covid-19 patients were female (86.30%), aged 25–34 years (56.20%), married (54.40%), and permanent residents of saudi arabia (46.30%). furthermore, most of them were staff nurses (87.50%), had a bachelor’s degree (76%) with 1–5 years’ experience in clinical setting (34.20%), and assigned to the covid isolation unit (29.10%) and ed (27.20%). nurses with undergraduate qualifications accounted for 20.4%, while bsn and postgraduates were 76% and 3.5%, respectively. in terms of professional experience, 20% were recently employed, 34.2% had been practicing for up to five years, 23.3% had an experience of 6–10 years; and 22.4% were expert nurses with 11 or more years of nursing practice. table 1 shows that sometimes nurses felt that they had to do their job because of their professional and ethical duties (m = 3.40; sd = 1.024). given the chance, they wanted doi 10.18502/sjms.v16i2.9295 page 288 sudan journal of medical sciences maria jocelyn b. natividad et al table 1: nurses’ feelings during covid-19 pandemic. indicators mean sd i feel that i had to do my job as it was my professional and ethical duty 3.40 1.024 if given a chance, i would have chosen to work in a unit where i would not be exposed to covid-19 3.03 0.978 i feel nervous about contracting the virus 2.97 1.036 i feel scared because i am exposed to covid-19 patients 2.96 1.025 i am unhappy to do overtime 2.96 1.057 i feel that employees not directly exposed to covid-19 avoided me 2.80 1.095 i feel angry that my workload increased compared to employees not exposed to covid-19 2.67 1.113 i think of calling for a leave 2.59 1.120 i will quit my job if the covid19 outbreak recurred 2.36 1.239 composite mean 2.86 0.689 scores for feelings during the covid-19 pandemic: 1.00–1.49: never; 1.50–2.49: seldom; 2.50–3.49: some of the time; 3.50–4.00: most of the time. to work in a unit where they were not exposed to covid-19 (m = 3.03; sd = 0.978). they were nervous with the feeling of contracting the disease (m = 2.97; sd = 1.036), unhappy to do overtime work (m = 2.96; sd = 1.057) and scared because of exposure to positive patients (m = 2.96; sd = 1.025), respectively. on the contrary, they seldom felt that they would quit their jobs if the covid-19 outbreak recurred (m = 2.36; sd = 1.239). table 2 shows factors increasing participants’ stress. starting from the highest impact, the nurses thought that they could transmit covid-19 to their families and friends, which has the highest score (m = 3.36; sd = 0.0874), followed by the inadequacy of personal protective equipment (m = 3.30; sd=0.796) and that they might be positive to the disease whenever they had respiratory symptoms (m = 3.22; sd = 0.813). the lowest scored factor that caused stress among them was lack of cure for covid-19 (m = 3.02; sd = 0.871). participants often found comfort in their religion or spiritual beliefs (m = 3.20; sd = 0.866); getting advice from friends, family, and coworkers (m = 3.18; sd = 0.852); and trying to see the situation in a different perspective (m = 3.13; sd = 0.873) as their coping strategies during the period of covid-19 pandemic (table 3). the least used coping strategies were making jokes out of the situation (m = 2.07; sd = 1.007) and expressing negative feelings through social media (m = 2.11; sd = 1.109). table 4 discloses that there was a significant difference in the coping strategies when grouped according to gender (p = 0 .002), which shows that females have greater coping doi 10.18502/sjms.v16i2.9295 page 289 sudan journal of medical sciences maria jocelyn b. natividad et al table 2: factors causing stress. indicators mean sd an increasing number of covid-19 cases were reported by the media 3.17 0.905 lack of cure for covid-19 3.02 0.871 having close contact with asymptomatic people 3.16 0.908 seeing my colleagues stressed or afraid of the current situation 3.04 0.931 prolonging the use of personal protective equipment during my clinical duty 3.35 0.799 thinking of inadequacy of personal protective equipment 3.30 0.796 displaying covid19-like symptoms of my colleagues 3.04 0.876 thinking that i might have covid-19 whenever i have respiratory symptoms 3.22 0.813 considering that i could transmit covid-19 to my family and friends 3.36 0.874 conflicting perception between my duty and safety 3.17 0.844 experiencing physical stress 3.18 0.829 showing emotional exhaustion 3.16 0.854 composite mean 3.18 0.523 scores for factors causing stress: 1.00–1.49: never; 1.50–2.49: seldom; 2.50–3.49: some of the time; 3.50–4.00: most of the time. strategies. as for the age, the response differed with feelings (p = 0.018) and coping strategies (p = 0.036). the differences were observed in 18–24-year-olds for feeling and 25–34-year-olds for coping as revealed by the post-hoc test. married staff (p = 0.001) had greater coping strategies compared to singles, while filipinos experienced more negative feelings as well as factors causing stress but had greater coping strategies. concerning the area of assignment, the responses differed on feelings during covid19 in opd and the factors causing stress in covid isolation ward. a significant difference was also noted in coping strategies when grouped according to nursing qualification (p = 0.022) and from the post-hoc test conducted; this was found in those with bachelors’ degrees. lastly, a significant difference was observed in feelings during covid-19 and coping strategies when grouped according to years of experience as staff. table 5 presents the association of staff feelings during covid-19, factors causing stress, and coping strategies. as seen from the results, r-values indicate a moderate direct correlation and reveal that the computed p-values were <0.01 alpha level. doi 10.18502/sjms.v16i2.9295 page 290 sudan journal of medical sciences maria jocelyn b. natividad et al table 3: coping strategies of nurses. indicators mean sd i’ve been… refusing to believe that it is happening 2.39 1.090 expressing my negative feelings through social media 2.11 1.109 making jokes about it 2.07 1.077 focusing on my work to divert my attention from the current situation 2.90 0.973 saying good things to relieve my unpleasant feelings 3.10 0.913 getting help and advice from my family, friends, and coworkers 3.18 0.852 sleeping more than the usual number of hours 2.63 1.069 spending more time on my hobbies 2.46 1.054 playing digital or online games to divert my attention 2.38 1.118 eating more than usual 2.38 1.061 spending my time on social media 2.69 0.973 watching movies and tv series to think about it less 2.47 1.050 engaging more time to do exercises 2.24 1.013 spending time cleaning and rearranging things in my room 2.70 1.018 trying to find comfort in my religion or spiritual beliefs 3.20 0.866 reading and listening to inspirational messages and podcasts 2.81 0.961 using meditation and yoga to relax 2.20 1.070 listening to my favorite music 2.72 1.015 thinking what is to be done, one step at a time 2.97 0.860 trying to see the situation from a different perspective, to make it more positive 3.13 0.873 composite mean 2.64 0.549 scores for coping strategies for nurses: 1.00–1.49: never used; 1.50–2.49: seldom used; 2.50–3.49: often used; 4. discussion researchers faced difficulties in the online survey because of the low response rate which could be associated with the stress and exhaustion nurses faced during the period of disease outbreak. only 51%, which accounts to 139 nurses, participated in the online survey out of the 275 target samples. limitations of the online surveys could also be linked to respondents’ poor engagement in answering time, inclusion of non-nursing staff, computer literacy, and weak or no access to internet. this means assistance from training and education nursing units through face-to-face surveys was sought to come up with the needed data. nurses working in the frontline during disease outbreak had mixed feelings and experienced psychological repercussions because of stress of the covid-19 outbreak. doi 10.18502/sjms.v16i2.9295 page 291 sudan journal of medical sciences maria jocelyn b. natividad et al table 4: comparison of staff feeling, factors causing stress, and coping strategies when grouped by demographic profile. nurses’ feelings factors causing stress coping strategies mean ±±± sd mean ±±± sd mean ±±± sd gender male 2.77 ± 0.646 3.18 ± 0.423 2.40 ± 0.495 female 2.88 ± 0.696 3.18 ± 0.423 2.67 ± 0.548 p-value 0.338 0.982 *0.002 age group (yr) 18–24 3.02 ± 0.708 3.16 ± 0.472 2.65 ± 0.649 25–34 2.87 ± 0.669 3.21 ± 0.535 2.70 ± 0.524 35–44 2.75 ± 0.582 3.14 ± 0.501 2.45 ± 0.489 45–54 2.36 ± 1.019 3.04 ± 0.672 2.50 ± 0.467 55–64 2.78 ± 0.729 3.08 ± 0.821 2.42 ± 0.369 p-value *0 .018 0 .689 *0.036 marital status married 2.83 ± 0.665 3.19 ± 0.491 2.54 ± 0.486 single 2.90 ± 0.718 3.17 ± 0.561 2.75 ± 0.598 p-value 0 .377 0.743 *0.001 nationality saudi 2.92 ± 0.640 3.23 ± 0.461 2.56 ± 0.587 filipino 2.96 ± 0.722 3.24 ± 0.561 2.81 ± 0.478 indian 2.66 ± 0.713 3.01 ± 0.567 2.65 ± 0.522 egyptian 2.62 ± 0.676 3.19 ± 0.543 2.20 ± 0.240 p-value *0.016 *0 .019 *0.000 area of assignment out-patient department 3.05 ± 0.405 3.14 ± 0.346 2.83 ± 0.432 critical care unit 2.62 ± 0.775 2.99 ± 0.605 2.59 ± 0.537 emergency & triage department 2.89 ± 0.582 3.24 ± 0.453 2.71 ± 0.532 covid isolation ward 3.03 ± 0.685 3.35 ± 0.483 2.55 ± 0 570 medical–surgical ward 2.82 ± 0.707 3.07 ± 0.512 2.69 ± 0.571 p-value *0.003 *0.000 0.167 job title staff nurse 2.90 ± 0.687 3.18 ± 0.520 2.63 ± 0.562 in-charge 2.65 ± 0.634 3.19 ± 0.520 2.64 ± 0.425 head nurse 2.51 ± 0.712 3.21 ± 0.620 2.65 ± 0.510 p-value 0.067 0.863 0.899 educational qualification diploma/associate 2.78 ± 0.551 3.16 ± 0.456 2.48 ± 0.505 bachelor of science 2.89 ± 0.720 3.18 ± 0.541 2.68 ± 0.557 master/doctorate degree 2.60 ± 0.703 3.31 ± 0.527 2.53 ± 0.476 p-value 0.219 0.695 *0.022 years of experience <1 3.02 ± 0.708 3.18 ± 0.491 2.68 ± 0.661 1–5 2.84 ± 0.739 3.12 ± 0.581 2.77 ± 0 564 6–10 2.94 ± 0.641 3.29 ± 0.446 2.59 ± 0.465 ≥11 2.67 ± 0.603 3.15 ± 0.526 2.45 ± 0.437 p-value *0.019 0 .198 *0.002 *significant at p < 0.05. doi 10.18502/sjms.v16i2.9295 page 292 sudan journal of medical sciences maria jocelyn b. natividad et al table 5: correlation between staff feelings during covid 19, factors causing stress, and coping strategies feeling factors coping strategies feelings r-value 1 0.553∗∗ 0.368∗∗ p-value 0.000 0.000 factors r-value 0.553∗∗ 1 0.224∗∗ p-value 0.000 0.000 coping r-value 0.368∗∗ 0.224∗∗ 1 p-value 0.000 0.000 **correlation is significant at the 0.01 level (two-tailed). this cross-sectional survey divulged that nurses aged 18–24 years vary in feelings when caring for covid-19 patients compared to other age groups which are influenced by the emotional maturity that develops during the transition from late adolescents to young adults as the latter have better control over things [23–25]. at the same time, it is significant to note that filipino nurses experience more negative feelings and stress but cope better among others as they are well-known for their resilience. nurses working in a foreign land with different cultures may experience stigma when being isolated due to exposure to infectious diseases [26], that is why they need to effectively use coping strategies to enhance their mental health considering they are away from their support system. perhaps, nursing administration and management should consider extending more support among expatriate nurses. looking into the area of assignment, nurses in opd and covid-19 isolation wards had different feelings and stress toward their exposure to positive patients. the nurses working in the direct treatment of covid-19 had more uncertainty against those nurses who had a short period of interaction with positive patients [27–29]. hence, a more planned and rational allocation of workforce by pairing expert nurses and beginners should be considered to ensure effective delivery of nursing care. moreover, this study discloses that female, married staff nurses aged 2534 years coped better during covid-19 outbreak compared to males. the study finding could be associated with the reality that female nurses have a better understanding of the prevention of covid-19 [30]. correspondingly, married and young adults have better ways of controlling their emotions, thus they cope effectively unlike singles who are more likely to develop depression [31]. however, finding differs from the findings of the study conducted in italy and pakistan which revealed that males have better mental health and coping strategies during the disease outbreak compared to females [32, 33]. likewise, chinese female nurses exhibited more severe anxiety than males [17]. establishing doi 10.18502/sjms.v16i2.9295 page 293 sudan journal of medical sciences maria jocelyn b. natividad et al guidelines per nurses’ demographics must be a requisite among healthcare institutions to strengthen their mental health. current findings are congruent with the report during the mers-cov epidemic in south korea, wherein nurses went through “inevitable fear, being alone, exhausted strength, extreme stress, and stigma from society [15; likewise, nurses working in saudi arabia felt nervous and scared during the outbreak [14]. however, such fears did not prevent nurses from attending to their professional and ethical responsibilities, which is evident in the current study. international studies also support these findings. a study during the ebola outbreak reported that nurses and midwives faced the risk in caring for patients as they believed that they have the responsibility to their profession, community, and religion [34]. similarly, a report in hubei, china stated that front liners endured longer working hours despite fatigue due to their social and professional obligations [11, 12]. nevertheless, maintaining a “positive attitude” helps nurses to deal effectively during stressful situations [35, 37]. among the factors that cause most of the stress is the anxiety that they could transmit the disease to their family and friends (m = 3.36), which is different from the stressors of nurses during mers-cov in which safety is their primary concern [14]. the long period of pandemic scares nurses concerned about their family health. correspondingly, the prolonged use of ppe also added to their stress (m = 3.35), which is also congruent to the study in hangzhou, china, as their personal needs like eating and toileting were limited [38]. the disease being a public emergency creates a negative impact on performing daily activities by the affected population as well as nurses as they are the ones primarily exposed to positive patients [39], which causes shame that in turn affects their mental health and further intensifies their stress [7, 40]. therefore, identifying stressors could counteract their negative effects through effective coping, and thus, fostering optimism among nurses. to help ease negative feelings and stress, nurses secure comfort through their religion and spiritual beliefs (m = 3.20). working in saudi arabia, the center of islamic religion, inspired nurses to be more optimistic despite global health crises. the help and advice from their family, friends, and coworkers were also a significant finding as commensurate with the previous report whereby nurses got “high support from family and colleagues but unfortunately low from their community” [41]. support systems during a pandemic reduce stress and enhance self-worth. in addition, the positive attitude of nurses toward the working condition significantly contribute to their coping [14]. overall, the study implies that the more negative the feelings are, the more intensified the effects of the factors causing stress and vis-a-vis; and therefore, the more coping doi 10.18502/sjms.v16i2.9295 page 294 sudan journal of medical sciences maria jocelyn b. natividad et al strategies are utilized. henceforth, the nursing administration should re-evaluate their guidelines in staffing, workforce, management of resources, protocol compliance, and debriefing approaches to uplift the physical, psychological, emotional, and social wellbeing of nurses. 4.1. the implication to nursing practice the result of the study will be an inspiration for nurses that despite the health crises they are facing, the pledge to the profession matters the most. strong spirituality, despite cultural differences, helps them to fulfill their duties and obligations to their patients. nursing administration may consider reviewing their guidelines in human resource management and taking into consideration enhancing the psychological wellness of nurses by creating a mental health program. the study could influence novice and future nurses to be more engaged in rendering quality care despite the imposed risks. correspondingly, the modified instrument can be used to investigate feelings, factors causing stress, and coping strategies concerning the quality of care rendered by nurses. 4.2. limitations and considerations for future studies the present study has a few limitations in which not all healthcare workers were considered as a sample that could have resulted in selection bias. the study was conducted only in one city of saudi arabia. future studies using all hcps as samples and follow-up surveys that link to the effectiveness of nursing care are recommended to be conducted after the covid-19 ends. considering other cities in the country will further augment the reliability of results. 5. conclusion staff nurses aged 18–24 years had different feelings when caring for covid-19 patients. nurses who were female, married, had a bachelor’s degree, and were aged 25–34 years had more significant coping strategies. separately, filipino nurses assigned in opd and covid-19 isolation ward had more negative feelings and encountered several factors causing stress but coped better compared to others. notably, nurses’ commitment to their profession is an intrinsic motivation to continue caring for covid-19 patients despite the risk of transmitting the disease to their families, friends, and colleagues. comfort with religion, spiritual beliefs, and the presence of a doi 10.18502/sjms.v16i2.9295 page 295 sudan journal of medical sciences maria jocelyn b. natividad et al support system were the best coping strategies for them to lessen the stress and negative feelings during the covid-19 outbreak. acknowledgements the authors are thankful to ms. glezzielyn pascua of king fahad hospital, madinah, saudi arabia ethical considerations ethical approval was obtained from the institutional review board of the general directorate of health affairs in madinah (h-03-m-084). informed consent was drafted with all information about the study and attached to the questionnaire for participants to be reminded of the conditions agreed upon. participants were assured of their anonymity and confidentiality of the data provided by them. thus, their participation was voluntary, and no coercion was involved. the data collected were stored in one file and can be accessed only by the researchers. availability of data and materials data used in the study are available from the corresponding author upon reasonable request. funding this study was funded by taibah university in madinah under the moe in saudi arabia. references [1] world health organization. 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(2021). working conditions and health status of 6,317 front-line public health workers during the covid-19 epidemic across5 provinces in china: a cross-sectional study. bmc public health, vol. 21, article 106. doi 10.18502/sjms.v16i2.9295 page 300 introduction objectives of the study materials and methods study design instrument data collection data analysis results discussion the implication to nursing practice limitations and considerations for future studies conclusion acknowledgements ethical considerations availability of data and materials funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9942 production and hosting by knowledge e research article the impact of cataract surgery on depression in elderly iranian patients: a case–control study kiumars nowroozpoor dailami1, mohammad ali heidari gorji2, seyed hamzeh hoseini3, and asadollah farookhfar1 1department of ophthalmology, school of medicine, mazandaran university of medical sciences, sari, iran 2department of medical–surgical nursing, nasibeh school of nursing and midwifery, mazandaran university of medical sciences, sari, iran 3psychiatry and behavioral sciences research center, addiction institute, mazandaran university of medical sciences, sari, iran orcid: asadollah farookhfar: https://orcid.org/0000-0002-5584-7423 abstract background: cataract-related vision impairment is clearly associated with depressive symptoms in old age. this study aimed to evaluate the effect of cataract surgery on depression among elderly iranian patients. methods: in this case–control study, a total of 113 elderly patients with and without cataract who were admitted to buali-sina hospital in sari, mazandaran, iran were evaluated. ophthalmological examinations were first performed at the beginning of the study and then four months later; demographic and clinical characteristics were obtained for all patients. additionally, depression was assessed using the hospital anxiety and depression scale (hads) for all patients during the study period. results: a statistically significant difference was found between the mean depression score in patients without cataract (3.28), patients with cataract surgery (3.74), and patients without cataract surgery (5.60) (p = 0.024). on the other hand, there was no statistically significant differences between the mean depression score in patients with cataract surgery and patients without cataract (p = 0.582). however, a statistically significant difference was observed between the mean depression score after cataract surgery in men (1.70) and women (4.94) (p < 0.001). visual function improved in all bilateral cataract patients who had surgery in one eye. also, the results of this study showed that in all unilateral cataract patients who had eye surgery, visual function in the left and right eyes improved. conclusion: we conclude that depression is more prevalent in patients with cataract compared to those without cataract. in addition, cataract surgery seems to be associated with reduced depression and better visual acuity in elderly patients with cataract. keywords: depressive disorder, cataract, cataract extraction, aged how to cite this article: kiumars nowroozpoor dailami, mohammad ali heidari gorji, seyed hamzeh hoseini, and asadollah farookhfar (2021) “the impact of cataract surgery on depression in elderly iranian patients: a case–control study,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 439–449. doi 10.18502/sjms.v16i4.9942 page 439 corresponding author: asadollah farookhfar; email: drfarookhfar@yahoo.com received 20 august 2021 accepted 08 november 2021 published 31 december 2021 production and hosting by knowledge e kiumars nowroozpoor dailami et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:drfarookhfar@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences kiumars nowroozpoor dailami et al. 1. introduction cataract is the most prevalent cause of reversible blindness worldwide. it has been estimated that cataract causes 35% of blindness and 24% of all visual impairment in the world [1, 2]. globally, cataract surgery is one of the most prevalent surgeries, with 1.7 million surgeries performed in united states per year [3–5]. despite recent advances in technology, which have significantly improved cataract-related visual impairments [6–8], severe cataract-related disorders have significant negative effects on patients’ quality of life, especially their mental health [9, 10]. it has been previously demonstrated that cataract-related visual impairments are clearly associated with depression in elderly people [10, 11], which is further associated with increased risk of cognitive impairment, disability, and mortality [12–14]. the results of an australian study showed that 43.4% of elderly people had eye diseases [15]. in addition, it has been shown that depressive symptoms are more common in cataract patients than in patients with other eye diseases [15]. in iran, although studies in this field are very limited, the results of a study showed that 45.7% of cataract patients had moderate to severe levels of depression [16]. meanwhile, cataract surgery seems to be effective in treating depression. many study have revealed that the symptoms of depression can significantly reduce after a cataract surgery [17–19], however, some studies have reported conflicting results. according to a japanese study, no statistical significance was found in the reduction of depression symptoms in elderly patients after cataract surgery [20]. additionally, the results of a study in the united states showed that vision improvement after cataract surgery in elderly patients had no significant effect on reducing depression symptoms [21]. considering the importance of potential negative psychosocial consequences of cataract and conflicting available evidence regarding the effect of cataract surgery on depressive symptom in older people, we aimed to evaluate the impact of cataract surgery on depression among elderly patients. 2. materials and methods 2.1. study design and sample in this case–control study, a total of 68 cataract patients and 45 elderly patients (60 years of age and older) without cataracts who were admitted to buali-sina hospital in sari, mazandaran, iran were evaluated. data were collected using purposeful sampling. the case group consisted of 36 patients with cataract surgery (19 patients with bilateral doi 10.18502/sjms.v16i4.9942 page 440 sudan journal of medical sciences kiumars nowroozpoor dailami et al. and 17 with unilateral cataract) and 32 cataract patients without surgery (15 patients with bilateral and 17 with unilateral cataract). in addition, the control group consisted of 45 elderly patients without cataract disease. 2.2. inclusion and exclusion criteria the inclusion criteria were patients with unilateral or bilateral age-related cataracts, diagnosed by an ophthalmologist, aged ≥60 years, and a visual acuity of <0.4 with glasses. additionally, patients with neurological diseases such as alzheimer’s, parkinson’s, or history of coronary heart disease, traumatic cataracts, and advanced eye diseases such as retinal detachment, strabismus, macular degeneration, diabetic retinopathy, and glaucoma were excluded. 2.3. data collection data were collected using two questionnaires, one including demographic and clinical characteristics of the patients (such as age, sex, weight, medication consumption, supplemental health insurance, vehicle, occupation, underlying diseases, visual acuity, and presence of refractive error), and other being the hospital anxiety and depression scale (hads). the hads questionnaire was designed to assess the severity of depressive and anxiety symptoms in patients [22]. validity and reliability of this scale was assessed previously and was good. this self-reporting scale consists of 14 items, with subscales of anxiety (7 items) and depression (7 items), with scores ranging from 0 to 21. each item consists of a 4-point likert scale, from a score of 0 to 3. scores between 0 and 7; 8 and 10; and 11 and 21 were considered as normal state, mild, and severe depression, respectively [23]. all patients were evaluated by an ophthalmologist on the day of admission. snellen chart, with and without glasses, was used to evaluate the visual acuity of the patients. also, presence of refractive errors was assessed using retinoscopy. after eye examinations by an optometrist, the hads questionnaire was completed by participants. during surgery, an intraocular lens was implanted in all patients in the case group. four months after the cataract surgery, visual acuity and refractive errors were measured and, if necessary, corrective glasses were prescribed. also, the hads questionnaire was completed again by patients. all participants in the control group completed the hads questionnaire during the study period and their visual acuity was measured using a snellen chart with and without glasses. doi 10.18502/sjms.v16i4.9942 page 441 sudan journal of medical sciences kiumars nowroozpoor dailami et al. 2.4. statistical analysis data were analyzed using the statistical package for the social sciences (spss) software (version 16.0, chicago, il, usa). the mean (standard deviation) and the number (percentage) were used to evaluate quantitative and qualitative variables, respectively. the t-test and anova were used to evaluate the main variables of the study. p-value < 0.05 was considered as statistically significant. 3. results a total of 113 patients, including 68 cataract patients and 45 elderly patients without cataract, were included in the present study. of the patients with cataract, 42.6% were male and 51.5% were aged 66–70 years (the mean and standard deviation of ages in patients with and without cataract was 69.12 ± 1.83 and 68.51 ± 2.21 years, respectively; p = 0.412). of the patients without cataracts, 57.8% were male and 68.9% were aged 61– 70 years. table 1 presents the demographic characteristics of patients with and without cataract. based on the results of the present study, there was a statistically significant difference between the mean depression scores in patients without cataract (3.28), patients with cataract surgery (3.74), and patients without cataract surgery (5.60) (p = 0.024). on the other hand, there was no statistically significant difference between the mean score of depression in patients with cataract surgery and patients without cataract (p = 0.582). the mean posttest depression score of bilateral cataract patients who had surgery in one eye (3.26) was lower than the mean pretest of the same group before cataract surgery (7.63) (p < 0.001). however, the mean posttest depression of unilateral atacract patients who had eye surgery (4.31) was lower than the mean pretest of the same group before cataract surgery (6.50) (p = 0.005). there was no statistically significant difference between the mean depression of unilateral cataract patients who had eye surgery (4.31) and bilateral cataract patients who had surgery in one eye (3.26) (p = 0.356). moreover, there was a statistically significant difference between the mean depression of patients with cataract surgery (3.74) and patients without cataract surgery (5.60) (p = 0.187) (table 2). there was a statistically significant difference between the mean depression of patients without cataract surgery (5.60) and patients without cataract (3.28) (p = 0.031). however, there was no statistically significant difference between the mean depression of patients without cataract in the pretest (2.95) and the posttest (3.28) stages (p = doi 10.18502/sjms.v16i4.9942 page 442 sudan journal of medical sciences kiumars nowroozpoor dailami et al. table 1: demographic characteristics of patients with and without cataract (n = 113). variables group with cataract without cataract (n = 68) (n = 45) age (yr) 60–65 7 (10.3) 10 (22.2) 66–70 35 (51.5) 31 (68.9) >70 26 (38.2) 4 (8.9) sex male 29 (42.6) 26 (57.8) female 39 (57.4) 19 (42.2) underlying diseases none 47 (69.1) 33 (73.4) blood pressure 14 (20.6) 8 (17.8) diabetic 7 (10.3) 4 (8.9) medication consumption yes 50 (73.5) 35 (77.8) no 18 (26.5) 10 (22.2) supplemental health insurance yes 38 (55.9) 39 (86.7) no 30 (44.1) 6 (13.3) vehicle yes 14 (31.1) 31 (68.9) no 53 (77.9) 15 (22.1) occupation freelancer 17 (25) 4 (8.9) retired 13 (19.1) 27 (60) unemployed/ housewife 38 (55.9) 14 (31.1) weight (kg) <60 36 (52.9) 9 (20) 61–70 14 (20.6) 12 (26.7) >70 18 (26.5) 24 (53.3) data are presented as number (%). table 2: comparison of the severity of depression in patients with and without cataract surgery (n = 68). mean standard deviation degrees of freedom p-value patients with cataract surgery 3.74 2.93 66 0.018 patients without cataract surgery 5.60 5.12 0.284). in addition, there was a statistically significant difference between the mean depression score after cataract surgery in men (1.70) and women (4.94) (p < 0.001). however, based on the results of the present study, there was no statistically significant association between the mean depression score and age (p = 0.914). visual function improved in all bilateral cataract patients who had surgery in one eye. also, the results of this study showed that in all unilateral cataract patients who had eye surgery, visual function in the left and right eyes improved (table 3). doi 10.18502/sjms.v16i4.9942 page 443 sudan journal of medical sciences kiumars nowroozpoor dailami et al. table 3: visual acuity of unilateral and bilateral cataract patients after surgery. visual acuity score eye glasses va-cc va-sc manual-retinoscopy auto-refractor os od os od os od os od unilateral cataract patients 0.5– 0.7 2 (22.2) 2 (25) 3 (33.3) 3 (37.5) 2 (22.2) 1 (12.5) 1 (11.2) 0 (0) 0.8– 0.10 7 (77.7) 6 (75) 6 (66.6) 5 (62.5) 7 (77.7) 7 (87.5) 8 (88.8) 8 (100) bilateral cataract patients 0.5– 0.7 7 (36.84) 8 (42.10) 10 (52.63) 9 (47.36) 6 (31.57) 6 (31.57) 4 (21.05) 5 (26.31) 0.8– 0.10 12 (63.15) 11 (57.89) 9 (47.36) 10 (52.63) 13 (68.62) 13 (68.62) 15 (78.94) 14 (73.68) data are presented as number (%). od: right eye; os: left eye; va-cc: visual acuity-with correction; va-sc: visual acuity-without correction. 4. discussion the results of the present study showed that cataract aggravates depression in elderly patients. however, cataract surgery in each eye can reduce the symptoms of depression. in addition, patients without cataract surgery suffer more from depression than normal people. moreover, a statistically significant relationship was observed between patients’ gender and depression and cataract surgery. in addition, depression symptoms were significantly lower in men than in women who had cataract surgery. visual function improved in all patients with bilateral cataract surgery. cataract disease is associated with an increased risk of mental disorders, such as depression and psychological distress, it is usually associated with reduced quality of patient’s [24]. this finding is consistent with the results of studies from vietnam [25, 26], iran [18], australia [10], and a joint study in kenya, the philippines, and bangladesh [24]. on the other hand, contrary to the findings of the present study, the results of a study in the united states [21] showed that cataract surgery has no significant effect on reducing patients’ depression symptoms. similarly, the results of an australian study [27] also showed that cataract surgery increases vision-related quality of life, however, its effect on depressive symptoms was unknown. one possible explanation for this inconsistency may be the higher severity of depression in patients before surgery in the present study [25]. on the other hand, in the present study, the symptoms of depression in men were significantly lower than in women who had cataract surgery, which was inconsistent with previous studies in canada [28, 29], the united states [30], and vietnam [25]. it has been previously shown that the prevalence of depression in iranian female patients is higher doi 10.18502/sjms.v16i4.9942 page 444 sudan journal of medical sciences kiumars nowroozpoor dailami et al. than male patients [31, 32]. therefore, higher severity of depression in women than men can be the reason for the lower severity of depression in women after cataract surgery [25]. it has been shown that bilateral cataract surgery is associated with improved visual function and cognitive function after surgery [18]. therefore, the negative effect of visual impairment on cognitive status in these patients can be attributed to cataracts [33–36], and surgical intervention can improve patients’ visual and cognitive impairment [37, 38]. the results of jefferis et al.’s study revealed that visual and cognitive function improved after bilateral cataract surgery [39]. inconsistent with this finding, a study in the united states [40] showed an improvement of cognitive function and vision in older patients without cataract surgery. 5. conclusion in conclusion, it seems that cataract can cause and exacerbates depression, and surgery can reduce the severity of depression in elderly patients. moreover, in all patients who had unilateral cataract and were operated, increased vision was observed in both the right and left eyes. however, there is still insufficient evidence for cognitive improvement and reducing depression in patients after cataract surgery. future studies are needed to validate our findings in different study population. limitations this study has some limitations. our study was observational and correlational in nature, and hence causality could not be established. there is a need for other well-designed cohort studies, preferably with longer duration of follow-up, to confirm the results of the present study. additionally, only those patients who were referred to a teaching hospital in north of iran were evaluated in this study, therefore, generalizability of the findings to other populations in different geographic regions is unclear. acknowledgments none. doi 10.18502/sjms.v16i4.9942 page 445 sudan journal of medical sciences kiumars nowroozpoor dailami et al. ethical considerations this study was approved by the university ethics committee. the objective of the study was explained to all participants and a written informed consent was obtained from all prior to the study. furthermore, for the confidentiality of patient information, participants’ names were removed from the questionnaires. competing interests the authors have no conflicts of interest to declare for this study. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding this study has been financially supported by the deputy of research and technology, mazandaran university of medical sciences, sari, iran. references [1] ackland, p., resnikoff, s., and bourne, r. 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(2005). effect of cataract surgery on cognitive function in older adults. journal of the american geriatrics society, vol. 53, no. 12, pp. 2140–2144. doi 10.18502/sjms.v16i4.9942 page 449 introduction materials and methods study design and sample inclusion and exclusion criteria data collection statistical analysis results discussion conclusion limitations acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9946 production and hosting by knowledge e research article knowledge of icu nurses regarding the ongoing nursing assessment of icu patients in khartoum city, 2020 ahmed osman∗, montaha mohammed, and sahar ahmed department of medical nursing, faculty of nursing sciences, university of khartoum, khartoum, sudan orcid: ahmed osman: https://orcid.org/0000-0002-9838-3059 abstract background: an ongoing nursing assessment is the most significant point in the nursing process to be executed in the beginning of every shift which can be accomplished by using different approaches. it needs to be conducted accurately to guide professional nurses’ decision-making ability to further provide holistic nursing care to patients in the intensive care units (icus). this study was aimed to assess the icu nurses’ knowledge regarding ongoing nursing assessment of icu patients. methods: this descriptive cross-sectional hospital-based study was conducted in khartoum city, and included 86 out of the 135 participants working in the critical care units of the main governmental hospitals in khartoum city. data were collected using a structured self-administered questionnaire after being tested for validity and then analyzed using mean, standard deviation, and correlation. data were then presented as frequencies and percentages. results: the study participants were aged between 20 and 40 years with a female to male ratio of 3:1, and varied levels of experience. overall, 71.7% of the studied participants scored good on the standardized knowledge classification tool used, with few areas of knowledge gap, impacted by increased experience. moreover, 36% of the participants used the abcde approach for ongoing nursing assessment, followed by the head-to-toe assessment approach (21%). conclusion: the nurses’ knowledge regarding ongoing nursing assessment was good with a few areas of weakness raising the need for continuous educational and training programs. keywords: icu ongoing nursing assessment, critical care unit continuing nursing assessment, critical care room evolving nursing judgment how to cite this article: ahmed osman∗, montaha mohammed, and sahar ahmed (2021) “knowledge of icu nurses regarding the ongoing nursing assessment of icu patients in khartoum city, 2020,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 489–498. doi 10.18502/sjms.v16i4.9946 page 489 corresponding author: ahmed osman; email: ahmedosman.90@hotmail.com received 15 august 2021 accepted 26 november 2021 published 31 december 2021 production and hosting by knowledge e ahmed osman et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ahmedosman.90@hotmail.com mailto:ahmedosman.90@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ahmed osman et al. 1. introduction a nursing assessment is the assembly of data about a patient’s physiological, psychological, sociological, and spiritual needs in order to categorize the existing and potential patient care requirements. the nursing process is a problem-solving approach to meet patient’s or client’s healthcare and nursing needs, and includes five systematic steps: assessment, formulation of nursing diagnosis, putting a plan for intervention, intervention, and evaluation [1–4]. nursing assessments are non-static, one of the aspects of the nursing assessment procedure is that a set of customized results are agreed upon, which can be achieved through established teamwork and efficient communication [5]. an accurate collection of assessment data leads the decision-making and personalized risk assessment required to define a plan of care with specific interventions to be made for each patient [6]. an ongoing nursing assessment is a type of nursing assessment done at the beginning of every shift on every client and the assessment data thereof is used to formulate a plan of care. a prime concern for nursing professionals when admitting a patient with an acute medical condition to hospitals is to ensure their safety. however, many studies published over the last 20 years have showed that significant harm is caused to patients unintentionally through nurses’ inability to recognize the signs of clinical deterioration [4]. patients in intensive care units (icus) are generally admitted due to their critically ill health or injury that may develop life-threatening deteriorations. these patients usually experience problems with consciousness and have limitation in mobility and sensation due to sedation and/or the disease processes [7]. basically, the nursing observation of patients has included the measurement and documentation of vital signs. and over the past decade, vital signs measurements were used to develop protocol-based early warning score (ews) tools that aim to detect patient’s clinical deterioration at an early stage [4]. initial nursing assessment is registered on the flowsheet and the following assessments or changes are registered in the progress notes [5]. a study done on hospitalized patients compared the effects of nursing assessment on predictive delirium models, and showed that nursing assessment data can improve performance of delirium prediction models better than the demographic, laboratory, diagnosis and procedure and previous transfer data [8]. doi 10.18502/sjms.v16i4.9946 page 490 sudan journal of medical sciences ahmed osman et al. because of the limited data regarding the application of ongoing nursing assessment in the icus of hospitals in khartoum city, the study was aimed to assess the icu nurses’ knowledge regarding ongoing nursing assessment. 2. materials and methods this descriptive, cross-sectional, hospital-based study was conducted in the icus of four governmental hospitals including: the khartoum teaching hospital, the soba university hospital, the alshaab teaching hospital, and the national center for neurological science. 2.1. sampling technique a full-coverage sampling method was used. 2.2. sample size out of the 135 icu nurses in the selected khartoum hospitals, 86 nurses who were qualified with bsc and higher degrees and agreed to participate in the study were included. nurses who were absent during the study period (either on vacation at the time of study or on a sick leave) were excluded. 2.3. data collection data were collected using a structured self-administered questionnaire to assess nurses’ knowledge, and the results were evaluated using a standardized evaluation tool by classifying the knowledge level in percentage as: excellent (≥90%), very good (89– 80%), good (79–70%), average (69–60%), poor (59–50%), and very poor (<50%). the questionnaire was tested by piloting to ensure its validity and reliability, and then distributed to the participants by the researchers. following the data collection, the data were analyzed using the statistical packages for social sciences (spss) version 20 using mean, standard deviation, and correlation. the authors excluded 49 questionnaires which were not properly filled resulting in a total of 86 questionnaires with a response rate of 64%. doi 10.18502/sjms.v16i4.9946 page 491 sudan journal of medical sciences ahmed osman et al. figure 1: distribution of participants by hospital. 3. results this descriptive study was conducted in the icus of the four main governmental hospitals in khartoum city, including a total of 86 participants with response rate of 64% (figure 1). the majority of the participants (91.9%) were aged between 20 and 30 years, while only 8.1% were 30 to 40 years old, with a mean age range of 20–30 years (sd 0.27). of them, 24.4% were male while 75.6% were female, with a male-to-female ratio of 1:3 (sd 0.43). with respect to the qualifications, the majority of the participants (94.2%) had a bsc degree, 3.5% had an msc, and only 2.3% had a phd degree (sd 0.35), this indicates that the majority had the same level of qualification. moreover, 72.1% of the participants had an experience of <2 years, 19.8% had 2– 5 years, 3.5% had 6–10 years, and 4.7% had >10 years. this is largely due to the migration (brain drain) of the experienced staff to the arabian gulf region leaving the juniors without proper guidance (table 1). additionally, 22.3% of the participants worked in the general icus of the khartoum teaching hospital and soba university hospital, 22.1% in the respiratory icu of the alshaab teaching hospital, 25.6% in the cardiothoracic icu of the alshaab teaching doi 10.18502/sjms.v16i4.9946 page 492 sudan journal of medical sciences ahmed osman et al. table 1: participants’ demographic data. age (yr) 20–40 gender 24.4% (male), 75.6% (female) qualifications 94.2% (bsc), 3.5% (msc), 2.3% (phd) experience (yr) >1–10< hospital, 14% in the neurological icu, and 15% in the neurosurgical icu of the national center for neurological science. regarding the position of nurses in the studied icus, 8.1% were head nurses and 91.9% were staff nurses, this is reasonable as usually there is only one head nurse in each unit. regarding the use of ongoing nursing assessment approaches in the area of study, 36% of the participants used the abcde approach, 10.5% used the body systems approach, 20.9% had the head-to-toe approach, 5.8% did not indicate the exact approach used (mostly because they do not know if they have an approach they have to follow or not), while 23% had no approach for ongoing nursing assessment to follow in their units. table 2 shows that the icu nurses’ knowledge was excellent in the areas of nursing process definition, components of patient’s orientation assessment, and if the bed sores are assessed as part of the skin assessment. moreover, knowledge was very good regarding the definitions of assessment and seriously ill patient, approaches commonly used in the assessment, pupillary and lung field assessment, if the ventilator settings are needed to be checked as part of the ongoing assessment, if the ostomy and drains should be assessed when assessing the abdomen, and if it’s part of ongoing assessment to assess the other tubes and lines connected to the patient. further, the patients scored good in areas of ongoing nursing assessment definition, vital signs components, rectal assessment, sensory, and edema assessment. average knowledge was scored in a question about abdominal classification when assessing for bowel sound. however, the icu nurses’ knowledge in the rest of assessment questions was very poor. the researchers selected the results of those questions that are most representative of the knowledge of the ongoing nursing assessment and correlated them to the nurses’ qualifications and years of experience to evaluate the impact these data had on the participants’ knowledge (table 3). table 3 shows that the qualifications had a significant negative impact on the participants’ knowledge regarding question 7 (the most known protocols used in ongoing assessment may involve the body systems approach and the abcde approach) (p = doi 10.18502/sjms.v16i4.9946 page 493 sudan journal of medical sciences ahmed osman et al. table 2: knowledge score per question in percentage. no. questions percentage of the correct responses sd 1 nursing process is defined as methodological, rational manner of planning and performing of individualized nursing care 91.1 0.3 2 elements of the nursing process in a sequence are: evaluation, diagnosis, planning, intervention, and assessment 39.5 0.5 3 assessment is defined as systematic collection, verification, ordering, interpretation, and registration of data by healthcare members 84.9 0.6 4 components of assessment are: history of illness, physical assessment, and laboratory and diagnostic investigations 91.7 0.4 5 ongoing (shift) nursing assessment is defined as: the assessment that should be done each time the nurse encounters a patient for the first time in each shift 77.9 0.5 6 seriously ill patients are the patients who are at great risk for actual or eminent life-threatening health problems 87.2 0.4 7 the most known protocols used in ongoing assessment may involve the body systems approach and the abcde approach 81.4 0.6 8 the ongoing assessment may start with introduction of self and general survey 75.6 0.6 9 level of consciousness can be assessed by using (avpu) alert, verbalization, pain, and unresponsive 81.4 0.5 10 the total glasgow coma scale score is 12 89.5 0.3 11 patient orientation is assessed by asking the patient regarding place, person, and time 95.3 0.3 12 vital signs assessment involves respiratory rate, pulse rate, blood pressure, temperature, and pain assessment 74.4 0.5 13 pupillary assessment is for shape, size, and reaction to light, symmetry, and accommodation 84.9 0.6 14 when assessing the neck veins, the patient should be in a 15º position 25.6 0.9 15 lung fields should be assessed for air entry, symmetrical chest movements, and adventitious sounds 86 0.5 16 regarding mechanical ventilation, the nurse needs to evaluate the settings and functioning of the mechanical ventilator 89.5 0.4 17 oxygen saturation (spo2) should be assessed when assessing the abdomen 72.1 0.5 18 heart sounds that should be assessed are s1 and s2 and extra sounds (s3 and s4) 51.2 0.9 19 capillary refill time gives us clue regarding the peripheral tissue perfusion 82.6 0.6 20 abdominal assessment involves assessing for the presence of ostomy and abdominal drain 81.4 0.6 21 to assess bowel sounds, we may need to classify the abdomen into four quadrants 69.8 0.8 22 rectal assessment involves assessing for bowel motion 77.9 0.7 23 motor assessment involves assessing for optic neuropathy 37.4 0.7 24 sensory assessment includes light touch identification, sharp versus dull determination, pain and temperature sensation 79.1 0.6 25 peripheral edema is assessed by pressing the skin against bony prominences 75.6 0.6 doi 10.18502/sjms.v16i4.9946 page 494 sudan journal of medical sciences ahmed osman et al. table 2: table continued. 26 skin assessment involves assessment for bed sores 94.2 0.4 27 braden scale is used to assess skin status 38.4 0.9 28 morse scale is used to assess falls risk 26.7 0.9 29 pain assessment is referred to as the 6𝑡ℎ vital sign 26.7 0.8 30 assessment for tubes and lines is a part of ongoing assessment 81.4 0.6 total knowledge score 71.7 table 3: correlation between questions 1, 3, 7, 9, 12, 15, 19, 20, 26, and 30 and nurses’ qualifications and experiences. questions q1 q3 q7 q9 q12 q15 q19 q20 q26 q30 correlation with the qualification –0.066 0.126 –0.309 0.031 0.003 0.047 0.002 –0.104 –0.057 0.217 correlation with the years of experience –0.150 0.136 0.207 0.070 0.068 0.076 0.100 –0.078 0.012 0.152 0.004). however, an insignificant negative impact was seen on the participants’ knowledge regarding questions 1 (nursing process is defined as methodological, rational manner of planning and performing of individualized nursing care) (p = 0.5); 20 (abdominal assessment involves assessing for the presence of ostomy and abdominal drain) (p = 0.3); and 26 (skin assessment involves assessment for bed sores) (p = 0.6). nevertheless, a significant positive impact was noted regarding question 30 (assessment for tubes and lines is a part of ongoing assessment) (p = 0.045) and an insignificant positive impact on the participants’ knowledge regarding the rest of the questions. the years of experience had an insignificant negative impact on the participants’ knowledge regarding questions 1 (p = 0.17) and 3 (p = 0.2), while the impact was insignificantly positive regarding the other questions. 4. discussion the results from this study suggest that the icu nurses’ knowledge score regarding the ongoing nursing assessment of icu patients was good according to the standardized knowledge classification tool used. there was an obvious knowledge deficit in stating the components of nursing process, the degree of positioning the patient when assessing the neck vein, involved parts of motor assessment, indications for use of braden & morse scales, and indicating pain assessment as the 6𝑡ℎ vital sign (table 2). these lower percentages indicate a knowledge gap in these areas mostly because of the common negligence of these assessment components by icu nurses when they assess their patients; it is also noticed that even the critical care workshops are less likely doi 10.18502/sjms.v16i4.9946 page 495 sudan journal of medical sciences ahmed osman et al. to include the areas relating to use of braden scale for skin assessment and morse scale for fall risk assessment. in contrast, the findings in the other areas of knowledge revealed a very good score as they are the commonly practiced and discussed elements in the training courses (p > 0.001). these results are very important for evaluating the icu nurses’ knowledge as it is considered that the assessment is a major step of the entire nursing process “base or foundation.” and in the light of these, nurses may formulate an appropriate nursing diagnosis and then plan and implement an accurate intervention as it is known that with an improper assessment, nurses may formulate an inappropriate nursing diagnosis and then plan and implement wrong interventions [9]. in comparison, a study conducted to assess the ongoing patient’s assessments involving 127 icu nurses of a university hospital in sao paulo, brazil had revealed that most of the participating nurses were women, with a mean age of 31.1 years, had graduated >5 years ago, and had a work experience of 1 to 3 years. regarding the highest score for glasgow coma scale, nurses who had graduated >5 years prior showed poor knowledge (p = 0.0476). as for the interval of the scale to signal for moderate brain trauma, those with most experience showed a high knowledge score (p = 0.0251). in contrast, in the same study, nurses from the icus had less knowledge compared to the nurses from emergency room (p = 0.0143). moreover, nurses who had graduated >5 ago had a lower knowledge score (p = 0.0161), while those with more experience scored better (p = 0.0119) in most questions [10]. the researchers attempted to find a link between the icu nurses’ knowledge and their level of qualification and years of experience. the results did not prove that increased qualification and more years of experience can have an impact on the icu nurses’ knowledge. 5. limitations this study had a few limitations.. thirty six percent of the participants did not submit their questionnaire to the researcher. some participants were working in more than one hospitals and some of them were working as a substitute for others at the time of the study, this reduced the study sample size. doi 10.18502/sjms.v16i4.9946 page 496 sudan journal of medical sciences ahmed osman et al. 6. conclusion this study concluded that the total knowledge score of the participants was 71.7% which is considered as good according to the standardized knowledge classification tool used in this study. there were some specific areas of knowledge gap regarding the ongoing nursing assessment. the increasing number of years after graduation (experience) has negative impact on some areas of the ongoing nursing assessment knowledge, raising the need for continuous educational and training programs. acknowledgements the authors would like to thank all the nursing teachers, colleagues, and friends who supported them throughout the study, particularly the nursing director of soba university hospital, samia m. diefalla who provided the authors with a valuable resource. ethical consideration permission was obtained through official letters from the general directors of all four governmental hospitals included in the study, and verbal agreements were taken from the study participants. competing interests the authors disclose that there was no funding body for this study and it was totally dependent on the authors own fund and there is no conflicting interest. availability of data and material the data related to the study is available whenever needed. references [1] hinkle, j. l. and cheever, k. h. (2018). brunner and suddarth’s textbook of medical surgical nursing (14𝑡ℎ ed., pp. 254–280). wolters kluwer. doi 10.18502/sjms.v16i4.9946 page 497 sudan journal of medical sciences ahmed osman et al. [2] karns, d. s. (2010). meaningful learning development in student nurses: the traditional nursing care plan versus the concept map care plan approach (doctoral dissertation). retrieved from: https://digscholarship.unco.edu/cgi/viewcontent. cgi?article=1177&context=dissertations [3] adenova, a., tazhieva, a., ramazanova, m., et al. (2014). nursing process based on the principles of evidence-based medicine. bulletin of the kazakh national medical university, vol. 1, pp. 434–435. [4] atkinson, d. (2013). nursing observation and assessment of patients in the acute medical unit (doctoral dissertation). retrieved from: https://usir.salford.ac.uk/id/eprint/29466/1/e_thesis_da.pdf [5] ceesay, b. (2018). the importance of assessment and communication as fundamental skills of nursing practice. links to health and social care, vol. 3, no. 2, pp. 24–39. [6] solà-miravete, e., lópez, c., martínez-segura, e., et al. (2018). nursing assessment as an effective tool for the identification of delirium risk in older in-patients: a case– control study. journal of clinical nursing, vol. 27, no. 1–2, pp. 345–354. [7] ukessays. (2018). the assessment process of patients in intensive care [internet]. retrieved from: https://www.ukessays.com/essays/nursing/the-assessment-processof-patients-in-intensive-care-nursing-essay.php?vref=1 (accessed 2021 may 18). [8] veeranki, s. p., hayn, d., kramer, d., et al. (2018). effect of nursing assessment on predictive delirium models in hospitalised patients. studies in health technology and informatics, vol. 248, pp. 124–131. [9] higginbottom, g. m., richter, m. s., mogale, r. s., et al. (2011). identification of nursing assessment models/tools validated in clinical practice for use with diverse ethnocultural groups: an integrative review of the literature. bmc nursing, vol. 10, no. 1, p. 16. [10] santos, w. c., vancini-campanharo, c. r., lopes, m. c., et al. (2016). assessment of nurse’s knowledge about glasgow coma scale at a university hospital. einstein, vol. 14, no. 2, pp. 213–218. doi 10.18502/sjms.v16i4.9946 page 498 https://digscholarship.unco.edu/cgi/viewcontent.cgi?article=1177&context=dissertations https://digscholarship.unco.edu/cgi/viewcontent.cgi?article=1177&context=dissertations introduction materials and methods sampling technique sample size data collection results discussion limitations conclusion acknowledgements ethical consideration competing interests availability of data and material references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8934 production and hosting by knowledge e research article an insight into the practice of iron therapy: contribution to the on-going debate with special reference to lowand middle-income countries dr randa alsadig almahdi1 and prof. dr. sami a. khalid2 1assistant professor vice dean, faculty of pharmacy, university of science & technology mail address: faculty of pharmacy, university of science and technology, omdurman, p o box 477 2dean, faculty of pharmacy, university of science & technology professor of phytochemistry faculty of pharmacy, university of khartoum orcid: randa alsadig almahdi: http://orcid.org/0000-0002-4319-8112 abstract background: iron deficiency anemia is a public health problem of a sizable proportion in developing countries. recently, emerging biochemical knowledge coupled with the discovery of hepcidin have greatly advanced our understanding of iron metabolism and offered a better insight into its associated pathophysiology. this knowledge should be applied to iron-deficiency anemia therapy to avoid subsequent sequelae of tissue damage associated with reactive oxygen radicals that are catalyzed by iron, because current practices do not include these advances in the treatment guidelines. in the light of recent progress, the existing iron therapy program in many healthcare settings is controversial. this necessitates adjusting the magnitude of iron dose with respect to the very limited iron bioavailability, as gauged by hepcidin. the current study was therefore aimed to incorporate newly emerging biochemical knowledge into the current iron-deficiency anemia treatment practice methods: literature relevant to iron-deficiency studies published in english between 1964 and 2020 and available online was covered. conclusion: evidently, the existing iron-therapy schedule is both inefficient and toxic. the intricate metabolism of iron should be translated into a more rational iron intervention program with special bias towards lowand middle-income countries requiring a more individualized approach. keywords: iron deficiency anemia, hepcidin, oxidative stress, iron therapy 1. introduction anemia is a worldwide health problem affecting one-third of the global population, and iron-deficiency anemia (ida) accounts for half of them [1, 2]. ida affects populations of how to cite this article: dr randa alsadig almahdi and prof. dr. sami a. khalid (2021) “an insight into the practice of iron therapy: contribution to the on-going debate with special reference to lowand middle-income countries,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 17–32. doi 10.18502/sjms.v16i1.8934 page 17 corresponding author: randa alsadig almahdi; email: randaalsiddig2018@outlook.com randa.almahdiust@ust.edu.sd received 17 january 2021 accepted 19 march 2021 published 31 march 2021 production and hosting by knowledge e dr randa alsadig almahdi and prof. dr. sami a. khalid. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:randaalsiddig2018@outlook.com mailto:randaalsiddig2018@outlook.com mailto:randa.almahdiust@ust.edu.sd https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid both developed and developing countries [3, 4]. the developing countries, categorized by the world bank as lowand middle-income countries (lmics), present the highest incidence as well as more severe anemia, especially in specific populations [1, 5]. the lmics lack efficient resource allocation; hence they form a large proportion of the world’s population with the greatest disease burden [6].6 iron deficiency in lmics is the most common micronutrient malnutrition. its prevalence is high due to poverty that leads to lack of nutritious food, inadequate food intake, inadequate healthcare, diseases, infections, and blood loss [7]. however, in the developed countries, ida is not a major health problem. in these countries, it only endangers certain groups like young children, adolescents, pregnant women, elderly, blood donors, vegetarians, endurance athletes, and migrants [8]. 2. materials and methods 2.1. impact of iron deficiency on the health of vulnerable population iron deficiency occurs when dietary iron intake cannot meet the iron needs over a period of time [9]. the vulnerable population usually includes infants, children with increased growth demands, menstruating girls and women, and pregnant women [4, 10]. it has been estimated that about half of all pregnant women experience ida [11], which causes a heavy health burden due to its negative impact on children, coupled with effects on brain development and functioning due to reduced oxygen delivery to tissues [12]. in adults, ida causes fatigue [13]. furthermore, severe anemia at hemoglobin levels < 7 mg/dl can result in devastating outcomes, such as maternal mortality, reduced birth weight, and reduced cognitive ability [10]. 2.2. common causes of iron deficiency in lmics the populations in the lmics are usually characterized by nutritional deficiencies, low iron-containing food, or problems in absorption of dietary iron due to viral and parasitic infections, for example, malaria (since these pathogenic microbes consume iron as well), and high prevalence of helicobacter pylori infection [14]. moreover, ida may arise secondary to partial gastrectomy, coeliac disease, crohn’s disease, some drugs that reduce iron absorption [15], hemorrhage associated with childbirth, or heavy menstrual blood loss. it can also result secondary to impaired absorption due to high intake of doi 10.18502/sjms.v16i1.8934 page 18 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid phytate that impairs iron absorption or altered nutrient metabolism [12]. malnutrition causes a wider segment of the population in lmics to be at risk of ida. a recently identified risk factor for ida is oxidative stress induced by high unbound iron that eventually damages erythrocytes and results in ida [16, 17]. 2.3. iron: an integral component for cellular functions iron is a biologically essential component for all living organisms. in humans, it exists as protein-bound, heme compounds, which include hemoglobin containing 25% of the body iron and myoglobin containing 15% [18], or non-heme compounds like transferrin and ferritin [19]. heme enzymes and other iron-containing enzymes are involved in electron transfer and oxidation-reduction processes [20]. the human body obtains iron from three sources: environment (mother to fetus), recycled or mobilized form from iron storage sites (major source), and diet (limited source) [21–25]. the quantity of iron in the body is well-regulated and tightly controlled through a robust network at both cellular and systemic levels [26]. most of the iron in the body is recycled and reserved within the body, leaving only a small quantity to be acquired exogenously either from diet or iron supplements with limited bioavailability [27]. iron has always shown to be an intricate element in conflicting mechanisms. iron can be described as beneficial as a micronutrient, as well as harmful to body tissues as a catalyst in a series of reactions that produce the toxic reactive oxygen species (ros) [26, 28]. therefore, both iron deficiency and overload can have serious health effects [29]. this paradoxical role has always confronted scientists regarding the body’s mechanisms to coordinate iron delivery to tissues [30, 31]. to understand the biochemical mechanisms involved in iron absorption and the various factors associated with these processes, two facts should be considered. most of the iron in the body is reserved within the body and recycled from different storage sites, including senescent erythrocytes to other tissues. this implies that iron from exogenous sources has very limited bioavailability [27]. this entails that iron trafficking requires effective tissue communication and orchestration between the iron consuming cells, for example, erythrocyte precursors, and the iron storage sites, for example, duodenal enterocytes, hepatocytes, and tissue macrophages [2]. doi 10.18502/sjms.v16i1.8934 page 19 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid 2.4. absorption of iron from the gut absorption is the most important mechanism in iron haemostasias [7]. iron haemostasias has been described in the literature as a partially understood process. therefore, it has been subjected to extensive research for decades to fill the gaps of knowledge about its absorptive mechanisms [2]. dietary iron is available in two main forms: organic haem iron and non-haem inorganic iron [4, 32]. the non-haem inorganic iron is available mostly in oxidized ferric form besides its availability in its reduced ferrous form [33]. the duodenum and upper jejunum have long been identified as the absorptive sites for iron [22]. initially, ferrous iron is up-taken in the gut by the enterocytes through the protein carrier dmt-1 [20], while ferric iron is reduced to ferrous before being up-taken or carried by a different pathway (mobilferrin–integrin) [32]. the ferrous complex with dmt-1 is influenced and regulated to a great extent by iron deficiency, whereas the ferric–mobilferrin–integrin complex is not [23]. iron exits from the enterocytes into the plasma via the export protein ferroportin [19, 27], and it is then carried by transferrin to either fuel erythropoiesis in the bone marrow or to be stored in ferritin [27]. eventually, the quantity of iron that actually reaches plasma is the iron released from the enterocytes as transferrin-bound iron via ferroportin and not that up-taken by the enterocytes from the gut [34]. the level of amount of iron absorbed is maintained by cellular and systemic pathways [35]. at the cellular level of the mucosal block, large quantities of iron are detained by enterocyte ferritin, a natural nano-protein mucosal acceptor. thus, one ferritin molecule cages 4,500 iron atoms [15, 25], while the excess iron stored in ferritin eventually gets unloaded in the gut when enterocytes get sloughed at the end of their life span [36]. signaled by the quantities of intracellular iron [23, 27, 32, 37–39], a reduction in brush border enzymes occurs resulting in inhibition of iron absorption for more than 4–5 hr after a single oral iron dose [39]. the systemic protective mechanism against excess iron is controlled by hepcidin. therefore, we will elaborate on the important discovery of hepcidin as a safety gauge. inside the cell, an important fraction of iron known as labile iron pool (lip) remains bound to low molecular weight chelates, such as citrates, adenosine triphosphate, ascorbic acid, or pyrophosphate. usually, lip represents <5% of total cellular iron at iron blood level of 50–100 µm [26], however, its quantity may rise substantially by the induction of certain biochemical stimuli, such as iron overload or iron levels that exceed cell haemostasias [26, 30]. doi 10.18502/sjms.v16i1.8934 page 20 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid 2.5. gauging iron absorption (inhibition vs enhancement) exogenous iron absorption is largely dictated by the body’s iron requirement [23]. consequently, the absorption of iron from the gut or mobilization from storage sites is accelerated by plasma iron turnover to produce more erythrocytes in response to stimulation by the erythropoietin hormone [2, 23]. nevertheless, absorption of iron is influenced by many other factors and substances coexisting in the gut, either by inhibition or enhancement. enhancers include ascorbic acid, meat, and poultry, while inhibitors are tannins, dairy products, polyphenols, and phytates [40, 41], as well as some trace elements like zinc and copper, which are found in the enzymes involved in iron metabolism [12, 41]. 2.6. damaging role of oxidative stress triggered by free (unbound) iron lip is chelatable transient iron and a critical factor in producing catalytic iron that generates ros and nitrogen species through the haber–weiss reaction [26, 28], which is responsible for initiating the fenton’s reaction [30, 42]. fenton’s reaction is considered as a major mechanism for generating ros in biological systems [43]. it causes corruption of the lipid membranes, proteins, and dna [44]. peroxidation of membrane lipids can damage the membrane structure, decrease the cell deformability, enhance immunoglobulin-g binding, and complement activation [45]. this damage promotes a state of oxidative stress [26, 37], and eventually leads to degradation of erythrocytes that damages tissues and organs [15, 16]. oxidative stress can be induced by high intake of iron during iron supplementation with doses that exceed the capacity of endogenous antioxidant proteins (e.g., glutathione), which could lead to the generation of ros. this could result in tissue damage, specifically of the intestinal mucosa that is vulnerable to oxidative damage [45], inflammation of the colon, and disturbances of the microbiome [46]. generally, our body is capable of detoxification and neutralization of ros by the naturally occurring endogenous antioxidants to restore the pro-oxidants–antioxidants balance and prevent the damage of oxidative stress. moreover, other natural protective mechanisms exist to prevent the oxidative stress related to free unbound iron through hepcidin and chelation of lip iron [30, 35, 42]. recently, there has been equivocal evidence about the important role of oxidative stress in the pathophysiology of ida through increased free cellular iron [47] and the doi 10.18502/sjms.v16i1.8934 page 21 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid systemic and cellular handling of iron haemostasias [27, 39, 48, 49]. this new knowledge causes the co-ingestion of exogenous antioxidants to become a rational adjunctive to iron therapy [50]. 2.7. strategies to control iron-deficiency anemia the persistence of ida as a worldwide health problem requires a novel and innovative interventional approach by the provision of appropriate and bioavailable forms of iron dosage that avoid iron toxicity. meanwhile, several constraints exist in the resources of poor health settings in lmics, including proper diagnosis, prevention, and effective management of ida. iron replete is crucial for healthy development of children and the well-being of all people in lmics. therefore, it is especially important to develop strategies mainly addressing lmics to protect such vulnerable populations from the negative impacts of ida. historically, there were different approaches to control ida, including food fortification and iron salts supplementation [51]. despite the continuous efforts by various international organizations to come up with appropriate guidelines on iron supplementation, and more than 17 guidelines proposed by the world health organization alone [12], none of these guidelines are based on evidence-based clinical study. implementation of anemia control programs in lmics requires careful baseline epidemiologic evaluation to select the appropriate interventions that suit the most affected populations, in line with the currently available scientific evidence to ensure safety and effectiveness [5]. to meet iron requirements in lmics where iron deficiency is widespread, adequate intervention programs are recommended. however, iron is known to influence the pathogenesis of a number infectious disease (e.g., malaria), which are especially common among the populations of the lmics [51, 52]. earlier evidence has already demonstrated the dose-related deleterious effect of iron therapy in malaria endemic regions [53]. in some of the lmics with a high malaria burden, hepcidin blocks iron absorption from the gut as well as inhibits its mobilization, resulting in prevention of efficient iron uptake. this means that iron supplementation in malaria endemic areas would be less effective [34]. this represents a challenge for policy-makers, and the urgent need to develop efficient therapeutic approaches with minimal infection-related risks. moreover, it requires individualizing the therapeutic regimen according to iron deficiency, infection risk, and inflammatory status of the individuals [52]. doi 10.18502/sjms.v16i1.8934 page 22 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid 2.8. pathophysiology of iron-deficiency anemia iron deficiency develops gradually in states of negative iron balance in three stages. it typically evolves through storage iron depletion (latent anemia), iron-deficient erythropoiesis, and finally overt iron-deficiency anemia (defined as concomitant iron deficiency plus anemia) [54]. 2.9. diagnosis of iron-deficiency anemia in lmics the most commonly used indicator of ida in many poor resource settings like the lmics is hemoglobin. however, to confirm iron deficiency in patients with low hemoglobin, a low serum ferritin level must be established [10, 55]. in cases of coexisting infectious disease and/or inflammation, serum ferritin, which is an acute phase reactant, may give false results [56], because its levels increase in infection and/or inflammation [12, 57]. in such situations, a simpler approach that optimally uses serum ferritin in ida diagnosis is considering values <15 μg/dl as diagnostic for ida and those >100 μg/dl to rule out ida [58]. alternatively, other inflammatory markers should be included in the assessment, such as c-reactive protein and alpha-1 glycoprotein [12], considering that transferrin saturation is a very sensitive parameter to evaluate body iron stores [45]. ida should be classified to determine its severity for appropriately guided therapy. there are a number of cut-off values for hemoglobin to determine severity of ida, for example, mild ida at hemoglobin of 10–10.9 g/dl, moderate ida at hemoglobin level of 7–9.9 g/dl, and severe ida at levels <7 g/dl [13]. 2.10. iron supplementation scheme after a confirmed ida diagnosis, the longstanding trend of treatment is iron supplementation either by oral or intravenous route. the choice is largely dependent on factors such as the patient’s age, sex, severity of anemia, and timeframe for acceptable iron correction [59]. the orthodox treatment of ida to replenish the iron stores fully is oral administration of 100–200 mg elemental iron twice per day [39, 60], for three months [4, 54]. the oral route has always been the first-line choice due to its safety, cost-effectiveness, and convenience [61]. frequently used oral iron salts, such as ferrous fumarate, ferrous sulphate, and ferrous gluconate, have similar bioavailability and slightly different elemental iron content [60]. doi 10.18502/sjms.v16i1.8934 page 23 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid 2.11. current debate on iron therapy practice the magnitude and spacing of oral iron dose are becoming issues of great concern and controversy due to the inefficiency and toxicity of the iron dose in use [27, 39]. based on the discovery of hepcidin, moretti et al. have questioned the need for large daily doses of iron as compared to the much smaller dose of bioavailable iron at 12.5% of the dose. this has raised safety concerns regarding the potential risk of oxidative stress and involvement of unbound iron in fenton’s reaction [26, 61]. this concern has been addressed and consolidated experimentally for the first time by a good evidencebased clinical trial [39]. it is necessary to remember that pregnant women are among the vulnerable groups for ida due to the higher risk of potential iron toxicity related to oxidative stress that is associated with the mitochondria-rich placenta [61]. oral iron salts remain the standard ida treatment option in current use, associated with dose-dependent toxicity [57], and subsequently have been known to compromise compliance to treatment. therefore, there is a need for a better and safer treatment options to replenish iron stores in ida patients. 2.12. call for a safer and more effective iron therapy the oral route remains the first-line choice in the wider population of patients [46]. its advantages include cost-effectiveness and ease of monitoring, especially in health settings with limited resources [64]. the challenge for ida treatment in the poor-resource settings of lmics are facing many constrains with respect to the diagnosis, prevention, and treatment of ida. effective management often requires treatment of the underlying cause prior to iron supplementation, restoration of hemoglobin to normal levels, and treatment of complications if they exist [65]. many reviews and studies have concluded that there is an urgent and compelling need to revisit the iron therapy guidelines that are currently in use [65, 66]. some have proposed recommendations for safer regimens [39, 45, 65]. recent reviews are in favor of smaller iron doses and intermittent dosing rather than daily doses [67]. with respect to iron supplementation, it is important to bear in mind that certain individuals may be at a higher risk with high iron doses, such as severely ill patients with inflammatory diseases [68], ida patients with chronic renal diseases [69], and patients with underlying infections or malignancy [70]. in such patients, iron supplementation may be deleterious and/or even harmful [70]. doi 10.18502/sjms.v16i1.8934 page 24 sudan journal of medical sciences dr randa alsadig almahdi and prof. dr. sami a. khalid 3. conclusion the discovery of hepcidin and its role in ida should be considered as a turning point in iron therapy and a great advance in our knowledge about ida. it is of paramount importance to consider this in therapeutic decisions while determining the iron dose, spacing, and duration, to avoid inefficiency of iron bioavailability, for example, twice per week or intermittent dosing. furthermore, the potential of high iron supplementation to increase free unbound iron and fuel the deleterious effect of catalyst iron in fenton’s reaction is indicative of the need to reduce the iron dose magnitude. from the aforementioned information, it can be concluded that what matters most with iron therapy is not iron replete, but rather the iron supplementation with an appropriate methodology. development of efficient and rational iron therapy program in lmics should be done through individualized approaches with special concern to the widespread infectionrelated health issues, for example, malaria, tuberculosis, and hiv infections, which have negative interactions with iron therapy. acknowledgements ethical considerations not applicable. competing interests the authors declare that there is no conflict of interest. availability of data and material the data that support the findings of this study are available from the corresponding author upon request and most are openly 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(2011). iron deficiency anemia and pregnancy. prevention and treatment. journal de gynécologie obstétrique et biologie de la reproduction, vol. 40, no. 3, pp. 185–200. retrieved from: https: //pubmed.ncbi.nlm.nih.gov/21333465/ doi 10.18502/sjms.v16i1.8934 page 32 https://academic.oup.com/jn/article/133/5/1700s/4558571 https://academic.oup.com/jn/article/133/5/1700s/4558571 https://www.thelancet.com/journals/lanhae/article/piis2352-3026(17)30194-1/fulltext https://www.thelancet.com/journals/lanhae/article/piis2352-3026(17)30194-1/fulltext https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/alternate-strategies-for-improving-iron-nutrition-lessons-from-recent-research/9ca74c7d1dde5d1d5586c87acded84c0 https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/alternate-strategies-for-improving-iron-nutrition-lessons-from-recent-research/9ca74c7d1dde5d1d5586c87acded84c0 https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/alternate-strategies-for-improving-iron-nutrition-lessons-from-recent-research/9ca74c7d1dde5d1d5586c87acded84c0 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd009218.pub3/abstract https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd009218.pub3/abstract https://link.springer.com/article/10.1186/cc2862 https://ashpublications.org/blood/article/113/21/5277/26378/regulation-of-iron-homeostasis-in-anemia-of-chronic-renal-failure https://ashpublications.org/blood/article/113/21/5277/26378/regulation-of-iron-homeostasis-in-anemia-of-chronic-renal-failure https://pubmed.ncbi.nlm.nih.gov/21333465/ https://pubmed.ncbi.nlm.nih.gov/21333465/ introduction materials and methods impact of iron deficiency on the health of vulnerable population common causes of iron deficiency in lmics iron: an integral component for cellular functions absorption of iron from the gut gauging iron absorption (inhibition vs enhancement) damaging role of oxidative stress triggered by free (unbound) iron strategies to control iron-deficiency anemia pathophysiology of iron-deficiency anemia diagnosis of iron-deficiency anemia in lmics iron supplementation scheme current debate on iron therapy practice call for a safer and more effective iron therapy conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9950 production and hosting by knowledge e research article frequency of insulin resistance in people with thyroid dysfunction shaza abdalla elwali1* and sulaf i abdelaziz2 1department of clinical skills, faculty of medicine, sudan international university, khartoum, sudan 2department of internal medicine, faculty of medicine, university of khartoum, khartoum, sudan orcid: shaza abdalla elwali: https://orcid.org/0000-0002-1152-776x abstract background: thyroid dysfunction is an endocrine disorder with a recognized association with type 2 diabetes mellitus. thyroid hormones have a remarkable effect on glucose metabolism and can cause insulin resistance (ir). this study was aimed at assessing the relationship between ir and thyroid dysfunction. methods: this case–control study was conducted at the endocrinology outpatient clinics of ibrahim malik hospital and omdurman military hospital in khartoum state, sudan between may 2018 and january 2019. fasting blood glucose (fbg), fasting insulin level, and thyroid function test (tft) were measured for each candidate and ir was estimated using the homa-ir equation. results: thirty-one patients with thyroid dysfunction and fifty-seven control participants were enrolled. the highest mean fbg was found among cases (105.3 ± 15.7 mg/dl) compared to the controls (97 ± 12.1 mg/dl), but the difference was not statistically significant (p-value = 0.598). the mean fasting insulin level was 9.22 ± 4 iu/ml in the cases and 9.4 ± 4.2 iu/ml in controls, without a significant difference (p-value = 0.681). the highest homa-ir score was found among cases (2.4 ± 1.2). it was 2.4 ± 1.3 in hyperthyroidism, 2.3 ± 1.1 in hypothyroidism, and 2.4 ± 1.2 in controls, and the difference was insignificant (p-value = 0.859). ir was higher in the cases (58.1%) compared to the controls (52.6%) but again not statistically significant (p-value = 0.396). among cases, ir was encountered in 61.9% and 50% of hyperthyroid and hypothyroid patients, respectively. conclusion: patients with thyroid dysfunction have some level of ir that was not statistically significant when compared with controls. keywords: thyroid dysfunction, insulin resistance, type 2 diabetes mellitus how to cite this article: shaza abdalla elwali and sulaf i abdelaziz (2021) “frequency of insulin resistance in people with thyroid dysfunction,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 531–539. doi 10.18502/sjms.v16i4.9950 page 531 corresponding author: shaza abdalla elwali; email: shaza092009@hotmail.com received 21 september 2021 accepted 03 december 2021 published 31 december 2021 production and hosting by knowledge e shaza abdalla elwali and sulaf i abdelaziz. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:shaza092009@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz 1. introduction thyroid disorders are the second most common endocrine disorder after diabetes mellitus. the global epidemiology of thyroid disorders varies from one zone to another depending on iodine sufficiency and deficiency in the area. in sudan, according to a national study conducted in 1997, the overall burden of all types of goiter was 22%, ranging from 5% in khartoum to 42% in upper nile states [1]. on the other hand, the study by perros et al. showed the overall prevalence of thyroid diseases in people with diabetes mellitus was 13.4%. the occurrence of insulin resistance (ir) in patients with thyroid disorders leads to increased morbidity through its role in the existence of the metabolic syndrome [2]. the thyroid hormones thyroxine (t4) and triiodothyronine (t3) have a large effect on glucose metabolism. maintaining a normal blood glucose level requires a balance between the intake and production, which is organized by hormones that decrease the blood glucose level, such as insulin, and those that increase it, such as thyroid hormone, glucagon, and glucocorticoids [3]. normally, thyroid hormones stimulate the nuclear transcription of several genes in almost all body cells, leading to higher total cellular metabolic enzymes. concerning their role in carbohydrate metabolism, in addition to increasing insulin secretion [3], they elevate glucose uptake by cells, increasing gastrointestinal absorption by upregulating glucose transporter 4 (glut4), which elaborates glucose transport, and, through the same action, stimulate glycolysis by upregulating phosphoglycerate kinase. thus, they act synergistically with insulin to improve glucose utilization in the peripheral tissues [4]. in hyperthyroidism (hr), there is high hepatic glucose generation via the aforementioned mechanisms, and elevated fasting postprandial insulin and pro-insulin levels. moreover, it correlates with ir. in the tissues, it leads to impaired glucose uptake because of insulin insensitivity, which is caused by the secretion of adipokines such as interleukin 6 (il6) and tumor necrosis factor alpha (tnf alpha) by adipose tissue [5]. in hypothyroidism, numerous in vitro studies were conducted compared to those in humans, and it was found that there is ir in the peripheral tissues caused by deregulated metabolism of leptin [4]. other features comprise changed blood flow, impaired glut4 translocation, reduced glycogen synthesis, and diminished muscle oxidative capacity. in human studies, a decrease in glucose extraction and blood flow in the muscles and adipose tissue of hypothyroid patients was noticed, causing ir [5]. other aspects of those with subclinical hypothyroidism are impaired lipid regulation and the occurrence of the metabolic syndrome [4]. doi 10.18502/sjms.v16i4.9950 page 532 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz ir is characterized by insufficient tissue response to the action of insulin, causing high insulin secretion which leads to metabolic abnormalities such as cardiovascular disease, type 2 diabetes mellitus, polycystic ovary syndrome, nonalcoholic fatty liver disease, and others [6]. this study investigates the relationship between ir and thyroid disorders compared to healthy individuals. 2. materials and methods this case–control study was conducted at the endocrinology outpatient clinics of omdurman military hospital and ibrahim malik hospital (khartoum, sudan) between may 2018 and january 2019. thirty-one patients with thyroid dysfunction and fifty-seven control participants were randomly enrolled in the study. all patients with a history of thyroidectomy, diabetes mellitus, chronic kidney disease, multiple comorbidities, and pregnant women were excluded. moreover, 6 ml of venous blood was drawn from all candidates for testing insulin, glucose levels, and thyroid hormones. the blood samples were stored at –20ºc until all samples were collected and were then tested at the same time. the reference values were as follows: thyroid-stimulating hormone (tsh): 0.4–7.8 mu/l, t3: 0.8–3.0 nmol/l, t4: 50–150 nmol/l, fasting blood glucose (fbg) < 100 mg/dl, and insulin level: 1.1–32.0 iu/ml. homa-ir stands for homeostatic model assessment of ir. this is an equation that helps calculate the presence and extent of ir in an individual. it reveals the dynamics between the baseline fbg and the amount of insulin produced in response. low homair means good insulin sensitivity. a small amount of insulin is sufficient to maintain glucose homeostasis, while a higher homa-ir denotes more ir. the healthy ir range is 0.5–1.4; <1.0 indicates optimal insulin sensitivity; >1.9 indicates early ir; and >2.9 indicates significant ir. homa-ir equation = (fasting glucose [mg/dl] × fasting insulin [µu/ml] / 405). all subjects were given verbal and written information concerning the study and, after entering the study, signed a written consent form regarding all information received. the study protocol was approved by the ethics committee of the sudan medical specialization board (smsb), the director of the omdurman military hospital and ibrahim malik hospital. doi 10.18502/sjms.v16i4.9950 page 533 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz 2.1. statistical analysis data were analyzed using the statistical package for social sciences (spss v.21.0). the analyzed data are presented in tables designed by microsoft excel 2010. the anova test was used for continuous variables and the chi-square test for categorical variables. also, pearson’s correlation was used between homa-ir score and thyroid profile among the case group. the p-value was considered as significant at the level of 0.05. 3. results this study enrolled 31 thyroid disease patients (21 with hr and 10 hypothyroidism) as a case group and 57 normal individuals as a control group. table 1 presents the demographic characteristics of the participants. the thyroid function test (tft) profile showed that tsh was significantly higher in controls than in hypothyroidism and hr patients (4.6 mu/l [1.7–7.2] vs 2.1 mu/l [0.6–14.4] vs 0.6 mu/l [0.005–15.4]; p-value = 0.001), t3 was higher among hr patients than in hypothyroidism and control group, it was 4.3 nmol/l (0.38–102.7) vs 1.5 nmol/l (0.46– 16.9) vs 1 nmol/l (0.8–2.0), respectively; p-value = 0.001. similarly, t4 was significantly higher among hr patients compared to hypothyroidism and controls 101 nmol/l (14–338) vs 79 nmol/l (3.9–116) vs 93 nmol/l (67–134), respectively; p-value = 0.001. the highest mean of fbg was found among hr patients (108.8 ± 16.5 mg/dl) followed by controls (97 ± 12.1 mg/dl) and hypothyroidism (91.9 ± 28.7 mg/dl), but the difference was not statistically significant (p-value = 0.598). the mean fasting insulin level was 10.1 ± 3.3 iu/ml in hypothyroidism, 9.4 ± 4.2 iu/ml in controls, and 8.8 ± 4.3 iu/ml in hr, without a statistically significant difference (p-value = 0.681). the highest homa-ir score was found in hr (2.4 ± 1.3) followed by hypothyroidism (2.3 ± 1.1) and controls (2.2 ± 1.1), and the difference was not significant (p-value = 0.859) (table 2). table 3 illustrates that patients in the case group (58.1%) showed more ir than those in the control group (38.6%), however, the difference was not statistically significant (p-value = 0.396). table 4 reveals that ir occurred in 61.9% of hr patients and in 50% of hypothyroidism patients without a statistically significant difference (p-value = 0.403). by using pearson’s correlation, the homa-ir score exhibited a weak, insignificant negative correlation with tsh levels (r = –0.175; p-value = 0.345) and t4 levels (r = – 0.224; p-value = 0.216), and a weak positive correlation with t3 levels (r = 0.092; p-value = 0.623) (table 5). doi 10.18502/sjms.v16i4.9950 page 534 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz 4. discussion the aim of this study was to assess the relation between ir and thyroid dysfunction, to find out if there is a link between hypo/hr and fasting insulin levels and ir, and to compare the presence of ir in people with thyroid dysfunction and healthy people without thyroid disorder. the study did not show a significant difference in both insulin levels (p-value = 0.681) and homa-ir scores (p-value = 0.859), as well as ir (p-value = 0.396), and this could be due to the small sample size and the patients were using their anti-thyroid drugs or thyroxine, which may have affected the results. despite it being insignificant, fbg was higher in hr patients than in controls and hypothyroidism patients (108.8 ± 16.5 mg/dl vs 97 ± 12.1 mg/dl vs 91.9 ± 28.7 mg/dl; pvalue = 0.598). this is supported by ohguni et al., who cited that there was no statistically significant difference in fasting plasma glucose among thyroid disease patients and controls [7]. however, on the other hand, maratou et al. reported hr and subclinical hyperthyroidism (shr) had higher glucose levels compared to the euthyroid group (p < 0.05) [8]. insignificantly, fasting insulin is greater in hypothyroid patients (10.1 ± 3.3 iu/ml) followed by controls (9.4 ± 4.2 iu/ml) and hr (8.8 ± 4.3 iu/ml). the first part is supported by purohit et al., as they found insulin levels were greater in the hypothyroid group followed by the hyperthyroid and euthyroid groups [9]. this is also supported by other studies done on subclinical hypothyroidism [10, 11], and on hypothyroidism and subclinical hypothyroidism versus euthyroid [12]. in contrast, kunal et al. (2012) reported insulin levels were raised in hr more than in hypothyroidism and euthyroid state. in our study, insulin levels in hyperthyroid patients were lower than in controls, which could be due to the effect of medications. the study demonstrated that homa-ir scores were higher in hr (2.4 ± 1.3) than in hypothyroidism (2.3 ± 1.1) and in controls (2.2 ± 1.1). in addition, ir was encountered in 61.9% and 50% of hyperthyroid and hypothyroid patients, respectively. this relation is supported by previous statistically significant studies which found homa values were significantly higher in the hyperthyroid and hypothyroid groups as compared to the eu group [13], and other two studies done on subclinical hypothyroidism/subclinical and overt hypothyroidism [14, 15]. however, another study reported the opposite of the above mentioned, citing that homa-ir is greater in hypothyroid (17.29 ± 15.61) and lower in hyperthyroid (1.72 ± 2.46) compared to euthyroid (3.33 ± 0.78) [9]. doi 10.18502/sjms.v16i4.9950 page 535 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz the main limitation of this study is the small sample size, and the current use of medications affects thyroid functions as well as ir parameters. 5. conclusion ir affects both hypo and hr due to high insulin secretion and impaired tissue sensitivity to it. acknowledgements the authors would like to thank the patients and staff at ibrahim malik hospital and omdurman military hospital for their assistance in obtaining the data used in this study. ethical considerations ethical clearance was obtained from the council of internal medicine, sudan medical specialization board (smsb). all enrolled patients signed a written consent form before they joined the study groups. competing interests the authors declare that they have no competing interests to disclose. availability of data and material all data is available upon request. funding the authors declare that no funds or grants were involved in supporting this work. doi 10.18502/sjms.v16i4.9950 page 536 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz table 1: the characteristics of the study group. case (n = 31) control (n = 57) p-value age (yr) <30 14 (45.2%) 33 (57.9%) 0.503 30–50 15 (48.4%) 23 (40.4%) 51–70 2 (6.5.%) 1 (1.8%) gender female 29 (93.5%) 55 (96.5%) 0.442 male 2 (6.5%) 2 (3.5%) bmi (kg/m2) underweight 0 (0%) 10 (17.5%) 0.070 normal 21 (67.7%) 27 (47.4%) overweight 5 (16.1%) 11 (19.3%) obese 5 (16.1%) 9 (15.8%) thyroid disorder hyperthyroidism 21 (67.7%) — hypothyroidism 10 (32.3%) — bmi: body mass index. table 2: the laboratory investigations of study group. hyperthyroidism (n = 21) hypothyroidism (n = 10) control (n = 57) p-value tsh (mu/l); median (max– min) 0.6 (0.005–15.4) 2.1 (0.6–14.4) 4.6 (1.7–7.2) 0.001 t3 (nmol/l; median (max– min) 4.3 (0.38–102.7) 1.5 (0.46–16.9) 1 (0.8–2.0) 0.001 t4 (nmol/l); median (max– min) 101 (14–338) 79 (3.9–116) 93 (67–134) 0.001 fbg (mg/dl); mean ± sd 108.8 ± 16.5 91.9 ± 28.7 97 ± 12.1 0.598 fasting insulin (iu/ml); mean ± sd 8.8 ± 4.3 10.1 ± 3.3 9.4 ± 4.2 0.681 homa-ir score; mean ± sd 2.4 ± 1.3 2.3 ± 1.1 2.2 ± 1.1 0.859 tsh: thyroid stimulating hormone; t3: triiodothyronine; t4: thyroxine; fbg: fasting blood glucose; ir: insulin resistance. table 3: the distribution of insulin resistance among the study group. case (n = 31) control (n = 57) p-value insulin resistance yes 18 (58.1%) 30 (52.6%) 0.396 no 13 (41.9%) 27 (47.7%) doi 10.18502/sjms.v16i4.9950 page 537 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz table 4: the insulin resistance among hypothyroidism and hyperthyroidism patients. hypothyroidism (n = 10) hyperthyroidism (n = 21) p-value insulin resistance yes 5 (50%) 13 (61.9%) 0.403 no 5 (50%) 8 (38.1%) table 5: the pearson’s correlation between homa-ir score and thyroid profile among case group. correlation coefficient (r) p-value hom-ir *tsh –0.175 0.345 hom-ir *t4 –0.23 0.216 hom-ir *t3 0.092 0.623 references [1] medani, a. m. m., elnour, a. a., and saeed, a. m. (2011). endemic goitre in the sudan despite long-standing programmes for the control of iodine deficiency disorders. bulletin of the world health organization, vol. 89, no. 2, pp.121–126. [2] perros, p., mccrimmon, r. j., shaw, g., et al. (1995). frequency of thyroid dysfunction in diabetic patients: value of annual screening. diabetic medicine, vol. 12, no. 7, pp. 622–627. [3] hall, j. e. (2016). guyton and hall textbook of medical physiology (13𝑡ℎ ed.). available at: https://dokumen.pub/guyton-and-hall-textbook-of-medical-physiology13nbsped.html (accessed 2021 april 28). [4] wang, c. (2013). the relationship between type 2 diabetes mellitus and related thyroid diseases. journal of diabetes research, vol. 2013, p. 390534. [5] brenta, g. (2011). why can insulin resistance be a natural consequence of thyroid dysfunction? journal of thyroid research, vol. 2011, article 152850. [6] einhorn, d., reaven, g. m., cobin, r. h., et al. (2003). american college of endocrinology position statement on the insulin resistance syndrome. endocrine practice: official journal of the american college of endocrinology and the american association of clinical endocrinologists, vol. 9, no. 3, pp. 237–252. [7] ohguni, s., notsu, k., and kato, y. (1995). correlation of plasma free thyroxine levels with insulin sensitivity and metabolic clearance rate of insulin in patients with hyperthyroid graves’ disease. internal medicine, vol. 34, no. 5, pp. 339–341. [8] maratou, e., hadjidakis, d. j., peppa, m., et al. (2010). studies of insulin resistance in patients with clinical and subclinical hyperthyroidism. european journal of endocrinology, vol. 163, no. 4, pp. 625–630. doi 10.18502/sjms.v16i4.9950 page 538 sudan journal of medical sciences shaza abdalla elwali and sulaf i abdelaziz [9] purohit, p. (2012). estimation of serum insulin, homeostasis model assessment-insulin resistance and c-peptide can help identify possible cardiovascular disease risk in thyroid disorder patients. indian journal of endocrinology and metabolism, vol. 16, no. 1, pp. s97–s103. [10] al sayed, a., al ali, n., bo abbas, y., et al. (2006). subclinical hypothyroidism is associated with early insulin resistance in kuwaiti women. endocrine journal, vol. 53, no. 5, pp. 653–657. [11] tuzcu, a., bahceci, m., gokalp, d., et al. (2005). subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia. endocrine journal, vol. 52, no. 1, pp. 89–94. [12] maratou, e., hadjidakis, d. j., kollias, a., et al. (2009). studies of insulin resistance in patients with clinical and subclinical hypothyroidism. european journal of endocrinology, vol. 160, no. 5, pp. 785–790. [13] kapadia, k. b., bhatt, p. a., and shah, j. s. (2012). association between altered thyroid state and insulin resistance. journal of pharmacology & pharmacotherapeutics, vol. 3, no. 2, pp. 156–160. [14] vyakaranam, s., vanaparthy, s., nori, s., et al. (2014). study of insulin resistance in subclinical hypothyroidism. international journal of health sciences and research, vol. 4, no. 9, pp. 147–153. [15] singh, b. m., goswami, b., and mallika, v. (2010). association between insulin resistance and hypothyroidism in females attending a tertiary care hospital. indian journal of clinical biochemistry, vol. 25, no. 2, pp. 141–145. doi 10.18502/sjms.v16i4.9950 page 539 introduction materials and methods statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8945 production and hosting by knowledge e research article clinico-pathological diagnosis of facioscapulohumeral dystrophy in a 22-year-old male biniyam a. ayele1, riyad ibrahim2, keberte tsegaye3, tadele birhanu4, hanna assefa3, and wondwossen ergete4 1department of neurology, college of health sciences, addis ababa university, addis ababa, ethiopia 2department of internal medicine, wolkite university, wolkite, ethiopia 3department of neurology, college of health science, addis ababa university, addis ababa, ethiopia 4department of pathology, college of health science, addis ababa university, addis ababa, ethiopia orcid: biniyam a. ayele: https://orcid.org/0000-0002-7955-6030 abstract background: facioscapulohumeral dystrophy (fshd) is a rare hereditary disease with a prevalence of 2.03–6.8 per 100,000 individuals. fshd is the third most common type of muscular dystrophy after the duchene muscular dystrophy and myotonic dystrophy. to the best of our knowledge, the current case report is the first to report probable fshd case mainly diagnosed using clinico-pathological evidence from sub-saharan africa (ssa). case report: a 22-year-old right-handed male college student presented with progressive proximal muscular weakness associated with wasting. the weakness started from the bilateral facial muscles and progressively involved proximal upper and lower limbs muscles associated with scapular winging, waddling gait, and bilateral foot drops. his bulbar, sensory, autonomic, and cognitive systems were spared. muscles emg showed myopathic patterns and normal serum ck. muscle biopsy from affected muscles showed variation in fiber size with groups of angular fibers, preserved fibers, and hypertrophic fibers with marked fibrosis and adipose tissue replacement with no apparent inflammation and necrosis which is consistent with pathological features of muscular dystrophy. considering the clinical semiology, physical findings, emg findings, and pathological findings diagnosis of fshd of scapuloperoneal variant was made. the patient was managed with analgesics, nutritional advice, and ankle prosthesis for foot drops. currently, the patient is in a similar condition with modest improvement in his musculoskeletal pain complaints. conclusion: this case highlights the fact that a careful clinical evaluation with thorough utilization of diagnostic investigations available at our disposal may support the diagnosis of fshd in resource-limited areas where the necessary genetic tests were not available. keywords: facioscapulohumeral muscular dystrophy, dystrophy, clinico-pathology, sub-saharan africa how to cite this article: biniyam a. ayele, riyad ibrahim, keberte tsegaye, tadele birhanu, hanna assefa, and wondwossen ergete (2021) “clinicopathological diagnosis of facioscapulohumeral dystrophy in a 22-year-old male,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 135–142. doi 10.18502/sjms.v16i1.8945 page 135 corresponding author: biniyam a. ayele; assistant professor of neurology, department of neurology, college of health sciences, addis ababa university, addis ababa, ethiopia po box 6396 mobile: +251-983091652; home: +251-11557-4181 email: biniyam.alemayehu@aau .edu.et biniyam.a7@gmail.com received 4 december 2020 accepted 9 march 2021 published 31 march 2021 production and hosting by knowledge e biniyam a. ayele et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:biniyam.alemayehu@aau.edu.et mailto:biniyam.alemayehu@aau.edu.et mailto:biniyam.a7@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences biniyam a. ayele et al 1. introduction facioscapulohumeral muscular dystrophy (fshd) is a rare hereditary disease with a prevalence of 2.03–6.8 per 100,000 individuals [1]. fshd is the third most common type of muscular dystrophy after the duchene muscular dystrophy and myotonic dystrophy [1, 2]. the pathology of fshd is a result of an intricate interaction of genetics, involving the protein product of the dux4 gene and the chromosomal location and number of repeats of the d4z4 microsatellite. the result of this interaction is the inappropriate expression of the dux4 protein product; however, it is sporadic in 30% [1–3]. fshd is classified into two categories: fshd 1 and fshd 2 [1]. the vast majority (95%) of patients meeting clinical criteria for fshd will have fshd1, while the remaining 5% constitute for fshd 2 [1]. the disease often onsets in the second decade of life; however, the onset during infancy and adulthood have also been reported [4]. the muscular weakness initially involves proximal muscles such as facial, shoulder girdle, and arm muscles and subsequently progresses downward to involve lower limb and pelvic girdle muscles; however, fshd relatively spares extra ocular, pharyngeal, lingual, respiratory, and the myocardial muscles compared to other muscular dystrophies [1, 3, 5–8]. diagnoses of fshd depends on the fulfillment of clinical criteria, genetic study, electromyographic (emg), and histopathological evidence [1, 2, 4–7, 9, 10]. to date, there is no proven diseasemodifying therapy for fshd; however, supportive treatments such as nutritional advise, spine alignment surgery, and ankle prosthesis could be beneficial to patients with fshd [1, 4, 10, 11]. to the best of our knowledge, this is the first case report on the diagnosis of fshd based on clinico–pathological pieces of evidence from sub-saharan africa (ssa). 2. case report a 22-year-old male presented with progressive weakness and wasting (atrophy) of muscles of the bilateral face, shoulder, arm, pelvic girdles, and distal limb over a fouryear period. in addition, he had associated atrophy of proximal muscles of shoulder and pelvic girdles. progressively, he developed difficulty in combing and washing his hair, standing from a sitting position, and waddling gait. furthermore, he reported severe back and joint pain which worsened when he walked and relieved with rest due to his hyperlordosis. otherwise, no mentation changes, cognitive impairment, bladder or bowel complaint, and no bulbar dysfunction were reported. the patient had no family history of similar illness, no previous history of tuberculosis treatment. he is a third-year doi 10.18502/sjms.v16i1.8945 page 136 sudan journal of medical sciences biniyam a. ayele et al university student but discontinued his education because of progressive extremities weakness and gait abnormality. the patient lives with his mother and one younger brother, both of whom are healthy. his father died when he was young, cause unknown. general appearance was emaciated. vital signs were normal. atrophied shoulder muscles, bilateral pectorals muscles, intercostal muscles, proximal arm and pelvic muscles with relative preserved muscle bulk of bilateral forearm and bilateral scapular winging were noted (figures 1a and 1b). the patient had prominent lordosis and positive gower sign. neurological examination showed bilateral facial diplegia (figure 1c), atrophied muscles with a power of 3/4 in proximal muscles and 4/5 in distal muscles in both upper limbs. bilateral foot drop was noted. reflexes, tone, sensory examination, and plantar reflexes were normal. routine investigations were normal. serology tests for hiv and hbsag were negative. creatinine kinase was normal. echocardiography (echo), electrocardiography (ecg), and nerve conduction test (ncs) were normal. electromyography (emg) showed myopathic patterns without features of active denervation potentials (figure 2). muscle biopsy from affected muscles showed variation in fiber size with groups of angular fibers, preserved fibers, and hypertrophic fibers with marked fibrosis and adipose tissue replacement with no apparent inflammation and necrosis which is consistent with the pathological features of muscular dystrophy (figures 3a and 3b). a b c figure 1: (a) image showing significant muscular atrophy of intercostal, pectoralis, arm, and shoulder girdle muscles. (b) image showing bilateral scapular winging while the patient extends his upper limbs. (c) image showing slim elongated face with modest facial diplegia. considering the clinical semiology and the physical, emg, and pathological findings, the diagnosis of fshd of scapuloperoneal variant was made. a definitive diagnosis of fshd requires genetic study confirming mutations in a smchd1 gene. however, genetic studies were not available in ethiopia and if at all available, are not affordable by the patients. therefore, we solely based the diagnosis of fshd in our patient on the typical clinical presentation, emg findings, and histopathological evidence. the patient and his doi 10.18502/sjms.v16i1.8945 page 137 sudan journal of medical sciences biniyam a. ayele et al figure 2: electromyography (emg) image showing small amplitude and duration muscle action unit potential (muap) suggesting myopathic patterns. a b figure 3: e&m muscle biopsy from affected muscles showed variation in fiber size with groups of angular fibers, preserved fibers, and hypertrophic fibers with marked fibrosis and adipose tissue replacement with no apparent inflammation and necrosis which is consistent with pathological features muscular dystrophy. family were advised on the available treatment options and prognosis of the disease. he was started with nsaids for his back pain and joint pain. in addition, nutritional advice was given in order to improve his muscle bulk. ankle prosthesis was prescribed for his bilateral foot drop. currently, the patient is in a similar condition with modest improvement in his musculoskeletal pain complaints. doi 10.18502/sjms.v16i1.8945 page 138 sudan journal of medical sciences biniyam a. ayele et al 3. comments we present a young male who presented with progressive proximal muscular weakness and wasting. the weakness started from the bilateral facial muscles and progressively involved proximal upper and lower limbs muscles associated with scapular winging, waddling gait, and bilateral foot drops. his bulbar, sensory, autonomic, and cognitive systems were spared. muscles emg showed myopathic patterns and normal serum ck, and histopathological examination from affected muscles revealed muscular dystrophy. his overall evaluation suggested fshd. since genetic tests were not done, fshd classification was not settled. the patient was managed symptomatically. fshd commonly occurs in the second or third decade of life [5]. our patient is a 22-year-old male, which, in line with the typical age of fshd symptoms onset. we did conduct a genetic study of our patient because of the unavailability of genetic tests. despite the absence of a positive family fshd history in our patient, the fact that his father died of unknown cause could remotely support the underlying genetic etiology. however, nearly 30% of fshd patients could be sporadic [12]. accurate diagnosis of fshd requires presences of hallmark clinical semiology such as proximal onset muscle weakness and wasting (facial diplegia) and progressive involvement of shoulder, pelvic, and distal lower limbs muscles, sparing ocular, bulbar, sphincter, respiratory, and cardiac muscles [1, 3, 6, 7, 13, 14]. likewise, our patient’s clinical features started with bilateral facial weakness which resulted in difficulty of closing his eyes, whistling, and blowing chicks. furthermore, progressive weakness and wasting of shoulder, intercostal, and arm muscles resulted in scapular winging. in addition, pelvic girdle muscles and distal legs muscles weakness resulted in waddling gait and foot drops, respectively. myopathic pattern, emg findings, and normal or elevated serum ck often support the diagnosis of fshd [7]. our patient’s emg findings were suggestive of myopathic pattern. however, the serum ck of our patient was normal, which could be an expected possibility in patients with fshd. muscle biopsy is important in order to support the diagnosis of fshd in resource-limited areas like us. histopathological analysis from affected muscles could indicate angular muscle fibers atrophy and scanty inflammatory cells, which will help us differentiate fshd from other inflammatory myopathies [1]. therefore, the combination of clinico–pathological evidence and emg findings could be highly valuable in diagnosing muscular dystrophies such as fshd in resource-limited regions such as ssa. in the absence of supportive genetic evidence for fshd, it is important to rule out other dystrophies with similar clinical features such as emery–dreifuss muscular dystrophy (edmd), a slowly progressive x-linked muscular doi 10.18502/sjms.v16i1.8945 page 139 sudan journal of medical sciences biniyam a. ayele et al dystrophy with a late onset and a slightly reduced average lifespan [15]. the classic overall triad of edmd consists of early contractures, progressive muscle weakness and atrophy, and cardiac abnormalities. the absence of muscular contracture and normal cardiac function in our case makes the diagnosis of edmd less likely. currently, the treatment options of fshd are limited to symptomatic managements such as relieving musculoskeletal pain, spine-alignment surgery, ankle prosthesis, and nutritional advice [1, 5, 6]. thus far, our patient was treated with analgesics for his musculoskeletal pain, nutritional advice to increase his lean body mass, and ankle prosthesis for his foot drops. spine alignment surgery for hyperlordosis was not done, as the service was not available in ethiopia. this case highlights the fact that a careful clinical evaluation with thorough utilization of diagnostic investigations available at our disposal may support the diagnosis of fshd in resource-limited areas where the necessary genetic tests are not available. acknowledgements the authors would like to acknowledge the departments of neurology and pathology and the patient for their participation in the study. statement of ethics the author’s institutions does not require ethical approval letter for publication of a single case. the patient has given written informed consent for publication of the case. the copy of the written consent will be available from the corresponding author upon reasonable request from the journal editor. competing interests the authors have no conflicts of interest to declare. funding none doi 10.18502/sjms.v16i1.8945 page 140 sudan journal of medical sciences biniyam a. ayele et al authors’ contributions all authors were involved in the conception, writing and critical review of the study. all authors were involved in patient’s evaluation, investigation, treatment, and follow-ups. the final version of the article has been approved by all authors for publication. references [1] padberg g, editor. md thesis university of leiden. 1982. facioscapulohumeral disease isbn 9070176718. [2] petrov, a., laoudj, d., and vassetzky, y. (2003). genetics and epigenetics of progressive fascioscapulohumeral (landouzy-dejerine) muscular dystrophy. russian journal of genetics vol. 39, pp. 147–51. [3] desimone, a. m., pakula, a., lek, a., et al. (2017). facioscapulohumeral muscular dystrophy. comprehensive physiology, vol. 7, no. 4, pp. 1229–1279. [4] tawil, r., kissel, j. t., heatwole, c., et al. (2015). evidence-based guideline summary: evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy. neurology, vol. 85, no. 4, pp. 357–364. [5] hamel, j. and tawil, r. (2018). facioscapulohumeral muscular dystrophy: update on pathogenesis and future treatments. neurotherapeutics, vol. 15, no. 4, pp. 863–871. [6] engel, w. k. (2015). diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view. biochimica et biophysica acta molecular basis of disease, vol. 1852, no. 4, pp. 563–584. retrieved from: http://dx.doi.org/10.1016/j.bbadis.2014. 11.015 [7] padberg, g. w., lunt, p. w., koch, m., et al. (1991). diagnostic criteria for facioscapulohumeral muscular dystrophy. neuromuscular disorders, vol. 1, no. 4, pp. 231–234. [8] rabi tawil, john t. kissel, chad heatwole et al (2015). evidence-based guideline summary: evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy. neurology: vol. 85 [9] diniz, g. (2016). the histopathological features of muscular dystrophies, pp. 1–18. smgroup. [10] pasotti, s., magnani, b., longa, e., et al. (2014). an integrated approach in a case of facioscapulohumeral dystrophy. bmc musculoskeletal disorders, vol. 15, pp. 1–6. doi 10.18502/sjms.v16i1.8945 page 141 http://dx.doi.org/10.1016/j.bbadis.2014.11.015 http://dx.doi.org/10.1016/j.bbadis.2014.11.015 sudan journal of medical sciences biniyam a. ayele et al [11] lu, j., yao, z., yang, y., et al. (2019). management strategies in facioscapulohumeral muscular dystrophy. intractable & rare diseases research, vol. 8, no. 1, pp. 9–13. [12] nih. genetics home reference your guide to understanding genetic conditions. retrieved from: https://nnlm.gov/all-of-us/cp/resource/genetics-home-referenceyour-guide-understanding-genetic-conditions [13] lamperti, c., fabbri, g., vercelli, l., et al. (2010). a standardized clinical evaluation of patients affected by facioscapulohumeral muscular dystrophy: the fshd clinical score. muscle and nerve, vol. 42, no. 2, pp. 213–217. [14] ramos, v. f. m. l. and thaisetthawatkul, p. (2012). a case of fascioscapulohumeral muscular dystrophy misdiagnosed as becker’s muscular dystrophy for 20 years. age and ageing, vol. 41, no. 2, pp. 273–274. [15] heller, s. a., shih, r., kang, p. b., et al. (2020). emery-dreifuss muscular dystrophy. muscle and nerve, vol. 61, no.4, pp. 436–448. doi 10.18502/sjms.v16i1.8945 page 142 https://nnlm.gov/all-of-us/cp/resource/genetics-home-reference-your-guide-understanding-genetic-conditions https://nnlm.gov/all-of-us/cp/resource/genetics-home-reference-your-guide-understanding-genetic-conditions introduction case report comments acknowledgements statement of ethics competing interests funding authors' contributions references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9944 production and hosting by knowledge e research article effects of curcumin on iron overload in rats gülüzar özbolat1* and arash alizadeh yegani2 1faculty of health science, sinop university, sinop, turkey 2department of pharmacology, faculty of veterinary, mustafa kemal university, hatay, turkey orcid: arash alizadeh yegani: https://orcid.org/0000-0003-0334-8152 abstract background: iron overload, common in patients with hematological disorders, is a key target in drug development. this study investigated the effects of curcumin on iron overload in rats. methods: forty male wistar rats weighing 139.78 ± 11.95 gm (mean ± sd) were divided into three equal groups: (i) controls; (ii) iron overload group that received six doses of iron dextran 1000 mg/kg−−1 by intraperitoneal injections (i.p.); and (iii) iron overload curcumin group that received six doses of curcumin (1000 mg/kg bw by i.p.). in addition to six doses of iron dextran 1000 mg/kg−−1 by i.p., we studied the effects of curcumin on liver function enzymes (alanine aminotransferase [alt] and aspartate aminotransferase [ast]); antioxidant enzymes (malondialdehyde [mda], total oxidant status [tos], total antioxidant status [tas]); hematological parameters (hemoglobin [hb], hematocrit [hct], red blood cells [rbc], white blood cells [wbc], mean corpus volume [mcv], mean corpuscular hemoglobin [mch], mean corpuscular hemoglobin concentration [mchc]); and iron parameters (serum iron profile, transferrin, total iron-binding capacity [tibc], ferritin, and transferrin saturation [ts%]). results: curcumin caused a significant decrease in the hct and hb concentrations in group iii (p < 0.05). it also significantly reduced the serum levels of alt (52.45 ± 4.51 vs 89.58 ± 4.65 u/l) and ast (148.03 ± 6.47 vs 265.27 ± 13.02 u/l) at the end of the study (p < 0.05). the tibc, transferrin levels, and ts significantly decreased when the rats were administered curcumin serum iron (p < 0.05). the tas level significantly increased in group iii in comparison to group i (the control group) (p < 0.05). at the end of the study, curcumin significantly reduced the serum levels of tos (12.03 ± 2.8 vs 16.95 ± 5.05 mmol h2o2/l) while the tas (1.98 ± 0.42 vs 1.06 ± 0.33 mmol trolox equiv./l) was increased. conclusion: the findings of the present study suggest the therapeutic potential of curcumin against iron overload. keywords: curcumin, iron overload, tibc, tas, tos, mda how to cite this article: gülüzar özbolat and arash alizadeh yegani (2021) “effects of curcumin on iron overload in rats,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 464–475. doi 10.18502/sjms.v16i4.9944 page 464 corresponding author: gülüzar özbolat; email: guluzarozbolat@gmail.com received 19 september 2021 accepted 07 december 2021 published 31 december 2021 production and hosting by knowledge e gülüzar özbolat and arash alizadeh yegani. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:guluzarozbolat@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani 1. introduction iron is crucial for all living organisms, including humans and animals. it is required as a cofactor for a multitude of proteins with diverse biological functions. however, because iron is a transition metal, it can participate in the fenton reaction resulting in the generation of reactive oxygen and free radicals [1, 2]. in the body, iron is an essential element involved in numerous physiologic processes, such as mitochondrial respiration, energy production, atp production, dna synthesis, and oxygen consumption [3, 4]. while iron is tightly regulated physiologically, the human body has no controlled mechanism to excrete its excess amounts. iron overload occurs when excess iron accumulates in the body, causing organ dysfunction. under such circumstances, iron chelation therapy is required, particularly in repeatedly transfused patients suffering from sickle cell anemia or β-thalassemia [5–8]. at the same time, iron becomes potentially more toxic since the redox cycling catalyzes the production of hydroxyl radicals. iron can readily undergo redox cycling between its two predominant oxidation states, fe3+and fe2+, acting as an electron donor or acceptor [9, 10]. however, when iron is present in excess, iron-mediated oxidative stress occurs. in the presence of molecular oxygen generating oxygen-derived free radicals such as hydroxyl radicals, the highly reactive hydroxyl radicals attack the cell membrane, destroying dna base sequences and sugar groups [11–16]. iron chelation therapy is the optimum alternative for treating iron overload. currently, three iron chelators are licensed to treat iron overload, the most widely used of which is desferrioxamine-b. the principal drawbacks of desferrioxamine are lack of oral activity, high cost, and low compliance. moreover, the two oral chelators that are currently available have various disadvantages. therefore, there exists an urgent clinical need for new chelation agents for iron. consequently, the successful design of a nontoxic, orally active, selective iron chelator has become a much sought-after goal [11–20]. desferrioxamine, also known as deferoxamine (dfo; generic and desferal [brand name]), is a drug that is commonly utilized in the treatment of iron overload. in addition to its iron-chelation property, other features have been identified. dfo is injectable iron chelator indicated for chronic iron overload in patients aged three years or more [23–26]. this iron chelator has proven effective in preventing lipid peroxidation, reducing deaths by cardiac disease, and extending the lifespan in iron overloaded patients; it also has a mild toxicity profile. the most common adverse effects of dfo are discomfort at the injection site and gastrointestinal disturbances. although rare, ototoxicity, nephrotoxicity, and visual impairment are other side effects of dfo. fortunately, most of the toxicity is doi 10.18502/sjms.v16i4.9944 page 465 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani reversible when dfo therapy is discontinued. however, this therapy increases the risk of infections, including those caused by vibrio and yersinia [27–30]. deferiprone (dfp), a tablet orally administered three times daily, was first introduced in clinical trials in the 1980s and approved in 2011. it was also the first oral iron chelator to be clinically assessed, and it is pharmacologically effective in achieving iron excretion [13]. dfp is indicated for the treatment of transfusional iron overload. it appears to be particularly effective with regards to cardiac iron removal [28]. however, although dfp has good compliance, some serious side effects have been reported, including agranulocytosis, gastrointestinal disturbances, arthropathy, neutropenia, and a transient rise in serum transaminases. in comparison to deferasirox (dfx), dfp appears to be less successful in controlling iron overload in thalassemia. dfx is used as the second-choice treatment in thalassemia when dfp is not available [29–31]. dfx is an orally administered iron chelator that has been successful in clinical trials in patients with transfusional iron overload; it has demonstrated high effectiveness in the reduction of iron burden. although dfx is well-tolerated with a high safety profile, it leads to several adverse side effects, including gastrointestinal disturbances, increased liver enzymes, increased serum creatinine levels, and maculopapular skin rash. it also entails changes in kidney and liver function, diarrhea, nausea, abdominal pain, auditory impairment, skin rash, and headaches [32, 33]. curcumin (diferuloylmethane) is the biphenolic active compound of turmeric. various studies have shown that it has anti-arthritic, anti-infectious, cardioprotective, antiinflammatory, antioxidant, hepatoprotective, chemo preventive, thrombo suppressive, and anti-carcinogenic activities. this compound is a polyphenol, and it readily complexes with several different metal ions. it has been found to be an effective chelator of fe (iii) [34–39]. this study aimed to investigate the effect of curcumin on iron overload in rats by measuring the activities of hematological parameters (hemoglobin [hb], hematocrit [hct], red blood cells [rbc], white blood cells [wbc], mean corpus volume [mcv], mean corpuscular hemoglobin [mch], mean corpuscular hemoglobin concentration [mchc]), serum iron profile, transferrin, total iron-binding capacity (tibc), transferrin saturation (ts%), total oxidant status (tos), total antioxidant status (tas), malondialdehyde (mda), aspartate aminotransferase (ast), and alanine aminotransferase (alt). doi 10.18502/sjms.v16i4.9944 page 466 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani 2. materials and methods forty male wistar rats weighing 139.78 ± 11.95 gm (mean ± sd) were divided into three groups: (i) the control group; (ii) the iron overload group receiving six doses of iron dextran 1000 mg/kg i.p. injection; and (iii) the iron overload curcumin group receiving six doses of curcumin (1000 mg/kg bw by i.p. injection). in addition to six doses of iron dextran 1000 mg/kg by i.p. injection, at the end of the experiments, the rats were anesthetized with ketamine/xylazine. blood samples were collected by a heparinized tube. hematological parameters were assayed by an automated hemoanalyzer. blood samples were centrifuged at 1000 x g at 4ºc for 10 min, and serum samples were separated to measure the serum alt and ast levels using standard diagnostic kits (roche). serum transferrin levels were measured using a transferrin kit by elisa method. the tibc was measured by a colorimetric, spectrophotometric method using the randox tibc kit and fe serum levels were measured using randox kit. tas and tos were measured spectrophotometrically using a commercially available kit. 2.1. determination of mda as an indicator of oxidative stress a total of 200 µl of liver tissue homogenates were used to estimate the mda content, which was measured spectrophotometrically [40, 41]. 2.2. statistical analysis differences between the two groups were assessed using student’s t-test and anova. data are shown as mean ± sem. p-values < 0.05 were defined as statistically significant. 3. results we examined the hematological parameters of all three groups. based on our results, curcumin administration did not significantly affect the hb and hct in group-iii rats (table 1). mda levels significantly increased in group-ii rats compared to the controls and group iii. curcumin significantly reduced the levels of mda (34.52 ± 6.34 compared with 152.46 ± 6.99 u/l in group ii) (p < 0.05) (table 2). tas level increased significantly in group iii compared with group i (p < 0.05). the tos was found to be higher in the second group compared with the first (p < 0.05). doi 10.18502/sjms.v16i4.9944 page 467 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani table 1: comparison of hematological parameters (hb, hct, rbc, wbc, mcv, mch, mchc) in the three groups of rats. hematological parameters group i group ii group iii wbc count 3.22 ± 0.16 3.24 ± 0.65 4.02 ± 0.42 rbc (×10/µl) 7.524 ± 0.08 5.642 ± 1.35 7.795 ± 0.28 hemoglobin (gm/dl) 14.52 ± 0.18 12.98 ± 0.54 12.96 ± 0.48 hematocrit (%) 45.12 ± 0.88 39.89 ± 1.12 40.75 ± 1.45 mcv (fl) 60.95 ± 0.52 59.45 ± 1.32 60.06 ± 0.22 mch (pg) 19.58 ± 0.15 19.52 ± 0.18 20.28 ± 0.14 mchc (gm/dl) 32.45 ± 0.33 32.87 ± 0.46 34.07 ± 0.24 the results are expressed as mean ± sd. table 2: the effect of iron overload and curcumin on mda (nmol/gm tissue), tos (mmol h2o2/l), and tas (mmol trolox equiv./l) activities of rats. group i group ii group iii mda (nmol/gm wet tissue) 59.12 ± 4.02 152.46 ± 6.99𝑎 34.52 ± 6.34𝑏 serum tos (mmol h2o2/l) 34.86 ± 2.76 46.95 ± 5.05𝑎 30.03 ± 2.8𝑏 serum tas (mmol trolox equiv./l) 15.32 ± 0.24 14.06 ± 0.33𝑎 18.58 ± 0.42𝑏 the results are expressed as mean ± sd. 𝑎significant difference with group i; 𝑏significant difference with group ii; 𝑐significant difference with group iii at p < 0.05. at the end of the study, curcumin significantly reduced serum tos levels (46.95 ± 5.05 vs 30.03 ± 2.8 [mmol h2o2/l]) and increased tas (14.06 ± 0.33 vs 18.58 ± 0.42 [mmoltroloxequiv./l]). the enzyme assays of serum transaminases demonstrated that iron overload significantly increased the levels of alt and ast to 89.58 and 265,27 u/l, respectively (p < 0.05). curcumin was able to effectively inhibit the enzyme activity. the levels of ast and alt were reduced to 52.45 and 148.03 u/l, respectively (p < 0.05) (table 3). in this study, serum iron, tibc, and transferrin levels were significantly increased in the iron overload rats. at the end of the study, curcumin significantly reduced the serum levels of iron (205.24 ± 4.50 vs 330.45 [𝜇g/dl]), transferrin (1.49 ± 0.07 compared with 2.35 ± 0.04 [gm/l]), and tibc (96.43 ± 6.46 compared with 109.22 ± 9.74 [𝜇g/dl]) (table 4) (p < 0.05). table 3: the effect of iron overload and curcumin on alt and ast activities. group i control group ii group iii alt (u/l) 65.14 ± 8.85 89.58 ± 4.65𝑎 52.45 ± 4.51𝑏 ast (u/l) 160.15 ± 10.62 265.27 ± 13.02𝑎 148.03 ± 6.47𝑏 𝑎significant difference with the control group; 𝑏significant difference with the iron overload group at p < 0.05. doi 10.18502/sjms.v16i4.9944 page 468 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani table 4: the effect of iron overload and curcumin on the serum iron profile of rats. group i group ii group iii transferrin (gm/l) 1.45 ± 0.02 2.35 ± 0.04𝑎 1.49 ± 0.07𝑏 transferrin saturation (%) 66.76 ± 4.12 76.16 ± 3.38𝑎 68.24 ± 3.65𝑏 iron (𝜇g/dl) 220.38 ± 3.45 330.45 ± 6.11𝑎 205.24 ± 4.50𝑏 tibc (𝜇g/dl) 104.25 ± 5.30 109.22 ± 9.74𝑎 96.43 ± 6.46𝑏 the results are expressed as mean ± sd. 𝑎significant difference with group i; 𝑏significant difference with group ii; 𝑐significant difference with group iii at p < 0.05. 4. discussion iron overload condition in the body can be defined as an increase in iron deposition with no consideration as to the presence of tissue destruction. curcumin, also known as diferuloylmethane, is a bright yellow chemical produced by plants of the curcuma longa. curcumin molecule has been reported to be the active site involved in the chelation of iron. it has chemical properties consistent with iron chelator activity [42–44]. this study aimed to investigate the effect of curcumin on iron overload in rats. we studied the effects of curcumin on liver function enzymes (ast, alt), antioxidant enzymes (tos, tas, mda), hematological and iron parameters (serum iron profile, transferrin, tibc, ferritin, ts%). based on our results, curcumin administration did not significantly affect hb and hct in rats in group iii. yadav et al. reported a statistically nonsignificant change in the rbc and wbc counts and the hb values observed in rats administered with extract of curcumin. hussain reported that curcumin caused a significant decrease in rbc and mhc in aged rats [45, 46]. iron overloaded rats had a significantly higher level of mda in the liver than controls. treatment with curcumin significantly lowered the level of mda. the decrease in the level of mda suggests that curcumin might be effective in the prevention of lipid peroxidation. mda in the liver of iron-overloaded rats was statistically higher than that in other corresponding groups (p < 0.01). these changes may be the result of oxidative damage associated with ros production and hepatic iron accumulation, which may ultimately lead to chronic diseases [47]. these results confirmed that curcumin significantly elevated the levels of tas and that tos was found to be higher in the second group compared with the first and the third groups. at the end of the study, curcumin significantly reduced serum tos levels. this study also demonstrated that curcumin significantly reduced pathological changes in the liver by reducing ast and alt levels as shown in table 2. iron overload was associated with significant increases in the activities of the alt and ast (p < 0.05) compared with group i. the injection of curcumin significantly decreased the serum levels of doi 10.18502/sjms.v16i4.9944 page 469 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani ast and alt compared to iron overloaded rats (p < 0.05). a previous study did not find any significant changes in ast and alt levels following curcumin administration [48]. other studies showed that curcumin treatment reversed the elevated enzymes; alp, alt, and ast. moreover, fu et al. found that curcumin significantly protected the liver from injury by reducing the activities of serum alp, ast, and alt [49]. in another study by manjunatha et al., rats injected with iron showed hepatic toxicity as measured by elevated serum enzymes, ldh, alt, and ast and an increase in lipid peroxides [50]. in the present study, serum iron, tibc, and transferrin levels were significantly elevated in the iron-overloaded rats. in rats administered with curcumin tibc, serum iron, transferrin levels, and ts% significantly decreased (p < 0.05). evidence for iron toxicity in another study was exhibited by the significant increase in serum, liver, and kidney iron concentrations, serum tibc, transferrin, and ts% in iron-overloaded rats while serum uibc was significantly reduced. such increases have been associated with increased oxidative stress state and changes in antioxidants. these results are in agreement with those recorded in several models of iron overload [51]. 5. conclusion in conclusion, the present study confirms previous reports on the therapeutic potential of curcumin. our results confirm the hypothesis that curcumin acts as an iron chelator and our in-vivo results suggest that curcumin-oxime has the potential to exhibit a positive effect on iron overload. acknowledgements none. ethical considerations this study was performed in accordance with the declaration of helsinki. ethical approval was obtained for the studies from the hatay mustafa kemal animal experiments local ethics committee (2018/10-1). competing interests none to declare. doi 10.18502/sjms.v16i4.9944 page 470 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding the funding of this study was supported by the authors. references [1] lasocki, s., gaillard, t., and rineau, e. 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[48] zaribaf, f., entezari, m. h., hassanzadeh, a., et al. (2014). association between dietary iron, iron stores, and serum lipid profile in reproductive age women. journal of education and health promotion, vol. 3, p. 15. [49] mohammadi, e., tamaddoni, a., qujeq, d., et al. (2018). an investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in ß-thalassemia major patients: a double-blind randomized controlled clinical trial. phytotherapy research, vol. 32, no. 9, pp. 1828–1835. doi 10.18502/sjms.v16i4.9944 page 474 sudan journal of medical sciences gülüzar özbolat and arash alizadeh yegani [50] sadeek, e. a. and el razek, h. a. (2010). the chemo-protective effect of turmeric, chili, cloves and cardamom on correcting iron overload-induced liver injury, oxidative stress and serum lipid profile in rat models. journal of american science, vol. 6, no. 10, pp. 702–712. [51] lebda, m. a. (2014). acute iron overload and potential chemotherapeutic effect of turmeric in rats. indian journal of pure & applied biosciences, vol. 2, no. 2, pp. 86–94. [52] el-maraghy, s. a., rizk, s. m., and el-sawalhi, s. s. (2009). hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. african journal of biochemistry research, vol. 3, no. 5, pp. 215–221. doi 10.18502/sjms.v16i4.9944 page 475 introduction materials and methods determination of mda as an indicator of oxidative stress statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9959 production and hosting by knowledge e research article saving the fundaments: impact of a military coup on the sudan health system alhadi k. osman1,2,3, mona ibrahim 4, karrar karrar5 hassan salih6,3, mohamed elsheikh7,8 1julius global health, university medical center utrecht, utrecht, the netherlands 2federal ministry of health, sudan 3the national ribat university, sudan 4university of oxford, united kingdom 5save the children-uk, united kingdom 6johns hopkins university, bloomberg school of public health, united states of america 7university of sussex, united kingdom 8mycetoma research center-university of khartoum, sudan orcid: alhadi k. osman: https://orcid.org/0000-0003-0738-103x mohamed elsheikh: https://orcid.org/0000-0001-9474-4219 mona ibrahim: https://orcid.org/0000-0001-8070-0530 abstract military coups are not uncommon occurrences, particularly in developing nations where political systems might be less firmly entrenched or still evolving. developments of this nature can often have profound implications for the affected nation’s healthcare systems, both in the immediate aftermath and over the longer term. this paper narrates some notable consequences of political instability on the national health system, particularly placing them in the context of the military coup in october 2021 – emphasizing the context behind the political turbulence, its acute and direct consequences, and the possible long-term legacies of political shocks on the already overwhelmed health system. as a descriptive piece, this narrative does not only look at the impact of the military coup on hospitals, but further considers the different dimensions of the healthcare system as defined by the who, therefore reflecting the wider implications on health funding from multi-laterals, service delivery, human resource availability, and medical and vaccine supply chains in sudan. keywords: healthcare system, military coup, health, political, impact, sudan 1. introduction military coups are not uncommon in lowand middle-income countries; for example, there have been 10 military coups in african countries in the past five years alone [1]. the most recent occurred on october 25, 2021, when the sudanese army deposed the transitional government (the 17𝑡ℎ such event in sudan since its independence in 1956). this article uses this event as the focal lens to examine the impact of military coups on sudan’s healthcare system, exploring some of the longer-term implications (such as the how to cite this article: alhadi k. osman, mona ibrahim , karrar karrar hassan salih, mohamed elsheikh (2021) “saving the fundaments: impact of a military coup on the sudan health system,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 567–573. doi 10.18502/sjms.v16i4.9959 page 567 corresponding author: alhadi k. osman; email: alhadikhogaliosman@gmail.com received 24 november 2021 accepted 16 december 2021 published 31 december 2021 production and hosting by knowledge e alhadi k. osman et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:alhadikhogaliosman@gmail.com mailto:alhadikhogaliosman@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences alhadi k. osman et al. availability of financial and human resources, and the acquisition of new medicines and technologies). 2. a leadership vacuum the negative results of a leadership vacuum have been well-documented. high governance and leadership turnover-rates and a lack of succession planning can result in disruption to healthcare organizations and an inability to create and sustain change [1]. this train of events was visible in the immediate aftermath of the october coup in sudan, which saw the dismissal of both the federal minister and the undersecretary of the federal ministry of health (fmoh). these two positions are critical to the management of the sudanese health systems, monitoring the progress of the different functions, coordinating partners and stakeholders locally and globally, and working toward the goal of achieving universal health coverage in sudan (figure 1). the removal of these two officials had a significant negative impact on these processes. changes in healthcare leadership can result in drastic changes in healthcare policies, which can be driven by individual interests rather than systematic, resilient, and evidence-based priorities. the sudanese healthcare system has experienced this on multiple occasions; in the last three years alone the fmoh has had three ministers, four undersecretaries, and numerous changes on the general directorates’ level. these high-level staffing changes trickle down to the mid-level leadership, which sees a further series of turnovers. in a hurried and unplanned change, such as occurs in the aftermath of a military coup, international relations can experience a period of turmoil as foreign organizations involved in healthcare are unsure of who to contact. this intensifies the strategic and operational challenges facing a new government and healthcare leadership. 3. interrupted funding and donor insecurity financing healthcare services is often one of the greatest challenges in the months following a military coup and change in government. in sudan, this difficulty will perhaps be intensified due to pre-existing tensions experienced by the previous government which faced rising out-of-pocket expenditures and falling government financial contributions (leaving the healthcare sector increasingly reliant on donor contributions). in addition, the country was already undergoing sweeping financial reforms which resulted in economic stresses and rising inflation – these factors are likely to be intensified doi 10.18502/sjms.v16i4.9959 page 568 sudan journal of medical sciences alhadi k. osman et al. as some channels of financial support from the international community have been temporarily frozen in the wake of the military coup. the usa alone has already suspended over usd 700 million of direct assistance to sudan’s government. developments such as this make it imperative that the new government is established and stabilized as swiftly as possible, in order to regain foreign donor trust and re-open funding channels for the healthcare systems. in the case of sudan, there is the added concern that the country’s suspension from the african union might also disqualify it for receipt of healthcare funding in the foreseeable future; for example, membership in the african union is a prerequisite to receiving the acquisition fund for covid-19 vaccination (2). although independent funders and development agencies like unicef continue to deliver assistance in eastern and southern sudan, failure to transition to civilian leadership will put the financial security of the healthcare system at risk. an already underfunded and overstretched system like sudan’s is in jeopardy of losing the existing infrastructure, burdening the future administration with overwhelming recovery and repair costs. 4. suspended service delivery service delivery interruption is typically one of the most immediate consequences of a military coup or unexpected change in government as communications systems and power infrastructure can be disabled, and healthcare workers are often being unable to make it to their workplaces (due to unrest in the streets, the closure of transport networks, or blockading activities by various factions). for example, in the 2021 sudanese coup, workers in khartoum and other major cities were unable to get to the healthcare facilities owing to creation of roadblocks by a group opposing the coup. service delivery can often suffer further interruptions as the existing leadership is removed and a new leadership takes time to emerge. this can be exacerbated by similar developments in adjacent social safety nets, education systems, and public services. in line with sudan’s history of an interrupted healthcare system functionality in times of political stress, most healthcare services (with the exception of emergency services and critical care) were suspended in the october 2021 military coup. thirdly, service delivery issues are further intensified by the pronounced urban rural divide in sudan. initially stresses are greater in cities which bore the brunt of the damage in the wake of the coup, but as financial stresses intensify, the rural areas will see an increased impact owing to the growing scarcity of medical resources combined with doi 10.18502/sjms.v16i4.9959 page 569 sudan journal of medical sciences alhadi k. osman et al. existing pressures stemming from the deteriorating socioeconomic determinants of health in rural areas. in the case of the 2021 coup, the damage to healthcare service delivery is very acute in khartoum and other big cities perhaps due to the higher rate of resistance in these educated, urban areas. however, over time, as financial stresses intensify, the rural areas will see an increased impact owing to the growing scarcity of medical resources combined with existing pressures stemming from the deteriorating socioeconomic determinants of health in rural areas. finally, there is a high possibility that less attention will be given to illnesses that have a history of being overlooked – such as services linked to mental health, reproductive health, and other neglected tropical diseases. this will undoubtedly widen existing health disparities across the country. while the coup is an acute event, these consequences will likely prevail for the foreseeable future. that being said, if properly planned and efficiently implemented, a military coup does not necessarily negatively impact the healthcare system. for example, in guinea’s most recent military takeover, healthcare services were not interrupted by the coup [4], and the covid vaccine rollout remained intact [5]. 5. diminishing human resources for health on one side, medical doctors are being targeted following coups; well-educated, relatively affluent, white-collar individuals, health professionals can often play a significant role in local and national politics. in myanmar, for example, reports suggested that doctors are being dismissed from their posts, arrested, or going into hiding in fear for their lives following the coup of 2021 [6]. in sudan, the participation of health cadres in political disobedience, and the treatment of injured protesters is seen provocative to some army soldiers; therefore, doctors and other healthcare professionals become target to the subdue. following the coup, medical doctors have been working under stressful conditions, especially as they continue to be first responders to events with mass casualties, extensive traumatic injuries, and serious concerns for patient confidentiality. this is difficult to handle considering their under-resourced and limited capacities. however, medical doctors and other healthcare staff are individuals living within a larger society, they interact with the social and political changes in that community. the increasing restriction of civil freedoms and violation of human rights following the coup may well discourage doctors and other specialized professionals from staying in sudan – it may further discourage sudanese professionals in the diaspora from returning. as a doi 10.18502/sjms.v16i4.9959 page 570 sudan journal of medical sciences alhadi k. osman et al. result, catastrophic shortage in the health workforce may remain as a challenge in the coming years, given the compiling struggles to meet basic healthcare demands. another critical dimension of the human resources in health is the disruption of academic and professional health training, which will undoubtedly have a knock-on effect on the health workforce and capacity over at least the coming year. 6. medical products, vaccines, and other supply chain disruptions medicines and related technologies are central to any functioning healthcare system. in situations of increased political fragility, access to pharmaceutical products can proxy healthcare access. the vast uncertainty due to the military coup will typically impact all four critical domains of the medical supply chain – availability, accessibility, affordability, and acceptability. in sudan, there is limited domestic resources for medical products manufacturing and supply chain; despite the country’s sizable domestic generic pharmaceutical industry, <15% of licensed medicines are manufactured locally, meaning the healthcare system is heavily reliant on imports [7]. in short terms, there will be less pressure, as the who delivered 283 tons of medicines and health supplies to khartoum just a day before the coup [8]; however, the continuity of drug procurement could be jeopardized if the current state is prolonged. the historic economic sanctions, currency devaluation, and the state of hyperinflation has limited the purchasing power of the government and balanced finite hard currency reserves. the heavy reliance on imports makes the healthcare system vulnerable to supply chain disruptions and it needs access to large volumes of hard currency (e.g., usds and euros) to procure pharmaceutical commodities internationally. the coup may affect the internal production and external import of medical commodities. further, the shipment of medications through land and sea has been halted. for example, the shutdown of port sudan–khartoum roads by the residents in eastern sudan has directly hindered the distribution of imported medicines. 7. future considerations it is crucial to consider the impacts of political instability on emerging healthcare systems which come at the cost of increased morbidity and mortality rates. there is a need for more understanding of the political determinants of health in sudan. further critical exploration must be done on the impact of political instability in sudan, particularly doi 10.18502/sjms.v16i4.9959 page 571 sudan journal of medical sciences alhadi k. osman et al. figure 1: a theory of change in the potential impact of the military coup in october 2021 on the sudanese healthcare system. in the healthcare system. also, there might be a need for innovative financing and resource mobility systems that can resist the impact of political and economic shocks to help healthcare leadership, finance, and operating systems be resilient to political instability. in conclusion, this article highlighted several potential challenges that the sudanese coup might inflict on the healthcare system in sudan, these challenges include leadership vacuum, interrupted health funding, suspended service delivery, diminished human resources for health, and disrupted medical supply chain. notes abdel fattah al-burhan, the commander of the sudanese army and the head of the transitional sovereign council, announced a halt in the transition phase to democracy stating the urgent need for “constitutional correction.” this entailed the dismissal of the leading governing bodies, the prime minister, four ministers, leading politicians; some activists were also reported to have been taken into custody at undisclosed locations. a state of emergency was declared, and the transitional sovereign council was immediately suspended. detainees, including the deposed prime minister abdalla hamdok, were not seen or heard for just over one month. according to the central committee of sudan doctors (ccsd), at least 40 people were killed and more than 400 injured during this period as a result of live ammunition, violent encounters, and tear gas bombs against civil protestors. simultaneously, the country experienced a militaryordered nationwide blackout, halting communications, networks, and internet across doi 10.18502/sjms.v16i4.9959 page 572 sudan journal of medical sciences alhadi k. osman et al. the country. as a result, many in the international health community have warned that the fatality and morbidity rates may have been under-reported. over the past decade, the healthcare system in sudan has been challenged many times, including: the country’s separation from south sudan and the immense loss of healthcare funding that followed; the many political movements against omar albashir’s presidency and their associated political instability – including the successful revolution in 2019; and the twin burden of the covid-19 pandemic in conjunction with continuous mass protests, pushing the healthcare system to the verge of collapse. the country continues to be burdened with chronic political unrest. references [1] mcdonagh, k. j., bobrowski, p., hoss, m. a. k., et al. (2014). the leadership gap: ensuring effective healthcare leadership requires inclusion of women at the top. open journal of leadership, vol. 03, no. 02, pp. 20–29. [2] reliefweb. (2021 august 5). africa announces the rollout of 400m vaccine doses to the african union member states and the caribbean. reliefweb. retrieved from https://reliefweb.int/report/world/africa-announces-rollout-400mvaccine-doses-african-union-member-states-and-caribbean [3] rocha, i. c., cedeño, t. d., pelayo, m. g., et al. (2021). myanmar’s coup d’état and its impact on covid-19 response: a collapsing healthcare system in a state of turmoil. bmj military health. retrieved from https://militaryhealth.bmj.com/content/ early/2021/05/21/bmjmilitary-2021-001871 [4] adepoju, p. (2021 september 7). will guinea’s coup interrupt the country’s health responses? devex. retrieved from https://www.devex.com/news/will-guineas-coup-interrupt-the-country-s-health-responses-101562 [5] diallo, b. (2021 november 10). guinea to vaccinate children against covid-19 in capital. world news | us news. retrieved from https://www.usnews.com/news/ world/articles/2021-11-10/guinea-to-vaccinate-children-against-covid-19-in-capital [6] shepherd, a. (2021). myanmar medics resist military coup. bmj, vol. 372, no. march, p. n368. [7] diligencia. (2020 december 1). pharmaceuticals in frontier markets: part 3 sudan. diligencia. retrieved from https://www.diligenciagroup.com/insightsresources/pharmaceuticals-in-frontier-markets-part-3-sudan/ [8] devi, s. (2021). sudan coup prompts fresh health and humanitarian fears. lancet, vol. 398, no. 10313, p. 1790. doi 10.18502/sjms.v16i4.9959 page 573 https://reliefweb.int/report/world/africa-announces-rollout-400m-vaccine-doses-african-union-member-states-and-caribbean https://reliefweb.int/report/world/africa-announces-rollout-400m-vaccine-doses-african-union-member-states-and-caribbean https://militaryhealth.bmj.com/content/early/2021/05/21/bmjmilitary-2021-001871 https://militaryhealth.bmj.com/content/early/2021/05/21/bmjmilitary-2021-001871 https://www.devex.com/news/will-guinea-s-coup-interrupt-the-country-s-health-responses-101562 https://www.devex.com/news/will-guinea-s-coup-interrupt-the-country-s-health-responses-101562 https://www.usnews.com/news/world/articles/2021-11-10/guinea-to-vaccinate-children-against-covid-19-in-capital https://www.usnews.com/news/world/articles/2021-11-10/guinea-to-vaccinate-children-against-covid-19-in-capital introduction a leadership vacuum interrupted funding and donor insecurity suspended service delivery diminishing human resources for health medical products, vaccines, and other supply chain disruptions future considerations notes references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9285 production and hosting by knowledge e research article mapping the reproductive health communication landscape: a state-of-the-art review amanuel gebru woldearegay addis ababa university, school of journalism and communication, addis ababa, ethiopia orcid: amanuel gebru woldearegay: https://orcid.org/0000-0003-4743-7317 abstract background: reproductive health communication encompasses family planning, maternal, neonatal and child health, and sexual and reproductive health communications for adolescents and youth as fundamental elements for intervention. the objective of this study was to summarize, examine, and identify gaps in the theoretical, methodological, empirical, and measurement literature on reproductive health communication as it relates to ethiopia. methods: a systematic search was conducted using electronic databases such as the medical literature analysis and retrieval system (medline), cumulative index to nursing and allied health literature (cinahl), psychological information (psychinfo), and google scholar to locate theoretic, psychometric, and empirical literature on reproductive health communication. results: local literature identified by the databases were mainly based on crosssectional designs, had small sample size and lacked essential psychometric protocols. results showed that most studies replicatively focused on spousal communication centering reproductive choices and decisions. a common strategy was to use student populations as data sources limiting the generalizability of findings. conclusion: the need for more diverse designs and areas of investigation using better instrumentation is indicated. keywords: communication, reproductive, family planning, child, spouse, health 1. introduction globally, reproductive health communication has taken a center stage in a broad array of topics that concern individual, family, and community well-being, subsuming important areas such as health informatics, client–provider interchanges, cross-cultural medical encounters in reproductive realms, sexuality, interagency cooperative communications how to cite this article: amanuel gebru woldearegay (2021) “mapping the reproductive health communication landscape: a state-of-the-art review,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 146–158. doi 10.18502/sjms.v16i2.9285 page 146 corresponding author: amanuel gebru woldearegay; addis ababa university, school of journalism and communication, addis ababa, ethiopia email: amanuel.gebru@aau.edu.et received 16 april 2021 accepted 25 may 2021 published 30 june 2021 production and hosting by knowledge e amanuel gebru woldearegay. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://orcid.org/0000-0003-4743-7317 mailto:amanuel.gebru@aau.edu.et https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences amanuel gebru woldearegay among reproductive health institutions, program support services, reproductive healthcare marketing, reproductive health promotion services, and mediated national policy and practice discourses on key reproductive topics [1–3]. in addition, reproductive health is taken as encompassing seven domains that include physical health, psychological well-being, physical functioning, sexual health, vigor and vitality, cognitive functioning, and pain and discomfort. further categorization includes adolescent health; child health; maternal, fetal, and perinatal health; population and health; and women’s sexual and reproductive health [4, 5]. while the definitional core typically includes gynecological, obstetric, contraceptive well-being and functioning, more standardized definitions address more domains. the research challenge nevertheless is how reproductive health communication has addressed these fundamental issues requiring self-management as well as more institutionalized care. the use of mass communication technologies has been the core of reproductive health communication, especially those called legacy media such as broadcast modalities including radio and tv as well as print-based media interventions. a meta-analytic study of the period between 2005 and 2015 covering 31 countries of saharan african found that exposure to mass media family planning communication campaigns indeed had a modest effect [6]. traditional media/legacy media, and more recently digital affordances, have been a significant asset in reproductive communication given their efficiency as mass communicators and their ability to affect behavior and induce change in particular reference to reproductive health and family planning programs at the national level [7, 8]. media can set the national agenda highlighting certain topics such as reproductive health as national priorities. what this means is that they induce national conversation on the subject and help to involve important stakeholders to grapple with the issues identified as particularly salient. the impact is on creating more behavior change communication at the interpersonal, familial, group, and intergroup levels [9]. this change can be further aided via spiritual communication, workplace, school, and neighborhood conversations demonstrating the triple effect of mass media communications on reproductive health. media can further frame issues in ways they find appropriate ensuring messages are understated in certain preferred ways, dispelling myth through appeal to authority of experts, and to take messages seriously with regard to, for instance, health threats from unsafe sexual practices [10]. doi 10.18502/sjms.v16i2.9285 page 147 sudan journal of medical sciences amanuel gebru woldearegay there have been several projects in africa and elsewhere in the developing world involving the use of mhealth for reproductive health promotion [11]. a global survey showed that while mhealth for reproductive communication is widespread, the developing world has yet to catch-up. of the 17 projects surveyed involving mhealth for srh, two were from ethiopia involving marie stopes and pathfinder ethiopia on contraceptives, family planning, and hiv aids issues [12]. in several other studies, cellphones have been considered as ideal for addressing youth in srh promotion because they are closer to technology than other groups in addition to being cost-effective and efficient [13]. the technology in use helps address security and confidentiality concerns in srh given the cultural and interpersonal sensitivities involved in face-to-face interchanges with providers. however, the affordances do not provide absolute protection of anonymity in the face of the culture of mobile phone sharing in parts of the developing world and so challenges remain in the adoption of the technology for srh promotion and sensitive topics such as hiv aids and sexual stigmas. with deeper cellphone penetration as a result of affordability and telecom infrastructural expansions as well as software developments aiding more privacy control, mhealth has a huge promise as a technology of huge import in lowand middle-income countries including ethiopia. their relevance in terms of empowering women and girls in particular is set to increase demonstrating the emancipative power of technology in terms of a more equitable modality of gender relations [14]. a survey of 44 pertinent studies showed that the behavior change communication (bcc) was undertaken with a focus on african countries and the topics of aids and family planning. the literature indicates that a broader evidence base of current interventions is in demand to scale-up interventions with modifications [15]. another large-scale study found that women were limited in their cellphone access freedoms due to partner inspection, or were of limited competence receptively and expressively, and those with aids and reproductive issues were worried about the absence of privacy and anonymity protection which their health conditions and information needs place them at risk of identifiability [16]. a review of studies showed communication campaigns employed included systematic reviews, experimental and randomized, longitudinal, time series, multi-method, test–retest, cross-sectional, content analysis, and other designs [17]. doi 10.18502/sjms.v16i2.9285 page 148 sudan journal of medical sciences amanuel gebru woldearegay 2. materials and methods 2.1. methods a systematic search was conducted using electronic databases such as the medical literature analysis and retrieval system (medline), cumulative index to nursing and allied health literature (cinahl), psychological information (psychinfo), and google scholar to locate theoretic, psychometric, and empirical literature on reproductive health communication. 3. results a significant focus in recent scholarship has been on measurement issues and theorizing in reproductive health communication. there is also a limited but growing field studies literature on the subject. 3.1. measurement of reproductive health communication measurement is vital to gauge the quality of communication and information services in medical settings and to determine the impact of any overhaul and attendant communication design changes as part of a major strategy to improve patient experience. measures are also important to benchmark in order to compare the future measures with. patient trust, hospital and doctor reputation, client’s word of mouth can be elevated using strategic communication that is systematically planned and evaluated. the measures that tap the patient perspective can be modified or translated as may be necessary to suit local contexts but it is important that the necessary validation is done expertly before these foreign-origin inventories and scales are deployed [18, 19] in areas such as family planning [20, 22]. instrument development has covered in more specific terms: decision-making [23], sexual coercion in intimate relationships scale [24], attitudes toward gender norms (gem scale) [25], reproductive autonomy scale [26], sexual relationship power scale [27], sexual assertiveness scale [28], revised conflict tactics scale [29], the quality of marriage index (qmi) [30]. doi 10.18502/sjms.v16i2.9285 page 149 sudan journal of medical sciences amanuel gebru woldearegay 3.2. theorizing reproductive health communication in healthcare settings, communication may be defined as a verbal and nonverbal transaction that is a purpose-driven, targeted process with intended behavioral modification outcomes expressed in terms of the adoption of healthy behaviors and lifestyles. in theoretical terms, communication can be complex due to the fluidity of its constituent elements as well as the dynamic character of interchanges, yet it can be planned and measured. the human agency in morbidity and mortality is well-documented and behavior which can be modified using strategies of communication is center stage as the subject of interventions using principles and theories that delineate human health behavior. thus, theory-based communication interventions are believed to make a significant difference in wellness and illness. the use of appropriate theory in health communication planning and intervention helps several functions that include description, explanation, and prediction as well as diagnosis and measurement of potential outcomes for instance in the matter of reproductive and sexual health. a growing body of evidence indicates that theoretically informed health interventions including those aimed at reproductive health promotion are highly likely to meet goals they set out to achieve [31]. several theories underpin reproductive health promotion and the pathways to outcomes. a common observation is that interventions are not theory-driven [32], which does hamper conceptually driven goals, inputs, processes, and measurement of evidence. for instance, a study found that safe sex messages in reproductive health leaflets did not target cognitive and behavioral issues and were in consequence of limited strategic utility in regard to condom use promotion [33]. optimal outcomes require a careful consideration of theoretical insights and conceptually-driven health messages [34]. these may be typologized broadly as intrapersonal (transtheoretical model-stages of change, theory of planned behavior, health belief model, protection motivation theory), interpersonal (social cognition), community level (ecological models), and other (e.g., diffusion of innovations theory) [35]. reproductive health promotion has employed a diverse set of these health communication theories but the most commonly used are limited. several reviews of these have addressed the major conceptual underpinnings [36, 38]. doi 10.18502/sjms.v16i2.9285 page 150 sudan journal of medical sciences amanuel gebru woldearegay 3.3. field studies the international empirical literature on reproductive health communication is varied and vast. however, the use of theory-to-guide communication interventions seems to be rather limited. there is also the tendency to depend entirely or mostly on questionnaires with the worst part being that the questionnaires used were unstandardized, unpiloted whose psychometric properties were highly questionable. local studies also tended to be replicative and the focus of the majority of the studies was adolescent child–parent communication with regard to reproductive and sexual issues. findings typically mentioned the cultural factor as an impediment to more fruitful sexual communication at the household level but comparison across studies would be complicated because of the differences in instrumentation. further reports of psychometric properties of instruments in local studies are rare. thus, we do not know how valid or reliable the measures in use are which leads to questioning the utility of findings reported. however, there were also large-scale studies that showed media had a significant impact on reproductive services use in both urban and rural settings [39]. however, the studies failed to disaggregate impact by media type, that is, broadcast versus print media, limiting the study’s utility. another study of spousal communication centering on reproductive decisions was reported as involving a significant percentage (60 %) of change effects in shared decision-making in ethiopia’s amhara region [40]. the significance of the broadcast media is demonstrated in an ethiopian study based in addis ababa which reports that the typical woman receives her family planning information from radio and television [41]. another ethiopian study employing a quasi-experimental study design reported that men in the treatment group had significantly higher levels of readiness for family communication on reproductive issues than the control group [42]. however, issues of lack of statistical sophistication and the necessary controls are disturbing. for instance, sample size and effect size considerations are not worked out with regard to issues of precision. considering that they were commissioned, campaign evaluation studies seemed to fare better. for instance, those of population media center are planned, large sample based, and multi-method studies. informed by entertainment education theories, a population media center serial radio drama broadcast through ethiopia yeken kignit (“looking over one’s daily life”) over the period june 2, 2002 and november 27, 2004 was rated as successful in terms of producing behavioral modification in reproductive and sexual health. program impact was measured taking a baseline survey in may 2002 doi 10.18502/sjms.v16i2.9285 page 151 sudan journal of medical sciences amanuel gebru woldearegay and a post-broadcast survey in december 2004. the following effects were reported. while mass media-delivered communication campaigns in developing countries have reported mixed results [43, 44], the impact the ethiopian study seems to have shown a significant effect of mass communication reproductive health promotion [45, 46]. while the results are impressive, there is nevertheless a need of a benchmarking to compare the results across countries which is complicated by a number of national variables including cultural issues. however, best practices for mass media-based reproductive health communication can be identified [47]. studies have included reproductive health communication strategies [48], adolescent sexuality [49], sexual communication bottlenecks [50], adolescent–parent communication [51 ], parent–adolescent discussion on rh issues [52], assessment of the awareness and attitude of both study groups on major family life education (fle) components [53], and assessment of the level and factors influencing communication between school students and parents on sexual and rh issues [54, 59]. 4. conclusion interventions in health programs at all levels remain incomplete unless they address the communication component which is extremely vital in healthcare in particular. it is therefore not only important to measure a patient’s communication experience but also to do so using valid and reliable instrumentation. communication is also an important correlate of diverse hospital outcomes including litigation issues arising from inadequate communication in diagnosis and dispensing. based on the principle that the biomedical orientation is inadequate, the study has reviewed important dimensions of patient experience that pertain to available theories of heath communication, identify psychometric properties of measures of reproductive communication, and vet empirical studies of heath communication interventions at the dyadic and mass communication levels. ethiopian studies on the subject were reviewed extensively. further research is called for that addresses the use of media in reproductive health communication context interpersonally, medially and in a broad variety of other formats. ethical considerations no animal or human studies were carried out by the author. doi 10.18502/sjms.v16i2.9285 page 152 sudan journal of medical sciences amanuel gebru woldearegay conflict of interest the author reports no conflict of interest. funding the author received no financial support for the research, authorship, and/or publication of this article. references [1] pillai, v. k. and gupta, r. 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(2018). parent–adolescent communication about sexual and reproductive health and associated factors among preparatory school students in haiyk town, north east ethiopia. research in medical & engineering sciences, vol. 5, no. 2, pp. 417–423. doi 10.18502/sjms.v16i2.9285 page 158 introduction materials and methods methods results measurement of reproductive health communication theorizing reproductive health communication field studies conclusion ethical considerations conflict of interest funding references sudan journal of medical sciences volume 16, issue no. 1, doi 10.18502/sjms.v16i1.8942 production and hosting by knowledge e research article the effectiveness of sovodak in the treatment of patients with chronic hepatitis c farshad talebian1, baran parhizkar2, behzad mohsenpour3, pezhman sharifi4, amirreza hajati5, and farshad sheikhesmaeili6 1assistant in internal medicine, student research committee, kurdistan university of medical sciences, sanandaj, iran. 2assistant professor, liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. 3assistant professor, liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. 4msc of microbiology sciences, liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. 5assistant in internal medicine, student research committee, kurdistan university of medical sciences, sanandaj, iran. 6assistant professor, liver and digestive research center, research institute for health development, kurdistan university of medical sciences, sanandaj, iran. orcid: farshad talebian: https://orcid.org/0000-0002-3380-8909 baran parhizkar: https://orcid.org/0000-0003-3043-3504 behzad mohsenpour: https://orcid.org/0000-0001-8675-4492 pezhman sharifi: https://orcid.org/0000-0001-7953-9487 amirreza hajati: https://orcid.org/0000-0002-5911-6820 farshad sheikhesmaeili: https://orcid.org/0000-0003-2067-5032 abstract background: recently, interferon-free treatment has been considered for the treatment of chronic hepatitis c due to their high therapeutic success and lack of serious side effects. the combination of sofosbuvir and daclatasvir is effective in the treatment of the disease because of its pan-genotype. in the present study, the effectiveness of sovodak, which is a combination of the aforementioned two drugs in one tablet, in the treatment of patients with chronic hepatitis c and cirrhosis was investigated. methods: patients with chronic hepatitis c whose diagnosis was confirmed by hcv rna–pcr test were included in the study. these patients received one sovodak tablet daily (for 12 weeks for non-cirrhotic patients and 24 weeks for cirrhotic patients). sustained virologic response (svr) was assessed by pcr test 12 weeks after the end of the treatment and one year later. also, serum levels of liver enzymes, platelet count, and liver stiffness (using elastography method) were measured and their levels were compared before and after treatment in patients. results: findings related to the pcr test in patients showed that the level of svr was 100% in patients 12 weeks after treatment (svr-12). in three cirrhotic patients who received only 12 weeks of drug treatment, the disease recurred a year later. according to the results, alt and ast serum levels were significantly decreased (p < 0.001), and platelet count level was increased (p < 0.001) one year after the end of how to cite this article: farshad talebian, baran parhizkar, behzad mohsenpour, pezhman sharifi, amirreza hajati, and farshad sheikhesmaeili (2021) “the effectiveness of sovodak in the treatment of patients with chronic hepatitis c,” sudan journal of medical sciences, vol. 16, issue no. 1, pages 111–121. doi 10.18502/sjms.v16i1.8942 page 111 corresponding author: dr. farshad sheikhesmaeili; tohid hospital, sanandaj, iran. email: dr_s_smaili@yahoo.com received 28 january 2021 accepted 5 march 2021 published 31 march 2021 production and hosting by knowledge e farshad talebian et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:dr_s_smaili@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences farshad talebian et al the treatment period. also, the liver stiffness index measured using fibroscan was significantly decreased in patients 12 weeks after the end of the treatment (p < 0.001). conclusion: the results of this study, in line with other studies, showed the effective role of sovodak in completely eliminating the hcv virus in patients with chronic hepatitis c. cirrhotic patients need to receive treatment for at least six months. keywords: sovodak, hepatitis c, sustained virologic response, effectiveness, liver cirrhosis 1. introduction chronic hepatitis is one of the most important health challenges in the world due to the difficulty of its treatment. chronic hepatitis c can lead to liver cirrhosis, hepatocellular carcinoma, liver failure, and finally, death [1]. it is estimated that about 60–113 million people worldwide are affected by this disease and the prevalence is increasing [2]. its prevalence in iran is reported to be about 0.3–0.5% [3] and is expected to increase further if the current conditions persist [4]. hepatitis c virus (hcv) is a single-stranded rna and enveloped virus belonging to the flaviviridae family and has six genotypes and a large number of subtypes [5– 8]. treatment for chronic hepatitis c, before the development of direct-acting antiviral (daa) drugs, mainly involved the administration of pegylated interferon (ifn) alfa with ribavirin. treatment is successful when hcv rna is undetected at the end of treatment [9]. the side effects of interferon are sometimes so severe that the drug cannot be used completely. particularly in patients with cirrhosis, thrombocytopenia, and anemia, it is often impossible to use this substance. sometimes interferon aggravates the liver disease and even death. the treatment period with interferon can last up to one and a half years and includes weekly injections of the drug along with five to six tablets of ribavirin daily. with all of the above, even if the drug is fully used, the response to treatment is about 60% or up to 70%, and many patients, such as those with cirrhosis or hiv, respond less to the treatment [10]. with the introduction of daa drugs, chronic hepatitis c can now be treated without interferon and there is a lot of hope for effective treatment of this disease to the point that some studies have even suggested the possibility of eradicating the disease as the eradication of the first chronic viral disease in the world [11]. the approach of most doi 10.18502/sjms.v16i1.8942 page 112 sudan journal of medical sciences farshad talebian et al therapies based on daas is sofosbuvir, which alone is not effective and should be used in combination with other medicines such as daclatasvir or ledipasvir. the most familiar drug is harvoni, a combination of sofosbuvir and ledipasvir in one tablet. this drug is effective only on genotypes 1 and 4, which includes a maximum of 50–60% of iranian patients [12]. the combination of daclatasvir and sofosbuvir is effective on all genotypes (pan-genotype) and can be used even without checking the genotype. the combination of these two drugs in one tablet is only available in iran, which is known as sovodak [13]. the present study investigated the effectiveness of sovodak in the treatment of patients with chronic hepatitis c and cirrhosis. 2. materials and methods 2.1. study design in this non-experimental study (before and after), all patients with chronic hepatitis c referred to the outpatient clinic of the liver and gastrointestinal unit of tohid hospital, sanandaj, iran in 2018, were selected by census method. 2.2. patients the inclusion criteria of the study comprised of patients aged between 20 and 80 years and a confirmed diagnosis of the disease by hcv rna–pcr test. patients with renal failure (egfr < 30 ml/min), heart rate < 50, co-infection with hbv and hiv, and patients taking amiodarone were excluded from the study. 2.3. treatment and intervention methods one sovodak tablet (sofosbuvir [400 mg] + daclatasvir [60 mg] made in rojan pharma, tehran, iran) was prescribed daily for all patients. non-cirrhotic patients were treated for 12 weeks and patients with liver cirrhosis were treated for 24 weeks. the drugs were given to patients monthly and were evaluated for side effects and proper use of the drug. doi 10.18502/sjms.v16i1.8942 page 113 sudan journal of medical sciences farshad talebian et al 2.4. paraclinical investigation serum levels of liver enzymes including alanine aminotransferase (alt) and aspartate aminotransferase (ast) were measured by kinetic method (pars azmoon co., tehran, iran). platelet count was also measured at the beginning and 12 weeks after the end of the treatment in all patients. all experiments were conducted in a laboratory. the rate of hepatic fibrosis in the patients was assessed by the transient elastography method using a fibroscan (echosens, paris, france) at the beginning and one year after the end of the treatment period. fibrosis results were reported in kilopascal (kpa). diagnosis of cirrhosis in patients was based on the results of fibroscan (f > 14 kpa) and the incidence of clinical manifestations including a set of clinical symptoms, physical findings, laboratory, and radiological findings such as ascites, cytopenia, splenomegaly, esophageal varices. to evaluate the response to treatment, 12 weeks after the end of treatment and to evaluate the recurrence, one year after the end of treatment, hcv rna–pcr test was performed with a diagnostic accuracy of 25 viral units per ml (copies/ml) of all patients. 2.5. statistical analysis statistical analysis was performed using spss software version 20. the kolmogorov– smirnov test was used to analyze the hypotheses for the normality of quantitative data. qualitative variables were calculated as frequency (percentage), quantitative variables with normal mean distribution (se), and qualitative variables with abnormal distribution with mean (iqr). due to the abnormality of data distribution, the wilcoxon signed-rank test was used to compare changes before and after the treatment of variables. p-value < 0.05 was considered as a significant level. 3. results a total of 50 patients were enrolled in the study, and excluding 3, all 47 of them completed the treatment period. the demographic and clinical characteristics of the studied patients are summarized in table 1. the mean age of patients was 49.30 ± (10.71) years (with a minimum of 25 years and a maximum of 71 years). overall, 42 patients (84%) were men and 8 (16%) were women. most patients (32, 64%) were aged between 40 and 60 years, 10 (20%) were under 40 years old, and only 8 people were doi 10.18502/sjms.v16i1.8942 page 114 sudan journal of medical sciences farshad talebian et al over 60 years old. pretreatment viral load in 25 patients (71.4%) was <600,000 iu/ml and in 10 patients (28.6%) ≥600,000 iu/ml. seven patients (14%) were genotype 1, seven (14%) were genotype 3, and the genotype of the remaining thirty-six patients (72%) was not determined. based on the results of fibroscan, 13 patients (26%) had cirrhosis of the liver. findings related to the pcr test in patients revealed that the level of sustained virologic response (svr) 12 weeks after the end of treatment in patients was 100%. moreover, at one-year follow-up, recurrence was not observed in 47 patients (94%). in three cirrhotic patients who were treated for only three months due to non-referral to complete the second trimester of the treatment, although the response to treatment was complete, the disease recurred after one year. the patients were re-treated for 24 weeks, the response to treatment was complete and a year later, no recurrence of the disease was observed in them. table 2 shows the level of liver enzymes and the platelet count before and 12 weeks after the end of the treatment period in the studied patients. based on the results, serum alt and ast levels in patients after treatment were decreased (p < 0.001), and platelet count increased (p < 0.001) significantly. also, the liver stiffness index measured using fibroscan was decreased (p < 0.001) significantly in patients after the end of the treatment period. one year after the end of treatment, patients had a median of 18% reduction in liver stiffness index measured by fibroscan, from 6.95 (iqr; 5.15–15.00) kpa to 5.70 (iqr; 3.57–14.40) kpa (p < 0.001) compared to the data before sovodak administration. table 1: baseline characteristics of the study patients (n = 50). variables age (yr), mean ± (sd) 49.30 ± (10.71) sex, n (%) male 42 (84.0%) female 8(16.0%) viral load, n (%) <600,000 iu/ml 25 (71.4%) ≥600,000 iu/ml 10 (28.6%) genotypes, n (%) 1 7 (50.0%) 2 0 (0%) 3 7 (50.0%) degree of fibrosis; n (%) normal 25 (50.0%) f1 3 (6.0%) f2 3 (6.0%) f3 6 (12.0%) f4 13 (26.0%) doi 10.18502/sjms.v16i1.8942 page 115 sudan journal of medical sciences farshad talebian et al table 2: comparison of alt, ast, platelet count, and liver stiffness index before and after treatment in patients with chronic hepatitis c. variables before treatment 12 weeks after completing therapy p-value med (iqr) med (iqr) alt, u/l 42.00 (27.50–72.50) 27.50 (24.00–32.25) <0.001 ast, u/l 50.00 (30.75–70.50) 25.00 (22.00–28.00) <0.001 platelet count, μl 179000.00 (102500.00–215250.00) 200500.00 (109250.00–225250.00) <0.001 alt: alanine aminotransferase; ast: aspartate aminotransferase 4. discussion the main findings of this study indicate that the administration of sovodak for 12 and 24 weeks in non-cirrhotic and cirrhotic patients with chronic hepatitis c, respectively, is completely effective in treatment, and that if the treatment is given to cirrhotic patients for only 12 weeks, there is a possibility of recurrence of the disease despite the success of svr-12. in recent years, studies have been conducted on the effectiveness of sovodak or its family in the treatment of chronic hepatitis c. in the study of mehdipour et al. (2019), as in our study, the level of svr12 in patients with hcv infection and genotype 1 treated with sovodak was reported to be 100%. although in this study, the duration of treatment for cirrhotic patients was the same as for non-cirrhotic patients, that is, 12 weeks, ribavirin was included in their treatment diet [14]. in another study on the effectiveness of sovodak on the treatment of 1,361 patients with hepatitis c and different genotypes, the level of svr-12 was reported to be 98%. in this study, the duration of treatment in cirrhotic patients was 24 weeks and if ribavirin was administered with sovodak, it was 12 weeks. there was no significant difference between the svr12 levels in cirrhotic patients treated with sovodak for 12 weeks with ribavirin and 24 weeks without ribavirin [15]. in other studies, the level of svr-12 in the treatment of patients with hepatitis c with sofosbuvir and daclatasvir has been reported to be 84.9– 100% [16–21]. differences in svr12 between several studies may be due to differences in inclusion criteria (patients with cirrhosis or not), specific genotype, previous treatment history, treatment failure, recurrence, multidrug usage, and use of other antiviral drugs such as ribavirin with sofosbuvir/daclatasvir. nelson et al. reported that in patients with hcv genotype 3, 12 weeks of treatment with sofosbuvir and daclatasvir resulted in svr-12 levels of up to 90% in patients without cirrhosis and 86% in patients with cirrhosis [22]. in another study, pol et al. reported 96% and 88% of svr12 in patients without cirrhosis and cirrhosis with hcv doi 10.18502/sjms.v16i1.8942 page 116 sudan journal of medical sciences farshad talebian et al and genotype 1 treated with sofosbuvir and daclatasvir, respectively [16]. merat et al. (2017) in a study evaluated the effectiveness of treatment with sovodak and ribavirin for 12 weeks in cirrhotic patients with hepatitis c and genotypes 1 and 3, in which the svr12 level was 98%. in two patients in which the recurrence occurred, one patient had genotype 1 and other one had genotype 3 [23]. in the study of leroy et al. (2016), svr12 in cirrhotic patients with hcv genotype 3 infection with 12 and 16 weeks of treatment with sofosbuvir/daclatasvir with ribavirin were 83% and 89%, respectively [24]. in the present research, it was shown that if cirrhotic patients were treated for 24 weeks, their svr12 was 100% and there was no recurrence of the disease at the one-year followup. however, in three patients who continued treatment for only 12 weeks, although they achieved svr12, recurrence occurred a year later, with re-treatment for 24 weeks, complete response to treatment, and no recurrence for up to a year. in the present study, unlike the other aforementioned studies, the treatment period in cirrhotic patients was 24 weeks and ribavirin was not used. the results of the present study showed that the rate of liver stiffness, measured by fibroscan, after taking sovodak in these patients decreased significantly. sustained viral response (svr) is associated with cessation of disease progression and reduction of its complications, including reduced incidence of hepatocellular carcinoma [25–27]. in previous studies, liver tissue healing after an svr has been reported [28–31] . the results of a study revealed that treatment of chronic hepatitis c with daa drugs in patients with cirrhosis of the liver or advanced liver fibrosis is associated with cessation of cirrhosis and regression of liver fibrosis in about 50% of patients [32]. other findings of this study showed that taking sovodak in patients with chronic hepatitis c would significantly decrease the liver enzyme levels. this finding was in agreement with the results of other studies that have been conducted in this field [14, 19, 20] which indicates the effect of sovodak on reducing liver enzymes levels to normal, which could be due to the preventive effect of sovodak on further destruction of liver tissue by hcv and possibly liver tissue healing. also in our study, platelet count, in line with the effect of sovodak in removing the virus, showed changes in recovery so that cirrhotic patients had an increase in platelet count to normal range. the main limitations of this study were the small number of sample and the lack of genotype of all patients. doi 10.18502/sjms.v16i1.8942 page 117 sudan journal of medical sciences farshad talebian et al 5. conclusion the results of our study in line with other research, the effective role of sovodak in removing the hcv virus in patients with chronic hepatitis c was 100%. therefore, this drug is recommended due to the pan-genotype of the drug and its cheapness compared to similar cases, without the need to determine the genotype and high cost of testing and also the lack of significant drug side effects, for the treatment of all patients with chronic hepatitis c in both cirrhotic and non-cirrhotic patients regardless of the type of hcv genotype. acknowledgements the authors would like to thank the vice-chancellor for research, kurdistan university of medical sciences, sanandaj, iran, for financial support. ethical considerations the study protocol was approved by the ethics committee of kurdistan university of medical sciences, sanandaj, iran (no. ir.muk.rec.1398.254) and before the study, informed consent was obtained from all participants. competing interests the authors declare that they have no competing interests. availability of data and material all data are available upon reasonable request. funding this research has been funded by kurdistan university of medical sciences (grant number: 1398.254). doi 10.18502/sjms.v16i1.8942 page 118 sudan journal of medical sciences farshad talebian et al references [1] lauer, g. m. and walker, b. d. 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(2020). changes in hepatic fibrosis stages after achieving svr following direct-acting anti-viral treatment: a prospective study. gastrohep, vol. 2, no. 1, pp. 39–48. doi 10.18502/sjms.v16i1.8942 page 121 introduction materials and methods study design patients treatment and intervention methods paraclinical investigation statistical analysis results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9952 production and hosting by knowledge e research article understanding factors contributing to nurses’ intention to care for covid-19 patients using the theory of planned behavior khalid a. aljohani1, mohammad s. aljohani2, maria jocelyn b. natividad2, paul reinald b. gracia2, and ibtehal i. qazanli3 1community health nursing department. college of nursing, taibah university, saudi arabia 2medical-surgical nursing department. college of nursing, taibah university, saudi arabia 3community health nursing, ministry of health, saudi arabia orcid: khalid a. aljohani: https://orcid.org/0000-0003-3242-082x abstract background: globally, the nursing community has lost several colleagues during the coronavirus disease 2019 (covid-19) battle. one of the negative consequences of the disease is the pressure on healthcare services and demands that exceed the system’s capacity to provide sufficient resources. similarly, the experiences of care providers might trigger emotional and physical stress, which could affect the healthcare system’s readiness to manage infectious outbreaks. this study was aimed at investigating nurses’ intention to care for covid-19 patients and determining factors contributing to their intentions to care at the ministry of health facilities in saudi arabia. methods: this descriptive cross-sectional survey design was used to recruit 336 nurses working in al madinah ministry of health hospitals where covid-19 patients received medical and nursing care. the instrument was created following the framework of the theory of planned behavior. results: nurses’ intention to care for covid-19 patients was significantly correlated with their education level, nationality, knowledge about covid-19, and nurses’ exposure during their earlier education for emerging infectious diseases. factors related to social pressure from friends, colleagues, and workplace administration support needed improvement. examining the model fits through multiple regression revealed that the combination of six subscales – “attitude, subjective norms, perceived behavioral control, behavioral beliefs, normative beliefs, and control beliefs” – accounted for a significant (89%) variability of intention to care, r2 = 0.892, adjusted r2 = 0.793, f (6-329) = 201, p ≤ 0.000. conclusion: providing nursing education is the main predictor of higher nurses’ intention to care for covid-19 patients, it is imperative that nursing education courses should continue investing in enhancing nurses’ capabilities in caring for covid-19 patients. keywords: nurses, intention, covid-19, saudi arabia how to cite this article: khalid a. aljohani, mohammad s. aljohani, maria jocelyn b. natividad, paul reinald b. gracia, and ibtehal i. qazanli (2021) “understanding factors contributing to nurses’ intention to care for covid-19 patients using the theory of planned behavior,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 546–557. doi 10.18502/sjms.v16i4.9952 page 546 corresponding author: khalid a. aljohani; email: kajohani@taibahu.edu.sa received 06 september 2021 accepted 02 december 2021 published 31 december 2021 production and hosting by knowledge e khalid a. aljohani et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:kajohani@taibahu.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences khalid a. aljohani et al. 1. introduction what is known? 1. theory of planned behavior is a reliable approach to explain nurses’ intention to provide nursing care. 2. caring for covid-19 is a perceived challenge in terms of continuity and efficiency of nursing care. what is new? 1. continuing nursing education courses may enhance nurses’ intention to care for emerging infectious diseases such as covid-19. 2. social influence from friends, colleagues, and workplace administration support may contribute to nurses’ willingness to care for covid-19 patients. emerging infectious diseases (eid) refers to infectious diseases that emerged during the past 30 years with the probability to increase in the future [1]. in the last two decades, the remarkable examples of eid are the middle east respiratory syndrome coronavirus (mers-cov), severe acute respiratory syndrome coronavirus (sars-cov), and ebola virus disease (evd). these diseases are the outcomes of the interactions of biological, social, ecological, and technological factors [2]. the focus of this paper is coronavirus disease 2019 (covid-19) that was caused by a coronavirus and affects respiratory functions. the disease is highly contagious affecting all age groups with increased severity risk for older people and patients with comorbidities. corresponding with other countries, cases in saudi arabia are increasing steadily [3]. the disease is highly contagious. the international nursing community lost several members during the covid-19 battle. therefore, global initiatives to combat the infection should focus on protective measures to stop spreading the infection [4]. one of the diseases’ negative consequences is the pressure on healthcare services demands that exceed the system’s capacity to provide resources for care. such pressure leads to unprecedented workload, anxiety, and depression on healthcare providers especially nurses [5]. international nursing literature revealed significant stress on nurses as frontline healthcare team members [6, 7]. in detail, nurses who care for patients with eids as part of their duties suffer from several negative psychological consequences including depression, anxiety, and post-traumatic stress response [5, 8]. importantly, some nurses declined eid patients’ care duties and quit their jobs resulting in risky consequences for the entire healthcare system [9]. doi 10.18502/sjms.v16i4.9952 page 547 sudan journal of medical sciences khalid a. aljohani et al. previous studies in saudi arabia were focused on knowledge and stress during the mers-cov epidemic crisis [7]. mers epidemics have an effect on medical students’ discernment and their psychological agony all through the epidemic, which further shows that female students had higher stress while two-thirds of the sample reported mild anxiety [10]. furthermore, studies found that mers’s physiological effects on emergency department (ed) residents have made their colleagues afraid of cross-infection because of their tasks in the unit [11]. it was notable that 4% of the sample considered changing jobs. the major rationale for such a decision was their intention not to expose their families to infection. as indicated by earlier studies, healthcare providers’ experiences during eid outbreaks may trigger their stress and they might decide to leave their jobs, which in turn affects the healthcare system’s readiness to manage infectious outbreaks. searching the literature did not identify saudi studies exploring these issues among nurses during the covid-19 outbreak. this study aims to investigate nurses’ intention to care for covid19 patients and be part of the responding healthcare team in saudi arabia. in specific, the study question is: what factors could predict nurses’ intention to care for covid-19 patients at saudi arabian health facilities? the finding could influence policymakers, education sectors on potential interventions and policies to improve healthcare system readiness on eid outbreaks. 2. methods 2.1. study design a descriptive cross-sectional survey design was utilized to recruit nurses working in al madinah ministry of health (moh) hospitals that were designated to provide medical and nursing care for covid-19 patients. the inclusion criteria were nurses working in medical wards, intensive care units, and eds, while the exclusion criteria were nurses with less than one year of experience and those who were not directly working with patients such as in nursing office staff. the total sample size was 337 calculated using raosoft𝑇𝑀 with inputs as 5% margin of error: 95% confidence level adjusted to population size 2700; and 50-response distribution [12]. however, the target sample was 437 nurses taking into account the drop rate. doi 10.18502/sjms.v16i4.9952 page 548 sudan journal of medical sciences khalid a. aljohani et al. 2.2. the study instrument the study instrument included three parts. first, sociodemographic data such as age, sex, education, marital status, living arrangement, work experience, position, and working units. second, work experience and training related to covid-19 consisting of fouritem questions: do you have experience in caring for patients with covid-19?; have you been trained in the use of personal protective equipment?; have you been trained on eid?; and have you been trained in the care of covid-19? the last part comprised items using the theory of planned behavior (tpb) framework to measure nurses’ intention to care for covid-19 patients. before utilizing the instrument, researchers sought permission from the author who previously used it for the nurse caring for sars patients’ intention to care for sars patients [5, 13]. however, due to differences in context, the researchers modified the instrument with the guidance of the original author’s instructions to develop the constructs [14]. 2.3. validity and reliability the modified bilingual instrument went through two phases of face validity followed by expert consultation. an academic nurse psychologist reviewed the instrument with a recommendation of minimal changes in the wording methods for five questions. initial psychometric assessment of the instrument revealed an acceptable level with a pilot sample of 15 participants. however, tpb instruments recommendation suggested a minimum of 80 subjects to assess the instruments [14, 15]. therefore, the researchers applied further assessment utilizing the entire study sample. the result was confirmed by an overall instrument cronbach alpha of 0.958. the instrument’s subscales cronbach’s alpha were attitude (0.72); subjective norms (0.68); perceived behavioral control (0.89); intention (0.96); behavioral beliefs (0.73); normative beliefs (0.90); and control beliefs (0.91). these scores supported the instrument’s ability to measure nurses’ intention to care for covid-19 patients [16]. the revised instrument consists of the components of tpb that are behavioral beliefs; normative beliefs; control beliefs; attitude; subjective norm; perceived behavioral control; and intention [14]. participants answered the 35-item instrument based on sevenpoint likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). doi 10.18502/sjms.v16i4.9952 page 549 sudan journal of medical sciences khalid a. aljohani et al. 2.4. statistical analysis descriptive statistics were used to identify participants’ and instrument characteristics. t-test and one-way anova tests were used to identify correlations between participants’ characteristics and their overall scores. statistical analysis was performed using spss v.20. 3. results in total, 417 nurses participated in the study with a response rate of 95%. however, 336 were involved in this study after examining violations of the exclusion criteria and incomplete responses. table 1 shows that females represented 82% of the participants and 54% were in their early career stage. twenty-one percent of the sample did provide nursing care to covid-19 patients, ninety-four had training on the use of personal protective equipment (ppe) such as correct steps to wear protective gowns, claves, and masks. similarly, 68% were knowledgeable about the disease. nurses’ intention to care for covid-19 patients was significantly correlated to their education level, nationality, covid-19, and previous eid continuing education. nurses with postgraduate qualifications had a higher intention to care (m = 5.98, sd = 0.1.54) than those with bachelor degrees (m = 4.93, sd = 1.83) and diplomas (m = 4.83, sd = 2.03; f = 3.17; p = 0.043). saudi nurses had higher intention to care for covid-19 patients’ mean score (m = 5.23, sd = 1.98) than expatriate nurses (m = 4.79, sd = 1.79), t = 2.1; p = 0.036. from a continuing education standpoint, participants who had previously received covid-19 education had higher mean intention to care (m = 5.13, sd = 1.72) than those who did not attend covid-19 continuing education sessions (m = 4.72, sd = 2.06) t = 1.95, p ≤ 0.051. similarly, nurses with previous eid education had a higher mean score (m = 5.20, sd = 1.71) than those who did not (m = 4.46, sd = 2.10), t = 3.41; p = 0.001. finally, the nursing position almost reached the significance level. head nurses (m = 5.38, sd = 1.72) had higher intention to care than the in-charge nurses (m = 5.09, sd = 1.70) and staff nurses (m = 4.83, sd = 2.03), f = 2.82, p = 0.060). descriptive results in table 2 indicate that the highest subscales ”dimensions” among the participants were attitudes toward caring for covid-19 patients (m = 5.47, sd = 1.26) and behavioral beliefs (m = 5.24, sd = 1.36). however, subjective norms such as social pressure from friends, colleagues, and workplace administration support did not support participants’ caring for covid-19 patients (m = 3.83, sd = 1.47). nevertheless, the overall mean indicated good support in caring for covid-19 patients (m = 4.75, sd = 1.29). doi 10.18502/sjms.v16i4.9952 page 550 sudan journal of medical sciences khalid a. aljohani et al. table 1: participants and characteristics and intention to care correlations. variable categories n % nurses’ intention m ± sd t/f p-value gender male 61 18 4.67 (2.14) 0.137 0.17 female 275 82 5.03 (1.81) age group (yr) 18–34 183 54 5.04 (1.82) 1.5 0.223 35–44 120 36 5.00 (1.96) ≥45 33 10 4.43 (1.82) marital status married 218 65 4.86 (1.92) 1.44 0.151 not married 118 35 5.17 (1.78) living arrangements alone 61 18 4.85 (1.96) 1.03 0.355 with family 171 60 5.11 (1.90) with friends 104 20 4.80 (1.87) position staff 222 66 4.80 (1.94) 2.82 0.06 in-charge 37 11 5.09 (1.70) head nurse 77 23 5.8 (1.72) education diploma/associate82 24 4.83 (2.03) 3.17 0.043 bachelor 234 70 4.93 (1.83) master 20 6 5.98 (1.54) experience 01-may 87 26 5.01 (1.86) 0.043 0.958 06-oct 99 30 4.93 (1.81) ≥11 150 44 4.96 (1.94) nationality saudi 135 40 5.23 (1.98) 2.1 0.036 expatriates 201 60 4.79 (1.79) caring for covid19 yes 71 21 5.30 (1.80) 1.75 0.083 no 265 79 4.88 (1.89) ppe training yes 316 94 4.99 (1.86) 0.751 0.461 no 20 6 4.63 (2.10) covid-19 education yes 199 60 5.13 (1.72) 1.95 0.051 no 137 40 4.72 (2.06) eid education yes 229 68 5.20 (1.71) 3.41 0.001 no 107 32 4.46 (2.10) table 3 presents the relationship between the theory of planned behavior variables. a positive correlation was evident between “intention” and “attitudes” (0.724) indicating that the better the attitude, the more positive the intentions are. strong positive correlations were also evident between ”intention” and perceived behavioral control (0.808), behavioral beliefs (0.765), normative beliefs (0.700), and control beliefs (0.663). doi 10.18502/sjms.v16i4.9952 page 551 sudan journal of medical sciences khalid a. aljohani et al. table 2: subscales and overall estimations. subscale #items mean sd min–max attitude 5 5.47 1.26 4.43–6.00 subjective norms 5 3.83 1.47 3.38–4.23 perceived behavioral control 5 4.81 1.65 3.88–5.44 intention 5 4.97 1.87 4.84–5.23 behavioral beliefs 5 5.24 1.36 4.75–5.67 normative beliefs 5 4.54 1.74 3.75–4.87 control beliefs 5 4.39 1.79 4.19–4.50 overall 35 4.75 1.29 3.38–6.00 table 3: correlation matrix for the study variables in the theory of planned behavior (n = 336). attitudes subjective norms perceived behavioral control behavioral beliefs normative beliefs control beliefs intention 0.724 0.432 0.808 0.765 0.7 0.663 attitudes 1 0.347 0.614 0.664 0.586 0.49 subjective norms 1 0.419 0.336 0.585 0.48 perceived behavioral control 1 0.654 0.644 0.68 behavioral beliefs 1 0.64 0.468 normative beliefs 1 0.669 control beliefs 1 *significant at p < 0.001. on the other hand, a moderate positive correlation was present between attitude and subjective norms (0.347), normative beliefs (0.586), and control beliefs (0.490), and strong positive correlation to perceived behavioral control (0.614) and behavioral beliefs (0.664). in general, the result reveals that the better the attitude, the better are the other tested subscales. 4. discussion this study aimed to answer the research of what factors could predict nurses’ intention to care for covid-19 patients at saudi arabian health facilities. interestingly, a higher intention to care is evident among saudi nurses. participants showed good intention to provide direct care, assist, support team, accept any task, and take the challenge to provide nursing care for covid-19 patients (m = 4.97). this result was higher than the studies presented in korea (4.31) and taiwan (3.45) among nurses caring for eid [5, 17]. doi 10.18502/sjms.v16i4.9952 page 552 sudan journal of medical sciences khalid a. aljohani et al. education was a critical factor in a higher intention to care among the participants. in detail, the study showed that higher education background was correlated to a better intention to care. moreover, attending covid-19 continuing education had also supported a higher intention to care. the results could guide education entities within the ministry of health (moh) to focus their efforts on providing the required education that will intensify nurses’ commitment to care for clients with eid. interestingly, saudi nurses showed a higher intention to care for covid-19 patients than expatriate nurses. this could be a result of the nurses’ commitment to their duty in serving the country during this critical time. the comparisons with international studies in this regard were not applicable due to the lack of the nationality variable. however, there is significant evidence supporting the government initiatives toward saudization to ensure an effective healthcare system [18]. from the scientific contribution stand, the study development of a bilingual (englisharabic) instrument to measure nurses’ intention to care for covid-19 patients could offer a valuable contribution in the nursing field especially in the middle east where countries have similar contexts. international studies showed that physical and psychological stress are the struggles of care providers that need to be taken care of [19, 20]. tpb instruments were used widely to assess nurses’ intention to provide care, use specific medical equipment, and adopt nursing behavior [17, 21]. according to lee and kang, a new instrument must be developed to compensate for the weaknesses of older instruments [5]. the recent instrument has fewer items than similar international instruments. therefore, it may suit busy nurses during the eid outbreaks. besides, the english–arabic items support the direct adaptation of the instrument in different settings and populations. moreover, it is more likely that health organizations who use the instrument will be able to target specific areas of improvement such as attitude and perceived behavioral control. the developed instrument showed higher psychometric properties than earlier ones [5, 9]. 4.1. implication for nursing practice the study implication for nursing practice is twofold. first, the study results encourage nursing bodies to focus their efforts on designing and providing continuing nursing education courses in such a way that gives nurses confidence in managing covid-19 cases. similarly, organizational factors should be efficiently governed to provide a positive work environment that supports nurses’ contribution to national health emergencies. the study provided a ready-to-use bilingual instrument (english–arabic) supporting doi 10.18502/sjms.v16i4.9952 page 553 sudan journal of medical sciences khalid a. aljohani et al. healthcare organizations in exploring the nurses’ intention to care for covid-19 patients and measuring contributing factors that may affect nursing care outcomes in such cases. 4.2. limitations and considerations for future work utilizing an online questionnaire may increase the proportion of younger nurses’ participation. the workplace location was not included in the independent variable in the study aims, however, it would be paramount to include this variable in forthcoming studies to differentiate their effect on the nurses’ intention to care. considering that it is the initial study to investigate factors contributing to nurses’ intention to care for covid19 patients in saudi arabia, this could form a foundation in building appropriate task force strategies to respond to infectious diseases and alleviate the tremendous demand on healthcare providers. the study outcomes could inform policymakers, educational organizations, and clinical leaders about underlying issues in the nurses’ intention to care for covid-19 patients. 5. conclusion the current study provided insights on nurses’ intentions to care and its contributing factors, which could offer sturdy healthcare system support during the pandemic. as recommended by this paper, providing nursing education is the main predictor of enhanced nurses’ intention to care for covid-19 patients, healthcare organizations are encouraged to explore their nurses’ concerns using the developed instrument, which is a public domain. acknowledgments none. ethical considerations permission to conduct the study was granted by the nursing college institutional review board, the researchers’ affiliation. data were collected through an online questionnaire using survey monkey from the period of april-may, 2020. study information was presented on the front page of the questionnaire with an invitation letter to participate. doi 10.18502/sjms.v16i4.9952 page 554 sudan journal of medical sciences khalid a. aljohani et al. competing interests the authors declare that they have no competing financial, professional, or personal interests that might have influenced the presentation of the work described in this study. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding this study was not funded by any agency/institution. references [1] oaks jr., s. c., shope, r. e., and lederberg, j. 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(2016). job satisfaction of saudi nurses working in makkah region public hospitals, saudi arabia. life science journal, vol. 13, no. 12, pp. 22–33. [19] huh, s. (2020). how to train health personnel to protect themselves from sars-cov2 (novel coronavirus) infection when caring for a patient or suspected case. journal of educational evaluation for health professions, vol. 17, no. 10. doi 10.18502/sjms.v16i4.9952 page 556 http://chuang.epage.au.edu.tw/ezfiles/168/1168/attach/20/pta_41176_7688352_57138.pdf http://chuang.epage.au.edu.tw/ezfiles/168/1168/attach/20/pta_41176_7688352_57138.pdf sudan journal of medical sciences khalid a. aljohani et al. [20] legido-quigley, h., mateos-garcía, j. t., campos, v. r., et al. (2020). the resilience of the spanish health system against the covid-19 pandemic. the lancet public health, vol. 5, no. 5, pp. e251–e252. [21] via�clavero, g., guàrdia-olmos, j., gallart-vivé e., et al. (2019). development and initial validation of a theory of planned behavior questionnaire to assess critical care nurses’ intention to use physical restraints. journal of advanced nursing, vol. 75, no. 9, pp. 2036–2049. doi 10.18502/sjms.v16i4.9952 page 557 introduction methods study design the study instrument validity and reliability statistical analysis results discussion implication for nursing practice limitations and considerations for future work conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9703 production and hosting by knowledge e review article effectiveness of gum arabic in diabetes and its complications: a narrative review suzy munir salama1, hammad ali fadlalmola2, manal mohammed abdel hafeez3, samia ali mohamed ahmed4, rafiah awad mohamed5, nora mohammed ali elatta6, and abdalbasit adam mariod7 1indigenous knowledge and heritage center, ghibaish college of science and technology, ghibaish, sudan 2nursing college, taibah university, ksa 3department of family education, umm al-qura university, ksa 4police hospital diabetic center, khartoum, sudan 5college of family science and community development, international africa university, sudan 6college of nursing science, omdurman islamic university, sudan 7college of sciences and arts-alkamil, university of jeddah, alkamil, ksa orcid: suzy munir salama: https://orcid.org/0000-0003-0430-1436 hammad ali fadlalmola: https://orcid.org/0000-0002-5065-9626 manal mohammed abdel hafeez: https://orcid.org/0000-0003-2451-9651 samia ali mohamed ahmed fayet: https://orcid.org/0000-0001-7172-4215 rafiah awad mohamed: https://orcid.org/0000-0002-3025-2351 nora mohammed ali elatta: https://orcid.org/0000-0002-9792-6744 abdalbasit adam mariod: https://orcid.org/0000-0003-3237-7948 abstract gum arabic (ga) is a gummy exudation from acacia species, rich in soluble fibers. it is a dietary fiber used traditionally by the natives of many countries of the arabian peninsula, pakistan, and india as therapeutic natural product for treating various diseases including kidney diseases, impotence, obesity, and epilepsy. diabetes represent a global health problem causing many complications and health risk to people of different ages. the current study aimed at identifying the role of gum arabic in treating diseases especially diabetes. many studies have been conducted on the role of gum arabic in experimentally induced diabetes as well as randomized clinical studies. this narrative review was written based on a database search in common libraries such as pubmed, cochrane, web of science, and scopus. the libraries were searched for english articles published between 1995 and 2020 focusing on the role of gum arabic in different preclinical and clinical trials of early and advanced level of diabetes. keywords: gum arabic, diabetes, animals, human, nanoparticles 1. introduction gum arabic (ga) is an air-dried glutinous or gummy exudation obtained from the branches and trunks of acacia species, mainly acacia senegal (hashab), and a nearly associated a. seyal (talha) species, which belongs to the fabaceae family. both species how to cite this article: suzy munir salama, hammad ali fadlalmola, manal mohammed abdel hafeez, samia ali mohamed ahmed, rafiah awad mohamed, nora mohammed ali elatta, and abdalbasit adam mariod (2021) “effectiveness of gum arabic in diabetes and its complications: a narrative review,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 436–453. doi 10.18502/sjms.v16i3.9703 page 436 corresponding author: suzy munir salama; email: s.salama999@hotmail.com received 16 july 2021 accepted 23 august 2021 published 30 september 2021 production and hosting by knowledge e suzy munir salama et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:s.salama999@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences suzy munir salama et al. are naturally grown in the african belt. nigeria, sudan, and chad are the main gumproducing countries. ga tree is a familiar medicinal plant in arabian peninsula, pakistan, and india. gum is a nonviscous secretion that contains high percentage of soluble fibers collected principally from the a. seyal and a. senegal trees. the quality of ga extracted from a. senegal is considered of the highest quality while those extracted from a. seyal as of the lowest [1]. ga is normally produced and collected from a five-year age-ripened tree which is selected when hard nodes are formed on the branches from the dried gum [2]. ga exhibits surprising chemical composition which have been elucidated by several studies. ga is composed from complex neutral or acidic polysaccharide that is formed from mixed magnesium, calcium, and potassium salt derivative of the polysaccharide acid. the units 1,3-connected β-d-galactopyranosyl form the main chain of the polysaccharide acid, while 2–5 units of 1,3-connected β-d-galactopyranosyl form the side chains. the side chain is connected to the main chain by 1,6-linkages. in addition, the units β-d-glucopyranosyl and 4-o-methyl-β-d-glucopyranosyl constitute the end of the main and side chains of the polysaccharide acid, respectively. ga has changeable chemical composition depending on some factors such as the species and age of the tree, climate, and structure of the soil. mariod (2018) found that although, all types of ga contain a similar composition of carbohydrates, where the percentage of reducing sugars in the type of a. senegal was higher, they differed in their content of proteins [3]; the composition of amino acids and the percentage of protein in gum of a. senegal was 3% while the percentage of secondary compounds was 3–6%. the percentage of mineral salts was 3–5%, while the average ash content was 3.27% [3]. neither the stomach nor the small intestine are able to digest the soluble dietary fiber constituent of ga. therefore, fermentation of ga by the intestinal bacteria reflects its prebiotic characteristic of ga and its capability of increasing the bifido bacteria. supplementation of the consumer with 10 gm of ga on daily basis can have prebiotic potential as reported by [4]. at the homeostasis level, metabolic disturbance of proteins, lipids, and carbohydrates causes two types of diabetes; type i diabetes where beta cells of the pancreas are unable to manufacture sufficient insulin or type ii diabetes where the produced endogenous insulin is irresponsive [5]. according to the world health organization (who), chronic diabetes is growing very fast globally showing twofold increase between the years 1980 and 2014. additionally, about 50% of the deaths were hyperglycemic and below the age of 70 [6]. oxidative stress plays key role in diabetic disorders via the increase in the ratio of oxidants/antioxidants leading to damage of biological doi 10.18502/sjms.v16i3.9703 page 437 sudan journal of medical sciences suzy munir salama et al. macromolecules (proteins, carbohydrates, fats, and nucleic acids) which generates more reactive oxygen species and progressive cellular damage [7]. traditionally, ga has been used in treating many health disorders such as impotence, hyperglycemia, weight increase, epilepsy, etc. [1]. ga has great intestinal tolerance and the significantly fewer side effects compared to other substrates used as prebiotic. the rapid interest in ga treatment globally came from its potency in the treatment of many ailments and their complications as well in addition to its safety and economical low cost. ga was found to be biologically active natural product due to its immunity-enhancement, antimicrobial, antihepatotoxic, antiulcer, anti-inflammatory, antioxidant, anti-mutagenic, and anti-cancer properties. it reduces glucose levels by increasing the stool’s mass, reducing stool water content, trapping bile acids, and enhancing vital activities of the body [8]. at the industry level, ga showed thickening, emulsification, and stabilizing characteristics. therefore, it is accepted in food industry as having a distinctive taste [9]. induced diabetes mainly causes increase in blood sugar and hba1c. in addition, serum urea and creatinine, triglycerides, low-density lipids (ldl), malondialdehyde (mda) are elevated. on the other hand, reduction of high-density lipids (hdl), glutathione level (gsh), catalase (cat), and superoxide dismutase (sod) activities are significantly recorded. at the histological level, kidneys from experimentally induced diabetes in rats displayed highly significant changes in the glomerular and tubular parts of diabetic kidneys. although the results obtained experimentally were abnormal, supplementing diabetic rats with ga revealed significant hypolipidemia, hypoglycemia, and antioxidant activity in comparison with the control group with no effect on the blood level of urea and creatinine [10]. intake of ga in parallel with insulin altered the negative effects of diabetic mellitus on the blood biochemistry and the tissue histology as well [10]. 2. materials and methods based on [11], the present narrative review was conducted by searching for related articles in the common libraries such as pubmed, cochrane, web of science, and scopus published between 1995 and 2020 using the keywords “gum arabic,” “gum acacia,” “gum arabic-nanoparticles,” “diabetes,” “complications of diabetes,” or “chronic diabetes.” we concentrated our search on english studies that include experimentally induced diabetes and clinical cases with different stages of complications showing the efficacy of ga supplementation on early as well as advanced stages of diabetes. doi 10.18502/sjms.v16i3.9703 page 438 sudan journal of medical sciences suzy munir salama et al. 3. results the articles’ findings on the potential activity of gum arabic in different types of preclinical and clinical studies were significantly concentrated and interpreted. additionally, the mechanistic outcomes from the different studies on the effectiveness of gum arabic in diabetes were illustrated and summarized on figures for better understanding. 4. discussion diabetes mellitus (dm) is a chronic illness with steadily increasing frequencies in all countries [12], microvascular and macrovascular complications of diabetes that may result in mortality and morbidity [13]. prevention and early treatment of hyperglycemia is able to delay the occurrence of complications and improve the life status of diabetic patients. 4.1. role of ga in reducing lipid profile and obesity studies suggest that patients who were given 30 mg of ga mixed with 20 mg of atorvastatin have recorded remarkable reduction of their lipid profile after one month of intervention compared to those given atorvastatin only [14]. a study on broiler chickens has shown that the intake of diet supplemented with 5% and 7.5% ga has a hypolipidemic effect via reduction of serum cholesterol and triglycerides [15]. another published study reported that mice fed with diet rich in fat together with 7% ga for about four and half months had a significant reduction in serum cholesterol and triglycerides. scientists have referred the hypolipidemic efficacy of ga to different mechanisms. one pathway suggests that ga increases bile salts’ excretion in the stool resulting in the consumption of cholesterol by the liver in manufacturing new bile salts and reduction of body fat together with serum cholesterol [16, 17]. further, ga in the diet given to the mice downexpresses the genes responsible for formation of cholesterol and over-expresses the genes involved in fat oxidation in the body of mice [18]. another mechanism of ga in reducing lipid profile was suggested by jangra et al. [18] who mentioned that overexpression of fasting-induced adipose factor (fiaf) gene in the mice fed with ga induces lipolysis process and reduces the accumulation of fat in their bodies. the contribution of fiaf gene responsible for modulating lipid metabolism in type ii diabetes has been supported by other studies [19, 20]. doi 10.18502/sjms.v16i3.9703 page 439 sudan journal of medical sciences suzy munir salama et al. studying antidiabetic potential of ga on alloxan-induced diabetes in experimental rats given single intraperitoneal injection dose of alloxan (105 mg/kg) revealed significant hypoglycemic effect. based on the studies, the lowest concentration of ga showed effective improvement in body weight gain and the serum contents of albumin, total protein urea and creatinine in experimentally induced diabetic rats. additionally, ga altered the negative effect on the relative weight of rats’ internal organs [21]. dyslipidaemia in patients with type ii diabetes presents high effect on the cardiovascular health. it was claimed that ga could be a beneficial supplementation in diabetes type ii patients [22]. babiker et al. [23] reported that supplying diabetic patients with ga, 30 gm daily for three months was influential in reducing body weight and regulating fatty tissue problem. also, the tested dose has increased hdl and decreased triglyceride blood levels reducing the risk of cv agents in diabetic patients. 4.2. role of ga in reducing fasting plasma glucose and hba1c documented studies suggested that ga has antidiabetic effect in human and animals as well. addition of ga at a dose of 10 gm per day for 16 weeks to the diet of experimental prediabetics and diabetics recorded noticeable suppression in fasting blood glucose level and glycated hemoglobin (hba1c) as well. the study revealed that ga treatment has recorded increased excretion of urinary ca2+ and decreased plasma level of phosphate and urea [13]. recent studies explained the therapeutic effect of ga reporting that ingestion of 60 gm of ga on a daily basis for 90 days can induce minor decrease in the body mass index (bmi) of diabetics, and slight change in their glycated hemoglobin (hba1c). this may be attributed to increased intake of carbohydrates in 60% of the respondents and disrespect of 32% of participants to the regular ingestion of ga dose prescribed [24]. babiker et al [25] observed the beneficial effect of ga in glycemic control diabetic patients receiving 30 gm of gum for four months. ga has an intrinsic glycemic index of proximately zero since it is not absorbed in small intestine [26], while ibrahim et al. [24] published that in type ii diabetic patients, ingestion of 60 gm/day of ga produced no significant or appreciable effect on blood glucose concentration and bmi. 4.3. role of ga in diabetic oxidative stress based on many researches, oxidative stress is involved in the pathogenesis of diabetes [27] including diabetic hepatopathy [28]. in addition, oxidative stress plays an effective doi 10.18502/sjms.v16i3.9703 page 440 sudan journal of medical sciences suzy munir salama et al. role in diabetic retinopathy through lipid peroxidation, dna damage, and apoptosis of endothelial retinal cells resulting in ocular diseases such as cataract and glaucoma [29]. further, hyperglycemia induces oxidative stress by shifting glycolysis process to hexosamine pathway that increases the formation of diphosphate-n-acetyl glucosamine [30] enhancing the production of defective genes responsible for magnification diabetes complications [31]. intervention dose of ga, 15% in drinking water for 60 days, was proved to alter the complications of type i diabetes resulting from elevated damage produced from alloxan monohydrate-induced oxidative stress induced in rats. ga protected the diabetic liver via enhancement of antioxidant enzymes’ overexpression. hepatic sod and glutathione peroxidase (gpx) were considerably overexpressed and mda level was remarkably reduced in the hepatic tissue of diabetic animals [7]. figure 1: chemical composition of gum arabic (acacia senegal). 4.4. role of ga in kidney problems nephropathy is considered one of the diabetic complications resulting in renal failure. cytokines were found to play major role in the renal complications in diabetes including renal nephropathy. transforming growth factor tgf-β1 is a pro-fibrotic protein and one of the cytokine indicators in the pathogenesis of kidney problems [32] in diabetic patients via stimulation of collagen iv leading to fibrosis in the kidney and sclerosis in the glomeruli which eventually causes kidney failure as previously published [32, 33]. researchers showed that the intake of 10% ga in drinking water reduced the doi 10.18502/sjms.v16i3.9703 page 441 sudan journal of medical sciences suzy munir salama et al. figure 2: the role of gum arabic (acacia senegal) in diabetes. alt: alanine aminotransferase; sod: superoxide dismutase; ast: aspartate aminotransferase; bun: blood urea nitrogen; cat: catalase; ggt: gamma glutamyl transferase; ckd: chronic kidney failure; gpx: glutathione peroxidase; hba1c: glycated hemoglobin; mda: malondialdehyde; tgf-β1: transforming growth factor beta 1. overexpression of renal tgf-β1in streptozotocin (stz)-induced diabetic mice when treated for a month [33]. qureshi et al. [34] and el tobgy [35] found that in the investigation on diabetic rats the anti-hyperglycemic influence of ga mediated by a decrease in intestinal glucose absorption decreased the plasma glucose level, and thus the insulin level. in addition to that, consumption of ga decreased urinary volume and glucose urea. the doi 10.18502/sjms.v16i3.9703 page 442 sudan journal of medical sciences suzy munir salama et al. preventive and protective impact of ga with respect to the complications of diabetes was documented. ga improved neuropathy [36], nephropathy [7] and albuminuria. in addition, it significantly reduced serum phosphate concentration, proteinuria, and improved glomerular filtration rate which eventually progress renal functions [10]. al za’abi et al. [37] reported that adenine-fed rats showed significant decrease in body weight along with increase in diet intake and urination. at the biochemical level, the study revealed increase in the ratio between albumin/creatinine in urine and elevation in the plasma level of creatinine, urea, phosphorus, and indoxyl sulfate. additionally, induced diabetes by alanine mixed with stz further worsened most kidney parameters assessed. ga has considerably reduced the damage in the biochemistry and histopathology profiles of the kidney caused by adenine or adenine mixed with stz. a recent study also reported that ga could protect the rats from renal toxicity induced by colistin [38]. experiments on diabetic dogs and cats showed that supplementation of these animals with fermentable fibers such as ga could enhance insulin secretion through increase in short chain fatty acids which accordingly increase the production of glucagon-like peptide-1 (glp-1) [39]. 4.5. role of ga in diabetic hyperphosphatemia hyperphosphatemia is one of the main factors of death probabilities in chronic renal diseases and renal nephropathy. diet rich in phosphorus-binding agents were found to have potential effect in reducing absorption of phosphorus in the small intestine of diabetic patients with chronic renal problems. ga was proved to be one of these agents due to its high ability to bind to phosphorus and reducing the hazardous effects of phosphorus absorption on kidneys [40]. recently, farman et al. [41] stated that supplementation of chronic renal failure patients with ga, 30 gm daily for 180 days noticeably suppressed serum content of phosphorus. 4.6. role of ga in stomach gastroparesis gastrointestinal problems are considered one of the complications of high blood glucose in diabetic patients [42]. stomach gastroparesis is a disorder in long-term hyperglycemic patient that causes different degrees of weakness in the stomach motility, gastric paralysis, and delay in stomach emptying [43]. previous studies have reported that ga protects the stomach against gastroparesis induced by uremia in rats [44]. additionally, ga as a soluble fiber and due to its polysaccharide constituent was recently doi 10.18502/sjms.v16i3.9703 page 443 sudan journal of medical sciences suzy munir salama et al. suggested to have significant effect on reducing the symptoms of stomach gastroparesis in diabetic patients [45]. 4.7. role of ga in diabetic testicular degeneration and erectile dysfunction complications of diabetes are accompanied by erectile dysfunction and impotence due to disruption in the nervous or vascular communication [46]. ga possesses high antioxidant capacity and is applied in researches in inhibiting the toxic impact of type i diabetic rats on reproductive male organs. treating experimental animals with ga has successfully ameliorated the histology alterations observed on the testicular tissue of rats. experimental data revealed that ga remarkably improved the injurious changes of testes [47]. another study showed that consumption of ga resulted in decreased lipid peroxidation, amelioration in degenerative testicular tissue of alloxan-induced diabetic rats, and enhanced sperm quality, activity of the endogenous antioxidant enzymes together with their expressed proteins were collectively found to be increased. these effects might have roles in the treatment of reproductive problems in diabetic males [48]. a recent study reported that ga effectively enhanced male fertility [49]. 4.8. role of ga in wound healing and diabetic foot diabetes is accompanied by induction of abnormalities in neural and vascular structure and function as a complication symptom [50]. consequently, inhibition of angiogenesis and amputated diabetic foot are clearly symptomized in chronic hyperglycemia [51]. recently, studies showed that dressing wounds with hydrogel prepared from ga polysaccharides enhanced wound healing in rats through its antioxidant capacity [52]. 4.9. role of ga in diabetic neuropathy pathogenesis of diabetes related to hyperglycemia was suggested to be linked to autonomic neuropathy that may lead to gastrointestinal dysfunction [53]. hailah et al. [54] reported that ga improved experimental diabetic peripheral neuropathy as evidenced biochemically through improvement of lipid profile and antioxidant indices, and sciatic nerve histopathology. further, dowidar et al. [55] published that ga reduced the complications resulting from type ii diabetes initiated by supplementing the diet of rats doi 10.18502/sjms.v16i3.9703 page 444 sudan journal of medical sciences suzy munir salama et al. with high fat and high fructose for three 3 months. ga revealed a remarkable alleviation of insulin resistance and suppression of glucagon secretion and lipid parameters. 4.10. role of ga in diabetic cardiomyopathy at the research level, one of the main reasons of mortality among diabetic patients in developing countries is long-term hyperglycemic complications in cardiovascular system resulting in cardiomyopathy [54]. based on the study of jia et al. [55], hyperglycemia is associated with cardiac hypertrophy via microvascular dysfunction. mechanistically, increase in blood glucose level for long term in diabetic subjects leads to cardiac insulin resistance [56], stress due to oxidants, and deterioration of calcium conduction in the mitochondria due to mitochondrial dysfunction [57]. recently, one study stated that ga reduced the progress of diabetic cardiomyopathy (dcm) through the improvement of hyperglycemia, hyperlipidemia-mediated oxidative stress. for that, it may have the therapeutic potential of ga for human dcm [58]. studies published that heat shock protein (hsp20) was proved to have an impact in cardiac injury stimulated by long-term hyperglycemia through restoration of cardiac dysfunction [59]. the anti-inflammatory efficacy of hsp20 protects against overproduction of cytokines of inflammation implicated in cardiac hypertrophy [60]. additionally, increased secretion of hsp20 by cardiomyocytes has been induced by ga intervention in diabetic rats for eight weeks resulting in altering the status of diabetic cardiomyopathy [61]. another report stated that adding ga 15% to drinking water of mice for one month protected their hearts from the injurious effect of water pipe smoke via its significant reduction of pro-inflammatory cytokines and stress due to oxidants [62]. cardiovascular diseases (cv) are incidentally increasing in people with type ii diabetes [63]. previously, glover et al. (2009) published that supplementing diet with dietary fiber, including ga has resulted in significant decrease in the average value of systolic blood pressure in normal individuals [64]. 4.11. ga and nanoparticles ashraf et al. exposed that ga capped-silver nanoparticles exhibited inhibitory effect on the advanced glycation end products that contribute in the pathology of many diseases such as diabetes, alzheimer’s disease, and eurosclerosis. recently, silver nanoparticles biosynthesized from a mixture of three aqueous extracts – ga, parsley, and corn silk – showed significant antioxidant activity through increased blood level doi 10.18502/sjms.v16i3.9703 page 445 sudan journal of medical sciences suzy munir salama et al. of glutathione in alloxan-induced dm in experimental rats [65]. studies published that nanoparticles formed from ga and maltodextrin showed significant antioxidant power in reducing oxidative stress in diabetes [66, 67]. another study reported than nanoparticles prepared from chitosan and ga showed significant activity in bone regeneration in rabbits [68]. nanoparticles formed from ga and calindula officinalis has proved in vitro potential activity in wound healing and skin engineering via enhancement of fibroblast cells proliferation [69]. additionally, silver nanofibers prepared from ga has recently showed significant antimicrobial wound healing activity due to the improvement to the proliferation of fibroblast cells of mouse embryos in vitro [70]. 5. conclusion food supplementation with ga reduces blood sugar level and glycated hemoglobin hba1c in prediabetic and diabetic small experimental rats via its hypolipidemic, antiinflammatory activities, and enhancement of antioxidant enzymes. in addition, ga suggested hypoglycemic effect through its activation to insulin secretion. moreover, randomized clinical trials revealed significant efficacy of ga supplementation in ameliorating serum glucose level. acknowledgements authors are grateful to prof. dr. abdalbasit adam mariod for his supervision and permission for submission. also, authors appreciate the contribution of prof. hammad ali fadlalmola for his review to the manuscript before submission. thanks to all authors for their efforts in collecting the data and material of the manuscript. ethical considerations not applicable. availability of data and material all the data and materials of the present narrative review are mentioned in the manuscript and clearly cited in the body text along with the references section. doi 10.18502/sjms.v16i3.9703 page 446 sudan journal of medical sciences suzy munir salama et al. funding none received. competing interest authors declare no conflict of interest. references [1] jaafar, n. s. 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(2020). synthesis and characterization of antimicrobial wound dressing material based on silver nanoparticles loaded gum arabic nanofibers. international journal of biological macromolecules, vol. 155, pp. 119–130. doi 10.18502/sjms.v16i3.9703 page 453 introduction materials and methods results discussion role of ga in reducing lipid profile and obesity role of ga in reducing fasting plasma glucose and hba1c role of ga in diabetic oxidative stress role of ga in kidney problems role of ga in diabetic hyperphosphatemia role of ga in stomach gastroparesis role of ga in diabetic testicular degeneration and erectile dysfunction role of ga in wound healing and diabetic foot role of ga in diabetic neuropathy role of ga in diabetic cardiomyopathy ga and nanoparticles conclusion acknowledgements ethical considerations availability of data and material funding competing interest references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9941 production and hosting by knowledge e editorial a brief guide to author self-promotion dr emily choynowski knowledge e, dubai, uae orcid: emily choynowski: https://orcid.org/0000-0002-6681-1709 every researcher hopes to publish their research. it affirms the value of our work, allows us to engage with our peers, and contribute to discussions and debates within our field. however, it is not enough to be published. as researchers, we also want our work to be read and quoted, to know that our own studies are helping others develop their work – not languishing on a dusty shelf or unused website. authors can think that their involvement with their article ends with the acceptance letter from a journal’s editor-in-chief. once, this might have been true: the published article would be printed, and copies of the journal sent to various libraries, where it waited to be read by the small coterie of relevant experts. the best way to ensure an article’s impact was to publish in a high-impact journal, and the only additional promotion opportunity open to the author would be self-citations in future articles. this is no longer the case. in our digital era, with the increasing prominence of electronic education resources and the huge popularity of social media platforms, there are now a wealth of opportunities and avenues for authors to promote their research and enhance their impact. authors now have the ability to dramatically increase the visibility of their articles and boost readership levels – especially when publishing in open access journals like the sudan journal of medical sciences. this editorial will outline some of the key steps authors can take to promote themselves and their research to a global audience and increase their impact. 1. professional profiles an up-to-date online professional profile is vital for academics and researchers. the profile should include qualifications, career history, any awards or funding received, a list of invited positions held, and a complete list of publications. this information is sometimes included on the professional page with an employer/ institution. however, it can be difficult to update this page with new information, and it can be lost when moving to a new institution. how to cite this article: dr emily choynowski (2021) “a brief guide to author self-promotion,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 436–438. doi 10.18502/sjms.v16i4.9941 page 436 corresponding author: dr emily choynowski; email: emily@p-m.uk.com published 31 december 2021 production and hosting by knowledge e emily choynowski. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:emily@p-m.uk.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences emily choynowski platforms such as orcid (orcid.org) address this issue by allowing researchers to collect all their professional and publication information in one place, connecting their research with their permanent digital profile. researchers can also create scopus and google scholar profiles, which incorporate the information from the orcid account. 2. enhancing visibility the proliferation of digital content and social media platforms lets authors promote their research to global audiences. authors can post summaries and links to articles on mainstream platforms such as twitter and facebook, and academic platforms such as research gate and academia.edu. they can write engaging blog posts about research and submit them to relevant scientific communities and list serves, and attract a far larger readership than would be possible with traditional print publications. in addition to making content more visible to readers around the world, researchers can also make it more accessible. published research is typically written for a niche audience of specialists in a specific field. this means the content can often be quite dense and difficult to understand for researchers in other fields and people outside academia. authors can address this issue by offering engaging summaries which showcase their work to broader non-specialist audiences. for example, a short video abstract discussing the key points in the article can present research in a new way, making it more accessible to non-specialists. there are also services such as kudos (which our publisher, knowledge e, provides for free to our authors) which helps researchers to maximise and measure the impact of their research, explain their work to a new audience and track its dissemination across multiple platforms. 3. engaging with the community finally, authors can increase the impact of their research by engaging with their scholarly communities. formerly, this was only really possible at conferences, but now authors can use social media to forge new connections and debate key issues with people all over the world. new connections and communities can be identified via relevant hashtags and key organizational social media accounts. researchers can also subscribe to list serves and association websites in our subject or subfield and engage with new publications and doi 10.18502/sjms.v16i4.9941 page 437 sudan journal of medical sciences emily choynowski events via online comments and discussion forums. liking, commenting upon, sharing content, and tagging people will also help to increase visibility. the more connections a researcher makes, the more visible they will be, and the more opportunities there are for people to learn about their research and read their work. doi 10.18502/sjms.v16i4.9941 page 438 professional profiles enhancing visibility engaging with the community sudan journal of medical sciences volume 12, issue no. 2, doi 10.18502/sjms.v12i2.918 production and hosting by knowledge e research article effect of body composition on ventilation parameters in a group of young sudanese females n. a. alaagib1 and m. y. sukkar2 1assistant professor, department of physiology faculty of medicine, university of khartoum 2professor of physiology and dean of nile college, khartoum, sudan abstract background: lung function test helps (lft) in the diagnosis and follow up of patients with pulmonary or cardiac diseases. ignoring bmi and body composition during interpretation of lft results may lead to wrong diagnosis and unnecessary use of drugs. objective: this study was conducted to test the hypothesis that differences in body composition between individuals can explain some of the features of lft that are explained by variations in age, sex, and height only. methods: this observational analytical cross sectional study which included 150 young adult females. those with history of amenorrhea, smoking, asthma or cardiac disease were excluded. anthropometric measurements including: bmi, waist circumference (wc) and body fat percent calculated from skinfold thickness measurements were done. dynamic spirometric tests were performed using digital spirometer; fev1, fvc, fev1% were measured. results: both obese and underweight subjects had a significant reduction in fev1 (p = .002) and fvc (p = .004) compared to normal ones. fev1% was significantly higher in the overweight and obese group compared to the other two groups (p = .02). body weight, bmi, and wc had significant positive correlation with fev1 and fev1% in young healthy females. conclusion: increase in bmi, body weight, wc and body fat showed positive significant correlation with fev1% and may give a restrictive pattern in lft. underweight subjects may show significant reduction in lung function if their bmi is not considered. keywords: fev1, fvc, fev1%, bmi, waist circumference, body fat %, obesity how to cite this article: n. a. alaagib and m. y. sukkar, (2017) “effect of body composition on ventilation parameters in a group of young sudanese females,” sudan journal of medical sciences, vol. 12 (2017), issue no. 2, 78–88. doi 10.18502/sjms.v12i2.918 page 78 corresponding author: n. a. alaagib and m. y. sukkar; email: nouralsalhin@gamil.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e n. a. alaagib and m. y. sukkar. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:nouralsalhin@gamil.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e من يعانون الذين المرضى ومتابعة تشخيص يف يساعد الرئة وظيفة اختبار الخلفية: أمراض رئوية أو قلبية. تجاهل مؤشر حجم كتلة الجسم وتكوين الجسم أثناء تفسير نتائج اختبار وظيفة الرئة قد يؤدي إىل التشخيص الخاطئ واالستخدام غير الضروري لألدوية. الهدف: أجريت هذه الدراسة الختبار الفرضية القائلة بأن االختالفات يف تكوين الجسم بين األفراد يمكن أن تفسر مالمح اختبار وظيفة الرئة التي يتم تفسيرها من خالل االختالفات يف العمر والجنس واالرتفاع فقط. الشابات اإلناث من ١٥٠ شملت والتي مقطعية تحليلية رصدية دراسة هذه : الطريقة: أمراض أو والربو والتدخين الطمث انقطاع تاريخ من يعانين من واستبعدت البالغات. ونسبة الخصر محيط الجسم، كتلة مؤشر ذلك: يف بما األنثروبومترية القياسات القلب. الدهون يف الجسم محسوبة من قياسات سماكة الجلد. تم إجراء اختبارات قياس التنفس .٪fvc، fev١ ،fevالديناميكي باستخدام مقياس التنفس الرقمي؛ تم قياس ١ = p) fevالنتائج: كان لكل من السمنة ونقص الوزن ىف المدروسات انخفاض كبير يف ١ .٠٠٢) و fvc (p = .٠٠٤) مقارنة مع تلك العادية. وكان fev١٪ أعلى بكثير يف مجموعة زيادة الوزن والبدانة مقارنة مع المجموعتين األخريتين (p= ٠٫٠٢). وزن الجسم، مؤشر كتلة اإلناث يف ٪fev١ و fev١ مع كبيرة إيجابية عالقة على كان الخصر ومحيط الجسم، الصحيحات. الخالصة: إن الزيادة يف مؤشر كتلة الجسم، وزن الجسم، محيط الخصر ونسبة الدهون يف يف انحصاريا نمطا تعطي أن ويمكن ٪fev١ مع كبيرة إيجابية عالقة على كانت الجسم اختبار وظيفة الرئة. االناث مع نقص الوزن قد تظهر انخفاضا كبيرا يف وظائف الرئة إذا لم يتم النظر يف مؤشر كتلة الجسم. 1. introduction assessment of the lung functions (lf) helps in the diagnosis and management of patients with pulmonary or cardiac diseases. lung volume measurements made during forced expiration are interpreted by comparing them with the expected values given the age, height and sex of the patient. body mass index (bmi) is rarely used. this may lead to wrong diagnosis, unnecessary use of drugs, and failure to detect significant improvement in fev1(forced expiratory volume in the first second) [1]. racial or ethnic differences in lung volumes have been reported. usa blacks were found to have lower lung volumes than whites. the differences in the body size and shape were suggested to be the reason for these differences in spirometric findings [2]. obesity is known to affect the lf and may increase the effect of an existing airway disease [3]. obese subjects may have a decrease in lung volume and expiratory flow rates [4] and may experience dyspnea at rest [5, 6]. some studies found that bmi has a strong positive association with risk of adult-onset asthma [5–8]. other studies showed that obese individuals can have dyspnea but not airway obstruction [6, 9]. many obese doi 10.18502/sjms.v12i2.918 page 79 sudan journal of medical sciences production and hosting by knowledge e subjects were using bronchodilators without evidence of airflow obstruction [6]. jones and nzekwu found that bmi has significant effects on all lung volumes [10]. it has been observed that bmi improved the predictions for both volumes and flows, regardless of sex. bmi or body weight (bw) gain has been related to the decrease in fev1 and forced vital capacity (fvc) in adults [11–13]. the addition of waist circumference (wc) to bmi improved the prediction of health risk than bmi alone [14]. chen et al. reported that wc, but not bmi, is negatively associated with lf [15]. some studies suggest that upper body fat distribution [16, 17] and abdominal adiposity [18] are better predictors of lf than bw or bmi. body fat distribution also affects the lf [17]. fat% and fat free mass (ffm) index improved the descriptions of fvc and of changes in fev1 and fvc [14]. this study was conducted to test the hypothesis that differences in body composition between individuals can explain some of the features of lft that are explained by variations in age, sex, and height only. 2. materials and methods this study is an observational analytical cross sectional study, done on 150 young female university students. the main objective of the study was to determine the effect of overweight and obesity on the ventilatory parameters (fev1, fvc, fev1%). the secondary objectives were: to determine the effect of bmi on each of the ventilatory parameters, and to verify the relation between bmi, percentage of body fat and waist circumference and each of the ventilatory parameters. subjects were volunteers from the practical groups who considered themselves healthy with no history of amenorrhea, smoking, asthma or cardiac disease. their age was between 17-23 years. all subjects had completed a questionnaire personal data and additional questions on smoking, history of asthma, other respiratory or cardiovascular disease, or any other disease that can affect the lung function. each subject underwent complete physical examination to exclude any abnormality and signed an informed consent. dynamic spirometric tests and anthropometric measurements including: bw, height, bmi, wc, skinfold thickness were done. weight (kg): was measured to the nearest 100 g using standardized digital weight scale (beurer, germany) with the subject in standing position wearing light clothes and without shoes. standing height (m) was measured without shoes with the subject’s back to avertical standardized height scale (seca, germany) to the nearest mm. then bmi (kg/m2) was calculated as a ratio between body weight (kg) and squared height (m2). doi 10.18502/sjms.v12i2.918 page 80 sudan journal of medical sciences production and hosting by knowledge e waist circumference (cm) was measured using a tape to the nearest 0.1 cm at the end of a normal expiration from exposed relaxed abdomen, at the level of the umbilicus in standing position. body composition was estimated using three steps: (a) skinfold thickness was measured in mm using holtain skinfold caliper (crymych company, united kingdom) from the triceps and subscapular region to the nearest 1 mm [19] by the same investigator. (b) body fat % (bf%): using the method of paríková and bůžková [20], bf% was calculated from the triceps and subscapular skinfold separately as follows: y1 = 4.019 + 0.894 x1 y1 = 2.333 + 0.988 x2 where y1 = bf% of the body weight; x1 triceps skinfold (mm); x2 subscapular skinfold (mm). (c) fat free mass (ffm) (kg) was calculated from the body weight and bf%. dynamic spirometric tests were performed using electronic spirometer (chest corporation, japan) in the sitting position and with a nose clips. first subjects were instructed in the fvc maneuver then the appropriate technique was demonstrated by the investigator. each subject inhale from frc and then insert the breathing tube into her mouth, making sure her lips are sealed around the mouthpiece before starting the fvc maneuver. the subject must have a complete inhalation before beginning the forced exhalation. each subject attempted to perform at least three acceptable fvc maneuvers according to the ats (american thoracic society) acceptability and reproducibility criteria [21]. the highest result was used for statistical analysis. fev1, fvc, and fev1% were measured. data analysis: data was saved and analyzed using spss version 10. subjects were classified into 3 bmi groups: underweight, normal and obese (include both overweight and obese bmi > 25 kg/m2) according to who classification [22]. descriptive statistics were calculated for all the variables according to bmi classes. correlations of body measurements with ventilatory parameters were done using pearson correlation. to verify the effect of bmi class on the ventilatory parameters their mean values was compared between underweight, normal, obese groups using analysis of multiple variances (anova) test. 3. results this study included 150 young healthy females. subjects were classified according to bmi class into 3 groups underweight, normal, obese (include both overweight and doi 10.18502/sjms.v12i2.918 page 81 sudan journal of medical sciences production and hosting by knowledge e variables mean ± se underweight (n = 54) normal bmi (n = 64) overweight & obese (n = 32) height (m) 1.62 ± 0 .01 1.6 ± 0 .01 1.61 ± .02 weight (kg) 47.9 ± 1.6 61.1 ± 1.3 75.1 ± 1.1 bmi (kg/m2) 18.2 ± 0.5 22.5 ± 0.4 29.0 ± 0.5 waist circumference(cm) 64.4 ± 0.9 71.7 ± 0.8 80.9 ± 1.1 triceps skinfold(mm) 12.8 ± 0.7 18.1 ± 0.6 26.4 ± 0.9 fat % (t) 15.4 ± 0.6 20.2 ± 0.5 27.7 ± 0.8 subscapular skinfold(mm) 13.5 ± 0.7 17.7 ± 0.6 28.0 ± 0.9 fat % (s) 15.7 ± 0.7 19.8 ± 0.6 30.0 ± 0.9 ffm (t) (kg) 40.6 ± 0.7 47.5 ± 0.6 55.0 ± 0.8 ffm (s) (kg) 40.5 ± 0.6 47.7 ± 0.6 53.0 ± 0.8 fev1 (l) 2.592 ± .059 2.856 ± .053 2.781 ± .075 fvc (l) 3.139 ± .069 3.418 ± .061 3.202 ± .088 fev1% 82.63 ± .72 83.68 ± .64 85.59 ± .93 t 1: anthropometric and spirometric measurements according to bmi class. *ffm: fat free mass, (t): calculated using triceps skinfold, (s): calculated using subscapular skinfold. obese bmi > 25kg/m2) according to who classification [22]. table 1 shows means of anthropometric and spirometric measurements in different to bmi classes. to assess the effect of anthropometric measurement on lung function test (lft) parameters pearson correlation was done (table 2). bmi and wc showed significant positive correlation with fev1( (p = .016) and (p = .003) respectively),and fev1% ( (p = .005) and (p < .005) respectively). body fat % showed a highly significant positive association with fev1% (p = 0.002). to determine the effect of overweight and obesity in lung function test anova test was done to compare the means of the three bmi groups. underweight subjects had a significantly lower fev1 than normal bmi and obese subjects (p = 0.03) (figure 2). fvc was significantly higher in normal bmi subjects compared to the other two groups (p = 0.01). there was no significant difference between underweight and obese subjects in fvc (figure ??). fev1% was significantly higher in the overweight and obese group compared to the other two groups (p = .02). doi 10.18502/sjms.v12i2.918 page 82 sudan journal of medical sciences production and hosting by knowledge e body measurements fev1 fvc fev1% weight 0.294 (p = .000)* .184 (p = .024) * .231 (p = .005) * bmi .196 (p = .016) * .084 (p = .306) .229 (p = .005) * waist circumference .245 (p = .003) * .107 (p = .191) .309 (p = .000) * fat % t .064 (p = .438) -.010 (p = .899) .191 (p = .020) * fat % s .067 (p = .414) -.025 (p = .764) .248 (p = .002) * ffmt .392 (p = .000) * .289 (p = .000) * .189 (p = .021) * ffms .407 (p = .000) * .318 (p = .000) * .139 (p = .090) t 2: correlations between body measurements and lung function parameters. * p values (<0.05 is significant, <0.005 is highly significant). (-) indicates negative correlation. figure 1: means of fev1 in different bmi groups. figure 2: means of fvc in different bmi groups. 4. discussion in this study obese subjects had the highest mean of bf %, but they also had the highest mean of ffm as well (table 1). the increase in bw in the study group could be explained partially by the physical growth involving skeletal frame, muscles and fat. this means that subjects in the obese group were overfed females with excessive energy intake and minimal exercise, therefore they deposited more fat. they had a good nutritional status which leads to development of good muscle bulk (more ffm). doi 10.18502/sjms.v12i2.918 page 83 sudan journal of medical sciences production and hosting by knowledge e 4.1. effect of body composition on ventilation parameters we found that the subgroup with normal bmi had the highest mean of both fev1 and fvc, while underweight ones had the lowest mean of both fev1 and fvc. welldeveloped muscles especially of the chest wall are expected to influence all forced expiratory parameters. being underweight with small muscle bulk may reduce the lung volumes. fvc showed a significant positive association with bw (p = .02). the increase in bw in this young females group reflects increase in both muscle bulk and body fat with predominant effect of muscle bulk on lf. contrary to expectations fvc had no significant association with bmi in the present sample. the effect of bmi may be clearer in older age group. bf% showed a negative correlation with fvc but it was not significant. the present results agreed partially with lazarus et al results who found that adjusted fvc was not significantly associated with bmi, but was negatively associated with bf% in men and women [17]. therefore, it was justified to look for the ffm and its correlation with lf parameters because: the number of overweight and obese is too small to show the effect of increased bmi or body fat on lf. fvc showed positive correlation with bw and not with bmi. in addition, underweight had the lowest fvc. from the previous results muscle mass is more likely to affect the lung parameters. the results showed a highly positive association between ffm and fvc (p = .000) as shown in table 2; which agrees with lazarus et al results [17]. in cotes et al study, this association was insignificant in women but not for women who perform much exercise [14]. unlike the results of chen et al in which wc, but not bmi, is negatively associated with lf [15]; there was no association between wc and fvc in this sample. this is most probably due to the opposing effects of fat and muscle in these young females. fev1had highly significant positive association with bw, ffm and wc (p < .005); and a positive significant association with bmi (p = .01). this can be explained by the effect of the good muscle bulk on forced expiration. fev1 % had a highly significant positive correlation with bw and bmi (p = .005), because these measures caused a significant increase in fev1 and a slight or no increase in fvc (table 2). in contrary to heather et al results which showed a negative association between wc and fev1 % [18], there was a highly significant positive correlation between them in this study (p < .005). the increase in wc in these young females was associated with the increase in muscles mass (causing increase fev1) as well as fat (causing insignificant effect on fvc) and therefore a positive association with fev1 %. in addition, there was a positive highly significant association between fev1 % and bf% calculated from the subscapular skinfold (p = .002) and triceps skinfold (p = .02). fev1% was significantly higher in the overweight and obese group compared doi 10.18502/sjms.v12i2.918 page 84 sudan journal of medical sciences production and hosting by knowledge e to the other two groups (p = .02). thus, results of lft in healthy obese persons may give a restrictive pattern. this may be due to the mechanical load impeding expansion of the chest wall during inspiration. future studies may yield more conclusive results if more sensitive estimates of muscle mass are employed in different age group. 4.2. effect of bmi on ventilation parameters in this study bmi class had a significant effect on fev1 (p = .004), fvc (p = .008) and on fev1 % (p = .04). underweight subjects had significantly lower fev1compared to normal bmi and obese subjects. there was no significant difference in fev1 between obese and normal bmi subjects, which support the hypothesis that the effect of increase muscle mass is likely to offsets the effect of fatness on fev1. in agreement with previous studies which have demonstrated that a rise in bmi lowers fev1 and fvc [12, 13]; this study showed that fvc was significantly reduced in the obese and underweight group compared to normal bmi subjects (p < .05). there was no significant difference in fvc between obese and underweight subjects. this means that both obese and underweight had a significant reduction in fvc compared to normal weight females. 5. conclusion the higher fev1% in the overweight and obese group compared to the other two groups and the positive association of body fat, body weight, wc and high bmi with fev1% suggests that obese subjects may show a restrictive pattern in lft. on the other hand, underweight subjects may have a significant reduction in lung function. we suggest that more anthropometric measurements should be taken into account for the assessment of lung function. 6. ethics approval this study was approved by the department of physiology-faculty of medicineuniversity of khartoum. each participant signed an informed consent form. 7. competing interests no areas of competing interest of this study. doi 10.18502/sjms.v12i2.918 page 85 sudan journal of medical sciences production and hosting by knowledge e 8. acknowledgements we would like to thank the members of physiology department faculty of medicine university of khartoum for their collaboration. great appreciation and thanks to professor mohammed khair abdalla professor of genetics in faculty of agriculture, university of khartoum for data management and statistical advices. 9. the author contributions 1. study concept and design: professor mohammed yousif sukkar. 2. collection of data: dr. nouralsalhin abdalhamid alaagib. 3. analysis and interpretation of data professor mohammed yousif sukkar and dr. nouralsalhin abdalhamid alaagib. 10. availability of data and material data is available in excel form and can be provided when requested. references [1] d. j. chinn, j. e. cotes, and j. w. reed, “longitudinal effects of change in body mass on measurements of ventilatory capacity,” thorax, vol. 51, no. 7, pp. 699–704, 1996. 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[20] j. parízková and p. bůzková, “relationship between skinfold thickness measured by harpenden caliper and densitometric analysis of total body fat in men.,” human biology, vol. 43, no. 1, pp. 16–21, 1971. [21] american thoracic society, “standardization of spirometry, 1994 update,” american journal of respiratory and critical care medicine, vol. 152, no. 3, pp. 1107–1136, 1995. doi 10.18502/sjms.v12i2.918 page 87 sudan journal of medical sciences production and hosting by knowledge e [22] world health organization, obesity and overweight. world health organization global strategy on diet, physical activity and health, 2003. doi 10.18502/sjms.v12i2.918 page 88 introduction materials and methods results discussion effect of body composition on ventilation parameters effect of bmi on ventilation parameters conclusion ethics approval competing interests acknowledgements the author contributions availability of data and material references sudan journal of medical sciences volume 12, issue no. 2, doi 10.18502/sjms.v12i2.916 production and hosting by knowledge e research article basic clinical characteristics and hospital outcomes of acute coronary syndrome patients sudan taha a. m.1 and mirghani h. o.2 1assistant professor of internal medicine, faculty of medicine, omdurman islamic university 2assistant professor of internal medicine, faculty of medicine, university of tabuk abstract background: there are variation in the presentation of the acute coronary syndrome between countries. the present study aimed to investigate the basic clinical characteristics and in-hospital outcomes among acute coronary syndrome patients in the sudan. material and methods: a cross-sectional comparative study conducted among 202 consecutive acute coronary syndrome patients at a reference coronary care unit in omdurman teaching hospital between july 2014 and august 2015. participants signed a written informed consent, and then a case report form was filled. information collected include vascular risk factors, vital signs, echocardiographic findings, and in hospital complications. the local ethical committee approved the research, and the chi-square test was used to compare st-segment elevation (stseacs) and none st-segment elevation acute coronary syndrome (nstseacs). results: (out of 202 women (53.75%) in (nseacs) p = 0.009). prior myocardial infarction, hypertension, diabetes mellitus, and, smoking were evident in 19.8%. 53.%, 30.2%, and 16.6% of acute coronary syndrome respectively, 97% of patients presented with chest pain, 54% presented to the hospital after 24 hours. hypotension, heart failure, low ejection fraction, and in-hospital complications were more in (stseacs) than (nstseacs), while (nsteacs) patients received less thrombolysis and percutaneous coronary angioplasty p-value < 0.05. conclusions: acute coronary syndrome patients were younger and had more complications than others in the west. st-segment elevation myocardial infarction patients are more likely to develop in-hospital complications and to receive reperfusion therapy. the limitation of the study is the lack of followup information after discharge. keywords: acute coronary syndrome, primary, hospital outcomes how to cite this article: taha a. m. and mirghani h. o., (2017) “basic clinical characteristics and hospital outcomes of acute coronary syndrome patients sudan,” sudan journal of medical sciences, vol. 12 (2017), issue no. 2, 52–62. doi 10.18502/sjms.v12i2.916 page 52 corresponding author: mirghani h. o.; email: h.mirghani@ut.edu.sa received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e taha a. m. and mirghani h. o.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:h.mirghani@ut.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e هدفت البلدان. بين الحادة التاجي الشريان متالزمة أعراض يف تباين هناك الخلفية: داخل والنتائج األساسية السريرية الخصائص على التعرف إىل الحالية الدراسة المستشفى بين مرضى متالزمة الشريان التاجي الحادة يف السودان. متالزمة مرضى من متتابعا مريضا ٢٠٢ بين أجريت مقطعية دراسة والطرق: المواد درمان أم مستشفى يف التاجية للرعاية المرجعية الوحدة يف الحادة التاجي الشريان التعليمي بين يوليو / تموز ٢٠١٤ وأغسطس / آب ٢٠١٥. ووقع المشاركون موافقة خطية عوامل جمعها تم التي المعلومات وشملت الحالة. تقرير نموذج ملء تم ثم مستنيرة، ىف والمضاعفات القلب، صدى تخطيط ونتائج الحيوية، والعالمات الوعائية، الخطر المستشفى بعد موافقة اللجنة األخالقية المحلية على البحث. وتم استخدام اختبار كاى سكوير لمقارنة النوعين من التغييرات ىف تخطيط القلب الكهرباىئ من متالزمة الشريان التاجي الحادة (ارتفاع وصلة س ىت وعدم ارتفاع وصلة س ىت). النتائج: من أصل ٢٠٢ كانت نسبة الذكور(٥٧٫٥٪). (٥٣٫٧٥٪) من النساء يمتالزمة الشريان التاجي الحادة مع عدم ارتفاع وصلة س ىت p= ٠٫٠٠٩. تاريخ سابق الحتشاء عضلة القلب وارتفاع ضغط الدم وداء السكري، والتدخين كانت واضحة يف ١٩٫٨٪. ٥٣.٪، ٣٠٫٢٪، و ١٦٫٦ ٪ من متالزمة الشريان التاجي الحادة على التوايل، و ٩٧٪ من المرضى الذين يعانون من الدم، ضغط انخفاض وكان ساعة. ٢٤ بعد المستشفى إىل قدمت ٪٥٤ و الصدر، يف آالم متالزمة يف كثر أ المستشفى داخل والمضاعفات المنخفض، الطرد وجزء القلب، وفشل الشريان التاجي الحادة مع ارتفاع وصلة س ىت من تلك التى بدون ارتفاع لوصلة س ىت، يف حين تلقى المرضى بمتالزمة الشريان التاجي الحادة بدون ارتفاع لوصلة س ىت نسبة أقل .٠٫٠٥> p العالجات الحالة للجلطات الجلطات والدعامات التاجية عن طريق الجلد من تعقيدا كثر وأ سنا أصغر الحادة التاجي الشريان متالزمة مرضى كان اإلستنتاجات: كثر أ ىت س وصلة ارتفاع مع الحادة التاجي الشريان متالزمة مرضى الغرب. يف غيرهم من الحد التروية. اعادة عالج على والحصول المستشفى يف المضاعفات لتطوير عرضة الدراسة هو عدم وجود معلومات المتابعة بعد الخروج من المستشفى. 1. introduction irrespective of the income classification, ischemic heart disease nowadays is the world leading cause of adult and old age morbidity and mortality, representing 12.7% of global mortalities, the burden is involving all countries and communities [1]. compared to male, many studies showed that females have a higher incidence of non-st-segment elevation myocardial infarction than unstable angina or st-segment elevation myocardial infarction, while males had a higher incidence of st-segment elevation myocardial infarction (stemi) than non-st-segment elevation myocardial infarction (nstemi) or unstable angina. men affected by all variety of ischemic heart disease at a younger age than women, due to the higher incidence of risk factors and protective effect of estrogens [2, 3]. doi 10.18502/sjms.v12i2.916 page 53 sudan journal of medical sciences production and hosting by knowledge e there has been a shift in the clinical presentation of acute coronary syndrome towards milder forms and unstable angina [4, 5]. lower case fatalities in patients admitted with acute coronary syndrome had also been observed [6]. differences in acute coronary syndrome presentation had been found not only between developed and developing countries but also between north-south areas of western european countries [7, 8]. national socioeconomic characteristics in various countries, the severity of acute coronary syndrome, and the subsequent management are to blame as the primary causes of the differences in the clinical presentation and outcome in coronary syndrome [9–11]. sudan is taking about 2% of the earth’s surface with economic, social, and ethnic diversity. furthermore cardiac care centers are lacking and mainly focused in the capital of the country, there is poverty of staff trained in cardiac care, and transportation is either insufficient in outreaching underserved areas or overcrowded with marked traffic congestion in the major cities, thus, we conducted this research to study the pattern of acute coronary syndrome in omdurman teaching hospital in sudan to see whether the above-mentioned differences and barriers to coronary care affect the presentation and outcome of acute coronary syndrome patient. 2. material and methods a cross-sectional descriptive longitudinal study was conducted at the coronary care unit in omdurman teaching hospital during the period from july 2014 to august 2015. the acute coronary care unit is serving a vast area including omdurman city and the adjacent western regions. the study included 202 (125 males, and 87 females) consecutive patients with the diagnosis of the acute coronary syndrome. the patients (18 years and above) were approached in a ratio of 1:1 and severely ill patients and those who were unable to give their consent were excluded. the diagnosis of st-segment elevation myocardial infarction (stemi), unstable angina, none st-segment elevation myocardial infarction (nstemi)was based on typical chest pain, electrocardiographic (ecg) changes, and elevated cardiac biomarkers following the american college of cardiology guidelines [13]. nstemi and unstable angina were collectively referred to as none st-segment elevation acute coronary syndrome (nsteacs). all patients signed a written informed consent, then interviewed and examined by the assigned acute coronary care unit physician. a case report form was filled including basic clinical and cardiovascular risk factors,(hypertension, diabetes mellitus, family history of myocardial infarction, and smoking). the presenting complaint, vital signs (pulse, blood pressure, respiratory rate) were recorded and followed. the ejection fraction (ef) has been registered by echocardiography, as was the intramural doi 10.18502/sjms.v12i2.916 page 54 sudan journal of medical sciences production and hosting by knowledge e thrombus. the ejection fraction (ef) was categorized to severe left ventricular (lv) dysfunction: (ef) < 30%, moderate lv dysfunction: ef = 30-40%, mild lv dysfunction: ef = 40-55%, and normal lv function: > 55% [2]. treatment by thrombolytic therapy or percutaneous coronary angioplasty (pci) was recorded, patients were then followed for the development of complications (including arrhythmias, heart failure, cardiogenic shock, and death). the following definitions were adopted for the purpose of this research; diabetes mellitus: self-reported or being on oral hypoglycemic agents and/or insulin, hypertension: self-reported, on antihypertensive therapy, history of systolic blood pressure more than 140 mmhg or diastolic blood pressure more than90 mmhg, current smoking: cigarette, cigar, pipe, or shisha smoking during the last year, family history of premature coronary artery disease: history of angina, myocardial infarction, or sudden cardiac death in first-degree relatives at age less than 65 years in females and less than 55 age in males, heart failure: shortness of breath on exertion and/or at rest, paroxysmal nocturnal dyspnea associated with clinical signs of pulmonary and/or peripheral edema requiring treatment with diuretic therapy, and cardiogenic shock: persistent hypotension unresponsive to fluid administration and requirement for intravenous inotropic therapy or insertion of intra-aortic balloon pump . various parameters were then compared between stemi and nstemacs. the ethical committee of omdurman teaching hospital approved the research and, the statistical package for social science (spss) version 20 was used for data analysis, the chi-square test was used to compare categorical data. the data were presented as ranges, percentages or mean ± sd with a p-value < 0.05 considered significant. the primary objective of the research was to study the pattern of the acute coronary syndrome patients admitted to the coronary care unit in omdurman teaching hospital, sudan. the secondary objectives were to assess the basic clinical characteristics, symptoms at the presentation, the time the patients were presented to the hospital, the mode of therapy received, and the complications that developed inside the hospital. the research was self-funded and not supported by any organization. 3. results out of two hundred and two acute coronary syndrome patients, 57.5% were males. women dominance was evident in nsteacs (53.75 vs. 31.25) p-value = 0.009.prior myocardial infarction, hypertension, diabetes mellitus, and, smoking were evident in 19.8% (p-value = 0.158), 53.% (p-value = 0.573) , 30.2% (p-value = 0.762) and 16.6% (p-value = 0.180 respectively with no significant statistical difference between stemi and nsteacs patients. the majority of patients presented with ischemic chest pain (96.8% in stemi vs. 95.2 % nsteacs with no significant difference between the two doi 10.18502/sjms.v12i2.916 page 55 sudan journal of medical sciences production and hosting by knowledge e groups p-value = 0.778. it is interesting to show that: the majority (58%) of acute coronary syndrome patients presented to the hospital later than 24 hours with no significant difference between groups, p-value = 0.636. table (1) illustrated the basic clinical characteristics of the acute coronary syndrome patients. table (2) depicted the hospital course of acute coronary syndrome patients in which tachycardia and irregular pulse were detected in 44.3%, and 23.7% of patients with no significant statistical difference between stemi and nsteacs (p-value = 0.120). hypotension was more common among patient with stemi (35.3% vs.16%) with statistical significant difference p-value = 0.012, as were low ejection fraction (71.8% vs, 53.7%) p-value = 0.009, and intraventricular thrombus (7.2% vs.3.7%) in stemi and nsteacs p-value = 0. 357. a high significant statistical difference was found between stemi and nsteacs regarding reperfusion therapy: thrombolytic was given to 25% and 1.8% of the patient respectively, p-value < 0.001, while 15.6% and 5.6% of stemi and nsteacs underwent pci respectively p-value = 0.023. in-hospital complications developed in 68.7% of stemi and 50.9% of nsteacs patients with significant statistical difference p-value = 0.015 arrhythmias were found in 27% of stemi and 34% of nsteacs; heart failure was evident in 51% and 47% of patients with stemi and nsteacs respectively. cardiogenic shock developed in 11.4% of stemi and 10.3 of nsteacs while in hospital mortality was reported in 7.3% and 5.6% of patients with stemi and nsteacs respectively (table3). 4. discussion the current study showed that acute coronary syndrome patients in sudan were younger and had more complications than their western counterparts. st-segment elevation myocardial infarction patients are more likely to develop in-hospital. in the current study nsreacs (52.5%)was commoner than stemi in accordance with the previous studies [16]. the high rate of stemi can be explained by the younger age of this sample that is less by more than a decade compared to developed countries; similar results had been observed in gulf states and malaysia [17]. in this study, nsteacs was more common in females similarly el-menyar et al., and dey et al. reported the higher prevalence among women [18, 19]. regarding coronary risk factors, hypertension was detected in 53.5% of acute coronary syndrome patients in agreement with alhabib et al. [20] who published a study in saudi arabia and reported high blood pressure in 55.3% of acute coronary syndrome patients, but diabetes mellitus was almost double the rate of the present study that may be due to obesogenic diet and adoption of work involving inactivity in saudi arabia. doi 10.18502/sjms.v12i2.916 page 56 sudan journal of medical sciences production and hosting by knowledge e variable overall % stemi % nsteacs % p-value odd ratio sex males 57.5 68.8 46.3 0.009 females 42.5 31.2 53.7 prior myocardial infarction 19.8 23.9 16 0.158 0.669 diabetes mellitus 30.2 31.2 29.2 0.762 0.936 hypertension 53.5 55.7 51 0.573 1.09 smoking 16.6 18.7 14.5 0.18 ischemic chest pain 96.8 95.2 0.778 duration of pain <6 hours 3 2.1 3.9 0.636 6-12 hours 39 37.5 40.5 >12 hours 58 60.4 55.6 t 1: basic clinical characteristics of acute coronary syndrome patients. the lower rates of smoking (16.6%), especially among females (1.2%), may be due to the conservative society in sudan, higher rates were reported by akram h. al-khadra [21] and mohammed et al. [22] in saudi arabia. in this study stemi patients were more likely to have hypotension, low ejection fraction, and high in-hospital complications (35.4%, 71.8%, and 68.7% respectively as compared to nsteacs counterparts (16%, 53.7%, and 50.9% respectively) p-values < 0.05), in agreement with study conducted in western european countries and found lower rates of complication in nstemi as compared to stemi [22]. in the current study only 3.5% of acute coronary syndrome patients arrived at hospital before 6 hours, this could be due to lack of knowledge about how dangerous is chest pain, shortage of life support health teams, and traffic congestion, furthermore 25% and 1.8% of stemi and nsteacs received thrombolytic therapy, and 15.6% and 5.6% of stemi and nsteacs received pci respectively. the rates of thrombolysis and pci were lower than the rates in western european countries in [22] which thrombolysis and pci were recorded in 20.8% and 53.3% respectively). the delayed arrival at hospital and the subsequent management could explain the higher rates of complications in acute coronary syndrome patient (low ejection fraction in 62.6%, cardiogenic shock in 10.8%, and in-hospital death in 6.5%), alhabib et al. [20]. in saudi arabia reported death in 3% and cardiogenic shock in 4.3% and were lower than our results. doi 10.18502/sjms.v12i2.916 page 57 sudan journal of medical sciences production and hosting by knowledge e character overall % stemi % n = 96 nstemi % n = 106 p-value odd ratio tachycardia 44.3 48.1 40.5 0.102 irregular pulse 23.5 29.1 17.9 0.102 hypotension 25.7 35.4 16 0.012 thrombolysis 13.4 25 1.8 0 0.075 pci 10.6 15.6 5.6 0.023 0.362 low ejection fraction 62.7 71.8 53.7 0.009 intraventricular thrombus 5.5 7.2 3.7 0.357 0.518 hypertriglyceridemia 16.4 17.7 15.1 0.704 0.852 hypercholesterolemia 17.8 17.7 17.9 0.1 1.012 renal impairment 20.5 25 16 0.119 0.642 in-hospital complications 59.8 68.7 50.9 0.015 0.741 t 2: hospital course of acute coronary syndrome patients. complication overall % stemi % nstemi % p-value arrhythmias 30.5 27 34 0.31 heart failure 49 51 47 cardiogenic shock 10.9 11.4 10.3 death 6.5 7.3 5.6 t 3: in-hospital complications of acute coronary syndrome patients [1] complications and to receive reperfusion therapy. 5. conclusion this study presented a sample of acute coronary syndrome sudanese patients with many unwanted features including the late presentation to hospital, reduced rates of reperfusion therapy and high in-hospital complications. raising the awareness of the public about the seriousness of chest pain, recruitment and training of acute coronary care management providers, and the establishment of an effective basic life support network are needed to improve management and thus the outcome of acute coronary syndrome. adherence to coronary care management guidelines is badly needed to avoid under treatment particularly of those with nsteacs patients. larger multicenter studies are highly required to assess the causes of the delayed presentation to doi 10.18502/sjms.v12i2.916 page 58 sudan journal of medical sciences production and hosting by knowledge e the hospital and the low rate of reperfusion therapy among patients with the acute coronary syndrome. limitation of this study is that it was conducted at a single tertiary care center so generalization cannot be insured, the relatively small sample of patients is also. of note. we did not record the effects of drug therapy and followed patients for longterm complications, this calls for larger multicenter studies to assess the obstacles to an efficient coronary care program. 6. ethical approval the ethical committee of omdurman teaching hospital approved the research. 7. competing interests the authors declared that there is nothing to disclose in term of funding or any relationship or activity that interfere with the present study. 8. availability of data material the authors declare that all the data collected including the questionnaires, master sheet, and the statistical output are available. 9. funding the current study is self-funded by the researchers and not supported by anybody or organization. 10. abbreviations and symbols stseacs: st-segment elevation acute coronary syndrome nsteacs: non-st-segment elevation acute coronary syndrome stemi: st-segment elevation myocardial infarction nstemi: non-st-segment elevation myocardial infarction ecg: electrocardiograph ef: ejection fraction lv: left ventricle pci: percutaneous coronary angioplasty doi 10.18502/sjms.v12i2.916 page 59 sudan journal of medical sciences production and hosting by knowledge e spss: statistical package for social sciences sd: standard deviation bioethics: all the participants signed a written informed consent after the approval clearance was obtained from omdurman teaching hospital ethical committee. references [1] j. a. finegold, p. asaria, and d. p. francis, “mortality from ischaemic heart disease by country, region, and age: statistics from world health organisation and united nations,” international journal of cardiology, vol. 168, pp. 934–945, 2012. 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[20] k. f. alhabib, a. hersi, h. alfaleh et al., “baseline characteristics, management practices, and in-hospital outcomes of patients with acute coronary syndromes: results of the saudi project for assessment of coronary events (space) registry,” journal of the saudi heart association, vol. 23, no. 4, pp. 233–239, 2011. [21] a. h. al-khadra, “clinical profile of young patients with acute myocardial infarction in saudi arabia,” international journal of cardiology, vol. 91, no. 1, pp. 9–13, 2003. doi 10.18502/sjms.v12i2.916 page 61 sudan journal of medical sciences production and hosting by knowledge e [22] o. s. mohammed, h. o. mirghani, and a. a. alyoussuf, “pattern and outcomes of acute myocardial infarction in tabuk, saudi arabia,” basic research journal of medicine and clinical sciences, vol. 4, no. 7, pp. 193–198, 2015. doi 10.18502/sjms.v12i2.916 page 62 introduction material and methods results discussion conclusion ethical approval competing interests availability of data material funding abbreviations and symbols references sudan journal of medical sciences volume 12, issue no. 2, doi 10.18502/sjms.v12i2.920 production and hosting by knowledge e research article hepatitis b virus_surface gene mutations and their clinical implications yassir m. hamadalnil1 and sahar bakheit2 1department of microbiology, faculty of medicine, shendi university, sudan 2institute of endemic diseases, university of khartoum, sudan abstract hepatitis b infection is a major public health problem caused by hepatitis b virus (hbv). factors associated with host immunity such as (hbv specific tand/or bcell) production and antigen presentation failure and viral determinants such as the hbv genotypes and their evolving variants, have largely contributed to and justified variations that occur in the hbv surface gene. hepatitis b surface gene mutations may influence the accuracy of the results obtained with currently used serological diagnostic tests and may represent a great risk for the community, since neither hepatitis b vaccines nor hepatitis b immunoglobulin will prevent the infection by hbv. out of 96 published papers from (1988 till 2016) downloaded from google scholar and pubmed and evaluated according to the relevance of scientific data for the surface gene mutations of hepatitis b virus then52 papers of them were selected and included in this study, then we reviewed and evaluated the current published papers about the surface gene mutations worldwide in which g145r represents the most common hepatitis b surface gene mutation reported in the literature. furthermore, we reviewed their clinical implications and their impact on hepatitis b vaccination and treatment. keywords: hbv escapes mutants, hbsag, hbsag gene, hamadalnil & bakheit, hb virus_surface gene mutations and their clinical implications how to cite this article: yassir m. hamadalnil and sahar bakheit, (2017) “hepatitis b virus_surface gene mutations and their clinical implications,” sudan journal of medical sciences, vol. 12 (2017), issue no. 2, 96–113. doi 10.18502/sjms.v12i2.920 page 101 corresponding author: yassir m. hamadalnil; email: aboalyoosr21@hotmail.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e yassir m. hamadalnil and sahar bakheit. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:aboalyoosr21@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e عدوى التهاب الكبد الفيروسى الوباىئ هي مشكلة صحية عامة رئيسية ناجمة عن فيروس التهاب الكبد الوباىئ. العوامل المرتبطة بحصانة المضيف مثل انتاج الخاليا التائية والبائية مثل الفيروسية ومحددات المستضد تقديم وعدم الوباىئ الكبد لفيروس المحددة وبررت كبير حد إىل ساهمت له، المتطورة والمتغيرات الوباىئ الكبدي اللتهاب المورثات االختالفات التي تحدث يف الجين لسطح هذا الفيروس. الطفرات التى تحدث للمستضد السطحي لفيروس التهاب الكبد الوباىئ قد تؤثر على دقة النتائج التي يتم الحصول عليها ىف اختبارات التشخيص المصلية المستخدمة حاليا وقد تمثل خطرا كبيرا على المجتمع، عن العدوى تمنع الوباىئ الكبد التهاب لفيروس مناعية غلوبولينات أو لقاحات ال حيث طريق هذا الفيروس. من أصل ٩٦ من األبحاث المنشورة ىف الفترة (١٩٨٨ حتى ٢٠١٦) تم تحميلها من باحث جوجل والبيب ميد تم تقييمها وفقا ألهمية البيانات العلمية للطفرات هذه يف وادرجت منها ورقة ٥٢ اختيار تم الوباىئ الكبد التهاب فيروس لسطح الجينية لسطح الجينية الطفرات حول الحالية المنشورة األوراق وقييمنا استعرضنا ثم الدراسة، فيروس التهاب الكبد الوباىئ يف جميع أنحاء العالم والتى مثل فيها الجين g١٤٥r الطفرة يف ذكرت التى الوباىئ الكبد التهاب فيروس لسطح الجينية الطفرات من شيوعا األكثر ضد والتطعيم العالج على وأثرها السريرية آثارها استعرضنا ذلك، على وعالوة األدب. التهاب الكبد الوباىئ. 1. introduction hepatitis b is considered a life -threatening liver infection caused by hepatitis b virus. it affects about 350 million people around the world and it is associated with high risk of liver cirrhosis and hepatocellular carcinoma (hcc) [1]. chronic hepatitis b infection is considered as an important healthcare problem worldwide due to the significant morbidity and mortality as well as being the cause of at least 50% of worldwide cases of hepatocellular carcinoma and approximately 30% of liver cirrhosis [2]. according to world health organization (who) more than 780,000 deaths occur worldwide annually due to chronic complications of hbv associated liver disease [3]. the prevalence of hbv carriers varies from 0.1% to 2% in low prevalence areas (united states and canada, western europe, australia and new zealand followed by 3% to 5% in intermediate prevalence areas (mediterranean countries, japan, central asia, middle east, and latin and south america) and 10% to 20% in high prevalence areas (southeast asia, china, sub-saharan africa) [4].the seroprevalence of hbsag in central sudan is 17.5% [5]. hbv genome is a circular double stranded dna of full length negative strand (3020 – 3320) and incomplete positive strand (1600 – 2800). it is composed of four partially overlapping open reading frames (s, c, p and x) [6]. the s orf encodes the surface envelope protein of the virus (hbsag) and can be subdivided into pre s1, pres2 and s regions. as illustrated in figure 1, the core gene (c gene) is divided into pre core doi 10.18502/sjms.v12i2.920 page 102 sudan journal of medical sciences production and hosting by knowledge e and core regions where p gene (polymerase protein) is about 800 amino acids that is divided into three domains. the x orf protein domain (hbxag) is involved in signal transduction, dna repair and transcriptional activation. the mechanism of hbxag is not completely understood but it may contribute to oncogenic activity of hbv [7]. studies suggested that there are a lot of virus genotypic variants and associated spectrum of pathogenicity. mutations in the s gene region occur under the selection of passive or active immunoprophylaxsis and antiviral treatment or spontaneously [8]. the aim of this review was to highlight the most common mutations of hbv surface gene and their clinical impacts. 2. material and methods pubmed (www.ncbi.nlm.nih.gov) and google scholar was searched with keywords like “hbv”, “hepatitis b virus”, “hepatitis b virus surface gene mutations” and related words, to finalize this review article. ninety-six research and review articles were selected. the selection criteria, of these research and review articles, were to include the data which represent the global burden of s gene mutations. the exclusion criteria were irrelevant scientific data. finally, 52 papers selected and included in this study. this review done during the period of 4 moths from sep – dec 2016. 2.1. host immune response to hbv innate immunity eventually plays a role immediately after infection to limit the virus multiplication and initiates the development of an adaptive immune response. innate host responses during the establishment of viral infections are mainly characterized by the production of cytokines such as type 1 interferon (ifn)a/b and the activation of natural killer (nk) cells. production of type 1 ifns can be induced directly by virus replication via cellular mechanisms that detect the presence of viral rna or dna. nk cells are activated by the recognition of stress-induced molecules and/or the alteration of the quantity of major histocompatibility complex (mhc) class i molecules on the surface of infected cells [9]. in adaptive immune response the antigen presenting cells kupffer cells and dendretic cells responsible for the activation of hbv specific t cells and production of interleukin 12(il12) and tnf a, which induce ifn g production and proliferation of cd8+ t cells which is the main effector in hbv clearance. in contrast depleted cd8+ t cells in acutely infected individuals associated with the persistence of hbv infection. the synergistic effect of cytokines and cytolytic activity of cd8+ t cells allows for clearance of the virus without progressive liver damage and is consistent doi 10.18502/sjms.v12i2.920 page 103 www.ncbi.nlm.nih.gov sudan journal of medical sciences production and hosting by knowledge e with viral and lymphocyte kinetics noticed in chimpanzees following acute hbv infection. activated t-helper cell type 2 (th2) cd4+ t-cells shown to induce b-cell production of hbsab, hbcab and hbeab in patients undergone hbv clearance [10, 11]. 2.2. virology and genotypes the hbv genome is a relaxed double-stranded circular dna molecule of 3.2 kb in length [12]. it is classified into ten genotypes (a-j) that are scattered at different geographical areas and each has specific clinical outcome. genotyping is usually done using different techniques such as line probe assay, genotype specific polymerase chain reaction and restriction fragment length polymorphism [13]. acute infection with genotype d is considered as the main cause of acute liver failure than other genotypes [14] while genotype a appears to have more favorable outcome than genotype d [15]. genotype c appears to have a significantly higher viral load than genotype b [16]. 2.3. hbv life cycle the replication process started with the entry of the hbv into the hepatocytes, then the virion undergoes uncoated process and transported to the nucleus in which rc dna is converted into covalently closed circular dna (cccdna), cccdna is transcribed into subgenomic rna (sgrna) and pregenomic rna (pgrna) [17, 18]. the subgenomic transcriptis used for the translation of envelope protein and x protein. the pgrna is used as a template for reverse transcription, translation of hbcag and hbv pol [19]. in the cytoplasm the pgrna is undergo reverse transcription to a nucleocapsid contain dna which is enveloped to be secreted as progeny virion through the endoplasmic reticulum [20]. 2.4. epidemiology and clinical infection the geographical distribution of hbv genotypes and hbsag is as follows; genotype a is found in north america and northwestern europe, genotypes b and c are found in east asia, genotype d is highly prevalent in the mediterranean and the middle east, genotype e identified in west africa, genotypes f and h are most prevalent in central and south america, and genotype g is found in the united states and europe [21, 22]. in 2008 scientists isolated genotype i and the genotype j from japanese patients [23, 24]. hbv is transmitted by exposure to infected blood or other body fluids. hbv transmission has been reported with several forms of human contact such as mother to child, household, sexual, needle stick and occupational/health care related. the highest concentrations of infectious hbv are found in blood and serum. however, other body doi 10.18502/sjms.v12i2.920 page 104 sudan journal of medical sciences production and hosting by knowledge e figure 1: hbv genome showing open reading frames, major rna transcripts and the regulatory elements of the virus [19]. with permission from prof stephen locarnini. fluids, such as semen and saliva, are also infectious [25]. hbv infection may result in subclinical or asymptomatic infection, acute self-limited infection, or fulminant hepatitis requiring liver transplantation. people infected with hbv can develop chronic hbv infection, which may lead to cirrhosis or hepatocellular carcinoma, the likelihood that newly infected individuals will develop chronic hbv infection is related to their age at the time of infection [26]. 2.5. hepatitis b surface antigen (hbsag) hepatitis b surface antigen is a complex macromolecular structure that provides the envelope protein of hbv, it is composed of 75% proteins and 25% carbohydrates and host derived lipids. hbsag produced during the infection of hepatocytes in the form of lipoprotein of 22nm diameter. the hbv envelop proteins composed of pres1, pre-s2 and s. the s protein, which codes for the s gene which is made up of 226 amino acids and is the main component of the viral envelop protein [27]. the three envelop proteins can be translated as l (large), m (middle) and s (small) or collectively hbsag. within the later the site between the aa 100-160 termed as major hydrophilic region (mhr). this region comprised of aa 99-160 refers to ”a” determinant region. mhr proposed to have two major loops and one minor loop which defined by some disulphide bridge that join the epitope cluster for which majority of anti hbs directed are against the epitope between aa 107-137 or (138), 139-147 or(149) and 121-124 [28]. doi 10.18502/sjms.v12i2.920 page 105 sudan journal of medical sciences production and hosting by knowledge e the ”a” determinant is considered as the main neutralizing epitope and its common in all hbv genotypes, for this reason the anti hbs against the ”a” determinant are widely protective against reinfection by hbv [29]. changes in the conformation which can successively lead to failure of binding of neutralizing antibodies may develop due to amino acid substitutions within the” a” determinant [30]. mutations in hbv occur due to low fidelity of polymerase, high replication rate and overlapping reading frames. the pre-s1/s2/s orfs codes for three envelope proteins (large, middle and small) which are responsible for virus assembly and attachment to hepatocytes. l protein pre-s1 domain (amino acids 21–47) is the substrate for viral receptor attachment; m protein (pre-s2 domain) function is not well understood and, finally, s protein (s domain) is the hbsag. mutation in hbv is either vaccine induced or drug induced and these mutations can lead to occult hepatitis b infection, hbv reactivation and reinfection. also it may lead to diagnostic assay failure [31]. hbsag contains the epitope for ”a” determinant region between the amino acid residue 99169 and amino acid changes in this site that lead to mutations that escape the immune response that provided by the vaccine [32]. 2.6. mutations in hbv genes several published studies suggested that hepatitis b virus (hbv) mutants must be considered in occult hbv infection (obi) which is characterized by the presence of hbv infection without detectable hbsag. however, it is not known how widespread these mutants are and how they change the course of liver diseases. jin lin hou et al. studied 2,565 individuals with chronic hepatitis b infection, hemodialysis patients, blood bank donors and cryptogenic liver cirrhosis. they found that 51 of them had occult hepatitis b infection and 43% of them had mutations in the mhr region includes the following q101k, t115a, k122n, t123a, t126n, q129n, g130r, t131i, m133t, f134l, c138y, k141e, p142s, g145r, n146s, and c147f/r1 [33]. the existence of occult hbv patients caused by hbsag mutants has implications for their possible transmission role through sexual contact and by blood transfusion. naturally occurring mutations may envolve the polymerse gene as the tyrosine –methionine-aspartate-aspartate (ymdd-motif) mutations can occur spontaneously without using of antiviral therapy. accumulation of base mismatch due to the natural features of viral polymerase might be the cause of this mutation [34]. 2.7. vaccine escape mutants hbv vaccine is a recombinant dna vaccine that contains hbsag genetically engineered from the yeast sacchromyces cerevisiae. it provides seroprotection rate of 85 – 100 % doi 10.18502/sjms.v12i2.920 page 106 sudan journal of medical sciences production and hosting by knowledge e that seen one month after the last dose of vaccine and it confers immunity for at least 10 years [35]. vaccine escape mutants at the ”a” determinant region occurred under selection pressure of hbv vaccine administration or hepatitis b immunoglobulin (hbig) or both [36]. the first hbsag gene mutation was observed in vaccinated italian child who was presented with both hbsag and anti hbs. gene sequencing showed substitution in which glycine replaced by arginine at site 145(g145r mutant) [37]. this g145r represents the most prevalent hbsag mutation in the literature. it is addressed as a public health concern because of its capability of escaping the immune system and it found in immunocompromised patients and infant of hbeag positive mother with prevalence of 3.1%. it may accompany other mutations such as t126i-t131ac139y-e/d144g, t126i-m133l, and p120q-t126i in 37.5% [38]. ngui et al. studied 17 hbv-infected mother and infant pairs as the infants became infected with hbv inspite of immunoprophylaxis administration. the s gene was sequenced for all patients and 15 mother/infant pairs showed complete concordance, while in the other two pairs showed the following: in one infant there were three nucleic acid changes (p120q, f134y and d144a) and the other harbored the i126n substitution, mutations that might interfere with hbsag/anti-hbs binding [39]. furthermore, multiple point mutations such as deletions and recombination were discovered in the pres region. apart from the pres variants, a number of mutations had also been detected within the ”a” determinant of the major hydrophilic region (mhr) of the surface antigen, against which natural or vaccine induced neutralizing antibodies are generated [40]. 3. abbreviations v: vaccine, lmv: lamivudine, hbig: hepatitis b immunoglobulin, a: alanine, r: arginine, d: aspartate, c: cystine, f: phenylalanine, g: glycine, h: histidine, i: isolucine, l: lucine, m: methionine, p: proline, q: glutamine, r: arginine, s: serine, t: thrionine, w: tryptophane, y: tyrosine. hbv mutants remain stable over time and their transmission can occur horizontally or vertically [41]. missense mutations within the ”a” determinant were responsible 3.5% in 177 restaurant employee in china [42]. the high endimicity areas represent the most common regions in which vaccine escape mutants were abundant [43]. monica et al. reported a case about a caucasian man who develop acute hepatitis b infection inspite of having anti-hbs after vaccination, surprisingly this man acquired a mutant strain with diminished affinity for anti-hbs due to three amino acid substitutions discovered as follows (m125t, t127p and q129h),these mutations were rarely reported together [44]. doi 10.18502/sjms.v12i2.920 page 107 sudan journal of medical sciences production and hosting by knowledge e amino acid position wild type mutant cause 118 s w hbig 120 s/p q/s v-hbig 125 m t hbig 127 t p hbig 128 a v lmv 129 q h v-hbig 133 m l/i/t v-hbig 134 f/y n/r hbig 142 p s v 143 s l lmv 144 d a/e v-hbig 145 g a/r v/lmv/hbig 182 w s lmv 190 v a lmv 193 s l lmv 195 i m lmv 204 m v/i lmv t 1: the most studied hbv mutations: wild type, mutant type and the cause of mutations. done by the authors [33, 38, 39, 44]. 4. drug induced mutations the desired goal of treatment of chb infection is to arrest the progression of liver injury and to improve the quality of life by preventing progression to cirrhosis, hcc and death. so far, eradication of the virus is impossible and current antiviral treatment aims to reduce liver failure and hcc and to increase survival,through the effective hbv dna suppression [45]. united states food and drug administration (fda) has approved six drugs for the treatment of the chb infection, of these immunomodulator (pegyinterferon), nucleos(t)ide analogues (lamivudine, enticavir, telbivudine, adifovir and tenofovir) [46]. since the orf encoding hbsag overlaps with that of the polymerase, mutations within the former may affect the latter or vice versa, therapy with lamivudine results in several mutations in the polymerase gene, some of them are associated with alterations in the ‘a’ determinant of hbsag [47]. lamivudine is responsible for the highest rate of resistance reaching up to 70% by year 4 of continuous therapy [48]. naturally occurring mutations are restricted to the ”a” determinant region, whereas drug-associated mutations generally occur downstream to the mhr, kazim et al. has studied 57 patients with histological proven chb infection and were on lamivudine treatment of 100mg/day. serum samples were taken at base line then after lamivudine therapy, dna extracted and the region of mhr and flanking area were amplified and sequenced. the result showed that two patients (3.5%) have naturally occurring doi 10.18502/sjms.v12i2.920 page 108 sudan journal of medical sciences production and hosting by knowledge e mutations in the ”a” determinant of the s gene and 24.5% mutations was lamivudine induced and mainly occurs downstream of the mhr and associated with corresponding mutations in the polymerase gene. lmv selected mutations downstream of ”a” determinant considered as a cause of decrease in antigenicity of protein and binding to antihbs antibodies. in other recent studies, 8 out of 57 patients developed (rt204i/vdd) lamivudine resistant polymerase mutant that lead to surface gene mutations such as sw196stop, si195m and sw196l [49, 50]. gloria selabe et al. studied 17 patients with chronic hepatitis b infection who received 150mg/day lamivudine treatment at johannesburg general hospital between 1997 and 2004. mutations in the ymdd region were determined in 13 patients, of those 7 carried rtm204i, 2 of them were hepatitis b e antigen(eag) positive and 5 with eag negative, and the remaining 6 showed rtm204v mutation, 4 eag positive and 2 eag negative. additionally, the switching from rtm204i to rtm204v was reported in one patient after 24 months of therapy which indicates that lamivudine resistance may develop at similar rates in hbeag-positive and negative patients [51]. recently it was concluded that there is no benefit in continuing lamivudine therapy after emergence of ymdd mutations [52]. 5. conclusion the emergence of natural mutations should be expected due to the characteristics of the hbv genome such as proofreading capacity failure and viral factors such as the mechanisms of viral production and clearance. the mutations alter the binding of antibodies developed against wild-type s protein to virions and subviral particles and it can lead to diagnostic assay failure also. most patients with chronic 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[38] s. l. ngui, s. o’connell, r. p. eglin, j. heptonstall, and c. g. teo, “low detection rate and maternal provenance of hepatitis b virus s gene mutants in cases of failed postnatal immunoprophylaxis in england and wales,” journal of infectious diseases, vol. 176, no. 5, pp. 1360–1365, 1997. [39] s. datta, s. chatterjee, v. veer, and r. chakravarty, “molecular biology of the hepatitis b virus for clinicians,” journal of clinical and experimental hepatology, vol. 2, no. 4, pp. 353–365, 2012. [40] c. he, f. nomura, s. itoga, k. isobe, and t. nakai, “prevalence of vaccine-induced escape mutants of hepatitis b virus in the adult population in china: a prospective study in 176 restaurant employees,” journal of gastroenterology and hepatology (australia), vol. 16, no. 12, pp. 1373–1377, 2001. 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[52] j.-h. kao, “molecular epidemiology of hepatitis b virus,” korean journal of internal medicine, vol. 26, no. 3, pp. 255–261, 2011. doi 10.18502/sjms.v12i2.920 page 113 introduction material and methods host immune response to hbv virology and genotypes hbv life cycle epidemiology and clinical infection hepatitis b surface antigen (hbsag) mutations in hbv genes vaccine escape mutants abbreviations drug induced mutations conclusion references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9693 production and hosting by knowledge e editorial healthcare worker stress and burnout in the time of covid-19: a call for action ahmed s. a. el sayed1,2 1department of surgery, faculty of medicine, alzaiem alazhari university, khartoum north, sudan 2director, alazhari health research center, khartoum, sudan orcid: ahmed s. a. el sayed: https://orcid.org/0000-0001-7422-7169 the covid19 pandemic has come as a shock to the whole world. since it first became apparent in wuhan, china [1] in late 2019, till june 9, 2021, 174 million people were infected, and 3.76 million people had died [2]. the risk of infections among healthcare workers has been observed to be higher than in the general community [3], and this risk is carried on to people in their households [4]. the who has devised a protocol to help in this respect [5]. as of june 9, 2021, sudan had recorded 36,004 proven infections and 2,711 deaths [6]. moreover, 109 deaths were reported in doctors between january 14, 2020 and march 12, 2021 [7]. however, in this article, it is argued that this is only the tip of the iceberg. it is a well-established fact that healthcare workers suffer from an undue amount of stress and burnout [8], and our yet unpublished data show sudan is not an exception. the current covid 19 pandemic has further exacerbated this situation by increasing the stress levels among healthcare workers, as shown by data from countries as diverse as china [9], italy [10], and saudi arabia [11]. however, in sudan, the stress levels are expected to be comparatively more due to the current economic situation in the country with rampant inflation [12] and other consequent problems such as frequent power cuts. these effects of work-related stress, burnout, and other mental health consequences have been shown by previous epidemics (e.g., middle east respiratory syndrome) to have long-term consequences [11, 13, 14]. these long-term consequences, if not mitigated, would ultimately lead to decreased work productivity and less efficiency in the workplace [15]. unfortunately, in developing countries, a barrier to identifying and dealing with these mental health consequences is the stigma associated with these conditions [16]. this social stigma forces these individuals to either keep them a secret or withdraw from society [17]; as a consequence, they may not disclose their symptoms to healthcare professionals or even to their family and relatives [18]. another barrier is that even if the individual does not have a stigma, there is, unfortunately, a lack how to cite this article: ahmed s. a. el sayed (2021) “healthcare worker stress and burnout in the time of covid-19: a call for action,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 320–5. doi 10.18502/sjms.v16i3.9693 page 320 corresponding author: ahmed s. a. el sayed; email: asaelsayed@hotmail.com received 22 august 2021 accepted 08 september 2021 published 30 september 2021 production and hosting by knowledge e ahmed s. a. el sayed. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:asaelsayed@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ahmed s. a. el sayed of adequately trained individuals to treat them as it has been reported that for severe mental health disorders, there is a deficiency in treatment of 76–90% in lowand middleincome countries (lmics), respectively [19]. from the above, it becomes evident that in lmics, prevention is the way forward. this is easier said than done, as proven by a 2015 cochrane review that looked at published literature until then and concluded that that there was low-quality evidence that neither personal nor organizational interventions had any effect, if at all, in reducing stress [20]. this review concluded that organizational interventions need better focus on the reduction of specific stressors. researchers are continuing to look at possible solutions, and recently there have been some positive results [21]. from the perspective of sudan and in the current pandemic, some more recent literature looks more relevant. the most relevant of these was the coping with covid study [22], which mainly pointed out that for healthcare workers feeling valued by higher hospital authorities led to lower stress. this was confirmed by a subsequent work [23]. however, further data from the same group that has published the coping with covid study group [24] showed that in a large united states-based study of nearly 21,000 healthcare workers from 42 different organizations, 38% had anxiety/depression, 49% had burnout, and 50% felt not valued. the authors suggested that organizations should explore the causes of this (e.g., increased workload), and after that, organizations should consider targeted interventions such as peer support programs and changes in care infrastructure to facilitate support. the authors further developed a conceptual model portraying potential contributors and mitigators of stress and burnout, as shown in figure 1. figure 1: potential contributors and mitigators of stress and burnout [24]. following the above, similar interventions can easily be done in sudan after taking into consideration the local culture, as shown in the saudi arabian study [11], which showed stress and fear of contracting covid19 was particularly high amongst those who had vulnerable elderly family members at home which is highly likely to be true in our similar circumstances. doi 10.18502/sjms.v16i3.9693 page 321 sudan journal of medical sciences ahmed s. a. el sayed finally, a firm action should be taken on the unquestionably present scourge of stress and burnout among sudanese healthcare workers by identifying the risk factors and mitigating them. references [1] sun, j., he, w., wang, l., et al. (2020). covid-19: epidemiology, evolution, and crossdisciplinary perspectives. trends in molecular medicine, vol. 26, no. 5, pp. 483–495. [2] john hopkins university & medicine. (n.d.). john hopkins university coronavirus resource center. retrieved from: https://coronavirus.jhu.edu/map.html [3] nguyen, l. h., drew, d. a., graham, m. s., et al. (2020). risk of covid-19 among front-line health-care workers and the general community: a prospective cohort study. lancet public health, vol. 5, no. 9, pp. e475–e483. [4] shah, a. s. v., wood, r., gribben, c., et al. (2020). risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study. bmj, vol. 371, m3582. [5] world health organization. (2020). protocol for assessment of potential risk factors for 2019-novel coronavirus (covid-19) infection among health care workers in a health care setting. retrieved from: https://www.who.int/publications/i/item/protocolfor-assessment-of-potential-risk-factors-for-2019-novel-coronavirus-(2019-ncov)infection-among-health-care-workers-in-a-health-care-setting [6] john hopkins university & medicine. (n.d.). john hopkins university corona virus resource center – regional data (sudan). retrieved from: https://coronavirus.jhu.edu/ region/sudan [7] ibnouf, m. a. m. (2021). university staff and student protection from covid-19: strategic measures for teaching and learning in resource-limited setting. sudan journal of medical sciences, vol. 16, no. 1, pp. 1–4. [8] national academies of sciences engineering and medicine. (2019). taking action against clinician burnout: a systems approach to professional wellbeing. washington, dc: the national academies press. retrieved from: https://www.nap.edu/catalog/25521/taking-action-against-clinician-burnout-asystems-approach-to-professional [9] lai, j., ma, s., wang, y., et al. (2020). factors associated with mental health outcomes among health care workers exposed to coronavirus disease 2019. jama network open, vol. 3, no. 3, e203976. doi 10.18502/sjms.v16i3.9693 page 322 https://coronavirus.jhu.edu/map.html https://www.who.int/publications/i/item/protocol-for-assessment-of-potential-risk-factors-for-2019-novel-coronavirus-(2019-ncov)-infection-among-health-care-workers-in-a-health-care-setting https://www.who.int/publications/i/item/protocol-for-assessment-of-potential-risk-factors-for-2019-novel-coronavirus-(2019-ncov)-infection-among-health-care-workers-in-a-health-care-setting https://www.who.int/publications/i/item/protocol-for-assessment-of-potential-risk-factors-for-2019-novel-coronavirus-(2019-ncov)-infection-among-health-care-workers-in-a-health-care-setting https://coronavirus.jhu.edu/region/sudan https://coronavirus.jhu.edu/region/sudan https://www.nap.edu/catalog/25521/taking-action-against-clinician-burnout-a-systems-approach-to-professional https://www.nap.edu/catalog/25521/taking-action-against-clinician-burnout-a-systems-approach-to-professional sudan journal of medical sciences ahmed s. a. el sayed [10] rossi, r., socci, v., pacitti, f., et al. (2020). mental health outcomes among frontline and second-line health care workers during the coronavirus disease 2019 (covid19) pandemic in italy. jama network open, vol. 3, no. 5, e2010185. [11] alenazi, t. h., bindhim, n. f., alenazi, m. h., et al. (2020). prevalence and predictors of anxiety among healthcare workers in saudi arabia during the covid-19 pandemic. journal of infection and public health, vol. 13, no. 11, pp. 1645–1651. [12] ocha. (2021). sudan inflation hits 342 per cent in march. retrieved from: https: //reports.unocha.org/en/country/sudan/card/6yvup9af6k/ [13] lee, s. m., kang, w. s.,cho, a.-r., et al. (2018). psychological impact of the 2015 mers outbreak on hospital workers and quarantined hemodialysis patients. comprehensive psychiatry, vol. 87, pp. 123–127. [14] preti, e., di mattei, v., perego, g., et al. (2020). the psychological impact of epidemic and pandemic outbreaks on healthcare workers: rapid review of the evidence. current psychiatry reports, vol. 22, no. 8, p. 43. [15] stavroula, l., griffiths, a., and cox, t. (2003). work organisation and stress: systematic problem approaches for employers, managers and trade union representatives. protecting workers’ health series no. 3. [16] thornicroft, g., alem, a., and dos santos, r. a. (2010). wpa guidance on steps, obstacles and mistakes to avoid in the implementation of community mental health care. world psychiatry, vol. 9, no. 2, pp. 67–77. [17] link, b. g., cullen, f. t., struening, e. l., et al. (1989). a modified labeling theory approach in the area of mental disorders: an empirical assessment. american sociological review, vol. 54, no. 3, pp. 400–423. [18] shibre, t., negash, a., kullgren, g., et al. (2001). perception of stigma among family members of individuals with schizophrenia and major affective disorders in rural ethiopia. social psychiatry and psychiatric epidemiology, vol. 36, no. 6, pp. 299– 303. [19] patel, v., maj, m., flisher, a. j., et al. (2010). reducing the treatment gap for mental disorders: a wpa survey. world psychiatry, vol. 9, no. 3, p. 169. [20] ruotsalainen, j. h., verbeek, j. h., marine, a., et al. (2015). preventing occupational stress in healthcare workers [review]. cochrane database of systematic reviews, vol. 4, cd002892. [21] niks, i., de jonge, j., gevers, j., et al. (2018). work stress interventions in hospital care: effectiveness of the discovery method. international journal of environmental research and public health, vol. 15, no. 2, p. 332. doi 10.18502/sjms.v16i3.9693 page 323 https://reports.unocha.org/en/country/sudan/card/6yvup9af6k/ https://reports.unocha.org/en/country/sudan/card/6yvup9af6k/ sudan journal of medical sciences ahmed s. a. el sayed [22] linzer, m., stillman, m., brown, r., et al. (2021). preliminary report: us physician stress during the early days of the covid19 pandemic. mayo clinic proceedings: innovations, quality & outcomes, vol. 5, no. 1, pp. 127–136. [23] feingold, j. h., peccoralo, l., chan, c. c., et al. (2021). psychological impact of the covid-19 pandemic on frontline health care workers during the pandemic surge in new york city. chronic stress. retrieved from: https://doi.org/10. 1177{%}2f2470547020977891 [24] prasad, k., mcloughlin, c., stillman, m., et al. (2021). prevalence and correlates of stress and burnout among u.s. healthcare workers during the covid-19 pandemic: a national cross-sectional survey study. eclinical medicine, vol. 35, 100879. doi 10.18502/sjms.v16i3.9693 page 324 https://doi.org/10.1177{%}2f2470547020977891 https://doi.org/10.1177{%}2f2470547020977891 references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9698 production and hosting by knowledge e review article knowledge and adherence to covid-19 preventive measures: a continental review olabode e. omotoso1, elizabeth f. omotoso2, kehinde o. paimo1, john o. teibo3, and abolaji o. olagunju1 1department of biochemistry, university of ibadan, nigeria 2department of guidance and counseling, university of ibadan, nigeria 3department of biochemistry and immunology, university of sau paulo, brazil orcid: olabode omotoso: http://orcid.org/0000-0002-9291-9289 john teibo: http://orcid.org/0000-0002-0833-4828 abstract background: the burden of the novel coronavirus disease (covid-19) has been on the rise since it was first reported in december 2019. covid-19 has devastated global economy, public health, social interaction, and has claimed millions of lives globally within a few months. due to the severe effect of some of the instituted guidelines on citizens and the economy, some of the policies in place to curtail the spread were receded. hence, the present review aims to assess existing literature on the knowledge and adherence of africans toward the covid-19 preventive measures. methods: studies focused on africans’ knowledge and adherence to covid-19 preventive measures were selected using google scholar, scopus, and pubmed databases. preprints that have not been peer-reviewed, reviews, and non-covid-19 studies were excluded. results: all selected studies showed a satisfactory knowledge of respondents about covid-19 but poor level of adherence to the preventive measures. good knowledge and satisfactory level of adherence was common mostly among the clinical health workers, highly educated, and those with higher professional qualification, while poor knowledge and poor practice was observed mostly among rural dwellers, people of poor educational background, and those unable to read and write. conclusion: this review identified a relatively good knowledge about covid-19 from all the studies, however, the level of adherence to preventive measures was poor. we recommend that the populace adhere to the laid guidelines to ensure the spread of the virus is curbed while also enhancing the eradication of the pandemic. keywords: covid-19, adherence, knowledge, preventive measures, africa 1. introduction the rampaging novel coronavirus disease (covid-19) has become prevalent. the highly pathogenic severe acute respiratory syndrome coronavirus 2 (sars-cov-2), which causes covid-19, has spread globally, claiming over a million lives within a few how to cite this article: olabode e. omotoso, elizabeth f. omotoso, kehinde o. paimo, john o. teibo, and abolaji o. olagunju (2021) “knowledge and adherence to covid-19 preventive measures: a continental review,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 371–385. doi 10.18502/sjms.v16i3.9698 page 371 corresponding author: olabode e. omotoso; email: olabodeomotoso@gmail.com received 12 june 2021 accepted 09 september 2021 published 30 september 2021 production and hosting by knowledge e olabode e. omotoso et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:olabodeomotoso@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences olabode e. omotoso et al. months of its outbreak [1, 2]. coronaviruses are members of a large family of respiratory viruses, which cause mild to severe disease symptoms; ranging from common cold to severe respiratory illnesses [3]. sars-cov-2 is related to sars-cov and middle east respiratory syndrome (mers-cov) epidemics [4]. in humans, sars-cov-2 is transmitted through droplets, respiratory secretion, and direct contact with infected patients or surfaces [5]. the world health organization (who) on march 11, 2020 declared covid-19 a pandemic [6]. covid-19 outbreak in africa was predicted to be very lethal due to the prevalence of poor healthcare structure, lifestyle factors, poverty, and immunocompromised population (due to malaria, hepatitis virus, hiv/aids, etc.) in most african countries [7, 8]. high mortality due to covid-19 has been reported in the elderly and those with compromised immune system associated with chronic diseases [9]. although africa was eventually hit by the pandemic with index cases reported in egypt [10] and nigeria [11], surprisingly, the continent boasts of 84% recovery rate, which at this stage of the pandemic is higher than oceania (70%), north america (61%), and europe (48%) [2, 12]. the ongoing vaccination with covid-19 vaccines is a step in the right direction. however, a large percentage of the human population is still not being reached, especially those in lowand mid-income countries. hence, with the increasing daily covid19 human-to-human transmission, it is necessary to curtail the spread by instituting preventive and public health measures. the knowledge, attitude, and adherence of every individual toward covid-19 preventive guidelines are very germane to curtail the spread of the disease. the general knowledge, attitude, and practice help justify the need to determine the effectiveness of the measures put in place to control the spread of this disease [13]. this review article aims to review the knowledge and adherence to the covid-19 preventive measures in african population. 2. materials and methods 2.1. literature search a literature search was conducted in december 2020 on google scholar, scopus, and pubmed using the following keywords: “covid-19,” “knowledge,” “adherence,” “preventive measures,” restricting the search only to africa (being a continental review). preprints that have not been peer-reviewed, non-covid-19-related studies, and review articles were excluded (figure 1). doi 10.18502/sjms.v16i3.9698 page 372 sudan journal of medical sciences olabode e. omotoso et al. figure 1: flow chart illustrating the inclusion and exclusion criteria of the review. 2.2. studies on knowledge and adherence to covid-19 preventive measures the selected articles on knowledge and adherence to covid-19 preventive measures used for this review used questionnaires as research instruments with the number of respondents ranging from 141 to 3712 for a total of 14,911. the respondents consisted of correctional officers, healthcare workers, and chronic disease patients, residents of a conflict-affected area, urban slum dwellers, and sample populations from nigeria, egypt, cameroon, kenya, uganda, sudan, sierra leone, libya, and ethiopia. 2.3. knowledge about covid-19 table 1 presents 13 selected articles on the knowledge about covid-19 among healthcare workers and correctional officers in nigeria, hospital staff in libya, residents in a conflict-affected area in cameroon, chronic disease patients in ethiopia, and sample populations from egypt, sudan, sierra leone, kenya, and uganda. all reviewed articles reported satisfactory levels of respondents’ knowledge about covid-19. a study [14] on 446 healthcare workers including clinical and nonclinical staff in northcentral nigeria showed that the clinical staff (doctors = 18.86 ± 2.56; nurses = 18.96 ± 1.92; pharmacists = 18.6 ± 2.34; physiotherapist/lab scientist = 18.66 ± 2.42) had a higher knowledge about covid-19 compared to nonmedical staff (admin/accountant = 18.41 ± 2.41; transport/works = 17.83 ± 2.4). the healthcare workers’ knowledge about doi 10.18502/sjms.v16i3.9698 page 373 sudan journal of medical sciences olabode e. omotoso et al. covid-19 was significantly associated with their different job cadre with f value = 3.691; p = 0.001. furthermore, 79.9% of the 318 libyan healthcare workers studied had satisfactory knowledge about covid-19 [15]. their major sources of information about covid-19 were health practitioners (33.3%), social media platforms (30.2%), and journal articles (29.2%). in kenya, among 353 respondents sampled, most (83.97%) had very good knowledge about covid-19 [16]. social media platforms serve as a major source of information for 55% of the respondents. despite this, only half (50%) of the respondents have trust in the news and information on social media about the pandemic. among the 404 chronic disease patients (mean age 56.5 ± 13.5 years) in northwest ethiopia, only few (33.9%) had a good knowledge of covid-19 [17]. respondents’ age, illiteracy (unable to read and write), rural dwellers, and low monthly income were factors associated with poor knowledge of covid-19. this calls for concern as most severe covid-19 cases are seen in infected patients with comorbidities. hence, more drastic measures are needed to sensitize the high-risk individuals about the novel covid-19. in a study of 3712 egyptians, most (70.2%) had high satisfactory knowledge of covid19 [18]. high educational level was associated with good knowledge. this corroborates with another study in nigeria where there was a significantly higher knowledge level among 141 correctional officers sampled with higher educational qualifications [19]. in a binational study, egyptians were reported to be 1.8 times (95% ci: 0.43–0.74; p < 0.001) more likely to have more satisfactory knowledge about covid-19 than nigerians [20]. this disparity might be a result of public health literacy and the specific and peculiar measures implemented in both countries in curbing the spread of the pandemic. of the 362 respondents (mean age 33.5 ± 10.4 years) sampled in uganda [21], 264 (93.9%) had good knowledge about covid-19. television (77.4%) and social media (73.2%) were the major sources of information and there was no difference in respondents’ sociodemographic with respect to their knowledge about covid-19. among the 545 respondents (mean age 30.03 ± 11.2 years) sampled in conflictaffected areas in southwest cameroon [22], only 21.9% had very good knowledge about covid-19, while others had intermediate (43.8%), poor (34.4%), and no knowledge (11.92%). the respondents live in an anglophone crisis-affected area; hence, the knowledge gap observed might be a result of poor health literacy and adjustment to normal communal living. those with no knowledge of covid-19 (11.92%) were not included in the analysis. in line with earlier reports [21, 23], television (64.2%) and social media (38.8%) were also respondents’ major sources of information about the pandemic and doi 10.18502/sjms.v16i3.9698 page 374 sudan journal of medical sciences olabode e. omotoso et al. there was no association between respondents’ sociodemographic and their knowledge about covid-19. out of the 2336 respondents in sudan, the majority (84.7%) had a good level of knowledge. age (≤17 years), education (primary or lower school), low-income earner, and those who reside outside khartoum were related to lower covid-19 knowledge score [24]. a good knowledge level was also reported among 1253 respondents in sierra leone [25], 589 respondents from north-central nigeria [23] and a study of 1006 respondents from cameroon [13] with most (84.19%) having a high knowledge score. in all, a high proportion of the targeted populace in nigeria, kenya, ethiopia, uganda, sudan, south-west cameroon, sierra-leone, libya, and egypt had a good and satisfactory knowledge of covid-19. the knowledge of covid-19 is mainly acquired through health practitioners, social media and internet, which have proven to be a chosen tool to adapt to the physical constraint measure of prevention during the pandemic outbreak as especially among the young adults where social media is the source of disseminating information and communication. in contrast to this, the level of trust in social media is low amongst the respondents in kenya [16]. in a similar study on indian citizens, roy et al. [27] noted that the citizens considered social media as a threat to their state of mind, often causing them to worry about receiving updates on covid-19. the level of education, literacy, gender, educational background, and age of the respondents are major contributory factors to increased knowledge about covid-19 [20]. however, in the south-west cameroon, no association has been noted between respondent’s sociodemographic factors and knowledge about covid-19. the different studies reviewed have also shown a low level of knowledge in sudan and south cameroon which is partly associated with the age difference, illiteracy, low income, and respondent’s residence [17, 28]. poor knowledge, health illiteracy, poverty, poor health infrastructure, as well as distrust in government’s intervention can serve as major obstacles to the global effort against covid-19. 2.4. adherence to covid-19 preventive measures an increased adherence to the health regulations laid down by the who would drastically reduce the covid-19 burden. table 2 represents articles on adherence and practice of covid-19 preventive measures conducted in africa. the study on 446 healthcare workers in jos, nigeria [14] showed that clinical healthcare workers had higher satisfactory practice scores (9.01 out of 12) compared to nonclinical healthcare workers (with an average score of 6.59). this gap could be attributed to their need for doi 10.18502/sjms.v16i3.9698 page 375 sudan journal of medical sciences olabode e. omotoso et al. more precaution due to their relative closeness to patients and knowledge discrepancies when compared to nonclinical healthcare workers. in another study of 318 libyan healthcare workers [15], 39.6% took vitamins and supplements and majority (69.5%) ate healthy food to avoid infection. although most participants wash their hands with soap, use alcohol-based hand rub, maintain social distancing, and avoid touching the face with unwashed hands, their practice of wearing masks was poor. as frontline workers and with a very low availability of covid-19 vaccines in africa, it is pertinent for healthcare workers to strictly adhere to the precautionary measures. among the 353 kenyans [16], the level of adherence is poor as about half (50%) had visited a crowded place. although most (91%) wear face masks, 83% apply hand sanitizers and 67% maintain social distancing in public places. majority (60%) indicated that other people do not adhere to the preventive measures. this could be deleterious due to the observed high human–human transmission of the virus. among the 141 correctional officers in nigeria [19], 87.9% regularly washed their hands with soap and water, 84.4% wore face masks when outside, 83% maintained a safe distance from others, and 58.9% distanced from crowded places. knowledge and practice showed a statistically significant, moderate, positive correlation (r = 0.375, p < 0.001). a study on 3712 egyptians showed good knowledge but poor adherence to covid19 preventive measures. poor practice was found associated with young age (or = 2.41, 95% ci: 1.94–2.98), unemployment (or = 4.95, 95% ci: 4.07–6.02), and low educational level [18]. in a binational study of nigerians and egyptians [20], most residents (96%) recognized the important role of maintaining social distancing and self-isolation; but very few (36%) adhered to all preventive guidelines. among the studied ugandans, less than half (48.3%) of the 362 respondents adhered to practicing the instituted preventive guidelines [21]. the respondents who had the highest level of adherence had up to secondary school education (71.4%), were >45 years of age (61.2%), self-employed (57.3%), female (56%), and are anglicans (53%). poor adherence observed was also found among cameroonians living in a conflict-affected area [22], where although most participants identified the importance of face mask (93.5%) and hand sanitizers (88.8%), only 21.7% and 32.9% of them had purchased them for use, respectively. this is in contrast with another report on cameroonians, where all 1006 respondents used face masks, 94.5% washed hands and/or used hand sanitizers, and 83.8% observed social distancing [13]. this disparity can be a result of the direct consequences of conflict on inhabitant’s health and social lifestyle. in a study of 404 chronic disease patients in ethiopia [17], the adherence level was also not satisfactory as only 105 (25.9%) had a good practice of the preventive measures. doi 10.18502/sjms.v16i3.9698 page 376 sudan journal of medical sciences olabode e. omotoso et al. more so, only 224 (55.2%) disinfect frequently touched surfaces, 154 (38.1%) refrained from overcrowded places, 148 (36.6%) used face masks in public places, and 121 (29.9%) practiced social distancing. this calls for concern as covid-19 has been reported to be severe in patients with comorbidities [7]. to adhere to the lockdown policy and social distancing rule, most of the studies utilized web-based surveys, which serve as a major limitation to the studies due to the low internet penetration rate in most african countries. this likewise skewed the respondents toward young people and highly educated individuals or professionals who are the major internet users. the present review shows that a good number of the population although having a good knowledge of the disease outbreak failed to adhere strictly to the covid-19 preventive measures. a high number of healthcare providers have a good practice of the measure of prevention while others do not. this is the case with libyan healthcare workers where only very few (<30 %) wear face masks and/or gloves as part of preventive measures against covid-19 infection [15]. this calls for concern as healthcare workers are at the forefront of combatting the pandemic. this is in contrast to 353 kenyans [16], who also had low level of adherence but a good practice of wearing facemask. the associated myths, misinformation circulated on social media, health illiteracy, distrust in government’s policies, and low mortality due to covid-19 in most african countries could have contributed to the poor adherence to the preventive measures. 2.5. relevance of assessing knowledge and adherence to covid19 preventive measures the present review showed the discrepancies between the studies that reported on the level of knowledge and adherence toward instituted guidelines against covid-19, as discussed above. all 13 studies on knowledge showed a satisfactory knowledge of respondents about covid-19. it is a bit worrisome that despite a relatively good knowledge, the level of adherence to the preventive measures was poor. educational level (up to tertiary), being a clinical healthcare worker, and a very good knowledge of covid-19 were found to influence satisfactory adherence. increasing awareness and sensitizing the populace through health education would go a long way in mitigating the spread of covid-19. most participants of the selected studies used in this review identified social media, internet, tv, and health practitioners as the major sources of information [16, 21, 23]. these channels should be leveraged on to enhance adherence to covid-19 preventive measures. doi 10.18502/sjms.v16i3.9698 page 377 sudan journal of medical sciences olabode e. omotoso et al. ta bl e 1: se le ct ed st ud ie s on kn ow le dg e of a fr ic an ’s ab ou tc o v id -1 9. s/ n a u th o r s tu d y si te p a rt ic ip a n ts n o .o f p a rt ic ip a n ts k n o w le d g e sc o re k n o w le d g e re su lt 1 sh eh u jo s, n ig er ia h ea lth w or ke rs 44 6 d oc to rs (18 .8 6 ± 2 .5 6) n ur se s (18 .9 6 ± 1.9 2) ph ar m ac is ts (18 .6 ± 2 .3 4) n ur se a id e or ph ar m te ch (17 .18 ± 2 .2 8) a dm in /a cc ou nt an t (18 .4 1 ± 2 .4 1) ph ys io th er ap is t/ la b sc ie nt is t (18 .6 6 ± 2 .4 2) tr an sp or t/w or ks (17 .8 3 ± 2 .4 ) a tte nd an ts /ra di og ra ph er s (18 .4 8 ± 2 .3 ) th er e w as sa tis fa ct or y kn ow le dg e w ith a si gn ifi ca nt di ffe re nc e be tw ee n th e ca dr es of he al th ca re w or ke rs 2 m ur iu ki ke ny a 35 3 g oo d kn ow le dg e – 83 .9 7% th er e is a go od kn ow le dg e le ve la bo ut c o v id -1 9 w hi ch ch an ge s w ith re sp on de nt s’ so ci od em og ra ph ic fa ct or s. 3 o ko ro en ug u, n ig er ia c or re ct io na l of fic er s 14 1 sa tis fa ct or y kn ow le dg e – 77 .3 6% th er e w as a si gn ifi ca nt ly hi gh er kn ow le dg e le ve la m on g of fic er s w ith hi gh er ed uc at io na lq ua lifi ca tio ns . 4 ka se m y eg yp t 37 12 sa tis fa ct or y kn ow le dg e – 70 .2 % u ns at is fa ct or y kn ow le dg e w as as so ci at ed w ith lo w ed uc at io n [o r = 1.9 7, 95 % c i: 1.5 1– 2 .5 6] an d ru ra lr es id en cy (o r = 1.2 ,9 5% c i: 1.0 5– 1.4 1). 5 o ke llo u ga nd a 36 2 g oo d kn ow le dg e – 26 4 (9 3. 9% ) fe m al es w er e m or e kn ow le dg ea bl e ab ou tc o v id -1 9 th an m al es (a o r ,1 .0 1; 95 % c i, 0. 95 – 1.0 7) . 6 n ic ho la s so ut hw es t c am er oo n re si de nt s in co nfl ic t af fe ct ed ar ea 54 5 c or re ct kn ow le dg e – 21 .9 % in te rm ed ia te kn ow le dg e – 43 .8 % po or kn ow le dg e – 34 .4 % n o kn ow le dg e – 11 .9 3% th er e w as no as so ci at io n be tw ee n so ci od em og ra ph ic ch ar ac te ris tic s an d re sp on de nt s’ le ve lo fk no w le dg e. 7 h w ei ss a li by a h ea lth ca re w or ke rs 31 8 su ffi ci en tk no w le dg e – 79 .9 % th e kn ow le dg e sc or es ob se rv ed w er e si gn ifi ca nt ly as so ci at ed w ith re sp on de nt s’ ag e di ffe re nc e. 8 m ou sa kh ar to um , su da n c iti ze ns 23 36 c or re ct kn ow le dg e – 84 .7 % th e kn ow le dg e sc or e va rie d co ns id er ab ly am on g re sp on de nt s’ m ar ita ls ta tu s, ge nd er ,a ge gr ou ps ,o cc up at io n, ed uc at io na ll ev el s, an d re si de nt ia lp la ce s. 9 se ng eh si er ra le on e c iti ze ns 12 53 n a kn ow le dg e ga p di ffe rs be tw ee n re sp on de nt s’ ge nd er , ed uc at io na ll ev el s, re gi on s, an d ag e. 10 a ka lu et hi op ia c hr on ic di se as e pa tie nt s 40 4 sa tis fa ct or y kn ow le dg e – 33 .9 % a ge (a o r = 1.0 5 ,[ 95 % c i{ 1.0 1– 1.0 8} ]), ed uc at io na ls ta tu s of “c an ’t re ad an d w rit e” (a o r = 7.1 ,9 5% c i[ 1.5 8– 31 .9 3] ), ru ra l dw el le r (a o r = 19 .0 ,9 5% c i[ 6. 87 – 52 .6 6] ), an d m on th ly in co m e ea rn er (a o r = 0. 8, 95 % c i[ 0. 79 –0 .8 9] )w er e si gn ifi ca nt ly as so ci at ed w ith po or kn ow le dg e. 11 re ub en n or th -c en tr al n ig er ia re si de nt s 58 9 g oo d kn ow le dg e – 99 .5 % th ou gh w ith a hi gh kn ow le dg e sc or e, on ly fe w (2 9% )w ou ld ac ce pt c o v id -1 9 va cc in es w he n av ai la bl e. 12 n gw ew on do c am er oo n re si de nt s 10 0 6 h ig h kn ow le dg e sc or e – 84 7 (8 4. 19 % ) a ge (> 20 ye ar s) w as as so ci at ed w ith a hi gh sa tis fa ct or y kn ow le dg e of c o v id 19 . 13 h ag er e t a l. n ig er ia an d eg yp t c iti ze ns 14 37 sa tis fa ct or y kn ow le dg e – 61 .6 % re sp on de nt s’ ag e (18 –3 9 ye ar s) ,e du ca tio na ll ev el (c ol le ge /b ac he lo rs ), an d ed uc at io na lb ac kg ro un din flu en ce d kn ow le dg e le ve l. doi 10.18502/sjms.v16i3.9698 page 378 sudan journal of medical sciences olabode e. omotoso et al. ta bl e 2: se le ct ed st ud ie s on ad he re nc e of a fr ic an s to c o v id -1 9 pr ev en tiv e m ea su re s. a u th o r s tu d y lo ca ti o n p a rt ic ip a n ts a d h e re n ce sc o re a d h e re n ce re su lt sh eh u jo s, n ig er ia h ea lth w or ke rs d oc to rs (9 .4 9 ± 2 .6 5) n ur se s (8 .7 4 ± 2 .7 2) ph ar m ac is ts (8 .4 0 ± 2 .7 5) n ur se a id e or ph ar m te ch (8 .4 3 ± 2 .9 0) a dm in /a cc ou nt an t( 7. 70 ± 3. 02 ) ph ys io th er ap is t/ la b sc ie nt is t( 8. 41 ± 2 .0 0) tr an sp or t/w or ks (6 .9 5 ± 2 .9 2) a tte nd an ts /ra di og ra ph er s (8 .0 6 ± 3. 0 9) a dh er en ce w as go od w ith cl in ic al he al th w or ke rs , w hi le no ncl in ic al he al th w or ke rs ha d av er ag e sc or es . m ur iu ki ke ny a n a m aj or ity of re sp on de nt s fa il to ad he re to th e c o v id -1 9 pr ev en tiv e m ea su re s. o ko ro en ug u, n ig er ia c or re ct io na lo ffi ce rs n a th er e w as a si gn ifi ca nt m od er at e, po si tiv e co rr el at io n be tw ee n kn ow le dg e an d pr ac tic e. ka se m y eg yp t g oo d pr ac tic e – 49 .2 % po or pr ac tic e of pr ev en tiv e m ea su re s w as as so ci at ed w ith yo un g ag e (o r = 2 .4 1, 95 % c i: 1.9 4– 2 .9 8) ,l ow ed uc at io n (o r = 1.1 9, 95 % c i: 1.0 3– 1.3 7) ,a nd un em pl oy ed (o r = 4. 95 ,9 5% c i: 4. 07 –6 .0 2) . o ke llo u ga nd a g oo d pr ac tic e – 17 5 (4 8. 3% ) c om pa re d to m al es ,f em al es w er e m or e ad he re nt to th e pr ev en tiv e m ea su re s (a pr ,1 .2 3; 95 % c i, 1.0 1– 1.5 3) . n ic ho la s so ut hw es t c am er oo n n a a lth ou gh m os tp ar tic ip an ts kn ew ab ou tt he us e of fa ce m as k (9 3. 5% )a nd ha nd sa ni tiz er s (8 8. 8% ), on ly 21 .7 % an d 32 .9 % ha d pu rc ha se d th em fo r us e, re sp ec tiv el y. h w ei ss a li by a h ea lth ca re w or ke rs ph ys ic ia n – 8. 36 (7 .9 9 ± 8. 74 )p ha rm ac is t– 7. 99 (7 .7 0 ± 8. 27 )d en tis t– 8. 75 (8 .19 ± 9. 30 )t ec hn ic ia n – 7. 70 (7 .0 3 ± 8. 36 )n ur se – 8. 50 (6 .4 4 ± 10 .5 ) fe m al es ,o ld er re sp on de nt s, an d de nt is ts ha d hi gh er pr ac tic e sc or es co m pa re d to ot he r he al th ca re w or ke rs . m ou ss a kh ar to um ,s ud an c iti ze ns n a d es pi te th e pr ev en tiv e m ea su re s, so m e of th e re sp on de nt s ha d vi si te d cr ow de d ar ea s (3 0. 1% )a nd m os t( 50 .7 % )h ad no tw or n m as ks in pu bl ic pl ac es . doi 10.18502/sjms.v16i3.9698 page 379 sudan journal of medical sciences olabode e. omotoso et al. ta bl e 2: c on tin ue d. a u th o r s tu d y lo ca ti o n p a rt ic ip a n ts a d h e re n ce sc o re a d h e re n ce re su lt se ng eh si er ra le on e c iti ze ns n a h av in g a sa tis fa ct or y kn ow le dg e w as as so ci at ed w ith hi gh er od ds of w as hi ng ha nd s w ith so ap (m ed iu m kn ow le dg e: a o r 2 .1, 95 % c i1 .0 –4 .4 ;h ig h kn ow le dg e: a o r 4. 6, 95 % c i2 .1– 10 .2 ), an d av oi di ng cr ow de d pl ac es (m ed iu m kn ow le dg e: a o r 2 .0 ,9 5% c i1 .1– 3. 6; hi gh kn ow le dg e: a o r 2 .3 ,9 5% c i 1.2 –4 .3 ). a ka lu et hi op ia c hr on ic di se as e pa tie nt s sa tis fa ct or y ad he re nc e le ve l– 52 .7 % b ei ng un m ar rie d (a o r = 3. 9, 95 % c i[ 1.4 7– 10 .5 8] ), ca nn ot re ad an d w rit e (a o r = 2 .7 ,9 5% c i [1. 0 3– 7. 29 ]), ca n re ad an d w rit e (a o r = 3. 5 ,9 5% c i [1. 48 –8 .3 8] ), ru ra ld w el le r (a o r = 2 .7 ,9 5% c i [1. 0 9– 6. 70 ]), in co m e of < 72 52 et hi op ia n bi rr (a o r = 2 .3 ,9 5% c i[ 1.2 0 –4 .15 ]), an d po or kn ow le dg e (a o r = 8. 6, 95 % c i[ 3. 81 – 19 .4 5] )w er e si gn ifi ca nt ly as so ci at ed w ith po or ad he re nc e to pr ev en tiv e m ea su re s. re ub en n or th -c en tr al n ig er ia re si de nt s sa tis fa ct or y ad he re nc e le ve l– 79 .5 % m os tr es po nd en ts pr ac tic e so ci al di st an ci ng /s el f-i so la tio n (9 2 .7 % ), im pr ov ed pe rs on al hy gi en e (9 6. 4% ), an d us e fa ce m as k in pu bl ic pl ac es (8 2 .3 % ). n ge w on do c am er oo n re si de nt s sa tis fa ct or y ad he re nc e le ve l– 60 .8 % w om en ha d lo w er ad he re nc e le ve ls co re s co m pa re d to m en (o r = 0. 72 ;9 5% c i0 .5 6– 0. 92 ) h ag er e t a l. n ig er ia an d eg yp t c iti ze ns a dh er ed to al lp re ve nt iv e m ea su re s – 36 % 68 .9 % ha d sa tis fa ct or y at tit ud e to w ar d th e pr ev en tiv e m ea su re s. doi 10.18502/sjms.v16i3.9698 page 380 sudan journal of medical sciences olabode e. omotoso et al. some other factors that could account for the variations in the knowledge and adherence to the preventive measures to covid-19 include poor healthcare structure, social welfare of individuals as many did not have access to basic needs of life (especially those living in a conflict-affected area) and had to strive daily in making ends meet, economic capacity of various countries in the continent to access medication, funds for emergency interventions varied and perhaps was an inclusion factor to the discuss. political factors which include system of government, policy like lock down and closing of borders as well as bilateral agreement with countries making waves in the containment of the virus likewise paved the way for some. as stipulated by the reviewed reports, culture/tradition and habits, negligence, poor health literacy, poverty, and conspiracy theories about covid-19 might have contributed immensely to the low level of adherence to the preventive measures. 3. results the ongoing covid-19 pandemic comes with excruciating psychological, financial, social and public health challenges. the selected 13 studies on knowledge and practice reviewed showed a satisfactory knowledge, a positive attitude, and a relatively poor adherence to the covid-19 preventive measures. good knowledge and satisfactory level of adherence was common mostly among the clinical healthcare workers, highly educated, and those with higher professional qualification, while poor knowledge, negative attitude, and poor practice was observed mostly among the rural dwellers, people of poor educational background, and those unable to read and write. this poor practice and negative attitude occurs due to ignorance, negligence, and the inability to read and write. 4. conclusion there is a need for improvement in maintaining a good practice of the preventive measures. a better and simplified way of passing the information to the rural dwellers and those in war-torn communities needs to be encouraged which will in turn create more awareness alongside reducing the spread of the virus. doi 10.18502/sjms.v16i3.9698 page 381 sudan journal of medical sciences olabode e. omotoso et al. acknowledgements the authors appreciate the effort of all coauthors of the selected articles used in this review. we also appreciate the faculty of medicine and health sciences, omdurman islamic university, sudan for their support to this journal and for covering the cost of publication for the authors. ethical considerations not applicable. competing interests the authors declare no competing interests. availability of data and material all data used are available in public repositories and are adequately cited. funding none received. references [1] who. 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[16] muriuki, w., muriithi, b., duncan, k., et al. (2020). assessing knowledge, attitude and practices (kap) towards covid19: a cross-sectional study in kenya. global journal of medical research, vol. 20, no. 10. [17] akalu, y., ayelign, b., and molla, m. d. (2020). knowledge, attitude and practice towards covid-19 among chronic disease patients at addis zemen hospital, northwest ethiopia. infection and drug resistance, vol. 13, pp. 1949–1960. [18] kasemy, z. a., bahbah, w. a., zewain, s. k., et al. (2020). knowledge, attitude and practice toward covid-19 among egyptians. journal of epidemiology and global health, vol. 10, no. 4, pp. 378–385. [19] okoro, j., ekeroku, a., nweze, b., et al. (2020). attitude and preventive practices towards covid-19 disease and the impact of awareness training on knowledge of the disease among correctional officers. emerald open research, vol. 2, p. 51. [20] hager, e., odetokun, i. a., bolarinwa, o., et al. (2020). knowledge, attitude, and perceptions towards the 2019 coronavirus pandemic: a bi-national survey in africa. plos one, vol. 15, pp. 1–13. [21] okello, g., izudi, j., teguzirigwa, s., et al. (2020). findings of a cross-sectional survey on knowledge, attitudes, and practices about covid-19 in uganda: implications for public health prevention and control measures. biomed research international, vol. 2020, article 5917378. [22] nicholas, t., mandaah, f. v., esemu, s. n., et al. (2020). covid-19 knowledge, attitudes and practices in a conflict affected area of the southwest region of cameroon. pan african medical journal, vol. 35, no. 2, pp. 1–8. [23] reuben, c. r., danladi, m., saleh, a. d., et al. (2020). knowledge, attitudes and practices towards covid-19: an epidemiological survey in north-central nigeria. journal of community health [epub ahead of print]. [24] altayb mousa, k. n. a., saad, m. m. y., and tayseer bashir abdelghafor, m. (2020). knowledge, attitudes, and practices surrounding covid-19 among sudan citizens during the pandemic: an online cross-sectional study. sudan journal of medical sciences, vol. 15, pp. 32–45. [25] sengeh, p., jalloh, m. b., webber, n., et al. (2020). community knowledge, perceptions and practices around covid-19 in sierra leone: a nationwide, crosssectional survey. bmj open, vol. 10, no. e040328, pp. 1–8. [26] abdelhafiz, a. s., mohammed, z., ibrahim, m. e., et al. (2020). knowledge, perceptions, and attitude of egyptians towards the novel coronavirus disease (covid-19). journal of community health, vol. 45, no. 5, pp. 881–890. doi 10.18502/sjms.v16i3.9698 page 384 sudan journal of medical sciences olabode e. omotoso et al. [27] roy, d., tripathy, s., kar, s. k., et al. (2020). study of knowledge, attitude, anxiety & perceived mental healthcare need in indian population during covid-19 pandemic. asian journal of psychiatry, vol. 51, 102083. 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(2020). knowledge, attitudes and practices towards covid-19: an epidemiological survey in north-central nigeria. journal of community health, vol. 46, pp. 457–470. doi 10.18502/sjms.v16i3.9698 page 385 introduction materials and methods literature search studies on knowledge and adherence to covid-19 preventive measures knowledge about covid-19 adherence to covid-19 preventive measures relevance of assessing knowledge and adherence to covid-19 preventive measures results conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 12, issue no. 3, doi 10.18502/sjms.v12i3.924 production and hosting by knowledge e research article health care system in sudan: review and analysis of strength, weakness, opportunity, and threats (swot analysis) ebrahim m. a. ebrahim1, luam ghebrehiwot, tasneem abdalgfar1, and muhammad hanafiah juni2 1mph (master of public health) candidates, department of community health, faculty of medicine and health sciences, universiti putra malaysia 2associate professor, department of community health, faculty of medicine and health sciences, universiti putra malaysia abstract background: the republic of the sudan located in north-east of africa and is considered to be a lower-middle income country. the country has well established healthcare system with many drawbacks mainly due to economic and managerial reasons followed by prolonged political instability and sanctions. objective: the aim of this study is to give an insight over the health services system in sudan and to analyze the strength, weakness, opportunities, and threats (swot). materials and methods: the search was done from two electronic databases: medline/pubmed and from public search engines: google scholar and google with key search words used mainly as “healthcare system in sudan“. additionally, swot analysis of healthcare system in sudan was carried out based on the roemer’s model of health service system. results: the sudanese healthcare system was analyzed for different components of the system: the system in sudan has full package of strategic plans and policies be it in a long term or short. despite this there is poor implementation and organization along with frail health information system. the main external factors that drawback the system is the overall economic instability which resulted in cutting of the health expenditure. conclusion: the sudan is a rich country in terms of natural resources and population. its health service system has strengths and weaknesses. it needs to build on its qualified human work force, stress on its well-designed short and long-term strategies on health care system and the partnership with external funding institutions, while overcoming the challenges on creating the proper health information system, economic support system and centralization of health service and professionals. keywords: health care system, sudan, swot analysis how to cite this article: ebrahim m. a. ebrahim, luam ghebrehiwot, tasneem abdalgfar, and muhammad hanafiah juni, (2017) “health care system in sudan: review and analysis of strength, weakness, opportunity, and threats (swot analysis),” sudan journal of medical sciences, vol. 12 (2017), issue no. 3, 133–150. doi 10.18502/sjms.v12i3.924 page 133 corresponding author: muhammad hanafiah juni; email: hanafiah_juni@upm.edu.my, ebrahim m. a. ebrahim; email: dr.ibrahim.ibrahim@ gmail.com received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e ebrahim m. a. ebrahim et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:hanafiah_juni@upm.edu.my mailto:dr.ibrahim.ibrahim@gmail.com mailto:dr.ibrahim.ibrahim@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences production and hosting by knowledge e 1. introduction health services system of one country is complex, understanding it necessitates the development of a common framework showing the interlinked interactions of the input and output components. thus in 1984 dr. milton roemer came out with a useful comprehensive model that combines management, resources, organization, and funding as components that end in delivering a health service to the people [1]. this roemer model of the health services system allows to establish a baseline of a country’s health service status, future monitoring and development, and also allows for comparison with other countries [1]. although, health services system is important, it is not the only determinant of a population’s status of health [2]. figure 1 shows the components of the roemer’s model and the relationship between them aiming to study the national health system of any country. figure 1: roemer model of health services system. the management aspect of the model involves the processes of planning, administration, legislation, and regulation formulations which are carried out by various legal bodies and policy makers of individual country [3]. the mixture of public, private, charitable, and voluntary services providers are the organization component of the model and their size of contribution vary from one country to another. third is the resource production component which means all resources other than gross finance as healthcare manpower, facilities, technologies, commonalities, and knowledge [3]. fourth is the economic support which comes from different sources as insurance, governmental revenues, personal out of pocket, charity, or foreign aid [3, 4]. generally, the country’s cultural, political, and economic statuses influence the health services system. in addition to improving the health of its population, a country’s health services system is also a major sector of the economy in terms of development, employment, research and, exports, as drugs, instruments, and other medical technologies [3]. doi 10.18502/sjms.v12i3.924 page 134 sudan journal of medical sciences production and hosting by knowledge e figure 2: map of the republic of the sudan. the republic of the sudan is located in north-east of africa and is the third largest african country in terms of geographical range after algeria and democratic republic of the congo, covering an area of 1.9 million km2 states. sudan has international borders with seven countries: egypt, eritrea, ethiopia, south sudan, central african republic, chad and libya [5]. in 2011, under the terms of the comprehensive peace agreement, the republic of south sudan formed in formerly known as southern sudan states. after the separation, the sudan lost 75% of the oil resources and almost half of the country’s revenue. consequently, the sudanese economy suffered losses from the withdrawal of oil revenues and annual percentage of growth rate of gross domestic products (gdp) decreased from 7.8% in 2008 to 3.1% in 2014 [5]. the current estimated population of sudan is about 41,727,150 people according to the latest united nations report in the first month of 2017 in which 33.7% of the population were reported living in the urban areas [6]. the population growth is 2.41% in the annual report of 2017. sudan is a young population country with the median age 19.6 years [6]. the total life expectancy for male and female at birth, a measure of the general health condition and an indicator of the standard of living, was estimated around 62 and 66 years respectively, and this is considered the average of least developed countries [7]. the under-five child mortality rate was 77/1000 in 2015 compared to 128/1000 in 1990 and the maternal mortality ratio was 360/100,000 in 2015 compared to 720/100,000 in 1990 [7]. sudan is considered a lower-middle income country—with 47% of the population living below the poverty line [8]. in addition to excessive burden of communicable diseases such as malaria, tuberculosis, and schistosomiasis, sudan is predominantly susceptible to non-communicable diseases, natural and manmade disasters. drought, flood, internal conflicts, and outbreaks of violence are quite common which bring about a burden of traumatic disease and demand for high quality emergency health care [9]. doi 10.18502/sjms.v12i3.924 page 135 sudan journal of medical sciences production and hosting by knowledge e this review study is intended to identify the strength, weakness, opportunities, and threats of the current status on the health care system in the sudan. 2. materials and methods this is a review study about the healthcare system in the republic of sudan. review of several articles was used to gather information about the healthcare system in sudan. the search was done on 19th to 25rdof january 2016 from two electronic databases: medline/pubmed and from public search engines: google scholar and google (2000 – january 2017). the relevant keywords used in the search consisted of terms considered by the authors to describe targeted information about the healthcare system. the search query was tailored to the specific requirements of each database. search words used were “healthcare system”, “healthcare system in sudan”, “swot analysis of healthcare system in sudan”, and “who report on health care system in sudan”. later, swot analysis was carried out based on the roemer’s model five components of the health care services. swot analysis is a common systematic tools used by evaluation specialists in any field of study [10]. this method can be used for analysis, for strategic planning, and to discover solutions in public health sector. it specifies the system objectives and tries to identify both internal and external constructive and destructive issues to achieve its objectives [11]. in a broader sense the letters of swot include; strengths and weaknesses which are the internal characteristics of a system and compared with other systems to see the relative strength and things that need to be addressed respectively while opportunities and threats are the external chances or elements in the environment to make greater inputs to a system or that could cause troubles to the system [12]. swot analysis is an examination of an organization’s internal strengths and weaknesses, its opportunities for growth and improvement, and the threats in the external environment present to its survival [13]. 3. results and discussion from the reviewed literature, several strengths, weaknesses, opportunities, and threats were identified. in this section and these findings are presented and discussed based on the five components of roemer’s model. 3.1. swot analysis of sudanese hss the swot analysis of the hss in the sudan is summarized in table 1. doi 10.18502/sjms.v12i3.924 page 136 sudan journal of medical sciences production and hosting by knowledge e strengths weaknesses 1. hard and skilled with younger generation workers, 2. adequate number of health workers and; 3. increasing number of the supporting staff, 4. constitution of 25-year long term and 5-year short term strategic plans, and the national health policy extends till 2027 [14], 5. abundant availability of policies, plans, and strategies. 6. provide free primary health care and emergency services for all citizens mainly the poor [15] 7. existing basic package of health services 8. existing teaching, and state hospitals 9. enhanced human resource of health policies. 10. availability of academy of health sciences, accreditation system increasing number of medical and health sciences schools 11. active international health agencies and ngos [4]. 12. availability of updatable country cooperation strategy for who and sudan [16]. 1. no clear mechanisms for implementation, monitoring, and evaluation framework for policies and plans in the system 2. poor quality of data, utilization and dissemination of the information in all components of the health system 3. fragmented health information system [17] 4. imprecise managerial systems for coordination and guidance among federal and state ministries of health, armed forces, police, universities, private sector and the civil society [4] 5. not enough postgraduate training 6. weak hr functions at the decentralized levels and poor geographical distribution with bias towards urban (global health workforce alliance, 2012) 7. no continuing professional development policy for the health care 8. deterioration of civil services due to outdatedness 9. poor logistic supply (equipment, disposables, drugs. etc.) [19] 10. out-of-pocket payments has affected access and utilization of health services [4] 11. inequitable distribution of health care facilities [19] 12. lack of preventive medicine and health promotion (primary prevention) 13. poor referral system. 14. low spending on health and inefficiency in utilization of available resources [14] opportunities threats 1. recent political commitments 2. decentralization leading to better hrh decisions and actions 3. external funding opportunities (who, ghwa, gf, gavi, taf, mdtf, jica) 4. partnerships with international institutes and universities e. g. leeds, malaya, primafamed project (training opportunities) [20] 5. increase economic growth [21] 6. health system reform initiative 1. long-standing economic sanctions [22] 2. high attrition rate of well-trained medical officers and outside trained specialists to the nearby rich gulf countries for better quality of life and job satisfaction [9]. 3. most of health legislations are old and require changes to satisfy the new system reforms 4. most of health legislations are old and require change to satisfy the new system reforms. 5. economic instability after separation of the southern part of sudan in 2011 further lowered financing the healthcare system [5] t 1: swot analysis of hss in the sudan. doi 10.18502/sjms.v12i3.924 page 137 sudan journal of medical sciences production and hosting by knowledge e 3.2. health services system in the sudan 3.2.1. management policies and plans in sudan are produced at three levels federal, state, and district (also called locality) [4]. there is one federal ministry of health (fmoh) and 18 state ministries of health (smoh). the federal level is responsible for provision of nationwide health policies, plans, strategies, overall monitoring and evaluation, coordination, training, and external relations. the state level is concerned with state’s plans, strategies, and based on federal guidelines funding and implementation of plans. while the localities are mainly concerned with implementation and service delivery [23]. in 1992, a ten-year strategic plan was developed to cover the period 1993-2002 as a comprehensive national strategy of the country. its aim was to improve equity and provide basic health care to all and more sophisticated objectives were targeted including reduction or infant mortality rate, maternal mortality rate, eradication of epidemic and endemic diseases, and achieving 100% immunization coverage [4]. this 10 years plan had realized some of its goals and achieved some progress, however, there were some gaps that required to be filled. later and in response to the national government initiative of developing a twenty five years strategies for all sectors, a newer nation-wide 25 years strategy for years 2003-2027 was prepared for the health sector by the federal ministry of health [24]. other medium sized plans are available with different emphases at both federal and state levels [4]. it is important to highlight that although the policy making managerial component is well tailored and up to the standards to some degree, many weaknesses are faced. for example, plans and strategies for health care services although are made for both long and short terms are limitedly implemented [16]. this can be attributed to the high inflation rates, costs of civil wars, cuts in the public social expenditure, and political instability which makes health care a less priority and makes it difficult to implement the plans unless financial and political issues are solved [25, 26]. federal ministry of health, ministry of veterinary and animal resources, and agriculture and corps ministry are members of what is called the public health council which is the main national legislative body providing regulatory instructions particularly those regarding zoonotic diseases [4]. a major product of this council is the public health act of 1975. nevertheless, states and localities are empowered to set their own regulations and laws based on their needs. additional regulatory bodies are available including the medical council and the allied health council which are in charge for doctors and health provider’s certification and licensing [4]. national accreditation committee is also established to accredit all health facilities whether in public or private sectors [4]. similarly to the implementation of plans issue, the laws and regulations are doi 10.18502/sjms.v12i3.924 page 138 sudan journal of medical sciences production and hosting by knowledge e under practiced and weakly enforced from the legal bodies particularly over the private sector [4], this can be solved via the introduction of a new unit under each smoh responsible for such laws enforcement and to deal with the poor compliance of the health organizations and providers. furthermore, it is an identified problem that many acts and regulations require update or amendments [4] and thus legislative bodies like the public health council has to take forward actions in order to prevent further outdatedness and satisfy new changes and demands. decentralization of managerial authorities is a characteristic of the sudanese health system and this has been mainly done via the three tier system described earlier (federal, state, and district) [4]. another characteristic of the sudanese health system is the availability of the health information system (his) which is one of the first information systems in the region. it involves data collection, processing, analysis, and dissemination. it begins from the district level and goes up to the smoh and fmoh. the information obtained is used in producing periodic reports and in making decisions [27]. health information system is also a means for monitoring the progress of plans and strategies and in studying their impacts in the health status. additionally, it helps in allocating the resources more appropriately with less disparities [27]. on the other hand, the his also suffers from recognizable feebleness as well. first of which is that big amount of the community level information are not pooled into the his and that some programs collect and use data for their own activities and stop without disseminating their findings [17]. second is the limited capacity of analysis, utilization, and dissemination of data and findings [28]. the addressed issues were recommended to be solved via an easy to use electronic system that can be accessed from anywhere and to provide training to the statistical technicians [28]. 3.2.2. organization of the programs: health services in sudan are provided by the federal and state ministries of heath, military medical services, police, universities, and private sector. the districts or localities which are the closest to people are mainly providing primary health care, health promotion, and encouraging community participation in caring for their health and surrounding environment [4]. they are responsible for water and sanitation services as well. this well-established district system is a key component of the decentralization approach pursued in sudan which gives in turn a broader space for local management, administration and allow for overcoming the leadership and supervision efforts by superior bodies [15]. in 1976, sudan adopted primary health care (phc) as the principal strategy for health care and throughout the future plans and strategies phc was emphasized on [4]. the phc facilities are the phc units staffed by community health workers, dressing stations doi 10.18502/sjms.v12i3.924 page 139 sudan journal of medical sciences production and hosting by knowledge e rural/community hospitals 100,000 – 250,000 health center 20,000 – 50,000 basic health unit (phc unit, or dispensary) 5,000 t 2: standard population covered by health institutions. staffed by a nurse, dispensaries taken care of by a medical assistant, heath centers and rural hospitals run by doctors. health centers are receiving referrals from lower units and are both managed by the concerned localities. the rural hospitals also receive referrals from both the health centers and lower level facilities and are on average capable to receive between 40-100 patients and is managed by the state ministry of health. tertiary teaching, specialized, and general hospitals present in the capital cities of the states are also operated by the state ministry of health and by the federal ministry of health. there are many health programs served by these units, centers, and hospitals. the most important of which are those regarding maternal health and family planning, child care and immunization, and control programs of communicable diseases including malaria, schistosomiasis, tuberculosis, hiv/aids, leishmaniasis, sleeping sickness, filariasis, river blindness control and non-communicable disease control programs [4]. in addition to above, private sector of health care also provides wide range of health services and is mainly profitable. there are many private clinics, health centers, and hospitals all of various levels of care and specialized services [4]. on the other hand, non-profit organizations caring for many different programs are also widely spreading in sudan and are functioning in coordination with the federal ministry of health. for instance, médecins sans frontières (msf) ran a number of hospitals is some states particularly those undergoing armed conflicts and operated some health clinics [29]. these hospitals provided secondary care, consultations, and hospitalization when needed, while health clinics provided reproductive health, antenatal care, on top of other basic primary care services. furthermore, in collaboration with the fmoh, msf conducted vaccination campaigns and operated some newly introduced mobile clinics concerned with education, vaccination, and child and women care [29]. in general, the fmoh has always recognized the internal conflicts as a primary reason of health care decline [8]. this disruption of the health system is in the form of health infrastructure complete destruction or the need for maintenance and repair. this condition has been throughout the past decade and a study on health system indicated that many health facilities are not functional as a result of dilapidated buildings and lack of necessary equipment [28]. however, there are several new commitments that are people centered, long-term and has wider scope to achieve the sdgs. the sudan has doi 10.18502/sjms.v12i3.924 page 140 sudan journal of medical sciences production and hosting by knowledge e also made some health sector reforms in order to assure the health care is a right, universal, participatory, sustainable and provides equity in all levels [30, 31]. 3.2.3. resource production resource production of human, facilities, commodities and knowledge remains to be the mainstay of sudan healthcare system. human resources for health (hrh) are very important asset for health systems worldwide and sudan in particular [32]. recently the hrh is all the time more recognized as a significant area for health system progress so that the planning can address the workforce issues. there was a strategic plan for hrh from 2012 to 2016 in sudan: with the purpose of developing human resource plans and guidelines in all levels and areas of health system in a wide-ranging tactic [33]. the aim of the strategic plans defined towards reaching the aim accordingly by prioritizing the issues in the human resources planning, production and training, distribution, management and improving the existing policies [21]. training and production of health workforce in sudan increased tremendously in the past 2 decades as a result of increased numbers of medical training schools both on the public and private sectors. there are over 100,000 health workers making over 20 different professions [21]. the picture of sudan health workforce today shows almost equal distribution of female and male. the age structure points to a rather young health workforce probably due to the recent expansion of medical education and health training [4]. the ministry of higher education is responsible for pre-service training and production of health workers through a total of more than 13 universities with medical and health science facilities, and 250 allied health cadre’s schools and institutes. medical council is delegated with registration and licensing of doctors, pharmacists and dentists. majority of health workers are employed by the civil service under the federal and state ministry of health in addition to lower numbers in the army, police, universities and health insurance fund. exclusive private sector staff represents only 9%, taking into account that dual practice is very common [32]. the number, ratio and type of health workers differ from state to another. the doctors to nurses ratio was 1:1.7 in 2006, 6:1 in education conduit, and improved to 1:2.5 in 2013 [34]. the proportion of medical doctors, nurses and midwives is 1.23 per 1000 population the country is still within the critical shortage zone according to the who criteria of 2.28 health care professionals per 1000 population [4] and currently sudan has one physician for every 3,333 population according to world bank report [35]. in spite of the increasing production of manpower every year to meet the needs of the healthcare system, still there is deficiency in the human resources [33]. the main problem is migration of trained professionals like most african countries, in addition to the poor management and rationale distribution of the existing physicians and doi 10.18502/sjms.v12i3.924 page 141 sudan journal of medical sciences production and hosting by knowledge e paramedics [36]. so far sudan has lost almost 60% of its physicians due to outmigration [37]. when comparing sudan with cuba they both have equivalent level of economy. but cuba is one of the countries with the lowest number of patient to doctor ratio in the world. first medical education in cuba is free [38], all doctors interested in specializing must first serve two years working in primary care, and graduating doctors are not driven to specialize by salary incentives. this cuban approach towards medicine and medical education assures the human resources necessary to provide universal and preventative healthcare to all [39]. following on the geographical pattern of health services inequitable and uneven distribution of the health workforce is prominent in sudan. according to the 2006 survey report, nearly 70% of health personnel work in urban settings serving about 30% of the total country population. more than one-third of the total health workforce is located in the capital city. around 67% of health workers staff are working in secondary and tertiary facilities,as opposed to only 33% in primary healthcare settings among which 62% of the total specialist doctors and 58% of technicians are practicing in khartoum state [21] . the government of sudan introduced a law of compulsory one year placement similar to the cuban, nevertheless there is no enforcement of this policy [40]. moreover, the non-conducive environment discourages the health professionals from continuing their posting in the rural areas which attributes to the high production with low employment [41].in terms of knowledge, the research program for resource production part of the healthcare system in sudan was established as the health system research unit at 1998 with the help of who but has minimal contribution to the system [42]. there are limited information regarding commodities for instance, drugs. 3.2.4. economic support sudan is bestowed in terms of natural and human resources, but economic and social development have been below expectations. likewise, the data on health financing and expenditure is deficient and incomplete. it makes it difficult for decision makers to plan, distribute and clearly see the deficient area. regardless of the external threats such as brain drain, prolonged economic sanction and separation from south sudan that brought down the economic support to achieve the goals, the weaknesses with in the healthcare system internally is not satisfactory [43, 44]. the government is upholding towards ensuring that resources for health are used for intended purposes and to safeguard that the financial management system meets national and international standards, and produces reports appropriate for making decisions [8]. doi 10.18502/sjms.v12i3.924 page 142 sudan journal of medical sciences production and hosting by knowledge e the available information showed that the overall government health expenditure is very low and the health sector is under-funded [4]. as overall government expenditure, has increased largely due to growth in oil revenues, allocation to health sector in absolute terms have also increased until 2011. gdp per capita for 2001 estimated at $395 when compared to $282 in 2014. the total health expenditure as percentage of the gdp was 5.4-8.5% and 8.4% for the year of 2000 and 2014 respectively [7].the main resources for states health budget come from the ministry of finance. it is noted that at best the expenditure of the allocated budgets never exceed 70% and most of it comprise the salaries component. the national states support fund gives support to some states, which is automatically added to the state’s budget. part of the budget comes from household’s direct contribution through user fees or through health insurance premium [45]. the national health insurance scheme, introduced in the mid-1990s which covers about 8% of the population, most of them are government employees (75%), the remaining are poor families (6%), families of martyrs (3%) and students (2%). the program is reported to spend around us$ 90 million annually, 40% of which goes to health care services and 30% to drugs. it is estimated at around 1% of gdp. however, the coverage by the national health insurance fund (nhif) increased from 25% in 2007 to 34.3% in 2012 [46].in contrast the user fees for government health services were introduced in the mid-1990s, including exemptions for vulnerable groups and for emergency services. like most african countries, the sudan follows the out-ofpocket model and minimal national health insurance to some extent which benefit the better off. the increase in expenditure rose from 64% in 2008 to 70% in 2011 which is the highest in the regional countries and much higher than the who uppermost level (40%) [46]. this system resulted in gross disparities, that spending is highly skewed towards those who can afford only [45]. this also gave rise to deterioration of public health care in the area far from center due to lack of financial resources and managerial capacities. there are countries with minimal financial resource but still managed efficaciously by adapting different models. for instance, cuba is the best example that practices the extreme beveridge model in which the government entirely control all the healthcare system and successfully accomplished so much with so little to came up with all health indicators [47]. this system assured equal distribution and the government acts mostly at the phc stage making it easier for the expenditure by preventing the disease instead of treating [48]. the international assistance to the health sector in the past decade has not been significant but there were some international communities committed to work with the government for recovery and development including health services are managed by the world bank. the donors’ inputs for health through fmoh in the year 2002 doi 10.18502/sjms.v12i3.924 page 143 sudan journal of medical sciences production and hosting by knowledge e amounted to us $ 20 million, which comes to us $ 0.6 per person. while the allocated budget for the ngos working in sudan is estimated at us $ 41 million in 2002. the donors’ inputs are generally on control of communicable diseases (vaccine preventable diseases, malaria control, tb control, leprosy control, hiv/aids, g. worm control and control of river blindness), nutrition and phc and significant amount goes to other basic social services other than health [8, 15]. 3.2.5. health service delivery the health services provided in sudan follow the classical three basic arrangements, primary, secondary, tertiary health care. the primary health care is the first encounter for the patients and includes as mentioned in the organizations the dressing stations, dispensaries, primary health care units and health centers, the latter forms the referral point from the lower facilities [4]. the importance of phc is that it provides the essential care to all and improves the health status of the community as a whole [49]. in 2003 a package of health care services was introduced to the phc facilities. this package included vaccination of children, nutrition, reproductive health (rh), integrated management of childhood immunization (imci), management of common diseases and prescribing the essential medications [4]. this line of care is almost entirely provided by the public sector. on the other hand, both public and private sectors work together in the provision of the secondary and tertiary lines of care. though, the private sectors has been functioning mainly in urban areas [4]. screening, diagnostic, and therapeutic services are being provided in both health centers and hospitals as secondary care, where major surgical, rehabilitative, and subspecialized tertiary care is being provided mainly at larger public hospitals including teaching hospital, private hospitals, and in specialized centers. these hospitals and centers accepts patients without being referred from the lower facilities indicating a poor referral system [4]. in the last decade, the number of hospitals has been an increasing trend and it continues to be. it is agreed that a core component of primary health care is health promotion which is limited in sudan while health problems suitable for health awareness campaigns are present including the enormous communicable diseases, malnutrition, and even the non-communicable diseases [50]. furthermore, in regard to the services provided at the phc, these services are not achieving optimum utilization rates [4]. for example, only 81.6% of phc units provide vaccination for children and 67.3% provide family planning services. although, these numbers are improving in comparison to the past, they are not ideal and further emphasis on coverage, availability, and accessibility is required [51]. another notifiable weakness regarding phc, is that unlike the secondary doi 10.18502/sjms.v12i3.924 page 144 sudan journal of medical sciences production and hosting by knowledge e and tertiary services that are increasing in number, phc units are decreasing either due to cessation of function or in comparison to the population growth [4]. 4. lessons learned the analyses of sudan health system revealed strengths and weaknesses that can be learned to improve the system; 4.1. plans and strategies the strength of the system is that they have several long-term and short-term policies and strategies but as it was seen that it was insufficient because there is no sustainability and no continuous updating of the implemented plans. moreover, the deficiency of research and fragmented his didn’t assist the government to act accordingly and identify the pitfalls of the system. 4.2. human resource sudan ‘s human resource development has increased throughout the years which positively affected the service delivery but weak governance and management systems especially at state and locality levels resulted to the failure of deployment, revitalization and the poor distribution downsized the work force ability. it is critical to have effective governance for developing strategic policies, designing, funding, and implementing plans for human resource. 4.3. stakeholder the involvement of stakeholders like the army, police, universities agencies, ngo’s, banks, countries donors and others has contributed to the system definitely in supporting and maintaining health economic supplies but building partnership with the communities and civil society organizations is of paramount importance in changing health scenario as public is considered to be the pillar of the health system. 5. conclusion and recommendations a healthcare system is the organization of people, institutions, and resources that deliver health care services to meet the health needs of target populations. the sudan hss formation goes back to more than one century but healthcare in sudan is never without its problems. this paper tried to guise in to the system functionality internally doi 10.18502/sjms.v12i3.924 page 145 sudan journal of medical sciences production and hosting by knowledge e and externally. the weaknesses are predominantly seen but this desperate state of affairs is down to combination of many factors. one is lack of resources in general. the sudan is not a wealthy country and the long-standing economic sanctions have also severely impacted the country’s ability to run a functional, robust healthcare system along with constant attrition of health professional numbers. another reason for the recent downward spiral in healthcare provision is the economic impact after the sudanese post-secession economy dysfunction the one which had its staggering effect from one fiscal cliff to the next. the sudan has under gone decentralization; however, historically, it has experienced challenges and issues in coordination between hrh policies and overall health planning, as well as difficulty in translating national level planning to all levels of a decentralized health care system. coordination between health and education sectors has been weak, resulting in misdistribution and imbalance in the production of health workers in certain professions. the healthcare strategy enforcement, appropriate resource allocation changes and improved communication system in different level of the system components are the main pathways to accomplish the goals that needs to be achieved. recently sudan has also achieved several goals. the country worked with who along with other alliance to establish the national hrh observatory and developing a national comprehensive and evidence based hrh policy for the health sector with engagement of all related stakeholders. it also accomplished health-related millennium development goals (mdg), if not reach the goal it improved in a lot of senses. sudan needs to work more on the strengths it has and use the opportunities available in order to improve the basic health indicators. in order to improve the current healthcare system in the sudan, various actions may be considered. first, establishing law enforcement units in districts, smoh, and fmoh can greatly enhance compliance to existing policies. also, developing a communication system between all levels of policy making can allow for proper and timely decisions of continuation, amendment, or even termination of these policies. second, it is also recommended to not only monitor the implementation of the ongoing activities and programs but to pay extra attention to the outcome evaluation. it is also encouraged to further promote the use of his, improve quality of data, and emphasize on importance of dissemination of findings. third, providing medical personnel with incentives, providing fundamental infrastructures, and increasing the paramedic to physician ratio to meet the standard can potentially reduce the high attrition rate of professionals. lastly, upgrading the facilities of phc delivery services and building newer units to meet new demands and population growth is recommended as well as applying a bottom up approach with major emphasis on community empowerment, disease prevention, and health promotion. doi 10.18502/sjms.v12i3.924 page 146 sudan journal of medical sciences production and hosting by knowledge e references [1] m. i. roemer, national health systems and their reorientation towards health for all. guidance for policy-making. 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[49] h. christina, primary health care, why is it important? [internet]. 2015 [cited 2017 jan 23]. available from: http://www.phcris.org.au/news/newsfeed/2015/november/phcvideo.php. [50] i. elsubai, “health promotion prospects in sudan,” sudan j public heal, vol. 2, no. 1, pp. 10–20, 2007. doi 10.18502/sjms.v12i3.924 page 149 http://www.phcris.org.au/news/newsfeed/2015/november/phcvideo.php sudan journal of medical sciences production and hosting by knowledge e [51] a. louran, a. m. musa, t. hanan, n. a. mohammed, m. nazik nurelhuda et al., promoting access to high quality primary health care services in sudan [internet]. 2012. available from: https://www.researchgate.net/publication/229072353_promoting_access_to_ high_quality_primary_health_care_services_in_sudan. doi 10.18502/sjms.v12i3.924 page 150 https://www.researchgate.net/publication/229072353_promoting_access_to_high_quality_primary_health_care_services_in_sudan https://www.researchgate.net/publication/229072353_promoting_access_to_high_quality_primary_health_care_services_in_sudan introduction materials and methods results and discussion swot analysis of sudanese hss health services system in the sudan management organization of the programs: resource production economic support health service delivery lessons learned plans and strategies human resource stakeholder conclusion and recommendations references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9290 production and hosting by knowledge e research article prevalence of social anxiety disorder among medical students from six medical schools in khartoum state hazeem abdeljaleel suleiman1, sara ahmed elamin2, abdalaziz awad alobeid3, and wegdan elshame altaib4 1medical student, ain shams university, cairo, egypt 2medical student, omdurman al-ahlia university, omdurman, sudan 3medical student, omdurman islamic university, omdurman, sudan 4medical student, al neelain university, khartoum, sudan orcid: hazeem abdeljaleel suleiman: https://orcid.org/0000-0002-4812-7866 abdalaziz awad alobeid: https://orcid.org/0000-0003-3739-3031 sara ahmed elamin: https://orcid.org/0000-0002-9414-4544 wegdan elshame altaib: https://orcid.org/0000-0002-4541-1327 abstract background: social anxiety disorder (social phobia) is a type of anxiety disorder which is characterized by significant anxiety and discomfort about being embarrassed, humiliated, rejected, or looked down on in social interactions. although it affects about 30% of adults worldwide at some point in their lives, lifetime social anxiety disorder affects only about 4% of the world population. people with this disorder experience extreme fear of social interactions (e.g., public speaking and meeting new people). this anxiety affects daily functions and lasts at least six months. they may also experience strong physical symptoms like rapid heart rate, nausea, vomiting, and full-blown attacks. social phobia can be treated by a combination of psychotherapy and medical treatment (e.g., anti-anxiety, antidepressants, and beta-blockers). methods: this study was conducted using the arabic spin and a group of questions to assess the associated factors, complications, and sociodemographic determinate of social anxiety disorder and included a total of 375 medical students from different universities and educational years. results: the overall prevalence of social anxiety disorder among our participants was 61.3%, of which 19.2% had mild, 21.6% moderate, 10.9% severe, and 9.6% had very severe sad. there was a significant difference regarding self-esteem, academic achievement, and drug addiction between students with social phobia and students with no social phobia. conclusion: social phobia is quite prevalent among sudanese medical students, particularly the severe form of the disorder with no significant gender differences. it seems to affect self-esteem and academic achievement and can be associated with drug addiction. keywords: social phobia, prevalence, medical students, sudanese how to cite this article: hazeem abdeljaleel suleiman, sara ahmed elamin, abdalaziz awad alobeid, and wegdan elshame altaib (2021) “prevalence of social anxiety disorder among medical students from six medical schools in khartoum state,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 223–232. doi 10.18502/sjms.v16i2.9290 page 223 corresponding author: hazeem abeljaleel suleiman; medical student, ain shams university, cairo, egypt. email: 160994@med.asu.edu.eg received 5 april 2021 accepted 16 may 2021 published 30 june 2021 production and hosting by knowledge e hazeem abeljaleel suleiman et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://orcid.org/0000-0002-4812-7866 https://orcid.org/0000-0003-3739-3031 https://orcid.org/0000-0002-9414-4544 https://orcid.org/0000-0002-4541-1327 mailto:160994@med.asu.edu.eg https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hazeem abeljaleel suleiman et al 1. introduction social anxiety disorder (sad; also known as social phobia) is a type of anxiety disorder which is characterized by significant anxiety and discomfort about being embarrassed, humiliated, rejected, or looked down on in social interactions [1]. anxiety disorders are common and affect about 30% of adults worldwide at some point in their lives [1]. however, lifetime sad affects only about 4% of the world population [2]. interestingly, sad intends to show a direct relationship with average country income as its mean prevalence is shown to be 5.5% in high-income countries and 6.4% in the regions of america while it is 1.6% in lowincome countries and 1.2% in the regions of africa and middle east [2]. these differences can be explained by differences in regional diagnostic thresholds in higher-income countries, poor statistical services in middleand low-income countries, and higher demands for social performance in highincome countries may also play a role. people with this disorder experience extreme fear of social interactions (e.g., public speaking and meeting new people). this anxiety affects daily functions and lasts at least six months [1]. patients with social phobia may also experience strong physical symptoms. common examples are rapid heart rate, nausea, and vomiting, however, they may also experience full-blown attacks when confronting a feared situation [3]. social phobia can be treated by a combination of psychotherapy, group therapy, and medical treatment (e.g., anti-anxiety, antidepressants, and beta-blockers) [4]. many studies have been conducted to evaluate social phobia prevalence, risk factors, complications, and prevention efforts in different countries. however, to the best of our knowledge, studies addressing social phobia among sudanese medical students are scarce. therefore, the current study was conducted to measure the prevalence of social phobia in a group of medical students from six medical schools in khartoum, sudan. this study will help the healthcare organizations in sudan to take social phobia and anxiety disorders in general as a real threat to patient’s quality of life and to put suitable intervention for them. moreover, the study is quite important to medical students as they need to know about social phobia and how to manage it because their future career will inevitably require a lot of social interactions, presentations at clinical meetings and at large-scale academic and administrative events regardless of their chosen specialty. doi 10.18502/sjms.v16i2.9290 page 224 sudan journal of medical sciences hazeem abeljaleel suleiman et al 2. materials and methods 2.1. study population and design this cross-sectional study was conducted at the faculty of medicine of the six chosen universities. a convenient sample of 375 was calculated using sad prevalence among university students in saudi arabia that equaled 60% [7]. the confidence interval was 95%. the sample size was calculated using epi info 2002 program. 2.2. study tools data from december 15, 2020 to january 15, 2021 were collected using an online selfadministrated questionnaire that consisted of four sections. section one included sociodemographic characteristics (gender, age, study year, and university). section two included the arabic version of the social phobia inventory (spin) to assess the prevalence of sad and its degree among participants. the arabic spin was found to have excellent internal consistency and good test–re-test reliability. a cut-off score of 23 distinguished well between those with social phobia and those without. it was reliable and valid for the screening the population [5]. section three included factors that can be associated with sad, such as family history of similar conditions, suffering bullying in childhood, and presence of diseases that can be associated with stigma like congenital anomalies (e.g., on the face) and diseases causing involuntary movements (e.g., in parkinsonism). section four included the expected complications of sad, such as low selfconfidence, low academic achievement, drug addiction, and suicide attempts. 2.3. statistical analysis the collected data were revised, coded, entered into a pc, and analyzed using the spss version 16. the collected data were analyzed according to the type of variables. quantitative variables were presented by their mean and standard deviation and analyzed using t-test. qualitative variables were presented by frequency and analyzed using the chi-square test. p-value < 0.05 was considered as significant. doi 10.18502/sjms.v16i2.9290 page 225 sudan journal of medical sciences hazeem abeljaleel suleiman et al 3. results in total, 375 students responded to the questionnaire with a response rate of 28%. this low rate reflects the low awareness of sad among sudanese medical students. of the 375 participants, 123 (23.8%) were males and 252 (67.8%) females; 350 (93.3%) of them were in the 18–23 years and 25 (6.7%) in the 24–30 years age groups with a mean age of 21.4 years (sd = 1.46); 264 (70.4%) of them were in the first three levels and 111 (29.6%) were in the fourth and fifth levels (table 1). moreover, 94 (25.1%) participants were from omdurman islamic university (oiu), 70 (18.7%) from omdurman al-ahlia university (oau), 67 (17.9%) from khartoum university, 57 (15.2%) from al-zaiem alzhari university (aau), 69 (18.4%) from al-nilain university (nu), and 18 (4.7%) from sudan university of science and technology (sust) (table 1). in total, 230 (61.3%) students were found to have sad, of which 72 (19.2%) had mild, 81 (21.6%) moderate, 41 (10.9%) severe, and 36 (9.6%) had very severe sad (figure 1). out of the 123 males, 73 (59.3%) had sad and out of the 252 females, 157 (62.3%) had sad (figure 2). moreover, 65.6% of khartoum university students, 65.2% of nu students, 64.9% of oiu students, 59.6% of aau students, 52.8% of oau students, and 50% of sust students had sad (figure 2). figure 1: prevalence of sad among participants. doi 10.18502/sjms.v16i2.9290 page 226 sudan journal of medical sciences hazeem abeljaleel suleiman et al figure 2: prevalence of sad by gender and university. table 1: sociodemographic characteristics. sex males females 123 (32.8%) 252 (67.2%) age (yr) 18–23 24–30 350 (93.3%) 25 (6.7%) university khartoum 67 (17.9%) al-nilain 69 (18.4%) omdurman islamic university 94 (25.1%) omdurman alahlia university 70 (18.7%) al-zaiem alzhari 57 (15.2%) sudan university 18 (4.7%) level 1st–3rd 4th–5th 264 (70.4%) 111 (29.6%) initial analysis showed that 184 (80%) students with sad considered themselves shy in comparison to 40 (27.6%) students with no sad; 148 (64.3%) students with sad had low self-esteem in comparison to 25 (17.2%) students with no sad; 90 (39.1%) students with sad had high academic grades (b or higher) in comparison to 80 (55.1%) with no sad. these differences were found to be statistically significant (p-value < 0.05) (table 2). doi 10.18502/sjms.v16i2.9290 page 227 sudan journal of medical sciences hazeem abeljaleel suleiman et al table 2: associated factors of sad. normal social anxiety disorder p-value family history of social anxiety disorder n = 4 (2.75%) n = 6 (2.6%) 0.153 being bullied in childhood n = 64 (44.1%) n = 128 (55.6%) 0.120 are you a shy person? n = 40 (27.6%) n = 184 (80%) 0.000 presence of congenital anomalies n = 3 (2%) n = 11 (4.8%) 0.435 presence of diseases causes involuntary movements n = 0 (0%) n = 8 (3.5%) 0.178 suffering low self-esteem n = 25 (17.2%) n =148 (64.3%) 0.000 suicidal attempts n = 11 (7.6%) n = 17 (7.4%) 0.05 drug addiction n = 6 (4.1%) n = 16 (6.9%) 0.675 high academic achievement (b or higher) n = 80 (55.1%) n = 90 (39.1%) 0.002 table 3: poisson regression analysis of associated factors of sad. poisson regression analysis items p-value estimates of coefficients 95% wald confidence interval 95% wald confidence interval for exp (b) family history of social anxiety disorder p = 0.880 0.057 –0.600–0.429 0.549–1.536 being bullied at childhood? p = 0.905 0.011 –0.151–0.184 0.860–1.202 are you a shy person? p < 0.001 1.234 0.059–0.443 1.061–1.557 presence of congenital anomalies p = 0.805 –0.003 –0.390–0.431 0.677–1.539 presence of diseases causes involuntary movements p = 0.368 0.182 –0.371–0.671 0.690–1.975 suffering low self -esteem p < 0.001 0.626 –0.035–0.337 0.966–1.401 suicidal attempts p = 0.390 0.260 –0.258–0.405 0.772–1.499 drug addiction p = 0.037 0.079 –0.369–0.255 0.692–1.290 high academic achievement (b or higher) p = 0.046 0.22 –0.218–0.117 0.804–1.124 poisson regression analysis was done for further assessing the relation between the associated factors and social phobia; however, except for drug addiction (p = 0.037), no more significant differences between the two groups were found (table 3). 4. discussion the prevalence of sad in the present study was 61.3% which is lower than the other sudanese study that showed a 78.4% prevalence of anxiety [6] but is very similar to a doi 10.18502/sjms.v16i2.9290 page 228 sudan journal of medical sciences hazeem abeljaleel suleiman et al study conducted at king khalid university in saudi arabia that showed a prevalence of 60% [7]. furthermore, although a high prevalence (92.1%) was reported in a study conducted in saudi arabia on 1,447 medical students [8], a lower prevalence was reported in a study in norway [9] and england [10]. these differences can be attributed to the use of different evaluating tools, and gender and cultural differences between different populations may play a role. in our study, there was no significant difference in the prevalence of sad between males (59.3%) and females (62.3%). these findings were found to be lower than the saudi study which showed a prevalence of 92.8% in males and 91.7% in females [8] and higher than the findings of an indian study that showed a female prevalence of 16.28% and a male prevalence of 10.97% [11]. among students who had sad, the most common form was moderate sad (21.6%), followed by mild and severe (19.2 and 10.9%, respectively), and very severe sad (9.6%). these findings are higher than the findings of a study conducted in ethiopia [12]. our findings show that students with sad tend to get significantly higher grade than students with no sad (p = 0.001), which is consistent with the findings of king khalid university study [7]. however, it contrasts with another study conducted in iran [13]. additionally, our findings show a significantly positive association between sad and drug abuse, which is consistent with the findings of a systematic review published in the american journal of drug and alcohol abuse [14]. study limitations selective bias caused using convenient sampling. convenience sampling was used due to the lack of interest of students to participate in the study, which reflects the low awareness about sad, and this selection bias could have underestimated the true prevalence and severity of sad. 5. conclusion there was a moderate grade of social phobia between participants with no significant gender differences, and social phobia seems to affect self-esteem and academic achievement and can be associated with drug addiction. doi 10.18502/sjms.v16i2.9290 page 229 sudan journal of medical sciences hazeem abeljaleel suleiman et al recommendations (i) we recommend implanting programs to raise awareness about social phobia, especially among medical students. these programs can include defining illness and ways to cope with stress, reducing symptoms, and encouraging visiting a psychiatrist. (ii) we encourage more future studies that avoid our study limitations and include a wider population than medical students. also, there is a need for more studies focusing on therapeutic interventions, pre-enrolment assessment of medical students, and exploration of the link between both underachievement and drug addiction and sad. acknowledgements the authors are grateful to the medical students for their cooperation in the study. ethical considerations participation was voluntary and confidentiality was assured to all respondents. they were informed about the study’s objectives and that the data collected would be used only for the stated research purposes. competing interests none. availability of data and materials the study materials are available from the corresponding author upon request. funding the author received no funding for this research. doi 10.18502/sjms.v16i2.9290 page 230 sudan journal of medical sciences hazeem abeljaleel suleiman et al references [1] american psychiatric association. (n.d.). what are anxiety disorders? retrieved from: https://www.psychiatry.org/patients-families/anxiety-disorders/what-areanxiety-disorders [2] stein, d. j., lim, c. c. w., roest, a. m., et al. (2017). the cross-national epidemiology of the social anxiety disorder: data from the world mental health survey initiative. bmc medicine, vol. 15, article 143. [3] national institute of mental health. (n.d.). social anxiety disorder: more than just shyness. retrieved from: https://www.nimh.nih.gov/health/publications/socialanxiety-disorder-more-than-just-shyness/ [4] american depression & anxiety association. (n.d.). understand the facts – social anxiety disorder. retrieved from: https://adaa.org/understanding-anxiety/socialanxiety-disorder/. [5] ragheb, m., ramy, h., hussein, h., et al. (2007). psychometric properties of the arabic version of social phobia inventory (spin). current psychiatry, vol. 14, no. 1, pp. 36–44. [6] dafaalla, m., farah, a., bashir, s., et al. (2017). depression, anxiety, and stress in sudanese medical students: a cross sectional study on role of quality of life and social support. american journal of educational research, vol. 4, no. 13, pp. 937– 942. [7] alqarni, a. a., zalaa, m. a., el-hadad, a. a., et al. (2017). prevalence of social phobia among saudi medical students. medical journal of cairo university, vol. 85, no. 2, pp. 657–661. [8] alkhalifah, a. k., alsalameh, n. s., alhomaidhy, m. a., et al. (2017). prevalence of social phobia among medical students in saudi arabia. the egyptian journal of hospital medicine, vol. 69, no. 5, pp. 2412–2416. [9] kjeldstadli, k., tyssen, r., finset, a., et al. (2006). life satisfaction and resilience in medical school-a six-year longitudinal, nationwide and comparative study. bmc medical education, vol. 6, no. 48, pp. 1–8. [10] laidlaw, a. h. (2009). social anxiety in medical students: implications for communication skills teaching. medical teacher, vol. 31, no. 7, pp. 649–654. [11] jogdande, a. j. and gupta, a. (2017). social anxiety disorder in medical students: socio-demographic correlates. international journal of community medicine and public health, vol. 4, no. 9, pp. 3293–3296. doi 10.18502/sjms.v16i2.9290 page 231 https://www.psychiatry.org/patients-families/anxiety-disorders/what-are-anxiety-disorders https://www.psychiatry.org/patients-families/anxiety-disorders/what-are-anxiety-disorders https://www.nimh.nih.gov/health/publications/social-anxiety-disorder-more-than-just-shyness/ https://www.nimh.nih.gov/health/publications/social-anxiety-disorder-more-than-just-shyness/ https://adaa.org/understanding-anxiety/social-anxiety-disorder/ https://adaa.org/understanding-anxiety/social-anxiety-disorder/ sudan journal of medical sciences hazeem abeljaleel suleiman et al [12] desalegn, g. t., getinet, w., and tadie, g. (2019). the prevalence and correlates of social phobia among undergraduate health science students in gondar, gondar ethiopia. bmc research notes, vol. 12, article 438. [13] mazhari, s. h., ekhlaspour, m., and banazadeh, n. (2014). social phobia and its association with academic performance among student of kerman university of medical sciences, iran. journal of strides in development of medical education, vol. 11, no. 2, pp. 227–235. [14] lemyre, a., gauthier-légaré, a., and bélanger, r. e. (2018). shyness, social anxiety, social anxiety disorder, and substance use among normative adolescent populations: a systematic review. the american journal of drug and alcohol abuse, vol. 45, no. 3, pp. 1097–9891. doi 10.18502/sjms.v16i2.9290 page 232 introduction materials and methods study population and design study tools statistical analysis results discussion study limitations conclusion recommendations acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9292 production and hosting by knowledge e research article assessment of knowledge, qualification, experience, and medication dispensing practices in south karachi, pakistan nauman haider siddiqui1, abdullah dayo1, mudassar iqbal arain2, muhammad ali ghoto2, saira shahnaz3, ramesha anwar4, and jibran khan1 1department of pharmaceutics, faculty of pharmacy, university of sindh, jamshoro, pakistan 2department of pharmacy practice, faculty of pharmacy, university of sindh, jamshoro, pakistan 3department of pharmacy practice, faculty of pharmacy, nazeer hussain university, karachi, pakistan 4department of pharmacy practice, faculty of pharmacy, university of karachi, karachi, pakistan orcid: nauman haider siddiqui: http://orcid.org/0000-0002-1797-9927 abstract background: drug stores in pakistan are run by dispensers with varied knowledge, qualification, and experience. the current study was sought to explore the knowledge, qualification, experience, and dispensing practices among dispensers working in drugstores in south karachi, pakistan. methods: a cross-sectional survey was carried out using a structured questionnaire. data were collected from medical stores in south karachi which were then categorized, coded, and analyzed using spss version 23. relationship among different study variables with pharmacist’s availability and personal experience was assessed using statistical non-parametric chi-square test. a total of 385 samples obtained using a simple random sampling method were included in the study. however, only 210 responses on questionnaire were complete which were then selected for study analysis between october and december 2018. results: of the 210 surveyed drugstores, 9% of their staff had studied only till primary school, 5.7% till the eighth grade, 25.2% up to secondary school level, 26.7% till higher secondary school level, 15.7% had non-professional education, and 8.1% were professional graduate. only 9% of them had a degree in pharm. d or b. pharm, while 0.5% had a post-graduation qualification. furthermore, 44.8% of pharmacies had a valid pharmacy license but the pharmacist was physically absent in 91% of the drugstores. majority of pharmacies did not maintain appropriate temperature (refrigerator and/or room temperature). majority of dispensers did not review prescription particulars before dispensing medications and also dispensed medications on older prescriptions as well as without prescription. conclusion: in conclusion, the overall knowledge and practices of dispensers working in drugstores was poor. however, the presence of pharmacist was associated with good dispensing practices to a certain extent. keywords: community pharmacy, good dispensing practice, pharmacist, prescription review how to cite this article: nauman haider siddiqui, abdullah dayo, mudassar iqbal arain, muhammad ali ghoto, saira shahnaz, ramesha anwar, and jibran khan (2021) “assessment of knowledge, qualification, experience, and medication dispensing practices in south karachi, pakistan,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 245–258. doi 10.18502/sjms.v16i2.9292 page 245 corresponding author: nauman haider siddiqui; department of pharmaceutics, faculty of pharmacy, university of sindh, jamshoro. email: mudassarpk@live.com received 14 march 2021 accepted 22 may 2021 published 30 june 2021 production and hosting by knowledge e nauman haider siddiqui et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0002-1797-9927 mailto:mudassarpk@live.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences nauman haider siddiqui et al 1. introduction pharmacy services begin with prescription of medicines and continues till its dispensing and as medication’s effect is monitored [1]. good dispensing practices ensure that an effective form of correct drug is provided to the right patient, in correct dose and number of units, with clear instructions, and in a package that maintains the potency of drug. dispensing also incorporates all of actions that befall between the time prescription is dropped to pharmacy and the time when medication or other articles prescribed are delivered [2]. in pakistan, medications-use patterns vary among gender and age groups. selfmedication and polypharmacy are frequent amid the youth and elderly population, respectively [3–7]. likewise, the self-use of analgesics and antipyretics is very common among youth [3–5]. systematized dispensing practices are disregarded in community pharmacies as well as in hospitals [8]. unfortunately, majority of the drug dispensing at pharmacies and medical stores is carried out by untrained dispensers with no proper qualification in pharmacy. in such circumstances, there is a serious need to ensure the presence of a qualified pharmacist at all retail pharmacies so that the medications are safely dispensed [9, 10]. lack of physicians in the rustic regions has created an opportunity for the dispensers and quacks to fill the gap where they are the only decision-makers of the medications for the public [11]. furthermore, patients have to cover long distances to acquire basic medications. additionally, most of the medications can be purchased from private pharmacies without showing a legal prescription [3, 12, 13]. a study carried out in pakistan stated that numerous dispensers have irrelevant education and negligible or no competent training in managing drugstores [14]. provided that with inadequate knowledge concerning indications, contraindications, as well as side effects, their dispensing practices might have unwanted outcomes. although a system of healthcare facilities exists in pakistan’s public division as well as an overabundance of private division programs, 45% of people still face paucities to approach to healthcare facilities. however, to encounter healthcare necessities and decrease personal costs, people depend on unconventional healthcare systems such as chemists, contemporary medication specialists, faith healers, and homeopaths. huge disparities in formal healthcare division promote self-medication; therefore, knowledge as well as practices of dispensers become significantly valuable [15]. drugstores in developing countries like pakistan are frequently deficient of competent and trained dispensers to store, label, and handle medicines in suitable manner which may compromise drug safety and its therapeutic outcomes. therefore, the current study was sought doi 10.18502/sjms.v16i2.9292 page 246 sudan journal of medical sciences nauman haider siddiqui et al to explore the dispensing practices in medical stores/pharmacies in pakistan and to investigate the implementation of laws and regulations regarding selling, storage, and dispensing of medications. 2. materials and methods a cross-sectional survey was carried out using a structured questionnaire. the structured questionnaire was developed from the who surveillance form designed for perceiving medicine counselling and dispensing practices and was customized in accordance with the aims of this study [16]. data were collected from pharmacies/medical stores of south karachi. the city of karachi is divided into six districts, south, central, west, east, korangi, and malir. the southern district of karachi has the distinction of being the only district in the country with a representation of all ethnic and socioeconomic groups of the country [17]. the present study was conducted between october and december 2018 and included 384 samples obtained through simple random sampling method. the accuracy and consistency of data collection form was assessed in a pilot study of 20 pharmacies. each pharmacy was observed for one day. the response of pharmacies to participate in study was also estimated to calculate the sample size. the standardized questionnaire was tested on 30 participants before the actual data collection and it was modified into a list of questions that were comprehensive and unambiguous. a predesigned and pretested survey in english language was utilized to collect responses. a total of 385 samples were included in the study. the sample size was obtained using a simple random sampling method, out of which 210 responses on questionnaire were complete and selected for study analysis. conversely, those who did not understand english were questioned by researcher in local urdu and the answers were then translated into english. we used paper-based questionnaire. the structured questionnaire consisted of 33 questions containing information on demographics, level of education, experience, temperature control information, dispensing practices, presence of pharmacist, and status of pharmacy licensing. only participants who met the following criteria were included: male or female irrespective of age, retailers who were involved in the pharmaceutical drug sales, owner as well as employee in pharmacy, participant with any qualification and/or level of education with zero to any number of years of experience, pharmacies/medical stores in southern region of karachi involved in drug dispensing. conversely, participants who met the following criteria were excluded: wholesalers and distributors, retailers associated with sales other than pharmaceutical drugs, all inadequately filled questionnaires, pharmacies/medical stores doi 10.18502/sjms.v16i2.9292 page 247 sudan journal of medical sciences nauman haider siddiqui et al located in other areas than the south of karachi, participants working in store/stock management and administrative positions. data collected in the form of completed questionnaires were then categorized, coded, and analyzed. they were expressed as percentages and frequencies. the relationship among different study variables with pharmacists’ availability was assessed using a statistical non-parametric chi-square test at 0.05 level of significance with the help of spss version 23. 3. results table 1 indicates the demographics of study participants. it was observed that 3.8% of the questionnaire respondents were female while 96.2% were male; 9% of the participants had only studied till primary school, 5.7% till the eighth grade, 25.2% were qualified up to secondary school level, 26.7% till higher secondary school level, 15.7% had nonprofessional education, and 8.1% were professional graduate. however, only 9% of them had a degree in pharm. d or b. pharm, while 0.5% had a postgraduation qualification. furthermore, 74.3% were employed in pharmacy and 25.7% were the owner of the pharmacy. table 1: demographics of study participants. gender male 96.2% (202) female 3.8% (8) education primary school 9% (19) till the eighth grade 5.7% (12) secondary school 25.2% (53) higher secondary school 26.7% (56) non-professional graduation 15.7% (33) professional graduation 8.1% (17) pharm. d or b. pharm 9% (19) postgraduation 0.5% (1) employment status employed 74.3% (156) owner 25.7% (54) work experience (yr) <1 41% (86) 1–3 17.1% (36) 4–6 23% (48) >6 19% (40) doi 10.18502/sjms.v16i2.9292 page 248 sudan journal of medical sciences nauman haider siddiqui et al table 2 shows the figures of medication storage conditions, power backup, pharmacy license, and availability of pharmacy. while 44.8% of pharmacies had a valid pharmacy license, 55.2% did not. also, a pharmacist was physically absent in 91% of the pharmacies and present only in 9%. furthermore, 72.4% of pharmacies did not maintain the recommended temperature for medicines that need to be refrigerated (i.e., 2–8°c), only 27.6% maintained refrigerator temperature. it was observed that 57.6% of the pharmacies did not maintained room temperature (i.e., 25°c) but 42.4% of them did. table 2: medication storage conditions, power backup, pharmacy license, and availability of pharmacy. valid license for pharmacy yes 44.8% (94) no 55.2% (116) physical presence of a pharmacist yes 9% (19) no 91% (191) power backup yes 27.6% (58) no 72.4% (152) refrigerator temperature maintained (2–8∘∘∘c) yes 27.6% (58) no 72.4% (152) room temperature maintained (25∘∘∘c) yes 42.4% (89) no 57.6% (121) table 3 reveals the dispensing practices observed in pharmacies. it shows that 91.9% of study participants did not review prescription particulars before dispensing medications. only 8.1% of them responded that they reviewed prescription particulars before dispensing medications. furthermore, 18.1% did not dispense medications without prescription, while 81.9% of them did so. while dispensing medications on old prescriptions was observed in 81.9% of the participants, only 18.1% did not do so. medication categories dispensed without prescription included otc (41.4%), antibiotics (16.7%), analgesics (6.2%), antidiabetic (5.7%), anti-allergy (5.2%), antidiarrheal (3.3%), cough syrups (7.1%), antihypertensive (4.3%), and others (10%). it was also noted that 31% of the participants did not dispense herbal medications while 69% did so. alternative brands were not suggested in by 91.9% of the study participants while 8.1% of them dispensed alternative brands in case of nonavailability of the prescribed brand. furthermore, 59.5% of the study participants did not confirm the expiry date of the medicine before dispensing while 40.5% of them did so. doi 10.18502/sjms.v16i2.9292 page 249 sudan journal of medical sciences nauman haider siddiqui et al table 3: dispensing practices observed in pharmacy. reviewing prescription particulars before dispensing yes 8.1% (17) no 91.9% (193) dispensing without prescription yes 81.9% (172) no 18.1% (38) medicine categories dispensed without prescription otc 41.4 (87) antibiotic 16.7 (35) analgesic 6.2 (13) antidiabetic 5.7 (12) anti-allergy 5.2 (11) antidiarrheal 3.3 (7) cough syrups 7.1 (15) antihypertensive 4.3 (9) others 10 (21) dispensing of herbal medicines yes 69% (145) no 31% (65) dispensing medicines on older prescriptions yes 81.9% (172) no 18.1% (38) dispensing alternative brands in case of nonavailability of prescribed brand yes 8.1% (17) no 91.9% (193) expiry date confirmation before dispensing yes 40.5% (85) no 59.5% (125) table 4 shows awareness of participants regarding various essentials of pharmacy practice. it was found that 51.9% of the participants were not aware of abbreviations used in prescription. however, only 20% of the study participants were aware of ≤25% of abbreviations, 11% of 25–50% of abbreviations, 10.5% of 50–75% of abbreviations, and only 6.7% were aware of >75% of abbreviations. furthermore, only 8.1% of the study participants were aware of various schedules of medicines. awareness of participants regarding pregnancy categories of medicines was also quite low, that is, only 9%. awareness of participants regarding various look-alike and sound-alike medicines was also unsatisfactory, that is, only 35.2%. similarly, participant’s awareness regarding generic medicines, drug recall, adverse drug reactions, and life-saving medicines was 31, 35.2, 11.9, and 41.4%, respectively. doi 10.18502/sjms.v16i2.9292 page 250 sudan journal of medical sciences nauman haider siddiqui et al table 4: awareness regarding various essentials of pharmacy practice. awareness of various abbreviations used in prescriptions awareness of no abbreviations 51.9% (109) awareness of ≤25% of the abbreviations 20% (42) awareness of 25–50% of the abbreviations 11% (23) awareness of 50–75% of the abbreviations 10.5% (22) awareness of >75% of the abbreviations 6.7% (14) awareness of various schedules of medicines yes 8.1% (17) no 91.9% (193) awareness of pregnancy category of medicines yes 9% (19) no 91% (191) awareness of various look-alike and sound-alike medicines yes 35.2% (74) no 64.8% (136) awareness of generic medicines yes 31% (65) no 69% (145) awareness of drug recall yes 35.2% (74) no 64.8% (136) awareness of adverse drug reactions yes 11.9% (25) no 88.1% (185) awareness of lifesaving medicines yes 41.4% (87) no 58.6% (123) table 5 reveals relationship among different study variables with pharmacist availability. chi-square test was applied at 0.05 level of significance to check the association of different variables with the availability of a pharmacist at a drug store. it was found that there is a significant relationship between the presence of power backup at pharmacies, refrigerator temperature maintenance, room temperature maintenance, reviewing prescription particulars before dispensing, dispensing alternative brands in case of nonavailability of prescribed brand, and expiry date confirmation before dispensing and the availability of a pharmacist at a drug store at 0.000 (two-tailed). the level of significance and variables such as dispensing without prescriptions and dispensing on doi 10.18502/sjms.v16i2.9292 page 251 sudan journal of medical sciences nauman haider siddiqui et al older prescriptions had no significant relationship with the presence and availability of pharmacist at a drug store. table 5: cross-tabulation of variables. variables pharmacist availability pharmacist present pharmacist absent power backup yes 17 41 no 2 150 p-value 0.000 refrigerator temperature maintenance yes 17 41 no 2 150 p-value 0.000 room temperature maintenance yes 19 70 no 0 121 p-value 0.000 reviewing prescription particulars before dispensing yes 17 2 no 0 191 p-value 0.000 dispensing without prescription yes 0 172 no 19 19 p-value 0.098 dispensing medicines on older prescriptions yes 2 170 no 17 21 p-value 0.105 dispensing alternative brands in case of nonavailability of prescribed brand yes 17 0 no 2 191 p-value 0.000 expiry date confirmation before dispensing yes 19 66 no 0 125 p-value 0.000 4. discussion in the past century, pharmacy as a profession mostly included compounding. while the compounding roles have declined considerably in the last few decades, it has turned out primarily to be dispensing medications. nevertheless, merely dispensing doi 10.18502/sjms.v16i2.9292 page 252 sudan journal of medical sciences nauman haider siddiqui et al of medications does not satisfy the necessities, and not long ago, a new role had to be progressed for the profession [18, 19]. the aim of the pharmacy practice is to offer medicine in addition to further healthcare products and facilities, and to benefit people and community to make the best use of them [20]. pharmacists need to be part of clinical decision-making for sensible use of medications. the transforming position of pharmacist as patient counsellor/instructor as well as an intermediary to enhance therapy outcome is important for encouraging reasonable use of medications [21]. the system by which medications are procured, stored, distributed, as well as dispensed and information provided by pharmacist determines the quality use, consequently in terms of motivating rational practice of medications [22]. in our study, it has been observed that only 9% of the pharmacists were present in various pharmacies. rest of the pharmacies/medical stores had unqualified personals including personals who never attended school or those who had studied only till the eighth grade or had attended secondary or higher secondary school. others had a professional education and single study participant was a qualified postgraduate. a study reports that generally qualification, understanding, and schooling of drug dispensers functioning at community drugstores in pakistan is deficient. pharmacies are mostly run by unqualified as well as inexpert personals. however, it has been noticed that they have copious years of experience [23]. similar findings have been observed in our study that although majority of pharmacies had unqualified personals, they had plenty of experience. the existence of legitimately competent individuals is insignificant at drugstores. in majority of circumstances proprietors are operating instead of a trained individual [24]. however, in our study, it was observed that 74.3% of the participants were employee working in the pharmacy while 25.7% were the owner of the pharmacy. according to the drug acts of pakistan, pharmacy buildings must have suitable facilities to store drugs including refrigeration, cleanliness of outlets, hygienic and neat condition, and constant personal observation of a pharmacist [25]. however, in our study, it was revealed that majority of pharmacies did not took necessary measures for proper storage of medicines. medicines are not stored in hygienic conditions and appropriate temperature was not maintained. very few drugstores had power backup for refrigerator, which is a major distress as a consequence of extreme occurrence of power breakdown in city. these customs uncover that generally society is unaware or ignorant with regard to storage medications. in a related study from karachi, greater than half of the pharmacies stored medications in compromised storage settings [14, 15, 26, 27]. moreover, it was found in our study that 44.8% of the pharmacies had a valid pharmacy license, while 55.2% did not. however, it has been reported in a study that while 62.4% doi 10.18502/sjms.v16i2.9292 page 253 sudan journal of medical sciences nauman haider siddiqui et al of the participants had a license for retail sale, only 5.6% of them were license holder for wholesale. another one-fourth of the total drug sellers (26.9%) were those having no license at all. moreover, only 5.1% of the participants possessed license for the sale of controlled substances. but a total of 66% drug sellers were involved in selling of controlled substances [28]. about 81.9% of the study participants admitted selling medicines without prescription. similarly, 81.9% of them admitted selling medicines on older prescriptions too. moreover, a study from rawalpindi reported that almost 16% of the study participants disclosed that they dispense medication even without prescription, however, this might be an underestimate, considering that it disregards acceptable practices [15]. this has greatly to do with the reality that regulations concerning drug dispensing are not appropriately enforced, and drugstores are unrestricted to dispense medicines deprived of prescriptions. medication categories dispensed without prescription included otc (41.4%), antibiotics (16.7%), analgesics (6.2%), antidiabetic (5.7%), anti-allergy (5.2%), antidiarrheal (3.3%), cough syrups (7.1%), antihypertensive (4.3%), and others (10%). similar findings have been reported in other studies in which it was reported that analgesics, antibiotics, antidiarrheal agents, antihistamines, antipyretics, cough-suppressants, “tonics,” and vitamins are readily available without prescription from community pharmacies in pakistan [29–33]. 5. conclusion medical stores/pharmacies of south karachi surveyed in this study demonstrated poor dispensing practice. the structure and services do not meet the standards of who regarding medication-dispensing practice. the education level/qualification of dispensers is also questionable. the consequence of unsatisfactory procedures for medication dispensation can have damaging effects on public health and, for itself, those stores warrant great attention of public health researchers. there is a strong need for the implementation of laws and regulations in their full spirit. persistent inappropriate use of medicine among the population living in the region of the study indicates a strong need for public education on the appropriate use of medicine via educational interventions and awareness seminars. doi 10.18502/sjms.v16i2.9292 page 254 sudan journal of medical sciences nauman haider siddiqui et al acknowledgements the authors acknowledge the supporting staff and faculty members who guided them throughout the research process. ethical considerations the study was approved by the advance studies and research board of university of sindh jamshoro, pakistan. verbal as well as written informed consents were taken from respondents after concise introduction to study. competing interests the authors have no conflicts of interest to declare. availability of data and material all relevant data and methodological detail pertaining to this study are available to any interested researcher upon reasonable request to corresponding author. funding none. references [1] alam, s., osama, m., iqbal, f., et al. 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(2005). complementary and alternative medicine in pakistan: prospects and limitations. evidence-based complementary and alternative medicine, vol. 2, no. 2, pp. 139–142. doi 10.18502/sjms.v16i2.9292 page 258 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9951 production and hosting by knowledge e research article metal complexes and their potential therapeutic role against covid-19: recent developments in drug designing kanwal ashiq1,2, bushra naureen2, and sana ashiq3 1faculty of pharmaceutical sciences, superior university, lahore, pakistan 2punjab university college of pharmacy, university of the punjab lahore, pakistan 3department of chemistry, faculty of science, universiti malaya, 50603 kuala lumpur, malaysia 4centre for applied molecular biology, university of the punjab, lahore, 53700, pakistan orcid: kanwal ashiq: https://orcid.org/0000-0001-8193-5147 bushra naureen: https://orcid.org/0000-0001-9535-4490 sana ashiq: https://orcid.org/0000-0003-0418-4022 abstract covid-19 is a global pandemic caused by severe acute respiratory syndromecoronavirus 2 (sars-cov-2). being associated with high mortality rates, this pandemic has forced several countries worldwide to impose complete lockdowns to limit the spread of infection. despite the development of various vaccines, there is still an urgent need to design novel treatments backed with safety data for fighting sars-cov2 and its various mutants. currently, scientists are putting their strenuous efforts into finding the best treatment option for covid-19. in this regard, metal complexes being active antiviral agents and immunity enhancers have great potential against sarscov-2. herein, metal complexes’ therapeutic role and significance against treating sars-cov-2 or any of its target proteins are discussed. keywords: covid-19, sars-cov-2, pandemic, metal complexes 1. introduction in december 2019, a novel virus called severe acute respiratory syndrome-coronavirus 2 (sars-cov-2) was identified as a causative agent of covid-19. unfortunately, the swift spread of this virus resulted in loads of mortality and morbidity across the globe [1]. on march 11, 2020, the world health organization (who) declared this health emergency a pandemic and issued various safety measures to prevent the spread of infection. during the pandemic, almost all sorts of academic, social, cultural, and political activities were canceled, and a complete lockdown was observed worldwide to limit the spread of infection. throughout 2020, scientists were engaged in discovering, investigating, and analyzing various drugs to determine the cure of this lethal disease [2–4]. how to cite this article: kanwal ashiq, bushra naureen, and sana ashiq (2021) “metal complexes and their potential therapeutic role against covid-19: recent developments in drug designing,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 540–545. doi 10.18502/sjms.v16i4.9951 page 540 corresponding author: kanwal ashiq; email: kanwal.ashiq@superior.edu.pk received 08 august 2021 accepted 23 november 2021 published 31 december 2021 production and hosting by knowledge e kanwal ashiq et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:kanwal.ashiq@superior.edu.pk mailto:kanwal.ashiq@superior.edu.pk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences kanwal ashiq et al. 2. overview currently, many compounds are under clinical evaluation; however, the best treatment option is still not known. providentially, after strenuous efforts of scientists in collaboration with academia and pharmaceutical industries, many effective vaccines had been developed in 2020. these vaccines provide a prophylactic defense to healthy people but may be less useful in the emergence of virus variants and patients with a compromised immune system. therefore, it is necessary to seek additional novel cures for covid-19 [5]. in an attempt to find new treatments, researchers are also focusing on preparing and screening drug metal complexes. apart from being a potential candidate to treat covid-19, drug metal complexes could be a source of multifold benefits, for example, the human body needs metal ions to perform vital functions such as an iron-containing protein (hemoglobin) that carries oxygen to all tissues of the body. similarly, zinc fingers play a role in dna recognition and the regulation of gene functions [6, 7].moreover, trace elements including zinc and copper are essential for growth and play a role in the development and boosting of the immune system. in this aspect, different approaches can be considered to utilize drug metal complexes as effective therapeutic agents against covid-19 [8]. initially, drug repurposing strategy can be considered to assess previously established metallodrugs, such as a gold drug called auranofin seems a potential candidate, yet few other approved metal complexes are also creditable. secondly, chemically diverse libraries of inorganic compounds can be monitored to identify molecules with efficient activity against covid-19. this approach is the pathway-guided discovery which is based on basic knowledge of the mechanism of action and exploration of the chemical entities that effectively inhibit viral proteins responsible for covid-19 pathogenesis [9]. many computational tools are available that are frequently used in research to gauge the activity of chemical compounds based on an understanding of the drug and its target structure. in this respect, vanadium complexes were screened and found to be effective against covid-19 [10]. recently, copper complexes of two ligands, including chloroquine and hydroxychloroquine, were prepared, characterized by various techniques such as x-ray diffraction, spectroscopy, and thermal analysis, and screened via in silico method. the study outcomes verified that polar and non-polar groups in metal complexes were balanced compared to the parent drug. this balance in structure facilitates metallodrug binding to the active site of the viral adp-ribose-1 monophosphatase enzyme. as a result, the activity of this enzyme is inhibited, which is the desired effect to prevent doi 10.18502/sjms.v16i4.9951 page 541 sudan journal of medical sciences kanwal ashiq et al. covid-19 infection [11].another in silico study reported the synthesis of cu (ii) and co (ii) thiazole-based ligand complexes and described their role as facilitators for interacting with covid-19 proteins via molecular docking studies [12]. moreover, refat et al. confirmed the synthesis of binuclear schiff base complexes (zn[ii], cu[ii], co[ii], and ni[ii]) through elemental, electronic, and spectral analysis. the synthesized drug metal complexes were further screened for biological evaluations through molecular docking. the results of molecular docking studies revealed that ni(ii) complex displayed better binding efficiency for covid-19 protease (6lu7) [13]. furthermore, rad et al. proposed a new strategy for covid-19 treatment via simulation studies that involved transition metal (fe, cr, and ni) doped fullerenes–favipiravir complexes [14]. transition metals have a significant place in the field of inorganic chemistry. in the past few years, a lot of investigation was done on the therapeutic activities of the transition metals, and these could be proved beneficial for the covid-19 treatment. for example, in the latest research, various transition metals, including co(ii), cd(ii), mn(ii), cr(iii), ni(ii), hg(ii), zn(ii), and cr(iii) were tested with gibberellic acid (hga) which is a plant hormone to produce complexes. these novel complexes were screened by computational methods to evaluate their possible interaction with the covid-19 active site called 6lu7. the study results showed that mn(ii) exhibited higher binding energy with the active site and acted as a potential inhibitor of 6lu7. hence, it could be a beneficial therapeutic agent to cure covid-19 infection [15]. similarly, omar et al. reported synthesis and characterization of tridentate schiff base metal complexes of zn(ii), cu(ii), mn(ii), ni(ii), fe(iii), cd(ii), and cr(iii). they performed molecular docking studies via moe2008 software for screening the potential drug for covid-19. they explore the possible binding modes of all synthesized metal complexes against covid-19 main protease (sars-cov-2) in a complex with inhibitor uaw247 (pdb id: 6xbh). it was concluded from the data of interaction energies that the desired hit to lead (h2l) compound was cr(iii) complex. cr(iii) complex had lesser binding energy and stable interaction, suggesting the probability of intense antiviral activity against covid-19 [16]. zn(ii) is also a viral inhibitor (rna-dependent rna polymerase inhibitor) as well as an immunity enhancer. various studies have reported effects of intracellular zn(ii) levels on dna and rna viruses, particularly those affecting the respiratory tract, such as influenza, picornaviruses, and respiratory syncytial virus. one of the mechanisms for the success of chloroquine and hydroxychloroquine therapy for covid-19 treatment involves their roles as an ionophore of zn(ii), that is, bringing more zn(ii) into the cells. thus, among transition metals, zn(ii) is one of the promising and potential candidates doi 10.18502/sjms.v16i4.9951 page 542 sudan journal of medical sciences kanwal ashiq et al. responsible for direct inhibitory effect against the sars-cov-2 replicative cycle [17].the work of poupaert et al. also seconds the eminence grise of zn(ii) for covid-19 treatment. the authors provided evidence regarding zn++interactions at molecular levels via quantum mechanics molecular simulations. they propose firstand second-generation macrolides such as azithromycin (zn++-antibiotic complex) as a potential candidate for covid-19 treatment [18]. 3. conclusion to date, there is no specific treatment available for the covid-19, and in this regard, exploration of the metal complexes can be proved fruitful. the majority of the research was conducted by using in silico approach. it is suggested that the activity of the metal complexes should be appraised by using appropriate in vitro and in vivo models. further, issues of possible toxicity should be addressed to avoid any unwanted effects. acknowledgements none. ethical considerations not applicable. conflicts of interest the authors declare that they have no conflict of interest regarding this paper. availability of data and material not applicable. funding none. doi 10.18502/sjms.v16i4.9951 page 543 sudan journal of medical sciences kanwal ashiq et al. references [1] chan, a. h. y., rutter , v., ashiru-oredope, d., et al. (2020). together we unite: the role of the commonwealth in achieving universal health coverage through pharmaceutical care amidst the covid-19 pandemic. journal of pharmaceutical policy and practice, vol. 13, pp. 1–7. [2] ashiq, k., bajwa, m. a., and ashiq, s. (2021). covid-19 pandemic and its impact on pharmacy education. turkish journal of pharmaceutical sciences, vol. 18, no. 2, pp. 122–123. [3] ashiq, k., ashiq, s., bajwa, m. a., et al. (2020). knowledge, attitude and practices among the inhabitants of lahore, pakistan towards the covid-19 pandemic: an immediate online based cross-sectional survey while people are under the lockdown. bangladesh journal of medical science, vol. 69, special issue on covid19, pp. 69–76. [4] naureen, b. and asghar, m. (2020). how to cope with covid-19: global health and economic crisis. international journal of pharmacy and integrated health science, vol. 1, no. 1, pp. 3–4. [5] halimi, v., daci, a., stojanovska, s., et al. (2020). current regulatory approaches for accessing potential covid-19 therapies. journal of pharmaceutical policy and practice, vol. 13, no. 1, pp. 1–4. [6] naureen, b., miana, g., shahid, k., et al. (2021). iron (iii) and zinc (ii) monodentate schiff base metal complexes: synthesis, characterisation and biological activities. journal of molecular structure, vol. 1231, 129946. [7] tripathi, k. (2009). a review–can metal ions be incorporated into drugs? asian journal of research in chemistry, vol. 2, no. 1, pp. 14–18. [8] li, x., shenashen, m. a., wang, x., et al. (2017). hierarchically porous, and cu-and zncontaining ?-alooh mesostrands as adjuvants for cancer immunotherapy. scientific reports, vol. 7, no. 1, pp. 1–10. [9] cirri, d., pratesi, a., marzo, t., et al. (2021). metallo therapeutics for covid-19. exploiting metal-based compounds for the discovery of new antiviral drugs. expert opinion on drug discovery, vol. 16, no. 1, pp. 39–46. [10] vlasiou, m. c. and pafti, k. s. (2021). screening possible drug molecules for covid-19. the example of vanadium (iii/iv/v) complex molecules with computational chemistry and molecular docking. computational toxicology, vol. 18, 100157. doi 10.18502/sjms.v16i4.9951 page 544 sudan journal of medical sciences kanwal ashiq et al. [11] ali, a., sepay, n., afzal, m., et al. (2021). molecular designing, crystal structure determination and in silico screening of copper (ii) complexes bearing 8hydroxyquinoline derivatives as anti-covid-19. bioorganic chemistry, vol. 110, 104772. [12] almalki, s. a., bawazeer, t. m., asghar, b., et al. (2021). synthesis and characterization of new thiazole-based co (ii) and cu (ii) complexes; therapeutic function of thiazole towards covid-19 in comparing to current antivirals in treatment protocol. journal of molecular structure, vol. 2021, 130961. [13] refat, m. s., gaber, a., and alsanie, w. f., (2021). utilization and simulation of innovative new binuclear co (ii), ni (ii), cu (ii), and zn (ii) diimine schiff base complexes in sterilization and coronavirus resistance (covid-19). open chemistry, vol. 19, no. 1, pp. 772–784. [14] rad, a. s., ardjmand, m., esfahani, m. r., et al. (2021). dft calculations towards the geometry optimization, electronic structure, infrared spectroscopy and uv–vis analyses of favipiravir adsorption on the first-row transition metals doped fullerenes; a new strategy for covid-19 therapy. spectrochimica acta part a: molecular and biomolecular spectroscopy, vol. 247, 119082. [15] refat, m. s, altalhi, t., bakare, s. b., et al. (2021). new cr (iii), mn (ii), fe (iii), co (ii), ni (ii), zn (ii), cd (ii), and hg (ii) gibberellate complexes: synthesis, structure, and inhibitory activity against covid-19 protease. russian journal of general chemistry, vol. 91, no. 5, pp. 890–896. [16] mohamed, g. g.. omar, m. m., and ahmed, y. m. (2021). metal complexes of tridentate schiff base: synthesis, characterization, biological activity and molecular docking studies with covid-19 protein receptor. journal of inorganic and general chemistry, online version of record before inclusion in an issue. [17] hecel, a., ostrowska, m., stokowa-soltys, k., et al. (2020). zinc (ii)—the overlooked éminence grise of chloroquine’s fight against covid-19? pharmaceuticals, vol. 13, no. 9, p. 228. [18] poupaert, j. h., aguida, b., and hountondji, c. (2020). study of the interaction of zinc cation with azithromycin and its significance in the covid-19 treatment: a molecular approach. the open biochemistry journal, vol. 14, no. 1, pp. 33–40. doi 10.18502/sjms.v16i4.9951 page 545 introduction overview conclusion acknowledgements ethical considerations conflicts of interest availability of data and material funding references sudan journal of medical sciences sjms special issue 2020, doi 10.18502/sjms.v15i5.7147 production and hosting by knowledge e research article ramadan 2020 and beyond in the midst of the covid-19 pandemic: challenges and scientific evidence for action hala k. elmajnoun1, mohammed r.a. elhag1, hatem mohamed2, parvez i. haris1, and abu-bakr abu-median1 1leicester school of allied health sciences, faculty of health & life sciences, de montfort university, leicester, united kingdom. 2college of medicine, najran university, kingdom of saudi arabia. this review is dedicated to the memory of the corresponding author’s father, professor ahmed khalifa abu-median, and father-in-law, engineer salih mohammed ahmed mohammed osman, who both passed away during the preparation of the manuscript. abstract background: ramadan is a sacred month in islam, which involves 29–30 days of dawntill-dusk dry-fasting. millions of muslims observed ramadan fasting (rf) this year in the midst of the covid-19 pandemic. certain ethnic groups worldwide, including muslims, have been disproportionately affected by covid-19, raising fears that fasting could bring additional health risks. this directly impacted on the current challenges faced by health professionals. the covid-19 virus is expected to become seasonal. therefore, the evidence presented in this review is valid beyond ramadan as intermittent fasting is practiced more widely, irrespective of religion, throughout the year as a therapeutic and prophylactic means for several conditions. methods: a wide range of literature databases were searched for the effects of rf and intermittent fasting on human health and then linked to covid-19 impact to generate the evidence. results: this review presents a body of evidence proving rf is safe and beneficial for healthy people who adopt a balanced diet, drink plenty of fluids, and engage in regular physical activity. fasting reduces levels of pro-inflammatory cytokines (il-1β and il-6), which are associated with severe covid-19. furthermore, increased handwashing and hygiene during ramadan may reduce infection risks. for some, social isolation, physical inactivity, reduced access to food and stress – linked to the pandemic – may minimize the benefits that may have been achieved during a “normal” ramadan. conclusions: rf during the covid-19 pandemic is not a cause of concern for healthy people. ill people are exempt from fasting and should seek medical advice if they wish to fast. rf during the covid-19 pandemic is a unique experience and future research will reveal its impact on human health. keywords: covid-19; ramadan; fasting; health; mental; exercise; isolation; lockdown; diabetes; biomarkers how to cite this article: hala k. elmajnoun, mohammed r.a. elhag, hatem mohamed, parvez i. haris, and abu-bakr abu-median (2020) “ramadan 2020 and beyond in the midst of the covid-19 pandemic: challenges and scientific evidence for action,” sudan journal of medical sciences, vol. 15, special issue 2020, pages 85–110. doi 10.18502/sjms.v15i5.7147 page 85 corresponding author: abu-bakr abu-median, phd; leicester school of allied health sciences, faculty of health & life sciences, de montfort university, the gateway, leicester le1 9bh, united kingdom email: abu-bakr.abumedian@dmu.ac.uk telephone: +44 116 207 8009 received 31 may 2020 accepted 15 june 2020 published 23 july 2020 production and hosting by knowledge e hala k. elmajnoun et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abu-bakr.abu-median@dmu.ac.uk mailto:abu-bakr.abu-median@dmu.ac.uk https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences hala k. elmajnoun et al 1. introduction fasting can be defined as abstinence from food, either completely or partially, for a certain period of time [1, 2]. for thousands of years, people following various religions have believed that fasting for a period of time is the key to spiritual healing [3]. in recent years, there has been a surge in research on fasting, not as a religious practice, but as a means to improve health and fight disease. the type of fasting that has been most investigated is called intermittent fasting (if), which involves time-restricted feeding [4–6]. this kind of fasting is characterized by limiting daily consumed food over a specific period of time during the day with no calorie restriction, and such time limit can vary from 4 to 12 hr [4]. the vast majority of these studies reported beneficial effects of fasting on human health including protection against cancer, cardiovascular disease, diabetes, neurodegenerative disease, extending life span, cognitive function, intellectual performance, and metabolic regulation among healthy adults and patients with different disorders [7–9]. as a consequence of these research studies, if has become popular across the world for those wishing to improve their health. moreover, ramadan fasting (rf) is also a type of if [10, 11]. it is sometimes referred to as ramadan intermittent fasting in the scientific literature. if in various contexts and patterns is currently one of the most common health and fitness approaches throughout the globe. worldwide, rf is practiced once a year on the ninth month of the lunar calendar by millions of muslims from various ethnic backgrounds [3, 12]. during rf, muslims abstain from food and drink from dawn to sunset every day for a continuous period of 29–30 days. the period of daily fasting varies from 12–19 hr, as the islamic year is based on a lunar cycle, thus each year, the month of ramadan starts 11 days earlier than the gregorian calendar, and it can fall during any season throughout the year [12, 13]. in islam, rf is obligatory for all healthy muslims, both males and females who have reached the age of puberty. people with chronic or acute illnesses, travelling, menstruating and pregnant women, breastfeeding mothers, children who are below the age of puberty, and the elderly who cannot afford fasting are exempt from fasting [13]. during the month of ramadan, muslims usually have two to three meals after dusk till dawn, and there are no restrictions on the amount of food/drinks that can be consumed, as this is mainly driven by cultural habits [14]. spiritually, muslims take the month of ramadan as an opportunity to make meaningful alterations to their lifestyle in general that could have long-lasting effects and enable them to live a healthier and happier life with their families. additionally, it enhances an individual’s self-control and self-discipline [15]. as a result of these implications, some muslims who are exempt from fasting for medical reasons insist to fast during ramadan. however, while the vast majority of studies on rf show a positive impact on human health and physiology, it may also have some adverse effects such as dehydration and hypoglycemia [16, 17]. moreover, fasting during the current major global outbreak could lead to serious complications among high-risk patients. therefore, it is essential for these people to seek the best advice from physicians and religious scholars. doi 10.18502/sjms.v15i5.7147 page 86 sudan journal of medical sciences hala k. elmajnoun et al the purpose of this review is to provide recent scientific evidence on the following issues by taking into consideration the current covid-19 crisis and its impact on the lives of people: • the safety of rf and its effects on human health among healthy individuals and people who have medical conditions. • the effects of rf on immunity and mental health. • the benefits and drawbacks of observing fasting during covid-19 pandemic. • recommendations that may support muslims who are concerned that fasting during the current circumstances could impact their health. 2. methods a wide range of literature databases such as google scholar, pubmed, science direct, scopus, medline (ebsco), cochrane library, and web of science were searched for the effects of rf and if on human health and linked to covid-19 impact to generate the evidence. the most used terms in the search were rf and human health, rf and diabetes, islamic fasting and blood biomarkers, diurnal intermittent fasting (dif), covid19 and/or mental health, covid-19 and exercise, covid-19 and fasting. 3. results and discussion 3.1. the novel coronavirus (sars-cov-2) and the disease (covid19) during the last two months in 2019, cases of a fatal disease presenting with respiratory distress were reported in wuhan city in china [18]. the outbreak started in a seafood market, and the molecular investigation (pcr and next-generation sequencing) of samples from first patients identified the causative agent as a novel coronavirus with a high sequence identity at 79.6% and 96% to that of sars cov, which caused the outbreak of severe acute respiratory syndrome in 2002 and a bat coronavirus, respectively [18, 19]. coronaviruses that normally infect humans predominantly cause common cold-like symptoms, however, the newly emerging coronaviruses such as sars-cov in 2002 and mers-cov (middle east respiratory system coronavirus) in 2012 caused epidemics with mortality rates of 10% and 37%, respectively [20, 21]. the novel coronavirus was referred to as 2019-ncov and later named as sars-cov-2 [22]. the disease was recognized as covid-19 in january 2020 by the who and was declared as a pandemic in march 2020 [23, 24]. in addition to the four common human coronaviruses (hcov-229e, hcovoc43, hcov-nl63, and hku1), sars-cov, and mers-cov, sars-cov-2 is the seventh coronavirus to infect humans. clinically, the first covid-19 patients presented with dry cough, difficulty in breathing, pneumonia, fever and headache, with icu admission and mechanical ventilation due to respiratory failure [19, 25]. chest radiological evidence revealed multifocal opacities doi 10.18502/sjms.v15i5.7147 page 87 sudan journal of medical sciences hala k. elmajnoun et al [26]. evidence of venous thromboembolism is now emerging [27, 28]. by late january 2020, 80 patients died among 2,794 others infected [19]. the virus is transmitted via virus-laden droplets in the air and through human-to-human contact [19, 26, 29]. this resulted in the who’s recommendations for handwashing and social isolation. similar to the sars-cov and mers-cov, zoonotic origin has been postulated for sars-cov-2 based on genetic evidence, with control of primary host been suggested to stop the spread of covid-19 [19, 21, 30, 31]. the pandemic is evolving progressively in many parts of the world and at different patterns, with over seven million confirmed cases and over 400,000 deaths. by the time the number of cases dropped dramatically in china in march 2020, confirmed cases increased around the world reaching a peak in may 2020. for up-to-date information, real-time interactive reports are available from several sources such as the who (https://covid19.who.int/) and johns hopkins university (https://www.arcgis.com/apps/ opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6) [32]. as reported previously for sars-cov, sars-cov-2 has been found to bind the same receptor, the angiotensin-converting enzyme 2 (ace-2) receptor, for cell entry, leading to subsequent inflammation in the respiratory tract [19, 33]. it has been suggested that covid-19 infection is associated with dysregulation of the immune system [34]. this includes damage to lymphocytes, and in patients with severe disease, an increase in proinflammatory cytokines and chemokines are seen [34]. current research suggests that those severely affected by the disease are people with weaker immune system and having underlying conditions such as diabetes, hypertension, and chronic obstructive pulmonary disease (copd). furthermore, elderly men are more affected compared to women [35]. while there is no current research regarding the prevention or alleviation of covid19 disease by boosting the immune system through if, it is interesting to note that a recent study reported that a low-carbohydrate, high-fat ketogenic diet protected mice from influenza a virus [36]. ketones can also be produced through if, including rf. for example, one study reported that rf results in an increase in circulating ketone levels, which remained elevated during nine months after the end of the fasting period [37]. a recent study on mice reported that ketone production itself may not be sufficient to improve memory function and the gut microbiome [38]. they reported that a ketogenic diet impaired memory and led to a relative increase in harmful gut bacteria. in contrast, if, which also produces ketones, improved the memory function and gut microbiome. the authors suggested that microbiome-available carbohydrates, such as resistant starch, improve the gut microbiome composition. the findings of this research suggested that consumption of some carbohydrate-rich foods, especially resistant starch, during rf could be beneficial. it is difficult to state if changes induced by rf, such as increase in ketones, will be beneficial for the protection against covid-19, but it is certainly an area for further research. doi 10.18502/sjms.v15i5.7147 page 88 https://covid19.who.int/ https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 sudan journal of medical sciences hala k. elmajnoun et al 3.2. effects of ramadan fasting on human health and risks 3.2.1. effects of rf on stress investigating the effects of rf on human health is a continuing concern among muslim communities all over the world. it has been shown that rf has a favorable effect by helping to overcome stress; this was investigated on around 100 medical students using a specific scale in a questionnaire before and after ramadan [39]. in addition, a study carried out in saudi arabia among healthy volunteers (young adults) found that the level of the wake-promoting neurotransmitter, orexin-a, was significantly higher during the fasting hours in ramadan, indicating that rf has a positive impact on alertness [40]. likewise, if has been reported to decrease stress levels in humans, and this effect could be mediated by regulating the stress hormone (corticosterone) and inflammatory markers (il-6 and tnf-α) [41, 42]. therefore, these impacts could help some muslims who have experienced mild stress during the covid-19 outbreak, such as anxiety due to social isolation. on the other hand, some muslims complain of headaches during rf, and this perhaps results from lack of sugar, water, caffeine, and from some other restrictions [43]. moreover, it has been suggested that alteration of sleep pattern and circadian rhythm could have a role in changing the individual’s feelings/mood [43, 44] . one previous study reported that total sleep time is reduced by about 1 hr in ramadan and the epworth sleepiness scale increased by nearly 1 point [45]. thus, although these factors gradually disappear during the month of ramadan as the body gradually adapts, this could have negative effects on people who are already suffering from depression or severe anxiety. therefore, this highlights the importance of seeking medical advice before the month of ramadan, particularly for people with pre-existing medical conditions. 3.2.2. rf – the role of diet and nutrition to date, there is no clear conclusion about dietary patterns during the month of ramadan. there is great variability in the factors that could have an effect on diet composition, including cultural habits, geographical factors and duration of fasting [1]. the consumption of food during ramadan is generally reduced to two meals; the iftar meal (breaking of fast), which is the largest meal and consists of three-quarters of the daily calories, and the suhoor meal (before dawn), where a small amount of food is consumed around 25% of the total calories per day [46]. it has been reported that even though the number of meals is restricted to two meals in major muslims areas, most people consume the same calories they would consume before ramadan [14]. in other words, people do not tend to decrease the amount of food they eat during ramadan, instead in some areas such as middle eastern countries, they prepare recipes that contain high fat, such as fried chicken and meat [14]. in addition, they consume plenty of dairy products such as whole milk, yoghurt, and cheese. in contrast, a recent study with 160 healthy men revealed that food intake decreased with the exception of carbohydrates [47]. the finding regarding increased consumption of carbohydrate-rich foods during ramadan is consistent with the findings of other studies [48]. a significant doi 10.18502/sjms.v15i5.7147 page 89 sudan journal of medical sciences hala k. elmajnoun et al reduction in the body mass index (bmi) and body weight have been reported in some studies among healthy individuals [14, 49]. additionally, a recent two-arm randomized, controlled, single-blinded study conducted in ramadan revealed that consuming highfiber cereal had a positive effect on health and well-being, including improvement in blood lipids and bowel functions [50]. therefore, greater dietary advice and guidance to the public are needed while controlling the advertisement of unhealthy foods when nearing and during ramadan [51]. these observations indicated that fasting during covid-19 pandemic could have both positive and negative impacts. some people, who enjoy cooking, will be pleased to spend time in the kitchen preparing their iftar. however, this could be stressful and a concern for others, particularly those who have concerns about their finances and their inability to go out and buy the right types of foods. in addition, shortage of certain foods in some areas in the world is another concern. consequently, this would have the potential to adversely influence their health, as they might be unable to provide a balanced diet, which is required for good health. importantly, a well-balanced diet could have an important role in modulating the immune biomarkers. increased calorie intake (as in obesity for instance) has been shown to be associated with disturbance in the immune system and a risk of significant rise of infection [52]. moreover, inadequate nutrition (macronutrients and micronutrients) is significantly associated with an increased risk of immune deficiency, particularly in developing countries [53, 54]. consequently, this would lead to increased risk of recurrent infections and increased mortality and morbidity rates. in this context, although it is believed that consuming additional micronutrients such as vitamin a, vitamin d, and iron could boost immunity and support the body against the challenges of getting infections, this fact would only be effective in the case of a deficiency state, meaning that if these micronutrients are within normal levels, it will not be necessary to take these supplements [55]. however, a systematic review and meta-analysis concluded that vitamin d supplementation protected people against acute respiratory tract infection [56]. this is important in light of the fact that covid-19 is associated with respiratory tract infection. although there is no evidence regarding the prevention and treatment of covid-19 using vitamin d, a clinical trial is currently underway [57]. in the uk, public health england has been recommending people to take vitamin d supplements. in their coronavirus update, the uk national health service (nhs) states: consider taking 10 micrograms of vitamin d a day to keep your bones and muscles healthy. this is because you may not be getting enough vitamin d from sunlight if you’re indoors most of the day. there have been some news reports about vitamin d reducing the risk of coronavirus. however, there is no evidence that this is the case [58]. findings of the clinical trial that is underway may shed more light on the potential of vitamin d in the prevention or treatment of covid-19 [57]. meanwhile, individuals who are performing any type of if, under lockdown, should try and safely take advantage of any daily exercise permitted by the authorities to boost their vitamin d levels through sunlight exposure. furthermore, it is advisable to eat foods that are known to be rich in vitamin d including oily fish such as sardines, mackerel, and salmon. excessive intake of certain foods that have been linked to develop diabetes, such as rice and sugary drinks, doi 10.18502/sjms.v15i5.7147 page 90 sudan journal of medical sciences hala k. elmajnoun et al should be avoided. there is no specific dietary guideline available for those in covid19 quarantine, however, a balanced diet that is rich in immuno-supportive nutrients has been recommended by some researchers [59]. a combination of physical activities and balanced diet is the key aspect of a healthy lifestyle, as maintaining this synergistic action is essential to boost the immune system and protect against infections. 3.2.3. rf and lipid biomarkers many studies in the literature have investigated the effects of rf on lipid biomarkers. khattak et al. [60] found that fasting during ramadan improves the lipid profile, including the total cholesterol (tc), triglycerides (tgs), and low-density lipoproteins (ldl) with a remarkable reduction in all biomarkers in 25 volunteers, obese and non-obese, including young adults and adults. moreover, a recent systematic review and metaanalysis reported that if is beneficial for enhancing the lipid profile in humans [61]. conversely, another study reported that the levels of ldl, tc, and tgs were the same and did not change among healthy adults, whereas there were significant reductions in other values including lipoproteins (lp), apoprotein b, ratio of ldl/hdl, factor vii and fibrinogen level [62]. additionally, a recent systematic review and meta-analysis reported small improvements in tgs and hdl-cholesterol [63]. another systematic analysis highlighted that rf leads to improvements in lipid parameters, in particular hdl-c levels [64]. however, according to this study, men and athletic subjects benefited more. overall, like with other forms of if, rf helps in reducing the risk factors of atherothrombosis and atherosclerosis and in compensating for any metabolic alteration that might have occurred throughout the year before ramadan. social isolation and lockdown are likely to make it more difficult for people to be physically active, and therefore improvements in lipid markers seen during a previous ramadan may not be seen this year. therefore, people should make extra effort to be physically active at home and take opportunities to exercise outdoor as much as possible and as permitted under the lockdown rules. 3.2.4. rf and exercise a growing body of literature recognizes the importance of a healthy lifestyle and its beneficial effects on humans, including mental health, decreased risk of obesity, and chronic illnesses [55]. over the last few decades, the role of physical activities on activating the immune system to fight infections has been heavily examined [65, 66]. it has been established that moderate exercise/training is associated with a low incidence of upper respiratory tract infections (urti) in comparison to a sedentary lifestyle [67, 68]. therefore, regular exercise is recommended during the current covid-19 pandemic, as it could be an effective strategy to avoid the risk of infection with the virus [69]. for instance, people could be encouraged to practice home exercise, such as stretching, walking, and strengthening. a recent study reported that type 2 diabetics from saudi arabia displayed low physical activity and poor sleep behaviors during ramadan [70]. doi 10.18502/sjms.v15i5.7147 page 91 sudan journal of medical sciences hala k. elmajnoun et al during covid-19 lockdown, the type 2 diabetics who are fasting, need to take extra care to ensure that they are physically active and have sufficient sleep to better manage their diabetes. no study has investigated the impact of exercise on covid-19 yet, although carefully carrying out moderate exercise has been suggested in the literature [71,72]. the inability to carry out physical activity due to covid-19 quarantine has been identified as a serious health issue and some have suggested the types of physical activity that people can perform at home [71, 73]. the recommendations for doing exercise are based on studies that have reported a positive impact of exercise on the immune system, decrease in mortality from influenza and pneumonia, and reduction in severity and duration of acute respiratory infections [74, 75]. the effects of rf among athletes has been examined widely, and it has been reported that rf in combination with regular physical activity has had a positive impact on biochemical parameters and improved metabolic syndrome risk factors such as hyperglycemia, dyslipidemia, obesity, and hypertension [76, 77]. however, a recent systematic review and meta-analysis, that included all the studies up to july 2018, investigated the effects of rf on sleep patterns among athletes and concluded that the heterogeneity was very high among the studies in the literature, and that this was predominantly affected by the study design and location [78]. this suggested that more consistent studies are needed with focus on educational programs (healthy diet and exercise) on large samples of the population during rf. this will help to provide people and healthcare providers with scientific evidence on the beneficial and/or adverse effects of rf and physical activities. of great significance is a recent study that explored the effects of fasting on the expression of the muscular secreted proteins (myokines) in mice [79]. they have shown that the expression of myostatin gene (mstn) and il-6 were increased significantly with a reduction in the expression of irisin gene (fndc5) and the insulin-like growth factor-1 (igf-1) gene (ifg1) [79]. similarly, another study concluded that fasting for 6 hr in mice was associated with a significant rise in il-6 gene expression and in the circulation, suggesting that this myokine could have an important role in providing the required energy for the metabolic adaption during fasting [80]. moreover, fasting for around seven days in walking catfish was associated with a noticeable rise in the expression of myostatin [81]. it has been noticed that the contraction of skeletal muscle fibers during exercise stimulates the secretion of these molecules, suggesting that they might play a key role in mediating the beneficial effects of exercise on human health and could protect the human body from inflammation and any metabolic disturbance [82, 83]. despite the limited studies among humans, these observations indicated that it might be the combination of exercise with fasting that is essential to increase the expression of these molecules or the patterns of fasting had a key role in the secretion of these molecules. so far, one study has explored the effects of rf on the myokines circulating levels including adiponectin and irisin in young adults (male and female), with an average age of 20 years in jordan [84]. the blood samples were taken before and at the end of ramadan, and elisa was used to measure the serum level of these molecules [84]. it was established that there was a direct relationship between the physical activities and irisin level during rf and the levels of irisin and adiponectin were remarkably decreased doi 10.18502/sjms.v15i5.7147 page 92 sudan journal of medical sciences hala k. elmajnoun et al during ramadan. in this context, novel studies among humans are essential to examine the effects of different types of fasting on the myokines expression levels including rf in healthy individuals and in patients with medical conditions. the available data suggest that exercise in a fasting state decreases body weight and fat mass, although more controlled studies are needed for definitive recommendations to be made [85]. a moderate intensity exercise during fasting is recommended for the prevention of hypoglycemia. training in the evening compared to training in the morning while fasting may be more effective in enhancing aerobic performance. athletes may wish to train in the fasting state in the preseason as fasting increases the activity of fat-burning enzymes [85]. however, fasting can elicit negative effects on performance in some events, and hence modifications to the training schedules, for example, fasting during the preseason, may minimize such effects [85]. 3.2.5. rf and weight loss rf has been reported to be associated with a significant weight loss among healthy males and females [13, 86]. ali and abizari [87] have shown that rf was associated with a significant weight loss among 360 healthy teenagers from high schools, aged 16 years on average. furthermore, a meta-analysis and systematic review reported that rf resulted in minor improvements in five different metabolic syndrome components including waist circumference [63]. the authors also revealed a small reduction in body weight that was attributed to rf [88]. in addition, a meta-analysis of data derived from 70 publications concluded that rf resulted in a transient weight loss and a reduction in fat mass [89]. furthermore, sadeghirad et al. [86] have noticed that the percentage of weight loss was completely reversed within two weeks after the month of ramadan. on the other hand, weight gain among some muslims during rf has been reported as well [43, 90]. although weight loss after ramadan was stated by the majority of the studies, modulation of lifestyle is essential to maintain the beneficial effects of fasting. this could be achieved by eating healthy food and maintaining physical activities during the month of ramadan and the rest of the year. particularly in the current pandemic involving quarantine and lockdown, it could be argued that observing the month of ramadan is an opportunity to prevent the risk of gaining weight and obesity among people. moreover, it could be used as a means to lose weight for people with obesity or at risk of obesity. in this context, it has been shown that if was beneficial for weight loss and could be used as an effective therapeutic approach for obesity [91]. a study on obese mice revealed that if is effective in preventing weight gain despite consumption of foods that are rich in fat and sugar [92]. this may explain why most studies reported a slight decrease in weight after ramadan [63]. however, a combination of diet and exercise are most effective in improving lipids levels and body weight [92]. preventing the risk of obesity is essential in this pandemic. it is important to note that nhs audit has recently indicated that around 66% of seriously ill patients with covid-19 are obese [93]. this could be related to the fact that being overweight may significantly decrease one’s immunity and negatively impact on the function of the respiratory system [93, 94]. doi 10.18502/sjms.v15i5.7147 page 93 sudan journal of medical sciences hala k. elmajnoun et al 3.2.6. rf and medical conditions one of the most significant current arguments is how rf may affect people who have chronic medical conditions such as diabetes (t1d & t2d), acute cardiovascular disease (cvd), asthma, and chronic kidney disease. data from several studies suggested that fasting during ramadan has no impact on the incidence of cvd disorders such as myocardial infarction, ischemic stroke, and heart failure [95]. this was the conclusion of a systematic review and meta-analysis study, including all the studies in the literature with no restriction to a certain period. however, it has been noticed that the number of studies was limited, and more comprehensive international studies were needed to evaluate how rf could influence cardiac health, taking all the confounding factors such as diet and sleep pattern into consideration [95]. most of the research that has been conducted in relation to the effects of rf on the metabolic and glucose biomarkers in t2d were among adults and young adults (≥ 18 years old who are included in few studies) [96, 97]. the findings were highly controversial with massive variation in the study design and methods that were used to measure and assess the metabolic parameters [98]. it has been reported that rf is safe and that it has a significant impact on weight reduction among adult patients with t2d and no significant increase in the frequency of hypoglycemic/hyperglycemic attacks in comparison to the control population [99–102]. furthermore, it is associated with a remarkable improvement in glucose lipid biomarkers including hemoglobin a1c (hba1c), fasting blood glucose (fbg), fructosamine, tg, and ldl [97, 103]. on the other hand, the epidemiology of diabetes and ramadan 1422/2001(epidiar) study reported that rf was associated with a significantly increased frequency of hypoglycemic attacks among patients with t1d and t2d [104]. norouzy et al. [16] have established that rf was associated with a substantial disturbance in blood glucose control in t2d patients who are on diet control and antidiabetic pills, but it was also associated with a significant reduction in insulin level one month after ramadan, suggesting that rf could have a long-term positive effect. therefore, these observations suggest that rf could be safe among high-risk people as long as they receive close supervision from their physicians. the effects of rf on diabetes among children and adolescents have been examined mainly in t1d [105, 106]. evidence supported the fact that around 60% of children and teenagers with t1d are able to fast more than half of the month of ramadan and that they can fast safely in association with proper focused education before ramadan and close follow-up during ramadan, where patients are advised to break their fasting during hypo/hyperglycemia [107–109]. furthermore, most of the recent studies reported that rf was not associated with an increased risk of diabetic ketoacidosis (dka) [110]. however, other studies considered this group as a high-risk group who should not fast during the month of ramadan as it may increase the incidence of dka, dehydration, and hypoglycemia among t1d in these age groups [105]. the role of rf in glucose biomarkers among children and adolescents with t2d has not been examined yet. all these findings suggested that seeking medical advice is essential before the month of ramadan. under the covid-19 lockdown, children and adolescents may have benefited the most from ramadan 2020 by getting sufficient rest and sleep since they did not doi 10.18502/sjms.v15i5.7147 page 94 sudan journal of medical sciences hala k. elmajnoun et al need to travel to school, colleges, or take exams. parents who took their children to school and also had to go to work might have also got some relief from their daily routine. however, as a consequence, both parents and children may be less physically active, leading to weight gain. therefore, it is important to engage in physical activity of some form, even within the home environment during the lockdown. it has been reported that a 30-day if, such as rf, showed a significant increase in the levels of some gene products that correlated with immune system regulation, neuropsychiatric disorders, dna repair and carcinogenesis, that is, rf developed a serum proteome protecting against cancer, obesity, metabolic syndrome, inflammation, as well as numerous neuropsychiatric disorders [111]. also, ben fraj et al. [112] have concluded that rf has no impact on the lung function, and this was evaluated by using spirometry test and comparing spirometric data between the fasting and nonfasting healthy adolescents aged 12-15 years. the same observation has been reported among adults [113]. moreover, another piece of research has shown that the pulmonary function parameters did not alter in healthy young adults who were observing rf [114]. however, the effects of rf on asthma and copd patients have not been investigated widely. a pilot study among adult males (67-74 years old) with stable copd showed that hematological indices were markedly decreased by the end of ramadan [115]. however, authors have noticed that there was no significant effect on the inflammatory markers (erythrocyte sedimentation rate and c-reactive protein (crp)) [115]. in addition, it has been noticed that over a period of three years, the flow rate of patients in the emergency department decreased during the month of ramadan [116]. the vast majority of patients were complaining of gastrointestinal symptoms. this indicated that the incidence of developing serious medical conditions may reduce during rf. there is no scientific evidence that supports the effect of fasting during covid19 infection, while the benefits of fasting during several illnesses have been reported [117]. this has been examined among 1,422 individuals who were admitted to a clinic due to various reasons. they were asked to follow a specific fasting program based on a low-calorie intake (200-250 kcal/day) for a period between 4 and 21 days [117]. researchers have shown that practicing this kind of fasting during illness was associated with positive impacts on the patient’s well-being and reduced the risk of developing any serious complications. however, a study on a mice model reported that fasting might be beneficial in bacterial infections, but could have negative impacts on viral infections [118]. therefore, all muslims observing the month of ramadan should seek medical advice in case they have covid-19 infection as continuing to fast during the illness could affect their health. not many studies have been conducted to explore the impact of ramadan on infectious diseases. one study reported that individuals were less likely to be infected with a pathogenic species, shigella spp., during ramadan compared to the non-ramadan period [119]. other than this, the authors reported that the proportion of infecting pathogens were largely the same for both periods. reasons suggested for the decrease in shigella spp. included better hygiene associated with an increase in the frequency of hand and foot washing for special prayers during ramadan. in this context, one could doi 10.18502/sjms.v15i5.7147 page 95 sudan journal of medical sciences hala k. elmajnoun et al argue that an increase in handwashing during ramadan may reduce covid-19 infection. future research will reveal if ramadan increased or decreased the rate of infection. 3.2.7. rf and risk of dehydration several attempts have been made to evaluate the impacts of rf on water homeostasis (the total body fluid balance between fluid intake and fluid output per day) and the risk of dehydration. a study among malaysian muslims proved that rf has no effect on urine osmolality and urine volume overnight indicating that fasting is not associated with serious water deprivation [120]. on the other hand, studies in different countries found that urine volume was significantly reduced and this was associated with asignificant increase in osmolality, serum albumin, creatinine, sodium, and chloride during the day of rf with a tendency of osmolality to increase at the end of the month of ramadan [121, 122]. this suggested that fasting could result in a hypohydration state due to lack of fluid and this might lead to deterioration in water homeostasis. the risks of adverse effects are greater in those with medical conditions such as kidney disease who choose to fast during the month of ramadan. moreover, most of the existing bodies of research on hydration levels during rf suggested that healthy people who are observing the month of ramadan have to ensure that they have an adequate fluid intake during the non-fasting period [17, 43, 123, 124]. furthermore, it has previously been observed that if dehydration took place during the fasting hours in ramadan, there is an association with an increased incidence of migraine headache, dizziness, and fatigues, particularly among employees who are working for long hours and in hot weather [125]. however, this may not be applicable during the current lockdown where most people are not working or working at home at their convenience. therefore, this could have a positive outcome on muslims during ramadan. 3.2.8. effect of rf on gut microbiota gut microbiota is a term that refers to all bacteria, archaea, and eukarya that colonize the human gastrointestinal tract and have co-evolved with the host over thousands of years to form a sophisticated and mutually beneficial relationship [126]. these microorganisms bring many benefits to the host through a range of physiological functions. not only are changes in microbes present in the human gut linked with infectious diseases, but they are also associated with the pathogenesis of many other conditions including cancer, diabetes, obesity, asthma, autism, as well as neurodegenerative diseases [127, 128]. recent studies have reported the beneficial changes in the gut microbiome as a result of if, including rf. for example, one study with nine participants reported a significant increase in microbial richness after ramadan [129]. an increase in bacteria (akkermansia muciniphila and bacteroides fragilis groups) that are present in healthy individuals was observed [129]. studies on the impact of rf on the microbiome are still at their infancy, and the number of study participants investigated tends to be rather small. however, some of the findings reported thus far indicated changes that are considered to be beneficial. one of these studies revealed that after ramadan there is an increase doi 10.18502/sjms.v15i5.7147 page 96 sudan journal of medical sciences hala k. elmajnoun et al in akkermansia spp. and a decrease in alistipes spp. these changes are suggested to be beneficial for reducing inflammation [130]. modifying the microbiome through if is being explored on animal models as a strategy for treating diabetes [131–133]. further research on the link between if, the gut microbiome, and diabetes is needed. as yet, there are no data available regarding the impact of covid-19 infection on the gut microbiome. there are some discussions regarding the potential of modulating the gut microbiome as a therapeutic approach for covid-19 and its comorbidities [134]. this approach is most recently suggested as a potential therapeutic role of dietary probiotics to treat the dysbiosis that may occur in covid-19 patients. it follows the “national health commission of the people’s republic of china” recommendation to use the modulators of gut microbiome such as polysaccharides from a traditional chinese medicine lung cleansing and detoxifying decoction to preserve the intestinal microbial stability in severe and critical covid-19 cases [135]. it is interesting that research carried out so far suggested that rf brings about beneficial microbial changes that are useful for reducing inflammation. more research is required to investigate if if can be useful against viral infections. 3.2.9. effects of rf on immune system several studies have reported that rf attenuates proinflammatory cytokines and immune cells in healthy individuals [136, 137]. this included lymphocytes, monocytes, granulocytes, interleukin 6 (il-6), interleukin 1 beta (il-1β), and tumor necrosis factor α (tnf α). these proinflammatory markers were assessed over three stages; before, during, and one month after ramadan among a group of 50 self-controlled healthy volunteers in jordan [137]. this study indicated that rf had the potential effect to inhibit the expression of circulating cytokines. moreover, it provided good evidence that rf has the potential to be used as a preventive and therapeutic approach for autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis [137]. a more recent study also stated the beneficial effects of rf in patients with rheumatic diseases such as rheumatoid arthritis and spondylarthritis [138]. many studies investigated the effects of rf on different immune biomarkers and the results were controversial (table 1). this could be related to the study design and the confounding factors of a ramadan diet, physical activities, season, and hydration level. furthermore, a recent systematic review and meta-analysis found that rf had possible anti-inflammatory and antioxidative implications on healthy muslims [11]. this was examined by assessing the inflammatory markers (il-1, il-6, crp, and tnf-α) and the oxidative stress marker malondialdehyde (mda) by systematically reviewing and analyzing the available literature up until 2018, including 12 observational studies among different countries [11]. similarly, another research group have supported these findings based on a systematic review [139]. additionally, it has been shown that rf was associated with noticeable reductions in high-sensitivity crp and the gene expression of il-1 [140]. in patients suffering from covid-19, it has been reported that an uncontrolled immune response, including the release of proinflammatory cytokines and chemokines, causes a doi 10.18502/sjms.v15i5.7147 page 97 sudan journal of medical sciences hala k. elmajnoun et al “cytokine storm” that attacks different organs of the body, including the lung (reviewed by soy et al. [141]). this causes severe respiratory distress syndrome and eventually death. therefore, reducing the levels of cytokines and chemokines can be beneficial against severe covid-19 infection. in this context, a study by bahammam and coworkers revealed that dif, during and outside the month of ramadan, significantly decreased plasma levels of cytokines (il-1β, il-6, and il-8) [142]. this study suggests that people can fast even outside ramadan as a strategy for boosting the immune system and preventing disease. table 1: a summary of studies that have investigated the effects of rf on immune biomarkers. references country study design participants age range (mean) examined markers effects of rf [142] saudi arabia prospective study 12 males 25.1 ± 2.5 il-1β, il-6, and il-8 ↓↓ [136] turkey observational study 20 males 27.4 ± 5.2 il–2, il–8, tnf-α, crp. ↓↓ [143] india observational study 34 males 16–64 igf-1, il-2 ↓↓ [137] jordan observational study 50 (21 males and 29 females) 18-51 il-1, il-6, tnf-α ↓↓ [144] indonesia observational study 27 males 18-22 tnf-α ↓ [10] denmark nonrandomized, crossover, intervention study 10 males 18-35 il-6, tnf-α, il-10 ↔ [145] iran prospective observational study 30 males 20–35 il-6, hs-crp ↔ [146] turkey observational study 35 males 20–59 igg, igm, salivary iga ↓, ↔, ↓ ↓ decreased; ↔ unchanged interestingly, a cross-sectional study among young adult athletes conducted by khazaei et al. [147] showed that rf was associated with increased level of iga and c4 at the end of the fasting month. authors have indicated that this positive impact on the immune system may have an important role in decreasing the risk of respiratory infections in sports people. it is well-known that iga is predominantly present in the secretions of the upper respiratory tract and in saliva [148]. iga is also considered as the front-line defense mechanism against pathogens, particularly viral infections [148, 149]. however, another study showed that the levels of igg and iga are slightly decreased during rf, but still within the normal range [146]. it seems that the effects were varied and could be related to the fasting hours and physical activities. further, this might be related to immune modulations as the level of immune biomarkers could be increased after the period of fasting. therefore, the long-term effects of rf on the level of these molecules need to be explored. doi 10.18502/sjms.v15i5.7147 page 98 sudan journal of medical sciences hala k. elmajnoun et al 3.2.10. rf and autophagy autophagy is an intracellular fundamental process, characterized by the ability of cells to eliminate and recycle the intracellular pathogen and organelles in the lysosome [150, 151]. it has been reported that rf stimulates autophagy, where all the cellular debris and aggregated proteins are removed, and this could occur in the first week of ramadan as a consequence of severe depletion in the glycogen storage and massive amounts of free fatty acids (ffa) production [14, 151]. therefore, the liver starts to convert these molecules (acetyl coa and ffa) to form ketone bodies in a metabolic process called ketogenesis, which is stimulated by glucagon hormone [14]. ketone bodies are used as a source of energy for the cellular function in the brain cells, heart, and kidney. numerous studies have highlighted the key protective role of ketosis against pathological processes, such as reducing heart disease risk factors, decreasing the risk of diabetes, weight loss, and profound antioxidants defense [151– 154]. furthermore, it has been reported that autophagy mediates and regulates various inflammatory processes [155]. nosaka et al. [156] have recently reported that stimulating autophagy as a result of fasting in mice was associated with a substantial impact on regulating the inflammatory reactions due to acute lung injury, which is commonly caused by mechanical ventilation and acute respiratory distress syndrome. authors noticed that this effect was mediated by the role of autophagy in decreased production of il-1β from macrophage, an inflammatory marker that increases lung permeability and hypoxemia. the stimulation of autophagy and mitophagy through if allows cells to eliminate oxidatively damaged proteins and mitochondria, reduce protein synthesis, and enable recycling of undamaged molecules [157]. furthermore, the temporary reduction in global protein synthesis acts to conserve molecular resources and energy [157]. recently, targeting the autophagy process has been suggested as a therapeutic strategy against covid-19 [158]. 3.3. adverse effects of the covid-19 pandemic on mental health it is well-known that humans have an amazing power to overcome extreme conditions, such as lack of money, worries for ill family members, domestic conflicts/abuse. this ability to resist does vary between people. recently, brooks et al. [159] have discussed the psychological effects of quarantine by evaluating several factors involving frustration, quarantine duration, inadequate information, and infection fears. they suggested that the period of quarantine is one of the most important strategies in reducing the spread of infection, and this period is also often associated with substantial drawbacks. the study highlighted that officials should handle this period carefully for instance by providing full information to people regarding what is happening and ensuring that there are adequate supplies such as food and medicines [159]. moreover, the negative impacts of quarantine on mental health, increase in stress and anger were reported [160, 161]. there are several reports regarding high prevalence of mental health problems linked to covid-19 crisis in china and some of these were attributed to have impacts on daily life [162, 163]. it has also been reported that the mental health of children and older doi 10.18502/sjms.v15i5.7147 page 99 sudan journal of medical sciences hala k. elmajnoun et al people have been affected by the crisis [164, 165]. a significant rise in stress levels could negatively modulate the immune system and increase the risk of susceptibility to infections [166]. it has been shown that loneliness and psychological stress were markedly associated with recurrent influenza infections [167]. there is no current research available that assessed rf under quarantine and pandemic conditions and its relationship to mental health. there are several studies in the literature that report improvements in mental health associated with rf [168-170]. one study reported improvements in people with diabetes who experience depression [171]. a systematic review reported that rf does not cause new mental health problems or disorders and there were no major reasons to advise people not to fast, with the exception of people with major psychiatric disorders [172]. however, there is a report regarding a mental health patient, on medication, who suffered adverse effects that are attributed to fasting during ramadan [173]. in light of the current literature, fasting during ramadan may bring positive mental health benefits for healthy people, but those with pre-existing mental health issues should seek medical advice before engaging in fasting. 3.4. practicing ramadan fasting during the covid-19 pandemic based on the scientific evidence covered in this review on the effects of rf and several types of if on human health, it could be concluded that rf among healthy people is safe and has no serious impacts. however, fasting among high-risk individuals could be dangerous for their health, and medical advice is essential. to avoid the risk of spreading the infection between people, religious leaders such as saudi arabia’s grand mufti have advised that ramadan prayers to be done at home [174]. some healthy muslims are worried that fasting during the covid-19 pandemic may influence their health and their susceptibility to infections. this can be partially attributed to many rumors spreading in the social media regarding the prevention and cures for covid-19. one such rumor that has been circulating is that who has advised people to drink water frequently, and to keep the throat moist during the covid-19 pandemic [175]. we could not find evidence for such information from the who covid-19 guidance and indeed various news agencies have cited experts who have refuted the claims that frequent drinking of water, gargling, keeping the throat moist can prevent covid-19 infection [175, 176]. however, gargling, rinsing the mouth and brushing teeth are all permitted during ramadan fasting as long as water is not ingested. the main mode of transmission of the virus is by breathing in virus-laden droplets that are present in the air. rf involves dry-fasting, and drinking water and other fluids is not permitted from dawn till dusk. therefore, it is generally a common practice to drink plenty of fluids during the non-fasting period and prepare well for the fasting day and avoid dehydration. in any case, those with a medical condition that can be exacerbated by fasting are exempt from fasting. one of the key public health messages that were promoted during the covid-19 crisis was the need for regular handwashing. the practice of handwashing is encouraged doi 10.18502/sjms.v15i5.7147 page 100 sudan journal of medical sciences hala k. elmajnoun et al in many cultures and religions including islam, where it is necessary to wash hands before eating foods or performing prayers. in this context, the increase in frequency of handwashing during ramadan, in order to perform additional prayers has been suggested as a reason for lower infection from one particular pathogenic bacterial species [119]. in social gatherings, in many cultures, it is common for people to share food and consume from the same plates and/or bowls. in order to prevent the spread of covid-19 from person to person, some have suggested avoiding this practice [177]. moreover, social gatherings, which are culturally more frequent in ramadan, must be stopped and guidance for social and physical distancing must be followed as these measures are shown to be effective in reducing transmission of covid-19 [178, 179]. self-isolation is recommended for individuals with no or mild symptoms of covid19, however, in many parts of the muslim world, several disadvantaged communities have been disproportionately affected by covid-19, making it almost impossible to self-isolate in small crowded homes [180]. healthcare professionals who are fasting are particularly challenged during the pandemic as they are expected to deal with suspected or confirmed cases of covid-19 on regular basis and work for longer hours. the use of appropriate personal protective equipment (ppe) is essential under these circumstances particularly in isolation/quarantine centers and emergency departments where urgent procedures such as ventilation/intubation and cannulation are carried out. healthcare staff should follow guidelines and protocols from government on use of ppe [181–184]. more importantly, risk assessment must be carried out among health professionals and supporting staff so that the interaction of high-risk staff with suspected covid-19 cases is properly managed [185–189]. the disease has claimed the lives of many health workers at different levels despite the standards and quality of healthcare settings [190–192]. 4. conclusion it is important to stress that ramadan is more than fasting, the entire life changes during this month including an increase in prayers that requires one to be clean and wash their hands and other parts of the body regularly. research conducted on rf and other forms of if highlighted numerous health benefits including positive effects on the immune system, the microbiome, body weight, and body composition. many of these benefits may not be due to fasting per se, but other changes that occur during ramadan. in light of the current literature, fasting during the month of ramadan, in the midst of covid-19 pandemic, could have a positive impact on healthy muslims, provided a good diet, lifestyle, and physical activity are maintained. unfortunately, one or more of these latter activities may not be possible during the covid-19 lockdown and therefore the full benefits of if may not be achieved during ramadan. on the basis of current literature, additional fasting outside of the month of ramadan may provide beneficial effects that can be protective against diseases including covid-19. in the future, research needs to be conducted to assess the impact of covid-19 pandemic on the health of people who have been fasting during ramadan. some people may have benefited, whilst others may have suffered. public health bodies and doi 10.18502/sjms.v15i5.7147 page 101 sudan journal of medical sciences hala k. elmajnoun et al healthcare professionals around the world, who are challenged by changing working practices as a result of the pandemic, should provide support to people whose health may have deteriorated as a result of difficulties arising from fasting under the lockdown, due to poor nutrition, inactivity, social isolation, and anxiety. funding this manuscript did not receive any external funding for any part of the work. conflict of interest the authors have no conflicts of interest to report. author contributions hala elmajnoun worked on the study concept and design, literature search, drafting the article, interpretation of data, manuscript preparation and editing, accuracy and integrity of all aspects of the work. mohammed elhag and hatem mohamed contributed in drafting the article and checking the accuracy and integrity of all aspects of the work. parvez haris and abu-bakr abu-median worked on the study concept and design, editing and critical revision, and checking the accuracy and integrity of all 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(2020). characteristics of doctors’ fatality due to covid-19 in western europe and asia-pacific countries [published online ahead of print, 2020 may 6]. qjm, hcaa159. doi: 10.1093/qjmed/hcaa159. doi 10.18502/sjms.v15i5.7147 page 110 https://www.bbc.co.uk/news/uk-england-52404744 https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/covid-19-personal-protective-equipment-ppe https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/covid-19-personal-protective-equipment-ppe https://www.guidelines.co.uk/infection/covid-19-personal-protective-equipment-ppe/455274.article https://www.guidelines.co.uk/infection/covid-19-personal-protective-equipment-ppe/455274.article https://www.ecdc.europa.eu/en/publications-data/guidance-wearing-and-removing-personal-protective-equipment-healthcare-settings https://www.ecdc.europa.eu/en/publications-data/guidance-wearing-and-removing-personal-protective-equipment-healthcare-settings https://www.nhsemployers.org/covid19/health-safety-and-wellbeing/risk-assessments-for-staff https://www.nhsemployers.org/covid19/health-safety-and-wellbeing/risk-assessments-for-staff https://www.bma.org.uk/advice-and-support/covid-19/your-health/covid-19-risk-assessment https://www.bma.org.uk/advice-and-support/covid-19/your-health/covid-19-risk-assessment https://apps.who.int/iris/handle/10665/331511 https://www.bbc.co.uk/news/uk-england-london-52064450 https://www.bbc.co.uk/news/uk-england-london-52064450 introduction methods results and discussion the novel coronavirus (sars-cov-2) and the disease (covid-19) effects of ramadan fasting on human health and risks effects of rf on stress rf – the role of diet and nutrition rf and lipid biomarkers rf and exercise rf and weight loss rf and medical conditions rf and risk of dehydration effect of rf on gut microbiota effects of rf on immune system rf and autophagy adverse effects of the covid-19 pandemic on mental health practicing ramadan fasting during the covid-19 pandemic conclusion funding conflict of interest author contributions references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9288 production and hosting by knowledge e case report rare presentation of wilson disease in an 11-year-old sudanese girl mumen abdalazim dafallah1, elsanosi habour2, esraa ahmed ragab1, zahraa mamoun shouk1, fawzeia hamad2, musaab ahmed3, and mohamed h. ahmed4 1faculty of medicine, university of gezira, sudan 2wad medani pediatric teaching hospital, wad medani, sudan 3center of medical and bio-allied health sciences research, college of medicine, ajman university, ajman, united arab emirates 4department of medicine and hiv metabolic clinic, milton keynes university hospital nhs foundation trust, eaglestone, milton keynes, buckinghamshire, uk orcid: mumen abdalazim dafallah: http://orcid.org/0000-0002-4300-9481 elsanosi habour: http://orcid.org/0000-0003-1179-6705 esraa ahmed ragab: http://orcid.org/0000-0003-3048-5216 zahraa mamoun shouk: http://orcid.org/0000-0001-9037-9103 fawzeia hamad: http://orcid.org/0000-0003-4856-4238 abstract background: wilson disease is an inherited disorder in which excessive amount of copper accumulates in various tissues of the body. clinical features related to copper deposition in the liver may appear in the first and second decades followed by neurologic and psychiatric thereafter; however, many patients have a combination of these symptoms. case: we report a case of 11 year-old girl, admitted to wad medani pediatric teaching hospital with generalized body swellings for four days. initial investigations showed proteinuria and hypoalbuminemia, thought to be due to nephrotic syndrome. days later, patient developed jaundice and neuropsychiatric manifestations. a slit lamb examination confirmed the presence of kayser–fleischer ring (kf ring) and she scored high in the scoring system for the diagnosis of wilson disease. dpenicillamine treatment therapy was started and unfortunately the patient’s clinical condition deteriorated gradually, and eventually went into deep coma and died. wilson disease mainly affects the liver, but the initial presentation was completely compatible with nephrotic syndrome. conclusion: diagnosis of wilson disease should be suspected in a child presenting with generalized body swellings even in the absence of clinical evidence of hepatic and/or neuropsychiatric involvements. keywords: wilson disease, nephrotic syndrome, case report, pediatrics, sudan how to cite this article: mumen abdalazim dafallah, elsanosi habour, esraa ahmed ragab, zahraa mamoun shouk, fawzeia hamad, musaab ahmed, and mohamed h. ahmed (2021) “rare presentation of wilson disease in an 11-year-old sudanese girl,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 196–206. doi 10.18502/sjms.v16i2.9288 page 196 corresponding author: mumen abdalazim dafallah; faculty of medicine, university of gezira, sudan email: mumenabdalazim36@gmail.com received 26 april 21 accepted 22 may 2021 published 30 june 2021 production and hosting by knowledge e mumen abdalazim dafallah et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0002-4300-9481 http://orcid.org/0000-0003-1179-6705 http://orcid.org/0000-0003-3048-5216 http://orcid.org/0000-0001-9037-9103 http://orcid.org/0000-0003-4856-4238 mailto:mumenabdalazim36@gmail.com mailto:mumenabdalazim36@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mumen abdalazim dafallah et al 1. introduction wilson disease is an inherited disorder in which excessive amount of copper accumulates in various tissues of the body [1]. liver and the basal ganglia of the brain are the primary affected organs [2]. kayser-fleischer ring (kf) is the hallmark of wilson disease [3]. the disease affects 1 in every 30,000 individuals worldwide and it can affect people at any age [1]. although the presentation of the disease can vary widely, clinical manifestation due to disturbance of liver function, neuropsychiatric manifestations, and kf ring are the key features of wilson disease [3]. low serum ceruloplasmin in combination with kf rings is sufficient to make the diagnosis; however the scoring system proposed by the working party at the 8th international meeting on wilson’s disease, leipzig 2001 has a good diagnostic accuracy [3]. to the best of our knowledge, wilson disease has not been reported in sudanese children. in this case report, we report a case of wilson disease in a child presented with generalized body swellings. 2. case presentation we report a case of 11year-old girl with no prior medical history, admitted to wad medani pediatric teaching hospital, with generalized body swelling for four days.the swellings started in the face and gradually progressed and became generalized. two days later, the patient developed jaundice with dark urine and no change in the stool color or itching. the patient was a fifth class-primary school student with good academic performance. parents are first-degree cousins. no family history of similar condition and no other siblings have similar condition. clinical examination showed that the patient was conscious, oriented to time, place, and person.blood pressure was 125/85 mmhg, pulse 90 bpm, and respiratory rate 26 c/pm. despite the clinical evidence of ascites, the spleen and liver were not palpable (liver span = 10 cm). the speech was normal, recent and remote memories were intact, and no abnormal behavior. in addition, cranial nerves, sensory systems, reflexes, and sphincters were intact. upper and lower limbs bilaterally showed normal power, reflexes, and tone. examinations of other systems were unremarkable. urine analysis showed albuminuria(+++), albumin creatine ratio of 2mg/mmol(normal range < 3), uncountable rbcs, and no rbcs cast or granular casts in urine.international normalization ration = 1.1 (normal range is ≤ 1.1). table 1 presents the result of liver function tests. renal function tests and electrolytes were within normal range. serological tests for hepatitis b and c viruses and human immunodeficiency virus were negative.random doi 10.18502/sjms.v16i2.9288 page 197 sudan journal of medical sciences mumen abdalazim dafallah et al blood glucose was 66 mg/dl and complete blood count showed neutrophil leukocytosis.importantly, abdominal ultrasound confirmed the presence of moderate to-massive ascites with enlarged liver with coarse texture and irregular border (cirrhotic changes), thick-edematous gall bladder, and normal biliary system (figure 1). considering the generalized oedema, hypoalbuminemia, and proteinuria, the patient was diagnosed initially with nephrotic syndrome and put on prednisolone tablets 5mg at a dose of 1mg/kg/day (3 tablets every 8 hr), frusemide tablets 40mg twice daily, and penicillin 2 million units every 6 hr. in addition, amlodipine tablets5 mg once daily was administered to control her high blood pressure. after a few days, the patient showed a considerable clinical improvement in terms of reduction in body swelling, improvement in jaundice, and started to have a clear urine. however, amlodipine was increased to 5 mg twice a day due to persistent high blood pressure. unfortunately, two days later following the improvement in her clinical symptoms, she suddenly developed hand tremors,clumsiness, speech became slurred and dysarthric with drooling of saliva, shuffling gait with tendency to fall, and abnormal behavior (unintentional and purposeless jumping) was noted. she complained of vague right hypochondriac pain. blood pressure was found to be 140/88 mmhg, brain ct was normal (figure 2) .importantly, slit lamb examination by an ophthalmologist showed the presence of kf ring as shown in figure 3. due to the unavailability of these investigations in our hospital, we were unable to perform the 24-hr urine copper and serum ceruloplasmin levels. however, the scoring systems developed at the 8th international meeting on wilson disease in leipzig, 2001 may assist in establishing the diagnosis of wilson disease; a score of 4 is diagnostic of wilson disease (table 2). serum ceruloplasmin, coombs-negative hemolytic anemia, kf rings, and neurological symptoms must be applied to establish the scoring system. wilson disease scoring system provides a good diagnostic accuracy. our patient got a score of 4 (kfring = 2 points and severe neurological symptoms = 2 points) and the diagnosis of wilson’s disease was highly likely. immediately, d-penicillamine tablets 250 mg twice daily was started and zinc acetate syrup was later added as maintenance therapy. days later, the patient’s clinical condition deteriorated gradually, and she became comatose with glasgow coma scale score of 3. the patient was then put in regimen of hepatic encephalopathy including dextrose 5% 500ml every 8 hr, cefotaxime injection at a dose of 20ml/kg/day (900ml every 6hr), metronidazole injection 500ml every 8 hr and lactulose syrup 5ml twice daily. unfortunately, she could not recover and died two days later. doi 10.18502/sjms.v16i2.9288 page 198 sudan journal of medical sciences mumen abdalazim dafallah et al diagnostic challenges: 24-hr urine copper and serum ceruloplasmin levels were not done due to the un-availability of these investigations in our hospital. the scoring system developed at the 8th international meeting on wilson disease in leipzig 2001 was possible alternative. 3. discussion wilson disease is an autosomal recessive disorder due to inborn error of metabolism of copper [3]. high rate of consanguinity increases the chance of passing the genes to future generation. although the disease is common in children, the diagnosis is always difficult [4]. in developing countries, the prevalence has been estimated to be between 6 and 21% of children with chronic liver disease [5].the insidious process of the disease and complex clinical presentation in association with lack of diagnostic facility may leave clinician with only possible alternative diagnostic tool which is the use of wilson scoring system. the mean age of diagnosis of wilson disease in japan was found to be around 12 years [6]. in this case report, the patient’s age was 11 years. in addition, our patient presented with generalized body swellings, hypoalbuminemia, proteinuria, and a possible diagnosis of nephrotic syndrome. several case reports showed that the initial presentations of wilson disease can be similar to nephrotic syndrome [7, 8]. esezoboret al. reported a diagnosis of wilson disease in an eight year-old boy from nigeria, with an initial presentation of nephrotic syndrome that deteriorated gradually and developed into jaundice, severe coagulopathy, and prominent extrapyramidal features consisting of rigidity, tremors, shuffling gait, slurred speech, and emotional liability [8]. it was also suggested that any form of liver disease might be present in patients with wilson disease and the presentation varies from a symptomatic to fulminant hepatic cirrhosis and hepatic encephalopathy [3]. our patient developed jaundice, malaise, and abdominal pain during the course of the disease which raised the suspicion for liver failure. liver failure in wilson disease carries high mortality rate if left untreated [3] (table3). patients with wilson disease may first present with neuropsychiatric manifestations. tremors, muscle rigidity, dysphagia, dysarthria, ataxia, drooling of saliva, mood liability, and inappropriate behavior are common [1, 9, 10]. our patient developed neuropsychiatric manifestations very rapidly and subsequently became disabled and bedridden. in figure 4 we have shown the sequence of events in days in relation to the clinical presentation and how her condition deteriorated gradually. doi 10.18502/sjms.v16i2.9288 page 199 sudan journal of medical sciences mumen abdalazim dafallah et al the diagnosis was made by using the scoring systems developed at the 8th international meeting on wilson disease. this scoring system has a good diagnostic accuracy and a high sensitivity and specificity (a score of 4 established the diagnosis).serumceruloplasmin (the major carrier of copper in the blood), total serum copper (which includes copper incorporated in ceruloplasmin), neurological symptoms, and kf rings are the main components of the scoring system [3]. a score of 4 can make the diagnosis of wilson’s disease. the commonest ophthalmological finding in patients with wilson’s disease is kf ring. it is due to deposition of excess copper on the inner surface of the cornea in the descemet membrane. it mainly affects patients with neurological involvement in wilson’s disease and is typically not found in every wilson’s disease patient. it’s color is usually golden-brown and does not cause any symptoms. silt lamb examination is mandatory to confirm its presence. kf ring disappears with treatment over three to five years in the majority of cases [ 11–13]. pharmacological management including d-penicillamine, trientine, tetrathiomolybdate, and zink are the main stays of treatment [3, 14]. d-penicillamine, the commonly used drug, increases the urinary excretion of copper. the maintenance dose in pediatric is 20 mg/kg/day given in two or three divided doses [15]. zink salts are usually added to reduce copper absorption and is administered in a dose of 150 mg /day in three doses, 30 min before meals [3, 13]. despite all these therapies, liver transplantation is the treatment of choice for acute liver failure or decompensated liver cirrhosis due to wilson’s disease [16]. 4. conclusion the diagnosis of wilson’s disease needs a high rate of clinical suspicion. we conclude that generalized body swellings might be the first presenting manifestation of the disease even in the absence of clinical evidence of hepatic or neuropsychiatric involvements. acknowledgments the authors would like to express their gratitude to prof. ali babiker ali habour who supervised this work. doi 10.18502/sjms.v16i2.9288 page 200 sudan journal of medical sciences mumen abdalazim dafallah et al ethical considerations written informed consent was obtained from the parents of the patient for participation and publication of this case report and accompanying images. this study was approved by the research ethical committee, university of gezira faculty of medicine, sudan. competing interests none. availability of data and material not applicable. funding nil. figure 1: abdominal ultrasound showing enlarged liver with cirrhotic changes and moderate-to-massive ascites. doi 10.18502/sjms.v16i2.9288 page 201 sudan journal of medical sciences mumen abdalazim dafallah et al figure 2: brain ct scan of the patient showing normal basal ganglia (white arrow). figure 3: a slit lamb examination showing kayser–fleischer ring (red arrow). doi 10.18502/sjms.v16i2.9288 page 202 sudan journal of medical sciences mumen abdalazim dafallah et al kkkk presented with generalized body swellings + hypo albuminemia and proteinurea (diagnosed initially as nephrotic syndrome patient developed jaundice and dark urine abdominal ultrasound showed enlarged liver with cirrhotic changes and ascites pa�ent developed neuropsychiatric manifesta�ons slit lamb examina�on showed kf rings and diagnosed as wilson’s disease day1 day 3 day 4 day 7 day 10 figure 4: timeline describing patient’s key date in diagnosis. table 1: liver function tests. test day 1 day 10 normal values serum total protein 5.8 5.0 6.6–8.3 mg/dl serum albumin 2.2 1.8 3.5–5.3 mg/dl serum globulin 3.6 3.1 2.0–3.5 mg/dl serum bilirubin 0.9 0.4 up to 1.1 mg/dl conjugated bilirubin 0.3 0.1 up to 0.25 mg/dl unconjugated bilirubin 0.6 0.3 <0.7 mg/dl serum alanine transaminase 55 51 up to 40 u/l serum aspartate transaminase 123 123 up to 40 u/l serum alkaline phosphatase 253 247 up to 115 u/l doi 10.18502/sjms.v16i2.9288 page 203 sudan journal of medical sciences mumen abdalazim dafallah et al table 2: scoring systems developed at the 8th international meeting on wilson’s disease in leipzig 2001. typical clinical symptoms and signs evaluation score our patient score kayser–fleischer ring present 2 2 absent 0 neurological symptoms severe 2 2 mild 1 absent 0 serum ceruloplasmin normal (>0.2 g/l) 0 __ 0.1–0.2 g/l 1 <0.1 g/l 2 coombs-negative hemolytic anemia 0 present 1 absent 0 total score 4 table 3: prognostic index in wilson’s disease. parameter 1* 2* 3* 4* our patient results our patient score serum bilirubin (µmol/l) 100–150 151–200 201–300 >300 15.39 µmol/l _ ast (u/l) 100–150 151–300 301–400 >400 123 u/l 1 inr 1.3–1.6 1.7–1.9 2.0–2.4 >2.4 1.1 – wbc (109/l) 6.8–8.3 8.4–10.3 10.4–15.3 >15.3 15.5 109/l 4 albumin(g/l) 34–44 25–33 21–24 <21 22 g/l 3 total score 8 a score >11 is associated with high probability of death without liver transplantation total score diagnosis 4 or more diagnosis established 3 diagnosis possible, more tests needed 2 or less diagnosis very unlikely doi 10.18502/sjms.v16i2.9288 page 204 sudan journal of medical sciences mumen abdalazim dafallah et al references [1] chaudhry, h. s. and anilkumar, a. c. 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[13] członkowska, a., litwin, t., and chabik, g. (2017). wilson disease: neurologic features. in a. członkowska and m. l. schilsky (eds.), handbook of clinical neurology (vol. 142, pp. 101–119). science direct. doi 10.18502/sjms.v16i2.9288 page 205 https://www.ncbi.nlm.nih.gov/books/nbk441990/ https://www.ncbi.nlm.nih.gov/books/nbk441990/ https://doi.org/10.1186/1752-1947-6-200 sudan journal of medical sciences mumen abdalazim dafallah et al [14] wiggelinkhuizen, m., tilanus, m. e., bollen, c. w., et al. (2009). systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of wilson disease. alimentary pharmacology & therapeutics, vol. 29, no. 9, pp. 947–958. [15] ukuoka, n., morita, s., hamatani, s., et al. (2002). [appropriate administration schedule of d-penicillamine for pediatric wilson’s disease patients based on urinary copper excretion]. yakugakuzasshi, vol. 122, no. 8, pp. 585–588. [16] ranucci, g., di dato, f., spagnuolo, m. i., et al. (2014). zinc monotherapy is effective in wilson’s disease patients with mild liver disease diagnosed in childhood: a retrospective study. orphanet journal of rare diseases, vol. 9, p. 41 doi 10.18502/sjms.v16i2.9288 page 206 introduction case presentation discussion conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9294 production and hosting by knowledge e research article association between inflammatory cytokines and liver functions in rheumatoid arthritis patients mohamed abdelrhman eltahir1,2, kawthar abdelgaleil mohammedsalih3, elhaj noureldien mohamed3, faisal makki babekir4, and amar mohamed ismail5 1department of clinical chemistry, faculty of medical laboratory, sudan university of science and technology, khartoum, sudan 2department of clinical chemistry, faculty of medical laboratory, gadarif university, khartoum, sudan 3department of hematology, faculty of medical laboratory, sudan university of science and technology, khartoum, sudan 4blood bank and laboratory department, al-amal hospital, khartoum, sudan 5department of biochemistry and molecular biology, faculty of science and technology, alneelain university, khartoum, sudan orcid: mohamed abdelrhman eltahir: http://orcid.org/0000-0003-0172-8362 abstract background: rheumatoid arthritis (ra) is associated with abnormal liver tests, and the medications used for ra are often hepatotoxic. therefore, this study aimed to investigate an association between pro-inflammatory and anti-inflammatory cytokines and liver function tests in ra patients. methods: in this descriptive cross-sectional study, 88 ra patients were included, 84 of them were women and 4 men, aged 21–81 years. serum interleukin-10 (il-10), interleukin-17 (il-17), osteopontin (opn) were measured and liver function tests were conducted. results: the frequency of ra was higher among adults aged >41 years (72 [81.8%]) than young adults aged ≤41 years (16 [18.2%]). ra was more common in women (84 [95.5%]) than in men (4 [4.5%]) – approximately 21:1-fold. young adults had higher abnormal il-10 than adult ra patients (or = 3.72, p-value 0.044). abnormal il-17 (or = 5.67, p-value 0.034) was found to be increased in young-adult ra patients. no association was observed between age and opn and between the duration of disease and il-10, il-17, and opn. similarly, no association was noted between the types of treatment and il-10, il-17, and opn, nor between il-10, il-17, opn and liver parameters (ast, alt, alp, alb, tp, and ggt). conclusion: pro-inflammatory and anti-inflammatory cytokines are not associated with abnormal liver functions, as has been demonstrated in ra patients. keywords: rheumatoid arthritis, interleukin, liver function tests, cytokines how to cite this article: mohamed abdelrhman eltahir, kawthar abdelgaleil mohammedsalih, elhaj noureldien mohamed, faisal makki babekir, and amar mohamed ismail (2021) “association between inflammatory cytokines and liver functions in rheumatoid arthritis patients,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 276–284. doi 10.18502/sjms.v16i2.9294 page 276 corresponding author: mohamed abdelrhman eltahir; department of clinical chemistry, faculty of medical laboratory, sudan university of science and technology, khartoum, sudan. email: alsahaf33@yahoo.com received 23 april 2021 accepted 6 june 2021 published 30 june 2021 production and hosting by knowledge e mohamed abdelrhman eltahir et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com http://orcid.org/0000-0003-0172-8362 mailto:alsahaf33@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohamed abdelrhman eltahir et al 1. introduction rheumatoid arthritis (ra) is a common autoimmune inflammatory disease. although the prevalence of ra is lower globally (0.5–1%), it is associated with socioeconomic burden and higher risk of mortality rate [1]. recent studies have demonstrated that the treatments used for ra improved outcome, and also accounts as a risk for hepatic complications [2]. the adverse effects of ra treatments include asymptomatic elevations of liver enzyme, fibrosis, and sometimes fatal hepatic necrosis [3]. on the other hand, liver disorders have been noted in untreated ra patients [4]. increasing amounts of interleukin-10 (il-10), a potent anti-inflammatory cytokine [5], can be detected in the synovium of ra patients. additionally, considering that the activity of ra cannot be attenuated by il-10 administration [6], many researchers suggest that il-10 plays an important role in chronic liver diseases [7]. interleukin-17 (il-17), a proinflammatory cytokine, is upregulated in many autoimmune diseases such as ra; high levels of il-17 have been reported to be produced in different samples of ra [8, 9]. some investigators suggest that il-17 plays a key role in many liver diseases and is also associated with the progress of the disease [10–12]. osteopontin (opn) is a proinflammatory cytokine that induces ra [13–15], and included in many liver diseases, despite its role in liver problems are still controversial [16]. therefore, this study was carried out to find out the association between pro-inflammatory, anti-inflammatory cytokines and liver function tests among ra patients. 2. materials and methods this descriptive cross-sectional hospital-based study was conducted on 88 ra patients who were clinically diagnosed according to the criteria of the american college of rheumatology (acr) 1987 and were examined at the common ra clinics in khartoum state (military, alamal hospital, and zain clinic). all patients received treatment; the demographic data, type of treatment, and duration of disease for each patient were recorded – 4 men and 84 women aged 28–90 years. non-sudanese patients with ra and those with unclear diagnosis were excluded. serum from each subject were centrifuged at 3000 g for 10 min after clotting for 30 min at room temperature and stored at –40°c until analysis. all samples were investigated for opn, il-17, and il10 by sandwich enzyme-linked immune sorbent assay (elisa) (elisa development; thermo fisher scientific systems, usa) according to the manufacturer’s instructions. in addition, liver functions tests (tp, albumin, ast, alt, ggt, and alp) were done using doi 10.18502/sjms.v16i2.9294 page 277 sudan journal of medical sciences mohamed abdelrhman eltahir et al fully automated mindray chemistry analyzer (bs 200). data were statistically analyzed by statistical software package, version 16. results were expressed as numbers and percentages. chi-square test was used to determine the level of significance (p-value of 0.05 was considered to be statistically significant). 3. results ra is more common in adults (72 [81.8%]) than young adults (16 [18.2%]), the frequency of ra was found to be higher in women (84 [95.5%]) than in men (4 [4.5%]). moreover, 52 (59.1%) patients were receiving steroids while 36 (40.9%) were on non-steroid treatment. the duration of disease for 62 (70.5%) patients was ≤6 years and for 26 (29.5%) was >6 years. abnormal il-10 was found in 63 (71.6%) patients, while 25 (28.4%) had a normal percentage. the results of characteristic data show that while 80 (91%) ra patients had normal il-17, 8 (9%) had abnormal. normal opn was observed in 76 (86.4%) ra patients and abnormal opn in 12 (13.6%) (table 1). chi-square analysis revealed that young adults group had a higher abnormal il-10 than adult ra patients (or = 3.72, p-value 0.044). also, abnormal il-17 (or = 5.67, p-value 0.034) was found to be increased in young adult ra patients while no association was seen between age and opn (or = 2.67, p-value 0.144; table 2). furthermore, no association was reported between the duration of the disease and il-10, il-17, and opn with p-values 0.410, 0.176, and 0.502 and or 0.77, 0.37, and 1.30, respectively (table 3). similarly, no association could be derived between the types of treatment and il-10, il-17, and opn with p-value 0.246, 0.286, and 0.351 and or 1.53, 2.21, and 0.65, respectively (table 4). pearson’s correlation analysis revealed that there were no association between il-10, il-17, opn and liver parameters (ast, alt, alp, alb, tp, and ggt; table 5). 4. discussion abnormal liver functions were observed in ra patients. the researchers further attributed the abnormality to immune aggregations and others justified it by drugs toxicity. accordingly, this study was carried out to assess whether the pro-inflammatory or anti-inflammatory cytokines are associated with liver functions in ra patients. the current study revealed that there is no association between interleukins and liver function tests. in fact, abnormal liver tests were noted in patients with ra [17]. concurrent with many previous studies, the frequency of ra is higher in elderly subjects [18, 19]. a possible explanation might be that the protective mechanisms in elderly population are doi 10.18502/sjms.v16i2.9294 page 278 sudan journal of medical sciences mohamed abdelrhman eltahir et al table 1: demographic and baseline characteristics of ra patients. variables frequency (%) age (yr) ≤41 16 (18.2%) >41 72 (81.8%) sex male 4 (4.5%) female 84 (95.5%) treatment steroid 52 (59.1%) non-steroid 36 (40.9%) duration (yr) ≤6 62 (70.5%) >6 26 (29.5%) cut-off il-10 abnormal 63 (71.6%) normal 25 (28.4%) cut-off il-17 abnormal 8 (9%) normal 80 (91%) cut-off opn abnormal 12 (13.6%) normal 76 (86.4%) total 88 (100%) table 2: association between interleukins il10, il17, opn and age groups. variables age (yr) or ci-lower ci-upper p-value ≤≤≤41 >>>41 il-10 abnormal 14 (23.0%) 47 (77.0%) 3.72 (0.78–17.7) 0.04 normal 2 (7.4%) 25 (92.6%) il-17 abnormal 2 (40.0%) 6 (60.0%) 5.67 (1.24–25.7) 0.03 normal 12 (15.0%) 68 (85.0%) opn abnormal 4 (33.3%) 8 (66.7%) 2.67 (0.69–10.2) 0.14 normal 12 (15.8%) 64 (84.2%) decreased, resulting in decreased immunotolerance and decreased cytokines synthesis and t cells proliferation [20]. the demographic data indicated that the prevalence of ra was found to be 21-fold higher in women than in men. in contrast to a previous study in sudan, the female-to-male ratio was 9:1 [21]. since the change in sex hormones after doi 10.18502/sjms.v16i2.9294 page 279 sudan journal of medical sciences mohamed abdelrhman eltahir et al table 3: association between interleukins il10, il17, opn and duration of ra. variables duration (yr) or ci-lower ci-upper p-value ≤≤≤6 >>>6 il-10 abnormal 42 (68.9%) 19 (31.1%) 0.77 (0.28–2.13) 0.41 normal 20 (74.1%) 7 (25.9%) il-17 abnormal 4 (50.0%) 4 (50.0%) 0.37 (0.08–1.65) 0.17 normal 58 (72.5%) 22 (27.5%) opn abnormal 9 (75.0%) 3 (25.0%) 1.30 (0.32–5.25) 0.50 normal 53 (69.7%) 23 (30.3%) table 4: association between interleukins il10, il17, opn and types of treatment. variables treatment or ci-lower ci-upper p-value steroid non-steroid il-10 abnormal 38 (62.3%) 23 (37.7%) 1.53 (0.61–3.83) 0.24 normal 14 (51.9%) 13 (48.1%) il-17 abnormal 6 (75.0%) 2 (25.0%) 2.21 (0.42–11.6) 0.28 normal 46 (57.5%) 34 (42.5%) opn abnormal 6 (50.0%) 6 (50.0%) 0.65 (0.19–2.21) 0.35 normal 46 (60.5%) 30 (39.5%) puberty is associated with high prevalence of ra in women, a woman’s immune system is potentially more reactive than that of a man. the current study reports that young adults are more likely to have abnormal il-10 and il-17. however, these results disagree with previous studies [22, 23]. no association was found between age and opn level. concurrent with this finding, a relationship between age and opn has been previously reported [24]. similar to other results, no associations between il10, il17, opn levels and the duration of disease have been demonstrated [22, 23, 25]. despite reducing il-17 after the use of steroids therapy, il-10 was increased [26]. the present study revealed no associations between il-10, il-17, opn levels and the types of treatment. it has become clear that steroids directly modulate the pro-inflammatory cytokine or suppress cytokines-producing cells [26, 27]. doi 10.18502/sjms.v16i2.9294 page 280 sudan journal of medical sciences mohamed abdelrhman eltahir et al table 5: association between cytokines and liver function parameters (pearson’s correlation results). parameters p-value r2 il-10 ast 0.62 0.12 alt 0.20 0.66 alp 0.80 0.05 alb 0.16 –0.13 tp 0.56 0.02 ggt 0.25 0.15 il-17 ast 0.18 –0.15 alt 0.82 0.02 alp 0.82 –0.02 alb 0.23 0.12 tp 0.59 0.05 ggt 0.17 –0.14 opn ast 0.50 0.07 alt 0.25 0.12 alp 0.89 0.01 alb 0.29 –0.11 tp 0.49 0.07 ggt 0.98 –0.02 5. conclusion the data of present study shows that women are at a higher risk to have ra. moreover, young adult ra patients are more likely to have abnormal il-10 and il-17. furthermore, pro-inflammatory and anti-inflammatory cytokines are not associated with abnormal liver functions as has been demonstrated in ra patients. acknowledgements the authors would like to express their sincere gratitude to the dr. mariam abbas for her consultation and wisdom. may god bless her. ethical considerations ethical permits for the study were obtained from the ethical review committees at the sites where patients were recruited, and all patients gave informed consent for their participation in the study. doi 10.18502/sjms.v16i2.9294 page 281 sudan journal of medical sciences mohamed abdelrhman eltahir et al competing interests the authors declare no known conflicts of interest in relation to this paper. availability of data and material the study data are available with the author upon reasonable request funding none. references [1] 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(2018). the relationship between interleukin-17 and osteoporosis in patients with rheumatoid arthritis. turkish journal of osteoporosis, vol. 24, pp. 46–52. [24] iwadate, h., kobayashi, h., kanno, t., et al. (2013). plasma osteopontin is correlation with bone resorption marker in rheumatoid arthritis patients. international journal of rheumatic disease, vol. 17, no. 1, pp. 50–56. [25] al zifzaf, s. d., mokbel, n. a., and abdelaziz, m. d. (2015). interleukin-17 in bechet’s disease: relation with clinical picture and disease activity. egyptian rheumatology and rehabilitation, vol. 42, no. 2, pp. 34–38. [26] negera, e., walker, s., bobosha, k., et al. (2018). the effects of prednisolone treatment on cytokine expression in patients with erythema nodosum leprosum reactions. frontiers in immunology, vol. 9, pp. 1–15. [27] noack, m., ndongo, n., and miossec, p. (2016). evaluation of anti-inflammatory effects of steroids and arthritis-related biotherapies in an in vitro coculture model with immune cells and synoviocytes. frontiers in immunology, vol. 7, pp. 1–10. doi 10.18502/sjms.v16i2.9294 page 284 introduction materials and methods results discussion conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9695 production and hosting by knowledge e review article item analysis of multiple-choice questions (mcqs): assessment tool for quality assurance measures amani h. elgadal1 and abdalbasit a. mariod2 1department of pediatrics and child health, karary university, omdurman, sudan 2indigenous knowledge & heritage center, ghibaish college of science & technology, ghibaish, sudan orcid: amani h. elgadal: https://orcid.org/0000-0003-0934-2755 abdalbasit a. mariod: https://orcid.org/0000-0003-3237-7948 abstract background: integration of assessment with education is vital and ought to be performed regularly to enhance learning. there are many assessment methods like multiple-choice questions, objective structured clinical examination, objective structured practical examination, etc. the selection of the appropriate method is based on the curricula blueprint and the target competencies. although mcqs has the capacity to test students’ higher cognition, critical appraising, problem-solving, data interpretation, and testing curricular contents in a short time, there are constraints in its analysis. the authors aim to accentuate some consequential points about psychometric analysis displaying its roles, assessing its validity and reliability in discriminating the examinee’s performance, and impart some guide to the faculty members when constructing their exam questions bank. methods: databases such as google scholar and pubmed were searched for freely accessible english articles published since 2010. synonyms and keywords were used in the search. first, the abstracts of the articles were viewed and read to select suitable match, then full articles were perused and summarized. finally, recapitulation of the relevant data was done to the best of the authors’ knowledge. results: the searched articles showed the capacity of mcqs item analysis in assessing questions’ validity, reliability, its capacity in discriminating against the examinee’s performance and correct technical flaws for question bank construction. conclusion: item analysis is a statistical tool used to assess students’ performance on a test, identify underperformed items, and determine the root causes of this underperformance for improvement to ensure effective and accurate students’ competency judgment. keywords: assessment, difficulty index, discrimination index, distractors, mcq item analysis how to cite this article: amani h. elgadal and abdalbasit a. mariod (2021) “item analysis of multiple-choice questions (mcqs): assessment tool for quality assurance measures,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 334–346. doi 10.18502/sjms.v16i3.9695 page 334 corresponding author: amani h. elgadal; email: amanielgaddal@karary.edu.sd amanielgaddal@gmail.com received 27 july 2021 accepted 02 september 2021 published 30 september 2021 production and hosting by knowledge e amani h. elgadal and abdalbasit a. mariod. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:amanielgaddal@karary.edu.sd mailto:amanielgaddal@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod 1. introduction single or one best answer of multiple-choice questions (mcqs) is known as an item consisting of a stem with many options, generally three to five, one of them being the right option while the rest distractors. this form of assessment is used in many institutions due to its capability to significantly appraise curricula. it is an efficient and relevant tool to identify the strengths and weaknesses in student knowledge, reflection of educational methods and strategies, however, it needs time, effort, and skill to develop a high-quality one [1]. a well-build mcq assesses higher cognitive tackles of bloom’s taxonomy like data interpretation, synthesis, and knowledge application more than testing facts recall alone. the stem of the mcqs is a clinical case scenario that can adequately measure core competencies, the intended learning outcome (ilo), evaluating the power of students, give reliable feedback, and reform curricula [1–3]. there are six hierarchically assortments of cognitive scope in bloom’s taxonomy that are arranged in ordered factions: knowledge, comprehension, application, analysis, synthesis, and evaluation. tarran trivializes bloom’s taxonomy and creates two levels: k1 represents the fundamental knowledge and cognition; k2 embraces analyzing with implementation and analysis [4]. item analysis is a hokey and avail approach to assess the reliability and validity of test items, performed after the exam. it auditions the effectiveness of stem question and its distractors to enable the examiners to reconstruct/modify or delete questions before the creation of an exam bank for future tests [1–4]. item analysis shows the questions’ difficulty index (dif-i). ditto assesses the question’s capability to discriminate performance of good or poor students in the test, that is, the discrimination index (dis-i) [1–5]. bona mcqs assess perception, effectiveness, and psychomotor scopes better than other assessment methods due to its objectivity covering many subjects, minimizing the assessor’s alignment, and its comparative, reliable, conciliated, and easy netting [3–5]. in addition, it is also a relevant method that measures any impairment or strengths of the examinee’s knowledge, gaps in teaching methods, or strategies of the institute for better graduate outcomes. it provides a good chance to the staff members to stimulate them in building their mcq construction skills needed for the clarity of exam questions. [2] the standardization tool characteristics can influence its credibility. mcq designers ought to pay attention to the examination purpose and its content based on the examinee level, blueprint, and the minimum pass level (mpl). it should fit the purpose and consensus judgment with advantageous implementation. so meticulous evaluation is counseled. maintaining the standards in medical schools is crucial for high doi 10.18502/sjms.v16i3.9695 page 335 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod educational excellence, patient safety, and total quality management needed for both historic and newly established colleges [5–7]. the authors’ aim in this review was to accentuate some consequential points about psychometric analysis displaying its roles in evaluating mcqs, assessing its validity and reliability in discriminating the examinee’s performance, and impart some guide to the faculty members especially juniors when constructing their exam questions bank. 2. materials and methods databases such as google scholar and pubmed were searched for freely accessed english articles published since 2010. synonyms and keywords were also used in the search. the abstracts of the articles were first viewed and read to select suitable matches, and then full-text articles were perused and summarized. finally, recapitulation of the relevant data was done to the best of authors’ knowledge. 3. results in any educational institute, assessment is a way to measure supposed mastering of ilos. it is particularly consequential in clinical college graduates for protected patient care and community needs. hence, meticulous evaluation and education must be performed. standardized assessment of students’ performances involves measurement aspects that are peculiar of the statistical framework. this process consists of distinct phases, from the definition of the measurement objectives to the development of proper assessment tools, and the analysis of the results in terms of students’ achievement [5]. it should match student’s ability and items related to specific content domains. the development of a proper assessment method is a rather complex process that starts with the definition of item specifications and ends with the validation of the assessment method itself. it effectively measures the target competencies in a test, its content and format constraints, distractors plausibility, item difficulty, and test consistency. for this purpose, first, a pretest sample is given to an examinee, their responses are then analyzed and validated using psychometric methods before conducting the final exam [6]. doi 10.18502/sjms.v16i3.9695 page 336 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod 4. discussion item analysis is a conciliated and availed method to examine the reliability and validity of the pretested standardized examination items. it is conducted after the exam before banking questions for future tests [5, 6]. 4.1. methods of item analysis different methods can be used to investigate the psychometric properties of tests and test items. descriptive methods based on classical test theory (ctt) and models belonging to modern item response theory (irt) were reviewed. regarding the item level, the ctt model is a relatively simple methodology. it is the probative estimate of the examinee’s success rate on each item. the ctt appraises reliability, difficulty, dis-i, and the distractors’ efficiency (de) to check the appropriateness and plausibility of all distractors. the core of this theory is based on the functions of the true test score and the error of random measurement. on the other hand, the rasch technique of irt is more grounded to assess the examinee’s success at the item level [7]. irt besides apprizing the test reliability, di, and de, assesses the exam global rating similar to cronbach’s alpha. additionally, it checks the exam invariance that is conclusive for building exam banks with well-calibrated exam questions. item standardization can be classified as follows [5–8]: 1. relative approaches (norm-referenced): used for ranking the examinee when a predetermined rating of the examinee is wanted so that there is no fixed mpl and the level fluctuates in accordance with the examinee’s overall performance. 2. absolute approaches (criterion-referenced): judgment based on: (a) exam content: used in high-stake conditions like licensure; e.g., angoff (1971), nedelsky (1954), and ebel (1972) methods where the standards setter decides the borderline examinee’s criteria. (b) compromise: the well-known one is hofstee, which can be used in a lowresource setting. the designers decide the mpl after consensus. all of the above techniques should be executed before conducting the exam [5–8]. there are two types of angoff; the original and the modified methods, both of which are used to decide the cut-off scores for the exam items. the original method needs subject experts’ panel to decide the probability of a minimally competent student who doi 10.18502/sjms.v16i3.9695 page 337 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod can answer each item correctly. each expert estimates the probability ranging from 0 to 1 for every question and then calculating the average portability as a final cut-off score. the modified angoff needs test domain expertise and the probabilities choices are eight, e.g., 0.2, 0.3, 0.4, 0. 5, 0.6, 0.7, 0.8, or “do not know” [9]. angoff method is a predetermined criterion-referenced and test-centered method. the modified-angoff method allows the panel’s setter to discuss the cut-off score and the rating results. for this reason, the modified-angoff method is used for licensure and professions certification tests. since the standard-setting is a decision-making process, the criterion setting validity and rating consistency is evaluated by how the process is performed in accordance with the test principle. evaluation of the standard-setting validity is influenced by internal and external issues. it is consequential to ascertain that all standard-setting activities and measures are done consistently [10]. in the nedelsky method, three subject matter experts (smes) are used for the standard-setting of mcqs to assess the probability of a borderline/minimally competent student who will rule out the incorrect options or distractors. the probability is calculated as the reciprocal of the remaining items which the borderline/ minimally competent students are not sure if it is correct or not. for example, a group of experts assess the probability of borderline /minimally qualified students who are expected to rule out two distractors in a four-options item question. the rating will be half (1/2 = 0.50). the cut-off score for the exam is determined by adding up the average nedelsky values for each item [10, 11]. the ebel method needs subject experts to judge the difficulty and relevance level of each item in the exam. the panel examines each item to determine its appropriateness, difficulty or simplicity, its relevance, importance, and acceptability. each item is categorized according to its difficulty and relevance level. next, the panel experts assess the expected chances of a minimally competent student who can rule out item distractors. lastly, the number of items in each category is multiplied by the expected probability of correct answers, and the total results are added to calculate the exam cut-off score. relatively, this method is costly, time-consuming, and needs many standard experts setters. digital soft wire is important to gather the responses. backup by the criterionreferenced method is needed like borderline regression. it is widely used in high-stakes exams and if challenged, it can hold up in court [12]. eclectic hofstee method was developed in 1983 to address problems that resulted from predictions disagreement between criterionand norm-referenced items. in this method, the standard setter answers four enquires and presumptions about the candidates who will write the test. two of these queries are about their apt knowledge level doi 10.18502/sjms.v16i3.9695 page 338 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod (referred as k), while the other two are about the failure rate (referred as f); (1) what is the satisfactory maximum cut-off score, even if all of the examinees overreached it? (2) what is the acceptable minimum cut-off score even if all of the examinees do not achieve it? (3) what is the allowed maximum failure rate? (4) what is the minimally accepted failure rate? the first two questions assess the failure rates and range between zeros and a hundred percent; closer to 100% indicate test difficultly and hard for anyone to pass. the last two questions, however, are scored between zero and the total test items numbers, the higher the value, the more difficult the cut-off score [12]. selection of a suitable psychometric approach is influenced by different factors. it varies depending on the intended goals/objective. in low-resource setting, the ctt psychometric method may be good enough. in a high-stakes exam, irt and rasch measurement theory must be used, and the final decisions will depend upon the quantitative and qualitative item results. you can select a suitable method according to the psychometric properties you want like the reliability, validity, suitability of item response, scaling assumption, and acceptability [13]. 4.2. reliability the inherent concept is embedded within the ctt, reliability assesses the internal consistency of mcqs items [13, 14]. reliability and validity are important for defining the result obtained to meet the requirements and measure bias. reliability shows up to which level the assessments were consistent while validity assesses the assessment accuracy [15]. reliability-related concepts are internal consistency, stability, equivalence, and precision. reliability depends both on the standard error of measurement and the standard deviation of the examinee’s assessment. regarding the internal consistency, the estimation depends on the item’s average correlation for a test, also it estimates to which degree the mcqs can measure the same knowledge domain characteristics. typically, internal consistency is obtained by calculating the reliability coefficient. a reliability coefficient estimates the concordance between the observed and true scores of the examinees, it appraises the interlinks between scores obtained by two parallel exams. this estimation explains that an individual’s scores are expected to change when retested without alteration in knowledge and perception with the same or any equivalent test [14–16]. increasing the item numbers in a given exam can augment the reliability but it is expensive, needs time and average correlation effort. cronbach’s alpha of 0.8 or more is needed for high-stakes exams, however, usually, there is a fixed item number in licensure or high-stakes exams; so, you can use other alternatives by increasing doi 10.18502/sjms.v16i3.9695 page 339 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod the deployment of the obtained exam scores, for example, test variance. range of scores/performances as moderately difficult (di: 0.4–0.8) and sufficient discrimination point biserial correlation (rpb) more or equal to 0.2. it can also increase the standard deviation and the variance of the scores [23–25]. for the assumption that any test can contain score error, sem is used to estimate the interval within which the true score will be obtained. when the sem is small, the interval will be narrower and more precise. sem is inversely related to the reliability coefficient [14–16]. the kuder-richardson formula 20 (kr-20) measures internal consistency and reliability of an examination. it measures the interior uniformity of the exam with many options. kr-20 > 0.90 indicates a homogenous test. kr-20 = 0.8 is acceptable but >0.8 is nonreliable [17]. 4.3. statistical steps of item analysis the statistical analysis system (sas), statistical package for the social sciences (spss), and similar software are used in data analysis. after conducting the exam, data are gained manually or electronically and then entered into microsoft excel sheet, spss, or any other statistical methods of your choice. next, the data are analyzed to get: the mean, standard deviations (sd), unpaired t-test, and coefficient of variation, dif-i and dis-i, and (de) [18]. 1. difficulty index (dif-i) is described as the examinee’s incapability to reply to the item correctly. to calculate it: rank the examinees in order, then pick one-third of the high or greater achievers (ha) who correctly answered to the item and one-third of the lower achievers (la) who also choose the correct answer. it can be calculated using the following formula: dif-i = [(ha + la)/n] × 100, where: n is the total number of students in the two groups. the dif-i is expressed as a p-value, that is, the proportion of students who correctly answer questions in a given test. the dif-i can range from zero to a hundred percent. if it is >70%, it is an easy item; 30–70% means average/acceptable difficulty; <30% means a difficult item [18–23]. 2. discrimination index (dis-i) is defined as the ability of an item to differentiate between students with highand low exam scores. it ranges from –1.00 to +1.00. those with high value are good discriminator items. negative di can be obtained doi 10.18502/sjms.v16i3.9695 page 340 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod if the low achievers get more correct answers than the high achievers, and vice versa. dis-i can be calculated using the formula: dis-i = [(ha – la)/n] x 2, where: ha are the high achievers while la are the low achievers in the test. dis-i can range from 0 to 1; if it is <0.15, it means a poor discriminator; 0.15–<0.25 means good discriminatory items; >0.25 means excellent discriminator [9–12, 20– 23]. rpb is another way of measuring item discrimination, defined as the correlation between the item score and the total test score. it is mathematically equivalent to pearson’s correlation. both dis-i and biserial correlation are greatly correlated, and a dis-i or rpb < 0.2 is regarded low [10–16]. 3. distractor analysis aims to determine the capability of item options to distract the examinee when selecting the right answer. each distractor must be assessed for its frequency of selection by the examinee, it is called de [18–23]. de can be calculated using the formula: de = frequency of distractor selection ÷ total no. of item respondent × 100. de needs to be assessed in each mcq to test the presence or absence of nfd. if an mcq includes 0-nfd, 1-nfd, 2-nfd, or 3-nfd, it means that its capability to act as an efficient distractor is 100, 66.6, 33.3, or 0%, respectively [12–16]. de is classed as functional distractor (fd) when chosen by ≥5% of the examinee and as non-functional distractors (nfd) if chosen by <5%. nfds include options other than the right answer chosen by <5% of the examinees. implausible distractors can be noticed easily, so they ought to be modified or rejected [18–23]. 4.4. item flaws faults in item-writing can also influence the overall performance by making questions challenging or too easy. example: the use of absolute terms like always, never, or choosing the right option in a lengthy sentence. it is wise to refrain from. using negative words like none of the above or except. grammatical flaws may divert the examinee to the right answer and make the questions easy. items with many nfds reduce the de and dis-i [24–26]. doi 10.18502/sjms.v16i3.9695 page 341 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod 4.5. the number of item options some authors argue that mcq with three options needs much less time for construction with a greater chance for high reliability and validity than four–five options. others say that mcq choices can be three or even two and have the potency to give the same results as 4 or 5 options without affecting the examination quality [27–29]. as cited earlier, evaluation is an essential measure not only for competent graduates but also for college enhancement and quality assurance [30–33]. valid evaluation techniques aligned with accrediting authorities’ requirements are one of the desires for excellence and accreditation. it elevates the importance of the assessment-unit building to lead all evaluation activities within the institute. performing collaborative and organized on-job training enhances staff capabilities in the mcqs writing and analyses for higher student success and competence [30–36]. 5. conclusion item analysis of mcqs is a statistical tool used to assess students’ performance on a test, identify underperformed items, and determine the root causes of this underperformance for improvement in order to ensure effective and accurate students’ competency judgment. it is a potent tool to appraise the ilos in a short time, detect gaps in curriculum contents evident by student’s poor performance in a test, and identify strengths and weaknesses in teaching strategies and methods. exam reliability and validity are important for defining the result obtained to meet the requirements and measure bias. training and retraining of all faculty members are important to improve their skills in properly standardizing mcqs construction to overcome any assessment challenges. acknowledgments the authors would like to thank the sudanese researchers foundation for their unlimited support. ethical considerations not applicable. doi 10.18502/sjms.v16i3.9695 page 342 sudan journal of medical sciences amani h. elgadal and abdalbasit a. mariod competing interests none. availability of data and material all materials of this study are available from the corresponding author upon reasonable request. funding none references [1] hingorjo, m. r. and jaleel, f. 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(2020). evaluation of the effect of items’ format and type on psychometric properties of sixth year pharmacy students’ clinical clerkship assessment items. bmc medical education, vol. 20, no. 1, p. 190. doi 10.18502/sjms.v16i3.9695 page 346 introduction materials and methods results discussion methods of item analysis reliability statistical steps of item analysis item flaws the number of item options conclusion acknowledgments ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9697 production and hosting by knowledge e review article exploring the power and promise of in silico clinical trials with application in covid-19 infection abdelrahman h. abdelmoneim1, safinaz i. khalil2,3, hiba awadelkareem osman fadl4,5, ayesan rewane6, and sahar g. elbager7 1clinical immunology resident, sudan medical specialization board, khartoum, sudan 2department of pharmacology, faculty of medicine, university of medical sciences and technology, khartoum, sudan 3department of pharmacology, alfajr college of science and technology, khartoum, sudan 4department of hematology, faculty of medical laboratory sciences, al-neelain university, khartoum, sudan 5deapartment of medical laboratory, sudanese medical research association (smra), khartoum, sudan 6department of allergy and immunology, rush university medical center, chicago, illinois, usa 7department of hematology, faculty of medical laboratory sciences, university of medical sciences and technology, khartoum, sudan orcid: abdelrahman h. abdelmoneim: https://orcid.org/0000-0002-5037-8488 safinaz i. khalil: https://orcid.org/0000-0003-3843-0447 hiba awadelkareem osman fadl: https://orcid.org/0000-0002-3614-1994 sahar g. elbager: https://orcid.org/0000-0002-3891-6968 abstract background: covid-19 pandemic has dramatically engulfed the world causing catastrophic damage to human society. several therapeutic and vaccines have been suggested for the disease in the past months, with over 150 clinical trials currently running or under process. nevertheless, these trials are extremely expensive and require a long time, which presents the need for alternative cost-effective methods to tackle this urgent requirement for validated therapeutics and vaccines. bearing this in mind, here we assess the use of in silico clinical trials as a significant development in the field of clinical research, which holds the possibility to reduce the time and cost needed for clinical trials on covid-19 and other diseases. methods: using the pubmed database, we analyzed six relevant scientific articles regarding the possible application of in silico clinical trials in testing the therapeutic and investigational methods of managing different diseases. results: successful use of in silico trials was observed in many of the reviewed evidence. conclusion: in silico clinical trials can be used in refining clinical trials for covid-19 infection. keywords: in silico, clinical trials, covid-19, sars-cov-2, vaccine how to cite this article: abdelrahman h. abdelmoneim, safinaz i. khalil, hiba awadelkareem osman fadl, ayesan rewane, and sahar g. elbager (2021) “exploring the power and promise of in silico clinical trials with application in covid-19 infection,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 355–370. doi 10.18502/sjms.v16i3.9697 page 355 corresponding author: abdelrahman h. abdelmoneim; email: abduhamza009@gmail.com received 19 june 2021 accepted 07 august 2021 published 30 september 2021 production and hosting by knowledge e abdelrahman h. abdelmoneim et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abduhamza009@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abdelrahman h. abdelmoneim et al. 1. introduction computer simulations have been used in airplane and car design with great performance and accuracy for years [1, 2]. recently, companies and researchers have started to pay more attention to the use of computational modeling in areas like fluid dynamics, ventricular septal deceives, and movement mechanics of hip implants [3, 4]. the general commissioner of the american food and drug administration (fda) in 2017 recognized computer simulation as a possible solution for approved medical instruments. furthermore, in 2016, a guide for reporting computational modeling studies in medical device submissions was issued by the fda to provide clear recommendations for organizing and submission of these studies [5]. randomized clinical trials represent almost two-thirds of the approximately $2.6 billion needed to develop a new drug [6], it is a very long and expensive method for designing and validating new therapies and technologies with a very disturbing high failure rate [7]. furthermore, real clinical trials may indicate a drug to be ineffective, however, it rarely indicates the reason behind this failure. this leads to the rejection of the drug despite the possibility of it working with small modifications [8]. from here, the possibility of other methods like in silico simulation with coherent abilities to provide fast and accurate results seems very promising especially in times of pandemic like the current covid-19 where time is a very limited resource. the term in silico clinical trial (isct) was first coined in 2011 by the virtual physiological human (vph) institute which defined it as: the use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention. it is a subdomain of “in silico medicine, the discipline that encompasses the use of individualized computer simulations in all aspects of the prevention, diagnosis, prognostic assessment, and treatment of disease.” since then, the concept of changing clinical evidence with in silico evidence is slowly being more accepted, which was made evident by the fda acceptance of in silico simulation as a possible replacement for animal studies in the assessment of artificial pancreas technologies [9, 10]. in silico trials can be used for the noninvasive assessment of medical conditions. for example, in vivo computed tomography data were used to create individualized models that accurately predict the changes in vertebrae bone strength in mice [11], and the incidence of spine and hip fracture in humans [12]. from these observations, we doi 10.18502/sjms.v16i3.9697 page 356 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. contemplate that iscts can be used for choosing the specific mode of therapy with the appropriate doses for individual covid-19 patients, depending on their individualized parameters like immunodeficiency and renal impairment. this will be a significant step in the path of individualized medicine. furthermore, since this information can be available within hours to minutes to the clinical provider, this acts as a significant bonus when compared with the classical clinical trial. this work aims to discuss the possible use of in silico trials in the design and testing of therapeutic and preventive measures to either reduce, refine, or partially replace human clinical trials done on the common disease with a focus on the possible applications of these methodologies in covid-19 trials. 2. materials and methods 2.1. types and phases of clinical trials clinical trials have been for a long time the golden tool for validating the efficiency of new drugs and biomedical products. it is a very long and complicated procedure containing five basic phases: 1. preclinical phase: done in animals to understand the physiological action of the drug and four clinical trials in humans to assess the appropriate dose and duration of the drug and acquire data about shortand long-term side effects [13]. figure 1 shows a schematic representation of the clinical trials pathway to further elucidate the relation between the different phases. although randomized clinical trials are the gold standard for evaluating the effectiveness and safety of the new medication and biomedical products, nonrandomized studies could still provide valuable and reliable input especially in fields such as forensic mental health where the randomized clinical trial may be inappropriate, therefore assisting in the decision for accepting or rejecting the new products or procedures [14]. 2.2. covid-19 conventional therapeutic clinical trials in the past months since covid-19 appeared from wuhan, china, and spread around the world, over 3876 clinical studies have been recorded globally on clinical trial registries, including over 500 randomized controlled trials. doi 10.18502/sjms.v16i3.9697 page 357 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. figure 1: preclinical and clinical trial phases. fda: food and drug administration (https://www.fda.gov/) such rapid development and inauguration of clinical trials are remarkable but presents challenges, including the possibility for replication and rivalry [15]. the most common therapeutic agent being trialed presently is hydroxychloroquine (261 trials with some trials planning to recruit over 25,000 participants), followed by antiinfective and antiparasitic agents as illustrated in figure 2. figure 2: distribution of the most common therapeutic clinical trials on covid-19, as reported by clinicaltrials.gov. currently, there are many contestant drugs in preclinical and early phase development and these form a pipeline for future large clinical trials if current applicant therapies prove ineffective or unsafe [15]. with 15% of patients complaining of the severe form of the disease, hospitals being stunned worldwide, and a global mortality rate of 5.7%, new modes of therapy are instantly needed. new interventional clinical trials for covid-19 treatment encompass the recycling of an old antiviral drug formerly used to treat the ebola virus known as doi 10.18502/sjms.v16i3.9697 page 358 https://www.fda.gov/ sudan journal of medical sciences abdelrahman h. abdelmoneim et al. remdesivir or the combination of two antivirals: ritonavir + lopinavir, which has been used in the past to treat the hiv infection. additionally, active clinical trials comprise the use of drugs approved for different therapeutic indications, as in the case of using monoclonal antibodies against interleukin-6 receptor (anti-il-6r). this recycling strategy established on the reuse of approved drugs is commonly stated as drug repurposing and is largely effective, as verified by instances of repurposing treatments in cancer and other human diseases [16]. iscts could be very cost-effective in testing all possible therapeutic drugs for covid19 as it provides a fast and reliable method for acquiring data about the efficiency of these therapeutics with no or minimal human involvement. 2.3. covid-19 vaccine clinical trials the ideal design sars-cov-2 vaccine must address the need of vaccinating both the general population and high-risk individuals. furthermore, the designed vaccines must adhere to the basic standard for vaccines like non-allergenicity, antigenicity, potency, and ability to induce both cellular and humoral response among others [17, 18]. at the time of writing this paper, and according to the who, there were 47 covid-19 vaccine candidates around the world under clinical evaluation at different stages. most of these (14 trials) were using a protein subunit platform. furthermore, there are 155 trials currently under preclinical evaluation with the majority (55 trials) using protein subunit platforms [19]. figure 3 illustrates the distribution of these vaccines. a b figure 3: (a) the number of covid-19 vaccine candidates in preclinical evaluation trials. (b) the number of covid-19 vaccines clinical trials in clinical evaluation. doi 10.18502/sjms.v16i3.9697 page 359 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. 2.4. artificial intelligence and covid-19 artificial intelligence (ai) has been useful in designing drugs and vaccines against several organisms, including bacteria and viruses that are known to cause severe infections. in particular, ai has a great outlook on developing vaccines against diseases such as hiv and malaria that have been problematic [20–23]. the sars-cov-2 is a single-stranded, enveloped rna virus which has several antigenic proteins: the matrix (m) protein, nucleocapsid (n) protein, envelope (e) protein, and spike (s) surface glycoprotein [24]. the s protein has two subunits s1 and s2, majorly responsible for the viral fusion and binding, respectively. it is the primary focus of the development of serology tests and vaccines for the disease. understanding the complete sequence of the s glycoprotein has been explored to design a multi-epitope vaccine with vaxijen, toxinpred, and iedb servers. this resultant in silico vaccine was shown to have an excellent ability to stimulate a robust immune response against the virus [25]. 2.5. iscts 2.5.1. earlier applications the process of developing new biomedical products requires three steps: design, preclinical assessment, and clinical assessment; all of which can be enriched by the use of in silico simulations [10]. in silico trials can be used to refine clinical trials and reduce the number and duration of animals and humans involved in this experimentation. for example, when a surrogate measurement is used in the in silco trial, the reproducibility of the in vivo studies is highly improved, and hence the numbers required for statistical significance will be reduced, as illustrated in the study by orwoll et al., where bone fracture endpoint was replaced with a bone strength endpoint [26]. another use is where individualized models can partially replace animals or humans in a trial. an example of this is the approval by the fda of the complete replacement of experiments on animals (dogs) with a uva/padova diabetes type i simulator for the assessment of new artificial pancreas technologies [27]. doi 10.18502/sjms.v16i3.9697 page 360 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. 2.5.2. future applications regular use of in silico software may become the common theme in medical research, where simulation could be provided for a large number of virtual patients ( <1000) in a matter of minutes to hours, with tools to validate and replicate these trials. depending on the result of these in silico trials, new drugs and biomedical products can be approved by health agencies without the need for major human involvement in traditional randomized clinical trials. table 1 summarizes the difference between isct and traditional clinical trials. table 1: comparison between in silico and randomized clinical trials. types of trial cost duration human risk need for validation type of disease understudy traditional randomized clinical trial expensive several years low to moderate human risk current gold standard with no need for validation better in common disease and for detecting common side effects for drugs or procedures in silico clinical trial relatively cheaper minutes to hours no human risks currently need validation in most cases with subsequent small-size random clinical trials good for both common and rare diseases and rare side effects 2.6. available isct software 2.6.1. simulo simulo is a user-friendly clinical trial simulator developed by sgs exprimo. it uses monte carlo simulations and r code to assess study designs and compare different dosing strategies using mixed-effects models. this will help in the optimization of the steps of the clinical trial and the prediction of the probability of success, the optimal dose, the cost-effectiveness, and finally to go or not to go decisions. there are two available versions of the software – the basic free version and the expert version. while the basic version is suitable for small projects and demonstration purposes, the expert version provides more advanced tools like validation algorithms, which make it more acceptable for scientific publication (https://exprimo.com/simulo). this software was used in 2018 in a study done by murad melhem and colleagues to model neutrophil response to granulocyte colony-stimulating factor (g-csf) in patients doi 10.18502/sjms.v16i3.9697 page 361 https://exprimo.com/simulo sudan journal of medical sciences abdelrahman h. abdelmoneim et al. with chemotherapy-induced neutropenia [28]. the successful use of this software in this work is encouraging and shows that it can be useful in other diseases like the current covid-19 disease. 2.7. highly efficient clinical trials simulator (hect) hect is a web-based clinical trial simulator for the planning of adaptive trials (a type of trial that is more flexible than conventional clinical trials), written with statistical software r, with a friendly user graphical interface. this simulator allows the user to set multiple clinical trial parameters and investigate different settings such as varying treatment effects, control response, and adherence. it is open-source and is most useful for clinical trial investigators who don’t have the specialized statistical capacity or access to a commercial trial simulator. an important note here is that the simulation code in this software has been validated against six clinical trials designed by the designer of the software [29] (https://mtek.shinyapps.io/hect/). 2.8. previous studies on iscts in total, six iscts were retrieved from the pubmed database. these trials were used for common diseases such as breast cancer, diabetes, and tuberculosis. the first trial simulates a clinical trial of immunotherapies in metastatic breast cancer, which was carried out by hanwen wang and colleagues. in this study, a quantitative systems pharmacology model was built to integrate immune cancer cell interactions in patients with breast cancer, simulating central, peripheral, tumor-draining lymph node and tumor compartments. the proposed model provides a platform that can be further adapted to other types of immunotherapy which may contribute to the optimization of breast cancer treatment. the other in silico trial was carried out by susan g. hilsenbeck and c. kent osborne in breast cancer, where they identified the role of adjuvant tamoxifen in progesterone-positive breast cancer. regarding the non-small cell lung cancer, an isct was taken, comparing the photon and proton radiotherapy effect on this patient group, which showed a reduction of the integral dose (id) and the dose to the organ at risk (oar) with protons therapy instead of photons even with dose escalation. in addition, simulation of clinical trials was conducted to identify and individualize optimal isoniazid doses in children with tuberculosis, where they concluded that in children, isoniazid should be optimized based upon disease process, age, and acetylation status. doi 10.18502/sjms.v16i3.9697 page 362 https://mtek.shinyapps.io/hect/ sudan journal of medical sciences abdelrahman h. abdelmoneim et al. additionally, another isct was done, this time testing bioactive substance effect on healthy smokers. in this study, the result could explain the synergistic action mechanisms of the sanghuang–danshen (sd) bioactive in the regulation of vascular endothelial dilation, confirming the sd potential effect in releasing the vascular stiffness and decreasing blood pressure in healthy smokers. finally, an isct with the university of virginia tested the use of inhaled insulin using type i diabetes simulator which in this study provides superior postprandial control and smaller risks of hypoglycemic events [30–35]. table 2 summarizes these trials. table 2: summary of six iscts. authors num. of virtual patients disease understudy medication or device main outcome roberto visentin and colleagues [30] 100 type 1 diabetes militias inhaled technosphere insulin (afrezza) relative to insulin lispro, postmeal dosing, or split dosing of inhaled insulin, in combination with an appropriate titration rule, can achieve superior postprandial glucose control. prakash m. jeena and colleagues [31] 10,000 tuberculosis in children isoniazid none of the isoniazid routine doses (between 2.5 and 40 mg/kg/day) would achieve 80% effective concentration in most of the children (<90%). hanwen wang and colleagues [32] 18 metastatic breast cancer anti-ctla-4 and anti-pd-l1 immunotherapies in combination therapy, the reduction in tumor size is moderately enhanced, compared to the anti-pd-l1 monotherapy. furthermore, the proposed model display the potential to make predictions of tumor response of individual patients when sufficient clinical measurements are provided. susan g. hilsenbeck and c. kent osborne [33] 50,000 progesterone receptor(–/+) breast cancer arimidex and tamoxifen in pr– cases, initial therapy with an aromatase inhibitor is superior to tamoxifen. in pr+ cases, tamoxifen is only modestly inferior to arimidex at the outset, with a higher survival rate at 7.5 years. erik roelofs and colleagues [34] 25 non-small cell lung cancer photon and proton radiotherapy when compared with photon, passive scattered conformal proton therapy (pspt) will provide a larger dose to the tumor tissue with less damage to at-risk organs. yeni lim and colleages [35] 72 vascular stiffness in healthy smokers sanghuang– danshen (sd) bioactive compared to a placebo alone, sd consumption at 900 mg/day for four weeks improves pulse wave velocity (p = 0.0497), and reduces systolic blood pressure, therefore reducing vascular stiffness in healthy smokers. doi 10.18502/sjms.v16i3.9697 page 363 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. 3. results only six relevent icts were through pubmed. these trials were conducted for common diseases such as breast cancer, diabetes, and tuberculosis. the first trial simulateed a clinical trial of immunotherapies in metastatic breast cancer, which was carried out by hanwen wang and colleagues. in this study, a quantitative systems pharmacology model was built to integrate immune cancer cell interactions in patients with breast cancer, simulating central, peripheral, tumor-draining lymph node, and tumor compartments. the proposed model provides a platform that can be further adapted to other types of immunotherapy which may contribute to the optimization of breast cancer treatment. the other ict was carried out by susan g hilsenbeck and c kent osborne in breast cancer, where they identified the role of adjuvant tamoxifen in progesterone-positive breast cancer. table 2 summarizes the main aspects of the involved trials 4. discussion 4.1. validation of iscts validation of iscts is the procedure that evaluates the degree of how much the computer model and simulation agenda is capable of imitating a reality of interest. it is a necessary step before application in clinical studies. this step can be done either through comparison with existing literature or through standardizing the methodology used in these trials. assessing these two factors will help in proving the model integrity and hence the reliability of the isct [36, 37]. 4.2. limitation of iscts resistance from the research professionals with limited interest in physics and mathematics, and the difficulty in simulating the complex physiological systems with the specialized advanced technical requirement to create new simulator software are the major hurdle of isct simulations. doi 10.18502/sjms.v16i3.9697 page 364 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. 4.3. proposed isct protocol for covid-19 vaccine building on the previous evidence, we believe iscts could be a plausible option in the current covid-19 pandemic, as the software and models needed can be tested and validated against the preliminary results of the current covid-19 clinical trials. specially designed models or an already available one like the model designed by renz et al. simulating human alveolar macrophage with sars-cov-2 [38] can be used as a basis for the in silico trials. furthermore, the universal immune system simulator (uiss) platform which is an agent-based simulator is suggested by giulia russo and colleagues as a good choice for vaccine design studies [39]. other platforms like simulo and hect can also be used in the current covid-19 iscts with the following suggested parameters: 1. type of trials: adaptive randomized iscts. 2. number of patients: 10,000 virtual patients, between 6 and 59 years old who will receive two dosages of the vaccine or placebo. 3. dataset: data for comparison and validation can be retrieved from open online databases like uk datasevice or specialized research centers. 4. duration: 5 years. 5. drug: multi-epitope peptide vaccine using spike protein as an immunogenic target. 6. primary end target results: number of patients with positive and negative rt-pcr, death rate. 7. secondary end target results: number of patients with documented allergies or vaccine side effects. 4.4. study limitation the lack of standardized systemic review with appropriate statistical measurement in this work may undermine the acquired results and conclusion, however, the significance of this conclusion should not be overlooked. 5. conclusion iscts can truly transform the war against the covid-19 pandemic. it is an attractive and applicable tool to accelerate the rate of approval for new therapeutics and vaccines for doi 10.18502/sjms.v16i3.9697 page 365 sudan journal of medical sciences abdelrahman h. abdelmoneim et al. common and rare diseases. furthermore, it is probably the most cost-effective method to reduce, refine, and partially replace covid-19 conventional clinical trials ensuring both relevant results and minimal human risks. acknowledgements the authors would like to thank israa isam for helping in designing figure 1. ethical considerations not required. competing interests the authors declare that they have no conflict of interest regarding this paper. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding none. references [1] krus, p., braun, r., nordin, p., et al. 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(2020). in silico trial to test covid-19 candidate vaccines: a case study with uiss platform. bmc bioinformatics, vol. 21, no. 17, article 527. doi 10.18502/sjms.v16i3.9697 page 370 introduction materials and methods types and phases of clinical trials covid-19 conventional therapeutic clinical trials covid-19 vaccine clinical trials artificial intelligence and covid-19 iscts earlier applications future applications available isct software simulo highly efficient clinical trials simulator (hect) previous studies on iscts results discussion validation of iscts limitation of iscts proposed isct protocol for covid-19 vaccine study limitation conclusion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9947 production and hosting by knowledge e research article the effect of intravenous metoclopramide on pain, nausea, discomfort, and ease of insertion of nasogastric tube in emergency department: a double-blind randomized clinical trial seyed mohammad hosseininejad1, farzad bozorgi2*, asieh khodami3, mohammad hajizade juybari4, and hamed aminiahidashti5 1department of emergency medicine, diabetes research center, faculty of medicine, mazandaran university of medical sciences, sari, iran 2department of emergency medicine, orthopedic research center, faculty of medicine, mazandaran university of medical sciences, sari, iran 3student research committee, mazandaran university of medical sciences, sari, iran 4faculty of medicine, mazandaran university of medical sciences, sari, iran 5department of emergency medicine, faculty of medicine, mazandaran university of medical sciences, sari, iran orcid: farzad bozorgi: https://orcid.org/0000-0001-7582-9735 abstract background: placement of nasogastric tube (ngt) is a routine procedure in the emergency departments, which can be uncomfortable, painful, and cause nausea. the aim of this study was to investigate the effect of intravenous metoclopramide on the ease of ngt insertion, as well as reduction of patients’ pain, nausea, and discomfort during ngt insertion in the emergency department. methods: in this randomized, double-blind, placebo-controlled trial, 80 patients referred to imam khomeini hospital, mazandaran province, iran were enrolled. data were collected from december 2015 to march 2016. participants were selected via convenience sampling and randomly divided into two equal groups (placebo and intervention groups). in metoclopramide and placebo groups, 10 mg of metoclopramide and 10 mg of normal saline solution were administered, respectively. all of the ngt was inserted 15–20 mins after the intravenous infusion. patient-reported pain, discomfort, and nausea were evaluated using visual analogue scale (vas), at four time points including before (t0), immediately (t1), 30 min after (t2), and 1 hr after the ngt placement (t3). the ease of ngt insertion was evaluated as easy, moderate, and difficult to pass. results: none of the patients had pain, nausea, and discomfort in t0. additionally, for those who received intravenous metoclopramide, pain intensity significantly decreased compared with the placebo group in t1 (37.7 vs 55.0), t2 (26.2 vs 41.7), and t3 (20.5 vs 33.7), respectively (p < 0.001). nausea intensity decreased significantly over time among patients in the intervention group compared with the placebo group in t1 (32.7 vs 43.2), t2 (19.5 vs 31.2), and t3 (9.0 vs 21.7), respectively (p < 0.001). the intensity of patients’ discomfort decreased significantly among patients in the intervention group compared with the placebo group in t1 (39.5 vs 54.0), t2 (28.7 vs 40.2), and t3 (26.2 vs 39.6), respectively (p < 0.001). patients in the intervention group had easier placement of ngt compared with the placebo group (easy: 40.0% vs 0.0%, moderate: 45.0% vs 62.5%, and difficult: 15.0% vs 37.5%; p < 0.001). conclusion: based on the results of the present study, it seems that intravenous metoclopramide can be used as a promising modality for improving the ease of ngt placement and reducing patients’ pain, nausea, and discomfort during ngt insertion in the emergency department. keywords: metoclopramide, nasogastric tube placement, pain, nausea, discomfort how to cite this article: seyed mohammad hosseininejad, farzad bozorgi*, asieh khodami, mohammad hajizade juybari, and hamed aminiahidashti (2021) “the effect of intravenous metoclopramide on pain, nausea, discomfort, and ease of insertion of nasogastric tube in emergency department: a double-blind randomized clinical trial ,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 499–508. doi 10.18502/sjms.v16i4.9947 page 499 corresponding author: farzad bozorgi; email: drfarzadbozorgi@yahoo.com received 02 september 2021 accepted 05 december 2021 published 31 december 2021 production and hosting by knowledge e seyed mohammad hosseininejad et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:drfarzadbozorgi@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences seyed mohammad hosseininejad et al. 1. introduction placement of nasogastric tube (ngt) is a routine procedure in the emergency departments, which can be uncomfortable, painful, and cause nausea in patients [1]. although insertion of ngt is usually a simple procedure, it can be complicated without active patient involvement [2]. improper ngt placement has been associated with some complications such as epistaxis; inadvertent intracranial or tracheobronchial placement of ngt; pharyngeal, esophageal, or bronchial perforation; pneumothorax; and aspiration pneumonia [3, 4]. therefore, appropriate ngt placement strategies can reduce patients’ discomfort, pain, and nausea during and after the procedure [5]. previous research evidence indicated the potential efficacy of metoclopramide in prevention of nosocomial pneumonia and postoperative ileus in patients fed via ngt [6, 7]. metoclopramide is a central trigger-zone inhibitor and highly effective in reducing nausea [8]. this medicine has no cardiac side effects and should be intravenously administered 15 to 30 min before the procedure [9]. a study in turkey showed that the intravenous administration of metoclopramide reduces patients’ pain, discomfort, and nausea during ngt placement [10]. therefore, due to the importance of this issue, the present study was conducted focusing on the effect of metoclopramide on the ease of ngt insertion, as well as reduction of patients’ pain, nausea, and discomfort during ngt insertion in emergency department. 2. material and methods 2.1. study design and sample in this randomized, double-blind, placebo-controlled trial, 80 patients referred to imam khomeini hospital, mazandaran province, iran were enrolled. data were collected from december 2015 to march 2016. participants were selected via convenience sampling and randomly allocated into two equal groups (placebo and intervention). 2.2. inclusion and exclusion criteria adult patients older than 18 years, requiring ngt placement in emergency department were included. the exclusion criteria were patients with deformity of the nose and throat, doi 10.18502/sjms.v16i4.9947 page 500 sudan journal of medical sciences seyed mohammad hosseininejad et al. allergy to metoclopramide, a history of failure to ngt placement, and hemodynamic instability (systolic blood pressure of <90 mmhg). 2.3. randomization and blinding patients were randomly allocated to the metoclopramide or placebo groups in a 1:1 ratio. a computer-generated randomization schedule was prepared by the principal investigator who was not otherwise involved in the study. a unique code was assigned to each patient. this code indicated the assigned treatment to each patient and was matched with the study drug syringe. patients and outcome assessor were blinded to the treatment allocation and were not informed about the randomization procedure. metoclopramide or normal saline was prepared in the same size syringe and with same volume and appearance. 2.4. intervention in both groups, intravenous administration of metoclopramide or normal saline were conducted 15 min before the ngt placement using 2-ml syringes. the syringes were coded by five-digit codes. patients in metoclopramide and placebo groups received 10 mg (2 ml) of intravenous metoclopramide (alhavi pharma co., tehran, iran) or 2 ml of normal saline over 2 min, respectively. drug or placebo was given or performed by experienced emergency nurses who were interested to cooperate in the study and were blind to the group allocation. they were trained and asked to carefully match the highlighted codes on the study syringes and patients’ documents. all of the ngt were inserted 15–20 mins after the intravenous infusion. the ngt placement was performed by two experienced emergency nurses. an appropriate size of ngt was assigned for each of the patients. also, lubricant gel was used for all patients in both groups to improve the procedure. 2.5. outcomes primary outcomes were intensity of patient-reported pain, discomfort, and nausea based on the visual analogue scale (vas), at four time points including before (t0), immediately (t1), 30 min after (t2), and 1 hr after the ngt placement (t3). the intensity of pain, discomfort, and nausea of patients, based on the vas score, were collected thrice at four time points. based on the vas, 0 and 100 dictated the lowest and highest felt doi 10.18502/sjms.v16i4.9947 page 501 sudan journal of medical sciences seyed mohammad hosseininejad et al. table 1: clinical and demographic characteristics of participants (n = 80). groups p-value intervention placebo (n = 40) (n = 40) age (yr) 42.8 42.7 0.979∗ (sd = 18.3) (sd = 16.8) sex male 22 (55.0) 21 (52.5) 0.823∗∗ female 18 (45.0) 19 (47.5) reason for ngt placement gi bleeding 10 (25.0) 12 (30.0) 0.773∗ intoxication 7 (17.5) 5 (12.5) pancreatitis 23 (57.5) 23 (57.5) sd: standard deviation. data are presented as number (%) and mean (sd). ∗p-value obtained using chi-square test; ∗∗p-value obtained with t-test. disturbance by patients. the secondary outcome was the level of difficulty of ngt insertion, which was reported by an emergency nurse as easy, moderate, and difficult to pass. 2.6. statistical analysis data were analyzed using the statistical package for social sciences (spss v.16.0, spss inc., chicago, il, usa). the mean (standard deviation) and number (percentage) were used to show continuous variables. an independent sample t-test was applied to compare the means of pain, nausea, and discomfort between metoclopramide and placebo groups. the difficulty of ngt insertion was also compared using the chi-square test. a p < 0.05 was considered to be significant. 3. results 3.1. participants eighty out of the one hundred and twenty patients who needed an ngt placement were enrolled in the present study (figure 1). a total of 55% and 52.5% of patients in the intervention and control groups were male with a mean age of 42.8 (sd = 18.3) and 42.7 (sd = 16.8) years, respectively (table 1). doi 10.18502/sjms.v16i4.9947 page 502 sudan journal of medical sciences seyed mohammad hosseininejad et al. 3.2. outcomes table 2 presents the intensity of pain, nausea, and discomfort of patients, based on vas score, among placebo and intravenous metoclopramide groups. none of the patients had pain, nausea, and discomfort in t0. 3.2.1. pain intensity pain decreased among patients in the intervention group compared with placebo in t1 (37.7 vs 55.0), t2 (26.2 vs 41.7), and t3 (20.5 vs 33.7), respectively (p < 0.001). 3.2.2. nausea intensity intensity of patients’ nausea decreased significantly among patients in the intervention group compared with placebo in t1 (32.7 vs 43.2), t2 (19.5 vs 31.2), and t3 (9.0 vs 21.7), respectively (p < 0.001). 3.2.3. discomfort the intensity of patients’ discomfort significantly decreased among patients in the intervention group compared with the placebo group in t1 (39.5 vs 54.0), t2 (28.7 vs 40.2), and t3 (26.2 vs 39.6), respectively (p < 0.001). 3.2.4. level of difficulty of ngt placement as presented in figure 2, patients in the intervention group had easier placement of ngt compared with the placebo group (easy: 40.0% vs 0.0%, moderate: 45.0% vs 62.5%, and difficult: 15.0% vs 37.5%; p < 0.001). 4. discussion this study assessed the effect of intravenous metoclopramide on the ease of ngt insertion, reduction of pain, nausea, and discomfort in an emergency department. based on the findings of this study, intravenous metoclopramide had a significant effect on the ease of ngt placement, reduction of pain, nausea, and discomfort in patients who required ngt insertion. doi 10.18502/sjms.v16i4.9947 page 503 sudan journal of medical sciences seyed mohammad hosseininejad et al. table 2: pain, nausea, and discomfort of the patients based on vas among placebo and metoclopramide groups (n = 80). groups p-value intervention (n = 40) control (n = 40) pain t0 0.0 (sd = 0.0) 0.0 (sd = 0.0) <0.001 t1 37.7 (sd = 9.9) 55.0 (sd = 7.0) t2 26.2 (sd = 9.2) 41.7 (sd = 6.3) t3 20.5 (sd = 9.3) 33.7 (sd = 6.2) nausea t0 0.0 (sd = 0.0) 0.0 (sd = 0.0) <0.001 t1 32.7 (sd = 9.6) 43.2 (sd = 7.2) t2 19.5 (sd = 9.5) 31.2 (sd = 6.8) t3 9.0 (sd = 8.5) 21.7 (sd = 6.7) discomfort t0 0.0 (sd = 0.0) 0.0 (sd = 0.0) <0.001 t1 39.5 (sd = 10.6) 54.0 (sd = 7.0) t2 28.7 (sd = 10.4) 40.2 (sd = 6.9) t3 26.2 (sd = 10.2) 39.6 (sd = 6.7) sd: standard deviation; t0: before ngt placement; t1: immediately after ngt placement; t2: 30 min after ngt placement; t3: 1 hr after ngt placement. data are presented as mean (sd). p-value was obtained with t-test. figure 1: flowchart of the study. previous evidence has shown that ngt placement can be an unpleasant experience among admitted patients in the emergency department [11, 12]. the findings of the present study showed that pain, nausea, and discomfort among patients of the placebo group in t1, t2, and t3 were 55, 43, and 54, respectively. these results are relatively doi 10.18502/sjms.v16i4.9947 page 504 sudan journal of medical sciences seyed mohammad hosseininejad et al. figure 2: difficulty levels of ngt placement. similar to previous studies [13–15]. based on the present study, the pain intensity could be reduced to 68% if an intravenous dose of metoclopramide had been administered 15 min before the ngt placement. this reduction was around 25–30% regarding experienced nausea and discomfort by patients. however, previous evidence showed that pain, nausea, and discomfort were reduced around 80–90%, which is considerably higher than the findings of this study [14]. one possible explanation for this inconsistency may be the subjective measurement of study parameters and consequently a systematic overestimation of the parameters by patients in this study or underestimation by patients in the previous studies. findings the present study showed that pain in the intervention group in t3 was around 54% of pain in t1, while in the placebo group, it was around 60%. regarding nausea, this rate was around 50% in the placebo group and 27% in the intervention group, and in the case of discomfort around 66% in the intervention group and 73% in the placebo group. the results of a study among critically ill patients revealed that using 20 mg of intravenous metoclopramide significantly improved the success rate of post-pyloric placement of spiral nasojejunal tubes. in this study, metoclopramide was administered 10 min before nasojejunal tube insertion [16]. however, another study does not confirm the efficacy of 10 mg metoclopramide in improving post-pyloric placement of nasoenteral feeding tubes [17]. the emergency nurse who was responsible for the ngt placement reported that in the intervention group the insertion procedure was significantly easier compared doi 10.18502/sjms.v16i4.9947 page 505 sudan journal of medical sciences seyed mohammad hosseininejad et al. with the placebo group. this finding could be considered as an intermediate reason for less pain, nausea, and discomfort in the intervention group. as a consequence of the more comfortable ngt placement, the probability of serious complications of the insertion is expected to be lower [14, 18, 19]. on the other hand, due to the crowding of the emergency departments [20], easier procedures may be highly valuable not only for patients but also for healthcare providers. therefore, the use of intravenous metoclopramide before ngt insertion would lead to a higher quality of care in the emergency departments. nevertheless, there are some limitations in the present study that need to be addressed. although we tried to reduce the interpersonal variation during ngt insertion by using two experienced nurses, this method should be performed by different nurses on different patient populations to further generalize the results of this study. 5. conclusion in conclusion, according to the results of this study, it seems that using intravenous metoclopramide can significantly facilitate and improve the ease of ngt placement and reduce pain, nausea, and discomfort associated with ngt insertion in the emergency department. 6. acknowledgments the authors acknowledge the financial support of the deputy of research and technology of mazandaran university of medical sciences. 7. ethical considerations this study was approved by the institutional ethics committee of mazandaran university of medical sciences (ir.mazums.rec.94.1477). it was also registered under the iranian registry of clinical trials (irct2015083023696n2). the study objectives were explained to all participants. informed consent was obtained from the participants and they also had the right to withdraw from the study at any time without penalty. 8. competing interests none. doi 10.18502/sjms.v16i4.9947 page 506 sudan journal of medical sciences seyed mohammad hosseininejad et al. 9. funding this study has been financially supported by the deputy of research and technology, mazandaran university of medical sciences, sari, iran. clinical trial registration number: irct2015083023696n2, https://www.irct.ir/. references [1] metheny, n. a., krieger, m. m., healey, f., et al. (2019). a review of guidelines to distinguish between gastric and pulmonary placement of nasogastric tubes. heart & lung, vol. 48, no. 3, pp. 226–235. [2] heidarzadi, e., jalali, r., hemmatpoor, b., et al. (2020). the comparison of capnography and epigastric auscultation to assess the accuracy of nasogastric tube placement in intensive care unit patients. bmc gastroenterology, vol. 20, no. 1, pp. 1–6. [3] yang, f. h., lin, f. y., and hwu, y. j. (2019). the feasibility study of a revised standard care procedure on the capacity of nasogastric tube placement verification among critical care nurses. journal of nursing research, vol. 27, no. 4, p. e31. [4] walsh, s., gallagher, a., gallagher, r., et al. (2016). first do no harm: nasogastric tube placement and confirmation. quarterly journal of medicine, vol. 109, no. 3, p. 219. [5] rouhi, a. j., zeraatchi, a., rahmani, f., et al. (2020) effect of oral midazolam in pain relief of patients need nasogastric tube insertion: a clinical trial study. journal of research in pharmacy practice, vol. 9, no. 2, pp. 112–117. [6] liu, y., dong, x., yang, s., et al. (2017). metoclopramide for preventing nosocomial pneumonia in patients fed via nasogastric tubes: a systematic review and metaanalysis of randomized controlled trials. asia pacific journal of clinical nutrition, vol. 26, no. 5, pp. 820–828. [7] lubawski, j. and saclarides, t. (2008). postoperative ileus: strategies for reduction. therapeutics and clinical risk management, vol. 4, no. 5, p. 913–917. [8] kaneishi, k., imai, k., nishimura, k., et al. (2020). olanzapine versus metoclopramide for treatment of nausea and vomiting in advanced cancer patients with incomplete malignant bowel obstruction. journal of palliative medicine, vol. 23, no. 7, pp. 880– 881. [9] rumore, m. m., lee, s. e., wang, s., et al. (2011). metoclopramide-induced cardiac arrest. clinics and practice, vol. 1, no. 4, pp. 174–178. doi 10.18502/sjms.v16i4.9947 page 507 sudan journal of medical sciences seyed mohammad hosseininejad et al. [10] ozucelik, d. n., karaca, m. a., and sivri, b. (2005). effectiveness of pre-emptive metoclopramide infusion in alleviating pain, discomfort and nausea associated with nasogastric tube insertion: a randomised, double-blind, placebo-controlled trial. international journal of clinical practice, vol. 59, no. 12, pp. 1422–1427. [11] bong, c. l., macachor, j. d., and hwang, n. c. (2004). insertion of the nasogastric tube made easy. anesthesiology, vol. 101, no. 1, p. 266. [12] durai, r., venkatraman, r., and ng, p. c. (2009). nasogastric tube insertion technique and confirming position. nursing times, vol. 105, no. 16, pp. 12–13. [13] cullen, l., taylor, d., taylor, s., et al. (2004). nebulized lidocaine decreases the discomfort of nasogastric tube insertion: a randomized, double-blind trial. annals of emergency medicine, vol. 44, no. 2, pp. 131–137. [14] ozucelik, d., karaca, m., and sivri, b. (2005). effectiveness of pre-emptive metoclopramide infusion in alleviating pain, discomfort and nausea associated with nasogastric tube insertion: a randomised, double-blind, placebo-controlled trial. international journal of clinical practice, vol. 59, no. 12, pp. 1422–1427. [15] ducharme, j. and matheson, k. (2003). what is the best topical anesthetic for nasogastric insertion? a comparison of lidocaine gel, lidocaine spray, and atomized cocaine. journal of emergency nursing, vol. 29, no. 5, pp. 427–430. [16] hu, b., ye, h., sun, c., et al. (2015). metoclopramide or domperidone improves postpyloric placement of spiral nasojejunal tubes in critically ill patients: a prospective, multicenter, open-label, randomized, controlled clinical trial. critical care, vol. 19, no. 1, p. 61. [17] heiselman, d. e., hofer, t., and vidovich, r. r. (1995). enteral feeding tube placement success with intravenous metoclopramide administration in icu patients. chest, vol. 107, no. 6, pp. 1686–1688. [18] mandal, m. c., dolai, s., ghosh, s., et al. (2014). comparison of four techniques of nasogastric tube insertion in anaesthetised, intubated patients: a randomized controlled trial. indian journal of anaesthesia, vol. 58, no. 6, pp. 714–718. [19] pillai, j. b., vegas, a., and brister, s. (2005). thoracic complications of nasogastric tube: review of safe practice. interactive cardiovascular and thoracic surgery, vol. 4, no. 5, pp. 429–433. [20] hosseininejad, m., aminiahidashti, h., pashaei, s. m., et al. (2017). determinants of prolonged length of stay in the emergency department: a mixed method study from iran. emergency, vol. 5, no. 1, pp. 268–273. doi 10.18502/sjms.v16i4.9947 page 508 introduction material and methods study design and sample inclusion and exclusion criteria randomization and blinding intervention outcomes statistical analysis results participants outcomes pain intensity nausea intensity discomfort level of difficulty of ngt placement discussion conclusion acknowledgments ethical considerations competing interests funding references sudan journal of medical sciences volume 12, issue no. 3, doi 10.18502/sjms.v12i3.934 production and hosting by knowledge e research article candida albicans and napkin dermatitis: relationship and lesion severity correlation amani hussein ahmed karsani1, abdullateef azolaibani1,2, yasser farouq1, khalid zedan1, mohammed mohsen alotaibi1,3, ghada bin saif4, and ibrahim h. babikir1,3 1department of pediatrics, college of medicine, qassim university, saudi arabia 2department of dermatology, college of medicine, qassim university, saudi arabia 3department of pathology and laboratory medicine, college of medicine, qassim university, saudi arabia 4dermatology department, college of medicine, king saud university abstract introduction: napkin dermatitis (nd) is a common problem in infancy that affects almost every child during the early months and years of their lifetime. it is a skin disease that becomes a challenge for both parents and physicians because of its frequency and difficulty in eliminating all of the causative factors in diapered infants. usually napkin dermatitis is self-limiting but when associated with candida albicans (c. albicans) seems to be moderate to severe. aim: the aim of the present study was to determine the colonization of c. albicans in children with napkin dermatitis and to correlate between intensity of c. albicans colonization and the severity of napkin rash. patients and methods: this case-controlled study was conducted at qassim university pediatric outpatient clinics, during the period from august 2014 to july 2015. sixty patients with diaper dermatitis and 33 healthy controls were enrolled to this study. sociodemographic and clinical data were obtained from the parents of each participant using questionnaires paired (stool and skin) samples were collected from all cases and healthy control children. the samples were cultured on differential and selective chromogenic medium for isolation and initial identification of candida species. identification confirmation of the isolates was determined by the vitek 2 compact automated system. results: diaper dermatitis shows significant outcome to washing diaper area (per day) (p = 0.001), history of diarrhea last 7 days (p < 0.001), skin lab results (+/-) for candida albicans, (p < 0.001), skin colony count, (p < 0.001), however, there is no correlation to age (p = 0.828), gender (p = 0.368) and feeding style (p = 0.401). conclusion: the severity score of napkin dermatitis was significantly observed among cases with diaper dermatitis (p-value < 0.001) and control children (p-value < 0.001) respectively. keywords: candida albicans, napkin dermatitis, diaper dermatitis, vitek 2 compact system, qassim how to cite this article: amani hussein ahmed karsani, abdullateef azolaibani, yasser farouq, khalid zedan, mohammed mohsen alotaibi, ghada bin saif and ibrahim h. babikir, (2017) “candida albicans and napkin dermatitis: relationship and lesion severity correlation,” sudan journal of medical sciences, vol. 12 (2017), issue no. 3, 174–186. doi 10.18502/sjms.v12i3.934 page 174 corresponding author: amani hussein ahmed karsani; email: amanikarsani@ qumed.edu.sa received: 15 june 2017 accepted: 1 july 2017 published: 4 july 2017 production and hosting by knowledge e amani hussein ahmed karsani et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:amanikarsani@qumed.edu.sa mailto:amanikarsani@qumed.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences amani hussein ahmed karsani et al 1. introduction napkin dermatitis (nd), also called diaper dermatitis (dd), diaper rash, and nappy rash. nd is one of the most common skin diseases during infancy and in toddlers [1]. prevalence of diaper dermatitis varying under the conditions of each country and the most commonly used diaper. the prevalence for children has been reported in the japan, usa, uk, and italy 87%, 75%, 25%, and 15% respectively [2]. diaper dermatitis was the reason for 20% of all visits to the dermatologist of children, usually starts within the age of the third and 12th weeks and the peak of its incidence is the age of 6-12 months [3–5], up to the age of 5 years [6]. the highest incidence in infants is between 9 and 12 months of age [3–5]. conditions of dd were first noticed in the 1940s, but diapers were initially considered to be luxury items. thereafter, diapers began to be used on a mass scale by 1960s [7, 8]. by then diapers were ready-made containing many layers of cellulose, which made them more absorbent and resistant. [7, 8]. the cellulose layers can also cause acute dd and diaper rash, especially, when it is contaminated with urine and stool substances. most cases of dd clear up spontaneously in a day without treatment [7, 8], exacerbation of persistent cases (that last in 3 days or more) may be associated with different infections, especially candida yeasts infections [8–10]. there are, however, many causes of dd, irritant diaper dermatitis (idd) it is a type of irritant contact (eczema) regarded as a localized form of contact dermatitis caused by several factors including warmth, prolonged contact with urine and feces, and overhydration of the upper portion of the skin (stratum cornueum) [1, 11]. diaper dermatitis affecting predominantly the convex surfaces in closest contact with wet or soiled diapers. the buttocks, genitalia, lower abdomen, and upper thighs are usually the most severely affected, but the distribution depends on the position in which the infant is allowed to lie. the flexures are spared, particularly in the obese child. in the mildest forms there is only erythema, but with increasing severity, papules, vesicles, small erosions, and larger ulcers may occur. in chronic forms scaling is combined with glazed erythema. scaling may be conspicuous manifest particularly in the healing stages. diaper dermatitis may be graded according to severity into: (i) grade 1: slight erythema, perhaps with scaling; (ii) grade 2: moderate to severe erythema, perhaps with scaling; or few papules and some edema (iii) grade 3: moderate to severe erythema, perhaps with scaling, moderate to severe edema and papules, or early ulceration; and (iv) grade 4: severe erythema, perhaps with scaling, or severe edema, papules, and ulceration [12]. there is a challenge is candida a causative factor or it is a secondary contaminant that flourishes in the moist warmth environment [13]. many experts believe that the presence of candida infection plays a primary as well as a secondary role in the development of this frequently and sometimes painful eruptions [11, 14]. candidiasis doi 10.18502/sjms.v12i3.934 page 175 sudan journal of medical sciences amani hussein ahmed karsani et al and candida diaper dermatitis often complicates non infectious diaper dermatitis and occurs as an adverse effect of oral antibiotic treatment [15]. in general, candida exists in 3 morphological forms one of them is the yeast cells. the dimorphic yeasts of the genus candida are ubiquitous in the environment, however, candida albicans causes candidiasis in children and although it is not part of the indigenous skin flora, but it is a frequent transient on skin and may colonize the human alimentary tract and vaginal as a saprophytic organism [16]. certain environmental conditions notably elevated temperature and humidity are associated with increased frequency of isolation of c. albicans from skin. many bacterial species inhibit the growth of c. albicans and the use of antibiotics, conversely, alter the normal flora and may promote over growth of the yeast [17]. some apparently healthy infants, although, may reveal culture positive for candida and other organisms without exhibiting any symptoms [14], there seems to be a positive correlation between the severity of the diaper rash noted and the likelihood of secondary involvement [14, 18]. c. albicans was recovered from patients with diaper dermatitis more than from normal healthy control groups in many researches [19–21]. gastrointestinal carriage of c. albicans assists on its isolation from stool, skin and rectum of patients with contact dermatitis [22, 23]. it has also been demonstrated that bacterial infection does not play a substantial part in the development of dd [11], however, can act in synergy with bacteria such as escherichia coli [8, 24] and s. aureus [8, 18]. this study aimed to determine the colonization of c. albicans in children with napkin dermatitis and to correlate between intensity of c. albicans colonization and the severity of napkin rash. the role of c. albicans in diaper dermatitis has been studied in many countries but correspondingly this issue, to the best of our knowledge, was not studied in this country and particularly in qassim area. 2. subjects and methods a case-control study was conducted at qassim university pediatric outpatient clinics, during the period from august 2014 to july 2015. institutional review board approval was obtained from the research and ethical committee of the college of medicine and the deanship of scientific research, qassim university, saudi arabia. informed consent was obtained from all participants. the inclusion criteria were included erythema with or without papules, vesicles, bulla, scales, fissures or erosions only in napkin area. severity grades was assigned for all patients as mild, moderate or severe [12]. the exclusion criteria were excluded all children with immune suppression and those who had exposure to local treatment in the anogenital area in the past 7 days. the control group was selected from children attending for their routine and scheduled vaccination. stool samples and skin swab doi 10.18502/sjms.v12i3.934 page 176 sudan journal of medical sciences amani hussein ahmed karsani et al scrapping swabs has been collected from all individuals. sociodemographic and clinical data were obtained from the parents of each participant using structured pre-tested questionnaires. 2.1. collection and processing specimens paired specimen of stool and skin swabs were collected from each participant and directly transferred to the laboratory. in the medical laboratory, all samples were processed for wet preparation for microscopic exam, gram stain. samples were then cultured on selective and differential media and incubated for 24-72 hours. the identification of isolates was done according to several laboratory techniques. 2.2. laboratory diagnosis 2.2.1. processing of stool specimens stool samples were collected from all cases and controls directly or using a rectal swab (swab is inserted into the rectum and rotated gently) and then withdrawn (replaced in its container), carefully labeled and transferred to the laboratory within 30 minutes of collection or refrigerated (4∘c) until the time of analysis (within 12 hrs). initially, a 0.1 ml of stool or 0.1 gm of formed stools was diluted in 0.9 ml of sterile distilled water and serial dilutions were prepared (103 up to 108). a volume of 0.1 ml of each dilution was spread on sda supplemented with (0.05mg/1ml) chloramphenicol (oxoid uk, code: cm0041) and incubated at 37∘c for 24-48 hrs. suspected colonies were streaked on chromagar (watin-biolife cat#2020, riyadh, saudi arabia) to obtain pure colonies of c. albicans and calculated in form of cfu/gm or cfu/ml. c. albicans overgrowth was defined as growth of ≥105 cfu/ml or gram of stool. all faecal specimens were also examined macroscopically for morphology, consistency, colour, ph, and microscopically for pus cells, red blood cells, and presence of parasitic infections (as worm, ova, trophozoites and cysts). 2.2.2. processing of skin swab specimens samples were carefully scraped from the skin region covered by the diaper for all controls (normal skin area) and cases (from lesion rash area) by using a swab moistened with sterile distilled water. the skin swabs were collected from the affected (inguinal/peri-anal) area, replaced in its container, carefully labeled and transferred to the laboratory along with the stool swab. in the medical lab, the skin swabs were cultured on to sda supplemented with (0.05mg/1ml) chloramphenicol and incubated at doi 10.18502/sjms.v12i3.934 page 177 sudan journal of medical sciences amani hussein ahmed karsani et al 37∘c for 24-72 hrs. the subcultures were seeded into chromagar media and incubated at 35∘c for 48 hrs for presumptive identification and differentiation of candida species and to perform colony count in a form of cfu/ml. 2.2.3. isolation and identification of c. albicans the isolation and identification (id) of c. albicans was done based on a combination of morphological characteristics and automation technique. the morphological characteristics were including gram stain, colonial morphology (shape, size, texture, etc.) and yeast structures (shape, size, budding pattern, germ tube) [5, 7, 8]. the automation technique was done by using the fully automated vitek-2 compact system. prior application of vitek system, clinically significant isolates were sub-cultured for purity on sda plates and incubated aerobically at 35-37∘c in 5% co.2. isolated yeasts were differentiated according to their colonial morphology and the colour produced on chromagar [25] in addition to gram stain. then colonies were used to prepare a standardized saline inoculum for the appropriate vitek id card. special id and sensitivity (ast) cards (biomérieux, france) were used for identification of yeasts (yst). the automation methods were conducted as described by the manufacturers’ manual and techniques also described elsewhere [26]. the vitek-2 id and ast cards were logged and loaded into the vitek-2 compact system. the vitek-2 compact system automatically reported the results through software 06.01 the study has been approved by the ethics committees of the college of medicine research ethics review board at qassim university and informed consent was obtained from parents/caregiver of children. 3. statistics spss for window (version 16) was used for analyses. students’ t-test and chi-square (𝜒2) were used to compare continuous (normally distributed) data and proportions between the cases and controls, respectively. when data were not normally distributed the nonparametric (𝜒2 and 2-independent samples) tests were used. binary logistic regression was performed where the candidiasis was the dependent variables and clinical parameters were the independent variables. odds ratio and 95% ci were calculated. p-values (p < 0.05) was considered statistically significant. 4. results out of 123 children with diaper dermatitis, 28 (22.7%) had been excluded because they had incomplete data, or, not enough samples. a total of 95 children were enrolled in doi 10.18502/sjms.v12i3.934 page 178 sudan journal of medical sciences amani hussein ahmed karsani et al variables control (n = 35) cases (n = 60) p gender male 21(60) 38 (63.3) 0.828 feeding style breast feeding 6 (17.1%) 13 (21.7%) 0.401 bottle feeding 31 (88.6%) 49 (81.7%) diaper changing practices 3 times/day 13 (37.1%) 22 (63.9%) 0.460 4 times/day 27 (45%) 33 (55%) washing diaper area (per day) 1 time/day 3 (8.6%) 4 (6.7%) 2 time/day 9 (25.7%) 22 (36.7%) 0.001 more than 2 time/day 23 (65.7%) 34 (56.7%) history of diarrhea last 7 days 20 (33.3%) 0 (0.0%) 0.001 the presence of oral thrush 2 (5.7%) 9 (15%) 0.172 personal history of dermatologic conditions 1 (2.9%) 7 (11.7%) 0.136 family history of dermatologic conditions 4 (11.4%) 17 (28.3%) 0.055 t 1: comparing n(%) of control children and cases with napkin dermatitis. candida species cases (n = 60) controls (n = 35) p skin no candida 23 (38.3%) 28 (80%) <0.001 c. albicans 21 (35%) 6 (17.1%) other species of candidiasis 16 (26.7%) 1 (2.9%) stool no candida 25 (41.7%) 24 (68.6%) <0.001 c. albicans 23 (38.3%) 9 (25.7%) other species of candidiasis 12 (20%) 2 (5.7%) t 2: distribution of c. albicans and other species of isolated from stool and skin of children with napkin dermatitis and control participants. the study. the cases were 60 (63.2%) children of which 38 (40%) were males, where is 35 (38.8%) were apparently healthy counterparts as controls. there was no significant difference between the case and controls in the mean (sd) of the age 7.31 (5.144) vs. 7.28 (5.636), (p < 0.828), gender, feeding style, diaper changing practice and feeding practice. in comparison to the controls high number of cases had less times of changing diaper area and had family history of dermatological lesion, table 1 and figure 1. significantly a higher number of candidiasis was detected in skin in the cases than in the controls. there were 21 (35%) vs 6 (17.1%), 16 (26.7%) vs. 1 (2.9%) p < 0.001 of c. albicans and other species of candidiasis in the cases and controls, respectively, table 2. doi 10.18502/sjms.v12i3.934 page 179 sudan journal of medical sciences amani hussein ahmed karsani et al variables skin candidiasis stool candidiasis or 95, ci p or 95, ci p age 1.037 0.93−1.14 0.485 1.01 0.91−1.11 0.824 male gender 2.409 0.94−6.15 0.066 1.53 0.60−3.92 0.368 feeding practice 0.862 0.53−1.39 0.543 0.77 0.47−1.25 0.297 diaper changing practice 1.028 0.42−2.48 0.951 0.76 0.31−1.85 0.546 washing diaper area 1.245 0.58−2.66 0.572 0.93 0.41−2.07 0.865 oral thrush 1.190 0.23−6.09 0.835 0.45 0.07−2.72 0.388 personal history of skin lesion 8.431 0.79−62.1 0.087 9.19 0.78−39.5 0.078 family history of skin lesion 0.446 0.12−1.62 0.220 0.32 0.08−1.29 0.111 recent history of diarrhoea 2.470 0.82−7.42 0.107 1.89 0.63−5.64 0.251 cases vs. controls 7.86 2.51−24.8 <0.001 3.75 1.19−7.56 0.022 t 3: binary regression for the risk factors for skin and stool candidiasis in children with napkin dermatitis. females (n=22, 23.2%) controls (n=35, 36.8%) males (n=38, 40.0%) females (n=14, 14.7%) males (n=21, 22. 1%) cases (n=60, 63.2%) the enrolled subjects (n=95, 77.3%) the screen subjects (n=123) not fulfilled the criteria, incomplete data, samples (n=28, 22.7%) figure 1: schematic diagram of the study design. likewise, there were 23 (38.3%) vs. 9 (25.7%) and 12 (20%) vs. 2 (5.7%), p < 0.001 c. albicans and other species of candidiasis in the stool of cases and controls, respectively, table 2. doi 10.18502/sjms.v12i3.934 page 180 sudan journal of medical sciences amani hussein ahmed karsani et al in binary regression, while age, gender, feeding style, diaper changing practice, feeding practice were not associated with skin or stool candidiasis, the cases were significantly associated with skin (or = 7.8) and stool candidiasis (3.75), table 3. 5. discussion the main findings of the current study were; c. albicans colonization was detected in the stool and skin in the diaper area of both healthy children and cases with diaper dermatitis. skin colonization by c. albicans among cases and control was 37 (61.7) and six (17.1%) respectively. this finding support the hypothesis that candida, are not generally considered to be primary colonizers, and colonization of the diaper with candida species occurs secondarily as skin damage squally [27]. similarly, the study by d. forbes 2001 found that, candida species was predominantly isolates yeast, which were identified in the stools of 43 children (39%) with diarrhea and 26 (36%) without diarrhea. the concentration of candida species was positively associated with recent antibiotic use and with the presence of another enteric pathogen, but not with patient age, nutritional status, feeding style or duration of diarrhea. our findings are in concurrence with recent reports [4, 8, 9] as well as with a study done by martins n., et al 2014, the main predisposing factors for nd from the diaper area including c. albicans which has been isolated most frequently, regardless of the underlying condition of the skin [3].. although, c. albicans, has been widely implicated and account (80-90 %) in moderate-to-severe nd [3, 9, 28], in contrast, other organisms are not considered causative factors for nd [3]. similarly, bilal j et al 2013, the study of atopic dermatitis (ad) has recovered various bacterial flora from the skin of infants, s. aureus colonization was the most frequently isolated bacteria of skin lesions and non-lesional skin of 37.5% to 15% respectively [29]. based on the clinical findings, a nd of primary reaction to acute irritation (in 1-2 days) was diagnosed in 20 (33.3%) of cases and candidiasis was found in 12 (60%) of them (p≤0.001). klunk c., and his colleagues reported that, materials that made the diapers can cause a primary reaction to irritation acute dd (diaper rash), especially, when become contaminated with urine and stool substances, however, most of cases clear up spontaneously in a day without treatment [7, 8], exacerbation of persistent cases (that last in 3 days or more) may be associated with different infections, especially candida yeasts infections [8]. doi 10.18502/sjms.v12i3.934 page 181 sudan journal of medical sciences amani hussein ahmed karsani et al 6. conclusion according to the findings of this study, comparing to the control group, the severity of napkin dermatitis score was significantly observed among children cases with diaper dermatitis. washing diaper area per day, personal history of dermatologic conditions history of diarrhea last seven days were more vulnerable to candidiasis and napkin dermatitis. however, there were no relation to age, gender, family history of dermatologic conditions, the presence of oral thrush, and feeding style mode. 7. list of abbreviations dd: diaper dermatitis, idd: irritant diaper dermatitis, hr: hour, sda: sabouraud dextrose agar, chromagar: differential and selective chromogenic medium, id card: identification card, yst card: yeast card, ast card: antimicrobial susceptibility cards, vs.: versus, doi 10.18502/sjms.v12i3.934 page 182 sudan journal of medical sciences amani hussein ahmed karsani et al 8. declarations 8.1. ethics approval and consent to participate institutional review board approval was obtained from the deanship of scientific research, qassim university, saudi arabia. informed consent was obtained from all subjects. 8.2. consent for publication not applicable. 8.3. availability of data and materials all the data supporting our findings are contained within this work. 8.4. competing interests the authors declare that they have no competing interests. 8.5. funding this study was supported by grants from the deanship of scientific research, qassim university, saudi arabia. 8.6. authors’ contributions amani h. karsani, abdullateef a. alzolibani, yasser farouq and khalid zedan carried out the study and participated in drafting the manuscript. mohamed elotaiby and ghada bin saif participated in designing the study and participated in drafting the manuscript. ih babikir coordinated and participated in designing the study, statistical analysis and drafting the manuscript. ih babikir carried out the laboratory work. all the authors read and approved the final version. 8.7. acknowledgements this study was funded by the research deanship of qassim university, saudi arabia. we would like to thank the deanship of scientific research, qassim university, for doi 10.18502/sjms.v12i3.934 page 183 sudan journal of medical sciences amani hussein ahmed karsani et al approving and funding this study. the authors are very grateful to all children and their families for their contribution and participation in the study. references [1] r. fölster-holst, m. buchner, and e. proksch, 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[26] e. stefaniuk, a. baraniak, m. fortuna, and w. hryniewicz, “usefulness of chromagar candida medium, biochemical methods api id32c and vitek 2 compact and two maldi-tof ms systems for candida spp. identification,” polish journal of microbiology, vol. 65, no. 1, pp. 111–114, 2016. [27] k. a. brogden and j. m. guthmiller, interactions between candida species and bacteria in mixed infections. 2002. doi 10.18502/sjms.v12i3.934 page 185 sudan journal of medical sciences amani hussein ahmed karsani et al [28] s. borkowski, “diaper rash care and management,” pediatric nursing, vol. 30, no. 6, pp. 467–470, 2004. [29] j. ali bilal, m. issa ahmad, a. a. al robaee, a. a. alzolibani, h. a. al shobaili, and m. s. al-khowailed, “pattern of bacterial colonization of atopic dermatitis in saudi children,” journal of clinical and diagnostic research, vol. 7, no. 9, pp. 1968–1970, 2013. doi 10.18502/sjms.v12i3.934 page 186 introduction subjects and methods collection and processing specimens laboratory diagnosis processing of stool specimens processing of skin swab specimens isolation and identification of c. albicans statistics results discussion conclusion list of abbreviations declarations ethics approval and consent to participate consent for publication availability of data and materials competing interests funding authors' contributions acknowledgements references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9949 production and hosting by knowledge e research article practice and perception of radiographers on the positioning techniques of erect lateral cervical spine radiography in non-trauma adult patients b.s. weerakoon*, i.g.n.n.k. karunaratne, and j.m.w.s. jayasundara department of radiography & radiotherapy, faculty of allied health sciences, university of peradeniya, peradeniya, 20400, sri lanka orcid: b.s. weerakoon: https://orcid.org/0000-0003-0843-6389 abstract background: the visualization of the lower cervical spine (c-spine), including the c7-t1 junction on lateral radiograph is a challenge due to the overlapping of the shoulder girdle. therefore, the radiographers have adapted different positioning strategies to overcome this challenge. this study explores the current practice and perception of radiographers on positioning techniques of erect lateral cervical spine radiography in non-trauma adult patients. methods: this prospective study was conducted with a self-administered, structured questionnaire distributed among 50 radiographers working in four selected hospitals in sri lanka. results: the radiographers used weight-bearing and non-weight-bearing positioning techniques for the erect lateral c-spine radiography. most of them employed the standing breath-holding technique for image acquisition with or without exertion. while 54% of the radiographers utilized two water-filled cans during the weight-bearing technique, 82% used holding arms back with the shoulders down and pulling as low as possible in the non-weight-bearing technique. in addition, 88% of the radiographers believed that the weight-bearing position could increase the visibility of the c-spine. almost all the radiographers (100%) stated that correct positioning instruction could improve the visibility of the c-spine. conclusion: radiographers have mainly used two positioning techniques of weightbearing and non-weight-bearing for erect lateral c-spine radiography for non-trauma adult patients. in addition, most radiographers had a positive attitude toward the weight-bearing technique in the evaluation of lateral c-spine. these results highlight the importance of conducting studies to evaluate the effectiveness of the weightbearing technique in erect lateral c-spine radiography. keywords: cervical spine, erect lateral radiography, positioning techniques, current practice, non-trauma adult patients how to cite this article: b.s. weerakoon*, i.g.n.n.k. karunaratne, and j.m.w.s. jayasundara (2021) “practice and perception of radiographers on the positioning techniques of erect lateral cervical spine radiography in non-trauma adult patients,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 519–530. doi 10.18502/sjms.v16i4.9949 page 519 corresponding author: b.s. weerakoon; email: bsw888@gmail.com received 06 october 2021 accepted 18 november 2021 published 31 december 2021 production and hosting by knowledge e b.s. weerakoon et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:bsw888@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences b.s. weerakoon et al. 1. introduction although computed tomography (ct) and magnetic resonance imaging (mri) have been able to advance the imaging of the cervical spine (c-spine), plain radiography still plays a vital role in the initial assessment of any type of cervical spine injury due to its abundant availability and cost-effectiveness [1, 2]. the lateral view of the c-spine is an important examination in radiographic assessment as it can demonstrate all seven cervical vertebrae with their alignments and the cervico-thoracic (c7-t1) junction where 9–18% of injuries to the cervical region are found [3–5]. however, due to the overlap of the shoulder girdle and other anatomical structures such as the rib cage (figure 1), it is challenging to demonstrate the lower cervical vertebrae with the c7-t1 junction on lateral radiographs of the c-spine [3, 6, 7] therefore, different positioning techniques are proposed and adapted by researchers and radiographers to overcome this challenge [3, 8, 9] however, there is inadequacy in guidelines and directives for the use of different positioning techniques in the erect lateral c-spine radiography. nevertheless, a good positioning technique is significant in order to obtain correct diagnostic information and minimize unnecessary radiation exposure to a patient [10, 11]. inadequate awareness of usefulness could be a reason for the underuse of the recommended positioning techniques. therefore, it is essential to understand the current practice as it can explain the application of the optimal positioning techniques, the practical difficulties involved, and the level of awareness of the radiographers about positioning techniques. this study explores the current practice and perception of radiographers on positioning techniques of erect lateral cervical spine radiography in non-trauma adult patients. the outcomes of this study can be used to enhance the awareness of radiographers about the positioning techniques of erect lateral c-spine radiography, and thereby promote an accurate diagnosis through the effective usage of positioning techniques. 2. materials and methods this prospective study was conducted at four selected government hospitals in sri lanka. using the purposive sampling technique, 63 radiographers working in the plain radiography units were selected for the study. data were collected using a self-administered structured questionnaire. the questionnaire consisted of two sections. while the first section was dedicated to the collection of demographic data such as education level and years of experience in radiography, doi 10.18502/sjms.v16i4.9949 page 520 sudan journal of medical sciences b.s. weerakoon et al. the second part was dedicated to investigating the current practice of the positioning technique of the erect lateral c-spine radiography. a pilot study was conducted with four randomly selected radiographers (one from each hospital) to determine the readability, clarity, and comprehensiveness of the questionnaire. based on the responses received, the questionnaire was edited to correct minor ambiguities. the statistical package for social science (spss) v.20 was used for data analysis. the sample was described using frequency distributions. the non-parametric chi-square test was used to identify the significant differences between the variables. p-value < 0.05 was considered significant. 3. results a total of 50 questionnaires were returned with a response rate of 79%. overall, 92% (46) of the respondents had a diploma in diagnostic radiography and only 8% (04) had a degree or postgraduate qualification in diagnostic radiography. the majority of the radiographers (82%, 41) had more than five years of professional experience (table 1). as demonstrated in figure 3, the radiographers who participated in this study primarily used weight-bearing and non-weight-bearing positioning techniques for the erect lateral c-spine radiography. the majority of radiographers (76%, 38) stated that they would choose one of the above positioning techniques depending on the indication and the condition of the patient. besides, 28% (14) of the radiographers claimed that they apply the weight-bearing position for all sufficiently capable patients. in the meantime, 24% (12) claimed that they only use the weight-bearing position for obese and short neck patients depending on their ability to perform. the majority of radiographers use the standing breath-holding technique to obtain lateral c-spine radiographs (tables 2 and 3) with both weight-bearing and non-weight-bearing techniques. as shown in table 2, 54% (27) of the participants utilized two water-filled cans during the weight-bearing positioning, followed by sandbags (20%, 10). holding arms back with the shoulders down and pulling as low as possible was the highest (82%, 41) reported position in the non-weight-bearing technique. when considering the radiographers’ perception, 88% (44) of the participants believed that a weight-bearing position could increase the visibility of the c-spine than a non-weight-bearing position. further, all radiographers (100%, 50) mentioned that correct instruction during positioning can increase the visibility of the c-spine. patient discomfort (66%, 33) and extended time taken for a procedure (46%, 23) are the most common hindrances that radiographers have identified when performing lateral doi 10.18502/sjms.v16i4.9949 page 521 sudan journal of medical sciences b.s. weerakoon et al. radiography of the erect c-spine in non-trauma adult patients (figure 3). there is no significant association between the years of professional experience with the type of positioning technique used, the breathing instructions given, and the positive attitude toward the weight-bearing technique (table 4). 4. discussion the positioning of the patient in c-spine radiography is significant as it facilitates patient stability, clear exposure, and accurate diagnosis through correct anatomical positioning [12]. the obstruction of the visibility of the lower cervical vertebrae by the shoulder girdle and certain other anatomical structures make positioning difficult in erect lateral c-spine radiography [3, 6, 7]. therefore, different positions are used and suggested by researchers and radiographers to minimize the difficulties and challenges associated with the practical demonstration of lower cervical vertebrae [3, 8, 9] this study explores the current practice and perception of radiographers about positioning techniques of erect lateral cervical spine radiography in non-trauma adult patients. in general, the lateral erect c-spine radiography is performed in both sitting [13, 14] and standing positions [15, 16]. in this study, the majority of radiographers employed the standing position. the standing position is generally considered to be a comfortable and functional posture for spinal radiography. previous researchers have used the standing position to assess the sagittal alignment of the c-spine [16, 17] however, a standing position with arms by the sides prevents adequate visualization of the lower cervical spine [18]. therefore, one of the customized positioning techniques should be used based on patient’s capabilities. the use of the weight-bearing position in the lateral c-spine radiograph as an adjunct to improve the visualization of the lower c-spine is suggested [8]. however, no study was found in the literature that evaluates the effectiveness of the above technique. holding a weight in each hand is expected to project the shoulder masses below the level of c7. however, for the instances where patients tend to hunch their shoulders when attempting to firmly hold the weights, the desired anatomy will be obscured. therefore, this technique can be counterproductive insisting on a clear and proper explanation [19]. several previous researchers have proposed different positioning strategies for lateral c-spine radiography to improve the visibility of the lower cervical vertebrae. however, each strategy has its own strengths and weaknesses. certain studies have observed the effects of the swimmer’s view [3, 5, 20], supine oblique view [20], and arm traction technique []6, 21–23 on improving the visibility of lateral c spine radiography. however, doi 10.18502/sjms.v16i4.9949 page 522 sudan journal of medical sciences b.s. weerakoon et al. with the availability of many such strategies, it was revealed that the radiographers in this study have primarily used only the two positioning techniques of weight-bearing and non-weight-bearing for the erect lateral c-spine radiography. alternative positioning techniques such as the swimmer’s view may increase the time spent as it requires additional time for handling the patient. therefore, the results of the current study could be due to heavy workloads leading to time constraints or the scarcity of knowledge of other positioning techniques among radiographers. all radiographers in this study correctly recognized the fact that the lateral cervical spine radiography can be significantly improved with the use of proper breathing instruction [24]. in addition, this study found that most radiographers, with or without a weight-bearing technique, often instructed patients to hold their breath for lateral cervical radiography. most available resources suggested performing this examination with arrested expiration or full exhalation in order to lower the shoulders well out of the region of interest [8, 19]. in this study, the non-weight-bearing technique was primarily performed by the radiographers in the position of holding arms behind the back and pulling the shoulders down as low as possible. this technique helps the shoulder to be moved inferiorly and produce a clear view of the c-spine anatomy [24]. however, this downward pull can exacerbate an unstable injury. therefore, prior to using the this technique, it should be ensured that the patient is at a low risk of being further subjected to unstable injuries by assessing their clinical and physical symptoms [25]. according to the current study results, the patient’s discomfort and time expenditure are the greatest challenges encountered in the erect lateral cervical spine radiography. to ensure the visibility of the upper anterior cervical vertebra and posterior arch of the atlas, it is necessary to avoid the overlap of the angle of the mandible and occipital bone [26]. this requires bending or extending the head, and it might cause discomfort to the patient. further, it is impossible to obtain a good-quality radiograph without proper immobilization despite the significant amount of time that it requires [27]. 5. strengths and limitations there are certain limitations to this study. only 8% of the radiographers in this study had a degree or postgraduate qualifications making it hard to determine the impact of education level on other variables. hence, it is recommended that this study be repeated with a relatively equal number of graduates and non-graduates to determine the impact of education on their practice and attitudes. moreover, due to its feasibility, doi 10.18502/sjms.v16i4.9949 page 523 sudan journal of medical sciences b.s. weerakoon et al. table 1: demographic characteristics of the participants. variables percentage% (n) education level diploma 92 (46) graduate 4 (02) postgraduate 4 (02) professional experience (yr) 0–5 18 (09) 6–10 38 (19) >10 44 (22) table 2: details of the weight-bearing position. weight-bearing position positioning techniques percentage% (n) posture standing 72 (36) sitting 0 (00) both standing and sitting 12 (06) no response 16 (8) breathing instructions not given 8 (4) holding breath 54 (27) suspended inspiration 0 (00) suspended expiration 22 (11) missing 16 (08) type of the weight two water-filled cans 54 (27) two sandbags 20 (10) both 10 (05) no response 16 (08) only the radiographers in four selected government hospitals were included in this study. therefore, this study does not represent the entire population of radiographers across sri lanka, thus, it is recommended to conduct further research with a larger sample representing the radiographers from different regions in the country. however, this study is significant as there are no published studies available on this topic. further, this study provides baseline information to the imaging field about the usage of positioning techniques, although there are many recommended advanced techniques available. additionally, by assessing the current practice and the perception, it is possible to identify the value of strengthening the continuing education programs for radiographers. doi 10.18502/sjms.v16i4.9949 page 524 sudan journal of medical sciences b.s. weerakoon et al. table 3: details of the non-weight-bearing position. non-weight-bearing position positioning techniques percentage% (n) posture standing 78 (39) sitting 0 (00) both standing and sitting 14 (07) no response 8 (04) breathing instructions not given 8 (04) holding breath 64 (32) suspended inspiration 0 (00) suspended expiration 20 (10) no response 8 (04) types of positioning arms by sides with relaxed shoulders against the vertical cassette holder 2 (01) arms by sides with relaxed shoulders as far down and forward as possible 8 (04) arms hold behind the back with shoulders down and pull them down as low as possible 82 (41) no response 8 (04) table 4: association between the years of professional experience and other variables. variables type of positioning technique (weightbearing/nonweight-bearing) breathing instructions (weightbearing) breathing instructions (non-weight bearing) positive attitude towards the weight-bearing technique professional experience (yr) 0.51 0.22 0.12 0.58 6. conclusion although many strategies are available, the radiographers in this study have mainly used two positioning techniques of weight-bearing and non-weight-bearing for the erect lateral c-spine radiography of non-trauma adult patients. this highlights the urgency of providing regular, continuous professional development programs to radiographers to uplift their awareness on different radiological techniques. further, most radiographers had a positive attitude toward the weight-bearing technique when assessing the lateral c-spine. this finding shows the importance of conducting studies to assess the effectiveness of the weight-bearing technique in the erect lateral cervical spine radiography. doi 10.18502/sjms.v16i4.9949 page 525 sudan journal of medical sciences b.s. weerakoon et al. figure 1: erect lateral cervical spine radiographs. (a) the lower cervical spine and the c7-t1 junction are not obscured by the musculoskeletal structures. (b) the lower cervical spine and the c7-t1 junction are obscured by the musculoskeletal structures. figure 2: practice of weight-bearing and non-weight-bearing positioning techniques. doi 10.18502/sjms.v16i4.9949 page 526 sudan journal of medical sciences b.s. weerakoon et al. figure 3: challenges in erect c-spine lateral radiography of the non-trauma adult patients. however, it is essential to conduct further studies with larger samples to confirm and elevate the reliability of the results. 7. acknowledgements the authors would like to thank all hospitals involved in this study for granting permission to collect data. they would also like to express their sincere appreciation to all participants and parties who contributed to the successful completion of this study. 8. ethical considerations ethical approval was granted by the ethics review committee of the faculty of allied health sciences, university of peradeniya. permission to conduct the study was obtained from all selected hospitals. written consent was obtained from the participants prior to data collection, and voluntary participation was emphasized. the participants were assured of the confidentiality of their responses. 9. competing interests the authors declare that there is no conflict of interest related to this study. 10. funding this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. doi 10.18502/sjms.v16i4.9949 page 527 sudan journal of medical sciences b.s. weerakoon et al. references [1] izzo, r., popolizio, t., balzano, r. f., et al. 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(2017). imaging investigations in spine trauma: the value of commonly used imaging modalities and emerging imaging modalities. journal of clinical orthopaedics and trauma, vol. 8, no. 2, pp. 107–115. doi 10.18502/sjms.v16i4.9949 page 530 introduction materials and methods results discussion strengths and limitations conclusion acknowledgements ethical considerations competing interests funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9943 production and hosting by knowledge e research article association between smoking and foot ulcer among patients with diabetes mellitus, wad medani, sudan abeer abdelrahman elnour eltilib department of family medicine, faculty of medicine, university of gezira, university city, wad medani, gezira state, sudan orcid: abeer abdelrahman elnour eltilib: https://orcid.org/0000-0002-7093-2757 abstract background: this study aimed to assess the relationship between smoking and diabetic foot ulcer (dfu) among adult diabetic patients presenting to aldarga diabetic center, wad medani, sudan in 2020. methods: this comprehensive study is based on primary data obtained via a longitudinal cross-section random sample of 400 patients with diabetes mellitus who presented to aldarga diabetic health center in wad medani town, gezira state, sudan between september and december 2020. data were collected using a structured questionnaire. the core questions included two main dimensions: sociodemographic variables and smoking. data were analyzed using the spss software, v.20, using descriptive and inferential statistics, namely, frequency tables and graphs, showing the chi-square test of the relationship between the dependent and the independent variables. results: of the 400 participants, 96 were clearly diagnosed with foot ulcer giving a proportion of 33% in the sample. there was a statistically significant relationship between smoking and dfu. a chi-square test was done to measure the relationship between smoking and foot ulcer, which was significant at p = 0.043. conclusion: extensive awareness programs to control the negative effect of smoking in accelerating dfu and amputation are necessary. keywords: prevalence of diabetic foot ulcer, diabetic, diabetic food ulceration, smoking 1. introduction a total of 12,089 diabetic cases were reported in africa in 2010; this increased to 19,406.8 cases in 2019, which led to the prediction of the number for 2030 and 2045 as 28,629.4 and 47,133.7, respectively. according to the international diabetes federation (idf) diabetes atlas, 9𝑡ℎ edition [1]. how to cite this article: abeer abdelrahman elnour eltilib (2021) “association between smoking and foot ulcer among patients with diabetes mellitus, wad medani, sudan,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 450–463. doi 10.18502/sjms.v16i4.9943 page 450 corresponding author: abeer abdelrahman elnour eltilib; email: abeert17@yahoo.com received 02 october 2021 accepted 10 december 2021 published 31 december 2021 production and hosting by knowledge e abeer abdelrahman elnour eltilib. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:abeert17@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences abeer abdelrahman elnour eltilib prevention of diabetic foot ulceration is critical in order to reduce the associated high morbidity and mortality rates, and the danger of amputation. it is essential to identify the “foot at risk,” through careful inspection and physical examination of the foot followed by neuropathy and vascular tests. [2] dubský et al.’s study showed […] a high recurrence rate of dfu during 3-year follow-up period in patients with a primarily healed ulcer, despite regular follow-up and patient education. we also found that the independent risk factors for ulcer recurrence were plantar location of the ulcer, the presence of underlying osteomyelitis, poor glycemic control and an elevated crp at the time of diagnosis of the first foot ulcer. knowing these risk factors may allow clinicians and health care systems to target heightened efforts at prevention of ulceration after healing to selected high-risk patients. [3] furthermore, al busaidi et al. [4] stated that: diabetes is a chronic and costly disease; however, it can be prevented. the alarm of the rising tide of diabetes has not yet been successfully translated into action in the middle east. the governments in the region need to devise more intense, broader policies and preventive measure programs based on local sociocultural practices to effectively combat the situation. further improvements of the primary health care system and cross-governmental approaches are needed in the region to keep the growing epidemic of diabetes under control. 1.1. characteristics, prevalence, and outcomes of diabetic foot ulcers (dfus) in africa rigato and colleagues in a systemic review and meta-analysis reported as follows: fifty-five full-text papers and ten abstracts were retrieved, reporting data from 19 african countries on 56,173 diabetic patients. according to the data collected, the overall prevalence of foot ulcers was 13% and increased over time, especially since 2001. approximately 15% of patients with foot lesions underwent major amputation and 14.2% died during hospitalization. in patients with diabetic ulcers, insulin therapy was uncommon and neuropathy was the most common predisposing factor, but the prevalence of doi 10.18502/sjms.v16i4.9943 page 451 sudan journal of medical sciences abeer abdelrahman elnour eltilib peripheral arterial disease correlated with amputation rates. amputation and mortality decreased over time, probably as result of the implementation of screening programs in the last ten years. mortality was directly related to previous amputation. [5] moreover, elmadhoun and coworkers reported a high prevalence of diabetes mellitus (dm) and glucose intolerance in the urban population of the river nile state (rns) [6]. another study conducted in the same region showed that the prevalence of dfu was 18.1% and that the risk of development of dfu is increased with the increase in the duration of diabetes, especially in those with dm for more than 10 years [7]. additionally, another study [8] reported a strong relationship between smoking and foot ulcer, the results of the paper stated: the role of smoking for wound healing in patients with diabetic foot has been unclear. this meta-analysis examined the relationship between cigarette smoking and diabetic foot wound healing. observational studies for the association between smoking and diabetic foot wound healing of patients were systematically searched through pubmed and wanfang data, published up to june 2018. healing rates of wounds were recognized as outcomes. meta-analysis models were chosen by heterogeneity. a total of 3388 eligible studies were identified, of which 18 met all our inclusion criteria. in the smoking group, healing rate had an average of 62.1%, ranging from 20.0% to 89.6%; in the nonsmoking group, healing rate had an average of 71.5%, ranging from 40.2% to 93.8%. a significant association was found between smoking and the healing of diabetic foot. our meta-analysis indicated that smoking had an overall negative effect on the wound healing of diabetic foot individuals. this study provides evidence for the harm of smoking to diabetic foot and may help reduce the medical and economic burden on poor healing of diabetic foot. furthermore, taha and ball’s [9] study on smoking in africa showed that: cigarettes are heavily promoted in africa. smoking-related diseases have already made their appearance in africa. the 2 most common types of cancer in the natal bantu are lung and esophageal tumors. lung cancer in natal men has increased 6-fold and in women about 5-fold over the past 11 years. as a result, tobacco companies have started to diversify and intensify promotion of cigarettes and the growth of tobacco in the 3rd world. doi 10.18502/sjms.v16i4.9943 page 452 sudan journal of medical sciences abeer abdelrahman elnour eltilib dfu is one of the commonest complications of dm imputed to a number of morbidity and mortality cases in diabetic patients. nowadays, the incidence of dfu is increasing due to the increased prevalence of diabetes. however, the risk factors of the problem are less or not studied in gezira state, sudan. hence, this study was conducted to assess the determinants of dfu in relation to smoking among adult patients with diabetes attending aldarga diabetic center, wad medani, sudan in 2020. 2. materials and methods a longitudinal, cross-sectional design was used to conduct the study among patients presenting at aldarga diabetic health center in wad medani town, gezira state, sudan between september and december 2020. the center is located in the north of wad medani town, 186 km south of khartoum, the capital of sudan. it was opened as a specialized center for the central region of sudan. of the 400 participants who presented at the center, 96 had foot ulcer. 2.1. sample size and sampling design a random sampling method was used to select the sample of the study (total diabetic patients in 2020 reporting to the diabetic follow-up clinic). the simple random sampling equation for provisional sample size n* was calculated using the following formula: n = (t² × p × q) / (d²), where: n* = required sampling size; p = anticipated population proportion taken as 50% because it gives the maximum possible sample size. if we take the estimated prevalence rate of 0.15 for sudan as p, the sample size will be 195, however, we preferred a larger sample; t = confidence level, taken as 95%; and d = absolute precision required on either side of anticipated proportion taken as 5%. next, the provisional sample was multiplied by a design effect of 2 to give the final sample n: n = (2² × 50 × 50) / (25) = 400. a total of 400 participants were successfully compassed by field data collection team. the total diabetic patients who reported to the center in 2020 were 40,507 classified by months with an average of 3376 diabetic patients per month. the procedure used for selecting sampling units was twofold. first, we calculated the systematic sampling interval factor by dividing the number of diabetic patients during doi 10.18502/sjms.v16i4.9943 page 453 sudan journal of medical sciences abeer abdelrahman elnour eltilib the data collection period (november–december 2020) by the sample size, that is, n/n = 1823/400 = 4.55 ≅ 5. the sample unit number 5 was selected first. the rest of the sampling units were selected according to kish selection procedure to cater for gender [10]. 2.2. data analysis descriptive statistics was initially undertaken to analyze the composition of the sample. data were coded and entered into a computer using two of the latest versions of prepared packages of statistical analysis namely statistical package for social sciences (spss) v.24.0/25.0 for windows. the programs were used in different stages of data processing to process the raw data obtained from the questionnaires. quantitative analysis of the question responses obtained from the questionnaire were summarized, portrayed, and analyzed on a statistical basis in order to offer the researcher the opportunity to analyze the responses and identify whether the results are skewed [10]. the following statistical analyses were run: 1. a pilot study was conducted to establish content validity. 2. face validity was established through the circulation of the questionnaire to 60 pilot respondents. 3. the summary results of the descriptive statistics were presented using tables and graphs. 2.3. operational definitions 2.3.1. diabetic foot the international working group on diabetic foot (iwgdf) has defined the diabetic foot as infection, ulceration, or destruction of tissues of the foot of a person with currently or previously diagnosed dm, usually accompanied by neuropathy and/or peripheral arterial disease (pad) in the lower extremity. 2.3.2. diabetic foot ulcer (dfu) dfus are nondramatic lesions of the skin on the foot distal to malleoli of a person who has dm [11]. doi 10.18502/sjms.v16i4.9943 page 454 sudan journal of medical sciences abeer abdelrahman elnour eltilib 2.3.3. diagnostic criteria for dm or measurement of dm (i) random plasma glucose value of ≥200 mg/dl (≥11.1 mmol/l) or (ii) fasting plasma glucose value of ≥126 mg/dl (≥7.0 mmol/l) or (iii) a 2-hr oral glucose tolerance test (gtt) value in venous plasma ≥200 mg/dl (≥11.1 mmol/l), or (iv) glycated hemoglobin (hba1c) ≥6.5% (≥48 mmol/molhb) [12]. 2.3.4. smoking the act of inhaling and exhaling the fumes of burning plant material. a variety of plant materials are smoked, including marijuana and hashish, but the act is most commonly associated with tobacco smoked in a cigarette, cigar, or pipe. tobacco contains nicotine, an alkaloid that is addictive and can have both stimulating and tranquilizing psychoactive effects. [13] (i) respondents’ socioeconomic characteristics the survey data were initially analyzed using frequency tables and descriptive statistics. of the 400 sampled respondents, 55% were male and 44.5% were females living in predominantly extended (68%) families with the majority living in towns (56.8%). while only 8.5% reported high income level, 33.5% reported low income, and the majority were of medium income level (58%). table 1 shows the frequency distribution and descriptive statistics of the participant’s socioeconomic characteristics. the youngest patient in the sample was 30 years of age and the oldest was 89. the age distribution classified in five years age group shows an expected pattern with sharp skewness to the right, where the majority are over the age of 50 years (79%) and more than half are >60 years of age. the mean age is 59.9 years with approximately similar median and mode indicating that the distribution is mesokurtic showing a confidence interval of 59.9 ± 1.31. the majority of respondents were married (69.3%), 6.8% were single with abnormally nontypical high proportion of widows and divorcees (24%). the majority were either uneducated or had basic education (67.6), 20.3% had secondary education, and only 12.3% had a university degree. these tally very well with occupational classification, as 65.8% were either unemployed (38%), housewives (13.5%), or had unspecified jobs (14.3%). the general picture that can be drawn from the respondents’ socioeconomic status is that diabetic patients reporting to aldarga center are mostly of low social class category. (ii) factors related to respondents’ behavior doi 10.18502/sjms.v16i4.9943 page 455 sudan journal of medical sciences abeer abdelrahman elnour eltilib table 1: frequency distribution and descriptive statistics of major respondent’s indicators. variable n percentage (%) central tendency standard error of the mean age (yr) 30–34 15 3.8 35–39 10 2.5 40–44 31 7.8 mean = 59.5 1.31 45–49 28 7 median = 60 50–54 42 10.5 mode = 58 55–59 61 15.3 skewness = – 0.222 –0.012 60–64 48 12 65–69 57 14.3 kurtosis = 0.555 0.243 ≥70 108 26.8 total 400 100 marital status single 27 6.8 median = 2.0 married 277 69.3 skewness = 0.976 0.122 widow 72 18 mode = 2.0 divorced 24 6 kurtosis = 0.132 0.233 total 400 100 educational level illiterate 34 8.5 khalwa 77 19.3 median = 3.0 basic 159 39.8 skewness = 0.163 0.057 secondary 81 20.3 mode = 3.0 university 42 10.5 kurtosis = 0.232 0.223 postgraduate 7 1.8 total 400 100 occupation professional 4 1 business 60 15 median = 8.0 employee and uniform 38 9.6 skewness = 0.163 0.234 worker and farmer 35 8.8 mode = 9.0 housewife 54 13.5 kurtosis = 0.232 0.122 unemployed and others 209 52.3 total 400 100 source: researchers’ own survey, 2020. doi 10.18502/sjms.v16i4.9943 page 456 sudan journal of medical sciences abeer abdelrahman elnour eltilib figure 1: relationship between smoking and diabetic foot ulcer. figure 2: relationship of diabetic foot ulcer with smoking frequency per day. the majority of the respondents were nonsmokers and also nonalcoholic drinkers – 40.0% and 50.5%, respectively, and only 9.5% were snuffers. in addition, only 12% were smokers and about 4.3% of them smoked more than once daily (7.8%). a chi-square test was done to measure the relationship between smoking and foot ulcer, which was significant at p-value = 0.043. doi 10.18502/sjms.v16i4.9943 page 457 sudan journal of medical sciences abeer abdelrahman elnour eltilib figure 3: relationship of diabetic foot ulcer with drinking of alcohol. figure 4: relationship of diabetic foot ulcer with the use of snuff. 3. results 3.1. respondent’s socioeconomic characteristics and association with smoking the survey data were initially analyzed using frequency tables and descriptive statistics. of the 400 sampled respondents, 55.5% were males and 44.5% were females living doi 10.18502/sjms.v16i4.9943 page 458 sudan journal of medical sciences abeer abdelrahman elnour eltilib table 2: chi-square test of the relationship between the dependent (foot ulcer) and independent variables (smoking). decision df x2 sig decision smoking 1 4.08 0.043 frequency of smoking per day 2 4.09 0.129 alcohol intake 1 0.263 0.608 use of snuff 1 0.717 0.397 source: researchers’ own data. in predominantly extended (58%) families with the majority living in towns (56%). only 8.5% reported high income level, 33.5% reported low income, and the majority were of medium income level (58%). table 3 shows the frequency distribution and descriptive statistics of the participant’s socioeconomic characteristics. the youngest patient in the sample was 30 years old and the oldest was 89. the age distribution classified in five years age group shows an expected pattern with sharp skewness to the right, where the majority were >50 years (79%) and more than half >60 years of age. the mean age was 59.9 years with approximately similar median and mode indicating that the distribution is mesokurtic showing a confidence interval of 59.9 ± 1.31. the majority of respondents were married (69.3%), 6.8% were single with abnormally nontypical high proportion of widows and divorcees (24%). the majority were either uneducated or had basic education (67.6), 20.3% had secondary education, and 12.3% were in the category of university and over. these tally very well with occupational classification as 65.8% were either unemployed (38%), housewives (13.5%), or had unspecified jobs (14.3%). the general picture that can be drawn from the respondent’s socioeconomic status is that diabetic patients reporting to aldarga center are of low social class category. additionally, 20% of the respondents smoked, which was significant at p-value = 0.043, where the drinking of alcohol was only 3% and snuffer was 17%. 4. discussion this study, to the best of our knowledge, could be the first to estimate the association between smoking and dfu in gezira state, sudan. of the 400 dm participants included in this study, 96 had dfu, of which 12% were smokers, p-value = 0. .043the finding of this study is in line with the study of xia et al. [14], who stated that: doi 10.18502/sjms.v16i4.9943 page 459 sudan journal of medical sciences abeer abdelrahman elnour eltilib table 3: frequency distribution and descriptive statistics of the participant’s socioeconomic characteristics. total % �2 p-value age of the respondents (yr) 30–39 25 6.2 20.81 0.035 40–49 59 14.8 50–59 103 25.8 60–69 105 26.2 70–79 90 22.5 80–89 18 4.5 sex of the respondents male 222 55.5 1.682 0.116 female 178 44.5 residence of the respondents town 225 56 0 0.54 village 175 44 type of family nuclear 168 42 0.353 0.229 extended 232 58 income level low 134 33.5 0.736 0.612 medium 232 58 high 34 8.5 marital status single 27 6.8 0.451 0.93 married 277 69.2 widow 72 18 divorced 24 6 diabetic in the family yes 194 49 2.033 0.09 no 206 51 type of work of the respondent professional/business64 16 13.32 0.1 employee 35 8.8 worker 15 3.7 farmer 20 5 uniform 3 0.8 housewife 54 13.5 other 57 14.2 unemployed 152 38 educational level illiterate 34 8.5 7.496 0.186 khalwa/madrasa 77 19.3 basic 159 39.8 secondary 81 20.2 university/postgraduate49 12.2 smoking yes 77 20 4.08 0.043 no 323 80 frequency of smoking per day more than once in the day 50 13 4.09 0.129 daily 27 7 no application 323 80 drinking of alcohol yes 10 3 0.263 0.608 no 390 97 use of snuff yes 67 17 0.717 0.397 no 333 83 total 400 doi 10.18502/sjms.v16i4.9943 page 460 sudan journal of medical sciences abeer abdelrahman elnour eltilib at the end of this review, the current mainstream therapies for smoking cessation are also outlined. we believe that it is urgent for all diabetic patients to quit smoking so as to reduce their chances of developing foot ulcers and to improve the prognosis of diabetic foot ulcers. on the other hand, pal and colleagues [15] showed that: the diabetic patients who were smokers and/or chronic alcoholic underwent more amputations with concomitant longer hospital stay than the patients who had no addiction to these substances. the prognosis was worse in the subgroup of patients who were both smoker and chronic alcoholic. the study was done on 89 patients who were admitted in the surgical wards of the following teaching hospitals in india kpc medical college and hospital as in our study those they had foot ulcer compared in those not had dfu were more smokers, snuffers and alcoholic’s [12%, 7.3%,9.5%, 7.3%,1.5%, 1%] and as we know from medicine their effect on dealing wound healing and accelerating dfu. moreover, public databases, including pubmed and embase, were searched for articles published prior to february 29, 2016. heterogeneity was assessed using the cochran’s q statistic and the i2 statistic, and odds ratio (or) and 95% confidence interval (ci) were calculated and pooled appropriately. sensitivity analysis was performed to evaluate the stability of the results of the present meta-analysis which suggested that smoking is a notable risk factor for diabetic foot amputation. liu et al. reported that smoking cessation appears to reduce the risk of diabetic foot amputation [15]. all studies showed a strong association between increased smoking and dfu. the effects of cigarette smoking on dfus are clear from our study and other papers. our study found that smoking had a negative effect in wound healing in foot ulcer cases. hence, if the factors associated with dfu reduces such as quitting smoking, majority of our patients can be saved from dfu and disabilities arising thereof. acknowledgements the authors express their sincere appreciation to wad medani alderaga health center in gezira state, sudan for their cooperation. they are also thankful to the diabetic patients who willingly participated in the research. doi 10.18502/sjms.v16i4.9943 page 461 sudan journal of medical sciences abeer abdelrahman elnour eltilib ethical considerations before initiating the field survey, the objective of ethics in research was ensured by obtaining ethical clearance from the director of health affairs in wad medani locality of gezira state. a supportive formal letter was written to aldarga diabetic center. data collection was done after permissions were obtained from the center managers, and oral informed consent was obtained from the study participants to start data collection after assuring them of the ethical aspects regarding the confidentiality, privacy, and consent of the data. competing interests none declared. availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. references [1] international diabetes federation (idf). (2019). idf diabetes atlas (9𝑡ℎ ed.). idf. [2] alexiadou, k. and doupis, j. (2012). management of diabetic foot ulcers. diabetes therapy, vol. 3, article 4. [3] dubský, m., jirkovská, a., bem, r., et al. (2013). risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the eurodiale subgroup. international wound journal, vol. 10, no. 5, pp. 555–561. [4] al busaidi, n., shanmugam, p., and manoharan, d. (2019). diabetes in the middle east: government health care policies and strategies that address the growing diabetes prevalence in the middle east. current diabetes reports, vol. 19, no. 2, p. 8. doi 10.18502/sjms.v16i4.9943 page 462 sudan journal of medical sciences abeer abdelrahman elnour eltilib [5] rigato, m., pizzol, d., tiago, a., et al. (2018). characteristics, prevalence, and outcomes of diabetic foot ulcers in africa. a systemic review and metaanalysis. diabetes research and clinical practice, vol. 142, pp. 63–73. [6] elmadhoun, w. m., noor, s. k., ibrahim, a. a., et al. (2016). prevalence of diabetes mellitus and its risk factors in urban communities of north sudan: population-based study. journal of diabetes, vol. 8, no. 6, pp. 839–846. [7] almobarak, a. o., awadalla, h., osman, m., et al. (2017). prevalence of diabetic foot ulceration and associated risk factors: an old and still major public health problem in khartoum, sudan? annals of translational medicine, vol. 5, no. 17, p. 340. [8] fu, x.-l., ding, h., miao, w.-w., et al. (2018). association between cigarette smoking and diabetic foot healing: a systematic review and meta-analysis. the international journal of lower extremity wounds, vol. 17, no. 4, pp. 247–257. [9] taha, a. and ball, k. (1982). smoking in africa: the coming epidemic. world smoking health, vol. 7, no. 2, pp. 25–30. [10] kish, l. (2004). statistical design for research. john wiley & sons, inc. [11] netten, j. j., bus, s. a., apelqvist, j., et al. (2020). definitions and criteria for diabetic foot disease. diabetes/metabolism research and reviews, vol. 36, no. s1. [12] henningfield, j., rose, c. a., sweanor, d. t., et al. (2020). smoking. encyclopedia britannica. retrieved from: https://www.britannica.com/topic/smoking-tobacco [13] xia, n., morteza, a., yang, f., et al. (2019). review of the role of cigarette smoking in diabetic foot. journal of diabetes investigation, vol. 10, no. 2, pp. 202–215. [14] pal, b., raveender, n., and sudipta, p. (2016). a study on the impact of smoking and alcoholism as determinant factors in the prognosis and outcome of diabetic foot ulcer disease. international journal of research in medical sciences, vol. 4, no. 5, pp. 1720–1724. [15] liu, m., zhang, w., yan, z., et al. (2018). smoking increases the risk of diabetic foot amputation: a meta-analysis. experimental and therapeutic medicine, vol. 15, pp. 1680–1685. doi 10.18502/sjms.v16i4.9943 page 463 introduction characteristics, prevalence, and outcomes of diabetic footulcers (dfus) in africa materials and methods sample size and sampling design data analysis operational definitions diabetic foot diabetic foot ulcer (dfu) diagnostic criteria for dm or measurement of dm smoking results respondent's socioeconomic characteristics and association with smoking discussion acknowledgements ethical considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9945 production and hosting by knowledge e research article knowledge and awareness of diabetic retinopathy among diabetic sudanese patients, khartoum state, sudan, 2018 mohammed i. m. ahmed1, mawahib a. e. abu elgasim2, mehad a. t. mohamed3, manasik m. n. munir3, manasik s. n. abdelrahim3, zeinab m. m. ali ahmed4, and lobina abozaid5 1department of ophthalmology, faculty of medicine, omdurman islamic university, omdurman, sudan 2department of family and community medicine, college of medicine, qassim university, buraidah, saudi arabia 3sudan ministry of health, khartoum, sudan 4department of community medicine, faculty of medicine, omdurman islamic university, omdurman, sudan 5department of pathology, college of medicine, qassim university, buraidah, saudi arabia orcid: mawahib a. e. abu elgasim: https://orcid.org/0000-0001-5254-5107 abstract background: the level of awareness of diabetic retinopathy is considered an important factor for early diagnosis and management of diabetic retinopathy. this study aimed to assess the level of awareness of diabetic retinopathy among patients with diabetes mellitus in khartoum, sudan. methods: this cross-sectional study was conducted among diabetic patients attending zeenam and abdullah khalil diabetic centers between june and september 2018. a convenience sample of diabetic patients was used. information on the sociodemographic characteristics of the patients, patients’ knowledge, compliance with available treatments, and routine eye examinations was collected using a semistructured questionnaire. patients were also asked about the barriers that may interfere with a regular eye examination. results: a total of 200 patients were enrolled and 94 (47%) of them were female; 13% of the respondents were diagnosed with diabetic retinopathy, 31.5% were hypertensive, and 13.5% had hyperlipidemia. additionally, 88.5% of the patients were aware that dm can affect their eyes and 87% had never been diagnosed with diabetic retinopathy. although around 83% thought that diabetic retinopathy could lead to blindness, only 35.5% of them had undergone fundus examination by ophthalmologists. moreover, 39% of the participants had irregular diabetes follow-up and 43% monthly follow-up. only 31% went for regular eye check-up; however, their compliance with routine retinal assessment was poor, with a total of 72.5% of participants assuming that they have good vision and need not get their eyes checked up regularly. the chief factor that was related to increased awareness of diabetic retinopathy in the study was the level of education. conclusion: although a large proportion of diabetic patients in khartoum are aware that diabetes mellitus can affect their eyes, regular retinal assessment of patients was poor, thus hindering early diagnosis and management. keywords: awareness, diabetic retinopathy, diabetes mellitus how to cite this article: mohammed i. m. ahmed, mawahib a. e. abu elgasim, mehad a. t. mohamed, manasik m. n. munir, manasik s. n. abdelrahim, zeinab m. m. ali ahmed, and lobina abozaid (2021) “knowledge and awareness of diabetic retinopathy among diabetic sudanese patients, khartoum state, sudan, 2018,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 476–488. doi 10.18502/sjms.v16i4.9945 page 476 corresponding author: mohammed i. m. ahmed; email: sudanretinologist@gmail.com received 18 october 2021 accepted 19 december 2021 published 31 december 2021 production and hosting by knowledge e mohammed i. m. ahmed et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:sudanretinologist@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences mohammed i. m. ahmed et al. 1. introduction according to the international diabetes federation (ifd) data, in 2019, one out of five people over the age of 65 years had diabetes mellitus (dm), and 79% of adults with dm were living in lowand middle-income countries. moreover, dm was claimed to be the cause of 4.2 million deaths [1]. the mortality, morbidity, and cost-related complications of diabetes are on the rise globally and are a persisting global public health problem [2]. diabetic retinopathy (dr) is considered to be the commonest cause of microvascular complications of diabetes and vision loss [3, 4], causing blindness in 1.8 million out of 37 million cases (4.5%) worldwide [5]. many patients may not know about dm and its complications such as dr, and referral system from primary care may be inadequate [6]. screening programs are fundamental especially in low-income countries where the patient–physician ratio is low and services such as dilated fundus examination can be accessed only at certain locations, which could require travelling long distances for many individuals[7]. in a study done in saudi arabia, the prevalence of dr was 15.2%. the duration of dm, uncontrolled diabetes, hypertension, dyslipidemia, nephropathy, insulin treatment, and age were identified as strong predictors of dr among diabetics [8]. there is a variation worldwide in knowledge and practice regarding dm. the awareness among some middle east countries was as follows: in oman, the knowledge about dm diagnosis and eye care was found to be 72.9% and 18%, respectively, and the grade for their attitude toward eye involvement and eye care were 18% and 29.9%, respectively [9]; 75.62% of saudi diabetic patients were aware of the eye disorders dm can cause, 73.80% were aware of the need of a regular eye check-up, and 95% of all participants went for regular ocular examination [10]; in jordan, 88.2% of the patients were aware that diabetes can affect their eyes and 81% reported that dr can lead to loss of vision, 29.5% of participants have had an ocular examination in the previous year [11].while awareness about the importance of routine check-ups for the screening of dr is poor even in the developed countries, the situation is much worse in developing countries. a study in african countries revealed that: in south africa, only 37% of patients had annual eye examinations, 97% reported that dm could affect vision, 82% underwent regular medical follow-up, and 63% had no regular ophthalmic examination [12]; in kenya, 83% of the patients had heard about diabetic eye disease, 60% knew the relationship between diabetic eye disease and dm, and only 50% went for eye examination [13]; in nigeria, 77.7% of diabetic patients were aware that diabetes can affect their eyes, doi 10.18502/sjms.v16i4.9945 page 477 sudan journal of medical sciences mohammed i. m. ahmed et al. however, 58.8% did not know which part of the eye can be affected, only 13.5% were aware that the retina can be affected by diabetes and hypertension was found to be a comorbid factor 44.6% [14]. another study conducted in india aimed to determine the level of knowledge, attitude, and practice found that 42% of their patients had good information about diabetes, 4.5% had good knowledge about dr, and 61.1% did not have an annual eye examination. the most common barrier identified in this study was lack of awareness [15]. very limited literature exists on the knowledge and awareness of dr amongst people with diabetes in sudan. thus, in our research, we tried to assess the awareness of diabetic patients about dr in sudan. the aim of this study was to determine the awareness of dr among diabetic patients in sudan. 2. materials and methods 2.1. study design and setting this cross-sectional study targeted patients diagnosed with dm and attending zeeman and abdullah khalil diabetic centers (specialized centers offering diagnosis and management for diabetic patients, located in khartoum state, omdurman locality). all patients were referred from primary healthcare centers. 2.2. sampling data were collected using a convenience sampling technique. the sample size was calculated using the sample size of the unknown population (cochran’s formula): n = z2p (1–p)/d2, where; n: desired sample size; z: standard error of the mean which corresponds to 95% confidence level (1.96); and p = prevalence (unknown, so it was considered as 0.5). (1.96)2 × 0.5(1–0.5) ÷ (0.05)2 = 384. the study was done over a period of three months (june–september 2018). all patients who attended zeeman and abdullah khalil diabetic centers during the period were enrolled in this study, 200 diabetic patients who met the eligibility criteria of selection were enrolled in the study and informed consent was obtained from all participants. doi 10.18502/sjms.v16i4.9945 page 478 sudan journal of medical sciences mohammed i. m. ahmed et al. 2.3. data collection tools following a thorough literature review, a semi-structured questionnaire was formulated by the investigators. the questionnaire was prepared in english and translated to arabic. the content of the questionnaire was validated by submitting the tool to the experts in the field of ophthalmology for content validation and a pilot study was conducted on a representative population that was not included in the study. the response was then analyzed as to whether the questions were understood or not. four medical personnel were trained in administering the questionnaire. the participants were given the questionnaire and were required to fill it in the presence of the medical personnel after obtaining informed consent. the questionnaire consisted of four parts: (i) patients’ profile which included their names, gender, occupation, marital status, educational status, and their consent for the study; (ii) details of comorbid diseases, if any; (iii) dm-related information such as its duration, control, the modality of diabetes, dm treatment place, and follow-up of dm; and (iv) questions about dr awareness. 2.4. statistical analysis all collected data were entered, stored, and analyzed using the statistical package for social science (spss v.20 [spss inc.; chicago, il, usa]). the association of awareness of dr was evaluated between the groups using unilabiate analysis (chi-square test). p-value < 0.05 was considered statistically significant. 3. results 3.1. patient characteristics the demographic characteristics of diabetic patients recruited in this study are given in table 1. out of the 200 patients who were interviewed, 110 were male (55%) and 90 were female (45%). a total of 171 (85.5%) participants were >40 years of age, 14% were aged between 20 and 40, and only 0.5% were <20 years old, with a mean age of 58.54 +11.4 years. in terms of the level of education, 22.5% of the participants were illiterate, 37.5% were educated up to the primary school level, 23.5% up to the secondary school level, and 16.5% up to the university level (see table 1). doi 10.18502/sjms.v16i4.9945 page 479 sudan journal of medical sciences mohammed i. m. ahmed et al. table 1: demographic characteristics of the study population, n = 200. percentage (%) frequency age group (yr) <20 1 0.5 20–40 28 14 >40 171 85.5 gender group male 110 55 female 90 45 education level university 33 16.5 secondary 47 23.5 primary 75 37.5 illiterate 45 22.5 duration of dm (yr) <10 107 53.5 >10 93 46.5 figure 1: distribution of patients according to follow-up centers for dm. 3.2. dm-related characteristics on being asked about the duration of diabetes, 53.5% replied that they have been diabetic for <10 years, while 46.5% have had it for >10 years (see table 1). as regard to the follow-up centers, 51% of the respondents went to private clinics, 25% to governmental hospitals, 22% to primary healthcare centers, while 2% had no specific follow-up centers (see figure 1). regarding dm follow-up, 43% had a monthly follow-up, while 17%, 39%, and 1% had 3–6 month, irregular, and no follow-up, respectively (table 2). doi 10.18502/sjms.v16i4.9945 page 480 sudan journal of medical sciences mohammed i. m. ahmed et al. table 2: characterization of the sample according to the frequency of dm follow-up. frequency of follow-up visits for dm frequency percentage (%) monthly 86 43 3–6 months 34 17 <6 months 0 0 irregular 78 39 no follow-up 2 1 total sample 200 100 table 3: distribution of patients according to doctor’s advice about dr. percentage (%) frequency had your doctor informed you about dr? 77.5 155 yes 22.5 45 no 100.0 200 total sample figure 2: distribution of patients according to ophthalmic examination. the main source of information about dr, as shown in table 3, was counselling by their doctors for majority of the respondents (155 [77.5%]). table 4 shows that 88 (44%) patients used glucometer at home to monitor diabetes. moreover, with respect to ophthalmic examination, only 71 (35.5%) patients had been examined by an ophthalmologist (figure 2). furthermore, 26 patients were diagnosed with dr (13%), while 174 (87%) were not (figure 3). table 4: distribution of patients according to glucometer use at home. percentage (%) frequency glucometer use at home 44 112 yes 56 88 no doi 10.18502/sjms.v16i4.9945 page 481 sudan journal of medical sciences mohammed i. m. ahmed et al. figure 3: sample according to the diabetic patients diagnosed with dr. table 5: distribution of patients according to comorbid diseases. frequency percentage (%) hypertension yes 63 31.5 no 137 68.5 hyperlipidemia yes 27 13.5 no 173 86.5 3.3. comorbid disease sixty-three respondents (31.5%) were diagnosed with hypertension while only 27 (13.5%) were diagnosed with hyperlipidemia (see table 5). 3.4. knowledge and awareness of dr table 6 details the knowledge and awareness of participants regarding dr. overall, 77 (38.5%) respondents knew that diabetes can affect vision, while 123 (61.5%) did not. table 6: knowledge and attitude regarding diabetic retinopathy. knowledge and awareness yes no do you know that diabetes can affect vision? 77 (38.5) 123 (61.5%) do you know that diabetes can affect your retina? 177 (88.5%) 23 (11.5%) do you know diabetic retinopathy can lead to blindness? 166 (83%) 34 (17%) did you go for regular eye check-ups? 62 (31%) 138 (69%) why don’t you go for regular eye follow-up? n i think l have good vision 100 (72.5%) high cost 30 (21.7%) ophthalmologist not available in diabetic center 8 (5.8%) doi 10.18502/sjms.v16i4.9945 page 482 sudan journal of medical sciences mohammed i. m. ahmed et al. table 7: association between awareness of dr and selected variables. variable awareness p-value yes no age group (yr) <20 1 1 (100%) 0 0.137 20–40 28 24 (85.8%) 4 (14.2%) >40 171 155 (90.6%) 16 (9.4%) gender group male 110 100 (90.9%) 10 (9.1%) 0.377 female 90 74 (82.2%) 16 (17.8) educational level university 33 29 (87.8%) 4 (12.2%) *0.001 secondary 47 41 (87.2%) 6 (13.8%) primary 75 67 (89.4%) 8 (10.6%) illiterate 45 32 (71.1%) 13 (28.9%) duration of diabetes (yr) <10 107 90 (84.1%) 17 (15.9%) *0.003 >10 93 84 (90.3%) 9 (9.7%) moreover, while 177 (88.5%) patients knew that diabetes could affect the retina and cause retinopathy, 23 (11.5%) did not. in addition, 83% of the respondents answered that dr can lead to blindness, while 17% did not know. only 31% of the respondents went for regular eye check-ups, while 69% did not, 72% of whom thought that they had good vision (table 6). 3.5. association between awareness of dr and selected variables (gender, age, duration of dm, and educational level) table 7 shows that the awareness of dr was not significantly associated with patients’ age (p = 0.137) and gender (p = 0.377), but with patients’ duration of dm (p = 0. 003) and their level of education (p = 0. 001). table 8 indicates that glucometer use at home is significantly associated with the level of education (p = 0.003). as seen in table 9, most patients who went to a private clinic (87%) were advised by their doctors for ocular examination by ophthalmologist followed by those who went to a government hospital (73%), and a low percentage for who went to primary healthcare centers. a significant association was observed between the place of follow-up and doctors’ advice (p-value = 0.001). doi 10.18502/sjms.v16i4.9945 page 483 sudan journal of medical sciences mohammed i. m. ahmed et al. table 8: glucometer use at home (*educational level cross-tabulation). educational level illiterate primary secondary university glucometer use at home yes frequency 9 36 25 18 percentage 10.20% 40.90% 28.40% 20.50% no frequency 36 39 22 15 percentage 32.10% 34.80% 19.60% 13.40% total frequency 45 75 47 33 percentage 22.50% 37.50% 23.50% 16.50% p-value 0.003 table 9: dm treatment place (∗did your doctor advise you about dr cross-tabulation?). place of treatment did your doctor advise you about dr? yes no frequency 37 14government hospital percentage 73.6.0% 27.4.0% frequency 1 3none percentage 25.00% 75.00% frequency 28 16primary healthcare percentage 63.60% 36.40% frequency 87 15private clinic percentage 85.30% 14.70% frequency 155 45total percentage 77.50% 22.50% 𝑃-value 0.0001 4. discussion in this cross-sectional study, the majority of the participants were 40 years old and above (85%) which shows an increased incidence of dm with age, a similar finding was reported with a previous study done in south africa [12]. for the prevention of dm complications, especially microvascular complications such as retinopathy, awareness and knowledge, and time management are essential steps [3]. sudan is a country where there is a lack of awareness of dm and of the facilities and resources concerning diabetes with no suitable screening program for the disease. our study revealed that dr was 13% in our studied population, a similar result was obtained by a study in saudi arabia [8]. according to the present study, only 38.5% of the respondents knew that diabetes could affect their eyes, which may be attributed to a lack of awareness among participants. doi 10.18502/sjms.v16i4.9945 page 484 sudan journal of medical sciences mohammed i. m. ahmed et al. the study showed high awareness of dr occurring as a complication of dm among sudanese diabetics, a similar conclusion was suggested by studies done in some middle east countries: oman [9], saudi arabia [10], and jordon [11], and in some african countries: south africa [12], kenya [13], and nigeria [14]. regarding hypertension which is considered as the most common comorbid disease, the same finding was reported in nigeria [14], and was also reported as a risk factor for developing dr in a study done in saudi arabia [8]. although the results showed a high level of awareness about dr in the current study, on the contrary, there was low compliance for ophthalmic examinations to reduce the diabetes eye complications such as dr. there is a noticeable discrepancy between the levels of awareness and compliance in terms of a routine eye examination. only 31% of our participants went for regular eye check-ups that may be due to a lack of awareness and difficulty in the accessibility of services, a slightly comparable value to our finding was found in a kenyan study where only 50% went for eye check-ups [13] and india [15]. the percentage of regular ocular examination identified in our study is stated as being less than that in saudi arabia (95%) and south africa (82%), in which a high percentage of diabetic patients went for regular ocular examinations [10, 12]. when we asked the participants about the reasons that prevented them to get an early dr screening, we found that the main reason was that they need to get it only when their vision is affected. other reasons mentioned were the high cost and the availability of ophthalmologists at the diabetic center. a lack of accurate information about dr is the basic reason for low compliance in attending eye examinations. also, our study showed that 51% of the diabetic patients went to a private clinic, 25% went to government hospitals, and only 22% to primary healthcare centers for treatment which may be due to a lack of referral guidelines regarding dm and dr management for primary care or referral system from primary care being inadequate [6]. regardless of eye examinations, our results revealed that only 35.5% of the patients interviewed were referred to an ophthalmologist by their doctor. there is an urgent need for revision of the general strategy of referrals system to ophthalmologists to be adopted by all general practitioners in sudan. another important finding in this study, that is, the doctor is an important source of information on dr was reported by 77.5% of the participants, a similar result was reported among jordanians [11]. most patients who went to private clinics were advised about dr by the doctors (87%) and this study revealed a significant association between the place of follow-up and physician’s advice about retinopathy, this indicates the role of appropriate health doi 10.18502/sjms.v16i4.9945 page 485 sudan journal of medical sciences mohammed i. m. ahmed et al. education in the prevention of diabetic complications so health education should be a crucial part of the management of a patient with diabetes. the study found that there was a significant association between awareness and education which agreed with the finding of a study done in jordon [11]. in addition, there was an association between the use of glucometer at home and the level of education, these findings highlighted that the level of education is momentous for the prevention of diabetic complications such as dr. there is need for clear guideline protocol for diabetic patients and referral protocol. educational programs should be adopted to increase the awareness of diabetes complications and how to avoid them. diabetic patients must also be advised about regular visits to the diabetic and ophthalmic clinics, an educational brochure should be made available to each patient at diabetic centers. 5. limitations the limitations of this study are the small sample size as present study was conducted at two specialized centers for the treatment of diabetes. there is a need for future research for the examination of the prevalence of retinopathy over a larger variety of areas to find out actual awareness of dr among diabetic patients. 6. conclusion a majority of patients in this study reported a high level of awareness. however, the practice of checking blood sugar and eye check-ups regularly was found to be low among the patients. lack of knowledge concerning the need for a regular eye examination for dr was found to be a major barrier to compliance with a regular eye examination. there is a need to raise awareness for a regular eye examination. the doctors can be the best source for providing this awareness since a high proportion of patients reported that they received their first piece of information from their doctors.acknowledgements the authors are grateful to the staff of the abdullah khalil and zeenam diabetic center in omdurman for granting permission to conduct the study and for their great efforts in dealing with diabetic patients. doi 10.18502/sjms.v16i4.9945 page 486 sudan journal of medical sciences mohammed i. m. ahmed et al. ethical considerations this study was approved by the institutional review board of the faculty of medicine, omdurman islamic university. moreover, data were collected after taking the necessary agreement from the khartoum state ministry of health. competing intereststhere are no conflicts of interest. availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding none. references [1] international diabetes federation. (2019). idf diabetes atlas (9𝑡ℎ ed.). brussels, belgium: international diabetes federation. retrieved from: http://www.diabetesatlas.org (accessed 2020 april 11). [2] sepúlveda, j. and murray, c. (2014) diabetic retinopathy (dr) is the commonest cause of blindness in productive aged of individuals in developed countries. vol. 345, no. 6202, pp. 1275–1278. [3] duh, e. j., sun, j. k., and stitt, a. w. (2017). diabetic retinopathy: current understanding, mechanisms, and treatment strategies: jci insight, vol. 2, no. 14, p. e93751. [4] memon, m. s., shaikh, s. a., shaikh, a. r., et al. (2015) an assessment of knowledge, attitude and practices (kap) towards diabetes and diabetic retinopathy in a suburban town of karachi. pakistan journal of medical sciences, vol. 31, no. 1, pp. 183–188. [5] world health organization. (2012). state the world’s sight: vision 2020: the right to sight: 1999–2005. geneva: who. retrieved from: https://apps.who.int/iris/bitstream/ handle/10665/43300/9241593458_eng.pdf?sequence=1&isallowed=y [6] hipwell, a. e., sturt, j., lindenmeyer, a., et al. (2014)attitudes, access and anguish: a qualitative interview study of staff and patients’ experiences of diabetic retinopathy screening. bmj open, vol. 4, no. 12, p. e005498. doi 10.18502/sjms.v16i4.9945 page 487 https://apps.who.int/iris/bitstream/handle/10665/43300/9241593458_eng.pdf?sequence=1&isallowed=y https://apps.who.int/iris/bitstream/handle/10665/43300/9241593458_eng.pdf?sequence=1&isallowed=y sudan journal of medical sciences mohammed i. m. ahmed et al. [7] palmer, j. j., chinanayi, f., gilbert, a., et al. (2014) trends and implications for achieving vision 2020 human resources for eye health targets in 16 countries of sub-saharan africa by the year 2020. human resources for health, vol. 12, article 45. [8] magliah, s. f., bardisi, w., al attah, m., et al. (2018). the prevalence and risk factors of diabetic retinopathy in selected primary care centers during the 3-year screening intervals journal of family medicine and primary care, vol. 7, no. 5, pp. 975–981. [9] khandekar, r., al harby, s., al harthy, h., et al. (2010). knowledge, attitude and practice regarding eye complications and care among omani persons with diabetes a cross sectional study. oman journal of ophthalmology, vol. 3, no. 2, pp. 60–65. [10] al zarea, b. k. (2016). knowledge, attitude and practice of diabetic retinopathy amongst the diabetic patients of aljouf and hail province of saudi arabia. journal of clinical and diagnostic research, vol. 10, no. 5, pp. nc05–nc08. [11] bakkar, m. m., haddad, m. f., and gammoh, y. s. (2017). awareness of diabetic retinopathy among patients with type 2 diabetes mellitus in jordan. diabetes, metabolic syndrome and obesity, vol. 10, pp. 435–441. [12] phillipsa, k. c., mashigeb, k. p., and clarke-farrc, p. c. (2011). knowledge of diabetes mellitus in privately funded diabetic patients attending a rural optometric practice in malmesbury, south africa. the south african optometrist, vol. 71, no. 2, pp. 70–77. [13] mwangi, m. w., githinji, g. g., and wanjiru, f. (2011). knowledge and awareness of diabetic retinopathy amongst diabetic patients in kenyatta national hospital, kenya. international journal of humanities and social science, vol. 1, no. 21, pp. 140–146. [14] bodunde, o. t., odusan, o., ogunsemi, o. o., et al. (2014). awareness of ocular complications of diabetes among diabetic patients in a tertiary hospital in western nigeria. iosr journal of dental and medical sciences, vol. 13, no. 6, pp. 09–12. [15] srinivasan, n. k., john, d., rebekah, g., et al. (2017). diabetes and diabetic retinopathy: knowledge, attitude, practice (kap) among diabetic patients in a tertiary eye care centre. journal of clinical and diagnostic research, vol. 11, no. 7, pp. nc01–nc07. doi 10.18502/sjms.v16i4.9945 page 488 introduction materials and methods study design and setting sampling data collection tools statistical analysis results patient characteristics dm-related characteristics comorbid disease knowledge and awareness of dr association between awareness of dr and selected variables (gender, age, duration of dm, and educational level) discussion limitations conclusion ethical considerations availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 4, doi 10.18502/sjms.v16i4.9953 production and hosting by knowledge e research article expression of cyclin d1 in oral squamous cell carcinoma malak abdulrahman seid ahmed1, nazik omer2, ahmed m. suliman2, and mona ellaithi1 1faculty of medical laboratory sciences, al-neelain university, khartoum, sudan 2department of oral and maxillofacial surgery, division of oral pathology, faculty of dentistry, university of khartoum, sudan orcid: mona ellaithi: https://orcid.org/0000-0002-8380-0227 abstract background: cyclin d1 expression regulates normal cell cycle. its deregulation or overexpression may cause disruption in the normal cell cycle control and lead to cancer progression. in this study, we aimed to study the expression of cyclin d1 in oral squamous cell carcinoma (oscc) and find its association with the different grades of oral tumors, if any. methods: this cross-sectional study included 40 formalin-fixed paraffin-embedded tissue blocks specimens of oscc with variable grades. the expression of cyclin d1 was evaluated through immunohistochemical (ihc) staining. results: a total of 40 (9 female and 31 male) samples were included, with a maleto-female ratio of 3.4:1. the age ranged between 25 and 90 years with an average age of 65.5 years. twenty-five (62.5%) samples were diagnosed as well-differentiated squamous cell carcinoma (wdscc) and fifteen (37.5%) as poorly differentiated squamous cell carcinoma (pdscc). no cases of moderately differentiated squamous carcinoma were included in the study. the expression of cyclin d1 was detected in the cases of wdscc and a lesser expression was seen in the pdscc with a p-value of 0.0003, or 1581 and 95% ci (29.8239 to 83810.7113). conclusion: cyclin d1 is expressed in oscc and stronger expression was detected in wdscc. keywords: cyclin d1, oral squamous cell carcinoma (oscc), toombak, sudanese oral cancer, immunohistochemistry 1. introduction cyclin-dependent kinases (cdks) are a family of serine/threonine kinases controlling progression through the cell cycle [1]. the cyclin-cdks direct a linear progression of actions that transfer cells from a resting state (g0) to cell division (m). if any abnormalities occur in any of these phases, cdks start a signal that triggers a cell cycle arrest until the issue is resolved. there are 11 cyclins found in human cells with many having subfamily members (e.g., d-type cyclin d1, d2, and d3) [2]. if a mutation arises, it how to cite this article: malak abdulrahman seid ahmed, nazik omer, ahmed m. suliman, and mona ellaithi (2021) “expression of cyclin d1 in oral squamous cell carcinoma,” sudan journal of medical sciences, vol. 16, issue no. 4, pages 558–566. doi 10.18502/sjms.v16i4.9953 page 558 corresponding author: mona ellaithi; email: ellaithi_mona@gmail.com received 14 august 2021 accepted 16 november 2021 published 31 december 2021 production and hosting by knowledge e malak abdulrahman seid ahmed et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ellaithi_mona@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences malak abdulrahman seid ahmed et al. affects the cyclin function and can lead to derailed cellular proliferation and thus cancer. cyclin d1 overexpression is important for the development and progression of several cancers including breast, esophagus, bladder, and lung [3–10]. different studies have reported increased cyclin d1 in oral squamous cell carcinoma (oscc) [11–15]. however, the association of cyclin d1 with pathological grading was inconclusive. therefore, this study aimed to evaluate the expression of cyclin d1 in oscc in sudanese patients and its potential association with cancer grade. 2. materials and methods this cross-sectional study included a total of 40 formalin-fixed, paraffin-embedded tissue samples histopathologically diagnosed with different grades of squamous cell carcinoma of the oral cavity. the samples were recruited from the upper aerodigestive tract (uadt) biobank in collaboration with the pathology department, khartoum university during the years 2014–2016. then, the immunohistochemical (ihc) staining was carried out using the indirect streptavidin-biotin method. in the beginning, sections from each tissue block were cut to a thickness of 3 μm by rotary microtome, mounted in positively charged slides then de-paraffinized in an oven for 30 min and treated in xylene. rehydration was carried out in graded ethyl alcohol (100%, 90%, 70%, 50%, respectively) and transferred into distilled water for 2 min. antigen retrieval was performed by using a water-bath with a citrate buffer (ph 6.8). then, slides were incubated for 10 min in 0.3% hydrogen peroxide to block endogenous peroxidase activity. the slides were then treated with anti-cyclin d1 primary antibody for 20 min and washed in phosphate buffer saline (ph 7.4). after that, the slides were treated with biotinylated secondary antibody for 20 min and then incubated in streptavidin-horseradish peroxidase for 15 min, washed in phosphate buffer saline (ph 7.4), incubated in 3-3 diaminobenzidine tetrahydrochloride (dab) substrate solution for 7 min, and then washed in a running tap water. the slides were counterstained in mayer’s hematoxylin stain for 1 min, dehydrated in graded alcohol, cleared with xylene, and finally mounted in dpx mounting media [16]. all quality control measures were adopted; positive and negative control slides were used during ihc staining. detection of more than five cells with brown nucleus per one field is considered a positive result. data analysis was done using the spss v.16. the mean frequency and chi-square test values were calculated and p-value < 0.05 was considered significant. doi 10.18502/sjms.v16i4.9953 page 559 sudan journal of medical sciences malak abdulrahman seid ahmed et al. 3. results the study included 9 female and 31 male samples with a male-to-female ratio of 3.4:1. the age ranged between 25 and 90 years with an average age of 65.5 years. twenty five (62.5%) samples were diagnosed as well-differentiated squamous cell carcinoma (wdscc) and 15 (37.5%) as poorly differentiated squamous cell carcinoma (pdscc) (table 1). there was no moderately differentiated squamous cell carcinoma case at the time of the study. the expression of cyclin d1 was strongly detected in the cases of wdscc, while a lesser expression was seen in the cases of pdscc. cyclin d1 expression showed a p-value of 0.0003, or 1581, and 95% ci (29.8239 to 83810.7113) (table 2). 4. discussion cyclin d1 expression occurs during the g1 phase of the cell cycle. its fundamental role is to integrate extracellular growth factor signals with the cell cycle regulatory mechanism [17–19]. deregulation which leads to overexpression of cyclin d1 may shorten the g1 phase, increase cell proliferation, and reduce the need to growth factors [20], which in turn might result in an accumulation of unrepaired dna mutations resulting in loss of cell cycle control and thus tumor formation [21]. in the present study, the average age of the patients was 65.5 years, which is the common age in patients diagnosed with oral cancer. oral cancer develops mainly between the sixth and the seventh decades of life and incidence in younger people (aged <40 years) is infrequent [22 –28]. in the arab countries, including sudan, oral cancer patients were mostly in their 50s and 60s, and the rate at a younger age was reported [29]. in this study, males were three times more affected with oscc than females, an observation reported by many investigators [30–35], including sudanese scientists who had attributed males’ increased exposure to their frequent use of toombak [36, 31, 37]. furthermore, it is known that scc constitutes 90% of the oral cancer [38, 39] and that wdscc was more common than other types, thus our findings were expected. the study showed overexpression of cyclin d1 in 62.5% of cases examined. this was comparable with previous studies [40, 41, 42] who reported an overexpression in oral scc in 68%, 63%, and 70.7% of the cases, respectively. here, and based on the grade of oscc, cyclin d1 expression was mainly detected in wdscc and a lesser expression in pdscc. this observation is different from what was reported by mate et al. in 1996 [43] who found cyclin d1 expression significantly doi 10.18502/sjms.v16i4.9953 page 560 sudan journal of medical sciences malak abdulrahman seid ahmed et al. increases with the increase in differentiation of oscc, however, similar to saawarn et al., who showed lesser expression with the advanced grades [44]. the diverse technical and biological reasons play a role in cyclin d1 expression which is why the role of cyclin d1 in cancer initiation and progression appears to be complex [45]. this could explain the contradicting prognostic significance of cyclin d1 [46–49]. on the other hand, hpv infection remains to be the best prognostic factor for head and neck cancers. this is because patients diagnosed with hpv infection have better clinical outcomes than other patients who are not [50]. this might reflect the fact that the cyclin d1 is rarely amplified in hpv-infected tumors [51, 52]. although we do not have information on hpv infection on the studied samples, a previous study on sudanese patients diagnosed with upper aerodigestive tract cancers showed 26 (17.3%) out of 150 patients were positive for hpv [53]. in conclusion, cyclin d1 can be used in the diagnosis of oscc and its relationship with tumor progression needs to be further investigated. acknowledgements “the samples reported in this article were recruited from the uadt cancers (use the full name) biobank in collaboration with the department of oral and maxillofacial surgery, division of oral pathology, faculty of dentistry, university of khartoum which provided the paraffin embedded oral tissue samples. the establishment of uadt biobank was support of a return grant obtained within the framework of the international agency for research on cancer (iarc) research training and fellowship programme.” the uadt biobank was established from this fund. ethical consideration this project was approved by the national research ethical review committee health research council, republic of sudan national ministry of health in 2014. all samples are part of the uadt cancer biobank. informed consent was signed by all study participants. competing interests the authors declare that they have no competing interests. doi 10.18502/sjms.v16i4.9953 page 561 sudan journal of medical sciences malak abdulrahman seid ahmed et al. table 1: the different grades of oral cancer scc. oral cancer grade number of diagnosed patients percentage (%) wdscc 25 62.5 pdscc 15 37.5 total 40 100 table 2: the association of cyclin d1 and oc histopathology grade. cyclin d1 expression number of patients histopathology grade pvalue or 95% ci cyclin d1 strong expression 25 wdscc 0.0003 1581 29.8239 to 83810.7113 cyclin d1 weak expression 15 pdscc availability of data and material data published in this project will be available upon request; however, patients’ identity will be blocked in order to protect the study participants. funding no funding was received. references [1] malumbres, m. and barbacid, m. 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(2018) the genome-wide molecular landscape of hpv-driven and hpv-negative head and neck squamous cell carcinoma. in b. burtness and e. golemis (eds.), molecular determinants of head and neck cancer. current cancer research. cham: humana press. [51] hermida-prado, f., menéndez, s. t., albornoz-afanasiev, p., et al. (2018). distinctive expression and amplification of genes at 11q13 in relation to hpv status with impact on survival in head and neck cancer patients. journal of clinical medicine, vol. 7, no. 12, p. 501. [52] van kempen, p. m., noorlag, r., braunius, w. w., et al. (2015). clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma. cancer medicine, vol. 4, no. 10, pp. 1525–1535. [53] mohamed, f. e., aldayem, l. n., hemaida, m. a., et al. (2021). molecular detection of human papillomavirus-16 among sudanese patients diagnosed with squamous cell carcinoma and salivary gland carcinoma. bmc research notes, vol. 14, no. 1, p. 56. doi 10.18502/sjms.v16i4.9953 page 566 introduction materials and methods results discussion acknowledgements ethical consideration competing interests availability of data and material funding no funding was received. references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9701 production and hosting by knowledge e research article using logbooks to enhance students’ learning: lessons from a mixed-methods study in an undergraduate surgical rotation ahmad abdulazeem abdullah omer department of surgery, faculty of medicine, prince sattam bin abdul aziz university, alkharj, ksa orcid: ahmad abdulazeem abdullah omer: https://orcid.org/0000-0001-8311-8888 abstract background: logbooks are frequently used in medical education to enhance and monitor students’ learning. however, some barriers that may diminish their benefits have been reported. this study aims to evaluate the usefulness of logbooks to students’ learning and identify the factors, which may contribute to their outcomes in learning milieus. methods: the study used a mixed-methods approach. quantitative and qualitative data were collected from the medical students in the fourthand sixth-year classes and their teachers in the department of surgery at the faculty of medicine at university of tabuk in the academic year 2016–2017. data were collected using questionnaires, focused group discussions, and personal interviews. results: eighty-nine (49 fourth year and 40 sixth year) students and six teachers participated in the study. logbooks were perceived as useful to students’ learning by 83.3% of the teachers and 75.3% of the students. logbooks enhanced students’ learning through identification of areas of weaknesses, encouraged seeing more patients’ problems and reading in-depth about some topics, and improved students’ writing skills. barriers to learning from logbooks included poor-quality feedback, no opportunities for feedback discussion, and unfair marking. differences in the students’ perceptions of the usefulness of logbooks were observed based on their learning stage. conclusion: logbooks are useful to students’ learning in many aspects; however, certain factors could diminish their benefits. students’ attitude toward the logbook was more favorable during their early clinical experience. faculty development programs and careful supervision of students’ work may improve the outcome of logbooks in clinical placements. keywords: logbooks, clinical teaching, written feedback, surgery, saudi arabia 1. introduction the use of logbooks to enhance learning is well-known in the educational enterprise, including medicine, where they have numerous advantages to learners, instructors, how to cite this article: ahmad abdulazeem abdullah omer (2021) “using logbooks to enhance students’ learning: lessons from a mixed-methods study in an undergraduate surgical rotation,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 409–429. doi 10.18502/sjms.v16i3.9701 page 409 corresponding author: ahmad abdulazeem abdullah omer; email: a.omer@psau.edu.sa received 18 july 2021 accepted 25 august 2021 published 30 september 2021 production and hosting by knowledge e ahmad abdulazeem abdullah omer. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:a.omer@psau.edu.sa https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ahmad abdulazeem abdullah omer and educational institutions [1–3]. logbooks are applied in training programs based on the philosophy of the collection of evidence that learning has taken place [4, 5]. when designed and utilized properly, logbooks promote student learning, help in their assessment, and enhance their professional growth [6, 7]. they foster students’ progress in the acquisition of knowledge and skills in patient management and care and encourage self-directed learning [8–11]. logbooks positively influence students’ learning by providing a clear picture of what they have accomplished during their learning experiences [12]. this is argued to add structure and organization and help bridge gaps in the apprenticeship model of clinical teaching that was often ‘unstructured and opportunistic’ [13–16]. despite the extensive use of logbooks in undergraduate and postgraduate medical education nowadays, their application to enhance students’ learning was met with equivocal and sometimes contradicting results [17–20]. some studies showed that logbooks neither enhanced students’ learning nor did they assess their competency [4, 21, 22]. besides, it was pointed out that trainees might keep logbooks not because they are useful to their learning, but only because it is mandatory [23]. reported limitations to learning from logbooks stem from the quality of written feedback, unavailability of discussion opportunities of feedback, and issues related to the logbook’s structure and marking [18, 24, 25]. 1.1. setting and context the department of surgery in the faculty of medicine at university of tabuk, in northwest saudi arabia, recently introduced a structured logbook to aid students’ learning in the clinical courses run by the department. before that and for around two years, the department used to administer a portfolio that was later canceled due to poor students’ engagement and weak outcomes. however, it was observed that teachers’ and students’ opinions regarding logbook activity were still mixed. given these contrasting opinions, and subjective decisions, it was decided to study the use of logbooks and apply the findings to inform decisions regarding teaching and learning practices in the department aiming to enhance the students’ ability to learn better in the clinical environment. 1.2. aims and objectives this study aims to assess the usefulness of logbooks to promote students’ learning in our context and answer the following questions: how are logbooks perceived by doi 10.18502/sjms.v16i3.9701 page 410 sudan journal of medical sciences ahmad abdulazeem abdullah omer students and teachers about achieving learning outcomes? what aspects of the logbooks are experienced as enablers or barriers to learning? furthermore, how students’ individual characteristics (gender, level of study, and academic performance) affect learning experienced with logbooks? 2. materials and methods 2.1. study design the study involved a mixed-method (pragmatic) approach [27] and followed an “explanatory model” in which qualitative data were used to explain an initial set of quantitative results [28]. the quantitative part was designed to find out whether logbooks are useful to students’ learning or not and assess the influence of the learner’s characteristics (gender, stage of learning, and academic excellence). the qualitative part aimed to figure out how logbooks and the included feedback may support or hinder learning. 2.2. materials and subjects the study population consisted of 69 sixth-year students; 37 males and 32 females (in the 12-week surgical module) and 70 fourth-year students; 38 females and 32 males (in the 15-week clinical skills module) in addition to six teachers involved in teaching both modules (excluding the researcher to minimize bias) in the academic year 2016–2017. each module is run twice in a single academic year because male and female students were taught separately. a logbook was designed to mirror the activities that students were expected to do in the hospital during their clerkships period aligned to the course objectives [1, 18]. these include clinical, diagnostic, procedural, and patient management skills. at the beginning of each module, students were introduced to the rationale and benefits of logbooks, and how to use them effectively for their learning [29]. students were required to submit the logbook weekly to the department in order to receive timely feedback. each logbook received a mark out of 5 (based on the marking criteria) weekly, and all marks were averaged at the end of each module to give rise to 5% of the summative final course mark. this small mark was meant to incentivize students’ work and encourage them to do their best in the logbook exercise and, at the same time, minimize significant variations in their final course grades [14]. doi 10.18502/sjms.v16i3.9701 page 411 sudan journal of medical sciences ahmad abdulazeem abdullah omer 2.3. statistics 2.3.1. quantitative data a self-administered questionnaire was developed following a review of the relevant literature of learning from logbooks and written feedback given the study goals. two versions of the questionnaire were developed; one for students and another for teachers, both were piloted using a selected sample of students and teachers, respectively. each questionnaire included closed-ended and likert-type questions with 5-point options for teachers and forced 4-point options for students (to encourage them to provide clear answers) [30]. the final logbook mark and the updated grade point average (gpa) were recorded for each student. quantitative data were analyzed using the spss computer software (spss inc. chicago, illinois) version 16, and responses were presented as frequencies and percentages of the total [31]. alpha cronbach statistic was used to assess the internal consistency of the questionnaire’s items and validate their results [32]. correlations were made between the students’ perceptions of the usefulness of logbooks to their learning in one hand and their individual characteristics (gender, stage of learning, and level of academic performance [inferred from their gpa and logbook marks]) on the other hand, and significance of results was tested using the independent sample t-test. the likert-type questions were analyzed using the likert-scale method. 2.3.2. qualitative data qualitative data were collected from students and teachers through focus group discussions and personal interviews, respectively. appointments for the interviews and the focus group discussions were agreed with participants based on their convenient time and place to enhance enrollment. two faculty members from other departments in the college and the researcher conducted the interviews and the focus group discussions. questions posed in the focus group discussions and interviews addressed the main objectives of the study, as mentioned earlier, and prompts were provided wherever needed. data were transcribed to papers owing to the difficulty of audiotape recording of the focus group discussions, particularly with the female students. thematic analysis was applied to analyze the qualitative data, which were categorized under common emerging themes [33]. doi 10.18502/sjms.v16i3.9701 page 412 sudan journal of medical sciences ahmad abdulazeem abdullah omer 3. results table 1 shows the number and the distribution of the student participants over the two classes in addition to the participation rates in the questionnaire and focus group discussion rounds. the alpha-cronbach reliability score of the students’ questionnaire was 0.78, which indicates the homogeneity and consistency of the questionnaire items. table 1: questionnaire response rate, number, and groups of the students’ focus group discussion sessions (n = 89). questionnaire response rate total male students female students sixth-year students 12 (32.4%) 28 (82.4%) 40 (56.3%) fourth-year students 24 (63.2%) 25 (78.1%) 49 (70%) total 36 (52.2%) 53 (73.6) 89 (63.1%)𝑎 gender/class participation in the focus group discussion total male students female students 1st group 2nd group 1st group 2nd group sixth-year students 9 3 16 9 37 (52.1%) fourth-year students 8 9 17 7 41 (58.6%) total 29 (42%) 49 (68.1%) 78 (55.3%)𝑎 𝑎the total number of students in both classes = 141. table 2 shows students’ responses to the closed-ended questions. table 3 shows correlations between the students’ perception of the usefulness of logbook and written feedback to their learning on one side and their gender and stage of learning on the other. table 4 highlights the relationship between the students’ perception of the usefulness of logbooks to their learning and their academic excellence. a statistically significant difference in the students’ perception of the logbook was noted concerning their stage of learning; the fourth-year students perceived the logbook more positively than their senior counterparts. gender and academic excellence did not give rise to significant differences. table 2: students’ overall responses to the closed-ended questions (n = 89). no. item students’ responses total number of responses yes no 1. were logbooks useful to your learning? 67 (75.3%) 22 (24.7%) 89 2. do you think the written feedback provided has improved your learning? 60 (67.4%) 29 (32.6%) 89 3. do you think the feedback provided has enabled you to improve from one logbook activity to another? 63 (70.8%) 26 (29.2%) 89 doi 10.18502/sjms.v16i3.9701 page 413 sudan journal of medical sciences ahmad abdulazeem abdullah omer table 3: students’ responses to the closed-ended questions according to their level of study and gender (n = 89; fourth year = 49, sixth year = 40, males = 37, females = 52). no. item fourth-year students sixth-year students p-value useful not useful useful not useful 1. do you think the logbook was useful to your learning during the course? 45 (91.8%) 4 (8.2%) 22 (55%) 18 (45%) 0.000 2. have you been involved in receiving written feedback during your previous studies? yes no yes no 0.186 29 (61.7%) 18 (38.3%) 30 (75%) 10 (25%) 3. do you think the written feedback provided has improved your learning? 39 (79.6%) 10 (20.4%) 21 (52.5%) 19 (47.5%) 0.007 4. do you feel the feedback provided has enabled you to improve from one logbook activity to another? 36 (73.5%) 13 (26.5%) 27 (67.5%) 13 (32.5%) 0.538 no. item male students female students p-value useful not useful useful not useful 1. do you think the logbook was useful to your learning during the course? 29 (78.4%) 8 (21.6%) 38 (73.1%) 14 (26.9%) 0.568 2. have you been involved in receiving written feedback during your previous studies? yes no yes no 0.847 24 (66.7%) 12 (33.3%) 35 (68.6%) 16 (31.4%) 3. do you think the written feedback provided has improved your learning? 27 (73%) 10 (27%) 33 (63.5%) 19 (36.5%) 0.345 4. do you feel the feedback provided has enabled you to improve from one logbook activity to another? 27 (73%) 10 (27%) 36 (69.2%) 16 (30.8%) 0.702 table 4: correlation between students’ perceptions of usefulness of logbook to their learning and their final logbook mark and gpa (n = 89). usefulness/ item useful not useful total number of responses p-value n mean sd n mean sd final logbook mark 57 4.52 0.33 19 4.3 0.68 76* 0.07 gpa 49 4.01 0.43 20 4.04 0.35 69* 0.29 *missing values. doi 10.18502/sjms.v16i3.9701 page 414 sudan journal of medical sciences ahmad abdulazeem abdullah omer table 5 compares the overall students’ responses to the likert-type questions according to their level of study and gender. a statistically significant difference was observed between the students based on their learning stage. table 5: comparison between the overall response of the students to the likert-type questions according to their level of study and gender (n = 89). level of study n mean sd p-value* fourth year 44** 3.56 0.66 0.016 sixth year 40 3.23 0.58 gender level of study n mean sd p-value* males fourth year 24 3.53 0.52 0.194 sixth year 12 3.28 0.53 females fourth year 19** 3.60 0.82 0.062 sixth year 28 3.2 0.61 *p ≤ 0.05; **missing values. while all teacher participants perceived their feedback as useful to students, only five (83.3%) indicated that the logbook is useful to students’ learning. 3.1. results of the thematic analysis of the qualitative data figure 1 summarizes the factors perceived by the study participants to support or hinder learning from logbooks emerging from the focus group discussions and interviews. figure 2 summarizes the factors that converged on and influenced students’ acceptability of written feedback as emerged from the focus group discussions and interviews. iden�fica�on of mistakes encourage to see cases comprehensio -n of knowledge prepare for future job improved wri�ng skills quality feedback poor feedback focus on grammar and spelling inconsistency of feedback lack criteria of good performance unfair marking no interac�on support learning hinder learning figure 1: overarching themes, subthemes, and their relationship to each other regarding the perceived usefulness of logbooks to student learning (arrows indicate a dual role for the factors). doi 10.18502/sjms.v16i3.9701 page 415 sudan journal of medical sciences ahmad abdulazeem abdullah omer feedbackfeedback perceived asppeerrcceeiivveedd aass useful anduusseeffuull aanndd accepted feedback quality consistency of feedback percep ons of teacher’s ability discussion and interac on focus on knowledge figure 2: overarching themes, subthemes, and their relationship to each other regarding the perceived usefulness and acceptability of feedback (arrow indicates a dual role for the factor). 4. discussion this study aimed to investigate the usefulness of logbooks to students’ learning from students’ and teachers’ perspectives and how they may influence learning, whether positively or negatively. study findings will be discussed under three headings: perceptions of the usefulness of logbooks to learning, the role of logbooks as promoters and hinderers of learning, and the role of the individual characteristics of learners in the process. 4.1. perceptions of the usefulness of logbooks to students’ learning the usefulness of logbooks to enhance students learning is frequently reported as mentioned earlier, however, some studies have shown the contrary. for example, busemann et al. (2011) elaborated on the use of a logbook to enhance students’ learning in a surgical clerkship. they reported that <35% of the students perceived logbook as useful to their learning [34]. they argued that, although the logbook is a powerful learning tool, it should be adapted to the students’ needs or otherwise may demotivate them and inhibit their learning (e.g., teacher’s guidance and structured training). although both students and teachers perceived the logbook and written feedback as useful, contrary to their teachers, some students were not pleased with the quality of feedback they received in logbooks, which they often described as unclear, unfair, doi 10.18502/sjms.v16i3.9701 page 416 sudan journal of medical sciences ahmad abdulazeem abdullah omer inconsistent, and does not involve suggestions for improvement. this was evident in some students’ comments like: “i used to receive the same comments, no improvement because it did not show me how to do that.” sy6f (please refer to the list of abbreviations at the end of the article) “sometime feedback is contradicting, what is correct for one teacher is not necessarily so for others.” sy4f such discrepancies in the perceptions of feedback between students and teachers are one of the documented barriers to effective use of feedback as a powerful tool for learning. carless (2006), and abraham and singaram (2019) have reasoned discrepancy in the feedback perception to the different interpretations of the feedback message between students and teachers [35, 36]. in consonance, boud and molloy (2013) have affirmed the importance of interaction and closure of the loop in the feedback process, which depicts feedback as a dynamic process between the feedback parties [37]. however, and in relevance to the context of this study, rae and cochrane (2008) highlighted the difficulty of the provision of feedback in modular systems of teaching where, owing to the tight schedules, the feedback provided tend to be summative rather than formative [38]. also, dahllof et al. (2004) noticed that although students in their study perceived feedback as useful, they still suffered different opinions on clinical knowledge among teachers and insufficient feedback volume. they argued, ”students’ need of feedback is difficult to satisfy” [39; p. 169]. for instance, a fourth-year student stated: “some teachers’ comments were based on their experience and did not necessarily agree with other teachers or, sometimes, with what is reported in the literature.” sy4f despite the difficulties in the process of feedback execution, many reports have encouraged teachers to invest time and effort to provide meaningful feedback and avail opportunities to discuss the logbook work with their students [4, 15, 24, 40, 41]. 4.2. logbooks as promoters of students’ learning 4.2.1. role of feedback many students valued the logbook’s role in showing them their mistakes and aspects of their work which require revision and correction and, occasionally, suggestions on doi 10.18502/sjms.v16i3.9701 page 417 sudan journal of medical sciences ahmad abdulazeem abdullah omer how to improve [18]. such benefits coincide with the findings of barbieri et al. (2015) and are exemplified in the following students’ quotes: “it was helpful to know your mistakes and avoid them in the future.” sy4f “it gives different views of points and experiences from teachers’ side on how to improve.” syf6 similar to the findings of smith et al. (2014), safari et al. (2017), and other researchers, such benefits can be attributed to the regular feedback that students received through the weekly submission of the logbook and demonstrates the vital role of timely feedback in the process [4, 36, 42, 43]. this ties in with the teachers’ results in the current study and underlines one of the essential advantages of the logbook to learning; assessment of students’ progression in acquisition of knowledge and skills during their learning, which was frequently reported [10, 44–46]. carless (2006) and carless et al. (2011) have pointed to the role of the short feedback cycles in the multistage tasks strategy pertinent to the logbook exercise which enable teachers to see the “echo” of their feedback; the learner’s response and improvement [35, 47]. in the same vein, a teacher commented: “they come to know what was positive and what was negative regarding their performance, they learned about the deficiencies and the strengths in their work and then planned to improve it.” t1 the logbook demonstrated how students assimilated and responded to the feedback on previous work to show improvement in their future assignments. barbieri et al. (2015) have shown similar results in an online logbook project in an anesthesia training program, in addition to some other researchers. therefore, logbooks may potentially improve the structure of training and enable students to demonstrate progression in learning and accomplishment of educational objectives [18, 43, 47]. 4.2.2. provision of opportunities to learn from patients many students and teachers indicated that the logbook encouraged seeing more and a variety of cases and learn from them. the logbook and the accompanying feedback were perceived as a trigger for learning. similar results were shown by chiesa et al. (2013) using logbooks in a clinical rotation and safari et al. (2014) applying logbooks in anatomy teaching [15, 43]. the following quotes demonstrate such benefits to students learning: doi 10.18502/sjms.v16i3.9701 page 418 sudan journal of medical sciences ahmad abdulazeem abdullah omer “it allows writing in-depth about some cases, and the feedback helps to refine the documented information.” sy6m “i was encouraged to see variety of cases and read about them.” sy4fm “it encouraged students to see cases in the hospital and how to communicate with patients and how to do procedures.” t1 logbooks promote learning from the individual cases reported in them and may prove exposure to an appropriate case-mix which are essential parts of the clinical learning. watters et al. (2006) commented on the use of logbooks in a surgical rotation in australia and asserted that individual cases reported in logbooks drive students learning. wright et al. (2017) and buckley et al. (2009) have shown similar supporting evidence of logbooks and portfolios in the medical education [9, 20, 21]. however, and interestingly, some fourth-year students claimed not to benefit from seeing cases in the hospital. two of them commented: “cases were repeating over time thus the benefit was limited.” sy4m “it was just repetition, doing the same task again and again.” sy4m this aligns with the reported difficulties that junior students may experience in learning from logbooks. raghoebar-krieger et al. (2001) indicated that junior students may find difficulty to report all the cases that they came across in the hospital because their knowledge and skills at that stage are insufficient [14]. they added, junior students engage in a process of socialization due to their unfamiliarity with hospital environments, and may, therefore, overlook some of the cases that they have seen during their training. interestingly, uther and ooi (2016) have noticed that the students in their series tended to report the same cases regardless of the hospital or season of training. they reasoned such observation to the tendency of students to overlook some cases [48]. poor students’ guidance due to clinicians’ heavy workloads and busy schedules, in addition to the burden of data entry and limited opportunities to interact with patients on the learner’s side may also be responsible factors [1, 9, 50]. likewise, alabbad et al. (2019) have argued that senior students may benefit from logbooks more than their junior counterparts, where they tend to select cases that provide more significant learning opportunities; however, no correlation to their final course grades was observed [4]. by contrast, shaban et al. (2018) have noticed that the final-year medical students in their series have seen less than the expected cases and procedures in a shift of emergency medicine [49]. it was argued that students might not learn from the experiences that they doi 10.18502/sjms.v16i3.9701 page 419 sudan journal of medical sciences ahmad abdulazeem abdullah omer encounter in the hospitals, and to prove the contrary, evidence (outcome measure) that learning has ensued should be provided [49]. watters et al. (2006) commented on the use of a logbook system in a surgical placement and argued that an evidence of learning from the logbook exercise and the contribution of supervisors to students’ achievements should be demonstrated [21]. therefore, careful supervision and mentoring of junior students with their logbook work in addition to claiming students’ follow-up exercises (e.g., assignments, write-ups, and case-based discussion) based on their logbooks’ entries might be reasonable strategies to heighten their engagement and benefit from the exercise. 4.2.3. improve writing skills many students, also supported by some teachers, indicated that the logbook had improved their writing skills. this applies to the medical terms and knowledge as well as to the english language and grammar. this is highlighted in the following students’ comments: “it was useful for correction of spelling mistakes and writing in grammatical order.” sy6m “it helped me to improve my spelling mistakes.” sy4m “it improved their handwriting, spelling and english language. in general, this is one of their few chances in the college to learn that.” t4 however, other students suffered due to too much focus of feedback on grammar and spelling mistakes at the cost of medical information. a student commented: “concentration was mainly on grammar and handwriting, feedback on knowledge was ignored.” sy6f ruscher et al. (2010) studied feedback behaviors in a multiracial setting and asserted that high-quality feedback has to focus on student’s work leading to transferable skills rather than just correcting grammatical and spelling errors [51]. moreover, bing-you et al. (1997) indicated that students may tend to disregard feedback that is “stylish” in nature and if there is too much focus on unimportant areas [52]. therefore, a balanced written feedback that addresses students’ work mainly from clinical and disciplinary points of view with attention to the principles of english language and scientific writing is often worth consideration. doi 10.18502/sjms.v16i3.9701 page 420 sudan journal of medical sciences ahmad abdulazeem abdullah omer 4.2.4. relation to students’ future career a unique advantage of the logbook indicated by some teachers in this study is that it prepares students for their future career; however, students did not mention that. a teacher said: “the nature of exercises in the logbook, e.g., writing medical notes and doing patient follow-up, is the same kind of practice that they would carry out in their future career.” t24 it was reported that portfolio work increased students’ preparedness to conduct the same tasks in the future and taught them to keep data to perform an audit, all of which have essential implications for their professional life [9, 18, 21]. for instance, buckley et al. (2009) argued that keeping a reflective learning document in the undergraduate phase prepare students for the higher stages of training [20]. in the same vein, shahi et al. (2015) evaluated students’ participation in three training settings through analysis of their logbook entries. they reported higher patient engagement and better students’ preparedness for future practice in the rural setting [46]. if this information is communicated to the students early in the logbook trial, it might have increased their engagement and benefit from the exercise and perhaps should be considered in future experimentation [18, 43]. 4.3. barriers to learning from logbooks on the other hand, poor-quality feedback, subjectivity in marks and the marking process, and issues related to the logbook structure (e.g., a strictly prescribed format) were perceived as barriers to learning from logbooks. these were reflected in the following students’ quotes: “marking was not fair, and i have received marks from only a few teachers.” sy6f “the logbook was structured to just “fill-in-the-blank;” we wanted more space to write freely, more freedom in writing.” sy6f in consonance, svendsen et al. (2019) recommended a user-friendly logbook and warned against a bureaucratic one which involves extensive load of data entry [1]. likewise, jud et al. (2020) was skeptic about the possibility of using logbooks appropriately to enhance students’ learning unless proper guidance and supervision of students doi 10.18502/sjms.v16i3.9701 page 421 sudan journal of medical sciences ahmad abdulazeem abdullah omer in the wards is implemented [17]. involving enthusiastic physicians and mentors among the hospital staff in regular review and monitoring of their students’ work supplemented with faculty development programs were proposed to increase the acceptability of the logbook and feasibility of the process [29, 40, 53]. besides, effort should aim to improve the structure of the logbook to adjust the burden of data entry and refine rubrics to add fairness to the marking process [1, 18, 49]. 4.4. role of learners’ individual characteristics 4.4.1. stage of learning the fourth-year students perceived the logbook activity more significantly useful to their learning than the sixth-year students. al-haqwi et al. (2012), in a study of feedback in saudi arabia, found that medical students’ perceptions of feedback were more positive in early undergraduate years, which they attributed to the more prolonged exposure of senior students to weaknesses in the feedback practice. they argued, the longer exposure enabled senior students to produce more accurate judgments about the process than their junior counterparts [54]. as such, students’ engagement with the logbook might decrease if careful planning, follow-up, and meticulous measures are not taken to ensure proper implementation of the logbook, and, with time, senior students are more likely affected. this may also point to the possible role of the academic environment and the hidden curriculum, which often sends strong messages about the process and demand further analysis in future studies. 4.4.2. level of academic performance no difference was found in the students’ perception of the usefulness of logbooks based on their academic performance. this is in contrast to some studies, which indicated that students who have good knowledge and clinical skills and excel in their academic performance appreciate feedback as more useful than their counterparts who are less knowledgeable [52, 54]. in addition, it was also noted that high-achieving students concentrate on the feedback message and try to understand the meaning behind it [36]. however, the restricted ranges of gpa and logbook marks may have resulted in poor discrimination among the students’ academic abilities and contributed to this finding [24]. besides, some gpa and logbook marks were missing, and this could have affected the data analysis and the conclusion made out of it. doi 10.18502/sjms.v16i3.9701 page 422 sudan journal of medical sciences ahmad abdulazeem abdullah omer 4.4.3. gender similarly, gender did not give rise to differences in the students’ perception of the logbook, which is in line with fong et al. (2016) [55]. however, there were marked differences in the participation rates in this study between female and male students, particularly in the sixth-year, with a larger number of females being involved (82.4% and 32.4%, respectively, as shown in table 1). this difference could be interpreted as a more positive attitude, higher interest, and better engagement of female students with the logbook experience than their male counterparts. in contrast, streeter (2013) showed better engagement of males than females in using a music therapy logbook for patients with neurological disabilities, which they attributed to more confidence and positive attitude that males had toward the logbook activity [56]. further studies to assess learners’ characteristics in engagement with and benefit from logbooks are required. limitations some factors may have limited the findings of this study and are worth to be mentioned. the sample size, particularly that of teachers, was small. the study involved students at specific academic years and in selected courses, which may have introduced a selection bias. however, there is no logical reason to expect different results if students at other learning stages in our context were involved. also, the results of this study might not be generalizable to other settings. nevertheless, the findings of this study would provide essential data to curriculum planners and course coordinators to set the stage for improving the procedure and outcome of logbooks in our academic environment. 5. conclusion logbooks are one of the tools that are used to enhance learning in the realm of medical education, where they might foster students’ learning through multiple aspects. it encourages students to see cases in the hospital from which they can learn a lot. it is a mechanism to show them their mistakes and suggest to them plans for improvement. besides, it improves their writing skills of medical notes and their use of english. however, several barriers to effective use of logbooks were also reported. these include: poor-quality feedback, biased marking, absence of dialogue in the feedback process, and problems with the structure and acceptability of the logbook. doi 10.18502/sjms.v16i3.9701 page 423 sudan journal of medical sciences ahmad abdulazeem abdullah omer to improve students’ learning from the logbook, faculty members should be trained on constructive feedback principles. in addition, discussion of the logbook work and careful supervision of students, particularly at the beginning of their clinical training are essential to promote learning from logbooks. acknowledgments the author would like to thank dr. mandy moffat, who kindly supervised this work. he is also grateful to the fourthand sixth-year students in the college and his colleagues in the department of surgery who shared their precious time during data collection. ethical considerations this study has been approved by the ethical committee of university of tabuk. the principles of ethical conduction of research according to the declaration of helsinki [26] were followed except that the researcher has participated in data collection because no other suitable alternative was found. the researcher acknowledges that this could have influenced participants’ responses in some way. competing interests the author reports no conflict of interest. the author alone is responsible for all work submitted in this manuscript. availability of data and material all relevant data of this study are available to any interested researchers upon reasonable request to the corresponding author. funding none. doi 10.18502/sjms.v16i3.9701 page 424 sudan journal of medical sciences ahmad abdulazeem abdullah omer 6. abbreviations s: student y: year m: male f: female t: teacher 4: fourth year 6: sixth year references [1] svendsen, ø., helgerud, c., duinen, a., et al. 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(2013). taking gender into account: brief report on a survey of music therapists’ attitudes for future use of a proposed computer aided evaluation system: the music therapy logbook. the arts in psychotherapy, vol. 40, pp. 404–408. doi 10.18502/sjms.v16i3.9701 page 429 introduction setting and context aims and objectives materials and methods study design materials and subjects statistics proxima-nova-bold-italic.otfquantitative data proxima-nova-bold-italic.otfqualitative data results results of the thematic analysis of the qualitative data discussion perceptions of the usefulness of logbooks to students' learning logbooks as promoters of students' learning proxima-nova-bold-italic.otfrole of feedback proxima-nova-bold-italic.otfprovision of opportunities to learn from patients proxima-nova-bold-italic.otfimprove writing skills proxima-nova-bold-italic.otfrelation to students' future career barriers to learning from logbooks role of learners' individual characteristics proxima-nova-bold-italic.otfstage of learning proxima-nova-bold-italic.otflevel of academic performance proxima-nova-bold-italic.otfgender limitations conclusion acknowledgments ethical considerations competing interests availability of data and material funding abbreviations references sudan journal of medical sciences volume 16, issue no. 2, doi 10.18502/sjms.v16i2.9296 production and hosting by knowledge e research article workplace violence against doctors in khartoum state, sudan, 2020 muna mohamed elamin1, salih boushra hamza2,3, khabab abbasher4, khalid elsir idris3,5, yassin abdelrahim abdallah2,3, khadija ala abdalmaqsud muhmmed3,6, tibyan hassan mustafa alkabashi7, radi tofaha alhusseini8, sidieg elias sidieg mohammed3,9, and ahmed alsayed mohammed mustafa3,10 1community department, faculty of medicine, omdurman islamic university, khartoum, sudan 2department of internal medicine, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 3pso_research unit 4faculty of medicine, university of khartoum, khartoum, sudan 5department of microbiology, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 6department of anatomy, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 7department of pathology, faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 8department of anatomy, alzaiem alazhari university, khartoum, sudan 9faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan 10faculty of medicine and health sciences, omdurman islamic university, khartoum, sudan orcid: salih boushra hamza: https://orcid.org/0000-0002-0231-2206 khalid elsir idris: https://orcid.org/0000-0002-7780-9436 yassin abdelrahim abdallah: https://orcid.org/0000-0003-1981-8665 yassin abdelrahim abdallah: https://orcid.org/0000-0003-0369-5138 tibyan hassan mustafa alkabashi: https://orcid.org/0000-0002-0897-1528 radi tofaha alhusseini: https://orcid.org/0000-0002-7778-5331 sidieg elias sidieg mohammed: https://orcid.org/0000-0002-1819-489x abstract background: workplace violence against healthcare workers and especially doctors are now clearly taken as a rapidly rising health problem in sudan with great political and legal concerns. the current study was aimed at exploring the prevalence of verbal and physical workplace violence, the major factors associated with it, and its consequences reported by medical staff in khartoum, sudan government hospitals in 2020. methods: this cross-sectional study utilized self-administered questionnaires to collect data on aspects of workplace violence against doctors working in the government hospitals of khartoum, sudan. a nine-item self-reported workplace violence scale was used. an online survey of self-reported work-related violence exposure during the preceding 12 months was sent to conveniently selected doctors. in total, 387 doctors completed the questionnaire in 2020. data were analyzed using the spss version 26. how to cite this article: muna mohamed elamin, salih boushra hamza, khabab abbasher, khalid elsir idris, yassin abdelrahim abdallah, khadija ala abdalmaqsud muhmmed, tibyan hassan mustafa alkabashi, radi tofaha alhusseini, sidieg elias sidieg mohammed, and ahmed alsayed mohammed mustafa (2021) “workplace violence against doctors in khartoum state, sudan, 2020,” sudan journal of medical sciences, vol. 16, issue no. 2, pages 301–319. doi 10.18502/sjms.v16i2.9296 page 301 corresponding author: salih boushra hamza; department of internal medicine, faculty of medicine and health sciences, omdurman islamic university, omdurman, khartoum, sudan. phone number: +249999253222 email: salihboushra@gmail.com received 27 march 2021 accepted 9 may 2021 published 30 june 2021 production and hosting by knowledge e muna mohamed elamin et al. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com https://orcid.org/0000-0002-0231-2206 https://orcid.org/0000-0002-7780-9436 https://orcid.org/0000-0003-1981-8665 https://orcid.org/0000-0003-0369-5138 https://orcid.org/0000-0002-0897-1528 https://orcid.org/0000-0002-7778-5331 https://orcid.org/0000-0002-1819-489x mailto:salihboushra@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences muna mohamed elamin et al results: one hundred and ninety five (50%) respondents reported they were victims of violence in the previous 12 months; 92% of them experienced nonphysical violence; while female doctors were more likely to experience this type of violence (67%), younger respondents <30 years of age were more likely to encounter violent episodes. results show an association between exposure to physical violence and working at an emergency department. the assailants were mostly males in the age group of 19–35 years (70.2%), most of them were under no influence (60.8%). conclusion: approximately one in every two doctors had experienced some degree of violence, either physical or nonphysical or both, and it was negatively reflected on their psychological status as well as their work performance. keywords: violence, workplace, doctors, physical, nonphysical 1. introduction the word “violence” originates from the latin word violentia, which means a behavior involving physical force intended to hurt, damage someone [1]. workplace violence (wpv) is an act of aggression, physical assault, or threatening behavior that occurs in a work setting and causes physical or emotional harm to an employee [2]. wpv is a well-recognized occupational hazard for victims with physical, emotional, and behavioral effects [3]. it can be defined as violence or threat of violence against workers. it can occur at or outside the workplace and can range from threats, verbal abuse to physical assault and homicide [4]. the world health organization (who) defines wpv as incidents where staff are abused, threatened, or assaulted in circumstances related to their work including commuting to and from work involved and explicit or implicit challenge to their safety, well-being, or health. according to the who, wpv can be classified as physical, psychological (emotional), sexual, and racial [5]. 1.1. violence against doctors the medical profession, once thought to be dignified and treasured, is losing its reputation. it is in danger particularly from the patients and their relatives. gone are the days when doctors used to put all of their efforts to breathe life into patients in the near-death state, sadly frequent attacks on doctors are changing the scenario [6]. violence toward doctors is regarded as a major public health challenge. healthcare staffs are vulnerable doi 10.18502/sjms.v16i2.9296 page 302 sudan journal of medical sciences muna mohamed elamin et al to wpv [7] because they work at the core of the healthcare system and have a direct interaction with patients and their families [8]. 1.2. factors that increase wpv the rising cases of violence against doctors have made society think about the causes and prevention of such incidences. in many instances, after a patient dies, the patient’s relatives start blaming doctors for negligence over the treatment [6]. poor image of doctors and the role of the media are other important factors [6]. the increasing cost of healthcare combined with low faith in the jurisdictive process is sufficient to cause debt and frustration in many families. although many medical institutions are emphasizing the cognitive and psychomotor domain of the healthcare students (e.g., pharmacy students), they lack in developing the effective domain [9]. this is resulting in a gap between doctors and patients. doctors are taught clinical behavior but not empathy. less time is given to communicate the prognosis of the disease and the outcome of treatment, resulting in dissatisfaction with healthcare services among patients. government hospitals top the list of wpv due to lack of resources and time. sometimes patients have to wait for a long time outside the doctor’s chamber as the crowd makes them panic. oftentimes patients do not get emergency care within the golden hour. these are some of the precipitating factors. occupational safety and health administration (osha), usa, describes workers who provide services, work in remote or high-crime areas, and those who work shift hours and/or have a great deal of contact with the public are at risk. this group includes healthcare workers such as physicians, nurses, other providers (both communityand hospital-based), social workers, and psychiatric evaluators [10]. 1.3. impact of wpv wpv against healthcare workers has long-lasting, deleterious effects on the victim’s health resulting in stress, emotional shock, reduced efficiency and productivity due to physical and psychological trauma, and sometimes changing or even leaving the profession [11]. according to gilbert burnham and colleagues’ study, the number of medical specialists in baghdad declined by 22% between 2004 and 2007 due in part to violent deaths (1.65%), threats (3%), and kidnappings (0.67%) [12]. iraqi doctors are getting assaulted, violated, and humiliated, and as a result, more physicians are leaving the country. doi 10.18502/sjms.v16i2.9296 page 303 sudan journal of medical sciences muna mohamed elamin et al more than 2,000 doctors have been killed since 2003 [13]. a cross-sectional study was conducted in ghana to determine the effect of wpv on nurses’ emigration intentions between 2013 and 2014. both purposive and random sampling techniques were used to select 12 public hospitals and 592 professional nurses. the results showed that 48.9% of the participants had emigration intentions. junior nurses were 2.8 times more likely to have emigration intentions compared to senior nurses, and those who experienced violence were also more likely than their counterparts who were not involved in such incidents (physically abused 2.1 times; verbally abused 1.8 times, and sexually harassed 2.4 times) to have intention to emigrate [14, 15]. 1.4. wpv against healthcare workers in sudan wpv against healthcare workers and especially doctors in sudan is an issue that has yet not received considerable critical attention from the local healthcare system authorities even with the increasing rate of violence against healthcare workers in khartoum state, sudan. violence in workplace and in healthcare sector has a significant impact on the efficacy of health systems, especially in developing countries [16, 17], which ultimately leads to negative patient outcomes. several studies have shown that wpv affects the physical and mental health of healthcare workers [18–22]. this study aims to assess the rate of attacks in the last 12 months, measure violence rates by sociodemographic factors, and possible risk factors for wpv against physicians working in governmental hospitals in khartoum state, sudan. the study also examines the consequences of violence, related psychosocial results and their effect on the doctors and their performance, professionals’ incident reporting patterns, and existing violence prevention and safety measures applied by hospital authorities from healthcare workers’ perspectives. 2. materials and methods 2.1. participants this cross-sectional study targeted doctors working in the government hospitals of khartoum state, sudan and included a total of 387 doctors. data were collected using a convenience sampling technique. doi 10.18502/sjms.v16i2.9296 page 304 sudan journal of medical sciences muna mohamed elamin et al the sample size was calculated using the sample size of the unknown population (cochran’s formula): n0 = 𝑧2𝑝(1−𝑝) 𝑒2 , where, z = z-value (1.96 for 95% confidence interval); p = probability of wpv (p is unknown, so it was considered as 0.5); e = error margin; and n0 = (1.96) 2 x 0.5(1–0.5) ÷ (0.05)2 = 384. 2.2. measures a reliable and validated well-structured questionnaire was obtained from a previous study conducted by mohamad kitaneh and motasem hamdan (with their due permission) [23]. the study instrument was prepared on the basis of the questionnaires used in the two previous studies [24, 25]. reliability test revealed a 0.7 cronbach’s alpha (considered reliable). all pearson’s correlations were above critical value (considered valid). the instrument was modified to fit the objectives of the study and the palestinian hospital context and was translated into arabic. it was reviewed by five experts (nurses and physicians) for its validity. experts assessed the clarity, relevance, comprehensiveness, and sensitivity of the tool to the culture. in essence, the expert comments were about the definitions of violence, in specific sexual violence, and the clarity of some questions. the modified questionnaire was then pilot tested. the questionnaire consisted of four sections: the first section included sociodemographic data, the second one was about the history of exposure to physical violence, the third section was about nonphysical violence (threats, verbal violence, and sexual violence), and the last section contained questions on the characteristics of perpetrators, magnitude, and consequences of violence, incident reporting, availability of policies/procedures, training programs, and safety measures in the workplace. 2.3. procedure as our study was conducted in unusual circumstances, where most social activities were restricted to a maximum reduction in person-to-person contacts as part of covid-19 pandemic control measures, data were collected using an internet-mediated questionnaire. the questionnaire was restrictedly distributed throughout the doctor’s group in social media. doi 10.18502/sjms.v16i2.9296 page 305 sudan journal of medical sciences muna mohamed elamin et al 2.4. data analysis data were analyzed using the statistical package for social science (spss) version 26 and are presented in tables and graphs, after being primarily analyzed by google form. descriptive analysis was used to describe the demographic data, incidence of violence, and the magnitude and consequences of violent events. pearson’s chi-square analysis was used to test the differences in exposure to violence (physical and nonphysical violence) according to respondents’ characteristics. odds ratios and 95% confidence intervals were used to assess potential association between exposure to violence in general (yes/no) and respondents’ characteristics including gender, age, years of experience, educational level, and hospital department. an adjustment was then made for the same pre-mentioned covariates using a logistic regression model; the dependent variable was exposure to violence (yes, no). a p-value < 0.05 was considered statistically significant. 3. results 3.1. demographic characteristics of the total participants, 297 (76.7%) were aged ≤30 years and most of them were female 236 (61%). moreover, majority of them were medical officers (128 [33.1%]) holding a bachelor’s degree in medicine (318 [82.2%]). 3.2. incidence of violence against doctors in government hospitals 3.2.1. doctor’s exposure to violence about 195 (50%) participants experienced one type of violence, either physical or nonphysical (verbal or sexual abuse, or threat), within the preceding year; 92% of them (49% of all participants) experienced nonphysical and 8 participants (1% of all participants) experienced physical violence. 3.2.2. nonphysical violence most participants (40%) experienced verbal abuse and threat at the same time, followed by only verbal violence by 36% and exposure to both physical and nonphysical violence during the past 12 months (figure 1) by 15%. doi 10.18502/sjms.v16i2.9296 page 306 sudan journal of medical sciences muna mohamed elamin et al 3.2.3. association between exposure to violence and respondent’s characteristics table 3 shows the descriptive association between respondents’ characteristics and exposure to physical and nonphysical violence in the past 12 months. the results indicated that there is an association between gender and exposure to nonphysical violence (p-value = 0.004). however, female doctors were more likely to be exposed to nonphysical violence than their male counterparts. similarly, those aged <30 years reported experiencing a higher incidence of violence (64.4%) than those aged >30 years (p-value = 0.024). moreover, medical officers reported the highest incidence (65%), followed by house officers (62.7%) and registrars (61%) (p-value = 0.02). those who worked in shifts had a significantly increased risk (63%) (p-value = 0.04). there were no associations between work experience or department and exposure to nonphysical violence, and between exposure to physical violence and gender, age, profession, education, years of experience, or work shift. however, an association was found between exposure to physical violence and working at the emergency department (p-value = 0.0001) (table 1). multivariate logistic regression analysis identified significant predictors for violence exposure. while males were 1.5 times more likely to be victims of violence compared to females (p-value = 0.044), healthcare workers in the emergency department experienced violence 2.5 times more compared to the other departments (p-value = 0.001). adjusted linear regression revealed no significant difference when multivariate analysis for age and sex, and age and rank was conducted and no interaction was found. holding a bachelor’s degree was associated with a half-time decrease in violence exposure compared to holding a higher degree (p-value = 0.009). although participants aged ≤30 years were twice more likely to experience violence than those aged >30 years, this association became insignificant after adjustment (table 2). 3.2.4. characteristics of perpetrators and violent events most perpetrators (70.2%) were in the age group of 19–35 years. the attacks on our participants mostly occurred (71.6%) during the past 12 months and were usually carried out by males. the worst violent attacks mostly occurred during the working days (69.9%) with few incidences occurring on weekends (16.2%) while the rest were unsure (14.8%). most physical assaults (54%) occurred in the evening, and most perpetrators were under no influence (60.8%) when they attempted to attack our participants. few of them were doi 10.18502/sjms.v16i2.9296 page 307 sudan journal of medical sciences muna mohamed elamin et al table 1: association between exposure to violence and respondents’ characteristics. physical violence nonphysical violence n % x2 pvalue n % x2 p-value gender male 34 22.5 1.846𝑎 0.174 79 52.3 8.305𝑎 0.004 female 40 18.6 158 67 age (yr) <30 60 20.2 0.964𝑎 0.326 191 64.3 5.069𝑎 0.024 >30 14 15.5 46 51 profession house officer 16 14.5 6.363𝑎 0.174 69 62.7 11.724𝑎 0.020 medical officer 34 25 83 65 registrar 24 19 77 61 specialist 2 11.7 8 47 consultant 0 0 0 0 education bachelor’s degree 3 7.6 3.663𝑎 0.056 18 46 4.159𝑎 0.041 >bachelor’s degree 71 20.4 219 63 experience (yr) ≤10 70 18.67 1. 617𝑎 0.203 191 64.3 5.069𝑎 0.695 ≥10 4 33 46 51 work in shift yes 71 20.4 3.663𝑎 0.056 219 63 4.159𝑎 0.041 no 3 7.7 18 46 department emergency 29 36.7 19.854𝑎 0.000 55 69.6 2.937𝑎 0.087 others 45 14.6 182 59 under the influence of drugs taken as a form of addiction. regarding the tool of attack used, most perpetrators used their hands and feet (77%) to attack our participants. few male perpetrators (5.4%) used knives and few female perpetrators (2.7%) used the surrounding objects as a tool of attack. the results related to the magnitude of the violent incidents showed that the majority of the participants reported exposure to single physical violent (71.7%) and single nonphysical violent (25.5%) event; repeated events were 28.3% and 74.4%, respectively. physical violence occurred mostly in the examination room (36.1%) (table 3). doi 10.18502/sjms.v16i2.9296 page 308 sudan journal of medical sciences muna mohamed elamin et al table 2: unadjusted and multivariate-adjusted odds ratios for exposure to violence among respondents. unadjusted p-value adjusted* p-value or 95% ci or 95% ci gender male 1.513 0.988–2.318 0.057 1.589 1.012–2.495 0.044 female 1.0 reference 1.0 reference age (yr) ≤30 1.835 1.134-2.972 0.014 1.660 0.984–2.801 0.057 >30 1.0 reference 1.0 reference department emergency 2.686 1.464–4.930 0.001 2.914 1.561-5.441 0.001 others 1.0 reference 1.0 reference education bachelor’s degree 0.412 0.211–0.408 0.009 0.397 0.193–0.819 0.012 >bachelor’s degree 1.0 reference 1.0 reference experience (yr) <10 0.942 0.278–3.188 0.924 0.404 0.103–1.591 0.195 ≥10 1.0 reference 1.0 reference *adjusted for independent variables: gender, experience, education, age, and department. or: odds ratios, ci: confidence interval; reference: reference category in the logistic regression model. 3.2.5. consequences of violent events while the most frequent consequences of physical and nonphysical violence was anger (22.7% and 23.4%, respectively), the rarest was difficulty in sleeping (6% and 4%) but only 0.3% and 3.6% had no consequence, respectively. most participants did not seek treatment for both physical and nonphysical violence (64.3% and 78.7%, respectively). most of them treated themselves following a physical and nonphysical violence (32.8% and 23.7%, respectively). most participants’ problems did not persist following the physical or nonphysical violence (63.5% and 69%, respectively). likewise, most participants had no change in work after a physical or nonphysical violence (53% and 71%, respectively). the most frequent change in work was absence from work due to physical violence (19.4%) and work restrictions regarding nonphysical violence (16.6%). while 79.1% of the respondents did not report the incident, only 20.6% of them reported and most of them (79.9%) took no legal action on their cases. of those who did not report the event, 34.5% indicated they did so because it was useless, from their experience no action would be taken; 13.4% did not know to whom they should report; 8.5% indicated that reporting was not important; 5% were afraid of negative consequences or fear of feeling guilty or ashamed; and 1.4% cited other causes. the majority of respondents (79.3%) indicated the absence of standard procedures doi 10.18502/sjms.v16i2.9296 page 309 sudan journal of medical sciences muna mohamed elamin et al table 3: characteristics of perpetrators. male (%) female (%) 60 (81.1) 14 (18.9) total % violent attempts in the last 12 months weekly 2 (2.7) 0 (0.0) 2.7 monthly 17 (22.9) 1 (1.3) 24.2 everyday 1 (1.3) 0 (0.0) 1.3 once 40 (54) 13 (17.5) 71.5 time of worst violence weekend 10 (13.5) 2 (2.7) 16.2 workdays 41 (55.4) 10 (13.5) 68.9 not sure 9 (12.1) 2 (2.7) 14.8 perpetrator’s age group (yr) <18 0 (0.0) 1 (1.3) 1.3 19–35 45 (60.8) 7 (9.4) 70.2 30–60 15 (20.2) 6 (8.1) 28.3 perpetrator’s status under influence of drugs* 3 (4) 0 (0.0) 4 under influence of disease 5 (6.7) 0 (0.0) 6.7 not under influence 33 (44.5) 12 (16.2) 60.7 not sure 19 (25.6) 2 (2.7) 28.3 time of violence morning 18 (24.3) 4 (5.4) 29.7 evening 28 (37.8) 2 (2.7) 40.5 after midnight 13 (17.5) 7 (9.4) 26.9 not sure 1 (1.3) 1 (1.3) 2.7 tool of violence hands and feet 46 (62.1) 11 (14.8) 76.9 knife 4 (5.4) 0 (0.0) 5.4 surrounding objects 0 (0.0) 2 (2.7) 2.7 not sure 10 (13.5) 1 (1.3) 14.8 *drugs such as opiates. for reporting violence or any encouragement to report events. most of them also indicated that the hospitals had no specific policy/procedure or training programs on wpv (85–95%). some participants had received training on some of the following issues: safety measures (10.6%), dealing with violence (4.7%), communication (34.1%), and stress management (8.3%). a very low percentage indicated the availability of violencepreventing policies/procedures related to verbal abuse (5.2%), health and safety (10.6%), physical violence (10.9%), threats (5.9%), and sexual harassment (5.7%). the respondents were also asked about the measures that exist in the work environment to deal with violence. the most frequently rated safety measures were as follows: security personnel doi 10.18502/sjms.v16i2.9296 page 310 sudan journal of medical sciences muna mohamed elamin et al table 4: characteristics and consequences of violent assault. physical nonphysical n % n % symptoms/feeling anger 48 22.7 161 23.4 depression 27 12.7 81 11.8 fear/stress 27 12.7 102 14.8 headache/fatigue 18 8.3 60 8.7 frustration 42 19.9 113 16.4 confusion at work 36 17 116 16.9 difficulty in sleeping 3 6 28 4 nothing 1 0.3 25 3.6 treatment no treatment 47 64.3 294 78.7 physician 1 1.3 0 0 i treated myself 24 32.8 92 23.7 psychiatrist 1 1.3 3 9 persistent problem as a result yes 27 36. 4 123 31 no 47 63.6 274 69 work change as a result no changes 41 53 275 71.1 transfer to another location 6 7.7 23 6.6 restrictions 12 15.5 62 16.6 absence 15 19.4 27 8.1 other 3 3.8 0 0 (79.6%), security alarms (2.6%), video monitoring systems (16.8%), cell phones (2.8%), and metal detectors (1.6%) (table 4). 4. discussion most respondents in the current study were females (61%) which is similar to the kitaneh and hamdan’s study [23], however, in the current study [23], the most common age group of respondents was ≤30 years while their respondent’s ages ranged from 20 to 29 years. most respondents in this study were medical officers (33.1%) followed by registrars (32.6%) and house officers (28.4), and most of them (20.4%) worked in the emergency department which is similar to the study of kitaneh and hamdan [23]. doi 10.18502/sjms.v16i2.9296 page 311 sudan journal of medical sciences muna mohamed elamin et al our study showed that 65% of the participants were exposed to wpv during the past 12 months. although there were some differences in the targeted professional groups and in the methodology used, the study outcomes are comparable with previous regional and international studies. in general, the exposure to violence of healthcare workers working in the government hospitals of khartoum (65%) was greater than in a study conducted in egypt (60%) [26], however, both studies had a similar rate of physical violence against physicians (15.1% in egypt and 16% in sudan). a study from pakistan revealed that violence against doctors was found to be almost similar to our findings (63.8 %) [27], another similar study from nigeria showed a low incidence of violence against physicians (57.4%) [28], while a palestinian survey exhibited an 80% incidence of violence which is greater than our finding [23]. the fact that the majority of respondents were exposed to some type of violence is in itself a matter of concern. a conceivable explanation for these results could be related to the unsatisfactory working conditions including frequent deficiencies of medications and supplies, overcrowded hospitals, and delays in getting care as well as neglected patient needs or expectations, long working hours, and poor working environment for government doctors, which makes them vulnerable to committing mistakes and more prone to violence. it can be accepted that the fragile financial conditions of the nation might be another important causative factor. difficult living conditions, disappointment, and stress within the sudanese lifestyle increase the forceful conduct against doctors; in any case, these variables were not inspected in this study. surprisingly, both genders were equally exposed to violence and no statistically significant difference was seen; however, when adjusted, it showed an or = 1.5; ci = 95 among males in comparison to females (p-value = 0. 04). this contradicts the literature that males and females are equally likely to encounter wpv [25, 29, 30]. the emergency ward is a characteristically high-pressure environment and experiences a high load of patients. due to several factors involving the patient’s condition at arrival and the state of severe anger and anxiety that patients and co-patients feel when they arrive at emergency departments, this makes these areas the venue of the highest rates of patient or visitor violence [17, 31–34]. in our study, we found that healthcare workers in the emergency department experienced violence 2.5 times more compared to other departments (p-value = 0.001) before and after adjustment with or = 2.68 and 2.91, respectively. one interesting finding was that holding a bachelor’s degree was a factor associated with violence exposure (p-value = 0.009) and it was strengthened after adjustment (p-value = 0.01; or = 0.41 and 0.39, respectively; ci = 95%). doi 10.18502/sjms.v16i2.9296 page 312 sudan journal of medical sciences muna mohamed elamin et al inconsistent with other studies from arab countries in the region [23, 28, 35, 36], our study showed that males more than females were exposed to violence (81.1%), however, it aligned with other studies [23, 28, 35–37] that revealed that respondents with lower educational level were associated with higher exposure rate to violence (p-value = 0.01). many studies have recognized that the emergency department is a particularly violent environment [38, 39], in our study also, healthcare workers in the emergency department experienced violence 2.5 times more compared to those in other departments (p-value = 0.001). these departments are usually attended by aggressive and stressed patients/visitors and those patients who are impaired by drugs and are more likely to commit violence against health workers [40–42]. the attacks on our patients mostly occurred in the past 12 months and were generally carried out by males; the results of our study are in line with the previous study which noticed that the majority of the incidents were single events [23]. the majority of perpetrators were in the age group of 19–35 years, which can be explained by the strength of youth. the attack mostly occurred during working days (from sunday to thursday) with few incidences occurring on the weekends. the time of the attack was mostly in the evening. similar results have been reported in previous studies in the region [23, 35, 36, 40, 41]. moreover, most perpetrators were under no influence of drugs or alcohol when they attempted to attack our participants, this result is similar to a previous study [23]. in most cases, the perpetrators used their hands and feet to attack our participants. few male perpetrators used knives and few female perpetrators used the surrounding objects as a tool of attack; hence, men are more likely and physically capable of enacting physical violence than women who are more likely to enact verbal violence [29, 38, 40, 41]. as mentioned in many previous studies, the patients and their relatives are reported as the core of violence [5, 16, 18, 20, 26, 42, 43]. most participants who were exposed to physical or nonphysical assault did not receive any kind of treatment (63.5% and 75.4%, respectively). this should be highlighted, especially as evidence shows that wpv usually results in shortand long-term effects on the victims’ physical, psychological state, and professional performance [43,44]. it is not a surprise that most of our respondents indicated psychological and emotional feelings such as anger, fear, depression, stress, and frustration. in previous studies, it appeared that individuals who experience nonphysical violence endured feelings/symptoms over time, with a possible risk for adverse mental health outcomes such as acute stress disorder or posttraumatic stress syndrome [32, 33]. anger was slightly higher among those who experienced nonphysical violence, mostly due to the large number of participants who experienced doi 10.18502/sjms.v16i2.9296 page 313 sudan journal of medical sciences muna mohamed elamin et al this type of violence compared to physical violence. we can see that about 152 (77.9%) of those who experienced physical or nonphysical violence reported subsequent changes in their work status, including absence, subsequent transfer to another location, and restrictions in work. however, this seems to be much higher than the available data [18, 26]. 5. conclusion violence remains a special concern to doctors working in healthcare facilities in sudan. according to our data, approximately one in every two doctors has experienced some degree of violence, either physical or nonphysical. exposure to violence is negatively reflected in the psychological status and the level of their work performance. the prevalence of wpv on doctors in sudan identified in this study was high, and in many events, the associated factors were found. underreporting plays a major role in augmenting the violent incidences, there is a serious lack of reporting procedures and even encouragement to report these events. there is also a lack of violence prevention policies in healthcare facilities. we are holding useful data that can be used by researchers to address and further study this issue. recommendations since the majority of violent events were nonphysical, strategies to decrease and control this type of violence are recommended. because most of the affected persons were working in the emergency department and most incidents occurred in the evening, strategy to control violence in that particular setting and time is mandatory. the hospital reporting system for violence is highly needed to be reviewed and improved, and doctors should be encouraged to report. training workshops to deal with and avoid violence should be conducted. further studies are recommended after a while to assess the effectiveness of sudan’s law on the protection of doctors, medical staff, and health establishments, may 29, 2020. future studies should be done to explore the violence determinants and how to avoid them. limitations 1. an online questionnaire was used to collect data in this study. although it is a flexible and cost-effective way of data collection, it has low acceptance as a doi 10.18502/sjms.v16i2.9296 page 314 sudan journal of medical sciences muna mohamed elamin et al data collection tool, and due to a lack of interactivity between the respondent and researcher, it affects the researcher’s ability to authenticate an individual’s responses. 2. difficulty reaching certain types of participants, such as those who do not have internet access, is another limitation. 3. in some responses, exposure to violence may be under/over-reported by the participating doctors due to the fluctuation of their memory because of the time gap between the violence incidence and the questionnaire-filling date. acknowledgements none. ethical considerations permission to conduct the study and ethical approval was obtained from the ethical committee of the faculty of medicine and health sciences, omdurman islamic university, federal ministry of health. a written consent was obtained from all participants after explaining the aim of the study and assuring the confidentiality of their data. all methods were performed following the relevant guidelines and regulations. competing interests the authors declare that they have no competing interests. availability of data and materials the materials and datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request. funding this research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. doi 10.18502/sjms.v16i2.9296 page 315 sudan journal of medical sciences muna mohamed elamin et al references [1] violence. 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(2002). violence against nurses in healthcare facilities in kuwait. international journal of nursing studies, vol. 39, no. 4, pp. 469–478. doi 10.18502/sjms.v16i2.9296 page 319 introduction violence against doctors factors that increase wpv impact of wpv wpv against healthcare workers in sudan materials and methods participants measures procedure data analysis results demographic characteristics incidence of violence against doctors in government hospitals doctor's exposure to violence nonphysical violence association between exposure to violence and respondent'scharacteristics characteristics of perpetrators and violent events consequences of violent events discussion conclusion recommendations limitations acknowledgements ethical considerations competing interests availability of data and materials funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9699 production and hosting by knowledge e research article association of serum adenosine deaminase levels in cytologically suggested cases of tubercular lymphadenitis: the experience of a tertiary care centre ina garg, deepti arora, himanshu joshi, ashutosh kumar, and seema awasthi department of pathology, teerthanker mahaveer medical college & research centre (tmmc&rc), moradabad, uttar pradesh, india orcid: deepti arora: http://orcid.org/0000-0001-5461-8592 abstract background: tuberculosis (tb), a communicable disease, caused by mycobacterium tuberculosis requires a simple, rapid test, which can be easily carried out in a laboratory. unfortunately, despite a battery of investigations, no definite test is available till date. adenosine deaminase (ada), a biochemical marker has been proposed as a useful surrogate marker for tb as its levels can be measured in body fluids. methods: a one-and-a-half-year prospective study of 154 cases presenting with lymphadenitis from january 2019 to june 2020 was undertaken. using cytology, lymphadenitis subjects were divided into two groups: tubercular (104 patients) as a case group and reactive (50 patients) as a control group. all cases were followed by serum ada assay by colorimetric method. nonparametric tests were performed to compare the two groups. results: the mean age of the participants was 28.99 ± 13.26 years with a f:m ratio of 1.81:1. involvement of cervical lymph nodes was most frequent (89.42% cases). the mean s.ada level for tubercular and reactive lymphadenitis was 41.71 ± 11.53 u/l and 21.16 ± 4.16 u/l, respectively (p-value < 0.05). the cut-off value calculated was 32.6 u/l. the sensitivity, specificity, ppv, npv, and accuracy were calculated as 79.81%, 100%, 100%, 70.42%, and 86.36%, respectively. conclusion: a statistically significant increase was found in serum ada levels in tubercular lymphadenitis cases compared to reactive lymphadenitis. hence, it can be used as an adjunct to fnac and is a fairly sensitive and specific test. since it is difficult to always demonstrate afb in fnac smears, ada can be helpful in establishing a definite diagnosis despite smear negativity. keywords: adenosine deaminase, lymphadenitis, tuberculosis 1. introduction tuberculosis (tb), a transmittable disease, is amongst the top 10 worldwide causes of death and is the principal cause of fatality from a single infectious vehicle ranking how to cite this article: ina garg, deepti arora, himanshu joshi, ashutosh kumar, and seema awasthi (2021) “association of serum adenosine deaminase levels in cytologically suggested cases of tubercular lymphadenitis: the experience of a tertiary care centre,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 386–398. doi 10.18502/sjms.v16i3.9699 page 386 corresponding author: deepti arora; email: deepti.a15@gmail.com received 02 july 2021 accepted 14 september 2021 published 30 september 2021 production and hosting by knowledge e ina garg et al.. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:deepti.a15@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ina garg et al. over hiv/ aids [1]. in 1993, tb was declared as a public health emergency on a global level by who [2]. depending upon the locus of involvement, tb can have two different manifestations clinically: pulmonary tb, wherein infection is situated in the lungs and extrapulmonary tb, involving any site other than the lungs, for example, abdomen, lymph nodes, meninges, skin, or genito-urinary tract [3]. the most common manifestation of mycobacterial extra-pulmonary disease is the involvement of peripheral lymph nodes, usually of the cervical area [4]. several research studies conducted in india have also shown mycobacterium tuberculosis (m. tb) to be the pathogen that was commonly isolated from mycobacterial lymphadenitis taking in account most of the cases [5–7]. an expeditious diagnosis is a mainstay for an efficient tb curbing program. a variety of methods for pulmonary tb detection are available but these do not yield sufficient specificity or sensitivity. the sensitivities of tb diagnosis using culture and ziehlneelsen staining are 8–49% and 10–40%, respectively [8]. the gold standard test for the detection of tb is the culture of the causative organism [9]. the technique of choice for extrapulmonary tb detection is histopathological examination. this includes excisional biopsy followed by culture and ziehl-neelsen stain. however, being an invasive modality and due to the lack of availability in peripheral centers makes its feasibility limited in low-resource areas [10]. fine-needle aspiration is an economic, rapid, and simple technique that has high specificity and sensitivity for extrapulmonary tb and can be performed on an outpatient basis. when extrapulmonary tb is considered, acid fast bacilli (afb) positivity is not always found due to paucibacillary nature particularly for those cases which are associated with immunosuppression. in endemic nations like india, even without afb positivity, the mere presence of granuloma with/without caseation and with/without giant cells-langhan’s type is taken as and treated for tb [11]. we need an easy, reliable, and rapid test that can easily be executed in the laboratory setting. therefore, we thought of using serum adenosine deaminase (ada) as an adjunctive diagnostic tool considering the fact that fluid ada levels are already in use for tubercular effusions since 1978. various articles have found the test to have high sensitivity-92% and specificity-89% for early detection of extrapulmonary tb in cases of tuberculous pericarditis, meningitis, pleuritis, and ascites [12]. although a good amount of data has validated the yield of ada in tubercular effusions, we cannot always access these fluids. instead, serum levels can be easily performed but there is a paucity of literature correlating it to tubercular lymphadenitis. therefore, we undertook this doi 10.18502/sjms.v16i3.9699 page 387 sudan journal of medical sciences ina garg et al. study intending to demonstrate the association of serum ada activity in cytologically suggested tubercular lymphadenitis cases. 2. material and methods this prospective cross-sectional study was carried out in the department of pathology of a tertiary care center from january 2019 to june 2020. all peripheral lymph node fine needle aspirations with clinical suspicion of tb during this period were included in this study. a total of 154 subjects were enrolled. 2.1. inclusion criteria 1. both genders and all age groups were included. 2. patients referred for fine needle aspiration cytology of lymph nodes with clinical and cytological suspicion of tubercular lymphadenitis or reactive lymphadenitis. 2.2. exclusion criteria 1. all causes of raised serum ada levels other than tb. 2. patients who did not give consent for the study. the study was approved by the ethical and research committee of the institute. patients were selected in accordance with predefined inclusion and exclusion criteria of the study. all selected patients were briefed on the nature of the study and a written informed consent for fnac and serum ada estimation was obtained. the relevant clinical details, demographic data of the patients such as the name, age, and sex were recorded. the prepared smears were stained by giemsa and ziehl-neelsen stain. all the stained slides were thoroughly analyzed by two independent trained pathologists with more than eight years’ experience and were examined for the features of tubercular and reactive lymphadenitis. out of the 154 subjects, 104 with cytologically suggested diagnosis of tubercular lymphadenitis were taken as the case group while 50 ageand sex-matched individuals presenting as reactive lymphadenitis were included as control group. the tubercular lymphadenitis cases were segregated based on the cytologic patterns described by dasgupta et al. [13] as follows: doi 10.18502/sjms.v16i3.9699 page 388 sudan journal of medical sciences ina garg et al. 1. pattern a: epithelioid granuloma without necrosis, 2. pattern b: epithelioid granuloma with necrosis, and 3. pattern c: necrosis with/without neutrophilic infiltrate. a 2-ml blood sample from the patient was then collected into a plain vial and serum ada estimation using non-guisti’s method was done (adenosine deaminase assay kit, erba mannheim, transasia bio-medicals ltd.) on semi-automated analyzer. cytologically suggested cases of tb lymphadenitis were followed-up to assess clinical response to therapy (no evening rise of temperature, improvement in appetite, and weight gain) after one month, and in case of no response, the case was excluded. 2.3. statistical analysis the data obtained were analyzed using descriptive statistics, unpaired t-test, oneway anova test, and chi-square test. spss program for windows, version 25.0 was employed for statistical analysis. p-value < 0.05 was considered as statistically significant for all statistical tests. to determine optimal cut-off value of serum ada levels in tubercular lymphadenitis, a receiver operating characteristics (roc) analysis was done and area under the curve and its standard deviation (auc_sd), sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), and accuracy were calculated. 3. results out of the 104 patients that presented with cytological features suggestive of tubercular lymphadenitis, 37 were male and 67 female. female dominance was present in our study with a f:m ratio of 1.81:1. the age of the patients ranged from 5 to 70 years. the mean age in the case group was 28.99 ± 13.26 years. the involvement of cervical lymph nodes was most frequent and was observed in 89.42% of cases. on fnac, pattern b (figure 1) (69 cases, 66%) was most frequently encountered, followed by pattern a (figure 2) (25 cases, 25%) and then by pattern c (figure 3) (9 cases, 9%). out of the 104 cases of tubercular lymphadenitis, afb positivity (figure 4) was seen in 24.04% of the cases. maximum afb positivity was observed in cases belonging to pattern c. the mean serum ada level in tubercular lymphadenitis was 41.71 ± 11.53 u/l and in reactive lymphadenitis was 21.16 ± 4.16 u/l (figure 5). doi 10.18502/sjms.v16i3.9699 page 389 sudan journal of medical sciences ina garg et al. the mean serum ada level was statistically more significant among tubercular lymphadenitis compared to reactive lymphadenitis (p-value < 0.001) (table 1). no significant difference in the distribution of serum ada levels between afb-positive and -negative groups was observed (p-value = 0.669) (table 2). no significant difference was reported in the mean ada levels among patterns a, b, and c (p-value = 0.438) (table 3). the optimal cut-off value for serum ada level was calculated to differentiate cases having tubercular lymphadenitis from reactive lymphadenitis using roc curve. the optimal cut-off value for identifying tubercular lymphadenitis was found to be 32.6 u/l with resulting sensitivity (79.81%,), specificity (100%), ppv (100%), npv (70.42%), and accuracy for serum ada level calculated as 86.36% (figure 6). figure 1: photomicrograph showing epithelioid cell granuloma with a necrotic background (pattern b); 100x (mgg). table 1: comparison of mean serum ada levels in reactive lymphadenitis (control) and tubercular lymphadenitis (cases) (department of pathology, tmu from january 2019 to june 2020) n = 154. mean (u/l) standard deviation mean difference t-test value p-value reactive lymphadenitis 21.16 4.16 –20.55 –12.213 <0.001* tubercular lymphadenitis 41.71 11.53 unpaired t-test; *significant difference. doi 10.18502/sjms.v16i3.9699 page 390 sudan journal of medical sciences ina garg et al. figure 2: photomicrograph showing epithelioid cell granuloma (pattern a); 100x (mgg). figure 3: photomicrograph showing caseous necrosis (pattern c); 100x (mgg). 4. discussion tb has been a public health emergency as well as the chief cause of fatality for a long time. the mainstay for controlling this infection is an early unerring diagnosis followed by an appropriate prompt treatment [1]. in the case of tubercular lymphadenitis, a proper diagnosis will require either an fna-obtained material or a biopsy which will doi 10.18502/sjms.v16i3.9699 page 391 sudan journal of medical sciences ina garg et al. figure 4: photomicrograph showing acid fast bacilli; oil-immersion 1000x (ziehl-neelsen stain). figure 5: comparison of serum ada levels between cases of tubercular and reactive lymphadenitis (department of pathology, tmu, january 2019 to june 2020) n = 104. then be followed by culture, afb confirmation via staining or other molecular techniques. problem rises due to the paucity of demonstrable acid-fast bacilli at such locations thereby impeding a definite diagnosis. in such situations, we require an adjunctive tool that might facilitate a diagnosis [9, 10]. serum ada estimation is one such modality which, in addition to being noninvasive, is a simple method for disease detection. ada can serve as an indicator of cell-mediated doi 10.18502/sjms.v16i3.9699 page 392 sudan journal of medical sciences ina garg et al. figure 6: roc analysis of optimal cut-off value for serum ada level to differentiate cases of tubercular lymphadenitis from reactive lymphadenitis (department of pathology, tmu from january 2019 to june 2020) n = 104. the test result variable(s): ada has at least one tie between the positive actual state group and the negative actual state group. statistics may be biased 1. under the nonparametric assumption and 2. null hypothesis: true area = 0.5. auc 0.953 (95% ci, 0.923–0.983, p < 0.001*), sensitivity 79.81% (70.81–87.04%), specificity 100% (92.89– 100.00%), positive predictive value 100%, accuracy 86.36% (79.91–91.36%), and negative predictive value 70.42% (61.90–77.72%). table 2: correlation of serum ada levels with afb status (demonstration on ziehl-neelsen-stained smear) in cases of tubercular lymphadenitis (department of pathology, tmu from january 2019 to june 2020) n = 154. serum ada afb mean (u/l) std. deviation mean difference t-test value p-value positive 40.95 10.41 –1.02 –0.388 0.699# negative 41.97 11.93 unpaired t-test; #non-significant difference. table 3: correlation of serum ada levels with different cytological patterns of tubercular lymphadenitis (department of pathology, tmu from january 2019 to june 2020) n = 104. serum ada pattern mean standard deviation f-value p-value a 44.21 11.42 0.833 0.438# b 40.98 11.75 c 40.12 10.07 one-way anova test; #non-significant difference. immunity. its utility in pleural effusions was first demonstrated by piras et al. [14]. many studies [15–17] have established the utility of fluid ada levels for the diagnosis of tuberculous peritoneal, pleural, pericardial effusions, and even in csf but they are doi 10.18502/sjms.v16i3.9699 page 393 sudan journal of medical sciences ina garg et al. not always accessible. therefore, we thought of using serum levels which we found elevated more in tubercular aetiologias as compared to nontubercular diseases. in the present study, patients age ranged from 5 to 70 years. the age group most frequently involved among the patients with tubercular lymphadenitis was 21–30 years followed by 11–20 years. in this study, subjects belonging to the case group showed a slight female predominance with a female:male ratio of 1.81:1. mugulkod et al., khajuria et al., and purohit et al. [15–17] exhibited a minor female dominance as well. among the sites of involvement, the commonest was the cervical group of lymph nodes which comprised 89.42%. in the study by mugulkod et al. [15], of the 230 cases of extrapulmonary tb, 184 (80%) were of lymphadenitis. similar to our study, they also showed the cervical group of lymph nodes as most frequently involved. the tubercular lymphadenitis cases were segregated based on the cytologic patterns described by dasgupta et al. [13]. of the 104 subjects, patterns a, b, and c were observed in 25, 69, and 9 cases, respectively. the commonest pattern in this study was pattern b (66.34% cases) showing epithelioid granuloma with necrosis. the same was observed by bhattacharya et al. [18] and khanna et al. [19] in 69.4% and 50.5% cases, respectively. the presence of epithelioid cells was seen in 91.34% cases. giant cells were noticed in 35.57% cases. in the present study, afb positivity (figure 4) was noted in 24.04% cases which was comparable to the ones reported as 25.65% and 26.1% by mugulkod et al. [15] and nassaji et al. [20], respectively. the mean serum ada levels in tubercular and reactive lymphadenitis were calculated as 41.71 ± 11.53 u/l and 21.16 ± 4.16 u/l, respectively. maximum cases, that is, 43.3% showed an ada value in the range of 41–60 u/l followed by 30.8% cases in the range of 31–40 u/l. the mean serum ada level was significantly high among tubercular lymphadenitis compared to reactive lymphadenitis. results similar to our study were also demonstrated in the studies by sulakshana et al. [21], ahmed et al. [22], abdelsadek et al. [23], mugulkod et al. [15], and stevanovic et al. [3]. this was in contrast to the findings of conde et al. [22]. they concluded that although serum ada2 levels might help in differentiating pulmonary tb cases from controls, its utility in distinguishing it from other respiratory diseases is limited. the cut-off value for tubercular lymphadenitis calculated using the roc curve was 32.6 u/l. at this cut-off, sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) were 79.81%, 100%, 100%, and 70.42%, respectively. in the present study, 20 (19.23%) cases had a serum ada level below the cut-off value of 32.6 u/l while none of the control group subjects crossed this value. in contrast, salmanzadeh et al. [24] reported a sensitivity and specificity of 35% and 91%, doi 10.18502/sjms.v16i3.9699 page 394 sudan journal of medical sciences ina garg et al. respectively, for patients with pulmonary tb. they suggested that due to high specificity, ada can be employed to rule out tb in suspected patients having a negative culture for afb. similarly, farazi et al. [25] also reported a low sensitivity with a high ppv. limitations the small sample size of the study may limit statistical relevance. only patients with positive clinical response to treatment were included as cases while those who did not respond to treatment like mdr and xdr cases were excluded. recommendations further investigations with appropriate research methodology setup are needed to conclusively opine about the accuracy of serum ada alone compared to ada as an adjunct tool to fnac in making tb diagnosis. 5. conclusion the raised serum ada level can be considered as a reliable indicator of tubercular lymphadenitis and is a fairly sensitive and specific test. the use of non-guisti’s method makes it a rapid test that can be carried out easily even in remote areas with limited facilities. the best cut-off value calculated in our study was 32.6 u/l at which the sensitivity (79.81%) and specificity (100%) were found to be good enough for this test to help distinguish tubercular from non-tubercular aetiologias and also in detecting afb smear-negative cases. so, in a country like india where tb is endemic, serum ada can be used as an adjunct to fnac for a definite diagnosis of tuberculous lymphadenitis especially in difficult situations or diagnostic dilemma. it can also be used as an early guide in subjecting the patient to fnac considering the cut-off of 32.6 u/l below which we can say with the confidence of 86.36% that it is likely a non-tubercular or tubercular etiology. acknowledgements the authors would like to thank all patients who kindly participated in the study. doi 10.18502/sjms.v16i3.9699 page 395 sudan journal of medical sciences ina garg et al. ethics considerations prior ethical approval was taken from the institutional ethics committee (iec), teerthanker mahaveer medical college & research centre (tmmc&rc), moradabad vide letter no. tmmc&rc/iec/18-19/020 dated 27/12/2018. competing interests the authors declare hereby that there are no conflicts of interest. availability of data and material the raw data used during the current study are available from the corresponding author on reasonable request. funding this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. references [1] world health organization (who). 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[13] dasgupta, a., ghosh, r. n., poddar, a. k., et al. (1994). fine needle aspiration cytology of cervical lymphadenopathy with special reference to tuberculosis. journal of indian medical association, vol. 92, no. 2, pp. 44–46. [14] piras, m. a., gakis, c., budroni, m., et al. (1978). adenosine deaminase activity in pleural effusions: an aid to differential diagnosis. british medical journal, vol. 2, no. 6154, pp. 1751–1752. [15] mugulkod, p., chavan s., s. (2017). serum adenosine deaminase levels and other laboratory parameters in the diagnosis of extrapulmonary tuberculosis: a clinicopathological study. international journal of research in medical sciences, vol. 5, no. 7, p. 3140. [16] khajuria, r., goswami, k. c., singh, k., et al. (2006). pattern of lymphadenopathy on fine needle aspiration cytology in jammu. jk science, vol. 8, no. 3, pp. 157–159. [17] purohit, m. r., mustafa, t., mørkve, o., et al. (2009). gender differences in the clinical diagnosis of tuberculous lymphadenitis-a hospital-based study from central india. international journal of infectious diseases, vol. 13, no. 5, pp. 600–605. doi 10.18502/sjms.v16i3.9699 page 397 sudan journal of medical sciences ina garg et al. [18] bhattacharya, s., raghuveer, c. v., and adhikari, p. (1998). fnac diagnosis of tuberculosis–an eight years study at mangalore. indian journal of medical sciences, vol. 52, no. 11, pp. 498–506. [19] khanna, a., khanna, m., and manjari, m. (2013). cytomorphological patterns in the diagnosis of tuberculous lymphadenitis. international journal of medical and dental sciences, vol. 2, no. 2, pp. 182–188. [20] nassaji, m., azarhoush, r., ghorbani, r., et al. (2014). acid fast staining in formalinfixed tissue specimen of patients with extrapulmonary tuberculosis. international journal of scientific and research publication, vol. 4, no. 1, pp. 2250–3153. [21] sulakshana, m. s., ahmed, s. m., and jayakumar, c. k. (2015). study of serum adenosine deaminase levels in fnac confirmed cases of tuberculous lymphadenitis. international journal of recent advances in multidisciplinary research, vol. 2, no. 6, pp. 0476–0480. [22] ahmed, i., sabah, s., alam, b., et al. (2020). role of serum ada in patients of extra-pulmonary tuberculosis in a tertiary care hospital of bangladesh. international journal of medical research professionals, vol. 6, no. 3, pp. 63–67. [23] alaarag, a., mohammad, o., and farag, n. (2016). diagnostic utility of serum adenosine deaminase level in the diagnosis of pulmonary tuberculosis. egyptian journal of bronchology, vol. 10, no. 2, pp. 133–139. [24] conde, m. b., marinho, s. r., de fatima pereira, m., et al. (2002). the usefulness of serum adenosine deaminase 2 (ada2) activity in adults for the diagnosis of pulmonary tuberculosis. respiratory medicine, vol. 96, no. 8, pp. 607–610. [25] salmanzadeh, s., tavakkol, h., bavieh, k., et al. (2015). diagnostic value of serum adenosine deaminase (ada) level for pulmonary tuberculosis. jundishapur journal of microbiology, vol. 8, no. 3, p. e21760. [26] farazi, a., moharamkhani, a., and sofian, m. (2013). validity of serum adenosine deaminase in diagnosis of tuberculosis. pan african medical journal, vol. 15, p. 133. doi 10.18502/sjms.v16i3.9699 page 398 introduction material and methods inclusion criteria exclusion criteria statistical analysis results discussion limitations recommendations conclusion acknowledgements ethics considerations competing interests availability of data and material funding references sudan journal of medical sciences volume 16, issue no. 3, doi 10.18502/sjms.v16i3.9704 production and hosting by knowledge e research article the early milestones of team-based learning: the key is sustained practice ahmad abdulazeem abdullah omer department of surgery, college of medicine, prince sattam bin abdu aziz university, al-kharj, ksa orcid: ahmad abdulazeem abdullah omer: https://orcid.org/0000-0001-8311-8888 abstract background: to explore students’ perceptions of team-based learning (tbl) initial implementation in a medical school in saudi arabia. methods: this descriptive study used the validated tbl-student assessment instrument (tbl-sai) to gauge students’ perception of tbl in three subscales: accountability, preference, and satisfaction. study participants were fourth-year students at the college of medicine in prince sattam bin abdul aziz university, studying a nine-week introductory surgery course in the academic year 2019–2020. descriptive statistics using the mean scores were used to highlight the results. results: thirty-three students participated in the study. while the mean scores for the three subscales were: accountability 30 (sd 6.6) (neutral score = 24), preference 43.2 (sd 10.8) (neutral score = 48), and satisfaction 25.2 (sd 8.9) (neutral score = 27), the mean of the total questionnaires’ scores was 98.4 (sd 21.8) (neutral score = 99). students expressed a minor level of accountability, poor preference and satisfaction, and an overall low rating of tbl activities. conclusion: low students’ engagement with tbl is likely attributed to their unfamiliarity with this approach and the hostility that they may experience when challenged to refrain from passive learning habits and take an active role toward their learning. lack of the necessary skills and experience to facilitate tbl encounters and the educational climate where didactic teaching is pervasive may be other factors. exposure to tbl may initially be associated with poor students’ perception. perseverance, strong commitment alongside adequate institutional support are necessarily required to mitigate poor outcomes. keywords: active learning, passive learning, team-based learning, saudi arabia 1. introduction teaching medicine has recently witnessed some significant shifts in its educational paradigms to comply with the overarching roles of today’s physicians and the rapidly changing perspectives and standards of local and international healthcare delivery systems [1]. such pressures implied the move-away from passive learning environments how to cite this article: ahmad abdulazeem abdullah omer (2021) “the early milestones of team-based learning: the key is sustained practice,” sudan journal of medical sciences, vol. 16, issue no. 3, pages 454–474. doi 10.18502/sjms.v16i3.9704 page 454 corresponding author: ahmad abdulazeem abdullah omer; email: ahmedsilik@gmail.com received 08 july 2021 accepted 17 september 2021 published 30 september 2021 production and hosting by knowledge e ahmad abdulazeem abdullah omer. this article is distributed under the terms of the creative commons attribution license, which permits unrestricted use and redistribution provided that the original author and source are credited. editor-in-chief: prof. mohammad a. m. ibnouf http://www.knowledgee.com mailto:ahmedsilik@gmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ sudan journal of medical sciences ahmad abdulazeem abdullah omer to strategies where students take an active role and participate effectively in their learning [2]. team-based learning (tbl) has recently emerged as an active learning method that transfers the advantages of small group learning into the premises of large traditional classes [3, 4]. since its first description by michelsean in the early 1990s in business schools, it is currently widely implemented in the realm of medical education [5, 6]. tbl is a form of collaborative learning in which students first perform preparatory readings and then come to the classroom to undertake a series of tests and application exercises individually and in teams [3]. thus, class time is invested in the application of knowledge in real-world problems rather than the passive transmission of information or mere recall of facts [7]. within this student-centered approach to learning and where it is nourished with discussion and proper teacher guidance, students’ learning is enhanced, and their professional skills can be significantly empowered [4, 8]. tbl has been admired for several advantages that it brings to contemporary medical education programs. some reports have asserted better student engagement, knowledge retention, and academic performance in tbl approaches than traditional lectures [8–11]. students also valued tbl activities for making difficult material comprehensible and for the immediate feedback integrated into the process [1]. tbl cultivates essential professional skills like problem-solving, critical thinking, leadership and management, and general clinical skills, which are all essential for physicians to perform their future roles [12, 13]. as students work together to accomplish the goals of their learning, with repeated practice, they develop teamwork skills, particularly communication and shared decision-making [1, 14]. such abilities are of paramount importance to medical students as they reflect the nature of their future work with other healthcare givers where decisions regarding patient care are taken collaboratively, and tasks are usually shared [2, 12, 15]. although tbl employs the same concept of active and small group learning as in flipped classrooms and problem-based learning (pbl), it is unique in some perspectives. tbl grants teachers some control over the learning process by identifying pre-reading assignments and preparing for in-class application exercises. in such a way, tbl is tinged with some teacher directedness while still maintaining its student-centered approach to learning [9, 14]. tbl is also flexible since sessions can be managed by one tutor in a single classroom where the students are seated around tables, which has essential implications, particularly to resource-limited settings [5, 8, 16]. these characteristics might elucidate supremacy of tbl over other active learning pedagogies and may have contributed to its endearment and growing use currently observable in many medical schools around the world [4, 5, 7, 17]. doi 10.18502/sjms.v16i3.9704 page 455 sudan journal of medical sciences ahmad abdulazeem abdullah omer the college of medicine at prince sattam bin abdul aziz university (psau) in saudi arabia administers a hybrid curriculum with integrated system-based teaching in preclinical years (second and third) and discipline-based approach in the clinical years (fourth, fifth, and sixth). the college has recently employed a new curriculum where active small group learning strategies were introduced in conjunction with traditional didactic methods that were pervasive since its establishment. tbl has been introduced in this academic year as part of the new curriculum to lever students’ academic performance and popularize its use in the college. the method is first applied in the introductory surgery course (surgery-1), a nine-week course that introduces the fourth-year students to the basic clinical knowledge and skills for evaluation of common surgical conditions. this study aims to evaluate students’ perceptions of tbl as an innovative method in the new curriculum to enhance their learning. although it may be too early, understanding how students perceive and respond to this active pedagogy may help ease transition from a didactic curriculum into a stage where students take responsibility toward their learning. such preliminary data would provide evidence of tbl acceptance and applicability in our setting and inform decisions regarding its future implementation. bedside, such findings could also be of interest to other medical schools intending to undertake such initiative particularly given the increased fortitude of student-centered methodologies in modern medical education. 2. materials and methods 2.1. study design this descriptive cross-sectional study aimed to assess students’ perceptions of tbl in a medical school where it was implemented for the first time. eight sessions in the course in which this study took place were taught by a tbl approach while the rest of the teaching material was delivered by a combination of methods including simulation, bedside teaching, and didactic lectures [5]. 2.2. subjects and materials the study population consisted of 42 fourth-year students, who were just starting their clinical rotations, at the college of medicine in psau, in al-kharj, saudi arabia. the study participants were enrolled in the basic clinical skills course in surgery (surgery-1) in the academic year 2019–2020. students were recruited voluntarily to participate in the doi 10.18502/sjms.v16i3.9704 page 456 sudan journal of medical sciences ahmad abdulazeem abdullah omer study in february 2020, three months after the conclusion of the surgical rotation. data were collected from participants using the tbl-sai, a validated 33-item questionnaire with documented high reliability and content validity [18]. the instrument assesses students’ perceptions of tbl in three subscales; accountability to team learning, satisfaction, and preference to tbl or lectures (see the appendix). items of the questionnaire were rated by a 5-point likert scale where strongly agree = 5, agree = 4, neutral = 3, disagree = 2, and strongly disagree = 1. the neutral point of comparison for ach subscale was set at the mid-point plus 10% of the total score. arabic translations were added besides the original tbl-sai questions to address the language concerns which may be raised by the students, and to increase the credibility of the results. 2.3. data analysis data were analyzed using the spps computer software (ibm inc. chicago, illinois) version 25. descriptive statistics using the mean score and standard deviation were carried out to highlight the results in each of the three domains of the tbl-sai. besides, the average of the total score of all questionnaires was used as a measure of overall students’ perception of tbl. internal consistency and reliability of students’ responses to the tbl-asi items were assessed using the alpha cronbach statistics. 2.4. the tbl procedure we adopted a tbl strategy that involves all the essential steps, as initially described by michaelsen [4]. students were deliberately divided into six groups of seven students based on their grade point average (gpa) to create groups of homogenous academic ability [3, 9]. in the first session, students were introduced to the objectives and rationale of using tbl and its expected advantages [1, 3]. in lieu of teaching new subject matter, we opted for broad “capstone” topics to assist students to comprehend important curricular areas [3]. in the classroom, each student answered alone 10-item multiplechoice questions as the individual readiness assurance test (irat), and then they attempted the same questions working in their teams as the group readiness assurance test (grat). students then received immediate feedback about their performance where the facilitator clarified concepts and resolved misunderstandings. students’ valid appeals on wording, structure, or truthfulness of questions were accepted and rewarded once referenced to the study material [1, 4]. in the application phase (tapp), students worked in teams to solve clinical problems designed to test the application of knowledge doi 10.18502/sjms.v16i3.9704 page 457 sudan journal of medical sciences ahmad abdulazeem abdullah omer acquired during the previous exercises. the “4s” principle was typically followed; that is, students attempted the same problem, which is significant to which they made specific choices that they reported simultaneously [4]. teachers were advised to act as facilitators rather than subject experts, for example, to solicit student participation, encourage them to articulate their views and reflect on those of their peers, avoid premature closure of discussion, and prepare students to accept some degree of uncertainty [4]. finally, the session was concluded with a short wrap-up followed by peer evaluation and evaluation of the teams by the facilitator. 3. results thirty-four students (out of 42) participated in the study and completed the questionnaire, giving rise to a response rate of 81%. the cronbach alpha reliability of the questionnaire’s items were 0.82, 0.85, and 0.91 for accountability, preference, and satisfaction subscales, respectively, and that of the overall tbl-sai was 0.92 indicating high internal consistency in resonance with the high reliability documented for its original version. the range of scores, the mean, and the neutral scores for each subscale and that of the total questionnaires’ scores are shown in table 1. in summary, students showed a minor level of accountability, poor satisfaction, more preference for lectures, and an overall low rating of tbl activities. table 1: summary of the students’ scores in the three subscales of the tbl-sai (n = 34). subscale scores range mean standard deviation neutral score accountability (possible score 8–40) 16–40 30.0 ±6.6 24 preference (possible score 16–80) 16–62 43.2 ±10.8 48 satisfaction (possible score 9–45) 9–37 25.2 ±8.9 27 total score (possible score 33–165) 41–128 98.4 ±21.8 99 table 2: detailed students’ responses to the tbl-sai (n = 34). no. item strongly agree (x5) agree (x4) neutral (x3) disagree (x2) strongly disagree (x1) average (÷÷÷34) accountability subscale total possible marks (for each student) = (8 x 5) = 40. neutral point = midpoint mark (40/2) + 10% of the total marks (40/10) = 20 + 4 = 24 1. i spend time studying before class in order to be prepared 13 12 7 1 1 4.0 2. i feel i have to prepare for this class in order to do well 13 10 5 2 4 3.8 doi 10.18502/sjms.v16i3.9704 page 458 sudan journal of medical sciences ahmad abdulazeem abdullah omer no. item strongly agree (x5) agree (x4) neutral (x3) disagree (x2) strongly disagree (x1) average (÷÷÷34) accountability subscale total possible marks (for each student) = (8 x 5) = 40. neutral point = midpoint mark (40/2) + 10% of the total marks (40/10) = 20 + 4 = 24 3. i contribute to my teammembers‘ learning 18 5 6 1 4 3.9 4. my contribution to theteam is not important 7 3 8 8 8 2.8 5. my team members expect me to assist them in their learning 12 11 8 1 2 3.9 6. i am accountable to myteam‘s learning 12 15 4 1 2 4.0 7. i am proud of my ability to assist my team in their learning 15 13 2 2 2 4.1 8. i need to contribute tothe team‘s learning 10 8 8 5 3 3.5 total 30.0 preference for lectures or tbl total possible marks = (16 x 5) = 80. neutral point = midpoint (80/2) + 10% of the total marks (80/10) = 40 + 4 = 44 9. during traditional lectures, i often find myself thinking of nonrelated things 7 7 6 8 6 3.0 10. i am easily distractedduring traditional lectures 4 8 9 6 7 2.9 11. i am easily distracted during team-based learning activities 3 0 10 8 13 2.2 12. i am more likely to fall asleep during lecture than during classes that use team-based learning activities 2 5 7 8 12 2.3 13. i get bored during team-based learning activities 4 3 7 9 11 2.4 14. i talk about nonrelated things during team-based learning activities 1 1 7 10 15 1.9 15. i easily remember what i learn when working in a team 4 12 5 9 4 3.1 16. i remember material better when the instructor lectures about it 2 9 11 8 4 2.9 17. team-based learning activities help me recall past information 3 14 7 3 7 3.1 doi 10.18502/sjms.v16i3.9704 page 459 sudan journal of medical sciences ahmad abdulazeem abdullah omer no. item strongly agree (x5) agree (x4) neutral (x3) disagree (x2) strongly disagree (x1) average (÷÷÷34) accountability subscale total possible marks (for each student) = (8 x 5) = 40. neutral point = midpoint mark (40/2) + 10% of the total marks (40/10) = 20 + 4 = 24 18. it‘s easier to study for tests when the instructor has lectured over the material 6 8 8 5 7 3.0 19. i remember information longer when i go over it with team members during the grats used in team-based learning 4 5 15 6 4 3.0 20. i remember information better after the application (tapp) exercise used in team-based learning 3 6 15 6 4 2.9 21. i can easily remembermaterial from lectures 1 5 13 8 7 2.6 22. after working with my team members, i find it difficult to remember what we talked about during class 2 3 13 9 7 2.5 23. i do better on exams when we use team-based learning to cover the material 4 6 10 9 5 2.9 24. after listening to the lecture, i find it difficult to remember what the instructor talked about during class 2 4 11 9 8 2.5 total 43.2 students satisfaction subscale total possible marks = (9 x 5) = 45. neutral point = midpoint (45/2) + 10% of the total marks (45/10) = 22.5 + 4.5 = 27 25. i enjoy team-basedlearning activities 3 13 9 1 8 3.1 26. i learn better in a teamsetting 3 12 10 3 6 3.1 27. i think team-based learning activities are an effective approach to learning 6 12 7 0 9 3.2 28. i do not like to work inteams 2 2 7 10 13 2.1 29. team-based learningactivities are fun 5 9 11 2 7 3.1 30. team-based learning activities are a waste of time 1 3 9 8 13 2.1 doi 10.18502/sjms.v16i3.9704 page 460 sudan journal of medical sciences ahmad abdulazeem abdullah omer no. item strongly agree (x5) agree (x4) neutral (x3) disagree (x2) strongly disagree (x1) average (÷÷÷34) accountability subscale total possible marks (for each student) = (8 x 5) = 40. neutral point = midpoint mark (40/2) + 10% of the total marks (40/10) = 20 + 4 = 24 31. i think team-based learning helped me improve my grade 2 5 10 6 11 2.4 32. i have a positive attitude toward team-based learning activities 4 13 8 3 6 3.2 33. i have had a good experience with team-based learning 4 11 7 3 9 2.9 total 25.2 average total questionnaires points for all students (=total average of all subscales) total possible marks = (33 x 5) = 165. neutral point = midpoint (165/2) + 10% of the total marks (165/10) = 82.5 + 16.5 = 99 98.4 4. discussion this study aimed to explore students’ perception of tbl activities following its first implementation in our setting. results have shown minor levels of accountability and reduced satisfaction with tbl, an inclination to didactic lectures, and overall poor rating of tbl. livingstone et al. (2014) evaluated the application of tbl strategy in a graduate gross anatomy course for physical therapy students in three consecutive years using the tbl-sai and reported similar findings to this study. they highlighted a slight preference to tbl in comparison to didactic lectures (mean scores of 51.3– 55.1) which they reasoned to the struggle that students often experience when they shift from passive learning to student-centered learning strategies particularly at the beaning of such trials. in addition, they pointed a high accountability score (31.5–33.0) which they attributed to the value that students place on teams and teamwork in the tbl strategy [19]. in consonance, mennenga (2015) explored students’ perceptions of tbl upon its first implementation in a community health course in nursing. she reported high accountability score (35.5) and neutral preference for tbl over lectures (47.8). however, students were generally satisfied with the tbl approach (mean score 113.2) upon its introduction [20]. also, branney et al. (2018) examined nursing students’ perceptions of tbl in an undergraduate pathophysiology course where one topic was experimented in the tbl format. they asserted a high accountability score (93% of the students) which they related to the tendency of students to support their team members and contribute doi 10.18502/sjms.v16i3.9704 page 461 sudan journal of medical sciences ahmad abdulazeem abdullah omer to team learning. they also reported a lower preference score than that of the other subscales which they linked to the familiarity of students with lectures [9]. such results may explain the weak accountability and low preference scores in this study. by contrast, some of the results of the aforementioned studies were contradicting the findings of this study, which might shed light on the possible role of the context and the learning environment. moreover, livingstone et al. (2014) argued that “millennial” students have learning styles which may match the tbl methodology, which is not supported by this study. nevertheless, moor-davis et al. (2015) argued that reforming a course into tbl design in clinical rotations is daunting and necessitates considerable effort from teachers, and possibly all parties in the educational climate [19]. besides, junca et al. (2017) argued that short duration of the course, like the case in this study, might not permit adequate exposure to the tbl method and may likely diminish students’ perception of its usefulness to their career and learning [14]. it is well-known that some barriers converge on tbl upon its initial experimentation and may critically determine its acceptability and outcomes. these involve a complex interplay of factors related to students, teachers, the prevailing instructional methods, and the institution’s educational climate [17], and will be discussed below in more details. 4.1. barriers to tbl implementation 4.1.1. unfamiliarity with tbl sharma et al. (2017), who reported findings similar to this study, attributed their results to the short duration and unfamiliarity of instructors with tbl usage [21]. in consonance, livingstone et al. (2014) reported a slight preference to tbl over didactic lectures that they reasoned to the unfamiliarity of students in their series with student-centered learning strategies as mentioned earlier [19]. several studies have pointed out the difficulty that students and teachers often face to engage with tbl approaches when they are not accustomed to this active pedagogical method [2, 8, 9, 14, 21–23]. 4.1.2. changing learners and teachers’ roles in a tbl medium, students are expected to comprehend pre-reading assignments and participate effectively with their teammates to discuss and solve in-class exercises in order to achieve the envisaged goals of their learning. therefore, students’ role would shift to that of an active learner rather than a passive listener, and the expectations doi 10.18502/sjms.v16i3.9704 page 462 sudan journal of medical sciences ahmad abdulazeem abdullah omer would drift away from just receiving information to sound application of knowledge in real-world problems [10, 24]. this significant change in the students’ role added to the workload of pre-class reading and unfamiliarity with tbl would risk bring some of them out of their “comfort zone” and hamper their acceptability and engagement with tbl activities. this is particularly eminent, where passive reception of information in traditional classes is the norm in their learning atmosphere [3, 12, 24]. it was explicated that students who tend to attain ”non-participatory” anonymity in didactic lectures can no longer maintain that in an active tbl environment where they found themselves exposed to their peers and teachers and may, therefore, resent such promising learning methods [9]. in fact, one of the desired skills of facilitation in tbl sessions is the ability to spot and engage those students who tend to sit in far corners to hide themselves [25]. in addition, some students’ traits may play a role as it has been noted that students with introverted personalities and passive attitude toward learning may face trouble in engaging with tbl activities [26]. teachers, who play a crucial role in the process, may also suffer alike where they find themselves unacquainted to the knowledge and skills required to manage tbl classes and lack the necessary training to facilitate its activities [8, 24]. teachers should accept the responsibility to espouse behavioral and attitudinal changes that resonate with their new role as facilitators rather than knowledge transmitters and to prepare exercises that engage students and nourish discussion, which, although difficult can be learned [3, 25]. fujikura et al. (2013) reported similar results to this study from a medical school in japan, where a new curricular design similar to what is applied in this study was experimented [27]. they highlighted low preference to tbl among the fourth-year students compared to other forms of small-group learning, which they related to the quality of the preparation material. moreover, they highlighted the dissatisfaction that teachers exhibited with the tbl approach due to the burden of selecting and preparing useful teaching guides. such difficulties that tbl poses to students and teachers are perceived as the inaugural cost that they need to endure before they embark on the method and embrace its benefits [24]. 4.2. improving perceptions toward tbl 4.2.1. early and sustained practice some researchers have demonstrated improvement in tbl perceptions after some period of practice. mennenga (2015) studied reform of a community health course in doi 10.18502/sjms.v16i3.9704 page 463 sudan journal of medical sciences ahmad abdulazeem abdullah omer nurse education into tbl format at one time and two years later. she pointed to an initial period of students’ frustration with the tbl approach and how they resented its implementation as the prime instructional method. she quoted some students verbalization of this resentment like; “this (tbl) isn’t the way we learn”(p. 77). however, two years later, she reported substantial improvement in students’ perceptions and attitude toward tbl and increased acceptance. she concluded that students need some period of adjustment to cope with their demands and new roles in tbl exercises [20]. likewise, figurero et al. (2015) evaluated application of tbl in a women health clerkship where she reported that the majority of students were initially unaware of the tbl and that more than half of them doubted the benefit of the method to their learning. however, after some period of practice, 60% of the students preferred tbl over lectures and all of them perceived a positive impact on their learning. even later, and during their internship, 55% of the students felt that tbl has improved their practical skills, for example, decision-making [28]. also, livingstone et al. (2014) examined the use of tbl for graduate physical therapy students in three consecutive years as mentioned earlier. they displayed an increase in the students’ scores of all subscales of the tbl-sai, particularly the satisfaction component (mean scores of 32.7–38) and confirmed an overall positive perception of tbl in the third trail in comparison to the first two cohorts. some reports have revealed that early exposure to tbl, particularly when used as the major instructional method, is imperative to its successful application [7, 16, 22]. other studies recommended the early introduction of flipped classrooms in the curriculum and in association with tbl to shift the pendulum movement toward active learning strategies and accustom students for their use early in the course of their studies [21]. this is supported by rajalingam et al. (2018) at a medical college in singapore who showed positive results of tbl where it was used as the prime teaching strategy [29]. it was argued that students tend to prefer passive rather than active learning methods when both strategies are used simultaneously, like the case in this study [3, 26)]. mooredavis et al. (2015) suggested that designing a course in the tbl format requires teachers to work hard to revamp their educational material into one that suits the new learning model. however, once created, they could carry it over and consequently experience less pressure in terms of time and effort. they also added that students might initially feel frustrated with the tbl activities; however, this would likely change over some period of practice [16, 19, 20, 23, 30]. fortunately, it was shown that students would still perceive tbl activities positively when they appreciate the vital implications that tbl conveys to their future career [9, 29, 31]. branney and priego-hernández (2018) explained the positive perception of students to tbl in their setting to the relevance of tbl activities doi 10.18502/sjms.v16i3.9704 page 464 sudan journal of medical sciences ahmad abdulazeem abdullah omer that the latter have seen to the nature of work in the clinical environment [9]. having mentioned the importance of early incorporation of tbl activities in the curriculum, it should be emphasized that careful balance and coordination of tbl activates within and among courses beside consideration of the examination schedules is essential to avoid overwhelming the students with daunting workload and hence decrease the outcomes [16, 27]. in contrast, zachry et al. (2017) highlighted that students in their series preferred traditional lectures to tbl and concluded that the former “still has a place in the college classroom” [21; p. 7]. of course, the provision of some instruction at the end of tbl sessions to clarify concepts and resolve remaining uncertainties would allow for proper closure and could be as vital in tbl as in formal lectures [5, 7, 9, 12, 14, 22, 25]. moordavis et al. (2015) investigated revision of a didactic midwifery masters level course into a tbl design. they reported improvement in students’ evaluation of the tbl method when teachers added recorded lectures. they argued that modification of the tbl method might be necessary to address the needs of the students. likewise, branney priego-hernández (2018) noted a low preference to tbl sessions among the students in their study. they explained that tbl might not be applicable in every setting, and that alignment of the process to the context is important [30]. thus, it appears that the judicious use of mixed instructional methods customized to the nature of the subject, the educational climate, and the level of familiarity and expertise of faculty and students is a practical strategy [24, 27]. 4.2.2. faculty development the importance of faculty development programs to train teachers to accomplish their roles as facilitators and to create functional application exercises that engage students and promote learning and teamwork cannot be overemphasized [1, 16, 22]. the desired teachers’ skills also encompass thoughtful formation of students’ groups, communication of goals, selection of appropriate pre-reading material, and careful planning for the sessions, including time management, which, although challenging at the beginning can be mastered [3, 25]. tbl hinges on appropriate students’ orientation to the objectives and methodology of the process and its numerous advantages to their career and course coordinators should address these concerns assiduously. of course, such efforts should be complemented with educational values and institutional norms that endear the deliberate use of active learning strategies at all stages of study and encourage students and teachers to buy-in the process [3, 8, 16]. doi 10.18502/sjms.v16i3.9704 page 465 sudan journal of medical sciences ahmad abdulazeem abdullah omer finally, consideration of the aforementioned strategies would enable all parties in the educational process to exploit the benefits of tbl and create a learning environment conducive to active learning [2, 21, 32, 33]. it has been emphasized that students’ perception of tbl depends after all on the interplay of all the factors mentioned earlier and their influence on each other rather than the mere execution of tbl steps [3, 16, 26]. for instance, thompson et al. (2007) reported on the application of tbl in 10 medical schools at one time and then two years later. they highlighted faculty experience with the method, the confidence that they acquire with repeated practice, and professional development as crucial ingredients of the tbl process. they also substantiated the vital roles of the administrative support and the learning environment in defining tbl outcomes [16]. the results of some studies were encouraging and demonstrated a positive transformation in students’ perceptions and attitude toward tbl after a preliminary period of poor results [9, 16, 29]. however, some other studies reported mixed results [5, 29, 34]. therefore, longitudinal studies are required to explore in-depth role and interaction of the factors ambient to the tbl strategy in our environment. this study is limited by the small number of participants and being conducted in one course and a single class in the college. as such, the results cannot be generalized to other settings. it is also limited by the small number of tbl activities conducted in the course (eight sessions) to the other teaching methods. however, the findings of this study would still provide an insight into the factors that revolve around tbl implementation in our environment and set the stage to improve its future practice. further studies would be required to explore the perils and promises of the tbl approach and inform the best way of its implementation in our setting. 5. conclusion tbl is an active, student-centered approach to learning that is widely used nowadays in medical education programs. the method has been introduced recently in our setting to enhance students learning and promote their professional growth. preliminary results showed a minor level of accountability, weak preference and satisfaction, and an overall poor tbl rating. these results can be attributed to the unfamiliarity of students and teachers with tbl approaches and the difficulty that they may experience to attain their new roles to cope with it. perseverance and strong commitment to sustain tbl approaches are crucial at the beginning of such projects and would eventually set the stage for better outcomes. with repeated practice and adequate institutional support, doi 10.18502/sjms.v16i3.9704 page 466 sudan journal of medical sciences ahmad abdulazeem abdullah omer tbl knowledge and skills would fleet into the college’s atmosphere, and gradually all parties would reap its numerous advantages to practice and learning. acknowledgments the author would like to express his gratitude to the copyright holder of the tbl-sai who granted permission to use it in this study. he is also grateful to the fourth-year students for their participation in this research. ethical considerations this study was approved by the institutional review board of the college of medicine (psau/com/rc/irb/p/78 and supported by the deanship of scientific research at prince sattam bin abdul-aziz university, al-kharj, saudi arabia. the copyright holder granted permission to use the tbl-sai in this study. questionnaires were administered anonymously by the department of medical education three months after the conclusion of the course. competing interests the author reports no conflict of interest. availability of data and material all relevant data and methodological details pertaining to this study are available to any interested researchers upon reasonable request to corresponding author. funding none. references [1] branson, s., boss, l., and fowler d. 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(2009). medical students’ attitudes about team-based learning in a preclinical curriculum. medical education online, vol. 14, no. 1, p. 4503. doi 10.18502/sjms.v16i3.9704 page 470 sudan journal of medical sciences ahmad abdulazeem abdullah omer appendix •the tbl-sai; arabic translations were added beside the original questions to address the language concerns and increase the credibility of the results. department of surgery surgery-1 course, 2019-2020 team-based learning evaluation study this instrument asks you about your experience with team-based learning. there are no right or wrong answers. please be honest and report your reaction to each question by circling the number for the response that best describes your answer. الرجاء وأماںة. دقة ب سئ ا ع جابة ا الرجاء فريق. التع لية عن إںطباعك لتقي مت ستباںة ا ستباںة ا ع ك إ كتابة عدم 1. accountability scale الفريق) اه سؤولية ا :(مقياس this subscale assesses student preparation for class and contribution to the team: الفريق ته مسا و للنشاط الطالب ض مدى مقياس no item strongly agree agree neutral disagree strongly disagree 1. i spent time studying before class in order to be prepared. للنشاط ںف ز جيدا لدراسة أقوم 2. i feel i have to prepare for this class in order to do well. فيه يد ا داء ا من كن ا ح للنشاط التحض ية أشعر 3. i contribute to my team members‘ learning. التع ع الفريق زم مساعدة أسا 4. my contribution to the team is not important. الفريق نشاط جيدا أسا 5. my team members expect me to assist them in their learning. التع ع م مساعد م يتوقعون الفريق زم 6. i am accountable to my team‘s learning. فري تع اه سؤولية أشعر 7. i am proud of my ability to assist my team in their learning. . التع ع رم مساعدة ع قدر ور ا 8. i need to contribute to the team‘s learning. الفريق تع لية ة سا ل وجة أشعر 2. preference for lecture or team-based learning: فريق) التع لية أم ات ا ا :(أفضلية this subscale assesses student ability to recall material and student attention level in lecture and team-based learning: doi 10.18502/sjms.v16i3.9704 page 471 sudan journal of medical sciences ahmad abdulazeem abdullah omer فريق التع لية و ات ا ا ب مقارںة ںتباه ا مدى و علومات ا إستحضار ع الطالب مقدرة مقياس no item strongly agree agree neutral disagree strongly disagree 9. during traditional lectures, i often find myself thinking of non-related things. ص ا ليست أشياء أفكر ںف أجد , التقليدية ات ا ا ل خ ة ا 10. i am easily distracted during traditional lectures. . التقليدية ات ا ا اثںاء و ب و أ 11. i am easily distracted during team-based learning activities. فريق. التع لية ل خ و ب و أ 12. i am more likely to fall asleep during lecture than during classes that use team-based learning activities. فريق. التع لية اثںاء مںه ات ا ا ل خ اك م أ إن ل إح 13. i get bored during team-based learning activities. فريق. التع نشاطات أثںاء لضحر أشعر 14. i talk about non-related things during team-based learning activities. فريق. التع نشاطات أثںاء وضوع ا عن خارجة أشياء أت 15. i easily remember what i learn when working in a team. فريق. أتع عںدما و ب علومات ا أستح أن أستطيع 16. i remember material better when the instructor lectures about it. طريق عن أتلقاها عںدما أك بصورة علومات ا أستح أن أستطيع ة. ا ا 17. team-based learning activities help me recall past information. السابقة. علومات ا إستحضار ع فريق التع نشاطات تساعد 18. it‘s easier to study for tests when the instructor has lectured over the material. ة. ا ا طريق عن علومات ا أتل عںدما ختبارات ل التحض ل ي 19. i remember information longer when i go over it with team members during the grats used in team-based learning. ماعية ا ںاقشة ا ل خ من أتلقاها عںدما أطول ة لف علومات ا أستح الفريق. 20. i remember information better after the application (tapp) exercise used in team-based learning. النشاطات ل خ من أتلقاها عںدما أطول ة لف علومات ا أستح الفريق. ماعية ا و التطبيقية 21. i can easily remember material form lecture. . و ب ات ا ا من علومات ا إستحضار أستطيع 22. after working with my team members, i find it difficult to remember what we talked about during class. لںا ل خ زم مع ا قش ال علومات ا إستحضار بصعوبة أشعر كفريق. doi 10.18502/sjms.v16i3.9704 page 472 sudan journal of medical sciences ahmad abdulazeem abdullah omer no item strongly agree agree neutral disagree strongly disagree 23. i do better on exams when we use team-based learning to cover the material. لتغطية فريق ل خ من أتع عںدما ختبارات ا أفضل بش أؤدي قرر. ا 24. after listening to the lecture, i find it difficult to remember what the instructor talked about during class. ات. ا ا أثںاء معلومات من إلقاؤه ما إستحضار صعوبة أجد 3. student satisfaction subscale فريق) التع لية عن الطالب ر :(مدى this subscale assesses student satisfaction with team-based learning: فريق: التع لية عن الطالب ر مدى قياس no item strongly agree agree neutral disagree strongly disagree 25. i enjoy team-based learning activities. فريق. التع بنشاطات أستمتع 26. i learn better in a team setting. فريق ن العمل ل خ من أفضل بصورة أتع 27. i think team-based learning activities are an effective approach to learning. . للتع فعا طريقة فريق التع لية أن أعتقد 28. i do not like to work in teams. فريق. ن ل أ أن أحب 29. team-based learning activities are fun. تعة. فريق التع نشاطات 30. team-based learning activities are a waste of time. للوقت. مضيعة فريق التع نشاطات 31. i think team-based learning helped me improve my grade. . درجا س ع ساعدت فريق التع لية أن أعتقد 32. i have a positive attitude towards team-based learning activities. فريق. التع لية اه ميول و جيد إحساس لدي 33. i have had a good experience with team-based learning. فريق. التع لية مع جيدة ربة لدي 4. please add any comments you may have about your experience with teambased learning: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . thank you for your time doi 10.18502/sjms.v16i3.9704 page 473 sudan journal of medical sciences ahmad abdulazeem abdullah omer copy right of mennenga ha (2012). permission was granted by the copyright holder to administer this instrument to evaluate tbl implementation in surgery-1 course 20192020. doi 10.18502/sjms.v16i3.9704 page 474 introduction materials and methods study design subjects and materials data analysis the tbl procedure results discussion barriers to tbl implementation proxima-nova-bold-italic.otfunfamiliarity with tbl proxima-nova-bold-italic.otfchanging learners and teachers' roles improving perceptions toward tbl proxima-nova-bold-italic.otfearly and sustained practice proxima-nova-bold-italic.otffaculty development conclusion acknowledgments ethical considerations competing interests availability of data and material funding references appendix