404 not found 151 journal of rawalpindi medical college (jrmc); 2020; 25(2): 151 editorial hesitancy in getting covid-19 vaccine – an alarming concern riaz ahmed1 1 dean orthopaedics, neurosurgery & trauma department, rawalpindi medical university, rawalpindi. cite this article: ahmed, r. hesitancy in getting covid-19 vaccine – an alarming concern. journal of rawalpindi medical college. 30 jun. 2021; 25(1): 151. doi: https://doi.org/ 10.37939/jrmc.v25i2.1720 access online: recent findings and publications indicate that vaccine hesitancy for coronavirus (covid-19) is growing in all age ranges. in a newly released correspondence, it was reported that prospective healthcare practitioners would need assistance and adequate education in order to assist society in combating the covid-19 pandemic.1 also medical students, who are most likely to come into contact with covid-19 patients, are reluctant to receive vaccinations.2 thus, it is strongly advised that adequate education be provided about the protection and effectiveness of vaccinations to alleviate the problem. a cross-sectional analysis found that 28.8 percent of working-age population participants choose to forego vaccination entirely, which was closely correlated with many previously described causes, including lower educational level, weak conformity with prior vaccine guidelines, and lower expectations of covid-19 seriousness.3 the reluctance to vaccinate can be seen as a deterrent for medical personnel who treat patients afflicted with covid-19, as they are at the greatest risk of infection. apart from protection and effectiveness, as described, it is critical to 'educate, advise, and interfere.' on a related note, public trust in biomedical research must be considered, since it influences citizens' willingness to participate in the vaccine campaign. given the overwhelming number of people's reluctance, it is proposed that public health programmes be restructured. educating and raising awareness about the new vaccination would help build public confidence in the battle against the pandemic. reference 1. rehman k, hakim m, arif n, ul s, lady i. covid-19 vaccine acceptance, barriers and facilitators among healthcare workers in pakistan. res sq. 2021;65(3):1–15. https://doi.org/10.21203/rs.3.rs-431543/v2 2. malik a, malik j, ishaq u. acceptance of covid-19 vaccine in pakistan among health care workers. medrxiv. 2021;24(3):20–4. doi: https://doi.org/10.1101/2021.02.23.21252271 2. schwarzinger m, watson v, arwidson p, alla f, luchini s. covid-19 vaccine hesitancy in a representative working-age population in france: a survey experiment based on vaccine characteristics. lancet public heal. 2021;6(4):e210–21. https://doi.org/10.1016/s2468-2667(21)00012-8 192 journal of rawalpindi medical college (jrmc); 2019; 23(4): 192-193 editorial development of paediatric surgery department in the resource-limiting country 1mudassir fiaz gondal, 2naeem liaqat 1 associate professor & head of department, paediatric surgery, rawalpindi medical university 2 assistant professor, paediatric surgery, rawalpindi medical university cite this article: gondal, f. m. & liaqat, n. (2019). development of paediatric surgery department in the resource-limiting country. journal of rawalpindi medical college, 23(4), 192-193 access online: https://journalrmc.com/index.php/jrmc/article/view/1313 care of paediatric surgery patients demands a high level of commitment, expertise and logistic support as the child needs exclusive care from all aspects. at the same time, these services are neglected and not up to the mark, particularly in developing countries.1 it makes it compulsory to provide adequate and required infrastructure, equipment, trained staff and other logistics to take care of the increasing burden of these patients. 1,2 paediatric surgery services are far lacking in pakistan generally.1 as per american paediatric surgical association, the number of paediatric surgeons must be at least a 1/100,000 population of 0-15 years.3 as per the census of pakistan done in 2017, the total population of 0-15 years was 43.4% of the total population.4. however, the total of paediatric surgeons working in pakistan in 2019 was less than 200. the number of paediatric surgeons in pakistan per 100,000 population is 0.26 5, which is far less than the minimum required qualified consultants. rawalpindi division is the fourth most populated city of pakistan and has a population of 10.1 million as per census 6 and approximately 43.5 lacs are of the age 0-15 years.4 rawalpindi is a densely populated division of punjab.6 paediatric surgery services are lacking in pakistan generally, and in northern punjab especially. enactment area of teaching hospitals of rawalpindi includes a huge population of northern areas of punjab (including four districts of rawalpindi), khyber pakhtunkhwa, northern areas of pakistan and azad jammu kashmir. as only one public sector unit of paediatric surgery is available at federal level, so teaching hospitals of rawalpindi have to provide care to a large population which reciprocates the burden exceeding the available resources. it results in provision of compromised care to the paediatric surgery patients. developing paediatric surgery services at public sector hospitals is direly needed. paediatric surgery department at holy family hospital (hfh) started in july 2016. initially, it started its services from a 4bedded room and one day for outpatient department (opd) patients. there was only one faculty member. however, later on, department progressed and soon teaching activities including rotation of postgraduate residents (pgrs) was allowed. afterwards, in january 2018, this department got recognized for the training of pgrs for fcps program by the college of physicians and surgeons (cpsp) and master of surgery program (ms) by university of health sciences (uhs), which populated the department. currently paediatric surgery department, hfh is taking care of a huge number of patients presenting in opd. it is providing its services in opd for 3 days a week. the operation theatre services are being provided three days a week and 24/7 emergency cover for paediatric surgery cases is being provided. there are 4 faculty members now in paediatric surgery department, hfh and 7 trainees of both fcps and ms programs are being trained. developing a paediatric surgery department at rawalpindi medical university (rmu) had been arduous. paediatric surgery department cannot work alone; rather it is a team-based approach which needs 193 journal of rawalpindi medical college (jrmc); 2019; 23(4): 192-193 exclusive support from paediatric medicine, anaesthesia and intensive care units (icu) staff (7, 8). similar problems had been here as there was no trained staff for the care of paediatric surgery patients, no faculty member from other units was there to join a newly developing department. however, luckily, the paediatric surgery department found extensive support from the administration, general surgery; anaesthesia and paediatric medicine departments which made it possible to develop a collaborative approach for these patients. developing more and more departments is direly needed for the provision of standardized and compassionate care to the patients regarding paediatric surgical services. it is need of the time to develop maternal and child health centres like children hospitals so that multidisciplinary care may be available in a standardized fashion to children (1, 2). as the minimally invasive surgery services are developing globally, there is a need to develop these services at different centres of pakistan. we suggest the development of more centres and provision of logistic support to the newly developing departments in our country. reference 1. sohail ah, maan mha, sachal m, soban m. challenges of training and delivery of pediatric surgical services in developing economies: a perspective from pakistan. bmc pediatr. 2019;19(1):152. 2. akhtar j. postgraduate training program in pediatric surgery: a way forward. apsp journal of case reports. 2011 jan;2(1):1. 3. o'neill ja, jr., cnaan a, altman rp, donahoe pk, holder tm, neblett ww, et al. update on the analysis of the need for paediatric surgeons in the united states. j pediatr surg. 1995;30(2):204-10; discussion 11-3. 4. the population of children 0-14 years in pakistan 2017 [available from http://www.pbs.gov.pk/content/population-5-year-agegroup-pakistan]. 5. krishnaswami s, nwomeh bc, ameh ea. the paediatric surgery workforce in lowand middle-income countries: problems and priorities. semin paediatric surg. 2016;25(1):32-42. 6. the population of rawalpindi, pakistan 2017 [available from: http://www.pbs.gov.pk/sites/default/files/bwpsr/punjab/r awalpindi_blockwise.pdf. 7. shin k, moreno-uribe lm, allareddy v, burton rg, menezes ah, fisher md, et al. multidisciplinary care for a patient with syndromic craniosynostosis: a case report with 20 years of special care. spec care dentist. 2019. 8. weigl m, heinrich m, keil j, wermelt jz, bergmann f, hubertus j, hoffmann f. team performance during postsurgical patient handovers in paediatric care. european journal of pediatrics. 2019 dec 19:1-0. 290 journal of rawalpindi medical college (jrmc); 2020; 24(4): 290-291 letter to the editor fallow time and managing aerosol generation in dental clinics–current evidence and financial investment implications fazal ghani1 1 head of prosthodontics department & dean and director, postgraduate dental programs, peshawar dental college, warsak road, peshawar. author’s contribution 1 conception of study 1 experimentation/study conduction 1 analysis/interpretation/discussion 1 manuscript writing 1 critical review 1 facilitation and material analysis corresponding author dr. fazal ghani, head of prosthodontics department & dean and director, postgraduate dental programs, peshawar dental college, warsak road, peshawar email: fazalg55@hotmail.com article processing received: 13/10/2020 accepted: 15/10/2020 cite this article: ghani, f. fallow time and managing aerosol generation in dental clinics– current evidence and financial investment implications. journal of rawalpindi medical college. 30 dec. 2020; 24(4): 290-291. doi: https://doi.org/10.37939/jrmc.v24i4.1492 conflict of interest: nil funding source: nil access online: introduction recently, the scottish dental clinical effectiveness programme (sdcep) was tasked to perform a rapid review on the guidelines related to factors mitigating the effect of aerosol generation during dental procedures and reduction in fallow-time. review1, reflecting the tireless work by the sdcep review board can be truly considered as a report that the profession has been looking for. the sdcep’s review comes at a time when the science has not been comprehensive and doesn’t outline how to best ensure public and staff safety in the dental clinic.2 he hopes that the government policy and any new instructions will now reflect the recommendations made in this review. considering the issues of continued frustration of the dental profession, towards the end of june, the office of the chief dental officers (cdos) in the uk tasked the sdcep to get to grips with the matter. it is worthnoting that sdecp3 has been held in high regard for its outstanding work on antimicrobial resistance, antibiotic prophylaxis, dental amalgam, and periodontal care, and has been praised by all the cdos in the uk four countries including england, scotland, wales, and northern ireland. in response, the sdcep immediately convened a multidisciplinary working group to identify and appraise all the available evidence concerning the generation and mitigation of aerosol dentistry and the associated risk of covid-19 transmission. the aim was to reach a number of agreed position statements informing policy and clinical guidance. the review members’ dedication, commitment, and clinical and academic expertise have been hugely impressive.2 all worked for almost three months and there were; remarkable academics, virologists, physicists, public health officials, and other wetfingered dentists. the process required hours of virtual meetings piled on top of intensive review work. to complete the review, everyone almost felt like being a student again waking up to spend hours on physics of relevance to aerosol and epidemiology of airborne viral diseases. recommendations it would be certainly surprising to many dental care professionals, practitioners, and even dental academics, to know that aside from severe acute respiratory syndrome (sars) and middle-east 291 journal of rawalpindi medical college (jrmc); 2020; 24(4): 290-291 respiratory syndrome (mers), there has been a dearth of historic research on dental aerosols and the aerosol-related infectious diseases transmission. not only this has been acknowledged in the sdcep after it had assessed past and current scientific evidence for aerosols and mitigation factors from around the globe but it also became clear that the existing evidence also was of low quality. consequently, sdcep could not draw recommendations from the evidence alone. hence the review is not to be taken as government guidance. rather it aims to inform policymakers. the review has compiled and presented ‘considered judgments’ to help the profession at this unprecedented time. each judgment had been supported by a majority of 75% of the review board to strike the best path forward. the review is also a living document and the group will have to be recalled when new evidence arises or developments unfold. as per the advice of the review board, the current recommendations should not be considered as the final ones, and as such the current restrictions might become stricter or more relaxed, in case of the pandemic becoming more or less severe. the review1 outlines the methodology and agreed on positions and gives a series of recommendations on the generation and mitigation of aerosols in dental practice and the associated risk of covid-19 transmission. the review while admitting us as professionals to be familiar with agps but for the first time it has delineated between the different categories of agps including:  high-risk dental procedures that require fallow time and …  lower risk dental procedures that can be dealt with using standard control precautions. in the dental clinical areas, a protocol of mechanical ventilation that ensures at least 10 changes per hour will bring the fallow time down to 10-minutes. keeping this in view, the reviewers have agreed that a pragmatic fallow time of 10-60 minutes is recommended to reduce the risk of coronavirus transmission through the use of a series of mitigation techniques including: 1. the use of high-volume suction, already estimated to be used by 94% of dental practices in the uk, could reduce fallow time to 20-minutes if applied effectively. 2. likewise, the use of rubber dams for all restorative dental procedures that produce aerosol is also recommended. but the key to reducing fallow time is ensuring a high ventilation rate. 3. dental care providers must investigate the air change rate to ensure they comply with the guidance that clinical treatment rooms should have at least 10-air-changes per hour an open window is probably not enough. 4. mechanical ventilation ensuring at least 10-airchanges per hour should bring the fallow time down to 10-minutes, plus 10-minutes cleaning time will be in line with recommendations made in the review. financial investment implication with the recommendations and enforcements, if the fallow time was reduced to 10-minutes then the working capacity of a dentist would increase significantly and possibly up to 70% of the precovid-19 capacity. certainly, that would vastly improve the current threat to dentist viability and would help to tackle the worrying impact that lockdown has inevitably had on the population's oral health. however, to get to achieve this by instituting redesigning dental clinical areas, there are potentially vast costs involved. hence the huge capital investment in dentistry is thus essential to move forward. having said, this, it is not as frivolous as a single practice taking on some renovation but this is a public health measure and it is a reasonable asking from the government to help get dentistry back on its pre-covid level. this act would show the kind of commitment to our profession that we have needed and asked for since the outbreak first took shape. references 1. sdcep. mitigation of aerosol-generating procedures in dentistry a rapid review. version 1.0. 25 september 2020. https://www.sdcep.org.uk/wpcontent/uploads/2020/09/sdcep-mitigation-of-agps-indentistry-rapid-review.pdf(accessed 04 oct 2020). 2. armstrong m (2020). sdcep, fallow time and agps what you need to know. https://www.bda.org/newscentre/blog/pages/sdcep-fallow-time-and-agps-what-youneed-to-know.aspx?utm_campaign=sdcep-fallow-timeagp&utm_source=twitter&utm_medium=social(accessed – 04 oct 2020). 3. scottish dental clinic effectiveness programme. https://www.sdcep.org.uk/(accessed 04 oct 2020). 575 journal of rawalpindi medical college (jrmc); 2021; 25(4): 575-577 case report bilateral chylothorax post blunt trauma: a case report muhammad waseem1, maryam rafiq2, m haseeb malik3 1 assistant professor & hod, department of pulmonology, sahiwal medical college, sahiwal. 2 assistant professor, department of pathology, sahiwal medical college, sahiwal. 3 medical officer, basic health unit, jandraka, okara. author’s contribution 1 conception of study 1 experimentation/study conduction 1 analysis/interpretation/discussion 2 manuscript writing 2 critical review 3 facilitation and material analysis corresponding author dr. maryam rafiq, assistant professor, department of pathology, sahiwal medical college, sahiwal. email: mariamsheikh15@yahoo.com article processing received: 04/10/2021 accepted: 07/12/2021 cite this article: waseem, m., rafiq, m., malik, m.h. bilateral chylothorax post blunt trauma: a case report. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 575-577. doi: https://doi.org/10.37939/jrmc.v25i4.1788 conflict of interest: nil funding source: nil access online: abstract introduction: blunt trauma is a rare cause of chylothorax. in this study, an uncommon case of traumatic chylothorax after blunt trauma is described along with treatment options. report on a case: a 50-year-old male was admitted to the hospital with sudden onset of shortness of breath for one day. he had a history of road traffic accidents 2 days ago, in which he received a strong jerk while trying to avoid impact with the dashboard of the vehicle. he has no past medical history. on examination, he was fully conscious and oriented. air entry on both sides of the chest was reduced. the x-ray of the chest revealed bilateral blunting of costo-phrenic angels due to pleural effusion. pleural fluid was sent for biochemical, microbiological, and histopathological analysis. fluid triglyceride and cholesterol levels were elevated. culture and sensitivity were negative while cytopathological analysis revealed increased wbcs. ct scan of the chest did not reveal any malignancy or mediastinal lymph nodes. bilateral chest intubation was done to treat severe shortness of breath, that drained milky white fluid. the patient was observed without any particular treatment other than chest intubation. the patient responded well and was discharged uneventfully after five days. conclusion: despite its rarity, chylothorax can occur after blunt trauma. diagnosis should be confirmed by laboratory testing. conservative management with or without chest intubation is a common treatment option. keywords: blunt chest trauma, chylothorax, triglyceride. 576 journal of rawalpindi medical college (jrmc); 2021; 25(4): 575-577 introduction chylothorax is a buildup of milky fluid (chyle) between the visceral and parietal pleura, due to leakage from the thoracic duct. bartolet first described it in 1633, and the first case was reported by quinke in 1875.1 chylothorax can be classified as congenital, neoplastic, traumatic, and miscellaneous.2 the most common cause of chylothorax is cancer that causes obstruction of the thoracic duct.3,4 surgical intervention or percutaneous catheter implantation are the most common iatrogenic causes of chylothorax.5,6 traumatic chylothorax (tc) commonly occurs from penetrating injuries to the thoracic duct. blunt trauma is a relatively uncommon cause of chylothorax. it should, however, be evaluated in cases that develop pleural effusion after blunt trauma, as it can result in lethal consequences.5 the purpose of this study is to describe a case of chylothorax caused by blunt chest trauma and to discuss treatment options. case report a 50-year-old male was admitted to the hospital with sudden onset of shortness of breath for one day. he had a history of road traffic accidents 2 days ago. during the accident, he received a strong jerk. on examination, he was fully conscious and oriented. air entry on both sides of the chest was reduced. the x-ray of the chest revealed bilateral blunting of costo-phrenic angels due to pleural effusion ct scan of the chest also showed bilateral pleural effusion, it did not reveal any malignancy or mediastinal lymph nodes (figure 1). figure 1: bilateral pleural effusion with no lymph nodes or malignancy evidence pleural fluid was sent for biochemical, microbiological, and histopathological analysis. triglyceride (tg) and cholesterol levels in the pleural fluid were found elevated. the level of tg was 2406mg/dl and cholesterol was 108mg/dl. tg culture and sensitivity revealed occasional wbcs, and culture was negative. histopathology confirmed that the pleural fluid was a fat-rich fluid with few inflammatory cells. the patient was intubated bilaterally. drain output was monitored in both chest drains to below 0.5 litre per day. the icc drainage per day of admission is shown in (figure 2). figure 2: intercostal catheter volumes (ml) per day of admission 577 journal of rawalpindi medical college (jrmc); 2021; 25(4): 575-577 chest tubes were removed by day five of admission without complications. the patient was uneventfully discharged on day five of admission. discussion a rare but serious consequence of chest trauma is disruption of the thoracic duct. blunt trauma can result in traumatic chylothorax by a direct breach in diaphragmatic crura, hyperextension of the spine, or direct injury due to vertebral fracture or ribs.7 in our case it could be due to hyperextension of the spine during accident leading to injury to any tributaries of the thoracic duct as the patients responded well to conservative management. nonetheless, a partial tear of the primary thoracic duct spilling chyle with high lipid concentrations cannot be ruled out altogether. symptoms of chylothorax appear gradually, after 2 to 7 days of injury.8 to establish the diagnosis of chylous effusion, triglyceride or cholesterol levels in the pleural fluid were measured quantitatively, which were both grossly elevated. to classify effusions into chylous or non-chylous, staats et al. measured triglyceride levels in 142 effusions by lipoprotein electrophoresis. they found that fluid with a triglyceride value greater than 110 mg/dl has a 99 percent chance of being chylous, while chances are less than 5% if a triglyceride value is less than 50 mg/dl.6 the results of culture and sensitivity negative and cytopathology revealed scattered reactive inflammatory cells. these laboratory data confirmed chylothorax as culture is usually negative in chylothorax, owing to the bacteriostatic characteristic of chyle.9 conservative management is successful in 88% of cases. however, cause, clinical presentation, and volume of drainage all have a role in determining management strategies.10 as chyle is an irritating fluid that causes pleurodesis, there is spontaneous closure of the leak. lung intubation causes the lung to expand, thereby improving clinical conditions. the patient was also kept npo to reduce chyle production. conservative treatment should preferably be provided for two weeks; however, it can be stretched to four weeks (11). when the daily chyle leak surpasses 1 liter/ day for more than 5 days, surgical intervention generally is better than conservative therapy.11 the most common surgical procedure is thoracic duct ligation. video-assisted thoracoscopic surgery (vats) or an open thoracotomy may be used to accomplish this.12 conclusion chylothorax can be a complication of blunt chest trauma, albeit it is relatively rare. before addressing management, the diagnosis should be validated with laboratory tests. patients with chylothorax are given conservative treatments. references 1. jahsman we. chylothorax; brief review of literature; report of three non-traumatic cases. ann intern med. 1944 oct 1;21(4):669-78. https://doi.org/10.7326/0003-4819-21-4669 2. demeester t. the pleura. in: spencer e, editor. surgery of the chest. 4ed. philadelphia: wb saunders; 1983. 3. doerr ch, allen ms, nichols iii fc, ryu jh. etiology of chylothorax in 203 patients. in mayo clinic proceedings 2005 jul 1 (vol. 80, no. 7, pp. 867-870). elsevier. 4. mcwilliams a, gabbay e. chylothorax occurring 23 years post‐irradiation: literature review and management strategies. respirology. 2000 sep;5(3):301-3. doi: 10.1046/j.14401843.2000.00263.x 5. seitelman e, arellano jj, takabe k, barrett l, faust g, angus lg. chylothorax after blunt trauma. j thorac dis. 2012 jun 1;4(3):327–30. doi: 10.3978/j.issn.2072-1439.2011.09.03 6. pillay tg, singh b. a review of traumatic chylothorax. injury. 2016 mar 1;47(3):545-50. doi: 10.1016/j.injury.2015.12.015 7. kamal idris ms, hefny af, khan nh, abu-zidan fm. blunt traumatic tension chylothorax: case report and mini-review of the literature. world j clin cases. 2016 nov 16;4(11):380. doi: 10.12998/wjcc.v4.i11.380 8. ikonomidis js, boulanger br, brenneman fd. chylothorax after blunt chest trauma: a report of 2 cases. can j surg. 1997 apr;40(2):135. 9. golden p. chylothorax in blunt trauma: a case report. am j crit care. 1999 may 1;8(3):189. 10. demos nj, kozel j, scerbo je. somatostatin in the treatment of chylothorax. chest. 2001 mar;119(3):964– 6. doi: 10.1378/chest.119.3.964 11. dugue l, sauvanet a, farges o, goharin a, le mee j, belghiti j. output of chyle as an indicator of treatment for chylothorax complicating oesophagectomy. br j surg. 1998 aug;85(8):1147– 9. doi: 10.1046/j.1365-2168.1998.00819.x 12. patterson ga, todd tr, delarue nc, ilves r, pearson fg, cooper jd. supradiaphragmatic ligation of the thoracic duct in intractable chylous fistula. ann thorac surg. 1981 jul;32(1):44– 9. doi: 10.1016/s0003-4975(10)61372-0. 13. m shackford sr, dunne ce, karmy-jones r, et al. the evolution of care improves outcome in blunt thoracic aortic injury: a western trauma association multicenter study. j trauma acute care surg. 2017 dec;83(6):1006–13. doi: 10.1097/ta.0000000000001555 100 journal of rawalpindi medical college (jrmc); 2020; 24(2): 100-102 editorial covid-19 pandemic and department of medicine, rawalpindi medical university muhammad khurram1 1 professor of medicine & dean, department of medicine, rawalpindi medical university cite this article: khurram, m. (2020). covid-19 pandemic and department of medicine, rawalpindi medical university. journal of rawalpindi medical college, 24(1), 1-2. doi: https://doi.org/10.37939/jrmc.v24i2.1419 access online: in wuhan, china a sudden surge of pneumonia cases was noted in the last quarter of 2019. as the disease spread widely, workup showed that coronavirus infection was responsible for this sudden boom. this disease was termed as a novel corona virus infection/disease. it was reported to the world health organization on 31 december 2019 and illness was eventually named corona virus disease 2019 (covid19) in february 2019.1 covid-19 virus belongs to the genus betacoronavirus. the disease spreads through direct contact and droplets. airborne transmission of covid-19 is controversial. the incubation period is 45 days; this may however be up to 14 days.2 based on severity, covid-19 infection is divisible into mild to moderate, severe, and critical illness. patients with mild to moderate illness have no or mild pneumonia. they may have a cough, fever, headache, aches, and gastrointestinal symptoms. they constitute up to 80% of covid-19 patients. patients with severe covid-19 infection are breathless, tachypneic, hypoxemic, and have >50% pulmonary involvement on chest x-ray. 14% of covid-19 patients are categorized to have severe infection.3-6 5% of covid-19 patients have critical illness i.e., they are in respiratory failure or have a shock. its case fatality rate is variable. it is however considered to be about 2.3%.3 rawalpindi medical university (rmu), rawalpindi attached three hospitals (holy family hospital-hfh, benazir bhutto hospital bbh, and dhq hospitaldhqh) are providing health care facilities to not only rawalpindi but other adjoining and non-adjoining of khyber pakhtunkhwa and gilgit baltistan, etc. bbh was initially declared a focal center for covid-19 patient management for rmu. rawalpindi institute of urology and transplant (riu&t) was later dedicated as the covid-19 treatment hospital under rmu by the government of punjab. it is worth mentioning that the riu&t covid-19 management center started with one-person, medical superintendent dr. khalid randhawa. consultant physician (dr. qaiser aziz) who has been exclusively involved in patient management and sorting other riu&t issues was shifted from taxila here. vice-chancellor, rmu in collaboration with punjab health department, rawalpindi administration, and philanthropists pushed to make the hospital in working status. recently bbh is has been designated as covid-19 specific hospital. riu&t was without staff initially, so health care workers and other ancillary staff were provided by other rmu allied hospitals. nursing staff, medical officers and other staff were recruited for riu&t in the meantime. consultant and senior registrar (sr) cover to riu&t cover is being provided by medicine & allied department of rmu (hfh, bbh, dhq hospitals). it is thus important to note that the department of medicine and allied rmu is managing general medical patients at indoor, intensive care, outpatient, and emergency in addition to the provision of similar covid-19 patient management at rmu allied hospitals. department of medicine & allied rmu professorial staff includes 3 professors, 2 associate professors (1 medicine and 1 department of infectious diseases did), 7 assistant professors (4 workings in medicine department, 1 intensive care, 1 pulmonology, and 1 emergency medicine). additionally, 1 fcppulmonology and 1 fcps medicine specialists involved in icu management are there. two 101 journal of rawalpindi medical college (jrmc); 2020; 24(2): 100-102 professors and 1 assistant professors are dedicated to bbh. 1 professor is dedicated at dhqh. did associate professor had been on leave due to covid19 till recently. for hfh, dhq, and riu&t, we were left with 1 professor, 1 associate professor, 6 assistant professors (2 intensivist categorized, 1 pulmonologist), 1 sr pulmonologist, and 1 intensive care sr equivalent, in addition to single consultant physician of riu&t. to facilitate working in addition to 24 hour sr cover at riu&t, there are 3 teams for patient management. senior intensive care team comprising riu&t consultant physician, assistant professor pulmonology, and one pulmonologist. medical team comprising two assistant professor medicine, and 3rd junior intensive care team including doctors with experience in icu patient management. for hfh intensive care team comprises assistant professor with icu experience and one icu specialist. 1 professor, 1 associate professor, and 2 assistant professors along with srs provide medical cover here in addition to the medical floor and rmu related working. in charge of medical, icu hfh is providing cover to both riu&t and hfh. dean of medicine and allied is providing consultation/cover wherever asked. as per government policy senior registrars (srs) from hfh, bbh, and dhq medicine departments have been working on a 6/24 hourly roster for one week followed by two weeks off period at riu&t. professorial staff is working without rest/quarantine due to staff deficiency. since bbh has withdrawn srs recently, it has been suggested that srs from hfh and dhq will have to work for one week followed by rest for one week. out of senior clinical team, department of infectious diseases head of department an associate professor, one assistant professor medicine, and two intensive care team members have suffered from covid-19 infection. covid-19 infection is pandemic now. in pakistan, the first covid-19 patient was noted on 26th february 2020. initial covid-19 infections were linked to iran's visit. in subsequent week confirmed cases were noted at rawalpindi and islamabad.7 till today (17th june 2020), 154,760 patients have been diagnosed to be suffering from covid-19 in pakistan. 2975 deaths have been attributed to covid-19 infection and closed case fatality is 5%.8 first covid-19 confirmed the patient was reported from rmu allied hospitals on 23rd march 2020. till today 1841 confirmed covid 19 patients have been managed at rmu allied hospitals.956 improved, and 252 patients expired. 366 patients are currently admitted, and 247 (67.48%) of these are severe to critically ill.9 closed case fatality at rmu allied hospitals is 20.86%. fear and anxiety of getting covid-19 were noted in health care workers when they were involved in covid-19 patient management. questions were raised concerning the quality of personal protective equipment (ppe). manipulation in this context ended only when it was announced that ppe is provided by government and complains about it can be made at a specific phone number. similarly, clinical team seniors were held responsible and penalized for administrative issues and government policies. this however has improved with time. despite all challenges, the department of medicine and allied is working utmost for better patient management. treatment protocols, hcw exposed to covid-19 sops, return to work criteria for hcw, the involvement of surgery, gynecology-obstetric teams, etc, and mortality reports are few of the documents prepared by dean of medicine and allied office. covid-19 situation is worsening nowadays. beds, oxygen provision, and testing facilities are being improved. the recruitment of hcw is on cards. the senior clinical team cover remains the same. it is high time that deficient professorial staff and srs should be filled. intensive care and pulmonology teams require the most in this context. it is high time that the medical and allied team has to reinforced at least for stable patients by other departments until the dedicated staff is available. we pray allah to bestow us health, life, strength, wisdom, and courage to tackle this pandemic at our area reference 1. who director-general's remarks at the media briefing on 2019-ncov on 11 february 2020 [internet]. who.int. 2020 [cited 15 june 2020]. available from: https://www.who.int/dg/speeches/detail/whodirector-general-s-remarks-at-the-media-briefing-on2019-ncov-on-11-february-2020 2. lauer sa, grantz kh, bi q, jones fk, zheng q, meredith hr, azman as, reich ng, lessler j. the incubation period of coronavirus disease 2019 (covid-19) from publicly reported confirmed cases: estimation and application. annals of internal medicine. 2020 may 5;172(9):577-82. https://doi.org/10.7326/m20-0504 3. wu z, mcgoogan jm. characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72 314 cases from the chinese center for disease control and prevention. jama. 2020 apr 7;323(13):1239-42. doi:10.1001/jama.2020.2648 102 journal of rawalpindi medical college (jrmc); 2020; 24(2): 100-102 4. li q, guan x, wu p, et al. early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia. n engl j med 2020; 382:1199. doi: 10.1056/nejmoa2001316 5. guan wj, ni zy, hu y, liang wh, ou cq, he jx, liu l, shan h, lei cl, hui ds, du b. clinical characteristics of coronavirus disease 2019 in china. new england journal of medicine. 2020 apr 30;382(18):1708-20. doi: 10.1056/nejmoa2002032 6. iqtadar s, ahmad j, ghani u. covid-19 standard operation procedures & guidelines. lahore: government of punjab; 2nd revision, 28th march 2020. 7. 3 coronavirus cases detected in rawalpindi. nation.com.pk. 28 february 2020. archived from the original on 4 march 2020. 8. chan jf, yuan s, kok kh, to kk, chu h, yang j, xing f, liu j, yip cc, poon rw, tsoi hw. a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. the lancet. 2020 feb 15;395(10223):514-23. https://doi.org/10.1016/s0140-6736(20)30154-9 9. pakistan coronavirus154,760 cases and 2,975 deaths worldometer [internet]. worldometers.info. 2020 [cited 17 june 2020]. available from: https://www.worldometers.info/coronavirus/country/ pakistan/ 10. zafar b, khurram m, khan mm, umar m. covid-19 in rmu and allied hospitals june 2020. researchgate, 10.13140/rg.2.2.36277.50402.council of editors proposed to up quality of research journals. https://academiamag.com/council-of-editorsproposed-to-up-quality-of-research-journals/. accessed march 21, 2020. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 45-47 45 original article mass in right iliac fossaclinicopathogical evaluation tasleem akhtar 1, atif sharif 1, mumtaz akhtar 1, naeem zia 1, muhammad hanif 2 1. department of surgery , unit i , benazir bhutto hospital and rawalpindi medical college, rawalpindi; 2. department of surgery unit ii, benazir bhutto hospital abstract background: to identify clinico-pathological entities presenting as mass in right iliac fossa. methods: in this observational study patients of mass in right iliac fossa were recruited. all patients who presented with sign and symptoms of mass in right iliac fossa were investigated and subjected to conservative or operative managements depending upon the cause and response to conservative management. results: appendicular mass (33.7%) was the commonest finding, followed by cecal carcinoma(9.8%), ileocecal tuberculosis(9.8%), psoas abcess (7.6%), retroperitoneal dermoid(3.3%), worm infestation (3.3%) and lymphoma (3.3%). conclusion: appendicular mass is the main cause of mass in right iliac fossa, with a wide range of other causes. key words: mass in right iliac fossa, appendicular mass, psoas abscess. introduction a mass in the right iliac fossa is a ‘temple of surprises’ and a common presentation at surgical floor, requiring skill and acumen to diagnose. the mass arises either from the normal structures present in the area between the symphysis pubis, umbilicus and anterior superior spine iliac.1 sometimes the mass arises from the structures abnormally situated in the region.2among the multiple diagnoses of right iliac fossa mass, some are operable, some need staging, still others need conservative management and still more are initially conservatively managed with a later surgery.3 it is utmost important to differentiate each condition and have a diagnosis and a management plan due to vast variability in management.3 female patients pose a greater diagnostic dilemma due to their different pelvic anatomy. detailed history and examination is a key to clinch the appropriate diagnosis. a set of investigations are ordered to reach at a definite diagnosis.5 these include complete blood count, ultrasonography and contrast enhanced computer tomography (cect) which are usually done in all cases. additional tests like esr, pregnancy tests, tumor markers, biopsies and spinal surveys may be needed.2 patients with mass in right iliac fossa may be confronted by a general practitioner, a surgeon or a gynecologist and knowledge of anatomy, detailed history, clinical examination referring towards the pathological process followed by lab analysis and imaging lead to a diagnosis. the most common differential diagnosis encountered by surgeons4,5 are: appendicular mass, appendicular abscess, ileocecal tuberculosis, right ovarian mass, right ectopic kidney, rectus sheath hematoma, carcinoma caecum and ameboma.4,5 an important differential diagnosis is often between an appendicular mass, carcinoma of the caecum and ileocecal tuberculosis.1 in subcontinent, tuberculosis has been the main cause of intestinal obstruction and perforation.4,6cecal carcinoma is more common in the elderly and higher socio-economic group consuming less fibrous diet.2,4 crohn disease is a disease of western world.2 appendicular masses are seen in relatively younger people with both conservative and operative strategies. other less common causes are diagnosed and managed accordingly5. patients and methods this study was carried out at benazir bhutto hospital, a tertiary care hospital of pakistan draining urban, semi urban and rural areas of northern punjab, from january 2014 to july 2015. all patients with suggestive history of pain or mass right iliac fossa and mass palpable on clinical examination were included. patients who underwent emergency surgery were excluded. upon arrival of the patients in the ward, a fluid and electrolyte resuscitation and empirical antibiotics were started according to provisional diagnosis. patients with clinical suspicion and previous history of tuberculosis were also initially kept on conservative regime. all patients underwent complete blood count and ultrasonography. cect scan was done in patients with unsure diagnosis and in whom mass was suspected to be other than inflammatory appendicular mass secondary to appendiceal pathology. the additional investigations included pregnancy test (done in all women of child bearing age); colonoscopy for suspected cecal journal of rawalpindi medical college (jrmc); 2017;21(1): 45-47 46 carcinomas; x ray erect abdomen for patients with obstructive symptoms; esr , x ray lumbosacral spine and cxr for suspected tuberculosis and ultrasound to detect psoas abscess ; percutaneous ultrasound guided biopsies for tumors needing histopathological proofs and diagnostic laparoscopy and proceed for still undiagnosed cases. the variables studied included demographic details, time between onset of symptoms and arrival in ward, symptoms, investigations done, type of treatment offered and operative findings and definitive diagnosis. the data were statistically analyzed using statistical package for social sciences (spss, version 16.0). results a total of 92 cases were included in the study, out of which 52(56.5%) were males and 40(43.5%) were females. patients ranged between 8 to 70 years average age was 30.35 years (figure 1). commonest presentation was mass in rif (table 1). appendicular mass in 33.7%,ceacal carcinoma in 9.8%,ileocecal tuberculosis in 9.8%and psoas abscess in 7.6% making the most common causes (table 2). twenty nine (32.7%) appendectomies for appendicular masses, all done after initial resuscitation and antibiotics. wound infections were seen in 17.24% patients postoperatively. operating appendicular masses with initial optimization was the strategy in our hospital. conservative management on oshner sherren regimen, for delayed treatment of acute appendicitis, was done in 2 patients. 19(20.7%) right hemicolectomies for carcinoma cecum and iliocecal tuberculosis, 7 (7.6%)incision and drainage for abcesses, 3(3.3%) nephrectomies for kidney diseases, 2 (2.2%) marsupialization for right ovarian cysts, 2(2.2%) wedge resections for meckel’s diverticulitis, 4(4.3%) enterotomies for worm infestation and phytobezoars, 2(2.2%) salpingotomies for ectopic tubal pregnancies,1 cystectomy for pseudo pancreatic cyst, 1 tah with bso for ovarian ca which came out to be secondary from stomach, 1 hernioplasty for lumbar hernia 1 patient underwent orchidectomy and 1 retroperitoneal lymph node dissection(1.1%) for testicular malignancies and 9(9.8%) patients were managed conservatively including gist, lymphomas, tuberculous psoas abscess and appendicular masses. table 1: symptoms of patients with pain rif symptom no % mass in rif 43 46.7 pain in rif 39 42.4 mass along with pain in rif 7 7.6 subacute intestinal obstruction 3 3.3 figure 1: age distribution table 2: causes and percentage of mass in rif causes no. percentage appendicular mass 31 33.7 cecal carcinoma 9 9.8 ileocecal tuberculosis 9 9.8 carcinoid tumor 1 1.1 retroperitoneal dermoid 3 3. retroperitoneal sarcoma 1 1.1 gist involving lymphnodes 1 1.1 worm infestation 3 3.3 psoas abcess 7 7.6 ectopic pregnancy 2 2.2 right ovarian cysts 2 2.2 phytobezoar 1 1.1 enteric fever 1 1.1 meckel’s diverticulum 2 2.2 hydatid cyst 2 2.2 rectus sheath hematoma 2 2.2 leomyosarcoma 1 1.1 rhabdomyosarcoma 2 2.2 renal cell carcinoma 1 1.1 pckd 1 1.1 pseudopancreatic cyst 1 1.1 lymphoma 3 3.3 krukenberg tumor with primary in stomach 1 1.1 undescended malignant testicular tumor 1 1.1 metastatic testicular malignancy 1 1.1 paraganglioma 1 1.1 discussion mass in rif poses a diagnostic dilemma for surgeons all over the world. the present study was carried out to study various clinico pathological aspects and diagnoses of mass in rif in relation to age and sex distribution along with clinical presentations followed journal of rawalpindi medical college (jrmc); 2017;21(1): 45-47 47 by subsequent managements. there were 27 differential diagnoses for mass rif in our study including the rarer conditions.age group ranged from 8-75years similar to the literature.1-4 there was a male preponderance accounting for 56.5 % contrary to study by anuradha5 where females were more than 50% but similar to narendran who evaluated pathological nature of the right iliac fossa mass and its management and he found male preponderance in appendicular pathology.3-5 main clinical sign was mass in rif accounting for 46.7% followed by pain in 42.4% patients. pain was the main symptom in literature majorly for appendicular masses done by shetty with tenderness in 92% and mass in 100%.3-5,18 mass in rif mainly was due to appendicular pathology accounting for 33.7%, 29 underwent surgery after initial resuscitation and antibiotics and 2 were managed on oshner sherren regimen. 27.32% patients got wound infection in postoperative period. surgery remained the main stay for appendicular mass management in our hospital. appendicular abcesses were excluded from study group. the incidence was similar to literature with 50% appendicular masses in an indian study.3,5 however oshner sherren regime was the main management strategy in various studies. tuberculosis (9.8%) and cecal carcinoma (9.8%) ranked 2nd in incidence. cecal carcinoma11 patients underwent right hemicolectomies after staging as in other studies17. the patients with tuberculosis were started anti tuberculous therapy (att), 8 patients underwent right hemicolectomy, 1 patient improved on att. 4 (4.4%) incision and drainage for psoas abcesses which were superinfected and att was given for others. similar results were seen in other studies.5-10age group was also similar in these studies.2-5,16,18 imatinib was started for gist of lymph nodes and chemotherapy for lymphomas. similar management option are valid in various studies across the world.13-16 conclusion 1.maximum incidence of rif mass was the appendicular mass which was most common in the mean age of 30+/16.04 years and having male predominance. 2. detailed history and thorough clinical examination can solve the enigma of rif mass and helpful for correct clinical diagnosis. references 1. panarese a, pironi d, pontone s, vendettuoli m. a case of symptomatic mass in the right iliac fossa:a bermuda triangle which often lies the right diagnosis. ann. ital. chir 2014; 24;85-88 2. juniorsundresh.n, narendran.s,ramanathan.m. evaluation of pathological nature of the right iliac fossa mass and its management. j biomed sci res. 2009; 1 (1): 55 58 3. madhushankar l, satish kumar r, sanjay sc. role of ultrasonography in pre-operative evaluation of right iliac fossa mass. journal of evolution of medical and dental sciences 2013; 2(126):9030-36 4. howell s and knapton pj. ileo-caecal tuberculosis. gut ; 5: 524-529. 5. dnyanmote as, sinha n, chavan s, sable s. clinico pathological study of right iliac fossa mass. webmedcentralgeneral surgery 2014;5(11):wmc004766 6. bakhshi g d, deshpande s, jadhav k v, shenoy s s, yadav r.abdominal koch's: an analysisan indian perspective. international journal of medical and applied sciences. 2013;2(3):248-54. 7. shaikh r, khalid ma, malik a . abdominal tuberculosis profile of 26 cases. pakistan j surg 2008; 24:217-19. 8. sharma yr. abdominal tuberculosis a study of 25 cases. kathmandu university medical journal 2003;2(6):137 41. 9. abro a, siddiqui fg, akhtar s, memo as. spectrum of clinical presentation and surgical management of intestinal tuberculosis. j ayub med coll abbottabad 2010;22(3):9698. 10. chalya pl, mchembe md, stephene, rambau pf, jaka h, mabula jb. clinicopathological profile and surgical treatment of abdominal tuberculosis: a single centre experience in northwestern tanzania. bmc infectious diseases 2013;13:270-73. 11. saaiq m, shah sa, zubaim. abdominal tuberculosis: epidemiologic profile and management experience. j pak med assoc 2012; 62,(7): 112-15 12. das s, sahu d, wani m, reddy pk. a curious discourse of krukenberg tumor: a case report. journal of gastrointestinal oncology. 2014;5(6):117-20. 13. mahajan a, varma a, singh m, singla sp, singla a. eventration of right hemidiaphragm, right ectopic kidney, intra-abdominal seminoma in cryptorchid testis: a rare combination or a possible sequence?. arch int surg 2014;4:190-92 14. mukhopadhyay m , chattopadhyay sd, karmakar nc, mukherjee r. echinococcal lump: an unusual differential diagnosis for a right iliac fossa lump. hellenic journal of surgery 2015;87(4):342-44 15. armstrong a, coulstonj, mackeyp,saxbyc. bezoar: an unusual palpable mass in the right iliac fossa. indian journal of surgery 2015;77(1):73-74. 16. kumar ms, mohan, babu s, hongaiah d, kumar p, balakrishna ma. demographic data comparison of prevalence of mass in right iliac fossa: a prospective hospital based study. international journal of bioassays 2014.;3(3):970-73 17. budamala s, penugonda a, ramanaiah nv, rao bs, prakash gv. a rare presentation of carcinoma caecum: as appendicular abscess. jebmh 2015;2(15):2371-74 18. shetty sk, shankar m. a clinical study of right iliac fossa mass. the internet journal of surgery. 2013;30(4):40-43 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 90-92 90 original article effect of high dose ginger on plasma testosterone and leutinising hormone levels in male rats after lead induced toxicity fatima riaz1, kirn-e-muneera2, muhammad adnan saeed3 1. department of physiology, islamic international dental college, riphah international university, islamabad;2 department of biochemistry, islamic international dental college, riphah international university, islamabad;3 nuclear medicine department, atomic energy cancer hospital, nori, islamabad abstract background: to study the effect of high dose ginger on plasma testosterone and leutinising hormone levels in male rats after lead induced toxicity methods: in this quasi experimental study, 30 adult male sprague dawley rats were divided in two equal groups. group a was given 0.3% lead acetate in drinking water and kept as lead control while the group b was given a dose of 1.5gm/kg body weight ginger orally along with 0.3% lead for 42 consecutive days. rats were then sacrificed and serum testosterone and lh levels were analyzed using elisa technique. data was expressed as mean±sd. p-values <0.05 were considered as statistically significant. results: at the end of 42 days, mean serum testosterone level in group a (control group) was 2.2667± 0.45617ng/ml as compared to group b (experimental group) 2.2667 ± 0.45617ng/ml and showed statistically insignificant change(p>0.05). comparison of mean serum lh levels in group a (5.3200 ± 0.72526ng/ml)revealed statistically insignificant difference (p>0.05) as compared to group b (5.7467 ± 0.70190ng/ml). conclusion: high dose ginger (>1gm/kg body weight) failed to enhance the suppressed testosterone level due to lead toxicity in male rats. key words: lead toxicity, high dose ginger, plasma testosterone and lh levels introduction the toxic effects of lead, an environmental pollutant, on the body systems are well documented. with the increased incidence of male infertility cases, researches regarding the antioxidant and androgenic activity of herbs have also been increased with different dimensions. lead poisoning has been reported as a major public health risk, particularly in developing countries which affects multiple organ systems.1 both clinical and animal studies have shown that lead affects sperm count, motility and testosterone level, hence causing infertility in males.2,3 the underlying common mechanism in all the environmental pollutants is oxidative stress which disrupts the prooxidant/antioxidant balance in the body. 4 researchers have conducted multiple studies on herbal products as natural antioxidants in lead poisoning because of their fewer side effects and cheap availability. 5numerous studies have documented a decrease in the level of free radicals with the concomitant administration of herbal products such as ginger. 6 ginger (zingiberofficinale roscoe, zingiberaceae)is routinely used as a household spice and its antioxidant, anti-inflammatory and androgenic activity has been documented in various animal studies. 7,8 it significantly lowers lipid peroxidation by increasing the levels of antioxidant enzymes. ginger’s protective role has also been studied in animal models, in various reproductive toxicities like those induced by cyclophosphamide, cisplatin, malathion and diabetes. 9-11 it is a well-known fact that lead poses a deleterious effect on male reproductive organ.12 in one study, it was shown that when ginger in doses of 0.5 to 1gm/kg body weight was co-administered along with lead, plasma testosterone level resumed to near normal levels. 13 regarding the use of herbs for health purposes, patients and physicians usually lack accurate information about safety, efficacy and proper dosage of herbal remedies. over the last few years, interest in ginger or its various components as valid preventive/therapeutic agents has increased markedly, and so is the focus on verification of ginger’s pharmacological and physiological actions. however no specific dosing studies have been performed on ginger in animal models. most research journal of rawalpindi medical college (jrmc); 2017;21(1): 90-92 91 has used ginger between doses of 250 mg and 1 g of the powdered root, taken one to four times daily. 14 however, one study by xianglurong has documented that at a very high dose (2000 mg/kg), ginger led to slightly reduced absolute and relative weights of testes. 15 materials and methods in this experimental study thirty adult male sprague dawley rats, weighing 130 200 grams were randomly selected. they were divided into two groups with fifteen rats in each group. group a served as normal control, which was given 0.3% lead acetate dissolved in drinking water, whereas group b was given ginger in a dose of 1.5 gm/kg body weight along with 0.3% lead acetate. ginger powder was added to lead acetate solution and mixed thoroughly. it was given in clean, inverted drinking bottles specific for the rat cages. all the groups were fed on standard pellet diet and water ad libitum in the animal house of national institute of health (nih), islamabad and kept in separate standard cages designed accordingly. drinking water consumption in all the groups was recorded daily and rats were weighed on weekly basis to adjust the dose of ginger. treatment in all groups continued for six weeks. after the last experimental day, they were sacrificed and three to five ml blood was drawn by intra cardiac catheterization. samples were immediately transferred into labeled gold top vacutainers without anticoagulant kept in an ice packed rack. serum was separated by centrifugation, transferred into labeled 1.5 ml eppendorf tubes, frozen and stored at -20 °c till assayed. testosterone and lh levels in both groups were quantitatively measured using solid phase elisa. using semi-algorithmic graph paper a standard curve was constructed by plotting the mean absorbents obtained from each standard against its concentration with absorbance values at y-axis and concentration on the horizontal xaxis. thus the corresponding concentration for each sample was determined from the standard curve. statistical analysis was done using spss-23. mean±sd of all observations were calculated. for the quantitative comparison of both the tests independent t-test was used. p-value<0.05 was taken as significant. results all the 30 rats in the two groups were sacrificed a day after the last experimental day. at the end of day 42 mean serum testosterone level in group a (control group) was 2.2667± 0.45617ng/ml as compared to group b (experimental group)level of 2.2667 ± 0.45617ng/ml and showed no statistically significant change(p>0.05). comparison of mean serum lh levels in group a(control group) 5.3200 ± 0.72526ng/mlrevealed statistically insignificant difference (p>0.05) as compared to group b(experimental group)5.7467 ± 0.70190ng/ml (table ). table 1: comparison of plasma testosterone and lh levels among lead treated (group a) and lead ginger treated (group b) hormone levels (ng/ml) lead treated (group a) lead+high dose ginger(group b) testosterone 2.267 ± .45617 2.267 ± .45617 lh 5.320 ± .18726 5.746 ± .18123 discussion lead induced suppressed reproduction and testosterone level is a known fact. male rats exposed to lead acetate showed a significant decrease in the weight of both the testes, along with decreased plasma testosterone level. 16,17 in a previous study, 0.5% lead administration in drinking water to male rats led to statistically significant reduction in plasma testosterone level with no statistical significant change in lh levels.. 18 an increase in oxidative stress biomarkers is common among all these heavy metals along with lead. 19 day by day, the use of herbs is increasing in our daily life considering their health benefits.the rich phytochemistry of ginger scavenges free radicals produced in biological systems. these anti-oxidative and androgenic properties of ginger have been explored in various in vitro and in vivo tests. 6,20 regarding the current scenario it has been documented in another study that ginger ameliorates lead toxicity by enhancing serum testosterone levels at doses of 0.5 and 1gm/kg body weight when given concomitantly.13 we can find similar studies regarding gingers antioxidant and androgenic role in between the doses of 250 mg and 1 g of the powdered root, taken one to four times daily. 9,2,22 although ginger is generally considered to be safe, we need to be cautious about its consumption.careful scientific research is required in establishing the safety and efficacy of potential therapeutic plant remedies. according to badrelin review on toxicological properties of ginger, it was considered safe to consume up till 1gm/kg of ginger to pregnant female rats with no teratogenic or toxic effects on reproductive organs.some minor adverse effects observed at higher doses were mild diarrhea and heart burn.. 22 the results of toxicological studies showed a broad safety range for ginger usage. in a 35-day toxicity study the oral administration of ginger powder up to 2 g/kg journal of rawalpindi medical college (jrmc); 2017;21(1): 90-92 92 once daily did not cause any mortality or abnormal changes of the general condition in either male or female rats. all the hematological and biochemical parameters presented normally except for serum lactate dehydrogenasein dose dependent manner in males. the male rats also showed a slight but significant decrease of testes weight and the ratio of the testis weight to body weight in rats. 15 no further research so far has been shown regarding its effect on serum testosterone levels at this dose(2g/kg/b.w) conclusion high dose ginger (>1gm/kg body weight) failed to enhance the suppressed testosterone level due to lead toxicity in male rats. references 1. karrari p, mehrpour o, abdollahi m. a systematic review on status of lead pollution and toxicity in iran; guidance for preventive measures. daru. 2012;20(1):2-5. 2. vigeh m, smith dr, hsu pc. how does lead induce male infertility? iran j reprod med. 2011;9(1):1-8. 3. el-sayed ys, el-neweshy ms. impact of lead toxicity on male rat reproduction at “hormonal and histopathological levels”. toxicological & environmental chemistry. 2010;92(4):765-74. 4. kim hc, jang tw, chae hj, choi wj, ha mn. evaluation and management of lead exposure. ann occup environ med. 2015;27:30-34. 5. flora g, gupta d, tiwari a. toxicity of lead: a review with recent updates. interdiscip toxicol. 2012;5(2):47-58. 6. mashhadi ns, ghiasvand r, askari g, hariri m. antioxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence. int j prev med. 2013;4(suppl 1):s36-42. 7. rahmani ah, shabrmi fm, aly sm. active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities. int j physiol pathophysiol pharmacol. 2014;6(2):125-36. 8. memudu a, akinrinade id1 , ogundele, om1. investigation of the androgenic activity of ginger (zingiber officinale) on the histology of the testis of adult sparague dawley rats. journal of medicine and medical sciences, 2012; 3(11): 697-702. 9. mohammadi f, nikzad h, taghizadeh m, taherian a, azami-tameh a, hosseini sm, et al. protective effect of zingiber officinale extract on rat testis after cyclophosphamide treatment. andrologia. 2014;46(6):680-86. 10. rehman mu. zingerone protects against cisplatininduced oxidative damage in the jejunum of wistar rats. september 2015;15( 3): 199 206. 11. james w. daily my, da sol kim, sunmin park. efficacy of ginger for treating type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. 2015;2(1):211-15 12. mills arn. impact of the environment on male sexual health ,2016;8(1):1-8. 13. riaz f, khan ua, ayub m, shaukat s. protective role of ginger on lead induced derangement in plasma testosterone and luteinizing hormone levels of male sprague dawley rats. j ayub med coll abbottabad. 2011;23(4):24-27. 14. awwad ia and eai a. a study of cardiovascular toxic effects of zingiber officinale (ginger) in adult male albino rats and its possible mechanism of action. mansoura j forensic med clin toxicol.vol. xvii. 15. rong x, peng g, suzuki t, yang q, yamahara j, li y. a 35-day gavage safety assessment of ginger in rats. regul toxicol pharmacol. 2009;54(2):118-23. 16. dorostghoal m, seyyednejad sm, jabari a. protective effects of fumaria parviflora l. on lead-induced testicular toxicity in male rats. andrologia. 2014;46(4):437-46. 17. wang l, xun p, zhao y, wang x, qian l, chen f. effects of lead exposure on sperm concentrations and testes weight in male rats: a meta-regression analysis. j toxicol environ health a. 2008;71(7):454-63. 18. riaz f,shaukat s, ahmed sa. effects of lead toxicity on serum testosterone and lh levels in adult male rats. jiimc. 2011; 6(1):28-32. 19. reddy ua, prabhakar pv, rao gs, rao pr. biomarkers of oxidative stress in rat for assessing toxicological effects of heavy metal pollution in river water. environ sci pollut res int. 2015;22(17):13453-63. 20. el-sharaky as, newairy aa, kamel ma, eweda sm. protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats. food chem toxicol. 2009;47(7):1584-90. 21. ghlissil z. antioxidant and androgenic effects of dietary ginger on reproductive function of male diabetic rats. international journal of food sciences and nutrition 2013;64(8). 22. ali bh, blunden g, tanira mo, nemmar a. some phytochemical, pharmacological and toxicological properties of ginger (zingiber officinale roscoe): a review of recent research. food chem toxicol. 2008;46(2):409-20. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 75-77 75 original article incidence of external ear canal folliculitis mohammad iqbal1, kamran iqbal2,sahibzada fawad khan3,wasim ahmad4 1.department of otolaryngology, head & neck surgery, bannu medical college bannu;2.department of ent, gomal medical college d.i.khan; 3.department of ent, nowshera medical college;4.department of biotechnology, faculty of biological sciences, university of science & technology, bannu abstract background: to analyze the incidence of external ear canal folliculitis (eecf) in adult population of district bannu. methods: in this descriptive study 100 patients with ear ache, presented in four quarters of the year were included. complaints, and findings on physical examination including otoscopy results, diagnosis were recorded. inclusion criteria was adults (18+) with ear pain as a major complaint. we included the cases with another major complaint only when it was related to the ear pain (e.g. referred pain from sinusitis, tonsillitis).exclusion criteria was antibiotic treatment in the last 10 days was marked as exclusion criteria. both the rates of external ear canal folliculitis and the rate of non-external ear canal folliculitis were compared. we also subdivided the different diagnostics under the title "folliculitis channel of the non-outer ear." the prevalence of the external ear canal folliculitis diagnosis was calculated, including subdivisionby sex and age groups, by location in the ear canal including posterior vs. anterior and by the quarters of the year. results: 35% of cases represented eecf were included. the ratio of male to female was observed 3: 2. the condition was maximum in 2nd& 3rd quarter of the year where as it was minimal in 1st and 4th quarters. earache in adult patients was the most common principal inflammation, which is generally termed as eecf. conclusion: different factors are being involved in its prevalence including poor hygiene, over crowding, bath in a contaminated water, hot weather, ear wax and lack of specialized care. since treatment is only possible upon clinical diagnosis, doctors will likely be more reserved about oral antibiotics if eecf can be diagnosed appropriately. key words: ear canal, folliculitis, otoscopy introduction external ear canal folliculitis is a confined skin infection of the external ear canal involving hair follicles, typically instigated by staphylococcus aureus. folliculitis is termed as an inflammation and infection of hair follicles, the minute openings in the skin from which hair nurtures. folliculitis is due to an incursion of bacteria that enter the follicles and cause a bacterial infection.1 folliculitis is most frequently the outcome of an infection of bacteria, staphylococcal. this causes inflammation and a red rash that is jarring and scratchy. the rash can happen on the skin or scalp any where. the body attempts to combat the bacterial infection by transporting white blood cells to the infected follicles. this can end in the formation of pus-filled sores. in some cases folliculitis can lead to the formation of a boil.the inflammation can be either limited to the superficial aspect of the follicle with primary involvement of the infundibulum or the inflammation can affect both the superficial and deep aspect of the follicle. deep folliculitis can eventuate from chronic lesions of superficial folliculitis or from lesions that are manipulated, and this may ultimately result in scarring.2perifolliculitis, on the other hand, is defined as the presence of inflammatory cells in the perifollicular tissues and can involve the adjacent reticular dermis. folliculitis and perifolliculitis can manifest independently or together as a result of follicular disruption and irritation. the complaints of ear pain are very common in primary care practice. the diagnosis is classically based on medical history and thorough physical exam. the diagnosis of the clinician can be influenced, possibly negatively, by preconceived notions of prevalence that are partly based on personal experience and partly according to their medical knowledge. it is possible that a diagnosis of a folliculitis can be missed or delayed because some symptoms, such as a skin rash are similar to symptoms of other diseases or conditions. external ear canal folliculitis is an inflammation of one or more hair follicles on any part of the skin including the scalp. the condition may result in scarring or hair loss. folliculitis occurs when bacteria enters a follicle that has suffered some sort of trauma or injury such as where clothing rubs against the skin. a localized infection of the skin external auditory meatus journal of rawalpindi medical college (jrmc); 2017;21(1): 75-77 76 comprising one or more hair follicles is usually caused by staphylococcus aureus. patients have an area of tenderness corresponding to the area of pain reported in the external channel.3currently, very little eecf mention can be found in the professional literature using pubmed and other internet search engines.4 this notwithstanding, there seems to be acknowledged among the patient-centered websites this condition carries clinical relevance. 5, 6we submit that it is a relatively common problem in primary care practice, largely misunderstood by most clinicians. the first step in treating folliculitis is averting it existence.7prevention includes maintaining hot tubs appropriately in the proper ph and using the right amount of chlorine. this ensures that the bacterium pseudomonas aeruginosa do not grow in the water, which can get into follicles and cause an infection.in some cases it might be recommended that a person not use hair removal methods, such as waxing, shaving, and tweezing in order to prevent folliculitis. mild folliculitis may need little or no treatment and often clears up on its own.8medications that may be recommended include topical antibiotics and oral or topical medications to minimize itching.severe folliculitis or folliculitis that does not go away on its own requires medical care. people with chronic diseases or conditions that lower resistance to infection should also seek prompt medical care if they develop any symptoms of folliculitis. treatment includes oral antibiotics and not removing hair in the affected area for several months. treatment also includes avoiding hot tubs until after the infection is cleared up. patients and methods in this descriptive study , performed in ent department dhq hospital, bannu , patients were enrolled during 4 quarters. in ent unit of dhq hospital bannu. patients (n=100) with earache as the presenting complaint were included. during each visit, we documented demographic information including patient age, sex etc, the date (month of the year), complaints, and findings on physical examination including otoscopy results, diagnosis etc.inclusion criteria was adults aged 18 years or older with ear pain as a major complaint. we included the cases with another major complaint only when related to the ear pain (e.g. referred pain from sinusitis, tonsillitis).exclusion criteria was antibiotic treatment in the last 10 days .both the rates of "external ear canal folliculitis” and the rate of "non-external ear canal folliculitis" were compared. we also subdivided the different diagnostics under the title "folliculitis channel of the non-outer ear." the prevalence of "the external ear canal folliculitis" was calculated, including subdivision by sex and age groups, by location in the ear canal including posterior vs. anterior and by the quarters of the year. results we examined 100 patients having a major problem of ear pain and who met our stated inclusion criteria. 35.0% of these cases represented eecf (table 1). the largest number of cases of eecf produced in the 2nd(april-june) and 3rd quarters (july-sep) of the year(15 & 28) (table 2). the common substitute diagnosis for the chief complaint of ear pain that was not eecf was otitis media (n=15) and some cases had no specific findings (n=12) (table 3). no significant difference was observed in rates among left and right ear or among male and female patients. table 1: external ear canal folliculitis – demographic profile dx=eecf dx=not eecf n= 35 (35%) 65 (65%) average age in years 40-45 30-40 gender (male) 19 (54.2%) 42 (65%) gender (female) 16 (46) 23 (35%) table 2: distribution of cases of eecf per quarter quarter no of cases quarter 2nd (april-june) 2014 10 quarter 3rd (july-sep) 2014 15 quarter 4th (oct-dec) 2014 6 quarter 1st(jan-march) 2015 4 table 3: other diagnosis along with eecf otitis media 15 myringitis 4 no specific findings 15 malignant otitis 1 total 35 discussion the results of this clinical trial show that ear ache in adult patients most often comes from pivotal inflammation, what we call eecf. the basic implementation of this descriptive study was our own clinical experience in primary education care, in which we found that frequent explanation of earaches in adults was a little focus of localized inflammation. doctors who deal with complaints of earache in adults detect the same findings of the clinical examination journal of rawalpindi medical college (jrmc); 2017;21(1): 75-77 77 that we do. we mean that doctors see an inflammatory focus and frame their diagnosis into an otherwise "respectable" familiar diagnosis. suggest that during this elementary diagnostic procedure, physicians are almost inevitably influenced by representativeness bias 9,10. when patients present with earache, physicians expect to find evidence of infection during otoscopy. when it is detected in the external auditory canal, physicians usually define it as external otitis. we find it possible to accept that eecf is a subtype of external otitis that was defined "as redness or swelling of external auditory canal or debris within the canal, accompanied by pain, itchiness". 11-18that notwithstanding, we feel that the distinction between folliculitis and external otitis is more significant than a semantic one.firstly, our perception is that the psychological impact of the diagnosis is perhaps significant to both the patient as well as the doctor. the diagnosis of a minor infection (or "boil") in the ear canal is probably less threatening to the patient than the diagnosis of external otitis. secondly, diagnosis and treatment following an examination of a complaint of earache are almost always consequences of clinical judgment. there is no strong evidence for preferable treatment in external otitis. a plethora of empiric treatments is in use. although instillation of drops containing antiseptics or antibiotic combinations with or without steroids is traditionally recommended, oral antibiotics are given in a considerable proportion of cases, without any evidence of their effectiveness, while being potentially harming. 19-20 since treatment derives from clinical diagnosis, physicians will be probably more restrained about oral antibiotics, when their diagnosis is only"folliculitis", than in case of "external otitis". conclusion 1. different factors are involved in the prevalence of external ear canal folliculitis, including poor hygiene, over crowding, bath in a contaminated water, hot weather, ear wax and lack of specialized care. 2. since treatment is only possible upon clinical diagnosis, doctors will likely be more reserved about oral antibiotics if eecf can be diagnosed appropriately. references 1. mushtaq a and rahmat ak. external ear canal folliculitis in idps of kpk. j pak med asso 2012; 54: 212-15 2. jamil m, farooq k, shaista j. folliculitis of the ear: causes and management. med forum 2015;29: 54-57 3. greenes d. evaluation of earache in children. 2012. up to date 4. otitis externa. nice pathways, clinical knowledge summaries 2002. 5. kenny t. boil (furuncle) in the ear canal. patient, 2014. patient.co.uk 6. moses s. ear canal furuncle, aka: ear canal furuncle, localized otitis externa, ear canal folliculitis. family practice notebook. 2014 7. kiran s and khan m. eecf management and risk factors. j ayub med coll, 2013; 45: 121-24 8. sudheer k and kamla r. eecf causes in rural vs urban area population of distric karnatka. ind. j med sci 2014; 25: 4448 9. kiderman a, marciano g,bdolah-abram t. bias in the evaluation of pharyngitis and antibiotic overuse. arch intern med 2009; 169: 524-25. 10. kahanman d and tversky a subjective probability: a judgment of representativeness. cognitive psychology 1972; 3:430-54. 11. van balen fa, smit wm, zuithoff np. clinical efficacy of three common treatments in acute otitis externa in primary care: randomised controlled trial. bmj 2003; 327: 1201-05. 12. rowlands s, devalia h, smith c, hubbard r, dean a. otitis externa in uk general practice: a survey using the uk general practice research database. br j gen pract2001; 51: 533-38. 13. chambers hf. the changing epidemiology of staphylococcus aureus? emerg infect dis 2001;7:178-82 14. cosgrove se, sakoulas g, perencevich en, schwaber mj. comparison of mortality associated with ear canal folliculitis: a meta-analysis. clin infect dis 2003;36:53-59 15. groom av, wolsey dh, naimi ts. eecf in a rural american indian community. jama 2001;286:1201-05 16. sattler ca, mason eo jr, kaplan sl. prospective comparison of risk factors and demographic and clinical characteristics of eecf in children. pediatr infect dis j 2002;21:910-17 17. community-associated external ear canal folliculitis in pacific islanders -hawaii, 2001-2003. mmwr morb mortal wkly rep 2004;53:767-70 18. morin ca, hadler jl. population-based incidence and characteristics of ear canak infections with bacteremia in 4 metropolitan connecticut areas, 1998. j infect dis 2001;184:1029-34 19. watt jp, o'brien kl, benin al. eecf among navajo adults, 1989-1998. clin infect dis 2004;38:496-501 20. lee mc, rios am, aten mf. management and outcome of ear canal folliculitis in children. pediatr infect dis j 2004;23:123-2 http://www.uptodate.com/contents/evaluation-of-earache-in-children http://www.uptodate.com/contents/evaluation-of-earache-in-children http://www.patient.co.uk/health/boil-furuncle-in-the-ear-canal http://www.fpnotebook.com/legacy/ent/derm/ercnlfrncl.htm http://www.fpnotebook.com/legacy/ent/derm/ercnlfrncl.htm http://www.fpnotebook.com/legacy/ent/derm/ercnlfrncl.htm http://www.ncbi.nlm.nih.gov/pubmed/19273784 http://www.ncbi.nlm.nih.gov/pubmed/19273784 http://www.ncbi.nlm.nih.gov/pubmed/19273784 http://datacolada.org/wp-content/uploads/2014/08/kahneman-tversky-1972.pdf http://datacolada.org/wp-content/uploads/2014/08/kahneman-tversky-1972.pdf http://datacolada.org/wp-content/uploads/2014/08/kahneman-tversky-1972.pdf http://www.ncbi.nlm.nih.gov/pubmed/14630756 http://www.ncbi.nlm.nih.gov/pubmed/14630756 http://www.ncbi.nlm.nih.gov/pubmed/14630756 http://www.ncbi.nlm.nih.gov/pubmed/11462312 http://www.ncbi.nlm.nih.gov/pubmed/11462312 http://www.ncbi.nlm.nih.gov/pubmed/11462312 http://www.ncbi.nlm.nih.gov/pubmed/11462312 560 journal of rawalpindi medical college (jrmc); 2021; 25(4): 560-563 case report polycythemia secondary to pheochromocytoma raheel raza1, saima ambreen2, hassan mumtaz3, shazaib ahmad4, hadin darain khan5 1 post-graduate trainee, department of medicine, medical unit-i, holy family hospital, rawalpindi. 2 associate professor & hod, department of medicine, medical unit-i, holy family hospital, rawalpindi. 3 physician, critical care medicine, krl hospital, islamabad. 4 mbbs student, king edward medical university, lahore. 5 mbbs student, shalamar medical & dental college, lahore. author’s contribution 1 conception of study 2 experimentation/study conduction 5 analysis/interpretation/discussion 3 manuscript writing 4 critical review corresponding author dr. hassan mumtaz, physician, critical care medicine, krl hospital, islamabad. email: hassanmumtaz.dr@gmail.com article processing received: 30/04/2021 accepted: 08/12/2021 cite this article: raza, r., ambreen, s., mumtaz, h., ahmad, s., khan, h.d. polycythemia secondary to pheochromocytoma. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 560-563. doi: https://doi.org/10.37939/jrmc.v25i4.1655 conflict of interest: nil funding source: nil access online: abstract polycythemia, also known as polyglobulia, is a clinical condition characterized by an increased number of red blood cells (rbc) or haematocrit concentrations in the peripheral blood. it can either be primary (polycythemia vera) or secondary, which can be congenital or acquired; the most common causes include obstructive sleep apnoea, obesity, hypoventilation, pickwickian syndrome, chronic obstructive pulmonary disease (copd), and lastly, pheochromocytoma. here we present a case of a 54-year-old male with a four-day history of altered state of consciousness (asoc), right-sided body weakness, and respiratory difficulty. after a thorough history, examination, and investigation, he was diagnosed as a case of polycythemia secondary to pheochromocytoma. early diagnosis and intervention are critical to saving the patient’s life. keywords: polycythemia, pheochromocytoma, tumor, management. 561 journal of rawalpindi medical college (jrmc); 2021; 25(4): 560-563 introduction pheochromocytoma is a rare tumor of the adrenal gland /chromaffin tissue. functional tumor leads to excessive secretion of catecholamines and is responsible for 0.1% of cases of hypertension.1 about 80% occur in the adrenal medulla, while 20% occur elsewhere in the body and are known as paragangliomas. about 40% are inherited, and 15% show features of malignancy.2 paraneoplastic syndromes are commonly seen in certain tumors. polycythemia secondary to pheochromocytoma is due to the production erythropoietin (epo) that normally stimulates erythropoiesis to increase blood cell production.3 polycythemia due to underlying pheochromocytoma is a rare occurrence. we present a case of pheochromocytoma presenting with signs and symptoms of polycythemia diagnosed on a complete blood picture. case report a 54-years-old male patient was referred to the emergency department of holy family hospital rawalpindi from a primary healthcare facility with a four-day history of altered state of consciousness (asoc), right-sided body weakness, and difficulty breathing. on presentation, the vitals of the patient was as follows: blood pressure (bp): 210/130 mmhg, pulse: 82/min, respiratory rate (rr): 22/min, temp: a/f, o2 saturation: 89% at room air. on examination, the patient had a glasgow coma scale score (gcs) of 11/15, right-sided planter up going and left-sided down-going, right-sided upper limb and lower limb power of 3/5 for each limb, pupils normal bilaterally and reactive to light, no signs of meningeal irritation, in all four limbs mascular tone was normal, cranial nerves could not be assessed as the patient was unconscious. occasionally, coarse crepitus was auscultated bilaterally in the chest; the rest of the systemic examination was unremarkable. lab investigations were done in the er department (see table 1), and the results showed some derangements viz. hemoglobin: 18.8 g/dl, hct: 60, wbc: 15.5 cells/microliter, urea: 67 mg/dl, creatinine: 1.5 mg/dl. serum electrolytes, serum total bilirubin, coagulation profile, and ecg were within normal. plain ct brain showed left middle cerebral artery infarct with apparently no mass effect and midline shift. chest x-ray (cxr) showed bilateral infiltrates. bedside funduscopic examination of the patient showed a bilateral hyperemic disc with tortuous vessels, bilateral hemorrhages, and grade-ii papilledema, indicating hypertensive retinopathy. initially, differentials of malignant hypertension, aspiration pneumonitis, and cerebrovascular accident (cva) were made. the patient had a history of cva 3 years back with complete recovery, and hypertension was diagnosed at that time. for the management of hypertension, oral antihypertensive medication was prescribed, but the patient was poorly compliant. the patient was shifted to the high dependency unit (hdu) of the medical ward and managed with an antiplatelet drugs regimen, i.e., aspirin, iv antibiotics, ppi, antihypertensives, iv fluids, nebulization with atem and clenil, and oxygen inhalation. good nursing care, chest and limb physiotherapy were provided. nasogastric tube feeding was started. phlebotomy and venesection with 450 ml blood volume were performed. initial complete blood count (cbc) showed a raised hb and hct, suggestive of polycythemia. serial cbc on the following days also showed the same trend. secondary causes of polycythemia, i.e., hypoxia, smoking, diuretic use, high altitude, obesity, and alcohol access, were ruled out. further workup for polycythemia was done, which included jak-2 v617f mutation, and was found absent. twenty-four hours urine vma levels were measured, which were markedly raised, i.e., vma= 42.3 mg/24 hours (normal= 13mg/24 hours). the test was repeated, and levels were found elevated again, i.e., 43.1 mg/24 hours. suspicion of polycythemia secondary to pheochromocytoma was made. when serum creatinine and urea were within normal limits, ct abdomen was performed, which showed a left-sided adrenal mass, suggestive of pheochromocytoma. serum erythropoietin levels were measured, which were found to be elevated. thus, confirming pheochromocytoma as the source of polycythemia. surgical consultation of the patient was sought, but surgical removal of the pheochromocytoma could not be carried out due to the critical condition of the patient. gcs and clinical condition of the patient gradually deteriorated, and eventually, the patient succumbed to his illness. 562 journal of rawalpindi medical college (jrmc); 2021; 25(4): 560-563 table 1: laboratory investigations of the patient during hospital stay parameters test dates 22/6 23/6 24/6 25/6 26/6 rbc (x1012/l) 8.5 7.2 9.1 hb (mg/dl) 18.8 17.7 19 hct 60 56 63 mcv (fl) 89 62 mch (pg) 29 288 tlc (x103/microliter) 15.5 16.2 15.2 neutrophils (%) 89 86 81 lymphocytes (%) 6.7 8.7 11.6 platelets (x103/microliter) 257 231 183 pt/aptt 27/55 13 28/ 51 urea (mg/dl) 67 55 40 43 46 creatinine (mg/dl) 1.5 1.1 0.8 0.9 0.9 serum total bilirubin 0.8 0.5 0.7 na+ 140 145 142 k+ 3.5 4.6 3.7 ca2+ 9.3 dic profile norm al (asse ssed on 28/6) discussion polycythemia, as a paraneoplastic syndrome, due to benign or malignant conditions is common; the common tumor conditions involving polycythemia include renal cell carcinoma, cerebellar hemangioblastoma, ovarian carcinoma, leiomyoma, hepatocellular carcinoma, and pheochromocytoma.4 pheochromocytoma usually follows “rule of 10s”: 10% are malignant, 10% extra-adrenal, and 10% are malignant. pheochromocytoma has a rare association with neurofibromatosis, von hippel lindau syndrome, and multiple endocrine neoplasia 2 (men-2).5-6 clinical features in polycythemia stem from greater viscosity of blood due to an increased number of rbcs and involve headache, pruritis, dizziness, and visual deterioration.7 while common signs and symptoms in pheochromocytoma arise from catecholamine production causing vasomotor instability, hypertension and its complication like stroke, hypertensive retinopathy, myocardial infarction and left ventricular failure.8 other features include glucose intolerance, constipation, pallor, flushing, palpitations, anxiety, and certain others. catecholamines like epinephrine and norepinephrine are produced and released in excess and their degradation products are detected in the body fluids viz, serum or urine. this forms the basis of investigative testing of pheochromocytoma.9 out of a constellation of investigations for polycythemia, the following investigations are important in terms of greater specificity and sensitivity (see table 2): (1) plasma metanephrine testing (2) 24hour urinary collection for catecholamines and metanephrines (3) ct scan, mri, miodobenzylguanidine (mibg) imaging, pet scan. table 2: specificity and sensitivity of different markers of pheochromocytomas10 test sensitivity (%) specificity (%) plas ma free metanephrines 97-99 82-96 catecholamines 69-92 72-89 urine fractionated metanephrine 96-97 45-82 catecholamines 79-91 75-96 total metanephrines 60-88 89-97 vanillylmandeli c acid 46-77 86-99 imag ing usg abdomen 83-89 30-60 ct abdomen 85-94 29-50 mri abdomen 93-100 50-100 1231-mibg 83-100 95-100 18f-dopa pet 100 100 24-hour urinary tests are considered superior because tumors often secrete catecholamines intermittently, and the short half-life of catecholamines can result in normal plasma catecholamines levels. 24-hour urinary levels plus an imaging test like mibg and ct scan can give a fair assessment of the tumor.11 primary treatment is surgery (laparoscopic surgery common). the mechanism of action of catecholamines is by their agonist action on alpha and beta receptors. these mediators act on alpha 1 receptors of blood vessels to cause vasoconstriction and beta 1 receptor on the heart to cause tachycardia. that’s why the 563 journal of rawalpindi medical college (jrmc); 2021; 25(4): 560-563 preoperative therapy includes alpha blockers like phenoxybenzamine, doxazosin; beta-blockers like atenolol, propranolol, metoprolol, and a high salt diet for around 7-10 days. calcium channel blockers may also be used in place of alpha or beta-blockers with an added benefit of no interference with plasma metanephrine assays along with optimum blood pressure control.12 complete surgical resection, if possible, is the treatment of choice with adjuncttargeted radiation therapy using13 i mibg in case of a malignant tumor. the paraneoplastic syndromes are caused by the chemical mediators produced by the tumor cells in some neoplasias. the removal of the underlying tumor generally resolves the condition.13 conclusion the presence of polycythemia secondary to pheochromocytoma is an uncommon presentation but can present with features of vasomotor instability and hypertension. we recommend that physicians take this differential into account while managing a patient with these symptoms. 24-hours urine metanephrines and vml levels are important investigations for pheochromocytoma. prompt diagnosis with the available investigations and intervention could have been beneficial in saving the patient's life. references 1. neumann hph, young wf jr, eng c. pheochromocytoma and paraganglioma. n engl j med. 2019 aug 8;381(6):552-565. doi: 10.1056/nejmra1806651. pmid: 31390501. 2. aygun n, uludag m. pheochromocytoma and paraganglioma: from epidemiology to clinical findings. sisli etfal hastan tip bul. 2020 jun 3;54(2):159-168. doi: 10.14744/semb.2020.18794. pmid: 32617052; pmcid: pmc7326683. 3. pang y, gupta g, yang c, et al. a novel splicing site irp1 somatic mutation in a patient with pheochromocytoma and jak2v617f positive polycythemia vera: a case report. bmc cancer. 2018 mar 13;18(1):286. doi: 10.1186/s12885-0184127-x. pmid: 29534684; pmcid: pmc5850917. 4. yeung scj, gagel rf. endocrine paraneoplastic syndromes ("ectopic" hormone production) in kufe dw, pollock re, weichselbaum rr, et al., editors. holland-frei cancer medicine. 6th edition. hamilton (on): bc decker; 2003. available from: https://www.ncbi.nlm.nih.gov/books/nbk12609/ 5. sourty b, rousseau a. hereditary predisposition to tumors of the central and peripheral nervous systems. ann pathol. 2020 apr;40(2):168-179. epub 2020 mar 17. pmid: 32192808. 6. lenders jw, pacak k, walther mm, linehan wm, mannelli m, friberg p, et al. biochemical diagnosis of pheochromocytoma: which test is best? jama. 2002;287:1427–34. 7. unger n, pitt c, schmidt il, walz mk, schmid kw, philipp t, et al. diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. eur j endocrinol. 2006;154:409–17. 8. naranjo j, dodd s, martin yn. perioperative management of pheochromocytoma. j cardiothorac vasc anesth. 2017 aug;31(4):1427-1439. doi: 10.1053/j.jvca.2017.02.023. epub 2017 feb 4. pmid: 28392094. 9. guller u, turek j, eubanks s, delong er, oertli d, feldman jm. detecting pheochromocytoma: defining the most sensitive test. ann surg. 2006;243:102–7. 10. garg mk, kharb s, brar ks, gundgurthi a, mittal r. medical management of pheochromocytoma: role of the endocrinologist. indian j endocrinol metab. 2011 oct;15 suppl 4(suppl4): s32936. doi: 10.4103/2230-8210.86976. pmid: 22145136; pmcid: pmc3230088. 11. shulkin bl, ilias i, sisson jc, pacak k. current trends in functional imaging of pheochromocytomas and paragangliomas. ann n y acad sci. 2006;1073:374–82. 12. clinical staff conference. pheochromocytoma: current concepts of diagnosis and treatment. combined clinical staff conference at the national institutes of health. ann. intern. med. 65: 1302-1326, 1966. 13. pelosof lc, gerber de. paraneoplastic syndromes: an approach to diagnosis and treatment. mayo clin proc. 2010 sep;85(9):838-54. doi: 10.4065/mcp.2010.0099. erratum in: mayo clin proc. 2011 apr;86(4):364. dosage error in article text. pmid: 20810794; pmcid: pmc2931619. 404 not found 68 journal of rawalpindi medical college (jrmc); 2022; 26(1): 68-71 original article frequency of impacted third molar in mandibular angle fractures in patients presenting to ayub teaching hospital jawad ahmad1, alaf khan2, muhammad jamal3, anam javed4 1 ex-trainee, department of oral and maxillofacial surgery, ayub teaching hospital, abbottabad. 2 district specialist dentistry, king abdullah teaching hospital, mansehra. 3 associate professor, oral and maxillofacial surgery, islamabad medical and dental college, islamabad. 4 dental surgeon, king abdullah teaching hospital, mansehra. author’s contribution 1 conception of study 1 experimentation/study conduction 1,2,3 analysis/interpretation/discussion 2,3,4 manuscript writing 4 critical review 3 facilitation and material analysis corresponding author dr. muhammad jamal, associate professor, oral and maxillofacial surgery, islamabad medical and dental college, islamabad email: jamal_kcd@hotmail.com article processing received: 08/07/2021 accepted: 18/01/2022 cite this article: ahmad, j., khan, a., jamal, m., javed, a. frequency of impacted third molar in mandibular angle fractures in patients presenting to ayub teaching hospital. journal of rawalpindi medical college. 31 mar. 2022; 26(1): 68-71. doi: https://doi.org/10.37939/jrmc.v26i1.1727 conflict of interest: nil funding source: nil access online: abstract objective: the objective of the study is to determine the frequency of impacted third molar in mandibular angle fracture. materials and methods: this descriptive cross-sectional study was performed for a period of six months on one hundred and twenty-two patients (122) with mandibular. opg was done to determine the state of 3rd molar tooth. after approval from the institutional ethical review committee, informed consent was taken from all patients. a proper history and required examination and investigation were undertaken to rule out pathologies associated with 3rd molar impaction. the data was collected using a pro forma including the patient’s biographical data in addition to studying variables such as angulation and level of occlusion (using pell and gregory classification) along with cause and direction of fracturing force. the collected data was analyzed using statistical package for social sciences (spss) version 21. results: the frequency of 3rd molar impaction in fractures of the angle of the mandible was 36.1%. young age (less than 31 years in this study) was significantly associated with impacted 3rd molar tooth (p < 0.05). conclusion: individuals with impacted 3rd molar should be educated about the possibility of the fracture of the mandibular angle so that preventive measures can be adopted. keywords: mandible fractures, 3rd molar, impaction, traumatic dental fractures. 69 journal of rawalpindi medical college (jrmc); 2022; 26(1): 68-71 introduction the incidence and etiology of maxillofacial trauma vary widely due to social, economic, cultural consequences, awareness of traffic rules, and alcohol consumption.1,2 interpersonal violence, road traffic accidents and stumble and fall are the main causes of maxillofacial trauma with relative percentages of 39.7%, 29.2%, and 27.2%.2 mandibular fractures are one of the commonest maxillofacial injuries. fractures take place at various locations.3 the incidence of parasymphysis, condyle, and angle fracture was found to be 41.1%, 29.09%, and 26.72% respectively.4 mandibular angle fracture susceptibility in addition to being associated with the type and direction of impact is also associated with impacted 3rd molar. the frequency of 3rd molar impaction in a study population was found to be 26%.5 a study conducted in margalla institute of dental sciences reported that impacted 3rd molar increases angle fracture susceptibility 2.3 folds.4 in the same study out of 134 fractures 38 (28.35%) angle fractures were reported with impacted third molar.6 angulation and depth of impaction have been associated with an increase or decrease in susceptibility to angle fracture.7 a study conducted in india reported the most common angulation to be mesioangular (39%) and the most common level of occlusion to be level b.8 various theories have been put forward to explain the relationship between angle fracture and impacted third molar. a finite element analysis using micro ct in a cadaver mandible showed that the reason for the increased risk of angle fracture is due to stress concentration around the apex of the root of the third molar.9 impacted third molar also possesses various other problems in addition to angle fracture that includes; pain, infection, acute or chronic pericoronitis, periodontal damage to 2nd molar, increased susceptibility of interdental caries, presence of cyst or tumor, external or internal tooth/root resorption and adjacent tooth damage, orthodontic reason, and preparation of orthognathic.10 the rationale of this study is to determine the frequency of impacted third molar in mandibular angle fractures which would help the surgeon to evaluate the outcome of whether 3rd molar should be extracted early or not. materials and methods this descriptive cross-sectional study was performed in the department of oral and maxillofacial surgery, ayub teaching hospital, abbottabad for a period of six months after the approval of the synopsis sample size of 122 was calculated using the who software for sample size determination for health studies (confidence level=95%, anticipated proportion of impacted third molar in mandibular angle fracture=28.35%6, absolute precision=8%). nonprobability consecutive sampling technique was used. all patients aged between 18-60 years of both genders having mandibular angle fractures were included in the study. the angulation and level of occlusion of the mandibular third molar were confirmed on radiographs. impactions associated with other pathologies such as keratocyst, dentigerous cyst, or ameloblastoma and patients who are not willing to contact or follow up were excluded from the study. after approval from the institutional ethical review committee, informed consent was taken from all patients. a proper history and required examination and investigation were undertaken to rule out pathologies associated with 3rd molar impaction. the data was collected using a pro forma including the patient’s biographical data in addition to study variables such as angulation and level of occlusion ( using pell and gregory classification) along with cause and direction of fracturing force. the collected data was analyzed using statistical package for social sciences (spss) version 21. frequencies and percentages were calculated for categorical variables like gender, angulation, level of occlusion, and cause of fracture. mean± sd was calculated for numerical variables like age. outcome variables were stratified by age and gender. post-stratification chi-square test at a 5% significance level was used to know the relationship of 3rd molar with angle fracture. all the data was collected by the researcher himself results in this descriptive cross-sectional study, the mean age was 31.65± 6.25. males comprised the significant majority of the study population 93; (76.23%); there were 29 (23.77%) females. 69 (56.6%) patients had erupted third molars, 44(36.1%) had impacted third molars and 9 (7.3%) had missing third molars. of the 44 patients with impacted molars, 30 (24.59% of total study participants) had level c impaction, 8 (6.56% of 70 journal of rawalpindi medical college (jrmc); 2022; 26(1): 68-71 total study participants) had level a and 6 (4.92% of total study participants) had level b impaction of the third molar. interpersonal violence was the most common (42.62%) cause of mandibular fracture in our study, followed by road traffic accidents (32.79%) and falls/slips (24.59%). the commonest angulation in this study was vertical (54.92%), followed by mesioangular (30.33%), distoangular (13.11%), and horizontal (1.64%). when the outcome variable, i.e., impaction of 3rd molar was stratified by age and gender of study participants, a statistically significant association was seen with age (p=0.05), while no statistically significant association was observed with the sex of study participants. table 1: age of study participants variable mean standard deviation mini mum maxi mum age 31.65 6.25 21.00 42.00 table 2: sex of study participants sex frequency percent male 93 76.23 female 29 23.77 total 122 100.0 table 3: cause of mandibular fracture in study population cause of fracture frequency percent interpersonal violence 52 42.62 road traffic accidents 40 32.79 slips and falls 30 24.59 total 122 100.0 table 4: frequency of mandibular third molar angulations in study participants angulation of mandible frequency percent vertical angulation 67 54.92 mesioangular angulation 37 30.33 distoangular angulation 16 13.11 horizontal angulation 2 1.64 total 122 100.0 table 5: state of third molar in study participants state of 3rd molar frequency percent erupted 69 56.56 impacted 44 36.07 missing 9 7.38 total 122 100.0 table 6: frequency of impaction level of 3rd molar in study participants types of impaction of 3rd molar frequency percent level c 30 24.59 level a 8 6.56 level b 6 4.92 no impaction 78 63.93 total 122 100.0 table 7: cross-tabulation of 3rd molar impaction with age of study participants 3rd molar impaction age (years) total pvalue up to 31 years more than 31 years yes 25 19 44 0.05 no 30 48 78 total 55 67 122 table 8: cross-tabulation of 3rd molar impaction with sex of study participants 3rd molar impaction sex total pvalue male female yes 37 7 44 0.13 no 56 22 78 total 93 29 122 discussion in the present study, 3rd molar impaction was found in 44 (36.1%) patients with fractures of the mandibular angle. interestingly, a study from karnataka, india reported that 73% of the mandibular 3rd molar teeth were impacted majority having position a, class ii, and mesioangular impaction of the third molar.10 there was male predominance in their study with the mean average age being 29 years similar to that found in the present study (76.23% male, mean age 31.65± 6.25), however, the study sample was older than the above-mentioned study. a road traffic accident was the primary cause of fracture in their study (observed more on the left side) while in the current study interpersonal violence was the main reason for mandibular fractures. in the total sample, the mandibular third molar was present in 90% of the cases with angle fracture.11 interestingly, another study from india reported that angle fractures of the mandible had a statistically significant association (84%) with the impacted or partially erupted third molar tooth (p=0.000). they found that out of 104 fractures, angle fracture was 71 journal of rawalpindi medical college (jrmc); 2022; 26(1): 68-71 present in 25 (24.038%) cases and among these fractures, 18 (72%) showed the presence of an impacted third molar (10 mesioangularly inclined, 4 class 3, 2 class 2, 2 vertically impacted position c). partially erupted third molars (vertical inclination) were present in 3(12%) cases.12 a study from tanzania reported the presence of an impacted third molar in more than half (59.7%) of the fractures of mandibular angles.13 out of 268 opgs, angle fracture was present in about a quarter (25.4%) of them. they found that most of the impacted thirds molars had the mesioangular inclination (44.3%), class ii (72.2%), and position a (60.8%) with the presence of impacted molars in more than half (59.7%) of the mandibular angle fractures. they concluded that there are about nine times higher chances of mandibular fractures in the presence of an impacted third molar.13 another study reported that the prevalence of impacted mandibular third molars was 26.04%.14 after analyzing panoramic radiographs and intraoral periapical radiographs of patients. they found 960 patients with the third molars, out of which 250 patients had impacted mandibular third molar. there was males (60.8%) predominance in their study and an almost equal distribution of impacted third molars on both left (45.8%) and right (54.2%) sides. the most common impactions were mesioangular (49.2%) while the least common were transverse in their study (2%).14 likewise, a study from nepal found a strong association between impacted third molar and angle mandibular fractures.15 in this retrospective study, 300 cases with mandibular angle fractures were enrolled in the present study. males in the 2nd to 3rd decade were more commonly affected than females. most fractures were caused by road traffic accidents (60.83%), followed by falls (22.5%), assault (9.16%), and sports activities (5.83%). mesioangular, class 1, and position a were the most common type of impacted teeth. angle fractures were more common on the left side (65%) than on the right side.15 conclusion the present study concluded that an impacted third molar is associated with the fractures of the angle of the mandible. individuals with impacted 3rd molar should be educated about the possibility of the fracture of a mandibular angle so that preventive measures can be adopted. prophylactic removal of impacted third molar can be considered in high-risk individuals to decrease the possibility of mandibular angle fractures. this was a single-center-based study with small sample size; hence results should be interpreted with caution. association of 3rd molar tooth with fractures of nearby regions of mandible was not explored. the preponderance of angle fractures in either side of the jaw/face was not studied. references 1. al-qahtani f, bishawi k, jaber m, thomas s. maxillofacial trauma in the gulf countries: a systematic review. eur j trauma emerg surg. 2020 https://doi.org/10.1007/s00068-020-01417-x. 2. arsalan e, solakogiu a, komut e. assessment of maxillofacial trauma in emergency department. world j emerg surg. 2014;13(9):69-90. 3. rostyslav y, yakovenko l, irina p. fractures of the lower jaw in children (causes, types, diagnosis and treatment). retrospective 5 year analysis. jobcr. 2020; 10(2):1-5. 4. barde d, mudhol a, madan r. prevalence and pattern of mandibular fracture in central india. natl j maxillofac surg. 2014; 5(2):153-6. 5. amanat n, mirza d, rizvi kf. frequency of third molar impaction: frequency and types among patients attending urban teaching hospital of karachi. pak oral dent j. 2014; 34(1):34-7. 6. shah a, aslam a, yunus m. third molar and angle fracture.pak j oral dent. 2015; 35(1):24-9. 7. al-harbawee a, ahmed t, ahmed s, avery c, fagiry r, hamzah h, afzal f et al. a retrospective analysis of the impaction status of mandibular third molars as a risk factor for fractures of angle or condylar region of the mandible. adv ora maxillofac surg. 2021:100018. 8. jain s, debbarma s, prasad sv. prevalence of impacted third molars among orthodontic patients in different malocclusions. indian j dent res. 2019;30 (2):238-42. 9. takada h, abe s, tamatsu y, mitarashi s, saka h, ide y. threedimensional bone microstructures of the mandibular angle using microct and finite element analysis: relationship between partially impacted mandibular third molars and angle fractures. dent traumatol 2016; 22: 18-24. 10. patel s, mansuri s, shaikh f, shah t. impacted mandibular third molars: a retrospective study of 1198 cases to assess indications for surgical removal, and correlation with age, sex and type of impaction—a single institutional experience. j maxillofac oral surg. 2017; 16(1):79-84. 11. subbaiah mt, ponnuswamy ia, david mp. relationship between mandibular angle fracture and state of eruption of mandibular third molar: a digital radiographic study. j indian acad oral med radiol 2015; 27:35-41. 12. menon s, kumar v, v s, priyadarshini y. correlation of third molar status with incidence of condylar and angle fractures. craniomaxillofac trauma reconstr. 2016; 9(3):224-8. 13. sohal ks, moshy jr, owibingire ss, m. simon en. association between impacted mandibular third molar and occurrence of mandibular angle fracture: a radiological study. j oral maxillofac radiol 2019; 7:259. 14. passi d, singh g, dutta s, srivastava d, chandra l, mishra s, srivastava a, dubey m. study of pattern and prevalence of mandibular impacted third molar among delhi-national capital region population with newer proposed classification of mandibular impacted third molar: a retrospective study. natl j maxillofac surg 2019; 10:59-67. 15. shah d, jain mk, jagdeesh sn. co-relation between fractures of the mandibular angle with the presence or absence of impacted third molar -a retrospective and radiographic analysis. int j curr med pharm res. 2018; 4(11):3865-69. 386 journal of rawalpindi medical college (jrmc); 2021; 25(3): 386-389 original article alanine transaminase levels in patients of dengue fever in the suburbs of islamabad hassan mumtaz1, irfan afzal mughal2, amna faruqi3, noor-ul-ain irfan4, shamim mumtaz5, asma irfan6 1 house officer, holy family hospital, rawalpindi. 2 associate professor, department of medicine, hbs medical & dental college, islamabad. 3 associate professor, department of medicine, islamabad medical & dental college, islamabad. 4 final year mbbs student, islamabad medical & dental college, islamabad. 5 professor, department of medicine, islamabad medical & dental college, islamabad. 6 associate professor, department of physiology, islamabad medical & dental college, islamabad. author’s contribution 1,3,6 conception of study 2 experimentation/study conduction 2,4 analysis/interpretation/discussion 3,6 manuscript writing 4,5 critical review 1,5 facilitation and material analysis corresponding author dr. asma irfan professor of physiology, islamabad medical and dental college, islamabad email: asma.irfan@imdcollege.edu.pk article processing received: 01/04/2021 accepted: 23/09/2021 cite this article: mumtaz, h., mughal, i.a., faruqi, a., irfan, n., mumtaz, i., irfan, a. alanine transaminase levels in patients of dengue fever in the suburbs of islamabad. journal of rawalpindi medical college. 30 sep. 2021; 25(3): 386-389. doi: https://doi.org/10.37939/jrmc.v25i3.1619 conflict of interest: nil funding source: nil access online: abstract objective: this study was carried out to observe hepatic damage in patients with dengue fever (df) by measuring alanine transaminase levels. materials and methods: a cross-sectional study of three months duration was carried out in the department of medicine, dr. akbar niazi teaching hospital affiliated with islamabad medical & dental college, pakistan. the sampling technique was non-random consecutive sampling and 118 patients were included in our study. serum alanine transaminase (alt) (normal = 7-56 iu/l), serum aspartate transaminase (ast) (normal = 10-40 iu/l) were determined and ultra-sound abdomen was performed. statistical analysis was done using spss version 24. the chi-square test was used to observe the relationship between categorical variables. phi, cramer’s v, pearson’s, and spearman’s correlation tests were used to study the association of age and gender with alt levels. results: there were 72% males (n=85) and 28% females (n=33). patients were grouped according to age and mean alt (95+86 iu/l) and ast (134.7+ 98 iu/l) levels were calculated in the different age groups. these levels were found to be significantly raised (p=0.00) in the age groups of 9-18 years and 19-25 years as compared to the other age groups. moreover, males had high alt levels as compared to females, however, a significant difference was not observed. there was also no association seen of gender with raised alt levels (p=0.564), phi & cramer’s v=0.56, and spearman’s correlation coefficient=0.320. conclusions: alt and ast levels were elevated above the normal in our sample indicating hepatic involvement. keywords: dengue, serum alanine transaminase, serum aspartate transaminase, hepatic dysfunction. 387 journal of rawalpindi medical college (jrmc); 2021; 25(3): 386-389 introduction dengue is a widespread infectious illness seen in countries located in the tropics and is fast spreading in all zones of who worldwide.1 this disease is viral in nature and is mosquito-borne. dengue virus spreads by the bite of female mosquitoes, mainly of the aedes aegypti species, which also transmits chikungunya, yellow fever, and zika infections and, to some extent, by another species of mosquito, the aedes albopictus. dengue infection is prevalent in the tropics, with local disparities in risk depending on temperature, rain, and unexpected fast migration of people to urban areas.2 in the 1950s, documentation of severe dengue was done, during a dengue epidemic in the philippines and thailand. presently, most asian and latin american countries are affected by it and have become a major reason for hospitalization and death, particularly among children. it has been assessed, that every year approximately 0.39 billion cases of dengue are observed and out of these, about 25% of patients present with clinical manifestations of this disease.2 in south-east asia, the fatality rate is about 1%, but in india, indonesia and myanmar higher rates (3%-5%) have been recorded.3 in pakistan, the initial documented outbreak of dengue fever occurred in 1994. thereafter, an explosive occurrence of dengue cases, at the end of the year 2005 in karachi, led to it being recognized as a yearly epidemic trend.4,5 an epidemic of dengue fever has afflicted pakistan since the year 2010. the city of lahore recorded 257 fatalities and 16,580 patients were confirmed positive. moreover, from the remaining parts of the country, the number of reported cases was 5000, while some sixty people died due to dengue complications. in pakistan, the epidemic has affected mainly the provinces of punjab, sindh, and khyber pakhtunkhwa.4,5 clinically, the illness of dengue fever (df) ranges from an asymptomatic form to a wide range of syndromes with serious clinical manifestations. symptomatic infection may present as a mild but incapacitating df to a highly fatal dengue haemorrhagic fever (dhf), as well as a dengue shock syndrome(dss) condition due to plasma escape in dhf patients.1 in some cases, hepatic and central nervous system damage has also been seen.6 observed hepatic dysfunction ranges from minor damage reflected by raised transaminases to extensive injury and failure of the hepatic cells, with patients exhibiting jaundice.6 deranged functioning of the liver has been observed more commonly in patients of dss and dhf.7,8 thus, in order to reduce associated morbidity and mortality, this ailment should be diagnosed at the earliest possible so that appropriate therapy may be instituted. there is a minimal data record of altered liver activity in such patients in pakistan. the purpose of our study was to assess the spectrum of hepatic disorder in patients suffering from dengue fever. materials and methods this cross-sectional study, with a duration of three months, was carried out in the department of medicine, dr. akbar niazi teaching hospital affiliated with islamabad medical & dental college, bharakahu islamabad, pakistan. who calculator was used to calculate the sample size. the estimated minimal sample size required for this study was 111 cases of dengue infection with absolute precision required to be 0.07. non-random consecutive sampling was performed. as per who guidelines, all clinically suspected patients between 9 and 70 years of age presenting at the opd, from july 2019 to oct 2019 were screened. serologically confirmed cases by dengue ns1 antigen, dengue virus igg, and igm were included in our study. all cases were subjected to detailed history taking, followed by a thorough clinical examination. in addition to routine investigations, serum alanine transaminase (alt) (normal = 7-56 iu/l), serum aspartate transaminase (ast) (normal = 10-40 iu/l), and ultra-sound abdomen were performed for detection of liver pathology. patients suffering from other liver diseases e.g. hepatitis, alcoholic hepatitis, drug-induced hepatitis, etc. were excluded from our study. statistical analysis was performed using spss version 24. the chi-square test was used to observe the relationship between categorical variables. phi, cramer’s v, pearson’s, and spearman’s correlation tests were used to study the association of age and gender with alt levels. results a total of 118 patients were enrolled in our study, with 72% males (n=85) and 28% females (n=33) (figure 1). patients were grouped according to age (figure 2) and mean alt (95+86 iu/l) and ast (134.7+ 98 iu/l) levels were calculated in the different age groups (table 1). these levels were found to be significantly raised (p=0.00) in the age groups of 9-18years and 19388 journal of rawalpindi medical college (jrmc); 2021; 25(3): 386-389 25 years as compared to the other age groups (table 2). thus, younger age was found to be positively associated with raised alt levels (table 3). in addition, more males had high alt levels as compared to females; however, there was no significant difference. there was also no association or relationship seen of gender with raised alt levels (p=0.564), phi & cramer’s v = 0.56, and spearman’s correlation coefficient =0.320. figure 1: distribution of dengue patients according to sex figure 2: distribution of dengue patients according to age table 1: alt and ast levels in different age groups age groups(yrs) number of patients=n alt iu/l (mean + sd) ast iu/l (mean + sd) 9-18 15 117.9+108 186.1+120 19-25 32 101.2+112 133.7+124 26-35 36 84.5+59 118.1+65 36-45 19 89.2+73 127.6+83 46-55 10 70.2+135 96.1+41 56-65 2 212.5+152 276.5+173 66-75 4 85.50+77 158.0+98 table 2: relationship between age groups and alt levels chi-square tests value df asymptomatic significance (2-sided) pearson chi-square 132.132 72 0.001 likelihood ratio 71.966 72 .479 linear-by-linear association 1.426 1 .232 n of valid cases 118 *** highly significant table 3: association and relationship of age and alt levels value significance nominal by nominal phi 1.058 0.001 cramer' s v .432 0.0001 interval by interval pearson's r .110 .234 ordinal by ordinal spearman correlation .096 .300 n of valid cases 118 discussion we witnessed in our study that in pakistan, the spread of dengue infection mainly occurred in august and september and we found our results to conform to a national report published previously. the probable reason for this being that this is soon after the rainy season, when the environment is extremely humid and thus, favourable for the breeding of mosquitoes.9 in our present study, we observed that mostly the younger age groups were affected as compared to the older ones, which might be due to their greater exposure to the outdoor environment. it was observed that most of our patients were in the 15-35 year age bracket. another interesting finding was that twice as many males were affected as females, owing probably to females being confined indoors, as compared to males who take on most outdoor work and responsibilities. similar results have been observed in previous studies.10 hepatic dysfunction is a common occurrence in dengue infection, as it is believed to attack the reticuloendothelial system of the patient.9,11,12 hepatic damage could be a result of either the virus directly attacking the cells or, because of an excessive immune reaction of the host to the viral antigens.9 some studies conducted in other countries, like thailand and india 389 journal of rawalpindi medical college (jrmc); 2021; 25(3): 386-389 have shown that the foremost reason for sudden liver failure in the younger age group, was dengue infection in about 34% and 18% of the cases, respectively.13 another previous study observed that complications and deaths due to acute dengue fever were significantly associated with abnormal liver function and high levels of aminotransferases. patients with dengue hemorrhagic fever, dengue septic shock, hepatic and respiratory failure, as well as patients with encephalopathy, all had significant elevation of ast. moreover, ast levels were found to be raised twice as much as alt, in contrast to other viral infections. similarly in another study carried out in alexandria hospital.10 from november 2003 till december 2004, showed that 90.6% of patients had raised ast and 71.7% had raised alt levels. raised aminotransferases were also reported by souza et al.14, wong15, chinh, and colleagues.16 it was found that ast level was raised more than alt.14,16,17 in a similar study conducted by trung and colleagues in south vietnam, 650 df patients were recruited and raised transaminases were found in all patients. this was also associated with the severity of illness in terms of vascular leakage and bleeding.15 conclusion thus, we can conclude that raised alt level can be considered an important parameter in determining morbidity and mortality in young patients suffering from dengue, and as such can be employed as an early marker for assessment of disease severity. the limitation of our study was that our data was limited to just a suburb of islamabad and our sampling was not done at a national level. references 1. khetarpal n, khanna i. dengue fever: causes, complications, and vaccine strategies. journal of immunology research. 2016;2016. 2. dengue and severe dengue who.https://www.who.int/news-room/factsheets/detail/dengue-and-severe-dengue 3. kalenahalli jagadishkumar, mbbs, md,* puja jain, mbbs, vaddambal g. manjunath, mbbs, dch, dnb, and lingappa umesh, hepatic involvement in dengue fever in children ncbi iran j pediatr. 2012 jun; 22(2): 231–236 4. dengue fever/ programmes/ pakistanwho emro http://www.emro.who.int/pak/programmes/dengue-fever.html 5. khan j, khan i, ghaffar a, khalid b. epidemiological trends and risk factors associated with dengue disease in pakistan (1980–2014): a systematic literature search and analysis. bmc public health. 2018 dec 1;18(1):745. 6. kalenahalli jagadishkumar, mbbs, md,* puja jain, mbbs, vaddambal g. manjunath, mbbs, dch, dnb, and lingappa umesh, hepatic involvement in dengue fever in children iran j pediatr. 2012 jun; 22(2): 231–236. 7. petdachai w. hepatic dysfunction in children with dengue shock syndrome. dengue bulletin. 2005;29: 112–7. 8. itha s, kashyap r, krishnani n, saraswat va, choudhuri g, aggarwal r profile of liver involvement in dengue virus infection. natl med j india. 2005 may-jun; 18(3):127-30 9. khan e, kisat m, khan n, nasir a, ayub s, hasan r. demographic and clinical features of dengue fever in pakistan from 2003–2007: a retrospective cross-sectional study. plos one. 2010;5(9). 10. gubler dj, trent dw. emergence of epidemic dengue/dengue hemorrhagic fever as a public health problem in the americas. infect agents dis. 1993; 2:383393. 11. ganeshkumar p, murhekar mv, poornima v, saravanakumar v, sukumaran k, anandaselvasankar a, john d, mehendale sm. dengue infection in india: a systematic review and meta-analysis. plos neglected tropical diseases. 2018 jul 16;12(7):e0006618. 12. khan j, khan a. incidence of dengue in 2013: dengue outbreak in district swat, khyber pakhtunkhwa, pakistan. ijfbs. 2015; 2(1):50-56. 13. kumar r, tripathi p, tripathi s, kanodia a, venkatesh v prevalence of dengue infection in north indian children with acute hepatic failure.ann hepatol. 2008 jan-mar; 7(1):59-62. 14. souza ljd, alves jg, nougueira rmr, gicovate neto c, bastos da, siqueira ewds, et al. aminotransferase changes and acute hepatitis in patents with dengue fever: analysis of 15,85 cases. brazilian j infect dis 2004; 8:156-63. 15. wong m, shen e. the utility of liver function test in dengue.ann acad med singapore 2008; 370:82-3. 16. trung dt, le thi, thu thao tt, hien nth, vinh nn, hien ptd, chinh nt, et al. liver involvement associated with dengue infection in adults in vietnam. am j trop med hyg 2010; 83:774-80. 17. asim ahmed, aftab haider alvi, ambreen butt, arif amir nawaz and asif hanif. assessment of dengue fever severity throughliver function tests. journal of the college of physicians and surgeons pakistan 2014, vol. 24 (9): 640-644. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 60-63 60 original article diagnostic accuracy of transcerebellar diameter for gestational age ruqyyah salim, sobia nawaz, farzana kazmi department of gynae/obs dhq hospital and rawalpindi medical college, rawalpindi abstract background: to determine the correlation of mean transcerebellar diameter and mean gestational age in third trimester of pregnancy methods: in this cross sectional study all pregnant women with previous regular menstrual period aged 25-35 years, gestational age between 26 to 38 weeks assessed on lmp and having single fetus assessed on ultrasound were enrolled. ultrasound measurements of tcd (in mm) were made. results: mean age of the patients was 29.53 ±3.60 years. mean gestational age of the patients was 32.56 ±3.51 weeks. there were 61% nulliparous and 39% multiparous women. spearman’s correlation test was applied to see the relationship of tcd with gestational age. strong positive correlation was observed (rho 0.968, p-value <0.001). conclusion: strong positive correlation of mean transcerebellar diameter and mean gestational age is observed in third trimester of pregnancy key words: gestational age, third trimester of pregnancy, transcerebellar diameter introduction the accurate knowledge of gestational age is a keystone in an obstetrician's ability to successfully manage the antepartum care of a patient and is of critical importance in ante-natal tests and successful planning of appropriate therapy or intervention. failure can result in iatrogenic prematurity which is associated with increased perinatal morbidity and mortality. ultrasonography of fetal measurements is highly reliable in the first and second trimester of pregnancy but reliability of any ultrasound method greatly diminishes as gestation advances. in third trimester, reliability of any single ultrasound parameter is poor.1 since the last decade, ultrasound parameter ‘transcerebellar diameter (tcd)’ is considered a reliable predictor for gestational age in third trimester.2-3size of cerebellum is less affected by deviation in fetal growth restriction or growth acceleration.4the predicted gestational age by tcd between 22 – 28 weeks is within 0-2 days, between 2936 weeks is within 05 days and at 37 week is 09 days of actual gestation. tcd normogram predicts gestational age with accuracy of 94% in the third trimester.4 although both bpd and tcd are accurate biometric parameters at 36 weeks of gestation, transcerebellar diameter is more reliable method of gestational age determination in third trimester of pregnancy than biparietal diameter.5tcd can be used as a tool to assist in the assessment of gestational age in third trimester.6 regression analysis indicated a strong relationship between tcd and gestational age indicating tcd is a good marker for estimation of gestational age.7 transverse cerebellar diameter varied in a linear fashion in third trimester, while transverse cerebellar diameter/abdominal circumference (tcd/ac) ratio remained constant in second half of pregnancy. all the parameters were expressed by regression equations and correlation coefficients were found to be statistically significant (r=0.99 for tcd, r=0.98 for tcd/ac all p<0.0001).4 patients and methods this cross sectional study was performed in department of obstetrics and gynaecology, dhq hospital, rawalpindi, from october, 2014 to april, 2015. inclusion criteria was all pregnant women between age 25-35 years with previous regular menstrual period ,gestational age between 26 to 38 weeks (assessed on lmp ) and single fetus assessed on ultrasound. exclusion criteria was pregnant women not willing to participate, not sure of date of last menstrual period,with hypertensive disease or multiple pregnancies or fetal malformation detected on ultrasound and smokers . fetal tcd was measured using the widest diameter of the cerebellum by usg in mm. gestational age was assessed by lmp. ultrasound measurements of tcd (in mm) were made as per operational definition with commercially available real time ultrasound.the measurement of tcd was obtained by placing electronic callipers at outer margins of cerebellum. the landmarks of the journal of rawalpindi medical college (jrmc); 2017;21(1): 60-63 61 thalami, cavum, septum pellucidum and third ventricle were identified thereby slightly rotating the transducer below the thalamic plane. the posterior fossa is revealed with the characteristics butterfly like appearance of cerebellum. in all cases cerebellum was seen as two lobules on either side of midline in the posterior cranial fossa. the statistical evaluation between fetal transverse cerebellar diameter and gestational age was assessed. pearson correlation coefficient “r” in the range of (+1, -1) was calculated. p value ≤0.05 was significant. stratification of age and parity was done to control effect modifiers. correlation was calculated post stratification and p value less than or equal to 0.05 was taken as significant. results mean age of the patients was 29.53 ±3.60 years. majority of the patients (64%) were presented with ≤30 years of age. mean gestational age of the patients was 32.56 ±3.51 weeks. majority of the patients (76%) presented with ≤32 weeks of gestation (figure 1). there were 61% nulliparous and 39% multiparous women.mean tcd of the patients was 37.60 ±7.02 mm (table 1). table 1: gestatinoal age and transcerebellar diameter mean ±sd min max age of the patients (years) 29.53 ±3.60 25 35 gestational age (weeks) 32.56 ±3.51 26 38 transcerebellar diameter (mm) 37.49±5.651 27 38 figure 1: gestational age spearman’s correlation test was applied to see the relationship of tcd with gestational age. strong positive correlation was observed (rho 0.968, p-value <0.001).stratification was done to see the effect of age and parity on the outcome. discussion the transcerebellar diameter (tcd) has been one of the most reliable ultrasound parameters for growth. the tcd was shown to be a reliable parameter that is significantly correlated with gestational age by the end of the second trimester.8 there is relative preservation of normal cerebellar growth even in fetal growth restriction and a similar rate of growth in both singleton and multiple pregnancies.9accurate gestational dating is of paramount importance and the cornerstone for management of pregnancies, easily reproducible sonographic fetal biometric parameters for gestational dating are clinically important for the optimal obstetric management of pregnancies. this is especially true in determining timing of a variety of gestational tests, assessing adequacy of growth and timing of delivery for the optimal obstetric outcome.2 campbell et al. demonstrated that 45% of pregnant women are uncertain of menstrual dates as a result of poor recall, irregular cycles, bleeding in early pregnancy, or oral contraceptive use within 2 months of conception.2 even if menstrual history is correct, the exact time of ovulation, fertilization, and implantation cannot be known. women may undergo several “waves” of follicular development during a normal menstrual cycle, which may mean ovulatory inconsistency during any given cycle.11 tcd with some combination of other fetal biometric parameters, including head circumference, biparietal diameter, and femur length. nevertheless, the best combination of biometric measurements remains to be determined. furthermore, our analysis, especially for large fetuses, was based on a fairly small number of observations (n = 16), warranting caution in the interpretation of our results. future large studies are therefore required to corroborate our findings. until the results of these studies become available, on the basis of the encouraging results of this and previous studies, we recommend that tcd be used as an important sonographic biometric parameter in singleton iugr and large fetuses for accurate prediction of ga.12 the conventional methods used to estimate gestational age are date of onset of the last menstrual period (lmp), clinical assessment of the fundal height and fetal weight, and ultrasonographic fetal biometry.13 naegle’s rule is the most common, and, if reliable, an accurate method of pregnancy dating. the expected date of delivery (edd) is calculated by counting back three months from and adding seven days to the onset journal of rawalpindi medical college (jrmc); 2017;21(1): 60-63 62 of lmp. estimation of the gestational age based on menstrual dates is, sometimes however, erroneous or inaccurate. some pregnant women are not sure of their menstrual dates or do not have regular 28-day cycles. in addition, bleeding in early pregnancy or a recent use of hormonal contraception may lead to incorrect assumption of the date of ovulation.14 clinical examination is inaccurate in estimating the ga. it may be affected by fetal growth disorders and liquor volume, and subject to errors due to maternal obesity or inter-and intra-observer variations.14 sonographic fetal biometry is a method devoted to the measurement of the several parts of fetal anatomy and their growth. several diameters and circumferences have been studied concerning their correlation to the true gestational age. the most reliable diameters used in estimation of the ga in the second and early third trimester is the biparietal diameter (bpd); femur length (fl) is the most accurate for the late third trimester. the measurement of bpd in second trimester routine scan is performed in all good antenatal care centers.15 regression analysis indicated a strong relationship between tcd and gestational age indicating tcd is a good marker for estimation of gestational age.7 transverse cerebellar diameter varied in a linear fashion in third trimester, while transverse cerebellar diameter/abdominal circumference (tcd/ac) ratio remained constant in second half of pregnancy. all the parameters were expressed by regression equations and correlation coefficients were found to be statistically significant (r=0.99 for tcd, r=0.98 for tcd/ac all p<0.0001).4 in our study, spearman’s correlation test was applied to see the relationship of tcd with gestational age. strong positive correlation was observed (rho 0.968, pvalue <0.001). the bpd is, however, subject to inaccuracy related to its affection by growth abnormalities of the fetal head e.g. in fetal growth restriction and also in congenital fetal malformations of the head or intracranial structures e.g. hydrocephalus.16 in the current study, analysis of agreement showed insignificant differences between estimated gestational age using lmp/crl and each of bpd/fl and tcd. some authors stated that there may be a slight fluctuation in the growth curve of the fetal cerebellum, indicating multiple conditions that would lead to difficulties in measuring the tcd in late gestations.2 hill et al., reported that the tcd was within two standard deviations in only 40% of iugr cases, and in 60% of cases was greater than two standard deviations below the mean. however, they included 44 consecutive singleton gestations with an estimated fetal weight of less than the 10th percentile, and it was unclear whether fetuses with chromosomal abnormalities were excluded.16 lee et al., reported that the tcd was a useful predictor of gestational age for fetuses with asymmetric, but not symmetric, growth restriction.17 vinkesteijn et al.18, performed a retrospective, crosssectional analysis of 360 normally developing fetuses between 17 and 34 weeks and 73 growth-restricted fetuses between 24 and 34 weeks gestation, and demonstrated that the tcd measurement is typically spared in cases of iugr. even in severe growth restriction, the tcd was only mildly affected. they also concluded that the second half of pregnancy is characterized by a more than twofold increase in fetal tcd. smulian et al., stated that the perspective from a biological point of view confirms that cerebellar size is relatively unaffected by fetal growth disturbances. this is at variance with several other biometric parameters, especially abdominal circumference, which may be drastically altered by extremes of fetal growth.19 chavez et al.20, observed that although there was a positive correlation between gestational age and fetal tcd throughout the assessed period (1340 week of gestation), a number of studies have revealed that as the pregnancy approaches full term, there is a slight fluctuation in the growth curve of the fetal cerebellum, indicating multiple conditions that would lead to difficulties in measuring the tcd after the 36th week of gestation. malik et al., stated that the fluctuation may be explained that when the fetal head goes into the pelvis, a relative reduction of the amniotic fluid around the cephalic pole occurs; a very close contact between the mother’s uterine musculature and cranial vault; a low penetration of the ultrasound beam into the posterior fossa of the fetus and the occipito-posterior position of the head of the fetus at the end of the gestation.4 chavez et al, prospectively demonstrated that their institution-specific tcd nomogram was both reliable and accurate in predicting gestational age, even at extremes of fetal growth. 2 whereas the majority of data suggests that the tcd is extremely valuable when the gestational age is unknown or iugr is suspected. chavez et al , also concluded that additional small improvements in accurate gestational dating can be achieved by incorporating the results of tcd with some combination of other fetal biometric parameters, journal of rawalpindi medical college (jrmc); 2017;21(1): 60-63 63 including head circumference, biparietal diameter, and femur length, and recommended that tcd be used as an important sonographic biometric parameter in singleton iugr and large fetuses for accurate prediction of ga.2in a recent study conducted on 228 pakistani women at 36 weeks of gestation, the accuracy of tcd in corresponding to gestational age by lmp was higher than that of bpd (91.7% vs. 77.2%).21tcd can be used as a tool to assist in the assessment of gestational age in third trimester.6 conclusion strong positive correlation of mean transcerebellar diameter and mean gestational age is observed in third trimester of pregnancy references 1. ultrasonography in pregnancy. acog practice bulletin no. 98. american college of obstetricians and gynecologists. obstet gynecol. 2008; 112:1419-44. 2. chavez mr, ananth cv, smulian jc, vintzileos am. fetal transcerebellar diameter measured for prediction of gestational age at the extremes of fetal growth. j ultrasound med. 2007;26:1167-71. 3. araujo ej, pires cr, nardozza lm. correlation of the fetal cerebellar volume with other fetal growth indices by three dimensional ultrasound. j matern fetal neonat med. 2007;20:581-87. 4. malik g, waqar f, abdul ghaffarzaidi h. determination of gestational age by transverse cerebellar diameter in third trimester of pregnancy. j coll physicians pak. 2006;16(4):249-52. 5. naseem f, fatima n, yasmeen s, saleem s. comparison between transcerebellar diameter with biparietal diameter of ultrasound for gestational age measurement in third trimester of pregnancy. j coll physicians surg pak. 2013 may;23(5):322-25. 6. orji mo, adeyekun aa. ultrasound estimation of foetal gestational age by transcerebellar diameter in healthy pregnant nigerian women. west afr j med. 2014 janmar;33(1):61-67. 7. gupta ad, banerjee a, rammurthy n, revati p, jose j. gestational age estimation using transcerebellar diameter with grading of fetal cerebellar growth. njca. 2012; 1(3): 115-120. 8. pinar h, burke sh, huang cw, singer db, sung cj. reference values for transverse cerebellar diameter throughout gestation. pediatr. dev. pathol. 2002;5(5):48994. 9. goldstein i, tamir a, zammer ez, itckovitzeldor j. growth of fetal orbit and lens in normal pregnancies. ultrasound obstetrics and gynecology. 1998;12(3):87-91. 10. campbell s, warsof sl, little d, cooper dj. routine ultrasound screening for the prediction of gestational age. obstet gynecol 1985;65:613–20. 11. baerwald ar, adams gp, pierson ra. a new model for ovarian follicular development during the human menstrual cycle. fertil steril 2003;80:116–22. 12. hill lm, guzick d, fries j, hixson j, rivello d. the transverse cerebellar diameter in estimating gestational age in the large for gestational age fetus. obstet gynecol 1990;75:981–85. 13. mongelli m, benzie r. ultrasound diagnosis of fetal macrosomia: a comparison of weight prediction models using computer simulation. ultrasound obstet. gynecol. 2005;26(5):500-503. 14. hoffman cs. messer lc, mendola p, savitz da, herring ah, hartmann ke. comparison of gestational age at birth based on last menstrual period and ultrasound during the first trimester. paediatr. perinat. epidemiol. 22008;22 (6):58796. 15. shehzad k, ali m, zaid s. fetal biometry. pak. j. med. sci. 2006;22: 503-508. 16. hill lm, guzick d, rivello d, hixson j, peterson c. the transverse cerebellar diameter cannot be used to assess gestational age in the small for gestational age fetus. obstet. gynecol. 1990;75:329-33. 17. lee w, barton s, comstock ch, bajorek s, batton d, kirk js. transverse cerebellar diameter: a useful predictor of gestational age for fetuses with asymmetric growt retardation. am. j. obstet. gynecol. 1991;165:1044-50. 18. vinkesteijn asm, mulder pgh, wladimiro vjw. fetal transverse cerebellar diameter measurements in normal and reduced fetal growth. ultrasound obstet. gynecol. 2000;15:47-51. 19. smulian jc, ananth cv, vintzileos am, guzman er. revisiting sonographic abdominal circumference measurements: a comparison of outer centiles with established nomograms. ultrasound obstet. gynecol. 2001;18:237-43. 20. chavez mr, ananth cv, smulian jc, lashley s, kontopoulos ev. transcerebellar diameter nomogram in singleton with special emphasis in the third trimester: a comparison with previously published nomograms. am. j. obstet. gynecol. 2003;189: 1021-25. 21. naseem f, fatima n, yasmeen s, saleem s. comparison between transcerebellar diameter with biparietal diameter of ultrasound for gestational age measurement in third trimester of pregnancy. j. coll. physicians surg. pak. 2013;23(5):322-25. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 201-204 201 original article status of hepatitis be antigen in chronic hepatitis b patients from various regions of pakistan agha babar hussain 1, muhammad ali rathore 2, inaam qadir javed hashmi 3, eijaz ghani 4, muhammad idrees khan5 1. department of pathology,rawalpindi institute of cardiology, rawalpindi;2. armed forces institute of transfusion , rawalpindi; 3. department of pathology, mohi-ud-din islamic medical college (mimc), mirpur azad jammu & kashmir;4. department of virology , armed forces institute of pathology, rawalpindi;5 division of molecular virology, centre of excellence in molecular biology, university of the punjab abstract background: to determine the distribution of hbeag in chronic hepatitis b patients from different regions of pakistan. methods: in this study a total of 677 individuals infected with hepatitis b for a minimum period of 6 months, were included in the study. the information like age, gender along with area of residence, were recorded in a proforma filled for each study subject. a 3 ml blood sample was taken from each person. hbsag,hbeag and anti hbe testing was carried out by elisa. results: out of 677 study subjects, 517 (76.4%) were males and 160 (23.6%) females with an overall mean age of 35.42 +12.4 years. hbeag was positive in 66 (9.7%) . all hbeag positive cases were negative for anti hbe. hbeag positivity was 9.4% in punjab, 14.8% in kpk, 4.89 % in sindh, 8.3% in aj & k and 13.3% in gilgit baltistan. conclusion: there was a male predominance among hepatitis b virus infected patients .maximum cases were between 20 to 50 years of age. hbeag positive cases were significantly less as compared to hbeag negative cases. key words: hbsag, hbeag, anti hbe, introduction hepatitis b virus infection is one of the major health problems in pakistan. lot of advances have been seen in the recent past regarding management of this infection. hepatitis b e antigen (hbeag) status of hepatitis b infected person has a great role in management of hepatitis b, in the light of guidelines by american association for study of liver diseases (aasld). study of hbeag status in a population can give us an idea about magnitude of the aggressive disease in that particular area, which would be beneficial for all concerned and decision makers for allocation of resources for the management of the patients, as well as for implementing the control/ preventive measures. it is a global health problem and an estimated 257 million people are living with hbv infection (defined as hepatitis b surface antigen positive) worldwide.1 hbv is found in almost every region of the globe and is highly endemic in asia, subsaharan africa, south america and the middle east.2 world health organization (who) has divided the world into areas of high (more than 8%), high intermediate (5-7%), low intermediate (2-4%) and low (less than 2%) endemic areas for hbv, based on hepatitis b surface antigen (hbsag) prevalence rates.3 being a chronic disease the risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma (hcc) is increased in carriers of hbv as compared to general public because 15% to 40% of hbv infected may develop serious sequelae during their lifetime.4 life-long surveillance of hbv infected individuals is therefore, required through testing them repeatedly for hbv dna and parameters like hepatitis be antigen (hbeag), antibodies to hepatitis be antigen (anti hbe) and alanine aminotransferase (alt). hbv infected persons are divided into various categories like active carriers, inactive carriers, and resolved hbv infection, based upon their hbeag, anti hbe serostatus, hbv dna load and alt levels.5 presence of hbeag in chronic hbv infection is generally associated with active viral replication and infectivity, whereas anti hbe shows loss of infectivity and viral replication. few exceptions are those patients with core/ pre-core mutations, where there is viral activity in the absence of detectable hbeag.6 hbeag is a surrogate marker for hbv and is used as an alternate to hbv dna in decision making for treatment, in patients with hbeag positive serostatus along with alt level more than twice of the upper limit of the normal.7 in majority of cases the loss of hbeag is associated with a decrease in levels of hbv dna, journal of rawalpindi medical college (jrmc); 2017;21(3): 201-204 202 normalization of alt and significant clinical improvement despite the presence of hbsag.8 the prevalence as well as severity of the disease is not uniform in all segments of society because of certain high risk groups, high prevalence of hdv co-infection in certain areas as well as difference of hbv genotypes.9 according to a nationwide survey compiled by pakistan medical research council, the prevalence of hbsag is 2.5% in pakistan. therefore, in a country of 180 million people, there are approximately 4.25 million hepatitis b carriers.10 as hbeag positivity indicates active disease, generally requiring treatment, testing for hbeag in different areas can give us an idea about severity of the disease in that population. this information can help us in allocation of resources for prevention/ control measures. patients and methods ethical approval of research ethics committee of armed forces institute of pathology (afip) rawalpindi was obtained. total 677 hepatitis b carriers (hbsag positive for a minimum period of 6 months), were included . those, with hcv or hiv coinfection, on immunosuppressive drugs, patients on antiviral therapy for hbv and those not willing for participation in study, were excluded. hbsag,hbeag and anti hbe testing was carried out with enzyme linked immunosorbent assay (elisa). patients’ serum was incubated with horseradish peroxidase linked antibody for formation of antigen antibody complexes, the presence of which is detected by adding a substrate. the resulting change in colour was read calorimetrically with help of an elisa micro plate reader. positive and negative controls were run in each batch. results hbsag tested positive in all 677 cases. majority (76.4%) were males. mean age of the patients was 35.42+12.4 years. hbeag was positive in 66 (9.7%) out of 677 tested (table 1) .the maximum study subjects 446 (65.9%) were from punjab (table 2). all hbeag positive cases were negative for anti hbe. table 2: distribution of study population area no(%) punjab 446(65.9) khyber pakhtunkhwa 108(16) sindh 62 (9.2) azad jammu & kashmir 36(5.3) baluchistan 10(1.5) gilgit baltistan 15(2.2) table 1: hbeag percentage positivity in different regions of pakistan patients’ number hbeag postive percentage positivity punjab 446 42 9.4% khyber pakhtoonkhwa 108 16 14.8% sindh 62 3 4.89% azad jammu and kashmir 36 1 3.8% balochistan 15 2 13.3% gilgit baltistan 10 2 20% total 667 66 9.89% discussion pakistan generally is a male dominated society where men have a central role in the families, being mostly responsible for earning bread and butter for their home-mates. in this study, there was a male preponderance which might be due to the better access and opportunities for males to the testing and treatment facilities for hbv infected cases. this male predominance was also observed in different studies carried out by ghani et al, khokhar et al and khan et al.11-13 the age of hbv infected persons in this study ranged between 1 to 80 years, with a mean of 35.42 years (sd+12.3). this was similar to a study conducted in hong kong by yuen et al, in which the mean age of presentation was 38 years with an age range of 1 to 85 years. 14 in both genders, the maximum cases were between 21 and 50 years. similar result were seen in studies conducted by khan et al and castolo et al. 13,15 this age distribution indicates ongoing acquisition of hbv peri-natally and during childhood and highlights the importance of complete and comprehensive childhood immunization coverage against hbv infection. the overall result indicates that maximum number of patients have this problem during the prime of their lives when they are supposed to be the most useful members of their families as well as the society. the maximum study subjects (446) were from province of punjab followed by 108 from kpk 62 from sindh, 36 from ajk, 15 from gb and 10 from baluchistan. this region wise distribution of the cases in our study was logical keeping in view geography of the country, the population density in various regions and location of the testing laboratory. this study was carried out in northern punjab, so the maximum cases were from this province. the next highest number was from the province of kpk, the boundaries of which are journal of rawalpindi medical college (jrmc); 2017;21(3): 201-204 203 common with the northern punjab. the sindh province is situated in the southern part of the country and it was difficult for the study subjects to report due the distances involved, as was the case in balochistan, ajk and gb. a male preponderance was seen in all our regions under study including punjab, sindh, kpk, baluchistan, ajk and gb., a similar male predominance was observed in various studies conducted in different areas of punjab including manzoor et al in 1997, alam et al in 2007, moosa et al in 2009 and khan et al in 2011, in which males were more as compared to females. 16-18 this was also observed in patients from kpk as well and mentioned in a study conducted by farooqi et al in peshawar in 2007. out of 62 persons from sindh, 57 (91.9%) were males and 5 (8.1%) were females. 19 this trend was also noticed in a study conducted by aziz et al in sindh in 201020. the total number of cases from ajk was 36, out of which 26 (72.2%) were males and 10 (27.8%) females. a similar male to female ratio was also seen in a study conducted by naz et al in muzaffarabad in 2002.21 the mean age of patients from punjab was 35.46+12.9 years,, 33.06+14.2 years for patients from kpk, 40 + 9.5 years for ajk patients and 31+6.2 years for patients from sindh, the lowest mean age for sindhi patients can be understood due to the fact that the disease generally reported from sind areas is relatively aggressive. the higher mean age of the patient from ajk needs to be further explored because of the limited number of patients from ajk in this study. the overall hbeag positivity in our study was 9.7 % which is higher than 7.5% reported in neighboring india, and less than a study conducted in southern china, where the hbeag positivity was 18.5%. 22,23 this difference was probably due to higher prevalence of hbv in southern china. in another study conducted in italy, an overall hbeag positivity of 11% was noted which was close to our percentage. 24 in this italian study the immigrant group had a much higher hbeag positivity of 18 % as majority of them were from developing countries. in bangladesh, the prevalence of hbeag was found to be 19.2% which was higher as compared to our study. 25 moreover, in this study it was established that the hbeag positivity decreased with increasing age showing that sero-conversion occurs with advancing age. the percentage of positivity for hbeag in punjab (9.4%) was almost same as reported for all cases (n=677). it was however, higher (14.9%) in cases from kpk. the less positivity of hbeag in sindh (4.89%) might be incidental as the number of patients was low, otherwise areas of sindh and adjoining southern punjab are well known for the aggressive nature of the disease.there was a lower percentage (3.8%) in cases from ajk but the total number of the patients was only 26 which is too low a number to give any statistically significant results. the number of patients was also less in baluchistan as well as for the patients from gb. these studies show that hbeag positivity is different in different geographical areas. there was no previous study showing hbeag distribution in different areas of pakistan. this study can serve as base-line for future studies of the problem from different angles. conclusion 1. a male predominance was noted in this study. the maximum numbers of chronic hepatitis b carriers were found between 20 to 50 years. 2. hbeag positive cases were less as compared to what has been reported earlier. references 1. world health organization. hepatitis b. world health organization fact sheet 204 . 2. zampino r, boemio a, sagnelli c, alessio l, adinolfi le, sagnelli e. hepatitis b virus burden in developing countries. world j gastroenterol. 2015;21(42):11941-53. 3. schweitzer a, horn j, mikolajczyk r. estimations of worldwide prevalence of chronic hepatitis b virus infection. the lancet. 2015; 386(10003):1546–55. 4. kim ga, lee hc, kim mj, ha y. incidence of hepatocellular carcinoma after hbsag sero-clearance in chronic hepatitis b patients. j hepatol.2015;62:1092-99. 5. terrault na, bzowej nh, chang km, hwang jp, jonas mm, murad mh. aasld guideline for treatment of chronic hepatitis b. hepatology.2016;63:261–83. 6. chen eq, feng s, wang ml, liang l.serum hepatitis b corerelated antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular dna in chronic hepatitis b. scientific reports. 2017;7:173-76. 7. asian-pacific association for the study of the liver. asianpacific clinical practice guidelines on the management of hepatitis b: a 2015 update.hepatol int. 2016;10:1–98. 8. liaw yf, lau gk, kao jh,gane e. hepatitis b e antigen seroconversion: a critical event in chronic hepatitis b virus infection. dig dis sci. 2010;55, 2727–34. 9. butt fa, amin i, idrees m, iqbal m. hepatitis delta virus genotype-1 alone cocirculates with hepatitis b virus genotypes a and d in pakistan. eur j gastroenterol hepatol. 2014;26(3):319-24. 10. pakistan medical research council. the first prevalence report on hepatitis b and c in pakistan. 11. ghani e and karamat ka, categorization of hepatitis b carriers in pakistan.j coll physicians surg pak. 2000;10(1):27-28. 12. khokhar n and gill ml. serological profile of incidentally detected symptomatic hbsag positive subjects (idahs).j coll physicians surg pak. 2004;14(4):208-10. 13. khan f, shams s, qureshi id, m, khan h. hepatitis b virus infection among different sex and age groups in pakistani https://www.ncbi.nlm.nih.gov/pubmed/?term=zampino%20r%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=boemio%20a%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=sagnelli%20c%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=alessio%20l%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=adinolfi%20le%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=adinolfi%20le%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=sagnelli%20e%5bauthor%5d&cauthor=true&cauthor_uid=26576083 https://www.ncbi.nlm.nih.gov/pubmed/26576083 https://www.ncbi.nlm.nih.gov/pubmed/?term=butt%20fa%5bauthor%5d&cauthor=true&cauthor_uid=24129252 https://www.ncbi.nlm.nih.gov/pubmed/?term=amin%20i%5bauthor%5d&cauthor=true&cauthor_uid=24129252 https://www.ncbi.nlm.nih.gov/pubmed/?term=idrees%20m%5bauthor%5d&cauthor=true&cauthor_uid=24129252 https://www.ncbi.nlm.nih.gov/pubmed/?term=iqbal%20m%5bauthor%5d&cauthor=true&cauthor_uid=24129252 https://www.ncbi.nlm.nih.gov/pubmed/24129252 https://www.ncbi.nlm.nih.gov/pubmed/24129252 http://www.pakmedinet.com/jcpsp http://www.pakmedinet.com/jcpsp http://pakmedinet.com/jcpsp http://pakmedinet.com/jcpsp http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&term=%20khan%20f%5bauth%5d http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&term=%20shams%20s%5bauth%5d http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&term=%20qureshi%20id%5bauth%5d http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&term=%20khan%20h%5bauth%5d journal of rawalpindi medical college (jrmc); 2017;21(3): 201-204 204 punjab. virol j. 2011;8:225-28. 14. m-f yuen, h-j yuan, c-k hui, d k-h wong.a large population study of spontaneous hbeag seroconversion and acute exacerbation of chronic hepatitis b infection: implications for antiviral therapy. gut.2003;52:416–19. 15. castolo mc, ndez-ruiz lh, ibarra-robles ie, rate ihfn. prevalence of hepatitis b virus infection and related risk factors. am j trop med hyg. 2001;65(6):759-63. 16. manzoor sa, malik ia, wuz t: hepatitis b related chronic liver disease in rawalpindi islamabad. j coll physicians surg pak. 1997;7:43-46. 17. alam s, ahmed nd, mustafa g, alam k. characteristics of treatment naïve chronic hepatitis b. younger populations are more affected; hbeag negatives are more advanced. the saudi journal of gastroenterology. 2008;14(1): 15-19. 18. moosa fa, shaikh ba,choudhry ms, khan fw. frequency of hepatitis b and c in pre-operative elective surgery. jlumhs. 2009;8(02):112-15 19. farooqi ji, farooqi rj, khan n, mussarat. frequency of hepatitis b and c in selected groups of population in nwfp.j postgrad med inst. 2007;21(3):165-68. 20. aziz s, khanani r, noorulain w, rajper j. frequency of hepatitis b and c in rural and periurban sindh.jpma. 2010;60:853-56 21. naz s, ahmad m, asghar h. prevalence of hepatitis ‘b’ among combined military hospital (cmh) muzaffarabad. international journal of agriculture & biology. 2002;4(2):227-30. 22. acton qa. hepatitis b virus: new insights for the healthcare professional: 2013 edition. page 265. 23. chen p, yu c, wu w, wang j. serolological profile among hbsag-positive infections in southeast china: a communitybased study.hepat mon 2013;13(1):7604 06. 24. stroffolini t, almasio pl, sagnelli e. evolving clinical landscape of chronic hepatitis b: a multicenter italian study.j med virol. 2009;81(12):1999-2006. 25. chowdhury a, santra a, chakravorty r. community-based epidemiology of hepatitis b virus infection in west bengal, india: prevalence of hepatitis b e antigen-negative infection and associated viral variants.j gastroenterol hepatol. 2005;20(11):1712-20. http://www.pakmedinet.com/author/javed+iqbal+farooqi http://www.pakmedinet.com/author/rukhsana+javed+farooqi http://www.pakmedinet.com/author/nowshad+khan http://www.pakmedinet.com/author/mussarat http://www.pakmedinet.com/jpmi http://www.pakmedinet.com/jpmi http://www.ncbi.nlm.nih.gov/pubmed?term=chen%20p%5bauthor%5d&cauthor=true&cauthor_uid=23483608 http://www.ncbi.nlm.nih.gov/pubmed?term=yu%20c%5bauthor%5d&cauthor=true&cauthor_uid=23483608 http://www.ncbi.nlm.nih.gov/pubmed?term=wu%20w%5bauthor%5d&cauthor=true&cauthor_uid=23483608 http://www.ncbi.nlm.nih.gov/pubmed?term=wang%20j%5bauthor%5d&cauthor=true&cauthor_uid=23483608 http://www.ncbi.nlm.nih.gov/pubmed/23483608 http://www.ncbi.nlm.nih.gov/pubmed?term=stroffolini%20t%5bauthor%5d&cauthor=true&cauthor_uid=19856477 http://www.ncbi.nlm.nih.gov/pubmed?term=almasio%20pl%5bauthor%5d&cauthor=true&cauthor_uid=19856477 http://www.ncbi.nlm.nih.gov/pubmed?term=sagnelli%20e%5bauthor%5d&cauthor=true&cauthor_uid=19856477 http://www.ncbi.nlm.nih.gov/pubmed/19856477 http://www.ncbi.nlm.nih.gov/pubmed/19856477 https://www.ncbi.nlm.nih.gov/pubmed/16246191 https://www.ncbi.nlm.nih.gov/pubmed/16246191 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 37-41 37 original article soft tissue tumours with epithelioid morphoogy muhammad zain mehdi, sajid mushtaq, noreen akhtar, usman hassan, asif loya, mudassar h ussain and muhammad azam department of histopathology, shaukat khanum hospital and research centre abstract background: to study the morphological findings of soft tissue sarcomas with epithelioid morphology and their distribution with respect to the age, gender and location. methods: in this descriptive study, soft tissue sarcomas (n=100) with epithelioid morphology were evaluated by two histopathologists cinical and morphological features like age, gender, site and type of tumor were quantified and documented. epithelioid morphology was defined as cells with polygonal to polyhedral shape, abundant cytoplasm and round nuclei .all cases were diagnosed with help of a panel of immunohistochemical (ihc) stains, i.e., ck ,ema, desmin, s100, cd31, cd34, ini-1, cd99 and tfe3 in conjunction with clinical history and morphology. lca and hmb45 ihc stains were also utilized to rule out the possibility of a lymphoproliferative disorder and melanoma. results: mean age of presentation was 36 years, with patients ranging in age from 1 to 80 years. there were n=37 females as compared to n=44 males. most common site was thigh (n=21) followed by arm (n=13), head and neck region (n=5) and inguinal region (n=4).epithelioid sarcoma (n=29) was the most common soft tissue sarcoma in our study followed by sclerosing epithelioid fibrosarcoma (n=10), alveolar soft part sarcoma (n=9), biphasic synovial sarcoma and epithelioid angiosarcoma (n=8), epithelioid malignant peripheral nerve sheath tumours (mpnst) (n=7), epithelioid hemangioendothelioma, undifferentiated epithelioid sarcoma, epithelioid angiomyolipoma and epithelioid leiomyosarcoma(n=6). rare tumors included in the study were 2 cases of epithelioid rhabdomyosarcoma and one case each of pseudomyogenic hemangioendothelioma, malignant rhabdoid tumor and dedifferentiated liposarcoma with rhabdoid features. conclusion: soft tissue sarcomas with epithelioid morphology require careful morphological and immunohistochemical evaluation to differentiate them from carcinomas, lymphomas and melanoma because of the differences in their clinical management and prognosis. introduction soft tissue sarcomas constitute 1% of all malignant neoplasms. epithelioid morphology, a defining feature of most carcinomas and melanomas characterizes many of these soft tissue tumors, and therefore knowledge of these tumors is imperative to avoid misdiagnosis. soft tissue sarcomas represent a heterogeneous group of rare malignant neoplasms. these tumors account for almost 1% of all adult solid malignancies and about 20% of pediatric tumors.1sarcomas can be divided into three broad categories based on their light microscopic appearance on h&e. these categories include the spindle cell sarcomas, round cell sarcomas and sarcomas with epithelioid morphology.epithelioid morphology can be defined as polygonal to polyhederal cells with abundant cytoplasm, round to oval nuclei and distinct nucleoli. epithelioid morphology literally meaning epithelial like is characteristic of carcinomas, however it can be seen in almost all tumor lineages especially melanomas. soft tissue sarcomas with epithelioid morphology therefore present a unique challenge to the pathologist who has to differentiate it from carcinomas, melanomas and other soft tissue sarcomas of similar morphology.2,3 sarcomas known to display epitheliod morphology include epithelioid sarcoma,epithelioid malignant peripheral nerve sheath tumor, epithelioid angiosarcoma, sclerosing epithelioid fibrosarcoma, pseudomyogenic hemangioendothelioma, malignant extra renal rhabdoid tumor , synovial sarcoma, epithelioid rhabdomyosarcoma, epithelioid leiomyosarcoma and myxofibrosarcoma.3,4,5 a thorough knowledge of these entities and use of immunohistochemical stains enables us to make definite diagnosis in majority of these cases. patients and methods histology slides of the 100 cases of soft tissue sarcomas with epithelioid morphology were evaluated by two histopathologists with special interest in soft tissue pathology. epithelioid morphology was provisionally defined as cells with polygonal to polyhedral shape, abundant cytoplasm and round nuclei. soft tissue journal of rawalpindi medical college (jrmc); 2017;21(1): 37-41 38 sarcomas with rhabdoid features were also included in the study. the cases were selected solely on the basis of morphology. clinical and morphological features like age, gender and site were assessed and documented. cases with poor fixation, history of radiation therapy or carcinosarcomas were excluded from this study. all of the reported cases were diagnosed with help of a panel of immunohistochemical (ihc) stains; ae1/ae3, ema, desmin, cd31, cd34, ini-1, cd99 and tfe3 in conjunction with clinical history and morphology. lca and hmb45 ihc stains were also utilized to rule out the possibility of a lymphoproliferative disorder and melanoma. results mean age of presentation was 35.80±15.57 years, with patients ranging in age from 1 to 80 years. there were n=51 females as compared to n=49 males in our study. most common site was lower limbs (n=37) followed by upper limbs (n=25), head and neck region (n=9) and chest and abdomen (n=15). epithelioid sarcoma (n=29) was the most common soft tissue sarcoma (table 1).rare tumors included in the study were 2 cases of epithelioid rhabdomyosarcoma and one case each of pseudomyogenic hemangioendothelioma, malignant rhabdoid tumor and dedifferentiated liposarcoma with rhabdoid features. the panel varied from case to case depending on the morphology and the closest histological and clinical differentials. most common ihc stains positive in epithelioid sarcoma were cytokeratin ae1/ae3, ema and cd34. ini-1 was recently acquired by our institute and it showed loss of expression in cases it was applied. synovial sarcoma was positive for cytokeratin, ema , cd99(100%) and tle 1(100%). fish studies were not performed in these cases. epithelioid hemangioendothelioma and epithelioid angiosarcoma were in most cases positive for cd31 and cd34. erg, fli-1 and factor-viii were also used in a few cases to support the diagnosis. epithelioid leiomyosarcoma was positive for sma, caldesmon and desmin. both the cases of epithelioid rhabdomyosarcoma were positive for myogenin and desmin. epithelioid mpnst was positive in all cases for s100 and negative for both hmb45 and melan a. new neural markers sox-10 and pgp 9.5 were applied 0n one case each and showed positive staining. hmb-45 was consistently positive in all cases of epithelioid angiomyolipoma (table 2;figure 1-3). undifferentiated epithelioid sarcoma was a diagnosis of exclusion in cases which did not show any specific lineage. table 1 summary of the important clinical features according to individual tumor type type of tumour total no. of cases mean age ±s.d (in years) male to female ratio most common sites epithelioid sarcoma 29 33.24± 13.19 2.63:1 upper and lower limbs sclerosing epithelioid fibrosarcoma 10 40.59± 19.07 2:3 chest and abdomen, upper limb, lower limb and back alveolar soft part sarcoma 9 32.56± 5.46 1:2 lower limb biphasic synovial sarcoma 8 31.38± 14.69 1:1 upper and lower limbs epithelioid angiosarcoma 8 49.00± 17.79 1:3 chest and abdomen, head and neck epithelioid mpnst 7 37.29± 12.50 2:5 upper and lower limb epithelioid hemangioendothelioma 6 34.00± 10.01 2:1 chest and abdomen, upper and lower limb epithelioid angiomyolipoma 6 31.50± 17.80 2:1 kidney, liver epithelioid leiomyosarcoma 6 43.33± 17.01 0:6 uterus, lower limb undifferent iated epithelioid sarcoma 6 43.50± 20.20 1:2 upper and lower limb journal of rawalpindi medical college (jrmc); 2017;21(1): 37-41 39 table 2: ihc markers used in the major subtypes tumor subtype ck ema cd34 cd31 s100 hmb45 tfe3 epithelioid sarcoma +(100%) +(100%) +(80%) negative negative negative na sclerosing epithelioid fibrosarcoma +(50%) negative negative na +(20%) negative na alveolar soft part sarcoma negative negative na na negative negative + (100%) biphasic synovial sarcoma +(67%) +(100%) negative na negative na na epithelioid angiosarcoma negative negative +(57%) +(43%) negative negative na epithelioid mpnst negative na negative negative +(100%) negative na epithelioid hemangioendothelioima negative na +(100%) +(100%) negative na na epithelioid angiomyolipoma negative na na na na +(83%) na epithelioid leiomyosarcoma +(40%) negative na na negative na na figure 1: (a) low power h&e of epithelioid sarcoma. the tumor shows a well-circumscribed growth pattern on low magnification. infiltrative growth pattern often in the form of single cells and small tumor cell nests. central necrosis, a common feature of epithelioid sarcoma is also seen. ( b) high power h&e showing polyhedral looking tumor cells.(c) the tumor shows positive expression of ck (d) ck 5/6 is negative in tumor cells with positive internal control( e) loss of ini-1 expression. figure 2:(a,b) h&e epitheliodangiosarcoma.microscopically areas of well-formed anastomosing vessels to solid sheets of epithelioid cells with abundant eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. the vascular spaces are lined by markedly atypical endothelial cells. extensive haemorrhage and necrosis are frequently present. (c) cytokeratin expression in epithelioidangiosarcoma. (d) cd34 staining in tumors cells. figure 3: (a) h &e showing epithelioid malignant peripheral nerve sheath tumor. the neoplastic cells typically grow in a distinctly nested pattern, at least in part, with other areas usually showing a cord-like pattern of growth. (b) diffuse s100 staining in mpnst (c) h&e of a rare case of pseudomyogenichemangioendothelioma. the tumor shows infiltrative margins with loose fascicular and sheetlike architecture. plump spindle cells with vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. there are focal prominent stromal neutrophils. ( d) cytokeratin staining in a case of pseudomyogenichemangioendothelioma (e) h&e showing epithelioid hemangioendothelioma. the tumor is composed of endothelial cells forming small sized vessels. the tumor cells form lumens of various sizes which occasionally contain red blood cells. sometimes the intracytoplasmic vacuoles are so large that they compress the nucleus and give signet ring cell morphology. there is a sclerotic background. (f): erg immunohistochemical stain showing positive expression in tumor cells. discussion soft tissue sarcomas comprise a heterogenous group of tumors with variable behavior, prognosis and colour page journal of rawalpindi medical college (jrmc); 2017;21(1): 37-41 40 treatment depending on the type, grade and stage. therefore, correct diagnosis of these tumors is of utmost importance. clinical data including exact site, age of the patient and radiological findings are essential for diagnosis. first step in diagnosis of a sarcoma is determination of the pattern and cytological features to make a differential which can be later confirmed using immunohistochemistry and cytogenetics. most sarcomas display either spindle cell or round cell morphology and only a few variants display epithelioid features. epithelioid morphology is more commonly associated with carcinoma and melanoma. presence of epithelioid features can be a diagnostic challenge to the pathologist who has to differentiate them not only from other sarcomas, but also carcinomas (notably sarcomatoid carcinomas) and melanomas. immunohistochemistry, as an adjunct can help in making the definite diagnosis. 6-10 most of sarcomas in our study were of adult age group. a single case of malignant rhabdoid tumor was included in the study. the patient was 2 months old at presentation presented with mass in sub hepatic region. the tumor cells were a mixture of rhabdoid and spindle shaped cells displaying loss of expression of ini-1 and positive staining for ck. epithelioid sarcoma was the most common sarcoma in our study.mean age and site of the patients were comparable to other studies. the tumors consistently expressed epithelial markers (pan ck, ema) and cd34. loss of ini-1 expression (smarcb-1) is now considered the standard for diagnosis and is applied in any tumor where differential diagnosis includes epithelioid sarcoma. sclerosing epithelioid fibrosarcoma(sef) was diagnosed mainly on its histological appearance of epithelioid round to oval cells arranged in cords and acini in a sclerotic background. 14,15 hybrid features i.e sarcoma showing features of both sclerosing epithelioid fibrosarcoma and low grade fibromyxoid sarcoma was identified in one case.most cases showed only focal positivity for keratins and muscle markers. muc-4 is considered the most specific and sensitive marker for sef.16 the new marker was positive in two out of 4 cases it was applied on. tfe3 was by far the best ihc stain for alveolar soft part sarcoma. pas positivity served a useful adjunct with the morphology. most cases of biphasic synovial sarcoma were positive for epithelial markers. tle-1 is considered an extremely sensitive marker of synovial sarcoma, and is now included in our panel. translocation for x:18 was not performed in any of these cases which is now considered gold standard for diagnosis. however, all new cases are being confirmed by fish. 17 epithelioid angiomyolipoma is a potentially aggressive lesion and part of spectrum of poorly understood pecoma group of tumors. most tumors in our study were renal in origin except one which was identified in liver. the category of undifferentiated epithelioid sarcoma was reserved for neoplasms which displayed epithelioid morphology but did not fall into any known category. one rare case of recently identified entity pseudomyogenic hemangioendothelioma was also diagnosed. the 24 year male presented with lytic lesion of right proximal humerus and microscopic examination showed bland looking epithelioid to spindle shaped cells with moderate eosinophilic cytoplasm. the neoplasm was positive for sma, fli-1, ck and cd31. pseudomyogenic hemangiomas present as subcutaneous nodules but are known to invade muscle and bone. the main differential is epithelioid sarcoma. however, negativity for cd34 and intact ini1 expression differentiates it from the latter.18 conclusions 1.the rare occurence of these tumors, their deceptive morphology and inconsistent expression of most immunostains makes diagnosis of these tumors a challenge for the pathologist. 2.a multi-disciplinary approach along with immunohistochemistry and cytogenetics is the best approach to diagnose these tumors. in case of doubt referrel to a specialist soft tissue pathologist should also be considered. references 1. lahat g, lazar a, lev d: sarcoma epidemiology and etiology: potential environmental and genetic factors. surg clin north am 2008; 88(3):451–81. 2. hornick jl, brooks sj. soft tissues. in: mills se. sternberg’s diagnostic surgical pathology. 6th ed. new york. wolters kluver, 2015. 3. wibmer c1, leithner a, zielonke n, sperl m, windhager r. increasing incidence rates of soft tissue sarcomas? a population-based epidemiologic study and literature review.ann oncol,2010;21(5):1106-11. 4. yang j, du x, wang g, sun y , chen k, zhu x. mesenchymal to epithelial transition in sarcomas. european journal of cancer ,2014; 50, 593– 601 5. singer s, m. r. . soft tissue sarcoma. in h. r. de vita, principles & practice of oncology, 9th edition:1534-1621. new york , 2011: wilkins and williams. 6. miettinen m, fanburg-smith jc, virolainen m.epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. hum pathol ,1999;30: 934–42. 7. hornick jl, dal cin p, fletcher cd. loss of ini1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. am j surg pathol 2009;33:542–550. http://www.ncbi.nlm.nih.gov/pubmed/?term=wibmer%20c%5bauthor%5d&cauthor=true&cauthor_uid=19858086 http://www.ncbi.nlm.nih.gov/pubmed/?term=leithner%20a%5bauthor%5d&cauthor=true&cauthor_uid=19858086 http://www.ncbi.nlm.nih.gov/pubmed/?term=zielonke%20n%5bauthor%5d&cauthor=true&cauthor_uid=19858086 http://www.ncbi.nlm.nih.gov/pubmed/?term=sperl%20m%5bauthor%5d&cauthor=true&cauthor_uid=19858086 http://www.ncbi.nlm.nih.gov/pubmed/?term=windhager%20r%5bauthor%5d&cauthor=true&cauthor_uid=19858086 http://www.ncbi.nlm.nih.gov/pubmed/19858086 journal of rawalpindi medical college (jrmc); 2017;21(1): 37-41 41 8. lee ys, choi yj, kang cs, kang sj, kim bk. purely epitheliod nerve sheet tumour of the vulva. j korean med sci. 1997 ;12(1):78-81. 9. doyle la, wang wl, dal cin p. muc4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with fus gene rearrangement. am j surg pathol ,2012;36:1444–51. 10. foo wc, c. m. immunohistochemical staining for tle1 distinguishes from histological mimics. am j clin pathol , 2011;135:839-44. 11. thway k and fisher c.synovial sarcoma: defining features and diagnostic evolution. hyperlink ,2014 :18(6 ): 369– 80 12. zarrin-khameh n, kaye ks. alveolar soft part sarcoma. arch pathol lab med. 2007;131:488–91 13. mete o and kwast thvd. epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms. arch pathol lab med ,2011;.135: 655-70 14. hart j and mandavilli s. epithelioid angiosarcoma. a brief diagnostic review and differential diagnosis. arch pathol lab med ,2011; 135:268–72 15. sardaro a, bardoscia l, petruzzelli mf. epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. oncology reviews 2014; 8:259-62 16. doyle la, wang wl, dal cin p, lopez-terrada d. muc4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with fus gene rearrangement. am j surg pathol 2012; 36(10):1444 51. 17. kosemehmetoglu k, vrana2 ja,folpe al. . tle1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms. modern pathology ,2009;22: 872–78 18. hornick jl and fletcher cdm. pseudomyogenic hemangio-endothelioma: a distinctive,often multicentric tumor with indolent behavior. am j surg pathol ,2011; 35:190–201 http://www.ncbi.nlm.nih.gov/pubmed/?term=doyle%20la%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/?term=wang%20wl%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/?term=wang%20wl%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/?term=wang%20wl%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/?term=wang%20wl%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/?term=wang%20wl%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/?term=wang%20wl%5bauthor%5d&cauthor=true&cauthor_uid=22982887 http://www.ncbi.nlm.nih.gov/pubmed/22982887 512 journal of rawalpindi medical college (jrmc); 2021; 25(4): 512-515 original article comparison of analgesic and functional outcomes of intra-articular ketorolac versus triamcinolone acetone injection in patients of knee osteoarthritis soban sarwar gondal1, abeera zareen2, muhammad haroon anwar3, jawad zaheer4, muhammad salim5 1 consultant neurosurgeon, rawalpindi medical university, rawalpindi. 2 assistant professor, department of anesthesiology, rawalpindi medical university, rawalpindi. 3 medical officer, rawalpindi medical university, rawalpindi. 5 professor, department of anesthesiology, rawalpindi medical university, rawalpindi. 6 professor, department of anesthesiology, islamic international medical college, rawalpindi. author’s contribution 1 conception of study 3 experimentation/study conduction 3 analysis/interpretation/discussion 2 manuscript writing 4 critical review 4 facilitation and material analysis corresponding author dr. muhammad haroon anwar, medical officer, rawalpindi medical university, rawalpindi. email: haroonanwar22@gmail.com article processing received: 02/08/2021 accepted: 07/12/2021 cite this article: gondal, s.s., zareen, a., anwar, m.h., zaheer, j., salim, m. comparison of analgesic and functional outcomes of intra-articular ketorolac versus triamcinolone acetone injection in patients of knee osteoarthritis. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 512-515. doi: https://doi.org/10.37939/jrmc.v25i4.1750 conflict of interest: nil funding source: nil access online: abstract objective: to compare the analgesic and functional outcomes of intra-articular ketorolac with corticosteroids in patients of knee osteoarthritis (oa). materials and methods: in this randomized double-blind comparative study, we included patients of knee oa who were planned for intra-articular injections from january-2020 to december-2020 in the department of anesthesia and pain medicine at rawalpindi medical university. patients having symptomatic knee oa of kellgren-lawrence grades 2 or 3 and age 40-70 years were allocated to two groups using block randomization, each block contained 30 patients and received an injection of either triamcinolone (group t) or ketorolac (group k). vas score and western ontario and mcmaster universities osteoarthritis index (womac) score were noted at 1 week, 1 month, and at 3 months of injection. results: mean baseline womac score was 46.60±5.64 in group k and 47.0±5.27 in group t (p-value 0.74). mean womac score was reduced significantly at 1st week and 1 month and 3 months follow-up in both groups, with an insignificant statistical difference in group k and t (p-value 0.39, 0.18 & 0.15 respectively). the baseline vas score was 7.02±1.34 in group k versus 7.27±1.03 in group t (p-value 0.36). vas score was also reduced at 1 week, 1 month, and 3 months follow-up, however the mean vas at intervals was not statistically different between group k and t with a p-value of 0.13, 0.08, and 0.49 respectively. treatment was successful in 22 (55%) patients in group k versus 24 (60%) patients in group t (p-value 0.65). conclusion: intraarticular ketorolac has similar functional and analgesic outcomes as that of triamcinolone. keywords: knee osteoarthritis, ketorolac, triamcinolone. 513 journal of rawalpindi medical college (jrmc); 2021; 25(4): 512-515 introduction osteoarthritis (oa) is one of the progressing musculoskeletal disorders affecting joints, the common sites of joint involvement are hip and knee joints.1,2 roughly about 250 million population suffer from oa every year worldwide. the prevalence is rising every year because of the increase in obesity and other oarelated comorbidities in the general population.3 approximately 10% of the world men population and 13% of women's population over 60 years suffer from oa.4 among all cases, knee arthritis accounts for >85% cases of oa.5 primary oa of the knee is a type of arthropathy associated with inflammation. this inflammation causes a release of inflammatory mediators such as histamines and bradykinins and damages the articular and adjoining structures. the released inflammatory mediators sensitize nociceptors and modulate pain perception.6,7 the treatment of knee oa involves both conservative and surgical options. conservative options include; weight loss, exercise, non-steroidal anti-inflammatory drugs (nsaids) and analgesic medications, bracing, and intra-articular injections.8 intra-articular therapy involves the administration of corticosteroids, nsaids, hyaluronic acid, and plateletrich plasma (prp). the corticosteroids are the gold standard intra-articular therapy in knee oa patients.9,10 corticosteroids achieve these goals using several mechanisms such as inhibiting the release of cytokines, inflammatory cell adhesion & migration.11 hepper et al in a systematic review of outcomes of corticosteroids administration with placebo drugs reported that intra-articular corticosteroids administration significantly improves pain and knee movements as compared to placebo drugs.12 however, corticosteroids are associated with varying amounts and duration of pain control.13 moreover, repeated administration of steroids is associated with a higher risk of cartilage breakdown, articular cartilage elasticity loss, and repeated joint infections.14,15 other drugs which are used for pain relief are nsaids. ketorolac is an nsaid with strong analgesic. since the last decade, it is being used worldwide for pain relief in arthroplasty, arthroscopy, and other concomitant procedures and has been reported to be safe and effective in these patients.17 some studies have suggested that nsaids can be alternative to corticosteroids for intra-articular administration as they have fewer side effects such as damage to the articular cartilage, ligaments, and knee kinetic functions.16 however, limited literature is available regarding the efficacy of ketorolac in comparison to corticosteroids for intra-articular injection in knee oa patients. therefore, in this study, we compared analgesic and functional outcomes of intra-articular ketorolac with corticosteroids in patients of knee oa in terms of vas score and western ontario and mcmaster universities osteoarthritis index (womac) score were noted at 1 week, 1 month, and at 3 months following the intervention. materials and methods our pilot randomized comparative study included 60 patients with sample size calculated according to open-epi calculator with a two-sided significance level (1-alpha): 95, power (1-beta, % chance of detecting): 80, ratio of sample size, unexposed/exposed: 1, percent of unexposed with the outcome: 5, percent of exposed with the outcome: 59, odds ratio: 27, risk/prevalence ratio: 12, sample size 30 in each group so 30+30=60. our study duration was of 12 months i.e., 1st, january 2020 to 31st, december 2020 in the department of anesthesia and pain medicine at rawalpindi medical university. ethical approval was taken from irb. 1 day before the intervention, the patients were informed regarding adverse effects such as pain at the injection site, swelling after injection, risk of damage to surrounding tissues such as ligaments, nerves, or bone, and informed consent was taken. a total of 60 patients having symptomatic oa of kellgren-lawrence grades 2 or 3 and age 40 to 70 years were included. patients who had a recent intra-articular injection (past 3 months), having traumatic oa, drug abuse patients, pregnant females, and having an allergy to the study medications were excluded. patients were allocated a computer-generated random number and were divided into two groups with the t group receiving triamcinolone (80mg) and the k group receiving ketorolac (30mg). each group had 30 patients. before injections, patient vital monitoring which included blood pressure, pulse rate, respiratory rate, and oxygen saturation were measured. during the procedure, 1.0% lidocaine injection was given to anesthetize the superficial skin and tissues, and then under aseptic techniques and ultrasonographic guidance medications were injected in joint space while the patient was in a supine position. 514 journal of rawalpindi medical college (jrmc); 2021; 25(4): 512-515 following drugs were injected:  triamcinolone (80 mg) to the patients belonging only to the t group.  ketorolac (30 mg) to the patients belonging only to the k group.  5 ml (0.5%) lidocaine to both groups.  2.5 ml (25 mg) sodium hyaluronate to both groups. after injecting the drugs, the syringe was withdrawn, the bandage was applied and vital monitoring was done every 15 minutes for 1h and then follow-up was performed at 1 week, 1 month, and at 3 months. data were collected according to a self-structured questionary having two parts (attached in annexure a). baseline study characteristics such as age, body mass index (bmi), gender, laterality, duration, and intensity of pain as well as vas score and western ontario and mcmaster universities osteoarthritis index (womac) score were noted before intervention. the overall treatment response was assessed using the vas scale, western ontario and mcmaster universities osteoarthritis index (womac) score at 1 week, 1 month, and 3 months intervals. patients having good and excellent results were labelled as having a successful outcome. data were analyzed with spss v23 software. baseline and study characteristics of participants were compared using chi-square and independent sample ttests for qualitative and quantitative variables respectively. results baseline characteristics are demonstrated in table 1 whereas outcomes have been shown in table 2. table 1: baseline characteristics group k group t pvalue age (y) 55.6±9.2 57.2±8.30 0.42 gender; male/female 14 (35%)/26 (65%) 16 (40%)/24 (60%) 0.64 oa grade; 2/3 23 (57.5%)/17 (42.5%) 25 (62.5%)/15 (37.5%) 0.64 laterality; right/left 18 (45.0%)/22 (55.0%) 17 (42.5%)/23 (57.5%) 0.82 vas score 7.02±1.34 7.27±1.03 0.36 womac score 46.60±5.64 47.0±5.27 0.74 table 2: comparison of study outcomes group k group t p-value womac score at 1st week 32.60±3.05 33.22±3.13 0.39 1 month 22.65±2.49 21.92±2.35 0.18 3 months 21.55±2.87 20.62±2.89 0.15 vas score at 1st week 3.12±0.51 3.30±0.0.53 0.13 1 month 2.70±0.79 2.97±0.62 0.08 3 months 2.15±0.57 2.25±0.71 0.49 treatment success yes 22 (55.0%) 24 (60.0% 0.65 no 18 (45.0%) 16 (40.0%) discussion in our study, we compared the analgesic and functional outcomes in patients of knee oa who received ketorolac with those who received corticosteroids as intra-articular injections. those having good and excellent results on follow-up were declared to have successful outcomes. in our study, the vas score decreased over the period of time following the intervention whereas womac scores improved. our study did not show any statistically significant difference regarding analgesic and functional outcomes, with 3 months success rate of 55% in the ketorolac group and 60% in the corticosteroids group. above mentioned findings are consistent with a number of studies.18-20 jianda et al in a study of 84 patients of knee oa comparing corticosteroids with ketorolac reported similar analgesic and functional outcomes, with a success rate of 59.5% in corticosteroids and 57.1% in the k group.18 in our study, there was an insignificant difference between the mean womac score at 3 months follow up with score being 21.55 ± 2.87 for the ketorolac group while for the corticosteroid group it was 20.62 ± 2.89 (p-value 0.15). similarly, the vas score showed no statistical difference at 3 months follow up with the mean score being 2.15 ± 0.57 for the ketorolac group and 2.25 ± 0.71 for the corticosteroid group (p-value 0.49). our findings are consistent with those of jianda et al.18 in his study the mean womac score at 3 months follow-up was 22.81 ± 4.46 in corticosteroids and 21.98 ± 4.35 in the ketorolac group and the mean vas score was 2.20 ± 0.52 in the corticosteroids group and 2.26 ± 0.63 in ketorolac group with insignificant pvalues of 0.18 and 0.70 respectively.18 in another study mean vas scored decreased in both patient groups 515 journal of rawalpindi medical college (jrmc); 2021; 25(4): 512-515 that either received ketorolac or triamcinolone and no statistical difference was found (p-value=0.98).19 however, patients receiving corticosteroids have a better functional outcome as compared to those receiving nsaids.19 in a study by jurgensmeier et al other scales were used to measure analgesic and functional outcomes.20 but still, the type of drug was an insignificant variable when considering the outcome and there were no statistical differences in the outcomes when drugs were considered singly.20 the institutional cost price of ketorolac injection per patient was rs.30 whereas triamcinolone injection costs about rs.734 per patient. as there is no statistical difference between analgesic and functional outcome following either intra-articular injection of nsaids or corticosteroid, therefore treatment of knee oa with intra-articular ketorolac injection is cost-effective. in a number of studies, nsaids were proven to be costeffective as compared to steroids.20,21 this study is limited by a smaller study population, however, we included only a homogenous population and the control of strict inclusion and exclusion criteria made our results reliable. studies with a larger sample population are needed that can explore statistically significant differences that these small sample studies failed to explore. conclusion intraarticular ketorolac has similar functional and analgesic outcomes as that of triamcinolone and is a cost-effective treatment for knee oa. references 1. bortoluzzi a, furini f, scirè ca. osteoarthritis and its management epidemiology, nutritional aspects and environmental factors. autoimmun rev. 2018;17(11):1097-104. https://doi.org/10.1016/j.autrev.2018.06.002 2. nelson ae. osteoarthritis year in review 2017: clinical. osteoarthritis cartilage. 2018;26(3):319-25. https://doi.org/10.1016/j.joca.2017.11.014 3. primorac d, molnar v, rod e, jeleč ž, čukelj f, matišić v, et al. knee osteoarthritis: a review of pathogenesis and state-of-the-art nonoperative therapeutic considerations. genes. 2020;11(8). https://doi.org/10.3390/genes11080854 4. zhang y, jordan jm. epidemiology of osteoarthritis. clin geriatr med. 2010;26(3):355-69. https://doi.org/10.1016/j.cger.2010.03.001 5. lipton rb, schwedt tj, friedman bw. gbd 2015 disease and injury incidence and prevalence collaborators. global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015. lancet. 2017 jan 5; 388 (10053): 1545–602. 6. bonnet cs, walsh da. osteoarthritis, angiogenesis and inflammation. rheumatology (oxford). 2005;44(1):7-16. https://doi.org/10.1093/rheumatology/keh344 7. la hausse de lalouvière l, ioannou y, fitzgerald m. neural mechanisms underlying the pain of juvenile idiopathic arthritis. nat rev rheumatol. 2014;10(4):205-11. 8. khan m, adili a, winemaker m, bhandari m. management of osteoarthritis of the knee in younger patients. cmaj. 2018;190(3):e72-e9. https://doi.org/10.1503/cmaj.170696 9. chevalier x, sheehan b, whittington c, pourrahmat mm, duarte l, ngai w, et al. efficacy and safety of hylan g-f 20 versus intra-articular corticosteroids in people with knee osteoarthritis: a systematic review and network meta-analysis. clin med insights arthritis musculoskelet disord. 2020;13:1179544120967370. https://doi.org/10.1177/1179544120967370 10. oo wm, liu x, hunter dj. pharmacodynamics, efficacy, safety and administration of intra-articular therapies for knee osteoarthritis. expert opin drug metab toxicol. 2019;15(12):1021-32. https://doi.org/10.1080/17425255.2019.1691997 11. migliore a, anichini s. intra-articular therapy in hip osteoarthritis. clinical cases in mineral and bone metabolism: the official journal of the italian society of osteoporosis, mineral metabolism, and skeletal diseases. 2017;14(2):179-81. https://doi.org/10.11138/ccmbm/2017.14.1.179 12. hepper ct, halvorson jj, duncan st, gregory aj, dunn wr, spindler kp. the efficacy and duration of intra-articular corticosteroid injection for knee osteoarthritis: a systematic review of level i studies. j am acad orthop surg. 2009;17(10):638-46. https://doi.org/10.5435/00124635-200910000-00006 13. matzkin eg, curry ej, kong q, rogers mj, henry m, smith el. efficacy and treatment response of intra-articular corticosteroid injections in patients with symptomatic knee osteoarthritis. j am acad orthop surg. 2017;25(10):703-14. https://doi.org/10.5435/jaaos-d-16-00541 14. kumar n, newman rj. complications of intraand peri-articular steroid injections. br j gen pract. 1999;49(443):465-6. https://bjgp.org/content/49/443/465.short 15. wernecke c, braun hj, dragoo jl. the effect of intra-articular corticosteroids on articular cartilage: a systematic review. orthopaedic journal of sports medicine. 2015 apr 27;3(5):2325967115581163. https://doi.org/10.1177/2325967115581163 16. xu j, qu y, li h, jiang t, zheng c, wang b, et al. effect of ketorolac in intra-articular injection analgesia for postoperative pain in patients undergoing shoulder arthroscopy: a pilot-controlled clinical study. j pain res. 2019;12:417-22. https://doi.org/10.2147/jpr.s178413 17. shapiro ps, rohde rs, froimson mi, lash rh, postak p, greenwald as. the effect of local corticosteroid or ketorolac exposure on histologic and biomechanical properties of rabbit tendon and cartilage. hand (new york, ny). 2007;2(4):165-72. https://doi.org/10.1007/s11552-007-9042-6 18. xu j, qu y, li h, zhu a, jiang t, chong z, et al. effect of intraarticular ketorolac versus corticosteroid injection for knee osteoarthritis: a retrospective comparative study. orthopaedic journal of sports medicine. 2020;8(4):2325967120911126. https://doi.org/10.1177/2325967120911126 19. bellamy jl, goff bj, sayeed sa. economic impact of ketorolac vs corticosteroid intra-articular knee injections for osteoarthritis: a randomized, double-blind, prospective study. j arthroplasty. 2016;31(9 suppl):293-7. https://doi.org/10.1016/j.arth.2016.05.015 20. jurgensmeier k, jurgensmeier d, kunz de, fuerst pg, warth lc, daines sb. intra-articular injections of the hip and knee with triamcinolone vs ketorolac: a randomized controlled trial. j arthroplasty. 2021;36(2):416-22. https://doi.org/10.1016/j.arth.2020.08.036 21. park kd, kim tk, bae bw, ahn j, lee wy, park y. ultrasound guided intra-articular ketorolac versus corticosteroid injection in osteoarthritis of the hip: a retrospective comparative study. skeletal radiology. 2015 sep;44(9):1333-40. https://doi.org/10.1007/s00256-015-2174-9 270 journal of rawalpindi medical college (jrmc); 2021; 25(2): 270-274 original article frequency of post-operative bleeding after dental extraction among patients on chronic low dose aspirin naseer ahmed1, sunia gul2, eruj shuja3, arsalan maqbool4, wasim ibrahim5, muhammad adil asim6 1 post-graduate resident, armed forces institute of dentistry, rawalpindi. 2 post-graduate resident, islamic international dental hospital, islamabad. 3 assistant professor, watim dental college, rawalpindi. 4 post-graduate resident, rashid latif medical complex, lahore. 5 professor, foundation university college of dentistry and hospital, islamabad. 6 assistant professor, shifa college of dentistry, rawalpindi. author’s contribution 1 conception of study 2 experimentation/study conduction 3 analysis/interpretation/discussion 4 manuscript writing 5 critical review 6 facilitation and material analysis corresponding author dr. eruj shuja, lecturer, assistant professor, watim dental college, rawalpindi email: erujshuja@hotmail.com article processing received: 10/03/2021 accepted: 27/05/2021 cite this article: ahmed, n., gul, s., shuja, e., maqbool, a., ibrahim, w., asim, m.a. frequency of post-operative bleeding after dental extraction among patients on chronic low dose aspirin. journal of rawalpindi medical college. 30 jun. 2021; 25(2): 270274. doi: https://doi.org/10.37939/jrmc.v25i2.1607 conflict of interest: nil funding source: nil access online: abstract introduction: anti-platelet drugs are widely used for primary and secondary prevention of cardiovascular and cerebrovascular diseases. the purpose of this study was to determine the frequency of post-operative bleeding after dental extraction among patients on chronic low-dose aspirin. materials and methods: this is a descriptive case series in which a total of 378 patients on low-dose aspirin of( 75-100mg) for various cardiovascular causes were included in the study. the duration of the study was from november 2016 to may 2017 total of 6 months. results: out of 378 cases, 247 patients (65.4%) were male while 131 patients (34.6%) were female. the mean age of the patients was calculated as 54.8±13.1 years. regarding pre-morbid, 127 patients (33.6%) were diabetic and 109 patients (28.9%) were hypertensive. the mean duration of taking aspirin was calculated as 3.5±1.7 years. postextraction bleeding was noted in 16 patients (4.2%). this was statistically insignificant i.e p-value >0.005. conclusion: we concluded that simple tooth extraction is safe in patients on a long-term maintenance dose of aspirin, without discontinuation of the drug as it doesn’t cause any significant postoperative bleeding. keywords: aspirin, dental extraction, post-extraction bleeding. 271 journal of rawalpindi medical college (jrmc); 2021; 25(2): 270-274 introduction aspirin is a drug that belongs to the nsaids group part of salicylic acid derivative and has antiinflammatory, antipyretic, and analgesic effects.1 it inhibits the cyclooxygenase pathway and thromboxane a2 causing reduced platelet aggregation which is irreversible, leading to a reduction in the incidence of embolism.2 aspirin inhibits platelet function irreversibly for 10 days.1 in clinical practice, a lot of patients, visiting oral & maxillofacial surgeons for tooth extraction or other surgical procedures, are on anti-platelet therapy for a long time, for primary or secondary prevention of cardiovascular or cerebrovascular events. in this regard, the most commonly prescribed anti-platelet drug is aspirin (acetylsalicylic acid), given 75mg daily.3 such patients put the maxillofacial surgeons in a dilemma whether to stop aspirin before the procedure or not, as the literature is controversial in this aspect, making different opinions from related experienced personnel.2 multiple studies have been performed in this regard, to assess the effect of aspirin on postoperative bleeding in patients undergoing tooth extraction. various studies advocated that aspirin should be stopped before tooth extractions or other minor oral surgical procedures.4 cessation of aspirin however can result in associated systemic thromboembolic events (such as deep vein thrombosis and pulmonary embolism) that are more dangerous than postoperative bleeding after extraction.5 later studies favoured that aspirin should not be discontinued in patients taking it chronically, for any logical reason as mentioned earlier, and tooth extraction or other maxillofacial procedures can be safely performed with no worse outcomes. anyhow, precautions or local measures should be taken to avoid post-extraction prolonged bleeding.6,7 other studies supported the fact that patients on lowdose aspirin (75-100mg) didn’t show any significant post-operative bleeding with minor surgical procedures.8 many studies suggest that patients on dual antiplatelet therapy show significant postoperative bleeding as compared to single antiplatelet therapy.9 the purpose of the study is to check the frequency of post-operative bleeding in patients on low-dose aspirin after extraction. materials and methods this is a descriptive case series conducted in the department of oral and maxillofacial surgery of armed forces institute of dentistry, rawalpindi for a period of six months i.e. from november 2016 to may 2017. a sample size of 378 was calculated using the who calculator with a confidence level of 95%, the anticipated population proportion is 3.938, and the absolute precision required is 1.965%. non-probability purposive sampling technique was adopted. a total of 378 patients were included in the study. inclusion criteria of the study included patients who were already on low dose aspirin (75-100mg) from a period of 1 to 8 years for various cardiovascular known comorbidities like(myocardial infarction, angina, etc), patients aged above 40 years and below 70 years, and patients of both genders. exclusion criteria consisted of patients with anemia, liver disease & polycythemia. patients with psychiatric disorders, patients with epistaxis, patients with established bleeding disorders like hemophilia & von willebrand disease. extraction of teeth was carried out with the use of 2% lidocaine with 1:100,000 epinephrine. the patients were then asked to press on saline-soaked gauze for 30 minutes and assessed for bleeding. patients with no post-operative bleeding were discharged with written instructions and reviewed clinically 24 hours after the extraction. bleeding was labeled positive if the extraction socket was filled with blood without clot formation even after 30 minutes, for such instances the patients were retained for another 30 minutes and asked to press on saline-soaked gauze. additional local haemostatic measures such as transamine soaked gauze and epinephrine soaked gauze and figure of 8 suturing over the extraction socket were adopted for cases where the bleeding was not controlled by saline-soaked gauze. data were analyzed using spss version 17, stratification with regard to age gender, and medical condition was carried out. time duration of aspirin intake was also noted. post-operative bleeding was noted and expressed in percentage .p-value of < 0.005 was considered statistically significant. results a total of 378 patients were included in this study during the study period of six months from november 2016 to may 2017. out of 378 cases, 127 (33.6%) were 272 journal of rawalpindi medical college (jrmc); 2021; 25(2): 270-274 diabetic and 109 patients (28.9%) were hypertensive and 142 (37.5%) had no known co-morbidities (table 1). duration of intake of aspirin was noted in all individuals and it was divided into two groups of patients on aspirin for less than one year and patients on aspirin for 1 to 8 years. in the first group (< 1 year) out of 101 patients, 4 patients showed post-operative bleeding and 97 patients had no bleeding. in the second group (1-8 years) out of 277 patients, 12 patients showed postoperative bleeding while 265 patients showed no bleeding. the mean duration of taking aspirin was 3.5 ± 1.7 years (table 2). post-extraction bleeding occurred in 16 patients (4.2%) in total, there was no bleeding in 362 patients (95.8%) in total (table 3). table 1: stratification with regard to the medical condition medical condition post-extraction bleeding total pvalue yes no diabetes 11 116 127 (33.6%) 0.008 hypertension 3 106 109 (28.9%) normal 2 140 142 (37.5%) total 16 362 378 table 2: stratification with regard to the duration of taking aspirin duration post-extraction bleeding total pvalue yes no < 1 year 4 97 101(26.7%) 0.873 1-8 year 12 265 277(60.0%) total 16 362 378 table 3: post-extraction bleeding bleeding number percentage yes 16 4.2% no 362 95.8% total 378 100.0 discussion the decision regarding the stoppage of antiplatelet therapy before extraction depends on the surgeon’s ability to judge and weigh the benefits versus risks of the associated intake of medicine. many factors need to be considered while taking this decision. mandatory factors account for patients intrinsic risk factors for continued or prolonged bleeding, the surgical severity of the procedure undertaken, and the potential risk of thromboembolitic events if the antiplatelet therapy is discontinued.9 in addition to these factors, hemorrhagic peptic ulcers, an additional ongoing treatment that increases the bleeding risk or hemorrhagic stroke increases the possibility of bleeding.9 a metanalysis of 135,000 patients by the ant platelets trialists showed that prophylactic use of aspirin in mi, angina, and stroke reduces mortality by 12% and vascular events by 2025%.10 other risk factors like patient’s demographics, gender predisposition, old age, hypertension, obesity, oral hygiene habits, old age, obesity, diabetes, renal and liver failure also account for prolonged postoperative bleeding.11 studies show that in cases of chronic low dose aspirin intake sudden withdrawal of the drug can be fatal and this increases the risk of cardiovascular disorders by 30%.12 according to gerstein ns et al13 there is no need for discontinuation of aspirin before planned surgical procedures except for intracranial, transurethral, and ophthalmic surgeries. this favors our results which show no significant post-extraction bleeding i.e. 16 patients (4.2%) out of total 378 patients in total. in contrast to our study, schrodi et al14 and ryzman et al11 reported increased bleeding on surgical manipulation in patients who were on aspirin therapy. however, in both above-mentioned studies gingival inflammation, periodontitis, and poor oral hygiene were major factors contributing towards continued bleeding after minor surgical endeavors. from the above discussion, it can be concluded that postextraction bleeding is not only dependent on aspirin use, but it also depends upon local factors like periodontitis which leads to hyperaemia and eventually more bleeding postoperatively.14 shah et al8 also reported increased bleeding complications after tooth extraction in patients taking aspirin, who have undergone tooth extraction due to periodontitis as compared to bleeding which was less in patients who have undergone tooth extraction due to dental caries which does not favor the results of our study. hassan s, et al15 study showed prolonged bleeding time in only 2% of patients after 30 minutes of extraction which is statistically non-significant and favors the result of our study as well. simple dental 273 journal of rawalpindi medical college (jrmc); 2021; 25(2): 270-274 extractions were performed in experimental group patients on continued aspirin therapy (�=25) and control group patients who stopped aspirin 7 days before extractions (�=19). the experimental group patients were on aspirin doses in the range of 75– 300mg. there was no significant post-operative bleeding in the experimental group which did not discontinue the aspirin intake. the aforementioned study favors our result as well.16 there is the unanimous decision of national medical and dental groups against interruption of antiplatelet therapy before minor dental procedures.17 many dentists fail to presume the actual threat of acute thromboembolitic events on cessation of aspirin therapy. this serious side effect is low but isn’t zero in statistics.15,17 stoppage of aspirin therapy for 7-10 days was thought to be prodent18 but sonsksen et al19 showed that interruption of 2 days is viable to control postoperative bleeding. brennen et al20 recommended not more than 3 days of cessation before dental surgery. malik ah et al21 evaluated 100 patients after minor oral surgery on aspirin therapy none showed any significant bleeding. a decision regarding the cessation of antiplatelet therapy should be the final decision of the treating physician rather than the operating dentist.17 in our study, only 4.2% of the patients developed postoperative bleeding after dental extraction, in patients who were already taking aspirin due to some chronic disease or prophylaxis. most of the studies mentioned above are comparable with our findings.12, 13, 15, 16 the limitation of our study was that we didn’t consider patient-related factors such as the habit of smoking, compliance with post-operative extraction instructions such as spitting avoidance of hot and cold food with regard to local causes contributing to postoperative bleeding and haemostasis. conclusion it was concluded in this study that simple tooth extraction is safer in patients who are on a long-term maintenance dose of aspirin, without discontinuing it. so, it is recommended that if the risk of hemorrhagic events is less likely and if post-operative bleeding can be controlled easily by local haemostatic measures then there is no need to stop aspirin before tooth extraction. references 1. osafo n, agyare c, obiri dd, antwi ao. mechanism of action of nonsteroidal anti-inflammatory drugs. nonsteroidal anti-inflammatory drugs. 2017 aug 23:1-5. 2. arif h, aggarwal s. salicylic acid (aspirin).2018. 3. jahan ss, younis m, gul s, shah aa, naaz n. aspirin intake and significant post extraction bleeding-are they related. int j contemporary med res. 2018;5(3):c30-3. 4. nathwani s, martin k. exodontia in dual antiplatelet therapy: the evidence. british dental journal. 2016 mar;220(5):235-8. 5. raber i, mccarthy cp, vaduganathan m, bhatt dl, wood da, cleland jg, et al. the rise and fall of aspirin in the primary prevention of cardiovascular disease. the lancet. 2019 may 25;393(10186):2155-67. 6. saxena a, kumar ga, hiralkar p, mahajan sb, rubeena s, tabasum d, et al. evaluation of post extraction bleeding on aspirin patient-a clinical study. doi: 10.21276/sjm.2019.4.8.4 7. shenoy a, panicker p, vijayan a, george al. prospective comparative evaluation of post-extraction bleeding in cardiovascular-compromised patients with and without antiplatelet medications. journal of maxillofacial and oral surgery. 2019 dec 7:1-0. 8. shah a, shah st, shah i, zia-ur-rehman post extraction bleeding associated with long term maintenance dose of aspirin 75–150 mg. pakistan oral dent j 2012;32:199–202 9. krishnan b, prasad ga, madhan b, saravanan r, mote np, akilesh r. post-extraction bleeding complications in patients on uninterrupted dual antiplatelet therapy—a prospective study. clinical oral investigations. 2021 feb;25(2):507-14. 10. singh s, mandal s, chugh a, deora s, jain g, khan ma, et al. clinical post-operative bleeding during minor oral surgical procedure and in vitro platelet aggregation in patients on aspirin therapy: are they coherent?. journal of maxillofacial and oral surgery. 2020 aug 20:1-6. 11. royzman d, recio l, badovinac rl, fiorellini j, goodson m, howell h, et al. the effect of aspirin intake on bleeding on probing in patients with gingivitis. j periodontol2004;75:679-84 12. mroczek a, bałabuszek k, radzka a, fałkowska u, pawlicka m, bednarski j. to continue or discontinue aspirin? the risk of perioperative complications. journal of education, health and sport. 2018 aug 19;8(8):743-7. 13. gerstein ns, albrechtsen cl, mercado n, cigarroa je, schulman pm. a comprehensive update on aspirin management during noncardiac surgery. anesthesia & analgesia. 2020 oct 1;131(4):1111-23. 14. . schrodi j, recio l, fiorellini j, howell h, goodson m, karimbux n. the effect of aspirin on the periodontal parameter bleeding on probing. j periodontol2002;73:871-6 15. hasan s, akhter m, khan sh, sharmin d, karim mm, rahman r. evaluation of post-extraction bleeding in patients taking low dose aspirin. update dental college journal. 2019 apr 27;9(1):32-6. 16. verma g. dental extraction can be performed safely in patients on aspirin therapy: a timely reminder. international scholarly research notices. 2014;2014. 17. wahl mj. antithrombotic drugs in dentistry: stop the interruption. academy of general dentistry. 2017 aug:1-3. 18. ogle oe, hernandez ar. management of patients with hemophilia, anticoagulation, and sickle cell disease. oral and maxillofacial surgery clinics of north america. 1998 aug 1;10(3):401-4 19. sonksen jr, kong kl, holder r. magnitude and time course of impaired primary haemostasis after stopping chronic low and 274 journal of rawalpindi medical college (jrmc); 2021; 25(2): 270-274 medium dose aspirin in healthy volunteers. british journal of anaesthesia. 1999 mar 1;82(3):360-5 20. brennan mt, valerin ma, noll jl, napeñas jj, kent ml, fox pc, et al. aspirin use and post-operative bleeding from dental extractions. journal of dental research. 2008 aug;87(8):740-4 21. malik ah, majeed s. post-surgical bleeding in patients on anti-platelet therapy in minor oral surgical patients-a comparative randomized study.2020 summary journal of rawalpindi medical college (jrmc); 2017;21(1):68-71 68 original article tele ent: a step forward in providing specialist services in far remote areas asif zafar malik 1, nousheen qureshi 2, tabassum azim, faisal murad 1 1.department of surgery, unit ii,holy family hospital and rawalpindi medical college, rawalpindi; 2. department of ent, holy family hospital and rawalpindi medical college abstract background: to study the utility of tele medicine in providing ent services to far remote areas methods: in this descriptive study 2 hourly weekly consultations were given by ent consultants on every friday in tele medicine office. four remote areas were connected through strong satellite connectivity of 512 kbs and 1 mb to pindi through video conferencing with real time imaging modality was used. the tools used to diagnose the patients were video otoscope to examine the ear, video endoscope and tongue depressor for oral cavity examination. routine blood and urine examination along with required other specific tests like x-ray, pure tune audiometry were advised accordingly, then patients were given treatment for their specific problem and given dates for follow up visit. some patients were booked for surgery and given date of admission in our hospital. only some patients with laryngeal and nasal problems were asked to visit the opd for a clearer and better diagnosis as nasal and laryngeal examination could not be done through video conferencing. patients who were given time for surgery got their investigations done in their home town and were admitted straightaway as they arrived in our hospital. these patients were scheduled for surgery on the next list, and were successfully operated and followed up post operatively. results: a total of 2159 patients were included in our study, two third of which were females and rest male. majority of our patients had ear problem followed by throat and nasal problems 1287 of our patients were successfully managed conservatively through video conferencing. a total of 792 patients were referred to us in holy family hospital out of which 661 were successfully operated and out of these patients 459 were followed up postoperatively through video conferencing. the major operations done were tonsillectomy, septoplasty, endoscopies (direct laryngoscopies and esophagoscopies), mastoidectomies, and thyroidectomy. a few emergency cases like foreign body nose and ear removal along with foreign body throat removal, incision of peritonsillar abscess and mastoid abscess were also done. conclusion: video conferencing in ent is an effective tool and method of assessing and treating ent conditions. through tele ent potential surgical admissions can be screened.. key words: tele medicine, ent, services introduction ear nose and throat problems are common among all general population in any country but unfortunately there are a few ent specialists in pakistan. more over the specialists are confined in major cities of pakistan the rural areas are devoid of not only the facilities but also of specialist. rural patients who develop ent disorders often do not seek or get specialty care due to multiple logistic and economical factors. our aim of the study was to provide ent specialist service and care to these people which are as good and up to the standards in any well equipped and well facilitated tertiary hospital. this method of treating the patients was a new experience for us and enabled us to provide better services at a lower cost to these patients located in far remote areas, and it saved them one or two journeys to a tertiary hospital for a pre-admission appointment.tele ent is a part of tele medicine. telemedicine is transfer of electronic medical data (high resolution images, sound, live videos and patient records) from one location to another. the who1 has defined the word tele medicine as “the delivery of health care services, where distance is a critical factor, by all health care professional using information and communications technologies for the exchange of valid information for diagnosis, treatment and prevention of disease and injuries, all in the interest of advancing the health of individuals and their communities”. 1 telemedicine has a great appeal and promise as a means of health service delivery to smaller communities at some distance from major health facilities. benefits include rapid delivery of diagnostic and other health services, avoidance of economic and social consequences of travel, for patients, their families and health professionals. telemedicine plays a journal of rawalpindi medical college (jrmc); 2017;21(1):68-71 69 major role in changing the way health care and health related information are accessed and delivered in developing and under developed areas which have poor physical facilities for communication, transport and limited number of medical facilities. the history of telemedicine dates back to 1906 when the first ecg transmission was made over telephone, followed by 1920 when physician linked with patients on ship through radio. 1 in 1955 nebraska tele psychiatry used closed circuit tv. in 1971 the nebraska medical centre was linked with omaha veterans. the first satellite telemedicine project (store and forward technique) was launched in which ear, nose and throat services were provided to remote alaskan and canadian villages via ats-6 satellites and this practise since 2002 has been continued to help the people living in these areas. 2 in 2005 this facility was used to provide relief to the affectees of earthquack in muzaffarabad in pakistan, where telemedicine centers were created. 3,4the telemedicine assets and capabilities were applied in this disaster in managing all the injured patients. doarn et al has also discussed the role of satellite tele medicine in managing mexico city earth quake in 1998. 5 gul s et al reported in 2008 on their work using telemedicine and paraplegic rehabilitation at a hospital in rawalpindi paki. 6 they have discussed how this modality helped rehabilitating 194 patients in rawalpindi. in 2011 dr ronald weinstein7 reviewed a from dr riffat latifi entitled” telemedicine for trauma emergencies and disaster management”. 7 in their article they highlighted telemedicine as a tool for teaching and implementing telemedicine in support of disaster response.alverson et al prepared a summary report on tele health tools for public health, emergency, or disaster preparedness and responses. 8 this method of treating patients enables us to give patients in remote locations better services at lower cost. it saves one or two journeys of the patients to the main hospital from a tertiary hospital for a preadmission appointment and also saves the patient a lot of time which is lost is travelling. patients and methods this study was conducted in holy family hospital in teleconference unit located is surgical unit ii. a total of 195 ent clinics were conducted between july 2008 to march 2012 in which consultations were facilitated for two thousand one hundred and fifty nine patients in tehsil head quarter hospital pindi gheb, dhq hospital attock, gujrat and di khan. from july 2008 to march 2012 patients of all ages and gender from remote area centers were included in our study. weekly 2 hour video conferencing in telemedicine center of holy family hospital was done. the tools used were videootoscope for ear examination, and video endoscope with tongue depressor for oral cavity examination (figure 1-3). .real time images and downloaded file were used to assess the patients.ent consultants were present at hub and trained nurse, doctor and it expert at remote areas. tele ent coordinator was present in both areas. the data of patients scheduled for clinics was uploaded on server and became available to the specialist. this data included the name, age, sex, and out patient department reference number along with brief history in a few words and any investigation that had been advised. a band width of 384 kbs was available for transmission of images and video conferencing provided by paksat satellite and wateen telecom wimax services.ent consultants conducted on weekly clinic .using telemedicine and audiovisual equipment full history and ent examination was performed. the consultant specialist examined the patients through video conferencing and correlated the clinical findings with related investigations ,like x-ray pns45,x-ray mastoid oblique views ,soft tissue neck ,blood test (complete picture, bt, pt, blood grouping ) were other test conducted. only some method of picture delay was encountered as we examined the patients. : an effort was made to reach out and provide specialist service in this field to patients in remote rural areas devoid of facilities and trained personnel. as in any well equipped tertiary hospital the facilities and consultations were extended and full measures were taken to provide adequate managements to these patients. this programme is a part of pakistan ministry of information technology rural support program. these centre capabilities were further enhanced by us state department support. video conferencing is an effective tool and method of assessing and treating ent conditions and for screening potential surgical admission.some patients were booked for surgery and ordered base line investigations .patients with nasal and laryngeal problems were mostly advised to visit holy family hospital. for better and faster services patients who were given time for surgery got their investigations done in their home town and were admitted straight away as they arrived in holy family hospital. these patients were put on the next immediate operating list and was success fully operated and followed up for weeks using this modality. investigations conducted for routine workup were complete blood picture , bleeding profile journal of rawalpindi medical college (jrmc); 2017;21(1):68-71 70 investigations as mentioned previously, profile for hepatitis a and b,ecg and chest x-ray for elderly. diagnosis and management plan formulated was recorded. in follow up repeat history and examination was done, plan for future consultation and on going management was recorded .review was also done of our referrals to other departments. results a total of 195 ent surgical clinics were perfomed in these tele ent sessions. a total of two thousand one hundred and fifty nine patients were included in our study. majority of our patients had ear and throat problems(table 1) . more than one thousand two hundred and eighty seven patients(1287) were managed conservatively on site by video conferencing and were followed up on out patient basis a total of (792) seven ninety two patients were referred to us and admissions were arranged in holy family hospital for six sixty one (661) patients requiring surgery. most patients three hundred and fifty (350) of them were followed up on video conferencing and one hundred and nine (109) patients came for a follow up in holy family hospital. out of 950 patients that presented with ear complaints the major complain was ear discharge associated with deafness (45%)(table 2). in throat the major complain was of chronic sore throat (58%)(table 3). in nasal problems nasal obstruction ( 58% ) was the commonest (table 4). the major operation done was tonsillectomy 50%(331)(table 5).we conducted (19) 2.9% of endoscopies,(laryngoscopies and bronchoscopies),3 .5% of myringoplasties and(11) 1.7% radicalmastoidectomys. a few emergency cases were also dealt like foreign body nose and foreign body removal from esophagus and larynx and bronchus . (12)1.9%, removal of tonsolith(5) .8 %, and drainage of peritonsillar abscess, mastoid abscess, tracheostomies and even (table 5).the follow up period was for one year. out of six sixty one (661) of operated patient four hundred and fifty nine (459) were followed up post operatively. three hundred and fifty (350) were followed up through video conferencing and the remainingone hundred and nine(109) patients were followed up in holy family hospital. table 1.percentage of ear nose and throat patients disease %age ear 45 throat 42 nose 13 table 2. tele entear symptoms ear symptoms %age ear deafness and discharge 45 % blockage of ear 38 % earache 9 % vertigo 6 % table 3 . tele entthroat symptoms throat symptoms %age chronic sore throat 60 % acute sore throat 20 % dysphagia 11 % hoarseness of voice 7 % swelling in neck 2 % table 4-tele entnasal symptoms nasal symptoms %agee nasal obstruction 58 epistaxis 15 nasal discharge 13.8 mass/foreignbody 12 table 5. tele ent-surgical services provided surgical service %atage tonsillectomy 50 wax removal 23 smr 20 fracture nasal bone 4.4 endoscopies 3.1 radical mastoidectomies 1.7 myringoplasties 0.5 figure 1:digital otoscope :patient being examined by digital otoscope figure 2:videosscopic orophararyngoscope figure 3: tele ent consultations inhfh prof ron merell(pioneer intele ent in america) from america sitting with ent consultant figure 4: usaid recognition of tele ent in holy family hospital colour page journal of rawalpindi medical college (jrmc); 2017;21(1):68-71 71 discussion telemedicine offers a unique opportunity for the delivery of health care to rural communities. telemedicine center attock is one of the spokes connected to holy family hospital hub. this center capabilities have been further enhanced and upgraded by us state department. through this modality we have extended specialist services to catchment area of rawalpindi teaching hospitals.a lot of fields including ent (emergency and normal clinic patients) have been attended in far off areas where there are limited health, staff and technical facilities.. 7 real time medicine as a means of gaining expert advices has gained fast recognition as a visible alternative to traditional referral system. bashshur l rashid in his book “history of telemedicine” has described the complex interrelationship between patients, policy and technology. in this book the rules of telemedicine scholarship are mentioned and the author has created a feeling that telemedicine is not simply an enabling technology, but more of an umbilical cord of health information. 9 the video endoscopic quality of otorhinological images that we obtained were of high resolution and quality for us to make the diagnosis. the management plan that we decided for the patient matched the management plan that we made as we saw some of the patients in our opd or emergency when we admitted the patient in our ward for any surgical intervention. sir pederson.10 s et al in his tele endoscopic pilot study has mentioned that “ although the video imaging is compressed before transmission over the telecommunication network our results show us that the quality of transmitted images were equivalent to the quality of images from a standard endoscopic examination” this clearly supports the fact that real time images not only help in making the correct diagnosis but also helps the specialist doctor in making accurate and precise management plan for patient.smith et al showed among the 68 patients seen via the videoconferencing and in person, the recorded diagnosis was the same in 99% of the cases. 11 the drawback that we faced in our study was delay of some seconds in receiving the picture otherwise the data and picture quality was excellent. our majority of patients were from attock which comprises of six tehsils and has an estimated population of 1.8 million. attock is eighty (80) km from the capital islamabad and its dhq at the time of our study did not cater for ent patients as no specialist services were available there. still there is just one ent medical officer available in that hospital the specialist services are lacking.patients with their problems had to travel a long distance, arrange for their boarding and lodging and were on and off referred to hospitals in islamabad and rawalpindi. this practiced has changed since we established a tele medicine center in attock. according to a survey conducted by who12, no national telemedicine and e-health policy frameworks have been designed in pakistan in contrast to which 55% states world wide have a proper ehealth policy designed .but this rural support programme especially in the field of teleent has been acknowledged and praised by one of the washigton journal (figure 4) . 13 conclusion 1. through tele ent it is possible to reach out and provide specialist services to patients in far remote areas devoid of specialist ent staff and equipment. 2. utility of tele medicine needs proper appraisal at higher levels references 1. geneva: world health organization.health telematics policy in support of who's health-for-all strategy for global health development.1998 2. ko kesh j, ferguson as, patriconki c. alaska experience using storeandforward telemedicine for ent cases. otolaryngol clin north am 2011 ; 44 (6): 135974. 3. malik az. telemedicine country reportpakistan. ninth international conference one-health networking applications and services.health, 2007.381611. 4. doarn cr. merrell rc. telemedicine and e. health in disaster response telemed je health: 2014 july: 20(7): 605-606. 5. doarn cr., nicogossian ae. merrell rc. applications of telemedicine in the united states space program. telemed j 1998;4:19–30 6. gul s., ghaffar h., mirza s., tauqir sf, malik az. multitasking a telemedicine training unit in earthquake disaster response: paraplegic rehabilitation assessment. telemed j e health 2008 ;14 : 280–83 7. weinstein rs. review of telemedicine for trauma emergencies and disaster management by rifat latifi. telemed j e health 2011;17:666–67 8. alverson dc., edison k., flournoy l., korte b. telehealth tools for public health, emergency, or disaster preparedness and response. telemed j e health 2010;16:112–114 9. bashshur rl, shannan g w. history of telemedicine isbn 13: 978-1-934854-11-2. 10. pedersen s md: hartvi kser g msc.tele consultaties of patients with otorhinolaryngologic conditions a telendoscopic pilot study. arch otolaryngol head neck surg,1994; 100 (2):221-25 11. smith ac, dowthwait s, agnew j. concordarce between realtime telemedicine assessment and face to face consultations in paediatric otolaryngology. mja 2008; 188: 457-60 12. world health organization; 2011. atlas ehealth country profiles: based on the findings of the second global survey on ehealth. 13. usagency for international development. success story saving lives online in pakistan: usaid/pakistan washingtondc20523-1000.http://storiesusaid.gov 112 journal of rawalpindi medical college (jrmc); 2020; 24(2): 112-116 original article comparison of conventional and newer iron preparations for the treatment of iron deficiency anaemia in children asmat parveen1, naima fazil raja2, imran mehmood khan3, hijab shaheen4, muhammad imran5, rizwan shafeeq ahmed6 1 consultant pediatrician, maryam memorial hospital, rawalpindi. 2 consultant pediatrician, tehsil headquarter hospital, taxila. 3 associate professor, islamabad medical & dental college, islamabad. 4 medical officer, pakistan institute of medical sciences, islamabad. 5 senior registrar, shifa college of medicine, islamabad. 6 assistant professor, islamabad medical & dental college, islamabad. author`s contribution 1,2,3,4,5,6 conception of study 1,4,5 experimentation/study conduction 1,2,3,4,5 analysis/interpretation/discussion 1,2,3,6 manuscript writing 2,3,6 critical review corresponding author dr. imran mehmood khan associate professor, islamabad medical & dental college, islamabad email: lifesaverforu@yahoo.com article processing received: 13/7/2019 accepted: 13/5/2020 cite this article: parveen, a., raja, n.f., khan, i.m., shaheen, h., imran, m. & ahmed, r.s.(2020). comparison of conventional and newer iron preparations for the treatment of iron deficiency anaemia in children. 24(2), 40-45. doi: https://doi.org/10.37939/jrmc.v24i2.1160 conflict of interest: nil funding source: pakistan institute of medical sciences, islamabad. access online: abstract introduction: commonly used iron salt, ferrous sulphate for the treatment of iron deficiency anemia, has several gastrointestinal side effects. nowadays new iron salts such as ferrous bisglycinate are marketed with claims of raising hemoglobin faster with fewer gastrointestinal side effects. objective: to compare the efficacy of ferrous sulphate with ferrous bisglycinate for the treatment of iron deficiency anemia in children. methods: this randomized controlled trial was carried out at children hospital, pims, islamabad from july 2015 to june 2016. a total of 136 children were selected through systematic sampling and randomized into 2 groups using a computer-generated table of random numbers; ferrous sulphate as group 1 and ferrous bisglycinate as group 2. clinical outcome was assessed based on a mean increase in hemoglobin after 12 weeks of therapy in both groups. the data was entered and analyzed using spss version 20. results: the baseline characteristics i.e. mean age, mean hemoglobin levels were similar in both study groups. after 12 weeks of treatment, the mean increase in hemoglobin was 1.8 ±1.59 g/dl in the ferrous sulphate group as compare to 2.5 ±1.31g/dl in ferrous bisglycinate group showing the higher level of rising with ferrous bisglycinate than ferrous sulphate, p =0.0033. conclusion: newer iron preparation, ferrous bisglycinate is a better treatment option than conventional preparation of ferrous sulphate for increasing hemoglobin in iron deficiency anemia in children. keywords: hemoglobin, iron, ferrous sulphate, ferrous bisglycinate, iron deficiency, anemia. 200 journal of rawalpindi medical college (jrmc); 2020; 24(2): 112-116 introduction anemia is defined as “a hemoglobin level of less than the 5th percentile for age”.1,2 about 30% of the world’s population is suffering from iron deficiency anemia (ida) mostly residing in developing countries.3 in pakistan, 65% of the general population including children and adults, is having ida.4 who statistics shows that in the world 43% & in pakistan 29% of children are suffering from iron deficiency.4 children less than 2 years of age have the highest risk due to the increasing demand for rapid growth.5,6 other causes of ida are premature births, early clamping of the umbilical cord, prolonged exclusive breastfeeding greater than 6 months without iron supplementation, delayed weaning, excessive intake of cow milk, low iron absorption, chronic blood loss, and parasite infestation.3,7,8,9,10 the most common sign of anemia is pallor which does not appear until hemoglobin (hb) falls to 7-8 g/dl. so ida is commonly missed by parents in early stages. other than anemia, iron deficiency also causes fatigue, poor concentration, and memory resulting in poor school performance.11,12,6 it also leads to pica and pagophagia (desire to ingest rice).3,13 there is a positive association of iron deficiency with febrile seizures, breath-holding spells, irritability, nausea and reduced immunity.3,14,13,6 to prevent ida, who recommends daily doses of 30 mg of iron and 250 µg of folic acid for 3 months.9,15 two commonly used iron preparations in children are ferrous sulphate and iron polymaltose complex. ferrous sulphate raises hb faster than iron polymaltose complex but has more side effects and less tolerability as compared to iron polymaltose complex.7,16,5 the side effects of ferrous sulphate include nausea, vomiting, abdominal pain, constipation, diarrhea and staining of teeth.16 so we need such iron preparation which rapidly increases hb level with good tolerability and fewer side effects. one such preparation is ferrous bisglycinate which is an amino acid chelate. it has higher bioavailability (90.9%) as compared to ferrous sulphate (26.7%).17,18 this is because it does not form insoluble compounds with iron absorption inhibitor found in high quantity in cereal-based diets like phytates, oxalates, and tannins.6 trials of ferrous bisglycinate versus ferrous sulphate in pregnant women showed that ferrous bisglycinate raises hb faster and has high compliance due to fewer side effects.19 one study in children showed that although hb increases significantly in both ferrous sulphate and ferrous bisglycinate group plasma ferritin which represents iron stores in the body increases significantly only in ferrous bisglycinate group.17 to date, no study has been conducted in pakistan to compare the efficacy of ferrous sulphate with ferrous bisglycinate for the treatment of newly diagnosed ida in children. therefore, we are going to conduct this study to compare the efficacy of ferrous sulphate with ferrous bisglycinate for the treatment of iron deficiency anemia in children. material & methods after seeking permission from the institutional ethics review board of pakistan institute of medical sciences (pims), islamabad, this randomized controlled trial was done at children hospital’s opd of pims, from july 2015 to june 2016. children of either gender with age ranging from 6 months to 60 months who were recently diagnosed as having ida with serum hb levels between 7 and 10.9 g/dl, mcv < 70, mchc < 20p g/dl; serum ferritin <10 μg/l were included in the study. children who have β thalassemia trait, chronic inflammatory diseases, renal insufficiency, active infections, or have been treated with drugs that interfered with iron absorption were excluded from our study. total 136 children (68 in each group) were taken as sample size by using who sample size calculator with following values of calculations; level of significance = 5%, power of test = 80%, mean hb p1 = 2.517+1.31, mean hb p2=1.817+1.59, pooled sd = 1.45. a total of 136 children fulfilling the above-mentioned inclusion criteria were enrolled in the study by using systematic sampling. a computer-generated table of random numbers was used to randomize the enrolled children into two study groups; ferrous sulphate as group 1 and ferrous bisglycinate as group 2. demographic features such as age and gender were asked and noted on a specially designed proforma. children randomized to group 1 were advised syrup ferrous sulphate with a daily dose of 5 mg of iron/kilogram of body weight in 2 divided doses for 12 weeks. children randomized to group 2 were advised syrup ferrous bisglycinate with a daily dose of 5 mg of iron/kilogram of body weight in 2 divided doses for 12 weeks. afterward, all the children in both the study groups were sent home with the advice of a follow-up visit 114 journal of rawalpindi medical college (jrmc); 2020; 24(2): 112-116 after 4 weeks of starting iron therapy. on 4 week follow up visit, history regarding the compliance of the patient to iron supplementation and any of the associated side effects was asked from mothers/ caregivers and advised another follow-up visit after 12 weeks of starting iron therapy. in this 2nd follow up visit, a blood sample was obtained from each enrolled child to examine the serum hb levels. all the laboratory data was recorded on specially designed proforma and analyzed using spss version 20. for continuous variables such as age and hb (at baseline, at 12 weeks and the increase in hb) mean ± standard deviation was calculated. frequencies and percentages were measured for categorical variables such as gender. for comparison of the increase in hb between the two study drugs, the student t-test was used and p-values were obtained. p-value ≤0.05 was considered significant. results in this study 136 children with ida were enrolled, 68 in each group. the mean age of children was 24±1.26 months in the ferrous sulphate group while it was 25±1.74 months in the ferrous bisglycinate group. in the ferrous sulphate group, 39 (57%) children were male and 29 (43%) children were female. whereas in the ferrous bisglycinate group 40 (59%) children were male and 28 (41%) children were female. baseline serum hb and post-treatment serum hb were analysed in both groups showing the more level of rising in ferrous bisglycinate group than ferrous sulphate group over the same period as shown in table 1. table 1: comparison between ferrous sulphate and ferrous bisglycinate groups parameters ferrous sulphate mean+sd ferrous bisglycinate mean+sd pvalue baseline hb (g/dl) 8.7±1.64 8.0±1.49 0.995 post treatment hb (g/dl) 10.5±0.81 10.5±0.22 0.500 increase in hb (g/dl) 1.8±1.59 2.5±1.31 0.0033 discussion iron deficiency is the most common micronutrient deficiency in the world.6 our study shows that in the ferrous sulphate group means the age of children was 24±1.26 months while it was 25±1.74 months in the ferrous bisglycinate group. in the ferrous sulphate group, 39 (57%) children were male and 29 (43%) children were female. whereas in the ferrous bisglycinate group 40 (59%) children were male and 28 (41%) children were female. baseline serum hb analysis shows that in the ferrous sulphate group means hb level was 8.7 ±1.64 while in ferrous bisglycinate groups mean hb level was 8.0 ±1.49. posttreatment serum hb analysis shows that in the ferrous sulphate group means hb level was 10.5 ±0.81 and in ferrous bisglycinate group mean hb level was 10.5 ±0.22. it shows that hb raises more with ferrous bisglycinate than ferrous sulphate over the same period. the findings of the current study are comparable to other similar studies. in a study conducted by duque et al on school children of mexico city, 200 children with decreased ferritin levels were compared and randomly assigned to two groups. one group was given ferrous sulphate and the other was given ferrous bisglycinate at a dose of 30 mg /day for 12 weeks. serum ferritin concentration was almost the same in both groups after 1 week of completing iron supplementation but after 6 months of completing iron supplementation; it was significantly higher in ferrous bisglycinate group as compared to ferrous sulphate group.6 in another study by ribeiro and sigulem showed that ferrous bisglycinate cause a significant increase in hb in children when given at the dose of 5mg/kg/day. in that study, the effect on serum ferritin concentration was not checked.20 rojas and her colleague did their study on preschool children by giving milk fortified with ferrous sulphate to one group and milk fortified with ferrous bisglycinate to other groups. after 2 months they found a significant increase in serum ferritin in the ferrous bisglycinate group as compared to the ferrous sulphate group (p=0.022). hb, hematocrit and adverse reactions were the same in both groups.21 a study by pineda et al. showed that although hb increases significantly in both ferrous sulphate and ferrous bisglycinate group serum ferritin increases significantly only in iron bisglycinate group after 28 days of iron supplementation at the rate of 5mg/kg/day (p < 0.005).17 bovell-benjamin et al studied college students who were given ferrous sulphate and ferrous bis-glycinate mixed with maize porridge in a breakfast meal. the iron from the ferrous bisglycinate was absorbed 4 115 journal of rawalpindi medical college (jrmc); 2020; 24(2): 112-116 times more than that from the ferrous sulfate (p < 0.05).18 iost et al. also reported that low hb concentrations in young children can be increased through daily consumption of fluid milk fortified with 3 mg of ferrous bisglycinate.22 various studies show that ferrous bisglycinate has lesser gastrointestinal side effects than ferrous sulphate. coplin et al reported that ferrous bisglycinate has better tolerability as compared to ferrous sulphate.23 although the current study shows that ferrous bisglycinate is better in terms of improvement in hb level. however, this study has a few limitations. serum ferritin levels which are more significant tests for the evaluation of ida could not be performed after completion of therapy. the study would have become more powerful if the tolerability of both forms of iron was assessed and compared. it is suggested that further studies should be done on related research areas so that the efficacy and tolerability of newer iron preparations are further evaluated. conclusion newer iron preparation, ferrous bisglycinate is a better treatment option than conventional preparations of ferrous sulphate for increasing hb in ida in children. acknowledgements we are thankful to all patients and their parents who participated in our study. references 1. janus j. evaluation of anemia in children. am fam physician [internet]. 2010;81(12):1462–71. available from: www.aafp.org/afp. 2. ahsan s, noether j. the harriet lane handbook. 21st ed. flerlage j, engorn b, editors. philadelphia: elsevier; 2017. 1272 p. 3. sills r. nelson textbook of pediatrics. 20th ed. kliegman rm, stanton bf, schor nf, editors. philadelphia: elsevier; 2016. 3473 p. 4. afzal m, qureshi sm, lutafullah m, iqbal m, sultan m, khan sa. comparative study of efficacy, tolerability and compliance of oral iron preparations (iron edetae, iron polymatose complex) and intramuscular iron sorbitol in iron deficiency anaemia in children. j pak med assoc. 2009 nov 15;59(11):764-8. 5. mahmood t. comparison of ferrous sulphate with iron polymaltose in treating iron deficiency anaemia in children. journal of rawalpindi medical college. 2017 dec 30;21(4):3769. 6. duque x, martinez h, vilchis-gil j, mendoza e, floreshernández s, morán s, navarro f, roque-evangelista v, serrano a, mera rm. effect of supplementation with ferrous sulfate or iron bis-glycinate chelate on ferritin concentration in mexican schoolchildren: a randomized controlled trial. nutrition journal. 2014 dec 1;13(1):71. 7. akhtar s, ahmed a, ahmad a, ali z, riaz m, ismail t. iron status of the pakistani population-current issues and strategies. asia pacific journal of clinical nutrition. 2013;22(3):340. 8. powers jm, buchanan gr, adix l, zhang s, gao a, mccavit tl. effect of low-dose ferrous sulfate vs iron polysaccharide complex on hemoglobin concentration in young children with nutritional iron-deficiency anemia: a randomized clinical trial. jama. 2017 jun 13;317(22):2297-304. doi:10.1001/jama.2017.6846 9. de regil lm, jefferds me, sylvetsky ac, dowswell t. intermittent iron supplementation for improving nutrition and development in children under 12 years of age. cochrane database of systematic reviews. 2011(12). https://doi.org/10.1002/14651858.cd009085.pub2 10. balarajan y, ramakrishnan u, özaltin e, shankar ah, subramanian sv. anaemia in low-income and middle-income countries. the lancet. 2011 dec 17;378(9809):2123-35. https://doi.org/10.1016/s0140-6736(10)62304-5 11. lozoff b, jimenez e, hagen j, mollen e, wolf aw. poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. pediatrics. 2000 apr 1;105(4):e51. doi: https://doi.org/10.1542/peds.105.4.e51 12. lukowski af, koss m, burden mj, jonides j, nelson ca, kaciroti n, jimenez e, lozoff b. iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory. nutritional neuroscience. 2010 apr 1;13(2):54-70. https://doi.org/10.1179/147683010x12611460763689 13. sajid a, ikram ma, shahid hm, saeed sm. iron deficiency anemia in children; common but commonly missed. pak pediatr j [internet]. 2014;38(2):91–5. 14. saeed t. association of iron deficiency anaemia and febrile seizures in children. journal of rawalpindi medical college. 2013 dec 30;17(2):175-7. 15. world health organization, world health organization. iron deficiency anaemia: assessment. prevention and control. a guide for programme managers. geneva: who. 2001:99. 16. khalid j, ahmed mm, khalid m, butt ma, akhtar km. iron deficiency anemia; comparison of efficacy of ferrous sulphate with iron polymaltose complex for treatment of iron deficiency anemia. professional medical journal. 2018 apr 1;25(4). 17. pineda o, ashmead hd. effectiveness of treatment of irondeficiency anemia in infants and young children with ferrous bisglycinate chelate. nutrition. 2001 may 1;17(5):381-4. https://doi.org/10.1016/s0899-9007(01)00519-6 18. bovell-benjamin ac, viteri fe, allen lh. iron absorption from ferrous bisglycinate and ferric trisglycinate in whole maize is regulated by iron status. the american journal of clinical nutrition. 2000 jun 1;71(6):1563-9. https://doi.org/10.1093/ajcn/71.6.1563 19. abbas am, abdelbadee sa, alanwar a, mostafa s. efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial. the journal of maternalfetal & neonatal medicine. 2019 dec 17;32(24):4139-45. https://doi.org/10.1080/14767058.2018.1482871 20. ribeiro lc, sigulem dm. tratamento da anemia ferropriva com ferro quelato glicinato e crescimento de crianças na primeira infância. revista de nutrição. 2008 oct;21(5):483-90. https://doi.org/10.1590/s1415-52732008000500001 116 journal of rawalpindi medical college (jrmc); 2020; 24(2): 112-116 21. rojas ml, sánchez j, villada ó, montoya l, díaz a, vargas c, chica j, herrera am. effectiveness of iron amino acid chelate versus ferrous sulfate as part of a food complement in preschool children with iron deficiency, medellín, 2011. biomédica. 2013 sep;33(3):350-60. doi: http://dx.doi.org/10.7705/biomedica.v33i3.775 22. iost c, name jj, jeppsen rb, dewayne ashmead h. repleting hemoglobin in iron deficiency anemia in young children through liquid milk fortification with bioavailable iron amino acid chelate. journal of the american college of nutrition. 1998 apr 1;17(2):187-94. https://doi.org/10.1080/07315724.1998.10718745 23. coplin m, schuette s, leichtmann g, lashner b. tolerability of iron: a comparison of bis-glycino iron ii and ferrous sulfate. clinical therapeutics. 1991;13(5):606-12. http://dx.doi.org/10.7705/biomedica.v33i3.775 535 journal of rawalpindi medical college (jrmc); 2021; 25(4): 535-539 original article comparison of ondansetron & dexmedetomidine for prevention of post spinal shivering sumbal rana1, faisal wahid2, ali arslan munir3, syed ehtesham haider naqvi4, zahoor iqbal mirza5, sohail raziq6 1,2,4,5 classified anaesthetist, armed forces institute of urology, rawalpindi. 3 classified anaesthetist, combined military hospital, rawalpindi. 6 classified urologist, armed forces institute of urology, rawalpindi. author’s contribution 1,2 conception of study 1,2,4 experimentation/study conduction 1,3 analysis/interpretation/discussion 3 manuscript writing 1,3 critical review 5,6 facilitation and material analysis corresponding author dr. sumbal rana, classified anaesthetist, armed forces institute of urology, rawalpindi. email: surgeon001733@yahoo.com article processing received: 02/09/2021 accepted: 07/12/2021 cite this article: rana, s., wahid, f, munir, a.a., naqvi, s.e.h., mirza, z.i., raziq, s. comparison of ondansetron & dexmedetomidine for prevention of post spinal shivering. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 535-539. doi: https://doi.org/10.37939/jrmc.v25i4.1767 conflict of interest: nil funding source: nil access online: abstract introduction: spinal anesthesia is a big component of an anesthetist’s toolset and is used commonly in anesthetic practices. a frequent problem following spinal anesthesia is shivering due to hypothermia. its incidence is 0000-% if no prophylactic measures are taken. hypothermia during an intraoperative period is caused by cold operating rooms, body cavity exposure, extremes of age, prolonged procedures, reduced metabolism, and direct inhibition by anesthetics. objective: to compare the efficacy of ondansetron and dexmedetomidine in preventing shivering under spinal anesthesia. setting: armed forces institute of urology. study design: randomized control trial. duration: 3 months. materials and methods: the selected patients were randomly allocated using computer-generated methods into 02 groups containing 50 patients each according to study drug. ondansetron group (0.1mg/kg) (group o), and dexmedetomidine group (1mcg/1kg) (group d). shivering incidences were noted at selected time intervals and rescue doses of pethidine were administered as required. results: our study shows that group o had high mean shivering scores at 5, 30, and 4 minutes as compared to group d. conclusion: our study concludes that dexmedetomidine provides better control of shivering than ondansetron under spinal anesthesia. keywords: dexmedetomidine, ondansetron, shivering, spinal anesthesia. 536 journal of rawalpindi medical college (jrmc); 2021; 25(4): 535-539 introduction core body temperature less than 36-degree c is defined as hypothermia. hypothermia during an intraoperative period is caused by cold operating rooms, body cavity exposure, extremes of age, prolonged procedures, reduced metabolism, and direct inhibition by anesthetics.1 in normal unanaesthetized patients the hypothalamus maintains core body temperature within a narrow interthreshold range. anesthetic agents inhibit central thermoregulation by interfering with hypothalamic reflex responses. the hypothalamic inter-threshold range is increased by both general and regional anesthetics but the (background) mechanism is different for both of them. intrathecal blocks cause hypothermia by the mechanism of vasodilatation and the internal distribution of heat. unanesthetized dermatomes also send feedback of altered temperature to the hypothalamus. hypothermia leads to myocardial ischemia, arrhythmias, and increased peripheral vascular resistance. there is an altered drug metabolism, impaired mental and renal function with a potential of coagulopathy & impaired wound healing including increased incidence of surgical site infections.2 shivering is the commonest complication of an intrathecal block with incidence ranging between 1040% in different studies. erroneous pulse oximeter & ecg recording are also noted. shivering can occur due to hypothermia or neurological effects of anesthetic agents & intrathecal block shivering may lead to increased oxygen consumption and cardiac output. the risk of myocardial ischemia is increased manifolds. intraocular and intracranial pressures are raised as well. temperature can be monitored from the tympanic membrane, nasopharynx, esophagus, bladder, rectum, and skin.3,4 nasopharyngeal probes measure accurate body temperature if placed near nasopharyngeal mucosa. there is a small risk of epistaxis that can be avoided by careful insertion & lubrication. perioperative hypothermia can be prevented by physical methods such as ambient operating room temperature, use of forced-air warming blankets, heated humidification of inspired gases, use of warm iv fluids & pharmacologic methods by administration of drugs like meperidine, tramadol, clonidine, and ketamine, etc. but their safety and efficacy remains unclear and inconsistent.5 ondansetron is a 5-ht3 receptor antagonistic commonly used as an antiemetic. it has recently been used effectively for the prevention and treatment of shivering with a favorable safety profile.6 dexmedetomidine is a selection α2 agonist which causes dose-dependent sedation, anxiolysis, and analgesia without depressing respiratory drive. it is used for hypothermia prevention with promising results. in this study, we compared ondansetron and dexmedetomidine for the prevention of post-spinal shivering.7,8 materials and methods it was a prospective (quasi-experimental) study. local ethical committee approval was obtained from afiu. each participant was informed in detail about the study protocol and complete written informed consent was obtained before enrollment in the study. 100 patients of both genders, aged 18-60 years, asa physical status i & ii, undergoing elective urological procedures were included in this trial. patients who were excluded were thyroid disorders, severe cardiopulmonary diseases pregnancy, uncooperative patients, patients requiring blood transfusion, and patients with severe hepatic and renal diseases. the selected patients were randomly allocated using computer-generated methods into 02 groups containing 50 patients each according to the study drug. ondansetron group (0.1mg/kg) (group o), and dexmedetomidine group (1mcg/1kg) (group d). preoperatively demographic characteristics as age, sex, height, and weight were recorded. after admission to the or, standard asa monitoring was applied to all patients in form of pulse oximetry, ecg, and noninvasive blood pressure (nibp). the temperature of or was maintained between 24°c to 26°c. before intrathecal block, each patient was preloaded with 15ml/kg of normal saline solution. the block was introduced at either l3/4 or l4/5 interspace with 2.5ml of 0.5% hyperbaric bupivacaine (12.5mg) by an attending anesthesiologist. after completion of intrathecal blocks, the patient lay supine and oxygen was administered via a facemask (4l/min) till the end of the procedure. nasopharyngeal temperature monitoring was done every 5 minutes for 45 minutes after intrathecal blocks. intravenous fluids were kept at room temperature (24°c to 26°c). all the patients were covered with a standard single blanket. just after the intrathecal injection, one of the study drugs was given slowly by iv route over five minutes. the study drugs were prepared, diluted to a volume of 5ml, and presented as coded syringes by an anesthetist. during and shortly after completion of surgical procedures; 537 journal of rawalpindi medical college (jrmc); 2021; 25(4): 535-539 the data of nibp, heart rate, oxygen saturation, core body temperature & types of procedures were recorded. the primary outcome was the incidence of shivering in the early 45 minutes after intrathecal block; as defined by a shivering score of 3 at any time of already defined assessment points (highest score). the shivering score was assessed at 5 minutes intervals for 45 minutes after intrathecal block and graded using a scale validated by tsai and chu. grade 0 no shivering. grade 1 piloerection or peripheral vasoconstriction but no visible shivering. grade 2 muscular activity in the only muscle group. grade 3 muscular activity in more than one muscle group but no generalized. grade 4 shivering involves the whole body. if shivering of grade 3 continued beyond 15 minutes despite iv administration of study drugs and we needed to administer a rescue dose of pethidine 0.5mg/kg, then it was considered a significant side effect of the intrathecal block. the investigations who were involved in data collection and analysis were blinded to the allocation of groups and caregivers well unaware of administered iv study drugs nature. statistical analysis: continuous parameters as age, weight, and height were presented as mean +sd. a p-value applying student t-test was used to find out the association between two variables. p-value <0.05 is considered significant. a post-test chi-square test was applied. confidence interval (ci) of 95%. statistical analysis was performed using spss version 17. results the study shows that the total number of participants was 100 with 50 in group o and 50 in group d respectively without exclusion of any participant. patients included in this group were asa class l & ll. mean and sd of age, weight, and height was calculated in both groups and was comparable. pvalue was found to be <0.0000001, 0.0000071 & 0.00073 at 05, 40 and 45 minutes respectively. no reported case of prolonged shivering occurred requiring rescue drug pethidine. results are tabulated in tables 1 & 2. table 1: incidence of shivering among groups shivering group d group o p-value 5 min negative 44 13 < 0.000001 positive 6 37 40 min negative 31 9 0.0000071 positive 19 41 45min negative 25 9 0.00073 positive 25 41 table 2: shivering scores among groups shivering score time group o group d 0 1 2 3 4 0 1 2 3 4 5 min 13 15 12 10 0 44 4 2 0 0 40 min 9 15 22 4 0 31 18 1 0 0 45 min 9 19 17 5 0 25 18 6 1 0 figure 1: scores after 5 min figure 2: scores after 40 min 538 journal of rawalpindi medical college (jrmc); 2021; 25(4): 535-539 figure 3: scores after 45 min table 3: type of surgery group o group d cysto-turbt 0 1 cystolitholapaxy 3 2 cystoscopy 4 4 dviu 5 2 hydrocelectomy 3 1 orchidectomy 5 1 turbt 4 8 turp 4 10 urs 16 16 vericocelectomy 3 3 vesicolithotomy 0 2 penile abcess 1 0 tured 2 0 table 4: group o group d male female total male female total no. of patients 42 8 50 39 11 50 age (years) 44.76 ± 13.35 36.75 ± 9.32 43.48 ± 13.05 49 ± 11.59 46.27 ± 12.67 48.4 ± 11.76 weight (kg) 66.05 ± 13.4 60.625 ± 8.53 65.18 ± 12.83 67.15 ± 10.23 58.18 ± 7.55 65.18 ± 10.34 height (cm) 169.26 ± 9.04 159.625 ± 8.78 167.72 ± 9.6 168.59 ± 7.68 160.54 ± 6.33 166.82 ± 8.08 discussion after conducting this study, we have found the efficacy of prophylactic use of dexmedetomidine & ondansetron in reducing the incidence and severity of shivering that arises after intrathecal blocks. side effects of both study drugs are very few and self-limiting; making them acceptable to most individuals. ondansetron side effects are: headache & slight prolongation of qt interval on ecg. dexmedetomidine side effects are: bradycardia, heart block, and hypotension.9-11 shivering during an intraoperative period can be caused by cold operating rooms & iv fluids, body cavity exposure, high flow of non-humidified gases, and prolonged procedures. moreover, anesthetic agents, spinal and epidural anesthesia cause vasodilatation and vasoconstrictor reduced response to hypothermia. although anesthetic agents alter the threshold for shivering; it is also caused by the body’s effort to increase core body temperature & increase heat production. though rarely shivering can be nonspecific neurologic signs during emergence and occasionally may be so intense leading to hyperthermia (38-39°c) and significant metabolic acidosis, which improve once shivering stops. rarely shivering is caused by sepsis, a drug reaction, or a transfusion reaction. intense shivering increases oxygen consumption, co₂ production, and cardiac output. patients with preexisting cardiopulmonary diseases tolerate it very poorly.12 shivering can be prevented and managed by forced-air warming devices, heated humidified gases, warm iv fluids, warming lights, and increasing ambient or temperatures. ondansetron reduces the incidence of shivering especially in a dose of 0.1mg/kg. ejiro et al conducted a study comparing ondansetron, tramadol & placebo and found shivering 20%, 16.7%, and 53% in these groups respective by making it comparable to tramadol in efficacy with minimal side effects.13 mittal g compared dexmedetomidine with tramadol for post-spinal shivering time taken for cessation of shivering was significantly short. a meta-analysis reviewing 8 rct’s found ondansetron associated with a significant reduction of shivering when compared with placebo.14 while no difference was seen between ondansetron and pethidine. the mechanism by which ondansetron exhibits its anti-shivering effects is unclear but is proposed to be mediated by central inhibition of serotonin reuptake at the level of the anterior hypothalamic region. in a trial, bajwa and colleagues 539 journal of rawalpindi medical college (jrmc); 2021; 25(4): 535-539 found significant effects of dexmedetomidine as an anti-shivering agent. they found a 5% incidence of shivering as compared to 42.5% in the control group.15 (23 main. megalla and colleagues16 conducted a comparative study between dexmedetomidine, nalbuphine, and placebo. for effective control of shivering, dexmedetomidine was 100% effective, 92% of patients in nalbuphine and 32% in placebo. a lower dose of dexmedetomidine (0.5mg/kg) is studied in this trial. (24 main) dexmedetomidine anti-shivering effects are exerted via α2 agonist action.17 it may have some minor side effects like bradycardia, hypotension, and ones sedation. no case of significant side effects of either drug was observed. conclusion these results showed a significant difference in antishivering effects between dexmedetomidine and ondansetron regardless of considered effect modifiers e.g. age, weight, height, gender, etc. references 1. gabriel p, höcker j, steinfath m, kutschick kr, lubinska j, horn ep. prevention of inadvertent perioperative hypothermia – guideline compliance in german hospitals. ger med sci. 2019;17: doc07. published 2019 jul 26. doi:10.3205/000273 2. torossian a, bräuer a, höcker j, bein b, wulf h, horn ep. preventing inadvertent perioperative hypothermia. dtsch arztebl int. 2015 mar 6;112(10):166-172. doi: 10.3238/arztebl.2015.0166 3. erdling a, johansson a. core temperature – the intraoperative difference between esophageal versus nasopharyngeal temperatures and the impact of prewarming, age, and weight: a randomized clinical trial. aana j. 2015 apr;83(2):99–105. pmid: 31587750 4. yi j, lei y, xu s, et al. intraoperative hypothermia and its clinical outcomes in patients undergoing general anesthesia: national study in china. plos one. 2017;12(6): e0177221. published 2017 jun 8. doi: 10.1371/journal.pone.0177221 5. becerra á, valencia l, ferrando c, villar j, rodríguez-pérez a. prospective observational study of the effectiveness of prewarming on perioperative hypothermia in surgical patients submitted to spinal anesthesia. sci rep. 2019;9(1):16477. published 2019 nov 11. doi:10.1038/s41598-019-52960-6 6. ghasemi m, behnaz f, hajian h. the effect of dexmedetomidine prescription on shivering during operation in the spinal anesthesia procedures of selective orthopedic surgery of the lower limb in addicted patients. anesth pain med. 2018;8(2): e63230. published 2018 apr 25. doi:10.5812/aapm.63230 7. botros jm, mahmoud ams, ragab sg, et al. comparative study between dexmedetomidine and ondansteron for prevention of post spinal shivering. a randomized controlled trial. bmc anesthesiol. 2018;18(1):179. published 2018 nov 30. doi:10.1186/s12871-018-0640-3 8. nasseri k, ghadami n, nouri b. effects of intrathecal dexmedetomidine on shivering after spinal anesthesia for cesarean section: a double-blind randomized clinical trial. drug des devel ther. 2017;11:1107-1113. published 2017 apr 3. doi:10.2147/dddt.s131866 9. tatikonda cm, rajappa gc, rath p, abbas m, madhapura vs, gopal nv. effect of intravenous ondansetron on spinal anesthesia-induced hypotension and bradycardia: a randomized controlled double-blinded study. anesth essays res. 2019; 13(2):340-346. doi: 10.4103/aer.aer_22_19 10. shen qh, li hf, zhou x, lu y, yuan xz. 5-ht3 receptor antagonists for the prevention of perioperative shivering undergoing spinal anaesthesia: a systematic review and metaanalysis of randomised controlled trials. bmj open. 2020; 10(10):e038293. published 2020 oct 5. doi:10.1136/bmjopen2020-038293 11. lopez mb. postanaesthetic shivering – from pathophysiology to prevention. rom j anaesth intensive care. 2018;25(1):73-81. doi: 10.21454/rjaic.7518.251.xum 12. alfonsi p, bekka s, aegerter p; sfar research network investigators. prevalence of hypothermia on admission to recovery room remains high despite a large use of forced-air warming devices: findings of a non-randomized observational multicenter and pragmatic study on perioperative hypothermia prevalence in france. plos one. 2019;14(12): e0226038. published 2019 dec 23. doi: 10.1371/journal.pone.0226038 13. gicheru m, mung’ayi v, mir s, kabugi j. comparison of weight-adjusted dose versus fixed dose ondansetron in preventing shivering following spinal anaesthesia for caesarean deliveries. afr health sci. 2019;19(3):2740-2751. doi:10.4314/ahs.v19i3.50 14. he k, zhao h, zhou hc. efficiency and safety of ondansetron in preventing postanaesthesia shivering. ann r coll surg engl. 2016;98(6):358-366. doi:10.1308/rcsann.2016.0152 15. bajwa sj, gupta s, kaur j, singh a, parmar ss. reduction in the incidence of shivering with perioperative dexmedetomidine: a randomized prospective study. anaesthesiol clin pharmacol. 2012;28(1)86-91. doi: 10.4103/0970-9185.92452. 16. megalla sa, mansour hs. dexmedetomidine versus nalbuphine for treatment of post spinal shivering in patients undergoing vaginal hysterectomy: a randomized, double blind, controlled study. egypt j anal chem. 2017;33: 47-52. doi: 10.1016/j.egja.2016.10.012 17. morgan, g. e., mikhail, m. s., & murray, m. j. (2013). clinical anesthesiology. new york: lange medical books/mcgraw hill medical pub. division. 18. indian j anaesth. 2014 may-jun; 58(3): 257–262. doi: 10.4103/0019-5049.135031. pmcid: pmc4090989 pmid: 250244 geeta mittal, kanchan gupta,1 sunil katyal, and sandeep kaushal1 495 journal of rawalpindi medical college (jrmc); 2021; 25(4): 495-498 original article frequency of capillary leak syndrome in dengue fever patients safina hameed qureshi1, sania hameed qureshi2, syed fahd shah3, farid ullah shah4, syed hussain shah5, syed zubair shah6 1,2 senior registrar, department of medicine, federal government poly clinic hospital, islamabad. 3 associate professor, department of surgery, federal general hospital, islamabad. 4 consultant physician, federal government poly clinic hospital, islamabad. 5 assistant professor, department of rehabilitation medicine, combined military hospital, lahore. 6 professor, department of paediatrics, combined military hospital, lahore. author’s contribution 1 conception of study 1,2,4 experimentation/study conduction 2 analysis/interpretation/discussion 3 manuscript writing 5,6 critical review 4 facilitation and material analysis corresponding author dr. sania hameed qureshi, senior registrar, department of medicine, federal government poly clinic hospital, islamabad. email: drsaniaqureshi@gmail.com article processing received: 28/06/2021 accepted: 01/11/2021 cite this article: qureshi, s.h., qureshi, s.h., shah, s.f., shah, u., shah, s.h., shah, s.z. frequency of capillary leak syndrome in dengue fever patients. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 495-498. doi: https://doi.org/10.37939/jrmc.v25i4.1716 conflict of interest: nil funding source: nil access online: abstract introduction: dengue is a viral disease and it is spread to the world by mosquitos. it is now common in many parts of the world. the severe form of dengue fever with bleeding manifestations is called dengue hemorrhagic fever. some of the dengue fever patients developed a capillary leak during a critical period of illness. this study aims at determining the frequency of capillary leaks in admitted dengue fever patients in tertiary care hospitals. materials and methods: the study was conducted over a period of one month from 1st october to 30th october 2019 at the department of medicine federal government polyclinic post graduate medical institute, islamabad. this cross-sectional study comprised of 200 consecutive hospitalized (≥14 years of both gender) dengue fever patients. results: capillary leak syndrome was found in 75 patients with dengue fever. all of them were primary dengue patients. both ascites and effusion were present in 31 patients. ascites were only found in 25 patients, pleural effusion bilateral in 7, right-sided pleural effusion in 11, and left-sided in 1 patient. conclusion: it is concluded that capillary leak syndrome is common in dengue patients and its early diagnosis helps us in better management during a critical phase of illness with a better outcome. keywords: dengue fever, capillary leak syndrome, dengue shock. 496 journal of rawalpindi medical college (jrmc); 2021; 25(4): 495-498 introduction dengue is a vector-borne viral human disease across the tropical and sub-tropical regions of the world. dengue virus is transmitted from one person to another person by the bite of female aedes aegypti and aedes albopictus.1 dengue is present worldwide with almost 128 countries are known to have dengue outbreaks. about 390 million cases occur per year.2 pakistan is a subtropical country having all four serotypes. dengue can be throughout the year but an outbreak occurs between the summer to autumn season especially after the monsoon.3 dengue epidemic is a major public threat since 2005 following millions of people at risk. during the current year, 2019 over 25,000 dengue cases have been confirmed from across the country.4 there are three phases of dengue fever illness phase i is the phase of febrile illness followed by the critical phase and then there is a recovery. patients who don’t develop increased capillary permeability in transition from febrile to afebrile phase usually get better and do not enter into the critical phase.5 the severity of capillary leak may be different in different patients and severe permeability to plasma and fluids may cause dengue shock or pleural effusion. an increase in pleural effusion may cause increased respiratory distress which is a sign of severe dengue.6 this study is only confined to those dengue patients who had capillary leak syndrome in the critical phase of dengue. capillary leak syndrome is one of the big problems of severe dengue. the main features of the capillary syndrome are hemoconcentration, hypoalbuminemia, pleural effusion, ascites, and pericardial effusion. anasarca is not a characteristic of capillary leak syndrome. capillary leak syndrome is the main pathological factor resulting in dengue shock syndrome and dengue haemerrohgic fever. the hematocrit in this condition is usually >40% but maybe as high as 55-60%.7 this increase in hematocrit is because of increased leakiness to plasma in the late stage of the febrile phase and after the setting of pyrexia may remain for 24 hours to 48 hours. timely identification of capillary leak syndrome is important for prompt fluid replacement and indicated progression to dengue shock syndrome. the present study conducted on dengue fever patients is an attempt to describe capillary leak syndrome who were admitted. materials and methods the study was conducted at department of medicine, government polyclinic post graduate medical institute, islamabad for the period of one month from 1st october to 30th october 2019 during an epidemic outbreak of dengue fever in pakistan. it included 200 consecutive confirmed dengue patients (≥14 years of both genders) who were hospitalized for management for dengue fever. out of the total of 200 patients with dengue fever, capillary leak syndrome was found in 75 patients. we included these 75 patients with capillary leak syndrome in this study. all these patients had a critical phase of dengue fever. demographic data, primary or secondary dengue, dengue test report, hematocrit, platelet counts, serum albumin, chest x-ray, ultrasonography chest and abdomen data were collected and recorded on specially designed proforma. laboratory diagnosis methods for dengue fever include detection of dengue ns1 antigen and antibodies (igm/igg) or both. primary dengue fever was diagnosed in cases that had either positive ns1 antigen or igm antibodies or both. secondary dengue fever was diagnosed if the patient had a positive ns1 antigen or igm antibodies along with igg antibodies or the presence of all three (ns1 antigen, igm, and igg antibodies). all patients with dengue fever were followed for capillary leakage and other complications by physical examination and laboratory tests (including complete blood count, biochemistry, and ultrasonography of abdomen and pleural cavities. all data were entered on a structured proforma and data was analyzed on spss version 21. results out of 200 patients with dengue fever, 75(37.5%) had capillary leak syndrome. males were 47(62.6%) and 28(37.3%) were females. the median age, age range, and male to female ratio are shown in figure 1. the tests results for ns1, igm, and igg antibodies are shown in table 2. all 75 patients (100%) were presented with dengue fever for the first time and no patient presented with dengue fever the second time. hematocrit > 37.5% in 49(65.3%) patients and >50% in 7(9.3%) patients. hypoalbuminemia was seen in 64(85.3%) patients. mild thrombocytopenia in 6(8%), moderate in 13(17.3%), and severe in 56(74.6%) patients. detail of plasma leaks in different sites and polyserositis (31 (41.3%) are detailed in table-3. 497 journal of rawalpindi medical college (jrmc); 2021; 25(4): 495-498 ascites were present in 25 (33.3%) patients and pleural effusion was present in 19(25.3%) patients with 11(14.6%) cases having right-sided, 7(9.3%) cases having bilateral and only 1 (1.3%) cases had isolated left-sided pleural effusion. there was no mortality in our study. figure 1: age wise presentation (n=75) table 1: laboratory result dengue serology nsi 73 igm 02 hematocrit 37.540.0 40.1-50.0 50.160.0 11 (14.6%) 38 (50.6%) 07 (9.33%) hypoalbumi nemia 3.5-3.0 2.9-2.5 <2.5 18 (24%) 38 (50.6%) 08 (10.6%) platelet count(x10 3 /c mm) <20 20-50 50-100 100150 32 24 13 06 table 2: site of capillary leak site of capillary leak no. of cases (%)(n=75) ascites + pleural effusion 31(41.3%) ascites only 25(33.3%) isolated right sided pleural effusion 11(14.6%) isolated left sided pleural effusion 01(1.33%) bilateral pleural effusion 07(9.33%) discussion dengue fever varies in severity and it can present just as febrile illness or with severe dengue fever disease.8 plasma leak which starts at the end stage of febrile illness and it may lead to dengue shock is characteristic of severe disease.9 capillary leak syndrome is a more common severe complication of dengue fever as compared to other feared complications which cause a lot of panic and distress such as severe bleeding and organ impairment.10 hematocrit ≥20%, hematocrit≤20% after fluid replacement and features such as pleural effusion, ascites, and hypoproteinemia are the hallmark of capillary leak syndrome.11 as hypoalbuminemia is generally not present and plasma leak is difficult to recognize that’s why it is difficult to predict that those with dengue fever may have severe complications.12,13 in our study hematocrit level of more than 37.5 was seen in 49(65.3%) cases. hypoaluminemia is moderate to severe in 46(61.3%) patients. ultrasound can be used to see even a little amount of pleural effusion and ascites thus helping in detecting a capillary leak.14 it is 100% accurate and 2009 who guidelines recommend ultrasound as a good tool for capillary leak syndrome assessment.15 thus ultrasound is better than hematocrit and hypoalbuminemia to assess the presence of capillary leak syndrome early in adult dengue patients 16 in our study 75 patients were reported to have capillary leak syndrome. according to who guidelines 2009 describes severe dengue is a shock, severe bleeding, organ failure, or respiratory failure due to leakage of plasma.17 many studies had demonstrated the prevalence of capillary leakage on ultrasound from 34% to 100%.18 in our study 75 cases (37.5%) out of 200 dengue hemorrhagic fever patients had a capillary leak on ultrasound. in this study of 75 cases of capillary leak syndrome, all of them had primary dengue fever (100%). capillary leak syndrome is as frequently seen in primary as well as in secondary dengue fever.19 the underlying mechanism of capillary leakage syndrome in dengue fever is not fully understood yet.20 previously the concept was that the most severe features of dengue develop in individuals who had the previous infection of dengue with any of the strains.21 second-time infection with another strain results in a low level of antibodies, these antibodies instead of removing the virus form an antigen-antibody complex.22 this causes an increase in virus entry into white cells and results in enormous replication of virus which activates many folds in cytokine synthesis and activation of complement factors. the vasoactive factors produced by the macrophages lead to many fold rise in vascular permeability causing leakage of plasma, decrease in circulating volume, and shock.23 meltzer et al noted that secondary infection is not mandatory to develop capillary leak syndrome and the 498 journal of rawalpindi medical college (jrmc); 2021; 25(4): 495-498 risk of severe disease may not be increased by secondary infection.23 in our study we have noted that it is not necessary that patients must have secondary dengue infection to develop the capillary leak syndrome or severe dengue infection.24 the idea that secondary infection leads to an enhanced immune response which in turn causes capillary leakage in dengue fever needs further evaluation. in the capillary leak, syndrome fluid was collected at multiple sites. in this study, polyserositis was present in 31(41.3%) patients, followed by ascites in 25(33.3%), pleural effusion in 19(25.3%) patients. the accumulated fluid was mild to moderate in present study patients and resolved in a week's time and no particular treatment was needed. we had some limitations in our study. as this study was conducted in a tertiary care hospital where severe cases are referred for management this may cause selection bias. secondly, a further study is needed on a larger sample conducted at multiple centers to validate our result. conclusion one of the most important things for the clinician is to recognize those patients who may progress to severe disease, so time management and hydration stop the progression of dengue fever to severe dengue fever and its complications. early ultrasonography for capillary leak syndrome is suggested in severe dengue patients. capillary leakage in primary dengue is as common as in secondary dengue fever. references 1. bhatt s, gething pw, brady oj, messina jp, farlow aw, moyes cl, et al. the global distribution and burden of dengue. nature 2013; 496:504– 7. doi: 10.1038/nature12060 2. gbd 2015 mortality and causes of death collaborators. global, regional, and national life expectancy, all-cause mortality, and causespecific mortality for 249 causes of death, 1980-2015: a systematic analysis for the global burden of disease study 2015. lancet. 2016 oct 8;388(10053):1459-1544. doi: 10.1016/s0140-6736(16)31012-1. 3. lee th, lee lk, lye dc, leo ys. current management of severe dengue infection. expert rev anti infect ther. 2017 jan;15(1):67-78. doi: 10.1080/14787210.2017.1248405. 4. malavige gn, ogg gs. t cell responses in dengue viral infections. j clin virol. 2013 dec;58(4):605-11. doi: 10.1016/j.jcv.2013.10.023. 5. yacoub s, wertheim h, simmons cp, screaton g, wills b. microvascular and endothelial function for risk prediction in dengue: an observational study. lancet. 2015 feb 26;385 suppl 1:s102. doi: 10.1016/s0140-6736(15)60417-2. 6. yacoub s, lam pk, le vu hm, le tl, ha nt, toan tt et al association of microvascular function and endothelial biomarkers with clinical outcome in dengue: an observational study. j infect dis. 2016 sep 1;214(5):697-706. doi: 10.1093/infdis/jiw220. 7. mongkolsapaya j, dejnirattisai w, xu xn, vasanawathana s, tangthawornchaikul n, chairunsri a et al original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. nat med. 2003 jul;9(7):921-7. doi: 10.1038/nm887. 8. chau tn, quyen nt, thuy tt, tuan nm, hoang dm, dung nt et al dengue in vietnamese infants – results of infection‐enhancement assays correlate with age‐related disease epidemiology, and cellular immune responses correlate with disease severity. j infect dis. 2008 aug 15;198(4):516-24. doi: 10.1086/590117. 9. kamaladasa a, gomes l, jeewandara c, shyamali nl, ogg gs, malavige gn. lipopolysaccharide acts synergistically with the dengue virus to induce monocyte production of platelet activating factor and other inflammatory mediators. antiviral res. 2016 sep;133:183-90. doi: 10.1016/j.antiviral.2016.07.016 10. fox a, le nm, simmons cp, wolbers m, wertheim hf, pham tk et al immunological and viral determinants of dengue severity in hospitalized adults in ha noi, viet nam. plos negl trop dis. 2011 mar 1;5(3):e967. doi: 10.1371/journal.pntd.0000967. 11. jeewandara c, gomes l, wickramasinghe n, gutowska-owsiak d, waithe d, et al. 2015. platelet activating factor contributes to vascular leak in acute dengue infection. plos negl trop dis. 2015 feb 3;9(2):e0003459. doi: 10.1371/journal.pntd.0003459. 12. hottz ed, lopes jf, freitas c, valls‐de‐souza r, oliveira mf, bozza mt et al platelets mediate increased endothelium permeability in dengue through nlrp3‐inflammasome activation. blood. 2013 nov 14;122(20):3405-14. doi: 10.1182/blood-2013-05-504449. 13. st john al, rathore ap, raghavan b, ng ml, abraham sn. 2013. contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. elife. 2013 apr 30;2:e00481. doi: 10.7554/elife.00481. 14. trung dt, wills b. 2010. systemic vascular leakage associated with dengue infections – the clinical perspective. curr top microbiol immunol. 2010;338:57-66. doi: 10.1007/978-3-642-02215-9_5. 15. beatty pr, puerta-guardo h, killingbeck ss, glasner dr, hopkins k, harris e. 2015. dengue virus ns1 triggers endothelial permeability and vascular leak that is prevented by ns1 vaccination. sci transl med. 2015 sep 9;7(304):304ra141. doi: 10.1126/scitranslmed.aaa3787. 16. glasner dr, ratnasiri k, puerta-guardo h, espinosa da, beatty pr,harris e. 2017. dengue virus ns1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components. plos pathog. 2017 nov 9;13(11):e1006673. doi: 10.1371/journal.ppat.1006673. 17. wills ba, oragui ee, dung nm, loan ht, chau nv, et al. 2004. size and charge characteristics of the protein leak in dengue shock syndrome. j infect dis. 2004 aug 15;190(4):810-8. doi: 10.1086/422754. 18. suwarto s, sasmono rt, sinto r, ibrahim e, suryamin m. 2017. association of endothelial glycocalyx and tight and adherens junctions with severity of plasma leakage in dengue infection. j infect dis. 2017 mar 15;215(6):992-999. doi: 10.1093/infdis/jix041 19. tang th, alonso s, ng lf, thein tl, pang vj, et al. 2017. increased serum hyaluronic acid and heparan sulfate in dengue fever: association with plasma leakage and disease severity. sci rep. 2017 apr 10;7:46191. doi: 10.1038/srep46191 20. chen hr, chuang yc, lin ys, liu hs, liu cc, et al. 2016. dengue virus nonstructural protein 1 induces vascular leakage through macrophage migration inhibitory factor and autophagy. plos negl trop dis. 2016 jul 13;10(7):e0004828. doi: 10.1371/journal.pntd.0004828. 21. ferreira ra, de oliveira sa, gandini m, ferreira lda c, correa g, et al. 2015. circulating cytokines and chemokines associated with plasma leakage and hepatic dysfunction in brazilian children with dengue fever. acta trop. 2015 sep;149:138-47. doi: 10.1016/j.actatropica.2015.04.023. 22. syenina a, jagaraj cj, aman sa, sridharan a, st john al. 2015. dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin fcγ receptors. elife. 2015 mar 18;4:e05291. doi: 10.7554/elife.05291. 23. meltzer e, heyman z, bin h, schwartz e. capillary leakage in travelers with dengue infection: implications for pathogenesis. am j trop med hyg. 2012 mar;86(3):536-9. doi: 10.4269/ajtmh.2012.10-0670. 24. avirutnan p, punyadee n, noisakran s, komoltri c, thiemmeca s, et al. 2006. vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein ns1 and complement. j infect dis. 2006 apr 15;193(8):1078-88. doi: 10.1086/500949. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 33-36 33 original article pattern of head injury and recovery in first and second rider in motor bike accidents yasir shehzad,. ayesha arshad, nadeem akhter, department of neurosurgery, dhq hospital and rawalpindi medical college,, rawalpindi abstract background: to compare the rate and pattern of head injury sustained by the first vs. second rider and mortality rate and functional outcome of the two groups. methods: in this cross sectional study all adult patients presenting with head injury resulting from a motorcycle accident, during the study period were enrolled.proforma’s were filled by the on-duty doctor, including the demographic details, details regarding helmet and first or second rider, neurological status, additional injuries and radiological pattern of injury. these patients were divided into two groups: group-1 (first riders) and group-2 (second riders) and both groups were compared for the above details, and followed. all patients received the standard treatment for their respective injuries and the two groups were compared for the mortality and neurological and functional outcome, assessed by using the extended glascow outcome scale. (egos). results: a total of 360 patients were included in the study. of these,65% patients were in group-1 and 35% were in group-2. the mean age of the two groups was 27.86 and 30.12 years respectively. all patients in group-1 were males while 61.9% in group-2 were males. majority of the riders in both groups were not wearing helmets at the time of accident. major injury in both the groups was facial injury but the frequency of facial injury was significantly higher in group-1 as compared to group-2 i.e. 20.5% vs. 11.9% (p = 0.040). ct brain showed normal scan in 15.4% patients in group-1 and in 2.4% patients in group-2. in group-1, ct brain showed highest frequency of traumatic brain contusions (24.4%) followed by extradural hematomas (14.1%) and cranium fracture (12.8%). in group-2, ct brain showed highest frequency of traumatic brain contusions (35.7%) followed by cranium fracture (16.7%), asdh (9.5%) and tsah (9.5%). complete recovery was significantly higher in group-1 as compared to group-2 (p = 0.011). conclusion: in motor bike riding head injury is a potential threat not only to the 1st rider but also to the 2nd rider as well. by using helmets head injury, which is fatal in most of the instances, can be avoided. key words: head injury, motor bike, helmet introduction head injury is the main cause of death in motorcycle accidents. motorcycle riders are much more vulnerable than vehicle drivers for several reasons: they are less protected and less visible than other road users, however their use is increasing given that motorcycle is an economical transportation among the youth, especially in a third world country like pakistan. many studies done worldwide have shown that wearing a helmet decreases the head injury as well as the mortality rate in motorcycle accidents, but little has been done so far to explore the injury pattern sustained by the first and the second rider, or to compare their mortality rates and functional outcome. 1-3 there are many possible causes of brain injuries (tbis), but one of the leading causes is motorcycle accidents1. motorcycle accidents combined with auto accidents are the biggest cause of tbis in the united states. for motorcyclists, one out of five involved in accidents sustains head or neck injuries which lead to most motorcyclist deaths. more than three thousand people die in the us each year in motorcycle accidents, while another fifty thousand sustain non-fatal injuries. motorcycle riders are much more vulnerable than vehicle drivers for several reasons: they are less protected and less visible than other road users as well being smaller than other vehicles, however their use is increasing given the increase in autoand fuel prices, hence making motorcycle an important vehicle for transportation among the youth, especially in a third world country like pakistan. but the cost of an accident that causes traumatic brain injury can be severe, a factor that is again more important in developing countries like ours. traumatic brain injury causes journal of rawalpindi medical college (jrmc); 2017;21(1): 33-36 34 brain damage that can range from a mild concussion to severe disabilities such as trouble in communicating, personality changes, schizophrenia, or even a coma. because the brain cannot heal itself the way other organs do, these are often lifelong problems that cost tens of thousands of rupees to treat. family members are also affected as they bear a serious emotional and financial burden. 4-5 many studies done worldwide have shown that wearing a helmet decreases the severity of head injury as well as the mortality rate in motorcycle accidents.2,3, nhtsa published a report in oct., 2008, that showed, helmet wearing is associated with decreased head and neck injuries. similar studies have been showing this same result time and again, but little has been done so far to explore the injury pattern sustained by the first and the second rider, or to compare their mortality rates and functional outcome. this is important because, especially in our culture, it is common for the lady to be the second rider, and it is common sight to see a lady sitting in the rear of motorcycle, in an awkward side-saddle position, her feet dangling dangerously, often with a baby in her lap. there is no concept for a helmet for these 2nd (and 3rd ) riders in our society. 6-9 patients and methods this cross-sectional comparative study was carried out at dhq hospital, rawalpindi from 1st oct 2014 to 31st march 2016 . dhq hospital, rawalpindi, is a reference centre for neuro-trauma, hence we get patients not only from all over the city and the adjacent areas, but also from the northern areas, ajk and most of the upper punjab as well. all adult patients presenting to dhq hospital, with head injury resulting from a motorcycle accident, during the study period were enrolled after informed consent by the patient or the family, in case of unconscious patients. children and patients or families unwilling for participation were excluded at this point. proformas were filled by the on-duty doctor, later handed over to the chief investigator, including the demographic details, details regarding helmet use and neurological status, additional injuries and radiological pattern of injury sustained by the first and/or second rider.total 360 patients fulfilling the inclusion criteria were included in the study through non-probability consecutive sampling. these patients were divided into two groups: first riders were included in group-1 and second riders were included in group-2. both groups were compared for the above details, and followed. all patients received the standard treatment for their respective injuries, as per our standard protocol, and no distinctive treatment was given to any of these patients for being part of the study, hence this was a strictly observational study, and no intervention done. the two groups were compared for the mortality and neurological and functional outcome, assessed by using the extended glascow outcome scale. (egos). qualitative variables were described as frequency and percentages and compared through chisquare test. a p-value < 0.05 was considered as significant. results a total of 360 patients were included in the study. of these, 234 (65%) patients were in group-1 and 126 (35%) were in group-2. average age in group-1 was 27.86 years (sd = 10.12) and in group-2 it was 30.12 years (sd = 15.71). both the groups were comparable with respect to age (p = 0.146). in group-1 all (100%) the individuals were males while in group-2, 78 (61.9 %) were males. majority of the riders in both groups were not wearing helmets at the time of accident but the frequency of not wearing helmet was significantly higher in group-2 (p = 0.003). majority of the patients in both the groups did not have any significant associated injuries. major injury in both the groups was facial injury but the frequency of facial injury was significantly higher in group-1 as compared to group-2 i.e. 20.5% vs. 11.9% (p = 0.040) (table-1). table 1: associated injuries frequency in the two groups of patients none neck fascial long bone fractur es chest others multip le syste m involv ement gp – 1 ist rider 122 5 47 18 3 20 14 gp – 2 2nd rider 80 2 17 5 0 12 8 ct brain showed normal scan in 15.4% patients in group-1 and in 3 (2.4%) patients in group-2. in group1, ct brain showed highest frequency of traumatic brain contusions (24.4%) followed by extradural hematomas (14.1%) and cranium fracture (12.8%). in group-2, ct brain showed highest frequency of traumatic brain contusions (35.7%) followed by journal of rawalpindi medical college (jrmc); 2017;21(1): 33-36 35 cranium fracture (16.7%), asdh (9.5%) and tsah (9.5%). the difference was statistically significant (p < 0.001). (table-2).complete recovery was significantly higher in group-1 as compared to group-2 (p = 0.011). frequency of good egos score (score: 5 – 8) was significantly higher in group-2 as compared to group-1 (p = 0.007). mortality rate was similar in both the groups (p = 0.781). (table-3) table2: comparison of ct brain between both the groups ct brain findings group-1 (n = 234) group-2 (n = 126) p-value normal 36(15.4%) 3 (2.4%) < 0.001 brain contusions 57 (%) 45 (%) 0.022 edh 33 (14.1%) 9 (7.1%) 0.050 cranium fracture 30 (12.8%) 21 (16.7%) 0.318 dai 21 (9%) 3 (2.4%) 0.017 tsah 15 (6.4%) 12 (9.5%) 0.285 asdh 12 (5.1%) 12 (9.5%) 0.111 icb 6 (2.6%) 9 (7.1%) 0.038 multiple 24 10.3%) 12(9.5%) 0.825 edh: extra dural haematoma;dai: diffuse axonal injury ; tsah: ; asdh: ; icb: intra cerebral bleed table-3: comparison of outcome between both the groups final outcome group-1 (n = 234) group-2 (n = 126) p-value complete recovery 144 (61.5%) 60 (47.6%) 0.011 good egos (5-8) 30 (12.8%) 30 (23.8%) 0.008 disability (egos <5) 24 (10.3%) 18 (14.3%) 0.256 death 36 (15.4%) 18 (14.3%) 0.781 discussion motor bike accidents are a frequent and rising cause of head injury in the urban areas as motor bike becomes more and more popular as an economical means of transport. 1 the rising prices of fuel and the cheaply available motorbikes, and that too on easy installments, have actually given rise to a trend of buying and riding motorbikes, especially among the youth and also in the lower middle class. unfortunately, both these groups lack the essential road civic sense and view the ownership of the motorbike as a means of trespassing the roads, rather than a responsibility. the sad result is too many motorbikes violating too many traffic rules, even on the busiest of roads and highways, thereby jeopardizing not only their own safety but that of the other road-users too. riding in the middle of the road, or crossing the road on a main highway, overtaking from the wrong side, forcing cars to stop or sway are favorites of the motorbike riders. not to mention here, the one-wheeling, a favorite pastime of our youngsters, but invariably fatal if and when done on busy roads and highways. hence the role of everyone in the society is important and must come into play, to decrease the motorbike related injuries in the riders, including the parents, the law-enforcement agencies and the government.3,4 strict laws should be made and enforced, parents should take timely and strict action to prevent their children from engaging in such activities and awareness campaigns should be launched to make all classes of our society familiar with the civic road sense and make them realize that driving and riding on a road is not so much a privilege as it is a responsibility. motorbikes come cheap, but the responsibility the ownership brings comes expensive, and the price that we pay for the lack of it is much too high.10-15 it has been proved time and again, in international studies, that helmet use is mandatory for motorbike riders to help prevent head injury.2-8 laws are in place and the implementation of these laws has decreased the mortality from head injury in motor cycle accidents.3,4 not only this, it has also decreased the hospital stay and financial burden of head injury from motor cycle accidents5,6. the cochrane systemic review done in 2004 has also found that helmet use decreases the frequency, severity and mortality from motor cycle related head injury. but again, in our society, this has been turned into a dilemma. first, because helmets are expensive, so to say, and like we mentioned before, motorbike comes cheap.. but what is not mentioned here, is the price of a head injury caused by the lack of a helmet, which ranges from well over a lac to millions in terms of time of work lost, family and social burden, etc. 16-20 in this study, we focused on the head injury pattern seen in the 1st and the 2nd rider in motorbike accidents, another important aspect of our irresponsible attitude towards road safety, because even people who believe and accept the need for helmet use, present a very interesting picture in our society. it is common belief and practice in our society that only the 1st rider needs and deserved maximum protection in case of accident. hence, if a guy would want to ride a motor-bike very safely, he would buy himself a helmet, but almost never for the 2nd rider, which unfortunately, more journal of rawalpindi medical college (jrmc); 2017;21(1): 33-36 36 often than not is a lady, and is usually sitting in a sidesaddle manner, her feet dangling on one side, often with a baby in her lap. may god help the poor creatures in case the motorbike has to stop suddenly or take a sharp turn, as can happen on a busy road. 21 can someone put an end to this horrible practice? since no sane man would put his whole family into danger knowingly, we can only give him the benefit of doubt by saying maybe he is himself not aware of the dangers of this practice. 22-25 conclusion 1. motor bike riders are at high risk for severe head injury and although the head injury pattern on ct brain is more severe for 1st rider in our study but the associated injuries as well as the outcome is comparable in both groups. 2. by using helmets head injury, which is fatal in most of the instances, can be avoided. references 1. richter m, otte d, lehmann u, chinn b, schuller e, doyle dl. head injury mechanisms in helmet-protected motorcyclists: prospective multicenter study. j trauma,. 2001;51(5):949-58. 2. sosin dm, sacks jj. motorcycle helmet-use laws and head injury prevention.jama. 1992 25;267(12):1649-51. 3. sosin dm, sacks jj, holmgreen p. head injury--associated deaths from motorcycle crashes. relationship to helmet-use laws.jama, 1990 ;264(18):2395-99. 4. macleod jb, digiacomo jc, tinkoff g. an evidence-based review: helmet efficacy to reduce head injury and mortality in motorcycle crashes: east practice management guidelines. j trauma,;69(5):1101-11. 5. mertz kj and weiss hb. changes in motorcycle-related head injury deaths, hospitalizations, and hospital charges following repeal of pennsylvania's mandatory motorcycle helmet law.am j public health, 2008;98(8):1464-67. 6. la torre g, van beeck e, bertazzoni g, ricciardi w. head injury resulting from scooter accidents in rome: differences before and after implementing a universal helmet law. eur j public health, 2007;17(6):607-11. 7. lardelli claret p, luna del castillo jde d, jimenez moleon jj.an assessment of the effect of helmet use among cyclists and the risk of head injury and death in spain, 1990 to 1999. med clin (barc), 2003;120(3):85-88. 8. richter m, otte d, lehmann u, chinn b, schuller e. head injury mechanisms in helmet-protected motorcyclists: prospective multicenter study. j trauma, 2001;51(5):94958. 9. liu b, ivers r, norton r, blows s, lo sk. helmets for preventing injury in motorcycle riders. cochrane database syst rev, 2004(2): 901-04 10. stella j, cooke c, sprivulis p. most head injury related motorcycle crash deaths are related to poor riding practices. emerg med, 2002;14(1):58-61. 11. muszynski ca, yoganandan n, pintar fa, gennarelli ta. risk of pediatric head injury after motor vehicle accidents.j neurosurg , 2005102(4 suppl):374-79. 12. friedland jf, dawson dr. function after motor vehicle accidents: a prospective study of mild head injury and posttraumatic stress. j nervment dis , 2001;189(7):426-34. 13. banerjee kk, agarwal bb, kohli a, aggarwal nk. study of head injury victims in fatal road traffic accidents in delhi. indian j med sci, 1998;52(9):395-98. 14. chung y., song t.j., yoon b.j. injury severity in deliverymotorcycle to vehicle crashes in the seoul metropolitan area. accid. anal. prev ,2014;62:79–86. 15. shaheed msb and gkritza k. a latent class analysis of singlevehicle motorcycle crash severity outcomes. anal. methods accid. res, 2014;2:30–38. 16. atchley p, shi j, yamamoto t. cultural foundations of safety culture: a comparison of traffic safety culture in china, japan and the united states.transp. res.part f traffic psychol. behav, 2014;26:317–25. 17. rome ld and senserrick t. factors associated with motorcycle crashes in new south wales, australia, 2004 to 2008. transp. res. rec. j. transp. rese. board, 2011;2195:54–61. 18. greene w.h. econometric analysis. 7th ed. prentice hall; upper saddle river, nj, usa: 2012. 19. kim c, wiznia dh, averbukh l, feng d. the economic impact of helmet use on motorcycle accidents: a systematic review and meta-analysis of the literature from the past 20 years. traffic inj. prev, 2015;16:1-7. 20. zeng q, huang h, pei x, wong s. modeling nonlinear relationship between crash frequency by severity and contributing factors by neural networks. anal. methods accid res, 2016;10:12–25. 21. wang w., guo x. traffic enginieering. 2nd ed. southeast university press; nanjing, china: 2011. 22. chin hcand haque mm. effectiveness of red light cameras on the right-angle crash involvement of motorcycles. j. adv. transp, 2010;46:54–66. 23. wang j and huang h. road network safety evaluation using bayesian hierarchical joint model. accid. anal. prev, 2016;90:152–58. 24. xu p and huang h. modeling crash spatial heterogeneity: random parameter versus geographically weighting. accid. anal. prev,. 2015;75:16–25. 25. mannering fl and bhat cr. analytic methods in accident research: methodological frontier and future directions. anal. methods accid. res ,2014;1:1–22. 10.1016/j.amar.2013.09.001. summary journal of rawalpindi medical college (jrmc); 2017;21(2): 127-130 127 original article door to needle time in acute myocardial infarction patients muhammad usman 1,hashaam khurshid 2, muhammad usama iftikhar 3 1. department of cardiology, benazir bhutto hospital and rawalpindi medical university; 2. department of medicine benazir bhutto hospital and rawalpindi medical university abstract background: to determine the current door-toneedle time for the administration of fibrinolytics for acute myocardial infarction (ami) in emergency room. methods: in this cross sectional study patients presenting with acute myocardial infarction (ami) were included. time interval from patient’s presentation to administration of streptokinase to the patient, was calculated . the total door-to-needle time was calculated and patient demographics and presentation, physician’s experience, clinical symptomology and reasons for delays in thrombolytic administration were analysed. results: sixty six patients, presented with ami, were given streptokinase. out of these, 6% received streptokinase within 15 minutes of arrival in emergency, 22.7%received streptokinase in 30 minutes, 33.33% received thrombolytic agent in 45 minutes, 27.27% received thrombolytic therapy in 60 minutes, and 10.7% received thrombolytic therapy in 90 minutes. the mean door to needle time calculated was 44.8 minutes. patients receiving reperfusion therapy within 30 minutes were 28.7%. conclusion: a significant number of patients were not thrombolysed within 30 minutes of presentation.the non-availability of senior doctors, difficulty in interpreting ecgs, atypical presentations and er system delays, prolonged the door-to-needle time in this study. key words: door to needle time , acute myocardial infarction, streptokinase introduction ischaemic heart disease (ihd) is a major cause of mortality and morbidity worldwide, especially in industrialised countries.1 in keeping with international studies, mortality from ihd was higher in males than females.2 myocardial infarction is the major cardiac emergency presented in benazir bhutto hospital rawalpindi. while primary prevention of ihd is considered the ideal, mortality and morbidity in patients presenting with acute myocardial infarction (ami) can be reduced with early interventions such as fibrinolysis or percutaneous coronary intervention (pci).3 many studies have shown that early pci is more advantageous in reducing mortality from reinfarction and the need for a coronary artery bypass graft (cabg) than fibrinolytic drug therapy.46 in rawalpindi, pci is limited to two tertiary hospitals, making fibrinolytic drug therapy the more accessible form of treatment for st elevation myocardial infarction (stemi) patients. in keeping with the mantra “time is muscle”, early administration of fibrinolytic therapy preserves left ventricular function by increasing patency of occluded vessel and thus limiting infarct size.7, 8 maximal benefit from fibrinolysis is seen when the fibrinolytic is given within the first hour of symptom onset.9, 10 delaying fibrinolytic therapy by one hour increases the hazard ratio of death by 20%, (95% confidence interval (ci) 7 88), and a delay of 30 minutes or more can reduce the average life expectancy by one year.11the period between the onset of symptoms to administration of fibrinolytic therapy can be divided as :1. interval between onset of symptoms to seeking medical attention; 2. period taken to transport patient to definitive care;3. interval between arrival at hospital to initiation of fibrinolytic (door-to-needle time).the first two components can be improved by public education and developing efficient pre-hospital systems. for example, north carolina has adopted a state wide stemi referral strategy that advises paramedics to "bypass" local hospitals and transport stemi patients directly to a pci-capable hospital, even if a non-pcicapable hospital is closer.this results in shorter reperfusion times.12 but door-to-needle time is the one in-hospital factor that can be addressed by medical practitioners.the american heart association/american college of cardiology (aha/acc) guidelines recommend a door-to-needle time of 30 minutes or less for administration of fibrinolytic for stemi patients. 1.compliance with this time period is considered a marker of quality of care. 14 european society of cardiology recommends first medical contact time to ecg time of less than 10 minutes and also recommends door to needle time of less than 30 minutes.15 journal of rawalpindi medical college (jrmc); 2017;21(2): 127-130 128 patients and methods this prospective study was conducted on all patients who received thrombolytics for ami in the emergency of bbh from august 2016 to october 2016.all adult patients with acute st segment elevation, new onset left bundle branch block (lbbb), or posterior infarct on electrocardiogram (ecg) meeting aha/acc criteria for thrombolysis, who received thrombolytics in the emergency bbh. exclusion criteria was patients who received pre-hospital thrombolysis or those thrombolysed at other centres before referral; patients receiving thrombolytic therapy for conditions other than myocardial infarction e.g. pulmonary embolism. the quality of data collected was dependent on the availability and accuracy of the case notes. incomplete documentation, and illegible and ambiguous notes were identified.data collated and analysed was patient demographics,pre-hospital ecg acquisition and presence or absence of attendants. time intervals calculated were time of presentation to hospital (taken from emergency slip) to time of ecg acquisition,time from ecg acquisition to actually commencing thrombolytics and the sum of the above time intervals constitutes the total door-to-needle time. simple descriptive statistics were used to describe the meantime to ecg, ecg to fibrinolytic, and total doorto-needle times. subgroup analysis was performed for determining prevalence of stemi patients fibrinolysed based on gender and age group; and pre hospital ecg acquisition. the symptoms on presentation were also assessed. typical symptoms were defined as an acute onset of chest pain with radiation to the left arm, neck or jaw with associated autonomic symptoms (sweating, nausea or vomiting).ethics approval was granted by the research committee of rawalpindi medical university. results sixty six patients presented with ami were given streptokinase. out of these, 6% (n=4) of these patients received streptokinase within 15 minutes of arrival in emergency and 22.7% (n=15) of these patients received streptokinase in 30 minutes (table 1).. the mean door to needle time calculated was 44.8 minutes (table 2). patients receiving reperfusion therapy within 30 minutes were 28.7%. majority (74%) had a typical presentation of ami (table 3) table 1 : door to needle time in minutes door to needle time in minutes %(n) n=66 within 15 minutes of arrival 6% (n=4) 16 30 minutes 22.7% (n=15) 31 – 45 minutes 33.33% (n=22) 46 – 60 minutes 27.27% (n=18) 61 – 90 minutes & more 10.7% (n=7) table 2: mean time achieved for each interval in minutes time interval mean time (minutes) door to ecg 17.4 minutes ecg to thrombolysis 27.4 minutes door to needle time 44.8 minutes table 3: demographic variables variable no percentag e sex male 43 65.2 female 23 34.8 age (years) 25-40 5 7 41-60 37 56 >60 24 37 pre-hospital ecg acquisition pre-hospital ecg 3 4.5 symptomology typical 49 74 atypical 17 26 discussion the prognosis of acute myocardial infarction patients depends on timely administration of fibrinolytic therapy.9,10,35 american heart association and european society of cardiology recommends door to needle time of 30 minutes for fibrinolytic therapy.13,15 but unfortunately these guidelines are not followed .adherence to these guidelines has improved care of patients with ami and is associated with significant reductions in in-hospital mortality rates.16,17,18,19 timely diagnosis of st‐segment elevation myocardial infarction (stemi) in the emergency department (ed) is made solely by ecg. obtaining this test within 10 minutes of ed arrival is critical to achieving the best outcomes as recommended by esc and aha.a recent study published in journal of american heart association in february 2017 evaluated performance of emergency department screening criteria for an early ecg to identify st‐segment elevation myocardial infarction .they examined stemi screening performance in 7 eds, with the missed case rate (mcr) as their primary end point. the overall mcr for all 7 eds was 12.8%. the lowest and highest mcrs were 3.4% and 32.6%, respectively. the mean difference in door‐to‐ecg times for captured and missed patients was 31 minutes, with a range of 14 to 80 minutes of additional myocardial ischemia time for missed cases. the prevalence of primarily screened ed journal of rawalpindi medical college (jrmc); 2017;21(2): 127-130 129 stemis was 0.09%.the 29.2% difference in mcrs between the highest and lowest performing eds demonstrates room for improving timely stemi identification among primarily screened ed patients.20 in a canadian registry of 3,088 ami patients in 2000– 2001, 63% of the patients failed to receive fibrinolytic therapy within 30 minutes of ed arrival.21 another study done in canadian province of quebec in 2003 in 1189 patients showed median delay of reperfusion therapy was 32 minutes in patients receiving fibrinolytic therapy.22 evaluation of door to needle time in a tertiary care hospital, in india in 2015 showed 73 percent of patients failed to receive thrombolytic therapy within 30 minutes.23 similar study done in 58 urban emergency departments in u.s. comprised of 3,819 patients who presented between 2003 and 2006, showed low to moderate concordance with guidelinerecommended processes of care for patients of ami.24 a data from punjab institute of cardiology lahore showed door-to-needle time of more than 30min in 46.2% patients.25 similar studies done in india, saudi arabia and vancouver showed that acca recommendation of door to needle time is not properly followed.26,27,28,31 in benazir bhutto hospital, the mean door to needle time as per present study is 44.8 min. only 28.7% patients received reperfusion therapy within 30min of arrival in er .so, a large proportion of patients did not receive fibrinolytic therapy in time. factors that contributed to the increase of door to needle time were, inappropriate referral of cardiac patients to the medical units by the triage personnel, delay in the acquisition of ecg, delay in interpretation of ecg as its interpretation and the decision to thrombolyse are reliable in more experienced doctors than junior doctor, patients presenting with atypical symptoms, non-availability of thrombolytics in the cardiac bay and delay in acquisition of thrombolytics from the emergency administration due to administrative issues.. 29these factors significantly increase door to needle time and can be addressed by application of different pre-emptive and emergency measures , e.g., early ecg acquisition for at-risk patients, emergency staff training, the presence of a senior doctor/physician on the floor or being readily available, better co-ordination between hospital administration, emergency staff and physicians, improve auxiliary services to enhance patient flow, the ready availability of fibrinolytic medicine in the cardiac bay.most quality improvement studies suggest a team-based approach to improving the time-toreperfusion therapy for mi patients.22,24,30 a study in armed forces institute of cardiology , rawalpindi showed that more than 70% of the patients were thrombolysed within 30 mins of arrival i.e. door to needle time <30 minutes.32 in hospital associated with andhra medical college, visakhapatnam, andhra pradesh, india, they have been able to reduce the door to needle time for intravenous thrombolysis to about ten minutes by ensuring the presentation of a patient, with chest pain, directly to iccu without going through the emergency room / outpatient registration.this revealed efficient hospital organisational strategy to handle cardiac patients.33similarly doctors at a rural district general hospital in new zealand conducted a research, which revealed that introducing a number of simple low-cost interventions that included educational sessions for junior doctors and cardiac nursing staff, as well as posters and training on the use of a remote electronic ecg interpretation system to streamline out-of-hours management, they have been able to achieve recommended door to needle time in 74 percent of patients as compared to 43 percent without these interventions.34 conclusion a significant number of patients were not thrombolysed within 30 minutes of presentation (71.3%).the lack of senior doctors, difficulty interpreting ecgs, atypical presentations and ec system delays prolonged the door-to-needle time in this study. references 1. yusuf s, reddy s, ounpuu s. global burden of cardiovascular diseases: part 1: general considerations, the epidemiological transition, risk factors and impact of urbanization. circulation 2001;104:2746-53. 2. statistics south africa. mortality and causes of death in south africa, 2008. findings from death notifications. http://www.statssa.gov.za 3. armstrong pw, bogaty p, buller ce. the 2004 acc/aha guidelines: a perspective adaptation for canada by the canadian cardiovascular society working group. can j cardiol 2004;20:1075-79. 4. de boer mj, hoorntje jc, ottervanger jpl. immediate coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: left ventricular ejection fraction, hospital mortality and reinfarction. j am coll cardiol 1994;23:1004-08. 5. stone gw, grines cl, browne kf. implications of recurrent ischemia after reperfusion therapy in acute myocardial infarction: a comparison of thrombolytic therapy and primary angioplasty. j am collcardiol 1995;26:66-72. 6. weaver wd, simes rj, betriu a. comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. jama 1997;278:2093-98. journal of rawalpindi medical college (jrmc); 2017;21(2): 127-130 130 7. wilcox rg, von der lippe g, olsson cg. trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. anglo-scandinavian study of early thrombolysis (asset). lancet 1988;8610:525-530. 8. second international study of infarct survival (isis-2) collaborative group. randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: isis-2. lancet 1988;8607:349-360. 9. fibrinolytic therapy trialists' (ftt) collaborative group. indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. lancet 1994;343: 311. 10. boersma e, maas ac, deckers jw. early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. lancet 1996;9030:771-75. 11. rawles jm (great group). quantification of the benefit of earlier thrombolytic therapy: five-year results of the grampian region early anistreplase trial (great). j am collcardiol 1997;30:1181-86. 12. emil l, fosbol, christopher b, james g. monk jl. the impact of a state wide pre-hospital stemi strategy to bypass hospitals without percutaneous coronary intervention capability on treatment times .circulation 2012;112:1184346. 13. o'gara pt, kushner fg, ascheim dd, casey de, chung mk. accf/aha guideline for the management of stelevation myocardial infarction: a report of the american college of cardiology foundation/american heart association task force on practice guidelines, j am collcardiol 2013; 61 :e78-e140) 14. kuppuswamy vc, webbed , gupta s. meeting the nsf targets for door-to-needle time in acute myocardial infarction the role of a bolus thrombolytic. br j cardiol 2006;13:36-41. 15. steg pg, james sk, atar d, badano lp, blömstromlundqvist c. guidelines for the management of acute myocardial infarction in patients presenting with stsegment elevation, eur heart j 2012; 33: 2569-2619 16. peterson ed, roe mt, mulgund j.association between hospital process performance and outcomes among patients with acute coronary syndromes. jama. 2006; 295:1912– 20. 17. mcnamara rl, herrin j, wang y. impact of delay in doorto-needle time on mortality in patients with st-segment elevation myocardial infarction. am j cardiol.2007; 100:1227–32. 18. mcnamara rl, wang y, herrin j. effect of door-to-balloon time on mortality in patients with st-segment elevation myocardial infarction. j am collcardiol. 2006; 47:2180– 86. 19. peterson ed, shah br, parsons l. trends in quality of care for patients with acute myocardial infarction in the national registry of myocardial infarction from 1990 to 2006. am heart j. 2008; 156:1045–55 20. yiadom, maameyaa ab. performance of emergency department screening criteria for an early ecg to identify st‐segment elevation myocardial infarction. journal of the american heart association 6.3 (2017): e00352 21. atzema cl, austin pc, tu jv, schull mj. emergency department triage of acute myocardial infarction patients and the effect on outcomes. ann emerg med. 2009; 53:736–45. 22. huynh t, o'loughlin j, joseph l. the ami-quebec study investigators. delays to reperfusion therapy in acute stsegment elevation myocardial infarction: results from the ami-quebec study cmaj 2006; 175(12):1527-32. 23. sarwar a, xavier aa, ragachandana k, dhanapal ck, sudarshan s. evaluation of door to needle time and predisposing factor to it in a tertiary care hospital, chidambaram." pharmatutor 4.11 (2016): 33-36. 24. tsai cl, david j, magid md. quality of care for acute myocardial infarction in 58 u.s. emergency departments. academerg med 2010;17:940-50. 25. jehangir w, daood ms, khan m. evaluation of the door-toneedle time in patients undergoing fibrinolytic therapy after acute myocardial infarction. pak j physiol 2009;5(2):38-39. 26. masurkar va, kapadia fn, shirwadkar g. evaluation of the door-to-needle time for fibrinolytic administration for acute myocardial infarction. indian journal of critical care medicine 2005;9(3):137-40. 27. abba aa, wanni ba, rahmatullah ra. door-to-needle time in administering thrombolytic therapy for acute myocardial infarction. saudi med j 2003;24(4):361-64. 28. zed pj, abu-laban rb, cadieu tm. fibrinolytic administration for acute myocardial infarction in a tertiary ed: factors associated with an increased door-to-needle time. am j emerg med 2004;22:192-196. 29. massel d. observer variability in ecg interpretation for thrombolysis eligibility: experience and context matter. j throm thrombolysis 2000;15(3):131-40. 30. ho mt, eisenberg ms, litvin pe. delay between onset of chest pain and seeking medical care. the effects of public education. ann emerg med 1989;18:727-731. 31. george l, ramamoorthy l, satheesh s, saya rp. prehospital delay and time to reperfusion therapy in st elevation myocardial infarction. j emerg trauma shock 2017;10:6469 32. ali s, sharif h, shehzad k. door to needle time and its impact on successful thrombolysis. jrmc; 2012;16(1):3-5 33. venkatachelam r, adilakshmi b, manohar t, rao m, abbaiah s.factors affecting time to arrival in hospital among patients with acute myocardial infarction (mi). journal of scientific and innovative research 2015; 4(2): 109-14. 34. mark j, and caesar j. improving door-to-needle times for patients presenting with st-elevation myocardial infarction at a rural district general hospital. bmj quality improvement reports 2016; 5.1:673-76. 35. puymirat n and etienne m.prognostic impact of noncompliance with guidelines-recommended times to reperfusion therapy in st-elevation myocardial infarction. the fast-mi 2010 registry. european heart journal: acute cardiovascular care 2017;6: 26-33. 378 journal of rawalpindi medical college (jrmc); 2020; 24(4): 378-383 original article comparison of paricalcitol (i.v) and alfacalcidol (i.v) in treatment of secondary hyperparathyroidism (shpt) in hemodialysis patients mansoor abbas qaisar1, zain ul abideen2, fateh sher chattah3, muhammad nadeem4, zahid hafeez5 1 nephrologist, diaverum, ksa. 2 medical officer, multan institute of kidney and diseases, multan. 3 nephrologist, prince sultan military hospital, riyadh, ksa. 4 nephrologist, gizan central hospital, ksa. 5 nephrologist, al-noor specialist hospital, makkah, ksa. author’s contribution 1 conception of study 1 experimentation/study conduction 3 analysis/interpretation/discussion 2 manuscript writing 5 critical review 4 facilitation and material analysis corresponding author dr. mansoor abbas qaisar, nephrologist, diaverum, ksa email: mansoorabbas106@gmail.com article processing received: 01/09/2020 accepted: 20/11/2020 cite this article: qaisar, m.a., abideen, z., chattah, f.s., nadeem, m., hafeez, z. comparison of paricalcitol (i.v) and alfacacidol (i.v) in treatment of secondary hyperparathyroidism (shpt) in hemodialysis patients. journal of rawalpindi medical college. 30 dec. 2020; 24(4): 378-383. doi: https://doi.org/10.37939/jrmc.v24i4.1468 conflict of interest: nil funding source: nil access online: abstract objective: to compare the efficacy of alfacalcidol (i.v) and paricalcitol (i.v) for the treatment of secondary hyperparathyroidism (shpt) in hemodialysis patients. material and methods: an open-label randomized clinical trial was carried out to compare the efficacy of intravenous paricalcitol and alfacalcidol. we recruited 80 patients with end-stage renal disease receiving maintenance hemodialysis in a tertiary care hospital dialysis unit. the participants were randomly divided into two groups. a wash-out period of one week was decided for each patient in whom he/she did not receive any medication for the treatment of hypocalcemia, hyperphosphatemia, or secondary hyperparathyroidism. afterward, patients received an expanding dosage of alfacalcidol or paricalcitol for a time of about four months, and then after a further washout period of one week, each group received opposite treatment (paricalcitol or alfacalcidol) for a further four months (16 weeks). results: the analyzed data for the same end-points revealed no difference between the two groups. no significant statistical difference in terms of calcium levels in both groups was noted. the study also found no big difference in the ability of both drugs to treat secondary hyperparathyroidism, while keeping serum phosphate and calcium levels inside the desired range. the study also found no distinction in the frequency of hypercalcemia and hyperphosphatemia as a side effect of vitamin d analogue’s treatment. conclusion: the study concludes that alfacalcidol and paricalcitol are equally effective in the treatment of secondary hyperparathyroidism in the dialysis population. since paricalcitol is expensive as compared to alfacalcidol, in an economically challenged country like pakistan, alfacalcidol can be a better choice when treating shpt as we did not find any gross difference in the ability of two drugs to restrict shpt. keywords: alfacalcidol, paricalcitol, secondary hyperparathyroidism, hemodialysis. 379 journal of rawalpindi medical college (jrmc); 2020; 24(4): 378-383 introduction secondary hyperparathyroidism is a common complication of chronic kidney disease especially in patients on hemodialysis. the reduced ability of kidneys to convert vitamin d to its active form results in hypocalcemia. hyperphosphatemia results due to the decreased ability of kidneys to remove enough po4 from the body. hypocalcemia is the main stimulant for the parathyroid hormone and ultimately patients with ckd go on to develops secondary hyperparathyroidism. management of bone mineral disease in dialysis patients sometimes becomes difficult as clinicians face the challenge of treating secondary hyperparathyroidism while keeping calcium and phosphate within normal ranges.1 vitamin d analogues are the usual treatment of choice for suppressing pth levels as it can treat underlying hypocalcemia as well. 1, 25 dihydroxycholecalciferol (calcitriol) is the active form of vitamin d and it not only stimulates the phosphate and calcium reabsorption from the gut but also plays a vital role in bone resorption and bone formation. however, at the same time, reabsorption of calcium and phosphate from the bones and gut can pose a risk for hypercalcemia and hyperphosphatemia. vascular calcification and coronary artery disease is the leading cause of death in the dialysis population. the basic reason behind these complications is considered to be because of hypercalcemia and hyperphosphatemia.2 so in this prospect, a vitamin d analogue that can treat secondary hyperparathyroidism with a limited effect on calcium and phosphorus levels can be of attention. alfacalcidol is a commonly used vitamin d analogue in pakistan; however, paricalcitol is not widely available. the comparison of their efficacy in tackling secondary hyperparathyroidism keeping calcium and phosphorus levels within the normal range can be helpful in our clinical settings. a study of a randomized controlled trial carried out by sprague sm et al compared the efficacy of paricalcitol and calcitriol in treating shpt. the study showed that paricalcitol took less time to bring pth levels within the desired range as compared to calcitriol with fewer events of hyperphosphatemia.3 effect on serum calcium levels was comparable in both groups. in another study conducted by brown aj et al showed that paricalcitol is less potent in stimulating intestinal calcium and phosphate absorption when compared with calcitriol.4 it has been proposed in a few other studies that alfacalcidol has relatively high calcemic and phosphatemic action than paricalcitol. paricalcitol is much more expensive than alfacalcidol although compliance is not an issue as both are given intravenously at the end of the dialysis session. the study aimed to look at whether paricalcitol worth it as for as suppression of pth is concerned when compared with alfacalcidol. materials and methods all the patients included in the study were 18 years old or more. patients were recruited from a tertiary care hospital and were receiving hemodialysis for at least 6 months. only stable patients, who were having no history of malignancy or current pregnancy and having a good life expectancy, were included. the wash-out period for drugs (if the patient is receiving any phosphate binder or calcium supplement) was set to be 1 week. included patients were not receiving any kind of vitamin d analogue, their calcium and phosphate levels were adequately controlled. i.e.; serum corrected calcium less than 10.2 mg/ dl and phosphate levels less than 5.5 mg/dl. all the patients had ipth levels of more than 600 pg/ml. we divided the patients into two groups. each group comprised of 40 patients, including males and females. for sample size calculation proportion of patients expected to achieve ≥ 30% decrease in ipth at the end of the treatment, the period was almost 50% in the alfacalcidol group and 68% in the paricalcitol group. we followed 0.7 controls to recognize a substantial peculiarity (p equal to 0.05 on mcnemar's test), 80 individuals had been taken and a randomization list was created by a computer. the first group of patients with shpt was treated with alfacalcidol (i.v) for about four months. afterward, alfacalcidol was stopped and for the next one week patients were off treatment and did not receive any vitamin d analogue, calcium supplement, or phosphate binders. after completing one week washout period the same group was treated with intravenous paricalcitol. the second group of patients received paricalcitol (i.v) initially for about four months, subsequently had a wash-out period of one week, and then treated with alfacalcidol for the next four months. both alfacalcidol and paricalcitol were given immediately after completing the hd session in i.v form. the initial dose of alfacalcidol was 2μg, 3 times per week and for paricalcitol, it was 5μg, 3 times 380 journal of rawalpindi medical college (jrmc); 2020; 24(4): 378-383 per week. however, the dose was adjusted according to the monthly ipth levels, to keep calcium and phosphorus within an acceptable range. the calcium concentration of dialysate was set to be 1.5mmol/l and the dialysis concentrate used for each patient was hda49. during pre-dialysis assessment, weight, blood pressure, pulse, and other vitals were checked for each patient as per routine. blood sample collection protocols were designed. before the start of hemodialysis, all the samples were drawn from the arterial bloodlines. serum calcium, phosphate, and ipth levels were checked every month. based on monthly lab results, required changes in the doses of calcium supplement and phosphate binders were made. the dose of vitamin d analogues was also adjusted based on lab results and clinical judgement. results we decided on the primary efficacy endpoint, secondary outcome, and safety endpoints. the total number of patients achieving equal or greater than 30% reduction in ipth levels in the last month of treatment with either paricalcitol or alfacalcidol was labelled as the primary efficacy endpoint. the secondary outcome was a change in serum calcium and phosphorus levels, and calcium-phosphorus product falling out of the desired range. safety endpoints were severe anemia (hb less than 8), thrombocytopenia (platelets less than 50), lymphopenia, severe infection, opportunistic infection, persistent hypercalcemia, and hyperphosphatemia or liver abnormalities (alt and ast more than 3 times upper limit of normal). diabetes was found in 37% of the patients. 64 % of the total patients were male. the mean age of the studied patients was 64.5 years (sd 14.5) and the median time on dialysis was 37 months (range 32-62 months) at randomization. the studied patients were in better condition as they had a stable hemoglobin 10.81mg/dl (sd 0.76) and albumin 40.2 g/l (sd 3.7) as compared to other patients. the analysis of the cross-over data for the percentage changes in pth revealed a significant period effect (t = -3.946; p). both vitamin d analogs suppressed secondary hyperparathyroidism successfully during both treatment periods. we could not detect any statistically significant difference in % changes between groups, and there was not any statistically significant difference in the proportion of patients reaching a 30% reduction in pth. the tables below show the confirmation of both periods i.e. periods 1 and 2. table 1: changes in pth during each period of alfacalcidol and paricalcitol treatment table 1-a: period 1 period 1 mean difference % ± sd change and pvalue alfacalcidol (n=40) paricalcitol (n=40) % ipth changes ±sd -54.1 ± 5.3 -62.7 ± 3.7 10.7 ± (p=0.102) table 1-b: period 2 period 2 mean difference % ± sd change and pvalue alfacalcidol (n=40) paricalcitol (n=40) % ipth changes ±sd -34.8 ± 6.98 -38 ± 6.71 6.02 ± 8.8 (p=0.613) table 2: number of patients reaching treatment goal during each period of alfacalcidol and paricalcitol treatment period 1 pvalue alfacalcidol (n=40) paricalcitol (n=40) ≥ ipth 33 (82%) 37 (93%) 0.190 pth < 420pg/ml (30% reduction) & phosphate <5.5mg/dl & ionized calcium <10.2mg/d l 7 (18%) 12 (31%) 0.310 period 2 pvalue alfacalcidol (n=40) paricalcitol (n=40) ≥ ipth 24 (59%) 27 (68%) 0.469 381 journal of rawalpindi medical college (jrmc); 2020; 24(4): 378-383 pth < 420pg/ml & phosphate <5.5mg/dl & ionized calcium <10.2mg/d l 12 (29%) 16 (41%) 0.466 the analysis of data for the same composite endpoints revealed no difference between groups as shown in table 3 below. table 3: number of patients with prolonged hypercalcemia or elevated ca x p product during alfacalcidol or paricalcitol treatment in the period end point no. and percentages of patients pvalue alfacalcidol (n=40) paricalcitol (n=40) ionized calcium > 10.2 mg/dl and ca x p > 55 mg2/dl2 for at least two consecutive blood drawn. 24 (61%) 25 (62%) 1.000 ionized calcium >10.2mg/dl for at least two consecutive blood drawn and ca x p ≥ 55 mg2/dl2 for at least four consecutive blood drawn. 15 (37%) 15 (38%) 1.000 the mean pth during the last four weeks of treatment was analyzed with baseline pth as a covariate and a significant baseline pth x treatment interaction was found (p=0.012) which means that treatment response depended on baseline pth in the paricalcitol group, whereas alfacalcidol suppressed pth across all baseline pth values. this interaction was also found for numerical changes in pth (p=0.012), percentage changes of pth (p=0.036) as for the number of patients reaching a 30% decrease in pth (p=0.047). mean pth during the last four weeks of period 2 were analyzed to describe the reproducibility of this interaction. the same tendency was found, although not statistically significant (p=0.10). however, as there were only 80 patients in this analysis, a small number of patients studied may be the reason for the lack of significance. in the present study, the differentiated pth response to paricalcitol across baseline pth levels may be largely due to the pronounced suppression of pth at the low baseline levels. 48% of the paricalcitol treated and 29% of the alfacalcidol treated patients reached a pth level of less than 220 pg/ml (p=0.110). the observed difference in the effect of alfacalcidol and paricalcitol on pth could be due to a difference in calcium levels. this study did not found any statistically significant difference between the calcium levels in the alfacalcidol group compared to the paricalcitol group when groups were separated according to baseline pth. discussion vitamin d is essential for the optimization of bone mineral health. kidneys produce calcitriol, which is the most important metabolite in upholding calcium and phosphorus homeostasis. in kidney disease, calcitriol levels eventually decrease, resulting in the development of secondary hyperparathyroidism (shpt).5 this randomized control crossover study was designed to observe the clinical effects of two vitamin d analogs and compare their efficacy in terms of treating secondary hyperparathyroidism in the dialysis population. paricalcitol is a relatively new drug and still, it is not widely available in the market. we compared paricalcitol with conventionally used alfacalcidol to compare their effectiveness and side effects profile. a similar study was carried out by ditte hansen et al in 2009 which showed comparable results for both paricalcitol and alfacalcidol.6 however, this comparison has never been performed in pakistan before. due to differences between the individuals, the end of the cross over a design was stochastic variation. deciding the duration of the treatment was a challenge because considering an extensive study period carries the risk of a large number of patients dropping out 382 journal of rawalpindi medical college (jrmc); 2020; 24(4): 378-383 sooner than the study finishes. a study carried out in denmark showed a mortality rate of 21.7% in the danish dialysis population.7 so we considered a study period of 8 months and included only stable patients with good life expectancy. a short study period would have been more liable to get biased results. we decided one a week washout period for both alfacalcidol and paricalcitol groups as keeping patients of secondary hyperparathyroidism without any vitamin d analog for a longer period of time can pose a risk for developing the serious bone mineral disease (bmd). a smaller wash-out period may reflect the carry-forward effect of drugs from one period to another. the half-life mentioned in literature for i.v alfacalcidol is 36 hours and 14-30 hours for i.v paricalcitol. secondary hyperparathyroidism (shpt), a common complication in the dialysis population, is conventionally treated with vitamin d analogs. several studies have been carried out in europe to compare the efficacy of paricalcitol and alfacalcidol. a similar study was carried out by xinghua geng et al in china where the researcher compared paricalcitol with other vitamin d receptor analogs and found that paricalcitol is better than others in controlling ipth levels. he also found that paricalcitol has mortality benefits compared to other vitamin d analogs.8 a randomized multicenter study was conducted by daniel w coyne et al in the usa recently which showed that both calcitriol and paricalcitol achieved an effective reduction in parathyroid hormone levels however paricalcitol suppressed ipth sooner than calcitriol with less incidence of hypercalcemia.9 this study was carried out in ckd stage 3-4 patients and not in the dialysis population. paricalcitol is a relatively new drug in pakistan however in the usa, it was launched in 1998. it is generally considered an effective treatment for shpt, especially in non-compliant patients. hyperphosphatemia and hypercalcemia are common side effects that need to be tackled effectively. in march 2019, yang liu et al published a meta-analysis of the safety and efficacy of paricalcitol in dialysis patients.10 after reviewing 13 studies, he proposed that paricalcitol has mortality benefits over other vitamin d analogs however its effectivity in reducing pth levels was comparable to others. however, two similar studies carried out in renal disease patients by yifeng xie et al and panpan cai et al could not provide conclusive evidence about the virtual efficacy of paricalcitol over other analogs.11,12 in our study, all the dialysis parameters were kept constant and almost identical for all the patients except dialyzer size and a dose of tinzaparin (used as an anticoagulant). the selected dialysis patients were in better condition than the general hemodialysis population, as they had higher hemoglobin 10.81mg/dl (sd 0.76) vs. 10.19 mg/dl (sd 2.27) and albumin 40.2 g/l (sd 3.7) vs. 38.8 g/l (sd 4.8). vitamin d analogs are frequently associated with hypercalcemia and hyperphosphatemia but that can be controlled with phosphate binders and adjusting the dose of vitamin d analog. the doses were adjusted by a consultant nephrologist on monthly basis after retrieving lab results. tackling hypercalcemia is important as it can lead to vascular calcification and increased cardiovascular incidents which can result in significant morbidity and mortality. in the past 20 years, there have been a few paradigm shifts as far as the management of secondary hyperparathyroidism is concerned. nephrologists have been using different forms of active vitamin d, paricalcitol, and cinacalcet in the near past preferring one over the other depending upon clinical scenario and local protocols. however, there is a need to avoid excessive use of vitamin d analogs and avoid treatment-related complications as mentioned earlier. conclusion the study concludes that there is no difference in the ability of alfacalcidol (i.v) and paricalcitol (i.v) to suppress secondary hyperparathyroidism while keeping phosphate and ionized calcium inside the desired range. based on this study although carried out in a small number of patients, we suggest that intravenous alfacalcidol is equally effective in treating shpt and due to the high price of paricalcitol, the former can a better choice especially in economically challenged countries. references 1. negrea l. active vitamin d in chronic kidney disease: getting right back where we started from?. kidney diseases. 2019;5(2):59-68. https://doi.org/10.1159/000495138 2. block ga, klassen ps, lazarus jm, ofsthun n, lowrie eg, chertow gm. mineral metabolism, mortality, and morbidity in maintenance hemodialysis. journal of the american society of nephrology. 2004 aug 1;15(8):2208-18. doi: https://doi.org/10.1097/01 3. sprague sm, llach f, amdahl m, taccetta c, batlle d. paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. kidney international. 2003 apr 383 journal of rawalpindi medical college (jrmc); 2020; 24(4): 378-383 1;63(4):1483-90. https://doi.org/10.1046/j.15231755.2003.00878.x 4. brown aj, finch j, slatopolsky e. differential effects of 19nor-1, 25-dihydroxyvitamin d2 and 1, 25-dihydroxyvitamin d3 on intestinal calcium and phosphate transport. journal of laboratory and clinical medicine. 2002 may 1;139(5):279-84. https://doi.org/10.1067/mlc.2002.122819 5. negrea l. active vitamin d in chronic kidney disease: getting right back where we started from?. kidney diseases. 2019;5(2):59-68. https://doi.org/10.1159/000495138 6. hansen d, brandi l, rasmussen k. treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol. bmc nephrology. 2009 dec 1;10(1):28. 7. the danish society of nephrology. danish national registry annual report. 2007. http://www.nephrology.dk [crossref] [ref list] 8. geng x, shi e, wang s, song y. a comparative analysis of the efficacy and safety of paricalcitol versus other vitamin d receptor activators in patients undergoing hemodialysis: a systematic review and meta-analysis of 15 randomized controlled trials. plos one. 2020 may 29;15(5):e0233705. https://doi.org/10.1371/journal.pone.0233705 9. coyne dw, goldberg s, faber m, ghossein c, sprague sm. a randomized multicenter trial of paricalcitol versus calcitriol for secondary hyperparathyroidism in stages 3–4 ckd. clinical journal of the american society of nephrology. 2014 sep 5;9(9):1620-6. doi: https://doi.org/10.2215/cjn.10661013 10. liu y, liu ly, jia y, wu my, sun yy, ma fz. efficacy and safety of paricalcitol in patients undergoing hemodialysis: a metaanalysis. drug design, development and therapy. 2019;13:999. doi: 10.2147/dddt.s176257. 11. xie y, su p, sun y, zhang h, zhao r, li l, et al.comparative efficacy and safety of paricalcitol versus vitamin d receptor activators for dialysis patients with secondary hyperparathyroidism: a meta-analysis of randomized controlled trials. bmc nephrology. 2017 dec 1;18(1):272. 12. cai p, tang x, qin w, ji l, li z. comparison between paricalcitol and active non-selective vitamin d receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. international urology and nephrology. 2016 apr 1;48(4):571-84. 404 not found 52 journal of rawalpindi medical college (jrmc); 2022; 26(1): 52-56 original article pathological spectrum of solitary fibrous tumours: a study of 25 cases diagnosed at a tertiary care institute zafar ali1, asna haroon2, ghazala mudassir3, summera moeen4 1 assistant professor, department of pathology, shifa international hospital, stmu, islamabad. 2 consultant histopathologist, department of pathology, shifa international hospital, stmu, islamabad. 3 associate professor, department of pathology, shifa international hospital, stmu, islamabad. 4 postgraduate resident, department of pathology, shifa international hospital, stmu, islamabad. author’s contribution 1 conception of study 2,4 experimentation/study conduction 2,4 analysis/interpretation/discussion 2,4 manuscript writing 1,2,4 critical review 1,3,4 facilitation and material analysis corresponding author dr. ghazala mudassir, associate professor, department of pathology, shifa international hospital, stmu, islamabad email: ghazala.scm@stmu.edu.pk article processing received: 23/06/2021 accepted: 10/12/2021 cite this article: ali, z., haroon, a., mudassir, g., moeen, s. pathological spectrum of solitary fibrous tumours: a study of 25 cases diagnosed at a tertiary care institute. journal of rawalpindi medical college. 31 mar. 2022; 26(1): 52-56. doi: https://doi.org/10.37939/jrmc.v26i1.1713 conflict of interest: nil funding source: nil access online: abstract objective: to evaluate the clinicopathological and immunohistochemical features of solitary fibrous tumor (sft) in shifa international hospital. materials and methods: this is a retrospective descriptive study. all cases of solitary fibrous tumor diagnosed on morphology from january 2012 till june 2018 were retrospectively retrieved from the histopathology department of shifa international hospital, islamabad. the hematoxylin and eosin (h&e) stained slides as well as ihc slides were reviewed. the diagnosis was established on current standard histopathological and ihc criteria provided by the world health organization (who) classification of soft tissue tumors. approval for the acquisition of the tissue specimens and supporting case information and retrieval of glass slides were obtained by institutional review board & ethics committee (irb & ec) wide reference number irb # 259-1079-2020 of shifa tameer-emillat university (stmu). results: there were 25 cases of sft in our study involving 12 males and 13 females. according to who 2013 criteria, eleven cases in our study were classified as malignant (44%) while 14 cases were in the benign group (56%). stat6 was available in our hospital in 2018 and since then all the subsequent cases of sft in the present study (seven in number) came positive for stat6 (sensitivity 100%) while cd34 which was done throughout the duration of this study (january 2012-june 2018) was positive in 20 cases (86.9%) and negative in three cases (13%). a follow-up of 16 cases is available. out of a total of 14 benign cases, follow-up of only seven (50%) cases could be traced and from a total of 11 malignant cases, follow-up of nine (81%) cases could be sought. all benign cases remained disease-free while among the nine malignant cases: three (33.3%) patients died, recurrence was reported in four (44.4%) patients. one (11.1%) patient remained disease-free while one (11.1%) patient is alive and on treatment. conclusion: malignancy in sft is common and must be evaluated meticulously. stat6 is a highly sensitive marker for the diagnosis of sfts. an immunohistochemical panel including stat6, cd34, cd99, and bcl-2 support morphology. malignant behavior is common and is evaluated by meticulous analysis of gross/microscopic features and close follow-up of the patient. however further advances in genetics and new tumor markers is in progress and must be followed for the definitive decision on tumor behavior and its subsequent treatment. keywords: solitary fibrous tumor (sft), stat6, cd34. 53 journal of rawalpindi medical college (jrmc); 2022; 26(1): 52-56 introduction the first case of solitary fibrous tumor (sft) was reported in 1870.1 a study on the clinicopathologic features of sft was done by england in 1989 on 223 cases.2 sfts are rare mesenchymal tumors representing less than 5% of all neoplasms involving pleura. these arise from the submesothelial connective tissue. more studies reveal sft may be found in any location of the body with two-thirds arising from the visceral pleura and the remaining one-third from the parietal pleura.2,3 these tumors also occur in extrapleural sites such as the meninges of cns, pericardium, anterior mediastinum, lung, breast parenchyma, nose & paranasal sinuses, orbit, parotid gland, liver, and thyroid gland.4 sft occurs with an equal incidence between men and women and at all ages but peaks in the sixth and seventh decades of life. paraneoplastic manifestations include clubbing of fingers and hypoglycemia. paraneoplastic syndromes are more common in tumors larger than 8 cm in size and are seen to resolve with surgical resection.5 grossly these tumors are wellcircumscribed, non-encapsulated, solitary, lobulated masses with an average size of 5-8 cm. there is much variation in the size of this tumor from 1 to 36 cm in diameter.6 cut surface is firm, white, and multinodular. according to who (2013) criteria for these tumors, the risk factors for sfts associated with recurrence and disease-specific mortality are a mitotic index of > 4/ 10 high-power fields (hpf), high tumor cellularity, high nuclear pleomorphism, atypia, hyperchromasia, and tumor necrosis. most cases are benign 78-88% while 12-22% are histologically malignant.7 immunohistochemically the sft generally is vimentin-positive and cytokeratin-negative. in addition, both the benign and malignant varieties of sft are cd34, cd99, and bcl-2-positive. further progress was made in 2013 as three groups discovered that the nab2-stat6 fusion gene resulted from the binding of transcriptional repressor nab2 with transcriptional activator stat6.8 this fusion gene is present in all sfts regardless of their site and clinical behavior (benign/ malignant). the detection of the nab2-stat6 fusion gene can help in diagnosing sft but molecular essays require specialist experts and are expensive. schweizer in 2013 demonstrated nab2stat6 fusion gene was rapidly detectable by stat6 immunohistochemistry, which exhibited strong nuclear expression 8. stat6 stain is a highly sensitive and specific marker for the genetic alteration (nab2stat6 gene fusion) found in sfts and is particularly useful in differentiating it from other spindle cell neoplasms.9 in this study we evaluated the clinicopathological and immunohistochemical features of sft cases in our hospital. materials and methods this is a retrospective longitudinal study. all cases of solitary fibrous tumor diagnosed on morphology from january 2012 till june 2018 were retrospectively retrieved from the records of the histopathology department of a tertiary care institute. the hematoxylin and eosin (h&e) stained slides as well as ihc slides were reviewed. the diagnosis was established on current standard histopathological and ihc criteria provided by the world health organization (who) classification of soft tissue tumors.7 four-micron thick sections from paraffin blocks were made of each sample and mounted onto glass slides. ihc staining for anti-stat6 antibody (biosb antibody, roche kit) was available in our hospital from 2018 onwards. it was performed on all suspected cases of sft using the manufacturer’s instructions. the quality of expression was graded and interpreted as absent staining, weak expression, or strong expression. the samples were graded based on diffuse (>50%) versus localized (<50% of tumor cells) staining, as well as localization of the stain within the cell (nuclear only, cytoplasmic only, or both nuclear and cytoplasmic). approval for the acquisition of the tissue specimens and supporting case information and retrieval of glass slides were obtained by institutional review board & ethics committee (irb & ec). results clinical data there were 25 cases of sft in our study involving 12 males and 13 females with a mean age of 49 years (range 24-84 years) (figure 1). these sfts arose in various body locations including the thorax (8 cases with 3 in the lung, 2 pleura, 2 mediastinum & 1 from the chest wall). the abdomen was the most commonest site of occurrence of this tumor in our study whereas this tumor was also reported one each in the nape of the neck, anterior thigh, retrobulbar mass, parasagittal mass, and 2 in the spinal cord (figure 2). there were no differences in age and sex between patients with benign and malignant sfts. tumor size was in the range of 1->10cm. tumors 54 journal of rawalpindi medical college (jrmc); 2022; 26(1): 52-56 larger than 10cm were mostly malignant (6 cases, 24%) (figure 3). microscopy the microscopic examination revealed a patternless architecture of bland spindle cells forming hypo and hypercellular areas in a collagenous stroma, areas of hyalinization, and interspersed staghorn-shaped vessels. eleven cases in our study were classified as malignant (44%) according to who 2013 criteria while 14 cases were in the benign group (56%) (figure 4). immunohistochemical findings stat6 was available in our hospital in 2018 and since then all the subsequent cases in our study (7 in number) of sft came positive for stat6 (sensitivity 100%) while cd34 which was done throughout the duration of this study was positive in 20 cases (86.9%) and negative in 3 cases (13%). immunohistochemistry was suggested in 2 cases but was not performed (figure 5). follow-up follow up of 16 cases is available. out of a total of 14 benign cases, follow-up of only 7(50%) cases could be traced and from a total of 11 malignant cases, followup of 9(81%) cases could be sought. all benign cases remained disease-free while among 9 malignant cases: 3(33.3%) patients died, recurrence was reported in 4(44.4%) patients. one (11.1%) patient remained disease-free while one (11.1%) patient is alive and on treatment. discussion solitary fibrous tumors are rare mesenchymal tumors most commonly arising in the pleura and representing less than 5% of all neoplasms involving the pleura.2 magdeleinat et al in 2002 carried out a study on 60 cases in which they found pleura to be the most common site and 36.63% cases were malignant out of which two later presented with local recurrence and one with metastasis.5 sung et al in 2005 published a study of 63 cases with 30.2% being malignant with three recurrences and distant metastasis in eight cases.10 in a study on 10 cases, carried out by erdag in 2007, the common site of occurrence was trunk and cheek, all were benign and there was no evidence of disease in 9 patients whereas one recurrence was reported.11 in our study eleven cases (44%) out of 25 total cases were found in the abdomen and out of the 8 cases (20%) in the thorax, only two (8%) were arising from pleura. devito et al 2015 studied 82 patients and found 49% to be malignant and out of those reported as benign, 11 recurrences were presented in addition to the two reported as atypical.12 our results were comparable to other studies as 44% of cases were malignant and our benign cases (56%) remained symptom-free. in our study follow-up of only 9 out of 11 malignant cases could be traced which showed 4 cases (44.4%) of recurrence and 3 patients (33.3%) succumbing to the disease. this may be due to presentation at a higher stage of the tumor. in a study carried out by han et al in 2015 out of 53 cases studied for stat6, cd34, and cd99 expression, 51 (96.2%) were stat6 positive, and 47 (88.7%) showed cd34 positivity and cd99 was positive in 50 (94.3%) cases.13 in the present study stat6 was positive in all cases tested (sensitivity 100%) while cd34 was positive in 20 cases (86.9%) and negative in 3 cases (13%). the three cases in which cd34 came negative in this study were recurrent malignant tumors, otherwise, it was positive in both benign and malignant tumors. immunohistochemistry was suggested in 2 cases but was not performed. fletcher in 2013 observed that cd34 is positive in many cases of sft but approximately 5-10% are negative8. the lost expression of cd34 is noted in high-grade foci or recurrent tumors.14 this process of conversion of cd34 positive to negative areas may be related to malignant transformation.15 cd34 is not entirely specific for sft as it can be expressed in a variety of mesenchymal tumors like dermatofibrosarcoma protubrans, hemangioendothelioma, and gastrointestinal stromal tumor (gist), but still it is highly sensitive for sft. 16,17 sft of cns is a different neuropathological entity from soft tissue sft, and who 2007 cns classification has retained the sft/hemangiopericytoma terminology for this entity only. tumors with sft phenotype are grade i while those of hpc phenotype are grade ii & iii. a study done on meningeal sft/hpc tumors by zubair et al. showed that the majority of the tumors were of grade ii & iii. these cases required not only complete surgical resection but also adjuvant radiotherapy. they observed that patients who had not received radiotherapy had a high recurrence rate.18 different nab2-stst6 fusion types seem to be associated with clinicopathologic subtypes of sft. nabb2ex4-stat6 ex2/3 variant is found in classic sft while nab2ex6-stat6 ex16/17 is found in sft showing aggressive behavior.19 the finding of fusion variants requires designing future molecular targeted therapies as conventional chemotherapeutic agents have demonstrated limited efficacy in treatment strategy.20 55 journal of rawalpindi medical college (jrmc); 2022; 26(1): 52-56 a study by patrick on 26 cases of sfts arising in dermis or sub-cutis found that cutaneous sfts are more common in females mostly occurring in the head region. these tumors are of low grade and behave in a benign manner. however, more studies are required to confirm this. he recommends that a proper histomorphology and ihc would differentiate it from other cd34 tumors arising in the skin.21 in my study most of the sft cases were reported in the abdomen and none in subcutaneous tissue were seen. in a study comprising 41 patients diagnosed with sft, it was concluded that this tumor when occurring in limbs had a better prognosis. this study also noted an association between tert promoter mutations and histologically malignant features.22 the h&e staining showed typical histological features, which were spindle tumor cells with hypo and hypercellular areas in a collagenous stroma. this patternless architecture was separated by branching staghorn-like vessels which were similar to other studies. the risk factors for sfts associated with recurrence and malignancy are the mitotic index of > 4/ 10 high-power fields (hpf), high tumor cellularity, high nuclear pleomorphism, atypia, hyperchromasia, and tumor necrosis as are specified by who (2013) criteria for these tumors.7,21 the findings of various studies are compared in table 1. table 1: comparison of various studies (ned* no evidence of disease) studies no. of cases commonest sites benign/malignant follow-up 1 magdeleinat et al. 2002 60 pleura 63.3% benign 36.6% malignant benign; no recurrence malignant; 2 local recurrences, 1 metastasis 2 sung et al. 2005 63 pleura 69.8% benign 30.2% malignant malignant; 3 recurrences, 8 metastasis 3 erdag et al. 2007 10 trunk & cheek all benign ned* in 9, 1 recurrence 4 de vito et al. 2015 82 pleura 51% benign 49% malignant benign; 2 atypical benign & 11 benign had recurrence 5 current study 2018 25 abdominal 56% benign 44% malignant benign; no recurrence malignant; 3 died, 4 recurrences, 1 disease-free conclusion malignancy in sft is common and must be evaluated meticulously. stat6 is a highly sensitive marker for the diagnosis of sfts. an immunohistochemical panel including stat6, cd34, cd99, and bcl-2 support morphology. malignant behavior is common and is evaluated by meticulous analysis of gross/microscopic features and close follow-up of the patient. however, further multi-center studies are suggested to analyze the biologic and clinical behavior of this tumor with follow-up of patients. a limitation of our study was many patients were lost in follow-up. a long-term follow-up is required to evaluate the rate of recurrence, overall survival, and clinical behavior of this tumor. more studies are required to further evaluate the genetics of this tumor as it would help in devising a targeted therapy. references 1. wagner e. das tuberkelähnliche lymphadenom (der cytogene oder reticulirte tuberkel). arch heilk (leipzig). 1870; 11: 497499. 2. england dm, hochholzer l, mccarthy mj. localized benign and malignant fibrous tumors of the pleura. a clinicopathologic review of 223 cases. am j surg pathol. 1989; 13 (8): 640-658. doi: 10.1097/00000478-198908000-00003. 3. drachenberg cb, bourquin pm, cochran lm, burke kc, kumar d, white cs, et al. fine needle aspiration biopsy of solitary fibrous tumors. acta cytologica. 1998; 42:1003-1010. doi: 10.1159/000331949 4. magdeleinat p, alifano m, petino a, lerochias jp, dulmet e, galateau f, et al. solitary fibrous tumors of the pleura: clinical characteristics, surgical treatment, and outcome. eur j cardiothorac surg. 2002; 21(6): 1087 – 1093. doi: 10.1016/s1010-7940(02)00099-4 5. baxter rc, holman sr, corbould a, stranks s, ho pj, braund w. regulation of the insulin-like growth factors and their binding proteins by glucocorticoid and growth hormone in nonislet cell tumor hypoglycemia. j clin endocrinol metab.1995; 80(9): 2700-2708. doi: 10.1210/jcem.80.9.7545698 56 journal of rawalpindi medical college (jrmc); 2022; 26(1): 52-56 6. ordonez ng. localized (solitary) fibrous tumor of the pleura. adv anat pathol. 2000; 7(6): 327-340. doi: 10.1097/00125480-200007060-00001 7. fletcher cdm, bridge ja, hogendoorn pcw, mertens f, editors. world health organisation classification of tumours of soft tissue and bone. in: 'extrapleural solitary fibrous tumour', fletcher cdm, bridge ja and jc l. 2013; 4th edition, volume 5. lyon: iarc press, 80-82. 8. mohajeri a, tayebwa j, collin a, nilsson j, magnusson l, von steyern fv, et al. comprehensive genetic analysis identifies a pathognomonic nab2/stat6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. genes chromosomes cancer. 2013; 52(10): 873–886. doi: 10.1002/gcc.22083 9. schweizer l, koelsche c, sahm f, piro rm, capper d, reuss de, et al. meningeal hemangiopericytoma and solitary fibrous tumors carry the nab2-stat6 fusion and can be diagnosed by nuclear expression of stat6 protein. acta neuropathol. 2013; 125(5): 651–658. doi: 10.1007/s00401-013-1117-6 10. sung sn, chang jw, kim j, lee ks, han j, park si. solitary fibrous tumors of the pleura: surgical outcome and clinical course. ann thorac surg. 2005; 79(1): 303-307. doi: 10.1016/j.athoracsur.2004.07.013 11. erdag g, qureshi hs, patterson jw, wick mr. solitary fibrous tumors of the skin: a clinicopathologic study of 10 cases and review of the literature. j cutan pathol. 2007; 34(11): 844850. doi: 10.1111/j.1600-0560.2006.00728.x 12. devito n, henderson e, han g, reed d, mui mm, lavey r, et al. clinical characteristics and outcomes for solitary fibrous tumor (sft): a single center experience. plos one. 2015; 10(10): e0140362. 13. han y, zhang q, yu x, han x, wang h, xu y, et al. immunohistochemical detection of stat6, cd34, cd99 and bcl2 for diagnosing solitary fibrous tumors/hemangiopericytomas. int j clin exp pathol. 2015; 8(10): 13166‐13175. 14. saeed o, zhang s, cheng l, lin j, alruwaii f, chen s. stat6 expression in solitary fibrous tumor and histologic mimics: a single institution experience. appl immunohistochem mol morphol. 2020; 28(4): 311-315. doi: 10.1097/pai.0000000000000745 15. yokoi t, tsuzuki t, yatabe y, suzuki m, kurumaya h, koshikawa t, et al. solitary fibrous tumour: significance of p53 and cd34 immunoreactivity in its malignant transformation. histopathology. 1998; 32(5): 423-432. doi: 10.1046/j.13652559.1998.00412.x 16. karanian m, perot g, coindre jm, chibon f, pedeutour f, neuville a et al. fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans. mod pathol. 2015; 28(2): 230-237. doi: 10.1038/modpathol.2014.97 17. rege ta, wagner aj, corless cl, heinrich mc, hornick jl. "pediatric-type" gastrointestinal stromal tumors in adults: distinctive histology predicts genotype and clinical behavior. am j surg pathol. 2011; 35(4):495-504. doi:10.1097/pas.0b013e31820e5f7d 18. ahmad z, tariq mu, din nu. meningeal solitary fibrous tumor/hemangiopericytoma: emphasizing on stat 6 immunohistochemistry with a review of literature. neurol india 2018;66:1419-26 19. tai hc, chuang ic, chen tc, li cf, huang sc, kao yc, et al. nab2–stat6 fusion types account for clinicopathological variations in solitary fibrous tumors. mod pathol 2015;28:1324– 1335. doi: https://doi.org/10.1038/modpathol.2015.90 20. thway k, ng w, noujaim j, jones rl, fisher c. the current status of solitary fibrous tumor: diagnostic features, variants, and genetics. international journal of surgical pathology. 2016;24(4):281-292. doi: 10.1177/1066896915627485 21. feasel p, al-ibraheemi a, fritchie k, zreik rt, wang wl, demicco e, et al. superficial solitary fibrous tumor: a series of 26 cases. am j surg pathol. 2018 jun;42(6):778-785. doi: 10.1097/pas.0000000000001027. pmid: 29438169. 22. bianchi g, sambri a, pedrini e, pazzaglia l, sangiorgi l, ruengwanichayakun p, et al. histological and molecular features of solitary fibrous tumor of the extremities: clinical 23. correlation. virchows arch. 2020; 476: 445–454. doi: https://doi.org/10.1007/s00428-019-02650-5 89 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 89-93 original article seroprevalence and associated factors of sars cov-2 antibodies among employees of imdc and its teaching hospital usman zafar1, farah rashid2, sadia zafar3, nadia tariq4, khalid hassan5 1 assistant professor, department of medicine, islamabad medical and dental college, islamabad. 2 hod, department of community medicine, islamabad medical and dental college, islamabad. 3 lecturer, department of community medicine, islamabad medical and dental college, islamabad. 4 associate professor, department of community medicine, imdc, islamabad. 5 professor, department of pathology, islamabad medical and dental college, islamabad. author`s contribution 1 conception of study 1 experimentation/study conduction 2 analysis/interpretation/discussion 2,3,4 manuscript writing 5 critical review 3,4 facilitation and material analysis corresponding author dr. nadia tariq associate professor, department of community medicine, islamabad medical and dental college, islamabad email: nadia.tariq@imdcollege.edu.pk article processing received: 03/05/2021 accepted: 12/08/2021 cite this article: zafar, u., rashid, f., zafar, s., tariq, n., hassan, k. seroprevalence and associated factors of sars cov-2 antibodies among employees of imdc and its teaching hospital. journal of rawalpindi medical college. 31 aug. 2021; 25 covid-19 supplement-1, 89-93. doi: https://doi.org/10.37939/jrmc.v25i1.1650 conflict of interest: nil funding source: nil access online: abstract introduction: this study aims to determine the prevalence of anti-sars-cov-2 antibodies among the employees of islamabad medical and dental college and its allied hospital akbar niazi teaching hospital. material and methods: this descriptive cross-sectional study was conducted among the staff and faculty of islamabad medical and dental college and its allied hospital, irrespective of their covid-19 infection history. the study was approved by the institutional review board of islamabad medical and dental college (ref # 37/imdc/irb-2020). 294 employees volunteered for the study from 23rd july to 30th july 2020 through elecsys® anti-sars-cov-2 (immunoassay for the qualitative detection of igg antibodies against sars-cov-2 in humans serum and plasma). spss was used for data analysis and a p-value <0.05 was considered significant. results: out of 284 volunteers, 87 (30.6%) were sars-cov-2 antibody positive, with the mean antibody level in seropositive individuals recorded as 24.44 ± 25.34. among housekeeping and sanitary workers, 48.3% were seropositive while among lab technicians 37.1% were seropositive. after housekeeping and sanitary staff, the second most affected workers were lab technicians (37.1% were positive compared to 62.9% negative). fever, loss of taste or smell, and breathing difficulty were the most significantly associated symptoms with covid-19 antibody seroprevalence as suggested by p-value 0.003, 0.004, and 0.032 respectively. out of the 13 pcr positive participants (in the preceding 3 months), 10 (76.9%) showed positive antibodies in their serum and 3 (23.1%) had not developed antibodies. conclusion: seroprevalence of sars-cov-2 antibodies was estimated to be high among the healthcare staff, with the housekeeping and sanitary staff to be the most affected employees, probably due to the breach of personal protection. fever, loss of taste or smell, and breathing difficulty were strongly associated with seropositivity of sars-cov-2 antibodies. keywords: sars-cov-2, antibody testing, covid-19, healthcare workers. 90 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 89-93 introduction since covid-19 first emerged in wuhan, china on december 12, 2019, it has played havoc and emerged as a massive pandemic. as of november 22, 2020, who has reported 57.8 million cases and 1.3 million deaths globally since this catastrophe hit the world. pakistan along with iran, jordan, morocco, iraq, and lebanon has reported the highest number of new cases in the eastern mediterranean region.1 clinically, covid-19 manifestations include fever, dry cough, and fatigue, severe pneumonia in almost half of the patients, and acute respiratory distress syndrome in one-third of the patients.2 regarding diagnostic testing, two types of tests are being widely used across the globe. one type is molecular testing (polymerase chain reaction) on a nasal or throat swab sample, which detects the presence or absence of genetic material (ribonucleic acid) of the virus. another type of test detects the development of an immune response to the virus in the form of antibodies for example igm, igg, iga produced by the body in response to infection. these antibody detection tests are not useful in the diagnosis and screening of early infection because the immune system requires time to counter the viral invasion, but they can have paramount importance in establishing the immune status of a population.3 serology testing for covid-19 antibodies is helpful to determine whether people had been previously exposed to sarscov-2. sars‐cov‐2 is a member of the β‐coronavirus genus, with the sequence similarity being high (87.9% and 98.7%). 3 to 6 days after infection with sarscov-2, the level of igm antibodies increases and becomes detectable, but then the levels rapidly diminish thereafter. approximately 8 days after the appearance of symptoms, igg antibodies form in the blood, with progressively increasing levels over the course of infection and continue to rise for an extended period of time.4 in the absence of a vaccine, the buildup of sars-cov-2 herd immunity through natural infection is theoretically possible.5,6 the objective of this research is to carry out the antibody test against covid-19 among the employees of anth, imdc, and allied health care professionals at islamabad medical and dental college and its allied hospital akbar niazi teaching hospital (anth). there’s still a long way to go with both virus and antibody testing for covid-19. this current study will attempt to piece together the complex puzzle of antibody-mediated immunity, aiming to achieve safe, effective, and sustained protection against this devastating disease. it is pertinent to investigate the level of sars-cov-2 antibodies among healthcare staff who are the most exposed group in the community. it may help policymakers in making informed decisions in the light of evidence generated locally. materials and methods study design and participants: it was a descriptive cross-sectional study conducted among the employees of islamabad medical and dental college and its allied teaching hospital, bhara kahu, islamabad. all members of the staff and faculty of islamabad medical and dental college and allied hospital akbar niazi teaching hospital were encouraged to get tested for sars-cov-2 antibodies and 294 employees volunteered for the study. the healthcare workers included doctors, nurses, laboratory technicians, unit receptionists, housekeeping and sanitary workers, finance and administration staff. the study was approved by the institutional review board of the institution. informed consent was taken from all the participants explaining the objectives of the research and complete confidentiality and anonymity were ensured. data collection procedure and details of antibody testing: a structured questionnaire was used to collect information about age, department, history of any symptoms during the past 3 months, and history of nasal or throat swab for covid-19 if done. sarscov-2 antibody testing was done from 23rd july to 30th july 2020, through elecsys® anti-sars-cov-2 (immunoassay for the qualitative detection of igg antibodies against sars-cov-2 in human serum and plasma). the assay was performed on cobas e 411 analyzers by roche. cutoff index of <1.0 was taken as non-reactive, while coi ≥ 1.0 was considered positive. the sensitivity of the kit ≥ 14 days post-pcr confirmation is 99.5%, while its specificity is 99.8% (as claimed by the manufacturers). data analysis: data was analyzed through spss v.26. mean and standard deviation was calculated for continuous variables and frequencies and percentages for categorical variables. a chi-square test was used to find the relationship between antibody positivity and other variables, with a p value <0.05 taken as significant. ethical considerations: the study was approved by the institutional review board of islamabad medical and dental college (ref # 37/imdc/irb-2020). all 91 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 89-93 participants were informed about the objectives of the study and participated in the study with their consent. results a total of 284 staff members were recruited. the mean age of the study participants was 30.8 ± 9.4 years. about 175 (61.6%) were males and 109 (38.4%) were females. out of 284, 7 (2.5%) were from senior management, 52 (18.3%) were doctors, 31 (10.9%) unit receptionists, 93 (32.7%) were from the nursing department, 35 (12.3%) lab technicians, 29 (10.2%) housekeeping and sanitary workers, and 37 (13%) were from finance and admin department. antibody testing was done from 23rd july to 30th july 2020 which showed that 197 (69.4%) were negative while 87 (30.6%) came out antibody positive. the mean antibody level in the sample was 7.54 ± 17.94 while the mean antibody level in seropositive individuals was 24.44 ± 25.35. during the covid-19 pandemic, symptom analysis showed that 17 (6%) developed fever, 17 (6%) developed cough, 9 (3.2%) reported a loss of taste or smell, 3 (1.1%) reported diarrhea, while 5 (1.8%) had difficulty breathing. about 255 (89.8%) developed none of these symptoms, while 29 (10.2%) showed one or more of these symptoms. participants were also inquired about the month in which they developed the symptoms which showed that all of them showed the symptoms during the three months preceding our study. table 1 depicts no significant difference between the various age and gender groups (p-value 0.642 and 0.792 respectively). on inquiring about the symptoms, 182 (71.4%) of the participants had no symptoms during the preceding 3 months and were antibody negative. while among those who had developed symptoms, 14 (58.3%) had also developed antibodies compared to 15 (51.7%) who were antibody negative at the time of the test (p-value 0.035). the mean antibody level in the participants with a history of symptoms was 11.98 ± 21.2 while it was 7.04 ± 17.51 among those who were asymptomatic. table 1 cross-tabulation of antibody test results with age, gender, symptoms, and department of study participants variable antibody level p-value age positive negative 25 and below 32 (28.8%) 79 (71.2%) 0.642 26-30 22 (37.3%) 37 (62.7%) 31-35 14 (31.8%) 30 (68.2%) 36-40 10 (32.3%) 21 (67.7%) >40 9 (23.1%) 30 (76.9%) gender male 55 (31.4%) 120 (68.6%) 0.792 female 32 (29.4%) 77 (70.6%) any symptom in the preceding 3 months yes 14 (48.3%) 15 (51.7%) 0.035 * no 73 (28.6%) 182 (71.4%) department senior management/ finance and admin 13 (29.5%) 31 (70.5%) 0.095 * doctors 9 (17.3%) 43 (82.7%) unit receptionists 9 (29%) 22 (71%) nursing 29 (31.2%) 64 (68.8%) lab technicians 13 (37.1%) 22 (62.9%) housekeeping and sanitary workers 14 (48.3%) 15 (51.7%) on analyzing the department of the study participants, housekeeping and sanitary staff were found to be maximally affected (48.3%) followed by lab technicians (37.1%). after housekeeping and sanitary staff, the second most affected workers were lab technicians (37.1% were positive compared to 62.9% negative). out of the nursing staff, 29 (31.2%) had positive antibodies, while 64 (68.8%) had negative antibodies (p-value 0.095) as shown below in figure 1. figure 1: sar-cov-2 seroprevalence among employees of imdc and its teaching hospital table 2 shows fever, loss of taste or smell, and breathing difficulty to be significantly associated with covid-19 antibody seroprevalence as suggested by the p values 0.003, 0.004, and 0.032 respectively. 92 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 89-93 table 2: seroprevalence and symptoms of covid-19 among employees symptoms antibody level p-value fever positive negative yes 11 (64.7%) 6 (35.3%) 0.003 * no 76 (28.5%) 191 (71.5%) cough yes 5 (29.4%) 12 (70.6%) 0.575 no 82 (30.7%) 185 (69.3%) loss of taste or smell yes 7 (77.8%) 2 (22.2%) 0.004 * no 80 (29.1%) 195 (70.9%) diarrhea yes 2 (66.6%) 1 (33.3 %) 0.195 no 85 (30.2%) 196 (69.8%) breathing difficulty yes 4 (80%) 1 (20%) 0.032* no 83 (29.7%) 196 (70.3%) (*p-value < 0.05 depicts significant difference) 54 study participants out of 284 also had their pcr test done in the 3 months preceding the study out of whom 13 (24.1%) were positive at the time of the test and 41 (75.9%) were negative. out of the 13 pcr positive participants, 10 (76.9%) showed positive antibodies in their serum and 3 (23.1%) had not developed antibodies (among these 1 participants had been pcr positive only 10 days before the antibody test, while the other 2 were pcr positive 1.5-2 months before the antibody test). out of the 41 participants who were pcr negative at the time of the pcr test, 12 (29.2%) got infected thereafter and developed antibodies. among the 230 study participants who never had pcr test for covid-19, 65 (28.2%) had positive antibodies for covid-19. discussion our study provides valuable insight into the sars cov-2 antibody positivity rate among healthcare workers, seroconversion in pcr positive individuals, and strongly suggestive symptoms of covid-19. healthcare workers are the most exposed individuals in this pandemic and large numbers of asymptomatic healthcare workers could be a potential source of infection for others. this study reveals the seroprevalence of sars cov-2 antibody to be 30.6% among healthcare workers in a tertiary care hospital with maximum prevalence among housekeeping and sanitary workers (48.3%) followed by lab technicians (37.1%). this is higher than studies conducted in hospital settings of other countries.7,8 this may be due to a breach of personal protective measures and a lack of awareness in the communities they come from. the low prevalence of antibodies among doctors in our study reflects that strict use of precautionary measures has an impact on infectivity, despite being maximally exposed to the patients coming to the hospital. in another study done among healthcare workers in a tertiary care hospital in new york city, 9.8% of the healthcare workers tested positive for antibodies. however, no significant difference was observed in sars-cov 2 antibody rate across various age groups, gender, and job titles. our study also shows similar results with insignificant pvalues (0.642, 0.792, and 0.095 respectively).9 lower seroprevalence among healthcare workers has been reported in studies carried out in other parts of the world.10,11,12 in a study done in sweden among healthcare workers, the most reported symptoms were headache, malaise, fever, loss of smell, cough, and loss of taste; while abdominal pain and dyspnea were reported less frequently. symptoms with the strongest association to seroprevalence were anosmia, ageusia, and fever while the symptom of sore throat did not differ among seropositive and seronegative which is comparable to our results.13 another study that offered insight into the experience of healthcare workers of a critically affected covid-19 referral hospital in italy reported fever (69.5%), followed by weakness (44.5%), loss of taste (36%), and loss of smell (40%) to be the most common symptoms.14 an observational cohort study was carried out in healthcare staff of the capital region of denmark loss of taste or smell to be the most strongly associated symptom with seropositivity.15 a study conducted among swiss hospital workers reported a history of fever and myalgia to be the most differentiating symptom between seropositive and seronegative participants.16 in our study, fever, loss of taste or smell, and breathing difficulty are strongly associated with seropositivity of sars-cov-2 antibodies. a study assessing pcr positivity and humoral response in patients with covid-19 in new york city reported that 37% of suspected sars-cov-2 infections seroconverted to the sars-cov 2 spike proteins after 4 weeks. in the same study, out of the 624 confirmed sars-cov 2 participants, all had seroconverted to the sars-cov 2 antibodies after 4 weeks except three.17 in our study, out of the 13 participants who had been pcr positive, 3 (23.1%) had not developed antibodies. among these three, 1 participant was probably negative for sars-cov 2 antibodies because her 93 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 89-93 antibody levels were checked 10 days after pcr positivity. a limitation of this study was the small sample size. voluntary participation might have instigated selection bias in our sample. many of the healthcare workers refusing to participate might have had a characteristic associated with an increased risk of covid infection (being too busy at covid-19 wards, for instance). limited data is available on the accuracy of serology tests, which may result in over or underestimation of covid-19 infection. conclusion seroprevalence of sars-cov-2 antibodies was estimated to be high among the healthcare staff, with the housekeeping and sanitary staff to be the most affected employees, probably due to the breach of personal protection. fever, loss of taste or smell, and breathing were strongly associated with seropositivity of sars-cov-2 antibodies. references 1. (oms) who. covid-19 weekly epidemiological update [internet]. 2020. available from: https://www.who.int/docs/defaultsource/coronaviruse/situation-reports/20201012-weekly-epiupdate-9.pdf 2. xie j, ding c, li j, wang y, guo h, lu z, et al. characteristics of patients with coronavirus disease (covid-19) confirmed using an igm-igg antibody test. j med virol. 2020 oct;92(10):2004-2010. doi: 10.1002/jmv.25930. 3. jacofsky d, jacofsky em, jacofsky m. understanding antibody testing for covid-19. j arthroplasty. 2020 jul;35(7s):s74-s81. doi: 10.1016/j.arth.2020. 4. yan m, zheng y, sun y, wang l, luan l, liu j, et al. analysis of the diagnostic value of serum specific antibody testing for coronavirus disease 2019. j med virol. 2020 jun 27:10.1002/jmv.26230. doi: 10.1002/jmv.26230. 5. randolph he, barreiro lb. herd immunity: understanding covid-19. immunity. 2020 may 19;52(5):737-741. doi: 10.1016/j.immuni.2020.04.012. 6. bhopal rs. covid-19 zugzwang: potential public health moves towards population (herd) immunity. public health in practice. 2020 nov;1:100031. doi: 10.1016/j.puhip.2020.100031. 7. chen y, tong x, wang j, huang w, yin s, huang r, et al. high sars-cov-2 antibody prevalence among healthcare workers exposed to covid-19 patients. j infect. 2020 sep;81(3):420-426. doi: 10.1016/j.jinf.2020.05.067. 8. garcia-basteiro al, moncunill g, tortajada m, vidal m, guinovart c, jiménez a, et al. seroprevalence of antibodies against sars-cov-2 among health care workers in a large spanish reference hospital. nat commun. 2020 jul 8;11(1):3500. doi: 10.1038/s41467-020-17318-x. 9. jeremias a, nguyen j, levine j, pollack s, engellenner w, thakore a, et al. prevalence of sars-cov-2 infection among health care workers in a tertiary community hospital. jama internal medicine. 2020 dec 1;180(12):1707-9. doi:10.1001/jamainternmed.2020.4214 10. korth j, wilde b, dolff s, anastasiou oe, krawczyk a, jahn m, et al. sars-cov-2-specific antibody detection in healthcare workers in germany with direct contact to covid-19 patients. j clin virol. 2020 jul;128:104437. doi: 10.1016/j.jcv.2020.104437. 11. fusco fm, pisaturo m, iodice v, bellopede r, tambaro o, parrella g, et al. covid-19 among healthcare workers in a specialist infectious diseases setting in naples, southern italy: results of a cross-sectional surveillance study. j hosp infect. 2020 aug;105(4):596-600. doi: 10.1016/j.jhin.2020.06.021. 12. lackermair k, william f, grzanna n, lehmann e, fichtner s, kucher hb, et al. infection with sars-cov-2 in primary care health care workers assessed by antibody testing. fam pract. 2020 aug 7:cmaa078. doi: 10.1093/fampra/cmaa078. 13. rudberg as, havervall s, månberg a, jernbom falk a, aguilera k, ng h, et al. sars-cov-2 exposure, symptoms and seroprevalence in healthcare workers in sweden. nat commun. 2020 oct 8;11(1):5064. doi: 10.1038/s41467-020-18848-0. 14. colaneri m, novelli v, cutti s, muzzi a, resani g, monti mc, et al. the experience of the health care workers of a severely hit sars-cov-2 referral hospital in italy: incidence, clinical course and modifiable risk factors for covid-19 infection. j public health (oxf). 2020 nov 3:fdaa195. doi: 10.1093/pubmed/fdaa195. 15. iversen k, bundgaard h, hasselbalch rb, kristensen jh, nielsen pb, pries-heje m, et al. risk of covid-19 in health-care workers in denmark: an observational cohort study. lancet infect dis. 2020 dec;20(12):1401-1408. doi: 10.1016/s14733099(20)30589-2. 16. kohler pp, kahlert cr, sumer j, flury d, güsewell s, lealneto ob, et al. prevalence of sars-cov-2 antibodies among swiss hospital workers: results of a prospective cohort study. infect control hosp epidemiol. 2020 oct 8:1-5. doi: 10.1017/ice.2020.1244. 17. wajnberg a, mansour m, leven e, bouvier nm, patel g, firpo-betancourt a, et al. humoral response and pcr positivity in patients with covid-19 in the new york city region, usa: an observational study. the lancet microbe. 2020 nov 1;1(7):e2839. 202 journal of rawalpindi medical college (jrmc); 2021; 25(2): 202-207 original article frequency and risk factors of low birth weight in rawalpindi, pakistan usman zafar1, sadia zafar2, nadia tariq3, farah rashid4, khalid hassan5 1 assistant professor, department of medicine, islamabad medical and dental college, islamabad. 2 lecturer, department of community medicine, islamabad medical and dental college, islamabad. 3 associate professor, department of community medicine, islamabad medical and dental college, islamabad. 5 professor and hod, department of community medicine, islamabad medical and dental college, islamabad. 6 principal and professor of pathology, islamabad medical and dental college, islamabad. author’s contribution 1 conception of study 1 experimentation/study conduction 2 analysis/interpretation/discussion 2,3,4 manuscript writing 5 critical review 3,4 facilitation and material analysis corresponding author dr. sadia zafar, lecturer, department of community medicine, islamabad medical and dental college, islamabad email: sadia.11@imdcollege.edu.pk article processing received: 06/01/2021 accepted: 25/05/2021 cite this article: zafar, u., zafar, s., tariq, n., rashid, f., hassan, k. frequency and risk factors of low birth weight in rawalpindi, pakistan. journal of rawalpindi medical college. 30 jun. 2021; 25(2): 202207. doi: https://doi.org/10.37939/jrmc.v25i2.1467 conflict of interest: nil funding source: nil access online: abstract introduction: low birth weight is a key determinant of infant survival health and development. there are many maternal and biological risk factors for it. the objective of this study is to determine the frequency and associated risk factors of low birth weight. materials and methods: this cross-sectional study was carried out in the department of obstetrics and gynecology; al razi hospital, rawalpindi from 1st june 2016 till 1st june 2020. the total sample size was 20,681 which was the total number of births during these years in this hospital setting results: the overall frequency of lbw was found to be 8.9%. female babies were more likely to have lbw (9.9%) as compared to male babies (7.9%) with a significant p-value. lbw babies had poor apgar scoring as compared to normal weight (p=0.000). 252 (75%) of the premature babies were lbw. among primigravida women, 796 (10.8%) gave birth to lbw babies. conclusion: it was concluded that gestational age, parity, maternal weight gain during pregnancy, history of miscarriages, and several antenatal visits were significantly associated with low birth weight. lbw was associated with a poor apgar score. keywords: frequency, low birth weight, pakistan. 203 journal of rawalpindi medical college (jrmc); 2021; 25(2): 202-207 introduction who defines low birth weight as any neonate weighing 2500 grams or less at birth whether it is preterm or term. very low birth weight babies (vlbw) are those weighing less than 1500 gms.1 the low birth weight (lbw) is taken as a sensitive index of the nation’s health and development. nearly a third of the newly born babies in south east asia is low birth weight. there are many causes of low birth weight which are greatly influenced by the interaction of both socio-demographic and biological factors. according to unicef, unfortunately, pakistan has the highest incidence of lbw babies in the south asian region.2 extremes of maternal age (under 17 and over 35 years) and mothers having deprived socioeconomic settings are at a greater risk of delivering lbw babies. there is ample evidence to show that maternal weight, height, body mass index (bmi), multiple gestations, birth interval, parity, the experience of any physical violence, and the lack of skilled antenatal care, maternal smoking are the risk factors associated with pregnancy outcomes.3,4 the problem is shared unequally between developing and developed countries of the world. the united nations children fund (unicef) reported that the low birth weight rate was 15.5% worldwide and the majority (95% of these lbw infants) belonged to the developing world.5 low birth weight is a risk factor for poor health outcomes at a later age. a decline in lbw can have a significant contribution in achieving sustainable development goal for reducing child mortality. in pakistan, despite the efforts made to achieve sustainable development goals, still, 25% of neonates are born with low birth weight.6 a high mortality rate is reported among low birth weight babies as compared to normal weight. reasons for mortality among lbw are attributed to neonatal sepsis and respiratory distress syndrome. incidence of complications due to lbw increases with a decrease in birth weight. primary causes of death in babies weighing 1000-2000 are congenital malformation, birth asphyxia, and intra-ventricular/ peri-ventricular hemorrhage. jaundice and hypothermia are also noticeably reported among low birth weight babies.7 pakistan is striving to reduce child mortality to achieve sdgs. low birth weight is a significant and useful predictor of the health of a child. until and unless we know the frequency of lbw and its associated factors, we will not be able to implement strategies to reduce its occurrence and ultimately contribute to decreasing child mortality. this research will be helpful to quantify the problem and its possible risk factors that will help in devising effective ways to reduce the incidence of low birth weight amongst newborn babies. materials and methods objectives:  to determine the frequency of low birth weight among babies born at al-razi hospital in rawalpindi islamabad.  to identify the various associated risk factors of low birth weight. a cross-sectional survey was conducted between 1st june 2016 to 1st june 2020 to determine the frequency of low birth weight born to expecting females reporting to the department of obstetrics and gynecology, at al-razi hospital, rawalpindi during a study period of 4 years. all unbooked cases reported in obstetrics and gynae emergency were excluded. a total of 20,681 babies were born (booked cases) at al-razi hospital during the study period. a structured pre-tested questionnaire was used. cronbach’s alpha for the tool was calculated to be 0.89. the information collected included the birth weight of newborn babies, gender, apgar scoring, maternal age, weight, maternal hemoglobin level, parity, history of miscarriages, and several antenatal visits. birth weight was recorded by using a digital scale within 24 hours of delivery and who definition was used to categorize birth weight. babies weighing more than 2500 grams were categorized as normal birth weight, 2500 grams or less as low birth weight, and greater than 4000 grams as macrosomic. data was analyzed using spss v 26. percentages were calculated for categorical variables while continuous variables analyzed using mean and standard deviation. inferential statistics calculated by using chisquare test (taking p-value less than 0.05 as significant. ethical considerations: the study was undertaken after getting approval from the ethical committee of al-razi hospital. informed consent was taken from all the participant mothers, explaining in detail the research topic and objectives. confidentiality and privacy were ensured. soft data was password protected ensuring data security. all procedures performed during this study and involvements of subjects were in accordance with the ethical standards of the institutional and national research committee and with the 1964 helsinki declaration and its later amendments. 204 journal of rawalpindi medical college (jrmc); 2021; 25(2): 202-207 results the mean weight of the sample was 2.996 ± 0.662. the mean weight among low birth weight babies was 2.112 ± 0.346 while among normal and macrosomic babies, the mean weight was 3.124 ± 0.511. out of total 20,681 live births (10,061)48.6% were female, (10,620) 51.3% were male. (255) 1.2% were twin/multiple births. the overall prevalence of lbw was found to be (1730) 8.4%, 112 (0.5%) were vlbw, and (18,839) 91.1% had normal birth weight (nbw). 229 (1.1%) babies were small for gestational age among the sample. gender-wise (996) 9.9% of female babies were lbw, 9065 (90.1%) nbw; while 846 (7.9%) male babies were found to be lbw and 9774 (91.8%) nbw. on application of chi-square it was inferred that female babies are more likely to have lbw as compared to male babies and this finding was statistically highly significant (p-value=0.000) figure i: distribution of birth weight apgar scoring was done just after the birth of all the babies and classified as concerning, (score 0=3), moderately abnormal (4-6), and reassuring (7-10) and turned out to be 219 (1%), 7252 (35%) and 13,210 (63.8%) respectively. among lbw babies, 87 (4.7%) had concerning apgar score, 658 (35.7%) had moderately abnormal scores and 1097 (59.6%) had reassuring apgar score. while among nbw babies, only 132 (0.7%) babies had concerning apgar scores, 6594 (35%) had moderately abnormal scores, and 12,113 (64.3%) had reassuring scores. this shows that lbw babies have poor apgar scoring and lbw is one of the significant factors (p=0.000) which affect the outcome of apgar scores. the frequency and percentages of maternal risk factors are shown in table 1. table 1: frequency and percentages of maternal risk factors for low birth weight maternal risk factors frequency (n) percentage (%) age <20 680 3.3 20-25 7668 37 26-30 8498 41.1 31-35 2997 14.5 36 and above 838 4.1 hemoglobin normal 11638 56.3 anemia 9043 43.7 parity primigravida 7348 35.5 1-2 9955 48.1 3 and above 3378 16.3 antenatal visits <4 5269 25.5 4 or more 15412 74.5 maternal weight <70kg 9465 45.8 70kg or more 11216 54.2 history of miscarriages 0 15852 76.7 1 3337 16.1 2 1007 4.9 3 and above 485 2.3 gestational age <37 weeks 20345 98.4 37 weeks or above 336 1.6 table 2: association of maternal risk factors with low birth weight (n = 20681) maternal risk factors birth weight pvalue lbw n (%) normal n (%) age <20 68 (10%) 612 (90%) 0.309 20-25 707 (9.2%) 6961 (90.8%) 26-30 717 (8.4%) 7781 (91.6%) 31-35 271 (9%) 2726 (90.9%) 36 and above 79 (9.6%) 759 (90.4%) hb (gm/dl) normal 1068 (9.2%) 10570 (90.8%) 0.233 anemia 774 (8.5%) 8269 (91.4%) parity 205 journal of rawalpindi medical college (jrmc); 2021; 25(2): 202-207 primigravida 796 (10.8%) 6552 (89.2%) 0.000* 1-2 766 (7.7%) 9189 (92.3%) 3 and above 280 (8.3%) 3098 (91.7%) antenatal visits <4 610 (11.6%) 4659 (88.4%) 0.000* 4 or more 1232 (8%) 14180 (92%) maternal weight <70kg 1103 (11.6%) 8362 (88.3%) 0.000* 70kg or more 739 (6.6%) 10477 (93.4%) history of miscarriages 0 1432 (9%) 14420 (91%) 0.004* 1 270 (8.1%) 3067 (91.9%) 2 81(8.1%) 926 (91.9%) 3 and above 59(12.2 %) 426 (87.8%) prematurity (gestational age<37 weeks) no 1590 (7.8%) 18755 (92.2%) 0.000* yes 252 (75%) 84 (25%) the most important factor for lbw was gestational age. 252 (75%) of the premature babies were lbw. while among term babies, only 7.8% were lbw (pvalue=0.000) the frequency of lbw was higher among mothers who were <20years of age and >30years, however, the p-value is not significant. the mothers who had less than 4 (recommended by who) antenatal visits were more likely to have lbw babies (p-value=0.00). lbw babies were reported more among primigravida women with 796 (10.8%) of the primigravida women giving birth to lbw babies (p-value= 0.000). with increasing, maternal weight frequency of lbw was reduced. 1103 (11.6%) of the mothers weighing <70kg gave birth to lbw babies, while among mothers weighing greater than 70kg the frequency of lbw babies was only 739 (6.6%) with a significant p-value. the history of miscarriages was also found to be an important factor for lbw. among women reporting a history of 3 or more miscarriages, 59 (12.2%) gave birth to lbw babies. (p-value=0.04) discussion the present study shows a frequency of low birth weight at 8.9% with female babies more likely to have lbw. apgar scoring done at the time of birth revealed that 40.4% of babies with low birth weight had moderately abnormal or concerning apgar scoring when compared to apgar score of normalweight babies. a study conducted in muzaffarabad, azad jammu kashmir on a sample of 1863 births reveals comparable findings with the frequency of lbw at 10.04% with more number of female babies having lbw but the difference between male and females to be statistically insignificant in their study8 as in another study done in layari general hospital, karachi which shows the frequency of lbw at 10.6%.9 prevalence of lbw was 10.2% according to a study conducted on data from the national survey of indonesia demographic and health survey (idhs).10 demographic and health survey from least developed countries as defined by the world bank including cambodia, colombia, indonesia, jordan, nepal, pakistan, tanzania, uganda, and zimbabwe reveals the overall prevalence of 15.9% of lbw babies11 while 13.8% were lbw according to a study conducted in rural maharashtra, india.12 proportion of lbw in nigeria demographic and health survey is found to be 7.3% which is lower than the studies done in other parts of the world. this might be because most of the deliveries that were taken into consideration in that study were non-institutional and babies are less likely to be weighed at birth in such a setting and data relied on self-reporting.13 maternal age is a useful predictor for lbw as shown by a study carried out by gulnaz et al where the incidence of lbw is found to be decreasing with increasing maternal age supported by nigeria demographic and health survey while this study shows that lbw was most frequent in less than 20 and more than 36 years of maternal age. the indian study reveals that odds of lbw were twice as high in maternal age less than 22 years which can be compared to our study. mothers with advanced age (35 to 49 years) had a significantly greater risk of delivering lbw babies than younger mothers according to a health survey from developing countries which is similar to our study. according to a study carried out in california, women aged 40 to 54 years were twice as likely to have an lbw infant as women in the 20 to 24 age group which is not in accordance with the above findings.14 this difference may be because in developed countries like the usa, 206 journal of rawalpindi medical college (jrmc); 2021; 25(2): 202-207 women tend to have children at late ages and fewer women are likely to give birth in less than 20 years of age. parity has an impact on the birth weight of the baby as demonstrated by this study in which lbw were mostly born to primigravida women who are in contrast to the study conducted in nigeria where among lbw babies, there was a greater proportion of multiparous women. our results are similar to a study conducted in maharashtra, india which shows that the odds of both pre-term delivery and lbw were reduced in multigravida compared with primigravida women, regardless of age. the association of maternal anemia with lbw is found to be statistically insignificant in this study. anemia was not significantly related to birth outcomes in a study conducted in california as well as india. on the contrary, is a study by gulnaz et al where regression analysis revealed that with an increase in hemoglobin level, there was a decrease in the incidence of lbw babies and a study conducted in layari where maternal anemia is significantly associated with lbw. mothers15 having less than 4 antenatal visits during pregnancy delivered more lbw babies as compared to those who had 4 or more antenatal visits. this is similar to a study conducted in south africa where women who attended fewer than five anc visits were predisposed to have low birth weight babies. according to a study in china, mothers who did not receive five anc visits had a higher risk of lbw babies than those who had received it.16 proportion of lbw babies was more (15.9%) in mothers who had not availed of full antenatal care also in an indian study.17 these consistent results show that several antenatal visits greatly impact the birth weight of the baby. history of abortions is significantly associated with term low birth weight according to an ethiopian study18 similar to our study that reveals a statistical association between having 3 or more abortions and having lbw babies. consistent results are shown by a study by bora m. showing mothers who had a previous history of abortions and stillbirth having a high percentage of lbw babies (28%).19 maternal weight was also significantly associated with the birth weight of a newborn in this study with more lbw babies born to mothers having weight less than 70 kg. low maternal weight was a significant risk factor for lbw babies in a study conducted in gujrat, india.20 weight gain has a significant effect on infant birth weight, a 1 kg increase in the pregnancy weight was associated with 94 g increase in bw according to a study conducted in mikelle city, northern ethiopia.21 conclusion the overall frequency of low birth weight was 8.9% which was significantly associated with maternal factors. the most important factor associated with birth weight was gestational age. low birth weight increased with extremes of maternal age. primigravida was more likely to have lbw babies. as maternal weight increased, the frequency of low birth weight decreased. less than four antenatal visits increased the incidence of lbw. women who had a history of more than 3 abortions significantly impacted birth weight. lbw was associated with baby gender with female babies more likely to have lbw. babies with lbw had poor apgar scores as compared to normal weight babies practical implications: our study strongly suggests antenatal visits and advice as a predictor of healthy newborn weight. our findings will be disseminated to various stakeholders and policymakers to help them strengthen the antenatal coverage and services to improve newborn health and contribute to the steps taken towards achieving sustainable development goals. references 1. tchamo me, prista a, leandro cg. low birth weight, very low birth weight and extremely low birth weight in african children aged between 0 and 5 years old: a systematic review. journal of developmental origins of health and disease. 2016 aug 1;7(4):408-15. 2. naqvi j, siyal aa, taqi t. frequency and outcome of low birth weight babies admitted in tertiary care hospital. national editorial advisory board. 2018 nov;29(11):32. 3. jamshed s, farah-khan ab, ali bb, akram z, ariff m. frequency of low birth weight and its relationship with maternal nutritional and dietary factors: a cross-sectional study. cureus. 2020 jun;12(6).doi: 10.7759/cureus.8731 4. rashid f, makhdoom s. maternal health in pakistan: where do we stand?. journal of islamabad medical & dental college. 2019 sep 29;8(3):99-100. 5. chanie h, dilie a. prevalence of low birth weight and associated factors among women delivered in debre markos referral hospital, east gojam, ethiopia, 2017. prevalence. 2018;53. 6. saeed a, saeed am. maternal predictors of low birth weight among women attending private hospitals of lahore, pakistan. progress in nutrition. 2017 sep 1;19(3):257-63. doi:10.23751/pn.v19i3.5036 7. shaikh f, laghari gs, syal ar, hameed a, nizamani ma. complications of low birth weight babies during first 72 hours of life. med channel. 2016 jan 1;22(1):18-24. 8. iltaf g, shahid b, khan m i. incidence and associated risk factors of low birth weight babies born in shaikh khalifa bin zayad al-nayan hospital muzaffarabad, azad jammu and kashmir. pak j med sci. 2017;33(3):626-630. https://doi.org/10.12669/pjms.333.12413 207 journal of rawalpindi medical college (jrmc); 2021; 25(2): 202-207 9. khan a, nasrullah f d, jaleel r. frequency and risk factors of low birth weight in term pregnancy. pak j med sci. 2016;32(1):138-142. http://dx.doi.org/10.12669/pjms.321.8120 10. siramaneerat i, agushybana f, meebunmak y. maternal risk factors associated with low birth weight in indonesia.the open public health journal. 2018;11: 377 11. mahumud ra, sultana m, sarker ar. distribution and determinants of low birth weight in developing countries. j prev med public health 2017;50:18-28 https://doi.org/10.3961/jpmph.16.087 12. ahankari a, bapat s, myles p, fogarty a, tata l. factors associated with preterm delivery and low birth weight: a study from rural maharashtra, india. f1000research. 2017;6. 13. dahlui m, azahar n, oche om, aziz na. risk factors for low birth weight in nigeria: evidence from the 2013 nigeria demographic and health survey. global health action. 2016 dec 1;9(1):28822. 14. ratnasiri aw, parry ss, arief vn, delacy ih, halliday la, dilibero rj, et al. recent trends, risk factors, and disparities in low birth weight in california, 2005–2014: a retrospective study. maternal health, neonatology and perinatology. 2018 dec 1;4(1):15. https://doi.org/10.1186/s40748-018-0084-2 15. tshotetsi l, dzikiti l, hajison p, feresu s. maternal factors contributing to low birth weight deliveries in tshwane district, south africa. plos one. 2019 mar 1;14(3). https://doi.org/10.1371/journal.pone.0213058 16. zhou h, wang a, huang x, guo s, yang y, martin k, et al. quality antenatal care protects against low birth weight in 42 poor counties of western china. plos one. 2019 jan 16;14(1).https://doi.org/10.1371/journal.pone.0210393 17. uppadhaya sk, agrawal n, bhansali s, garg k, singh m. utilization of antenatal health care services and its impact on birth weight of newborn in rural area of western rajasthan, india. international journal of community medicine and public health. 2017 mar;4(3):680. http://dx.doi.org/10.18203/2394-6040.ijcmph20170739 18. gebregzabiherher y, haftu a, weldemariam s, gebrehiwet h. the prevalence and risk factors for low birth weight among term newborns in adwa general hospital, northern ethiopia. obstetrics and gynecology international. 2017 jul 4;2017. https://doi.org/10.1155/2017/2149156 19. borah m, agarwalla r. maternal and socio-demographic determinants of low birth weight (lbw): a community-based study in a rural block of assam. journal of postgraduate medicine. 2016 jul;62(3):178-181. doi:10.4103/0022-3859.184275 20. parikh t, parikh a. maternal risk factors and outcome of low birth weight babies admitted to a gujarat adani institute of medical science, bhuj, kutch, gujarat, india-a cross-sectional study.international journal of medical pediatrics and oncology, april-june, 2017:3(2):54-56. doi:10.18231/24556793.2017.0015 21. tela fg, bezabih am, adhanu ak. effect of pregnancy weight gain on infant birth weight among mothers attending antenatal care from private clinics in mekelle city, northern ethiopia: a facility based follow-up study. plos one. 2019 mar 11;14(3).https://doi.org/10.1371/journal.pone.0212424 198 journal of rawalpindi medical college (jrmc); 2020; 24(3): 198-203 original article assessment of factors responsible for early menopause in interior sindh, pakistan latafat ali chughtai1, aliza sahito2, jawaid ahmed zai3, zaibunisa mughal4, jamshed warsi5, benazir mahar6 1,3,4 assistant professor, department of physiology, university of sindh, jamshoro, pakistan. 2 ms student, griffth university, queensland, australia. 5 associate professor, department of physiology, university of sindh, jamshoro, pakistan. 6 m. phil scholar, department of physiology, university of sindh, jamshoro, pakistan. author’s contribution 1 conception of study 1,2,3,4 experimentation/study conduction 1,2 analysis/interpretation/discussion 1,5,6 manuscript writing 5,6 critical review 1 facilitation and material analysis corresponding author ms. benazir mahar, m. phil scholar, department of physiology, university of sindh, jamshoro, pakistan email: beenafs@hotmail.com article processing received: 08/10/2019 accepted: 24/09/2020 cite this article: chughtai, l.a., sahito, a., zai, j.a., mughal, z., warsi, j., mahar, b. assessment of factors responsible for early menopause in interior sindh, pakistan. journal of rawalpindi medical college. 30 sep. 2020; 24(3): 198-203. doi: https://doi.org/10.37939/jrmc.v24i3.1175 conflict of interest: nil funding source: nil access online: abstract objective: to evaluate the factors leading to the early onset of menopause (<40 years) in the women in the interior of sindh. materials and methods: a cross-sectional study was conducted on 218 individuals among them 109 were postmenopausal women (with premature menopause) and 109 were normal menstruating females during the period of six months from november 2014 to april 2015, data was obtained from interior sindh, larkana, hyderabad, and benazirabad. factors considered were age, number of children, history of the obstetric process (ovarian and uterine), diseases, and premature menopause history in first-cousin marriages. the questionnaire data and blood samples were collected for hormonal assays such as lh, prolactin, and fsh. the hormone levels were analyzed by elisa method, spss version 17 was used for data analysis. results: out of 109 subjects the percentage of early menopause due to: anorexia nervosa was 17%, brain tumor 7%, ovarian cancer 6%, hormonal disorders 23%, hysterectomy 15%, oophorectomy 5%, pituitary gland dysfunction 4%, sheehan syndrome 24%, polycystic ovarian syndrome (pcos) 8%. conclusion: early menopause was found related to pathological and psychological factors including brain tumor, ovarian cancer, family history, anorexia nervosa, and certain surgical interventions. keywords: early menopause, ovarian cancer, family history, hormonal disturbance. 199 journal of rawalpindi medical college (jrmc); 2020; 24(3): 198-203 introduction the word menopause is derived from the greek word “meno” which means stop cease. this is an aging process due to a reduction in the ovarian hormones progesterone and estrogen.1 the normal age of menopause is about 44-55 years, but some women suffer from menopause before 40 years of age. menopause that occurs before 40 years of age, due to any reason, is called premature menopause. this can leads to earlier onset of chronic diseases of aging and therefore lengthen to later years as well. menopause is a major factor for bone degeneration.1-4 furthermore; premature or early menopause, also known as a premature ovarian failure (pof), is an important disorder that affects a significant population of young women.5 characteristics of this condition are amenorrhea, elevated gonadotropins, and decreased gonadal steroids. the effect of this condition is on both physical and psychological components, it is so because of the long term effects of the gonadotrophin depletion in the body. furthermore, the distressing result of this condition is infertility.6 proper functioning of the hypothalamus, pituitary gland, uterus, and ovaries are necessary for the normal menstrual cycle. the hypothalamus triggers the pituitary gland; the pituitary stimulates folliclestimulating hormone (fsh) and luteinizing hormone (lh). fsh and lh trigger the ovaries to produce hormones estrogen and progesterone.7 estrogens and androgens affect the skeleton during growth and skeletal homeostasis during adulthood. the decrease in estrogen concentration with menopause effects of female bone resorption.8 the study conducted in jordanian women with early menopause shows that the association factor for the early menopause history in first-cousin marriages.1 similar studies were carried out on early menopause and risk of fracture, osteoporosis, and mortality in swedish women aged 48 years with early menopause, later on at the age of 77, they had a risk ratio of 1.83 for osteoporosis, for fragility fracture risk ratio was 1.68 and mortality risk was 1.59.9 premature menopause results in adverse effects, which include cardiovascular diseases, psychiatric diseases, mortality, neurological diseases, osteoporosis, sheehan’s syndrome, and early death.10 hormonal therapies have succeeded to moderate levels with some risks but many others are still under the line and faced by the patients.11,12 this study was aimed to assess the factors which cause menopause at an early age and to check the prevalence of factors which are most common along with factors having raised fsh, lh & prolactin levels and those having low fsh, lh & prolactin levels in the women of interior of sindh as compared to the women of the same age without early menopause. also, inform the healthcare personnel about the situation so that they may consider the prevailing factors while treating the patients. materials and methods a cross-sectional study, for which participants were selected from interior sindh. the duration of the study was about six months. a convenient non-probability technique has been used for sampling. the sample size was 218 subjects. females with early menopause were included in the study as case, their age is 33.3 ± 3.23 whereas women with normal menstrual cycles were included as controls for the study of age 32.67 + 3.07 respectively. females on medication and suffering from any disease particularly any hormonal disorder were excluded. blood samples required for the study were collected from normal and affected individuals and written consent was obtained before the sampling. samples were collected in 5ml gel tubes and serum was separated. the elisa method was used to assess the concentration of prolactin, lh, and fsh hormones13,14, in their blood by using human diagnostic worldwide test kits with elisa reader uvm 340. the principle is based on monoclonal antibodies and another in antibody-enzyme conjugate solution. the sample is reacted with antibodies at the same time with antibodies resulting in the sandwiching of sample molecules between the solid phase and enzyme-linked antibodies. for this 100 µl of the conjugate is dispensed into the wells. 50 µl of calibrator was added into the 5 wells. 50 µl of control & samples into the wells and then the plate is covered with an adhesive sheet and incubated at 37oc for about 60 minutes. the solution is then removed from the wells and was washed with a wash solution for any unbounded antibodies. 100 µl of the substrate was poured into the wells and was covered with aluminum foil and incubated for about 15 minutes at room temperature and stop solution (100 µl) is added into the wells for any further color development and finally, od is observed at 450nm in a plate reader. all data obtained were put into spss version 17 for analysis of results. ethical consideration: the questionnaire was anonymously administered to the women/girls, with 200 journal of rawalpindi medical college (jrmc); 2020; 24(3): 198-203 the permission of the ethical review committee of the department of physiology. written consents were taken from the control and subject groups before managing the questionnaires. the present study will be used for the research purpose. results in this study, 109 cases and 109 healthy controls were studied. from cases, 104 were housewives, and 5 were office workers. the mean age of the cases involved in this study was 33.3 ± 3.23 while controls 32.67 + 3.07. the mean fsh, lh, and prolactin were higher in study cases than controls. the mean bmi value of controls was (24.14 + 3.78) and that of study cases was (23.78 + 4.56). in the case of anorexia nervosa (17%), the mean fsh level was lower in cases than in controls, similarly, the mean lh level of cases was lower than in controls. whereas, the mean prolactin level was higher in subjects than in controls. the results were significant as shown in table-1. in subjects of brain tumor (7%), the mean fsh level was higher than in the control; similarly, the mean lh levels were also higher in study subjects than in controls. the mean prolactin level was also elevated in subjects as compared to controls. women undergoing ovarian cancer (6%) have a mean fsh level, mean lh level, and mean prolactin level increased than controls. in the case of hormonal disorders (23%), the mean fsh level was greater in study subjects than controls, similarly the mean lh level and mean prolactin level were also notable than controls. post hysterectomy (15%) cases had a high level of fsh, lh, and prolactin as compared to the controls. in cases of oophorectomy (5%) the mean fsh level, mean lh level and mean prolactin level was higher than controls which herald early menopause. in the case of pituitary dysfunction (4%) the study subjects had a higher mean fsh level than in controls, similarly, the mean lh level of subjects was also higher than in controls and the mean prolactin level was also at an elevated level in subjects than in controls. similarly, in the case of sheehan syndrome, the cases had a greater mean fsh level mean lh level, and mean prolactin level than controls. women undergoing polycystic ovarian syndrome (8%) had raised levels of mean fsh, lh, and prolactin than normal women. table 1: differences in fsh, lh, and prolactin level in control & cases of early menopause in different conditions different conditions hormones case control t-value p-value anorexia nervosa fsh 7.79 + 1.95 10.8 + 1.66 4.85 <0.001 lh 13.5 + 3.17 20.30 + 1.75 8.86 <0.001 prl 22.01 ± 2.13 11.34 ± 1.94 15.71 <0.001 brain tumor fsh 14.04 ± 3.88 10.94 ± 1.85 1.972 0.09 lh 21.54 ± 5.21 21.05 ± 1.55 0.235 0.82 prl 27.41 ± 4.70 10.54 ± 1.88 9.631 <0.001 ovarian cancer fsh 40.4 ± 4.70 11.86 ± 1.04 13.60 <0.001 lh 60.9 ± 5.93 21.1 ± 2.35 15.63 <0.001 prl 40.2 ± 10.07 13.25 ± 2.98 6.22 0.002 hormonal disorder fsh 36.20 ± 6.97 10.21 ± 2.12 17 <0.001 lh 45.82 ± 8.80 20.38 ± 3.18 15.63 <0.001 prl 33.62 ± 6.04 13.12 ± 2.33 16.9 <0.001 hysterectomy fsh 32.74 ± 5.4 10.38 ± 2.38 13.9 <0.001 lh 42.07 ± 6.73 20.41 ± 3.73 9.64 <0.001 201 journal of rawalpindi medical college (jrmc); 2020; 24(3): 198-203 prl 30.54 ± 5.29 15.80 ± 4.33 6.87 <0.001 oophorectomy fsh 34.48 ± 4.25 7.46 ± 1.08 13.21 <0.001 lh 49.14 ± 9.77 17.26 ± 4.08 9.803 0.001 prl 26.48 ± 5.59 11.64 ± 1.54 6.904 0.002 pituitary dysfunction fsh 46.00 ± 2.25 10.30 ± 2.34 35.94 <0.001 lh 65.22 ± 4.25 20.92 ± 2.19 14.727 0.001 prl 40.95 ± 9.03 14.92 ± 3.31 6.643 0.007 sheehan syndrome fsh 38.40 ± 9.29 10.39 ± 2.30 14.284 <0.001 lh 54.27 ± 8.90 20.38 ± 3.28 18.801 <0.001 prl 38.49 ± 9.78 13.22 ± 4.36 10.511 <0.001 polycystic ovarian syndrome fsh 42.82 ± 3.37 10.81 ± 2.22 18.051 <0.001 lh 57.42 ± 6.26 21.08 ± 2.69 19.019 <0.001 prl 41.87 ± 6.28 12.98 ± 2.80 12.832 <0.001 all cases fsh 31.35 ± 13.4 10.4 ± 2.13 15.780 <0.001 lh 43.12 ± 17.3 20.39 ± 2.96 13.754 <0.001 prl 32.9 ± 9.26 13.08 ± 3.4 21.47 <0.001 as shown in table: 1; the serum fsh, lh, and prolactin level is significantly higher in menopausal women (in brain tumor, ovarian cancer, hysterectomy, oophorectomy, polycystic ovarian syndrome and in pituitary disorders) as compared to normal menstruating females. table 2: differences in bmi in control & cases of early menopause in different conditions bmi case control t-value p-value anorexia nervosa 25.94 ± 3.47 25.64 ± 3.92 1.000 0.332 brain tumor 23.42 ± 4.27 23.3 ± 4.24 0.711 0.515 ovarian cancer 23.0 ± 3.6 23.00 ± 3.68 1.147 0.289 hormonal disorder 25.43 ± 3.23 23.47 ± 3.95 0.2801 0.01 hysterectomy 25.3 ± 3.65 24.9 ± 3.78 1.000 0.334 oophorectomy 23.2 ± 2.28 23.1 ± 2.18 0.670 0.47 pituitary dysfunction 24.0 ± 2.82 22.50 ± 4.12 1.000 0.391 sheehan syndrome 25.79 ± 3.10 23.66 ± 3.88 2.797 0.01 polycystic ovarian syndrome 27.12 ± 2.79 24.62 ± 3.96 1.01 0.34 all cases 23.7 ± 4.56 24.14 ± 3.78 0.688 0.493 as illustrated in table no.2 bmi was slightly fluctuating in both case and control groups however not reaching the significance level. bmi is not a factor causing the onset of early menopause. 202 journal of rawalpindi medical college (jrmc); 2020; 24(3): 198-203 discussion early menopause is linked with long term multiple health consequences including diabetes15 cardiac problems, psychiatric disturbances, neurological disorders, osteoporosis along with increased mortality.16,17 however, the adverse effects could be minimizing by giving estrogen therapy but it is not much beneficial in treating all these health issues.16 this study is in conformation with reflective study18 where the trends of hysterectomy were studied in the rural tertiary level teaching hospitals in northern india. it was concluded that early menopause is either impulsive or driven. women suffering from menopause, because of bilateral hysterectomy, oophorectomy, or cancer treatment.19,20 this is all associated with early menopause. in contrast to this study, women with brain cancer had increased prolactin. the chances of infertility increase as a result of oncological treatment. it is postulated that chemotherapy and radiations used in cancer treatments lead to earlier menopause presented with much severe symptoms.21 in this study women who have undergone surgeries like hysterectomy and oophorectomy are nearly at increased risk of early menopause. furthermore, a study conducted in usa 22 also established that women undergoing surgeries have more risk for having early menopause.23,24 also conducted a similar study in women with and without hysterectomy. she also concluded that surgeries are related to earlier onset of menopause. also the study on the jordanian women, 2010 shows that the women who suffered from early menopause were having a history of premature menopause in their parents, siblings or child1 furthermore it is reported that inheritance/genetic accounts for about 25-30% in the onset of premature menopause cases.25 apart from the above-mentioned reasons one of the abnormalities of early menopause is the osteoporosis, estrogen depletion is linked with increased loss in bone mass and density, which results in approximately 9 million cases of bone fractures per year all around the globe.26,27 conducted a study that reveals that early menopause was associated with low (bmi) which is also in confirmation with this study that both low and high bmi are causes of early menopause. anorexia is also a sign of early menopause. the loss of weight is a ubiquitous feature of amenorrhea. it is reported that being underweight may speedup menopause.28 likewise a study also demonstrated the anorexia nervosa is one of the causes of amenorrhea leading to early onset of menopause.29 there are certainly other contributing factors that result in early menopause, females with low parity or null parity are highly prevalent to premature/early menopause, likewise, females who experience early menarche are also at greater risk.30,31 study conducted in the uk reported that twin females at higher risk of early menopause.32 apart from genetics and physiological factors many social and lifestyle factors are also linked with early and immature menopauselike cigarette smoking33,34 childhood malnutrition, emotional stress, and cognitive function during childhood greatly influence timings of menopause.35 study limitations the study was conducted on a small population due to fewer resources, big sample size could portray a clearer picture of the story. conclusion in the interior of sindh, women have symptoms of early menopause. results of the study revealed that there are many underlying causes of early menopause but the common factors observed were certain pathological conditions, poor diet, surgeries, and cancer. references 1. a. m. gharaibeh, a. e.-n. e. al-bdour, and h. f. akasheh, "premature and early menopause: risk factors in jordanian women," journal of the royal medical services, vol. 102, pp. 1-5, 2010. 2. lund kj. menopause and the menopausal transition. medical clinics of north america. 2008 sep 1;92(5):1253-71. https://doi.org/10.1016/j.mcna.2008.04.009 3. goswami d, conway gs. premature ovarian failure. human reproduction update. 2005 jul 1;11(4):391-410. https://doi.org/10.1093/humupd/dmi012 4. alzubaidi nh, chapin hl, vanderhoof vh, calis ka, nelson lm. meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure. obstetrics & gynecology. 2002 may 1;99(5):720-5. https://doi.org/10.1016/s0029-7844(02)01962-2 5. panay n, kalu e. management of premature ovarian failure. best practice & research clinical obstetrics & gynaecology. 2009 feb 1;23(1):129-40. https://doi.org/10.1016/j.bpobgyn.2008.10.008 6. maclaran k, panay n. premature ovarian failure. bmj sexual & reproductive health. 2011 jan 1;37(1):35-42. http://dx.doi.org/10.1136/jfprhc.2010.0015 7. m. a. b. r. c. beverly g reed, md., "the normal menstrual cycle and the control of," endotext, 2018. http://dx.doi.org/10.1136/jfprhc.2010.0015 203 journal of rawalpindi medical college (jrmc); 2020; 24(3): 198-203 8. manolagas sc, o'brien ca, almeida m. the role of estrogen and androgen receptors in bone health and disease. nature reviews endocrinology. 2013 dec;9(12):699. 9. svejme o, ahlborg hg, nilsson jå, karlsson mk. early menopause and risk of osteoporosis, fracture and mortality: a 34 year prospective observational study in 390 women. bjog: an international journal of obstetrics & gynaecology. 2012 jun;119(7):810-6. 10. shuster lt, rhodes dj, gostout bs, grossardt br, rocca wa. premature menopause or early menopause: long-term health consequences. maturitas. 2010 feb 1;65(2):161-6. 11. christin-maitre s, pasquier m, donadille b, bouchard p. premature ovarian failure. inannales d'endocrinologie 2006 dec (vol. 67, no. 6, p. 557). 12. k. f, "sheehan's syndrome," pituitary, vol. 6, pp. 181-8, pituitary. 2003;6(4):181-8. 13. marshall jc, anderson dc, fraser tr, harsoulis p. human luteinizing hormone in man: studies of metabolism and biological action. journal of endocrinology. 1973 mar 1;56(3):431-9. 14. maes m, mommen k, hendrickx d, peeters d, d’hondt p, ranjan r, et al. components of biological variation, including seasonality, in blood concentrations of tsh, tt3, ft4, prl, cortisol and testosterone in healthy volunteers. clinical endocrinology. 1997 may;46(5):587-98. 15. anagnostis p, christou k, artzouchaltzi am, gkekas nk, kosmidou n, siolos p, et al. early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis. european journal of endocrinology. 2019 jan 1;180(1):41-50. 16. naz s, memon ny, shaikh s. factors associated with early menopause. rawal medical journal. 2019 jan 1;44(1):141-4. 17. s. tsiligiannis, n. panay, and j. c. stevenson, "premature ovarian insufficiency and long-term health consequences," current vascular pharmacology, 2019. vol. 17, pp. 604-609, 18. verma d, singh p, kulshrestha r. analysis of histopathological examination of the hysterectomy specimens in a north indian teaching institute. int j res med sci. 2016 nov;4(11):4753-8. 19. foxcroft l. hot flushes, cold science: a history of the modern menopause. granta books; 2011 nov 3. 20. botkin mm. the association between osteoporosis and early menopause following hysterectomy. 21. crean-tate kk, faubion ss, pederson hj, vencill ja, batur p. management of genitourinary syndrome of menopause in female cancer patients: a focus on vaginal hormonal therapy. american journal of obstetrics and gynecology. 2020 feb 1;222(2):103-13. 22. moorman pg, myers er, schildkraut jm, iversen es, wang f, warren n. effect of hysterectomy with ovarian preservation on ovarian function. obstetrics and gynecology. 2011 dec;118(6):1271. 23. hansen ka. accelerated menopause with ovary-sparing hysterectomy?. obstetrics & gynecology. 2016 may 1;127(5):817-8. 24. farquhar cm, sadler l, harvey sa, stewart aw. the association of hysterectomy and menopause: a prospective cohort study. bjog: an international journal of obstetrics & gynaecology. 2005 jul;112(7):956-62. 25. chen q, ke h, luo x, wang l, wu y, tang s, li j, jin l, zhang f, qin y, chen x. rare deleterious bub1b variants induce premature ovarian insufficiency and early menopause. human molecular genetics. 2020 jul 27. 26. sathyapalan t, aye m, rigby as, fraser wd, thatcher nj, kilpatrick es, atkin sl. soy reduces bone turnover markers in women during early menopause: a randomized controlled trial. journal of bone and mineral research. 2017 jan;32(1):157-64. 27. fu y, yu y, wang s, kanu js, you y, liu y, et al. menopausal age and chronic diseases in elderly women: a cross-sectional study in northeast china. international journal of environmental research and public health. 2016 oct;13(10):936. 28. jungari sb, chauhan bg. prevalence and determinants of premature menopause among indian women: issues and challenges ahead. health & social work. 2017 may 1;42(2):7986. 29. mehler ps, krantz mj, sachs kv. treatments of medical complications of anorexia nervosa and bulimia nervosa. journal of eating disorders. 2015 dec;3(1):1-7. 30. mishra gd, pandeya n, dobson aj, chung hf, anderson d, kuh d, et al. early menarche, nulliparity and the risk for premature and early natural menopause. human reproduction. 2017 mar 1;32(3):679-86. 31. pérez alcalá i, sievert ll, obermeyer cm, reher ds. cross cultural analysis of factors associated with age at natural menopause among latin american immigrants to madrid and their spanish neighbors. american journal of human biology. 2013 nov;25(6):780-8. 32. ruth ks, perry jr, henley we, melzer d, weedon mn, murray a. events in early life are associated with female reproductive ageing: a uk biobank study. scientific reports. 2016 apr 20;6(1):1-9. 33. hyland a, piazza k, hovey km, tindle ha, manson je, messina c, et al. associations between lifetime tobacco exposure with infertility and age at natural menopause: the women's health initiative observational study. tobacco control. 2016 nov 1;25(6):706-14. 34. mishra gd, chung hf, cano a, chedraui p, goulis dg, lopes p, et al. emas position statement: predictors of premature and early natural menopause. maturitas. 2019 may 1;123:82-8. 35. canavez fs, werneck gl, parente rc, celeste rk, faerstein e. the association between educational level and age at the menopause: a systematic review. archives of gynecology and obstetrics. 2011 jan 1;283(1):83-90. 296 journal of rawalpindi medical college (jrmc); 2020; 24(4): 296-301 original article frequency of tuberculosis and malignancy in transudativepleural effusions: a rare but real finding abdul rasheed qureshi1, muhammad irfan2, huma bilal3, muhammad sajid4, zeeshan ashraf5 1,2 assistant professor, gulab devi teaching hospital, lahore. 3 women medical officer, gulab devi teaching hospital, lahore. 4 medical officer, gulab devi teaching hospital, lahore. 5 lecturer, department of statistics, gulab devi educational complex, lahore. author’s contribution 1 conception of study 2,3,4 experimentation/study conduction 1,2,3,4,5 analysis/interpretation/discussion 1 manuscript writing 1,5 critical review 2,3,4,5 facilitation and material analysis corresponding author dr. muhammad irfan, assistant professor, gulab devi teaching hospital, lahore email: irfan16d2@gmail.com article processing received: 30/11/2019 accepted: 08/07/2020 cite this article: qureshi, a.r., irfan, m., bilal, h., sajid, m., ashraf, z. frequency of tuberculosis and malignancy in transudative-pleural effusions: a rare but real finding. journal of rawalpindi medical college. 30 dec. 2020; 24(4): 296-301. doi: https://doi.org/10.37939/jrmc.v24i4.1159 conflict of interest: nil funding source: nil access online: abstract objectives: to determine the frequency of tuberculosis and malignancy in transudative pleural effusions. material and method: the study was conducted in pulmonology-opd, gulab devi teaching hospital lahore from oct. 2017 to feb. 2019. one hundred and twenty-eight consecutive patients with transudative pleural effusions and 14-69 years age, willing for invasive investigations & ada estimation were included, while those not willing for further investigations, participation in the study, and exudative effusions were excluded. the clinical features, pleural fluid analysis findings, ada (adenosine deaminase) estimation results, hematology, echocardiography, bronchoscopy, lymph node biopsy, ct-thorax, ultrasound chest & abdomen results were recorded on a preformed proforma. findings were summarized, tabulated, and analyzed statistically using spss16 software. results: out of 1370 cases of pleural effusion, 128 cases (9.34%) with pleural transudate were isolated. in all patients, pleural fluid protein/serum protein level was < 0.5. the age ranged 14-69 years with a mean of 39 years + 11.3. fifty-two cases (40.62%) had right-sided, 38 cases (29.68%) left-sided while 38 cases (29.68%) had bilateral pleural effusions. seventy-six aspirates (59.37%) were yellow, 20 (15.62%) reddish, 18 (14.06%) straw-colored and 14 fluids (10.93%) were watery in color. out of 128 transudative effusions, malignant etiology was found in 23 cases (17.96%), tubercular in 17 cases (13.28%) and 19 cases (14.84%) of para-pneumonic origin were detected. conclusion: tuberculosis and malignancy can be the possible etiology of transudative effusion. keywords: pleural transudate, malignancy, systemic disorders, tb. 297 journal of rawalpindi medical college (jrmc); 2020; 24(4): 296-301 introduction a pleural effusion is always due to underlying disease and can be exudative or transudative, depending upon the pleural fluid protein and serum protein content. classification into exudate or transudate is usually done according to the light’s criteria. transudative pleural effusions develop when the hydrostatic and oncotic pressures across the pleural membrane are disturbed & dynamic equilibrium between the fluid formation and absorption is lost. there is no change in the pleural membrane, the endothelium is usually intact and cells & protein content of effusion is low.1-4 about 5-25% of total pleural effusions are usually transudative in nature.5 according to conventional teaching, this effusion is considered mainly due to cardiac, hepatic, renal, and systemic disorders.6-7 but tuberculosis and malignancy can also be infrequent etiology.8 malignant cells have been detected in a significant number of transudates, representing advanced malignant processes with high morbidity and mortality, precluding the possibility of treatment with a curative approach. metastatic adenocarcinoma is the commonest histological finding, while the primary tumor is not identified in approximately 10% of patients of malignant pleural effusions.9-10 similarly, cases with tubercular etiology have also been reported in transudates and pleural fluid estimation of ada (adenosine deaminase) level is found a good diagnostic tool for tb diagnosis.11-12 because of this association of malignancy and tb (tuberculosis) with transudative pe, pleural fluid cytology and adenosine deaminase (ada) estimation should be employed for all transudative pleural effusions.11,13 we designed this study to identify and compute the proportion of tb and malignancy associated with transudative pleural effusions. materials and methods objectives: to determine the frequency of tubercular and malignant etiology in transudative pleural effusions & also to evaluate the need for performing cytology and ada estimation in pleural transudates. study design: prospective study. patients and methods: this study was conducted at the out-patient department of respiratory medicine, gulab devi chest hospital lahore a 1500 bedded tertiary care hospital, from october 2017 to february 2019. inclusion criteria: a total of 128 consecutive adult patients, with 14-69 years of age, no obvious evidence of tb or malignancy, no history of diuretic therapy, with transudative pleural effusion, willing for invasive investigations, and participation in the study, were included. exclusion criteria: patients below 14 years, exudates, incomplete data, on diuretic therapy, not willing for ada estimation, invasive investigation or participation in the study and known cases, or having radiological suspicion of tubercular or malignant etiology were excluded. method: the study was approved ethically by the irb of the hospital vide no. admin/gdec/18.491 and conducted over a period of 17-months. detailed clinical history including cigarette smoking and contact with a tb-patient were recorded. a thorough physical examination was performed. chest x-ray-pa and lateral views, ultrasound abdomen, pelvis, and chest were done which was followed by ultrasoundguided pleural aspiration, and the fluid sample was sent for biochemistry including ada & ldh estimation, cytology, and bacteriology. cbc with esr, serum protein, serum ldh, lfts, rfts, thyroid function tests, and viral markers for hepatitis was performed in pertinent cases. sputum was evaluated by gram stain, z-n stain & cytology. light’s criteria was applied for differentiating transudate from exudate. a transudative pleural effusion was defined by meeting at least one of the following criteria: 1. pleural fluid protein/serum protein level < 0.5., 2. pleural fluid ldh level < 2/3 of the upper limits of the normal serum value. 3. pleural fluid ldh/serum ldh value < 0.6. ecg, echocardiography, ct-thorax, bronchoscopy & biopsy along with bal (broncho-alveolar lavage) cytology were employed for precise diagnosis, in pertinent cases. lymph node biopsy and histopathology were carried out in the required cases. pleural fluid culture & sensitivity was utilized to isolate pyogenic etiology. pleural fluid ada level, 40 iu/l and above was considered as the cut-off for tbdiagnosis. tubercular patients were put on anti-tb therapy via standard dots regimen and were followed for six months. the response to treatment was noted. fluid immuno-staining and cytopathology diagnosed malignant etiology. all clinical findings were recorded in the pre-formed proforma. data was summarized; organized, tabulated, and spss-16 software was used for statistical analysis to reach the conclusion. descriptive 298 journal of rawalpindi medical college (jrmc); 2020; 24(4): 296-301 statistics including mean with + sd were calculated. categorical data were presented as a percentage. results out of 1370 cases of pleural effusion, 128 cases (9.34%) with pleural transudate were isolated. in all patients, pleural fluid protein/serum protein level was < 0.5. the age ranged 14-69 years with a mean of 39 years + 11.3. eighty-six patients (67.18%) were male while 42 patients (32.81%) were female. the male to female ratio was 2:1. majority of the patients presented with respiratory complaints (table 1). cigarette smoking (73.43%), history of contact with a tb-patient (10.15%), and diabetes mellitus (30.46%) were major risk factors. table 1: clinical presentation in 128 patients nos. clinical features observed cases percentage (%) 1. chest pain. 115 89.84 2. cough 102 79.68 3. fever 97 75.78 4. shortness of breath 93 72.65 5. weight loss 70 54.68 6. loss of appetite 62 48.43 fifty-two cases (40.62%) had right-sided, 38 cases (29.68%) left-sided while 38 cases (29.68%) had bilateral pleural effusions. seventy-six aspirates (59.37%) were yellow, 20 (15.62%) reddish, 18 (14.06%) straw-colored and 14 fluids (10.93%) were watery in color. cytology and bacteriology of 128 pleural fluids are tabulated (table 2). bal analysis revealed malignant cells in 03 cases while 01 case was diagnosed as tb on gene-xpert. out of 04, two lymph node biopsies showed lymphoma and two caseation granuloma. table 2: pleural fluid cytology and bacteriology n=128 pleural fluid cytology in 128 patients nos. microscopic appearance observed cases percentage 1. lymphocytic 102 79.68 % 2. neutrophillic 26 20.31 % 3. malignant cytology 18 14.06 % pleural fluid bacteriology in 19 patients 1. streptococcus pneumonie 06 31.57 % 2. staphylococcus aureus 05 26.31 % 3. gram –ve rods 03 15.78 % 4. pseudomonas 03 15.78 % 5. no-growth 02 10.52 % *n= total pyogenic transudates. out of 128 transudates, 105 patients (82.03%) were diagnosed with non-malignant while 23 cases (17.96 %) with malignant pathologies (table 3 & figure 1). table 3: frequency of non-malignant pathologies with ada values n=105 no diagnosis observed cases percentage of (n)* ada range iu/l mean ada value iu/l 1. tb pe 17 16.19 % 34-85.6 55.86 2. para-pneumonic 19 18.09 % 07-11 09.2 3. cardiogenic cause 35 33.33 % 07-16 8.66 4. cld 13 12.38 % 07-18 12.95 5. crf 10 9.52 % 9.8-12 11.34 6. hypo-proteinemia 03 2.85 % 14-19 16.5 7. non specific 04 3.80 % 12-15.5 13.7 8. sle 03 2.85 % 17-18 17.4 9. rheumatoid arthritis 01 0.95 % 14.0 14.0 * percentage is calculated for 105 non-malignant transudates. 299 journal of rawalpindi medical college (jrmc); 2020; 24(4): 296-301 figure 1: break-up of malignant etiology in 23 transudates discussion while investigating an undiagnosed pleural effusion, biochemistry is utilized for deciding exudative or transudative nature & transudate fluids are investigated by keeping a focus on systemic causes without including tuberculosis and malignancy in the list of differential diagnosis because of their documented exudative nature.14-15 this study last for a 17-month period during which 1370 pleural effusions were investigated and 128 cases (9.34%) of pleural transudates were isolated, which included 35 cases (27.34%) cardiac, 23 cases (17.96%) malignant, and 19 cases (14.84%) of para-pneumonic origin while 17 cases (13.28%) with tubercular etiology were also obtained. the study population had a mean age of 39 years + 11.3 and two of third patients were men. this age along with (73.43%) cigarette smoking and (30.46%) diabetes mellitus favor cardiac and renal etiology. we had 35/128 cases with cardiogenic and 10/128 cases with renal etiologies in our study. as smoking is more common in men, we had 67.18% of patients with the male gender. smoking is started early in childhood in males than in females, they consume more pack-year and are more vulnerable to the risk of smoking as compared to females. we had 73.43% of patients with smoking, which is itself an established risk factor for cardiac and malignant disorders.16-17 ferreiro l et al reported the prevalence of malignant transudative pleural effusion as 10% (18), ashchi m et al reported as 4.6% among 171 malignant pleural transudates.19 yuri moltyaner et al displayed 8% malignancy20 while our series exhibited a prevalence of 17.96% malignancy, in 128 transudates. the possible explanation for malignant transudate formation is that initially fluid is accumulated due to lymphatic-obstruction; low protein level-ultra-filtrate is formed without pleural seeding with malignant foci. confounding co-morbidities like heart failure may also be responsible for transudate formation. similarly, any tumor or lymph node causing bronchial obstruction and atelectasis can result in transudate formation.21 commonly the tumor of lung, breast, and lymphoma invading mediastinal lymph nodes cause lymphatic obstruction, resulting in transudate formation.22-23 bayhan gl and colleagues concluded their study by commenting that pleural tb can present in the form of transudates.24 doerr ch and co-workers reported 27% of patients with benign tumors, tuberculosis, and heart failure, for transudative effusions.25 agrawal v reported 14.28% tubercular transudates.26 a spanish study of 3077 cases during 19 years, revealed 9.0% etiology due to tuberculosis.27 we found 13.28% tubercular etiology in 128 transudates (19 months period) which is fairly comparable with these studies. in this study, 13/17 cases (76.47%) diagnosed as tuberculosis had a history of contact with a tb patient in their family, which created a high index of suspicion about tubercular etiology. tuberculosis was diagnosed by pleural fluid ada level in all cases except three with border-line values, two were diagnosed by lymph node biopsy and one case was detected by bal gene300 journal of rawalpindi medical college (jrmc); 2020; 24(4): 296-301 xpert. as tuberculosis is endemic in our region, all exudative lymphocytic pleural effusions are considered as tubercular, until proven otherwise.28 but transudative effusions are dealt with differently. on finding a transudative pleural effusion, the diagnostic plan is oriented toward systemic causes while tb & malignancy are over-looked, that is why transudates with tb and malignant pathologies remain undetected. it is very much pertinent to make this note that tuberculosis is a curable disease if diagnosed timely, if it is missed, it can be a risk for the patient and the community as well. as pleural fluid ada estimation is a useful biomarker for tb diagnosis in endemic areas, it should be frankly utilized for the workup of all tb-suspect transudates.29 similarly, malignant pleural effusions are almost always categorized as exudates. the presence of malignant cells in transudative effusion indicates a mitotic lesion with high-grade morbidity & mortality with a brief expected life span (only 4–9 months), that is why a timely diagnosis of such patients is valuable for the patient as well as for the treating physician. it can only be achieved by having a high index of suspicion. \although, british thoracic society does not recommend thoracentesis for bilateral pleural effusions, suspected to be transudate, if sampled, bts suggests cytology for all.30 porcel j.m. and associates analyzed 840 malignant effusions and found that cytology was 59% accurate in detecting malignancy.3132 in our study, 18/23 cases (78.26%) of malignancy were diagnosed by pleural fluid cytology, 03 cases (13.04%) by bal cytology, and 02/23 cases were diagnosed by lymph node biopsy. moltyaner y et al. suggested that every transudate should be investigated by cytology to maximize the diagnostic yield.20 the traditional teaching suggests performing cytology on a transudative pleural effusion in search of a malignant cause, might not be cost-effective. in the current era of cost-effective medicine, it is mandatory to ensure that we should not sacrifice the quality of care for cost. therefore, pleural fluid cytology seems to be essential in all transudative effusions to avoid the chances of missing malignant pathologies. additionally, ada estimation can be very much helpful in differentiating between malignant and tubercular transudates. 19/128 cases (14.84%) of transudate with pyogenic etiology is an eye-opening figure. bacteriologic workup (table-ii) reflecting the internal story, thus necessitates the need for culture and sensitivity examination for all pleural transudate. it is, therefore, suggested that in the absence of any obvious systemic etiology, all transudative pleural effusions must be subjected to fluid cytology, bacteriology & ada estimation. the main limitation of this study is that it is a singlecenter study performed on limited sample size (n=128). by further elongation of the study or a study with larger sample size and preferably, a multi-center study can further explore the subject and strengthen the study. our results can find very useful applications in populations with a high prevalence of tuberculosis and increasing malignant disorders due to heavy smoking, industrialization, environmental and occupational pollution, for diagnostic as well as disease control objectives. in the light of this discussion, we have no hesitation in commenting that a transudative pleural effusion is just a false re-assurance against malignancy and tuberculosis. therefore, all pleural transudates must be investigated from the perspective of tuberculosis and malignancy in addition to infective & systemic disorders. conclusion • tuberculosis and malignancy can be the possible etiology of transudative pleural effusions. • pleural fluid cytology and ada estimation & pyogenic culture and sensitivity should be included in the diagnostic algorithm of transudative pleural effusions. • the history of contact with a tb patient must be dug out to create a high index of suspicion about tuberculosis. references 1. thomas jm, musani ai. malignant pleural effusions: a review. clinics in chest medicine. 2013 sep 1;34(3):459-71. doi:https://doi.org/10.1016/j.ccm.2013.05.004 2. grabczak em, krenke r, zielinska-krawczyk m, light rw. pleural manometry in patients with pleural diseases–the usefulness in clinical practice. respiratory medicine. 2018 dec 1;145:230-6. 3. guinde j, georges s, bourinet v, laroumagne s, dutau h, astoul p. recent developments in pleurodesis for malignant pleural disease. the clinical respiratory journal. 2018 oct;12(10):2463-8. https://doi.org/10.1111/crj.12958 4. cornes mp, chadburn aj, thomas c, darby c, webster r, ford c, gama r. the impact of between analytical platform variability on the classification of pleural effusions into exudate or transudate using light's criteria. journal of clinical pathology. 2017 jul 1;70(7):607-9. 5. kugasia ia, kumar a, khatri a, saeed f, islam h, epelbaum o. primary effusion lymphoma of the pleural space: report of a rare complication of cardiac transplant with review of the 301 journal of rawalpindi medical college (jrmc); 2020; 24(4): 296-301 literature. transplant infectious disease. 2019 feb;21(1):e13005. https://doi.org/10.1111/tid.13005 6. farrag m, el masry a, shoukri am, elsayed m. prevalence, causes, and clinical implications of pleural effusion in pulmonary icu and correlation with patient outcomes. egyptian journal of bronchology. 2018 apr 1;12(2):247. doi: 10.4103/ejb.ejb_117_17 7. karki a, riley l, mehta hj, ataya a. abdominal etiologies of pleural effusion. disease-a-month: dm. 2019 apr;65(4):95. doi: 10.1016/j.disamonth.2018.09.001 8. riley l, karki a, mehta hj, ataya a. obstetric and gynecologic causes of pleural effusions. disease-a-month. 2019 apr1;65(4):109-14. https://doi.org/10.1016/j.disamonth.2018.09.003 9. dixit r, agarwal kc, gokhroo a, patil cb, meena m, shah ns, arora p. diagnosis and management options in malignant pleural effusions. lung india: official organ of indian chest society. 2017 mar;34(2):160. doi: 10.4103/09702113.201305 10. heffner je, klein js. recent advances in the diagnosis and management of malignant pleural effusions. inmayo clinic proceedings 2008 feb 1 (vol. 83, no. 2, pp. 235-250). elsevier. https://doi.org/10.4065/83.2.235 11. jolobe om. atypical tuberculous pleural effusions. european journal of internal medicine. 2011 oct 1;22(5):456-9. https://doi.org/10.1016/j.ejim.2011.03.011 12. ryu js, ryu st, kim ys, cho jh, lee hl. what is the clinical significance of transudative malignant pleural effusion?. the korean journal of internal medicine. 2003 dec;18(4):230. doi: 10.3904/kjim.2003.18.4.230 13. zhai k, lu y, shi hz. tuberculous pleural effusion. journal of thoracic disease. 2016 jul;8(7):e486. doi: 10.21037/jtd.2016.05.87 14. rao ks, kumar ha, rudresh bm, srinivas t, bhat kh. a comparative study and evaluation of serum adenosine deaminase activity in the diagnosis of pulmonary tuberculosis. 15. mishra op, yusaf s, ali z, nath g, das bk. adenosine deaminase activity and lysosyme levels in children with tuberculosis. j tropical pediatr 2013;46:175–178. 16. alaarag ah, mohammad oi, farag nm. diagnostic utility of serum adenosine deaminase level in the diagnosis of pulmonary tuberculosis. egyptian journal of bronchology. 2016 may 1;10(2):133. doi: 10.4103/1687-8426.184369 17. farhana a, islam ms, rehena z, yasmin f, nurullah a, talukder si, ferdousi s, rahman mq, ahmed an. adenosine deaminase and other conventional diagnostic parameters in diagnosis of tuberculous pleural effusion. dinajpur med col j. 2013;6(2):105-2. 18. ferreiro l, gude f, toubes me, lama a, suárez-antelo j, san-josé e, gonzález-barcala fj, golpe a, álvarez-dobaño jm, rábade c, rodríguez-núñez n. predictive models of malignant transudative pleural effusions. journal of thoracic disease. 2017 jan;9(1):106. doi: 10.21037/jtd.2017.01.12 19. ashchi ma, golish jo, eng ph, o'donovan pe. transudative malignant pleural effusions: prevalence and mechanisms. southern medical journal. 1998 jan;91(1):23-6. doi: 10.1097/00007611-199801000-00004 20. panacek e, marshall j, fischkoff s, barchuk w, teoh l. neutralization of tnf by a monoclonal antibody improves survival and reduces organ dysfunction in human sepsis: results of the monacrcs trial. chest. 2000 oct 1;118(4):88s-. 21. sahn sa. malignancy metastatic to the pleura. clinics in chest medicine. 1998 jun 1;19(2):351-61. https://doi.org/10.1016/s0272-5231(05)70082-4 22. bedient t.j., musani a.i. malignant pleural effusions. pak. j. chest med. 2015;18(1) 23. nam hs. malignant pleural effusion: medical approaches for diagnosis and management. tuberculosis and respiratory diseases. 2014 may 1;76(5):211-7. 24. bayhan gi, sayir f, tanir g, tuncer o. pediatric pleural tuberculosis. international journal of mycobacteriology. 2018 jul 1;7(3):261. doi: 10.4103/ijmy.ijmy_91_18 25. doerr ch, allen ms, nichols iii fc, ryu jh. etiology of chylothorax in 203 patients. inmayo clinic proceedings 2005 jul 1 (vol. 80, no. 7, pp. 867-870). elsevier. https://doi.org/10.4065/80.7.867 26. agrawal v, doelken p, sahn sa. pleural fluid analysis in chylous pleural effusion. chest. 2008 jun 1;133(6):1436-41. https://doi.org/10.1378/chest.07-2232 27. porcel jm, esquerda a, vives m, bielsa s. etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. archivos de bronconeumología (english edition). 2014 may 1;50(5):161-5. https://doi.org/10.1016/j.arbr.2014.03.012 28. fatima r, harris rj, enarson da, hinderaker sg, qadeer e, ali k, bassilli a. estimating tuberculosis burden and case detection in pakistan. the international journal of tuberculosis and lung disease. 2014 jan 1;18(1):55-60. doi: https://doi.org/10.5588/ijtld.13.0198 29. qureshi ar, mahmood h, irfan m, waqar a. diagnostic efficacy of pleural fluid adenosine deaminase level in diagnosing tb pleural effusion is excellent in a high prevalence area. annals of pims-shaheed zulfiqar ali bhutto medical university. 2018 apr 2;14(1):52-7. 30. hooper c, lee yg, maskell n. investigation of a unilateral pleural effusion in adults: british thoracic society pleural disease guideline 2010. thorax. 2010 aug 1;65(suppl 2):ii4-17. http://dx.doi.org/10.1136/thx.2010.136978 31. arnold dt, de fonseka d, perry s, morley a, harvey je, medford a, brett m, maskell na. investigating unilateral pleural effusions: the role of cytology. european respiratory journal. 2018 nov 1;52(5). 32. lepus cm, vivero m. updates in effusion cytology. surgical pathology clinics. 2018 sep 1;11(3):523-44. doi:https://doi.org/10.1016/j.path.2018.05.003 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 51-56 51 original article effect of delay in operative treatment on the range of motion in supracondylar humerus fracture junaid khan, riaz ahmed, rahman rasool akhtar, kanza batool, hashim riaz department of orthopaedics, benazir bhutto hospital and rawalpindi medical college, rawalpindi abstract background: to determine the relationship of delay in management of supracondylar fracture of humerus with reduced mobility of the joint. methods: in this descriptive study patients with isolated fracture of supracondylar of humerus without any associated trauma, were included. they were classified into groups according to gartlands’ classification based on antero-posterior and lateral view xrays of the affected elbow joint. patients were called for follow up 4,8 and 12 weeks after removal of backslab and kirschner wires. results: mean age of presentation for fractures of supracondylar of humerus was 5.67±2.064 years with fracture occurring predominantly in males. out of the 32 patients who sustained gartland type iii fractures, only 8(25%) patients were managed by closed reduction and internal fixation. in 28(75%) patients, open reduction and internal fixation had to be done. mean delay time for treatment in type-i and type-ii fractures was 2.86±2.25 and 2.56±1.42 days respectively. gartland type-iii injuries had a delay between injury and surgery of 4.88±2.95 days. range of motion was more reduced in flexion angle as compared to extension, supination and pronation. conclusion: an inverse relation was found between delay in presentation and range of motion. increase in delay to seek optimal treatment is associated with a reduction in range of movement at the supracondyle of humerus. in gartland type iii fractures, open reduction had to be done to achieve satisfactory results in most of the patients who presented after a delay of more than 3 days. follow up of the patients showed an improvement in mobility of the joint in the postoperative period but role of physiotherapy in achieving maximum mobility has not been determined yet. key words: supracondylar fracture of humerus, range of motion, pediatric fractures, open reduction introduction supracondylar fractures are the commonest fractures in children under the age of 10 years.it is a painful injury for the patient not only because of the associated complications but also due to the limitation in range of motion which may also arise postoperatively. competitiveness and broad range of activities in children have increased the incidence of extremity traumas in pediatric age group.1 there are several risk factors that have been identified which further predispose to fractures in children. these risk factors include genetic makeup, low weight at birth, malnourishment and poor living conditions.290% of the fractures in children comprise of upper limb fractures,out of which majority of the fractures affect elbow.3 commonest cause of these elbow fractures was attributed to fall.4 supra condylar fractures account for 75% of the elbow fractures.5patients present with edema of the elbow joint, limitation of movement and they may have disfigurement.2 the incidence of fractures of supracondyleof humerus is higher in boys as compared to girls.6neurovascular complications, compartment syndrome and malunion are few of the complications that have been associated with the elbow fractures.7the classification of supracondylar fractures is according to gartland's system based on which only the type iii fractures require surgical treatment whereas type i and ii can be managed conservatively.8,9 closed reduction with k wires is the preferred management procedure done in the paediatric age group. delay in presentation after the trauma has been seen to increase the chances of open reduction and internal fixation for the supracondylar fractures.10this delay in operative management maybe due to late presentation of the patient to the hospital or limitation of resources. initial treatment by quacks or temporary therapeutic management at small medical centers may also result in delayed presentation.11more delay has been observed in developing countries as compared to developed nations.12patients who are operated upon after much delay were reported to have poorer results post operatively.13 we carried out this study to determine the effect of delayed treatment on the range of motion in supracondylar humeral fractures in the pediatric aged group patients. journal of rawalpindi medical college (jrmc); 2017;21(1): 51-56 52 patients and methods this prospective, conveniently sampled, cohort study was conducted in the department of orthopaedics, benazir bhutto hospital, rawalpindi from 4thmarch 2015 to 3rdmarch 2016. inclusion criteria was all patients aged upto 15 years having a radiologically confirmed isolated supracondylar fracture of humerus. patients with open fracture, burns, bilateral supracondylar humerus fracture, associated neurovascular injury, multiple fractures and those receiving definitive management in some other hospital were excluded from the study. those who met the inclusion criteria, consent was taken from their parents or guardians. demographic and clinical information entered into a structured questionnaire. a lateral view of an x-ray centered at distal humerus, and a true antero-posterior view of the involved elbow were used to categorize patients according to gartland classification. undisplaced fractures were managed in a back slab while those having displaced fractured were admitted and underwent either closed or open reduction (crif/orif) with kirschner wires. all patients were given a complete follow-up plan. patients were reviewed at the orthopaedic outpatients’ clinic three weeks later for either removal of back slab or kirschner wires. elbow angle of immobilization was then measured. this angle in which the elbow was first immobilized was correlated with the rate of elbow range of motion (rom) restoration. patients were followed up to 12 weeks from initial presentation. the range of motion (rom) was measured, on the day of back slab removal, and thereafter, every 4 weeks up to 12weeks for each patient. the measurements of elbow rom were performed using standardized methods. with the forearm in neutral position, the elbow was placed in the angle at which the joint was immobilized. using gentle active rom, the limit of flexion, extension, forearm supination and pronation were measured using plastic goniometer. to measure flexion and extension, the goniometer was centered at the distal humerus, which represents the approximate axis of elbow flexion–extension. the arms of the goniometer were aligned parallel to the humerus and the forearm, respectively (fig. 1). 
 to determine the extent of maximal forearm rotation, the arm was immobilized against the chest wall, and the elbow was placed in the position of immobilization. the neutral position was defined as the position at which the extended thumb (pointer) had aligned with the humerus. one arm of the goniometer was made parallel to the radially abducted thumb (pointer), and the other arm remained exactly vertical (fig. 2). active rom was recorded as the maximum number of degrees the joint moves in each direction. all the measurements were performed by the same researcher. the mean and standard deviation of elbow rom in each direction at the day of back slab removal and at 4-week interval were calculated. during the study all patients were encouraged to attend physiotherapy sessions after back slab and or pin removal. at the end of the proposed follow-up period, patients were divided into two groups of attending or not attending physiotherapy. the patients were also encouraged to do daily elbow active rom at home as pain allows. t-test and χ2 tests were used to calculate the significance of determined results, 95% confidence interval and p value <0.05. results were presented in form of tables and bar graphs. fig 1 :measurement of elbow rom (flexion – extension) fig 2 :measurement of elbow rom (supination – pronation) results this study included 55 patients with supracondylar humerus fracture who were followed for 12 weeks after treatment. mean age was 5.67±2.064 (table 1). this study included 32 (58.18%) males and 23 (41.82%) females. 14 (25.45%) patients had gartland type-i injury, 9 (16.36%) type-ii and 32 (58.18%) with type-iii fracture (table 2). 29 (52.72%) had involvement of left elbow whereas 26 (47.27%) presented with right elbow fracture (table 3). as patients were grouped according to severity based on gartland classification, so they were managed accordingly (table 4). gartland i and ii fractures were treated non-operatively, while type-iii fractures were either managed by closed reduction internal fixation (crif) or open reduction internal fixation (orif). 25% cases of gartland type-iii were managed by crif whereas 75% with orif. mean time for treatment in journal of rawalpindi medical college (jrmc); 2017;21(1): 51-56 53 type-i and ii fractures was 2.86±2.25 and 2.56±1.42 respectively. gartland type-iii injuries had a mean interval between injury and surgery of 4.88±2.95 (figure 1). serial measurements of elbow flexion, extension, supination and pronation were done at 4, 8 and 12 weeks after backslab or kirschner wire (k-wire) removal. flexion angle was most markedly reduced, with a median recovery of only 63% of the expected normal range by 12 weeks post-treatment. the range of motion (rom) reached >90% of normal ranges in extension, supination and pronation.while the rom (flexion-extension) improved from 4 to 8 weeks , and from 8 to 12 weeks, the incremental change was greater in the early interval [median (iqr) 24⁰] than in the late interval [median (iqr) 6⁰], p<0.0001]. similarly, the improvement in the rom (supinationpronation plane) was greater from 4 to 8 weeks of kirschner wire (k-wire) and or backslab removal [median (iqr) 8⁰] than from 8 to 12 weeks posttreatment [median (iqr) 1⁰, p<0.0001]. thus, the rate of improvement in rom restoration tends to decrease over time, a non-linear decelerating time course of improvement. delayed surgical management was associated with reduced range of motion at 12 weeks post cast or k-wire removal. there was a significant inverse relationship between the time from injury to definitive management and the range of motion (in the flexion-extension axis) at 12 weeks (figure 2). assuming a linear relationship between the variables, for each additional day of delayed surgery, there was a reduction in rom (flexion) at 12 weeks of 1.9⁰ (p<0.005). the relationship between delay in management and reduced rom was primarily among patients undergoing orif (p=0.040). no significant relationship was seen between timing of non-operative management and outcome among patients with gartland type-i. ii injuries. table 1: age statistics mean standard deviation (s.d) minimum maximum age (n=55) 5.67 2.064 3 11 table 2: gender distribution according to gartland type gartland type total (n=55) i ii iii gender male 9 5 18 32 female 5 4 14 23 total (n=55) 14 9 32 55 table 3: distribution of elbow involvement according to gender side of injury total (n=55) left right gender male 18 14 32 female 11 12 23 total (n=55) 29 26 55 table 4: gartland type and management nonoperative crif orif total (n=55) gartland type i 14 0 0 14 ii 9 0 0 9 iii 0 8 24 32 total (n=55) 23 8 24 55 figure 3: gartland type and management table 5: percentage of recovery in range of motion [median (iqr)] 4 weeks 8 weeks 12 weeks flexion 18% (0-22) 47% (41-51) 63% (55-68) extension 66% (60-80) 84% (72-91) 92% (83-100) arc flexionextension (fe) 42% (30-51) 66% (57-71) 78% (69-84) supination 101% (100103) 111% (110113) 112% (110113) pronation 87% (78-93) 92% (85-96) 93% (86-100) arc supinationpronation (sp) 94% (89-98) 102%(98-105) 103%(98-107) journal of rawalpindi medical college (jrmc); 2017;21(1): 51-56 54 figure4:elbowrange of movement discussion delayed treatment of dislocated elbow joints is very common.14-20elbow fractures which present two days after the injury has occurred are termed as late presentations.21,22this may be attributed to delay in seeking medical attention due to poor transport facilities and unsatisfactory health delivery system or neglect on part of medical staff and overcrowding of emergencies. patients’ lack of awareness and approaching quacks for initial treatment further disposes to the delay in proper management of these fractures.11, 14-17patients also present with edema the cause of which maybe due to improper attempt at healing by a quack. in these cases it becomes essential to reduce the swelling before appropriate management is done. fractures of elbow in children need to be managed as early as possible. these fractures differ from other injuries in children because of the high vascularization of elbow which leads to quick healing therefore allowing only a short period of time for the proper management of the fracture that will lead to full recovery.23significant soft tissue injury is associated with fractures of supracondyle of humerus.24 isolated fractures of elbow without any other injuries associated with it show better results.25 fractures and dislocations of elbow joint are followed by reduced range of motion which is quite a common complication associated with these fractures.26better range of motion and decrease in occurrence of cubitus varus can be achieved if diagnosis of fracture is made early and treated aggressively.27 charlotte et all observed that at least 33% of all children under the age of 17 years sustained a fracture.24most of the children presenting to orthopedic ward with supracondylar fractures were under 10 years of age with peak incidence of occurrence of these fractures between 5-7 years.2these results were comparable to our study in which the mean age of supracondylar fractures was found to be 5.67±2.064. andrew j. mitchelson found this peak incidence to be from 5-6 years.28 a total of 55 cases were included in our study out of which 32(58.18%) were male patients and 23(41.82%) female patients. sahu rl carried out a similar study in which the male to female ratio of occurrence of supracondylar fracture was found to be 57.05: 42.95.29in a previous study, 57 patients were males and 43 were females.30 our study showed that gartland type iii fractures were the commonest with an incidence of 58.18% followed by type ii fractures which occurred in 16.36% of the patients. gartland type i fractures were sustained by only 25.45% of the patients. j. mangwani et al obtained similar results which were comparable to ours with 56% of the patients with gartland type iii fractures and 25% of the patients with gartland type ii fractures.31 dost et al showed that non dominant arm was more commonly affected with 62% patients sustaining fracture of left supracondyle of humerus as compared to 38% patients who had injury to the right supracondyle.32 29 (52.72%) had left supracondylar humeral fracture whereas in 26 (47.27%) patients right supracondyle was affected according to our results. similar results were obtained by farnsworth who reported more common fracture to the humeral supracondyle of nondominant limb.33 devnani observed an average delay of 5-6 days between time of injury and presentation to emergency for appropriate management in the studies carried out by him.34in our studies, we observed the mean time to be was 2.86±2.25 and 2.56±1.42 for type i and type ii gartland’s fractures respectively. it took 4.88±2.95 days on average to seek medical help in gartland fractures type iii. it has been shown in figure 1 that patients who had gartland type i fracture presented to the orthopedic department with a maximum delay of 5 days and those with gartland type iii fractures presented with a delay of 10 days.our results were similar to the results of a study by abdullah et all.10 a study by waikhom s et al in 2016 showed that delay in presentation to hospitals for treatment ranged from 2 to 14 days with an average of 7.5 days.35 as yet, no standard guidelines have been set for the management of delayed presentation of supracondylar fractures of humerus in children.36for gartland type i and ii fractures, nonoperative management was done whereas closed reduction internal fixation and open reduction internal fixation were employed for type iii fractures as the classification of these fractures was journal of rawalpindi medical college (jrmc); 2017;21(1): 51-56 55 based on their severity. closed reduction was not found to be appropriate management option after a delay in presentation of 3 days.37 delay in reduction resulted in open reduction in most cases.38, 39in a study carried out by ozgur ay et al40, it was seen that with a delay of 5 hours after 15 hours of injury, there was an increase of 4 fold in management of supracondylar fracture by open reduction and internal fixation(orif) instead of close reduction. late presentation increased the rate of open reduction from 3% to 46%.41-44our study showed that only 25% of the patients with gartland type iii fracture underwent closed reduction and internal fixation. for the remaining 75%, open reduction and internal fixation had to be done. delay in management of supracondylar fracture results in fibrosis of the joint. this stiffness which is present preoperatively might have some effect on the postoperative results.45open reduction and internal fixation is not without its consequences. there is increased incidence of infections and disfigurement when open reduction is performed.4,46increased incidence of elbow stiffness was observed in patients after their fracture was reduced by open reduction approach.22,47stiffness associated with open reduction was not found in patients treated by closed reduction and internal fixation.22limited mobility of injured humeral joint and prolonged immobilization post operatively also causes stiffness of the joint leading to decrease in range of movement.23, 48-50 approximately, one month is required to achieve full range of motion that is comparable to the pre fracture state.51,52range of motion showed maximum improvement in extension, supination, pronation and absolute relative arcs of motion in our study with greater than 90% of the original range of motion regained 12 weeks postoperatively. the rate of this improvement in rom was more from 4 -8 weeks observed when follow up at 4 weeks and 8 weeks was done but decreased between 8-12 weeks at 12 weeks follow up. flexion showed least improvement with return to range of movement that was only 63% of the original range. after removal of the back slab, the recovery of flexion angle was found to be minimum.53 figure 2 shows that greater delay in operative management was associated with an increase in restricted range of motion at 12 weeks follow up. it was observed that patients undergoing physiotherapy had a more rapid improvement in range of motion when follow ups were done a few weeks after operative management although this difference was not found to be significant on follow up done a year after fracture management.23nash54and keppler55concluded from their studies that physiotherapy and early mobilization not only resulted in increased rate of regain of original range of motion but also decreased the occurrence of complications. 55 sanjib et al stated that exercise caused an improvement in rom at 1 year follow up.35further work needs to be done to determine the role of physiotherapy and its effectiveness in improving the flexion angle postoperatively. conclusion 1. there is a significant relationship between delay in treatment of pediatric supracondylar humeral fracture and reduction in range of movement. 2. reduced range of motion was maximum in the patients who were treated with open reduction and internal fixation. references 1. kocher ms, walters pm, micheli lj. upper extremity injuries in the pediatric athletes. sports medicine. 2000;30(2):117-35. 2. arora r, fichadia u, hartwig e, kannikesnaran n. pediatric upper extremity fractures. healio. 2014;43(5):196-204. 3. dabis j, daly k, galfer y. supracondylar fractures of humerus in children: review of management and controversies. orthop muscular syst 5:206. 4. alam w, rehman su, jan r. outcome of open reduction and internal fixation of supracondylar fractures of humerus in children. pak j surg. 2014; 30(2): 146-49. 5. omid r, choi pd, skaggs dl. supracondylar humeral fractures in children. j bone joint surg am. 2008; 90(5): 1121-32. 6. landin la, danielsson lg. elbow fractures in children: an epidemiological analysis of 589 cases. actaorthopaedicascandinavica.1986 ;57(4): 309-12. 7. brubacher jw, dodds sd. pediatric supracondylar fractures of the distal humerus.curr rev musculoskelet med. 2008;1(34):190–96. 8. cekanauskas e, degliūte r, kalesinskas rj.treatment of supracondylar humerus fractures , according to gartland classification. medicina (kaunas), 2003;39(4):379-83. 9. abzug, joshua m, herman, martin j. management of supracondylar humerus fractures in children.american academy of orthopaedic surgeons.2012 10. ozgur ay, sema vu, fuad oo. timing of surgical treatment for type iii supracondylar humerus fractures in pediatric patients. j child orthop. 2009;3(4): 265–69. 11. abdullah e, melih g, bulent e. delayed surgical treatment of supracondylar humerus fractures in children using a medial approach. j child orthop.2008; 2(1): 21–27. 12. virsha m. neglected lateral condyle injuries .in proceedings of cme at 54th annual conference of the indian orthopedic association 2009. bhubaneswar india. 5-6. 13. shabbir ad, tahir ad, sharief aw. delayed operative management of fractures of the lateral condyle of the humerus. malaysian orthopedic journal. 2015;9(1):18-22. 14. seth m, flores m. management of neglected dislocation of elbow. indian j orthop. 1986;20:177-81. 15. bhattacharya d. open reduction for old unreduced posterior dislocation of the elbowa review of results. indian j orthop. 1979;13:34-38. 16. bruce c, laing p, dorgan j, klenerman l. unreduced dislocation of the elbow : case report and review of the literature. j trauma. 1993;35:962-65. 17. gill s, dhillon m, gupta r. neglected elbow dislocation in children. indian j orthop. 1997;31:193-95. http://www.ncbi.nlm.nih.gov/pubmed/?term=cekanauskas%20e%5bauthor%5d&cauthor=true&cauthor_uid=12738907 http://www.ncbi.nlm.nih.gov/pubmed/?term=degli%c5%abte%20r%5bauthor%5d&cauthor=true&cauthor_uid=12738907 http://www.ncbi.nlm.nih.gov/pubmed/?term=kalesinskas%20rj%5bauthor%5d&cauthor=true&cauthor_uid=12738907 medicinahyperlink%20%22http:/www.ncbi.nlm.nih.gov/pubmed/12738907%22%20(kaunas), journal of rawalpindi medical college (jrmc); 2017;21(1): 51-56 56 18. devnani as. outcome of longstanding dislocated elbows treated by open reduction and excision of collateral ligaments. singapore med j. 2004;45:14-19. 19. mehta s, sud a, tiwari a, kapoor sk. open reduction for later presenting posterior dislocations of the elbow. j orthopsurg( hong kong). 2007;15:15-21. 20. srivastava k, bhattacharya an. dislocation of elbow. indian j orthop. 1969;3:46-54. 21. tiwari a, konjia r.k, kapoor s.k. surgical management of late presentation of supracondylar humeral fracture in children. j orthopsurg (hong kong). 2007;15(2):177-82. 22. yarkreh j, koudouot, tembely j,dieth ag. delayed treatment of supracondylar elbow fracture in children. orthopedics and traumatology, 2012;98(7):808-12. 23. tamai j, lou j, nagda s, ganley t, flynn jm. pediatric elbow fractures: pearls and pitfalls. the university of pennsylvania orthopedic journal. 2002;15:43-51. 24. charlotte julie marion vigneron. supracondylar humeral fracture in the pediatric population : role of physiotherapy 2014. 25. kaziz h, naouar n, osman w, ayeche mlb. outcomes of pediatric elbow dislocations. malaysian orthopedic journal. 2016;10(1):44-49. 26. griffith a.t. therapist’s management of the stiff elbow. rehabilitation of the hand and upper extremity. mosby, st. louis london philadelphia sydney toronto,2002. 27. or o, weil y, simanovsky n, panski a, solaman v. the outcome of early revision of mal aligned pediatric supracondylar humerus fractures. injury;46 : 1585-90. 28. mitchelson aj, illingworth kd, robinson bs, elnimeiry ka, wilson cj, markwell sj,gabriel kr, mcginty j, saleh kj. orthopedics. 2013;36(6):700-06. 29. ramjilalsahu.percutaneous k-wire fixation in pediatric supracondylar fractures of humerus: a retrospective study. niger med j. 2013;54(5):329–34. 30. khan j, ahmed r,batool k, hussain m. are radiographs necessary before kirschner wire removal in supracondylar fracture of humerus in children? jrmc. 2016;20(3):188-92. 31. mangwani j, nadarajah r, paterson jmh. supracondylar humeral fractures in children. the bone and joint journal. 2006;88(3):362-365. 32. dost a, yilmaz b, kömür b, mutlu s. middle and long term radiologic and functional results of childhood supracondylar humeral fractures operated in first 24 hours with limited medial approach. jpma.2016; 66(4):52-54. 33. farnsworth cl, silva pd, mubarak sj.etiology of supracondylar humerus fractures. journal of pediatric orthopaedics.1998 ; 18(1) : 38-42. 34. devnani as. late presentation of supracondylar fracture of the humerus in children. clinorthop. 2005 ; 431 :36-41. 35. waikhom s, mukherjee s, ibomcha i, digendrea a. delayed open reduction and k wire fixation of widely displaced supracondylar fractures of humerus in children. journal of clinical and diagnostic research.2016 ; 10(8) : 6-10. 36. song ks, kang ch, bin mw. closed reduction and internal fixation of displaced unstable lateral condylar fractures of e humerus. j bone joint surg am.2008 ; 90 : 2673-81. 37. yildrim a, unal v, oken o, gulcek m. timing of surgical treatment for type iii supracondylar humerus fractures in pediatric patients. j child orthop. 2009; 3(4): 265-69. 38. otsuka nj, kasser jr. supracondylar fractures of the humerus in children. j am acadorthop surg. 1997; 5(1): 19-26. 39. walmsley pj, kelly mb, robo je, annan ih. delay increases the need for open reduction of type iii supracondylar fractures of the humerus. j bone joint surg br. 2006; 88(4): 528 30. 40. ozgur ay, sema vu, fuad oo. timing of surgical treatment for type iii supracondylar humerus fractures in pediatric patients. j child orthop. 2009; 3(4): 265–69. 41. cramer ke, devito dp, green ne. comparison of closed reduction and percutaneous pinning versus open reduction and percutaneous pinning in displaced supracondylar fractures of humerus . j orthop trauma. 1992; 6: 407-12. 42. peters cl, scott sm, stevens pm. closed reduction and percutaneous pinning of displaced supracondylar humerus fractures in children. j orthop trauma. 1995; 9 : 430-34. 43. danielsson l and petterson h. open reduction and pin fixation of severely displaced supracondylar fracture of the humerus in children. actaorthop scand. 1980; 51: 249-255. 44. walloe a, eung n, eikelund l. supracondylar fractures of the humerus in children: review of closed and open reduction . injury. 1985; 16:296-99. 45. dhillon ks, sengupta s, singh bj. delayed management of fractures of the lateral humeral condyle in children. actaorthop scand. 1988;59:419-24. 46. . parmaksizoglu as, fuatbilgili uof, sayan e. closed reduction of the pediatric supracondylar humerus fractures: the “joystick” method. arch orthop trauma surg. 2009. 129:1225– 1231. 47. gowda p.m and mohammad n. study of supracondylar fractures of humerus in children by open reduction & internal fixation. indian clinpract. 2014; 25(6): 572-76. 48. lieber j, zundel sm, luithle t, fuschs j, kirschner hj. acute traumatic posterior elbow dislocation in children. j pediatrorthop. 2012; 21(8) : 478-81. 49. reed mw and reed dn. acute ulnar nerve entrapment after closed reduction of a posterior fracture dislocation of the elbow. pediatr emerg care.2012 ;28(6) : 570-72. 50. mader k, koslowsky tc, gausegohl t. mechanical distraction for the treatment of post traumatic stiffness of the elbow in children and adolescents. j bone joint surg. 2007;89(1):26 35. 51. din s, shahab f, rehman k, hussain k. supracondylar humeral fracture in children: management by percutaneous lateral entry pin fixation. jpmi. 2015; 28(1): 103-06. 52. wang yl , chang wn, hsu cj. recovery of elbow range of motion after treatment of supracondylar and lateral condylar fractures of distal humerus in children. journal of orthopedic trauma. 2009;23(2):120-25. 53. claude km. impact of treatment timing on elbow range of motion post pediatric supracondylar humeral fractures. journal of orthopedic trauma. 2013;34(1):20-24. 54. nash ce, mickan sm, del mar cb. resting injured limbs delay recovery : a systemic review. j fam pract. 2004; 53(9): 706-12. 55. keppler p, salem k, schwarting b. effectiveness of physiotherapy after operative treatment of supracondylar humeral fractures . j pediatr orthop. 2014; 25(3) : 314-16. http://www.ncbi.nlm.nih.gov/pubmed/?term=sahu%20rl%5bauth%5d 99 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 review article living with covid-19 pandemic – emerging challenges for ultrasound physicians and their suggested solution shagufta malik1, musab riaz2 1 specialist radiologist and ultrasound practitioner working in private sector, islamabad. 2 director, institute of nuclear medicine, oncology and radiotherapy (inor), abbottabad. author`s contribution 1 conception of study 1 experimentation/study conduction 2 analysis/interpretation/discussion 2 manuscript writing 1 critical review 2 facilitation and material analysis corresponding author dr. musab riaz director, institute of nuclear medicine, oncology and radiotherapy (inor), abbottabad. email: musab.riaz@gmail.com article processing received: 19/6/2020 accepted: 17/7/2020 cite this article: malik, s. & riaz, m.(2020). living with covid-19 pandemic – emerging challenges for ultrasound physicians and their suggested solution journal of rawalpindi medical college, 24 covid-19 supplement-1, 99-107. doi: https://doi.org/10.37939/jrmc.v24isupp-1.1414 conflict of interest: nil funding source: nil access online: abstract background: the recent coronavirus disease (covid-19) pandemic is a serious health concern with far-reaching implications in every facet of human life. new challenges have emerged for ultrasound physicians engaged in diagnostic ultrasound examinations. methods: based on a comprehensive literature review the author has suggested a few precautionary measures that should be incorporated by the ultrasound physicians in their practice against the spread of coronavirus disease. suggestions: multi-level safeguard checks before, during, and after the ultrasound examination are suggested to protect ultrasound physicians, staff, and patients from covid-19. the importance of triage for patient screening is stressed. also, limiting patients by deferring non-urgent cases and cancelling aerosol-generating procedures is recommended. the need of counselling of patients and staff is stressed regarding the importance of facemasks, hand hygiene, and safe distancing. incorporating different types of barriers against the virus such as facemasks, face-shields, personnel protective suits for ultrasound physicians and staff, and shielding the equipment and transducer with disposable or wipeable plastic sheets is suggested. besides, the significance of cleaning and disinfection of the examination room and equipment by suitable disinfectants after each patient and at the end of the day is highlighted. conclusion: learning to live with the covid-19 pandemic is the need of the day both for the general public and medical community. being members of the medical community ultrasound physicians should gear up to the emerging challenges of covid-19 to protect themselves, their patients, and allied healthcare staff from coronavirus infection. keywords: covid-19, sars-cov-2, ultrasound, sonography, disinfection. 100 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 introduction in december 2019 several cases of atypical pneumonia were reported from the hospitals of wuhan city in china’s hubei province. the hospital physicians found these cases challenging and difficult to treat and when investigated a new strain of coronavirus was found to be the causative agent for these unusual cases. they named it 2019-novel-coronavirus (2019ncov). later many more cases were reported in more than 190 countries across the world. the world health organization (who) officially recognized this as public health emergency of international concern (pheic)1 on 30 january 2020 and later announced this a pandemic on 11 march 2020 in virtual press conference on covid-19. an official name was given to this disease as coronavirus disease 2019 (covid-19) and the virus was named severe acute respiratory syndrome coronavirus 2 (sars-cov-2) by coronavirus study group.2 the coronaviruses (covs) belong to a large family of viruses which may cause infections both in humans and animals such as snakes, civet cats, camels, bats, and pangolins. an intermediary animal is thought to be responsible for the spread of these viruses to humans, for example, a bat3, turtle4 or a malayan pangolins5 in covid-19 caused by sars-cov-2 in late december 2019, a civet cat6 in case of severe acute respiratory syndrome (sars) caused by sars-cov in 2003 and a dromedary camel7 in middle east respiratory syndrome (mers) caused by mers-cov in 2012. the coronaviruses are rna viruses with a crown-like, spheroid shape under an electron microscope hence the name coronavirus (coronam is the latin word for crown). the crown-like appearance is due to the presence of peplomers or spikes of glycoproteins arising radially out from the outer lipoprotein envelope of the virus. the approximate size of coronavirus is 120-160 nm.8 it is sensitive to heat and ultraviolet rays and can be effectively neutralized by lipid solvents9 including ether, alcohol (ethanol or isopropanol), chlorine-containing disinfectant (liquid bleach or sodium hypochlorite solutions), etc. the spread of covid-19 is through the droplet, contact, or airborne routes. the droplets are produced when a person infected with covid-19 coughs, sneezes, or speaks. once droplets containing virus particles have landed on surfaces, their viability depends on the type of surface and temperature. survival of the coronavirus particles on dry non-living surfaces such as metal, glass, plastic, ultrasound machine, and probes is between 48 and 96 hours.10,11 the most common symptoms are fever, malaise, body aches dry cough. in more severe cases patient develops pneumonia and difficulty in breathing requiring ventilator support. however, in most cases, the disease remains mild and patient recovers without any special treatment. signs and symptoms usually appear after an incubation period of 2-14 days after the exposure. ultrasound is an integral part of the healthcare system. it is considered to be a safe and essential diagnostic tool for patient care in a wide variety of medical conditions. however, ultrasound machines and probes can become potential vectors12 in the transmission of infections including covid-19 transmission to the ultrasound physician or their patients. a literature survey has shown that a considerable gap exists in knowledge of basic infection prevention and control measures in the field of diagnostic medical ultrasound.13 this article has tried to bridge this gap by bringing forward a few suggestions about infection prevention and control. however, this is only a humble effort and ultrasound practice guidelines are required to be developed at the national level in the pretext of covid-19. in pakistan, the effect of covid-19 on the medical community comprising of doctors, nurses, and paramedical staff is challenging. we are witnessing a steep rise of covid-19 cases14 virtually choking our available healthcare resource. the medical community in general and frontline healthcare workers, in particular, have an impending risk of occupational exposure of covid-19 to themselves with the secondary risk of exposure to their families. in this era of covid-19 crises, the medical community including ultrasound physicians has to determine how to reinvent their practices and adopt appropriate safeguard measures to provide safe ultrasound care to the community. safeguard checks safeguard checks for ultrasound clinics in the pretext of covid-19 various preventive measures/safeguard checks are required to be implemented at multiple levels in the ultrasound clinic or hospital setting to prevent the spread of covid-19. these can be divided into: 1. pre-examination safeguard measures 101 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 a. appointments all appointments for ultrasound examinations must be on the telephone or using it platforms such as e-mail or whatsapp; all offline walk-in appointments to be discouraged. all non-urgent appointments should be postponed15 including the appointments for aerosol-generating ultrasound procedures such as transesophageal ultrasound.16 besides, all high-risk ultrasound procedures such as ultrasound-guided biopsies should be deferred. while giving an appointment the patient is advised to come wearing a facemask and preferably without the attendant or in extreme cases only one attendant who will stay outside the clinic area. the patient’s hospital record, referral documents, and other relevant tests should be shared digitally with the ultrasound physician via e-mail or whatsapp on the day of the appointment. b. triage triage should be set-up straightaway next to the entry door of the clinic just before reception and registration desk.17 a suggested algorithm to be followed for patient triage is shown in figure 1. figure 1: triage scoring algorithm for patient screening at triage, it is ensured that the patient is wearing a facemask. every patient will undergo hand sanitization, forehead temperature check by non-contact ir thermal gun followed by a triage scoring on triage scorecard based on travel or contact history or symptoms (table 1). the patients with triage score ≥ 3 will not be allowed to move forward into the clinic for ultrasound examination and will be asked to contact general hospital opd for further evaluation and assessment regarding possible covid-19 infection. all patients with triage score < 3 will move forward for registration and ultrasound examination (figure 1.) the staff doing triage should know the importance of good contact history as there could be asymptomatic carriers of the virus. only patients will be allowed to pass through the triage while the entry of accompanying relatives or attendants will be restricted. for weak, debilitated, and old-age patients one attendant may be allowed but he or she will also undergo triage scoring and clearance. 102 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 table 1: triage score card covid-19 risk score a. exposure risk (14 days before or after the onset of symptoms) person undergoing triage (adult / child)  history of travel to an area of local transmission  history of contact with confirmed covid-19 case  working or attended healthcare facility where confirmed covid-19 patients were admitted 3 b. clinical signs and symptoms adult child  fever 2 2  dry cough 2 2  myalgia/fatigue 2 2  any of the following symptoms o sore throat o shortness of breath o runny nose 1 1 total score c. registration the registration counter must have a vertical glass shield interposed between the registration staff and the patient and applying the “principle of safe distance” (minimum of 1 m). based on available literature physical distance of 1m or more is associated with a much lower risk of infection18; and added benefits are more with even larger physical distances such as 2 m or more. after registration, the patient’s hospital record will be digitally shared with the registration staff, sharing of hospital record in the form of paper documents will be discouraged, however, in extreme cases the registration clerk will note down the salient features of the hospital record for later sharing with the ultrasound physician. d. waiting area the seating arrangement should be spaced keeping in mind the “principle of safe distancing”. the seats should be of a material that can be easily wiped and all floor carpets should be removed. the sars-cov2 is sensitive to many chemicals including sodium hypochlorite – an active ingredient of household bleach.19 the floor and seats in the waiting should be disinfected at the start of the day before the arrival of the patients by bleach solution, chlorine solution, or commercial surface cleaners containing 0.1% sodium hypochlorite solution. 2. safeguard measures during the ultrasound examination a. modifications in the examination room a flexible transparent plastic sheet should be interposed hanging vertically down between the patient couch on one side and ultrasound physician and ultrasound machine on the other side. a carpenter will be required to carry out this task (figure 2). a rounded hole will be made in the plastic sheet for the ultrasound probe and arm of the ultrasound physician for conducting an ultrasound examination through the sheet. the examination room floor and patient's couch should be disinfected by disinfectant solutions (0.1% sodium hypochlorite solution) at the start of the day and patient examination couch disinfected after each patient. figure 2: transparent sheet hanging vertically down between patient’s couch and ultrasound physician b. barrier shielding of ultrasound machine keyboard and console the ultrasound machine key-board and console should be covered by a thin transparent sheet at the start of the day which is later on removed and replaced with a new sheet on the next working day. 103 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 c. barrier shielding of ultrasound probes the ultrasound transducer or probe should be covered with latex sheath (condom) or cling wrap which is changed after each ultrasound examination. alternately it should be disinfected with a soft wipe of low to intermediate level disinfectant such as 0.1% sodium hypochlorite solution after each patient. d. use of personal protective equipment (ppe) the ultrasound physician will observe complete droplet, contact, and airborne precautions such as the use of disposable surgical gloves and gown, surgical cap, and a facemask (figure 3). ordinary disposable surgical gown and surgical facemask are sufficient in routine cases but for suspected or known covid-19 patients n-95, ffp2, ffp3 type of respirator (table 2) and personnel protective suits such as reusable commercially available tyvek suits or hazmat suits made of vinyl or non-porous material or single-use personnel protective suits is recommended. also, the use of eye protection (goggles and face-shield) is recommended for ultrasound physicians. the assisting staff or nurse in the examination room should also wear the same personnel protective equipment. the surgical gloves should be discarded after each patient and replaced with a new pair for the next patient. figure 3: ultrasound physician wearing personnel protective suit, head and eye shield while performing an ultrasound examination table 2: classes of disposable particulate respirators e. use single-use gel packets for external abdominal ultrasound examination of confirmed or suspected covid-19 patients, use single-use non-sterile gel packets or use gel bottles which should be disinfected with low-level disinfectant after each patient. however, these bottles should not be refilled or heated and the lid of the gel bottle must remain closed. f. avoid high-risk ultrasound procedures all aerosol-generating ultrasound procedures such as trans-esophageal ultrasound should be cancelled. also, ultrasound-guided biopsies should be deferred. 3. post-examination safeguard measures a. cleaning and disinfection: after the last ultrasound examination of the day is complete; disinfection and decontamination procedures are immediately instituted. it should be kept in mind that disinfectants are meant for disinfection only and are not meant for cleaning. therefore before applying disinfectant on any surface it is advisable to clean the surface first with some detergent solution to remove any organic material, dirt or soil, etc. cleaning and disinfection of equipment the ultrasound machine console, computer keyboard, and ultrasound probes, gel bottle should also be disinfected by wiping with gauze soaked in disinfectant. all external transabdominal probes or transducers must undergo cleaning followed by low-level disinfection to denature any presence of sars-cov-2. cleaning: class of respirator characteristics ffp1 80% filtration percentage used as a dust mask in home renovation ffp2 94% filtration percentage used against influenza virus and coronavirus ffp3 99% filtration percentage used against coronavirus and fine asbestos particles 104 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 for cleaning use purified (deionized) water or detergent solution and cleaning should be done with clean soft cloth or gauze or nonabrasive single-use sponge.20 do not use a brush as it will damage the transducer. for thick organic matter immerse the transducer in cleaning solution (purified water or detergent solution) for 30 minutes following by drying with a soft cloth; the heat should not be used for drying. disinfection: for disinfection, the chemicals recommended by the united states environmental protection agency (epa) effective against sars-cov2 can be used. for surface disinfection in an ultrasound setting, these are sodium hypochlorite (0.1 0.5%), ethyl alcohol (76.9 to 81.4%), or isopropyl alcohol (70%).21 disinfection of the transducers should be done by wiping and not by immersion in the chemical solution. after cleaning and disinfection is complete confirm that transducer shows no sign of peeling, damage, or deformation. the thin plastic sheet covering the ultrasound machine console may also be disinfected; however, it should be removed and replaced the next working day before the start of the ultrasound examination. the staff should wear gloves and perform hand hygiene before and after cleaning and disinfecting equipment. cleaning and disinfection of room surfaces the examination couch, room floors (examination room, waiting area room, and registration area room) and washrooms should be cleaned and disinfected by spraying bleach or sodium hypochlorite solution. a checklist for daily cleaning and disinfection should be made and displayed in the rooms mentioning areas to be cleaned such as tabletops, switches, door handles, mobile phones, intercoms, keyboards, and computer accessories, etc. the procedure should be done in the morning before the start of the work and after the last patient of the day. for disinfecting, surfaces use a 0.1% sodium hypochlorite solution. cleaning and disinfection of personal protective equipment the personal protective equipment which is reusable such as goggles and face-shields should also be cleaned and disinfected. according to world health organization recommendations, the utility gloves or heavyduty, reusable plastic aprons or ppes should be first cleaned with soap or detergent and water followed by disinfection after 30 min submersion in 0.5% sodium hypochlorite solution. b. waste disposal all the contaminated waste material utilized during ultrasound examination such as singleuse surgical gowns, facemasks, surgical gloves made of latex or nitrile, disposable personal protective suits are worn by ultrasound physician and staff, tissue papers, latex sheaths and cling wraps used to cover ultrasound probes and plastic sheets used to cover ultrasound machine console or computer keyboard should be disposed in off in a waste bin with a lid or cover and sent for incineration immediately. c. dealing with body fluids accidental spillage of body fluids of the patient such as blood, vomitus, urine, and other excreta may occur in the waiting area, ultrasound examination room, or else in the clinic. as per who recommendations use 0.5% sodium hypochlorite solution for disinfection of blood or bodily fluids spills in ultrasound clinics. d. self-disinfection at the end of the day when ultrasound examinations are over the ultrasound physician and nursing or paramedical assistant should perform hand hygiene and if possible take shower before leaving for home. e. digital means to deliver ultrasound examination report after the ultrasound examination is over, the report should be quickly typed on a computer and handed over to the patient in printed format; however to shorten the residence time of the patient in the waiting area the patient may be instructed to go home immediately after the examination and report digitally delivered by using electronic media such as email. any prolonged face-to-face discussion between the patient and the ultrasound physician or staff should be discouraged and phone or electronic media should preferably be used. 105 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 a summary of safeguard checks is given in table 3. table 3: summary of safeguard checks in ultrasound clinics safeguard checks before ultrasound examination limit appointments do triage, facemask and hand sanitization glass barrier at the registration desk patient counselling at the registration desk safe distancing in the waiting area a hand-washing facility in the waiting area awareness posters in the waiting area safeguard checks during an ultrasound examination avoid high-risk ultrasound procedures barrier sheet between doctor and patient barrier shielding of an ultrasound machine barrier shielding of an ultrasound transducer use of personal protective equipment (ppe) use of single-use ultrasound gel packet safeguard checks after an ultrasound examination cleaning and disinfection waste disposal dealing with body fluids self-disinfection digital ultrasound report types of disinfectants in healthcare settings such as ultrasound clinics low and intermediate level disinfectants can be used. it should be kept in mind that disinfectants are meant for disinfection only and are not meant for cleaning. therefore before applying disinfectant on inanimate surfaces or objects it is advisable to clean the surface first with some detergent solution to remove any organic material, dirt or soil, etc. as per recommendations of the usa environmental protection agency (epa) following types of disinfectants can be safely used in ultrasound clinics: 1. low-level disinfectants (lld)  quaternary ammonium compounds e.g., alkyl dimethyl benzyl ammonium chloride, alkyl dimethyl ethyl benzyl ammonium chloride. 2. intermediate level disinfectants (ild)  alcohols e.g., isopropyl alcohol, ethyl alcohol, and methylated spirits.  chlorine releasing agents e.g., bleach/sodium or calcium hypochlorite, sodium dichloroisocyanurate (nadcc).  improved hydrogen peroxide e.g., 0.5% enhanced action formulation hydrogen peroxide, 3% hydrogen peroxide. the advantages and disadvantages of different types of disinfectants are shown in table 4, below. for all practical purposes bleach (sodium hypochlorite solution) ethanol or isopropyl alcohol are sufficient in an ultrasound clinic setting; quaternary ammonium compounds are respiratory irritants and have limited virulence against viruses. alcohols are highly flammable therefore caution should be observed if alcohols are used as disinfectants. bleach or sodium hypochlorite solution has an offensive odor and should be prepared afresh each time because of its limited stability. hydrogen peroxide is a very good disinfectant but is not feasible due to its high cost. table 4: types of disinfectants used in ultrasound clinics; their advantages and disadvantages types of disinfectants advantages disadvantages quaternary ammonium compounds low cost respiratory irritant limited virulence against nonenveloped viruses alcohols (60-80%) low cost flammable rapid evaporates, therefore, time compliance over a large surface is low bleach / hypochlorite solutions low cost non-flammable offensive odor poor stability needs to be prepared fresh every day hydrogen peroxide detergent properties with high cost 106 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 added cleaning ability non-flammable additional recommendations 1. covid-19 awareness campaign a. training of staff: the doctors should take the lead to give awareness and training to nurses and other paramedical through lectures, internet resources, and electronic media highlighting the importance of triage for covid-19, detection of patients with suspected or early symptoms of covid-19. b. donning and doffing technique: the hospital or clinic staff should be trained in the proper use of personal protective equipment including putting on (donning) and putting off (doffing) the personal protective suits. the training of the ultrasound assistant and staff should be in their local language so that they comprehend and completely understand the technique.22 c. awareness posters in waiting area various colored posters should be posted in the waiting area to keep the patients and staff informed about covid-19, early symptoms, and protective measures such as safedistancing, hand hygiene, and coughing and sneezing etiquettes, etc. d. covid-19 awareness brochures awareness brochures of covid-19 must be placed at the reception counter and offered to the patients for reading. 2. developing liaison with covid-19 isolation facility a close liaison should be established with the nearest covid-19 isolation/quarantine facility so that any suspected covid-19 case can be immediately referred. 3. availability of handwashing facility in the waiting area a hand-washing facility must be provided in the waiting area with liquid soap dispenser and step-wise instructions of handwriting displayed by the side. 4. contingent measures every morning before the start of the day all the staff members must enter the clinic area after passing through the triage. if any of the staff members is found suspicion of having covid-19, has developed symptoms or gives a history of recent contact with covid-19 positive individual, should be isolated immediately and referred to covid-19 isolation center and all his/her contacts sent for home quarantine. an alternate contingent, the back-up plan must be in place to continue uninterrupted ultrasound services. conclusion covid-19 pandemic has brought significant challenges to the medical community including physicians who are engaged in providing diagnostic ultrasound services to the community. as no vaccine or cure is currently available to fight with this virus; physicians need to learn ‘how to live’ with the virus. appropriate preventive measures at multiple levels are required to be adopted by the ultrasound physicians to provide safe and uninterrupted ultrasound service to their patients. references 1. burki tk. coronavirus in china. the lancet respiratory medicine. 2020;8(3):238. doi:10.1016/s22132600(20)30056-4 2. gorbalenya ae, baker sc, baric rs, et al. severe acute respiratory syndrome-related coronavirus: the species and its viruses – a statement of the coronavirus study group. 2020. doi:10.1101/2020.02.07.937862 3. york a. novel coronavirus takes flight from bats? nature reviews microbiology. 2020;18(4):191-191. doi:10.1038/s41579-020-0336-9 4. luan j, jin x, lu y, zhang l. sars-cov-2 spike protein favors ace2 from bovidae and cricetidae. journal of medical virology. 2020. doi:10.1002/jmv.25817 5. lam, t.t., shum, m.h., zhu, h. et al. identifying sars-cov2 related coronaviruses in malayan pangolins. nature (2020). https://doi.org/10.1038/s41586-020-2169-0. 6. tu, c., crameri, g., kong, x., chen, j., sun, y., yu, m....wang, l. (2004). antibodies to sars-coronavirus in civets. emerging infectious diseases, 10(12), 2244-2248. https://dx.doi.org/10.3201/eid1012.040520. 7. hemida, m. g., chu, d., poon, l., perera, r., alhammadi, m. a., ng, h....peiris, m. (2014). mers coronavirus in dromedary camel herd, saudi arabia. emerging infectious diseases, 20(7), 1231-1234. https://dx.doi.org/10.3201/eid2007.140571. 8. covid-19/sars-cov-2 pandemic | fpm [internet]. fpm. 2020 [cited 9 june 2020]. available from: https://www.fpm.org.uk/blog/covid-19-sars-cov-2-pandemic/ 9. cascella m, rajnik m, cuomo a, et al. features, evaluation and treatment coronavirus (covid-19) [updated 2020 may 18]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2020 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk554776/ 10. nyhsen cm, humphreys h, koerner rj, et al. infection prevention and control in ultrasound best practice recommendations from the european society of radiology 107 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 99-107 ultrasound working group. insights imaging 2017; 8: 523-535. 2017/11/29. doi: 10.1007/s13244-017-0580-3. 11. kampf g, todt d, pfaender s, et al. persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. j hosp infect 2020; 104: 246-251. 2020/02/10. doi: 10.1016/j.jhin.2020.01.022. 12. skowronek p, wojciechowski a, leszczynski p, et al. can diagnostic ultrasound scanners be a potential vector of opportunistic bacterial infection? med ultrason 2016; 18: 326331. 2016/09/14. doi: 10.11152/mu.2013.2066.183.sko 13. westerway sc, basseal jm and abramowicz js. medical ultrasound disinfection and hygiene practices: wfumb global survey results. ultrasound med biol 2019; 45: 344-352. 2018/11/10. doi: 10.1016/j.ultrasmedbio.2018.09.019. 14. covid-19 health advisory platform by ministry of national health services regulations and coordination [internet]. covid.gov.pk. 2020 [cited 9 june 2020]. available from: http://covid.gov.pk/stats/pakistan 15. helping private practices navigate non-essential care during covid-19 [internet]. american medical association. 2020 [cited 9 june 2020]. available from: https://www.amaassn.org/delivering-care/public-health/helping-privatepractices-navigate-non-essential-care-during-covid-19 16. bracco d. safe(r) transesophageal echocardiography and covid-19 [published online ahead of print, 2020 apr 20]. can j anaesth. 2020;1‐3. doi:10.1007/s12630-020-01667-8 17. coronavirus disease 2019 (covid-19) [internet]. centers for disease control and prevention. 2020 [cited 9 june 2020]. available from: https://www.cdc.gov/coronavirus/2019ncov/hcp/non-us-settings/sop-triage-prevent-transmission.html 18. physical distancing, face masks, and eye protection to prevent person-to-person transmission of sars-cov-2 and covid-19: a systematic review and meta-analysis. lancet 2020; jun 1:[epub ahead of print]. 19. disinfecting sars-cov-2 | political economy | thenews.com.pk [internet]. thenews.com.pk. 2020 [cited 9 june 2020]. available from: https://www.thenews.com.pk/tns/detail/649251-disinfectingsars-cov-2 20. ultrasound system cleaning and disinfection for covid-19. canon medical systems. https://global.medical.canon/products/ultrasound/more_infor mation/ul_cleaning_covid_19. accessed june 9, 2020. 21. disinfectant use and coronavirus (covid-19) | us epa [internet]. us epa. 2020 [cited 9 june 2020]. available from: https://www.epa.gov/coronavirus/disinfectant-use-andcoronavirus-covid-19 22. world health organization (who). coronavirus disease (covid-19) outbreak 2020. available from: https://www.who.int/emergencies/diseases/novel-coronavirus2019 summary journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 141 original article validity of e-flow colour doppler indices in differentiating benign and malignant ovarian tumours sumera mushtaq, nuwayrah jawaid, ishtiaq hussain. department of radiology, foundation university medical college & hospital, rawalpindi abstract background: to determine the validity of pulsatility and resistive index of trans-abdominal doppler ultrasound(e-flow) in distinguishing between benign and malignant adnexal masses keeping histopathology as gold standard. methods: in this cross sectional study patients scheduled for elective surgery due to adenaxal masses were included. all patients were sonographically evaluated for pulsatility and resistance indices aided with colour e-flow doppler before the elective surgery of lesions. the performing radiologist had no information on the patients, to differentiate between benign and malignant adnexal masses based on doppler indices. the final diagnoses were based on pathological and operative findings, keeping histopathology as gold standard. results: two hundred and twenty-nine patients were recruited out of which 18 were excluded, since the masses were finally not proven to be adnexal. of the remaining 211 cases available for analysis, 163 were benign and 48 were malignant. the sensitivity and specificity of the pulsatility index for distinction were 89.57% and 85.42% and values for the resistance index were 89.57% and 89.58% respectively. conclusions: pulsatility and resistance indices with trans-abdominal doppler ultrasound (e-flow) have high accuracy in differentiating between benign and malignant adnexal masses. key words: adnexal mass, pulsatility index,resistance index,doppler ultrasound,ovarian tumours. introduction to differentiate between benign and malignant adnexal masses is of great value as therapeutic approach is markedly different between the two entities. 1 benign lesions like benign ovarian masses or functional changes need more conservative approach like either close observation or laparoscopic surgery, whereas malignant tumours require urgent laparotomy and in most of cases patient is being referred for further chemotherapy or radiotherapy by involving oncologists.2 several attempts have been made to distinguish between the conditions in the past but with the availability of high-resolution ultrasound machines, colour doppler ultrasound is a possible technique for differentiation of benign from malignant adnexal masses as well as for early diagnosis of ovarian carcinoma for several years. 3,4 some reports also showed the superiority of this technique in screening ovarian cancer while there are some other reports favouring its ability in differentiating benign from malignant tumours preoperatively. 5,6however, colour doppler application in such previous reports was often needed via transvaginal approach and this might be inconvenient to some patients. 7 currently, high-resolution colour doppler with extended flow (eflow) has been developed, resulting in higher sensitivity in detection of blood flow in minute vessels even during trans abdominal examination. 8,9therefore, the purpose of the present study was to determine the sensitivity and specificity of pulsatility index (pi) and resistance index (ri), derived from trans-abdominal colour doppler e-flow, in differentiating benign from malignant ovarian tumours. patients and methods this cross-sectional validation study was done at department of gynecology and radiology at fauji foundation hospital rawalpindi from january 2014 to december 2014.two hundred and eleven patients of ovarian masses were included in the study with nonprobability purposive sampling. all patients referred by gynecologist with suspected ovarian mass for diagnostic workup and who are going to be operated from indoor and outdoor department were included in the study. patients with disseminated disease and with severe co-morbid conditions and declared inoperable, patients with known diagnoses of ovarian malignancy which was scheduled for a second look operation and patients with past history of major pelvic surgery for non-ovarian pathological fibrosis or vascular changes journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 142 were excluded from study.doppler ultrasonography was performed using a curvilinear probe of aloka ssd 5500 in dimly lit room with comfortable temperature (22-24c) in supine position and resistive and pulsatility indices were calculated. both pulsatility index (pi) and resistance index (ri) were calculated. the value of each artery was calculated from a curve fitted to the average waveform over three cardiac cycles. the formulas used for pi and ri were pi = (sd)/ mean and ri = (s-d)/s respectively, when s is the peak doppler frequency shift and d is the minimum. signals from various areas within the tumour were determined but the lowest pi and ri were considered for data analysis. the area distribution of visualized vessels in the adnexal masses was also categorized and recorded as center of the mass, in the septum, in the papillae, at tumour wall or peri-tumor areas the final diagnosis as gold standard was based on either pathological findings or intraoperative findings in case of no pathological specimen. all of adnexal masses were divided into 2 groups as benign and malignant adnexal masses. the sensitivity and specificity of various cut-off levels of pi and ri were calculated and all data were analyzed using spss software version 16.0. resistive index (ri) is calculated as ri = [peak systolic velocity end diastolic velocity]/peak systolic velocity. value should be less than 4 for malignant mass.pulsatility index (pi) is defined as the difference between the maximum flow and the minimum flow divided by the mean and value should be less than 1 for malignant lesion. lesions were categorized as simple cyst (anechoic with a thin wall and acoustic enhancement, with or without a single thin septations), dermoid cyst(fluid layer or echogenic mural nodule with shadowing), or an endometrioma (cyst with diffuse low-level echoes with one or two thin septations and a thin wall).atypical features such as a thick wall or multiple irregular septations, lesions having nodules or solid elements.histopathological features of malignant tumours include nuclear atypia and degree of mitoses (> 12 per 10 high-power fields) p53, brca1/2 genes and other genetic mutations, solid and cystic areas, extensive haemorrhage and necrosis and degree of micro-invasion. results between january 2014 to december 2014, 229 patients initially diagnosed as ovarian tumours were recruited to undergo e-flow colour trans-abdominal, doppler ultrasound examinations. out of these eighteen patients were excluded because of pathological diagnoses of non-ovarian tumour including subserous myoma, hydrosalpinx and patients who lost follow up due to domestic reasons etc. the remaining 211 patients were analyzed. mean age (yrs) of 211 female patients was 45.29+10.51 with ranges from 20 to 80 years.histopathological examinations revealed 163 patients (77.25%) having benign tumours and 48 patients (22.75%) having malignant tumours.out of 211 patients, there were 151 patients who you were found benign (ri < 0.5) by doppler ultrasound, in which 146 patients were benign and 05 patients were found malignant histopathologically. similarly, out of 211 patients, there were 60 patients who you were found malignant (ri > 0.5) by doppler ultrasound, in which 17 patients were benign and 43 patients were found malignant histopathologically. so the sensitivity, specificity, ppv and npv of doppler ultrasound measurements (resistive index) was 89.57%, 89.58%, 96.69%, 71.67% respectively (table 1). out of 211 patients, there were 153 patients who were found benign (pi < 1) by doppler ultrasound, in which 146patients were benign and 07 patients were found malignant histopathologically. similarly, out of 211 patients, there were 58 patients who were found malignant (pi > 1) by doppler ultrasound, in which 17 patients were benign and 41 patients were found malignant histopathologically. sensitivity, specificity, ppv and npv of doppler ultrasound measurements (pulsatility index) was 89.57%, 85.42%, 95.42% and70.69% respectively(table 2). table 1:doppler usg (resistive index) with histopathology histopathology total benign malignant doppler measurements (resistive index) benign 146 5 151 malignant 17 43 60 total 163 48 211 table 2:doppler usg (pulsatility index) with histopathology histopathology total benign malignant doppler measurements (pulsatility index) benign 146 7 153 malignant 17 41 58 total 163 48 211 discussion ovarian pathology is 5th most common malignancy and is characterized by few early nonspecific symptoms and signs.10,11 the cure rate for disease at journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 143 early stage is 80-90 % and five-year relative survival rate for stage i is 95%. 12ultrasound abdomen is considered the best initial imaging technique while ct and mri also play a role in the minority of cases where ultrasound is inconclusive. the sonographic examination includes trans-abdominal and transvaginal scans combined with colour and pulsed doppler images. 13 the trans-abdominal scans, in comparison with transvaginal approach, also provide assessment of ascites, adenopathy, hydronephrosis, and liver metastases. on trans-vaginal studies, the field of view is much smaller compared to the field of view on trans-abdominal scans and it is also difficult to assess a mass high in pelvis. 14 many centers are now using colour doppler in early assessment of ovarian mass. combination of both morphology and doppler is more accurate than either used alone but there is no agreement as to which doppler index is best and at which level the threshold should be set to distinguish between high and low impedance flow. 15 considering the above mentioned limitations of transabdominal and endo-vaginal ultrasound we used to see the validity of e-flow colour doppler indices (pulsatility and resistive index) for detection of malignancy in ovarian tumours which were referred to radiology department for evaluation. differentiation of benign from malignant tumours is very important due to vast difference in mode of treatment and it might be achieved by several methods such as clinical signs and symptoms, serum ca 125 levels, and ultrasound.16,17 conventional ultrasound parameters for the differentiation of malignant from benign tumours are based merely on morphological features. the introduction of colour doppler ultrasound, especially high-resolution colour e-flow doppler with higher sensitivity in detection of blood flow in minute vessels, might allow a step forward from morphological to functional evaluation of the masses. the theoretical background comes from the observation that the new tumour vessels that grew as a result of angiogenesis differ from the normal vessels with respect to cellular composition, basement membrane structure and permeability. as a result, the haemodynamics of these vessels is changed. 18 considering angiogenesis as a neoplastic marker for malignancy, colour doppler ultrasound allows a better insight in the biological behaviour of the tumour and early diagnosis of cancer could become possible by detecting neo-vascularization in the tumour.19 in previous studies, some authors suggested the existence of clear cut-off points of pi and ri of benign and malignant tumours; kurjak et al reported only one false positive and two false negative results in a screening program involving 624 benign ovarian tumours and 56 malignant tumours by using a cut-off value of ri 0.4. 20 sengoku et al reported sensitivity and specificity of 81.3% and 91.7% respectively when the cutoff value of pi 1.5 was used. 21 in the present study 54% of benign and 100% of malignant including borderline tumours had detectable arterial blood flow in the tumours using a colour doppler unit. this information may enable us to conclude that tumour without detectable blood flow is very unlikely to be malignant. our cut-off pi value of 1.00, giving the sensitivity and specificity of 89.57% and 85.42%, respectively, was different from the study of sengoku et al but was consistent with the data reported by weiner et al.22 the scanning approach (trans-vaginal or trans-abdominal) and frequency of the probes might partially explain inconsistent results reported previously by different authors (zanetta et al). 23 unlike previous reports in which they firstly used trans-abdominal probe and then trans-vaginal probe is performed if trans-abdominal examination was unable to visualize, our study with e-flow colour doppler we could identify the tumour in all cases. this may be the advantage of new high-resolution ultrasound technology permitting us avoiding the inconvenience of trans-vaginal approach. all authors agree that recognition of angiogenesis as a reference point for malignant changes within the ovary has proved to be a highly sensitive parameter.24 neovascularization is an obligate event in malignant change. this recognition enables to observe the earliest stages in ovarian oncongenesis. the signs of neo-vascularization tumours, considered benign by conventional ultrasound, can be missed by insufficient evaluation of the vascularity, whereas the tumours with suspicion of malignancy would be examined more thoroughly until the expected lowest pi and ri were found.25 it is important to examine all arterial signals to find out the lowest ones in each case to reduce the bias described. the present study pertinently cater for it. conclusion 1. trans-abdominal e-flow colour doppler indices are a useful tool in preoperative diagnosis of ovarian tumours. 2.it is a objective sonological evaluation of the lesions and morphological features particularly those pointing to malignancy allows early detection and differentiation of benign and malignant tumours. thus, it can help in timely referral of malignant cases to specialist care resulting in better outcome. journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 144 references 1. yazbek j, raju sk, ben-nagi j, holland tk. effect of quality of doppler ultrasonography on management of patients with suspected ovarian cancer. lancet oncol 2015; 8:131–37. 2. chan jk, cheung mk, husain a, teng nn, west d.patterns and progress in ovarian cancer over 14 years. obstetgynecol2012, 108:521-28. 3. hamper um, sheth s, abbas fm, rosenshein nb. transvaginal color doppler sonography of adnexal masses: differences in blood flow impedance in benign and malignant lesions. ajr am j roentgenol 1993;160:1225-28 4. yazbek j, helmy s, ben-nagi j, holland t. value of preoperative ultrasound examination in the selection of women with adnexal masses for laparoscopic surgery. ultrasound obstet gynecol 2013; 30: 883-88. 5. stein sm, laifer-narin s, thomsom rd. value of gray-scale, color doppler, and spectral doppler sonography in differentiation of benign and malignant adnexal masses. american journal of roentgenology 2015; 184(2):281-86. 6. enakpene ca, omigbodun ao, goecke tw. preoperative evaluation and triage of women with suspicious adnexal masses using risk of malignancy index. j obstet gynaecol res 2009; 35:131–18. 7. fleischer ac, lyshchik a, jones hw jr. contrast enhanced transvaginal sonography of benign versus malignant ovarian masses: preliminary findings. j ultrasound med 2008; 27:1011–18. 8. marchesini ac, magrio fa, berezowski at. critical analysis of doppler velocimetry in the differential diagnosis of malignant and benign ovarian masses.j womenshealth . 2013;17(1):97-102. 9. madan r, narula mk, chitra r, bajaj p. e-flow color doppler imaging evaluation of adnexal masses. indian j radiol imaging 2014; 14:365-72. 10. murta ef and nomelini rs.early diagnosis and predictors of malignancy of adnexal masses.curr opin obstet gynecol 2014; 8: 14-19. 11. zafar af, fazil a, asifa a, karim a, akmaln. clinical manifestations of benign ovarian tumors. ann ke med coll. 2015; 11:258-59. 12. fields mm and chevlen e. ovarian cancer screening: a look at the evidence. clin j oncol nurs. 2014;10:77-81 13. timmerman d, valentin l, bourne th. measurements to describe the sonographic features of adnexal tumors: a consensus opinion from the international ovarian tumor analysis (iota) group. ultrasound obstet gynecol 2015;16:500-04. 14. vuento sh, pirhonen jp, mäkinen ji.comparison of tranvaginal ultrasonography with color doppler ultrasound in assessment of asymptomatic postmenopausal women with suspected ovarian tumours. cancer 2016; 92:114– 17. 15. ahmed kk, shaukat a, khosa hl, rashid n. the role of ultrasound in diagnosis of gynaecologic / pelvic tumors. ann ke med coll 2011; 7: 319-23 16. hogdall e: cancer antigen 125 and prognosis. curr opin obstet gynecol 2008, 20:4-8 17. umemoto m, shiota m, shimono t, hoshiai h. preoperative diagnosis of ovarian tumors, focusing on solid area based on diagnostic imaging. j obstet gynaecol res 2016; 32: 195201 18. chan jk, cheung mk, husain a.patterns and progress in ovarian cancerover 14 years.obstet gynecol2016, 108:52128 19. dock w, grabenwoger f, metz v, eibenberger k, farres mt. tumor vascularization: assessment with duplex sonography. radiology 2011; 181:241-44. 20. kurjak a, zalud i, alfirevicz. evaluation of adnexal masses with transvaginal color ultrasound. j ultrasound med.2012; 10, 295-97. 21. sengoku k, satoh t, saitoh s, abe m, ishikawa m. evaluation of transvaginal color doppler sonography, transvaginal sonography and ca 125 for prediction of ovarian malignancy. int j gynaecol obstet, 2004; 46, 3943. 22. weiner z, thaler i, beck d. differentiating malignant from benign ovarian tumors with transvaginal color flow imaging. obstet gynecol 2002;79, 159-62. 23. zanetta g, vergani p, lissoni a. color doppler ultrasound in the preoperative assessment of adnexal masses. acta obstet gynecol scand2014; 73, 637-41. 24. levine d, asch e, mehta ts, broder j.assessment of factors that affect the quality of performance and interpretation of sonography of adnexal masses. j ultrasound med 2008;27:721–28. 25. brown dl, doubilet pm, miller fh.benign and malignant ovarian masses: selection of the most discriminating grayscale and doppler sonographic features. radiology 1998; 208:103–110. http://www.ncbi.nlm.nih.gov/pubmed?term=%22marchesini%20ac%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22magrio%20fa%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22berezowski%20at%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed/18240986 https://www.ncbi.nlm.nih.gov/pubmed/?term=brown%20dl%5bauthor%5d&cauthor=true&cauthor_uid=9646799 https://www.ncbi.nlm.nih.gov/pubmed/?term=doubilet%20pm%5bauthor%5d&cauthor=true&cauthor_uid=9646799 https://www.ncbi.nlm.nih.gov/pubmed/?term=miller%20fh%5bauthor%5d&cauthor=true&cauthor_uid=9646799 summary journal of rawalpindi medical college (jrmc); 2017;21(3): 303-305 303 original article perception of medical students regarding case based learning tabassum naveed 1, naveed mazhar bhatti2 , romana malik 3 1.department of medical education, hitec institute of medical sciences, ,taxila;2.department of orthodontics, hitec institute of medical sciences,taxila cantt;3 department of forensic medicine & toxicology,hitecinstitute of medical sciences, taxila. abstract background: to determine perception of first year medical students about case based learning (cbl) in a modular curriculum. methods: in this cross sectional quantitative study convenient method of sampling was used to collect data from seventy-nine participants on a reliable survey tool (cronbach alpha reliability=.87). ethical approval was obtained and consent for the study was taken from study participants. the data was analyzed on spss version 22. results: the eight questions asked in the survey yielded a statistically significant result with friedman’s chi square=85.84 (df=7) p=.000<0.5, for perception of students in cbl session. we accepted the alternate hypothesis. conclusion: most of the students agree that cbl is useful. it promotes group discussions, interpersonal skills, feedback by students and teachers and helps them to correlate clinical data. key words: case based learning, interpersonal skills, group discussions, critical thinking. introduction case based learning (cbl) is a method of learning on a continuum of problem based learning. it is assumed to promote critical thinking and problem solving. the method is traditionally used in clinical years of undergraduate teaching and learning. in a traditional discipline based curriculum, the students learn the subjects of anatomy, physiology and biochemistry in a lecture based teaching and are assumed to apply the knowledge learned in preclinical years to solve patient problems when they enter the clinical years. in a discipline based curriculum students are unable to understand how the different parts of human body function together in normal and diseased state to solve a patient’s clinical problem. in contrast, an integrated curriculum allows the student to take a holistic view of patients and their problem. literature review showed that case based learning in basic science subjects of anatomy, physiology and biochemistry promotes development of clinical competence in preclinical years. cbl promotes vertical and horizontal integration of preclinical with clinical subjects. case based discussions are primarily used in post graduate clinical training where teacher selects a patient record and explores it with the learner. the teacher evaluates the application of basic, clinical knowledge and decision making on dimensions such as patient presentation, investigations and management options. application of case based learning exposes the student to clinical thinking and decision making without patient exposure in a safe environment. it provides a venue for students to apply basic science knowledge within clinical context. purpose of this study was to determine perception of first year mbbs students to learning in case based learning sessions in the subjects of anatomy, physiology, biochemistry taking into account the independent factors of usefulness of cbl, clinical cases, correlation of clinical cases with learning objectives, group discussions, interpersonal skills, feedback by students, feedback by teachers and overall impression. we hypothesized that there will be a statistically significant difference between the means of six levels of the eight within people (subject) factors (independent variable) and the perception about cbl (dependent variable). subjects and methods a cross sectional study was conducted to collect data from students regarding case based learning. a convenient method of sampling was used.the study was conducted at heavy industries taxila education city-institute of medical sciences (hitec-ims).the institute follows a modular curriculum approved by nums academic council. each basic science department of first year conducts one cbl in a week. survey form comprised of eight questions on a likert scale (table 1). each question was rated as 1=strongly disagree, 2= disagree, 3= slightly disagree, 4= slightly journal of rawalpindi medical college (jrmc); 2017;21(3): 303-305 304 agree, 5= strongly agree, 6= strongly agree. these six were taken as levels of a within subject factor also called the independent variables. the subjects or participants were the cases exposed to the six independent variables or questions and the same dependent variable i.e., perception bout cbl. minimum possible score on the scale was eight, maximum was forty-eight. the reliability of the survey tool was determined and was found to be good at 0.87. completely filled survey forms with consent were received from seventy-nine study participants. a nonparametric test was done by friedman chi square. dependent variable perception about cbl was not normally distributed violating the assumption for using repeated measures anova, histograms of all the independent variables or factors which are the eight questions of the survey form also showed that the data was not normally distributed hence nonparametric counterpart of repeated measures anova, friedman test was carried out. results maximum mean score 4.38±1.34 (table 1) was obtained on “cbl session promoted development of interpersonal skills” for which 34.2% participants “agreed” (table 2). lowest mean score 3.49±1.48 was obtained on, “cbl session was useful” for which 30.4% participants agreed(table 1&2). table 1: descriptive statistics for perception about cbl questions about perception of cbl mean standard error standard deviation 1.cbl session was useful 3.49 .16 1.48 2.clinical case given in cbl session was useful 4.46 .13 1.17 3.i was able to correlate clinical data in the case with learning objectives 3.98 .16 1.44 4.group discussion during cbl session was useful 4.30 .15 1.34 5.cbl session promoted development of interpersonal skills 4.38 .15 1.34 6.feedback provided by students was useful 3.65 .17 1.48 7.feedback provided by teacher was useful 4.64 .14 1.24 8.your overall impression of cbl session 3.67 .16 1.43 the mean of eight questions survey was 32.61±7.93 standard deviation (table 3).a statistically significant result was obtained with friedman’s chi square=85.84 (df=7)p=.000<0.5, for perception of students in cbl session when asked from seventy-nine participants (table 4).hence, we accept the alternate hypothesis that there is a statistically significant difference between the means of six levels of the eight within people (subject) factors (independent variable) and the perception about cbl (dependent variable). table 2:student response on survey response (levels) q1 q2 q3 q4 q5 q6 q7 q8 strongly disagree 15.2 1.3 7.6 6.3 3.8 12.7 3.8 11.4 disagree 11.4 6.3 10.1 6.3 8.9 12.7 5.1 12.7 slightly disagree 17.7 10.1 12.7 6.3 7.6 11.4 3.8 12.7 slightly agree 22.8 27.8 30.4 27.8 25.3 29.1 20.3 29.1 agree 30.4 35.4 24.1 38 34.2 27.8 44.3 29.1 strongly agree 2.5 19 15.2 15.2 20 6.3 22.8 5.1 table 3: overall survey statistics mean variance std. deviation n of items 32.61 62.83 7.93 8 table 4: friedman's test sum of squares df mean square fried man's chisquare sig between people 612.604 78 7.854 within people (subjects) between questions 103.342a 7 14.763 85.84 .000 residual 562.408 546 1.030 total 665.750 553 1.204 total 1278.35 631 2.026 grand mean = 4.0759 a. kendall's coefficient of concordance w = .081. discussion students had a positive perception about cbl, reflected in above average mean score. the results of the study are statistically significant and show that perception of students regarding cased based learning is affected by usefulness of the session, usefulness of clinical cases, their ability to correlate clinical cases, group discussion, interpersonal skills, feedback by students, teachers and their overall impression. present study is supported by a study conducted in united states of america where thirty-one medical schools reported that cbl was integrated in 75% of courses and more than half agreed that it promotes critical thinking a necessary condition for clinical journal of rawalpindi medical college (jrmc); 2017;21(3): 303-305 305 decision making and problem solving. , , another study proposes that perceived clinical relevance as provided by cbl should be used in curriculum as it promotes retention of basic science knowledge in clinical context and continued throughout the medical courses. , a study utilizing thematic analysis of a focus group discussion study of cbl learning identified the following themes; clinical situation, patient data and informing decisions, clinical knowledge, multiple ways of thinking, professional care and professional self-concept. a study conducted in pakistan regarding perception of medical students regarding case based learning and tutorial format concluded that case based method was significantly more favored by students compared to traditional tutorial format regarding group dynamics and behavioral influences of facilitators, learning process and environment. however, another study conducted in pakistan to compare students’ perception of the effectiveness of teaching methodologies concluded that students in structured interactive sessions applied clinical reasoning and group discussion better compared to case based learning and interactive lectures. feedback is an important component of the process of cbl. 44.4% students agreed that feedback provided by teachers was useful. studies have shown that students received feedback positively when it was directed towards learning. teachers conducting cbl were trained in the process of conducting it. they were also trained in critical thinking and feedback and this may be the reason for the perception of students as is also proved by a previous study. cbl provides early clinical exposure and develops relationship between basic and clinical sciences resolving an important issue of sequencing of basic and clinical subjects. it facilitates transition of students to clinical environment.21 conclusion students have a positive perception about cbl in the subjects of anatomy, physiology and biochemistry when introduced in a modular curriculum. it provides opportunity for good quality group discussions, development of interpersonal skills, critical thinking and hence the ability to solve clinical cases in a safe environment without actual patient exposure. references 1. parmar sk, rathinam ba. introduction of vertical integration and case-based learning in anatomy for undergraduate physical therapy and occupational therapy students. anat sci educ. 2011;4(3):170-83 2. sabbagh ma. application of case discussions to improve anatomy learning in syria. avicenna j med. 2013 ;3(4):8791. 3. böckers a, mayer c, böckers tm. does learning in clinical context in anatomical sciences improve examination results, learning motivation? anat sci educ. 2014 ;7(1):3-11. 4. johnson eo, charchanti av, troupis tg. modernization of an anatomy class:a case for integrated multimodalmultidisciplinary teaching. anat sci educ 2012;5(6):354-66. 5. kulak v, newton g. a guide to using case-based learning in biochemistry education. biochem mol biol educ. 2014;42(6):457-73. 6. jabaut jm, dudum r, margulies sl, mehta a. teaching and learning of medical biochemistry according to clinical realities. biochem mol biol educ. 2016 ;44(1):95-98. 7. qamar k, rehman s, khan ma. effectiveness of case-based learning during small groups sessions at army medical college. j coll physicians surg pak. 2016 ;26(3):232-33. 8. washburn se, posey d, stewart rh. merging clinical cases, client communication, and physiology to enhance students learning, and skills. j vet med educ. 2016 ;43(2):170-75. 9. lutsky k, glickel sz, weiland a, boyer mi. what every resident should know about wrist fractures: case-based learning. instr course lect. 2013; 62:181-97. 10. gholami m, saki m, toulabi t, kordestani mp. iranian nursing students' experiences of case-based learning: a qualitative study.jprof nurs. 2017 ;33(3):241-49. 11. vora mb, shah cj. case-based learning in pharmacology: moving from teaching to learning. int j appl basic med res. 2015;5(1):s21-23. 12. kantar ld, massouh a. case-based learning: what traditional curricula fail to teach.nurse educ today. 2015;35(8):8-14. 13. elangovan s, venugopalan sr, srinivasan s, karimbux ny. integration of basic-clinical sciences, pbl, cbl, and ipe in u.s. dental schools' curricula and a proposed integrated curriculum model for the future. j dent educ. 2016 ;80(3):281-90. 14. ilgüy m, ilgüy d, fişekçioğlu e, oktay i. comparison of casebased and lecture-based learning in dental education using the solo taxonomy. j dent educ. 2014 ;78(11):1521-27. 15. yoo ms, park jh. effect of case-based learning on the development of graduate nurses' problem-solving ability.nurse educ today. 2014;34(1):47-51. 16. malau bs, lee ay, cooling n. retention of knowledge and perceived relevance of basic sciences in a case-based learning curriculum. bmc med educ. 2013 ;13:139-41. 17. elangovan s, venugopalan sr, srinivasan s. integration of basic-clinical sciences, pbl, cbl, and ipe. dental schools' curricula and a proposed integrated curriculum model for future. j dent educ 2016;80(3):281-90. 18. hashim r, azam n, shafi m, majeed s. perceptions of undergraduate medical students regarding case based learning and tutorial format. j pak med assoc. 2015;65(10):1050-55. 19. rehan r, ahmed k, khan h, rehman r. a way forward for teaching and learning of physiology: students' perception of the effectiveness of teaching methodologies. pak j med sci. 2016 ;32(6):1468-73. 20. mehta f, brown j, shaw nj. do trainees value feedback in case-based discussion assessments? med teach. 2013 ;35(5):e1166-72. 21. mckenzie ct. dental student perceptions of case-based educational effectiveness. j dent educ. 2013 ;77(6):688-94. https://www.ncbi.nlm.nih.gov/pubmed/?term=kantar%20ld%5bauthor%5d&cauthor=true&cauthor_uid=25842004 https://www.ncbi.nlm.nih.gov/pubmed/?term=massouh%20a%5bauthor%5d&cauthor=true&cauthor_uid=25842004 https://www.ncbi.nlm.nih.gov/pubmed/25842004 https://www.ncbi.nlm.nih.gov/pubmed/25362693 https://www.ncbi.nlm.nih.gov/pubmed/25362693 https://www.ncbi.nlm.nih.gov/pubmed/25362693 https://www.ncbi.nlm.nih.gov/pubmed/?term=yoo%20ms%5bauthor%5d&cauthor=true&cauthor_uid=23518068 https://www.ncbi.nlm.nih.gov/pubmed/?term=park%20jh%5bauthor%5d&cauthor=true&cauthor_uid=23518068 https://www.ncbi.nlm.nih.gov/pubmed/23518068 https://www.ncbi.nlm.nih.gov/pubmed/26933103 https://www.ncbi.nlm.nih.gov/pubmed/26933103 https://www.ncbi.nlm.nih.gov/pubmed/26933103 https://www.ncbi.nlm.nih.gov/pubmed/26933103 185 journal of rawalpindi medical college (jrmc); 2022; 26(2): 185-189 original article relationship between empathy and personality traits in students of a public sector medical university naeem liaqat1, maria ata2, nida-e-haider3 1 fellow, nationwide children’s columbus, ohio, usa. 2,3 final year mbbs student, rawalpindi medical university. author’s contribution 1,2,3 conception of study 1,3 experimentation/study conduction 1 analysis/interpretation/discussion 1,2,3 manuscript writing 1,2 critical review 2 facilitation and material analysis corresponding author dr. naeem liaqat, fellow, nationwide children’s columbus, ohio, united states of america. email: simsonian.chaudary@gmail.com article processing received: 28/06/2021 accepted: 23/05/2022 cite this article: liaqat, n., ata, m., haider, n. relationship between empathy and personality traits in students of a public sector medical university. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 185-189. doi: https://doi.org/10.37939/jrmc.v26i2.1723 conflict of interest: nil funding source: nil access online: abstract introduction: empathy among medical students and doctors, is a rather unexplored part of medical flora and fauna which may vary with each personality. objective: to determine the correlation between empathy and personality traits of final-year medical students. materials and methods: this cross-sectional study was conducted at rawalpindi medical university, pakistan. a total of 144 medical students were included in the study. for personality traits assessment and empathy assessment, big five inventory and interpersonal reactivity index were used. all the data were analyzed using spss version 20. results: the mean score for the empathy scale was found to be 61.25 ± 10.0. females were more empathetic than males in all subscales but pointedly so in the empathetic concern scale. overall empathy scale was strongly correlated with agreeableness and neuroticism (p<0.001). perspective taking scale was positively related to agreeableness and openness, the empathy concern scale was positively related to agreeableness, and personal distress was positively related to conscientiousness and neuroticism. the demographic factors of age and gender explained only 1.7%, 6.8%, 2.4%, and 2.0% of the variance in the four scales of empathy. after adjustment for age and gender, perspective taking was positively associated with agreeableness and openness and personal distress was associated with agreeableness, neuroticism, and openness. conclusion: we conclude that personality traits have a substantial correlation with empathy and its subscales. so we need to evaluate the personality of a medical student and tailor a set of rules for each individual consistent with their persona to develop empathy for them. keywords: big five; personality; empathy; medical students; pakistan. 186 journal of rawalpindi medical college (jrmc); 2022; 26(2): 185-189 introduction in literature, empathy is defined as the ability to understand and share the feelings of another person i.e. “to put yourself in someone’s shoe”. from a medical viewpoint, empathy is elaborated as a physician’s ability to relate to and comprehend a patient’s physical and emotional circumstances.1 in a doctor-patient interaction, empathy build up on part of the doctor helps to improve patient compliance and satisfaction. it also helps cut down the unnecessary economic burden on the patient.2 characteristic traits, of certain healthcare providers, help to categorize them according to their personality types and serve to interpret the empathy index of those individuals. for example, clinicians with great emotional intellect or high emotional quotient (eq) generally demonstrate an extensively empathic and flexible façade.3 many research studies, conducted to assess the level of empathy in medical students, show that scholars at the commencement of their medical schooling have a greater magnitude of empathy which progressively declines as they sail through their careers. so when they get to virtually deal with the patients on their own, they just have shards of the trait left.4 in a study3, authors included 150 medical students and found a significant correlation between empathy and each of the five domains of personality. note that for neuroticism, the correlation was inverse, while for the other four domains, the correlation was positive. magalha˜ es5 included 350 medical students from six entering classes and found significant and positive correlations between the total score on the empathy scale and openness to experience (r¼0.22, p50.01), agreeableness (r¼0.24, p50.01), and conscientiousness (r¼0.14, p50.05). the magnitudes of correlations between personality and scores of self-reported empathy were low, ranging from _0.01 to 0.24. in another study, authors6 have found positive significant correlations between the total score of the empathy scale either with agreeableness (r¼0.628, p50.001) and openness to experience (r¼0.522, p50.001). however, insufficient studies have been conducted among medical students in pakistan on the vital subject matter of empathy7,8, and none of them has ever considered the correlation of empathy with personality traits. so we planned this study with the objective to determine the correlation between personality traits and empathy among medical students of a public sector medical college in pakistan. materials and methods this cross-sectional study was conducted at rawalpindi medical university, rawalpindi, pakistan. the total duration of the study was 2 months, from june 2019 to july 2019. after approval from the ethical review board of our university, this study was started. using a 5% margin of error and 80.5 power of the test, 144 sample size is calculated based on r=0.232 between big five inventory (bfi) and empathy.9 a total of 144 final-year medical students of our university were included in this study. we used 2 standardized questionnaires in this study. in order to assess personality traits, we used the bfi inventory having 44 items. all 44 items are scored on a likert scale ranging from strongly agree5 to strongly disagree.1 some of the items are scored as reverse and it gauges the personality in 5 domains namely extraversion, agreeableness, conscientiousness, neuroticism, and openness. in order to assess empathy in this study, we used interpersonal reactivity index (iri). it is a validated instrument having 28 items which are scored on a likert scale ranging from “does not describe me well” to “describes me very well”(0 to 4). it measures empathy on four scales namely perspective taking, fantasy, empathic concern, and personal distress scale.10 there is no cut-off value in this scale and it is reported as a continuous scale and higher scores indicate more empathy of the participant. for sampling, we used non-probability continuous sampling. all 144 participants were asked to fill in proforma. in order to maintain anonymity, only verbal count for individuals in the study was sought. they were asked to fill proforma by paper and pencil and it contained demographic details, a bfi questionnaire, and an iri questionnaire. all the data were analyzed using spss version 20. the demographic variables were presented as descriptive statistics. the personality traits and empathy scores for scales according to iri were presented as mean and standard deviation (sd). the student’s t-test was used to compare it for gender. to assess the correlation, person correlation was used. then hierarchical regression analysis (hmr) was done and 2 blocks of variables were used in the regression model in the following steps: step 1: demographic characteristics; step 2: five personality traits. the variance of empathy scores was explained by the relative importance of variables that were retained in the final model as the standardized β. standardized parameter estimates (the standardized β) were used to compare the magnitudes 187 journal of rawalpindi medical college (jrmc); 2022; 26(2): 185-189 of the correlations across independent variables. the fit of the model was assessed with the r2 value. results a total of 144 participants were included in this study. the mean age of the participants was found to be 22.91 ± 0.989 years. most of the participants in this study were female (n=117, 81.3%). regarding the empathy scale, the mean score for the empathy scale was found to be 61.25 ± 10.0. on the subject of its subscales, the highest score was obtained for perspective taking subscale. females were more empathetic than males in all subscales of empathy but a significant difference was noted in the empathetic concern subscale. all data is given in table 1. regarding personality traits, all data is given in table 2. overall empathy scale was strongly correlated with agreeableness and neuroticism (p<0.001). perspective taking scale was positively related to agreeableness and openness, the empathy concern scale was positively related to agreeableness, and personal distress was positively related to conscientiousness and neuroticism. all data are given in table 3. the demographic factors of age and gender explained only 1.7%, 6.8%, 2.4%, and 2.0% of the variance in the four scales of empathy, including perspective taking, empathic concern, personal distress, and fantasy scale respectively. however, the big five personality traits accounted for 19.4%, 6.3%, 26.4%, and 4.6% of the variance in perspective taking, empathic concern, personal distress, and fantasy scale respectively. after adjustment for age and gender, perspective taking was positively associated with agreeableness and openness. also, personal distress was associated with agreeableness, neuroticism, and openness. all data is given in table 4. table 1: empathy score and its subscales in this study total score male (n=27) female (n=117) pvalue personality taking 15.99 ± 4.37 15.0 ± 4.66 16.22 ± 4.29 0.192 fantasy scale 14.31 ± 3.66 13.77 ± 2.96 14.43 ± 3.81 0.403 empathic concern scale 15.84 ± 3.27 14.07 ± 3.78 16.24 ± 3.01 0.002 personal distress scale 15.1 ± 4.82 13.59 ± 4.54 15.45 ± 4.83 0.071 total empathy scale 61.25 ± 10.01 56.44 ± 8.98 62.35 ± 9.94 0.005 table 2: personality of participants according to bfi total score male (n=27) female (n=117) pvalue extroversion 23.96 ± 5.28 22.22 ± 4.67 24.36 ± 5.35 0.057 agreeable ness 32.84 ± 5.62 31.44 ± 6.71 33.16 ± 5.31 0.153 conscientiou sness 29.15 ± 5.70 29.88 ± 5.50 28.98 ± 5.76 0.459 neuroticism 25.58 ± 5.82 24.11 ± 5.81 25.92 ± 5.79 0.145 openness 34.41 ± 5.80 34.22 ± 7.20 34.12 ± 5.47 0.940 table 3: correlation of empathy and bfi variables 1 2 3 4 5 6 7 8 9 10 1. personality taking scale 1 2. fantasy scale .195* 1 3. empathic concern scale .244** .097 1 4. personal distress scale .126 .129 .263** 1 5. overall empathy scale .649** .545** .595** .670** 1 6. extroversion .160 .101 .147 -.133 .091 1 7. agreeableness .377** -.011 .194* .058 .252** .274** 1 8. conscientiousness .081 .073 .111 .243** -.019 .395** .184* 1 9. conscientiousness -.097 .091 .098 .483** .256** .338** -.134 .421** 1 10. openness .347** .145 .072 -.134 .164 .136 .327** .158 -.008 1 *significant at the 0.05 level (two-tailed) ** significant at the 0.01 level (two-tailed) 188 journal of rawalpindi medical college (jrmc); 2022; 26(2): 185-189 table 4: the results of hierarchical linear regression analyses variables perspective taking (β) empathic concern (β) personal distress (β) fantasy scale (β) step1 step2 step1 step2 step1 step2 step1 step2 step 1 age -0.337 -0.150 0.028 0.55 0.029 0.011 -0.127 -0.098 gender 0.970 0.780 0.269 0.235 0.160 0.068 0.033 0.022 step 2 extraversion 0.144 0.075 0.014 0.117 agreeableness 0.367** 0.146 0.179** -0.092 conscientiousness 0.081 0.150 -0.044 0.075 neuroticism 0.112 0.18 0.484** 0.143 openness 0.344** 0.001 -0.182** 0.136 f 1.240 6.698** 5.183** 2.953** 1.704 7.826** 1.414 1.368 r2 0.017 0.211 0.068 0.132 0.024 0.250** 0.020 0.066 △r2 0.017 0.194 0.068 0.063 0.024 0.264** 0.020 0.046 *significant at the 0.05 level (two-tailed) ** significant at the 0.01 level (two-tailed) discussion the objective of this study was to determine the correlation between personality traits and empathy among medical students. it was found that the big five personality traits accounted for 19.4%, 6.3%, 26.4%, and 4.6% of the variance in perspective taking, empathic concern, personal distress, and fantasy scale respectively. also, agreeableness and neuroticism were strongly associated with overall empathy scores. in a comparable study by mooradian ta, it was found that agreeableness and neuroticism were closely related to different scales of empathy.11 regarding medical students, studies have shown that different personality traits are strongly correlated with empathy scales. it has been confirmed by studies from portugese5, china12, and america.13 a study that included a sample from four countries including china, germany, spain, and the united states of america found that agreeableness and conscientiousness were the most dominant predictors of empathy.14 previously it has been shown that agreeableness, which represents the person being more adjustable, cooperative, understanding, and helpful, is more correlated with empathy. similarly, we have noticed it to be associated with perspective taking and empathic concern. as some authors consider empathy as cognitive (perspective taking and fantasy) and emotional (empathic concern and personal distress)12, we found the cognitive domain to be positively correlated with agreeableness and openness. the emotional domain was correlated more with agreeableness, conscientiousness, and neuroticism. neuroticism and consciousness which share the feature of being less emotionally stable and becoming distressed after seeing others in trouble make sense to be more associated with an emotional domain of empathy. it also shows the importance of inculcating these particular traits among medical students as the incidences of violence against healthcare workers is on the rise globally and generally the trust in doctors has dropped drastically. we found in this study that scores of empathy are higher in females than males in all subscales but this difference is significant for the empathic concern scale and overall empathy score. although in our study, females quite outnumbered the opposite gender, this skewness is commonly seen in our country among medical students as usually, 70% of students are females. a cross-sectional study was conducted including medical students, trainees, post-graduate residents, and specialists in poland. they found the highest empathy score for female doctors and it was lowest among male post-graduate residents.15 in another study from usa, empathy score was found significantly higher among females than males.3 many other studies have confirmed the finding of higher empathy among females as compared to males.16-18 at the same time, some studies have shown no difference between the two genders in terms of empathy scores.19 empathy is a complex concept having a large number of factors that may affect it. some authors have suggested that empathy changes with growing age and as the experience increases, the level of empathy also increases.20 however, some later studies have negated the concept.12 age, gender, and the experience of the physician are not the only factors that may influence empathy, rather it is the depiction of the whole personality and experiences of a person which 189 journal of rawalpindi medical college (jrmc); 2022; 26(2): 185-189 are difficult to have complied in a single study. as conflict among healthcare staff particularly junior doctors is also escalating worldwide, we need to look into factors triggering this upsurge of conflicts. many studies emphasize the importance of empathy in the resolution of conflicts.21 so empathy is an amalgam of many factors and the most important of them may be the personality traits, which nurture over the years in everyone’s peculiar circumstances.22 so our study has many implications, particularly for grooming a new generation of doctors in our setup. we want to highlight the importance of adding empathy to the curriculum of third-world countries like ours and conducting well-organized training sessions and workshops depending on certain personality-carrying students so that they may get enlightened for their future and may become good physicians. another previous study underlines the rotation of medical students into the hospitals and clinical settings earlier so that they may encounter the patients and acquire a better insight into the empathy concept.17 the strength of this study lies in that; it judges the correlation between personality traits and empathy among medical students of pakistan as compared to inadequate literature available on the topic in our country. however, there are a few limitations also. first curb, is a single-center study, so its results cannot be applied to other institutions. then, it is a crosssectional study and does not contemplate the change in empathy score over a period of time. therefore, we recommend studies including medical students of different nations and cultures to determine the correlation, so that an amenable statement may be put forth. conclusion we conclude that personality traits have a substantial correlation with empathy and its subscales. so we need to evaluate the personality of a medical student and tailor a set of rules for each individual consistent with their persona to develop empathy for them. references 1. baron-cohen s, wheelwright s. the empathy quotient: an investigation of adults with asperger syndrome or high functioning autism, and normal sex differences. j autism dev disord. 2004;34(2):163-75. 2. ha jf, longnecker n. doctor-patient communication: a review. ochsner j. 2010;10(1):38-43. 3. bertram k, randazzo j, alabi n, levenson j, doucette jt, barbosa p. strong correlations between empathy, emotional intelligence, and personality traits among podiatric medical students: a cross-sectional study. educ health (abingdon). 2016;29(3):186-94. 4. hojat m, vergare mj, maxwell k, brainard g, herrine sk, isenberg ga, et al. the devil is in the third year: a longitudinal study of erosion of empathy in medical school. acad med. 2009;84(9):1182-91. 5. magalhaes e, costa p, costa mj. empathy of medical students and personality: evidence from the five-factor model. med teach. 2012;34(10):807-12. 6. lourinho i, severo m. are personality traits really weak/moderate predictors of empathy? medical teacher. 2013;35(7):611. 7. ayub a, khan ra. measuring empathy of medical students studying different curricula; a causal comparative study. j pak med assoc. 2017;67(8):1238-41. 8. tariq n, rasheed t, tavakol m. a quantitative study of empathy in pakistani medical students: a multicentered approach. journal of primary care & community health. 2017:2150131917716233. 9. barrio vd, aluja a, garcía lf. relationship between empathy and the big five personality traits in a sample of spanish adolescents. soc behav personal. 2004;32(7):677-81. 10. davis mh. a multidimensional approach to individual differences in empathy. jsas catalog of selected documents in psychology. 1980;10:85. 11. mooradian ta, davis m, matzler k. dispositional empathy and the hierarchical structure of personality. am j psychol. 2011;124(1):99-109 12. song y, shi m. associations between empathy and big five personality traits among chinese undergraduate medical students. plos one. 2017;12(2):e0171665. 13. toto rl, man l, blatt b, simmens sj, greenberg l. do empathy, perspective-taking, sense of power and personality differ across undergraduate education and are they inter-related? advances in health sciences education: theory and practice. 2015;20(1):23-31. 14. melchers mc, li m, haas bw, reuter m, bischoff l, montag c. similar personality patterns are associated with empathy in four different countries. frontiers in psychology. 2016;7:2 15. bratek a, bulska w, bonk m, seweryn m, krysta k. empathy among physicians, medical students and candidates. psychiatria danubina. 2015;27 suppl 1:s48-52. 16. chen dc, kirshenbaum ds, yan j, kirshenbaum e, aseltine rh. characterizing changes in student empathy throughout medical school. medical teacher. 2012;34(4):305-11. 17. wen d, ma x, li h, liu z, xian b, liu y. empathy in chinese medical students: psychometric characteristics and differences by gender and year of medical education. bmc medical education. 2013;13:130. 18. shariat sv, habibi m. empathy in iranian medical students: measurement model of the jefferson scale of empathy. medical teacher. 2013;35(1):e913-8. 19. lee bk, bahn gh, lee wh, park jh, yoon ty, baek sb. the relationship between empathy and medical education system, grades, and personality in medical college students and medical school students. korean journal of medical education. 2009;21(2):117-24. 20. austin ej, evans p, magnus b, o'hanlon k. a preliminary study of empathy, emotional intelligence and examination performance in mbchb students. medical education. 2007;41(7):684-9. 21. fitness j, curtis m. emotional intelligence and the trait meta-mood scale: relationships with empathy, attributional complexity, self-control, and responses to interpersonal conflict. sensoria: a journal of mind, brain & culture. 2005;1(1):50-62 22. cassels tg, chan s, chung w. the role of culture in affective empathy: cultural and bicultural differences. journal of cognition and culture. 2010;10(3):309-26. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 205-207 205 original article effectiveness of vitamin d in prevention of dengue haemorrhagic fever and dengue shock syndrome sadaf zaman , muhammad rizwan mahmud ,mohammad ali khalid ,aqsa zahid,sadaf khalid,irum kabir, shehzad manzoor, haider zaigham baqai department of medicine unit i, benazir bhutto hospital and rawalpindi medical college, rawalpindi abstract background: to compare the risk and severity of development of dengue hemorrhagic fever (dhf) and dengue shock syndrome(dss) in patients receiving vitamin d supplement compared to those not receiving it. methods: diagnosed patients of df (n=124) were enrolled in this comparative study. patients were randomized into two groups having 62 participants in each group. group a received single dose of 200,000 iu vitamin d and group b received no intervention. both groups were followed for development of dhf or dss. chi square was applied to compare the groups. results: one patient (1.6%) in group a developed dhf. seventeen (27%) patients in group b progressed to dhf. the relationship between vitamin d and progression to dhf was significant, x2 (2, n=170) =16.43, p= 0.000). the calculated relative risk was 0.0588 (95% confidence interval, .0081 to .4285; p for trend = 0.0588). conclusion: vitamin d decreases the risk of dhf and may have a role in management of dengue fever. key words: vitamin d, dengue fever, dengue haemorrhagic fever introduction dengue is a febrile illness that is a major cause of morbidity throughout the tropical and subtropical regions. it is a caused by a flavivirus with four distinct serotypes (dv-1, dv-2, dv-3, and dv-4). dhf is characterized by all the symptoms of dengue fever (df) along with haemorrhagic manifestations such as spontaneous bleeding, decrease in platelet count and evidence of increased vascular permeability noted as increased haemo-concentration or pleural effusion or ascites. 1 virus spreads between humans by mosquito vectors of the aedes genus, i.e, aedes aegypti and aedes albopictus.2 approximately 2.5 billon people are at risk of getting infection and 50 million cases of dengue fever are reported every year.3 infection with any of the serotypes may be asymptomatic in the majority of cases or may result in a wide spectrum of clinical symptoms, known as dengue fever. the symptoms of dengue fever range from a mild flu-like syndrome to the most severe forms of the disease, dhf, which includes coagulopathy and increased vascular permeability. dhf may progress to hypovolemic shock known as dss.4 in asia the risk of developing severe disease is greater in dengue feverinfected children (≤15 years) than in adults.5 the life-threatening dss stage occurs at the time of or shortly after drop in blood pressure, which is characterized by a rapid, weak pulse, narrow pulse pressure (≤20 mm hg) or hypotension with cold, clammy skin in the early stage of shock. this may soon progress to more serious form of shock if patients do not receive prompt and appropriate treatment, in which pulse and blood pressure become undetectable, resulting in death within 12 to 36 h after onset of shock.6 low blood calcium levels have been associated in dengue. 7 calcium has proven to be essential for cytotoxic activity of the dengue type 2 viruses (dv)induced macrophage cytotoxic (cf2).8 calcium appears to play a role in the induction of denguespecific t-helper cells. dengue antigen has been shown to increase the influx of calcium into t-cells. the proliferation of dengue-specific t-helper cells appears to be dependent on calcium and is inhibited in the absence of calcium and by calcium channel antagonist drugs.9 there is some evidence that the production of nitrite in response to dengue virus infection is also calcium dependent and can be inhibited by calcium channel blocking drugs. 10 prevention and control of dengue and dhf has become the need of time with the expanding geographic distribution of disease and increased disease incidence in the past 20 years.11 unfortunately, tools available to prevent dengue infection are very limited. despite considerable work on vaccine for df and dhf over the years, an effective safe vaccine is yet to be developed because of various obstacles. mosquito prevention is also an important step in eradication of dengue fever. 12-14 few studies have also discussed role of vitamin d in reducing the severity of df,dhf and dss. a case journal of rawalpindi medical college (jrmc); 2017;21(3): 205-207 206 series published in 2009 showed 5 patients receiving vitamin d had overall improvement of clinical condition and reduced symptoms of df.15 a brazilian study found increase in vitamin d binding protein in df.16 the possible explanation of antidengue effects of vitamin d is because of involvement of cathelicidin (in the form of ll-37), human beta defensin 2, and through the release of reactive oxygen species.17 presently it is believed that patient of df will never progress to dhf or dss but wide variation in severity and outcome of disease make this doubtful. patients and methods a total of 124 patients with diagnosed dengue fever, who fulfilled the inclusion criteria were enrolled in to the study from 01.9.2016 to 31.1.2017 from benazir bhutto hospital after getting ethical review board approval. patients were randomized to two groups having 62 participants each. group a received 200,000 iu vitamin d and group b received no intervention. both groups were followed for development of dengue hemorrhagic fever or dengue septic shock. data was recorded in self-structured questionnaire. categorical data was presented as frequencies. pearson’s chi square was applied to compare the proportion of patients in each study group who will develop dhf & dss. relative risk was measured along with 95% confidence intervals to compare the risk of development of dhf & dss in both study groups. significant value was < 0.05. results total of 124 patients were enrolled after informed consent. mean age was 33.43 ± 16.20 table 1: dengue fevervariables at presentation variables mean std. deviation age (years) 33.43 16.22 calcium at admission (mg/dl) 8.81 .42 albumin at admission (g/l) 4.44 3.65 platelet at admission (x109 /l) 108.90 40.24 hct at admission(%) 41.9 4.62 wbc at admission(x109 /l) 3.73 1.27 platelet at discharge(x109 /l) 117.15 49.38 hct at discharge (%) 40.19 5.12 wbc at discharge(x109 /l) 4.56 1.51 . mean calcium level at admission was 8.81 ± 0.42. mean platelet at admission was 108.90 ± 40.24. mean platelet at discharge was 117.15 ± 49.38 (table 1).most of the patients were admitted on 3rd ,4th and 5th day(n=105)91.6% (table 2). one patient (1.6%) in group a receiving in vitamin d supplements developed dengue hemorrhage fever. seventeen (27%) patients in group b not receiving vitamin d supplements progressed to dengue hemorrhagic fever. none of the patients developed dss (table 3). the relationship between vitamin d supplements and progression to dhf was significant, x2 (2, n=170) =16.43, p= 0.000. vitamin d decreases the risk and severity of dhf. the calculated relative risk was 0.0588 (95% confidence interval, .0081 to .4285; p for trend = 0.0588) table 1: total no of days of illness no of days of illness frequency percent 1st day 2 1.6 2nd day 7 5.6 3rd day 37 29.8 4th day 32 25.8 5th day 36 29.0 6th day 10 8.1 total 124 100.0 table 3: vitamin d supplementation vitamin d dengue fever dengue haemorrhagic fever no(%) n0(%) yes 61(98.4) 1(1.6) no 45(73.0) 17(27.0) discussion in present study, in group receiving vitamin d, there was fewer progression of df to dhf. the relationship between vitamin d supplements and progression to dhf was significant, x2 (2, n=170) =16.43, p= 0.000. vitamin d decreases the risk and severity of dhf. the calculated relative risk was 0.0588 (95% confidence interval, .0081 to .4285; p for trend = 0.0588). a mexican study investigated the effect of treatment with vitamin d3 on two types of human cell lines (hepatic huh-7 and monocytic u937) infected with denv.18 pureta found that exposure to 1,25-dihydroxy vitamin d3 significantly reduced the number of infected cells, particularly in monocytic cells, and lowered the production of pro-inflammatory cytokines.18vitamin d3 significantly reduced the levels of pro-inflammatory cytokines (tnf-α, il-6, il-12p70 and il-1β) produced by infected u937 cells. these results suggest that vitamin d3 may represent a potentially useful antiviral compound. according to another study, vitamin d supplementation altered il12 expression and dendritic cell maturation.19 giving vitamin d to dengue patients improved clinical condition.19 standard treatment for dengue management is give electrolytic solutions administration, bed rest, measurements of body temperature, blood pressure, haematocrit, platelet count, and administration of antipyretics.19 journal of rawalpindi medical college (jrmc); 2017;21(3): 205-207 207 host nutritional status is a strong predictor of immunity.20 host nutritional status or micronutrient supplementation as adjuvant therapy could lower the probability of progressing from denv infection to overt/severe forms of disease or reduce disease severity in patients.22 low blood calcium levels have been associated with dengue.7 the mean calcium level at admission at our study was 8.81±0.42. in present study only 1 patient on vitamin d developed dhf. alagarasu et al showed that there might be an association related to the inducing effect of vitamin d on fcγ-receptor expression. fcy receptor enhances viral entry into cells, possibly leading to higher viral load in dengue cases with secondary infection and the development of dhf or dendritic cell-specific intercellular adhesion. studies vitamin d might influence viral entry into cell. 21 albuquerque compared protein levels in the plasma of patients with severe df with the protein levels of healthy individuals and found that a one of the proteins showing a significant increase in df patients was vitamin d-binding protein.18 sánchez-valdéz observed a significant increase in platelet count on receiving vitamin d in their clinical trial. the average platelet count changed from 136,000 ± 69,508 cells/mm3 before treatment to 179,600 ± 56,584 cells/mm3 after treatment.15 in our study the mean platelet at admission was 108.90±40.24, while at discharge it was 117.15±49.38. the mean haematocrit at admission was 41.9±4.62 while at discharge it was 40.19±5.12. sánchez-valdéz also observed a significant improvement in the overall clinical condition of the patients as well as reduction in the duration of signs and symptoms of the infection. sánchez-valdéz suggested that vitamin d supplementation may possibly restore free calcium rapidly, leading to the reduced thrombocytopenia as seen in his trial. conclusion vitamin d may have a role in dengue management. a larger clinical trial is needed to further investigate the relationship between vitamin d and dengue management. references 1. weaver sc, vasilakis n. molecular evolution of dengue viruses: contributions of phylogenetics to understanding the preeminent arboviral disease. infect genet evol. 2009;9:523–40. 2. thomas sj, strickman d, vaughn dw. dengue epidemiology: virus epidemiology, ecology, and emergence. adv virus res. 2003;61:235–89. 3. guha-sapir, d., schimmer b. dengue fever: new paradigms for a changing epidemiology. emerg. themes epidemiol. 2005; 2:1-4. 4. harris e e, videa l, perez e, sandoval y.clinical, epidemiologic, and virologic features of dengue in the 1998 epidemic in nicaragua. am j trop med hyg. 2000; 63:5-11. 5. kittigul, l., p. pitakarnjanakul, d. sujirarat, k.differences of clinical manifestations and laboratory findings in children and adults with dengue . j clin virol. 2007; 39:76-81. 6. world health organization. dengue haemorrhagic fever: diagnosis, treatment, prevention and control, 2nd ed. who, geneva, switzerland, 1997. 7. zaloga gp and chernow b. the multifactorial basis for hypocalcemia during sepsis. studies of the parathyroid hormone-vitamin d axis. ann intern med. 1987;107:36–41. 8. dhawan r, chaturvedi uc, khanna m, mathur a. obligatory role of ca2+in the cytotoxic activity of dengue virus-induced cytotoxin. int j exp pathol. 1991;72:31–39. 9. chaturvedi p, saxena v, dhawan r. role of calcium in induction of dengue virus-specific helper t cells. indian j exp biol. 1995;33:809–15. 10. misra a, mukerjee r, chaturvedi uc. production of nitrite by dengue virus-induced cytotoxic factor. clin exp immunol. 1996;104:406–11 11. monath t p. dengue: the risk to developed and developing countries. proc natl acad sci usa. 1994;91:2395–2400. 12. russell p k. progress toward dengue vaccines. asian j infect dis. 1978;2:118–20. 13. wisseman c l, jr, sweet b h, rosenzweig e c, rylar o r. attenuated living type 1 dengue vaccines. am j trop med hyg. 1963;12:620–23. 14. gubler d j. aedes aegypti and aedes aegypti-borne disease control in the 1990s: top down or bottom up. am j trop med hyg. 1989;40:571–78. 15. sánchez-valdéz e., delgado-aradillas m., torres-martínez j. a. clinical response in patients with dengue fever to oral calcium plus vitamin d administration. proceedings of the western pharmacology society. 2009;52:14– 17. 16. albuquerque lm, trugilho mro, chapeaurouge a. twodimensional difference gel electrophoresis (dige) analysis of plasmas from dengue fever patients. j proteome res. 2009;8:5431–41. 17. yano m, ikeda m, abe ki, kawai y. oxidative stress induces anti-hepatitis c virus status via the activation of extracellular signal-regualted kinase. hepatology. 2009;50:678– 88. 18. puerta-guardo h, medina f, de la cruz hernandez si. the 1alpha,25-dihydroxy-vitamin d3 reduces dengue virus infection in human myelomonocyte (u937) and hepatic (huh-7) cell lines and cytokine production in the infected monocytes. antiviral res. 2012;94:57–61. 19. clinical response in patients with dengue fever to oral calcium plus vitamin d administration.proc west pharmacol ssoc. 2009;52:14-17. 20. keusch gt. the history of nutrition: malnutrition, infection and immunity. j nutr. 2003;133:336s–40s 21. alagarasu k, bachal rv, bhagat ab. elevated levels of vitamin d and deficiency of mannose binding lectin in dengue hemorrhagic fever. virol j. 2012;9:86-90. 1 journal of rawalpindi medical college (jrmc); 2020; 25(1): 1-2 editorial covid-19 vaccine, myths, and facts sidrah saleem1 1 professor and head of microbiology department, university of health sciences, lahore. cite this article: saleem, s. covid-19 vaccine, myths, and facts. journal of rawalpindi medical college. 30 mar. 2021; 25(1): 1-2. doi: https://doi.org/ 10.37939/jrmc.v25i1.1611 access online: coronavirus pandemic has taken millions of lives worldwide. there was a period with no hope, but as time passed, humanity saw hope in the form of the vaccine. the good news is there finally, as a result of collaboration between scientists and pharmaceutical companies many vaccines have been developed and massive immunization programmes have been in effect. however, there has been some misinformation regarding covid-19 vaccine formulations, uses, side effects, and effectiveness. since the day of vaccine development, some people are excited to get vaccinated whereas others are afraid of having it. there are certain myths about the covid-19 vaccine which as a researcher in the field of microbiology/immunology, i feel need some clarification. first of all, it is common thinking that the vaccine has been developed in less time and is still in phase three trials so it might be unsafe for clinical use. this is not true, the fact is that the covid-19 vaccine has gone through all the essential steps of vaccine formation and the same food and drug administration processes have been ensured for its safety and efficacy too. there are other myths too as if this vaccine contains a tracking device and it might change human dna. again there is no truth in it. there is an optional version of this product which contains a microchip within the syringe label; the purpose is to confirm the vaccine dose’s origin. the chip itself is not injected into a recipient of the vaccine. similarly, a vaccine will not change dna; its function is to build the immune system by creating antibodies against the antigen that is present in the vaccine. another common myth is that vaccine has dangerous side effects. well, common side effects like headache, myalgia, and chills have been experienced by the volunteers, however, severe allergic reactions were not observed in healthy individual volunteers. this is why people with a history of allergy to any drug, food, chemical, etc. have been excluded from the vaccine trials. some other questions are also raised like vaccine may affect the fertility of women. the fact is that there is an amino acid sequence shared between viral spike protein and syncytin-1 (protein in the placenta), however, it is too small to initiate an immune response that can affect pregnancy. another myth in people’s minds is that individuals, who have had a natural infection of covid-19 disease, do not need to get vaccinated. again the fact, as clear from evidence across the globe, clears that the natural immunity against covid-19 does not last longer hence and it is advised to get vaccinated when it is your turn. it is also a common perception that wearing a mask is no longer needed once you are vaccinated. wearing a mask, hand washing, and social distancing are required not only for covid-19 protection, as well as these precautions, protect us from many other communicable diseases too. one important fact about the covid-19 vaccine is that no one can develop covid-19 disease from the vaccine since it does not contain a live virus. however, it is possible to get infected with the virus before the vaccine has had time to protect human bodies by the formation of antibodies. some other myths are also needed to be clarified here like people who have fewer comorbid conditions do not develop severe symptoms of the disease, hence do not need to be vaccinated, the answer is simple, even if one is relatively safe, and one still can acquire and spread the disease to others. so it is important to get vaccinated. another myth suggests that certain blood groups are least likely to develop severe symptoms of the diseases hence vaccine is not essential for such people. again, no evidence is available that supports this myth. similarly, this vaccine or any other fda-approved 2 journal of rawalpindi medical college (jrmc); 2020; 25(1): 1-2 vaccine can make you positive for viral detection test in pcr. research on the covid-19 vaccine will continue and will reveal more facts and dissolve many myths. it is advised to participate in getting yourself vaccinated to protect not only you but your family and community as well. reference 1. izda v, jeffries ma, sawalha ah. covid-19: a review of therapeutic strategies and vaccine candidates [internet]. vol. 222, clinical immunology. academic press inc.; 2021 [cited 2021 mar 17]. available from: https://pubmed.ncbi.nlm.nih.gov/33217545/ 2. harrison ea, wu jw. vaccine confidence in the time of covid-19. eur j epidemiol [internet]. 2020 apr 1 [cited 2021 mar 17];35(4):325–30. available from: /pmc/articles/pmc7174145/ izda v, jeffries ma, sawalha ah. covid-19: a review of therapeutic strategies and vaccine candidates [internet]. vol. 222, clinical immunology. academic press inc.; 2021 [cited 2021 mar 17]. available from: https://pubmed.ncbi.nlm.nih.gov/33217545/ 3. https://www.cdc.gov/vaccines/covid-19/info-byproduct/clinical-considerations.html summary journal of rawalpindi medical college (jrmc); 2017;21(1): 48-50 48 original article gastric outlet obstruction – an etiological breakup arslan shahzad 1, inayatullah khan adil2, mashood ali2, muhammad osama 1, mahrukh laghari2, zain sharif2 1. department of gastroenterology, holy family hospital and rawalpindi medical college;2.department of gastroenterology, pakistan institute of medical sciences (pims) islamabad abstract background: to evaluate the etiology of gastric outlet obstruction in pakistani population. methods: in this descriptive study patients with gastric outlet obstruction were included .all patients included in the study received intravenous fluids and electrolytes to correct dehydration and electrolyte imbalance. nasogastric suction with gastric lavage was done. diagnosis was established by ugi endoscopy and biopsy and was supported by ct scan and barium studies where required. results: the total number of patients was 39 with 19 males (48.7%) and 20 females(51.3%). the age of patients ranged from 15 years to 70 years. the mean age was 43.41 ±16.57. the most common pathology leading to gastric outlet obstruction was malignancy, in 21 (53.8%) patients whereas 18 patients (46.2%) had benign disease. among the malignancies, gastric carcinoma was the most common disease affecting 14 patients (35.9%) and among the benign diseases, caustic injury induced stenosis was the most common, involving 14 patients (35.9%). pancreatic carcinoma was found in 3 patients (7.7%) and peptic ulcer disease in 4 patients (10.3%). conclusion: gastric outlet obstruction is a serious and difficult to manage problem. malignancy was the most common cause (53.8%) of gastric outlet obstruction. post caustic gastric outlet obstruction has emerged as the second most common(35.9%) cause. caustic stricture leading to gastric outlet obstruction is emerging as a serious health care issue in developing countries, especially among young females with poor socioeconomic status. key words: gastric outlet obstruction, malignancy, castic stricture introduction gastric outlet obstruction is a clinical syndrome characterized by partial or complete mechanical impediment to the flow of gastric contents from stomach to the small gut. the causes may range from obstructing mass lesion intraluminally to extrinsic compression, edematous pylorus, scarring/cicatrization or fibrosis secondary to duodenal ulcers. it leads to electrolyte and acid-base imbalance, nutritional deficiencies and weight loss. the causes can broadly be classified into benign and malignant. till 1970’s peptic ulcer disease was thought to be most common cause of gastric outlet obstruction in upto 91% cases while malignancies accounted for 6%. 1 however, with the advent of h-2 blockers, proton pump inhibitors, h. pylori treatment and advanced techniques for early diagnosis with the help of flexible endoscopes the diagnosis of malignancy as cause of outlet obstruction has increased. at present malignancy accounts for 50-80% of cases. 2-4 in recent years a rise in the incidence of gastric outlet obstruction has been noted as a consequence of caustic injury which is largely unreported in developing countries, where prevention is lacking and it causes serious healthcare concern.5,6 corrosive agents contain acid and alkalis like hydrochloric acid, nitric acid, sulphuric acid, sodium hydroxide and other substances used in washroom cleaners, drain openers and batteries. these are ingested accidentally or to inflict self-harm. their ingestion may lead to visceral perforation, severe esophageal, gastric and duodenal injuries leading to strictures at these places. easy availability of hydrochloric acid as cheap toilet cleaners has made its widespread use in developing countries for suicidal purpose.7gastric outlet obstruction results when there is stenosis of pylorusor the duodenum. gastrojejunostomyor partial gastrectomy are the common treatmentmodalities.other malignancies causing gastric outlet obstruction are gastric lymphoma, duodenal carcinoma and ampullary carcinoma.extraluminal malignancies are pancreatic cancer and gall bladder cancer. patients and methods this descriptive prospective study was conducted in gastroenterology unit, pakistan institute of medical sciences (pims), islamabad,from july 2010-december 2011. all patients with clinical diagnosis of gastric outlet obstruction seen during the study period were consecutively included in the study. all patients recruited, received intravenous fluids to correct fluid and electrolyte imbalances, nasogastric suctions with journal of rawalpindi medical college (jrmc); 2017;21(1): 48-50 49 gastric lavage was done. patients with gastroparesis without mechanical obstruction were excluded along with those who were already diagnosed with cancer. diagnosis was established by upper endoscopy and biopsy, and was supported by ct scan and barium studies. data was analyzed using statistical package for social science (spss) version 21. mean + sd was calculated for quantitative variables like age while frequencies and percentages were calculated for qualitative variables, i.e gender and etiology results during the study period, a total of 39 patients of gastric outlet obstruction were enrolled. the age of patients ranged from 15 years to 70 years. the mean age was 43.41 ±16.57. there were 19 males (48.7%) and 20 females (51.2%). (table 1). the malignant gastric obstruction was found to be more common in males, however caustic strictures leading to obstruction were three times more common in females than males. the etiology of gastric outlet obstruction was malignant in 21 (53.8%) cases while 18 (46.1%) had benign disease (table 2). caustic injury was commonest among benign group (77.7%) whereas commonest malignant lesion was gastric cancer (66.6%). other malignancies included gastric lymphoma, pancreatic cancer, periampullary cancer and duodenal cancer. table 1. age group distribution age group (years) gastric cancer lymphoma pancreatic cancer periampullary cancer duodenal cancer peptic ulcer disease post caustic injury 15-20 4 21-30 1 8 31-40 1 1 2 41-50 2 1 51-60 7 1 2 2 1 2 61-70 3 71-80 1 total 14(35.8%) 1(2.5%) 3(7.7%) 2(5.1%) 1(2.6%) 4(10.3%) 14(35.8%) malignant benign 21(53.8% 18(46.2%) table 2. gender-wise etiology of gastric outlet obstruction (n=39) etiology male female no (%) gastric carcinoma 8 6 14 (35.8%) lymphoma 1 0 01 (2.5%) pancreatic carcinoma 2 1 03 (7.7%) periampullary carcinoma 2 0 02 (5.1%) duodenal carcinoma 1 0 01 (2.6%) peptic ulcer 2 2 04 (10.3%) caustic injury 3 11 14 (35.8%) discussion the malignant gastric obstruction was found to be more common in males, however caustic strictures leading to obstruction were three times more common in females than in males. the caustic stricture were found in relatively younger population below 40 years of age.the etiology of gastric outlet obstruction was malignant in 21 (53.8%) cases while 18 (46.1%) had benign disease. caustic injury was commonest among benign group (77.7%) whereas commonest malignant lesion was gastric cancer (66.6%). other malignancies included gastric lymphoma, pancreatic cancer, periampullary cancer and duodenal cancer. 3 gastric outlet obstruction has evolved in etiology over past decades from benign to malignant causes and poses significant diagnostic and therapeutic dilemma to treating doctors is developing countries lacking most resources therefore contributing to high morbidity and mortality. cancer of the distal stomach is a very common cause of malignant outlet obstruction however, prior to advent of proton pump inhibitors, peptic ulcer disease was the single major contributor of gastric outlet obstruction. a local study in 1993 reported gastric malignancy of only 0.82% patients while gastric ulcer, duodenal ulcer and gastritis was reported in 26% patients.9 with newer treatment options there was sharp decline in incidence of peptic ulcers and its complications. another rising cause of gastric outlet obstruction seen in adults is the sequel of caustic injury with reported incidence 60% of the pre-pyloric and pyloric channel obstruction.6 viscosity and specific gravity of corrosive acids are lower than that of liquid alkalis, hence acids are associated with rapid transit through the esophagus and the damage primarily occurs in the antrum and pyloric region of the stomach. antral spasm also causes pooling of the corrosive and more damage to the antrum. another reason for greater susceptibility of stomach is its columnar epithelium whereas esophagus has a more resilient squamous epithelium.10 the degree of mucosal injury depends on the nature of the agent, the amount and concentration ingested, the amount of food in the stomach at the time of ingestion and the mode of ingestion. the late complications of corrosive gastric injury include intractable pain, gastric outlet obstruction, late achlorhydria, protein-losing gastroenteropathy, mucosal metaplasia, and development of carcinoma.6 in pyloric stenosis secondary to caustic strictures, dilatation can be carried out with balloon or bougies (usually savary) without a clear advantage for each method.11 however, the failure rate after pneumatic dilatation is higher in caustic ingestion-related strictures than in other benign strictures.12 gastric resection reported in 59–93%, is safe, free of complications, and eliminates the long-term risk of malignancy. mucosal metaplasia with carcinoma has journal of rawalpindi medical college (jrmc); 2017;21(1): 48-50 50 been reported in adults13. hence gastric resection remains the treatment of choice.14-15 pyloroplasty, though advocated is not recommended for cicatrized pyloric obstruction because the scarring is not limited to the pylorus but affects the adjacent tissues as well, and is not an adequate long-term solution. the outcome of treatment of gastric outlet obstruction may be poor especially in developing countries where advanced diagnostic and therapeutic facilities are not readily available in most centers.16 failure of medical therapy is common and the option left is surgical, and significant obstruction is the indication of surgery; and almost 75% patients of gastric outlet obstruction require surgical intervention.17 this usually provides definitive treatment but may result in its own comorbid consequences. the most common surgeries performed related to peptic ulcer disease are vagotomy and antrectomy, vagotomy and pyloroplasty, truncal vagotomy and gastrojejunostomy. the management of malignancy is controversial. most tumors are unresectable at the time of diagnosis with poor 1-year survival rate. gastrojejunostomy is the treatment of choice to palliate malignant gastric and duodenal obstruction but the mortality and morbidity rates are quite high.18 conclusion 1. gastric outlet obstruction is a common problem in low socioeconomic population posing long term challenges in diagnosis and therapeutic intervention. 2. etiology of gastric outlet obstruction has evolved from benign to malignant causes. the benign gastric outlet obstruction is seen in relatively younger patients whereas malignancy is seen in older patients. benign causes of obstruction are changing in frequency from peptic ulcer disease to caustic stricture . 3. gastric cancer is the commonest malignant cause of gastric outlet obstruction. references 1. goldstein h, boyle jd. the saline load test: a bedside evaluation of gastric retention. gastroenterol 1965; 49(4): 375-80. 2. shone dn, nikoomanesh p, smith-meek mm, bender js. malignancy is the most common cause of gastric outlet obstruction in the era of h2 blockers. am j gastroenterol 1995; 90: 1769-70. 3. johnson cd, ellis h. gastric outlet obstruction now predicts malignancy. br j surg1990; 77: 1023-24 4. samad a, whanzada tw,shoukat i. gastric outlet obstruction: change in etiology. pak j surg 2007; 23(1) 2932. 5. zargar sa, kochhar r, nagi b. ingestion of strong corrosive alkalis: spectrum of injury to upper gastrointestinal tract and natural history. am j gastroenterol 1992; 87:337. 6. contini s, scarpignato c. caustic injury of the upper gastrointestinal tract: a comprehensive review. world j gastroenterol, 2013 ;19(25):3918-30. 7. agarwal s, sikora ss, kumar a, saxena r, kapoor vk. surgical management of corrosive strictures of stomach. indian j gastroenterol, 2004; 23:178–80. 8. howard kg, holmes cl. pyloric stenosis caused by ingestion of corrosive substances: report of case. surgclin north am ,1948; 28:1041-56. 9. hussain r, rathore ah. incidence of various upper gastrointestinal diseases as diagnosed by endoscopy in faisalabad. pak j gastroenterol, 1993; 7(1): 60-64 10. maggi al and meeroff m. stenosis of the stomach caused by corrosive gastritis. gastroenterol 1993; 24:573–78. 11. siersema pd, de wijkerslooth lr. dilation of refractory benign esophageal strictures. gastrointest endosc , 2009; 70:1000–12 12. sandgren k and malmfors g. balloon dilatation of oesophageal strictures in children. eur j pediatr surg, 1998; 8:9–11 13. mc auley ce, steed dl, webster mw. late sequelae of gastric acid injury. am j surg 1985; 149:412–15 14. feng j, gu w, li m, yuan j, weng y, wei m. rare causes of gastric outlet obstruction in children. pediatr surg int, 2005; 21:635–40 15. tekant g, eroglu e, erdogon e, yesildag e, emir h. corrosive injury – induced gastric outlet obstruction: a changing spectrum of agents and treatment. j pediatrsurg 2001; 36:1004–07. 16. appasani s, kochhar s, nagi b, guptav r, kochhar r. benign gastric outlet obstruction-spectrum and management. trop gastroenterol 2011; 32:259-66. 17. doherty gm, way lw (eds): current surgical diagnosis & treatment. 12th edition. new york: mcgraw-hill; 2006 18. dabizzi e, arcidiacono pg (2016) update on enteral stents. current treatment options in gastroenterology, 2016. 162 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 162-164 case report covid-19 leading to amputation in an eleven-year-old: a case report anam zafar1, nahdia zaman2, sonia fazal3 1,2,3 senior registrar, department of paediatrics, holy family hospital, rawalpindi. author`s contribution 1,2,3 conception of study 1,2,3 experimentation/study conduction 1,2,3 analysis/interpretation/discussion 1,2,3 manuscript writing 1,2 critical review 1,2 facilitation and material analysis corresponding author dr. anam zafar senior registrar, department of paediatrics, holy family hospital, rawalpindi. email: dr.anamzafar1@gmail.com article processing received: 24/04/2021 accepted: 01/07/2021 cite this article: zafar, a., zaman, n., fazal, s. covid-19 leading to amputation in an eleven-yearold: a case report. journal of rawalpindi medical college. 31 aug. 2021; 25 covid-19 supplement-1, 162-164. doi: https://doi.org/10.37939/jrmc.v25i1.1630 conflict of interest: nil funding source: nil access online: abstract covid-19 is an ongoing pandemic and all age groups are affected by sars-cov-2. past studies showed that children are less affected by it and symptoms are quite variable as compared to adults. multisystem inflammatory syndrome in children (mis-c) and kawasaki-like illness are observed along with covid-19 associated multiorgan failure, acute respiratory distress syndrome (ards), and coagulopathy in the paediatric age group. thrombotic complications in patients with covid-19 have variable presentation including venous thromboembolism and ischemic complications related to thrombosis of extremity, cerebral, coronary, and distal arteries. early recognition of acute limb ischemia and treatment can help to reduce mortality and maximize the chance of limb salvage. here, we report a case of 11 years old child who developed gangrene of bilateral lower limbs after mild covid-19 illness that ended in below-knee amputation. keywords: covid-19, pediatric, pandemic, coagulopathy. 163 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 162-164 introduction covid-19 pandemic continues to be a major threat to the human population worldwide. the causative organism is a novel virus, belongs to the family coronaviridae, and is named after severe acute respiratory syndrome coronavirus 2 (sars-cov-2).1 virus is first found in the city of china in december 2019.2 disease course in children is comparatively milder than seen in adults due to some reasons yet to be determined. a recent study conducted in china to assess the burden of the severity of disease among different age groups in children showed the highest rate in infants (10.6%) followed by the age group from 1-5 years (7.3%).3 according to a study done in france, a significant proportion of previously healthy patients (30%) encountered lethal manifestation of covid-19.4 here, we present a case of an eleven years old child who presented with limbs discoloration (a rare presentation), which was later diagnosed as dry gangrene post-covid-19 infection and ultimately led to below-knee amputation. case report an 11-year-old male child, presented to the pediatric emergency department of holy family hospital, rawalpindi in january 2021, with complaints of bluish discoloration of legs for the last 3 days which was associated with severe pain and inability to walk. the patient further gave a history of fever and sore throat 3 weeks back which got settled after few days without medication. the patient denied any history of hospital admissions in the past. all his family members were alive and healthy. there was no history of traveling for the last 2 weeks. on physical examination, his vitals were; temperature: 99o f, heart rate: 92/min, respiratory rate: 30/min, and blood pressure: 100/70mmhg. lower limbs examination showed bluish-black discoloration of left lower limb till midcalf and bluish discoloration of right lower limb till lower calf, and there was a line of demarcation present over the left lower limb. pulses including dorsalis pedis and posterial tibial arteries were not palpable bilaterally and the rest of the systemic examination including the respiratory system was unremarkable. figure 1: gangrene of lower limbs before belowknee amputation laboratory investigations were done and showed leukocytosis: 29.2×109 (normal reference range: 4.010.0×109) with neutrophilia: 91.9% (normal reference range: 40-80) and lymphopenia: 4.8% (20-40), crp was 68 (0-6) and esr was also high, 80 (0-15mm/hour). coagulation screening showed pt 15secs (10-16), aptt 38secs (24-39) and d-dimers 0.8mg/l (normal below 0.5). chest x-ray was normal and ecg showed a normal sinus pattern. arterial doppler revealed absent flow in distal, anterior tibial, posterior tibial, and dorsalis pedis arteries. venous doppler showed no evidence of deep vein thrombosis. the patient was managed empirically with broad-spectrum antibiotics, low molecular weight heparin, and pain killers. echocardiography was unremarkable with no evidence of intracardiac thrombus. the thrombophilic screening was advised keeping in view congenital thrombophilia which showed antithrombin iii 98% (85-122), protein c 81% (72-160), and protein s 74% (60-150). serum ana levels of 0.43 (normally less than 0.83) broadly excluded autoimmune vasculitis in this patient. rt-pcr for sars-cov2 was sent keeping in view variable presentation of covid-19, but it turned out to be negative so covid-19 serology was performed and immunoglobulin g levels were positive: 3.91 (negative <1.0). ct angiography further confirmed almost complete stenosis of bilateral anterior tibial and posterior tibial arteries with collateral vessel formation. despite management with anticoagulants and steroids, the patient developed gangrene of both limbs, and a line of demarcation of the right leg also appeared on day-5 of admission. surgical consultation was done and the fate of the patient was decided in terms of below-knee amputation. the patient was discharged 164 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 162-164 on warfarin after bridging with heparin. the patient was monitored serially with inr and one month after discharge, no further evidence of thrombotic event was found. discussion covid-19 infection is less prevalent in children but this age group is equally susceptible to this infection.5 according to chinese data, pediatric covid-19 cases are less severe as compare to adults but children have presented with variable symptoms than do adults.6 common signs and symptoms in children vary from myalgia, sore throat, fever, runny nose, headache, tachypnea, to gastrointestinal complaints of diarrhea and vomiting. other manifestations include coagulopathy, shock, renal failure, and cardiac dysfunction. multisystem inflammatory syndrome in children (mis-c), a term recently introduced in pediatric age group in which patient presents with mild inflammation to multi-organ failure and shock.7 being a hypercoagulable state, it can present with variable manifestations including peripheral arterial infarcts to pulmonary thromboembolism despite adequate anticoagulation.8 the underlying pathology behind this state is quite complex as viruses can initiate coagulation cascade and trigger cytokines production by activation of monocytes and macrophages. these phenomena are being called immuno-thrombosis. the disruption in normal antithrombotic property of endothelial cells and activation of the complement cascade can lead to possible complications associated with covid-19.9 a case study from iraq highlighted this complication in an adult patient with no comorbidities.10 iran-based studies proposed antithrombotic prophylaxis in children with covid-19 which states that patients with mild covid-19 should be kept under monitoring with coagulation markers keeping in view that some adult patients with mild symptoms had a worsening disease course afterward.9 our case is unusual in terms of its presentation and disease course as mild covid-19 cases are seldom seen with complications. our patient also presented late as gangrene of one limb was already established at the time of presentation and eventually, amputation had to be done. to our knowledge, no case has been reported from the paediatric age group being affected by covid-19 associated coagulopathy from pakistan. a case report has been written after taking consent from the patient’s family. conclusion though the spectrum of covid-19 is different in children, its associated complications are as lethal as seen in adults. our patient developed gangrene due to arterial thrombosis after mild infection, so mild covid-19 cases can present later with serious complications. effective monitoring and timely intervention of patients with covid-19 associated coagulopathy is the key to improve the outcome. health professionals should also have a high suspicion of covid-19 in such a case, particularly during this global pandemic. references 1. fraser n, brierley l, dey g, et al. preprinting the covid-19 pandemic. biorxiv. published online january 1, 2020:2020.05.22.111294. doi:10.1101/2020.05.22.111294 2. novara e, molinaro e, benedetti i, bonometti r, lauritano ec, boverio r. severe acute dried gangrene in covid-19 infection: a case report. eur rev med pharmacol sci. 2020;24(10):5769-5771. doi:10.26355/eurrev_202005_21369 3. henry bm, benoit sw, de oliveira mhs, et al. laboratory abnormalities in children with mild and severe coronavirus disease 2019 (covid-19): a pooled analysis and review. clin biochem. 2020;81:1-8. doi:10.1016/j.clinbiochem.2020.05.012 4. oualha m, bendavid m, berteloot l, et al. severe and fatal forms of covid-19 in children. arch pédiatrie. 2020;27(5):235238. doi: https://doi.org/10.1016/j.arcped.2020.05.010 5. lee p-i, hu y-l, chen p-y, huang y-c, hsueh p-r. are children less susceptible to covid-19? j microbiol immunol infect. 2020;53(3):371-372. doi:10.1016/j.jmii.2020.02.011 6. coronavirus disease 2019 in children united states, february 12-april 2, 2020. mmwr morb mortal wkly rep. 2020;69(14):422-426. doi:10.15585/mmwr.mm6914e4 7. kache s, chisti mj, gumbo f, et al. covid-19 picu guidelines: for highand limited-resource settings. pediatr res. 2020;88(5):705-716. doi:10.1038/s41390-020-1053-9 8. galanis n, stavraka c, agathangelidis f, petsatodis e, giankoulof c, givissis p. coagulopathy in covid-19 infection: a case of acute upper limb ischemia. j surg case reports. 2020;2020(6):rjaa204. doi:10.1093/jscr/rjaa204 9. karimi m, bozorgi h, zarei t, et al. antithrombotic prophylaxis in children and adolescents’ patients with sars-cov2 (covid-19) infection: a practical guidance for clinicians. acta biomed. 2020;91(4):e2020170. doi: 10.23750/abm.v91i4.10720 10. ahmed muhi f, mohammad aa, al-khalidi ha, lazim qj, hussein fi, alshewered as. case report: covid-19 in a female patient who presented with acute lower limb ischemia. (2020). doi: https://doi.org/10.12688/f1000research.25319.1 summary journal of rawalpindi medical college (jrmc); 2017;21(1):72-74 72 original article foreign bodies in ear, nose and throat a clinical audit muhammad kamran, qammar mirza, zia ul haq, ashar alamgir, muhammad musharaf baig department of ent, dhq teaching hospital and rawalpindi medical college, rawalpindi abstract background: to study the pattern of foreign bodies of ear, nose and throat. method: this prospective study was conducted on 85 patients who presented with complaint of foreign body insertion / impaction. results: these cases comprised of 46 (54%) males & 39 (46%) females having male: female ratio= 1.17: 1. out of all patients 37 (43.52%) presented with ear foreign bodies, 25 patients (29.4%) presented with nasal cavity foreign bodies, 23 patients (27.05%) presented with throat (oropharyngeal / hypopharyngeal) foreign bodies. general anesthesia was required in 16 cases (18.8%).most of foreign bodies were removed by house officers under supervision by consultants. conclusion: foreign bodies remain a major concern in ent practice .majority of children were children key words: foreign bodies, ear, nose, throat introduction a foreign body (fb) is an object or piece of exogenous material that has entered body by accident or design in a region where it is not meant to be and can cause damage by its presence if immediate medical attention is not sought.1 a foreign body of ent is an object which lodges into a craniofacial orifice which includes the ear, nose, or throat. foreign bodies (fb) in the ears, nose or throat are a common presentation in otorhinolaryngology (ent) emergency services. fbs can be introduced spontaneously or accidently in both adults and children. generally, fbs are more common in younger children; this may be due to various factors such as curiosity to explore orifices, imitation, boredom, playing, mental retardation, insanity, and attention deficit hyperactivity disorder, along with availability of the objects and absence of watchful caregivers.2 various methods of fb removal have been described. in the ear the most commonly used method for removal is by syringing, while other instruments like forceps, fine hook, hair clip and suctioning can also be used. live insects are first killed by drowning in methylated spirit followed by syringing.3,4,5 in the nose; removal is accomplished by the use of wax hook, forceps or eustachian tube catheter. in the throat, fb removal is accomplished by grasping with forceps while in the larynx and in the oesophagus removal is usually done under general anaesthesia.6,7,8 although fb removal is usually a simple procedure, its potential complications call for the aid of an ent physician. successful removal relies on a number of factors, including the location of the fb, what it is made of, the physician's dexterity, the equipment available, and patient cooperation. fb removal is often carried out in an operating room, with the patient under sedation or general anesthesia. delayed treatment has been correlated with larger and more severe lesions, in addition to more complications.9 fb are mostly removed by doctors on call under the supervision of consultants. foreign body impaction continues to impose a heavy burden of patients for otorhinolaryngologist which have been estimated to account for approximately 11% of the total cases seen in ent services.10 patients and methods this study was conducted in the department of ent,dhq hospital, rawalpindi. cases were included from the 3 months 1st november 2016 to 25th january 2017.consecutive patients presenting with foreign bodies in ear, nose, throat or aero digestive tract were included in the study. demographic data as well as site were obtained from the patient or the relatives in case of children. an informed consent was taken from patients or attendants. the type of anaesthesia, type of procedure involved in dealing & removing of foreign bodies were recorded. results a total of 85 cases of foreign body inserted were included in the study. majority (70%) of cases were children, aged less than 10 years. out of 85, 46 (54%) were males & 39(46%) were females giving male / female ratio of 1.17: 1 (table 1). the ears were the most common site of lodgment of foreign bodies (table 2;figure 1). this occurred in 37 (43.52%) patients. this was followed by the nasal cavities in 25 (29.4%) and throat (oropharynx & hypopharynx) in 23(27.05%) patients (figure 2). general anesthesia was required in 16(18.8%) patients which mostly included foreign bodies in hypopharynx and tracheobronchial tree . journal of rawalpindi medical college (jrmc); 2017;21(1):72-74 73 procedures which were done for removal of foreign bodies include simple removal with hook or forceps in most cases79(92.95%) of nasal & ear foreign bodies. removal with direct laryngoscope and hypopharyngoscopy was done in 6(7.05%) (table 3). most of foreign bodies were removed by house officers on duty (58 cases) under supervision of consultants. direct laryngoscopies (n=28) were peformed by consultants . fig.1. a centipede retrieved from ear of a patient fig 2. a battery cell removed from nose of a child table 1: gender wise distribution of patients gender no %age male 46 54% female 39 46% table 2: site of foreign bodies site no percentage % ear 37 43.52% nasal cavities 25 29.04% throat (oropharynx & hypopharynx) 23 27.05% table 3: type of procedure for removal of foreign body type of foreign body procedure for removal no. of cases (%) ear / nasal foreign bodies removal with forceps, syringing or hook 92.95% throat(oropharynx & hypopharynx)/for eign bodies direct laryngoscopic & hypopharyngoscopic removal 7.05% discussion foreign bodies in some studies were seen to be acquired inadvertently in some cases and deliberately in a few. we found higher incidence of foreign bodies among children under 10 years (>70% of cases).12 this is the experimental and inquisitive age when children are mainly in the primary school and prone to rough plays. this is consistent with studies done by other authors who observed that children less than ten years more prone to inserting foreign bodies into various orifices in head and neck region.13,14 we observed male preponderance with male to female ratio 1.17: 1, which is consistent with studies done earlier that males are more susceptible than female to foreign body insertion.15 the ears are the most common site of lodgment of foreign body with 37 patients (43.52%) followed by nose 25 patients (29.4%) and then throat (oropharyngeal / hypopharyngeal) 23 patients (27.05%) and this is coincident with earlier findings 16. general anesthesia was required for 16 (18.8%) of our patients. other researchers have discussed about anesthesia in ent emergencies particularly ga may be required for removal up to 30 % of objects, especially in pediatric population in case of aural foreign bodies .17,18 our study showed most of foreign bodies in ear and nose are removed with forceps, syringing or hook without ga. mostly techniques for removal of foreign bodies include irrigation, suction, or a combination of these.19 foreign bodies lodged in orophaynx and naso pharynx were also removed under la as office procedure without ga. usually rigid endoscope was used for removal of bone chips in hypopharynx and oesophagus under general anesthesia. it has been talked about that rigid endoscopy gives a much better view of hypopharynx, cricopharynx and first few centimeters of cervical oesopohagus.20 although rigid endoscope is traditionally believed optimal instrument for tracheo bronchial foreign bodies. 21 nowadays, standard 3.6mm pediatric flexible bronchoscopes are used.22,23 unfortunately these bronchoscopes are not available at our setup. in present study 58 cases (67.6%) of foreign bodies were removed by house officers under supervision of consultants and 27(31.76%) cases by consultants themselves which is close to study that found 62% ent emergencies are managed by senior house officers and 11% by senior registrars and 1% by consultant.24,25 journal of rawalpindi medical college (jrmc); 2017;21(1):72-74 74 conclusion 1. most vulnerable group, for foreign bodies in ear, nose and throat is children 2. ear is the commonest site. 3. foreign body should always be removed under supervision and in children preferably under general anesthesia. references 1. sarkar s, roychoudhury a, roychaudhuri bk. foreign bodies in ent in a teaching hospital in eastern india. indian j otolaryngol head neck surg 2010;62(2):118-20 2. shrestha i, shrestha bl, amatya rcm. analysis of ear, nose and throat foreign bodies in dhulikhel hospital. kathmandu univ med j (kumj) 2012;10(38):4-8 3. fasunla j, ibekwe t, adeosun a. preventable risks in the management of aural foreign bodies in western nigeria. the internet journal of otorhinolaryngology. 2007;7(1) doi: 10.5580/18fe. 4. ette vf. pattern of ear, nose and throat foreign bodies seen in uyo nigeria. ibom medical journal, 2012;5(1) : 67-70. 5. ogunleye aoa, sogebi roa. otic foreign bodies in children in ibadan, nigeria. nigerian journal of surgical research. 2005;7(3):305–308. 6. olajide tg, ologe fe, arigbede oo. management of foreign bodies in the ear: a retrospective review of 123 cases in nigeria. ear nose throat j. 2011;90(11):16–19. 7. heim sw and maughan kl. foreign bodies in the ear, nose, and throat. am fam physician, 2007;76(8):1185–89. 8. sogebi oa, olaosun ao, tobih je, adedeji to, adebola so. pattern of ear, nose and throat injuries in children at ladokeakintola university of technology teaching hospital, osogbo, nigeria. african journal of paediatric surgery, 2006;3(2):61–63. 9. tiago rs, salgado dc, corrêa jp, pio mr, lambert ee. foreign body in ear, nose and oropharynx: experience from a tertiary hospital. braz j otorhinolaryngol. 2006;72(2):177-81. 10. silva bsr, souza lo, camera mg, tamiso agb, castanheira lvr. foreign bodies in otorhinolaryngology: a study of 128 cases. int arch otorhinolaryngol. 2009;13(4):394-99. 11. chiun kc, tang ip, tan ty. review of ear, nose and throat foreign bodies in sarawak general hospital. a five-year experience. medical journal of malaysia, 2012; 67, 17-20. 12. shrestha i, shrestha bl, amatya rcm. analysis of ear, nose and throat foreign bodies in dhulikhel hospital. kathmandu univ med j (kumj) 2012;10(38):4-8 13. das sk. aetiological evaluation of foreign bodies in the ear and nose. j laryngol otol 1984;98(10):989-91 14. ray r, dutta m, mukherjee m, gayen gc. foreign body in ear, nose and throat: experience in a tertiary hospital. indian j otolaryngol head neck surg 2014;66(1):13-16 15. shrestha, i., shrestha, b.l. and amatya, r.c. analysis of ear, nose and throat foreign bodies in dhulikel hospital. kathmandu university medical journal (kumj),2012; 10, 48. 16. onyeagware n . dynamics in the trend of foreign bodies in ent practice in nigeria: any change, internet journal of otorhinolaryngology. 14:2-14426 17. ahdelmark b and hib doyle d. anesthesia for otolaryngologic surgery. chapter 8:90-93. 18. ansley jf. treatment of aural foreign bodies in children paediatrics , 1998. 101:638-41. 19. fritz s , kelen gd . siverston lt. foreign bodies of ear. emergency medicine clinics of north america, 1987. 5:183-92. 20. lam hc, wooj k. management of ingested foreign bodies a retrospective review of 5240 patients. journal of laryngology and otology, 2001. 115:954-57. 21. paraglue i, dogan r. bronchoscopic removal of foreign bodies in children retrospective analysis of 822 cases. thoracic and cardiovascular surgeon, 1991; 39:95-98. 22. ellam. tracheo bronchial foreign bodies otolaryngologic clinic of north america, 2000. 33:17-18. 23. swanson ki, prakash ub. bronchoscopic management of airway foreign bodies in children.chest ,2002; 121:16951700. 24. bleach nr. emergency workload in otolaryngology. annals of the royal college of surgeons of england, 1994;76:33538. 25. biswas d. night emergency cover for ent in england a national survey. journal of laryngology and otology, 2009. 123:899-902. 570 journal of rawalpindi medical college (jrmc); 2021; 25(4): 570-574 case report castleman disease mimicking neurogenic tumor radiologically: a case report haitham akaash1, fatima shahid2, nousheen qureshi3, nayer ayub4, asmara hussain5, sundas masood6 1,4,6 assistant professor, department of ent, holy family hospital, rawalpindi. 2,5 post-graduate trainee, department of ent, holy family hospital, rawalpindi. 3 associate professor, department of ent, holy family hospital, rawalpindi. author’s contribution 1,2,5 conception of study 1,2,3,5 experimentation/study conduction 2,5,6 analysis/interpretation/discussion 2 manuscript writing 3,4,6 critical review 3,4 facilitation and material analysis corresponding author dr. sundas masood, assistant professor, department of ent, holy family hospital, rawalpindi. email: sundas_masood242@live.com article processing received: 04/09/2021 accepted: 09/12/2021 cite this article: akaash, h., shahid, f., qureshi, n., ayub, n., hussain, a., masood, s. castleman disease mimicking neurogenic tumor radiologically: a case report. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 570-574. doi: https://doi.org/10.37939/jrmc.v25i4.1773 conflict of interest: nil funding source: nil access online: abstract introduction: castleman disease which is also called giant lymph node hyperplasia is an uncommon benign b cell lymphoproliferative disease.¹ paragangliomas on the other hand are rare tumors that develop from neural crest cells. they can arise from sympathetic or from parasympathetic ganglions.³ there are only a few case reports of enlarged lymph nodes affecting the carotid artery and mimicking neurogenic tumors radiologically. we have one such report to present case presentation: we present a case of a young male with painless, slow-growing mass in the left upper part of the neck mimicking paraganglioma on ct scan and mra, because of homogenous intense enhancement on computer tomography and rich blood supply from large-sized vessels respectively. the patient also had moderate bradycardia preoperatively, which is usually seen in vagal tumors. a postoperatively histopathology sample was sent which was identified as a case of castleman disease. this case has been described in detail in our report. conclusion: mass that was initially misunderstood as a case of neurogenic tumor and prepared accordingly turned out to be a case of castleman lymphadenopathy. thus the diagnosis of such a unique presentation was made due to castleman disease rarity and mostly asymptomatic presentation, it was difficult to diagnose. its similarity to lymphoma and paraganglioma radiologically further added to its difficulty in diagnosis. thus it was important to consider castleman disease as a differential diagnosis of such mass. keywords: paraganglioma, castleman disease, neck mass, carotid body tumor, castleman lymphadenopathy, hyaline type, plasma type. 571 journal of rawalpindi medical college (jrmc); 2021; 25(4): 570-574 introduction castleman disease, also called giant lymph node hyperplasia, is an uncommon benign b cell lymphoproliferative disease.¹ it usually occurs in young patients from 15-35 years with no gender predominance.¹² there are two subtypes of this disease, 1. unicentric castleman disease (localized with minimal symptoms) 2. multicentric castleman disease (systemic spread with anemia and splenomegaly). based on histology it can be divided into many subtypes. a. hyaline vascular b. plasma cell c. hhv-8 associated castleman disease d. multicentric castleman disease not otherwise specified.² paragangliomas on the other hand are rare tumors that develop from neural crest cells. they can arise from sympathetic or from parasympathetic ganglions.³ parasympathetic ganglia-derived tumors are almost always found in the head and neck and can be of 5 types according to the site of origin. jugulare, tympanicum, carotid body, vagale or laryngeal. these are usually benign and nonfunctional. castleman disease has an unknown etiology, but the most widely accepted theory is that castleman disease is a chronic low-grade inflammatory process. interleukin 6 plays important role in unicentric castleman disease and both interleukin-6 and hhv-8 are considered to be involved in multicentric castleman disease.6 in our patient, we were suspecting a nonfunctional paraganglioma most likely glomus jugulare based on a ct scan and surgical treatment was planned accordingly. pre-operatively computed tomography imaging confirmed the presence of a solid, homogenous, hypervascular, and well-delineated mass with homogenous intense enhancement after contrast. it was when the post-operative histopathological examination was done, we came to know that it was castleman lymphadenopathy with hyaline type. materials and methods we report a case of a 21-year-old male patient presented in the outpatient department of holy family hospital, rawalpindi complaining of an indolent swelling on the left upper neck for the past 2 and a half years with little to no pain over the involved area. there were no other associated complaints. no history of fever, cough, dysphagia, dysphonia, or dyspnea. the patient had no complaints of headache, palpitations, or sweating. the patient didn’t have to take any medications for the swelling. examination revealed 5*4 cm swelling below the left submandibular area, non-tender and firm inconsistency. the swelling was non-adherent to overlying skin and was mobile in the horizontal plane but fixed in the vertical plane. mass was non pulsatile and bruit was absent. his blood pressure, respiratory rate, and temperature were normal but his pulse showed bradycardia (ranging from 43-55 rpm). systemic examination was unremarkable and he didn’t have any such swelling on the rest of the body. ultrasound was performed which showed echo mixed swelling. fnac was done later on and it revealed atypical cells. ct scan neck showed a heterogenous mass with post-contrast enhancement surrounded by multiple tortuous vessels arising from the thyrocervical trunk. mra is suggestive of a nerve sheath tumor with blood supply from the external carotid artery. urine and blood cathecolamines were done and came out normal a presumptive diagnosis of nonfunctional paranganglioma, most probably glomus vagalae, was made. figure 1: ct scan neck with contrast well-defined 5.5 * 3.7*6.2cm oval avidly enhancing mass in left submandibular area with 572 journal of rawalpindi medical college (jrmc); 2021; 25(4): 570-574 lymphadenopathy. dilated torturous vessels surrounding the lesion figure 2: mra baseline investigations were done before planning a surgery including complete blood count, prothrombin time, partial thromboplastin time, and hepatitis b and c serology. all the investigations came out within normal range with hepatitis b and c non-reactive. figure 3: peroperative picture of the mass figure 4: mass delivered with dimensions 7.5 *4.5 *3.5cm 573 journal of rawalpindi medical college (jrmc); 2021; 25(4): 570-574 figure 5 black arrow: ijv, black dotted: carotid artery with bifurcation, yellow arrow: vagus nerve, yellow dotted: hypoglossal nerve, orange: spinal accessory nerve. figure 6: lymph nodes removed from left level 2 and 3 figure 7: hematoxylin and eosin (h and e) staining typical of castleman disease, hyaline type. discussion the classic ct appearance of castleman disease with hyaline vascular type is that of localized nodal masses that demonstrate homogeneous intense enhancement after contrast administration.5 ct scan findings in paraganglioma also show homogenous intense enhancement after contrast because of rich blood 574 journal of rawalpindi medical college (jrmc); 2021; 25(4): 570-574 supply. due to castleman disease rarity and mostly asymptomatic presentation, it is difficult to diagnose. its similarity to lymphoma and paraganglioma radiologically adds to the difficulty in its diagnosis. hyaline type is usually asymptomatic and unicentric. histopathologically in hyaline vascular castleman disease, lymph node follicles have widened mantle zones showing onion skin pattern which consists of concentric rings of lymphocytes. lymphocytes are surrounded by small atrophic germinal centers. on the other hand, plasma cell type is associated with many signs and symptoms. such patients can present with fever, malaise, sweating, weight loss, anemia, thrombocytosis, or hypergammaglobulinemia. they are usually associated with the multicentric disease. histologically they show hyperplasia instead of regression and have vascular interfollicular regions. the plasma cell type is most of the time inoperable and treatment includes radiotherapy, chemotherapy, or steroids.¹¹ recurrence rate in hyaline type is low. our patient had unicentric disease with hyaline type. the prognosis for the unicentric hyaline vascular type after surgical removal is usually curative.9 radiation is another good option in this case.¹º to conclude, this castleman disease should always be among the differential diagnoses in a progressively growing mass in the neck. thus patients should be examined and evaluated accordingly. conclusion mass that was initially misunderstood as a case of neurogenic tumor and prepared accordingly turned out to be a case of castleman lymphadenopathy. thus the diagnosis of such a unique presentation was made due to castleman disease rarity and mostly asymptomatic presentation, it was difficult to diagnose. its similarity to lymphoma and paraganglioma radiologically further added to its difficulty in diagnosis. thus it was important to consider castleman disease as a differential diagnosis of such mass. references 1. chaloupka jc, castillo m, hudgins p. castleman disease in the neck: atypical appearance on ct. ajr am j roentgenol. 1990;154(5):1051-1052. doi:10.2214/ajr.154.5.2108541 2. keller ar, hochholzer l, castleman b. hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. cancer. 1972;29(3):670-683. doi:10.1002/1097-0142(197203)29:3<670::aidcncr2820290321>3.0.co;2-# 3. gallivan mv, chun b, rowden g, lack ee. laryngeal paraganglioma. case report with ultrastructural analysis and literature review. am j surg pathol. 1979;3(1):85-92. doi:10.1097/00000478-197902000-00010 4. lack ee, cubilla al, woodruff jm, farr hw. paragangliomas of the head and neck region: a clinical study of 69 patients. cancer. 1977;39(2):397-409. doi:10.1002/10970142(197702)39:2<397::aid-cncr2820390205>3.0.co;2-c 5. mcadams hp, rosado-de-christenson m, fishback nf, templeton pa. castleman disease of the thorax: radiologic features with clinical and histopathologic correlation. radiology. 1998;209(1):221-228. doi:10.1148/radiology.209.1.9769835 6. soumerai jd, sohani ar, abramson js. diagnosis and management of castleman disease. cancer control. 2014;21(4):266-278. doi:10.1177/107327481402100403 7. nguyen dt, diamond lw, hansmann ml, et al. castleman's disease. differences in follicular dendritic network in the hyaline vascular and plasma cell variants. histopathology. 1994;24(5):437-443. doi:10.1111/j.1365-2559.1994.tb00552.x 8. kojima m, motoori t, nakamura s. benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patients. biomed pharmacother. 2006;60(10):663-672. doi:10.1016/j.biopha.2006.09.004 9. castleman b, iverson l, menendez vp. localized mediastinal lymphnode hyperplasia resembling thymoma. cancer. 1956;9(4):822-830. doi:10.1002/10970142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4 10. herrada j, cabanillas f, rice l, manning j, pugh w. the clinical behavior of localized and multicentric castleman disease. ann intern med. 1998;128:657–662. 11. weisenburger dd, nathwani bn, winberg cd, rappaport h. multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases. hum pathol. 1985;16(2):162-172. doi:10.1016/s0046-8177(85)80065-4 12. soumerai jd, sohani ar, abramson js. diagnosis and management of castleman disease. cancer control. 2014;21(4):266-278. doi:10.1177/107327481402100403 155 journal of rawalpindi medical college (jrmc); 2022; 26(1): 155-158 case report a rare case of tuberous sclerosis with giant cell astrocytoma sidra masood1, mudassar sharif bhatti2 1 postgraduate trainee, benazir bhutto hospital, rawalpindi. 2 associate professor, department of paediatrics, benazir bhutto hospital, rawalpindi. author’s contribution 1 conception of study 1 experimentation/study conduction 1,2,3 analysis/interpretation/discussion 1,2 manuscript writing 1,2,3,4 critical review 1,3,4 facilitation and material analysis corresponding author dr. sidra masood, postgraduate trainee, benazir bhutto hospital, rawalpindi email: masood.sidra@gmail.com article processing received: 01/10/2019 accepted: 18/01/2022 cite this article: masood, s., bhatti, m.s. a rare case of tuberous sclerosis with giant cell astrocytoma. journal of rawalpindi medical college. 31 mar. 2022; 26(1): 155-158. doi: https://doi.org/10.37939/jrmc.v26i1.1019 conflict of interest: nil funding source: nil access online: abstract tuberous sclerosis complex (tsc) is a neurocutaneous disease inherited in an autosomal dominant pattern with variable penetration. this case report is of a 12-year-old boy who presented with complaints of headache, vomiting, and fits. his neurocutaneous stigmata combined with radiological imaging led us to the diagnosis of tsc with sub-ependymal giant cell astrocytoma (sega). his family screening revealed interesting details of how the disease is running in his family. he is now scheduled for surgery at our neurosurgery department for the removal of sega. this case is significant because it is a typical depiction of the classic pattern of autosomal dominant inheritance of tsc with evident variable penetration within members of the same family. 156 journal of rawalpindi medical college (jrmc); 2022; 26(1): 155-158 introduction tuberous sclerosis complex (tsc) is a relatively rare but important neurocutaneous syndrome. it is a multisystem heterogeneous disease that is characterized by the formation of multiple benign tumors called hamartomas in various organs of the body. in the brain, these occur in the form of cortical and subcortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (segas). other organs involved in different degrees include kidneys, skin, heart, eyes, and lungs. disease manifestations can occur at any age, with no set clinical presentation.1 high index of suspicion often leads to the diagnosis. case report a 12-year-old boy was brought by his parents with complaints of headache, vomiting for one and a half months; and two episodes of generalized tonic fits. he was otherwise a developmentally normal child, a product of non-consanguineous marriage with unremarkable history. he had one elder brother who was a known epileptic on anticonvulsant medications with poorly controlled fits. he had one accompanying eeg which showed intermittent delta waves in bilateral parieto-occipital regions. on examination, he was vitally stable with bp within normal centiles. he had nodulopapular rash on his face (facial angiofibromas) and three hypomelanotic spots on his body. the rest of his general physical, systemic, and cns examination was unremarkable. his fundoscopic examination revealed bilateral papilledema. figure 1: (a) facial angiofibromas. (b) hypomelanotic macules of the index case he was admitted with initial suspicion of a spaceoccupying lesion. ct scan, followed by mri showed subependymal giant cell astrocytoma, subependymal calcifications, and cortical tubers with the tumour being just adjacent to foramen of monro and causing obstructive hydrocephalus; thus radiologically confirming tuberous sclerosis with giant cell astrocytoma. his echocardiography, retinal examination for hamartomas, renal ultrasonography, and chest x-ray, all performed for associated features of tsc were normal. thus 5 the major diagnostic criteria of tsc were fulfilled in the patient. (figure 2, figure 3) figure 2 (a) ct scan image showing giant cell astrocytoma and a single subependymal calcification. (b) an axial view of giant cell astrocytoma. (c) two subependymal calcifications in an axial view. figure 4: mri of the index case with a clear view of giant cell astrocytoma near the right foramen of monro. it appears hyperintense on t1wi 157 journal of rawalpindi medical college (jrmc); 2022; 26(1): 155-158 heterogeneously hyperintense on t2wi, and hyperintense on flair sequence; with heterogenous post-contrast enhancement his family was then screened and on examination, his elder brother, who was already an epileptic, also had facial angiofibromas and multiple hypomelanotic macules, fulfilling two of the major criteria for tsc. radiological features of tsc were absent. the patient’s mother also had facial angiofibromas but no other clinical features of tsc. figure 5: (a) facial angiofibromas in index case’s mother. (b) facial angiofibromas in index cases brother. he was medically managed with oral sodium valproate, and since his sega was symptomatic and warranted surgical intervention, neurosurgical consultation was sought. the child was then shifted to the neurosurgical department for surgery. discussion the name tuberous sclerosis is derived from the latin word tuber (root-shaped growths) and the greek word skleros (hard), referring to thick, firm ‘tubers’ found in the brains of patients with tsc. it was first described by desire-magloire bourneville in 1880.2 scarce literature estimating the incidence of tsc has been published in the last decade, but older studies estimate the birth incidence to be 1 in 6000 newborns.3 tsc is an autosomal dominant disorder with variable penetrance. it is caused by heterozygous mutations in either tsc1 or tsc2. tsc1 and tsc2 genes encode hamartin and tuberin proteins respectively. these two proteins bind and work together in a cell. thus the loss of either results in the non-functioning of the other. both tsc1 and 2 are tumour suppressor genes, and their loss of function is what results in the formation of the tsc characteristic benign tumours which are named hamartomas. there are more than 1,500 known pathogenic variants for tsc1 and tsc2, leading to loss of function effects on tsc1 and tsc2. (4) mutations in either tsc1 or tsc2 result in hyperactivation of the mtor gene, which in turn results in accelerated nucleotide and protein synthesis resulting in increased cell growth but with decreased autophagy.5 clinical manifestations vary widely among individuals suffering from tsc; as well as amongst members of the same family inheriting the same gene mutation. moreover, spectra of disease manifestations change and evolve during the lifetime of the patient.1 therefore, tsc is diagnosed based on a set diagnostic criterion, which encompasses some major and some minor components. the diagnostic criterion considers both clinical and radiological findings. the presence of two or more major or one major and two or more minor criteria confirm the diagnosis.6 (table 1 and table 2) table 1: major criteria cortical tubers subependymal nodules subependymal giant cell astrocytoma facial angiofibroma or forehead plaque ungal or periungal fibromas hypomelanotic macules (>3) shagreen patch multiple renal hamartomas cardiac rhabdomyoma renal angiomyolipoma pulmonary lymphangioleiomyomatosis table 2: minor criteria cerebral white matter migration lines multiple dental pits gingival fibromas bone cysts retinal achromatic patch confetti skin lesions non-renal hamartomas multiple renal cysts hamartomatous rectal polyps the hallmark of tsc is central nervous system involvement. the most common neurological 158 journal of rawalpindi medical college (jrmc); 2022; 26(1): 155-158 manifestations consist of epilepsy, cognitive impairment, and psychiatric or autism spectrum disorders. next commonly involved systems include the dermatological and renal systems.7 infants may present with infantile spasms with a hyps-arrhythmic eeg pattern; often followed by virtually any other seizure type, leading to refractory epilepsy in up to 75% of cases.8 once diagnosed, the patient should be screened for all the associated features. the family of the index case should also be screened. patients should be kept on long-term follow-up and a multidisciplinary approach should be used. follow-up screening included brain mri and renal imaging every 1-3 years. complications should be dealt with as encountered. rapamycin has a proven role in facial angiofibromas and hypomelanotic macules.9,10 everolimus is an fdaapproved drug with proven efficacy for both asymptomatic sub-ependymal giant cell astrocytomas (segas), as well as renal angiomyolipomas.11 everolimus is also gaining popularity for the treatment of multi-drug-refractory epilepsy.12 symptomatic segas require neurosurgical intervention. renal lesions are the main cause of death among patients with tsc and warrant vigilant surveillance. other causes include sudden death due to epilepsy and pulmonary lesions.13 prenatal screening should be offered to all expectant mothers suffering from or having a family history of tsc. fetal echocardiography for cardiac rhabdomyomas, and targeted genomic sequencing are the possible options.14 conclusion  a pediatrician should have a keen eye for any unusual skin spots or lesions to not let any neurocutaneous stigmata unnoticed.  on diagnosing a patient with tsc, the index case’s family must be screened keeping in mind varying clinical presentations of the disease.  each diagnosed case must be followed up yearly for disease progression and for performing screening mri. references 1. frost m, hulbert j. clinical management of tuberous sclerosis complex over the lifetime of a patient. pediatric health, medicine and therapeutics. 2015;6:139. 2. jansen fe, van nieuwenhuizen o, van huffelen ac. tuberous sclerosis complex and its founders. journal of neurology, neurosurgery & psychiatry. 2004 may 1;75(5):770-. 3. hallett l, foster t, liu z, blieden m, valentim j. burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review. current medical research and opinion. 2011 aug 1;27(8):1571-83. 4. caban c, khan n, hasbani dm, crino pb. genetics of tuberous sclerosis complex: implications for clinical practice. the application of clinical genetics. 2017;10:1. 5. lam hc, nijmeh j, henske ep. new developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. the journal of pathology. 2017 jan;241(2):219-25. 6. northrup h, krueger da, roberds s, smith k, sampson j, korf b, kwiatkowski dj, mowat d, nellist m, povey s, de vries p. tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. pediatric neurology. 2013 oct 1;49(4):243-54. 7. kingswood c, bolton p, crawford p, harland c, johnson sr, sampson jr, shepherd c, spink j, demuth d, lucchese l, nasuti p. the clinical profile of tuberous sclerosis complex (tsc) in the united kingdom: a retrospective cohort study in the clinical practice research datalink (cprd). european journal of paediatric neurology. 2016 mar 1;20(2):296-308. 8. curatolo p, moavero r, de vries pj. neurological and neuropsychiatric aspects of tuberous sclerosis complex. the lancet neurology. 2015 jul 1;14(7):733-45. 9. koenig mk, bell cs, hebert aa, roberson j, samuels ja, slopis jm, tate p, northrup h. efficacy and safety of topical rapamycin in patients with facial angiofibromas secondary to tuberous sclerosis complex: the treatment randomized clinical trial. jama dermatology. 2018 may 23. 10. arbiser jl. efficacy of rapamycin in tuberous sclerosis– associated hypopigmented macules: back to the future. jama dermatology. 2015 jul 1;151(7):703-4. 11. franz dn, belousova e, sparagana s, bebin em, frost md, kuperman r, witt o, kohrman mh, flamini jr, wu jy, curatolo p. long-term use of everolimus in patients with tuberous sclerosis complex: final results from the exist-1 study. plos one. 2016 jun 28;11(6):e0158476. 12. krueger da, wilfong aa, mays m, talley cm, tudor c, capal j, holland-bouley k, franz dn. long-term treatment of epilepsy with everolimus in tuberous sclerosis. neurology. 2016 dec 6;87(23):2408-15. 13. amin s, lux a, calder n, laugharne m, osborne j, o'callaghan f. causes of mortality in individuals with tuberous sclerosis complex. developmental medicine & child neurology. 2017 jun;59(6):612-7. 14. gu x, han l, chen j, wang j, hao x, zhang y, zhang j, ge s, he y. antenatal screening and diagnosis of tuberous sclerosis complex by fetal echocardiography and targeted genomic sequencing. medicine. 2018 apr;97(15). 134 journal of rawalpindi medical college (jrmc); 2020; 24(2): 134-138 original article comparison of rocuronium and succinylcholine for rapid sequence induction in patients undergoing surgery under general anaesthesia faisal wahid1, aftab hussain2, faiz-ur-rehman3, obaid-ur-rehman4 1,3 consultant anaesthetist, department of anaesthesia, combined military hospital, malir, karachi. 2 consultant anaesthetist, department of anaesthesia, combined military hospital, lahore. 4 assistant professor, department of orthopedics, rawalpindi medical college, rawalpindi. author`s contribution 1,2,3,4 conception of study 1,2,3,4 experimentation/study conduction 1,2,3 analysis/interpretation/discussion 1,2,3 manuscript writing 1,2 critical review 1,2,4 facilitation and material analysis corresponding author dr. aftab hussain consultant anaesthetist, department of anaesthesia, combined military hospital, lahore. email: kalwaraftab@hotmail.com article processing received: 16/1/2020 accepted: 08/4/2020 cite this article: wahid, f., hussain, s., rehman, f. & rehman, o.(2020). comparison of rocuronium and succinylcholine for rapid sequence induction in patients undergoing surgery under general anaesthesia. 24(2), 134-138. doi: https://doi.org/10.37939/jrmc.v24i2.1258 conflict of interest: nil funding source: nil access online: abstract objectives: to compare the frequency of excellent intubation condition with succinylcholine and rocuronium for rapid sequence induction in patients undergoing surgery under general anesthesia. design: randomized control trial. place and duration of study: department of anesthesiology and pain medicine, combined military hospital malir cantt karachi from 25th june to 10th august 2019. methodology: in this randomized control trial, a non-probability consecutive sampling technique was used. anesthesia was given through a standard approach. then patients were randomly divided into two equal groups. in group a, succinylcholine (1mg/kg) was given while in group b, rocuronium (1mg/kg) was given. laryngoscopy was attempted after 60 seconds. intubating conditions were labeled as excellent, good, poor, and impossible. all the data was collected in two groups, the data was entered and analyzed on spss version 21. results: the mean age of the patients was 40.11±9.49 years. the male to female ratio of the patients was 0.7:1. the study results showed the excellent intubation conditions were noted in 11 from group a and 9 from group b, good intubation condition was noted in 29 from group a and 25 from group b, poor conditions were noted in 17 from group a and 16 from group b and the impossible intubation conditions were noted in 13 from group a and 20 from group b. statistically insignificant difference was found between the study groups with intubation conditions i.e. p-value=0.570. conclusion: it has been proved in our study that both the succinylcholine and rocuronium are statically equally effective in terms of excellent intubation conditions in the management of rapid sequence induction in patients undergoing surgery under general anesthesia. keywords: general, anaesthesia, intubation, excellent, succinylcholine, rocuronium. 135 journal of rawalpindi medical college (jrmc); 2020; 24(2): 134-138 introduction rapid and safe endotracheal intubation is of paramount importance in general anaesthesia.1 difficult airway has been a focal point for research in the field of anaesthesiology. “cannot intubate, cannot ventilate” (cicv) after induction of general anesthesia can prove to be a nightmare of anesthesiologists.2 many researchers have long been looking for a set of anesthesia induction drugs to meet the requirements of both rapid intubation and instant recovery of spontaneous ventilation in case of cicv to prevent severe consequences.3 succinylcholine, a muscle relaxant, with standard dose (1 mg/kg) might increase apnea time, while a smaller dose of succinylcholine may not provide good intubation conditions, but could avoid the prolongation of respiratory depression.4 rocuronium is a steroidal nondepolarizing muscle relaxant with onset time comparable to succinylcholine.1 rocuronium has little or no adverse cardiovascular effects, nor does it cause histamine release5. for these reasons, it may be preferred over succinylcholine in compromised patients in whom hemodynamic or other changes are to be minimized. a dose of rocuronium usually used for rapid sequence induction (rsi) 1mg/kg, allows rapid paralysis (60 to 90 seconds) but the duration of action is prolonged (35-75 minutes), making it unsuitable in difficult airway scenarios in the unavailability of sugammadex6. one study by sørensen m et al7 has shown that with rocuronium, 93% of cases had excellent intubation, while with succinylcholine, 76% of cases had excellent intubation. the difference was found to be significant (p=0.045) and showed that rocuronium is more effective. another study by mencke t et al8 showed that with rocuronium, 57% of cases had excellent intubation, while with succinylcholine, 89% of cases had excellent intubation. the difference was found to be significant (p=0.0001) and showed that succinylcholine is more effective. the succinylcholine group showed significantly better intubating conditions as compared to the rocuronium group. a study conducted by larsen pb et al9 showed different results. this study showed that clinically acceptable conditions were present in 93.5% of patients in the succinylcholine group whereas 96.1% of patients in the rocuronium group (p=0.59). a local study by ahad a et al10 and another study by biswajit s et al11 showed that rocuronium and succinylcholine produce equally good intubating conditions. through literature, controversial results have been reported. some studies favor rocuronium while others supported succinylcholine. but there is limited local evidence present in this regard which can help us in implementing the use of the more effective drugs. so through this study, we want to confirm whether rocuronium is better or we should adopt succinylcholine for better intubation conditions. this will improve our knowledge as well as practice. material & methods objective the objective of our study is to compare the frequency of excellent intubation conditions with rocuronium and succinylcholine for rapid sequence induction in patients undergoing surgery under general anesthesia. operational definition excellent intubation it was measured as good jaw relaxation, immobile vocal cords, no response to laryngoscopy and intubation 60 seconds after induction of trial drug. study design randomized controlled trial setting department of anesthesia, cmh, malir cantt. sample size a sample size of 140 cases; 70 cases in each group are calculated with 80% power of the test, 5% level of significance, and taking the expected percentage of excellent intubation i.e. 93%6 with rocuronium and 76%6 with succinylcholine in patients undergoing surgery under general anesthesia. sampling technique non-probability, consecutive sampling. sample selection inclusion criteria  patients of age range 25-55 years of either gender undergoing elective surgery under general anesthesia with asa i & ii and mallapati score ≤ 2. exclusion criteria  patients with chronic pain syndromes, neurological deficits, and difficult airway (mallampati score >2).  patients with asa class 3 or greater.  patients are allergic to trial drugs (in history).  patients with class ii obesity (bmi>35kg/m2). data collection procedure 136 journal of rawalpindi medical college (jrmc); 2020; 24(2): 134-138 after approval from the hospital ethical committee, 140 patients fulfilling selection criteria were included in the study. informed consent and demographics of patients (name, age, gender, bmi) were obtained. anesthesia was given through a standard approach. then patients were randomly divided into two equal groups by using the lottery method. in group a, succinylcholine (1mg/kg) was given while in group b, rocuronium (1mg/kg) was given immediately after induction of anesthesia by the researcher himself. intubation conditions were graded from i to iv, 60 seconds after induction of the trial drug. (table 1) muscle relaxant was prepared by the assistant in advance in the absence of the researcher and was labeled as “muscle relaxant” rather by the drug name. the screen was used to cordon the area where neuromuscular transmission was being monitored to avoid observer bias. all the information was recorded on a specially designed proforma. table 1: grading of intubation conditions grade description i (excellent) good jaw relaxation, immobile vocal cords, no response to laryngoscopy and intubation 30 seconds after induction of trial drug. ii (good) slight reactive coughing but with relaxed vocal cords. iii (poor) moderate reactive coughing or bucking with some vocal cord movement. iv (impossible) vocal cords adducted or uncontrolled coughing and bucking. data analysis ibm spss 21.0 was used to enter and analyze the data. quantitative variables like age and bmi are presented as means and standard deviations. qualitative variables like gender and excellent intubation are presented as frequency and percentage. a chi-square test was used to compare the excellent intubation in both groups. p-value<0.05 was considered significant. post-stratification, the chi-square test was applied taking p-value<0.05 as significant. results in this study total, 140 patients were selected. 61(43.57%) patients were male and 79(56.43%) were female. the male to female ratio of the patients was 0.77 (figure 1). the mean age of the patients was 40.11±9.49 years with minimum and maximum ages of 25 & 54 years respectively. the study results showed that the mean value of age in group a was 38.73±9.74 years and its mean value in group b was 41.50±9.103 years. the study results showed that the mean bmi in group a was 24.67±2.92 kg/m2 and mean bmi in group b was 24.68±2.75 kg/m2. figure 1: frequency distribution of gender in this study, excellent intubation conditions were noted in 20(14.29%) patients, good conditions were noted in 54(38.57%) patients, poor conditions were noted in 33(23.57%) patients and impossible intubation condition was noted in 33(23.57%) patients. (figure 2) group a = succinylcholine group b = rocuronium figure 2: frequency distribution of intubation condition the study results showed the excellent intubation conditions were noted in 11 from group a and 9 from group b, good intubation conditions were noted in 29 from group a and 25 from group b, poor conditions were noted in 17 from group a and 16 from group b and the impossible intubation conditions were noted in 13 from group a and 20 from group b. statistically insignificant difference was found between the study groups with intubation conditions i.e. p-value=0.570. (table 2) 137 journal of rawalpindi medical college (jrmc); 2020; 24(2): 134-138 table 2: comparison of intubation condition with study groups intubation condition study groups total group a group b excellent 11(7.86%) 9(6.43%) 20(14.29%) good 29(20.71%) 25(17.85%) 54(38.57%) poor 17(12.14%) 16(11.43%) 33(23.57%) impossible 13(9.29%) 20(14.29%) 33(23.57%) total 70(50%) 70(50%) 140(100%) group a= succinylcholine group b= rocuronium chi value=2.011 p-value=0.570 (insignificant) discussion according to our study results, there is insignificant difference between two groups in managing the excellent conditions of intubation (p-value=0.570), however, the excellent intubation conditions were noted in 11 from succinylcholine group [group a] and 9 were from rocuronium group [group b], good intubation conditions were noted in 29 from group a and 25 from group b, poor conditions were noted in 17 from group a and 16 from group b and the impossible intubation conditions were noted in 13 from group a and 20 from group b. one study by sørensen m et al8 has shown that with rocuronium, 93% of cases had excellent intubation, while with succinylcholine, 76% of cases had excellent intubation. the difference was found to be significant (p=0.045) and showed that rocuronium is more effective. another study by sutradhar b et al9 and a local study by ahad a et al12 and showed that rocuronium produces equally good intubating conditions when compared to succinylcholine. another study by mencke t et al10 showed that with succinylcholine, 57% cases had excellent intubation conditions compared with 21% in case of rocuronium, while clinically acceptable conditions with succinylcholine were 89% compared to 59% of cases in rocuronium group the difference was found to be significant (p=0.001) and showed that succinylcholine is more effective. another study by larsen pb et al11 showed a contradiction that clinically acceptable intubation conditions were present in 93.5% and 96.1% of patients in the succinylcholine group and the rocuronium group, respectively (p=0.59), showing rocuronium 0.6mg/kg as equivalent to succinylcholine 1mg/ml. herbstritt 201213 is a short review looking at the use of equivalent doses of rocuronium and succinylcholine (1 mg/kg) for rsi. they included seven papers of varying quality (retrospective review, rct and metaanalysis), and concluded that there are no differences in intubating conditions between the two. one more study by stephan c marsch et al14 demonstrated in their study that the intubation conditions (succinylcholine 8.3 ± 0.8; rocuronium 8.2 ± 0.9; p = 0.7) and failed first intubation attempts (succinylcholine 32/200; rocuronium 36/201; p = 1.0) did not differ between the groups. the five paediatric trials (cheng 200215, kulkarni 201016) did not demonstrate a difference in creating excellent intubation conditions between the rocuronium and succinylcholine groups. on the other hand a study by tran dt et al17 concluded that succinylcholine was superior to rocuronium for achieving excellent intubating conditions: rr 0.86 (95% confidence interval (ci) 0.81 to 0.92; n = 4151) and clinically acceptable intubation conditions (rr 0.97, 95% ci 0.95 to 0.99; n = 3992, 48 trials). succinylcholine created superior intubation conditions to rocuronium in achieving excellent and clinically acceptable intubating conditions. conclusion it has been shown by our study that both the succinylcholine and rocuronium are statistically equally effective in terms of excellent intubation conditions in the management of rsi in patients undergoing surgery under general anesthesia. references 1. eichelsbacher c, ilper h, noppens r, hinkelbein j, loop t. rapid sequence induction and intubation in patients with risk of aspiration. recommendations for action for practical management of anesthesia. the anaesthesist. 2018;67(8):568583. doi:10.1007/s00101-018-0460-3 2. liu, e.h, asai t. cannot intubate cannot ventilate – focus on the ‘ventilate’. j anesth (2015) 29:323. https://doi.org/10.1007/s00540-014-1858-y 3. jiao j, huang s, chen y, liu h, xie y. comparison of intubation conditions and apnea time after anesthesia induction 138 journal of rawalpindi medical college (jrmc); 2020; 24(2): 134-138 with propofol/remifentanil combined with or without small dose of succinylcholine. international journal of clinical and experimental medicine. 2014;7(2):393-9 4. moro et, módolo nsp. rapid sequence induction of anesthesia. revista brasileira de anestesiologia. 2004;54(4):595606 doi: 10.1590/s0034-70942004000400015 5. venkateswaran r, chaudhuri s, deepak km. comparison of intubating conditions following administration of low-dose rocuronium or succinylcholine in adults: a randomized double blind study. anesthesia, essays and researches. 2012 jan;6(1):62. doi: 10.4103/0259-1162.103377 6. stefanutto tb, feiner j, krombach j, brown r, caldwell je. hemoglobin desaturation after propofol/remifentanil-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. anesthesia & analgesia. 2012 may 1;114(5):980-6. doi: 10.1213/ane.0b013e31824e5bc4 7. naguib m, samarkandi ah, bakhamees hs, magboul ma, el-bakry ak. histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. british journal of anaesthesia. 1995 nov 1;75(5):588-92. https://doi.org/10.1093/bja/75.5.588 8. sørensen mk, bretlau c, gätke mr, sørensen am, rasmussen ls. rapid sequence induction and intubation with rocuronium–sugammadex compared with succinylcholine: a randomized trial. british journal of anaesthesia. 2012 apr 1;108(4):682-9. https://doi.org/10.1093/bja/aer503 9. sutradhar b, choudhuri r, debnath j, singh s. a comparative study of pre-induction rocuronium with postinduction succinylcholine for rapid sequence intubation in emergency surgeries. j. evolution med. dent. sci. 2017 jan 26;6(8):595-9. 10. mencke t, knoll h, schreiber ju, echternach m, klein s, noeldge-schomburg g, silomon m. rocuronium is not associated with more vocal cord injuries than succinylcholine after rapidsequence induction: a randomized, prospective, controlled trial. anesthesia & analgesia. 2006 mar 1;102(3):943-9. doi: 10.1213/01.ane.0000194509.03916.02 11. larsen pb, hansen eg, jacobsen ls, wiis j, holst p, rottensten h, siddiqui r, wittrup h, sørensen am, persson s, engbaek j. intubation conditions after rocuronium or succinylcholine for rapid sequence induction with alfentanil and propofol in the emergency patient. european journal of anaesthesiology. 2005 oct;22(10):748-53. doi: https://doi.org/10.1017/s0265021505001249 12. ahad a, khaskheli ms, langah ia, meraj mm. comparison of succinylcholine and rocuronium for rapid sequence intubation in cesarean section. anaesthesia, pain & intensive care. 2018;22(4). 13. herbstritt a, amarakone k. towards evidence-based emergency medicine: best bets from the manchester royal infirmary. bet 3: is rocuronium as effective as succinylcholine at facilitating laryngoscopy during rapid sequence intubation? emergency medicine journal: emj. 2012;29(3):256-8 14. marsch sc, steiner l, bucher e, pargger h, schumann m, aebi t, hunziker pr, siegemund m. succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial. critical care. 2011 aug;15(4):r199. 15. cheng ca, aun cs, gin t. comparison of rocuronium and suxamethonium for rapid tracheal intubation in children. pediatric anesthesia. 2002 feb;12(2):140-5. https://doi.org/10.1046/j.1460-9592.2002.00771.x 16. kulkarni kr, patil mr, shirke am. comparison of intubating conditions of succinylcholine with two doses of rocuronium bromide in children. journal of anaesthesiology clinical pharmacology. 2010 jul 1;26(3):323. 17. tran dt, newton ek, mount va, lee js, mansour c, wells ga, perry jj. rocuronium vs. succinylcholine for rapid sequence intubation: a cochrane systematic review. anaesthesia. 2017 jun;72(6):765-77. https://doi.org/10.1111/anae.13903 531 journal of rawalpindi medical college (jrmc); 2021; 25(4): 531-534 original article cathetar related antimicrobial resistance pattern in intensive care unit patients: a single centre study romana bibi1, rafi ullah2, muhammad izhar3, sijad-ur-rehman4, kainaat sheikh5, kalsoom essa bhattani6 1 resident officer, department of gynaecology, khyber teaching hospital, peshawar. 2 resident officer, department of cardiology, lady reading hospital, peshawar. 3 resident officer, department of urology, hayatabad medical complex, peshawar. 4 associate professor, department of paediatrics, gajju khan medical college, swabi. 5 final-year mbbs student, khyber girls medical college, peshawar. 6 senior registrar, department of gynaecology, gomal university, dera ismail khan, kpk. author’s contribution 2 conception of study 1,3 experimentation/study conduction 1,3 analysis/interpretation/discussion 5 manuscript writing 4 critical review 6 facilitation and material analysis corresponding author dr. romana bibi, resident officer, department of gynaecology, khyber teaching hospital, peshawar. email: romanawazir14@gmail.com article processing received: 24/08/2021 accepted: 08/12/2021 cite this article: bibi, r., ullah, r., izhar, m., rehman, s., sheikh, k., bhattani, k.e. cathetar related antimicrobial resistance pattern in intensive care unit patients: a single centre study. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 531534. doi: https://doi.org/10.37939/jrmc.v25i4.1764 conflict of interest: nil funding source: nil access online: abstract introduction: urinary catheter is the most common cause of urinary tract infection (uti) which has been associated with a three-fold increase in risk in mortality. the primary aim of the study is to know the strain of pathogens; its drugs sensitivity and resistance in intensive care unit (icu) patients which help the physician in proper management and reduce the mortality and morbidity in urinary catheter-related complications. materials and methods: this study was conducted in intensive care unit patients of hayatabad medical complex peshawar pakistan over a period of 1 year from 1st january to 31st december 2019. medical charts were reviewed and 100 patients were selected based on inclusion criteria and their urine culture and sensitivity reports were noted to know about the most common pathogens, its drugs sensitivity, and resistance in these patients. clinical and laboratory standards institute (clsi) was used for uropathogen by culture and disc diffusion method to determine antimicrobial susceptibility pattern. results: the mean age (standard deviation) of patients was 51.60+26.59 years (median age 58.50 years). of the total, 64 were female and the remaining were male patients. it was found that the most common pathogens in urine samples were e. coli. maximum pathogens were sensitive to intravenous meropenem (65%) and fosfomycin (55%). chi-square test is used for correlation of sensitivity of meropenem and fosfomycin with the type of organism shows p-value=0.004 and 0.002. conclusion: it is concluded that resistance patterns of uropathogens change which results in treatment failure. further, based on clinical practice, meropenem, fosfomycin, and cefepime had high sensitivity profiles against catheter-related infection in icu. keywords: antimicrobial resistance, catheters, urinary tract infections (utis). 532 journal of rawalpindi medical college (jrmc); 2021; 25(4): 531-534 introduction the common presenting symptoms of urinary tract infections (utis) are fever, dysuria, and pain hypogastrium however some cases may be asymptomatic. common predisposing factors are urinary catheters, instrumentation, urolithiasis, and anatomic anomalies. urinary tract infections account for about 30 to 40% of all nosocomial infections. a high level of resistance was noted among the admitted patients for cephalosporins.1 urinary catheter is the most common cause of uti as 17.5% shown by the study done in 66 european hospitals suffered from catheter-related infection. nosocomial utis have been associated with a three-fold increase in the risk of mortality.2 in a study conducted in iran, 30.9% of intensive care patients with nosocomial infections developed urinary tract infections.3 pattern of bacterial resistance changes with antibiotics use.4 as study showed 28 (9.2%) patients among 306 admitted patients at icu were suffered from nosocomial uti. indiscriminate use of antibiotics is responsible for the development of drug-resistant strains of urinary tract bacteria.5 the present study focus for the first time on the strain of pathogens, its drugs sensitivity, and resistance in one of the largest public tertiary care set up from peshawar. materials and methods this descriptive study was conducted in intensive care unit patients of hayatabad medical complex (hmc) peshawar pakistan over a period of 1 year from 1st january to 31st december 2019. 100 patients' urine samples were taken from urine bags in cs bottles of icu patients having the urinary catheter is placed. urine culture and sensitivity reports were traced to know about the most common pathogens, its drugs sensitivity, and their resistance. only icu patients were included with comorbid conditions like diabetes, cardiac disease, chronic renal disease, immunocompromised patients. results a total of 100 samples were obtained from 100 intensive care patients with a urinary catheter. the mean ages (standard deviation) of patients were 51.60+26.59 years (median age 58.50 years). of the total, 64 were female and the remaining were male patients. . it was found that the most common pathogens in urine samples were e. coli (cephalosporinase producer 23%), followed by klebsiella pneumonia sp. (17.1%), pseudomonas aeruginosa 14(6.83%), enterococcus 12 (5.85%), candida species (1%). most of the pathogens were sensitive to intravenous meropenem (65%) and oral fosfomycin (55%). chi-square test is used for correlation of sensitivity of meropenem and fosfomycin with the type of organism shows pvalue=0.004 and 0.002. data were analyzed using spss version 20. the frequency along with percentage was calculated for each organism isolated from culture and the pathogens sensitivity and resistance for augmentin, meropenem, and fosfomycin as shown in the table below. table 1: age of patient mean 51.60 median 58.50 std. deviation 26.598 table 2: frequency percent proteus vulgaris (cephalosporinase producer) 2 2.0 e.coli(esbl producer) 12 12.0 providencia alcalifaciens(cephalosporinase producers) 2 2.0 klebsiella pneumoniae( esbl producers) 3 3.0 enterococcus species 7 7.0 e.coli (cephalosporinase producer) 23 23.0 klebsiella pneumonae (cephalosporinase producer) 3 3.0 candida species 15 15.0 klebsiella oxytoca (cephalosporinase producers) 8 8.0 pseudomonas aeruginosa 4 4.0 mixed skin organisms 12 12.0 morganella morganii ( cephalosporinase producers) 1 1.0 proteus mirabillis 2 2.0 staphylococcus saprophyticus 1 1.0 providencia sturtaii ( cephalosporinase producer) 1 1.0 serratia species (esbl producer) 1 1.0 actinobacter baumanni 1 1.0 e.coli 1 1.0 enterobacter species (cephalosporinase producer) 1 1.0 total 100 100.0 533 journal of rawalpindi medical college (jrmc); 2021; 25(4): 531-534 maximum pathogens were resistant to augmentin. table 3: frequency percent sensitive 5 5.0 resistant 63 63.0 not tested 32 32.0 total 100 100.0 least number of pathogens resistant to meropenem (iv) table 4: frequency percent sensitive 65 65.0 resistant 1 1.0 not tested 34 34.0 total 100 100.0 least number of pathogens was resistant to fosfomycin table 5: frequency percent sensitive 55 55.0 resistant 8 8.0 not tested 37 37.0 total 100 100.0 discussion the present study focused on icu patients suffering from urinary tract infections having a urinary catheter is placed that were present in the icu of hmc. this study showed the most common urinary pathogen is e. coli cephalosporinase producer) (23%), e. coli (esbl producer) (12%), candida species (15%), mixed skin organism (12%).¹,² out of these pathogen majorities were resistant to co-amoxiclav (augmentin) (63%). a maximum number of pathogens were sensitive to intravenous meropenem (65%) given in table 4 and oral foscin (55%).5,8 the spectrum of urinary tract pathogens isolated from urine samples in this study is similar to the findings of nicolle le et al.4 a study conducted in north india reported 76% resistance to ampicillin5. such a high level of ampicillin resistance has been documented in different studies conducted in different parts of india. a study in northern india reported 76% resistance to ampicillin.5 the first international surveillance program to determine the susceptibility of major urinary tract pathogens in 16 countries in europe and canada was 2525. e.coli isolates were cultured from 4734 women.6 another study conducted in west bengal by saha et al, (2008-2013) india, reported that escherichia coli was the primary uropathogen (67.1%) isolated, followed by klebsiella, (22%), and pseudomonas spp (6%).7 while a study from rajasthan reported 94.63%, 77.88%, and 74.75% resistance in e.coli to nalidixic acid, norfloxacin, and ciprofloxacin respectively.8 urinary tract infection is considered the most common infectious disease because it has reached a global incidence of 18/1000 persons per year in the general population.9,10 it has been previously reported that in 80% of acute and recurrent urinary tract infections in women, e. coli is the primary organism, followed by s. saprophyticus (10–15%). other less common urinary tract pathogens that can cause uti include klebsiella, enterobacter, serratia, proteus, pseudomonas, and enterococcus.¹¹ resistance to the antimicrobial agents occurs due to widespread use of antibiotics and the resistance pattern may change from time to time and even in the same region.12,13 some antibiotics which are used for treating utis such as trimethoprim may cause acute kidney insult.14 so the antibiotics may be carefully selected and so as the emergence of antimicrobial resistance may be monitored which will help to administer the proper drug.15,16,17 however, extended-spectrum betalactamase-positive organisms are sensitive to drugs like imipenem, polymixin, and nitrofurantoin; therefore these can be the drug of choice for such highly resistant bacteria.18 most bacteria colonize the indwelling catheter in the form of biofilm. microbial agents which grow in the biofilm are resistant to antibiotics mostly which may lead to sepsis.19 irrational use of drugs by practitioners has further worsened the situation, which in turn resulted in increased drug resistance.20 further studies are suggested to find out more common urinary pathogens in icu patients time by time due to higher resistance of pathogens to the drugs. the first worth limitation of this study is the small sample size and not taking the history of nephrolithiasis, bladder disorder, and other comorbid conditions. the second limitation includes the sampling technique and study design. thirdly patients were not followed up. fourthly urine c/s technique was not observed. 534 journal of rawalpindi medical college (jrmc); 2021; 25(4): 531-534 conclusion it is concluded that resistance patterns of uropathogens change which result in treatment failure. furthermore, based on observations, carbapenem and cefepime are the drugs of choice for empirical antibiotic treatment of catheter-related infections in intensive care units. references 1. talan, d.a., stamm, w.e. and hooton, t.m. 2000. comparision of ciprofloxacin (7 days) and trimethoprimesulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women: a randomized trial, j. american med. assoc. 283, 1583-1590. 2. zarb p, coignard b, griskevicienne j, muller a, vankerckho ven weist k, goossens mm, vaerenberg s, hopkins s, catry b, monnet dl, goosens h, suetens c. the european centre for disease prevention and control (ecdc) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. euro surveill. 2012;17(46):pil=20316moro 3. tessema b, kassu a, mulu a, yismaw g. predominant isolates of urinary tract pathogens and their antimicrobial susceptibility patterns in gondar university teaching hospital, northwest ethiopia. ethiop med j. 2007;45:61–7. doi: 10.22088/cjim.8.2.76 4. nicolle le. epidemiology of urinary tract infections. infect med. 2001;18:153–62. 5. gupta n, kundra s, sharma a, gautam v, arora dr. antimicrobial susceptibility of uropathogens in india. j infect dis antimicrob agents. 2007;24:13–8. 6. kahlmeter g. prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis europe. the eco. sens study. int j antimicrob agents. 2003; 22: 49–52. 7. saha s, nayak s, bhattacharyya i, saha s, mandal ak, chakraborty s, et al. understanding the patterns of antibiotic susceptibility of bacteria causing urinary tract infection in west bengal, india. front. microbiol., 2015; 5: 463.doi: 10.3389/fmicb.2014.00463 8. sood s and gupta r. antibiotic resistance pattern of community acquired uropathogens at a tertiary care hospital in jaipur, rajasthan. indian j community med. 2012; 37(1): 39– 441.doi: 10.4103/0970-0218.94023 9. bader ms, hawboldt j, brooks a. management of complicated urinary tract infections in the era of antimicrobial resistance. postgrad med. 2010;122(6):7–15. doi:10.3810/pgm.2010.11.2217. 10. mittal r, aggarwal s, sharma s, chhibber s, harjai k. urinary tract infections caused by pseudomonas aeruginosa: a minireview. j infect public health. 2009;2(3):101–11. doi: 10.1016/j.jiph.2009.08.003. doi.org/10.1016/j.jiph.2009.08.003 11. ronald a. the etiology of urinary tract infection: traditional and emerging pathogens. dis mon. 2003;49(2):71–82. doi: 10.1067/mda.2003.8.doi.org/10.1016/s00029343(02)01055-0 12. manjunath gn, prakash r, annam v, shetty k. changing trends in the spectrum of antimicrobial drug resistance pattern of uropathogens isolated from hospitals and community patients with urinary tract infections in tumkur and bangalore. int j biol med res. 2011;2:504–7. 13. murugan k, savitha t, vasanth s. retrospective study of antibiotic resistance among uropathogens from rural teaching hospital, tamilnadu, india. asian pac j trop dis. 2012;2:375– 80.doi.org/10.1016/s2222-1808(12)60082-6 14. crellin e, mansfield ke, leyrat c, et al. trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study. bmj2018;360:k341. doi: https://doi.org/10.1136/bmj.k341 15. baral r, timilsina s, jha p, bhattarai nr, poudyal n, gurung r, et al. study of antimicrobial susceptibility pattern of gram positive organisms causing uti in a tertiary care hospital in eastern region of nepal. health renaiss. 2013;11(2):119–124. doi: https://doi.org/10.3126/hren.v11i2.8218 16. bano k, khan j, begum rh, munir s, akbar n, ansari ja, et al. patterns of antibiotic sensitivity of bacterial pathogens among urinary tract infections (uti) patients in a pakistani population. afr j microbiol res. 2012;6(2):414–20. doi.org/10.5897/ajmr11.1171 17. gupta k, hooton tm, stamm we. increasing antimicrobial resistance and the management of uncomplicated communityacquired urinary tract infections. ann intern med. 2001;135(1):41–50.doi.org/10.7326/0003-4819-135-1200107030-00012 18. kausar a, akram m, shoaib m, mehmood rt, abbasi mn, adnan m, aziz h, asad mj. isolation and identification of uti causing agents and frequency of esbl (extended spectrum beta lactamase) in pakistan. amer jphytomed clin ther. 2014;2:96375. 19. stickler dj: bacterial biofilms in patients with indwelling urinary catheters. nat clin pract urol. 2008, 5 (11): 598-608. 20. hussain a, sohail m, abbas z. prevalence of enterococcus faecalis mediated uti and its current antimicrobial susceptibility pattern in lahore, pakistan. jpma. the journal of the pakistan medical association. 2016 oct 1;66(10):1232. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 42-44 42 original article pattern of breast cancer presentation faryal azhar, tausief fatima, tabinda aqsa, usman qureshi, gohar rasheed, jahangir sarwar khan. department of surgery unit i, holy family hospital and rawalpindi medical college abstract background: to study the various types of breast cancer presenting in local hospital to ensure better facilities, early diagnosis and better treatment options methods: in this descriptive study all breast cancer patients, over a period of two years were included. triple assessment of patients done for diagnosis and treatment given all were included in data. results: total number of patients who presented were 1982. benign breast disease patients were 1746 (88.0%). breast cancer were 236(11.90%). five hundred and two mammographies were done, 197 were birad 5. preferably confirmation was done through trucut biopsy (35), fnac was done in 74 and where needed incisional biopsy in fungating tumors (n=15) and excisional biopsy where in spite of all modalities diagnosis was not confirmed ( n=11). age varied from 24 to 75 years. majority (126) were in stage 3. forty two patients received neoadjuvant chemotherapy. modified radical mastectomy (n=114), breast conservation ( n=13) and simple mastectomy (n=17) were performed .receptor status was dtermined. conclusion: the most common stage of presentation is stage 3. such patients need down staging and then surgery. they required proper counseling and support for their treatment. females usually present late due to domestic issues. early diagnosis, treatment and full support is required to treat breast cancer. this study will help to provide better facilities for early diagnosis and treatment. key words:breast cancer, triple assessment, modified radical mastectomy. introduction with 1 million new incidents in the world each year, breast cancer is the commonest malignancy in women and encompasses 18% of all female cancers.1 in the united kingdom, the age standardised incidence and mortality is the maximum in the world. the incidence among women aged 50 approaches two per 1000 women per year, and the disease is the single commonest cause of death among women aged 40-50, accounting for about a fifth of all deaths in this age group. 1 there are more than 14 000 deaths each year, and the incidence is increasing particularly among women aged 50-64, probably because of breast screening in this age group. 2 of every 1000 women aged 50, two will recently have had breast cancer diagnosed and about 15 will have had a diagnosis made before the age of 50, giving a prevalence of breast cancer of nearly 2%. 1-4 in an initial report, we suggested that such a major change in breast-cancer incidence occurred in 2003 in the united states. compared to the 1990s when we saw an increase in the annual age adjusted incidence of breast cancer by an average of about 0.5% per year, the rise that was particularly evident among women who were 50 years of age or older.4 with this finding of fluctuation in incidence of carcinoma in breast it is important to find the current trends in our society. changes in reproductive factors, use of menopausal hormone-replacement therapy, mammographic screening, environmental exposures, and diet have all been proposed to explain the trend. of these factors, only the use of hormone replacement therapy altered considerably between 2002 and 2003. so it is most important to study incident and associated factors in patients with carcinoma breast. 6-10 despite the fluctuations in incidence research shows that as an outcome of changing experiences to reproductive and nutrition related factors over time women are at high risk of breast cancer. 11 incidence rates is rising in most countries and areas of the world in the past few decades. the most rapid upsurges are seen in developing countries, where breast cancer risk has previously been low relative to industrialised countries.12increasing tendencies in developing zones are often considered the result of the 'westernisation' of lives, an ill-defined replacement for changes in factors such as dietary habits, childbearing and exposure to exogenous oestrogen, towards a dispersal closer in report to that of women in industrialised countries. 12 many early breast carcinomas are asymptomatic, especially when discovered during a breast screening program. 13 larger tumors may present as a painless mass. the breast cancer presentation is usually late in our setup. there are various ways of presentation of breast cancer usually with painless lumps, hard fixed masses, ulcerated or fungating masses. 14 the worst journal of rawalpindi medical college (jrmc); 2017;21(1): 42-44 43 presentation is with bone pain, fracture, jaundice and breathing difficulties. triple assessment is used for diagnosing breast cancer, so that a diagnosis can be obtained with minimum degree of invasiveness. the aims of evaluation of a breast lesion are to judge whether surgery is required and, if so, to plan the most appropriate surgery. patients and methods in this descriptive and cross-sectional study all breast cancer patients , over a period of two years were included. triple assessment of patient was done for diagnosis and treatment . cases with benign breast diseases were also noted to assess ratio of malignant to benign disease that presented in breast clinic. data was collected regarding the number of biopsies done.number of patients in different stages were recorded. surgeries done for breast cancer.complications due to surgeries noted.histopathology types weree assessed. number of patients sent for down staging and the number who left against medical advice were recorded. results total number of patients presented were 1982. benign breast diseases were n=1746. breast cancer were n=236 (table 1). five hundred and two mammography were done out of which 197 were birad 5. preferably confirmation was done with trucut biopsy (n=135). fnac was done in 74 patients. invasive ductal carcinoma was commonest (table 2). for 15 patients with fungating tumors incisional biopsy was done. modified radical mastectomy was the commonest procedure performed (table 3)age groups presented was from 24 to 75 years. n=8 in stage 1. commonest stage was 3(table 4). table. 1: breast benign and malignant disease diseases number of patient benign breast diseases 236 malignant breast disease 1746 table.2: number of different types of malignant cancers. types of carcinoma number of patients lobular carcinoma 5 invasive ductal carcinoma 205 tubular variety of invasive ductal cancer 23 medullary carcinoma 3 forty two patients were sent to nori for down staging. modified radical mastectomy(n=114), breast conservation (n=13) and simple mastectomy (n=17) were the common surgical procedures performed .commonest complication was mostly seromas (n= 15).thirty nine patients left against medical advice. table 3. carcinoma breastoperation performed. name of operation number of operation mrm 114 wle 11 bcs 13 mastectomy 17 mrm, modified radical mastectomy. wle, wide local excision. bsc, breast conservative surgery. table. 4. carcinoma breaststages of disease carcinoma breast number of patients in different stages stage 1 8 stage 2 86 stage 3 126 stage 4 16 discussion cancer of the breast is the most common cancer in both developing and developed countries. 15,16 in pakistan deficiency in cancer registries at national level, lack of awareness, limited access to facilities and insufficient breast clinic services attribute to the delay in diagnosis and increase mortality rate.17 recent studies concluded that more than half of the patients who visited breast clinics suffer from benign diseases. as in our study, 88% are benign and 12% are malignant. breast lump is a very sensitive issue for the patient so a reliable, non invasive and prompt diagnosis helps to lessen the associated anxiety and leads to early definitive treatment. in conclusion, tts is an accurate and least invasive diagnostic test based on which definitive treatment can be initiated.18 diagnosis in our study was much accurate and easier with triple assessment i.e, physical examination, mammography and biopsy.19 mammography is an important screening tool which can effectively detect breast cancer earlier before it becomes palpable on breast self-examination.20 ultrasound is investigation of choice in young patients < than 35 years of age in our study.21 after confirmation of breast cancer, mammography was done in all young patients. study in iran , in 1500 patients, the mean age at diagnosis was 46.0 + 12.0 (sd) years. 22 compared to our study mean age group was 45 and most common age groups presented were between 35 to 45 years of age. journal of rawalpindi medical college (jrmc); 2017;21(1): 42-44 44 most patients in our study presented in stage 3 compared with study in nigeria.23 this study showed that most (62.1%) of the patients presented with advanced disease commonly with manchester stage iii 48(46.6%). this study also showed that invasive ductal carcinoma was the most common (82.5%) histological type followed by medullary carcinoma (5.8%). although the grading was not specified, other researchers have also found invasive ductal carcinoma occurring most commonly. breast cancer is the most frequent cancer of women in pakistan with the majority presenting with stage iii or iv lesions at initial diagnosis. patient and health system related factors are well known determinants of delay in presentation and diagnosis.24 similar with us the most common stage at presentation was stage 3.the patients sent for down staging were 42 and only 3 patients came back. rest either never came back or went to some hakim or faith healer and local treatment. our study reveals that the late presentation of breast carcinoma is associated with poor socioeconomic status, lack of access to proper health care facility and poor literacy rate. aziz s et al found delay in diagnosis was more pronounced in patients from low socio-economic strata. 6 they noted ignorance, poverty, illiteracy, lack of resources, disease stigma, use of alternate medicine and poor access to health care facilities were factors as key areas for delay in the diagnosis in our set up.25 due to late presentation and poor compliance the most common surgery done is modified radical mastectomy. patients refuse to seek treatment for down staging and left against medical advice. conclusion 1. despite much research focussed at understanding and monitoring breast cancer, it continues as a major health load. 2. the interpretation of breast cancer incidence and mortality patterns are complex in view of the many interactives known and supposed risk factors, the introduction of screening and the substantial improvements in therapy. it is therefore likely that the descriptive epidemiology of breast cancer will continue to provide insights into the complex causation of this important disease and will suggest the role of primary prevention, early diagnosis and treatment. references 1. mcpherson k, steel c, dixon j. abc of breast diseases. breast cancer--epidemiology, risk factors and genetics. br med j , 1994 ; 321(7261):624-28 2. bilimoria m and morrow m. the woman at increased risk for breast cancer: evaluation andmanagement strategies. ca cancer j clin . 1995; 45(5):263-78. 3. hartmann lc, sellers ta, frost mh, lingle wl, degnim ac, ghosh k, et al. benign breast disease and the risk of breast cancer. n engl j med ,2005 ;353(3):229–37. 4. ravdin pm, cronin ka, howlader n, berg cd.decrease in breast-cancer incidence in 2003 in the united states. n engl j med,; 2007:;356(16):1670–74. 5. ferlay j, héry c, autier p. global burden of breast cancer. breast cancer, 2010:10(2):978-81. 6. kelsey j, gammon m, john e. reproductive factors and breast cancer. epidemiol rev, 1993; 15(1):36-47. 7. pike m, spicer d, dahmoush l, press m. estrogens progestogens normal breast cell proliferation and breast cancer risk. epidemiol rev , 1993; 15(1):17-35. 8. mcpherson k, steel c, dixon j. breast cancer—epidemiology, risk factors, and genetics. bmj , 2000; 321(7261):624-28. 9. stewart b and wild c. world cancer report 2014. 2014 10. desantis c, ma j, bryan l. breast cancer statistics, 2013. cancer j clin , 2014; 64(1):52-62 11. iqbal m and kamal f. the frequency of malignancy in breast lumps on fnac in females under 35 years of age. ann king edward med , 2014; 20(1):13-18 12. bray f, mccarron p, parkin dm, ferlay j, bray f. the changing global patterns of female breast cancer incidence and mortality. breast cancer res , 2004;;6(6):229-32. 13. barton m, harris r, fletcher s. does this patient has breast cancer?: the screening clinical breast examination: should it be done? how? jama ,1999; 282(13):1270-80. 14. coleman r. metastatic bone disease: clinical features, pathophysiology and treatment strategies. cancer treat rev, 2001; 27(3):165-76. 15. jnr fng, anyanful a, eliason s. pattern of breast cancer distribution in ghana: a survey to enhance early detection, diagnosis, and treatment. int j , 2016; 12(1):90-93 16. asif h, sultana s, akhtar n, rehman j. prevalence, risk factors and disease knowledge of breast cancer in pakistan. asian pac j cancer ,2014; 15(11):4411-16 17. hussain n, bushra a, nadia n, zulfiquar a. pattern of female breast diseases in karachi. biomedica, 2005; 21: 36-38. 18. ghimire b, khan m, bibhusal t, singh y, sayami p. accuracy of triple test score in the diagnosis of palpable breast lump . j nepal med assoc. 2008 ;47(172):189-92 19. iqbal j, ginsburg o, rochon p, sun p. differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity . jama, 2015; 313(2):165-173. 20. screening for breast cancer in england: past and future. j med screening,2016; 2006;13(2):59-61. 21. mujagić s, burina m, mustedanagić-mujanović j. the importance of combining of ultrasound and mammography in breast cancer diagnosis. acta medica cordoba, 2011; 40(1):2733 22. vostakolaei f, broeders m, rostami n. age at diagnosis and breast cancer survival in iran. int j ,2012;11:90-73 23. nggada h, yawe k, abdulazeez j. breast cancer burden in maiduguri, north eastern nigeria. the breast ,2008;10:152427. 24. khokher s, qureshi m, mahmood s. determinants of advanced stage at initial diagnosis of breast cancer: adverse tumor biology vs delay in diagnosis. asian pacific j , 2016;17(2):759-765. 25. aziz z, sana s, akram m, saeed a. socioeconomic status and breast cancer survival in pakistani women. j pak med assoc ,2004; 54(9):448-53 https://www.ncbi.nlm.nih.gov/pubmed/19079392 https://www.ncbi.nlm.nih.gov/pubmed/19079392 390 journal of rawalpindi medical college (jrmc); 2021; 25(3): 390-394 original article comparison of frequency of low apgar score in babies born to normotensive patients with and without hyperuricemia in a tertiary care hospital faryal noman1, nusrat noor2, rabiah anwar3, rabiya akbar4, khan muhammad yaqub5 1 classified gynaecologist, department of gynae/obs, combined military hospital, rawalpindi. 2,3,4 assistant professor, department of gynae/obs, combined military hospital, rawalpindi. 5 associate professor, department of anaesthesia, combined military hospital, rawalpindi. author’s contribution 1 conception of study 1,2,4 experimentation/study conduction 3,5 analysis/interpretation/discussion 2,4 manuscript writing 3,5 critical review 3,5 facilitation and material analysis corresponding author dr. nusrat noor, assistant professor, department of gynae/obs, combined military hospital, rawalpindi email: nusratyaqub@gmail.com article processing received: 01/07/2021 accepted: 23/09/2021 cite this article: noman, f., noor, n., anwar, r., akbar, r., yaqub, k.m. comparison of frequency of low apgar score in babies born to normotensive patients with and without hyperuricemia in a tertiary care hospital. journal of rawalpindi medical college. 30 sep. 2021; 25(3): 390-394. doi: https://doi.org/10.37939/jrmc.v25i3.1658 conflict of interest: nil funding source: nil access online: abstract objective: to compare the frequency of low apgar scores in babies born to normotensive patients with asymptomatic hyperuricemia with those without hyperuricemia. materials and methods: this cohort study was conducted at the department of gynaecology/obstetrics, liaquat national hospital karachi from january 2015 to january 2016. the sample size was calculated by using openepic.com version 2, an open-source calculator. the sample size was calculated to be 165 in each group, which made a total of 330 patients. nonprobability consecutive sampling was chosen as the sampling technique. all normotensive pregnant females with blood pressure of less than 130/90 between 18 to 40 years of age, with singleton pregnancy at 37 weeks and beyond were included in the study. normotensive pregnant females with hyperuricemia were the exposed group while normotensive pregnant females with normal uric acid levels were the non-exposed group. the exclusion criteria included patients with multiple gestations, medical disorders like gout, chronic renal failure, apls, rheumatoid arthritis, etc, on anti-hypertensives and smokers. fetal outcomes were assessed in all patients after delivery and a comparison of outcomes was made between two groups. results: the study was designed to compare the frequencies of low apgar scores in babies born to normotensive patients with asymptomatic hyperuricemia to those without hyperuricemia. the main outcome in group a i.e. exposed group was 29 babies with low apgar score (<7) with 17.5% and in group b, which was non-exposed, 12 (7.57%) of babies had low apgar score (<7). p-value came out to be 0.0010. the difference was statistically significant. conclusion: it is concluded that there is a significant difference between the frequency of low apgar scores in babies born to normotensive patients with hyperuricemia to those without hyperuricemia. keywords: hyperuricemia, uric acid, apgar score. 391 journal of rawalpindi medical college (jrmc); 2021; 25(3): 390-394 introduction the continuous effort to optimize maternal and fetal health is of crucial importance in leading to extensive research in the field of obstetrics and gynecology. maternal health during pregnancy is of utmost importance for an acceptable fetal outcome. it is a fact that the majority of maternal and perinatal morbidity and mortality is contributed by pre-eclampsia which complicates around 2 – 8% of pregnancies.1 uric acid produced as a final byproduct of purine degradation in the liver by endogenous and exogenous precursor proteins is mainly excreted via kidneys (65%) and intestines (35%). at normal physiologic concentrations, excellent anti-oxidant activity is exhibited by uric acid, but in the case when uric acid exceeds normal levels in plasma, oxidative damage is triggered. a chronic rise in the uric acid level is a significant risk factor for inflammation and dysfunction of endothelial cells.2,3 the threshold values of 6 mg/dl (530 u /l) and 5.6mg/dl at 38 weeks of pregnancy have been extensively reported in the literature, whereas, a mean uric acid level of 363 umol /l or more is reported4,5 to be associated with unfavourable outcomes during pregnancy6. recent evidence has reported that hyperuricemia in the fetus itself is associated with infant respiratory distress syndrome.7 a research estimated that 20% of the general population suffers from asymptomatic hyperuricemia.8 though not proven, the circulating uric acid may be directly responsible for the adverse fetal outcome rather than these effects being observed due to pre-eclampsia and other diseases indirectly.9 it has been shown that uric acid freely crosses the placenta. it has also been demonstrated that levels of uric acid vary according to gestational age.10 serum uric acid estimation has been demonstrated as a marker for preeclampsia in hypertensive pregnancies.11 it is however not routinely recommended for use in normotensive pregnant patients. a very recent study demonstrated that asymptomatic hyperuricemia in normotensive patients carried a poor fetal outcome as they observed that 17.4% of neonates born to such females had significantly low apgar scores while only 7.3% of neonates born to females with normal serum uric acid had low apgar score.9 this is the only study undertaken previously to the best of our knowledge, but the issue highlighted is a grave one. with a 20% prevalence of asymptomatic hyperuricemia in population8, it may be the silent morbidity of many babies born with low apgar score to mothers with no obvious risk factors. no study has been done in pakistan till now; therefore this study aimed to assess the findings of this research in pakistan, both for investigation of this hypothesis and to provide a local context in the matter. materials and methods the cohort study was conducted at the obstetrics and gynecology department of liaquat national hospital karachi over a period of one year i.e., from 1st january 2015 to january 2016 after taking permission from the ethical committee of the hospital. the sample size was calculated by using openepi.com version 2, opensource calculation taking the prevalence of low apgar score in babies of mothers with hyperuricemia to be 17.4% and 7.3% to those babies born to mothers without hyperuricemia. the sample size was calculated to be 165 in each group, which made a total of 330 patients. non-probability consecutive sampling was chosen as sampling technique serum uric acid was considered raised in pregnancy based on gestational age i.e., at 37 weeks and 1 day and over more than 5.58 mg/dl. blood pressure of less than 130/90 mmhg was considered normal. apgar score was calculated at one and five minutes according to the table given below. signs 0 1 2 hr (bpm) not present < 100 >100 rr (bpm) not present slow, irregular good crying mt limp some flexion of extremities active motion response to catheter in nostril no response grimace cough or sneeze color blue, pale body pink extremities blue completely pink *hr=heart rate, rr=respiratory rate, mt=muscle tone a score of < 7 was considered as a low apgar score in this study. all normotensive pregnant females between the ages of 18 and 40 years with singleton pregnancies confirmed by ultrasound at 37 weeks of gestation and beyond confirmed from lmp or in case of not sure of dates from first dating scan were included in the 392 journal of rawalpindi medical college (jrmc); 2021; 25(3): 390-394 study. pregnant females with hyperuricemia were the exposed group (a) and pregnant females with normal uric acid levels were the non-exposed group (b). the exclusion criteria consisted of twins and higherorder gestation confirmed by ultrasound, patients on antihypertensive drugs, or having blood pressure of more than 130/90mmhg with a history of gout and chronic renal disease. patients who smoked or have a history of substance abuse and those with autoimmune illness were excluded from enrollment in the study. after taking informed written consent, the blood sample was drawn and a sample was sent for serum uric acid levels to the laboratory. upon receiving the results, patients were placed accordingly in either the asymptomatic hyperuricemia group (a) or the normal serum uric acid group (b). once delivered, the apgar score of the baby was calculated at one and five minutes. a proforma was used to record the patient’s demographic profile i.e., age, gestational age, parity, group of the patients, body mass index, mode of delivery, the value of apgar score at one minute and five minutes, and an outcome that is apgar score at 5 minutes, serum uric acid levels. data were analyzed by using spss version 13.0. mean values and standard deviations were computed for numerical variables like age, parity serum uric acid levels and apgar score. the outcome was a low apgar score that was labelled as positive when the score was < 7. the frequency of low apgar score was compared between the two groups and a chi-square test was applied and a p-value of <0.05 was considered significant in this study. results this study compared the frequencies of low apgar score in babies born to normotensive patients with asymptomatic hyperuricemia to those without hyperuricemia. a total of 330 patients were enrolled in the study. the age-wise distribution in 18-25 years in group a was 49 (29.69%) and group b was 46 (27.87%). in the age group, 26-30 years 27 patients (16.36%) belonged to group a and 42 (25.45%) patients belonged to group b. in the age group of 31-35 years, 58 (35.15%) were in group b. in 36-40 years age group, 31 (18.78%) patients belonged to group a and 36 (21.81%) patients belonged to group b. mean and sd for age, parity, bmi, serum uric acid and apgar score is given in tables below. 152 patients (92.12%) had a normal vaginal delivery and 13(7.87%) had a caesarean section in group a, whereas in group b 159(96.36%) patients had a normal vaginal delivery and 06(3.63%) had a caesarean section. the main outcomes i.e., babies born with low apgar score in group a were 29(17.5%) and in group b it was 12(7.57%) with a p-value of 0.0010. stratification of main outcomes with age, gestational age, parity, and mode of delivery is presented in tables: 4,5,6, and 7 respectively. table 1: age distribution n = 330 age group group a group b 18-25 years 49 (29.69%) 46 (27.37%) 26-30 years 27 (16.36%) 42 (25.45%) 31-35 years 58 (35.15%) 41 (24.84%) 36-40 years 31 (18.78%) 36 (21-81%) mean and sd for age 31+ 5.7 30 + 6.41 table 2: mean and sd for demographic variables n = 330 mean and sd group a group b age 31 + 5.7 30 + 6.41 parity 2 +0.81 2 + 0.97 bmi 26 + 1.17 26 + 1.67 serum uric acid 6.7 + 0.316 5.2 + 0.55 apgar score at 01 minute 9 + 1.34 9 + 0.99 apgar score at 05 minute 9 + 1.34 9 + 0.99 gestational age 38 + 0.93 38 + 0.94 table 3: frequencies and percentages for mode of delivery n=330 mode of delivery normal vaginal delivery groups a group b frequencies percentages frequencies percentages 152 92.19% 159 96.3% caesarean section 13 7.87% 06 3.6% 393 journal of rawalpindi medical college (jrmc); 2021; 25(3): 390-394 table 4: comparison of frequencies and percentages for low apgar score (main outcome) n=330 low apgar score the main outcome yes groups a group b frequencies percentages frequencies percentages 29 17.57% 12 7.57% no 136 82.42% 153 42.72% p-value = 0.0010 table 5: stratification of mean outcome with gestational age n= 330 gestational age main outcome of low apgar score group a group b pvalue 37 weeks yes 15 04 0.005 no 62 72 >37 weeks yes 14 08 0.189 0.189 no 74 78 table 6: stratification of mean outcome with mode of delivery n= 330 mode of delivery main outcome of low apgar score group a group b pvalue normal vaginal delivery yes 16 06 0.009 no 136 153 caesarean section yes 13 06 no 0 0 discussion adverse fetal outcomes are significantly associated with hyperuricemia in pregnancy. fetal growth is suppressed by a higher uric acid concentration during pre-eclampsia by directly inhibiting amino acid transfer in the placenta.12 it is known that the production of pro-inflammatory substances and vasoconstrictors is stimulated by uric acid, which lowers nitric oxide production and tends to increase the production of thromboxane in vascular smooth muscle cells.13 as result hyperuricemia is associated with endothelial dysfunction and raised serum uric acid levels which then precede hypertension. in normotensive pregnant females increased serum uric acid in midgestation is associated with insulin resistance and lower birth weights.14 the prevalence of hyperuricemia is reported to be increasing worldwide in recent years. an increase in serum uric acid levels and increased consumption of sugar-sweetened beverages, food rich in purines, and alcohol contribute to a higher prevalence of obesity.15,16 our study is comparable to a study done by amini e et al9, where it was observed that 17.4% of neonates born to females with asymptomatic, normotensive hyperuricemia had low apgar score while only 7.3% of neonates born to females with normal uric acid had apgar score. this difference was statistically significant. in another study by chang fm et al10, maternal and neonatal uric acid levels were measured simultaneously in pregnant women with and without gestational hypertension. there was a high correlation and minimal concentration difference between maternal and neonatal uric acid in either normal or hypertensive women suggesting free transfer of uric acid through the placenta in both directions. moreover, not only maternal and neonatal uric acid levels were significantly different among normal and hypertensive females but showed higher levels of serum uric acid in accordance with the severity of preeclampsia. both maternal and neonatal uric acid had a negative correlation with birth weight, one minute apgar score, and five minute apgar score. it is implied that uric acid levels at parturition might provide a reference index for fetal outcomes in pregnancy with gestational hypertension. elevated serum uric acid in pregnant women is associated with small for gestational age due to decreased amino acids uptake by the placenta.17 among normotensive pregnant females, hyperuricemia acts as a risk factor for adverse pregnancy outcomes and subsequent development of neonatal hypoglycemia and ivh. in one study, neonatal hyperuricemia was linked to infant respiratory distress syndrome and asphyxia.18 maternal factors that lead to increased maternal serum uric acid levels are younger age, primigravidity, increased weight gain, and deranged renal function during pregnancy. these associations have been pointed out by other studies.19 results of this study suggesting a significant association between umbilical, maternal, and neonate uric acid levels are supported by literature demonstrating the free transfer of uric acid through placenta tissue. it is suggested that the etiology of poor 394 journal of rawalpindi medical college (jrmc); 2021; 25(3): 390-394 neonatal outcomes might be associated with raised maternal uric acid levels. neonatal hyperuricemia can only be a reflection of maternal hyperuricemia which triggers an oxidation effect leading to inflammation and dysfunction of endothelial cells.20,21 limitation very few studies have been done regarding this topic, so more research needs to be done. taking this study as a reference point, further multicentered research with a larger sample size is recommended. conclusion there is a statistical difference between the frequency of low apgar score in babies born to normotensive patients with hyperuricemia to those without hyperuricemia. references 1. morris rk, riley rd, doug m, deeks jj, kilby md. diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre eclampsia: systematic review and meta analysis. bmj.2012 jul9;345:e4342.doi:10.1136/bmj.e4342.pmid:22777026;pmci d:pmc3392077 2. de oliveria ep, burini rc high plasma uric acid concentration: causes and consequences. diabetolmetabsyndr 4,12 (2012) https://doi.org/10.1186/1758-5996-4-12 3. sautin yy, johnson rj. uric acid: the oxidant-antioxidant paradox. nucleosides nucleotides nucleic acids 2008jun;27(6):608-19 doi: 10.1080/1527770802138558. pmid: 18600514; pmcid: pmc2895915 4. tejal p, astha d, relationship of serum uric acid level to maternal and perinatal outcome in patients with hypertensive disorders of pregnancy. gugarat med j. 2014;69(2):1-3(google scholar) 5. hawkins at, roberts jm, mangos gj, davis gk, roberts lm, brown ma, plasma uric acid remains a marker of poor outcome in hypertensive pregnancy. a retrospective cohort study. bjog. 2012; 119:484-492 http://doi.org/10.111/j-1471-0528. 2011.03232.x 6. parrish m, griffin m, morris r, darby m, owens my, martin jn jr. hyperuricemia facilitates the prediction of maternal and perinated adverse outcome in patients with severe/superimposed preeclampsia. j marten fetal neonatal med.2010dec; 23(12):1451-55. https://doi.org/10.3109/147670580 2010.500429. 7. basu p, som s, choudhuri n, das h. contribution of the blood glucose level in perinatal asphyxia. eur j pediatr. 2009jul;168(7):833-38. https://doi.org/10.1007/s00431-0080844-5. 8. zhu y, pandya bj, choi hk. prevalence of gout and hyperuricemia in the us general population: the national health and nutrition examination survey 2007-2008. arthritis rheum, 2011oct;63(10):3136-41. doi:10.1002/art.30520 9. amini e, sheikh m, hantoushzadeh s, et al. maternal hyperuricemia in normotensive singleton pregnancy, a prenatal finding with continuous postnatal effects, a prospective cohort study. bmc pregnancy childbirth. 14, 104(2014). https://doi.org/10.1186/1471-2393-14-104. 10. chang fm, chow sn, huang hc, hsieh fj, chen hy, lee ty, ouyang pc, chen yp. the placental transfer and concentration difference in maternal and neonatal serum uric acid at parturition; comparison of normal pregnancies and gestosis. biol res pregnancy perinatal. 1987;8(1st half):35-9.pmid:3580446 11. bhaskar n, kaur h, qazi n. serum calcium, magnesium and uric acid in pre eclamptic and normal pregnancies in a tertiary case hospital: a comparative analysis. indian j maternal child health 2011; 1:1-7 www.jpbms.info 12. akahori y, mosuyama h, hiramastu y. the correlation of maternal uric acid concentration with small for gestational fetuses in normotensive pregnant women. gynecolobstat invest 2012;73:162-167. https://doi.org/10.1159/000332391. 13. bainbridge sa, roberts jm. uric acid as a pathogenic factor in preeclampsia. placenta.2008mar;29 suppl a(suppla): s67-s72 doi: 10.1016/j.placenta.. 2007.11.001. epub 2008 feb 21. 14. laughon sk, catov j, roberts jm. uric acid concentrations are associated with insulin resistance and birth weight in normotensive pregnant women am j obstetgynecol.2009dec;201(6):582.e 1-6.doi: 10.1016/j.ajog.2009.06.043 15. meneses-leon j, denova – gutierrez e, castonon-robles s, et al. sweetened beverage consumption and the risk of hyperuricemia in mexican adults: a cross sectional study. bmc public health 14,445(2014). https://doi.org/10.1186/14712458-14-445 16. kim sy, devera ma, choi hk. gout and mortality. clinexprheumatol. 2008 sep-oct.26 (58upple 51): s115-9. s115-9. pmid: 19026153 17. bainbridge sa, von versen-hoynck f, roberts jm: uric acid inhibits placental system a aminoacid uptake. placenta.2009feb;30(2):195-200. doi: 10.1016/j.placenta. 2008.10.015. 18. daise ta, tasnim s, yasmin n, ahsan akm, khanam w, rahman m: maternal hyperuricemia and brith outcome in normotensive singleton pregnancy: a prospective cohort study. jmscr. 2018. oct; 06: 952-57. https://dx.doi.org/10.18535/jmscr/v6i10.160 19. iseki k, ikemiya y, inoue t, iseki c, kinjo k, takishita s. significance of hyperuricemia as a risk factor for developing esrd in a screened cohort. am j kidney dis. 2004 oct. 44(4): 642-50. pmid:15384015. 20. yang t, ding x, wang yl, zeng c, wei j, li h, et al. association between high sensitivity c-reactive protein and hyperuricemia. rheumatol int. 2016 feb 10. doi: 10.1007/s00296-016-3429-z 21. kim sy, guevara jp, kim km, et al. hyperuricemia and risk of stroke: a systematic review and meta-analysis. arthritis rheum. 2009 jul 15. 61(7): 885-92. https://doi.org/10.1002/art.24612. 507 journal of rawalpindi medical college (jrmc); 2021; 25(4): 507-511 original article nitrofurantoin and fosfomycin, effective oral empirical treatment options against multidrug resistant escherichia coli saima naseem1, ambreen fatima2, sahar iqbal3, fatima fasih4, syed talha naeem5, uzma bukhari6 1,3,4 associate professor, dow university of health sciences, karachi. 2,5 assistant professor, dow university of health sciences, karachi. 6 professor, dow university of health sciences, karachi. author’s contribution 1,6 conception of study 1 experimentation/study conduction 1,3 analysis/interpretation/discussion 1 manuscript writing 2,6 critical review 4,5 facilitation and material analysis corresponding author dr. saima naseem, associate professor, dow university of health sciences, karachi. email: saima.naseem@duhs.edu.pk article processing received: 26/07/2021 accepted: 11/12/2021 cite this article: naseem, s., fatima, a., iqbal, s., fasih, f., naeem, s.t., bukhari, u. nitrofurantoin and fosfomycin, effective oral empirical treatment options against multidrug resistant escherichia coli. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 507511. doi: https://doi.org/10.37939/jrmc.v25i4.1734 conflict of interest: nil funding source: nil access online: abstract objective: the present study is designed to monitor the antibiotic susceptibility pattern of escherichia coli to assist in forecasting empirical therapy of urinary tract infection. materials and methods: it is a retrospective cross-sectional study. it was carried out at dow diagnostic research and reference laboratory for a period of 3 months from february 2017 to april 2017. data of a total of 5000 urine culture and sensitivity test reports were taken from the medical record. the data were analyzed by spss version 16. results: out of 5000 urine samples processed, 1565 showed significant bacterial growth. escherichia coli was the most common pathogen isolated. meropenem, amikacin, fosfomycin, and nitrofurantoin respectively were found to be the most effective antibiotics against escherichia coli. conclusion: fosfomycin and nitrofurantoin are effective oral antibiotics against escherichia coli causing urinary tract infection. the present study may help clinicians in making a rational choice of empirical treatment of the patients. keywords: antibiotic resistance, antibiotic susceptibility, bacteria, escherichia coli, urinary tract infection. 508 journal of rawalpindi medical college (jrmc); 2021; 25(4): 507-511 introduction urinary tract infection (uti) is among the most common bacterial infections affecting all age groups.1 it has been estimated that utis cause around 8.1 million visits to health care personnel annually presenting as one of the major reasons for global economic burden.2 prevalence of uti is affected by multiple factors such as old age, poor personal hygiene, pregnancy, urinary catheterization, genitourinary tract abnormalities, and co-morbidities like diabetes, hiv infection.3 utis affect both genders but it is more common in the female population. it has been assessed that more than 50% of all women experience at least one uti during their lifetime, with 20–30% presenting with recurrent uti due to their anatomy and reproductive physiology.4 clinically uti may present as asymptomatic, acute, chronic, complicated, or uncomplicated depending upon the type of infectious agent, part of urinary tract involved, and patient’s immune response.5 most utis are treated empirically based on the culture and sensitivity pattern generated by regional microbiology laboratories. the spectrum of antimicrobial susceptibility of uti pathogens varies from time to time and in different geographic areas. therefore regular monitoring of the antibiotic susceptibility pattern of uropathogens is very important. however, due to the indiscriminate use of antibiotics, there is high emergence of antibiotic resistance among urinary pathogens making it a major public health problem.6 at present, new antibiotics that have been approved, are mostly for parental use, so for oral empirical treatment, we have very limited options. literature search shows that multidrug-resistant escherichia coli (e. coli) still retains susceptibility to two oral antibiotics are nitrofurantoin and fosfomycin. both maintain high urinary concentration and minimal toxicity in comparison to newer antibiotics and have been considered as safe and effective drugs for the treatment of uncomplicated urinary tract infection in women.7 with this background, a study is designed to determine the antibiotic susceptibility pattern of e. coli which may help in prescribing effective empirical treatment of urinary tract infection. materials and methods this retrospective cross-sectional study was conducted in the microbiology section of ddrrl. urine culture and sensitivity reports were collected from medical records of the microbiology section of ddrrl after taking approval from institutional review board (irb) having reference no. irb1794/duhs/approval/2021. this retrospective data record is maintained by the database of lis (laboratory information system) under the supervision of director ddrrl. the data contains information about the patient’s age, gender, isolated organism, and antibiotic susceptibility pattern. the culture reports included samples from both inpatient and outpatient departments during a period from february 2017 to april 2017. a sample size of 5000 subjects was taken which achieved 98% power to detect a difference of 3.9% between two diagnostic tests (fosfomycin & nitrofurantoin) whose sensitivities were 95.8% and 91.9% respectively. this procedure used pass version 15 software, a two-sided mcnemar test with a 95% confidence interval. the prevalence of disease in the population was 73.2%. the proportion of discordant pairs was 35.1%. all samples having information regarding the patient’s age, gender, and isolated organism were included in the study. however antibiotic susceptibility of antibiotics against only e. coli is included in the study. samples having a lack of the above-mentioned information were excluded from the study as well as antibiotic susceptibility against organisms other than e. coli is excluded from the study. urine culture samples were processed as per standard microbiological procedures and antibiotic susceptibility testing by disk diffusion method was performed according to clsi guidelines 2021.8 the antibiotic discs used for susceptibility testing against e. coli included amoxicillin / clavulanic acid 30g, ampicillin 10g, amikacin 30g, meropenem 10g, piperacillin / tazobactam 110g, gentamicin 10g, ceftriaxone 30g, cefuroxime 30g, ciprofloxacin 5g, cotrimaxazole 25g, cefixime 5g, nitrofurantoin 300g and fosfomycin 200g. the data was entered in spss version 16 and statistical analysis was done. descriptive statistics were measured in percentages. results in the present study, a total of 5000 urine culture and sensitivity test report data was taken from medical records for a period of 3 months from feb 2017 to april 2017. out of them, 1565 (31.3%) urine samples were found positive for bacterial growth. amongst these, 3303 (66%) samples were of female patients and 1697 (34%) samples were of male patients. the 509 journal of rawalpindi medical college (jrmc); 2021; 25(4): 507-511 frequency of significant bacterial growth was much greater in the patients between 51-60 years of age followed by 21-30 years of age as compared to other age groups. (figure 1) among the isolated microorganisms, gram-negative bacteria 1282 (81%) were more than gram-positive bacteria 283 (18%). of the gram-negative bacteria, the most frequent isolate was e. coli 938 (73%). (table 1) e. coli was found highly sensitive to meropenem, amikacin, fosfomycin, and nitrofurantoin respectively. (table 1) * showing a high percentage of uropathogens in age groups figure 1: age-wise distribution of uropathogens in % table i: bacteria isolated from urine samples total bacterial growth 1565 gram negative bacteria n=1282 (81.9%) gram positive bacteria n=283 (18.1%) name of bacteria frequency name of bacteria frequency escherichia coli 938 (73.2%) enterococcus 158 (56%) klebsiella species 160 (12.5%) streptococcus d 57 (20.1%) pseudomonas aeuroginosa 47(3.7%) citrobacter species 42 (3.3%) staphylococcus species 28 (9.9%) enterobacter species 35 (2.7%) proteus mirabilis 19 (1.5%) streptococcus species 28 (9.9%) acinetobacter species 16 (1.3%) pseudomonas species 10 (1%) staphylococcus aureus 12 (4.2%) proteus vulgaris 10 (1%) table 2: resistant pattern of e. coli in % antibiotics escherichia coli n=938 ampicillin 806 (86%) amoxicillin/clavulanic acid 445 (47.5%) piperacillin/tazobactam 140 (15%) ceftriaxone 684 (73%) cefixime 684 (73%) cefuroxime 684 (73%) meropenem 28 (3%)* gentamicin 318 (34%) amikacin 48 (5.2%)* ciprofloxacin 590 (63%) cotrimoxazole 647 (69%) fosfomycin 39 (4.2%)* nitrofurantoin 75 (8.1%)* *microorganisms showing significant sensitivity to antibiotics. discussion this study has emphasized on antimicrobial susceptibility pattern of e. coli. this may help physicians in the appropriate selection of antibiotics for empirical treatment of patients suffering from uti. the prevalence of uti in our study was found to be 31.3% which is similar to the results of the study done in rawalpindi by khan mi.9 out of positive bacterial growth samples, 38% were females and 24% were males. increased prevalence of uti in females was also found in a research study done by ullah a. in kohat teaching hospital.10 moreover, patients of age group 51-60 years (18%) and 21-30 years (17.5%) were the most commonly affected age group which was consistent with data presented by bitew a. in 2017.11 in the present study, out of 1565 (14 species), bacterial isolates were recovered, gram-negative bacteria constituted (81%) major portion as compared to gram510 journal of rawalpindi medical college (jrmc); 2021; 25(4): 507-511 positive bacteria (18%). this is in accordance with the study findings by yadav m.12 the most prevalent isolated bacteria were found to be e. coli (73.2%), also reported in a study conducted by khan mi.9 in the present study, e. coli was found to be highly sensitive to meropenem, amikacin, fosfomycin, and nitrofurantoin consistent with the results published in studies by khan iu., al-zahrani j. and pouladfar g.13-15 however it was found resistant to ampicillin 86%, cephalosporin 73%, ciprofloxacin 63% and cotrimoxazole 69%. a similar pattern was documented in many studies.9,16,17 literature shows that nitrofurantoin is an active drug against e. coli, the most common pathogen of urinary tract infection and overall resistance to it is uncommon and many multidrug-resistant pathogens are still found susceptible to it. therefore nitrofurantoin can be prescribed as a first-line antimicrobial option for the empirical therapy of suspected acute uncomplicated cystitis.18 susceptibility of fosfomycin was also found highly effective in multidrug-resistant e. coli in uti in comparison to other available antibiotics. similar results were found in many related studies19,20 which have shown that fosfomycin is can an effective antibacterial drug for empirical treatment of uti patients.21 the carbapenem group of antibiotics is still a reliable option for parental treatment of urinary tract infection as low resistance has also been observed in other studies.16,22 moreover, our study displayed low resistance against amikacin, compatible findings are noted in other studies as well done in india and turkey.12,16 therefore it can also be preferred as a parental drug for empirical therapy of uti. as most physicians prefer broad-spectrum antibiotics for the treatment of outpatient utis therefore ciprofloxacin had remained one of the most frequently prescribed antibiotics for uti treatment.23 however, a significant increase in antimicrobial resistance to ciprofloxacin has been noticed over a time period.24 in our study, e. coli showed 63% resistance to ciprofloxacin. similarly, high cephalosporin resistance has been recorded in multiple studies due to its unchecked prescription practices.17 they should be used with caution for empirical treatment in hospitalized patients due to their high resistance rates. furthermore, high resistance rates of ampicillin have also been noticed in other related studies by bitew a. and demir m.11,16 therefore, it is not appropriate to use it as a single agent in empirical treatment. cotrimoxazole resistance was also found high in our study which is in agreement with the studies done in 2019 and 2020 respectively.16,25 hence, it should not be considered a suitable option for empirical treatment in uti. the high emergence of antibiotic resistance is mainly due to unchecked doctor practices, self-medication, and non-compliance of the patients.26 the limitation of the study is that the data was retrospective therefore it was not known whether the patient was symptomatic, asymptomatic, or critically ill. likewise, the source of the urine samples could not also be identified whether it was midstream urine or taken from a urine bag or catheter. similarly, the data did not sort out inpatients and outpatients separately. moreover, patients submitting more than one sample with complaints of recurrent uti or colonization could not be identified. conclusion the present study revealed that fosfomycin and nitrofurantoin are very effective oral antibiotic options for empirical treatment against e. coli causing urinary tract infection. they should be prescribed cautiously by the physicians to avoid the emergence of antibiotic resistance. references 1. john as, mboto ci, agbo b. a review on the prevalence and predisposing factors responsible for urinary tract infection among adults. euro j exp bio. 2016;6(4):7-11. 2. schappert sm, rechsteiner ea. ambulatory medical care utilization estimates for 2006. 2008. 3. foxman b. epidemiology of urinary tract infections: incidence, morbidity, and economic costs. the american journal of medicine. 2002;113(1):5-13. 4. foxman b, barlow r, d'arcy h, gillespie b, sobel jd. urinary tract infection: self-reported incidence and associated costs. annals of epidemiology. 2000;10(8):509-15. 5. olowe o, ojo-johnson b, makanjuola o, olowe r, mabayoje v. detection of bacteriuria among human immunodeficiency virus seropositive individuals in osogbo, south-western nigeria. european journal of microbiology and immunology. 2015;5(1):126-30. 6. shaifali i, gupta u, mahmood se, ahmed j. antibiotic susceptibility patterns of urinary pathogens in female outpatients. north american journal of medical sciences. 2012;4(4):163. 7. gardiner bj, stewardson aj, abbott ij, peleg ay. nitrofurantoin and fosfomycin for resistant urinary tract infections: old drugs for emerging problems. australian prescriber. 2019;42(1):14. 8. humphries r, bobenchik am, hindler ja, schuetz an. overview of changes to the clinical and laboratory standards institute performance standards for antimicrobial susceptibility testing, m100. journal of clinical microbiology. 2021:jcm00213. 511 journal of rawalpindi medical college (jrmc); 2021; 25(4): 507-511 9. khan mi, xu s, ali mm, ali r, kazmi a, akhtar n, et al. assessment of multidrug resistance in bacterial isolates from urinary tract-infected patients. journal of radiation research and applied sciences. 2020;13(1):267-75. 10. ullah a, shah srh, almugadam bs, sadiqui s. prevalence of symptomatic urinary tract infections and antimicrobial susceptibility patterns of isolated uropathogens in kohat region of pakistan. moj biol med. 2018;3(4):85-9. 11. bitew a, molalign t, chanie m. species distribution and antibiotic susceptibility profile of bacterial uropathogens among patients complaining urinary tract infections. bmc infectious diseases. 2017;17(1):1-8. 12. yadav m, pal r, damrolien s, khumanthem sd. microbial spectrum of urinary tract infections and its antibiogram in a tertiary care hospital. int j res med sci. 2017;5(6):2718-22. 13. khan iu, mirza ia, ikram a, afzal a, ali s, hussain a, et al. antimicrobial susceptibility pattern of bacteria isolated from patients with urinary tract infection. journal of the college of physicians and surgeons pakistan. 2014;24(11):840-4. 14. al-zahrani j, al dossari k, gabr ah, ahmed a-f, al shahrani sa, al-ghamdi s. antimicrobial resistance patterns of uropathogens isolated from adult women with acute uncomplicated cystitis. bmc microbiology. 2019;19(1):237. 15. pouladfar g, basiratnia m, anvarinejad m, abbasi p, amirmoezi f, zare s. the antibiotic susceptibility patterns of uropathogens among children with urinary tract infection in shiraz. medicine. 2017;96(37). 16. demir m, kazanasmaz h. uropathogens and antibiotic resistance in the community and hospital-induced urinary tract infected children. journal of global antimicrobial resistance. 2020;20:68-73. 17. prasada s, bhat a, bhat s, mulki ss, tulasidas s. changing antibiotic susceptibility pattern in uropathogenic escherichia coli over a period of 5 years in a tertiary care center. infection and drug resistance. 2019;12:1439. 18. sanchez gv, babiker a, master rn, luu t, mathur a, bordon j. antibiotic resistance among urinary isolates from female outpatients in the united states in 2003 and 2012. antimicrobial agents and chemotherapy. 2016;60(5):2680-3. 19. tulara nk. nitrofurantoin and fosfomycin for extended spectrum beta-lactamases producing escherichia coli and klebsiella pneumoniae. journal of global infectious diseases. 2018;10(1):19. 20. patel b, patel k, shetty a, soman r, rodrigues c. fosfomycin susceptibility in urinary tract enterobacteriaceae. the journal of the association of physicians of india. 2017;65(9):14-6. 21. fajfr m, louda m, paterová p, ryšková l, pacovský j, košina j, et al. the susceptibility to fosfomycin of gram-negative bacteria isolates from urinary tract infection in the czech republic: data from a unicentric study. bmc urology. 2017;17(1):1-6. 22. mehrishi p, faujdar ss, kumar s, solanki s, sharma a. antibiotic susceptibility profile of uropathogens in rural population of himachal pradesh, india: where we are heading? biomedical and biotechnology research journal (bbrj). 2019;3(3):171. 23. shapiro dj, hicks la, pavia at, hersh al. antibiotic prescribing for adults in ambulatory care in the usa, 2007–09. journal of antimicrobial chemotherapy. 2014;69(1):234-40. 24. sanchez gv, baird amg, karlowsky ja, master rn, bordon jm. nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary escherichia coli from us outpatients. journal of antimicrobial chemotherapy. 2014;69(12):3259-62. 25. chanda w, manyepa m, chikwanda e, daka v, chileshe j, tembo m, et al. evaluation of antibiotic susceptibility patterns of pathogens isolated from routine laboratory specimens at ndola teaching hospital: a retrospective study. plos one. 2019;14(12):e0226676. 26. ali i, shabbir m, iman nu. antibiotics susceptibility patterns of uropathogenic e. coli with special reference to fluoroquinolones in different age and gender groups. jpma. 2017;67(1161). summary journal of rawalpindi medical college (jrmc); 2017;21(1): 64-67 64 original article correlating serum beta hcg levels with transvaginal sonographic features of ectopic pregnancy uzma saeed and naveed muzhar department of radiology,dallah hospital,riyadh, saudi arabia abstract background: to correlate beta hcg levels with transvaginal sonographic features of ectopic pregnancy methods: in this prospective study 204 patients with confirmed diagnosis of ectopic pregnancy (ep), by both trasnvaginal sonography (tvs) and histopathology were included . results of tvs and serum βhcg levels were obtained. other variables were age, gestational age, size, site and volume of ep, fetal cardiac activity and presence or absence of pelvic ascites. results: sensitivity and specificity of tvs for detection of ep was 98% and 87.5% respectively. the values of median and range for the age, gestational age, βhcg and volume of ep were 29 (17-43) years, 5(4-6) weeks, 3248.5 (14-53048) iu/l, 8648.36 (26880491) mm3 respectively. most common site of ep was adnexa (93.6%) and most common side was right (52%). fetal cardiac activity was evident in 4.4% cases and pelvic ascites was present in 64.7% cases. there was no significant difference between two βhcg groups (<2000, >2000) in terms of qualitative and quantitative variables except the volume of ep which was significantly different among groups (p value <0.0001). conclusion: serum βhcg level alone cannot diagnose or exclude ep confidently and it is significantly correlated with the size of ep. the combination of serum βhcg and tvs provide highly accurate diagnostic information. key words: pregnancy, ectopic, chorionic gonadotropin, transvaginal ultrasonography. introduction one of the most challenging problems in gynecology has been the early identification of ep. early diagnosis of ep goes in more favor of conservative management. tvs and serum beta human chorionic gonadotropin (βhcg) are fundamental non-invasive modalities for detection and exclusion of ep. to some extent they both complement each other in this regard. histopathology of the specimen is confirmatoryin the united states, ep is estimated to occur in 1-2% of all pregnancies and accounts for 3-4% of all pregnancyrelated deaths.1 in the uk, ep remains the leading cause of pregnancy-related first trimester death (0.35 per 1000 cases of ep). in the developing world 10% of women admitted to hospital with a diagnosis of ep, ultimately die from this condition.2 during the 1980s and early 1990s the non-invasive methods were introduced to detect ep, like beta subunit of human chorionic gonadotropin (βhcg) and ultrasonography (usg) .3, 4 later on, refinement of these modalities like development of rapid essays for βhcg and high frequency transabdominal and transvaginal sonography (tvs) produced comparable detection rates as compared to laparoscopy.5 in ep urine pregnancy test may confuse the clinicians and some suggested ultrasensitive urine test to minimize this confusion but quantitative measurement of serum βhcg proved much superior to it. 6-8 ep has lesser βhcg levels than normal intrauterine pregnancy.9 the threshold level of βhcg to detect normal or ectopic gestation is debatable. the concept of a ‘discriminatory βbcg level’ was introduced in 1985 to highlight the serum βhcg level when a pregnancy should be visible on an usg.2 the range in various studies is highly variable i.e. from 1000 to 6500 iu/l.10-12 due to these advances the ep related mortality ratio declined by 56.6%, from 1.15 to 0.50 deaths per 100,000 live births between 1980 to 1984 and 2003 to 2007in united states.13 the main focus of tvs to exclude ep relies on the detection of intrauterine gestational sac. the high frequency tvs can provide more diagnostic information about location of ep as compared to transabdominal usg. in most of the studies the main focus has been on role of tvs along with discriminatory zones of βhcg for diagnosis of ep.14 the combination of βhcg and usg still remains the best among non-invasive diagnostic modalities.15 the early detection of ep goes more in the favor of successful medical management.3 the purpose of this journal of rawalpindi medical college (jrmc); 2017;21(1): 64-67 65 study was to correlate and compare the serum βhcg levels with various sonographic features of ectopic gestation and to find out whether we can rely solely on serum βhcg. patients and methods this prospective study was conducted in dallah hospital, riyadh from january 2013 to october 2016, with close collaboration between departments of obstetrics and gynecology, medical imaging and pathology. only the patients who had confirmation of ep via both tvs and hp were included in the study and serum βhcg levels were obtained. the patients, in which the duration between tvs and βhcg sample collection was more than 12 hours, were excluded. the titer of βhcg was measured with amerlite, hcg-60 assay. tvs was performed with 6.5 mhz transducer c10-3 and transducer r1c5-9-d. the probe had angle variation from 30 to 180 degrees. sonologist was kept ignorant of βhcg levels. the ep was defined as adnexal mass, gestational sac or embryo with or without cardiac activity outside the uterus, in the absence of intrauterine pregnancy. the various features of ep like site, size and presence or absence of fluid in the cul-de-sac were also recorded. all patients were treated according to standard hospital protocols. the samples of ep were obtained laparoscopically or via open surgical procedures during the surgical management and were sent for hp. the quantitative variables were age of patient (in years), gestational age (in weeks), serum βhcg (in iu/l) and the volume of ep (3/4×length/2× width/2×width/2×π in mm3, assuming shape of ep as regular ellipsoid). none of the quantitative variable shows normal distribution as assessed by shapirowilk test for normality (p value <0.0001). these variables are expressed by median, interquartile range (iqr) and range. the qualitative variables are site of ep, side of ep, presence or absence of fetal cardiac activity and fluid in cul-de-sac. these variables are expressed as frequencies and percentages. the βhcg levels were categorized into two groups (<2000 and > 2000 iu/l, loosely based on βhcg level of 2000 iu/l was considered as the threshold of the discriminatory zone) and both groups were compared in terms of rest of quantitative and qualitative variables by independent samples mann–whitney u test and chi square tests. non parametric correlation (kendall’s tau b) between βhcg, gestational age and volume of ep was calculated. p value of < 0.05 was considered significant. results in this study, initially a total of 211 patients were included based on the tvs findings. later on hp excluded 7 cases and our final sample was 204 patients after fulfilling the inclusion and exclusion criteria. sensitivity, specificity, positive and negative predictive values of tvs for detection of ep was 98%, 87.5%, 99.51% and 63.64% respectively. majority were in age group 25-35 years (table 1). majorty had gestational age less than 5 weeks (table 2).the median (iqr, range) for the age was 29.00 (10, 17-43) years and gestational age was 5.00 (1, 4-6) weeks (table 1. figure 1 and ii show the age and gestational age distribution of patients. serum βhcg levels were 3248.50 (12762, 14-53048) iu/l and volumes of ep were 8648.36 (13708, 268-80491) mm3. we had 13 cases in which βhcg levels were below 100 and in five patients levels were below 50 iu/l. putting cutoff value of 2000 iu/l, we got 120 cases (58.8 %) with serum βhcg levels > 2000 iu/l. the most common observed site for the ep was adnexa (n= 191, 93.6%) followed by ovaries (n= 10, 4.9%), scar of previous caesarian section (n= 5, 1%) and cervix (n= 1, 0.5%). table 1: ectopic pregnancyage distribution age group (years) no(%) < 25 61(29.90) 25-35 101(49.50) > 35 42920.58) table 2. gestational age gestational age(weeks) no(%) <5 128(63) >5 76(37) table 3.comparison of qualitative variables parameter βhcg levels (iu/l) pearson chi square p value < 2000 >2000 side of ep right 48 58 3.260 0.20 left 36 59 site of ep adnexal 59 132 3.813 0.051 non adnexal 2 11 fetal cardiac activity yes 1 8 3.514 0.061 no 83 112 pelvic ascites yes 54 78 0.011 0.92 no 30 42 a total of 106 cases (52%) of ep noted on right side, 95 cases (46.6%) were found on left side while 2 cases in journal of rawalpindi medical college (jrmc); 2017;21(1): 64-67 66 scar area and one case in cervix. fluid in the cul-de-sac was present in 132 patients (64.7%). out of 204 eps, tvs detected fetal cardiac activity in 9 cases (4.4%).the qualitative and quantitative variables were compared among the groups (based on βhcg levels of less or more than 2000 iu/l) (table 3&4). the βhcg levels were significantly correlated with ep volume (tau b = 0.252, p value <0.0001, n = 204) but these were not correlated significantly with the gestational age (tau b = -0.042, p value = 0.423, n = 204). table 4: comparison of quantitative variable parameter βhcg levels (iu/l) pvalue < 2000 >2000 median (iqr, range) median (iqr, range) age (years) 28.50 (10, 18-43) 30.00 (11, 1743) 0.94 gestational age (weeks) 5.00 (0, 4-6) 5.00 (2, 4-6) 0.75 ep volume (mm3) 4089.17 (8299, 35960048) 10939.24 (12471, 26880491) <0.0001 discussion tvs is now considered to play important role in both normal and abnormal gestation. this imaging technique can be performed in the outpatient clinic or emergency department and has been reported to have a sensitivity of 90% and a specificity of 99.8%, with positive and negative predictive values of 93% and 99.8% respectively for the diagnosis of ep. 16 these findings vary a little from ours in the specificity and negative predictive values. tvs should identify the normal intrauterine gestation sac with almost 100% accuracy at a gestational age of 5.5 weeks.2the close correlation between serum βhcg and gestational sac size has important implication when the gestational sac is not visible inside the uterus and sonographic details are inconclusive.14 in our study the gestational age was not correlated with the βhcg levels which is contrary to many studies.3, 16 ep volume was significantly correlated with serum βhcg level (p value <0.0001). this correlation showed that 25% of the ranks were concordant. in 1982, ackerman et al. showed that size of ep is correlated with βhcg levels and these findings have been evident in other studies also. 14,17-19 we divided the βhcg levels into two categories, keeping 2000 iu/l as dividing line. this was based on the fact that βhcg level more than 2000 iu/l 95.2% specific for the diagnosis of ep.16 level of βhcg level < 10 iu/l has been reported in ep.20 no single level of βhcg is diagnostic of ep and serial measurements are better predictor of the ep and its course.21. so it is very difficult to ascertain the threshold of βhcg for the detection of ep. we found 2 cases with 13 and 14 iu/l who had positive sonographic evidence of ep. in our study we found that 64.7% patients had pelvic fluid detected by usg and previous studies showed the positive predictive value (ppv) of pelvic ascites for the detection of ep < 30%. our study showed the fetal cardiac activity in 4.4% cases and in these cases the mean βhcg level was 14572 iu/l (range 1623 to 33847). these results were different as compared to recent research data which shows the detection of 10% cases of ep with cardiac activity which were having the mean βhcg level of 20980 iu/l (range 135107949)20. in the past, the detection of fetal cardiac activity in ep has been in the range of 15 to 25%.20, 22, 23 our results showed the chances of fetal cardiac activity are more when the βhcg level> 2000 iu/l but this difference doesn’t reach the level of significance (p value 0.061). this difference may be due to the fact that advanced gestation has more chances of positive fetal cardiac activity. moreover, the presence of ep on right side has more dominance in patients with βhcg level >2000 iu/l and level of significance is just lacks behind the reference level of significance (p value 0.051). conclusion 1. the βhcg levels alone cannot confidently confirm or exclude the diagnosis of ep. combination of serum βhcg level with tvs is the best non-invasive technique for this purpose. 2. there is a significant correlation between βhcg level and size of ep. 3. right sided dominance with increasing βhcg levels needs further evaluation . references 1. centers for disease c, prevention. ectopic pregnancy mortality florida, 2009-2010. mmwr morb mortal wkly rep. 2012;61(6):106-09. 2. sivalingam vn, duncan wc, kirk e. diagnosis and management of ectopic pregnancy. j fam plann reprod health care. 2011;37(4):231-40. 3. ankum wm. diagnosing suspected ectopic pregnancy. hcg monitoring and transvaginal ultrasound lead the way. bmj. 2000;321(7271):1235-36. 4. jouppila p, tapanainen j, huhtaniemi i. plasma hcg and ultrasound in suspected ectopic pregnancy. eur j obstet gynecol reprod biol. 1980;10(1):3-12. 5. doganov n, dimitrov r, iarukov a, nachev a, raicheva i. the role of serum beta-hcg levels for the diagnosis of ectopic pregnancy. akush ginekol 1994;33(3):23-25. journal of rawalpindi medical college (jrmc); 2017;21(1): 64-67 67 6. schwartz ro, di pietro dl. beta-hcg as a diagnostic aid for suspected ectopic pregnancy. obstet gynecol. 1980;56(2):197-203. 7. buck rh, pather n, moodley j, joubert sm, norman rj. bedside application of an ultrasensitive urine test for hcg in patients with suspected ectopic pregnancy. ann clin biochem. 1987;24 ( 3):268-72. 8. seppala m and purhonen m. the use of hcg and other pregnancy proteins in the diagnosis of ectopic pregnancy. clin obstet gynecol. 1987;30(1):148-54. 9. abdul-hussein mm, abdul-rasheed of, al-moayed ha. the values of ca-125, progesterone, ss-hcg and estradiol in the early prediction of ectopic pregnancy. oman med j. 2012;27(2):124-28. 10. kadar n, devore g, romero r. discriminatory hcg zone: its use in the sonographic evaluation for ectopic pregnancy. obstet gynecol. 1981;58(2):156-61. 11. romero r, kadar n, jeanty p, copel ja, chervenak fa. diagnosis of ectopic pregnancy: value of the discriminatory human chorionic gonadotropin zone. obstet gynecol. 1985;66(3):357-60. 12. nyberg da, filly ra, laing fc, mack la. ectopic pregnancy. diagnosis by sonography correlated with quantitative hcg levels. j ultrasound med. 1987;6(3):145-50. 13. creanga aa, shapiro-mendoza ck, bish cl. trends in ectopic pregnancy mortality in the united states: 19802007. obstet gynecol. 2011;117(4):837-43. 14. gabrielli s, romero r, pilu g, pavani a, capelli m. accuracy of transvaginal ultrasound and serum hcg in the diagnosis of ectopic pregnancy. ultrasound obstet gynecol. 1992;2(2):110-15. 15. counselman fl, shaar gs, heller ra, king dk. quantitative b-hcg levels less than 1000 miu/ml in patients with ectopic pregnancy: pelvic ultrasound still useful. j emerg med. 1998;16(5):699-703. 16. condous g, kirk e, lu c, van huffel s. diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location. ultrasound obstet gynecol. 2005;26(7):770 75. 17. ackerman r, deutsch s, krumholz b. levels of human chorionic gonadotropin in unruptured and ruptured ectopic pregnancy. obstet gynecol. 1982;60(1):13-15. 18. cacciatore b, stenman uh, ylostalo p. diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hcg level of 1000 iu/l (irp). br j obstet gynaecol. 1990;97(10):904-08. 19. cartwright ps, moore ra, dao ah, wong sw. serum betahuman chorionic gonadotropin levels relate poorly with the size of a tubal pregnancy. fertil steril. 1987;48(4):679-80. 20. frates mc, doubilet pm, peters he, benson cb. adnexal sonographic findings in ectopic pregnancy and their correlation with tubal rupture and human chorionic gonadotropin levels. j ultrasound med. 2014;33(4):697703. 21. surampudi k and gundabattula sr. the role of serum beta hcg in early diagnosis and management strategy of ectopic pregnancy. j clin diagn res. 2016;10(7):qc08 10. 22. fleischer ac, pennell rg, mckee ms, worrell ja. ectopic pregnancy: features at transvaginal sonography. radiology. 1990;174(2):375-78. 23. condous g, okaro e, khalid a, lu c, van huffel s. the accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery. hum reprod. 2005;20(5):1404-09. 193 journal of rawalpindi medical college (jrmc); 2020; 24(3): 193-197 original article comparison of effectiveness of 7.5% povidone-iodine with 1% clotrimazole ear drops and lignocaine in otomycosis tabassum aziz1, nousheen qureshi2, mahwash khawaja3, rida ulfat4, tahir muhammad5, anum malik6 1 senior registrar, department of ent, holy family hospital, rawalpindi. 2 associate professor, department of ent, holy family hospital, rawalpindi. 3 senior registrar, department of ent, benazir bhutto hospital, rawalpindi. 4 medical officer, holy family hospital, rawalpindi. 5 assistant professor, peshawar medical college, peshawar. 6 consultant anaesthetist, wapda hospital, rawalpindi. author’s contribution 1 conception of study 1,4 experimentation/study conduction 1,2,3,6 analysis/interpretation/discussion 1,2,4 manuscript writing 1,2,6 critical review 2,5 facilitation and material analysis corresponding author dr. tabassum aziz, senior registrar, department of ent, holy family hospital, rawalpindi email: tabassumazizch@gmail.com article processing received: 13/07/2019 accepted: 03/09/2020 cite this article: aziz, t., qureshi, n., khawaja, m., ulfat, r., muhammad, t., malik, a. comparison of effectiveness of 7.5% povidone-iodine with 1% clotrimazole ear drops and lignocaine in otomycosis. journal of rawalpindi medical college. 30 sep. 2020; 24(3): 193-197. doi: https://doi.org/10.37939/jrmc.v24i3.1161 conflict of interest: nil funding source: nil access online: abstract objectives: our study is comparing the effectiveness of 7.5% povidone-iodine with 1% clotrimazole ear drops and lignocaine in the management of otomycosis to highlight the importance of replacing conventional antifungals in routine practice. setting: department of ent and head and neck surgery, holy family hospital, rawalpindi, pakistan. study design: a prospective randomized control trial methodology: this study was conducted for 12 months in our institute from july 2014 to june 2015. a total number of 148 patients with clinically diagnosed otomycosis between the ages group 15 to 55 years were studied. all patients with a clinical diagnosis of otomycosis presenting with all four features of earache, itching, earblockage, and ear discharge in ent opd were included. ear swabs were taken and sent for fungal culture. patients were divided into a and b groups each comprising of 74 patients. group a received 1% clotrimazole ear drops and lignocaine and group b received 7.5% povidone-iodine for 14 days after the results of cultures were received. at the end of 14 days, patients of both groups were compared based on the resolution of symptoms and signs. results: at the end of 14 days, 32 out of 74 patients (43%) in group a receiving 1% clotrimazole ear drops and lignocaine reported resolution of all symptoms, and 52 out of 74 patients (70%) showed complete resolution of all signs, while in group b,68 out of 74 patients (91%) showed complete resolution of symptoms and 69 out of 74 patients (93%) showed complete resolution of signs. our study showed significant improvement in signs and symptoms of otomycosis achieved by treatment with 7.5% povidone-iodine compared to that achieved by 1% clotrimazole ear drops and lignocaine. conclusion: 7.5% povidone-iodine is a more effective antifungal agent in the treatment of otomycosis as compared to 1% clotrimazole ear drops and lignocaine. keywords: otomycosis, povidone-iodine, clotrimazole. 194 journal of rawalpindi medical college (jrmc); 2020; 24(3): 193-197 introduction otomycosis is a superficial fungal infection of the external auditory canal and is worldwide in distribution characterized by inflammation, pruritus, scaling, and severe discomforts like suppuration and pain.¹ this disease can also spread to the middle ear if the tympanic membrane is perforated.² it is usually unilateral and more common in the younger age group². it is estimated that almost 5% to 25% of total cases of otitis externa (inflammation of the external auditory canal) are due to otomycosis.³ it is common in a hot and humid climate like the south asian region, mostly in people belonging to lower socioeconomic backgrounds.³ the most common causative agent isolated from otomycosis patients is from the genus aspergillus followed by candida species. among the genus aspergillus, aspergillus niger is most common followed by a.flavus and a.fumigatus.⁴ in patients of otomycosis, debris in the external auditory canal does not always consist of purely fungal elements but is mixed with bacterial invaders like pseudomonas aeruginosa, staphylococcus, and streptococcus.⁵ otoscopic examination reveals a grayish-white mass in the external auditory canal along with hyperemia and sometimes edema as well. patients commonly present with pain and itching in the ear.⁶ the diagnosis of otomycosis is based on history, otoscopic examination, and fungal culture. direct preparation of the specimen specifically with optic brightener, mycological culture, and histological examination is strongly recommended for correct diagnosis. the microscopic examination of fungal cultures after the preparation of slides with potassium hydroxide shows discrete clumps of hyphae with conidiophores.⁷ many pharmacological preparations like drugs from azole class, nystatin, 7.5% povidone-iodine, tolnaftate, acetic acid, and gention violet are currently used widely for the treatment of otomycosis without knowing the exact efficacy of drug class.⁸ further studies are required to find out the antifungal activity of each class of drugs and the comparison of their resistance patterns in detail to aid in evidencebased decision-making to prevent the potential risk of antifungal resistance which not only increases disease burden but is also cost-intensive. the purpose of this study is to evaluate the antifungal property of 7.5% povidone-iodine to promote an alternate, effective and cheaper treatment of otomycosis. povidone-iodine has effective antibacterial, antifungal, and antiprotozoal properties. previous studies have shown promising results of the antifungal activity of povidone-iodine in the treatment of otomycosis. we want to evaluate whether the same is true in our population and the comparative pros and cons of using it instead of 1% clotrimazole ear drops and lignocaine preparation. materials and methods a randomized control trial was conducted in our institution for 12 months. the institutional research board clearance was taken before the commencement of the study and detailed informed consent was also taken from the subjects. all the patients with clinically diagnosed otomycosis within the age range of 15 to 55 years were included in the study. patients with chronic suppurative otitis, media, malignant otitis externa, post-operative mastoidectomy cavities, and diabetes mellitus were excluded from this study. all the patients who presented to us through opd with symptoms of earache, itching, ear blockage, and ear discharge were included. these patients were diagnosed based on history, examination with an otoscope, and fungal culture of ear swab taken. the cultures were grown on sabouraud dextrose agar at 25⁰c and incubated for 24 hours. we also did an aural toilet with a suction machine. otoscope and suction machines were the main instruments used to aid in the diagnosis of otomycosis in our research. the symptoms and signs of these patients were documented after taking written informed consent from each of them. we divided the patients into two equal groups: a and b, comprising of 74 patients in each group. group a received 1% clotrimazole ear drops and lignocaine drops, 3 drops each to be instilled in the affected ear three times a day for 14 days. group b received 7.5% povidone-iodine ear drops also prescribed as 3 drops thrice a day for 14 days. the evaluation of patients in both the groups was done on the 14th day based on the resolution of symptoms and signs however on the 7th day all the patients were called for the suction toilet to clear the fungal debris. data was analyzed and entered using spss version 18. target sample size and rationale: the sample size was calculated using the who sample size calculator, keeping the power of test 90% level of significance 5%, resolution of otalgia in 195 journal of rawalpindi medical college (jrmc); 2020; 24(3): 193-197 clotrimazole group 100%, and resolution of otalgia in povidone-iodine group 86.7%. the sample size was 148. results in this study, out of a total of 148 patients, there were 46 (62.16%) males and 28 (37.8%) females in group a. in group b there were 51 (68.91%) males and 23 (31.01%) females. the male to female ratio in group a was1.6:1 and in group b was 2.2:1. the graphical representation of gender distribution is shown in fig.1 below. according to the culture results from ear swabs, aspergillus niger was isolated in 63% of culture results whereas candida albicans were detected in 33% of cultures from both the groups. the number of patients with persisting symptoms of earache, itching, ear blockage, and ear discharge in group a after 14 days of treatment was 35 (47%), 42 (57%), 31 (42%), 38 (51%) respectively out of a total of 74 patients, while in group b the number of patients with these persisting symptoms was 4 (54%), 3 (41%), 5 (67%)and 6 (8%) patients respectively as shown in figure 2 and table 1. signs of fungal debris, erythema of canal, and erythema of tympanic membrane persisting after 14 days were seen in 20 (27%), 22 (30%), and 7 (9%) patients respectively in group a while in group b they were seen in 2 (2.7%), 5 (6.7%) and 1 (1.3%) patients respectively out of a total of 72 patients in both groups as shown in figure 3 and table 2 along with their p values. figure 1: male to female ratio graph table 1: post-treatment symptoms (after 14 days) post treatment symptoms group a (1% clotrimazole & lignocaine) (n=74) group b (7.5% povidone iodine) (n=74) p value otalgia 35 (47 %) 4 (5.4%) 0.042 pruritus 42 (57%) 3 (4%) 0.031 ear blockage 31 (42 %) 5 (6.7%) 0.023 ear discharge 38 (51%) 6 (8%) 0.041 (n=148) figure 2: comparison of post-treatment symptoms of both groups table 2: post-treatment signs: (after 14 days) post treatment signs group-a (1%clotrimazol e & lignocaine) (n=74) group-b (7.5% povidoneiodine) (n=74) p value fungal debris 20 (27%) 2 (2.7%) 0.045 erythema of canal 22 (30%) 5 (6.7%) 0.032 erythema of tympanic membrane 7 (9%) 1 (1.3%) 0.812 (n=148) 196 journal of rawalpindi medical college (jrmc); 2020; 24(3): 193-197 figure 3: comparison of post-treatment signs of both groups discussion the treatment of otomycosis has often been presented as a clinical challenge in many ent practices. munguia et al found that aspergillus species and candida albicans are the most common causative organisms.¹² our study also found that aspergillus species and candida albicans are the most prevalent causative organism in our sample population. many drugs have been investigated for the treatment of otomycosis.⁸ antifungals from the azole class seem to be the most effective, followed by nystatin and tolnaftate.¹² 1% clotrimazole ear drops and lignocaine have been used for effective treatment of otomycosis for a long time in the medical field.¹º nneenia mgbor et al used clotrimazole in a comparative study in nigeria and found it to be an effective drug.¹¹ recently some researchers have also studied the efficacy of povidone-iodine in otomycosis treatment. in our clinical practice, we found that most patients do not show complete resolution of signs and symptoms of otomycosis with the azole group of antimycotics like clotrimazole. this leads to treatment failure and frequent relapses due to the persistence of spores as well as the risk of developing serious complications like tympanic membrane perforation, hearing loss, and invasive temporal bone infection, although seen sporadically and only in immunocompromised patients.18 it is because clotrimazole eardrops are irritating, if used alone compliance is difficult to achieve by prescribing additional lignocaine drops; hence there is the need for studying newer agents. frequent use of the azole group of antifungals might be the main factor for its increased resistance worldwide. van der linden et al performed a prospective nationwide multicenter surveillance study in netherland and found that there was statistically significant resistance to the azole group of antifungals in otomycosis.¹³ in another study acquired azole resistance in aspergillus fumigatous was detected in 11 out of 17 european centers in 9 countries.15 the overall prevalence of azole group resistance was 3.2% which was also associated with worse patient outcomes.14,15 povidone-iodine (pvp-i) also known as iodopovidone is an antiseptic used for skin disinfection before and after surgical procedures. maral gharaghani et al used povidone-iodine in their study and reported it to be an effective antifungal agent.16 ajay philip et al conducted a comparative study and also observed its effectiveness in the management of otomycosis⁸. pain, pruritis, and ear discharge are the most troublesome symptoms reported after otomycosis which were relieved earlier in the group receiving povidone-iodine compared to that receiving clotrimazole.17 povidoneiodine is an inexpensive, nontoxic agent with good antimycotic properties and no drug resistance reported so far. in developing countries like pakistan where cost-effectiveness is a serious issue, it is very important to study and advocate the use of cheaper and effective treatments like povidone-iodine on a larger scale by ent practitioners. only a few studies have been conducted in this regard in pakistan. our study also confirms a better resolution of signs and symptoms of otomycosis with 7.5% povidoneiodine compared to 1% clotrimazole ear drops and lignocaine. approximately one-third of patients (39.7%) in the 1% clotrimazole eardrops and lignocaine receiving group were not cured. on the other hand, only 6.7% of patients in the 7.5% povidone-iodine receiving group had treatment failure at the end of 14 days. this proves that 7.5% povidoneiodine is significantly better than 1% clotrimazole ear drops and lignocaine in the treatment of otomycosis and future ent consultants and specialists should prescribe it to the patients who are having fungal infections of the ears. conclusion 7.5% povidone-iodine is far effective in the treatment and management of otomycosis as compared to 1% clotrimazole eardrops and lignocaine. 197 journal of rawalpindi medical college (jrmc); 2020; 24(3): 193-197 references 1. kaur r, mittal n, kakkar m, aggarwal ak, mathur md. otomycosis: a clinicomycologic study. ear, nose & throat journal. 2000 aug;79(8):606-9. 2. ozcan km, ozcan m, karaarslan a, karaarslan f. otomycosis in turkey: predisposing factors, aetiology and therapy. the journal of laryngology & otology. 2003 jan;117(1):39-42. doi: https://doi.org/10.1258/002221503321046621 3. pradhan b, tuladhar nr, amatya rm. prevalence of otomycosis in outpatient department of otolaryngology in tribhuvan university teaching hospital, kathmandu, nepal. annals of otology, rhinology & laryngology. 2003 apr;112(4):384-7. https://doi.org/10.1177/000348940311200416 4. ozcan m, ozcan mk, karaarslan a, karaarslan f. concomitant otomycosis and dermatomycoses: a clinical and microbiological study. european archives of oto-rhinolaryngology. 2003; 260(1):24-7. 5. kumar a. fungal spectrum in otomycosis patients. jk science. 2005 jul;7(3):152-5. 6. ho t, vrabec jt, yoo d, coker nj. otomycosis: clinical features and treatment implications. otolaryngology—head and neck surgery. 2006 nov;135(5):787-91. 7. martín a, canut a, muñoz s, pescador c, gómez j. otomycosis: presentation of 15 cases. enfermedadesinfecciosas y microbiologiaclinica. 1989;7(5):248-51. 8. philip a, thomas r, job a, sundaresan vr, anandan s, albert rr. effectiveness of 7.5 percent povidone iodine in comparison to 1 percent clotrimazole with lignocaine in the treatment of otomycosis. international scholarly research notices. 2013;2013. 9. vennewald i, klemm e. otomycosis: diagnosis and treatment. clinics in dermatology. 2010;28(2):202-11. 10. jia x, liang q, chi f, cao w. otomycosis in shanghai: aetiology, clinical features and therapy. mycoses. 2012;55(5):404-9. 11. mgbor n, gugnani h. otomycosis in nigeria: treatment with mercurochrome. mycoses. 2001;44(9‐10):395-7. 12. munguia r, daniel sj. ototopical antifungals and otomycosis: a review. international journal of pediatric otorhinolaryngology. 2008;72(4):453-9. 13. van der linden jw, snelders e, kampinga ga, rijnders bj, mattsson e, debets-ossenkopp yj. clinical implications of azole resistance in aspergillus fumigatus, the netherlands, 2007– 2009. emerging infectious diseases. 2011 oct;17(10):1846. 14. van der linden j, arendrup m, warris a, lagrou k, pelloux h, hauser p, et al. prospective multicenter international surveillance of azole resistance in aspergillusfumigatus. emerging infectious diseases. 2015; 21(6):1041. 15. gonçalves ss, souza ac, chowdhary a, meis jf, colombo al. epidemiology and molecular mechanisms of antifungal resistance in candida and aspergillus. mycoses. 2016 apr;59(4):198-219. 16. gharaghani m, seifi z, mahmoudabadi az. otomycosis in iran: a review. mycopathologia. 2015 jun 1; 179(5-6):415-24. 17. dai y, she w, zhu w, zhang q, chen f, yu c, wang j, gao x. diagnosis and treatment of mycotic otitis media. lin chuang er bi yanhoutou jing waikezazhi= journal of clinical otorhinolaryngology, head, and neck surgery. 2009 jan 1; 23(1):11-3. 18. viswanatha b, naseeruddin k. fungal infections of the ear in immunocompromised host: a review. mediterranean journal of hematology and infectious diseases. 2011; 3(1). 187 journal of rawalpindi medical college (jrmc); 2020; 24(3): 187-192 original article prevalence of raised alanine amino transaminase (alt) in pregnant mothers: a cross-sectional study tabinda khalid1, rubaba abid naqvi2, nisar ahmed malik3, hamna sarwar4 1 senior registrar, department of gynae./obs., dhq hospital, rawalpindi. 2 assistant professor, department of gynae./obs., dhq hospital, rawalpindi. 3 senior medical officer, cantonment general hospital, rawalpindi. 4 4th year mbbs student, rawalpindi medical university, rawalpindi. author’s contribution 1 conception of study 1,4 experimentation/study conduction 1,3 analysis/interpretation/discussion 1 manuscript writing 2,3 critical review 2,3 facilitation and material analysis corresponding author dr. tabinda khalid, senior registrar, department of gynae./obs., dhq hospital, rawalpindi email: tabindakhalid@gmail.com article processing received: 13/07/2019 accepted: 14/09/2020 cite this article: khalid, t., naqvi, a.n., malik, n.a., sarwar, h. prevalence of raised alanine amino transaminase (alt) in pregnant mothers: a crosssectional study. journal of rawalpindi medical college. 30 sep. 2020; 24(3): 187-192. doi: https://doi.org/10.37939/jrmc.v24i3.1152 conflict of interest: nil funding source: nil access online: abstract objective: to determine the prevalence of raised alt, common causes, and associated fetomaternal morbidity in pregnant mothers presenting, at cantonment general hospital rawalpindi materials and methods: this was a cross-sectional study conducted at cantonment general hospital rawalpindi from july 2016 till june 2017. results: out of 1924 women, 102 were identified with raised alt making a prevalence of 5.3%. sixty-one (59.8%) were booked. the hypertensive group which included severe preeclampsia, chronic hypertension with superimposed preeclampsia/eclampsia were 55 (53.9%), intrahepatic cholestasis of pregnancy(icp) 32 (31.7%), acute viral hepatitis 9 (8.8%), acute fatty liver of pregnancy(aflp) 2 (1.96%), and unknown cause in 4 (3.92%). mean alt levels were 54.1 ± 6.94, 71.28 ± 23.25, 84.22 ± 27.82, 231.5 ± 47.37 respectively. in four cases no definitive cause could be identified with the available tests were labeled as an unknown group, having a mean alt level of 79.25 ± 10.07. (p=0.01). term delivery occurred in 71 (69.6%), while 31 (30.39%) were preterm. there was one termination of pregnancy. vaginal birth occurred in 42 (42.2%), and 53 (51.9%) underwent emergency cesarean. there was one peripartum hysterectomy. meconium stain of liquor was 19 (18.6%). the birth weight of most babies 73 (71.5%) was between 2-3 kilograms only three were ≤ 1 kilograms. eight cases of postpartum hemorrhage, three maternal deaths, and six perinatal/early neonatal deaths were observed. conclusion: raised alt in pregnancy leads to increased fetomaternal complications. severe preeclampsia and obstetric cholestasis were the commonest causes. women of younger age groups were having acute viral hepatitis. timely recognition and diagnosis are essential to institute appropriate management strategies. keywords: liver dysfunction, pre-eclampsia, acute fatty liver of pregnancy, cholestasis of pregnancy. 188 journal of rawalpindi medical college (jrmc); 2020; 24(3): 187-192 introduction liver function tests (lfts) are measured clinically as a biomarker for liver health. alanine amino transaminase (alt) is a transaminase enzyme is found in plasma, various body tissues, and mostly the liver. hepatic damage causes the release of these intracellular enzymes, leading to raised levels. interpretation of abnormal liver function tests is crucial, considering the widespread maternal adaptive response to an ongoing pregnancy. according to study pregnancy, related liver dysfunctions are reported to affect 3% of pregnancies.1 gestational hypertensive disorders, acute fatty liver of pregnancy, intrahepatic cholestasis of pregnancy(icp) are the major causes of liver derangements.2 hypertensive disorders (preeclampsia/eclampsia) are recognized causes of the maternal mortality rate of 15.5% according to a turkish study.3 increasing number of obstetric patients are admitted to intensive care units due to complications of preeclampsia.4 a multicentre trial in china showed 58.7% of obstetric patients in intensive care units had pregnancy-related hypertensive disorders.5 our pakistani study also reported the profound effect of preeclampsia on liver function tests when compared to normal pregnancies. the mean alt was 55.81 ± 31.93 compared to control 15.22 ± 3.30.6 help syndrome (hemolysis, elevated liver enzymes, low platelet) is a serious condition with a high rate of maternal mortality. disseminated intravascular coagulation(dic), acute renal failure, and major postpartum hemorrhage (pph) are the feared complicatons7 the incidence of icp is also high compared to the other populations. according to our local study it affects around 3.1% of our obstetric patients.8 patients with high alt are at 3.54 fold increased risk of adverse perinatal outcome. potential fetal risks include iatrogenic /spontaneous preterm birth, meconium, and fetal death.9 ursodeoxycholic acid(udca) has been shown to improve pruritis and liver function tests 10,11. early induction of labor after 37 weeks, can cause a major reduction in the stillbirth rate.12 acute viral infections such as hepatitis a, b, c, and e are unfortunately very prevalent in our country. according to our pakistani study vertical transmission of hepatitis b and c as the mode of exposure accounted for one-quarter of children under five years of age and the majority (72.5%) occurred in punjab province.13 another local study showed hepatitis e (53.8%), hepatitis b (17.3%), hepatitis c in 7 (13.5%) hellp syndrome in (13.5%), and acute fatty liver of pregnancy (aflp) in (3.57%) cases. maternal mortality of (28.8%) and fetal mortality (77%).14 in chronic liver disease, liver function tests may not worsen during pregnancy. however, in chronic hepatitis b, flares in alt (99-2522u/l) were seen in 6% during pregnancy and 10% within three months after delivery.15 an indian study showed the study frequency of chronic liver disease in pregnancy (0.4%), hepatic decompensation in 16%. a live birth rate of 76% was being better and complications such as variceal bleeding or decompensation of liver disease were less common than previously reported.16 acute fatty liver of pregnancy (aflp) is a rare but life-threatening emergency, characterized by microvesicular fatty infiltration of the liver, attributed to defect in mitochondrial beta-oxidation of fatty acids.17 raised bilirubin, transaminase, and coagulopathy occurring in 100%, hypoglycemia in 53%.18 liver dysfunction in pregnancy with markedly raised transaminase can lead to a severe adverse fetomaternal outcome. early diagnosis and prompt management can markedly improve fetomaternal morbidity and mortality. materials and methods this cross-sectional study was conducted at cantonment general hospital rawalpindi from july 2016 till february 2017. we recruited our pregnant patients whose ages ranged from 17-36 years, parity from 0-5, no history of prior cesarean delivery, with raised alt using a cut-off value of 45 iu/l. only those cases that had persistently raised levels at least on two or more occasions on serial monitoring were included. cases of chronic liver disease and chronic hepatitis, alcoholism, drug-induced hepatic dysfunction, hyperemesis gravidarum, and autoimmune causes were not included. the decision for induction, delivery, termination, etc was purely based on standard obstetric indications, and no upper limit of alt was defined for any intervention. each case was analyzed in detail, regarding maternal demographic characteristics (age, parity, booking status), the mean level of alt, gestational age at initial diagnosis, the possible cause of derangement in alt, mode and time of delivery, the incidence of meconium staining of liquor, birth weight, maternal morbidity mortality, perinatal /early neonatal deaths. 189 journal of rawalpindi medical college (jrmc); 2020; 24(3): 187-192 the collected data was analyzed using statistical package for social sciences version 20. one way anova, with a post hoc test (welch’s test) was applied to see the statistical significance in alt levels among various groups. results out of 1924 women delivered during the study period, we found 102 were having raised alt levels making a prevalence of 5.3%. their ages ranged from 17-36 years, and parity from 0-5. we found that younger women and low parity were at risk as 92 (90.1%) women below 31 years of age, and 86 (84.3%) women had parity between 0-3. gestational hypertensive disorders affected 55 (53.9%), mean alt was 54.10 ± 6.94, presented at a mean gestational age of 35.5 weeks, and delivered at a mean gestational age of 36.8 weeks. headache was the predominant symptom, uncontrolled blood pressure, vertigo, and visual symptoms. there were two cases of seizures. this group had the highest emergency cesarean section rate. out of 53 emergency cesarean sections, 28 (52.8% of total emergency cesarean sections) were performed in this group, out of which 9 were preterm. two of maternal deaths and three fetal/early neonatal deaths were observed in this group. one peripartum hysterectomy due to postpartum hemorrhage was performed in this group. icp was found in 32 (31.7%), with a mean alt level of 71.28 ± 23.25. pruritis was the chief complaint. one patient reported the recurrence of cholestasis in her all three pregnancies. one intrauterine fetal death was observed in this group. em lscs were 16, the main indications were failed induction, fetal distress, and meconium. acute viral hepatitis was seen in 9 (8.8%), five were having acute hepatitis b; three had hepatitis e, and one hepatitis a viral infection. the mean alt level being 84.22 ± 27.82, women in this group were younger mean age 22.55 ± 3.04, presented in early pregnancy mean gestational age at diagnosis was 29.08 weeks. nausea and abdominal pain were the main complaints. one termination of pregnancy was done due to hepatitis e infection with the worsening of maternal symptoms and liver dysfunction. there were two emergency cesarean for fetomaternal indication. we had only two cases of aflp (1.96%), who presented at a mean gestational age of 35.7 weeks. mean alt was highest in this group 231.5 ± 47.37. unfortunately, two fetal deaths and one maternal death occurred in this group. in four patients the cause of persistently raised alt could not be explained with available investigations in our hospital and was labeled as the unknown cause group. however, no significant feto-maternal morbidity was seen except one case of the meconium stain of liquor and emergency cesarean. there were 8 cases of postpartum hemorrhage, but 4 patients required extensive blood transfusion(>6 units) and blood products. eighteen women were admitted to the intensive care unit (icu) for monitoring and surveillance. nine stayed for 7 days or more. meconium stain of liquor was seen in 19 (18.6%), out of which 9 (8.8%) were in icp, 4 (3.92%) inactive viral hepatitis, 3 (2.9%) in hypertensive, 2 (1.96%) in aflp 1 (0.98%) in an unknown group. the birth weight of three babies was less than 1 kg, 73 were between 2-3 kg, 18 were between 3-3.5 kg, and 7 were above 3.5 kg. twenty-three babies were retained in the neonatal intensive care unit for observation, seventeen were admitted. however, only five remain stayed for 7 days or more. six perinatal/early neonatal deaths were reported, three in the hypertensive group, two in aflp, and one in the icp group. figure 1: mean alt levels in various groups 190 journal of rawalpindi medical college (jrmc); 2020; 24(3): 187-192 table 1: gender and age distribution of subjects group n=102 mean alt std deviation preeclampsia/eclampsia 55 54.10 6.94 icp 32 71.28 23.37 acute viral hepatitis 9 84.22 27.82 aflp 2 231.50 47.37 unknown cause 4 79.25 10.07 outcome: mean alt levels p=0.01 table 2: mean, the standard deviation for age, parity, gestational age at diagnosis and delivery groups age in years parity gestation at diagnosis in weeks gestation at delivery in weeks preeclampsia/ eclampsia mean std dev 23.60 4.23 1.78 1.34 35.52 1.49 36.83 0.79 icp mean std dev 25.19 3.31 2.19 1.36 32.47 1.77 36.98 0.62 acute viral hepatitis mean std dev 22.55 3.04 1.00 1.22 29.08 8.15 37.86 0.77 aflp mean std dev 28.50 4.24 3.00 1.41 35.70 0.56 35.70 0.63 unknown cause mean std dev 27.50 4.20 2.75 0.95 30.20 8.95 37.72 0.47 table 3: clinical presentation complain/symptom frequency percentage headache 27 26.5 visual/vertigo 12 11.8 uncontrolled b.p 10 9.8 decreased fetal movements 12 11.8 abdominal pain 9 8.8 nausea/vomiting 9 8.8 abnormal bleeding 6 5.9 pruritis 15 14.7 seizures 2 2.0 191 journal of rawalpindi medical college (jrmc); 2020; 24(3): 187-192 table 4: maternal morbidity and mortality group maternal morbidity maternal mortality preeclampsia/eclampsia em lscs aph/pph hysterectomy 29 4 1 2 ich emlscs aph/pph 18 2 1 aflp emlscs aph/pph 2 2 nil acute viral hepatitis emlscs top 3 nil unknown cause emlscs 1 nil top= termination of pregnancy table 5: fetal morbidity and mortality group meconium stain fetal mortality icp 9 (8.8%) 1 acute viral hepatitis 4 (3.92%) nil preeclampsia/eclampsia 3 (2.9%) 3 aflp 2 (1.96%) 2 unknown cause 1 (0.98%) nil discussion our study showed that alt was raised in 5.3% (102/1924) women using a cut-off value of 45 iu/l. raised levels of aspartate aminotransaminase (ast) are modestly predictors of adverse maternal outcomes. a study conducted in bangladesh mondal br, ahmed s and et al showed mean levels of total bilirubin and alt was found significantly high in both preeclampsia and eclampsia group as compared to controls.19 kojic r and et al found absolute magnitude of ast, alt, and lactate dehydrogenase (ldh) as predictor of adverse maternal complications(ast: roc auc 0.73 [95% ci 0.67 to 0.97]; alt: roc auc 0.73 [95% ci 0.67 to 0.79]; ldh: roc auc 0.74 [95% ci 0.68 to 0.81]).20 elad mei dan et al found alt level of 50 iu/l having a sensitivity of 3.3% (despite a specificity of 97%) in predicting severe preeclampsia.21 turkmen gg et al have shown mean alt, ast, and bile acids are significantly raised in the cholestasis group than the control.22 our local study using alt cut off level of 95iu/l level to predict adverse perinatal outcomes in intrahepatic cholestasis of pregnancy found a sensitivity of 76.47% and specificity of 78.8%.23 kondrackiene j, zalinkevicius r et al showed using the cut-off value for alt (31 iu/l) results in an increase of sensitivity to 92.2% vs 90.1% in diagnosing icp.24 early-onset icp patients presented with more worsening symptoms, leading to more premature deliveries and fetal distress. however difference in mean alt levels in early-onset cholestasis 159 ± 50, and late-onset cholestasis 142 ± 52 u/l was not statistically significant (p>0.05).25 our study had certain limitations. our inferences depend on hospital record, their accuracy about diagnosis and management, and records on birth certificates and discharge forms. we tried our best to countercheck and recheck to minimize the bias. secondly, the number of cases for some groups was very small e.g. aflp. we used anova with post hoc welch’s correction to find the p-value. we could not address the impact of chronic liver disease on alt during pregnancy. most of our obstetric patients do not maintain their previous antenatal records, so we cannot compare from previous alt levels. secondly, although screening for viral hepatitis is performed in our hospitals but liver function tests such as bilirubin, alt, ast, ldh are not done as a routine unless clinically indicated. so only acute cases with clinical features were recruited. 192 journal of rawalpindi medical college (jrmc); 2020; 24(3): 187-192 cases of hyperemesis gravidarim, alcoholism, druginduced abnormality in liver function tests, and autoimmune causes were also not included. conclusion aflp cases presented with the highest alt levels. severe pre-eclampsia/eclampsia affected the majority of our patients with high fetomaternal morbidity when compared to the cholestasis and viral hepatitis patients. while younger women were having viral hepatitis. early diagnosis of the cause and prompt management can improve fetomaternal outcome. references 1. ma k, berger d, reau n. liver diseases during pregnancy. clinc liver dis 2019 may; 23(2):345-361. doi:10.1016/j.cld.2018.12.013. epub 2019 feb 26. 2. zhou dx, bian xy, cheng xy, xu p, zhang yf, zhong jx, et al. late gestational liver dysfunction and its impact on pregnancy outcomes. снn expоbstet gynecol. 2016 jan 1;43(3):417-21. doi: 10.12891/ceog2130.2016 3. keskinkılıç b, engin-üstün y, sanisoğlu s, şahin uygur d, keskin hl, karaahmetoğlu s, et al. maternal mortality due to hypertensive disorders in pregnancy, childbirth, and the puerperium between 2012 and 2015 in turkey: a nation-based study. j turk ger gynecol assoc. 2017 mar 15;18(1):20-25. doi: 10.4274/jtgga.2016.0244. pmid: 28506946; pmcid: pmc5450206.. 4. vasquez dn, plante l, basualdo mn, plotnikow gg. obstetric disorders in the icu. inseminars in respiratory and critical care medicine 2017 apr (vol. 38, no. 02, pp. 218-234). thieme medical publishers. doi: 10.1055/s-0037-1600910 5. yogi l, tan g, chengming s, xuri s. the icu is becoming a main battlefield for severe maternal rescue in china: an 8year single-centre clinical experience. crit care med.2017 jul26. doi: 10.1097/ccm. 6. munazza b, raza n, naureen a, khan sa, fatima f, ayub m, et al. liver function tests in preeclampsia. j ayub med coll abbottabad. 2011 oct-dec;23(4):3-5. pmid: 23472397. 7. gedik e, yücel n, sahin t, koca e, colak yz, togal t. hemolysis, elevated liver enzymes, and low platelet syndrome: outcomes for patients admitted to intensive care at a tertiary referral hospital. hypertension in pregnancy. 2017 jan 2;36(1):21-9. doi: https://doi.org/10.1080/10641955.2016.1218505 8. hafeez m, ansari a, parveen s, salamat a, aijaz a. frequency of intrahepatic cholestasis of pregnancy in punjab pakistan: a single centre study. j pak med assoc. 2016 feb 1;66(2):203-6. 9. sultana r, sarwar i, fawad a, noor s, bashir r. neonatal outcome in obstetric cholestasis patients at ayub teaching hospital abbottabad. journal of ayub medical college abbottabad. 2009 dec 1;21(4):76-8. 10. joutsiniemi t, timonen s, linden m, suvitie p, ekblad u. intrahepatic cholestasis of pregnancy: observational study of the treatment with low-dose ursodeoxycholic acid. bmc gastroenterology. 2015 dec 1;15(1):92. 11. parízek a, simják p, cerný a, sestinová a, zdenková a, hill m, et al. efficacy and safety of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. annals of hepatology. 2017 jan 15;15(5):757-61. doi: https://doi.org/10.1186/s12876-015-0324-0 12. friberg ak, zingmarky, lyndrup j. early induction of labor in highrisk intrahepatic cholestasis of pregnancy: what are the costs? arch gynecol obstet 2016 oct;294(4):709-14. doi: https://doi.org/10.1007/s00404-016-4019-8 13. benova l, awad sf, abu raddad lj. estimate of vertical transmission of hepatitis c in pakistan in 2007 and 2012 birth cohorts. j viral hepat. 2017 jun29. doi: 10.1111/jvh.12748. 14. brohi zp, sadaf a, perveen u. etiology, clinical features and outcome of fulminant hepatic failure in pregnancy. age (years). 2013 sep 15;29(8.404):17-42. 15. chang cy, aziz n, poongkunran m, javaid a, trinh hn, lau d, nguyen mh. serum alanine aminotransferase and hepatitis b dna flares in pregnant and postpartum women with chronic hepatitis b. american journal of gastroenterology. 2016 oct 1;111(10):1410-5. doi: 10.1038/ajg.2016.296. 16. jena p, sheela cn, venkatachala rp, devarbhavi h. obstetric outcome in women with chronic liver disease. the journal of obstetrics and gynecology of india. 2017 aug 1;67(4):263-9. doi: https://doi.org/10.1007/s13224-016-0959-y. 17. anon b, barbet c, gendrot c, labarthe f, bacq y. acute fatty liver of pregnancy and mitochondrial fatty acid oxidation. consequences for the offspring. archives de pediatrie: organe officiel de la societe francaise de pediatrie. 2017 jun 21;24(8):777-82. doi: 10.1016/j.arcped.2017.05.012 18. liu g, shang x, yuan b, han c, wang y. acute fatty liver of pregnancy: analysis on the diagnosis and treatment of 15 cases. the journal of reproductive medicine. 2016;61(5-6):282. 19. mondal br, ahmed s, saha s, perveen si, paul d, sultana t, et al. alanine aminotransferase and total bilirubin concentration in preeclampsia and eclampsia. mymensingh med j. 2016 jan;25(1) 85-90. pmid: 26931255. 20. kozic jr, benton sj, hutcheon ja, payne ba, magee la, von dadelszen p. abnormal liver function tests as predictors of adverse maternal outcomes in women with preeclampsia. journal of obstetrics and gynaecology canada. 2011 oct 1;33(10):9951004. doi: https://doi.org/10.1016/s1701-2163(16)35048-4. 21. mei-dan e, wiznitzer a, sergienko r, hallak m, sheiner e. prediction of preeclampsia: liver function tests during the first 20 gestational weeks. the journal of maternal-fetal & neonatal medicine. 2013 feb 1;26(3):250-3. doi: https://doi.org/10.3109/14767058.2012.733771. 22. türkmen gg, timur h, yilmaz z, kirbas a, daglar k, tokmak a, et al. effect of intrahepatic cholestasis of pregnancy on maternal serum screening tests. journal of neonatal-perinatal medicine. 2016 jan 1;9(4):411-5. doi: 10.3233/npm-161618. 23. ekiz a, kaya b, avci me, polat i, dikmen s, yildirim g. alanine aminotransferase as a predictor of adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. pakistan journal of medical sciences. 2016 mar;32(2):418. doi: 10.12669/pjms.322.9057. 24. jurate k, rimantas z, jolanta s, vladas g, limas k. sensitivity and specificity of biochemical tests for diagnosis of intrahepatic cholestasis of pregnancy. annals of hepatology. 2017 nov 6;16(4):569-73. 25. zhou l, qi hb, luo x. analysis of clinical characteristics and perinatal outcome of early-onset intrahepatic cholestasis of pregnancy. zhonghua fu chan ke za zhi. 2013 jan;48(1):20. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 197-200 197 original article development of fundal varices in cirrhotic patients after eradication of esophageal varices muhammad ajmal, syed muhammad ali shah, mobeen hussain kayani, waqar akhtar department of medicine,aziz bhatti shaheed teaching hospital gujrat abstract background: to analyze the development of fundal varices in cirrhotic patients after eradication of esophageal varices methods: in this observational study 150 patients of liver cirrhosis, with the history of upper gastrointestinal tract bleed and esophageal varices of grade f2 and f3 but absence of fundal varices, were included. patients who had previous history of banding were excluded. results: eighty one (54%) patients were male. mean age of the patients was 49.34±11.45 years. twenty two (14.66%) developed fundal varices of which 2(1.33%) patients developed fundal varices at 2 months, 8(5.33%) patients developed fundal varices at 4 months following banding, and 12(8%) patients developed fundal varices at 6 months following banding of esophageal varices. fourteen (63.63%) patients had gov2 while 8(36.36%) had igv1. conclusion: new fundal varices develop with increasing frequency in patients treated with esophageal variceal band ligation, and the incidence has a time-dependent relationship. key words: fundal varices,cirrhosis, esophageal varices introduction liver cirrhosis and liver related diseases are one of the frequent causes of hospitalization and a major burden on health system. gastric varices are less prevalent than esophageal varices with a higher bleeding incidence for fundal varices. endoscopic variceal band ligation is the recommended form of endoscopic therapy for esophageal variceal bleeding. new incidence of fundal varices is found in 16% of patients after eradication of esophageal varices at follow up of 6 months. liver cirrhosis is the twelfth leading cause of death in usa. liver cirrhosis and liver related diseases are one of the most frequent cause of hospitalization in pakistan and a major burden on health system because of its grave complications and expenses.1 the most common cause of portal hypertension is liver cirrhosis which leads to development of gastroesophageal varices with or without bleeding, ascites, hepatorenal syndrome, and hepatic encephalopathy.2 gastroesophageal varices occur in 50% of cirrhotic patients at a rate of 10% per year. the clinical course of chronic liver disease is complicated by variceal hemorrhage in 30% of cases. with each episode of variceal bleeding the mortality is 20 30%. around 70% of survivors have recurrent bleeding after their first variceal hemorrhage.3 gastric varices are less prevalent than esophageal varices and are present in 25% of patients with portal hypertension with a higher bleeding incidence for fundal varices.4 secondary gastric varices have a significant association with child-pugh class, presenting grade, increasing number of ligation session and prior existence of gastric varices. 5 the commonly used classification system introduced by sarin comprises of four types of gastric varices based on gastric location and relationship with esophageal varices. gastro-esophageal varices (gov) either are an extension of esophageal varices for 2 to 5 cm along the lesser curve of the stomach (gov1) or extend along the greater curve into the fundus (gov2). 6 isolated gastric varices (igv) are located either in the fundus (igv1) or in other parts of the stomach (igv2). gov1 account for 74% of all gv, but the incidence of bleeding is highest with fundal varices (igv1 and gov2).4-8 endoscopic therapy is recommended in any patient who presents with upper gi bleeding. endoscopic variceal band ligation (evbl) is the recommended form of endoscopic therapy for acute esophageal variceal bleeding, although sclerotherapy may be used in the acute setting if ligation is technically difficult. endoscopic therapy with tissue adhesive (e.g. n-butylcyanoacrylate) is recommended for acute bleeding from isolated gastric varices (igv) and those gastroesophageal varices, type 2 (gov2), that extend beyond the cardia. evbl or tissue adhesive can be used in bleeding from gastro esophageal varices type 1 (gov1).8,9 journal of rawalpindi medical college (jrmc); 2017;21(3): 197-200 198 one local study suggests that new incidence of fundal varices is found in 16% of patients after eradication of esophageal varices at follow up of 6 months while presence of fundal varices at presentation before eradication was 7.4%.(5) another local study suggested the presence of fundal varices to be in 3.1% patients at presentation for upper gi endoscopy but no follow-up after eradication of esophageal varices was done.8 patients and methods this observational study was conducted at department of medicine, aziz bhatti shaheed teaching hospital gujrat from 15-06-15 to 15-03-17 . sample size was calculated to be 150 patients using 95% confidence level with 5% margin of error with an expected percentage of new fundal varices in 16% of patients after band ligation.5 non-probability consecutive sampling method was used and patients who had liver cirrhosis with the history of upper gi bleed and esophageal varices of grade f2 and f3 but absence of fundal varices on endoscopy were included in study. patients who refused to consent and who had previous history of banding were excluded from study. severity of liver disease was noted and was graded using child pugh score. patients with score of 5-6 were defined as child class a, 7-9 as child class b and 10-15 as child class c. cirrhosis was defined as moderate to severely coarse echotexture of liver on abdominal ultrasound. spleen size, presence of ascities and liver span were also noted. the dilated veins above the lower esopheageal sphincter found during endoscopy were considered as esophageal varices. gastric varices were classified according to classification described by sarin et al.6 out of gastric varices gastroesophageal varices type 2 (gov2) and isolated gastric varices type 1 (igv1) were considered as fundal varices as they are located in fundus of stomach.after initial resuscitation, the stabilized patients were admitted in the ward. a full history and examination was done and the patients were prepared for an elective endoscopy list. all baseline investigatioons were done and noted and child pugh score was calculated. consent was taken, upper gi endoscopy and band ligation was done by the consultant gastroenterologist. performa were filled by concerned doctor, and the patients were examined at regular interval of two months during study duration for a period of 6 months. those patients who developed fundal varices either at second or fourth month were not further followed and were included in our results. the presence or absence of fundal varices and the minimum time to develop fundal varices were recorded. all data were entered into a predesigned performa. results out of 150 patients, 81 patients (54%) were male and remaining 69 patients (46%) were female. mean age of the patients was 49.34±11.45 years. majority patients (70%) were 41-60 years of age (table 1) . only one patient (0.6%) was between 81-100 years of age. 55 patients were child class a, 67 child class b and 28 were child class c. mean hemoglobin was 7.62 ± 3.12 g/dl, mean platelet count was 79 ± 69 x 109/l, mean albumin was 3.2 ± 2.1 g/dl and mean bilirubin was 1.78±1.21 mg/dl. mean liver size was 12.13 ± 4.34 cm, mean spleen size 11.67 ± 3.11 cm and ascities and esophageal varices were present in all patients. f3 esophageal varices were present in 52.67% patients but none of patients had fundal varices (table 2). table 1: distribution of patients in age groups age (years) no(%) 20-40 27(18) 41-60 105(70) 61-80 17(11) table 2: patient characteristics total number of patients (n) 150 patients gender -male: 81 (54%) -female: 69 (46%) mean age 49.34±11.45 years mean hemoglobin (g/dl) 7.62 ± 3.12 mean platelet count (109/l) 79 ± 69 mean albumin (g/dl) 3.2 ± 2.1 mean bilirubin 1.78 ± 1.21 mean liver size (cm) 12.13 ± 4.34 mean spleen size (cm) 11.67 ± 3.11 ascites 150 (100%) esophageal varices 150 (100%) grades of esophageal varices at presentation f2 = 71 (47.33%) f3 = 79 (52.67%) number of sessions required for eradication of esophageal varices 3+2 sessions fundal varices at presentation none (0%) child pugh class -child class a= 55 (36.67%) -child class b =67 (44.67%) -child class c= 28 (18.66%) journal of rawalpindi medical college (jrmc); 2017;21(3): 197-200 199 table 3. frequency of fundal varix formation following esophageal variceal banding follow-up duration number percentage gov2 igv1 2 months 2 1.33% 2 0 4 months 8 5.33% 5 3 6 months 12 8% 7 5 total 22 16% 14 8 twenty two (14.66%) developed fundal varices. of these 12 patients (8%) developed fundal varices at 6 months following banding of esophageal varices (table 3). out of these 22 patients 14(63.63%) had gov2 while 8(36.36%) had igv1.there was no age corelation found (p-value 6.9) with the development of fundal varices in patients who were banded for esophageal varices. discussion gastric varices are less prevalent than esophageal varices and are present in approximately 25% of the patients with portal hypertension.4 eradication of esophageal varices has been identified as a risk factor for the development of fundal varices. this can be explained by the gastric hemodynamic changes that result from the blockage of shunting in the palisade zone and the formation of “new” or “secondary” gastric varices.5 yuksel et al found that 37 out of 85 patients had fundal varices before they underwent ligation of esophageal varices, increasing to 46 observed at 3 month follow up endoscopy after the procedure, a statistically significant increment of almost 10.59% after eradication. the severity of portal hypertensive gastropathy also increased.10 our study demonstrates a higher incidence at six months duration as to this study which reflects that formation of fundal varices is time dependent. in a large reterospective study by mumtaz et al. comprising 1436 patients, gastric varices were present in 220 (15%) patients at presentation. 12 secondary gastric varices were found in 23% of patients within 6 months after eradication of esophageal varices as compared to 14.66% of fundal varices in our study. this discrepancy may be due to small sample size in this study and that they included all types of gastric varices in their as compared to only fundal varices in this study. korula et al. in their 7 years follow up of patients receiving endoscopic sclerotherapy for variceal hemorrhage found fundal varices in 4.1% cases only. 13 method used for bleeding control in their study was sclerotherapy as compared of evbl in this study. there is also a difference in sample size and ethnic group. available local study has determined that the frequency of occurrence of secondary gastric varices six months after endoscopic variceal band ligation which approximated to 16.04%.5 our study demonstrated a similar result of 14.66% overall occurrence of fundal varices following esophageal variceal band ligation but in comparison our study has established that fundal varices develop as early as 2 months after band ligation of esophageal varices. in another local study by naseer et al. the frequency of fundal varices was found to be 3.1% in patients presenting for endoscopy. 8it is much less than our results(14.66%). they did not follow the patients after eradication of esophageal varices to determine the incidence after evbl which is hallmark of this study. the frequency of new fundal varix formation at two months was 1.33%, seen in only 2 patients out of a hundred and fifty patients being followed. at four months of follow up 8 other patients developed fundal varices, representing 5.33% of the study population. six months after esophageal variceal band ligation, another 12 patients (8%) who had been banded for esophageal varices developed fundal varices. our study thus comes as a first in reporting the development of new fundal varices in relation to time since banding. therefore, in order to screen for new fundal varices, patients must be subjected to an endoscopic surveillance program. according to our results, the frequency of occurrence, and the probability of developing a fundal varix was time dependant. however, there was no predilection for the development of fundal varices after esophageal variceal band ligation in any particular age group, nor does the sex of the patient predispose to increased incidence of developing a fundal varix. since limited data exists with regard to the development of new fundal varices following esophageal banding, there is plenty of space for future research, and studies are required with a larger patient pool, and with same expert endoscopist for the particular period of research. studies can also be done to observe the frequency of formation of fundal varices after esophageal banding in comparison with controls, and also in patients treated with beta-blockers. conclusion 1. new fundal varices develop with increasing frequency in patients treated with esophageal variceal band ligation, and the incidence has a time-dependent relationship. journal of rawalpindi medical college (jrmc); 2017;21(3): 197-200 200 references 1. shah sma, mashia sa, younus mf, ghauri a, ejaz r, alshalabi h et al hepatic cirrhosis-disease burden. j. rawalpindi med. coll 2015;19:17-20. 2. al-busafi sa, ghali p, wong p, deschenes m. endoscopic management of portal hypertension. inter j of hepa. 2012:1-12. 3. mehta g, abraldes jg, bosch j. developments and controversies in the management of oesophageal and gastric varices. gut 2010 ; 59(6):701-05. 4. sarin sk, mishra sr. endoscopic therapy for gastric varices. clin liver dis 2010 ;14:263-79. 5. samiullah s, memon ms, memon hg, ghori a. secondary gastric varices in hepatic cirrhosis. j coll physicians surg pak. 2011 oct;21(10):593-96. 6. sarin sk. long-term follow-up of gastric variceal sclerotherapy: an eleven-year experience. gastrointest endosc1997;46:8-14. 7. song wk. management of gastric varices. clinical liver disease. 2012 ;1(5):158-62. 8. naseer m, khan a, yasmeen r, gillani fm, saeed f. determination of frequency and treatment outcome in patients of fundal varices presenting with upper gastrointestinal bleeding. pak arm forces med j. 2012 ;48386. 9. franchis r. revising consensus in portal hypertension: report of the baveno v consensus workshop on methodology of diagnosis and therapy in portal hypertension. j of hepa. 2010;53:762–68. 10. yuksel o, koklu s, arhan m, yolcu of, ertugrul i. effects of esophageal varices eradication on portal hypertensive gastropathy and fundal varices: a retrospective and comparative study. dig dis sci 2006;51:27-30. 11. mumtaz k, majid s, shah ha, hameed k, ahmed a. prevalence of gastric varices and results of sclerotherapy with n-butyl 2-cyanoacrylate for controlling acute gastric variceal bleeding. world j gastroenterol 2007; 13:1247-51. 18. 12. korula j, chin k, ko y, yamada s. demonstration of two distinct subsets of gastric varices: observations during a seven-year study of endoscopic sclerotherapy. dig dis sci 1991; 36:303-09. 395 journal of rawalpindi medical college (jrmc); 2020; 24(4): 395-399 original article a clinico-mycological spectrum of superficial mycoses of the scalp in the paediatric population faiza zeeshan1, fakhur uddin2, bahram khan3, talat zehra4, sadaf razzak5, zareen irshad6 1,4,5 lecturer, department of pathology, jinnah sindh medical university, karachi. 2 medical technologist, basic medical sciences institute, jinnah postgraduate medical centre, karachi. 3 professor and head of the department, dermatology, jinnah postgraduate medical centre, karachi. 6 assistant professor, department of pathology, jinnah sindh medical university, karachi. author’s contribution 1,2,3,4,5,6 conception of study 1,2,3,4,5,6 experimentation/study conduction 1,2,3,5,6 analysis/interpretation/discussion 1,5,6 manuscript writing 1,2,3,4 critical review 1,4 facilitation and material analysis corresponding author dr. faiza zeeshan, lecturer, department of pathology, jinnah sindh medical university, karachi email: dr.faizazeeshan@gmail.com article processing received: 10/09/2020 accepted: 24/12/2020 cite this article: zeeshan, f., uddin, f., khan, b., zehra, t., razzak, s., irshad, z. a clinico-mycological spectrum of superficial mycoses of the scalp in the paediatric population. journal of rawalpindi medical college. 30 dec. 2020; 24(4): 395-399. doi: https://doi.org/10.37939/jrmc.v24i4.1476 conflict of interest: nil funding source: nil access online: abstract introduction: a clinico-mycological study was conducted to assess the profile of dermatophytes and nondermatophytes in patients with superficial mycoses of the scalp. material and methods: this descriptive cross-sectional study was conducted at the department of microbiology, basic medical sciences institute, in collaboration with the department of dermatology, jinnah postgraduate medical centre, karachi. the study was carried out from may 2019 to september 2019. a total of 114 children were enrolled in the study having a clinical diagnosis of superficial mycoses of the scalp. the hair specimens and scales from the scalp were collected by using sterilized forceps and a scalpel on a piece of filter paper. the specimens were processed for wet mounts (koh and cfw staining) and mycological culture on sabouraud’s dextrose agar (sda, with and without antibiotics) and dermatophyte test medium (dtm). results: the most common clinical presentation was found to be dermatophytoses (28.4%). non-dermatophytoses was seen in 16.41% of cases, while 55.2% of cases were culture negative. the most common isolated dermatophyte was trichophyton violaceum (334.35 5.4%), while among non-dermatophyte molds, aspergillus spp. accounted for 45% of cases. conclusion: tinea capitis in children is mostly caused by dermatophytic species but the role of nondermatophytes cannot be neglected the unambiguous diagnosis of scalp mycoses can be made by mycological culture and conventional techniques like koh mounts and cfw staining. the knowledge of the mycological spectrum of a disease is not only required for clinical management but it also signifies the local disease burden. keywords: calcofluor white stain, dermatophytes, koh mount, tinea capitis. 396 journal of rawalpindi medical college (jrmc); 2020; 24(4): 395-399 introduction superficial mycoses are the fungal infections of the skin, hair, and nail which are confined to the topmost layers of skin and its appendages. it is estimated that superficial mycoses constitute about 7-15% of childhood cutaneous infections.¹ the mycoses of the scalp are mainly amalgamated with tinea infections, commonly termed as tinea capitis. the tinea capitis is primarily associated with dermatophytes, while yeast and non-dermatophyte molds of anthropophilic and zoophilic origin are also found to be causative agents, but to a lesser extent.² tinea capitis and other superficial mycotic infections of the scalp are mostly seen in children, followed by adolescents and being relatively uncommon in adults.³ the superficial mycotic infections of the scalp were once considered as diseases of overcrowded and fiscally constrained populations of tropical and sub-tropical regions, but due to the changing dynamics of world population, the dermatomycoses of the scalp have spread to the entire globe. hence, the global prevalence of tinea capitis is in constant momentum. the etiologic agents of tinea capitis are trichophyton and microsporum species of dermatophytes. the species of dermatophytes which are involved in tinea capitis varies geographically. in the united kingdom, the united states of america, and canada t. tonsurans is the main causative agent. the situation in asian countries is somewhat discrete, as t. violaceum and t. mentagrophytes are found to be the culprit organisms. the lesions in tinea capitis are proportionally related to the causative species. the inflammatory types of lesions are predominantly seen with t.violaceum, t.tonsurans, t.mentagrophytes, t. rubrum, and some zoophilic species.4-5 the non-inflammatory lesions are observed in anthropophilic species but super-imposed bacterial infections can trigger inflammation.4 the clinical presentation of dermatomycoses ranges from dandruff, pruritus, and patchy alopecia to grey patches, black dots, pustules, and kerion. the tinea capitis often mimics alopecia areata, seborrheic dermatitis, psoriasis, and bacterial folliculitis, making its diagnosis complicated and confounding, therefore laboratory confirmation is a mandatory requirement. the laboratory diagnosis of fungi involves conventional as well as classical methods. wet mounts with 10% potassium hydroxide (koh), calcofluor white (cfw), and lactophenol cotton blue (lpcb) mount are among conventional methodologies, on the other hand, mycological culture is a classical gold standard diagnostic method, which yields fungus at the species level.5 the newer molecular techniques like polymerase chain reaction (pcr), matrix-assisted laser desorption/ionization mass spectrometry (malditof-ms) have become a benchmark in fungal diagnosis but their associated cost has made them an unaffordable technique in developing countries like pakistan. this study emphasizes the clinical presentation of scalp mycoses and the epidemiology of various species of dermatophytes and nondermatophytes among study subjects. materials and methods this cross-sectional study was conducted at the department of microbiology, department of microbiology, basic medical sciences institute, in collaboration with the department of dermatology, jinnah postgraduate medical centre, karachi. a total of 114 children under the age of 10 years, belonging to both genders were enrolled, who were clinically diagnosed as cases of superficial dermatomycoses (tinea capitis). the hair was collected by using sterilized forceps and scales were scraped from the skin with the help of a blunt scalpel on a glass slide.6 the specimens were packed in sterilized filter paper and were properly labeled with the subject’s details. half part of each sample of the specimens was immersed in 10% potassium hydroxide (koh) and was examined under the light microscope on low power objectives. simultaneously, calcofluorour white (cfw) staining was performed to visualize fungal elements under a fluorescent microscope. the samples were said to be positive if they show any sign of fungal hyphae or spores with fluorescent apple green colour. the remaining part of each specimen was inoculated on vials of sabaouraud’s dextrose agar (sda) with and without antibiotics (cycloheximide, chloramphenicol, and gentamicin) and dermatophyte test medium (dtm). the vials were observed daily for one week and then a periodical check was made for the presence of growth, colony morphology, pigmentation, and pigmentation on the reverse. the species were identified on lactophenol cotton blue (lpcb) mount, slide culture, and urease test. the vials which failed to show any significant growth within thirty days were considered as growth negative. data were analyzed on the statistical package for social sciences (spss), version 21. the frequencies were calculated by descriptive statistics, the association was found out by using the chi-square test, kappa statistics were used to determine the level of agreement between the tests. 397 journal of rawalpindi medical college (jrmc); 2020; 24(4): 395-399 results the mean age of children was found to be 7.01 ± 2.3 years with a male to female ratio of 1.28:1 (64/50). almost all patients belong to the low-income group 113 (99.1%). around 15.7% of subjects had a positive family history along with the habit of sharing common household items among family members. cervical and occipital lymph nodes were found to be enlarged in 43 (37.7%) children. a significant association was observed between culture positivity and lymph node enlargement when calculated by the chi-square test (p-value=0.001). the mean duration of illness among study subjects was found to be 3.39 ± 0.23 months. a majority of patients 96 (84.2%), presented with multiple complaints, the most common set of the clinical presentation was alopecia 72 (63.1%), dandruff 64 (56.1%), and pustules 56 (49.1%). about 21 (18.4%) subjects had a history of relapse of the same types of lesions. a substantial number of 69 (60.5%) patients have previously used either standard medical treatment, complementary treatment, or both to cure the ailment. the 74.6% were found to be fungal positive on koh mounts, while fluorescent microscopy gave 81.6% fungal positivity. the culture was found to be least sensitive, being positive in just 44.7% of cases. the most common isolated dermatophyte species was t. violaceum (34.35%), on the other hand, among nondermatophytes, aspergillus spp. (45%) topped the list. about 55.2% of cases showed no considerable fungal growth and were considered negative. table 1: demographic characteristics of the study population demographic feature mean ± sd/ n (%) gender male 64 (55.6) female 50 (43.85) age 7.01 ± 2.3 socioeconomic group low 113 (99.1) medium 1 (0.9) high mean duration of illness 3.39 ± 0.23 months complaints single 18 (15.8) multiple 96 (84.2) relapse cases 21 (18.4) previous treatment taken yes 69 (60.5) no 45 (39.47) table 2: association of lymph node enlargement and culture positivity enlarged lymph nodes culture result p-value positive negative cervical 26 6 0.001* occipital 7 4 total 33 10 *p-value less than 0.05 is considered significant table 3: comparison between direct microscopic techniques and culture test result direct microscopic techniques cult ure % pvalue kapp a index cfw staining % koh mount % 0.001 * 0.795 ** positive 74.6 81.6 44.7 negative 25.4 18.4 55.3 *p-value <0.05 is considered significant ** kappa index range for substantial agreement is 0.610.80 table 4: distribution of various species of dermatophytes and non-dermatophytes isolated fungi frequency n (%) dermatophytes t. violaceum t. mentagrophytes t. tonsurans t. soudananse m. canis m. gypseum 11 (34.35) 9 (28.12) 4 (12.54) 3 (9.37) 3 (9.37) 2 (6.25) non-dermatophytes 9 (45.0) 3 (15.0) 3 (15.0) 3(15.0) 1 (5.0) 1 (5.0) aspergillus penicillium alternaria curvularia candida mucor discussion the study was conducted to determine the clinical and mycological profile of dermatomycoses of the scalp among children, which is a frequent complaint recorded in the paediatric outpatient department. table 1 illustrated the demographic details of the study population. our study demonstrated that the mean age of children was about 7.01 ± 2.3 years. this 398 journal of rawalpindi medical college (jrmc); 2020; 24(4): 395-399 is in accordance with the study by farooqi et al.7 the children of this age are normally attending school or madrasa, therefore, they are more prone to contract fungal infections as the fungus has a propensity to disseminate via spores and can be transferred from one person to another. the study showed a slight male preponderance with a male to female ratio of 1.28:1. males have short hair and they tend to catch fungal infections more conveniently than females, as most of the female children in our society braid and tie up their hair, hence the female participants showed a comparatively lower level of fungal infestation.8 the dermatomycoses are generally considered as the disease of poverty, and our study reinforces the theory as the majority of children fall in low socio-economic strata. sharing of common household items like combs, hair-brushes, head-scarves, caps, hats, and pillows were seen in 15.7% of cases, a similar number of cases showed a positive family history of scalp lesions, indicating that fungus shows ping pong mechanism of transmission. our observation was in agreement with basyouni et al who reported the same results.10 multiple complaints were observed in children; the most frequently observed feature was patchy alopecia, seen in 63.1% cases, followed by dandruff and pustules, which were recorded in 56.1% and 50% patients respectively, although puri and puri documented black dot as the most common recorded complaint.9 another worth noticing characteristic was an association of enlarged lymph nodes with culture positivity, (p-value=0.001). it stipulated that enlarged cervical and occipital lymph nodes in superficial scalp mycoses are considerably related to the presence of fungal elements. our finding shows a complete agreement with fernandez et al, who have also elucidated the same association.11 the specimens were examined under light and fluorescent microscopes to dig out the presence or absence of fungal spores and hyphae. the sensitivity of koh wet mount and cfw mount was found to be 74.6% and 81.6% respectively. a substantial degree of agreement was observed between two tests, calculated by kappa index (k=0.795). our findings were in agreement with bonifaz et al who reported the kappa index of 0.808; however, gupta et al reported contradictory results, documenting 31.1% positive cases with microscopic methods.12,13 the effectiveness of microscopic techniques in detecting fungal pathogens carries a crucial role as these techniques are low budgeted and comparatively less time-consuming than culture. according to our study, culture was found to be the least sensitive in detecting fungal pathogens. about 44.1% of cases were culture positive, among them, dermatophytes were the predominating isolates (28%). t.violaceum was the most common isolated dermatophyte; similar results have been documented by zehn et al and puri and puri, but farooqi et al have reported t. soudananse as the main causative dermatophyte.13,10,8 non-dermatophytes were also identified in scalp lesions and aspergillus spp were the most common species identified, as shown in table 4. our results were in accordance with the work done by khaled et al and kaur et al, who have presented the same findings.16,15 although dermatophytes are found to be primary offenders in tinea capitis, the role of non-dermatophytes cannot be overlooked. conclusion tinea capitis is one of the most common dermatological complaints in the paediatric outpatient department. the clinico-mycological spectrum of disease highlights the disease burden in the local community. the knowledge of fungal species is related to their clinical manifestation, hence helping clinicians in making the diagnosis and related treatment. references 1. akbas a, kilinc f, yakut i, metin a. superficial fungal infections in children. medical science and discovery.2016 jul; 3(7):280-5. 2. bassyouni rh, el-sherbiny na, el raheem a, talal a, mohammed bh. changing in the epidemiology of tinea capitis among school children in egypt. annals of dermatology. 2017 feb 1;29(1):13-9. 3. el-khalawany m, shaaban d, hassan h, abdalsalam f, eassa b, abdel kader a, shaheen i. a multicenter clinicomycological study evaluating the spectrum of adult tinea capitis in egypt. acta dermatovenerol alp pannonica adriat. 2013 dec;22(4):77-82. 4. zaraa i, hawilo a, aounallah a, trojjet s, el euch d, mokni m, osman ab. inflammatory tinea capitis: a 12‐year study and a review of the literature. mycoses. 2013 mar;56(2):110-6. 5. dass sm, vinayaraj e, pavavni k, pallam a, rao ms. comparison of koh, calcofluor white and fungal culture for diagnosing fungal onychomycosis in an urban teaching hospital, hyderabad. indian j microbiol res. 2015;2(3):148-53. 6. khalid m. laboratory diagnosis of the causative dermatophytes of tinea capitis. world j. pharm. res.2019;8(6):85-90 7. farooqi m, tabassum s, rizvi da, rahman a, awan s, mahar sa. clinical types of tinea capitis and species identification in children: an experience from tertiary care centres of karachi, pakistan. j pak med assoc. 2014 mar 1;64(3):304-8. 8. sy o, diongue k, ba o, ahmed cb, elbechir ma, abdallahi ms et al. tinea capitis in school children from mauritania: a comparative study between urban and rural areas. journal de mycologie médicale. 2020; 13:101048. 399 journal of rawalpindi medical college (jrmc); 2020; 24(4): 395-399 9. bassyouni rh, el-sherbiny na, el raheem a, talal a, mohammed bh. changing in the epidemiology of tinea capitis among school children in egypt. annals of dermatology. 2017 feb 1;29(1):13-9. 10. puri n, puri a. a study on tinea capitis in the pre school and school going children. our dermatology online/nasza dermatologia online. 2013 apr 1;4(2). 11. fernandes s, amaro c, da luz martins m, inácio j, araújo t, vieira r, silvestre mj, cardoso j. kerion caused by microsporum audouinii in a child. medical mycology case reports. 2013 jan 1;2:52-4. 12. bonifaz a, rios-yuil jm, arenas r, araiza j, fernández r, mercadillo-pérez p, ponce-olivera rm. comparison of direct microscopy, culture and calcofluor white for the diagnosis of onychomycosis. revista iberoamericana de micología. 2013 apr 1;30(2):109-11. 13. gupta ak, zaman m, singh j. diagnosis of trichophyton rubrum from onychomycotic nail samples using polymerase chain reaction and calcofluor white microscopy. journal of the american podiatric medical association. 2008 may;98(3):224-8. 14. zhan p, li d, wang c, sun j, geng c, xiong z, seyedmousavi s, liu w, de hoog gs. epidemiological changes in tinea capitis over the sixty years of economic growth in china. medical mycology. 2015 aug 10;53(7):691-8. 15. khaled jm, golah ha, khalel as, alharbi ns, mothana ra. dermatophyte and non dermatophyte fungi in riyadh city, saudi arabia. saudi journal of biological sciences. 2015 sep 1;22(5):604-9. 16. kaur i, thakur k, sood a, mahajan vk, gupta pk, chauhan s, jaryal sc. clinico-mycological profile of clinically diagnosed cases of dermatophytosis in north india: a prospective crosssectional study. int j health sci res. 2016;6:54-60. 94 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 94-99 original article impact of covid-19 on ophthalmologists wajeeha rasool1, kanwal zareen abbasi2, maria zubair3, misbah munshi4, rehmah sarfraz5, fuad a k niazi6 1,3,4 senior registrar, department of ophthalmology, benazir bhutto hospital, rawalpindi. 2 associate professor, hbs medical college, islamabad. 5 professor, department of anatomy, islamabad medical & dental college, islamabad. 4 professor, department of ophthalmology, rawalpindi medical university, rawalpindi. author`s contribution 1,2 conception of study 1,2,3,4,5,6 experimentation/study conduction 1,3,4 analysis/interpretation/discussion 1 manuscript writing 5 critical review corresponding author dr. wajeeha rasool senior registrar, department of ophtalmology, benazir bhutto hospital, rawalpindi email: drwajeeharasool@gmail.com article processing received: 03/05/2021 accepted: 12/08/2021 cite this article: rasool, w., abbasi, k.z., zubair, m., munshi, m., sarfraz, s., niazi, f.a.k. impact of covid-19 on ophthalmologists. journal of rawalpindi medical college. 31 aug. 2021; 25 covid-19 supplement-1, 94-99. doi: https://doi.org/10.37939/jrmc.v25i1.1653 conflict of interest: nil funding source: nil access online: abstract objective: to determine the effects of the covid-19 pandemic on the professional lives of ophthalmologists. introduction: this survey aims to determine the effects of the covid-19 pandemic on the professional lives of ophthalmologists. the summative opinion of ophthalmologists can help to build an evolving better standard operative procedures for safe ophthalmic practices, later translated into policies. materials and methods: this cross-sectional survey was conducted for 6 months, july 2020 to december 2020, and used google forms for data collection. it was a descriptive, cross-sectional survey conducted (after synopsis, approval by erc, rmu).a likert questionnaire was developed , later converted into a google survey form, and sent via whatsapp to ophthalmologists (consultants and residents) of both government and private sectors (accompanied by an introduction, dept. correspondence, and reminders) results: the final assembled data sheet was generated by google sheets.a total of 68 respondents gave their likert responses for each of the 20 statements). the ordinal data was coded, and entered into an excel sheet. the median, mode, and interquartile range (iqr), of all respondent's likert sentiments for each statement (s), were calculated by excel and assembled. surprisingly the survey results showed a trend of ‘general consent and consensus’ over the statements (high central tendency and low dispersion with iqr-1 conclusion: the survey was small-scale yet clear-cut. the results showed compliance towards statements and harmony amongst opinions, thus endorsed that covid-19 has a definitive impact on the professional lives of ophthalmologists covid-19 has influenced the professional lives of ophthalmologists. keywords: covid-19, ophthalmologists. 95 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 94-99 introduction coronavirus disease (covid-19) is a highly infectious disease caused by acute respiratory distress syndrome coronavirus 2, also called (sars-cov-2).1 this virus spreads through close contacts and the droplets produced during coughing and sneezing become the reason for its spread.2 the virus started in wuhan city of china and till now has spread to 220 countries of the world including pakistan.3 till may 4, 2020, more than 3 million cases of covid 19 have been reported and the world health organization has declared this disease a pandemic.3 during this pandemic, the health professionals being the front liners are bearing the brunt of the burden.4 it is very obvious that ophthalmologists, due to the close contact nature of their work, are at higher risk of getting infected with covid-19.5 all doctors including the ophthalmologists need protection and support both mentally and physically.6 this survey aims to determine the effects of the covid-19 pandemic on the professional lives of ophthalmologists. the summative opinion of ophthalmologists can help to build an evolving better standard operative procedures for safe ophthalmic practices, later translated into policies. materials and methods it was a descriptive, cross-sectional survey conducted (after synopsis, approval by erc, rmu), from july 2020 to december 2020. a likert questionnaire was developed , later converted into a google survey form, and sent via whatsapp to ophthalmologists (consultants and residents) of both government and private sectors (accompanied by an introduction, dept. correspondence, and reminders). the sample size was not predetermined. sampling was done via simple random. results the final assembled data sheet was generated by google sheets. a total of 68 respondents participated in the study. numbers (n) and averages (%) of each likert sentiment, for each of the 20 statements (s) were calculated and displayed by google forms (figure 1), compiled in table 1. further, the ordinal data was coded, and entered into an excel sheet. the median, mode, and interquartile range (iqr), of all respondent's likert sentiments for each statement (s), were calculated by excel and assembled. (median and mode were chosen to measure central tendency while iqr to measure dispersion. iqr is the difference of the value of the 3rd and 1st quartile i.e, q3 and q1 respectively). median values showed that the respondents: “agreed” in twelve statements, “strongly agreed” in four statements “neutral” in two statements “disagreed” in two statements median and mode values for all statements remained the same, except for statement 19. the prevalent lower iqr values (1,0) suggest strong consensus among respondent's opinions (clustering). only three statements showed slight polarised respondent's opinions (iqr 2). two respondents gave their own opinions for statements 9 and 20. one respondent did not respond at all. few missed responses were also noted (s-4, 8, 19, 20). 96 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 94-99 table 1: numbers (n.). and averages (%) of sentiment, for each statement (s) s respondent sentiment strongly agree agree neutral disagree strongly disagree no answer n. % n. % n. % n. % n. % n. % 1 37 54.41 21 30.88 4 5.88 4 5.88 1 1.47 1 1.47 2 19 27.94 38 55.88 5 7.35 4 5.88 1 1.47 1 1.47 3 2 2.94 5 7.35 13 19.12 28 41.18 19 27.94 1 1.47 4 20 29.41 26 38.24 14 20.59 5 7.35 1 1.47 2 2.94 5 5 7.35 30 44.12 24 35.29 8 11.76 5 7.35 1 1.47 6 4 5.88 35 51.47 16 23.53 11 16.18 1 1.47 1 1.47 7 6 8.82 33 48.53 21 30.88 6 8.82 1 1.47 1 1.47 8 8 11.76 27 39.71 13 19.12 15 22.06 3 4.41 2 2.94 9 9 13.24 33 48.53 12 17.65 12 17.65 1 1.47 1 1.47 10 35 51.47 28 41.18 2 2.94 2 2.94 0 0 1 1.47 11 46 67.65 19 27.94 2 2.94 0 0 0 0 1 1.47 12 16 25.53 33 48.53 10 14.71 7 10.29 1 1.47 1 1.47 13 31 45.59 34 50 2 2.94 0 0 0 0 1 1.47 14 43 63.24 22 32.35 2 2.94 0 0 0 0 1 1.47 15 3 4.41 12 17.65 10 14.71 28 41.18 14 20.59 1 1.47 16 18 26.47 35 51.47 11 16.18 3 4.41 0 0 1 1.47 17 16 23.53 41 60.29 5 7.35 4 5.88 1 1.47 1 1.47 18 15 22.06 38 55.88 12 17.65 2 2.94 0 0 1 1.47 19 2 2.94 11 16.18 21 30.88 26 38.24 5 7.35 3 4.41 20 6 8.82 20 29.41 22 32.35 14 20.59 3 4.41 3 4.41 97 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 94-99 figure 1: pie chart showing number and percentage of the respondent’s sentiments for statements 01-20 98 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 94-99 discussion the extent of participation was less than expected, despite repeated requests. this points towards a general lack of interest in survey participation. statements from 1 to 8 were related to effects of covid on job and training of ophthalmologists in our survey, 54.41% of respondents believed that clinical and surgical skills are being affected. ferrara et al have given alarming figures of residents and fellows unable to perform cataract surgery. for that matter, our respondents agreed (55.88%) with the notion that training doctors need extra time to cover up their deficiencies. such prolonged delay during training will fail in clinical and surgical skill development so the extension of training is justifiable.7 the majority of the respondents (41.18%) did not consider the distant learning program as a substitute to practical clinical work, however, ting et al. are hopeful that virtual clinics and telemonitoring are helpful educational tools for distant learning of clinical skills.8 this in away depicts that our respondents understand that developing countries cannot bear these fancy options. 38% agreed that wet labs can help in improving surgical skills. in the western world, simulation-based models, especially eyesi surgical simulator have been adopted effectively for cataract surgery training.9 slight polarised opinion (iqr 2) in this regard can be related to the availability of such tools in our setups. but surgical telementoring,10, and surgical recorded videos are still a great help. 44.12% of respondents supported that there will be an improvement in theoretical knowledge. particularly the e-learning has given satisfactory results11. rather a concept of virtual curriculum in ophthalmology education has emerged.12 51.4% of respondents believed that there will be a rise in the trend towards research article writing. however strangely, anderson et al have found that in 2020 women had contributed less in covid-19 papers writing as the first author, as compared to 2019.13 many respondents (48.53%) admit the risk of downsizing in the health sector. this can be in reaction to news related to furloughing hospital workers in other countries, those not involved directly in patient care.14 39.71% of respondents believed that exams should be postponed. this can be a genuine demand also, as globally residency exams have repeatedly cancelled, with or even without an alternate date.15 statements from 9-15 were related to workplace concerns during the covid-19 pandemic. 48.5% of respondents agreed that their will to work in the hospital has reduced, but despite all the uncertainty and fear mostly ophthalmologists had to keep their practices afloat.16 this is very much true that compared to last year ophthalmologists are more composed now. 51.47% of respondents strongly believe that a hospital is a high-risk place for getting covid. in a recent case series, nearly 44% of the 179 covid cases were hospital-acquired.17 the highest i.e, 67.75% of respondents strongly agreed that slit lamp and fundus examination highly increases the risk of getting covid. ophthalmologists have close contact with the patient, so exposure to respiratory droplets (greater extent), and conjunctival secretions (lesser extent),18 impose great threat of transmitting sarscov-2. lacorzana j reported of 16% of ophthalmologists turning covid seropositive.19 48.53% of respondents agreed that focusing during ophthalmic examination is reduced. the reason for this withdrawal is multifactorial but depression has been found to be the one.20 45.59% of respondents strongly support that ppe makes ophthalmic practice difficult. although ppe has a vital role in protection tedious ppe doffing has resulted in tiredness which further leads to improper operations and high infection risk21. 63.24% of respondents strongly agreed that their family members are at risk of getting covid due to their profession. but fortunately, health workers were not found to be the main source of transmitting covid to families.22 41.18% of respondents disagree with the idea of leaving the job and show optimism, despite ophthalmology practice being badly affected globally.23 statements 16 to 20 were related to patient care 51.47% of our respondents agreed that patient care during covid-19 has deteriorated. the reason was curtailed ophthalmic practice worldwide.24 60.29% of respondents agreed that vision loss due to preventable ocular disease will rise. nearly 75% of vision loss is claimed to be treatable, but the disruption in the provision of eye care, especially in developing countries, is likely to lead to precious vision losses at a large scale.25 55.88% of respondents remained unsatisfied over the quality of clinical work and the reasons are multiple.20,21 38.24% of respondents disagree about the positive role of telemedicine in eye patient care. but in a recent pilot study, arntz et al. have given a very high-level satisfaction of both ophthalmologists and patients over ophthalmic telemedicine consultations.26 32.35% of respondents were neutral (slightly low consensus), over discouraging patient visits to eye clinics. there is no 99 journal of rawalpindi medical college (jrmc); 2021; 25 covid-19 supplement-1: 94-99 doubt a difficult decision but one has to weigh the risk of delaying sight-saving visits vs the risk of getting covid.27 conclusion the survey was small-scale yet clear-cut. the results showed compliance towards statements and harmony amongst opinions, thus endorsed that covid-19 has a definitive impact on the professional lives of ophthalmologists. further larger-scale studies in the future will be needed to address its long-term effects, especially regarding evolving ophthalmic practice. references 1. lai cc, shih tp, ko wc, tang hj, hsueh pr. severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and coronavirus disease-2019 (covid-19): the epidemic and the challenges. int j antimicrob agents. 2020 mar, 55(3):105924. doi: https//doi.org/10.1016/j.ijantimicag.2020.105924 2. li q, guan x, wu p, wang y, zhou l, tong y, et al. early transmission dynamics in wuhan, china of novel coronavirus-infected pneumonia. n engl j med. 2020 march; 382(13): 1199-1207. doi: https//doi.org/10.1056/ nejmoa 2001316 3. countries where covid-19 has spread. worldometer [internet]. 2021 july 23 [cited 2021 july 23]. available from: https://www.worldmeters.info/coronavirus/countrieswherecoronavirus-has-spread/ 4. sethi ba, sethi a, ali s, & aamir hs. impact of coronavirus disease (covid-19) pandemic on health professionals. pak j of med sci. 2020;36(covid19-s4):covid-19-s6-s11. doi: https://doi.org/10.12669/pjms.36.covid19-s4.2779 5. kuo ic, o'brien tp. covid-19 and ophthalmology: an underappreciated occupational hazard. infect control hosp epidemiol. 2020 oct;41(10):1207-1208. doi: https://doi.org/10.1017/ice.2020.238 6. urooj u, ansari a, siraj a, khan s, tariq h. expectations, fears and perceptions of doctors during covid-19 pandemic. pak j of med sci. 2020;36(covid19-s4):covid-19-s37-s42. doi: https://doi.org/10.12669/pjms.36.covid19-s4.2643 7. ferrara m, romano v, steel dh et al. reshaping ophthalmology training after covid-19 pandemic. eye. 2020 july;34(11):2089–2097. doi: https://doi.org/10.1038/s41433-020-1061-3 8. ting dsw, lin h, ruamviboonsuk p, wong ty, sim da. artificial intelligence, the internet of things, and virtual clinics: ophthalmology at the digital translation forefront. lancet digit health. 2020 jan;2(1):e8-e9. doi: https://doi.org/10.1016/s2589-7500(19)30217-1 9. lee r, raison n, lau wy, aydin a, dasgupta p, ahmed k, et al. a systematic review of simulation-based training tools for technical and non-technical skills in ophthalmology. eye. 2020 march;34(10):17371759. doi: https://doi.org/10.1038/s41433-020-0832-1 10. erridge s, yeung dkt, patel hrh, purkayastha s. telementoring of surgeons: a systematic review. surg innov. 2019 feb;26(1):95-111. doi: https://doi.org/10.1177/1553350618813250 11. backhaus j, huth k, entwistle a, homayounfar k, koenig s. digital affinity in medical students influences learning outcome: a cluster analytical design comparing vodcast with traditional lecture. j surg educ. 2019 may-jun;76(3):711-719. doi: https://doi.org/10.1016/j.jsurg.2018.12.001 12. mishra k, boland mv, woreta fa. incorporating a virtual curriculum into ophthalmology education in the coronavirus disease-2019 era. curr opin ophthalmol. 2020 sep;31(5):380-385. doi: https://doi.org/10.1097/icu.0000000000000681 13. andersen jp, nielsen mw, simone nl, lewiss re, jagsi r. covid-19 medical papers have fewer women first authors than expected. elife. 2020 jun 15;9:e58807. doi: https//doi.org/10.7554/elife.58807 14. pavola a. 266 hospitals furloughing workers in response to covid19. beckers hospital cfo report. financial management [internet]. 2020 aug [cited 2021 apr 2]. available from: https://www.beckershospitalreview.com/finance/49-hospitalsfurloughing-workers-in-response-to-covid-19.html 15. elishar r, fishban d, paret g, kashtan h. residency examinations in the course of the covid-19 crisis: the efforts of the israeli scientific council to execute the final board oral examinations during a local and worldwide pandemic. harefuah. 2020 dec; 159(12):851-855. hebrew. pmid: 33369296. 16. browm t. ophthalmology practices hit hard by covid-19 closures, changes. medscape medical news [internet]. 2020 may [cited 2021 apr 14]. available from: https://www.medscape.com/viewarticle/930431 17. richterman a, meyerowitz ea, cevik m. hospital-acquired sarscov-2 infection: lessons for public health. jama. 2020;324(21):2155– 2156. doi: https://doi.org/10.1001/jama.2020.21399 18. kuo ic, o'brien tp. covid-19 and ophthalmology: an environmental work hazard. j occup health. 2020;62(1):e12124. doi: https://doi.org/10.1002/1348-9585.12124 19. lacorzana j, ortiz-perez s, prats mr. incidence of covid-19 among ophthalmology professionals. med clin (engl ed). 2020 sep 11;155(5):225. doi: https//doi.org/10.1016/j.medcle.2020.05.014 20. khanna rc, honavar sg, metla al, bhattacharya a, maulik pk. psychological impact of covid-19 on ophthalmologists-in-training and practising ophthalmologists in india. indian j ophthalmol. 2020 jun;68(6):994-998. doi: https://doi.org/10.4103/ijo.ijo_1458_20 21. cheng, l, chen l, xiao l, zhang, j, cheng, y, zhou, l, et al. problems and solutions of personal protective equipment doffing in covid-19. open med (wars). 2020;15(1):605-612. doi: https://doi.org/10.1515/med-2020-0172 22. lorenzo d, carrisi c. covid-19 exposure risk for family members of healthcare workers: an observational study. int j infect dis. 2020 sep;98:287-289. doi: https://doi.org/10.1016/j.ijid.2020.06.106 23. donnelfield ed, devgan u. aao covid-19 survey shows revenue losses for private practices. healio news [internet]. 2020 may 21 [cited 2021 may 15]. available from: https://www.healio.com/news/ophthalmology/20200521/aao-covid19survey-shows-revenue-losses-for-private-practices 24. hoeferlin c, hosseini h. review of clinical and operative recommendations for ophthalmology practices during the covid-19 pandemic. sn compr clin med. 2021;3:3–8. doi: https://doi.org/10.1007/s42399-020-00633-1 25. ike pi. covid-19 is putting millions of people at risk of blindness. world economic forum [internet]. 2020 nov 16 [cited 2021 may 7]. available from: https://www.weforum.org/agenda/2020/11/covid-19is-pushing-millions-of-people-into-blindness/ 26. arntz a, khaliliyeh d, cruzat a, et al. open-care telemedicine in ophthalmology during the covid-19 pandemic: a pilot study. archivos de la sociedad espanola de oftalmologia. 2020 dec;95(12):586-590. doi: https://doi.org/10.1016/j.oftal.2020.09.005 27. teo kyc, chan rvp, cheung cmg. keeping our eyecare providers and patients safe during the covid-19 pandemic. eye 2020;34:1161– 1162. doi: https://doi.org/10.1038/s41433-020-0960-7 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 78-81 78 original article functional endoscopic sinus surgery( fess) nausheen qureshi , nighat arif department of ent, holy family hospital and rawalpindi medical college,, rawalpindi. abstract background: to study the management of the patients of various nasal and para nasal sinuses diseases with endoscopic sinus surgery in terms of age, gender, disease pattern, surgical procedures, complications and recurrence rate. methods: in this descriptive study 146 patients of different sinonasal disease treated with endoscopic sinus surgery were included. patients with csf leak, nasolacrimal duct obstruction , polyps,with and without history of allergy and asthama were included. patients with mucormycosis, invasive fungal sinusitis, malignancy and very elderly were not included. pre-operative ct scan was a pre requisite in all patients. fibreoptic light was passed through the canaliculi to identify the lacrimal sac or after dilating the puncta with a lacrimal probe,it was passed into the superior and inferior canaliculi to know the position of lacrimal sac .the lacrimal sac is located lateral to the maxillary line at its superior edge. drill was used to create a window.all patients had their visual acuity , colour vision and funduscopy done prior to surgery. flourescein dye was used for csf rhinorhea demonstration prior to csf leak repair preoperatively. on the 4th postoperative day the patients had removal of their crusts and had examination of nasal cavity. results: mean age was 33 years. the commonest presenting feature was nasal obstruction and nasal discharge. most of the patients had allergic fungal sinusitis though we did manage to do isolated cases of sphenoiditis, a couple of dcr and of csf rhinnorhea. the most common complication we encountered was recurrence of disease followed by periorbital pain and bruising and pain. conclusion: endoscopic sinus surgery is the standard of care in modern rhinology and more work is required in our country to promote its training and use for the betterment of patients. key words: functional endoscopic sinus surgery( fess) ,rhinology, sinus surgery introduction fess (functional endoscopic sinus surgery) is a relatively recent surgical procedure that uses nasal endoscopes using hopkin rod lens technology through the nostrils to avoid cutting the skin. fess came into existence due to the pioneering work of dr messerklinger and stamburger.1later on workers like wigand2 and others have shown convincingly that the keystone to the pathogenesis and persistence of chronic maxillary and frontal sinus infection is the osteomeatal complex.. 2 stamburger did experimental and fluoroscopic studies in which he showed that the muco ciliary movement of the para nasal sinuses always follow a definite pathway and is always towards the natural ostium. 3 nasal polyps are the common presentation of patients having chronic sinusitis or allergic fungal sinusitis.they are difficult to treat because of multifactorial causes. a nasal polyp is an oedematous hypertrophied mucosa and submucosa of nose and paranasal sinuses.the cause of eye involvement and proptosis is usually disease in the ethmoids.4 the technique utilizes telescopes 4mm (adult use) and 2.7 mm (pediatric use) with a variety of viewing angle (0degree to 30,45,70,90 and 120 degrees).these telescopes provide good illumination inside nasal cavity and sinuses. fess surgery is mostly directed towards the osteomeatal complex situated beneath the middle turbinate; this is the area which receives drainage from anterior ethmoids, maxillary and frontal sinuses. the term functional was introduced to distinguish this type of surgery from non endoscopic conventional procedures and this procedure has now been widely accepted as the treatment of choice for chronic inflammatory sinus disease.5 the diagnosis of chronic sinusitis is based on clinical presentation, nasal endoscopy and computed tomography scans. the scans highlight the extent of pathology its relation to roof of ethmoids and the orbit and the anatomy of the middle turbinate with the osteomeatal complex.6 high definition cameras, monitors and a host of tiny articulating instruments aid in identifying and restoring the proper drainage of these sinuses. biopsies can also be taken. we use powered instruments which include microdebrider or shaver having suction and irrigation facility attached. pathologies were addressed using micro forceps and shaver which cut and sucks the polyps. all sinuses can be assessed through this modality by means of this surgery. the steps are uncinectomy, infundibulotomy, journal of rawalpindi medical college (jrmc); 2017;21(1): 78-81 79 bulla resection , antrostomy , sphenoidotomy and frontal recess dissection. patients and methods this study was carried in the department of ent head and neck surgery holy family hospital from june 2010 to december 2013. a total of 146 patients of different sinonasal disease treated with endoscopic sinus surgery patients were studied retrospectively. there was no age or sex restriction. patients with csfleak , nasolacrimal duct obstruction , polyps,with and without history of allergy and asthama were included in our study. patients with mucormycosis, invasive fungal sinusitis, malignancy and very elderly were not included in our study. pre-operatively all patients were prepared for general anaesthesia. after admission all patients were given a course of antibiotic and steroids for five days and anti allergic if they had a family history of allergy. all patients were assessed if they were asthmatic and clinically if they had any wheeze. if their asthma was controlled at the time of admission they were prepared to be operated on the list . uncontrolled asthma patient were first referred and managed by the medical department and then referred back for surgery. pre-operative ct scan was a pre requisite in all patients where axial and coronal cuts at 5mm were done without contrast of nose,para nasal sinuses, orbit and brain. in patients with csf leak omnapaque dye was given to visualize the area of leak. all patients undergoing dcr underwent checking of their canaliculi in eye opd prior to endoscopic dcr. in this technique the fibreoptic light is passed through the canaliculi to identify the lacrimal sac or after dilating the puncta with a lacrimal probe,it is passed into the superior and inferior canaliculi to know the position of lacrimal sac, the lacrimal sac is located lateral to the maxillary line at its superior edge and we have used drill to create a window at this area because it created a wide exposure of sac without heating or damaging the surrounding structure at the edge of bone all patients had their visual acuity , colour vision and fundoscopy done prior to surgery. patients were given hypotensive anaesthesia so that there was minimal bleeding. use of 1:1000 adrenaline packs were done pledgets of which were placed intra-nasaly for 5 minutes prior to local injection in to the mucosa. savlon was used for defogging and saline for irrigation of nasal cavity to remove blood drops and to clear the nasal cavity. flourescein dye was used for csf rhinnorhea demonstration prior to csf leak repair preoperatively. all tissues removed as polyps or cheesy material were divided into two portions ..one was ,kept in formalin and sent for histopathology the other was kept in saline and sent for fungal staining and culture. postop nasal douching of nasal cavity with saline was started. patients with allergic fungal sinusitis were started on steroids for at least three months post operatively. the patients were discharged on 2nd post operative day and were called on 4 th post operative day for check up. on the 4th postoperative day the patients had removal of their crusts and had examination of nasal cavity and had nasal douching.along with checking of vision. post operatively for 6 weeks, patients were given preferably intranasal steroidsvision was checked in all patients and stents were removed in dcr patients after 6weeks.precautions was advised to all patients having csf rhinorhea repair. avoidance of nasal straining ,and use of stool softeners were used for patient with csf rhinorhea. antibiotics were continued for another two weeks and post operative ct scan were repeated after two months results out of one hundred and forty six (146) patients, one hundred and forty four(144) patients were available for follow up .the total number of males were 88, with a male to female ration of 1:2:1 the mean age was 33 years. maximum number of cases were done in 2013 followed by 2012,2011,and then 2010 (table1) . the most common symptom was nasal obstruction 60% (table2) . polyps(80%) and intra nasal discharge(70%) were the most common signs (40%) (table 3;figure 1&2). concha bullosa with paradoxical middle turbinate were common anatomical variations that we encountered(figure 1&2).the most common cases were of sinonasal polyposis due to allergic fungal sinusitis 71% ,followed by dacrocysto rhinostomy (20 %),dcr (14%) ,csf repair (5%),chronic sinusitis (3%), dns (1.3%), isolated sphenoiditis (1.3%), and epistaxis (2.3%). the recurrent rate is high after simple polypectomy.all patients were followed up for a period of one year.good results were achieved as 95% of our patients showed improvement in nasal obstruction and rhinorhea improved in 80% .we had a total of 17% patients who presented with recurrence of disease these were the patients of allergic fungal sinusitis, this was followed by 12 patients of post operative pain and peri-orbital swelling and bruising (table 4). table 1.number of cases in each year. year number of patients 2010 18 2011 23 2012 45 2013 60 journal of rawalpindi medical college (jrmc); 2017;21(1): 78-81 80 table 2: presenting symptoms nasal symptoms %age involvement nasal destruction 60 % sneezing 47 % anterior nasal discharge 44 % visual disturbance 20 % proptosis 20 % headache 15 % epiphora 12 % table 3: nasal signs nasal signs %age involvement polyp 80 % intra nasal discharge 70 % peri-orbital swelling 40 % low visual acuity 32 % hyperteleorism 15 % tenderness sinuses 15 % table 4.complications complication encountered number of cases nasal bleeding requiring transfusion nil csf leak nil peri-orbital fat exposure 3 orbital hematoma nil injury to internal carotid artery nil injury to optic nerve nil meningitis nil recurrence 15 peri-orbital bruising & emphysema 6 figure 1:preoperative scan of sphenoiditis fig 2 post op scan of sphenoiditis discussion functional endoscopic sinus surgery has become one of the most common surgical procedures performed in major cities of pakistan.it basically addresses the sinus disease at the osteomeatal complex which comprises uncinate process, the middle meatus,and hiatus semilunaris. it aims at the removal of tissue obstructing the osteomeatal complex and facilitation of drainage while conserving the normal nonobstructing anatomy and mucous membrane.use of powered instruments during fess requires great care and a wide knowledge of the anatomy related to the orbit. there are sufficient reports on the incidence of complications after endonasal surgery of paranasal sinuses .the most dangerous is blindness10 resulting from damage to optic nerve .however the frequency of this complication is very low. comparing our results with a study done by ghori et al the complications in our study group showed recurrence of polyps were 17%, while in their case was 12%. 11 they also had no major complication like our study though minor complications like peri orbital pain,bruising, headache and adhesions were present in their study as well. the major symptoms were the same in both the studies which were nasal obstruction and nasal discharge. good results were achieved also in both the studies. their patients had 92% improvement in nasal obstruction and 88% got better with reduced rhinorrhea( table 5) fess was well established by first third of the century. it is based on commendable anatomical studies of zuckerkandl ,onodi and greenwald. the term fess was coined by kennedy12.further pioneer work was done by messerklinger and stamburger.functional endoscopic sinus has become the standard for chronic polypoidal sinusitis .anatomical and technical knowledge gained from cadaver sections and surgical experience has helped us in preventing complications.the field of fess is not only limited to domain of otorhinolaryngology .it also extends to ophthalmology ,cranium and middle fossa pathological condition.the anatomy must be demonstrated with computed tomography before endoscopic surgery in order to avoid complications13.this field encompass surgery related to orbital decompression ,lacrimal obstruction ,optic nerve decompression and pituitary tumour surgey. journal of rawalpindi medical college (jrmc); 2017;21(1): 78-81 81 table 5.comparison with local study comparison variable study of ghori et al present study total no of patients 50 144 most common symptom nasal obstruction and nasal discharge nasal obstruction and anterior discharge major diagnosis sino-nasal polyposis sino-nasal polyposis major complication none none minor complications recurrence,periorbital pain and adhesions recurrence,pe riorbital pain and periorbital fat exposure one of fess protocols included conducting radiological studies of orbit ,brain and paranasal sinuses. this helped surgeons in appreciating the various anatomical variations ,the extent of the disease process and its relation with vital structures.the axial views help in showing the relationship of disease with medial rectus and lamina papyracea and the coronal views for sinus and orbital anatomy particularly at cribiform plate (floor of anterior cranial fossa). anatomical variations appreciated, on ct scan were dehiscent or abscent lamina papyracea, paradoxical middle turbinate, concha bullosa and rudimentary sphenoid sinus.these anatomical factors can lead to blockage of osteomeatal complex.14 ct scan only correlate with surgical findings in only 84% percent of the orbital complications of sinus involvement. 14 magnetic resonance imaging is better for fungal infections of the paranasal sinuses and orbit conclusion 1. sinus endoscopy is a method of diagnosing sinonasal symptoms and disease.functional endoscopic sinus surgery has provided a safe ,efficient method for dealing with identified nasal disease. 2. fess provides an illuminated way into the nasal cavity so that chronic sinusitis and sinus nasal polyposis can be managed with great success. references 1. messerklingerw.endoscopy of the nose,baltimore urban and schwarzeburg,1978. 2. wigand,e.m.endoscopic surgery of the paranasal sinuses and anterior skull base.new york thieme medical publishers inc.1990. 3. stammberger h.endoscopic endonasal surgery-concepts in treatment of recurring rhinosinusisitis part 1.anatomic and pathophysiologic consideration.part 2.surgical technique.otolaryngol.head neck surg, 2011;,94:143-56. 4. khannh,moin m , khan ma , hameed a. .unilateral proptosis:a local expereince.biomedica, 2012;20(2):111416. 5. haque mr.a study of functional endoscopic sinus surgery technique.mymensingh med j.2004;13:39-42. 6. mouling.radiologic imaging of chronic sinusitis in the adult.j radiol.2003;124:151-19. 7. jokinen k and karja j.endonasal dacrosysto rhinostomy.arch otolaryngol , 1974;100;41-44. 8. dalzivi. k systematic review endoscopic sinus surgery for nasal polyps.health technol ass ess 2013;7:1-159 9. israr a and azhar h. nasal polyps a recurrent problem.pakistan postgraduate medical journal1994;5:3034. 10. bernalsm,sudhoff h,dazert s .complications after endonasal surgery of the paranasal sinuses for inflammatory disease.laryngototology 2004;83:23-28. 11. ghori s m,aziz b,pal mb.an analysis of functional endoscopic sinus surgery(fess) for sinunasal disease. pjmhs 2012,6:827-830.11) 12. kennedy dw. functional endoscopic sinus surgery.technique.arch otolaryngol1985;11111:643-9. 13. drake lee ab.nasal polyps.hosp med.2004;65(5):264-67. 14. daniels dl,yu s, peck p haughton vm .computed tomography and magnetic resonance imaging of orbital apex.radiolclin north am 1987;24:803-17. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 57-59 57 original article total knee replacement –histopathological patterns ammara ijaz 1 , khalid aslam 2 , azhar mubarik 3 department of pathology, benazir bhutto hospital and rawalpindi medical colleg, rawalpindi; 2. department of orthopaedics, quaid-i-azam international hospital, rawalpindi; 3. department of pathology, quaid-i-azam international hospital, rawalpindi abstract background: to determine the frequency of different degenerative joint diseases and their morphological changes seen in total knee replacement specimens. methods: in this descriptive study total knee replacement specimen of 130 patients undergoing bilateral or unilateral knee arthroplasty were included. all specimens were received in 10% formaline fixative and routinely processed and stained with haematoxylin and eosin (h&e).these were examined microscopically and various histological patterns were evaluated. results: a total of 130 cases of total knee replacement specimen were evaluated. the age range was 43-81 years. the most frequent finding was osteoarthritis which was in 121 cases, 8 cases were of rheumatoid arthritis and one of gouty arthritis. conclusion: osteoarthritis with female predominance is the most common pathological finding amongst various patterns. key-words: total knee replacement, osteoarthritis, joint introduction total knee replacement is safe and effective procedure when nonsurgical treatments like medications and using walking supports are no longer helpful. the knee is the largest joint in the body and healthy knees are required to perform most everyday activities. the most common cause of chronic knee pain and disability is arthritis.1the knee joint is one of the complex joint in human body, comprising two long leg bones held together by muscles, ligaments and tendon.tendons are tough cords of connective tissue that connect muscles to bones. ligaments (anterior, posterior and lateral cruciate) are elastic bands of tissue that connect bone to bone. some ligaments provide stability and protection of the joint, other ligaments limit forward and backward movement of the tibia.1 3 although there are many types of arthritis, most knee pain is caused by osteoarthritis, rheumatoid arthritis, and post-traumatic arthritis. osteoarthritis is a degenerative joint disease occurring in knee in middle age and elderly individuals caused by multiple factors including age gender, genetic predisposition and mechanical stress. in osteoarthritis when there is damage of one component leads to the failure of other component, and collectively leading to joint failure and the clinical manifestation of osteoarthritis. rheumatoid arthritis is a chronic inflammatory degenerative disease with destruction of synovial membrane.1, 4-6in osteoarthritis there is replacement of articular cartilage by fibrous membrane, and in rheumatoid arthritis there is synovial hyperplasia with lymphoplasmacytic infiltrate.7,8,9 few cases of infective arthritis and gouty arthritis can be seen in these specimens. patients and methods a prospective study was carried out in the department of histopathology, quaid-i-azam international hospital, islamabad, during the period from january 2012 to june 2013. a total of 130 knee replacement specimens were received in one and half year period. the patients were diagnosed as osteoarthritis, rheumatoid arthritis and gouty arthritis depending on clinical symptoms, examination and radiological findings. the specimens were received in 10% formalin. gross examination of all the specimens was carried out, representative bony and soft tissue (including ligaments) sections were taken. bone was decalcified in 5% nitric acid and then processed. appropriate sections were prepared and stained with hematoxylin and eosin for light microscopy. results the age range in total knee replacement specimen(degenerative joint diseases) was 43-81 years (table 1). females constituted 76.15%, while males were 23.84%.the most frequent finding was osteoarthritis which was in 121 cases and 8 cases were of rheumatoid arthritis and one of gouty arthritis (table 2). on gross examination of these bony and soft tissue fragments, the changes in osteoarthritis included some thinning of cartilage, articular surface was journal of rawalpindi medical college (jrmc); 2017;21(1): 57-59 58 granular,rheumatoid arthritis showed thick hyperplastic synovium with bulbous fronds and chalky white surface of joints in gouty arthritis (table 3). histological changes seen in osteoarthritis included articular cartilage replacement by fibrous tissue, increased aggregation of macrophages with degenerative changes and congestion.in rheumatoid arthritis proliferation of synovial cells (table 4; figure 1-4). lymphoid follicle was often present, synovial giant cells were seen. in gouty arthritis urate deposits destroy cartilage, with appearance of tophi surrounded by histiocytes and foreign body type giant cells. table 1age range in different joint lesions histopatological finding number ( 43-50 years) number( 51-60 years) number (61-70 years) number 71-81 years) osteoarthritis 20 31 42 28 rheumatoid arthritis 3 4 1 0 gouty aryhritis 0 1 0 0 table 2.total knee replacement – diagnosis diagnosis no percentage osteoarthritis 121 93% rheumatoid arthritis 8 6.1% gouty arthritis 1 0.7% table 3: morphological changes seen in osteoarthritis (n= 121) morphological changes no percentage articular cartilage replaced by fibrous tissue 21 17.3% macrophages with degenerative changes and congestion 100 82.6% table 4: morphological changes seen in rheumatoid arthritis ( n=8 ) morphological changes no percentage proliferation of synovial cells 3 37.5% lymphoid follicle formation 5 62.5% figure 1: fibrovascular tissue with lymphocytes and macrophages in osteoarthritis figure 2: ffibrovascular tissue with degenerative changes in osteoarthritis figure 3: degenerative changes in articular cartlage in osteoarthritis figure 4: degenerative changes in articular cartilage and partly replaced by fibrous tissue in osteoarthritis discussion to analyze different diseases and their histological patterns we reviewed total knee replacement specimen received in laboratory. although degeneration and loss of cartilage was the main finding in these specimens, but we conducted the comprehensive analysis. in osteoarthritis main finding was replacement of articular cartilage by fibrous membrane, other findings included degeneration and macrophage infiltration. one iraqi study also discussed the findings but emphasis was on posterior cruciate ligament.1, 2these changes were degeneration, synovitis and inflammatory cell infiltration. one study showed hyalinization and fibrosis were main featuers but in our study these changes were present but in focal areas. most of the international studies compare the finding of posterior cruciate ligament with anterior cruciate ligament, but in present study ligaments were present but not mentioned separately. we also journal of rawalpindi medical college (jrmc); 2017;21(1): 57-59 59 processed bony tissue for their changes but thiswas not seen in other studies.11-14 in rheumatoid arthritis cases in our study showed synovial proliferation and lymphoid follicle formation, whereas in iraqi study fiber proliferation was the most frequent finding. inflammation is an important feature seen in both osteoarthritis and rheumatoid arthritis but more intense in the latter. histological evidence of inflammation was also seen in other studies but it was more pronounced in lining joints that cause damage to joints and cause destruction. osteoarthritiss is considered to be of primary chondrocytes failure and secondary involvement of bones and rheumatoid arthritis primarily involves synovial lining and then nodule can form with palisading of histiocytes. these changes are usually seen in late presentation of rheumatoid arthritis which is not seen in our study.1520a case of gouty arthritis was seen in one case. gouty arthritis can be differentiated from rheumatoid arthritis by the presence of tophi because in later stages rheumatoid nodule is formed which has necro-biotic centre has surrounded by palisading histiocytes and giant cells. conclusion 1.knee joint after showing damage by osteoarthritis, rheumatoid arthritis and other kind of infected arthritis show number of histological changes. these histological patterns are different in different stages of arthritis and aging, so it can lead to long term damage to the joints. 2. osteoarthritis is the most common finding with the female predominance amongst various patterns. 3. total knee replacement specimen is necessary for prevention of maximum disability, and by viewing these cases we can separate the type and extent of arthritis for any further management. references 1. al-sharqi sah, wahabms,hussainyskd. histopathological study in posterior cruciate ligament of osteoarthritis and rheumatoid arthritis.american journal of medicine and medical sciences 2013,3(1):10-16. 2. pritzkerk.p.h,gays. osteoarthritis cartilage histopathology:grading and staging.osteoarthritis and cartilage(2005) published by elsevier ltd.doi:10.1016/j.joca.2005.07.014. 3. pearson r.g,kurient,shu k.ss, scammel be.histopathology grading systems for characterization of human knee osteoarthritis.reproducibility,variability,reliability,correlatio n and validity.osteoarthritis and cartilage ,2011;19:324-31. 4. rutger m,vanpeltym.j.p,dhertyz w.j.al.evaluation of histological scoring systems for tissue –engineered,repaired and osteoarthritic cartilage. osteoarthritis and cartilage, 2010; 18:12-23. 5. anjum s,minhasla,mubarika.effects of free mobility verses restricted mobility on the degenerative changes induced by immobilization on the femoral articular cartilage of rabbit knee. jpma , 2012;62: 531-35. 6. yusuf e,kortekaas m c,watti,huizinga tw.do knee abnormalities visualized on mri explain knee pain in knee osteoarthritis? a systemic review. ann rheum dis 2011:70:60-67. 7. jiangd,zouj,huang l, shi q,zhux,wangg,and yang h.efficacyof intra-articular injection of celecoxib in a rabbit model of osteoarthritis.int. jmolsci 2010;11:4106-4113. 8. pritzkerkph.animal models for osteoarthritis:processes,problems and prospects.ann rheum dis 1994;53:406-20. 9. ayral x,dougadosm,listratv,bonvarlet jp,simonnetj.arthroscopic evaluation of chondropathy in osteoarthritis of the knee.jrheumatol 1996;23(4):698-706. 10. marshallkw.the case for a simple method of grading osteoarthritis severity at arthroscopy.jrheumatol 1996;23(4):582-85. 11. pelletier jp,boileauc,brunetj,boilym,lajeunessed.the inhibition of subchondral bone resorption in the early phase of experimental dog osteoarthritis by licofelone is associated with a reduction in the synthesis of mmp-13 and cathepsink.bone 2004;34(3):527-38. 12. mainil-varlet p,rieserf,grogans,muellerw,saagerc.articular cartilage repair using a tissue engineered cartilage-like implant:an animal study.osteoarthritis cartilage 2001;9(s a):s6-s15. 13. mainil-varletp,aigner t,brittbergm,bullough p,hollandera.histological assessment of cartilage repair:a report by the histology endpoint committee of the international cartilage repair society(icrs).j bone joint surg 2003;85( 2):45-57. 14. barwell r.a. treatise on diseases of the joints.2ndedn.newyork:williamwood&company 1881. 15. brittbergm,lindahla,nilssona,ohlssonc.treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.nengl j med 1994;331:889-95. 16. knutsen g,engebretsenl,ludvigsentc,drogsetjo ,grontvedtt.autologous chondrocyte implantation compared with microfracture in the knee.j bone joint surg am 2004;86-a:455-64. 17. saris db,vanlauwej,victorj,hasplm.characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee versus microfracture.am j sports med 2008;36:235-46. 18. walsh da,yousefa,mcwilliamsdf,hillr.evaluation of a photographic chondropathy score(pcs) for pathological samples in a study of inflammation in tibiofemoral osteoarthritis.osteoarthritis cartilage 2009;17(3):304-12. 19. fife rs,brandtkd,braunsteinem,katzbp, shelbournekd,kalasinskila.relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee. arthritis rheum 1991;34(4):377-82. 20. kijowski r,blankenbakerd,stantonp.arthroscopic validation of radiographic grading scales of osteoarthritis of the tibiofemoraljoint.ajr am j roentgenol 2006;187(3):794-99. 423 journal of rawalpindi medical college (jrmc); 2021; 25(3): 423-428 original article study of the factors that influence the completion of the thesis of master of health professions education graduates: a qualitative study salma ambreen shahab1, iram tassaduq2, ayesha haque3, aqsa naheed4, maleeha zafar5, iram zakria6 1 lecturer, department of medical education, hitec-institute of medical sciences, taxila. 2 hod, department of medical education, hitec-institute of medical sciences, taxila. 3 hod, department of anatomy, hitec-institute of medical sciences, taxila. 4 associate professor, department of dermatology, hitec-institute of medical sciences, taxila. 5 senior lecturer, department of anatomy, hitec-institute of medical sciences, taxila. 6 assistant professor, department of anatomy, hitec-institute of medical sciences, taxila. author’s contribution 1 conception of study 4,5,6 experimentation/study conduction 1,2,4,5,6 analysis/interpretation/discussion 1,3 manuscript writing 3 critical review corresponding author dr. salma ambreen shahab, lecturer, department of medical education, hitec-institute of medical sciences, taxila email: ambreenshahab@yahoo.com article processing received: 16/06/2021 accepted: 23/09/2021 cite this article: shahab, s.a., tassaduq, i., haq, a., naheed, a., zafar, m., zakria, i. study of the factors that influence the completion of the thesis of master of health professions education graduates: a qualitative study. journal of rawalpindi medical college. 30 sep. 2021; 25(3): 423-428. doi: https://doi.org/10.37939/jrmc.v25i3.1711 conflict of interest: nil funding source: nil access online: abstract objective: to investigate the experience of timely thesis completion by the graduates of the master of health professions education (mhpe) program in pakistan. study design: qualitative interpretative study design. settings: riphah university islamabad and hitec-ims taxila, from may 2018 to june 2019. materials and methods: data was collected by semi-structured interviews. all interviews were carried out in person. detailed notes were taken, and conversations were audio-recorded. three authors analyzed data independently using iterative thematic analysis. inconsistencies were resolved through discussion. results: two major themes out of five were identified: intrinsic attributes of the graduates and the role of the supervisor, including sub-themes of intrinsic motivation, self-regulation, age of the participant, supervisor-trainee relationship, supervisor’s availability, supervisor’s commitment, and personality traits of the supervisor. positive relationship with a committed supervisor who was readily available and had a friendly, yet professional attitude aided in the completion of the thesis on time while a supervisor lacking these traits posed challenges for the graduates. conclusion: several factors were identified which influenced thesis completion among the graduates of mhpe in pakistan. the five major ones consisted of the following, 1) research project-related problems; 2) support system; 3) supervisor guidance; 4) attributes of the researcher; 5) conducive research environment. these results can help influence policies to evaluate and improve this program. keywords: mhpe, education, thesis, health profession, intrinsic motivation, supervisor. 424 journal of rawalpindi medical college (jrmc); 2021; 25(3): 423-428 introduction for the last two decades, there has been a consistently increasing need for graduates in medical education. according to principles laid down by the pioneers of medical education, a rigorous curriculum implemented by a dedicated faculty actively engaged in research is essential for health care advancement.1 the curricula designed and implemented under guidance by experts in the field is critical for the improvement of the health education system and health system of the country, in the long term.2 to address this need, health care professionals are expected to advance their knowledge through postgraduate studies in medical education. this is particularly important in developing countries where the traditional way of teaching is prevalent and skills to practice evidence-based medicine are lacking.3 master’s in health professions education is one of the popular programs known to prepare leaders in educational theory and practice all over the world. to meet the global advancement in medical education, the national regulatory body in pakistan directed the establishment of departments of medical education (dme) throughout the country in 2008.2,8 this caused an upsurge in demand for trained faculty to run these departments. in response, the “master’s in health professions education” (mhpe) program was initiated in more than eight universities across the country.3,6 this blended teaching program consists of face-to-face sessions and online learning periods. medical doctors with diverse backgrounds who are interested in medical education join the course. along with coursework, thesis completion is a major requirement to complete the course. writing a research-based thesis requires evidence-based practice and experiential learning. under the guidance of a supervisor, personal effort on part of the trainees is required to synthesize and apply knowledge for the successful completion of the thesis. timely completion of the thesis is required to attain the degree.9 however, not all doctors who get enrolled in the mhpe program are able to complete this essential component of the course.10 several factors may be responsible for success or failure to conclude this task. although the mhpe program is being conducted in pakistan for over a decade, these factors have not been explored. above in view, this study was designed to explore the thesis experiences of graduates who completed their degrees in mhpe programs at different institutions in pakistan. recognizing challenges and understanding the experiences of these professionals, of this relatively novel specialty, may help guide planned interventions to promote and develop medical education programs in the future. this is especially critical in developing countries like pakistan where the importance of quality medical education cannot be understated.8 materials and methods study design and participants: after ethical approval was acquired from the institutional review boards (irb) of international riphah university and hitecinstitute of medical sciences, a qualitative interpretative study was conducted for over a year from may 2018 to june 2019. participants were selected through purposive sampling in which participants are intentionally selected to comprehend a critical phenomenon.10 individuals who had completed their mhpe degree from different universities of pakistan who were working in riphah university and hitec-ims were emailed about the study and 14 mhpe graduates who were willing to participate were included in this study whereas doctors who could not complete their mhpe were excluded. data collection method: after careful consideration, an interview form (if) was planned. section i of the if consisted of informed consent and section ii comprised of validated questions and space for answers. after a pilot study on two interviewees, language changes were made and if was finalized. afterward, using the if, semi-structured interviews of 14 participants were conducted in person, until data saturation was achieved. interview questions (23 items) based on a methodological conceptual framework of the components of thesis completion were developed. the interviews were recorded. the conversations were later transcribed precisely and emailed to participants for verification. data analysis: data was analyzed by using thematic analysis, major themes were identified as main challenges encountered during thesis completion. three authors analyzed audio recordings and written notes independently and identified a list of themes. these themes were then discussed amongst authors and sub-themes were defined. themes and sub-themes were discussed and revised until data saturation was reached. finally, findings were discussed with all the investigators which served as a means of member checking to ensure that the final themes were representative of the interviews that each investigator had conducted. 425 journal of rawalpindi medical college (jrmc); 2021; 25(3): 423-428 results initially, 40 doctors were invited through e-mail to participate. fourteen doctors were willing to be interviewed. table 1 shows the demographic information of the participants. response rate (38%). the mean time from commencement to completion of the mhpe program for these participants was 3.2 years (range = 2-4.6 years). two major themes were identified. 1. intrinsic factors: main personal attributes of the researcher that facilitated the completion of the thesis and their absence posed hindrance. 2. extrinsic factors: supervisor’s role to facilitate thesis-related challenges. seven sub-themes all interviewed graduates commented on one or more intrinsic and extrinsic factors that helped them succeed in completing their master’s thesis and results with representative quotes are presented in table 2 were considered under these two main themes. table 1: demographic characteristics of the study sample characteristic sample (n= 14) gender n (%) male 04 (29) female 10 (71) qualification mphil, mhpe 10 (29) fcps, mhpe 04 (71) designation professor 8(57.14) associate professor 6 (42.85) assistant professor lecturer age 35-45 8 (53) 46-55 6 (47) . table 2: intrinsic and extrinsic factors intrinsic factor: selfmotivation and regulation candidate #1: “self-motivation plays quite a significant role. i was motivated, i wanted to be an educationist. my motivation resulted in the completion of the thesis on time” candidate# 2: “self-motivation is very important especially for working people. for higher studies, working people have the burden of their work as well and if they do not complete their tasks in time so, it adds to their overall burden. no one can work without being self-motivated as that is need of the hour” candidate#6 “i must say the level of patience, passion, and determination are very important. no one can push you to do a post-graduation degree as you are an adult learner.” candidate # 9 “to me, i think the most important thing is time management and setting your priorities. if somebody is determined and prioritizes the tasks for timely completion, he generally accomplishes” main extrinsic factor: attributes of the supervisor candidate# 2 “supervisor is the most important person in your research” candidate# 5 “my supervisor was a very busy person, he did not guide me as i collected the data myself and analysed it by myself. my seniors and colleagues guided and helped me in this regard. the role of supervisor should be supportive otherwise research becomes very difficult.” candidate# 6: ''supervisor should be an experienced researcher and only then he/she can guide you well and can foresee all the upcoming problems. a supervisor can help the researcher sail through the storm.'' candidate# 9: supervisor matters a lot! one of the supervisors i know calls his trainees regularly and takes notice of their progress. one trainee was not responding so the supervisor went to his office to inquire about the problem. intrinsic factor: attributes of the researcher all participants commented on the attributes that helped them to complete their master’s thesis. the results are depicted in table 2. several factors were considered essential traits in the progression towards successful completion of their master’s course when present and their absence negatively affected the completion of a thesis. sub-themes were identified as self-motivation, self-regulation, age of the participant, and career progression. almost all the participants 426 journal of rawalpindi medical college (jrmc); 2021; 25(3): 423-428 believed that their self-motivation played a critical role in the progression of their thesis. the main motivating factors to complete the thesis were to be better teachers, progression in their career, and reaching a milestone. most of the respondents were motivated to learn to teach better as well as implement changes in their institutions. three of the interviewees also stated that during face-to-face sessions the level of motivation is better as compared to that during remote learning. the social interaction with other colleagues during face-to-face sessions motivates them to complete their thesis according to another participant. the presence of self-regulation was also described as an important attribute that played a crucial role in the completion of the thesis on time. the participants were able to complete the thesis when they set aside an allocated time for its completion. the busy schedule of most of the participants was their greatest hindrance to complete the thesis in time. according to one participant, had she regulated her work-life balance better, the thesis would have been completed in time. main extrinsic actor: attributes of the supervisor regarding the role of the supervisor in thesis completion, a few sub-themes were identified. these included the supervisor-student relationship, supervisor’s commitment, availability of supervisor, personality traits of the supervisor. one of the main factors responsible for the completion of a timely thesis was the relationship of the interviewee to his supervisor. the supervisor’s availability and commitment were also directly related to the timely completion of the thesis. according to one participant, thesis writing was positively affected by input from an international supervisor although his availability was limited. contrary to this, another participant communicated that thesis writing was greatly hampered by the inadequate availability of the supervisor. this problem was more pronounced when the supervisor was from another country and communication was possible only remotely and at specific times. among personality traits of the supervisor, friendliness and give timely feedback was appreciated by all interviewees. similarly, ability, knowledge, and readiness to share information were also considered as essential traits aiding the completion of the thesis. discussion the current study aimed to gain an insight into the factors which influenced the thesis writing of postgraduate medical educationists. among intrinsic determinants, one of the main factors considered by the interviewees was their personal motivation and self-regulation. self-regulation has been defined as the process by which students take charge of their learning and use individualized strategies to monitor their task achievement.12 furthermore, motivation goes hand in hand with self-regulation and is essential for the effective control of task completion.11 the participants suggested that after each face-to-face contact session, they became more motivated and selfregulated, but the motivation and self-regulation decreased over time especially during the intervals of remote learning. this is in line with previous studies which document difficulty to regulate learning and goal setting in distant learning environments.5 according to social-cognitive theory, motivation, and self-regulation are enhanced through reciprocal social and environmental interactions.15 lack of contact with peers and instructors may have decreased intrinsic motivation according to self-determination theory according to which social relatedness is essential and one of the basic psychological needs modulating motivation. it is suggested by empirical evidence that individuals tend to passively procrastinate during periods of low motivation.16 this passive procrastination is particularly associated with distance learning environments.17 to achieve their goals, they must formulate and modify strategies, manage their time, and individualize their learning. all this may overwhelm the trainee, posing difficulties to complete the given task on time.18 the second theme identified as a factor affecting the completion of the thesis was the role of the supervisor. it is well documented that the expertise provided by the supervisor is indispensable to develop research skills and produce a quality thesis.19 among the sub-themes, the supervisor-student relationship was considered important by all participants. the value of good communication and working relationship between supervisor and students have been shown previously 20 psychosocial interactions between the supervisor and student helps to develop confidence and self-efficacy. studies show that a supportive mentor-supervisor relationship plays a vital role in developing competencies like motivation, attention, problem-solving, and selfesteem.20 studies also link positive teacher-student relationships to better academic performance.20 there is a consensus among researchers, teachers, and 427 journal of rawalpindi medical college (jrmc); 2021; 25(3): 423-428 scholars that motivation is one of the variables that determine academic success and enhances learning. better relations between the supervisor and the students are critical to motivating them to learn through fulfilling their basic needs according to the theory of self-determination. therefore, students need to communicate with their supervisors for autonomy, competence, and relatedness.13 a supervisor who develops a personal and caring relationship and shows genuine interest, leads to the fulfilment of the need for relatedness. moreover, it is documented that need satisfaction enhances internal motivation.13 similarly, supervisor’s availability and commitment also impacted the completion of the thesis in our sample of participants. in the case where the supervisor was residing abroad, his time commitment and availability were compromised. detailed and timely feedback is critical. lack of commitment and limited availability of a supervisor can be major barriers to the completion of the thesis. another sub-theme identified relevant to the supervisor was his personality traits. most respondents considered the supervisor's personality to be a critical factor in the completion of their thesis. a supervisor having a positive influence on thesis completion was reliable, competent, had listening skills, encouraging students, provided timely feedback, and was understanding. this is in accordance with the social cognitive theory which suggests that the mentors can effectively regulate student learning through interaction and positive relationships. learning results from reciprocal interactions among personal behavioral and environmental factors.20 acting as role models, teacher’s constructive feedback and encouragement are directly linked to the trainee’s task achievement.20 motivation to learn and achieve increases when the student believes that the teacher cares about them. a warm and friendly environment facilitates adaptation and motivates the learner to interact. they can take intellectual risks, and this enhances their learning. on the other hand, relational conflict has been shown to lower self-esteem and is associated with lower achievement. students were inclined to work harder if they experienced a caring attitude from their teachers; that motivated students to learn better and learn by themselves.20 accordingly, steps can be taken to address the difficulties faced by mhpe trainees to enhance their thesis completion experience. above all, supervisors and teachers should be better trained to help trainees develop strategies to selfregulate and motivate during the periods of remote learning sessions. interaction opportunities during periods of distant learning should be provided. these may be in the form of video conferences/online forums to discuss progress and trainee virtual groups for group projects. senior fellows who are ahead in their thesis completion should pair up with juniors to provide peer mentorship. this may alleviate pressure and help novices to understand the requirements and expectations. the role of the supervisor is critical during this process; training sessions should be frequently organized to reinforce the importance of regular feedback and development of skills to supervise effectively. only those should be recruited as supervisors who can commit to the exhaustive time requirements of this position. limitations it should be mentioned that this study came with certain limitations which could change the results of the study. researchers who couldn’t complete their masters in health profession education could not be interviewed since were difficult to approach. certain intrinsic or extrinsic factors may have been over or underestimated due to this limitation. conclusion it is evident that the successful completion of the mhpe thesis depends on multiple factors. the rising demand for trained faculty in medical education necessitates further investigation of these factors. the development of self-regulation strategies through qualified and competent mentorship may play a key success factor in thesis completion. a structured program for the professional development of supervisors is essential. effective and timely feedback may increase internal motivation and self-regulation for timely thesis completion. it is advised that in future studies conducted on similar topics, the researchers should also mention the intrinsic and extrinsic factors from the perspective of the supervisors. acknowledgements we thank all the mhpe graduates who participated in this study. 428 journal of rawalpindi medical college (jrmc); 2021; 25(3): 423-428 references 1. dent j, harden rm. a practical guide for medical teachers. elsevier health sciences; 2017 isbn: 9780702068935 2. latif mz, wajid g. reforming medical education in pakistan through strengthening departments of medical education. pak j med sci. 2018;34(6):1439-1444. doi:10.12669/pjms.346.15942 3. sethi a, javaid a. accreditation system and standards for medical education in pakistan: it’s time we raise the bar. pak j med sci. 2017;33(6):1299–1300. doi: 10.12669/ pjms.336.14178 4. bleakley a, brice j, bligh j. thinking the post-colonial in medical education. med educ. 2008;42(3):266–270 doi: 10.1111/j.1365-2923.2007.02991.x 5. rizwan m, rosson nj, tackett s, hassoun ht. opportunities, and challenges in the current era of global medical education. int j med educ perspect. 2018;9:111–112. doi: 10.5116/ijme.5ad1.ce9a 6. khalid t. faculty perceptions about roles and functions of a department of medical education. j coll physicians surg pak. 2013;23(1):57–61 doi: https://jcpsp.pk/archive/2013/jan2013/13.pdf 7. department of medical education [internet]. king edward medical university. [cited 2018 jul 14]. available from: http://kemu.edu.pk/department-of-medical-education/ 8. list of recognised medical and dental institutions/ colleges / dai’s [internet]. pakistan medical & dental council. 2018 [cited 2018 jul 14]. available from: http://www.pmdc.org. pk/allrecognizedinstitutes/tabid/340/default.aspx 9. ives, g., & rowley, g. (2005). supervisor selection or allocation and continuity of supervision: phd students’ progress and outcomes. studies in higher education, 30(5), 535–555 doi:10.1080/03075070500249161 10. ac klassen, j creswell, vlp clark, kc smith best practices in mixed methods for quality of life researchquality of life …, 2012 doi: 10.1007/s11136-012-0122-x 11. batool s, raza ma, khan ra. pak. roles of medical education department: what are expectations of the faculty? j med sci. 2018;34(4):864-868. doi: 10.12669/pjms.344.14609. 12. sethi a, ajjawi r, mcaleer s, schofield s exploring the tensions of being and becoming a medical educator. bmc med educ. 2017; 17:62. doi: 10.1186/s12909-017-0894-3. [pmc free article] 13. ryan rm, deci el. self-determination theory and the facilitation of intrinsic motivation, social development, and wellbeing. am psychol.2000; 55:68-78. doi: 10.1037//0003066x.55.1.68 14. davis mh, karunathilake i, harden rm. amee education guide no. 28: the development and role of departments of medical education. med teach. 2005;27(8):665–675. doi: 10.1080/01421590500398788 15. a bandura. the explanatory and predictive scope of selfefficacy theory journal of social and clinical psychology, 1986 guilford press doi: https://doi.org/10.1016/03064603(90)90070-e 16. steel, p. (2007). the nature of procrastination: a metaanalytic and theoretical review of quintessential self-regulatory failure. psychological bulletin, 133, 65–94. doi:10.1037/00332909.133.1.65 17. ferla, j., valcke, m., & schuyten, g. (2010). judgments of self-perceived academic competence and their differential impact on students’ achievement motivation, learning approach, and academic performance. european journal of psychology of education, 25, 519–536. doi:10.1007/s10212-010-0030-9 18. pelikan, e.r., lüftenegger, m., holzer, j. et al. learning during covid-19: the role of self-regulated learning, motivation, and procrastination for perceived competence. 24, 393–418 (2021). doi: https://doi.org/10.1007/s11618-021-01002-x 19. heath, t. (2002). a quantitative analysis of phd students’ views of supervision. higher education research & development, 21(1), 41–53. doi: https://doi.org/10.1080/07294360220124648 20. ives, g., & rowley, g. (2005). supervisor selection or allocation and continuity of supervision: phd students’ progress and outcomes. studies in higher education, 30(5), 535–555 doi:10.1080/03075070500249161 21. paglis, l. l., green, s. g., & bauer, t. n. (2006). does adviser mentoring add value? a longitudinal study of mentoring and doctoral student outcomes. research in higher education, 47(4), 451–476. doi: https://doi.org/10.1007/s11162-005-9003-2 499 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 original article the impact of covid-19 pandemic on final year medical students: single center study ahmad ussaid1, farwa pervaiz2, wajid ali rafai3, faisal amin baig4, sarwat hassan syed5, ahsan masud6 1,3 senior registrar, department of medicine, university college of medicine and dentistry, lahore. 2 medical officer, chaudhary muhammad akram teaching and research hospital, lahore, 4 associate professor, department of medicine, university college of medicine and dentistry, lahore. 5 assistant professor, department of otolaryngology, services institute of medical sciences, lahore. 6 senior demonstrator, department of medicine, university college of medicine and dentistry, lahore. author’s contribution 4 conception of study 2 experimentation/study conduction 1,6 analysis/interpretation/discussion 3 manuscript writing 5 critical review 4 facilitation and material analysis corresponding author dr. wajid ali rafai, senior registrar, department of medicine, university college of medicine and dentistry, lahore. email: wajidalirafai@gmail.com article processing received: 28/06/2021 accepted: 11/12/2021 cite this article: ussaid, a., pervaiz, f., rafai, w.a., baig, f.a., syed, s.h., masud, a. the impact of covid-19 pandemic on final year medical students: single center study. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 499-506. doi: https://doi.org/10.37939/jrmc.v25i4.1717 conflict of interest: nil funding source: nil access online: abstract introduction: the covid-19 health emergency led to the adoption of unprecedented measures that have never been seen in recent times. the study examines the effect of covid-19 on final year medical students’ final professional examination preparedness, transition to house job, and earlier assistantship. materials and methods: this descriptive cross-sectional survey was conducted in september – october 2020 after institutional review board approval at the university college of medicine and dentistry (ucmd) in lahore, pakistan. of a total of 125 final years, medical students 112 responded to the survey questionnaire. data were analyzed using spss 25. the chi-square test was applied to evaluate the impact of covid 19 on variables of interest (p-value< 0.05 was considered significant). results: postponement of clinical rotations, written exams, ospes, and clinical ward tests was reported by 62%, 78%, 71%, and 48% students respectively whilst 29%, 13%, 18%, and 21% students respectively stated it to be formatted. a statistically significant impact (p<0.05) was observed for final professional examinations preparedness and confidence to assist earlier. conclusion: the study demonstrated the significant impact of covid-19 on final year medical students’ examination preparedness and confidence to assist earlier in the hospital. the improvised teaching methodology is urgently needed to fill in the lapses in their education. keywords: covid-19, medical education, final year mbbs professional examination, ospe, earlier assistantship, house job. 500 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 introduction pneumonia of unknown etiology emerged as an outbreak in wuhan city, hubei province, china in december 2019.1 in january 2020, world health organization (who 2020) named the etiological agent as “novel coronavirus 2019” (2019-ncov) responsible for causing this pneumonia-like illness.2 covid-19 was announced as a global pandemic by the world health organization (who) on march 11, 2020. a sars-cov-2 virus is transmitted by respiratory droplets.3,4 a study at wuhan hospital showed sars‐cov‐2 surface and aerosol presence at numerous areas of intensive care and wards. sars‐cov‐2 surfaced up with stronger pathogenicity and rampant transmissibility, proving itself as more infectious than sars‐cov and mers‐cov.5,6 the speedy transmission of covid-19 compelled governments across the globe including the pakistani government to enforce lockdown, shutting of markets, and closure of all educational activities. this has led to a dramatic impact on educational institutions worldwide particularly affecting medical education where student congregation and patient exposure go hand in hand. medical colleges as a result have halted their on-campus teaching and shifted to online teaching to bridge the gap.7,8 the pandemic has led to the introduction of new methods of teaching and assessments. there are various components of the curriculum, which led to the learning, and assessment of final year medical students. this has had a unique effect on final year mbbs students where in addition to classroom teaching, bedside teaching in wards is an integral part of the curriculum. these students are undergoing a lifetime transition from being students to doctors.9 the main aim of medical professionals is to provide patient care and handle epidemics but their role as a medical educators is also of vital importance. health professionals in these crisis times of pandemic have been put under great stress and consequently, their job as medical educator has also been impacted. therefore, hospital clinical rotations ward tests, ospes, and written examinations in final year medical students’ lives act coherently to make the doctor of tomorrow.10 medical colleges have curtailed clinical contact for students leading up to their final exams to minimize the risk of acquiring the virus. there has been a paradigm shift from traditional teaching methods to online lectures and audio-visual demonstrations for these students.7,10 online medical education poses many challenges like managing time, using a technological toolkit, examinations, face to face interaction. time will guide us about the ingenuities for medical education that we will see in the era of the covid-19 pandemic.11 therefore, we planned this study to explore the effect of covid-19 on final year medical students’ education and its effect on their preparedness for the final professional mbbs examination and house job as a consequence. this will furnish treasured understanding for medical colleges on how this global emergency has impacted medical teaching and lessons moving ahead. materials and methods a descriptive cross-sectional 10-item online questionnaire was circulated to final year medical students after ethical review board approval at the university college of medicine and dentistry (ucmd) in lahore, pakistan by using google forms. openended, closed-ended, and on a five-point likert response scale questions were used to collect the data. participation in the study was voluntary. noncooperative students were excluded. non-probability purposive sampling was used, and a total of 112 students participated out of class strength of 125. the impact of covid-19 was assessed on hospital clinical rotations, medical written exams, ospes, and clinical ward tests for final year medical students and their preparedness for final year professional examination and house jobs. confidence in regards to an earlier assistantship in the wake of covid 19 was also evaluated. statistical analysis was completed using spss 25. categorical data were computed as frequencies and percentages. fisher’s exact test was applied to evaluate the impact of covid 19 on variables of interest and pvalue < 0.05 was considered significant. results one hundred and twelve students (n=112) responded to the survey out of the total class strength of one hundred and twenty-five students (n=125). a total of one hundred and twenty students on average graduate per year in this medical school. the effect of covid-19 on clinical rotations, theory (written) exams, ospe, and clinical ward tests is shown in figure 1. 501 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 a large number of clinical rotations, written examinations, ospes and clinical ward tests were predictably postponed as reported by respondents 62% (n=69), 78% (n=87), 71% (n=79) and 48% (n=54) respectively (fig1a-1d). this was followed by format changed to online version as reported by 29% (n=32), 13% (n=15), 18% (n=20) and 21% (n=23) respectively (figure 1a-1d). however, a relatively small percentage of cohort reported cancellation of clinical rotations by 9% (n=10), written examinations by 4% (n=5), ospes by 4% (n=5) and clinical ward tests by 22% (n=25) respectively (figure 1a-1d). no change was reported by 1% (n=1), 4% (n=5), 7% (n=9) and 9% (n=10) amongst clinical rotations, written examinations, ospes and clinical ward tests respectively (figure 1a1d). the participants were additionally evaluated using a five-point likert scale of agreeable over five components as illustrated in figure 2. with regards to preparedness for house job, 68% (n=76) ‘strongly agree’ and 22% (n=25) ‘agree’ for being underprepared for house job. whilst evaluating satisfaction to covid-19 precautions related to changes in curricula, 29% (n=32) ‘strongly agree’ and 50% (n=56) ‘agree’ that these precautions were necessary. thirtytwo percent (32%, n=36) ‘strongly agree’ and 40% (n=45) ‘agree’ that commencing in hospitals earlier than anticipated time would augment their learning opportunities. taking into account the confidence of the students to assist earlier than anticipated, only 21% (n=24) ‘strongly agree’, 27% (n=30) ‘agree’ and the majority of the students that is 34% (n=38) remained ‘neutral’. no statistically significant impact was noted among the factors affecting preparedness for the house job (p>0.05). taking into account the students’ preparation for final year examinations, the alterations to clinical rotations and written exams had a significant impact (p=0.001 and p=0.024 respectively) as presented in table 1. furthermore, whilst evaluating how confident they are to start earlier than anticipated in the hospital, a statistically noteworthy effect was the interruption of clinical rotations and clinical ward tests (p=0.042 and p=0.041 respectively) as outlined in table 2. 502 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 figure 1: pie-charts outlining the effect of covid 19 on medical college (a) clinical rotations (b) written exams (c) ospe (d) clinical ward tests. (a-d), n = 112 a b c d 503 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 figure 2: stacked bar chart of likert questions illustrating answers by final year medical students on: supplemented learning following earlier assistance in hospitals, confidence in earlier assistance, satisfaction with covid-19 precautions, and level of preparedness for exams due to these precautions table 1: factors affecting preparedness for final year mbbs examinations preparedness total strongly disagree disagree neutral agree strongly agree pvalue affected: clinical rotations 0.001 postponed 69 5 5 5 10 44 format changed – online format 32 6 5 5 6 10 cancelled 10 2 0 0 2 6 no change 1 0 1 0 0 0 affected: written exams 0.024 postponed 87 6 7 6 10 58 format changed – online exam 15 0 0 0 5 10 cancelled 5 0 0 1 1 3 no change 5 0 2 0 1 2 affected: ospe responses 0.122 postponed 79 6 5 6 12 50 format changed – online assessment 20 2 5 0 5 8 cancelled 4 0 0 1 0 3 no change 9 3 2 0 1 3 504 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 affected: clinical ward tests 0.521 postponed 54 0 3 1 13 37 format changed – online video assessment 23 1 2 1 3 16 cancelled 25 0 0 1 6 18 no change 10 0 2 0 3 5 table 2: factors affecting the confidence to assist in hospitals earlier confidence total strongly disagree disagree neutral agree strongly agree pvalue affected: clinical rotations 0.042 postponed 69 5 23 10 16 15 format changed – online format 32 6 11 5 5 5 cancelled 10 1 6 0 1 2 no change 1 0 1 0 0 0 affected: written exams 0.567 postponed 87 5 8 29 18 27 format changed – online exam 15 2 3 0 5 5 cancelled 5 1 1 0 1 2 no change 5 0 3 0 1 1 affected: ospe responses 0.476 postponed 79 5 9 24 20 21 format changed – online assessment 20 5 5 8 3 8 cancelled 4 0 2 1 0 1 no change 9 4 3 0 2 0 affected: clinical ward tests 0.041 postponed 54 8 18 6 16 6 format changed – online video assessment 23 5 7 1 5 5 cancelled 25 5 10 0 5 5 no change 10 3 5 1 1 0 discussion our study showed hospital clinical rotations and clinical ward tests having a significant impact on the students’ final professional examination preparation and the confidence going into earlier assistantship in the hospital. the effect on the preparation for the house job did not display a statistically significant impact that was unexpected. one possible explanation of this was that the students in final year are more concerned and focused on their professional examination as they cannot progress to a house job without passing it. secondly, students at mid-way of their final year study do not realize the impact on their house job preparation. the majority of students reported a notable impact on hospital clinical rotations, written exams, ospe, and clinical ward tests in our study, which was similar to the findings in a study conducted on medical students in the penultimate year of medical school at ghent and leuven university, belgium.12 it was also in accordance with the findings in a national survey conducted in the united kingdom apart from written exams, which were not significantly affected.13 the effect of an ongoing pandemic on ospes, written exams, and student assistantship remarkably disrupted students’ readiness for foundation year training in a survey (respectively p = 0.025, 0.008, 0.0005)13, while in our study effect of covid-19 on hospital clinical rotations, written exams, ospes and clinical ward tests had no significant impression (p>0.05) on students’ preparedness for house job. findings of format changing to online classes in our study were consistent with the research carried out in germany.14 in our study, hospital clinical rotations being affected by covid-19 had the most remarkable impact on final professional examination (p=0.04) and assistantship in hospital (p=0.001) comparable to observations in a study (37%, p<0.05) conducted in our neighboring country india.15,16 about confidence in assisting earlier 505 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 than anticipated in hospital, 48.2% of our study population felt confident which was quite in line with already published literature.17-20 limitations there are a few limitations of our study. the students’ responses were recorded at one time when in lahore, pakistan the first wave of covid-19 pandemic had begun to decline. we did not record any follow-up responses from students going into the examinations & house jobs. subsequently, the effect of covid-19 on medical teaching, in the long run, could not be assessed. another important limitation was that it was a single-center study with small sample size, so it is not representative of all final year mbbs students in pakistan. moreover, our study population had uninterrupted access to well-organized online medical education during the suspension of on-campus and inhospital teaching. this is not being the case in all the medical colleges across pakistan because of technological and logistical limitations. there are 169 medical and dental colleges registered with the pakistan medical and dental college and many of them do not have dedicated information technology department (it). another limitation while assessing the preparedness of students for house jobs was that it was being evaluated before students appeared in the final professional examination. medical students have to pass their final professional examination before even commencing the process of house job allocation and their focus would be passing the final examination. they may not realize the actual impact of the pandemic on their house job preparation. recommendations 1. contingency teaching plans should be applicable in the face of such pandemics in order to minimize interruptions in students’ education. 2. improvisation in online teaching format will be required in order to fill in the gap created by the pandemic and to resurface the confidence of the students in regards to their preparedness for different format examinations. 3. clinical rotations/ward classes to be conducted with strict covid safety precautions in order to minimize the clinical hands-on experience to the students. 4. students and teaching faculty’s regular feedback and suggestions should be actively sought by managers of medical education at the institute along with close supervision to achieve the goal of making competent doctors even in times of crisis. 5. more studies with a larger sample size such as multi-institutional study should be carried out with an analytical type of study such as comparing before and after examinations to determine the more predictable effect size. conclusion the covid-19 has had extraordinarily affected medical teaching in pakistan. a large proportion of medical graduates feel underprepared for final professional examination and hospital assistantship, whereby interruptions to hospital clinical rotations and ward tests had a noteworthy impact on students’ readiness. a notable number of students felt optimistic in helping the manpower in the hospital during this health emergency, despite being underprepared. medical colleges’ and hospitals’ managers should keep in mind the covid-19 induced uncertainty to the final year mbbs students’ confidence and readiness. this pandemic has served as a catalyst to explore new avenues in medical education. medical educators will learn more lessons in times to come by to handle times like this in medical education. references 1. lu h, stratton cw, tang y-w. the wuhan sars-cov-2what’s next for china. j med virol. 2020;92(6):546–7. https://doi.org/10.1002/jmv.25738 2. world health organization (30 january 2020). novel coronavirus (2019-ncov): situation report, 10 (report). world health organization. hdl:10665/330775. 3. cucinotta d, vanelli m. who declares covid-19 a pandemic. acta biomed. 2020;91(1):157–60. https://doi.org/10.23750/abm.v91i1.9397 4. sommerstein r, fux ca, vuichard-gysin d, abbas m, marschall j, balmelli c, et al. risk of sars-cov-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from covid-19. antimicrob resist infect control. 2020;9(1):100. https://doi.org/10.1186/s13756-020-00763-0 5. anderson el, turnham p, griffin jr, clarke cc. consideration of the aerosol transmission for covid-19 and public health. risk anal. 2020;40(5):902–7. https://doi.org/10.1111/risa.13500 6. epidemiology working group for ncip epidemic response, chinese center for disease control and prevention. the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (covid-19) in china. zhonghua liu xing bing xue za zhi. 2020;41(2):145–51. https://doi.org/10.3760/cma.j.issn.0254-6450.2020.02.003 506 journal of rawalpindi medical college (jrmc); 2021; 25(4): 499-506 7. ahmed h, allaf m, elghazaly h. covid-19 and medical education. lancet infect dis. 2020;20(7):777–8. https://doi.org/10.1016/s1473-3099(20)30226-7 8. ferrel mn, ryan jj. the impact of covid-19 on medical education. cureus. 2020;12(3):e7492. https://doi.org/10.7759/cureus.7492 9. sandhu p, de wolf m. the impact of covid-19 on the undergraduate medical curriculum. med educ online. 2020;25(1):1764740. https://doi.org/10.1080/10872981.2020.1764740 10. tokuç b, varol g. medical education in turkey in time of covid-19. balkan med j. 2020;37(4):180–1. https://doi.org/10.4274/balkanmedj.galenos.2020.2020.4.003 11. rajab mh, gazal am, alkattan k. challenges to online medical education during the covid-19 pandemic. cureus. 2020;12(7):e8966. https://doi.org/10.7759/cureus.8966 12. kapila v, corthals s, langhendries l, kapila ak, everaert k. the importance of medical student perspectives on the impact of covid-19: medical student perspectives on the impact of covid-19. br j surg. 2020;107(10):e372–3. https://doi.org/10.1002/bjs.11808 13. choi b, jegatheeswaran l, minocha a, alhilani m, nakhoul m, mutengesa e. the impact of the covid-19 pandemic on final year medical students in the united kingdom: a national survey. bmc med educ. 2020;20(1):206. https://doi.org/10.1186/s12909-020-02117-1 14. loda t, löffler t, erschens r, zipfel s, herrmann-werner a. medical education in times of covid-19: german students’ expectations a cross-sectional study. plos one. 2020;15(11):e0241660. https://doi.org/10.1371/journal.pone.0241660 15. patil p, chakraborty s. where does indian medical education stand amidst a pandemic? j med educ curric dev. 2020;7:2382120520951606. https://doi.org/10.1177/2382120520951606 16. o’byrne l, gavin b, mcnicholas f. medical students and covid-19: the need for pandemic preparedness. j med ethics. 2020;46(9):623–6. https://doi.org/10.1136/medethics-2020106353 17. patel vm, dahl-grove d. disaster preparedness medical school elective: bridging the gap between volunteer eagerness and readiness. pediatr emerg care. 2018;34(7):492–6. https://doi.org/10.1097/pec.0000000000000806 18. farooq f, rathore fa, mansoor sn. challenges of online medical education in pakistan during covid-19 pandemic. j coll physicians surg pak. 2020;30(6):67–9. https://doi.org/10.29271/jcpsp.2020.supp1.s67 19. nepal s, atreya a, menezes rg, joshi rr. students’ perspective on online medical education amidst the covid-19 pandemic in nepal. j nepal health res counc. 2020;18(3):551– 5. https://doi.org/10.33314/jnhrc.v18i3.2851 20. singh k, srivastav s, bhardwaj a, dixit a, misra s. medical education during the covid-19 pandemic: a single institution experience. indian pediatr. 2020;57(7):678–9. https://doi.org/10.1007/s13312-020-1899-2 77 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 original article diagnostic value of hrct-thorax for pandemic covid-19 pneumonia in pakistan abdul rasheed qureshi1, zaheer akhtar2, muhammad irfan3, muhammad sajid4, zeeshan ashraf5 1,3 pulmonologist, department of pulmonology, gulab devi teaching hospital, lahore. 2 professor, department of pulmonology, gulab devi teaching hospital, lahore. 4 medical officer, gulab devi teaching hospital, lahore. 5 lecturer, department of statistics, gulab devi educational complex, lahore. author`s contribution 1 conception of study 1,3,4 experimentation/study conduction 3,4 analysis/interpretation/discussion 1,2,3,5 manuscript writing 2,5 critical review 2,4,5 facilitation and material analysis corresponding author dr. muhammad irfan pulmonologist, department of pulmonology, gulab devi teaching hospital, lahore. email: irfan16d2@gmail.com article processing received: 25/7/2020 accepted: 06/8/2020 cite this article: qureshi, a.r., akhtar, z., irfan, m., sajid, m. & ashraf, z.(2020). diagnostic value of hrct-thorax for pandemic covid-19 pneumonia in pakistan. journal of rawalpindi medical college, 24 covid-19 supplement-1, 77-84. doi: https://doi.org/10.37939/jrmc.v24isupp-1.1443 conflict of interest: nil funding source: nil access online: abstract background: in the scenario of, inadequate testing, the low sensitivity of the covid-19-pcr test, limited availability of testing kits, and low detection rate, we aimed to investigate the usefulness of high-resolution computed tomography of chest (hrct) for diagnosing pandemic coronavirus (covid-19) pneumonia. objective: to determine the diagnostic efficacy of hrct thorax in covid-19 pandemic pneumonia. materials and methods: this prospective, cross-sectional study was conducted in the pulmonology–opd of gulab devi teaching hospital, lahore-pakistan from 01-04-2020 to 15-07-2020. 121 patients with dry cough, fever, and dyspnea of sudden onset were included while patients with bronchial asthma, ild, tuberculosis, bronchiectasis, copd, and overt heart failure were excluded. patients were investigated with chest x-ray, hrct, covid-pcr, and hematological tests. hrct films were evaluated by a qualified and experienced radiologist. findings were summarized, organized and statistical analysis was done by using spss-26 software to make an inference. results: five patients were diagnosed as non-covid. out of 116-diagnosed covid-19 patients, 38(32.75%) showed sub-pleural consolidation, 19(16.37%) consolidation with air-bronchogram, 29(25.0%) crazy paving sign, one pleural effusion (0.86%) and 18 cases (15.51%) displayed reticulations. 11cases(9.48%) had isolated ground glass appearances, while all categories showed it to variable extent. 65 patients (56.03%) were pcr-positive while 51(43.96) patients with positive-hrct findings for covid-19 pneumonia had negative nasopharyngeal-pcr. hrct-thorax revealed sensitivity: 97.41 %, specificity: 80%, ppv: 99.12%, npv: 57.14%, and diagnostic accuracy of 96.69% for covid-19 pneumonia. conclusion: hrct-thorax, having high sensitivity and adequate specificity, can provide foundations for evidence-based early diagnosis and quantification of coronavirus pneumonia. it can be tremendously useful for decision making in pcr-negative patients and anticipating respiratory improvement or decline by serial scans. keywords: corona virus pneumonia-hrct thorax-high sensitivity, diagnostic value. 78 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 introduction the first case of coronavirus pneumonia was noticed in wuhan, china in december 2019 and was later on recognized as coronavirus disease 2019 (covid-19).1 this epidemic spread worldwide like wildfire. who (world health organization) declared it as a public health emergency of international concern (pheic).2 this disease is highly contagious and the number of cases multiplied rapidly over the globe. current literature suggests that one infected patient may lead to more than two new patients.3 some-times, the disease is too drastic to be controlled and the outcome is a disaster only. this disease has challenged almost all fields of medicine and has affected not only the public rather very senior health care providers and eminent figures from the society have been lost to this lethal disease. at the mid of july, we are having 255,769 confirmed cases and 5,386 mortalities in the country, indicating the load and damage caused by this fatal disorder. the presentation of covid-19 disease ranges from mild to an extensive disease requiring mechanical ventilation. early diagnosis is crucial for the good management and effective control to preclude further dissemination. usually patient presents with fever, dry cough, shortness of breath, and body aches and pains. the severity and acuteness of the symptoms, coupled with the propensity for an abrupt decline in respiratory function, necessitates the need to measure the magnitude of pulmonary involvement. nasopharyngeal-pcr is the gold standard for diagnosis but its availability and sensitivity are quite low, around 60%. about 30-40% of cases are missed by this technique due to a high false-negative rate.4 furthermore, this test is not capable of calculating the magnitude and expected respiratory decline in patients. chest x-ray pa view is limited in its ability to detect the early involvement of lung with covid19 infection.5 in contrast, hrct-thorax has been reported as a good tool for evidence-based diagnosis in the current epidemic, providing immediate results with high sensitivity and adequate specificity for covid-19 pneumonia and the extent of pulmonary disease.6-7 hrct-thorax can play a pivotal role by identifying the early phase lung infection and have been recommended as major evidence for clinical diagnosis in china.8 current researchers have reported the sensitivity of hrct for covid-19 infection more than 90% as compared to pcr around 60-70%. according to who, hrct can be very useful in determining the diagnosis, progression, and severity of the covid-19 disease.9-10 the use of hrct in pakistan is very limited due to profound fear, contagiousness & inadequate understanding and is tried only in selected cases.11-12 the chinese literature is rich in evidence, advocating the use of hrct-thorax while the european, british and american radiological societies which were not recommending this modality in the beginning, are changing their statements about the use of hrct.13-15 radiological society of pakistan has also suggested, the appropriate use of ct scan in selected patients as a tool to triage, in the background of increased incidence of covid-19 symptomatic patients.16 materials and methods this prospective study was conducted in pulmonology-opd of gulab devi teaching hospital, lahore. (a 1500 bed-tertiary care hospital in the capital city of punjab province). ethical approval was obtained from the irb of the hospital vide: no. admin/gdec/20/325. after informed consent, 121 opd patients, from 1st april 2020 to 15 july 2020 with a presumptive clinical diagnosis of covid-19 infection were included. history of dry cough, fever, and shortness of breath of sudden onset were the main complaints while patients with bronchial asthma, ild, tuberculosis, bronchiectasis, copd, and overt heart failure were excluded. all patients underwent routine hematological tests including white blood cell count, lymphocyte count, and hypersensitive creactive protein tests. the patients were subjected to an x-ray chest pa view, hrct thorax, ecg, and echocardiography. the x-ray chest (cxr) & hrct images were evaluated by a qualified radiologist with 20 years of experience at least. cxr was analyzed for haze and ill-defined consolidations with bilateral involvement. hrct films were evaluated for radiological morphology and distribution patterns. ecg & echocardiography explored cardiac status. all patients underwent the covid-19 pcr-test by nasopharyngeal sample. imaging findings, demographic and clinical data of the 121 patients were recorded on a preformed form. sensitivity, specificity, and diagnostic accuracy were calculated by considering nasopharyngeal-pcr as a gold standard. diagnostic yield was calculated on clinical, pcr, and hrct grounds independently. data was organized, summarized, tabulated and bio-statistical analysis was 79 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 done to conclude. for statistical analysis, spss-26 software was utilized. quantitative data were described by + sd and categorical variables were expressed by frequency (percentage). fissure exact test was used for comparison and a p-value < 0.05 was considered as significant. results this study included 121 patients age 18 to 67 years. the mean age was 42.64 years ± sd 17.62. male gender was noted in 67 patients while 54 patients were female, male to female ratio was 1.2. all patients had contact history from their familial clusters. patients presented with typical respiratory complaints (tablei). 56 cases (46.28%) were above the age of 50 years, obesity was found in 13 cases (10.74%), cigarette smoking 39 (32.23%) and diabetes mellitus (dm) was found in 39 cases (32.23%). 79 patients (65.28%) had elevated levels of crp with mean 8.7 + sd 6.2 mg/dl. only 65 patients (53.71%) were positive for covid-19 pcr-test. hrct findings were consistent with covid-19 in 113 patients while it was unremarkable for 03 patients. five patients, diagnosed as non-covid-19, consisted of abpa (allergic broncho-pulmonary aspergillosis) and bacterial pneumonia two cases each and one case was diagnosed nsip by correlation with clinicopathological data. table 1: frequency of symptoms in 121 patients the radiological morphology and radiographic appearance are described by figure 1 and figure 2. not even a single case of cavitation or pneumothorax was found in 116 cases. disease distribution pattern is depicted in table 2. table 2: frequency of symptoms in 121 patients nos. pattern of distribution no. of cases percentage 1. unilateral 00 00 2. bilateral 121 100 3. predominant right lung 57 47.10 4. predominant left lung 38 31.40 5. symmetrical bilateral 26 21.48 6. upper part predominant 26 21.48 7. lower part predominant 95 78.51 8. central lesions 35 28.93 9. peripheral lesions 86 71.07 10. scattered lesions 11 9.09 n = 121 figure 1: hrct-morphology of 116 covid-19 patients. (ggo: ground glass opacity) no s clinical feature no. of cases percentage 1. high-grade fever 96 79.33 2. dry cough 67 55.37 3. shortness of breath 109 90.08 4. muscle pain and weakness 99 81.81 5. vague chest pain 34 28.09 6. flu-like symptoms 21 17.35 7. no symptoms 12 9.91 80 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 a b c d *plain x-ray and hrct features e f g h i j k l m n o p figure 2: common radiological morphologies in covid-19 pulmonary infection *a: patchy ill-defined consolidations, b: bilateral haze, c: bilateral reticulations, d: diffused ggo (coronal scan), e: multifocal ggo, f: basal ggo, g: focal ggo, h & i: multifocal sub-pleural consolidation, j: crazy paving sign, k&l: peripheral multi-focal consolidations + reticulations, m&n: peripheral consolidation, o: consolidation with air-bronchogram, p: reticulations with minimal ggo. 81 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 calculations: 1. total number of included patients= 121 2. number of cases diagnosed as non-covid = 05 3. clinically proven cases of covid-19= 116 4. a number of covid-19 cases were indicated by cxr. = 86 5. number of cases diagnosed by nasopharyngeal-pcr = 65 6. number of cases diagnosed on hrct findings = 113 the sensitivity of pcr = 65/116 x100 =56.03% the sensitivity of cxr = 86/116 x 100 =74.13 % the sensitivity of hrct = 113/116 x 100 = 97.41% considering pcr as gold standard diagnostic test, tp=65, fn=51, tn=05, fp = 00 the calculated efficacy result is shown in table 3. similarly, if hrct is considered a new diagnostic test for covid-19 pneumonia, we have tp=113, fn = 03, tn = 04, fp=1, the calculated efficacy is depicted in table 3. tp: true positive, fp: false positive, tn: true negative, fn: false negative. table 3: diagnostic efficacy of pcr & hrct for covid-19 pneumonia biostatistics for the efficacy of pcr statistic value 95% confidence interval sensitivity 56.03% 46.52% to 65.24% specificity 100.00% 47.82% to 100.00% ppv 100.00% npv 8.93% 7.39% to 10.75% diagnostic accuracy 57.85% 48.54% to 66.77% biostatistics for the efficacy of hrct-thorax sensitivity 97.41% 92.63% to 99.46% specificity 80.00% 28.36% to 99.49% ppv 99.12% 95.14% to 99.85% npv 57.14% 28.66% to 81.57% diagnostic accuracy 96.69% 91.75% to 99.09% ppv: positive predictive value and npv: negative predictive value. the fisher exact test statistic values = 0.0006 which is < 0.05. discussion this study showed that the age range of 121 patients was from 18 to 67 years with a mean age of 42.64 years (± sd 17.62) which is comparable with the report of qiongjie hu and co-authors about chinese population, with mean age 39.2 years + sd 9.6.17 we had 67 male (55.37%) and 54 female (44.62%) patients and male to female ratio was 1.2. the male gender preponderance is in agreement with the published studies of badawi a, ryoo sg and channappanavar r, and co-authors.1819 this reduced susceptibility of females to covid-19 infection could be due to the protection from x chromosome and sex hormones, providing innate and adaptive immunity.20 in this study, 46.28% of patients found above the age of 50 years, shows that this age can be a relative risk factor for the disease. similarly, 39 cases (32.23%) with cigarette smoking, 39 cases (32.23%) with diabetes mellitus (dm), and 13cases (10.74%) with obesity were identified as co-morbidities (39+39+13=91) which is a significant number. current literature has described the comorbidity induced increased risk of disease and mortality in viral pneumonia.21-22 out of 116, only 65patients (56.03%) were diagnosed with covid-19 infection by pcr while 51 cases (43.96%) were not identified by the gold standard test. it means, if the pcr test report is negative, nobody can claim with confidence that patient is covid-19 free, because of poor sensitivity and a high false-negative rate of the test. the availability, virus specificity, quality of the testing kits, and under-testing due to resource limitations may be responsible factors for disease multiplication & dissemination in the community. but the good news here is that the virulence of virus in pakistani population appears to be relatively weak because the number of patients with severe disease is low while we have abundant patients with mild to moderate, covid-19 pneumonia. it is also worth mentioning that not every patient requires mechanical ventilation on the first day of infection. it takes adequate time for transition from mild to severe covid disease. the track of transition from mild to severe disease can be blocked by early diagnosis and prompt management. because this virus is highly contagious a very much unpredictable in behavior, its control needs early diagnosis for timely isolation or quarantine. in these circumstances, 82 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 there is an urgent need for some alternative high sensitivity test, capable of capturing the disease untimely, for achieving good control in population. on the other hand, 87/116 patients were identified by x-ray chest (cxr) with a sensitivity of 75.0%. although diagnostic yield is better than that of the gold standard (pcr) 25.0% patients were missed, while abnormal findings were noted on hrct images of the same patients which are in agreement with the report of van der bruggen-bogaarts ba1, van der bruggen hm.23 the current study showed that hrct thorax diagnosed viral pneumonia in 113 out of 116 cases with a sensitivity of 97.41%. although it furnishes specific signs regarding covid-19 pneumonia, it is not considered as specific as pcr, but according to the principles of differential diagnosis, we should always think about common issues. in the current on-going epidemic milieu, covid-19 infection is the commonest issue, so hrct can be utilized with confidence for its diagnosis. this study exhibited that both lungs were affected in 100% cases, the predominant affected part was the lower zone in 78.51 % of patients. ggo was the earliest and the commonest (82.75% cases) sign on hrct. out of 96 cases, 11 cases (11.45%) showed isolated ggo scattered in lung fields, 38/96 cases (39.58%) were associated with consolidation, and 29/96 cases (30.20%) were part of the crazy paving sign. modern literature shows that in covid-19 pneumonia, type ii alveolar epithelial cell injury, proteinaceous exudate, focal hyperplasia of pneumocytes and patchy inflammatory cellular infiltration, contribute to this ggo.24-26 consolidation was noted in 57cases, 38/57 cases (66.67%) showed sub-pleural, multifocal consolidation, and 19/57 cases (33.33%) were associated with the airbronchogram sign. all cases displayed ggo to a variable extent. these findings are very much comparable with the published report of cheng z, lu y and co-authors.27 when septal thickening occurs in addition to ggo, crazy paving appearance is manifested on hrct which is found in moderate to severe covid-19 pneumonia. this study communicated 29 cases (25.0%) with this morphology while x. he, j. zheng dr., and co-workers have also described 25.0% of patients with the crazy paving sign.28 these patients pose a practical challenge because of having a potential of transition into serious disease and anticipated mechanical ventilation, in the future. many precious lives have been lost to this pattern.29 we found only one case of pleural effusion in this study which was bilateral and cardiogenic, secondary to coronary bypass surgery with superimposed covid-19 infection. otherwise, pleural effusion is not a common sign of this disease. but huang et al. reported that pleural effusion may be noted in severe covid-19 pneumonia.30 this study displayed the efficacy of hrct-thorax as sensitivity: 97.41 %, specificity: 80%, ppv: 99.12 %, npv: 57.14%, diagnostic accuracy: 96.69 % for pulmonary covid-19 disease. the detailed efficacy of covid-pcr is described in table-iii. the p-value of 0.0006 is < 0.05 and is highly significant, showing a remarkable difference between the diagnostic potential of the two modalities. this value indicates that hrct has excellent capabilities of diagnosing covid-19 pulmonary disease in an epidemic. according to the current literature, the sensitivity of pcr is as low as 60%.31 false-negative results can create the risk of inadvertent contamination of noncovid-19 patients, wards, and the community. lower respiratory symptoms require tracheal aspirates or bal (broncho-alveolar lavage) for maximum diagnostic yield but there is a very high risk of aerosolization & disease transmission to healthcare workers during these procedures.32 while hrct is free of such drawbacks and was widely used in china as a diagnostic tool for covid-19 pulmonary disease. hrct can give rapid and valuable information for triaging isolation, and treatment procedures. it also determines the extent of lung involvement and is of tremendous help in anticipating the risk of rapid respiratory decline. no doubt, performing hrct for every respiratory patient is neither cost-effective nor long-term sustainable. but this modality can be used during an epidemic, especially where high sensitivity reliable laboratory testing tool for covid-19 is not available. in summary, hrct features of covid-19 pneumonia include ground-glass opacity, multi-focal, sub-pleural & basal consolidation, and crazy paving sign. reticulation is found in patients with 2-3 weeks of history. we hope, the current study findings can facilitate early identification and good management of symptomatic and suspected covid-19 pneumonia cases by adequate use of hrct thorax, under adequate biosafety measures. 83 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 limitations the main limitation of our study is that it is a singlecenter study performed on limited sample size (121), so the study may not reflect a full range of radiological morphology and distribution pattern of covid-19 pulmonary disease. to additionally elucidate, a study with larger sample size or preferably, a multi-center study can further explore the radiological behavior of the disease. the 15.51% cases with reticulations found in the current study need further interpretation by a longitudinal study whether these reticulations are going to resolve completely or going to develop into a new cluster of ild in the community. conclusion hrct thorax, having excellent sensitivity and significant specificity for covid-19 pulmonary infection, is a superb modality. it can play a positive role in early detection, quantification, and management of pulmonary coronavirus disease during a pandemic. if available, can be used with confidence for a re-evaluation of pcr-negative suspect for decision making about treatment and anticipating the risk of respiratory decline. acknowledgements the authors are thankful to dr. shahid raza and dr. muhammad jameel for their valuable co-operation. references 1. chen n, zhou m, dong x, qu jm, gong fy, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study;2020, lancet, 395(10223):507-513. 2. world health organization, 2020. novel coronavirus (2019-ncov) situation report -1. available at: https://www.who.int/emergencies/ diseases/novel-coronavirus2019/situation-reports. accessed june 5, 2020. 3. wu jt, leung k, leung gm, now casting and forecasting the potential domestic and international spread of the 2019ncov outbreak originating in wuhan, china: a modelling study;2020, lancet, 395(10225): 689-697. 4. kanne jp. chest ct findings in 2019 novel coronavirus (2019-ncov) infections from wuhan, china: key points for the radiologist. radiology. 2020 feb 4:200241. doi:10.1148/radiol.2020200241. [epub ahead of print] link, google scholar 5. wong hyf, lam hys, fong ah, et al. frequency and distribution of chest radiographic findings in patients positive for covid-19. radiology. 2020;296(2): e72-e78. doi:10.1148/radiol.2020201160 6. harrison x. bai*, ben hsieh*, zeng xiong, kasey halsey, ji whae choi, thi my linh tran, et al, performance of radiologists in differentiating covid19 from viral pneumonia on chest ct; 2020, radiologyvol. 296, no. 2; 200823. 7. pan y, guan h. imaging changes in patients with 2019ncov. eur radiol. 2020;30(7):3612-3613. doi:10.1007/s00330-020-06713-z 8. ming-yen ng, elaine yp lee, jin yang, fangfang yang, xia li, hongxia wang et al. imaging profile of the covid-19 infection: radiologic findings and literature review. radiology: cardiothoracic imaging; 2020;2(1):e200034. doi:10.1148/ryct.2020200034 link, google scholar 9. who. coronavirus disease 2019 (covid-19) situation report 32. (accessed feb 22, 2020). available online: https://www.who.int/emergencies/diseases/novelcoronavirus2019/situation-reports/ 10. ai t, yang z, hou h, zhan c, chen c, lv w, et al. correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases; radiology vol. 296, no. 2. 2020;200642.doi: 10.1148/radiol.2020200642 11. national institute of health islamabad pakistan [internet]. national institute of health islamabad [cited 2020 apr 21]. available from: https://www.nih.org.pk/, www.nih.org.pk › novel-coronavirus-2019-ncov. 12. salehi s, abedi a, balakrishnan s, gholamrezanezhad a. coronavirus disease 2019 (covid-19): asystematic review of imaging findings in 919 patients. ajr am j roentgenol 2020:1-7. doi: 10.2214/ajr.20.23034. 13. rubin gd, ryerson cj, haramati lb, sverzellati n, kanne jp, raoof s, et al. the role of chest imaging in patient management during the covid-19 pandemic: a multinational consensus statement from the fleischner society. chest 2020. doi: 10.1016/j.chest.2020.04.003. 14. bsti. covid-19: bsti /bsgar decision tool for chest imaging in patients undergoing ct for acute surgical abdomen [internet] the british society of thoracic imaging 2020 [cited 2020 apr 21]. available from: https://www.bsti.org.uk/media/resources/files/bsgar_bsti_joi nt_decision_tool_for_ct_v1_final_25.03.20_cm7vqla.pdf 15. nhs england.minimum operating standards: novel coronavirus (covid-19) patient pathway [internet] v 2.2 2020 february 20 [cited 2020 apr 21]. available from: https://www.england.nhs.uk/wpcontent/uploads/2020/02/coronavirus-patient-pathway.pdf. 16. aman nawaz khan, najam ud din, ummara siddique umer, covid-19 national pakistan guidelines: radiological society of pakistan (rsp) recommendations regarding utilisation of chest imaging; may 2020, volume 70, issue 5 17. 17. qiongjie hu1, hanxiong guan1, ziyan sun, lu huang, chong chen, tao ai et al. early ct features and temporal lung changes in covid-19 pneumonia in wuhan, china, full length article/ volume128, 109017, july 01, 2020.doi:https://doi.org/10.1016/j.ejrad.2020.109017 18. badawi a, ryoo sg. prevalence of comorbidities in the middle east respiratory syndrome coronavirus (mers-cov): a systematic review and meta-analysis. int j infect dis. 2016; 49:129–133. [pmc free article] [pubmed] [google scholar] 19. channappanavar r, fett c, mack m, ten eyck pp, meyerholz dk, perlman s. sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. j immunol. 2017; 198:4046–4053. [pmc free article] [pubmed] [google scholar] 20. jaillon s, berthenet k, garlanda c. sexual dimorphism in innate immunity. clin rev allergy immunol. 2019;56:308–321. [pubmed] [google scholar] 84 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 77-84 21. wang xf, shi gc, wan hy. clinical features of three avian influenza h7n9 virus-infected patients in shanghai. clin respir j. 2014; 8:410–416. [pmc free article] [pubmed] [google scholar] 22. kornum jb, thomsen rw, riis a, lervang hh, schønheyder hc, sørensen ht. diabetes, glycemic control, and risk of hospitalization with pneumonia: a population-based case-control study. diabetes care. 2008;31(8):1541-1545. doi:10.2337/dc08-0138 23. van der bruggen-bogaarts ba1, van der bruggen hm, van waes pf, lammers jw. a comparative study chest. 1996 mar; 109(3). 24. koo hj, lim s, choe j, choi sh, sung h, do kh, radiographic and ct features of viral pneumonia; (2018). radiographics, 38(3): 719-739. 25. xu z, shi l, wang y, zhang j, huang l, zhang c, et al. pathological findings of covid-19 associated with acute respiratory distress syndrome; (2020), lancet respir med, 2020 feb 18. pii: s2213-2600(20)30076-x. doi: 10.1016/s2213 2600(20)30076-x. [epub ahead of print]. 26. tian s, hu w, niu l, liu h, xu h, xiao et al. pulmonary pathology of early phase 2019 novel coronavirus (covid-19) pneumonia in two patients with lung cancer; (2020). j thorac oncol, 2020 feb 28. pii: s1556-0864(20)30132-5. doi: 10.1016/j.jtho.2020.02.010. [epub ahead of print] 27. zenghui cheng1, yong lu1, qiqi cao1, le qin1, zilai pan1 et al. clinical features and chest ct manifestations of coronavirus disease 2019 (covid-19) in a single-center study in shanghai, china.; american journal of roentgenology. 2020; 215: 121-126. 10.2214/ajr.20.22959 28. he x, zheng j, ren j, zheng g, liu l. chest high-resolution computed tomography imaging findings of coronavirus disease 2019 (covid-19) pneumonia. int j radiat res. 2020; 18 (2) :343349, url: http://ijrr.com/article-1-2926-en.html 29. chan jf, yuan s, kok kh, to kk, chu h, yang j, et al. a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster; (2020) lancet, 395(10223): 514-523. 30. huang c, wang y, li x. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. lancet. 2020 doi: 10.1016/s0140-6736(20)30183-5. published online jan 24. doi 31. yicheng fang, huangqi zhang, jicheng xie, minjie lin, lingjun ying, peipei pang, et al. sensitivity of chest ct for covid-19: comparison to rt-pcr. radiology 2020; radiologyvol. 296, no. 2, 200432. 32. roman woelfel, view orcid profilevictor max corman, wolfgang guggemos, michael seilmaier, sabine zange, marcel a muellerwoelfel et al. clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster.; medrxiv 2020.03.05.20030502; doi: https://doi.org/10.1101/2020.03.05.20030502 219 journal of rawalpindi medical college (jrmc); 2020; 24(3): 219-224 original article bacteriological profile and their susceptibility pattern in neonatal intensive care unit at tertiary care hospital in wah saba mushtaq1, sohail ashraf2, lubna ghazal3, rida zahid4, basharat hussain5, jamila6 1 assistant professor, department of paediatrics, wah medical college, wah cantt. 2 associate professor, department of paediatrics, wah medical college, wah cantt. 3 assistant professor, department of pathology, wah medical college, wah cantt. 4,5 post-graduate trainee, department of paediatrics, pof hospital, wah cantt. 6 professor, department of pathology, wah medical college, wah cantt. author’s contribution 2 conception of study 1,4,5 experimentation/study conduction 3 analysis/interpretation/discussion 3 manuscript writing 2,6 critical review 1,2,3,4,5 facilitation and material analysis corresponding author dr. lubna ghazal, assistant professor, department of pathology, wah medical college, wah cantt email: doctor.lubna@yahoo.com article processing received: 03/01/2020 accepted: 21/08/2020 cite this article: mushtaq, s., ashraf, s., ghazal, l., zahid, r., hussain, b., jamila. bacteriological profile and their susceptibility pattern in neonatal intensive care unit at tertiary care hospital in wah. journal of rawalpindi medical college. 30 sep. 2020; 24(3): 219224. doi: https://doi.org/10.37939/jrmc.v24i3.1310 conflict of interest: nil funding source: nil access online: abstract introduction: neonatal sepsis is a clinical syndrome characterized by multiple symptoms and signs of infection during the first month of life. the objective of this study is to determine the frequency of commonly isolated bacteria from patients of neonatal sepsis and their susceptibility patterns in pof hospital at wah. methods: this cross-sectional study was carried out in pof hospital neonatal intensive care unit and microbiology laboratory from january 2018 to december 2019. the blood samples of patients suspected of neonatal sepsis were processed as per standard methodology. results: out of ninety blood samples, fifty-one (56.7%) yielded the growth of gram-negative rods and thirty-nine (43.3%) yielded gram-positive cocci. among gram-positive bacteria, coagulase-negative staphylococci were the most common pathogen isolated from 53.8% cases followed by methicillin-resistant staphylococcus aureus (15.3%). among gram-negative bacteria, klebsiella pneumoniae (54.90%) was the most frequently identified bacteria followed by serratia marcescens (27.45%). the gram-positive cocci were the most susceptible to linezolid (100%) followed by vancomycin (87.2%). the gram-negative rods depict remarkable resistance to ciprofloxacin (92.2%), gentamicin (100%), and meropenem (54.9%). conclusions: the study concluded a predominance of gram-negative bacteria as a causative agent of neonatal sepsis in our setup. the bacterial isolates are highly resistant to commonly prescribed oral as well as injectable antibiotics. implementation of infection control policies is a dire need to combat the grave situation of increasing antibiotic resistance. keywords: neonatal sepsis, antibiotic susceptibility, bacteriological profile. 220 journal of rawalpindi medical college (jrmc); 2020; 24(3): 219-224 introduction neonatal sepsis (nns) is an invasive bacterial infection that occurs in the first month of life and a major cause of neonatal morbidity and mortality. it is a clinical syndrome characterized by multiple and nonspecific signs of infection which include lethargy, less vigorous sucking, apnea, bradycardia, temperature instability, respiratory distress, vomiting, diarrhea, and abdominal distention. the term also encompasses bloodstream infections, meningitis, and pneumonia.1 nns is the third most common cause of deaths among neonates, accounting for 225,000 deaths globally every year.1 neonatal sepsis is divided into two categories based on the time and peripartum pathogenesis. sepsis which occurs in the first 72 hours of life is defined as early-onset sepsis (eos) and that occurring beyond 72 hours is defined as late-onset sepsis (los). earlier onset of infection reflects vertical transmission from mother to infant, while the third day of life or later is likely to be acquired through horizontal transmission.2 the bacterial isolates which caused neonatal sepsis vary from place to place and they keep on changing with time at the same place. in industrialized countries, the commonest bacterial pathogens isolated from septic neonates are gram-positive cocci followed by gram-negative bacilli and fungi.3 however, the studies conducted in developing countries like india and pakistan revealed the predominance of gramnegative bacilli as causative agents of neonatal sepsis.4,5 the contribution of both gram-positive and gram-negative bacteria to cause neonatal sepsis is equal in a study in nigeria.6 the study which is carried out at the same hospital as ours revealed the predominance of klebsiella species followed by staphylococcus aureus.7 similarly, the susceptibility pattern also has geographical as well as temporal variations. in egypt, the commonest neonatal pathogen was coagulase-negative staphylococcus species. the isolates were sensitive to vancomycin, ciprofloxacin, and amikacin and resistant to commonly used first-line antimicrobial drugs.8 one of the studies conducted in india depicted rampant resistance to cephalosporins and susceptibility of gram-negative bacilli against piperacillin-tazobactam whereas vancomycin and linezolid were most effective against gram-positive isolates.9 the data by tehseen et al revealed that amikacin and vancomycin were the most effective antimicrobial drugs against gram-negative and gram-positive bacteria respectively.7 the variable microbiological pattern and their antibiograms render antibiotic susceptibility profile in one region at a specific period inapplicable to other regions or in another period. keeping in view, the present study was aimed to document the commonly isolated bacteria from patients of neonatal sepsis and their susceptibility patterns in pof hospital at wah. this will be an effort to rationalize the empirical treatment by paediatricians resulting in evidence-based practice and better results in terms of early recovery, shorter duration of hospital stay, and cost-effectiveness. moreover, this effort will contribute to safeguard the remaining therapeutic options left to the clinicians and encourage a focused, concerted effort for better patient care. materials and methods this cross-sectional study was conducted at the neonatal intensive care unit and laboratory of pakistan ordinance factories hospital from january 2018 to december 2019. the sample size was calculated by the who sample size calculator taking a confidence level of 95%, population size7 of 117, and a margin of error of 5%. the sample size (n) was 90. the samples were calculated by the non-probability consecutive technique. all neonates of either gender, irrespective of risk factors, with clinical suspicion of neonatal sepsis were included in the study. patients who were already on antibiotics were excluded. the blood culture samples were drawn from all neonates who were clinically suspected of neonatal sepsis, without any discrimination of gender, body weight, prematurity, and mode of delivery. according to institution protocol, 1-3 ml of blood was drawn from a peripheral vein and inoculated in brian heart infusion (bhi) broth for culture. the blood samples were incubated for 24 hrs at 35 + 2°c under aerobic conditions. blind subcultures were done by collecting the inoculums from bhi broth and inoculating on blood agar and macconkey agar after 24 hours, 72 hours, 5th day, and on 7th day. the subcultures were incubated at 35 + 2°c under aerobic conditions. after overnight incubation, the agar plates were examined for growth of bacteria and their colonial morphology. for gram-positive cocci identification, catalase test, coagulase test, growth on bile esculin agar, and salt tolerance test were employed. the gram-negative rods were identified based on gram staining, catalase test, oxidase test, and motility.10 microbact gram-negative 24e identification kits (oxoid, basingstoke, uk) were used for confirmation of gram-negative isolates. 221 journal of rawalpindi medical college (jrmc); 2020; 24(3): 219-224 antimicrobial susceptibility tests were performed on the muller–hinton agar plates with the disk diffusion method as recommended by the clinical laboratory standards institute.11 the bacterial suspensions of isolates equivalent to 0.5 mcfarland standard turbidity were applied on mueller-hinton agar (oxoid, basingstoke, uk). following antimicrobial disks (oxoid, basingstoke, uk) were evenly placed on the inoculated plates for gram-negative bacilli: ampicillin(10 µg), amoxicillin-clavulanate (20/10 µg), trimethoprin-sulfamethoxazole (1.25/ 23.75 µg), ceftriaxone (30 µg), cefotaxime (30 µg) ciprofloxacin (5 µg), gentamicin (10 µg), amikacin (30 µg), piperacillintazobactam (100/ 10 µg), doxycycline (30 µg) imipenem (10 µg) and meropenem (10 µg) and polymyxin b(300 units) the disks of penicillin (10 units), cefoxitin (30μg), amoxicillin/clavulanic acid (20/10 μg), erythromycin (15 μg), clarithromycin (15 µg), linezolid (30 μg), ciprofloxacin (5μg), clindamycin (2μg), doxycycline (30μg) and vancomycin (30μg) were applied for grampositive cocci. concurrent quality control testing was performed with escherichia coli atcc 25922 and staphylococcus aureus atcc 25923. after overnight incubation, the diameter of each zone of inhibition around the antimicrobial disk was measured. the susceptibility results were interpreted as sensitive, intermediate, and resistant according to recommendations of clsi.11 the data was entered and analyzed using spss version 21. for qualitative variables (gram-negative bacilli, gram-positive cocci, gender, bacteria isolated, and their susceptibility pattern) frequencies and percentages were calculated. mean ± sd was presented for age. association of gram-negative bacilli and gram-positive cocci with early and late-onset neonatal sepsis was determined by the chi-square test. p-value < 0.05 was considered significant. results a total of ninety positive blood cultures of neonates with bacterial sepsis were analyzed. the mean age of the neonates was 6.68 days + 7.17. in a total of ninety, forty-seven (52.2%) cases of neonatal sepsis were categorized as early onset and forty-three (47.8%) cases were categorized as late-onset. out of ninety, fifty-one specimens (56.7%) yielded the growth of gram-negative rods and thirty-nine (43.3%) specimens yielded gram-positive cocci. the gender distribution for 39 gram-positive cocci was 25 and 14 for males and females respectively. out of 51 gramnegative isolates, 31 were isolated from male patients and 20 were isolated from females. this gender distribution is presented in figure 1. there was no significant association of gram-positive cocci and gram-negative rods with early and late neonatal sepsis. (p=1.00) figure 1: distribution of gram-positive cocci and gram-negative bacilli isolated from the blood of neonatal sepsis in both genders (n=90) the most frequent bacteria isolated from the blood of neonatal sepsis were klebsiella pneumoniae followed by coagulase-negative staphylococci and serratia marcesens. among gram-positive bacteria, coagulasenegative staphylococci were the most common pathogen isolated from 53.8% cases followed by methicillin-resistant staphylococcus aureus (15.3%). among gram-negative bacteria, klebsiella pneumoniae (54.90%) was the most frequently identified bacteria followed by serratia marcescens (27.45%) and acinetobacter species (9.8%). (figures 2 and 3) 222 journal of rawalpindi medical college (jrmc); 2020; 24(3): 219-224 figure 2: gram-positive cocci responsible for neonatal sepsis (n= 39) figure 3: gram-negative bacilli responsible for neonatal sepsis (n= 51) the gram-positive cocci were markedly resistant (76.9%) to first-line drugs including penicillin. a moderate level of sensitivity was exhibited by grampositive isolates to amoxicillin-clavulanate, ciprofloxacin, clindamycin, macrolides, doxycycline, and gentamicin. amikacin and meropenem were effective in 65.7% and 61.5% of cases of neonatal sepsis caused by gram-positive pathogens. these organisms were the most susceptible to linezolid (100%) followed by vancomycin (87.2%). the exact number and percentages of the susceptibility of commonly used antimicrobials against gram-positive cocci are represented in table 1. table 1: cross-tabulation of gram-positive cocci against susceptibility pattern of antimicrobial drugs sensitive n (%) resistant n (%) total n (%) penicillin 9 (23.1) 30 (76.9) 39 (100) ciprofloxacin 17 (43.6) 22 (56.4) 39 (100) erythromycin 16 (45.7) 19 (54.3) 35 (100) clarithromycin 17 (48.6) 18 (51.4) 35 (100) doxycycline 19 (48.7) 20 (51.3) 39 (100) gentamicin 19 (48.7) 20 (51.3) 39 (100) amoxicillinclavulanate 20 (51.3) 19 (48.7) 39 (100) clindamycin 18 (51.4) 17 (48.6) 35 (100) meropenem 24 (61.5) 15 (38.5) 39 (100) amikacin 23 (65.7) 12 (34.3) 35 (100) vancomycin 34 (87.2) 5 (12.8) 39 (100) linezolid 39 (100) 0 (0) 39 (100) the gram-negative rods were 100% resistant to ampicillin and gentamicin. the commonly prescribed third-generation cephalosporins, ciprofloxacin, and amoxicillin-clavulanate were also markedly ineffective for gram-negative isolates. these rods were moderately sensitive to amikacin, meropenem, and piperacillin-tazobactam (41.2%, 45.1%, and 41.2% respectively). table 2 shows the susceptibility pattern of the gram-negative rods against various antibiotics. table 2: different age groups in the study population sensitive n (%) resistant n (%) total n (%) ampicillin 0 (0.0) 51 (100) 51 (100) gentamicin 0 (0.0) 51 (100) 51 (100) cefotaxime 1 (2.0) 50 (98.0) 51 (100) ceftriaxone 1 (2.0) 50 (98.0) 51 (100) amoxicillinclavulanate 4 (7.8) 47 (92.2) 51 (100) ciprofloxacin 4 (7.8) 47 (92.2) 51 (100) cotrimoxazole 6 (11.8) 45 (88.2) 51 (100) doxycycline 10 (20.0) 40 (80.0) 51 (100) amikacin 21 (41.2) 30 (58.8) 51 (100) piperacillintazobactam 21 (41.2) 30 (58.9) 51 (100) meropenem 23 (45.1) 28 (54.9) 51 (100) polymyxin 37 (72.5) 14 (27.5) 51 (100) 223 journal of rawalpindi medical college (jrmc); 2020; 24(3): 219-224 discussion neonatal sepsis is a life-threatening condition associated with poor maternal health, illiteracy, lack of medical facilities, non-compliance to antenatal visits, and non-professional handling of deliveries. the knowledge of causative pathogens and their antimicrobial susceptibility is of utmost importance to reduce neonatal morbidity and mortality. the current study assessed that gram-negative rods are responsible for the majority of cases (56.66%) of neonatal sepsis in our setup followed by grampositive cocci (43.34%). this is also noticed that there is a mild increase in the incidence of early onset of neonatal sepsis as compared to late-onset neonatal sepsis in our setup. this finding is congruent with the study conducted by adatara et al12 where they found the majority of their patients having the early onset of neonatal sepsis. the study conducted by dalal in india also showed a similar trend.13 early-onset neonatal sepsis is by the vertical transmission of pathogens from the female urogenital tract to the newborn either in utero or during delivery. other risk factors include chorioamnionitis, prematurity, and prolonged rupture of membranes. late-onset neonatal sepsis is caused by the postnatal acquisition of the pathogens which thrive in the hospital or home, after contact from healthcare workers or caregivers. a possible explanation for the lower incidence of lons could be improved practices and better understandings of cleanliness and the use of aseptic techniques by hospital staff.14 the incidence of nns, irrespective of the age of presentation, was seen more in male patients as compared to females. the literature review supports the increased propensity of male patients to sepsis which is attributed to genderspecific genes related to the immune system.15 our study revealed the predominance of gram-negative bacilli as the causative agent of neonatal sepsis which is comparable to a vast number of studies conducted in asia including pakistan.4,5,7 among gram-negative rods, klebsiella pneumoniae was the most frequent bacteria followed by serratia marcescens and acinetobacter species. this pattern is different when compared to the previous study at the same place.7 serratia and acinetobacter spp had emerged as new pathogens in our neonatal icu. moreover, a reduction in the susceptibility of gram-negative rods against amikacin and amoxicillin-clavulanate has been recorded from 76.9%, 24.8%, 41.2%, and 7.8% respectively. the susceptibility against gentamicin and ampicillin has been reduced to zero percent each from 39.35% and 6.8% respectively. only 2% of the isolates are sensitive to the commonly used third-generation cephalosporins. this trend of increased resistance is an alarming situation that emerged as a result of poor infection control measures as well as injudicious use of antibiotics. similar susceptibility patterns have been reported in other studies from pakistan.16 the current situation of antimicrobial resistance in most of the clinical setups is in contrast to data published in an english surveillance programme for antimicrobial utilization and resistance (espaur) report, 2018.17 the difference emphasizes the need for antimicrobial stewardship programmes and surveillance of antimicrobial resistance in our health care facilities. meropenem is the most commonly used carbapenem in the paediatric age group for life-threatening infections. the gram-negative isolates resistant to meropenem were 54.9% and the gram-positive isolates resistant to meropenem were 38.5%. these findings are congruent to data of li et al.18 in our study, gram-positive isolates were sensitive to linezolid (100%) followed by vancomycin (87.2%). comparison with the previous study at the same place revealed a decrease in the susceptibility of grampositive cocci against amikacin, amoxicillinclavulanate, and vancomycin from 74.5%, 60.8%, and 95.2% to 65.7%, 51.3%, and 87.2% respectively. interestingly, mild increases in the sensitivity of less commonly used antibiotics like erythromycin, penicillin, and doxycycline are noted in the index study. this depicts the fact of bacteria rolling back to sensitivity against the less commonly used traditional drugs. analysis of our study also showed the inclusion of enterococcus and streptococcus species in the list of bacterial pathogens of our nicu in addition to staphylococci. the situation is similar to various other studies.4,9,19 the gram-positive cocci are remarkably resistant to ciprofloxacin(56.45%) and clindamycin(51.4%). the misuse or overuse of antibiotics like ciprofloxacin due to its extended antimicrobial spectrum promotes bacterial resistance and limits their efficacy. in our set up linezolid and polymyxin are the most effective drugs for grampositive and gram-negative bacterial isolates of nicu, respectively. despite their maximum sensitivity, these should not be used indiscriminately and be kept as reserve drugs. the development of resistance to these drugs may leave us with no option in life-threatening infections by multidrug-resistant organisms. 224 journal of rawalpindi medical college (jrmc); 2020; 24(3): 219-224 conclusion the study concluded that gram-negative bacteria are the predominant causative agent of neonatal sepsis in our setup. the most frequent bacteria were klebsiella pneumoniae followed by coagulase-negative staphylococci and serratia marcesens. the bacterial isolates are highly resistant to penicillins, cephalosporins, and quinolones. implementation of infection control policies and antibiotic de-escalation approach is recommended to combat the grave situation of increasing antibiotic resistance. references 1. suman c, sindhu s, ramesh a, sally e, mike s, sankar m et al. neonatal sepsis in south asia: huge burden and spiraling antimicrobial resistance.bmj 2019; 364. doi: https://doi.org/10.1136/bmj.k5314 2. guo j, luo y, wu y, lai w, mu x. clinical characteristic and pathogen spectrum of neonatal sepsis in guangzhou city from june 2011 to june 2017. med sci monit. 2019 mar 29;25:2296-2304. doi: 10.12659/msm.912375 3. mutlu m, aslan y, acar fa, kader s, bayramoglu g, yilmaz g. changing trend of microbiologic profile and antibiotic susceptibility of the microorganisms isolated in the neonatal nosocomial sepsis: a 14 years analysis. j matern-fetal neo m. 2019; https://doi.org/10.1080/14767058.2019.1582633 4. joshi ha, shah ss. a study on bacteriological profile, drug sensitivity and resistance pattern of isolated organism in neonatal septicaemia in neonatal intensive care unit. int j contemp pediatr. 2017; 4 :1430-3. http://dx.doi.org/10.18203/23493291.ijcp20172680 5. abbasi nb, jabeen n, khatoon s. neonatal sepsis; common bacterial isolates and their antimicrobial susceptibility patterns in neonatal intensive care unit, islamabad. professional med j 2017;24(10):1455-1460. doi:10.17957/tpmj/17.3914 6. pius s, bello m, galadima gb, ibrahim ha, yerima st, ambe jp. neonatal septicaemia, bacterial isolates, and antibiogram sensitivity in maiduguri north-eastern nigeria. niger postgrad med j.2016; 23:146-51. doi:10.4103/1117-1936.190340 7. tehseen t, qureshi ah, ghazal l. bacterial isolates of neonatal sepsis and their susceptibility pattern in pof hospital wah cantt. idj. 2018; 27 (3):70-73, retrieved from https://www.mmidsp.com/publications 8. shehab el-din emr, el-sokkary ma, bassiouny mr, hassan r. epidemiology of neonatal sepsis and implicated pathogens: a study from egypt. biomed research international. 2015, article id 509484, 11 pages, 2015. doi: https://doi.org/10.1155/2015/509484. 9. panigrahi p, chandel ds, hansen ni, sharma n, kandefer s, parida s, et al. neonatal sepsis in rural india: timing, microbiology and antibiotic resistance in a population-based prospective study in the community setting. j perinatol. 2017; 37(8):911-921. doi: 10.1038/jp.2017.67. epub 2017 may 11. pmid: 28492525; pmcid: pmc5578903. 10. jorgensen jh, carroll kc, funke g, pfaller ma, landry ml, richter ss, warnock dw (editors). manual of clinical microbiology. 11thed. washington, d.c: asm press 2015. 61334 11. clsi. performance standards for antimicrobial susceptibility testing; 28th ed. clsi supplement m100. wayne, pa: clinical and laboratory standards institute; 2018 12. adatara p, afaya a, salia sm, afaya ra, konlan kd, agyabengfandoh e, et al. risk factors associated with neonatal sepsis: a case study at a specialist hospital in ghana. sci world j.2019. doi: https://doi.org/10.1155/2019/9369051 13. dalal p, gathwala g, gupta m, singh j. bacteriological profile and antimicrobial sensitivity pattern in neonatal sepsis: a study from north india. int j res med sci 2017;5: 1541-5. doi: http://dx.doi.org/10.18203/2320-6012.ijrms20171261 14. singh m, gray cp. neonatal sepsis. [updated 2019 jul 15]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2019 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk531478/ 15. lakhey a, shakya h. role of sepsis screening in early diagnosis of neonatal sepsis. jpn [internet]. 30 mar.2017;7(1) : 1103-10. available from: https://www.nepjol.info/index.php/jpn/article/view/16944 16. hussain m, aurakzai aa, irshad m, ihsan ullah. neonatal sepsis; frequency of various bacteria and their antibiotic sensitivity in neonatal sepsis. professional med j 2018; 25(11):1683-1688. doi:10.29309/tpmj/18.4719 17. public health england: english surveillance programme antimicrobial utilization and resistance (espaur) report publications gov.uk. 2018 18. li jy, chen sq, yan yy, yinghu y, wei j, lin zl, et al. identification and antimicrobial resistance of pathogens in neonatal septicemia in china— a meta-analysis. int j infect dis.2018; 71: 89-93. doi: 10.1016/j.ijid.2018.04.794 19. pius s, bello m, galadima gb, ibrahim ha, yerima st, ambe jp. neonatal septicaemia, bacterial isolates, and antibiogram sensitivity in maiduguri north-eastern nigeria. niger postgrad med j. 2016; 23:146-51. doi: 10.4103/1117-1936.190340. 490 journal of rawalpindi medical college (jrmc); 2021; 25(4): 490-494 original article inguinal hernia repair on day care basis during global covid-19 pandemic syed fahd shah1, zahid mehmood minhas2, malik jawad faisal3, syed hussain shah4, syed zubair shah5, sania hameed6 1 associate professor, department of surgery federal general hospital, islamabad. 2 consultant gastroenterologists, rawalpindi medical university, rawalpindi. 3 assistant professor, department of ent, pims, islamabad. 4 assistant professor, department of rehabilitation medicine, cmh, lahore. 5 assistant professor, department of paeds medicine, cmh, lahore. 6 senior registrar, department of rehabilitation medicine, cmh, lahore. author’s contribution 1 conception of study 1,4,5 experimentation/study conduction 6 analysis/interpretation/discussion 1 manuscript writing 2,3 critical review 4,5 facilitation and material analysis corresponding author dr. syed fahd shah, associate professor, department of surgery federal general hospital, islamabad. email: fdsurgeon@hotmail.com article processing received: 28/06/2021 accepted: 01/11/2021 cite this article: shah, s.f., minhas, z.m., faisal, m.j., shah, s.h., hameed, s., hameed, s. inguinal hernia repair on day care basis during global covid-19 pandemic. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 490-494. doi: https://doi.org/10.37939/jrmc.v25i4.1715 conflict of interest: nil funding source: nil access online: abstract introduction: covid-19 has affected the general surgical elective list and most of the surgical procedures are postponed. inguinal hernia surgery can be performed under local anesthesia on a daycare basis in the selected group of patients taking all necessary precautions for covid-19. materials and methods: this prospective study was conducted at the department of general surgery federal hospital, islamabad for a period of three months from 15th march 2020 to 15th june 2020. all patients were included in the study through purposive sampling and preference was given to patients elder than 50 years of age. this study included 59 adult patients with an inguinal hernia who were under mesh repair under local anaesthesia on a daycare basis. results: a total of 59 patients were included in the study. all patients were male. the age range was from 37 to 82 years (sd=± 10.23). 30 (50.84%) patients had an inguinal hernia on the left side while 26 (44.06%) had a hernia on the right side. the mean operative time was 35 min. the pain was chief complaint postoperatively 30 (50.8%) patients had moderate pain while 6 (10.1%) patients had severe pain in the first 24 hours after surgery. fever was present in 15 (25.42%) patients in the first 24 hours. all patients were negative for covid -19 preoperatively and after 2 weeks none of the patients develop any symptoms of covid-19. 3 (5.08%) patients needed readmission within 24 hours for pain and some haemorrhage. there was no mortality in our study conclusions: inguinal hernia surgery under local anaesthesia on a daycare basis is a very good practice at this time of the global pandemic of covid-19. this is a safe and reliable strategy. keywords: inguinal hernia, covid-19, local anaesthesia. 491 journal of rawalpindi medical college (jrmc); 2021; 25(4): 490-494 introduction covid-19 started in the chinese city of wuhan in china and in no time it became a pandemic.1 it has the highest infectious and transmissibility rate. the effective measures to control its spread are social distancing, frequent hand wash, and wearing a mask. in order to prevent people most of the countries adopted lockdown measures so that people can stay home.2 schools, public places, shopping malls, and mass gatherings closed. hospitals were no exemption to this strategy and the majority of the indoor and outdoor services were cancelled and the hospital only provided emergency services.3 most of the countries made dedicated hospitals or wards for the management of the covid19 patients. as a result, the general surgery elective operation list was stopped and only elective surgeries were performed for malignant patients. 4 many booked patients for routine elective surgeries were postponed up till the newly reported cases fell below the nationally acceptable numbers. inguinal hernia surgery is one of the common elective general surgical procedures performed. inguinal hernia affects all ages. most of the patients with inguinal hernia are asymptomatic. the indication for elective hernia surgery is discomfort, pain, dragging sensation, heaviness, irreducibility which increases the risk of obstruction, incarceration, and strangulation.5 older patients have other risk factors such as chronic cough, constipation, and bladder outlet obstruction which predispose the formation of hernia, enlargement, and aggravation of symptoms.6 some of these patients want their hernia should be repaired immediately as they can’t cope with swelling. at this time of covid-19 where elective operation theatres are almost closed. we conducted this study of performing inguinal hernia repair surgeries in older patients who persistent pain, irreducibility, and risk of obstruction and strangulation on a daycare basis. daycare surgery is ideal for such patients where patients stay in the hospital is minimised and they come from home on the day of surgery.7 this study aimed to evaluate the inguinal hernia operation services on a daycare basis under local anaesthesia for patients who need non-emergency surgeries on an urgent basis. a dedicated team of staff was created with all special precautions. this is will help in establishing local guidelines for our surgical patients till this pandemic ends. materials and methods this prospective study was conducted at the department of general surgery federal hospital, islamabad from 15th march 2020 to 15th june 2020. this study included 59 adult patients presented with the diagnosis of inguinal hernia. a detailed history and examination were performed. all these patients were tested for covid-19 by pcr 48 hours before putting them on the list. british national health services criteria for covid-19 surgical patients were used.7 all adult patients (preferably above 50 years) were included in the study who had persistent pain, irreducible hernia, or increase risk of obstruction. patients with copd, recurrent inguinal hernia, chronic liver disease, and patients with other co-morbid conditions such as ihd and renal failure were excluded from the study. all patients were advised to wear a mask all the time. all patients were kept in a single room and strict barrier nursing was provided. informed consent was obtained from all patients. only 2 patients were operated on on each elective list. after a stay of 8-10 hours in the hospital. when they tolerated oral fluids they were sent home. a dedicated phone and whatsapp number were given to all patients to contact. local anaesthesia was used in all patients. three-step tumescent local anesthesia technique was used in all patients.8 mesh repair was performed in all these patients with a stapler used to fix the mesh and closure of the skin. in the case of a bilateral inguinal hernia, painful side or patient requested side was done only. all patients were taught about symptoms of covid-19 and advised to immediately report to the hospital and selfisolate themselves at home. postoperatively patients were monitored for pain, haemorrhage, haematoma, mobility, nausea, vomiting. visual analogue score (vas) was used to monitor pain. pain score was classified as mild vas score 1–3, moderate vas score 4–7, and severe vas score 7-10.9 one-tailed t-test is used to calculate the p-value. a p < 0.05 is taken as significant. all patients were followed up for 2 weeks and were provided dressing and removal of surgical clip services at home. they were monitored for any symptoms of covid-19. all findings were recorded on a specially designed proforma analysis was done on spss version 21. 492 journal of rawalpindi medical college (jrmc); 2021; 25(4): 490-494 results a total of 59 patients were included in the study. all patients were male. the age range was from 37 to 82 years (sd=± 10.23) figure 1. there were no female patients in our study. 30 (50.84%) patients had an inguinal hernia on the left side while 26 (44.06%) had a hernia on the right side. the mean operative time was 35 min (table 1: clinical findings). the pain was chief complaint postoperatively 30 (50.8%) patients had moderate pain while 6 (10.1%) patients had severe pain in the first 24 hours after surgery. which was only mild in 45 (76.5%) and 55 (93.22 %) of the patients one week and 2 weeks postoperatively respectively. fever was present in 15 (25.42%) patients in the first 24 hours and was not reported by any patients later on. the detail on postoperative monitoring is mentioned in table 2. all patients were negative for covid -19 preoperatively and after 2 weeks none of the patients develop any symptoms of covid-19. 3 (5.08%) patients needed readmission within 24 hours for pain and some haemorrhage which was controlled by pressure dressing and patients were discharged after 24 hours. all patients’ surgery was performed under local anaesthesia and there was no need for general anaesthesia in any patient. there was no recurrence of hernia in our study. there was no mortality in our study. figure 1: age range (n=59) table 1: clinical findings (n=59) no of patients percentage side right 26 44.06 left 30 50.84 bilateral 3 5.08 reducible 55 93.23 irreducible 4 6.77 complete 15 25.42 incomplete 44 74.57 operative findings mean operative time 35 min contents omentum 47 79.67 intestine 12 20.33 procedure mesh repair anaesthesia local anaesthesia table 2: postoperative at home monitoring (n=59) 24 hours 1 week 2 weeks pvalue pain mild 23 (38.9%) 45 (76.27%) 55 (93.22) 0.001 moderate 30 (50.8%) 10 (16.9%) 4 (6.77%) 0.002 severe 6 (10.1%) 4 (6.77%) 0.005 nausea/ vomiting 10 (16.9%) 2 (3.38%) 0.001 fever 15 (25.42) 0.003 cough 5 (8.47%) 0.000 haematoma 2 (3.38%) 1 (1.69%) 0.001 seroma 2 (3.38%) 3 (5.08%) 0.001 infection 0 1 (1.69%) 0.002 mobility 45 (76.27%) 59 (100%) 59 (100%) 0.001 readmissio n within 24 hours 3 (5.08%) 0.000 493 journal of rawalpindi medical college (jrmc); 2021; 25(4): 490-494 discussion novel coronavirus disease started in the chinese city wuhan and spread rapidly all over the world.10 it is also called covid-19 and sars-cov-2 to differentiate it from previously known coronavirus infections sars and mers.11 in march who has declared it a globally pandemic and the best strategy for prevention and protection from covid-19 is social distancing, wearing the face mask, and frequent hand washing.12 despite having low mortality as compared to sars devastating effects of the covid-19 on people's health has overburdened the health system within a very short period of time.13 the effective strategy for social distancing adopted by many countries was a kind of partial or complete lockdown.14 there was the closure of shopping malls, markets, schools, all gatherings, and religious gatherings.15 even there was the closure of air travel and the closure of train travels to decrease the spread of the disease.16 as hospitals were overwhelmed by the patients during this pandemic. there was a need for an increase in the capacity of the hospital to accommodate such a large number of covid-19 patients. as a result majority of elective services were cancelled especially general surgery elective operation, indoor admissions, and outdoor clinics were closed.17 general surgery work was reduced to emergency work or elective surgeries for malignant patients.18 the fear of getting coronavirus from the hospital was so much that people with other conditions were reluctant to come to the hospitals.19 many patients who need elective surgery for their problem on an urgent basis and they don’t fall in the emergency are postponed during this time.20 they visited the hospital as they were booked for elective surgeries for their longstanding elective problems. inguinal hernia in elderly patients is one good example of such a problem where patients are waiting for their turn. many factors contribute to the unpleasant effects of the inguinal hernia in older age and these patients with other chronic problems want their surgery done immediately.7 chronic straining conditions such as bph, constipation, and chronic coughing along with muscular weakness lead to an increase in the size of the hernia.21 there is constant dragging sensation and pain and weight in scrotum keeps these elder patients disturbed and bothered all the time.22 they feel like surgery is the only resolution for their problem. in a time of covid-19 pandemic where the risk of getting an infection from the hospital is very high and most of the elective surgical procedures are postponed.23 in this study we performed hernia surgery on a daycare basis primarily for elderly people who could not tolerate the bothersome symptoms of the inguinal hernia but some of the other adult patients whose symptoms were bothersome were also included. daycare surgery is an ideal choice for inguinal hernia surgery. european hernia society recommends that inguinal hernia surgery on a daycare basis is safe and cost-effective independently of the type of surgical hernia repair.24 furthermore, elderly asa iii patients are also suitable for inguinal hernia surgery on a daycare basis assessment of individual health conditions.25 the benefit of daycare surgery for inguinal hernia is so much that it should be considered for all types of patients for inguinal hernia after checking individual comorbidities.26 as local anaesthesia was used in all patients there was no need for prolonged hospital stay this is usually needed in the case of general anaesthesia and spinal anaesthesia.27 also there was no need for prolonged fasting and these patients were allowed orally within one hour of surgery. there is no dedicated daycare surgery centre in our country. this pandemic has given us a chance to perform inguinal hernia surgery on a daycare basis and evaluate our services for daycare surgery. a total of 59 patients were included in the study. the mean age of patients in our study was 58.20 years. shah et al reported a mean age of 45.7 years for a group of 114 inguinal hernia surgery patients.9 the reason for this difference is that we specifically operated on the older patients and did not include younger patients in our study. all patients were male. the mean operative time was 35 min. while palumbo reported by the mean duration of the procedure was of 84.27 ± 22.38 minutes.28 the main reason could be all surgeries were performed by a consultant and a stapler was used to fix the mesh and approximate the skin. the pain was the chief complaint postoperatively 50.8% of patients had moderate pain on vas while 10.1% of patients had severe pain in the first 24 hours after surgery. which was only mild in 76.5% of the patients after one week. fever was present in 15 (25.42) patients in the first 24 hours and was not reported by any patients later on. all patients were managed very well at home. only 3 (5.08%) patients were readmitted for a complication such haematoma formation and severe pain. only one patient needed readmission for pain management otherwise all other patients' pain was managed by oral 494 journal of rawalpindi medical college (jrmc); 2021; 25(4): 490-494 analgesics at home and they did not need injectables for pain management. there was no recurrence in our study. none of our patients contracted covid-19 in a 2-week follow-up. this study has provided a very good insight into setting up daycare surgery in our local setups and demonstrated that daycare surgery is a feasible option. further study with a larger sample is needed to validate this study. conclusion inguinal hernia surgery under local anaesthesia on a daycare basis is a very good practice at this time of the global pandemic of covid-19. this is a safe strategy that provided services with a limited staff to cater to their need with a short hospital stay and early return to the safe environment of a home. references 1. jin yh, cai l, cheng zs, cheng h, deng t, fan yp, et al. a rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-ncov) infected pneumonia (standard version) mil med res. 2020;7(1):4. doi: 10.1186/s40779-020-0233-6. 2. estrada e. covid-19 and sars-cov-2. modeling the present, looking at the future. phys rep. 2020;869:1-51. doi:10.1016/j.physrep.2020.07.005 3. yu j, ouyang w, chua mlk, xie c. sars-cov-2 transmission in patients with cancer at a tertiary care hospital in wuhan, china. jama oncol. 2020 jul 1;6(7):1108-1110. doi: 10.1001/jamaoncol.2020.0980. 4. cho sy, kang jm, ha ye, park ge, lee jy, ko jh et al mers‐cov outbreak following a single patient exposure in an emergency room in south korea: an epidemiological outbreak study. lancet 2016; 388: 994– 1001. doi: 10.1016/s0140-6736(16)30623-7. 5. dalenbäck j, hjortborg m, rimbäck g. abc om ljumskbråck hos vuxna [inguinal hernia in adults]. lakartidningen. 2016;113:duey. 6. metzger j. asymptomatische inguinalhernie: ist eine operation überhaupt nötig? [is the presence of an asymptomatic inguinal hernia enough to justify repair?]. praxis (bern 1994). 2015; 104(23):1259-1263. doi:10.1024/1661-8157/a002177. 7. moletta l, pierobon es, capovilla g, et al. international guidelines and recommendations for surgery during covid-19 pandemic: a systematic review. int j surg. 2020;79:180-188. doi:10.1016/j.ijsu.2020.05.061 8. koyama r, maeda y, minagawa n, shinohara t. three-step tumescent local anesthesia technique for inguinal hernia repair. ann gastroenterol surg. 2020;5(1):119-123. doi:10.1002/ags3. 9. shah sf, hameed s, aurakzai jk, chaudhary ma, shah sh, shah sz. chronic pain after liechtenstein mesh repair for inguinal hernia: a review of 114 patients. rmj.2015: 40(4): 388-91. 10. hui ds, i azhar e, madani ta, ntoumi f, kock r, dar o, ippolito g, mchugh td, memish za, drosten c, zumla a, petersen e. the continuing 2019-ncov epidemic threat of novel coronaviruses to global health the latest 2019 novel coronavirus outbreak in wuhan, china. int j infect dis. 2020 feb;91:264-266. doi: 10.1016/j.ijid.2020.01.009. 11. bai y, yao l, wei t, tian f, jin dy, chen l, wang m. presumed asymptomatic carrier transmission of covid-19. jama. 2020 apr 14;323(14):1406-1407. doi: 10.1001/jama.2020.2565. 12. chang d, lin m, wei l, xie l, zhu g, dela cruz cs, sharma l. epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside wuhan, china. jama. 2020 mar 17;323(11):1092-1093. doi: 10.1001/jama.2020.1623 13. chen n, zhou m, dong x, qu j, gong f, han y, et al. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study. lancet. 2020 feb 15;395(10223):507-513. doi: 10.1016/s01406736(20)30211-7. 14. saglietto a, d'ascenzo f, zoccai gb, de ferrari gm. covid-19 in europe: the italian lesson. lancet. 2020 apr 4;395(10230):1110-1111. doi: 10.1016/s0140-6736(20)30690-5 15. atalan a. is the lockdown important to prevent the covid-9 pandemic? effects on psychology, environment and economy-perspective. ann med surg (lond). 2020;56:38-42. doi: 10.1016/j.amsu.2020.06.010. 16. nicola m., alsafi z., sohrabi c., kerwan a., al-jabir a., iosifidis c., agha m., agha r. the socio-economic implications of the coronavirus and covid-19 pandemic: a review. int. j. surg. 2020;78:185–193. doi: 10.1016/j.ijsu.2020.04.018. 17. diaz a, sarac ba, schoenbrunner ar, janis je, pawlik tm. elective surgery in the time of covid-19. am j surg. 2020;219(6):900-902. doi: 10.1016/j.amjsurg.2020.04.014 18. alemanno g, tomaiuolo m, peris a, batacchi s, nozzoli c, prosperi p. surgical perspectives and patways in an emergency department during the covid-19 pandemic. am j surg. 2020;220(1):50-52. doi: 10.1016/j.amjsurg.2020.05.010. 19. reznik a, gritsenko v, konstantinov v, khamenka n, isralowitz r. covid-19 fear in eastern europe: validation of the fear of covid-19 scale. int j ment health addict. 2020 may 12:1-6. doi: 10.1007/s11469020-00283-3. 20. pertile d, gallo g, barra f, pasculli a, batistotti p, sparavigna m, et al; spigc working group. the impact of covid-19 pandemic on surgical residency programmes in italy: a nationwide analysis on behalf of the italian polyspecialistic young surgeons society (spigc). updates surg. 2020 jun;72(2):269-280. doi: 10.1007/s13304-020-00811-9. 21. gong w, li j. operation versus watchful waiting in asymptomatic or minimally symptomatic inguinal hernias: the meta-analysis results of randomized controlled trials. int j surg. 2018;52:120-125. 22. de goede b, wijsmuller ar, van ramshorst gh, et al. watchful waiting versus surgery of mildly symptomatic or asymptomatic inguinal hernia in men aged 50 years and older: a randomized controlled trial. ann surg. 2018;267(1):42-49. doi: 10.1097/sla.0000000000002243. 23. tao kx, zhang bx, zhang p, zhu p, wang gb, chen xp; general surgery branch of hubei medical association, general surgery branch of wuhan medical association. recommendations for general surgery clinical practice in 2019 coronavirus disease situation. zhonghua wai ke za zhi. 2020;58(3):170-7. doi: 10.3760/cma.j.issn.05295815.2020.03.003. 24. simons mp, aufenacker t, bay-nielsen m, et al. european hernia society guidelines on the treatment of inguinal hernia in adult patients. hernia. 2009;13(4):343-403. doi: 10.1007/s10029-009-0529-7. 25. palumbo p, amatucci c, perotti b, et al. outpatient repair for inguinal hernia in elderly patients: still a challenge?. int j surg. 2014;12 suppl 2:s4-s7. doi: 10.1016/j.ijsu.2014.08.393. 26. bourgon al, fox jp, saxe jm, woods rj. outcomes and charges associated with outpatient inguinal hernia repair according to method of anesthesia and surgical approach. am j surg. 2015;209(3):468-472. doi: 10.1016/j.amjsurg.2014.09.021. 27. raiss h, hübner m, abrazhda d, demartines n, vuilleumier h. cure de hernie inguinale en ambulatoire [outpatient hernia surgery]. rev med suisse. 2011;7(300):1354-1356. 28. palumbo p, usai s, amatucci c, et al. inguinal hernia repair in day surgery: the role of mac (monitored anesthesia care) with remifentanil. g chir. 2017;38(6):273-279. doi: 10.11138/gchir/2017.38.6.273. 21 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 21-25 original article meeting the challenge of covid-19 in dhq orthopaedic department obaid ur rahman1, nayyar qayyum2, afzaal aleem khan3, mohammad ammar aslam4, zohaib haider5 1 assistant professor, department of orthpaedics, rawalpindi medical university, rawalpindi. 2 professor, department of orthopaedics, rawalpindi medical university, rawalpindi. 3,4 house officer, rawalpindi medical university, rawalpindi. 5 resident, department of orthpaedics, dhq hospital, rawalpindi. author`s contribution 1,2 conception of study 1,,4,5 experimentation/study conduction 1, analysis/interpretation/discussion 1,3 manuscript writing 1,2 critical review 2,3,4,5 facilitation and material analysis corresponding author dr. obaid ur rahman assistant professor, department of orthopaedics, rawalpindi medical university, rawalpindi. email: drobaid@hotmail.com.com article processing received: 19/6/2020 accepted: 15/7/2020 cite this article: rahman, o., qayyum, n., khan, a.a., aslam, m.a. & haider, z. (2020). meeting the challenge of covid-19 in dhq orthopaedic department. journal of rawalpindi medical college, 24 covid-19 supplement-1, 21-25. doi: https://doi.org/10.37939/jrmc.v24isupp-1.1416 conflict of interest: nil funding source: nil access online: abstract introduction: the world health organization (who) declared covid-19 as a pandemic on march 11, 2020. not only that the covid-19 pandemic has brought the world to a complete lockdown but also burdened healthcare systems across the world immensely. objective: in this paper, we discuss the different strategies we adopted in the orthopaedics department of district head quarter [dhq] hospital rawalpindi, during this ongoing pandemic and share our experience of successfully but cautiously providing orthopedic services to patients in a public hospital. we compare our workload and output of may 2020 [pandemic phase] to may 2019 [standard/normal phase]. methodology: the hospital policy was changed after the covid-19 pandemic. we increased public awareness and reduced load in the opd using different strategies. we postponed all elective cases; focusing our logistics and resources only on the patients in urgent need of surgical management. a minimum number of doctors and otas were allocated on each list. inwards, the patient stay was reduced. as a standard pcr test for covid-19 was expensive, we devised our screening through history, examination, and routine investigations. results: the average stay inwards was reduced from 6.4±4.6 days in may 2019 to 2.7±3.6 days in may 2020. the decrease in the stay was statistically significant (p=.0206) and was associated with a 24.4% increase in the number of total patient admissions in may 2020 (n=56) as compared to may 2019 (n=45). the number of surgeries performed month to month was very similar in normal and pandemic periods. our opd patient attendance dropped from 200-250 patients per day in 2019 to 60-70 during the ongoing pandemic phase. conclusion: we believe that sharing experiences between health care actors allows us to develop an effective strategy to provide the very best care to our patients during the covid-19 pandemic. keywords: covid-19, pandemic, orthopaedics. 22 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 21-25 introduction the covid-19 pandemic has become the largest global healthcare crisis in nearly a century. initial cases of coronavirus disease were reported in wuhan, china in november 2019 and then there was a rapid worldwide spread.1 the world health organization (who) declared covid-19 as a pandemic on march 11, 2020.2 the first confirmed case of covid-19 in pakistan was reported on february 28, 2020. as of june 15, 2020, reported confirmed cases in pakistan now exceed 140,000 and deaths 2,700. not only that the covid-19 pandemic has brought the world to a complete lockdown but also burdened healthcare systems across the world immensely. while hospitals have been converted into corona treatment centers; hotels, schools, sports complexes, and buildings have become quarantine centers. all disciplines of medicine and surgery have been grossly affected. each discipline has tailored its resources and manpower to cater to the need of patients, maintaining the continuity of health care and at the same time ensuring the protection of medical personnel. orthopedic surgery globally has limited its activities to trauma and selective cases of tumors. in some private clinics, daycare surgery [arthroscopy] with < 23 hours of stay has been allowed.3 although orthopaedic surgeons are not the frontline workers in controlling the pandemic, they have their role, in the greater healthcare system, to check the spread of the disease.1,4 in this paper, we discuss the different strategies we adopted in the dhq orthopedics department during this ongoing pandemic and share our experience of successfully but cautiously providing orthopedic services to patients in a public hospital. this is one of the pioneer papers from the public sector of pakistan. brief overview of dhq, orthopedic department dhq hospital, rawalpindi is located at the hub of the city. it is the sole public hospital providing services to its downtown area. as a part of rawalpindi medical university, it also gives tertiary care services to the city as well as neighboring districts of chakwal, jhelum, murree, and kashmir. the academic staff of the orthopaedic department of comprises of a professor, an assistant professor, 3 senior registrars and trainee residents. (table 1) it has a 32 bedded orthopaedic ward, a fully equipped major, and a minor operation theater. table 1: teaching staff, dhq ortopaedic department post qualifi cation year supervisor professor fcps 1996 yes asst. professor fcps 2006 yes sr. registrar fcps 2011 in-process sr. registrar fcps 2016 no sr. registrar fcps 2017 no dist. surgeon fcps 2015 no medical officer fcps – training complet ed 2015 no before the pandemic our department’s routine before the pandemic included conducting outpatient clinics twice a week. on each outpatient day, five to six consultants examined 200 to 250 patients in a single large room. a large crowd would be assembled in the waiting area and the corridors, with patients and attendants waiting for their turns on stretchers and wheelchairs. the waiting area would be so jam-packed that even the doctors, when finding their way to the outpatient room, found it difficult to squeeze through the crowd in the waiting area. the orthopaedic department of dhq hospital was performing a variety of elective surgical procedures such as joint replacement surgery, congenital anomalies, non-unions, hand surgery, sports injuries, tuberculosis, infections, tumors, polio, cerebral palsy, etc. however, like most orthopedic departments across the globe, the main bulk of our workload was musculoskeletal trauma. our operation lists were conducted four times a week and an average of 110 cases per month was performed in these elective lists. in addition to the elective surgeries, 10 to 15 emergency surgeries were performed in the evening by senior registrars and residents such as applying external fixators, k wire fixations, and reducing dislocations. 23 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 21-25 after the outbreak change in hospital policy in a series of meetings between the administration and heads of departments it was unanimously decided to postpone all elective, non-urgent surgical procedures.4 this allowed focusing our logistics and resources only on the patients in urgent need of surgical management. it also freed up beds and increased the hospital's capacity to treat suspected or covid-19 positive patients requiring hospitalization.4 it allowed the reduction of health workers while maintaining urgent surgery capabilities.5 postponing elective surgeries helped to minimize the spread of infection between symptomatic and asymptomatic patients and health care staff.6 only trauma and urgent tumor surgery patients were admitted. one attendant per patient was allowed and ward stay was kept at the minimal. most of the patients were discharged on the next day of surgery. patients were guided about rehabilitation and wound care at home.5 covid status of patients being a public sector hospital neither the hospital nor the patient could afford the cost of pcr tests for each of our patients being operated. in pakistan, the cost of the pcr test for coronavirus is about rs 7500. hence exercising a cautious approach every patient admitted to the orthopedic department and the operating room is considered to be covid-19 positive even if they are otherwise healthy adults with no comorbidities. utmost care should be provided to patients in the preoperative, intraoperative, and postoperative settings to minimize risks of infection.4,7,8 modification of trauma management fractures which could be managed by manipulation and cast were dealt conservatively, keeping the old legacy alive. surgical intervention was reserved for those cases where there was a definitive indication; moreover, consideration was given to surgical approaches that could decrease operating staff exposure and shorten case duration.6 operating theater discipline after a departmental meeting, it was decided to decrease operation room personnel.3,4 duty rosters were revised both for the doctors and the nursing staff /otas working in the theaters. a minimum number of doctors and otas were allocated on each list. each sr and registrar was required to do 1 or 2 lists per week. each list was supervised by a professor or assistant professor on alternate days. as the majority of the cases were trauma-related they were healthy otherwise. in old age patients, there were comorbid. each patient was screened in the ward through history, vital signs [esp. temperature and respiratory rate], the examination of the chest, blood tests, chest x-rays by the ward team as well as by the anesthetists in their preoperative assessment. if there was suspicion of covid-19 disease they were referred to the hospitals especially allocated for corona patients. all traffic in and out of the operating theater was minimized.6 intraoperatively full personal protection equipment including n95 ffp2 masks, protective glasses, and face shields are recommended.10 however, in practice, we were for the most part restricted by scant availability to using surgical masks, gloves, and normal ot clothes. face shields and n 95 masks were used by our anaesthetist colleagues. n 95 masks were used by some surgeons but most of the staff was wearing surgical masks made available by the hospital. we know that surgical face masks are not designed for personnel protection and do not closely fit around the face and mouth. their design is intended for preventing contamination of the surgical wound from the aerosols generating by the surgical team.3 outpatient clinic management to increase public awareness and reduce crowding in the opd different strategies were used.3,4 placards and posters were placed in opd with slogans like “keep yourself and your children safe: keep away from hospital”. personnel at the reception counter also discouraged patients from unnecessary visits. opd slips were not issued for minor ailments. only postoperative cases and fresh injuries were entertained. thus actions were taken to decrease the workload, minimize staff and patient contacts5,11 and social distancing was practiced at all times.11 novel technologies the emergence of such a crisis provided an opportunity for us to use novel technologies in the workplace. this includes the adoption of telemedicine initiatives, allowing patients to be consulted and followed-up in the comfort of their own homes.4,10,12,13 a telemedicine center was developed by rawalpindi medical university providing 24/7 services in our sister hospital. many countries over the world have started on line outpatient clinics in the wake of covid-19.3 results change in our patient dynamics as a result of the measures taken we successfully reduced hospital stay duration for admitted patients 24 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 21-25 thus reducing potential exposure for them. the average stay duration was reduced from 6.4±4.6 days in may 2019 (range 1-25 days) to 2.7±3.6 days in may 2020 (range 0-18 days). the decrease in the stay was statistically significant (p=0.0206). the mode for a duration of stay, i.e. most frequent stay period, showed a decrease from 7 days to just 4 days while comparing data for these two months, may 2020 and may 2019 (figures 1 & 2). figures 1: patient stay time in may-19 figures 2: patient stay time in may-20 although we postponed all elective surgeries we kept our doors open during the pandemic for trauma and emergency patients and recorded a 24.4% increase in the number of total patient admissions in may 2020 (n=56) as compared to may 2019 (n=45). the surgical workload was sustained at the same level as the previous year. the number of surgeries and distribution of major, minor, and local procedures performed month to month was very similar in preendemic and pandemic periods. (table 2, figure 3). although the plan was to reduce workload and number of patient interactions for health givers, the influx of trauma and emergency patients could not be denied treatment. table 2: comparison of orthopaedic surgery output early 2019 & early 2020 month/ year major cases [under general anaesth esia] major cases [under spinal anaesth esia] local anaesth esia tota l februa ry 2019 22 32 68 122 februa ry 2020 21 28 74 123 march 2019 26 34 88 148 march 2020 28 26 99 153 april 2019 20 31 85 143 april 2020 17 28 100 145 may201 9 20 37 70 127 may 2020 21 22 67 110 figures 3: total surgeries compared early 2019, 2020 our vigilant attitude combined with increased patient caution allowed us to effectively reduce opd congestion and unnecessary visits. thus opd patient attendance dropped from 200-250 patients per day in 2019 to 60-70 during the ongoing pandemic phase. this contributed to the curtailment of exposure possibilities amongst our orthopedic patients as well as health giver staff. 25 journal of rawalpindi medical college (jrmc); 2020; 24 covid-19 supplement-1: 21-25 future directions covid-19 testing of all potential surgical and admission cases must be added to a panel of preoperative tests such as hepatitis b & c etc. all cases which turn up covid-19 positive should be dealt in separate wards and operation theaters. failing this ward and operation theater equipment especially the anaesthesia machines will be infected by coronavirus. subsequent surgeries [patients and staff] may become infected. it will be advisable to review and revise short term and long term indications of many of the elective surgical procedures we will need to restart the surgery of those elective procedures in which time delay is not advisable. a covid-19 unit should be developed in the orthopedic surgery department in our sister hospital benazir bhutto hospital working under rawalpindi medical university. bbh has already been declared as a covid-19 hospital. separate operation theatre and wards have been allocated for covid-19 positive orthopedic patients. good hygiene practices and good surgical practices being introduced implemented and enforced per necessity in our population and hospitals must not be let up. rather they should be reinforced so that we mature and develop as a health conscience nation. conclusion we believe that sharing experiences between health care actors allows us to develop an effective strategy to provide the very best care to our patients during the covid-19 pandemic. we hope, once getting out of this crisis, we will continue to work together as valued team members. references 1. 1.r.u. ashford, j.s. nichols, j. mangwaniannotation: the covid-19 pandemic and clinical orthopaedic and trauma surgery. j clin orthop trauma (2020 apr) s0976566220301168 google scholar 2. 2.y. shi, j. wang, y. yang, z. wang, g. wang, k. hashimoto, et al.knowledge and attitudes of medical staff in chinese psychiatric hospitals regarding covid-19 brain behav immun health, 4 (2020 apr 1), p. 100064 articledownload pdfgoogle scholar 3. p. giacomo, s. damiano, d. elena, b. giulia, s. vincenzocovid-19, and ortho and trauma surgery: the italian experience.injury (2020 apr) s0020138320303430 4. z. chang liang, w. wang, d. murphy, j.h. po huinovel coronavirus and orthopaedic surgery: early experiences from singapore. jbjs [internet] [cited 2020 apr 18]; latest articles. available from: https://journals.lww.com/jbjsjournal/citation/9000/novel_cor onavirus_and_orthopaedic_surgery__early.99807.aspx (2020 apr 20) google scholar 5. s. ahmed, t.w. leong glenn, y.-l. chongsurgical response to covid-19 pandemic: a singapore perspective.j. am. coll. surg. (2020 apr) s1072751520303082 6. brindle, mary md, mph*; gawande, atul md, mph† managing covid-19 in surgical systems, ann. surg.: mar 23, 2020 volume publish ahead of print issue doi: 10.1097/sla.0000000000003923. google scholar 7. m.e. awad, j.c.l. rumley, j.a. vazquez, j.g. devineperioperative considerations in urgent surgical care of suspected and confirmed covid-19 orthopedic patients: operating rooms protocols and recommendations in the current covid-19 pandemic [internet]. jaaos j am acad orthop surg (2020 apr 15) [cited 2020 apr 18]; publish ahead of print. available from: https://journals.lww.com/jaaos/abstract/publishahead/peri_op erative_considerations_in_urgent_surgical.99132.aspx google scholar 8. z. tan, p.h.y. phoon, l.a. zeng, j. fu, x.t. lim, t.e. tan, et al.response and operating room preparation for the covid-19 outbreak: a perspective from the national heart centre in singapore. j cardiothorac vasc anesth. 2020 mar;s1053077020303001.4. viswanath a, monga p. working through the covid-19 outbreak: rapid review and recommendations for msk and allied health personnel j clin orthop trauma (2020 mar) s0976566220300977 google scholar 9. r. ellis, et al.operating during the covid-19 pandemic: how to reduce medical error. br. j. oral maxillofac. surg. (2020), 10.1016/j.bjoms.2020.04.002 10. a. viswanath, p. mongaworking through the covid-19 outbreak: rapid review and recommendations for msk and allied health personnel.j clin orthop trauma (2020 mar) s0976566220300977 11. k. tay, t. kamarul, w.y. lok, m. mansor, x. li, j. wong, a. sawcovid-19 in singapore and malaysia: rising to the challenges of orthopaedic practice in an evolving pandemic.malaysian orthopaedic journal, 14 (2) (2020) http://10.5704/moj.2007.001 google scholar 12. a.r. vaccaro, c.l. getz, b.e. cohen, b.j. cole, c.j.i. donnallypractice management during the covid-19 pandemic.[internet]jaaos j am acad orthop surg (2020 apr 15)[cited 2020 apr 18]; publish ahead of print. available from: https://journals.lww.com/jaaos/abstract/publishahead/practice _management_during_the_covid_19_pandemic.99131.aspx google scholar 13. a.e. loeb, s.s. rao, j.r. ficke, c.d. morris, l.h.i. riley, a.s. levindepartmental experience and lessons learned with accelerated introduction of telemedicine during the covid-19 crisis [internet] jaaos j am acad orthop surg (2020 apr 15) [cited 2020 apr 18]; publish ahead of print. available from: https://journals.lww.com/jaaos/abstract/9000/departmental_e xperience_and_lessons_learned_with.99128.aspx summary journal of rawalpindi medical college (jrmc); 2015;19(3):275-279 275 original article the effect of ferrous sulphate on the gross and histological changes in the body of gastric mucosa of adult albino rats shahnila nadir 1, nida qasim2 , ansa rabia 3 1.department of anatomy, women medical college, abbottabad;2.department of anatomy, university of health sciences, lahore;3.department of anatomy, cmh, lahore medical college, lahore. abstract background:to observe the effects of ferrous sulphate on the body of gastric mucosa of adult albino rats. methods: an experimental study was carried out on 30 adult albino wistar rats for 12 weeks.two groups were made; a and b. they were divided further into a1, a2, b1 and b2 for qualitative parameters and statistical purposes.group a was kept as control and divided into 2 sub groups; a1 and a2 and was given normal food and water. the experimental group b was divided into 2 sub groups b1 and b2. ferrous sulphate was given orally for 4 and 12 weeks respectively through gavage needle for maximum efficacy in the experimental group.albino rat’s stomach was dissected, fixed in 10% formalin and processed for light microscopy. the short and long term effects of ferrous sulphate were observed on 4th and 12th week respectively. for histological analysis h&e was used. body of gastric mucosa of adult albino rat was considered for this study. results: change in the colour of mucosa was found in 10 (100%) of cases at 12 weeks whereas only 8 (80%) cases showed changes after 4 weeks. haemorrhage was seen scattered in 4 (40%) cases after 4 weeks whereas present in all 10 (100%) cases after 12 weeks. ulcer was seen in 4 (40%) of cases after 12 weeks. epithelial changes were seen in 5 (50%) cases at 4 and 8 (80%) of cases after 4 and 12 weeks respectively. ulcerative changes were seen in 4 (40%), granulation tissue/ fibrosis was seen in 7 (70%) cases in experimental group only. there was a significant decrease in the weight of rats from 226.69 ±22.31mg to 169.43±22.39mg in the experimental group with p ˂.001. inflammatory cell count significantly increased from (4.03± 1.02) to 17.01±5.01 in the experimental group with p˂.001. conclusion: ferrous sulphate has detrimental effects on the gastric mucosa of adult albino rats. haemorrhages, ulcerated areas and change in colour of mucosa was observed with naked eye. inflammatory cell infiltrate was found to be the most common presentation. key words: ferrous sulphate, gastric mucosa introduction iron deficiency anaemia is a common nutritional deficiency caused by either decreased use or increased loss of iron. iron sulphate (feso4) is the most commonly administered drug to overcome iron deficiency anaemia in pregnancy and post partum period and is an important constituent of nutrition for growth of children and adultsiron is an important metal and is considered to be an integral part of many proteins as haemoglobin and myoglobin. it also plays an important role in dna synthesis1-3 in 19th century, oral iron therapy has been the most commonly used therapy for iron deficiency anaemia4. anaemia is the commonest cause of malnutrition affecting 43% of children worldwide as stated by who.5 more adverse effects were seen in patients getting simple ferrous sulphate than with extended release tablets.6 iron deficiency anaemia has found to be the foremost nutritional deficiency in pakistan. the prevalence of anaemia in pakistan is 83%, 78%, 85% and 82.9% among pregnant, lactating women, adolescent girls and children respectively.7 the importance of iron is also emphasized in surah hadith of holy quran where it is stated “and we also sent down iron in which lies great dangers and it has many uses for mankind”.8 iron is present in ferrous (fe2+) and ferric (fe3+) states.4,9 ferrous salts are 3 times more absorbed than ferric salts.4 feso4 tablet is the most commonly used oral form of iron (325mg tablet contains 65mg iron).10,11,13 other iron preparations are ferrous fumarate and ferrous gluconate.12 less commonly used are iron amino chelate and iron polymaltose.3 injectable forms are iron sucrose, iron dextran, sodium ferric gluconate and ferrumoxytol but experienced staff is required for intravenous use as there is risk of allergic reactions.14,15 oral iron tablets are easy to use, cheap, and easily journal of rawalpindi medical college (jrmc); 2015;19(3):275-279 276 available hence no hospital staff or methods are required for their use.16 feso4 is an important constituent of our nutrition yet it creates reactive oxygen species also known as free radicals.17,19,20 they are harmful for the body causing wide range of tissue and organ damage.19, 20 injury has been observed in a few cases in gastrointestinal tract due to the usage of oral iron tablets.21 oral iron mucosal injury has a prevalence of 0.7% and may be seen at only 5 days after the iron treatment has been initiated in humans.5 the difference between anatomy of human stomach and rat stomach is that human stomach has proper fundus, body and antrum with glandular simple columnar epithelium whereas in rat stomach, most of the stomach is covered by non glandular stratified squamous epithelium and a small lower part is composed of simple columnar epithelium. this leaves a small fundus, proper body and a very small antrum.18 material and methods the experimental study was carried out in the animal house of anatomy department, post graduate medical institute, lahore. thirty albino rats 55-60 days old of either sex weighing (150-250gms) were procured from nih, islamabad after ethical committee approval. two groups were made and each was further divided into 2 subgroups. one was control and other experimental group which was given feso4 at therapeutic dosage. the duration of study was one year and the experiment was conducted for 12 weeks. they were housed separately in climate controlled environment and were kept on normal feed and water. all rats used in the study were handled with international, natural and institutional guidelines for care and use of laboratory animals as promulgated by the canadian council of animal care (1984). they were housed in cages with bar lids used to hold water bottles and feed to prevent contamination with urine or faeces. they were kept in ventilated room at ambient temperature of 28±2.0º c and humidity (60±10%) under 12 hour light /dark cycles and water ad libitum. each rat was tagged randomly on the tail. following acclimatization of one week, each rat was weighed at the commencement of the study and on 4th and 12th week respectively. ferrous sulphate was obtained in the crystalline form and dose was given by dissolving ferrous sulphate in water. dose was calculated to be 27mg/kg/day. the dose was given through gavage needle to make sure that the drug had efficiently and completely reached the gastric mucosa. to make a model comparable to humans as there is little compliance to multivitamins, iron sulphate was given once a day in morning with empty stomach to observe the maximal effect. after 4th and 12th week, respective rats were put in chloroform chamber and cervical dislocation was done under deep anesthesia. the surgical procedure was carried out under sterile conditions. the anesthetized animal was placed with limbs stretched on the operating board. a midline incision was given from the centre of neck extending downwards till the end with a scalpel and knife. the two flaps were divided in two parts by giving horizontal incision in the skin of both sides. stomach was identified behind the liver and was opened along the greater curvature. it was washed with normal saline to remove food debris and secretions. the gastric mucosa was stretched out with the help of forceps. naked eye examination was done to see change in colour, hemorrhage and ulcer. the histological analysis of the mucosa was done through light microscope. the stomach was photographed before taking sections. sections were taken randomly from the body of the gastric mucosa and placed in cassette with labels and fixed in neutral 10% buffered formalin for 48 hours. tissue processing was done and blocks were kept in refrigerator. they were mounted on rotary microtome and 5µm consecutive thick sections were lifted on it. slides were labeled with a lab code and number was given accordingly. haemotoxylin and eosin stain was used to see the histological changes in the mucosa. quantitative parameters were assessed by eye piece micrometer scale which was calibrated against the stage micrometer. quantitative variables were given as mean ± standard deviation and categorical data was shown as frequencies and percentages. results on gross examination no significant change in colour of gastric mucosa in control groups a1 and b1 was observed. there was significant change in group a2 at 4 weeks (p˂ .007) and group b2 after 12 weeks (p˂ .001) was observed. the mucosa appeared dull, congested, oedematous and reddish (table 1).in group a1and b1, haemorrhage could not be visualized. in group a2 hemorrhagic areas were seen in 4 (40%) cases after 4 weeks (p˂.231) and 10 (100%) cases after 12 weeks of ferrous sulphate dosage (p ˂ .001). ulcer could not be visualized in any of cases in groups a1, a2 and b1. in group b2, 4 (40%) cases showed ulceration after 12 weeks (table 1; figure 1). in journal of rawalpindi medical college (jrmc); 2015;19(3):275-279 277 qualitative parameters ulcers were seen in 4 (40%) cases in group b2 only (table 2;figure 2 ). table 1: comparison of gross qualitative parameters after 4 and 12 weeks on body of gastric mucosa qualitative parameters contro l gp.a1 exp gp.b 1 pvalue contr ol gp.a2 exp gp.b 2 pvalue b1vs b2 p.value change in color of mucosa 0(0%) 8 (80% ) .007* * 0 (0%) 10 (100 %) <.0 01* ** .474 presence of lesion (erosion) 0(0%) 0(0% ) na 0(0%) 5(50 %) .10 1 .033* hemorrhage 0(0%) 4 (40% ) .231 0(0%) 10 (100 %) <.0 01* ** .011 ulcer 0(0%) 0(0% ) na 0(0%) 4(40 %) .23 .087 *p˂.05,**p˂.01, ***p˂.001, fischer exact test used for comparison;n=number of rats: a1 (n=5); a2 (n=5);b1 (n=10); b2 (n=10) table 2: comparison of histological qualitative parameters after 4 and 12 weeks on body of gastric mucosa *p˂.05, **p˂.01, fischer exact test used for comparison fig 1. body of gastric mucosa (group b1) showing congested and hemorrhagic vessels (red arrow) and neutrophils (black arrow) with mast cells (blue arrows) after 4 weeks of experiment granulation tissue and fibrosis was seen in 7 (70%) cases in group b (figure 2).in quantitative parameters there was a significant increase in weight of the rats in control group; 185.39±18.02 (mg) than experimental group; 199.99±16.33 (mg) at 4 weeks (group b1) and 226.69±22.31 (mg) after 12 weeks (group b2) (table 3). in group b1, there was a slight increase in the weight of the rats from 174.61±16.33 (mg) to 183.14±22.79 (mg) after 4 weeks of ferrous sulphate usage. in group b2, the weight of the rats significantly decreased from 177.19±18.62 (mg) to 169.43±22.39 (mg) after 12 weeks.there was significant increase in inflammatory cell count from 4.03±1.02 (µm) to 11.15±3.28 (µm) after 4 weeks of experiment (p˂ .001) and increased significantly to 17.01±5.01 (µm) after 12 weeks (p˂ .001) (table. 4 ; figure 3). fig 2. body of gastric mucosa (group b2) showing erosion and ulcerative changes(black arrow), congested and hemorrhagic vessels(red arrow) and inflammatory cell infiltrate (blue arrow) after 12 weeks of ferrous sulphate ingestion. table 3: comparison of groups showing significant change in weights after 4 and 12 weeks on body of gastric mucosa ***p˂.001 table 4: comparison of groups showing significant change in inflammatory cell count after 4 and 12 weeks in body of gastric mucosa quantitative parameters control exp gp. b1 exp gp. b2 anova mean± sd mean± sd mean± sd f p inflammatory cell count 4.03±1.02 11.15±3.2 8 17.01±5.0 1 33.8 8 <.001 * *p˂.0001 . 0 2 4 6 8 10 12 14 16 18 control exp gp. b1 exp gp. b2 m ea n inflammatory cell count inflammatory cell count figure 3:escalation in inflammatory cell count in body of gastric mucosa of albino rats at 4 and 12 week. journal of rawalpindi medical college (jrmc); 2015;19(3):275-279 278 discussion most of the previous light microscopic studies on ferrous sulphate focused on intestinal mucosa.3,19 little attention has been directed at changes occurring in the gastric mucosa. however, some studies showed the detrimental effect of feso4 on the gastric mucosa but the information is very scarce and limited.1,2,22,23 due to ethical considerations, adult albino wistar rats were taken for experiment. the similarities in the gastric mucosa of rats are more than the differences from the human gastric mucosa so the results concluded can be considered for humans.30 in the present study, the most important feature was increased inflammatory count. this finding was in accord with the one reported earlier by toblli et al; 2008 and kumar et al; 2013 after use of feso4 in the gastrointestinal mucosa of adult albino rats that inflammatory cell count is increased in body of gastric mucosa after utilizing feso4.3, 6 chronic inflammation after use of iron medication was documented earlier by hiraishi et al; 1991 augmenting the current study 22. increased inflammation was also observed by kaye et al; 2008 similar to the current study.23 erosions, haemorrhages and ulcers were visualized on gross and histological study by ji and yardley, 2004 and ciminomathews et al; 2010. these findings potentiated the current study.24,25 ulcers were also observed by marginean et al; 2006 and hashash et al; 2013 which were similar to the present study.27,28 it was documented by laine et al; 1998 and marginean et al; 2006 that ulcers were produced in the gastric mucosa of albino rats.26,27 it was proved by reagenshaw et al; 2007 that a few ulcerated or necrotic areas were seen along with deposits of iron in the gastric mucosa29. it was observed by toblli et al; 2008 that there was a significant change in the weight of rats receiving feso4. this owed to the disturbed bowel movements caused by the drug. this study potentiated the current study where rats lost weight after 12 weeks of iron sulphate ingestion.30 formation of fibrous bands and granulation tissue was also evaluated by zhang et al; 2008 in a study which also potentiated the current study.20 conclusion extensive use of ferrous sulphate used in common clinical practice can cause injury and harm to the gastric mucosa. acknowledgement special thanks to assistant. professor dr. aboidullah, university of punjab on helping immensely with this research. references 1. vijaykumar s. iron poisoningan over view. int j pharmacol toxicol. 2013. 3(2): 46-55. 2. fine js. iron poisoning. curr probi pediatr. 2000; 30: 71-90. 3. tobbli je, cao g, olivieri l, angerosa m. comparative study of gastrointestinal tract and liver toxicity of ferrous sulphate, iron amino chelate and iron polymaltose complex in normal rats. pharmcaol 2008; 82:127-37. 4. mimura mec, bregano jw, dichi jb, gregaorio ep. comparison of ferrous sulphate and ferrous glycinate chelate for the treatment of iron deficiency anemia in gastrectomized patients. nutrition 2008; 24: 66368. 5. cancelo-hidalgo mj, castelo-branco c, palacios s, haya palazuelos j. tolerability of oral iron supplements: a systematic review. curr med res opin 2013; 29(4): 291303. 6. kumar m, singh kk, singh dd, gupta mk. histopathological and histochemical study of free iron as an endogenous chemical mediator of inflammation in chicken. indian j vet pathol 2009; 33(2): 163-67. 7. akhtar s, ahmed a, ahmed a, ali z, riaz m and ismail t. iron status of the pakistani population-current issues and strategies. j of clin.nutr 2013; 22(3): 340-47. 8. quran 57:25 9. geissner p and burckhart s. the pharmacokinetics and pharmvskyacodynamics of iron preparations. pharmaceutics 2011; 3: 12-33. 10. hoffbrand av, catovsky d, tuddenham edg. post graduate hematology. 5th edition. victoria: wileyblackwell publishing; 2010. 11. brunton ll, lazo sj, parker lk. goodman and gillman’s pharmacological basis of disease. 11th edition. newyork : mc graw hill; 2006. 12. bayraktar ud, bayraktar s. treatment of iron deficiency anemia associated with gastrointestinal diseases. world j gastroenterol 2010; 16(22): 272025. 13. loo nm, arthur ak, lee mc. 31 year old woman with alopecia. mayo clin prog 2013; 88(10): 1147-50. 14. patil ss, khanwelker cc, patil sk. conventional and newer oral iron preparations. ijpms 2009;2(3): 16-22. 15. saljhougian m. parenteral irons: indications and comparison. us pharm 2010;35(11): 22-24. 16. wang j, o’ reilly b, venkataraman r, mysliwiec v, mysliwiec a. efficacy of oral iron in patients with restless legs syndrome and a low normal ferritin: a randomized, double blind, placebocontrolled study. sleep 2009; 10:97375. 17. conrad me, umbreit jn. pathways of iron absorption. blood cell mol dis 2002; 29(3): 336-55. 18. erichsen k, ulnik rj, grimstads t, berstad a, berge rk, hausken t. effects of ferrous sulphate and non-ionic ironpolymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease. ailment pharmacol ther 2005; 22: 83138. 19. mahjoub f, saffar h, najjafi m, moatamed f, seighali f. iron deposition in duuodenal mucosa: a review and report of threecases in pediatric age group. iran j pediatr 2011; 21(2):235-38. 20. zhang z, lian b, cui f. effect of feso4 treatment on glucose metabolism on diabetic rats. biometals 2008; 21: 68591. 21. ali a, fathy ga, fathy ha, el-ghaffar na. epidemiology of iron deficiency anemia: effect on physical growth in primary school children, the importance of hookworms. ijar 2011; 349(1): 5-7. 22. hiraishi h, terano a, ota s, mutoh h, razandi m, sugimoto t, et al. role of reactive oxygen speciesmediated journal of rawalpindi medical college (jrmc); 2015;19(3):275-279 279 cytotoxicity to cultured rat gastric mucosal cells. amj physiolgastrol 1991; 260: 55663. 23. kaye p, abdulla k, wood j, james p, foley s, ragunath k, et al. iron induced mucosal pathology of upper gastrointestinal tract: a common finding in patients on oral iron therapy. histopathol 2008; 53: 311-17. 24. ji h, yardley jh. iron medication associated gastric mcuosal injury. arch patho lab med 2004; 128(7):821-22. 25. ciminomathews a, broman jh, westa wh, illei pb. iron pill induced tumefactive mucosal injury of the hypopharynx. am j surg pathol 2010; 34(11): 901-03 26. laine la, bentley e, chandrasoma p. effect of oral iron therapy on the upper gastrointestinal tract. a prospective evaluation. dig dis sci 1998; 33(2): 172-77. 27. marginean ec, bennick m, cyezk j, robert me, jain d. gastric siderosis: patterns and significance. am j surg pathol 2006; 30(4): 514-20. 28. hashash jg, proksell s, kuan sf, behari j. iron pill induced gastritis. acg case rep j 2013; 1(1): 13-15. 29. reagan-shaw, s., nihal, m. and ahmad, n. 2007. dose translation from animal to human studies. faseb j 2010; 22: 659-61. 30. kararli tt. comparison of gastrointestinal anatomy, physiology and biochemistry of humans and commonly used laboratory animals. biopharmaceutics and drug disposition 1995; 16: 351-80. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 208-210 208 original article comparison of sublingual misoprostol and manual vacuum aspiration for the treatment of incomplete abortion in first trimester in terms of frequency of decreased haemoglobin levels saima khurshid ahmed, rubina ashraf , lubna ejaz khaloon department of gynaecology and obstetrics, holy family hospital and rawalpindi medical university, rawalpindi abstract background: to compare efficacy of manual vacuum aspiration with sublingual misoprostol for the treatment of incomplete abortion in terms of frequency of blood loss and decreased haemoglobin. methods: in this randomized controlled trial, patients with incomplete abortion, open cervical os, vaginal bleeding, history of vaginal bleeding during this pregnancy and uterine size of less than or equal to 12wks menstrual period were included. consenting women were randomized to either group a who received a single dose of 600 microgram of sublingual misoprostol or group b who underwent manual vacuum aspiration for evacuation of retained products of conception. both groups comprised of 150 patients each. pre and post (after 48 hours) treatment haemoglobin levels were measured. results: mean fall in haemoglobin level <1g/dl from baseline level was seen in misoprostol group while a mean fall of <0.5g/dl from baseline level was observed in mva group (p<0.001, 95% ci, t=1.64, eta squared=0.006). a significant association was found with haemoglobin level, parity and age, with p=0.001, p= 0.05, p=0.02 respectively conclusion: the efficacy of manual vacuum aspiration (mva) is indicated by lower level of blood loss (hb<0.5g/dl from baseline) as compared to 600µg sublingual misoprostol. mva is associated with less complications than misoprostol. key words: manual vacuum aspiration, misoprostol, haemoglobin level, gestational age introduction first trimester incomplete abortion is an important contributing factor of maternal mortality and morbidity.1 2 it is estimated that 80% of abortions are associated with first trimester and there is reduction in abortion rate with increasing gestational age.3 pakistan is a developing country with limited resources in health sector. pakistan has slow fertility rate decline as compared to other developing countries.4 according to a recent survey, approximately 2.2 million abortions occur in pakistan, signifying an annual abortion rate of 50 per 1,000 pregnancies.5 incomplete abortion in first trimester could be managed through medical and surgical interventions. most common medical intervention used in pakistan is misoprostol. this has been found to be safe, effective and acceptable among women who are not willing for invasive procedures.6 the most common surgical procedure is manual vacuum aspiration (mva). the success rate of mva is 91.5 to 100% but it is associated with complications like infections, uterine perforations and cervical lacerations.7 weeks et al. reported that misoprostol had less complications associated with incomplete abortion treatment as compared to mva.8 misoprostol group reported lower level of pain but greater amount of blood loss as compared to mva group. rates of acceptability were found to be similar in misoprostol and mva group while satisfaction rate was 94.2% in misoprostol and 94.7% in manual vacuum aspiration.9 incomplete abortion is associated with various gynecological complications in pakistan. limited data is available regarding comparison of misoprostol and mva efficacy in terms of blood loss during incomplete abortion.10 11 so it becomes very important to understand the efficacy of both treatments in order to develop guidelines regarding maternal health. patients and methods a randomized controlled trial (rct) with 1:1 ratio was conducted in department of obstetrics and journal of rawalpindi medical college (jrmc); 2017;21(3): 208-210 209 gynaecology unit-i, holy family hospital (hfh), rawalpindi, from june 2013 to december 2013. a sample size of 300 patients was obtained through who calculator with 95% confidence interval, 5% level of significance and 80% power of study. patients with incomplete abortion, open cervical os, vaginal bleeding, history of vaginal bleeding during on-going pregnancy and uterine size of less than or equal to 12 weeks menstrual period were included in study. exclusion criteria were known allergy to misoprostol or other prostaglandins, contraindication to prostaglandin therapy (asthma, hypertension, glaucoma) and suspected ectopic pregnancy. pelvic infection or sepsis, haemodynamically unstable patients, those with previous scar uterus, anaemia of <9g/dl, and history of surgical evacuation in previous miscarriages were also not included. approval was taken from institutional research forum / ethics committee of rawalpindi medical university. consenting women were randomized to either group a who received a single dose of 600 microgram of sublingual misoprostol or group b who underwent mva for evacuation of retained products of conception. pre and post (after 48 hours) treatment haemoglobin levels were measured. an independent ttest was performed to observe the results before and after intervention. chisquare test was used to see the association between different variables. results both groups comprised of 150 patients each. in group a (misoprostol), mean age of patients was 27.82 years ± 4.16 sd, mean parity 1.67 ± 1.44 sd and mean gestational age 11.08 weeks ± 2.37 sd. in group b (mva), mean age of patients was 27.15 years ± 4.82 standard deviation (sd), mean parity 1.46 ± 1.47 sd and mean gestational age was 11.21 weeks ± 1.94 sd (table 1). in group a, 60 patients were in 20-30 year age group. in group b, 60 patients were found in 20-30 year age group and 60 in age group 31-40 years (table 1). mean fall in haemoglobin level <1g/dl from baseline level was reported in misoprostol group while a mean fall of <0.5g/dl from baseline level was reported in mva group(p<0.001, 95% ci, t=1.64, eta squared=0.006). a significant association was found with haemoglobin level, parity, age with p=0.001,p= 0.05, p=0.02 respectively (table 2). in group a, 90(60%) patients had gestational age <11 weeks while 60(40%) had gestational age >11 weeks. in group b, 60(40%) patients had gestational age <11 weeks while 90(60%) had gestational age >11 weeks. the association was found to be statistically insignificant ((χ2=5.152, df=1, p=0.272). table 1 : age distribution in both interventional groups age distribution (years) group a (subligual misoprostol) group b(manual vacuum aspiration) no percentage no percentage 20-30 60 40% 60 40% 31-40 50 33% 60 40% >40 40 27% 30 20% total 150 100% 150 100% table 2: associations between two interventional groups and independent variables independent variables group a (misoprostol) (n=150) group b (mva)* (n=150) chi square value significance haemoglobin level χ2=8.39 0 0.004 <l g/dl from baseline 83 (55%) 67(45%) >1g/dl from baseline 67(45%) 83(55%) parity χ2=18.2 75 0.000 1 99(66%) 51(34%) >1 51(34%) 99(66%) age groups χ2=9.699 0.002 20-30 years 60(40%) 60(40%) 31-40 years 50(33%) 60(40%) >40 years 40(27%) 30(20%) *mva= manual vacuum aspiration discussion first trimester miscarriage is one of one most common complications of pregnancy occurring in 10-15% of clinically recognized pregnancies.12 13 in present study a total of 300 patients underwent interventions with a ratio of 1:1 between both groups. sochet et al. reported their mean age in misoprostol group was 28.1±7.2 sd while in mva group mean age was 28.7±7.1sd.14 15in our study mean fall in hemoglobin level <1g/dl from baseline level was reported in misoprostol group while a mean fall of <0.5g/dl from baseline level was reported in mva group. sexana et al. reported that mva group had shown lower side effects and higher pain scores as compared to misoprostol.14 16 oral misoprostol was reported as more acceptable and well suited in limited resource health sectors. women in misoprostol group were more willing to re use the method next time and were satisfied with the entire procedure.17 18 journal of rawalpindi medical college (jrmc); 2017;21(3): 208-210 210 fateen et al. and madden et al reported that misoprostol group is associated with less complications as compared to mva.10 19 other studies have reported that for uncomplicated incomplete abortion in first trimester mva and misoprostol are equally effective, safe and acceptable to the patients. 20 21 any procedure can be used according to the patient’s preference and available resources.22 23hou et al. reported that mean change in hemoglobin level among patients of both groups mva and misoprostol was similar (p<0.01). while heavy bleeding was rarely reported.24 another study reported that 400µg sublingual misoprostol is more effective and safe in areas where surgical treatment is unavailable.25 conclusion • efficacy of manual vacuum aspiration (mva) is indicated by lower level of blood loss (hb<0.5g/dl from baseline) as compared to 600µg sublingual misoprostol. • mva is associated with less complications than misoprostol. in developing countries like pakistan where maternal mortality and morbidity is an important issue, mva would be a safe and effective technique for uncomplicated abortion in first trimester. references 1. weeks a, alia g, blum j, winikoff b. a randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion. obstet gynecol. 2005 ;106(3):540– 47. 2. bique c, ustá m, debora b. comparison of misoprostol and manual vacuum aspiration for treatment of incomplete abortion. int j gynaecol obstet 2007 ;98(3):222–26. 3. dao b, blum j, thieba b, raghavan s. is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care?int j obstet gynaecol. 2007 ;114(11):1368–75. 4. shokry m, fathalla m, hussien m, eissa aa. vaginal misoprostol versus vaginal surgical evacuation of first trimester abortion. middle east fertil soc j 2014;19(2):96– 101. 5. wen j, cai qy, deng f, li yp. manual versus electric vacuum aspiration for first-trimester abortion: a systematic review. bjog. 2008;115 (4):5–13 6. allen rh, fitzmaurice g, lifford kl. oral compared with intravenous sedation for first-trimester surgical abortion. obstet gynecol. 2009;113 (6):276–83 7. prada e, atuyambe lm, blades nm, bukenya jn. incidence of induced abortion in uganda, 2013: new estimates since 2003. plos one . 2012;11(11):12-14. 8. tanha fd, golgachi t, niroomand n, ghajarzadeh m. sublingual versus vaginal misoprostol for second trimester termination. arch gynecol obstet. 2010;287:65–69. 9. lamina ma. prevalence of abortion and contraceptive practice among women seeking repeat induced abortion in western nigeria. j pregnancy. 2009;20 (3): 134-36. 10. fateen b, rabei n, mostafa wm. sublingual versus vaginal misoprostol for preoperative cervical priming in first trimester missed abortion. nat sci. 2013;11(8):72–77. 11. mohamed sf, izugbara c, moore am, mutua m. incidence of induced abortion in kenya: a cross-sectional study. bmc pregnancy childbirth . 2012;15(2): 121-24. 12. vlassoff m, mugisha f, sundaram a, bankole a. the health system cost of post-abortion care in uganda. health policy plan. 2014 ;29(1):56–66. 13. shochet t, diop a, gaye a, nayama m, sall ab. sublingual misoprostol versus standard surgical care for treatment of incomplete abortion in five sub-saharan african countries. bmc pregnancy childbirth. 2010 12(1):127-30. 14. saxena p, salhan s, sarda n. sublingual versus vaginal route of misoprostol for cervical ripening prior to surgical termination of first trimester abortions. eur j. obstet gynecol reprod biol. 2008;125(3):109–13. 15. bankole a, adewole if, hussain r, awolude o. incidence of abortion in nigeria. int perspect sex reprod health. 2009 ;41(4):170–81. 16. levandowski ba, mhango c, kuchingale e, lunguzi j. the incidence of induced abortion in malawi. int perspect sex reprod health. 2010 ;39(2):88–96. 17. hou s, zhang l, chen q, fang a, cheng l. oneand twoday mifepristone-misoprostol intervals for second trimester termination of pregnancy between 13 and 16 weeks of gestation. int j. gynaecol. obstet. 2011;111 (2):126–30. 18. ellis sc, kapp n, vragpvoc o, borgata l. randomized trial of buccal versus vaginal misoprostol for induction of second trimester abortion. contraception. 2007;81(1):441–45 19. madden t, westhoff c. rates of follow-up and repeat pregnancy in the 12 months after first-trimester induced abortion. obstet gynecol. 2009;113:663–68. 20. goldberg ab, dean g, kang ms. manual versus electric vacuum aspiration for early first-trimester abortion. obstet gynecol. 2004;103(2):101–07 21. zhang j, gilles jm, barnhart k. national institute of child health human development (nichd) management of early pregnancy failure trial. a comparison of medical management with misoprostol and surgical management for early pregnancy failure. n engl j med. 2005;353(1):761– 69. 22. tang os, lau wn, ng eh. a prospective randomized study to compare the use of repeated doses of vaginal with sublingual misoprostol in the management of first trimester silent miscarriages. hum reprod. 2003;18(3):176–81. 23. winikoff b, dzuba ig, creinin md. two distinct oral routes of misoprostol in mifepristone medical abortion. obstet gynecol. 2008;112(6):1303–10. 24. creinin md, schwartz jl, guido rs. early pregnancy failure. current management concepts. obstet gynecol surv. 2001;56(4):105–13 25. meckstroth kr, whitaker ak, bertisch s. misoprostol administered by epithelial routes: drug absorption and uterine response. obstet gynecol. 2006;108(3):582–90 163 journal of rawalpindi medical college (jrmc); 2022; 26(2): 163-164 editorial the journey of postgraduate education in pakistan jahangir sarwar khan1 1 professor of surgery, rawalpindi medical university, rawalpindi. cite this article: khan, j.s. the journey of postgraduate education in pakistan. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 163-164. doi: https://doi.org/10.37939/jrmc.v26i2.2004 access online: at the time of the creation of pakistan, there were only a few medical colleges that too mostly in crisis as most faculty and students migrated to india after the partition. in the 1950s, several new medical colleges were created to meet the requirements of training doctors in the country as there was a growing need for specialists in various medical fields. later, ms and md programs were started by a handful of universities, but their training standards were not up to the mark. major development regarding post-graduate education took place in 1962 when the college of physicians and surgeons (cpsp) in karachi, was established.1 the college introduced fellowships in various specialties; however, the number of trainees remained very low. in the 1970s, newer medical colleges were created to meet ever increasing demand for doctors. this resulted in the creation of limited teaching posts as well as training slots in most institutes. as the passing percentage of the cpsp fellowship program was low, a small number of postgraduate trainees and specialists were being trained locally. most teaching posts in the country were occupied by western trained doctors and most students preferred going abroad, especially to the united kingdom for training. in the 1990s, major changes were introduced at cpsp, including the introduction of the mcq pattern for primary exams and later replacing viva with ospe. this objectivity in assessment resulted in a higher pass percentage, and more locally produced specialists were now available. brain drains from pakistan still was a pressing issue as recruitment drives of specialists for the middle east increased and a number of doctors joined their health services. however, at the start of the twenty-first century, due to islamophobia, several doctors started returning from western countries. most academic units were now headed by cpsp fellows and international trained specialists. as a result, proper teaching units were established with regular fcps and mcps training programs being conducted. due to the saturation of big cities, more specialists started to move to rural facilities in pakistan thus improving access to health care. locally, a number of private colleges mushroomed as regulatory requirements were relaxed owing to the need of producing more doctors both at undergraduate and postgraduate levels. however, the brain drain continued as many joined the positions in the united kingdom especially in the mid-2000s, as the working hours for doctors were reduced by their national health services. major changes took place in the last decade in postgraduate education in pakistan. newer medical universities were established, and they started master of surgery (ms) and doctor of medicine (md) programs.2 mostly their curricula were modifications of the cpsp fellowship program. at the same time, cpsp started a regular online part 1 induction exam, and the number of entrants into the fellowship program started to increase. previously, after clearing the part 1 exam, induction of trainees was done as per the recommendations of supervisors. this resulted in most trainees preferring more developed cities for training and some complained of bias in selection. to address these issues, a central induction policy was introduced in punjab, which gave a major preference to doctors working in rural health services. seats were equally divided between cpsp and ms/md candidates. still, unfortunately, with a few exceptions, the standard of training has deteriorated. although cpsp is following a structured schedule of all training workshops for part 2 trainees, but much is desired regarding their quality. online monitoring and dissertation writing was made compulsory, but issues 164 journal of rawalpindi medical college (jrmc); 2022; 26(2): 163-164 of fake entries and paid research projects still need to be addressed. due to the increased induction, the number of trainees per supervisor is also very high resulting in compromises in training. for the young graduates, there are extreme difficulties in seeking training slots. at present for a single training slot, at least twenty candidates are waiting. this has created a lot of resentment among our young doctors.3 it is the need of the hour to upgrade the postgraduate medical curriculum in our country and bring it in accordance with international standards, ensuring the participation of all stakeholders. nowadays, training programs in most developed countries are competency-based, putting less emphasis on the formal exam. also, aptitude testing should be made compulsory before selecting a candidate for any specialty to ensure proper training. and lastly, the number of candidates who passed in fcps part 1 exam should be in accordance with the number of seats available in the country for post-graduation in that discipline. references 1. https://www.cpsp.edu.pk/history.php. 2. https://www.upmed.net/jcat/ 3. https://www.dawn.com/news/1628155 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 82-85 82 original article dry eye disease in younger age munir amjad baig1, nadir mehmood2, muhammad hamaza3, rabeeya munir4 1. department of ophthalmology, ajk medical college, muzaffarabad; 2. department of surgery,benazir bhutto hospital and rawalkpindi medical collegfe, rawalpindi;3. second year mbbs, student, rawalpindi medical college, rawalpindi; 4.rawal institute of health sciences, islamabad abstract background: to evaluate the personal and environmental risk factors attributable to dry eye disease (ded) among younger age group of islamabad. methods: in this cross-sectional study, 360 individuals aged 18-40 years of either sex were screened randomly. all patients visiting outpatient department with various symptoms and later diagnosed to have abnormal tests and symptoms of dry eye were included in this study. patients having any eye disease, systemic disease and those using antiallergic or steroid drugs were excluded. patient demographics and dry eye questionnaire (deq) was administered by a trained interviewer. dry eye tests like tear film breakup time (tbut), corneal fluorescein staining (cfs), schirmers test (st) and slit-lamp examination for presence of conjunctival injection, punctate epithelial erosions (pee), lid margins plugging and telengiectasias were used to diagnose dry eye. results:there were 55.6% males and (44.4% females. majority were urban (72.8%). major constituents were students (23.3%), teachers (17.2%), office workers (27.8%), housewives (13.9%) and labourers (17.8%). in this study, 81(22.5%) subjects, 42(11.7%)male, 39(10.8%) female were symptomatic defined as presence of one or more dry-eye symptoms often or all the time. two hundred and two (56.1%) subjects had low tbut, 140(38.9%) had low st and 180(50%) patients had abnormal plugging or telengiectasias of lid margins. common symptoms were burning 59.2%, eye strain 55.5%, watering 51.8% and fatigue 49.3%.dry eye symptoms were related to computer use 20(24.7%), blepharitis 19(23.4%), refractive errors 7(8.6%), contact lens use 3(3.7%), refractive surgery 1(1.2%), eye make-up use 10(12.3%), use of antiallergic medications 10(12.3%) and smoking 11(13.5%). conclusion : various environmental effects at work are related to eye and physical symptoms which affect quality of life. those students who are using computers and other screens develop dry eye symptoms. dry eye is a common condition presenting to ophthalmologists. it is underdiagnosed and variably treated with antiallergic /decongestants drops on empirical basis. key words: dry eye, tear film breakup time, corneal fluorescein staining,schirmers test (st), punctate epithelial erosions (pee) introduction dry eye is a multifactorial condition of tear film and ocular surface. it results in visual disturbance, tear film instability and damage to the ocular surface. it is associated with increased osmolarity of the tear film and inflammation of the ocular surface.1 de roth in 1950, named the term “dry eye”.2 in 1955 it was used as a problem of low tear production.3 in 2006 delphi panel proposed dysfunctional tear syndrome (dts) with the remarks that inflammation plays a role in the disease.4 the other names are keratoconjunctivitis sicca, any eye with some degree of dryness, xerophthalmiadry eye due to vitamin a deficiency and xerosis, extreme ocular dryness and keratinization due to severe conjunctival cicatrisation.5 in pakistan one study carried out in a tertiary care hospital showed de prevalence as 16%.6 a study conducted on elderly korean population found that female sex, age, and hormonal influence were risk factors for ded.7 the salisbury eye study in us shows the prevalence of ded to be 14.6%.8 about 3.2 million women and about one million men are involved in united states.9 the precorneal tear film is responsible for tear film stability, corneal transparency and the image quality onto the retina.10 blinking relieves the de symptoms. blinking moistures the eye surface during cold and dry weather.11 a slow blinking rate increases de symptoms while working at a computer, watching a movie or living in a dry weather.12 other risk factors include blepharitis, refractive errors, smoking, exposure to environment and use of various drugs. 13,15 patients and methods in this cross-sectional study, out of total 400 individuals, 360 willing subjects (response rate 90%) javascript:void(0); journal of rawalpindi medical college (jrmc); 2017;21(1): 82-85 83 aged18-40 years were selected randomly from ophthalmology out-patient department of federal government services hospital islamabad during jan ,2012 to dec ,2012. patients with any systemic or eye disease or those using medications were excluded. patient demographics including age, sex, education, occupation, smoking, make-up use and working environment were also recorded. the self assessment dry eye questionnaire concerning symptoms is administerd by a trained interviewer. all subjects underwent a complete ophthalmic examination in a fixed room sized 16x14 sqft. without fan or cooler and controlled lights. eye examination was conducted on the same day under same physical conditions by an ophthalmologist. dry eye questionnaire (deq), tear film breakup time (tbut), corneal fluorescein staining(cfs) for presence of conjunctival injection, punctate epithelial erosions (pee), schirmers test(st) and slit lamp examination for meibomian gland dysfunction (mgd)like plugging and telangiectasias of the lid margins were recorded. de was diagnosed with the presence of de symptoms, tear abnormality schirmer test ≤ 5 mm, tear breakup time ≤ 10 seconds and corneoconjunctival staining score of ≥1 points and any lid abnormality. results of total 360 study subjects aged 18-40 years, there were 200(55.6%) males and 160(44.4%) females comprising 192 (53.3%) of aged 18-30 years and 168(46.7%) of 30-40 years age group. urban subjects were 262(72.8%) and rural 98(27.2%). students 84 (23.3%), teachers 62(17.2%), office workers 100(27.8%), housewives 50(13.9%) and 64(17.8%) were labourers . majority (77.5%) subjects were asymptomatic, defined as no symptoms of dry eye at all or felt only rarely or sometimes. table-1: baseline characters and diagnostic tests sex male: 200(55.6%) females : 160(44.4%) residence urban : 262(72.8%) rural : 98(27.2%) ophthalmological tests low tear film breakup time (tbut): (56.1%) low schirmers test ( st) : 39% cfs corneal fluorescein staining: 48% in this study 81(22.5%) individuals, 42(51.8%) males and 39(48.2%) females, were symptomatic defined as reporting one or more dry-eye symptoms often or all the time. 202(56.1%) subjects had low tfbut, 140(38.9%) patients had low st and 180(50%) patients had abnormal meibomian glands appearances (table 1) the common complaints were burning 59.2%, eye strain 55.5%, watering 51.8% and fatigue (49.3%) (table 2). most females were using computers less than 3 hrs (41%) than males in this study.dry eye symptoms were related to computer use 20(24.7%), blepharitis 19(23.4%), refractive errors 7(8.6%), contact lens use 3(3.7%), refractive surgery 1(1.2%), eye makeup use 10(12.3%), use of antiallergic medications 10(12.3%) and smoking 11(13.5%)(table 3). table-2: dry eyesymptoms ocular complaints mae female present burning 26 22 48(59.2) eye strain 22 23 45(55.5) eye fatigue 20 22 42(51.8%) watering 20 20 40(49.3%) table-3: factors affecting dry eye factor male female present computer use 12 8 20(24.6%) blepharitis 11 8 19(23.4%) smokers 11 11(13.5%) antialergics 4 6 10(12.3%) eye make up 10 10(12.3%) refraction 6 5 11 (13.5%) discussion the 2007 international dry eye workshop (dews) reports the global prevalence of de to be between 5% to over 35% at various ages (21yr to >65 yr).1 clinically, de causes a drop in visual acuity and contrast sensitivity leading to decreased vision related activities like reading and driving.16 signs and symptoms include ocular dryness, grittiness, burning and foreign body sensation, redness and blurred vision that clears on blinking.17in this study de is present in 81 (22.5%) of young population. it is similar with one study showing that 18.7% of subjects younger than 20 years have dry eye symptoms compared to 30.1% of adults.18among younger age group (1840years), computer users of longer duration, both office workers and students, were having dry eye symptoms more than other.19 this study showed that the subjects using computers for longer time had more ocular complaints. benitez and lemp(2012) study suggest that blepharitis is present in 37 percent to 47 percent of all patients who undergo clinical examination20. this study shows journal of rawalpindi medical college (jrmc); 2017;21(1): 82-85 84 the similar results. it is an important health problem. in america prevalence is about 15 percent of the population, representing nearly 48 million americans.21 the schirmer and tear film breakup time tests are commonly used in the diagnosis of dry eye.22 the basal st evaluates the basic tear secretion and the tbut test reflects tear stability. in this study 56.1% patients had low tbut and 39% had low st values and 50% had abnormal meibomian gland appearances. the current study reveals 12% of subjects having refractive errors and using contact lens, myopia being the most common. it may be due to increased rubbing of eye.23 this study is consistent with other study.24 guillon et al also showed that dry eye disease was frequent in contact lens wearers than in non wearers. 25 other studies have shown that contact lens wearers experience dry eye symptoms more than non-contact lens users.26 smoking is one of the risk factors causing dry eye.27 large epidemiological studies indicate that female sex and older age increase the risk for dry eye.28 women are reported to be more prone to de, 12% of male and 22% of female patients had a diagnosis of de but some published studies based on regional population in china did not find any prevalence difference between males and females. 29,30 in current study male to female ratio was almost equal (42males vs 39females) and was not consistent with other study.2 in our study the female subjects used computers for lesser time periods than the males however females had more visual problems than the males29. other studies estimate that the prevalence of cvs ranges from 75 to 90 % among computer users. most of the studies have been among a limited number of computer workers and usually conducted within a single institution/organization.31 conclusion 1. dry eye disease (ded) is a frequently diagnosed eye problem. twenty-five percent of patients visiting eye clinics have symptoms of dry eye, making it a growing public health problem. 2. various environmental variations at work are related to eye and physical symptoms which affect quality of life. . those students who are using computers and other screens develop dry eye symptoms. 3. visual health related public awareness programmes should be started indicating risks of prolonged use of computers, cosmetics and smoking. references 1. the definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop. ocul surf, 2007 ;5(2):7592. 2. johnny l gayton.etiology, prevalence, and treatment of dry eye disease clin ophthalmol, 2009; 3: 405–12. 3. lemp ma. report of the national eye institute/industry workshop on clinical trials in dry eye. clao j, 1995;21:221-32 4. behrens a, doyle jj, stern l. dysfunctional tear syndrome. a delphi approach to treatment recommendations. cornea, 2006;25:90-97 5. weber tm, kausch m, rippke f, schoelermann am. treatment of xerosis with a topical formulation containing glyceryl glucoside, natural moisturizing factors, and ceramide. j clin aesthet dermatol , 2012;5(8):29-39. 6. malik ta, naqvi sah, shahid m. dry eye syndrome; frequency in adult patients attending the eye clinic in military hospital rawalpindi. professional med j, 2009;16(1):145–58. 7. han sb, hyon jy, woo sj, lee jj, kim t-h. prevalence of dry eye disease in an elderly korean population. arch ophthalmol , 2011;129:633–38 8. munoz b, west sk, rubin gs. causes of blindness and visual impairment in a population of older americans. arch ophthalmol, 2000;118:819–25. 9. schaumberg da, sullivan da, buring je. prevalence of dry eye syndrome among us women. am j ophthalmol, 2003;136 (2):318–26. 10. t. j. millar and b. s. schuett. the real reason for having a meibomian lipid layer covering the outer surface of the tear film a review. experimental eye research, 2015;137: 12538. 11. abelson mb and mclaughlin j. of biomes, biofilm and the ocular surface. rev ophthalmol,2012 ;19 (9):52-54. 12. korb dr and blackie ca. debridement-scaling: a new procedure that increases meibomian gland function and reduces dry eye symptoms. cornea, 2013 ;32(12):1554-57. 13. perry hd. dry eye disease: pathophysiology, classification, and diagnosis. am j manag care (2lemp ma, nichols kk. blepharitis in the united states 2009: a survey-based perspective on prevalence and treatment. ocul surf. 2009 apr;7(2 suppl):s1-s14.008) 14: s79–87. 14. jie y, xu l, wu yy, jonas jb. prevalence of dry eye among adult chinese in the beijing eye study. eye (lond). 2009 mar;23(3):688-93 15. hosaka e, kawamoritat,ogasawara y, nakayama n.interferometry in the evaluation of precorneal tear film thickness in dry eye. am j ophthalmol (2011) 151: 18–23. 16. grubbs jr jr.,tolleson-rinehart s,huynh k. a review of quality of life measures in dry eye questionnaires.cornea 2014;33:215–18 17. uchino, m., yokoi, n., uchino, y. prevalence of dry eye disease and its risk factors in visual display terminal users: the osaka study. am j ophthalmol. 2013;156:759–66. 18. hom m, de land p. prevalence and severity of symptomatic dry eyes in hispanics. optom vis sci. 2005;82:206–08. 19. keech, a., senchyna, m., jones, l. impact of time between collection and collection method on human tear fluid osmolarity. curr eye res. 2013;38:428–36. 20. benitez-del-castillo jm, lemp ma. anterior blepharitis. ocular surface disorders. jp medical publishers. 2012;90(249):1: 6-9 https://www.ncbi.nlm.nih.gov/pubmed/?term=gayton%20jl%5bauthor%5d&cauthor=true&cauthor_uid=19688028 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2720680/ https://www.ncbi.nlm.nih.gov/pubmed/?term=jie%20y%5bauthor%5d&cauthor=true&cauthor_uid=18309341 https://www.ncbi.nlm.nih.gov/pubmed/?term=xu%20l%5bauthor%5d&cauthor=true&cauthor_uid=18309341 https://www.ncbi.nlm.nih.gov/pubmed/?term=wu%20yy%5bauthor%5d&cauthor=true&cauthor_uid=18309341 https://www.ncbi.nlm.nih.gov/pubmed/?term=jonas%20jb%5bauthor%5d&cauthor=true&cauthor_uid=18309341 https://www.ncbi.nlm.nih.gov/pubmed/18309341 journal of rawalpindi medical college (jrmc); 2017;21(1): 82-85 85 21. sullivan,b.d. whitmer, d.,nichols, k.k. an objective approach to dry eye disease severity.invest ophthalmol vis sci. 2010;51:6125–130. 22. lemp, m.a., bron, a.j., baudouin, c. et al, tear osmolarity in the diagnosis and management of dry eye disease. am j ophthalmol , 2011;151:792–98 23. jie y, xu l,wu y, jonas jb. prevalence of dry eye among adult chinese in the beijing eye study eye, 2009; 23: 688– 93. 24. roni m shtein rm,post-lasik dry eye. expert rev ophthalmol , 2011; 6(5): 575–82 25. guillonm, cooperp, maissac, girard-claudonk. dry eye symptomatology of contact lens wearers and nonwearers. adv exp med biol , 2002;506:945–49. 26. guo b, lu p, chen x, zhang w, chen r. prevalence of dry eye disease in mongolians at high altitude in china: the henan eye study. ophthalmic epidemiol , 2010;17:234– 41 27. sahai a and malik p. dry eye: prevalence and attributable risk factors in a hospital-based population. indian j ophthalmol, 2005; 53: 87–91. 28. zhuang sj, lei sc,luo xd.epidemiologic survey of dry eye in a community of huidong county in guangdong province. chinese journal of experimental ophthalmology ,2012;30(2): 168–71 29. paulsen aj, cruickshanks kj, fischer me. dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. am j ophthalmol,2014;157(4):799-806. 30. galor a, feuer w, lee dj.prevalence and risk factors of dry eye syndrome in a united states veterans affairs population . the american journal of ophthalmology, 2011;152(3):377–84. 31. ranasinghe p, perera ys, lamabadusuriya da, kulatunga s, jayawardana n. work related complaints of neck, shoulder and arm among computer office workers: a cross-sectional evaluation of prevalence and risk factors in a developing country. environ health , 2011;10:70-74 for electronic submission of articles email of journal: journalrmc@gmail.com to view volumes of journal of rawalpindi medical college and to search by authors names , contents , keywords-visit website of the journal: www.journalrmc.com http://www.nature.com/eye/journal/v23/n3/full/6703101a.html#aff2 https://www.ncbi.nlm.nih.gov/pubmed/?term=shtein%20rm%5bauthor%5d&cauthor=true&cauthor_uid=22174730 mailto:journalrmc@gmail.com jrmc vol. 27 (issue 2) journal of rawalpindi medical college https://doi.org/10.37939/jrmc.v27i2.1804 (c) 2023 by rawalpindi medical university 239 page no. covid-19 vaccine acceptance and hesitancy among medical students of faisalabad mohi ud din1, umer shahid2, abdul qudoos3, roman ahmed4, muazzama sohail5, saima javed6 abstract introduction: the study was conducted to determine the covid-19 vaccine acceptance and hesitancy among medical students who are more susceptible to being infected being the frontline workers. materials and methods: this analytical cross-sectional study was conducted on medical students of 1st to final year mbbs of various medical institutions in faisalabad. the study duration was 3 months (august 2021 to october 2021). the sample size was 391 and divided into 2 age groups i.e. above and below 21 years and 245 (62.7%) comprised of females. the inclusion criteria were those students who gave consent and filled out the questionnaire and the exclusion criterion was who didn't concede. the data was analyzed on spss 25. the confidence interval was set to be 95% with a 5% margin of error. results: more than half of the participants i.e. 214 (54.7) had got the sinopharm vaccine. vaccine hesitancy was found in 28 (7.2%) students and a major reason was concern about vaccine safety. significant relationship (p = <0.05) was found between vaccine acceptance and hesitancy group, and vaccines made in europe or america are safer or more effective than those made in other regions (p-value = 0.003); get the covid-19 vaccine only because it is made mandatory for me by govt. authorities or college and not on my own and willing to motivate fellow students to take covid vaccine (p-value = 0.00); taking the covid19 vaccine is a societal responsibility (p-value = 0.00); i am concerned that the present covid-19 vaccines may not be effective enough (p-value = 0.001) and i am concerned about the serious adverse events from the currently available covid-19 vaccines (p-value = 0.007). conclusion: health education programs should be arranged to improve awareness and trust in the covid-19 vaccine. concerns of medical students should be addressed on priority as future healthcare providers. steps should be taken to improve covid-19 vaccine hesitancy through providing accurate and reliable information, addressing concerns and misinformation, building trust, engaging with communities, making vaccines accessible, and addressing vaccine equity. keywords: covid-19, medical students, vaccine acceptance, hesitancy. 1 assistant professor community medicine, aziz fatimah medical and dental college, faisalabad; 2,3,4,5,6 4th year mbbs student. correspondence: dr mohi ud din, assistant professor of community medicine, aziz fatimah medical and dental college, faisalabad. email: dr.md89@outlook.com cite this article: din, m. u., shahid, u., qudoos, a., ahmed, r., sohail, m., & javed, s. (2023). covid-19 vaccine acceptance and hesitancy among medical students of faisalabad. journal of rawalpindi medical college, 27(2). https://doi.org/10.37939/jrmc.v27i2.1804. received october 14, 2021; accepted may 05, 2023; published online june 24, 2023 1. introduction coronaviruses are a large family of viruses that are known to cause illnesses ranging from the common cold to more severe diseases such as severe acute respiratory syndrome coronavirus 2 (sars-cov-2 formerly called 2019-ncov) and middle east respiratory syndrome (mers).1 covid-19 is a major public health issue revolving in developed and developing countries and it created a lot of mega issues to the economy and the health-related status of nations.2 however, vaccination for covid 19 has already been started to combat the issue. but there are a lot of hurdles faced by the higher authorities regarding vaccination of the common public and medical students.3 vaccination started in pakistan in february, and stepwise vaccination took place according to specific age groups. the aim was to lower the risk of the virus and to fight against the virus as much as we can. common vaccines in pakistan are sinopharm and sinovac which are from china; mostly, the public is vaccinated by these. however, for foreign visits, moderna and pfizer are preferable.4 however, there were a lot of conspiracy theories spread related to vaccines. these theories created hesitancy among medical students as well as in public, which is a large hurdle for vaccination.5 up till now according to national command and operation centre (ncoc), 31,632,731 people are fully vaccinated and many of the population are still not vaccinated. it is a very poor sign for the elimination of the problem as covid-related deaths are increasing again due to delta variants and atypical symptoms are seen this time.6 jrmc vol. 27 (issue 2) journal of rawalpindi medical college 240 medical students continue to be on the front line of the nation’s fight against covid-19. by providing critical care to those who are or might be infected with the virus that causes covid-19, some healthcare personnel are at increased risk of infection from covid-19. all healthcare personnel are recommended to get vaccinated against covid-19.7 hesitancy can be defined as the quality or state of being hesitant, such as a lack of willingness or eagerness to do something. hesitancy against covid vaccine is the lack of willingness to vaccinate itself to combat the disease.8 many of our medical students are still hesitant about vaccination. the reasons for this problem are conspiracy theories that the covid vaccine will cause reduced fertility as it is the main side effect of the vaccine. secondly, many medical students are afraid of its side effects as this vaccine is new in the market.9 other factors for refusal included vaccine novelty, wanting others to receive it first, insufficient time for decision-making, and having a negative perception of vaccine efficacy and safety. some students are also afraid of overcrowding seen at vaccination centers and some have a notion that because even after vaccination, the risk of getting an infection is still there, there is no use for it. so, these are the barriers to vaccination and causes of hesitancy among medical students. but most medical students accept vaccination and willingly accept the covid vaccine.10 under all these circumstances, it is the need of an hour to explore the vaccine acceptance and hesitancy among medical students during the covid-19 pandemic and the factors related to it. this study is expected to measure the frequency of vaccine acceptance and hesitancy among medical students. the information gathered will aid in the identification of potential concerns that need to be addressed to ensure adequate vaccination coverage among this group, as well as the development of educational programs in counseling vaccine-hesitant patients. 2. materials & methods the study design was an analytical cross-sectional study. it was conducted on medical students of various medical institutions in faisalabad and their consent was taken beforehand. the study duration was 3 months (august 2021 to october 2021). ethical approval was taken from the ethical review committee. the total sample size was calculated keeping in mind the objectives of this particular study by considering different parameters and using a w.h.o. sample size calculator with a 95% confidence level, and a 5% margin of error, it was computed to be 391. non-probability purposive sampling was done. the inclusion criteria were those students who gave consent and filled out the questionnaire. a validated and structured questionnaire was used, developed by victoria c lucia et al titled “self-report to assess vaccine hesitancy and acceptance among medical students towards the novel covid-19 vaccine” based on a framework from previous studies about covid-19 vaccine acceptance and hesitancy.11-13 the questionnaire consisted of five sections: demographic data, covid infection and choice of vaccines, awareness and overall attitude regarding vaccine acceptance, perception of vulnerability to covid-19 and attitude regarding the use of the vaccine for community and concerns regarding covid-19 vaccines and trust of official information. confidentiality was maintained and spss version 25 was used for analysis of this data. a chi-square test of significance was applied to see the relationship between vaccine acceptance and hesitant group with demographics and participants’ awareness, attitudes, perceptions, and concerns regarding covid-19 vaccines. a p-value ≤ 0.05 was taken as significant. 3. results out of a total of 391 participants, 146(37.3%) were males and 245(62.7%) were females. most of the students had been vaccinated with sinopharm i.e., 214 (54.7%) followed by sinovac i.e., 134 (34.3%) participants. when asked “will you take the covid-19 vaccine when offered or hesitate/refuse if allowed?”, 14 (3.6%) students disagreed and also a similar number of participants were not sure about it so vaccine hesitancy was found in 28 (7.2%) students in which the most common reason in 50% of students was concern about vaccine safety followed by concerns about vaccine efficacy (28%) as shown in table 1. medical students were then divided into two groups based on vaccine acceptance and hesitancy and their awareness, attitude, perception of vulnerability and concerns regarding covid vaccination were recorded as shown in table 2. jrmc vol. 27 (issue 2) journal of rawalpindi medical college 241 table-1 reasons of covid-19 vaccine hesitation number (n) percentage (%) concerned about vaccine safety 14 50 concerned about the efficacy of the cine 8 28 not needed for young individuals like me 5 18 not needed as many people are now immune to the virus 1 4 internet/social media was the most common source of information regardingcovid-19 vaccines for the vaccine acceptance group. further, we found that a larger proportion of vaccine-hesitant students obtained vaccine-related information from government campaigns as in fig. 1. figure-1 main source of information regarding the covid-19 vaccine. table-2 responses of medical students belonging to vaccine acceptance and hesitance groups (n = 391) survey items vaccine acceptance group (n = 363) vaccine hesitancy group (n = 28) p-value demographics gender male 135 11 0.394 female 228 17 age group above 21 years 270 19 0.856 below 21 years 93 9 year of study 1st year 48 6 0.232 2nd year 54 1 3rd year 53 3 4th year 112 11 5th year 96 7 residence urban 310 26 0.754 rural 53 2 0 100 200 300 friends,family,com… institution vaccine hesitance group vaccine acceptance group jrmc vol. 27 (issue 2) journal of rawalpindi medical college 242 currently, are you? day scholar 216 12 0.239 hostelite 147 16 father/guardian occupation government job 132 9 0.524 private job 59 6 self-employed 172 13 covid infection and choice of vaccines diagnosed covid disease in present or past yes 77 4 0.52 no 286 24 have any of your diagnosed covid positive family members or friends stayed with you yes 200 12 0.21 no 163 16 consider it important to choose between different available covid 19 vaccines agree 283 14 <0.001* disagree 36 8 not sure 44 6 vaccines made in europe or america are safer or more effective than those made in other regions agree 135 8 0.003* disagree 112 10 not sure 116 10 awareness and overall attitude regarding vaccine acceptance mbbs students are eligible for vaccination yes 352 26 0.095 no 3 0 not sure 8 2 get the covid-19 vaccine only because it is made mandatory for me by govt. authorities or college and not on my own agree 119 12 <0.001* disagree 232 12 not sure 12 4 willing to take part in covid vaccine trial agree 204 11 0.037* disagree 61 9 jrmc vol. 27 (issue 2) journal of rawalpindi medical college 243 not sure 98 8 share information regarding vaccine safety with family, friends and the community yes 345 22 0.001* no 18 6 willing to motivate fellow students to take covid vaccine agree 339 16 <0.001* disagree 6 7 not sure 18 5 concerned if the vaccine is not offered to you yes 316 19 <0.001* no 28 5 not sure 19 4 perception of vulnerability to covid-19 and attitude regarding the use of the vaccine for community ‘i am likely to get covid-19 in the course of my duties as a medical student.’ agree 297 22 0.509 disagree 26 3 not sure 40 3 ‘covid-19 vaccine can reduce the spread of the disease in the community.’ agree 300 14 <0.001* disagree 26 7 not sure 37 7 ‘covid-19 vaccine can help reduce severe covid-19 disease.’ agree 327 19 <0.001* disagree 11 3 not sure 25 6 ‘covid-19 vaccine should be made mandatory for everyone above 18 years agree 324 16 <0.001* disagree 14 5 not sure 25 7 taking the covid-19 vaccine is a societal responsibility agree 333 17 <0.001* disagree 6 3 not sure 24 8 concern regarding covid-19 vaccines and trust in official information jrmc vol. 27 (issue 2) journal of rawalpindi medical college 244 ’i am concerned that the present covid-19 vaccines may not be effective enough agree 162 15 0.001* disagree 110 5 not sure 91 8 ‘i am concerned about the serious adverse events from the currently available covid-19 vaccines’ agree 147 18 0.007* disagree 145 5 not sure 79 5 ‘i am concerned about the present covid-19 vaccines might not have been tested rigorously before launch’ agree 138 13 0.006* disagree 126 7 not sure 99 8 ‘i trust the information i am receiving about the covid19 vaccine from the government or public health experts.’ agree 274 15 0.009* disagree 24 6 not sure 65 7 5. discussion vaccine apprehension is a stumbling block in world wide efforts to contain the current pandemic, which is wreaking havoc on human health a nd the economy. understanding and increasing student acceptability of vaccination is critical for the development of an effective post-pandemic approach.14 a study done by amar ibrahim omer yahia et al showed that covid-19 vaccine hesitancy was higher among women and those living in urban areas.15 these results are similar to our study where female participants and urban dwellers showed more resistance to vaccination. a study done by jyoti jain et al showed vaccine hesitancy was found among 10.6% of medical students. lack of trust in vaccine safety and efficacy, less number of vaccine trials and less trust in public health experts and government officials were the main concerns.16 these results were almost similar to our study in which 7.2% of vaccine hesitancy was found in medical students and their concerns were also the same except that they have trust in government officials regarding covid vaccination. a study done by arati k. kelekar showed that 23% of medical students were hesitant about receiving the covid-19 vaccine which is almost 200% more than our study.13 a study done by serena barello et al reported that 13.9% of students would not or be not sure to vaccinate.17 a study done by cheuk chi tam et al showed that only 26.1% of participants reported they would take covid-19 vaccines which means that almost 3/4th of participants refused/hesitated to take covid vaccine which is opposite to our study results.18 prior covid-19 infection has also impacted participants’ choice about vaccine acceptance and hesitancy. a study done by saud mohammed raja et al depicted that among different factors associated with vaccine acceptance, one is the history of covid-19 infection.19 these results are similar to our study where vaccine hesitancy is more in participants who have no prior covid-19 infection. a systemic review done by debendra nath roy et al showed that “vaccine safety” was recognized mostly in the asian population among factors which have a greater influence on vaccination coverage. these results are similar to our study where more than half of study participants are concerned about vaccine safety.20 a study done by victoria c lucia et al showed that nearly all participants had positive attitudes towards vaccines and agreed they would likely be exposed to covid-19; jrmc vol. 27 (issue 2) journal of rawalpindi medical college 245 however, only 53% indicated they would participate in a covid-19 vaccine trial. these results are similar to our study where 52.17% of students agreed to participate in vaccine trials despite having vaccine acceptance in more than 90% of medical students.11 a study done by shimaa m. saied showed that most participants believe that everyone in the community should get it (92.6%), vaccination should be compulsory for the general population (69.7%), especially for health care workers (92.1%). despite that good percentage of students believed that the way to overcome the covid-19 pandemic is through mass vaccination (67.9%) and that getting vaccinated is the best preventive measure (56.5%), most of them had concerns regarding the adverse effects of the vaccine (96.8%), its ineffectiveness (93.2%) and enough testing (80.2%), safety (54.0%). students perceived themselves at elevated risk to acquire covid-19 (77.6%).12 these results are similar to our study where 87% of participants believe that everyone above 18 years should be vaccinated, including medical students who are eligible for vaccination (96.7%). although 89.5% of students believe that covid-19 vaccine uptake is a societal responsibility and more than 80% of students agree that covid vaccine is critical in reducing the spread of the disease in the community and also decreasing its severity, still many students have concerns regarding its efficacy (45.3%), adverse effects (39.6%) and prior rigorous testing before launch (38.6%). a study done by rahul shekhar et al showed that only 8% of hcws do not plan to get the vaccine. safety (69%) and effectiveness (69%) were noted as the most common concerns regarding covid-19 vaccination.21 these results were similar to our study where around 7% of medical students had hesitation regarding vaccination and their most common concerns also included efficacy and adverse effects related to the vaccine. a systemic review done by mei li et al showed that the range of acceptance of covid vaccine varied widely from 27.7% to 77.3%. although in healthcare workers, vaccine hesitancy was common but still had a positive towards covid-19 vaccines. men, older age and physicians showed more positive attitudes towards vaccine acceptance as compared to women and nurses who had more vaccine hesitancy. barriers included concerns for the safety, efficacy and effectiveness of the vaccine and distrust of the government which were similar to our study except that our participants trust the government and public health experts regarding covid vaccine.22 our study was limited by the fact that it was undertaken after covid-19 immunisation had begun. as a result, it's possible that it underestimated the initial vaccination apprehension of those who eventually changed to the vaccine acceptance group and were vaccinated. the denominator for calculating the response rate could not be calculated since participation in this survey was based on peer-to-peer communication via social media networks. the generalisability of vaccination hesitancy among medical students could not be determined due to the study's nonprobability sampling approach. the breadth of information that could otherwise be captured is frequently missed by online data collection as compared to qualitative methods applied in face-to-face settings. 5. conclusion health education programs should be arranged to improve awareness and trust in the covid-19 vaccine. concerns of medical students should be addressed on priority as future healthcare providers. steps should be taken to improve covid-19 vaccine hesitancy through providing accurate and reliable information, addressing concerns and misinformation, building trust, engaging with communities, making vaccines accessible and addressing vaccine equity. conflicts of interestnone financial support: none to report. potential competing interests: none to report contributions: m.u.d, u.sconception of study m.u.d, u.s, a.q, r.a, s.jexperimentation/study conduction m.u.d, a.q, r.a, s.j-analysis/interpretation/discussion m.u.d, m.smanuscript writing m.u.dcritical review m.u.dfacilitation and material analysis references [1] young young be, ong sw, ng lf, anderson de, chia wn, chia py, ang lw, mak tm, kalimuddin s, chai ly, pada s. viral dynamics and immune correlates of coronavirus disease 2019 (covid-19) severity. clin. infect. dis. 2021 nov 1;73(9):e2932-42.. 2020. https://doi.org/10.1093/cid/ciaa1280 [2] wu hl, huang j, zhang cj, he z, ming wk. facemask shortage and the novel coronavirus disease (covid-19) outbreak: reflections on public health measures. jrmc vol. 27 (issue 2) journal of rawalpindi medical college 246 eclinicalmedicine. 2020 apr 1;21:100329. https://doi.org/10.1016/j.eclinm.2020.100329 [3] gaebler c, nussenzweig mc. all eyes are on a hurdle race for a sars-cov-2 vaccine. nature publishing group; 2020. [4] imran m, khan s, khan s, uddin a, khan ms, ambade p. covid‐19 situation in pakistan: a broad overview. respirol. (carlton, vic.). 2021 sep;26(9):891. doi: 10.1111/resp.14093 [5] douglas km. covid-19 conspiracy theories. group process. integer. relat. 2021 feb;24(2):270-5. doi: 10.1177//1368430220982068 [6] siddiqui a, ahmed a, tanveer m, saqlain m, kow cs, hasan ss. an overview of procurement, pricing, and uptake of covid-19 vaccines in pakistan. vaccine. 2021 aug 8;39(37):5251. vaccine. 2021. doi: 10.1016/j.vaccine.2021.07.072 [7] heinzerling a, stuckey mj, scheuer t, xu k, perkins km, resseger h, magill s, verani jr, jain s, acosta m, epson e. transmission of covid-19 to health care personnel during exposures to a hospitalized patient—solano county, california, february 2020. mmwr morb mortal wkly rep. 2020 apr 4;69(15):472. doi: 10.15585/mmwr.mm6915e5 [8] dror aa, eisenbach n, taiber s, morozov ng, mizrachi m, zigron a, srouji s, sela e. vaccine hesitancy: the next challenge in the fight against covid-19. eur. j. epidemiol. 2020 aug;35:775-9. doi: https://doi.org/10.1007/s10654-020-00671y [9] soares p, rocha jv, moniz m, gama a, laires pa, pedro ar, dias s, leite a, nunes c. factors associated with covid-19 vaccine hesitancy. vaccines. 2021 mar 22;9(3):300. vaccines. https://doi.org/10.3390/vaccines9030300 [10] khan yh, mallhi th, alotaibi nh, alzarea ai, alanazi as, tanveer n, hashmi fk. threat of covid-19 vaccine hesitancy in pakistan: the need for measures to neutralize misleading narratives. am. j. trop. med. hyg. 2020 aug;103(2):603. doi: 10.4269/ajtmh.20-0654 [11] lucia vc, kelekar a, afonso nm. covid-19 vaccine hesitancy among medical students. j public health. 2021 sep;43(3):445-9. https://doi.org/10.1093/pubmed/fdaa230 [12] saied sm, saied em, kabbash ia, abdo sa. vaccine hesitancy: beliefs and barriers associated with covid‐19 vaccination among egyptian medical students. j med virol. 2021 jul;93(7):4280-91. https://doi.org/10.1002/jmv.26910 [13] kelekar ak, lucia vc, afonso nm, mascarenhas ak. covid-19 vaccine acceptance and hesitancy among dental and medical students. j am dent assoc. 2021 aug 1;152(8):596603. https://doi.org/10.1016/j.adaj.2021.03.006 [14] qiao s, friedman db, tam cc, zeng c, li x. vaccine acceptance among college students in south carolina: do information sources and trust in information make a difference?. medrxiv. 2020 dec 4:2020-12. doi: https://doi.org/10.1101/2020.12.02.20242982 [15] yahia ai, alshahrani am, alsulmi wg, alqarni mm, abdulrahim tk, heba wf, alqarni ta, alharthi ka, buhran aa. determinants of covid-19 vaccine acceptance and hesitancy: a cross-sectional study in saudi arabia. hum. vaccines immunother. 2021 nov 2;17(11):4015-20. https://doi.org/10.1080/21645515.2021.1950506 [16] jain j, saurabh s, goel ad, gupta mk, bhardwaj p, raghav pr. covid-19 vaccine hesitancy among undergraduate medical students: results from a nationwide survey in india. medrxiv. 2021 mar 12:2021-03. doi: https://doi.org/10.1101/2021.03.12.21253444 [17] barello s, nania t, dellafiore f, graffigna g, caruso r. ‘vaccine hesitancy’among university students in italy during the covid-19 pandemic. eur. j. epidemiol. 2020 aug;35:7813. doi: https://doi.org/10.1007/s10654-020-00670-z [18] tam cc, qiao s, li x. factors associated with decision making on covid-19 vaccine acceptance among college students in south carolina. psychol health med. 2022 jan 2;27(1):150-61. https://doi.org/10.1080/13548506.2021.1983185 [19] raja sm, osman me, musa ao, hussien aa, yusuf k. covid-19 vaccine acceptance, hesitancy, and associated factors among medical students in sudan. plos one. 2022 apr 7;17(4):e0266670. https://doi.org/10.1371/journal.pone.0266670 [20] roy dn, biswas m, islam e, azam ms. potential factors influencing covid-19 vaccine acceptance and hesitancy: a systematic review. plos one. 2022 mar 23;17(3):e0265496. https://doi.org/10.1371/journal.pone.0265496 [21] shekhar r, sheikh ab, upadhyay s, singh m, kottewar s, mir h, barrett e, pal s. covid-19 vaccine acceptance among health care workers in the united states. vaccines. 2021 feb 3;9(2):119. https://doi.org/10.3390/vaccines9020119 [22] li m, luo y, watson r, zheng y, ren j, tang j, chen y. healthcare workers’(hcws) attitudes and related factors towards covid-19 vaccination: a rapid systematic review. postgrad. med. j.. 2021 jun 30. http://dx.doi.org/10.1136/postgradmedj-2021-140195 404 not found 404 not found 242 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 original article evaluation and susceptibility pattern of staphylococci isolated from clinical specimens in pof hospital, wah cantt. lubna ghazal1, saba mushtaq2, sohail ashraf3, saima rafique4, muhammad bilal5, naila iqbal6 1 assistant professor pathology, wah medical college, wah cantt. 2 assistant professor pediatrics, wah medical college, wah cantt. 3 associate professor pediatrics, wah medical college, wah cantt. 4 assistant professor pharmacology, wah medical college, wah cantt. 5,6 senior lecturer pathology, wah medical college, wah cantt. author’s contribution 1,3 conception of study 3,5,6 experimentation/study conduction 2,3 analysis/interpretation/discussion 2 manuscript writing 1,3 critical review 4 facilitation and material analysis corresponding author dr. lubna ghazal, assistant professor of pathology, wah medical college, wah cantt. email: doctor.lubna@yahoo.com article processing received: 21/10/2021 accepted: 30/03/2022 cite this article: ghazal, l., mushtaq, s., ashraf, s., rafique, s., bilal, m., iqbal, n. evaluation and susceptibility pattern of staphylococci isolated from clinical specimens in pof hospital, wah cantt. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 242-248. doi: https://doi.org/10.37939/jrmc.v26i2.1815 conflict of interest: nil funding source: nil access online: abstract objective: to determine the frequency and association of the antibiotic susceptibility pattern between methicillin-resistant and sensitive staphylococci and find out the association between age, gender, the outcome of patients, and type of specimens with methicillin resistance in methicillin-resistant and sensitive staphylococcal isolates materials & methods: this cross-sectional study was carried out in the microbiology department of pof hospital, wah from january 2019 to september 2020. one hundred and eighty-four staphylococci isolated from clinical specimens were processed as per standard methodology. results: out of 184, methicillin-resistant s. aureus and methicillin-resistant coagulase-negative staphylococci were 38.04% and 13.04% respectively. infections caused by methicillin-resistant staphylococcal isolates were higher among the age group 31-40 years (71.4%, or=2.68). out of thirty expired patients, 33.3% had been infected with methicillin-resistant staphylococcus aureus and 20% with methicillin-resistant coagulase-negative species. the methicillin-resistant staphylococci were most frequent in the miscellaneous category of clinical specimens (80.0%, or=4.63). the susceptibility analysis revealed that methicillin-resistant staphylococci are 100% resistant to penicillin, meropenem, and amoxicillin-clavulanate (p=0.000). a significant association of methicillin resistance was also noticed against amikacin (p=0.002), ciprofloxacin (p=0.001), clindamycin (p=0.005), and erythromycin (p=0.000). moxifloxacin, linezolid, and vancomycin are the most effective choices for infections caused by methicillin-resistant staphylococci. conclusions: the methicillin-resistant staphylococci are highly resistant to commonly used oral as well as injectable used antibiotics. the establishment and implementation of infection control policies are required to combat the grave situation of increasing antibiotic resistance. keywords: antibiotic susceptibility, methicillin-resistant staphylococci, ciprofloxacin, clindamycin. 243 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 introduction staphylococci are gram-positive spherical bacteria that rapidly develop resistance to many antimicrobials resulting in therapeutic failures. high-throughput species identification of staphylococci is possible by pcr coupled to electrospray ionization-mass spectrometry in research laboratories.1,2 although the aforementioned methods have revolutionized diagnostic modalities but routine laboratories in developing countries have limited access to advanced technologies due to their high costs and technical expertise. despite limitations, biochemical tests like coagulase activity are used for presumptive identification of clinical isolates of staphylococcus aureus, especially in laboratories with constrained resources.3 the coagulase of staphylococci is the virulent protein that binds prothrombin to form a complex with thrombin and leads to fibrin polymerization.4 the detection of coagulase in staphylococci obtained from human specimens is usually equated with the species identification of s. aureus and clinically, common species of staphylococci other than s.aureus are referred to as coagulasenegative staphylococci.5 among all species of staphylococci, s.aureus is considered to be the most pathogenic, being responsible for a variety of infections, ranging in severity from food intoxication or boil to septicaemia. s.aureus and the coagulase-negative staphylococci are members of normal human microbiota which colonize the skin and mucous membranes but may become pathogenic following breaks in the cutaneous epithelial barrier through trauma or medical interventions. advancements in the fields of medicine, surgery, and bioengineering have paved the way for the increased use of prosthetic implants and medical devices. the most frequently isolated coagulasenegative s.epidermidis is associated with implanted appliances and devices, especially in patients of extreme age and immunocompromised conditions.5 the significance of staphylococcal isolated from a specimen requires clinical correlation to determine whether it’s a contaminant, colonizer, or pathogen. multidrug-resistant strains of staphylococci particularly methicillin-resistant staphylococci are well-documented etiological agents of nosocomial infections and are associated with increased morbidity and mortality. the literature review indicates that the frequency of methicillin-resistant staphylococci is heterogenous within the country as well as across the country.6 the resistance against beta-lactams developed because of the adaption of s. aureus to the exogenously acquired sccmec, deletion, and mutation of genes implicated in general metabolism and general stress response and the adjustment of metabolic networks resulted in an increase of β-lactams minimal inhibitory concentration. multiple studies based on whole genome sequencing technologies indicated that meca developed from a harmless core gene (meca1) encoding the penicillin-binding protein d (pbpd) from staphylococcal species of animal origin (s.sciuri group). the emergence of the resistance determinant involved a distortion of the pbpd active site, an increase in meca1 expression, the addition of regulators (mecr1, meci), and integration into a mobile genetic element (sccmec). sccmec was then transferred into species of coagulase-negative staphylococci (cons) that is transferred to s.aureus of human origin.7 colonization of skin and mucous membranes of the inpatient by multidrug-resistant cons strain and its transmission by hands of health care workers is a critical step in the making cons a successful nosocomial pathogen. the dynamic antimicrobial resistance phenomenon renders the antibiotics susceptibility profile of a specific region at a specified period inapplicable to other regions or in another time period.8 the emerging antimicrobial resistance has been declared as one of the top ten global public health threats of the modern century.9 it’s an established fact that antimicrobial susceptibility data from any given regional, national, or international surveillance study cannot reliably predict the drug resistance profiles of pathogens isolated from an individual patient. the local susceptibility profiles serve to rationalize the empirical treatment resulting in evidence-based practices and better outcomes in terms of enhanced recovery from infections, shorter duration of hospital stay, and costeffectiveness. the current study was planned to i. determine the frequency and association of the antibiotic susceptibility pattern between methicillin-resistant and sensitive staphylococci isolated from clinical specimens as a result of culture and sensitivity. ii. find out the association of age, gender, the outcome of patients, and type of specimens with methicillin resistance in methicillinresistant and sensitive staphylococcal isolates. 244 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 materials and methods it was a descriptive cross-sectional study that was conducted at the department of microbiology, pof hospital, wah from january 2020 to march 2021. the sampling technique was non-probability, consecutive sampling. one hundred and eighty-four clinical specimens of either gender, of all ages, yielding growth of staphylococci were included in the study. duplicate samples of the same patient from the same site were not included. the specimens were inoculated on appropriate culture mediums like blood agar, macconkey agar, and cysteine lactose electrolyte deficient agar (urine). these were incubated at 35-37˚c under aerobic conditions for 24 hours. after overnight incubation, the agar plates were examined for the growth of bacteria and their colonial morphology. the isolates were stained by the gram method. the gram-positive cocci with positive catalase reaction were considered staphylococci. further differentiation of staphylococci into coagulasenegative staphylococci and staphylococcus aureus was done based on coagulase test and dnase tests.1 all staphylococci were screened for methicillin susceptibility by using a 30 µg cefoxitin disc. the antimicrobial susceptibility tests were performed by the disc diffusion method according to clinical laboratory standards institute recommendations. the bacterial suspensions of isolates equivalent to 0.5 mcfarland standard turbidity were placed on muellerhinton agar (oxoid, basingstoke, uk). the discs of penicillin (10 iu), amoxicillin-clavulanate (20/10 µg), trimethoprim-sulfamethoxazole (1.25/ 23.75 µg), cephradine (30 µg), cefoxitin (30 µg), ciprofloxacin (5 µg), clindamycin (2 µg), meropenem (10 µg) and linezolid (30 µg) were placed on the mueller–hinton agar followed by incubation at 37 °c for overnight. after overnight incubation, the diameter of each zone of inhibition around the antimicrobial disc was measured. the susceptibility testing results were interpreted according to recommendations of clsi as sensitive, intermediate, and resistant. concurrent quality control testing was performed with staphylococcus aureus atcc 25923.10 vancomycin mic by epsilometer test (e-test) was determined by following the manufacturer’s instructions. the 0.5 mcfarland standard suspension of the isolate was applied on the mueller-hinton agar plate. the vancomycin e-test strip (liofilchem, italy) was applied over the plate with the help of an applicator within 5 min of lawn culture. plates were incubated at 37 °c for 24 h. a teardrop zone of inhibition was observed. the zone edge intersecting the graded strip at the minimum concentration of the antibiotic was interpreted as the mic. the isolates of s.aureus were reported sensitive to vancomycin with mics of ≤2 µg/ml, intermediate susceptible with mics of 4-8 µg/ml, and resistant with mic ≥8 µg/ml. the isolates other than s.aureus were interpreted as sensitive to vancomycin with mics of ≤4 µg/ml, intermediate susceptible with mics 8-16 µg/ml, and resistant with mic ≥32 µg/ml.10 the data was entered and analyzed using spss version 23. the numerical data were analyzed by chisquare test, odd ratio, and 95% confidence interval to determine the statistical difference in the age, gender, and specimens. the association of antibiotic susceptibility patterns for methicillin resistance and methicillin-sensitive s.aureus as well as methicillin resistance and methicillin-sensitive coagulase-negative staphylococci were determined by the chi-square test. a p-value less than 0.05 was considered significant. results a total of one hundred and eighty-four staphylococci were analyzed. out of which, methicillin-resistant s.aureus and methicillin-resistant coagulase-negative staphylococci were 38.04% and 13.04% respectively. (figure 1) figure 1: staphylococci isolated from clinical specimens in pof hospital (n=184) the frequency of male patients was found to be 49.1% and 50.9% for methicillin-resistant staphylococci and methicillin-sensitive staphylococci respectively. 245 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 similarly, the frequency of female patients was 51.4% and 48.6% for methicillin-resistant staphylococci and methicillin-sensitive staphylococci respectively. (table 1) infections caused by methicillin-resistant staphylococcal isolates were higher among the age group 31-40 years (71.4%, or=2.68) followed by the age group 11-20 and 21-30 years. (66.7%, or=0.365) infections caused by methicillin-sensitive staphylococci were higher among the age group 51-60 years (66.6%, or=0.48) followed by neonates (65.7%, or=0.35). (table 1) out of thirty expired patients, 53.3% had been infected with methicillin-resistant staphylococcal infections and 49.4% with methicillin-sensitive staphylococcal infections. (or= 1.17) the specimen-wise distribution showed that methicillin-resistant staphylococci were most frequent in the miscellaneous category (80.0%, or=4.63) followed by pus (53.8%, or=1.30). on the other hand, the methicillin-sensitive staphylococci were most frequent in the blood (60.5%, or=0.45) followed by pus (46.2%, or=1.30). the susceptibility analysis revealed that methicillinresistant staphylococci are 100% resistant to penicillin (p=0.000) followed by meropenem (93.9%, p=0.000) and amoxicillin-clavulanate (74.2%, p=0.000). a significant association of methicillin resistance was noticed for amikacin, ciprofloxacin, clindamycin, and erythromycin. (table 2) table 1: methicillin resistance of staphylococci isolated from clinical specimens in pof hospital (n=184) variables staphylococcal isolates methicillinresistant n(%) methicillin sensitive n(%) x2 or 95% confidence interval p value lower limit upper limit gender male 110 54(49.1%) 56(50.9%) 0.090 0.91 0507 1.647 0.764 female 74 38(51.4%) 36(48.6%) age (groups) in years neonates 70 24(34.3%) 46(65.7%) 11.16 0.35 0.190 0.656 0.001 <10 80 30(37.5%) 50(62.5%) 8.846 0.40 0.223 0.740 0.003 11-20 6 4(66.7%) 2(33.3%) 0.689 2.04 0.365 11.453 0.406 21-30 6 4(66.7%) 2(33.3%) 0.689 2.04 0.365 11.453 0.406 31-40 14 10(71.4%) 4(28.6%) 2.783 2.68 0.810 8.889 0.095 41-50 10 6(60.0%) 4(40.0%) 0.423 1.53 0.418 5.630 0.515 51-60 6 2(33.3%) 4(66.6%) 0.689 0.48 0.087 2.737 0.406 >60 26 16(61.5%) 10(38.5%) 1.612 1.72 0.738 4.037 0.204 outcome of patients expiry 30 16(53.3%) 14(46.7%) 0.159 1.17 0.536 2.568 0.690 shift out 154 76(49.4%) 78(50.6%) specimens blood 86 34(39.5%) 52(60.5%) 7.074 0.45 0.250 0.814 0.008 pus 78 42(53.8%) 36(46.2%) 0.801 1.30 0.727 2.348 0.371 miscellaneous 20 16(80.0%) 4(20.0%) 5.947 4.632 1.484 14.450 0.004 x2 = chi square, or = odd ratio, n = total number of staphylococci isolated table 2: comparison of antibiotics susceptibility pattern between methicillin-susceptible and resistant staphylococci isolated from clinical specimens antibiotics drug susceptibility methicillin-resistant staphylococci methicillin sensitive staphylococci p value penicillin susceptible 0 (0 %) 24 (26.1%) 0.000 resistant 92(100%) 68 (73.9%) amoxycillinclavulanate susceptible 0 (0 %) 58(100%) 0.000 resistant 92(74.2%) 34(27.0%) amikacin susceptible 52 (41.9%) 72 (58.1%) 0.002 resistant 40 (66.7%) 20 (33.3%) 246 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 ciprofloxacin susceptible 25(34.2 %) 48(65.8%) 0.001 resistant 67(60.4%) 44(39.6%) clindamycin susceptible 43(41.0%) 62(59.0%) 0.005 resistant 49(62.0%) 30(38.0%) clarithromycin susceptible 44(43.6 %) 57(56.4%) 0.054 resistant 48(57.8%) 35(42.2%) cotrimoxazole susceptible 28(45.2 %) 34(54.8%) 0.349 resistant 64(52.5%) 58(47.5%) doxycycline susceptible 42(43.8 %) 54(56.3%) 0.077 resistant 50(56.8%) 38(43.2%) erythromycin susceptible 16(27.6%) 42(72.4%) 0.000 resistant 76(60.3%) 50(39.7%) gentamicin susceptible 41(44.1 %) 52(55.9%) 0.105 resistant 51(56.0%) 40(44.0%) linezolid susceptible 90(50.0 %) 90(50.0 %) 1.000 resistant 2(50.0 %) 2(50.0 %) meropenem susceptible 0(0 %) 86(100 %) 0.000 resistant 92(93.9%) 6(6.1 %) moxifloxacin susceptible 64(50%) 64(50%) 1.000 resistant 28(50%) 28(50%) vancomycin susceptible 88( 49.7%) 89(50.3 %) 1.000 resistant 4(57.1%) 3(42.9 %) discussion methicillin-resistant staphylococci are the most frequent etiological agents of nosocomial and devices related infections. existing literature on mrsa has demonstrated that there is a significant geographical variation in the frequency of staphylococci within and between countries. the incidence of mrsa is 66.7% as reported in a study conducted by hussain et al in pakistan.11 another local study showed isolation of mrsa from 76% of clinical isolates.12 these results are in contrast to data of our study which revealed a relatively less frequency of mrsa which is 38.04%. in pakistan, the data regarding the susceptibility pattern of coagulase-negative staphylococci are scarce. a study published in 2013 which was conducted in karachi revealed that 70% of cons was methicillinresistant and resistance to other commonly prescribed ciprofloxacin, erythromycin and doxycycline was 35.2%, 58.3%, and 24.7% respectively.13 study conducted by latif et al at rawalpindi concluded a rise in methicillin resistance rate in cons from 22.7% to 59.6% in three consecutive years.14 the contrasting results of our study may be explained by differences in hospital catchment areas and surgical interventions including biological implants and prostheses fabrications. the hospital environment and the normal human microbiota of patients and health care personnel play crucial roles as the reservoirs and vectors for the spread of antibiotic-resistant bugs. the methicillin-resistant staphylococci are resistant to betalactam antimicrobials including penicillins, β lactam combination agents, cephems except for ceftaroline and carbapenems.15 limited treatment options are left behind for the treatment of methicillin-resistant staphylococcal isolates, thus rendering the situation more cumbersome. a significant association of methicillin-resistant staphylococcal isolates is found with the resistance pattern of beta-lactam drugs including penicillin, amoxicillin-clavulanate, and meropenem. our study concluded an insignificant association of gender with methicillin resistance in staphylococci. humphrey et al reviewed the epidemiology of mrsa which shows a male predominance in cases of bloodstream infections and poorer outcomes for female patients. the multifactorial reasons including comorbidities behavioral and physiological factors explain the difference.16 in a recent study conducted by aratani et al, methicillin resistance was not significantly associated with mortality of patients with s.aureus bacteremia.17 our study also concluded the same. the limitations of our study are that the history of antibiotics use and underlying diseases of patients were not available. some strains of the staphylococci which harbour genetic elements for methicillin resistance also carry the genes that confer resistance to non-beta lactam antimicrobials.18 analysis of our data revealed a 247 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 significant association of resistance of methicillinresistant staphylococci against amikacin, ciprofloxacin, and erythromycin which are commonly used non-beta lactam antibiotics in our setup. this finding is in concordance with those reported by shah et al.19 similar resistance patterns have been reported in other studies from islamabad20 and nepal.21 this situation is entirely different when compared to the frequency and susceptibility pattern of methicillinresistant staphylococcal isolates prevailing in england as published in the english surveillance programme for antimicrobial utilization and resistance (espaur) report, 2019.22 the contrasting results provide evidence of injudicious and imprudent use of antibiotics in our settings. according to the literature review, linezolid and vancomycin are the most convenient and effective choices for methicillin-resistant staphylococci owing to their high susceptibility patterns.23,24 our data supports the fact that moxifloxacin, linezolid, and vancomycin are the most effective therapeutic options for staphylococcal infections in our setup. there is an insignificant association between methicillin-resistant staphylococcal isolates with resistance patterns of moxifloxacin, linezolid, and vancomycin. these results of susceptibility of staphylococcal isolates against linezolid and vancomycin are closer to findings as reported by rosatto et al.25 judicious use of these antibiotics should help physicians treat patients with multidrug-resistant infections. strict infection control measures and antibiotic stewardship may prevent the development of resistance to these last-resort antibiotics. more in-depth studies and research on the dynamics of resistance development are required in our setup to consolidate the current treatment measures for a better health outcome. conclusion the methicillin-resistant staphylococci are highly resistant to commonly prescribed oral as well as injectable antibiotics. the establishment and implementation of infection control policies are required to combat the grave situation of increasing antibiotic resistance. references 1. rychert j. commentary: benefits and limitations of malditof mass spectrometry for the identification of microorganisms. j infectiology. 2019; 2(4): 1-5. doi: 10.29245/26899981/2019/4.1142 2. reckem ev, vuyst dl, leroy f, weckx s. amplicon-based high-throughput sequencing method capable of species-level identification of coagulase-negative staphylococci in diverse communities. microorganisms. 2020;8(6):897. doi: 10.3390/microorganisms8060897 3. becker k, skov rl, eiff cv. staphylococcus, micrococcus, and other catalase-positive cocci. in: jorgensen jh, carroll kc, funke g, pfaller ma, landry ml, richter ss, warnock dw (eds.). manual of clinical microbiology. 11th ed. washington, d.c: asm press, 2015; 354-82 4. kaiser g. isolation and identification of staphylococci. (2021, august 1). https://bio.libretexts.org/@go/page/3454) 5. carroll kc, hobden ja. the staphylococci. in: brooks carroll kc, hobden ja, miller s, morse sa, mietzner ta, detrick b, mitchell tg, mckerrow jh, sakanari ja. (eds.) jawetz, melnick, & adelberg’s medical microbiology. 27th ed. new york: mcgraw hill, 2016. 203-12 6. tasneem u, mehmood k, majid m, rahmat s, andleeb s. methicillin resistant staphylococcus aureus: a brief review of virulence and resistance. j pak med assoc. 2022: 72 (3).509-515. doi: https://doi.org/10.47391/jpma.0504 7. miragaia m. factors contributing to the evolution of mecamediated β-lactam resistance in staphylococci: update and new insights from whole genome sequencing (wgs). front microbiol. 2018. 9:2723. doi: 10.3389/fmicb.2018.02723 8. abebe m, tadesse s, meseret g, et al. type of bacterial isolates and antimicrobial resistance profile from different clinical samples at a referral hospital, northwest ethiopia: five years data analysis. bmc res notes. 2019. 12; 568 https://doi.org/10.1186/s13104-019-4604-6 9. world health organization. antimicrobial resistance, [internet], 2020 [cited 13 october]. available from: https://www.who.int/news-room/factsheets/detail/antimicrobial-resistance) 10. clsi. performance standards for antimicrobial susceptibility testing; 29th ed. clsi supplement m100. wayne, pa: clinical and laboratory standards institute; 2019 11. hussain ms, naqvi a, sharaz m. methicillin-resistant staphylococcus aureus (mrsa); prevalence and susceptibility pattern of (mrsa) isolated from pus in tertiary care of district hospital of rahim yar khan. professional med j. 2019; 26(1):122-127. doi: 10.29309/tpmj/2019.26.01.2510 12. saeed a, ahsan f, nawaz m, iqbal k, rehman ku, ijaz t. incidence of vancomycin resistant phenotype of the methicillin resistant staphylococcus aureus isolated from a tertiary care hospital in lahore]. antibiotics (basel). 2019;9(1):3. doi: 10.3390/antibiotics9010003 13. ehsan mm, memon z, ismail mo, fatima g. identification and antibiotic susceptibility pattern of coagulase-negative staphylococci in various clinical specimens. pak j med sci 2013; 29(6): 1420 1424. doi: http://dx.doi.org/10.12669/pjms.296.4064 14. latif m, usman j, gilani m, munir t, mushtaq m, anjum r, et al. coagulase negative staphylococci — a fast emerging threat. j pak med assoc. 2015;65(3): 283-6 15. carroll kc, hobden ja. antimicrobial chemotherapy. in: brooks carroll kc, hobden ja, miller s, morse sa, mietzner ta, detrick b, mitchell tg, mckerrow jh, sakanari ja.(eds.) jawetz, melnick, & adelberg’s medical microbiology. 27th ed. new york: mcgraw hill, 2016. 363-96 16. humphreys h, fitzpatick f, harvey bj. gender differences in rates of carriage and bloodstream infection caused by methicillin resistant staphylococcus aureus: are they real, do they matter and why? clin infect dis.2015;61(11):1708–14. doi: 10.1093/cid/civ576 17. aratani t, tsukamoto h, higashi t, kodawara t, yano r, hida y, et al. association of methicillin resistance with mortality 248 journal of rawalpindi medical college (jrmc); 2022; 26(2): 242-248 of hospital-acquired staphylococcus aureus bacteremia. j int med res.2021: 49(11);1–12. doi: 10.1177/03000605211058872 18. khana a, sulochan gc, gaire a, khanal a, estrada r, ghimire r, et al. methicillin-resistant staphylococcus aureus in nepal: a systematic review and meta-analysis. international journal of infectious diseases.2021;103: 48-55. doi: https://doi.org/10.1016/j.ijid.2020.11.152. 19. shah aa, ali y, maqbool a, abbasi sa. antimicrobial susceptibility pattern of methicillin-resistant staphylococcus aureus isolates in fauji foundation hospital rawalpindi. jpma. the journal of the pakistan medical association. 2020;70(9):1633-1635. doi: 10.5455/jpma.41422. pmid: 33040125 20. rasheed y, imdad k, yasmin r, gul a, jamil a, & aslam u. antimicrobial susceptibility pattern of staphylococcus aureus strains in islamabad, pakistan. pak armed forces med j. 2021: 71(3), 1056-60. doi: https://doi.org/10.51253/pafmj.v71i3.5451 21. khana a, sulochan gc, gaire a, khanal a, estrada r, ghimire r, et al. methicillin-resistant staphylococcus aureus in nepal: a systematic review and meta-analysis. international journal of infectious diseases.2021;103: 48-55. doi: https://doi.org/10.1016/j.ijid.2020.11.152. 22. public health england: english surveillance programme antimicrobial utilization and resistance (espaur) report publications gov.uk. 2019 23. gao c, fan y, zhao f, ren qc, wu x, chang l, et al. quinolone derivatives and their activities against methicillinresistant staphylococcus aureus (mrsa). european journal of medicinal chemistry.2018; 157: 1081-95. doi: https://doi.org/10.1016/j.ejmech.2018.08.061. 24. costa tmd, cuba gt, morgado pgm, nicolau dp, nouér sa, santos krn, et al. pharmacodynamic comparison of different antimicrobial regimens against staphylococcus aureus bloodstream infections with elevated vancomycin minimum inhibitory concentration. bmc infectious diseases .2020: 20:7483. doi: https://doi.org/10.1186/s12879-020-4782-9 25. rossato am, primon-barros m, rocha ldl, reiter kc, dias cag, d'azevedo pa. resistance profile to antimicrobials agents in methicillin-resistant staphylococcus aureus isolated from hospitals in south brazil between 2014-2019. rev soc bras med trop. 2020 nov 6;53: e20200431. doi: 10.1590/0037-86820431-2020 404 not found 404 not found 404 not found 404 not found 141 journal of rawalpindi medical college (jrmc); 2022; 26(1): 141-145 original article outcome of subtrochanteric femur fractures treated by proximal femoral nail in a tertiary care hospital rahman rasool akhtar1, riaz ahmed2, omair ashraf3 1 assistant professor, department of orthopaedics, rawalpindi medical university, rawalpindi. 2 professor & hod, department of orthopaedics, rawalpindi medical university, rawalpindi. 3 house officer, rawalpindi medical university, rawalpindi. author’s contribution 1,2 conception of study 1,2 experimentation/study conduction 3 analysis/interpretation/discussion 1,3 manuscript writing 1,2 critical review 2 facilitation and material analysis corresponding author dr. rahman rasool akhtar, assistant professor, department of orthopaedics, rawalpindi medical university, rawalpindi email: virgo_r24@hotmail.com article processing received: 15/02/2022 accepted: 07/03/2022 cite this article: akhtar, r.r., ahmed, r., ashraf, o. outcome of subtrochanteric femur fractures treated by proximal femoral nail in a tertiary care hospital. journal of rawalpindi medical college. 31 mar. 2022; 26(1): 141-145. doi: https://doi.org/10.37939/jrmc.v26i1.1913 conflict of interest: nil funding source: nil access online: abstract objective: to determine the outcome of subtrochanteric femur fractures treated by proximal femoral nail in a tertiary care hospital. materials and methods: this prospective study was conducted from 1st july 2017 to 30th june 2019. the inclusion criteria were all the patients of both genders above 16 years of age who presented to the emergency department with subtrochanteric fractures of the femur. exclusion criteria included pathological fractures, fractures in children, old neglected fractures, and multiple fractures. radiographs were taken and all the patients were classified according to seinshemers classification. all the patients underwent internal fixation with proximal femoral nail. the outcome of all patients was assessed by using the modified harris hip score. results: a total of one hundred and ten patients were enrolled in the study. the average age of patients was 30.05±8.59 years. 81 (73.63%) patients were males and 29 (26.36%) were females. according to seinshemers classification, we had 54 patients with type ii fractures, 35 patients with type iii fractures, 19 patients had type iv fractures and 02 patients had type v fractures. the average duration of stay in the hospital was 06 days while the average time required for full weight-bearing was 12 weeks. in our study, excellent results were found in 71 patients (64.5%), good results in 28 patients (25.4%), fair results in 06 patients (5.4%), and poor results in 03 patients (2.7%).02 patients were lost in follow-up. the mean harris hip score was 93.5± 5.42. 14 patients (12.7%) had minor complications including 06 patients with superficial wound infections, 03 patients with deep infection, 01 patients with deep vein thrombosis, and 04 patients had fractures from the distal tip of the nail. all the fractures unite within 6 months period and no implant failure was observed. conclusion: proximal femoral nail is a good choice implant for the fixation of subtrochanteric femur fractures leading to a high rate of union, fewer implant-related complications, and excellent functional outcomes. keywords: subtrochanteric, femur fracture, proximal femoral nail, modified harris hip score, seinshemers classification, complications. 142 journal of rawalpindi medical college (jrmc); 2022; 26(1): 141-145 introduction strong deforming stresses at the fracture site, a shaky blood supply, and enormous load-bearing forces exerted through the peri-trochanteric region make subtrochanteric femur fractures challenging to treat. to improve patient outcomes, proper reduction and secure fixation are essential when treating these fractures.1,2 subtrochanteric fractures account for around 7% to 34% of all femur fractures. they are equally maintained by males and females. according to studies, the bisphosphonate alendronate was administered to 7% of individuals with atypical subtrochanteric femur fractures. the one-year mortality rate for older patients with subtrochanteric femur fractures has been reported to be 25%.3 nonunion problems can occur in both intracapsular and extracapsular hip fractures due to inherent therapeutic limitations.1 non-union of the subtrochanteric fracture is difficult to treat. even though revision with either an intramedullary or extramedullary device has been recommended with satisfactory results, problems that necessitate further procedures still occur.2 the 95° plates, femoral reconstruction nails, or trochanteric femoral nails with interlocking options can all be used to effectively fix these fractures. nails form very stable structures and can be inserted consistently with the patient in the lateral position on the radiolucent table or supine on the fracture table.4 increased stiffness, rigidity, and a shorter moment arm of intramedullary nails provide a biomechanical benefit, resulting in a stronger build and less strain on the implant.5 because the surgeon should be aware of the adjustable elements that can improve surgical results, such as nail entrance site and construct design, fracture reduction and stability can be affected.6 an unfavourable entrance location at the greater trochanter is typically the source of operational complications when applying femoral locking nails. the nail is required to follow the cortical abutted medullary canal, especially in fractures that are further away. the tension between the nail and the femur is invariably caused by an incorrectly specified entry site, whether in the mediolateral or dorso-ventral directions. in this case, a forceful insertion could result in iatrogenic comminution on the fracture side or further fractures on the proximal femur.7 for the treatment of subtrochanteric fractures, antegrade femoral intramedullary nailing through a greater trochanteric insertion site has been recommended. the properties of the currently available trochanteric nails differ, and the best insertion position for proper subtrochanteric fracture alignment has yet to be discovered.8 complications after surgical management of subtrochanteric femur fracture are high and in a poor resource country including pakistan, it is important to lessen the postoperative complications to reduce the cost of surgery for patients as well as from hospital administration. so, there is a vast need to conduct trials to improve the practice of surgical management of subtrochanteric femur fracture. therefore, we aimed to conduct this study to get evidence for the management of subtrochanteric femur fracture by using proximal nailing. this would help us to get local evidence, and, in the future, we will implement the proximal femoral nails for such fractures in order to improve our practice and achieve more success and patients satisfaction. this study was done to determine the outcome of subtrochanteric femur fractures treated by proximal femoral nail in a tertiary care hospital materials and methods study design: prospective quasi-experimental study setting: department of orthopedic surgery, benazir bhutto hospital, rawalpindi. study duration: two years i.e. 1st july 2017 to 30th june 2019. sample size: the sample size of 110 cases was estimated by using a 95% confidence level, 7.5% margin of error, and percentage of subtrochanteric fractures i.e. 20% in all femur fractures. sampling technique: non-probability, consecutive sampling. selection criteria: patients of age 16-60 years, of both gender, with subtrochanteric femur fractures were enrolled. patients with recurrent fractures of the same site, patients with implant failure, patients who already had deep vein thrombosis, pathological fractures, old neglected fractures, fractures in children, gunshot injuries, and multiple fractures on the same site were not included in the study. data collection method: patients fulfilling above stated selection criteria were enrolled from emergency and opd. informed written consent was obtained. demographics like name, age, gender, bmi, duration between fracture, current presentation, and cause of fracture were obtained. radiographs were taken and all the patients were classified according to seinshemers classification. then patients underwent internal fixation with proximal femoral nail by consultant orthopedic surgeon under spinal 143 journal of rawalpindi medical college (jrmc); 2022; 26(1): 141-145 anesthesia. duration of surgery was noted. after surgery, patients were shifted to post-surgical wards and were followed up there till discharge. for at least two weeks after surgery, patients have been advised a standard antibiotic regimen along with standard medical treatment. all patients were discharged when they were able to move on their own and can move around the bed with a stick. total hospital stay was noted. then patients were followed-up in opd for about 6-12 months, fortnightly for 6 months, and then monthly after 6 months. on each visit, radiographs were performed to determine the callus formation to see union. duration of complete union was noted. then patients were evaluated for full weight-bearing and time of full weight-bearing without stick or help was noted. after 6 months, patients were examined for modified harris hip score and outcome in terms of excellent, good, fair, and poor was noted. patients were also examined for complications including wound infection either deep or superficial, deep vein thrombosis, fracture from the distal tip of the nail, and implant failure. all the data was collected in a proforma, specially designed for this research work. analysis plan: all the collected information was entered and analyzed by using spss v. 25. the outcome in terms of excellent, good, fair, and poor on modified harris hip score, and complications was presented as frequency and percentage while outcome like hospital stays duration, duration required for full weight-bearing, union duration was presented as mean and standard deviation. results a total of one hundred and ten patients were enrolled in the study. the average age of patients was 30.05±8.59 years. there were 81 (73.63%) male patients and 29 (26.36%) were females. the mean bmi of patients was 29.82 ± 13.21 kg/m2. the mean duration of fracture was 3.21 ± 1.48 days. the major cause of fracture was road traffic accidents which were involved in 51 (46.4%) cases, followed by falls from height [29 (26.4%)], fight or being beaten up brutally by someone [21 (19.1%)] while 9 (8.2%) patients had a history of trivial fall. according to seinshemers classification, we had 54 patients with type ii fractures, 35 patients with type iii fractures, 19 patients had type iv fractures and 02 patients had type v fractures. (table 1) the mean duration of hospital stay was 6.0 ± 1.2 days and the mean time of full weight-bearing was 12.1 ± 3.6 weeks. the mean duration of the union was 14.2 ± 2.9 weeks. in our study, excellent results were found in 71 patients (64.5%), good results in 28 patients (25.4%), fair results in 06 patients (5.4%), and poor results in 03 patients (2.7%). 02 patients were lost in follow-up. the mean harris hip score was 93.5± 5.42. 14 patients (12.7%) had minor complications including 06 patients with superficial wound infections, 03 patients with deep infections, 01 patients with deep vein thrombosis, and 04 patients had fracture from the distal tip of the nail. all the fractures united within 6 months period and no implant failure was observed. (table 2) the preoperative, postoperative and follow-up radiological images can be seen in figure 1. table 1: baseline features of patients feature mean ± sd, (f (%) n 110 age 30.05±8.59 gender male 81 (73.63%) female 29 (26.36%) bmi 29.82 ± 13.21 duration of fracture (days) 3.21 ± 1.48 cause of fracture road traffic accident 51 (46.4%) fall from height 29 (26.4%) fight / beaten by someone 21 (19.1%) trivial fall 9 (8.2%) seinshemers classification type ii fracture 54 (49.1%) type iii fracture 35 (31.8%) type iv fracture 19 (17.3%) type v fracture 2 (1.8%) table 2: outcome of patients after surgery outcome f(%), mean±sd duration of hospital stay (days) 6.0 ± 1.2 duration of union (weeks) 14.2 ± 2.9 duration of full weight-bearing (weeks) 12.1 ±3.6 modified harris hip score 93.5 ± 5.42 excellent 71 (64.5%) good 28 (25.4%) fair 6 (5.4%) poor 3 (2.7%) complications wound infection 9 (8.2%) superficial wound infection 6 (5.5%) deep wound infection 3 (2.7%) deep vein thrombosis 1 (0.9%) fracture from distal tip of nail 4 (3.6%) implant failure 0 (0.0%) lost to follow-up 2 (1.8%) 144 journal of rawalpindi medical college (jrmc); 2022; 26(1): 141-145 figure 1: pre operative, post operative and follow-up of patients discussion within 5 centimeters of the lesser trochanter, the subtrochanteric area is delineated. intertrochanteric fractures are frequently seen in conjunction with subtrochanteric fractures. a characteristic deformity is created by the strong gluteal and thigh muscles. abduction, flexion, and external rotation are all held by the proximal component.3 the incidence of these fractures has been estimated to be between 15 and 20 per 100,000 people.9 the age distribution for these fractures is bimodal: those younger than 40 years old account for around 20% of subtrochanteric fractures, while those older than 50 years account for more than two-thirds of subtrochanteric fractures.10 the frequency of these fractures appears to be roughly equal between males and females at younger ages; but, as people get older, the incidence of these fractures increases disproportionately in females.10,11 subtrochanteric femur fractures are a rare complication in orthopaedics, but when they do occur, they can be difficult to treat.12 intramedullary fixation has essentially established the gold standard for the treatment of subtrochanteric femur fractures.12 the exact and professional technical performance of insertion is the basic surgical prerequisite in stabilizing the subtrochanteric fractures by using the proximal femoral nail. to minimize treatment failure, anatomical reduction along with little soft tissue handling and the use of adequate implants are required.13 in our trial, we observed that the average duration of stay in the hospital was 06 days and the average time required for full weight-bearing was 12 weeks. in our study, excellent results were found in 64.5% of patients, good results in 25.4% cases, fair results in 5.4% cases, and poor results in 2.7% cases. the mean harris hip score was 93.5±5.42 at end of the followup. about 14 patients (12.7%) had minor complications including 06 patients with superficial wound infections and 03 patients with deep infections. because of the small site and minimal surgical dissection, the risk of postoperative infection with cephalomedullary nailing is quite low. another study found one case of surface infection (5%), and one case of deep infection (5%), both of which occurred 3 months after surgery.14 three out of 42 patients treated with a russell-taylor reconstructive nail developed an infection, according to rethnam and colleagues: one had a superficial wound infection that was managed with antibiotics, and the other two required surgical debridement.15 two of the 42 cases developed an 145 journal of rawalpindi medical college (jrmc); 2022; 26(1): 141-145 infection, as reported by alvarez et al.16 shah et al., looked at 51 subtrochanteric fractures treated with intramedullary nailing and reported good results, with one case of delayed union due to malignancy and one case of fixation failure.17 a further study found that after a year, total harris hip scores were 90.1.12 the surgeon can choose between a piriformis entry site and a bigger trochanteric entry site while doing an anterograde intramedullary nailing. reduced incidence of varus malreduction and medial cortical damage with reaming are two advantages of the piriformis entry site.18 the holland nail had a radius of 300 cm and a proximal bend of 10 degrees, according to another study. 5 degrees and 350 cm for the trochanteric antegrade nail, 6 degrees and 150 cm for the trochanteric fixation nail, 4 degrees and 300 cm for gamma 2, and 4 degrees and 200 cm for gamma 3. regardless of the nail, the tip beginning point resulted in the most neutral alignment. with all of the nails, the lateral starting point resulted in varus. with the holland and trochanteric fixation nails, the medial starting point resulted in valgus of >6 degrees; the gamma and trochanteric antegrade nail had better alignment with valgus of 4 degrees.8 kumar et al. showed that the mean duration required for a complete union was 17.08 weeks (range 13 to 32 weeks), and the complete union was obtained in 92 percent of cases. in 68 percent of the cases, closed reduction was achieved, but 32 percent of the cases were done with open reduction. in 12% of instances, there were several per-operative complications, and in 26% of cases, there were delayed issues. in 86 percent of cases, good anatomical results were obtained, while 14 percent had fair results. according to the “harris hip score”, exceptional findings were seen in 28%, good in 56%, and fair in 16%. for subtrochanteric femur fractures, the long proximal femoral nail is a durable implant with a high incidence of bony union and negligible soft tissues injury. intramedullary fixation has some biological as well as bio-mechanical benefits, but it is a surgically challenging procedure.19 conclusion proximal femoral nail is a good choice implant for the fixation of subtrochanteric femur fractures leading to a high rate of union, fewer implant-related complications, and excellent functional outcomes. so in the future, we recommend this implant for such types of fractures. references 1. babcock s, kellam jf. hip fracture nonunions: diagnosis, treatment, and special considerations in elderly patients. advances in orthopedics. 2018;2018:1912762. doi: 10.1155/2018/1912762. ecollection 2018 2. lo yc, su yp, hsieh cp, huang ch. augmentation plate fixation for treating sub-trochanteric fracture nonunion. indian journal of orthopaedics. 2019;53(2):246-50. doi: 10.4103/ortho.ijortho_476_17 3. medda s, reeves ra, pilson h. sub-trochanteric femur fractures. treasure island (fl): statpearls publishing; 2022. 4. lundy dw. sub-trochanteric femoral fractures. jaaos journal of the american academy of orthopaedic surgeons. 2007;15(11):663-71. 5. wang j, ma xl, ma jx, xing d, yang y, zhu sw, et al. biomechanical analysis of four types of internal fixation in sub-trochanteric fracture models. orthopaedic surgery. 2014;6(2):128-36. doi: 10.1111/os.12109 6. garrison i, domingue g, honeycutt mw. sub-trochanteric femur fractures: current review of management. efort open rev. 2021;6(2):145-51. doi: 10.1302/2058-5241.6.200048 7. gausepohl t, pennig d, koebke j, harnoss s. antegrade femoral nailing: an anatomical determination of the correct entry point. injury. 2002;33(8):701-5. doi: 10.1016/s0020-1383(02)00158-4 8. ostrum rf, marcantonio a, marburger r. a critical analysis of the eccentric starting point for trochanteric intramedullary femoral nailing. j orthop trauma. 2005;19(10):681-6. doi: 10.1097/01.bot.0000184145.75201.1b. 9. dell rm, adams al, greene df, funahashi tt, silverman sl, eisemon eo, et al. incidence of atypical nontraumatic diaphyseal fractures of the femur. journal of bone and mineral research. 2012;27(12):254450. doi: 10.1002/jbmr.1719 10. ng a, drake m, clarke b, sems s, atkinson e, achenbach s, et al. trends in sub-trochanteric, diaphyseal, and distal femur fractures, 1984– 2007. osteoporosis international. 2012;23(6):1721-6. doi: 10.1007/s00198-011-1777-9 11. napoli n, schwartz av, palermo l, jin jj, wustrack r, cauley ja, et al. risk factors for sub-trochanteric and diaphyseal fractures: the study of osteoporotic fractures. the journal of clinical endocrinology & metabolism. 2013;98(2):659-67. doi: 10.1210/jc.2012-1896 12. jackson c, tanios m, ebraheim n. management of sub-trochanteric proximal femur fractures: a review of recent literature. advances in orthopedics. 2018;2018:1326701. doi: 10.1155/2018/1326701 13. kanthimathi b, narayanan v. early complications in proximal femoral nailing done for treatment of sub-trochanteric fractures. malays orthop j. 2012;6(1):25-9. doi: 10.5704/moj.1203.009 14. el-mowafi h, eid t, el-sayed a, zalalo s. fixation of subtrochanteric fracture femur using a proximal femoral nail. menoufia medical journal. 2014;27(1):208-14. 15. rethnam u, cordell-smith j, kumar tm, sinha a. complex proximal femoral fractures in the elderly managed by reconstruction nailing– complications & outcomes: a retrospective analysis. journal of trauma management & outcomes. 2007;1(1):1-7. doi: 10.1186/1752-2897-1-7 16. alvarez jr, gonzalez rc, aranda rl, blanco mf, dehesa mc. indications for use of the long gamma nail. clinical orthopaedics and related research®. 1998;350:62-6. 17. shah a, shah m. functional outcomes of sub-trochanteric femur fractures treated by intramedullary proximal femur nail. international journal of orthopaedics. 2017;3(2):876-81. doi: https://doi.org/10.22271/ortho.2017.v3.i2j.95 18. nicolaou d, watson jt. nailing proximal femur fractures: how to choose starting point and proximal screw configuration. journal of orthopaedic trauma. 2015;29:s22-s7. doi: 10.1097/bot.0000000000000285 19. kumar m, akshat v, kanwariya a, gandhi m. a prospective study to evaluate the management of sub-trochanteric femur fractures with long proximal femoral nail. malays orthop j. 2017;11(3):36-41. doi: 10.5704/moj.1711.014 404 not found 169 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 original article comparison of efficacy of halstead and vazirani akinosi block technique in achieving mandibular anesthesia eruj shuja1, sadia daaniyal2, osama mushtaq3, naseer ahmed4, ammarah afreen5, zarah afreen6 1,5,6 assistant professor, oral & maxillofacial surgery, watim dental college, rawalpindi. 2,3 senior registrar, oral & maxillofacial surgery, watim dental college, rawalpindi. 4 medical officer, oral & maxillofacial surgery, shifa international hospital, islamabad. author’s contribution 1 conception of study 1 experimentation/study conduction 1,2 analysis/interpretation/discussion 2 manuscript writing 4,5 critical review 3,6 facilitation and material analysis corresponding author dr. eruj shuja, assistant professor, oral & maxillofacial surgery, watim dental college, rawalpindi email: erujshuja@hotmail.com article processing received: 16/04/2021 accepted: 02/03/2022 cite this article: shuja, e., daaniyal, s., mushtaq, o., ahmed, n., afreen, a., afreen, z. comparison of efficacy of halstead and vazirani akinosi block technique in achieving mandibular anesthesia. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 169-173. doi: https://doi.org/10.37939/jrmc.v26i2.1627 conflict of interest: nil funding source: nil access online: abstract objective: to compare the efficacy of halstead and vazirani akinosi block techniques in achieving mandibular anesthesia during exodontia among subjects reporting to watim teaching hospital. study design: randomized controlled trial. place and duration of study: this study was conducted in the department of maxillofacial surgery, watim dental hospital, rawalpindi from july 2019 to january 2020. materials and methods: this is a randomized control trial of 60 patients. duration of onset of anesthesia, pain during injection, the incidence of aspiration, success, and failure of halstead and vazirani akinosi techniques and their mean doses were analyzed and compared by using spss version 17. comparison of categorical variables was done by chi-square test. comparison of non-categorical variables was done by independent sample t-test. a p-value of less than or equal to 0.005 was considered significant. results: 28(93.3%) experienced moderate while 2(6.7%) experienced severe pain in the halstead group, while 30(100%) experienced mild pain in the vazirani akinosi group. halstead technique was successful in 22(73.3%) while unsuccessful in 8(26.7%) patients. vazirani akinosi technique was successful in 29(96.7%) and unsuccessful in 1(3.3%) patients. conclusion: it may be concluded from analysis in the present study that the vazirani akinosi technique was statistically superior in all parameters such as duration of onset, pain during injection, aspiration, and success rate as compared to the conventional halstead block technique. keywords: extraction tooth, local anesthesia, nerve block, vazirani-akinosi technique. 170 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 introduction the main objective of an oral surgeon during performing any kind of surgical procedure is adequate anesthesia.1 there are different techniques available for achieving mandibular anesthesia including the halstead technique, vazirani akinosi, and gow gates mandibular block techniques.2 painful stimulus is reversibly blocked by the use of a local anesthetic agent such as lignocaine which acts on preventing the generation of action potential on a nerve.3 2% lignocaine with 1:100,000 epinephrine is the drug of choice for exodontia and minor local anesthetic procedures.1 the inferior alveolar nerve is the primary sensory nerve supply of the mandible, innervating mandibular teeth and their surrounding soft tissue, tongue, and floor of the mouth.1 maxillary anesthesia is easily achieved as compared to mandibular anesthesia owing to the fact that maxillary bone is less compact as compared to the mandibular bone so the infiltration technique that is the deposition of local anesthetic near the root apices provides adequate anesthesia with less expertise and within a shorter duration of time.3 halstead block is the most common technique used in providing adequate analgesia during minor surgical procedures however previous studies have revealed that the failure rate for it is around 20-25%.2 various reasons for failure to achieve mandibular anesthesia with the halstead technique are patient apprehension, anatomical variation, technical failure, infected tissue at the injection site, and accessory innervations.4 vazirani akinosi technique also known as the closed mouth block is mainly indicated in cases of trismus.5 it aims to anesthetize the inferior alveolar nerve at a higher level as compared to the halstead technique.2 anatomic variability and accessory innervations account for failure in achieving adequate anesthesia in the case of open mouth technique however vazirani akinosi technique has proved to overcome these shortcomings as it requires less expertise in identifying the anatomic landmarks and by bathing nerves at a deeper level.5 the rationale of the study is to compare the efficacy of the two block techniques in terms of duration of onset of anesthesia, pain during injection, the incidence of aspiration, and anesthetic success. materials and methods this is a randomized control trial of 60 patients, 30 patients in each group. the sample size was calculated using the who calculator. this study was conducted at the department of maxillofacial surgery watim dental hospital rawalpindi. the duration of the study was 7 months from july 2019 to january 2020. ethical clearance was obtained from the institution prior to the commencement of the study. a written consent form was obtained by all the participants for inclusion in the study. a single operator was used for administering both techniques. patients were randomly divided into two groups by lottery method. group a (halstead technique) and group b (vazirani akinosi technique). inclusion criteria comprise d of healthy patients both males and females with no known medical history that reported to the oral and maxillofacial surgery department for extraction of mandibular teeth. exclusion criteria comprised patients that had a medical history of cardiac disease, diabetes mellitus, renal condition, smokers, allergy to local anesthesia, established infection, and pregnant females. both groups received 2% lignocaine with 1:100,000 epinephrine. an aspirating syringe of 40 mm with a 27 mm gauge was used with a total amount of 1.5 ml solution. the anesthetic solution was injected slowly within the duration of 60 seconds into an inferior alveolar nerve. for group a i.e. the conventional inferior alveolar block technique the patient was instructed to open his/her mouth, the external oblique ridge was palpated and the coronoid notch was identified. the target area for injection was the medial side of the ramus lateral to the pterygomandibular raphe. the syringe was positioned at the level of opposite premolars after initial aspiration. 1.5ml solution was deposited after the 2/3rd needle had penetrated the soft tissue and bone contact was positive. a needle was then retracted and local anesthesia for deposited for the lingual nerve. for group b i.e. vazirani akinosi block technique patient was put in a supine position and instructed to close his/her mouth in maximum intercuspation. the maxillary mucobuccalfold opposite to the 2nd molar was penetrated and almost whole of the length of the needle was inserted within the soft tissue after aspiration 1.5 ml of solution was deposited. subjective assessment for the onset of anesthesia was made by the patient, describing onset by the achievement of lower lip numbness and numbness of ipsilateral half of the tongue. objective assessment for anesthetic success was made by periodontal probing in the gingival sulcus in the area of anesthetized tissues. 171 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 the time for onset of anesthesia was noted using a stopwatch. pain during the administration of individual techniques was measured by vas scale from 0 to 10mm and was divided into three groups mild (0-4) moderate (5-7) and severe (8-10). aspiration of blood was noted as positive or negative by use of a self-aspirating syringe at the time of initial administration of the block technique. failure of anesthetic technique was labeled when the patient did not report numbness of the lower lip and tongue along with pain on probing after 10 minutes of administration of the respective block. in such instances, supplemental injections were given to achieve the desired result. duration of onset of anesthesia, pain during injection, the incidence of aspiration, success, and failure of technique, and mean dose were analyzed and compared by using spss version 17. percentages and frequencies along with mean± s.d were calculated for various variables. comparison of categoric variables was done by chi-square test. comparison of noncategoric variables was done by independent sample ttest. a p-value of less than or equal to 0.05 was considered significant. results a total of 60 patients 27 (45%) males and 33 (55%) females, mean age 36.90±12.67 years were included in our study. in group a, alstead block technique, 16 patients were female while 14 were males. in group b, vazirani akinosi block technique 16 patients were female while 14 were males. the mean duration of onset of anesthesia in the halstead technique is 172.67±41.55 seconds which is much earlier compared to the vazirani akinosi technique i.e. 198.56+18.18 seconds (table 1). the independent sample t-test showed a p-value ˂ 0.001. a comparison of the intensity of pain during injection in the halstead technique and vazirani akinosi showed that 28(93.3%) experienced moderate while 2(6.7%) experienced severe pain in the halstead group, while 30(100%) experienced mild pain in vazirani akinosi group chi-square test showed significant difference p-value ˂ 0.001. (table 2) aspiration during administration was compared between the groups. it was positive in 6(20%) and negative in 24(80%) patients in the halstead technique and positive in 1(3.3%) and negative in 29(96.7%) in the vazirani akinosi technique. this was statistically significant on chi-square test p-value˂ 0.004. (table3) a comparison of the rate of success in achieving anesthesia was noted for each group. halstead technique was successful in 22(73.3%) while unsuccessful in 8(26.7%) patients. vazirani akinosi technique was successful in 29(96.7%) and unsuccessful in 1(3.3%) patients. this was statistically significant on the chi-square test with a p-value ˂ 0.001(table 4). the total dose of local anesthesia used was calculated in ml. a mean dose of 2.28±0.80 was observed in the halstead group which was higher as compared to the mean dose of1.86±0.32 for the vazirani akinosi group. the independent sample t-test shows statistical significance with a p-value ˂ 0.001. table 1: statistics for duration of onset of anesthesia local anesthesia technique mean duration ±sd (seconds) p-value halstead technique 172.67±41.55s <0.001 vazirani akinosi technique 198.56±18.18s table 2: statistics for pain during the administration of local anesthesia local anesthetic technique mild pain moderate pain severe pain p-value halstead technique 0% 93.3% 6.7% <0.001 vazirani akinosi technique 100% 0% 0% table 3: statistics for aspiration during the administration of local anesthesia local anesthesia technique positive aspiration (%) negative aspiration (%) p-value halstead technique 20% 80% <0.004 vazirani akinosi technique 3.3% 96.7% table 4: statistics for rate of success in achieving anesthesia local anesthesia technique successful (%) unsuccessful (%) pvalue halstead technique 73.3% 26.7% <0.001 vazirani akinosi technique 96.7% 3.3% 172 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 discussion this study was done to compare the efficacy of the halstead block and vazirani akinosi block technique. the first parameter that was measured is the onset of anesthesia. according to our research, the onset of the duration of anesthesia in the halstead technique is 172.6 seconds and 198.6 seconds for the vazirani akinosi technique which are consistent with the results of debojyoti roy et.al1, kiran bs et al2 study also supports the results of our study. however jendisk et al4 show contradictory results with respect to the onset of anesthesia which was 78.36 seconds for the halstead technique and 104.24 seconds for the vazirani akinosi technique. this discrepancy in results could be attributed to a decrease in the concentration of adrenaline i.e. 1:1200,000 used in their study. the intensity of pain during anesthesia injection administration was compared between the two selected techniques. 28(93.3%) experienced moderate while 2(6.7%) experienced severe pain in the halstead group, while 30(100%) experienced mild pain in the vazirani akinosi group. nakkeeran kp et al8 favor our study with a mean pain score of 3.05 for the halstead technique and 1.93 for the va technique this was statistically significant with a p-value less than 0.001. mild pain experienced during the vazirani akinosi technique could be attributed to the fact that during injection no bony landmark is contacted with the needle and also the buccal soft tissue in the maxillary region is less sensitive and less resistant to penetration with less musculofascial bands in the concerned region.9 sangeethakarunakaran et al10 show that both the inferior alveolar nerve group and vasirani akinosi group experienced mild pain on injection. differences in pain perception might be due to subjective understanding of pain. in another study by costa fa et al11 pain perception by subjects was reported as being mild for both the techniques. misra s et al12 in their study revealed mild pain was experienced by the va group and moderate pain by the ian group which is consistent with our study. this is due to anatomical divergence of medial pterygoid muscle from the ramus thus providing greater pterygomandibular space and preventing the risk of penetration of medial pterygoid muscle.12 a comparison of aspiration in our study between the two study groups revealed positive aspiration in 20% of the ian group and 3.3% in the va group, the difference was statistically significant. jendisk et al4 reported positive aspiration in 15% of the ian group and 3% in the va group which is supporting the current study. mohajerani h at el13 study results is also consistent with our results showing 15% aspiration in the ian group and 5% in the va group this is statistically significant p-0.04. this study revealed that the halstead technique was successful in 22(73.3%) while unsuccessful in 8(26.7%) patients. vazirani akinosi technique was successful in 29(96.7%)and unsuccessful in 1(3.3%)patients. saatchi m et al14 checked the efficacy of ian block with a success rate of 44%. haas et al8 showed an increased success rate in vazirani akinosi as compared to the conventional block technique. aggarwal v et al15 in their study the success rate of conventional ian block was 36% and of va was 41% this contradiction of results with our study may be due to assessment of pain associated with irreversible pulpitis as compared to our study in which participants experienced pain during extraction of teeth. alhindi m et al16 favour our result as well. the mean dose used in the ian block was more as compared to the vazirani-akinosi block.17,18 there were a few limitations in this research such as the detailed complications and their incidences associated with anesthesia administration were not recorded. individual nerves and their responses were also not calibrated. thus this study can be improved with a larger sample size and taking into account above mentioned factors. conclusion it may be concluded from our analysis that the vazirani akinosi technique was statistically superior to the conventional block technique in parameters such as duration of onset, pain during injection, aspiration, and success rate as compared to the conventional halstead block technique. we found that vazirani akinosi is an underestimated inferior alveolar nerve block as it provides better outcomes. references 1. roy d, talukdar b. comparison between conventional inferior alveolar nerve block with vazirani-akinosi technique and gow-gates technique of the mandibular nerve block.ijrr vol 6,issue 8,august 2019. 2. kiran bs, kashyap vm, uppada uk, tiwari p, mishra a, sachdeva a. comparison of efficacy of halstead, vaziraniakinosi and gow gates techniques for mandibular anesthesia. journal of maxillofacial and oral surgery. 2018 dec;17(4):570-5. 3. maqsood a, asim ma, aslam f, khalid r, khalid o. comparison of efficacy of gow-gates mandibular nerve block and inferior alveolar nerve block for the extraction of mandibular 173 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 molars. annals of abbasi shaheed hospital and karachi medical & dental college. 2018 dec 31;23(4):177-83. 4. jendi sk, thomas bg. vazirani–akinosi nerve block technique: an asset of oral and maxillofacial surgeon. journal of maxillofacial and oral surgery. 2019 dec;18(4):628-33. 5. nagendrababu v, ahmed hm, pulikkotil sj, veettil sk, dharmarajan l, setzer fc. anesthetic efficacy of gow-gates, vazirani-akinosi, and mental incisive nerve blocks for treatment of symptomatic irreversible pulpitis: a systematic review and meta-analysis with trial sequential analysis. journal of endodontics. 2019 oct 1;45(10):1175-83. 6. haas da. alternative mandibular nerve block techniques: a review of the gow-gates and akinosi-vazirani closed-mouth mandibular nerve block techniques. the journal of the american dental association. 2011 sep 1;142:8s-12s. 7. ghoddusi j, zarrabi mh, daneshvar f, naghavi n. efficacy of ianb and gow-gates techniques in mandibular molars with symptomatic irreversible pulpitis: a prospective randomized double blind clinical study. iranian endodontic journal. 2018;13(2):143. 8. nakkeeran kp, ravi p, doss gt, raja kk. is the vaziraniakinosi nerve block a better technique than the conventional inferior alveolar nerve block for beginners?. journal of oral and maxillofacial surgery. 2019 mar 1;77(3):489-92. 9. haghighat a, jafari z, hasheminia d, samandari mh, safarian v, davoudi a. comparison of success rate and onset time of two different anesthesia techniques. medicina oral, patologia oral y cirugiabucal. 2015 jul;20(4):e459 10. sangeethakarunakaran bd, alankruthagangasani bd, priyanka unnam bd. evaluation of efficacy and pain in open mouth versus closed mouth ianb technique for third molar extraction. saudi j oral dent res, july, 2020; 5(7): 317-320. 11. costa fa, souza lm, groppo f. comparison of pain intensity during inferior alveolar nerve block. revista dor. 2013 sep;14(3):165-8 12. mishra s, tripathy r, sabhlok s, panda pk, patnaik s. comparative analysis between direct conventional mandibular nerve block and vazirani-akinosi closed mouth mandibular nerve block technique. int j adv res technol. 2012 nov;1(6):112-7. 13. mohajerani h, pakravan ah, bamdadian t, bidari p. anesthetic efficacy of inferior alveolar nerve block: conventional versus akinositechnique.journal of dental school 2014;32(4):210-215. 14. saatchi m, shafiee m, khademi a, memarzadeh b. anesthetic efficacy of gow-gates nerve block, inferior alveolar nerve block, and their combination in mandibular molars with symptomatic irreversible pulpitis: a prospective, randomized clinical trial. journal of endodontics. 2018 mar 1;44(3):384-8. 15. aggarwal v, singla m, kabi d. comparative evaluation of anesthetic efficacy of gow-gates mandibular conduction anesthesia, vazirani-akinosi technique, buccal-plus-lingual infiltrations, and conventional inferior alveolar nerve anesthesia in patients with irreversible pulpitis. oral surgery, oral medicine, oral pathology, oral radiology, and endodontology. 2010 feb 1;109(2):303-8. 16. alhindi m, rashed b, alotaibi n. failure rate of inferior alveolar nerve block among dental students and interns. saudi medical journal. 2016 jan;37(1):84. 17. shah fa, jan iu, ahsan a, afridi ru, zain m, haider s. comparison of anesthetic efficacy of inferior alveolar nerve block and vazirani-akinosi techniques in patients with irreversible pulpitis. pakistan oral & dental journal. 2019 sep 30;39(3):301. 18. lee cr, yang hj. alternative techniques for failure of conventional inferior alveolar nerve block. journal of dental anesthesia and pain medicine. 2019 jun;19(3):125. 19. sakdejayont w, chewpreecha p, boonsiriseth k, shrestha b, wongsirichat n. does the efficacy of direct inferior alveolar nerve block depend on patient position?.m dent j volume 36,2016 may-august. 20. devarakonda bv, issar y, goyal r, vadapalli k. difficult airway ‘made easy’ with vazirani-akinosi (closed mouth) technique of mandibular nerve block. medical journal, armed forces india. 2019 apr;75(2):225. 402 journal of rawalpindi medical college (jrmc); 2022; 26(3): 402-407 original article bacteriological spectrum of pediatric urinary tract infection and its drug sensitivity and resistance pattern nadia mumtaz1, qaisar shahzad humayoun2, israr liaquat3, tariq mehmood4, muhammad hafeez5, hifza zeb6 1,6 registrar paediatrics, holy family hospital, rawalpindi. 2assistant professor paediatrics, holy family hospital, rawalpindi 3,4 senior registrar paediatrics, holy family hospital, rawalpindi. 5 associate professor paediatrics, watim medical & dental college, rawalpindi author’s contribution 1 conception of study 1 experimentation/study conduction 1,2,3,4,5,6 analysis/interpretation/discussion 2,6 manuscript writing 2,5 critical review 2,3,4,5 facilitation and material analysis corresponding author dr. israr liaquat, senior registrar paediatrics, holy family hospital, rawalpindi email: fmc414@hotmail.com article processing received: 03/11/2021 accepted: 03/06/2022 cite this article: mumtaz, n., humayoun, q.s.., liaquat, i., mehmood, t., hafeez, m., zeb, h. bacteriological spectrum of pediatric urinary tract infection and its drug sensitivity and resistance pattern. journal of rawalpindi medical college. 30 sep. 2022; 26(3): 402-407. doi: https://doi.org/10.37939/jrmc.v26i3.1823 conflict of interest: nil funding source: nil access online: abstract introduction: urinary tract infection (uti) is a common infection in children. it has high morbidity and long-term sequelae. objective: to determine the frequency of bacteriological organism of pediatric uti and its drug sensitivity and resistance pattern and to improve the treatment of uti according to culture sensitivity, hence minimizing the resistance pattern and disease burden. materials and methods: it was a descriptive cross-sectional study conducted in 2018 over a period of 6 months. a total of 225 children with utis were enrolled. urine culture and sensitivity reports were evaluated and an isolated microorganism along with their sensitivities to the mentioned drugs was entered through designed performa. results: the average age of the children was 7±.18 years. common bacteriological agents leading to uti were e.coli (59.1%), followed by pseudomonas aeruginosa (14.2%), klebsiella (13.8%), staphylococcus aureus (8.9%), and enterococcus (4%). the most common organism isolated was e.coli ( 133 cultures). it was fully resistant to amoxicillin-clavulanate and ofloxacin (100%), while the resistance pattern with other antibiotics was ceftriaxone (88.7%), imipenem (88.7%), and ciprofloxacin (75.9%). the most effective antibiotic for e.coli was amikacin (81.2%). pseudomonas aeruginosa was the second most common isolate (32 cultures). its drug resistance pattern was amikacin (84.4%), amoxicillin & clavulanate (90.6%), imipenem (100%), and ofloxacin (100%). conclusion: a most common organism that causes uti was e.coli followed by pseudomonas aeroginosa and klebsiella. these isolates were highly resistant to commonly used antibiotics. therefore new antibiotics policy should be adopted to treat these infections. keywords: urinary tract infection, e.coli, bacteriological organism. 403 journal of rawalpindi medical college (jrmc); 2022; 26(3): 402-407 introduction uti is a common infection in children. it has high morbidity and long-term sequela and can occur in all age groups, especially in the pediatric age group. it occurs in 1-3% of females and 1% of males by 10 years of age.1 e. coli (71.4%), and klebsiella spp. (9.6%) are common organisms that cause utis. while less common causes include enterococcus fecal (6.4%), pseudomonas aeruginosa, staphylococcus aureus, serratia spp, enterobacter spp, and proteus.2,3,4 both clinical features and urinalysis help in diagnosis. however gold standard for diagnosis of uti is urine culture having >105 organisms per ml of urine.5 its sensitivity yield is roughly up to 18%.6 drug sensitivity and resistance patterns are measured by the standard disc diffusion method. treatment of utis includes empirical oral treatment for uncomplicated utis and intravenous treatment for complicated utis and later on, culture-based.7 over the past decade, the multidrug resistance of organisms causing utis is alarmingly increasing. a study by rezaee et al confirms the presence of multi-drug resistant organisms causing utis. in this study drug sensitivity patterns of e.coli were ciprofloxacin (15%), nitrofurantoin (11%), nalidixic acid (25%), and 30 to 75% for amikacin, gentamicin, ceftriaxone, ceftazidime, cefotaxime, and co-trimoxazole. the sensitivity pattern of e.coli was very low [8] for ciprofloxacin (15%), nitrofurantoin (11%), nalidixic acid (25%), and 30 to 75% for amikacin, gentamicin, ceftriaxone, ceftazidime, cefotaxime, and cotrimoxazole. over all ciprofloxacin and amikacin were highly effective against gram-negative and grampositive organisms.2,4 in another study conducted in pakistan, pseudomonas aeruginosa was isolated in 254 cultures (5.4%). it was highly resistant to commonly used antibiotics, augmentin (97.6%), nalidixic acid (98.8%), cefuroxime (99.2%), cotrimoxazole (99.2%), and amoxil/ampicillin (99.6%).9 however gram-negative organisms showed better sensitivity to antibiotics like amikacin (63%), cefotaxime (55%), amoxicillin (49%), and ciprofloxacin (49%). while drug sensitivity pattern of gram-positive organisms was 66.6% for chloramphenicol, co-trimoxazole, gentamicin, amikacin, ciprofloxacin, and cefotaxime. however, the drug sensitivity pattern was 33.3% with ampicillin, amoxicillin, tetracycline, and norfloxacin.11 untreated uti leads to renal parenchymal damage which in turn leads to chronic renal failure and secondary hypertension esp. in a patient having urinary tract anomalies i.e. vesicoureteric reflux.1 to adopt a new antibiotic policy in the scenario of changing drug resistance patterns, this study is designed to know the current bacterial spectrum of uti and its drug sensitivity and resistance pattern in our unit. materials and methods it was a descriptive cross-sectional with a nonprobability consecutive sampling technique, conducted over a period of 6 months in the indoor and outdoor department of paediatric holy family hospital, rawalpindi in children ranging between 2 to 10 years of age. patients who are confirmed cases of uti based on urine c/s reports were enrolled. those who have taken any antibiotic before urine c/s and who are diagnosed to have any secondary infections were excluded. all the patients fulfilling the inclusion criteria were included in the study. midstream urine samples were taken under absolute aseptic measures. the collected samples were transported immediately to the laboratory for urinalysis, culture, and sensitivity. cultures were done directly on cled agar medium for 48 hours. sensitivities were checked for trimethoprim-sulfamethoxazole, amoxycillin/ clavulanic acid nalidixic acid, and others. basic demographic information including name, age, gender, weight, and height was collected. urine culture and sensitivity reports were evaluated and isolated microorganisms along with their sensitivities to the mentioned drugs were entered in already designed performa. all the information collected was entered into spss version 20.0 and was analyzed through its statistical package. frequencies with percentages were calculated for categorical variables like gender, pathological type of microorganism, socioeconomic status, residence, sensitivity, and resistance. for continuous variables like age, weight, and height, the mean with standard deviation was calculated. effect modifiers like age, gender, weight, and height were controlled by stratification. post-stratification chisquare was applied. p value <0.05 was significant. results a total of 225 children with utis enrolled for the study. their mean age was 7±.18 years. their average 404 journal of rawalpindi medical college (jrmc); 2022; 26(3): 402-407 height and weight along with mean age are presented in table 1. there were 155 (68.99%) male and 70 (31.11%) female. most of the children belong to middle-class families (58.11%). out of 225 children, 123 (54.67%) were from urban and 102(45.33% were from rural areas. a total of 225, 196(87.11%) children had gram-negative organisms and 29(12.89%) had gram-positive organisms. common bacteriological agents leading to uti were e.coli (59.1%), followed by pseudomonas aeruginosa (14.2%) and klebsiella (13.8%)as presented in figure 1. the drug sensitivity and resistance pattern for gramnegative organism is shown in table 2 and 3. the drug resistance pattern of e.coli was amoxicillinclavulanate (100%), ceftriaxone (88.7%), imipenam (88.7%), ciprofloxacin (75.9%), and ofloxacin (100%). the most effective antibiotic for e.coli was amikacin (81.2%). pseudomonas aenroginosa was the second most common isolate (32 cultures). its drug resistance pattern was amikacin (84.4%), amoxicillin-clavulanate (90.6%), imipenam (100%), and ofloxacin (100%). klebsiella was the third most common isolate (31 cultures). the drug resistance pattern was ceftriaxone (87.1%), ciprofloxacin (100%), and ofloxacin (100%). staphylococcus aurus was the fourth most common isolate (20 cultures). its drug resistance pattern was imipenam (80%), ciprofloxacin (85%), and ofloxacin (85%). enterococcaii is isolated into 9 cultures. its drugs resistance pattern was amikacin (88.9%), amoxicillin-clavulanate (100%), ceftriaxone (89%), trimethoprim-sulfamethoxazole (89%), and ofloxacin (88%). stratification analysis was performed and observed that the rate of e.coli and klebsiella was significantly high above 5 years of age children while other organisms were not statistically significant among different age groups as presented in table 4. table 1: descriptive statistics of characteristics of patients (n=225) variables mean std. deviation 95% confidence interval for mean lower bound upper bound age (years) 7.00 2.18 6.72 7.29 weight (kg) 27.89 8.91 26.72 29.06 height (cm) 128.23 19.32 125.69 130.77 figure 1: frequency of bacteriological organism of paediatric patients with uti (n=225) table 2: drug sensitivity and resistance pattern for gram negative organism of paediatric patients with uti (n=255) antibiotics e. coli n=133 klebsiella n=31 psendomonas aenroginosa n=32 sensitive resistant sensitive resistant sensitive resistant amikacin 81.2% 18.8% 25.8% 74.2% 15.6% 84.4% amoxicillin clavulanate 0% 100% nt 9.4% 90.6% 405 journal of rawalpindi medical college (jrmc); 2022; 26(3): 402-407 ceftriaxone 11.3% 88.7% 12.9% 87.1% nt nalidixic acid 36.1% 63.9% nt nt trimethoprim-sulfamethoxazole nt nt 21.9% 78.1% imipenam 11.3% 88.7% nt 0% 100% ciprofloxacin 24.1% 75.9% 0% 100% nt ofloxacin 0% 100% 0 100% 9.4% 90.6% table 3: drug sensitivity and resistance pattern for gram-positive organism of paediatric patients with uti (n=255) antibiotics staphylococcus aurus n=20 enterococcus n=9 sensitive resistant sensitive resistant amikacin 25% 75% 11.1% 88.9% amoxicillin clavulanate nt 0% 100% ceftriaxone nt 11% 89% nalidixic acid nt nt trimethoprim-sulfamethoxazole 35% 65% 11% 89% imipenam 20% 80% 22% 78% ciprofloxacin 15% 85% 21 79% ofloxacin 15% 85% 12% 88% table 4: frequency of bacteriological organism of paediatric patients with uti by age groups organism age groups (years) p-value 2-4 n=27 5-7 n=92 8-10 n=106 e.coli 8(29.6%) 62(67.4%) 63(59.4%) 0.002 klebisella 8(29.6%) 7(7.6%) 16(15.1%) 0.012 psendomonas aenroginosa 3(11.1%) 16(17.4%) 13(12.3%) 0.521 staphylococcus aurus 5(18.5%) 5(5.4%) 10(9.4%) 0.106 enterococcal 3(11.1%) 2(2.2%) 4(3.8%) 0.113 discussion bacteriological infections are the leading cause of morbidity and mortality among the paediatric age group.12 generally uti has a benign course in adults but in children, it can result in marked morbidities like hypertension and renal failure due to inconspicuous clinical manifestations.13 empirical treatment for utis normally failed nowadays due to resistance of urinary pathogens, that’s why effective antibiotics are very important. early information regarding appropriate antibiotics will lead to effective treatment, will lessen hospital stays, and prevent outbreaks as well.14,15 incidence of uti varies according to age and gender with more susceptibility of females due to physiologic and anatomic mechanisms.16,17 in our study there were 155 (68.99%) male and 70 (31.11%) female patients. this might be due to gender preference in our society.18 gram-negative bacteria are one of the important causes of urinary tract infection among them e-coli being the most common.19 apart from gram-negative bacteria, gram-positive bacteria like staphylococcus spp., and streptococcus spp. are also being reported.17,20 in our study 196 (87.11%) children had utis due to gram-negative organisms and 29 (12.89%) due to gram-positive organisms. common bacteriological agents leading to uti were e.coli (59.1%), followed by pseudomonas aeruginosa (14.2%), klebsiella (13.8%), staphylococcus aureus (8.9%), and enterococcus (4%). hussain et al and pandit et al reported similar patterns in their studies.21,22 but in another study fenta et al reported klebsiella spp. as a common organism causing utis in children.16 over the last decade, antibiotic resistance to uropathogens is alarmingly increasing.23 amin et al and woo et al observed high resistance to commonly used antibiotics. e-coli isolates mainly responded to amikacin (18.8% resistant).24 gunduz et al reported 406 journal of rawalpindi medical college (jrmc); 2022; 26(3): 402-407 amikacin being the most sensitive drug in utis.24,25 one of the problems in clinical practice is resistance to pseudomonas aeruginosa and its predominance among immunocompromised patients.26 in our study pseudomonas aeroginosa was isolated in 32 cultures and the most resistant drugs were imipenam (100%) and ofloxacin (100%) followed by amikacin (84.4%) and amoxicillin-clavulanate (90.6%). the resistance to ampicilin was 45%, 50%, and 100% in canada, europe, and africa respectively.26,27 in the present study resistance to ampicillin/amoxicillin was very high with all the gram-negative and positive bacteria. due to the prevalence of multidrug-resistant organisms in utis it is suggested that appropriate antibiotics should be administered to lessen the chances of resistance. every county must have its own epidemiological data, and guidelines for the treatment of utis in paediatrics. so appropriate antibiotic cover and prophylaxis should be given. some leading treatment centres must identify uropathogens causing utis and their culture sensitivity pattern should be studied. these parameters can help form guidelines in treatment to decrease the chances of resistance. conclusion e. coli is the most common cause of uti in children followed by klebsiella. bacterial organisms isolated in this study are highly resistant to commonly used antibiotics. there is a need to review the antibiotics policy. irrational and unsupervised use of antibiotics should be discouraged. references 1. behrman re, klieg man rm, jenson hb (edi). epidemiology of infections. nelson textbook of paediatrics 21th ed. philadelphia pa; saunders 2020; 996-1004. 2. mahony m, mcmullan b, brown j, kennedy se. multidrugresistant organisms in urinary tract infections in children. pediatric nephrology. 2020 sep;35(9):1563-73. 3. zavala-cerna mg, segura-cobos m, gonzalez r, zavalatrujillo ig, navarro-perez sf, rueda-cruz ja, satoscoy-tovar fa. the clinical significance of high antimicrobial resistance in community-acquired urinary tract infections. canadian journal of infectious diseases and medical microbiology. 2020 jun 5;2020. 4. leung ak, wong ah, leung aa, hon kl. urinary tract infection in children. recent patents on inflammation & allergy drug discovery. 2019 may 1;13(1):2-18. 5. thapaliya j, khadka p, thapa s, gongal c. enhanced quantitative urine culture technique, a slight modification, in detecting under-diagnosed pediatric urinary tract infection. bmc research notes. 2020 dec;13(1):1-6. 6. folliero v, caputo p, della rocca mt, chianese a, galdiero m, iovene mr, hay c, franci g, galdiero m. prevalence and antimicrobial susceptibility patterns of bacterial pathogens in urinary tract infections in university hospital of campania “luigi vanvitelli” between 2017 and 2018. antibiotics. 2020 may;9(5):215. 7. bader ms, loeb m, leto d, brooks aa. treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents. postgraduate medicine. 2020 apr 2;132(3):234-50. 8. caneiras c, lito l, melo-cristino j, duarte a. communityand hospital-acquired klebsiella pneumoniae urinary tract infections in portugal: virulence and antibiotic resistance. microorganisms. 2019 may;7(5):138. 9. rasool ms, siddiqui f, ajaz m, rasool sa. prevalence and antibiotic resistance profiles of gram negative bacilli associated with urinary tract infections (utis) in karachi, pakistan. pakistan journal of pharmaceutical sciences. 2019 nov 1;32(6). 10. mubashir f, sattar m, essa f, hafiz s. spectrum and antibiotic resistance pattern of uropathogens causing urinary tract infection among inpatients and outpatients: an experience of a tertiary care hospital in karachi, pakistan. proteus. 2021;1:20. 11. meena m, kishoria n, meena ds, sonwal vs. bacteriological profile and antibiotic resistance in patients with urinary tract infection in tertiary care teaching hospital in western rajasthan india. infectious disorders-drug targets (formerly current drug targets-infectious disorders). 2021 feb 1;21(2):257-61.iftikhar aj, kokila l. in: paediatric surgery: a comprehensive text for africa.amehea, bickler s,nwomehk, poenaru d, editors. global help; 2010; 92–7. 12. kaufman j, temple-smith m, sanci l. urinary tract infections in children: an overview of diagnosis and management. bmj paediatrics open. 2019;3(1). 13. vazouras k, velali k, tassiou i, anastasiou-katsiardani a, athanasopoulou k, barbouni a, jackson c, folgori l, zaoutis t, basmaci r, hsia y. antibiotic treatment and antimicrobial resistance in children with urinary tract infections. journal of global antimicrobial resistance. 2020 mar 1;20:4-10. 14. kot b, grużewska a, szweda p, wicha j, parulska u. antibiotic resistance of uropathogens isolated from patients hospitalized in district hospital in central poland in 2020. antibiotics. 2021 apr;10(4):447. 15. fenta a, dagnew m, eshetie s, belachew t. bacterial profile, antibiotic susceptibility pattern and associated risk factors of urinary tract infection among clinically suspected children attending at felege-hiwot comprehensive and specialized hospital, northwest ethiopia. a prospective study. bmc infectious diseases. 2020 dec;20(1):1-0. 16. khan a, jhaveri r, seed pc, arshad m. update on associated risk factors, diagnosis, and management of recurrent urinary tract infections in children. journal of the pediatric infectious diseases society. 2019 jun;8(2):152-9. 17. hameed t, al nafeesah a, chishti s, al shaalan m, al fakeeh k. community-acquired urinary tract infections in children: resistance patterns of uropathogens in a tertiary care center in saudi arabia. international journal of pediatrics and adolescent medicine. 2019 jun 1;6(2):51-4. 18. mortazavi-tabatabaei sa, ghaderkhani j, nazari a, sayehmiri k, sayehmiri f, pakzad i. pattern of antibacterial resistance in urinary tract infections: a systematic review and meta-analysis. international journal of preventive medicine. 2019;10. 19. gebremariam g, legese h, woldu y, araya t, hagos k, gebreyesuswasihun a. bacteriological profile, risk factors and antimicrobial susceptibility patterns of symptomatic urinary tract 407 journal of rawalpindi medical college (jrmc); 2022; 26(3): 402-407 infection among students of mekelle university, northern ethiopia. bmc infectious diseases. 2019 dec;19(1):1-1. 20. pandit r, awal b, shrestha ss, joshi g, rijal bp, parajuli np. extended-spectrum β-lactamase (esbl) genotypes among multidrug-resistant uropathogenic escherichia coli clinical isolates from a teaching hospital of nepal. interdisciplinary perspectives on infectious diseases. 2020 oct;2020. 21. hussain m. bacteriological spectrum and sensitivity pattern in culture proven urinary tract infection in children. journal of rawalpindi medical college. 2017 sep 30;21(3):290-. 22. amin ek, zaid am, abd el rahman ik, el-gamasy ma. incidence, risk factors and causative bacteria of urinary tract infections and their antimicrobial sensitivity patterns in toddlers and children: a report from two tertiary care hospitals. saudi journal of kidney diseases and transplantation. 2020 jan 1;31(1):200. 23. woo b, jung y, kim hs. antibiotic sensitivity patterns in children with urinary tract infection: retrospective study over 8 years in a single center. childhood kidney diseases. 2019;23(1):22-8. 24. gunduz s, uludağ altun h. antibiotic resistance patterns of urinary tract pathogens in turkish children. global health research and policy. 2018 dec;3(1):1-5. 25. yerega belete da, woldeamanuel y, yihenew g, gize a. bacterial profile and antibiotic susceptibility pattern of urinary tract infection among children attending felege hiwot referral hospital, bahir dar, northwest ethiopia. infection and drug resistance. 2019;12:3575. 26. jafari-sales a, soleimani h, moradi l. antibiotic resistance pattern in klebsiella pneumoniae strains isolated from children with urinary tract infections from tabriz hospitals. health biotechnology and biopharma. 2020;4(1):38-45. 389 journal of rawalpindi medical college (jrmc); 2022; 26(3): 389-394 original article comparison of surgical outcome of open versus laparoscopic nephrectomy akhtar nawaz1, fazl e manan2, nasrum minallah3, romana bibi4, khalil-ur-rehman5 1 assistant professor, urology and transplant, institute of kidney diseases, peshawar. 2,3 registrar, urology and transplant, institute of kidney diseases, peshawar. 4 post-graduate resident, khyber teaching hospital, peshawar. 5 medical officer, urology and transplant, institute of kidney diseases, peshawar. author’s contribution 1,3 conception of study 1,2,4 experimentation/study conduction 2,3,4,5 analysis/interpretation/discussion 2,3,4,5 manuscript writing 1 critical review 2,3,4,5 facilitation and material analysis corresponding author dr. fazl e manan, registrar, urology and transplant, institute of kidney diseases, peshawar email: fazlemanan500@yahoo.com article processing received: 02/11/2021 accepted: 07/09/2022 cite this article: nawaz, a., manan, f., minallah, n., bibi, r., rehman, k.u. comparison of surgical outcome of open versus laparoscopic nephrectomy. journal of rawalpindi medical college. 30 sep. 2022; 26(3): 389-394. doi: https://doi.org/10.37939/jrmc.v26i3.1817 conflict of interest: nil funding source: nil access online: abstract introduction: removal of a kidney is a common surgical procedure for a long time. the procedure was traditionally done by open surgery. since the advent of laparoscopic surgery, nephrectomy is being done increasingly laparoscopically. the laparoscopic approach has obvious advantages. better cosmetics, less operative time, lesser need for blood transfusions, fewer analgesia requirements, early mobility, and oral feed, early return to work, and fewer intraoperative and post-operative major complications all contribute to the superiority of laparoscopic nephrectomy. objective: to compare surgical outcomes of open versus laparoscopic nephrectomy. materials and methods: this retrospectives study was conducted in the department of urology, institute of kidney disease, hayatabad, peshawar over a period of 2 years from january 2018 to january 2020. results: our study included a total of 78 cases, 48.7% males and 51.3% females. the patient means the age of 42.69 years. 39.7% had hypertension and 19.2% had diabetes mellitus. open nephrectomy was done in 40 patients and laparoscopic nephrectomy in 38 patients. the average operating time for open nephrectomy was 160.5 minutes and 130.9 minutes for laparoscopic nephrectomy. the average blood loss during open and laparoscopic nephrectomy was 361.25ml and 59.86ml. blood transfusion rate in open and laparoscopic nephrectomy was 55% and 10.5% (p=0.001). overall, the post-operative complication rate was 52.5% and 21.5% for an open and laparoscopic approach. post-operative pain was noted in 7.9% of patients in laparoscopic and 97.5% for an open approach. fever was noted postoperatively in 26.3% and 62.5% of patients in laparoscopic and open approaches (p=0.001). the average hospital stay in the laparoscopic approach was 2.8days and 4.5days in the open approach. the mean tumor size was 5.65cm in laparoscopic while 8.1cm in the open approach. catheter and drain removal was on average 1.18 days and 1.32days post-op day in the laparoscopic group while it was 2.35days and 2.3days post-op day in an open group, respectively. there were no per-op complications in the laparoscopic approach as compared to 2 cases of minor ivc injury in open. conclusion: in our study, we conclude that the laparoscopic approach for nephrectomy is far superior as compared to the open approach and it is recommended that laparoscopic simple and radical nephrectomy should be considered a gold standard treatment. keywords: open nephrectomy, laparoscopic nephrectomy, tumor, htn, dm. 390 journal of rawalpindi medical college (jrmc); 2022; 26(3): 389-394 introduction removal of a kidney is a common surgical procedure for a long. there are a number of indications for the procedure like non-functioning kidney (symptomatic, hydro/pyonephrotic, with a stone, uncontrolled htn secondary to scarred kidney), renal trauma, or tumours. the procedure was traditionally done by open surgery. since the advent of laparoscopic surgery, nephrectomy is being done increasingly laparoscopically (clayman 1991).1 the laparoscopic approach has obvious advantages. better cosmetics, less operative time, lesser need for blood transfusions, less post-operative analgesia requirements, early mobility and oral feed, early return to work, and fewer intra-operative and post-operative major complications all contribute to the superiority of laparoscopic nephrectomy.2 lap nephrectomy is better tolerated by esrd patients as compared to open.3 lap donor as similar graft outcomes.4 lap nephrectomy can be discharged on the same day.5 even a handassisted laparoscopic nephrectomy is considered better than an open nephrectomy.6,7 after long experience, development of better vision8, miniaturization of working instruments, and advent of sophisticated energy devices for accurate dissection and vessel sealing, laparoscopic nephrectomy is considered to be the gold standard.9 our unit (team a at ikd) is a urology and transplant unit where a variety of urological procedures are performed day in and day out including endoscopic, laparoscopic, and open procedures and renal transplantation. in this comparative analysis, we wanted to report the similarities and differences that we observed between laparoscopic and open nephrectomy. objective: to compare the surgical outcome of open versus laparoscopic nephrectomy materials and methods setting: department of urology, institute of kidney disease, hayatabad, peshawar. duration: 2 years from january 2018-january 2020. study design: retrospective study. retrospective analysis of all the nephrectomies performed from january 2018 to january 2020. data was collected by retrospectively reviewing the patients’ files. all the patients undergoing nephrectomies during this period were included in the study. note that donor nephrectomies are not included. similarly, pediatric laparoscopy is not routine, so patients undergoing nephrectomy but at or below 14 years of age were excluded. a total of 78 files of nephrectomies patients were retrieved from the record room and thoroughly reviewed by a single observer for the entries of all the parameters in question. all the patients were operated on by a single experienced surgeon. patients undergoing both simple and radical nephrectomy were included. the open simple nephrectomy (osn) was performed by retroperitoneal approach and supra twelve incision and the standard nephrectomy steps were followed. all the laparoscopic simple nephrectomies (lsn), laparoscopic radical nephrectomies (lrn), and open radical nephrectomies (orn) were performed transperitoneally. the lsn, lrn, and orns were performed by standard techniques except that only three ports were used for the left-sided and four ports for the right-sided laparoscopic procedures as opposed to the standard of four and five ports respectively. the laparoscopic specimen was retrieved through different incision sites according to the surgeon’s preference, mostly through the extension of the 10mm port site incision subcostal. the information retrieved was about age, gender, co-morbidities (diabetes, hypertension, renal impairment), clinical t-stage, hospital stay, operating time, estimated blood loss, post-operative analgesia requirement, laterality, indication for nephrectomy, placement of drain and catheter and their removal, conversion and its indications, per-operative complication, and early and late complications. all the data were analyzed by spss version 22. the categorical data were compared using the chi-square test and the numerical data by student t-test and a p-value of less than 0.005 were considered to be statistically significant. results our study included a total of 78 cases, 38(48.7%) males and 40(51.3%) females. the patient's ages ranged from 17 to 100 years with a mean of 42.69 years. 37 (47.4%) had left-sided nephrectomies and 41(52.6) had rightsided. 31(39.7%) had hypertension and 15(19.2%) had diabetes mellitus. open nephrectomy was done in 40 patients (17 simple and 23 radical) and laparoscopic nephrectomy in 38 patients (28 simple and 10 radical) as shown in (table 1). the average operating time for open nephrectomy was 160.5minutes (minimum 80 min and maximum 240 min) and 130.9 minutes (minimum 70 min and maximum 240 min) for laparoscopic nephrectomy. the average blood loss 391 journal of rawalpindi medical college (jrmc); 2022; 26(3): 389-394 during open and laparoscopic nephrectomy was 361.25 ml (minimum 50 ml and maximum 750 ml) and 59.86 ml (minimum 10 ml and maximum 300 ml) respectively. blood transfusion rate in open and laparoscopic nephrectomy was 55% and 10.5% respectively (p=0.001). in the laparoscopic group, 3 patients required a single pint transfusion, and 1 patient required 2 pints. while in the open group 9 patients required a single pint, 9 patients 2 pints, 3 patients 3 pints and 1 patient required 5 pints of blood transfusion. overall, the post-operative complication rate was 52.5% and 21.5% for an open and laparoscopic approach. post-operative pain was noted in 7.9% (3) patients with a laparoscopic approach and 97.5% (39) for an open approach. fever was noted postoperatively in 26.3% (10) and 62.5% (25) patients in laparoscopic and open approaches respectively (p=0.001). student’s t-test was used to calculate the pvalue. the average hospital stay in the laparoscopic approach was 2.8 days (minimum 2 days and maximum 6 days) and 4.5 days (minimum 2 days and maximum 23 days) in the open approach. the mean size of the tumor was 5.65 cm (minimum 4.0cm and maximum 9.0 cm) in the laparoscopic approach while 8.1cm (minimum 3.5 cm and maximum 16.8 cm) in the open approach. catheter and drain removal were on average 1.18 days (minimum 1 day and maximum 3 days) and 1.32 days (minimum 1day and maximum 2 days) post-op day in the laparoscopic group while it was 2.35 days (minimum 1 day and maximum 11 days) and 2.3 days (minimum 1 day and maximum 5 days) post-op day in an open group, respectively. there were no per-op complications in the laparoscopic approach as compared to 2 cases of minor ivc injury in the open approach. there were no conversions from laparoscopic to open. table 1: procedure simple nephrecto my radical nephrecto my total appr oach open 17 23 40 laparo -scopic 28 10 38 total 45 33 78 table: 2 approach total open laparoscopic dm no 31 32 63 yes 9 6 15 total 40 38 78 table 3: approach total open laparoscopic htn no 19 28 47 yes 21 10 31 total 40 38 78 discussion open surgery is being replaced by a laparoscopic approach since 1986 when the first laparoscopic cholecystectomy was done. over a period of time, laparoscopic nephrectomy has become the gold standard treatment.9 in our study, we have, retrospectively, done a comparative analysis of the outcomes of open and laparoscopic nephrectomy. in our study, the file records of a total of 78 patients, who underwent nephrectomies from january 2018 to january 2020, were reviewed and various parameters were observed. our study included a total of 78 cases, 38(48.7%) males and 40(51.3%) females. the patient's ages ranged from 17 to 100 years with a mean of 42.69 years. the mean age of patients in the laparoscopic group was 38.34 years (min 17-max 73) and it was 46.83 years (min 18 – max 100). the mean age in our study shows a younger population for the laparoscopic group (28 simple and 10 radical) as compared to the open group (17 simple and 23 radical). but it is worth mentioning here that our study was not limited to only malignant cases but also simple nephrectomies and patients with nonfunctioning kidneys may present at an early age, as opposed to the findings in the study of yang et al. however, our study showed a similar trend in laterality of the pathology.10 37 (47.4%) had left-sided nephrectomies and 41(52.6) right-sided. 31(39.7%) had hypertension and 15(19.2%) had diabetes mellitus. diabetes was present in 6(15%) cases in the laparoscopic group and 9(22%) in open cases while hypertension was present in 10(26.3%) cases in the laparoscopic group and 21(52.5%) cases in an open group. this finding is supported by the findings of hakmin lee et al.11 open nephrectomy was done in 40 patients (17 simple and 23 radical) and laparoscopic nephrectomy in 38 patients (28 simple and 10 radical). the average operating time for open nephrectomy was 160.5 minutes (minimum 80 min and maximum 240 min) and 130.9 minutes (minimum 70 min and maximum 240 min) for laparoscopic nephrectomy (pvalue). here we can see the difference of 29.6 minutes with an advantage to the laparoscopic group. 392 journal of rawalpindi medical college (jrmc); 2022; 26(3): 389-394 similarly, the difference in time has been shown in many other studies where laparoscopy has an advantage over the open approach.2,8,9,12 xu h et al noted advantage of 27.9 minutes for open surgery13 while reifsnyder je et al noted it to be 42 minutes in favour of laparoscopy14. this time advantage may be due to several reasons but the prominent one is that laparoscopy has smaller incisions which are quicker to be made and quicker to be closed as compared to o[pen surgery. the dissection of the kidney and especially the pedicle is easier in laparoscopy as compared to the open approach. the average blood loss during open and laparoscopic nephrectomy was 361.25 ml (minimum 50 ml and maximum 750 ml) and 59.86 ml (minimum 10 ml and maximum 300 ml) respectively (p-value). we noted a significant difference in blood loss with advantage laparoscopy. our findings are endorsed by many.12,14,15 however, xu h et al noted no difference between the two groups13, and lee h et al noted an increased blood loss in the laparoscopic group. in our opinion, the decreased amount of blood loss in the laparoscopic group may be the result of improved magnified vision and access to visualize and coagulate even the smaller bleeders which may, by the end of the procedure, contribute to the overall blood loss. blood transfusion rate in open and laparoscopic nephrectomy was 55% and 10.5% respectively (p=0.001). in the laparoscopic group, 3 patients required a single pint transfusion, and 1 patient required 2 pints. while in the open group 9 patients required a single pint, 9 patients 2 pints, 3 patients 3 pints and 1 patient required 5 pints of blood transfusion. overall, the post-operative complication rate was 52.5% and 21.5% for an open and laparoscopic approach. post-operative pain was noted in 7.9% (3) patients with a laparoscopic approach and 97.5% (39) for an open approach. fever was noted postoperatively in 26.3% (10) and 62.5% (25) patients in laparoscopic and open approaches respectively (p=0.001). the average hospital stay in the laparoscopic approach was 2.8 days (minimum 2 days and maximum 6 days) and 4.5 days (minimum 2days and maximum 23 days) in the open approach. 8(9.2-7.6) 9(5.0&2.6) the mean size of the tumor was 5.65 cm (minimum 4.0cm and maximum 9.0 cm) in the laparoscopic approach while 8.1 cm (minimum 3.5 cm and maximum 16.8 cm) in the open approach. this is a similar finding as shown by parker pa et al.16 catheter and drain removal were on average 1.18 days (minimum 1 day and maximum 3 days) and 1.32 days (minimum 1 day and maximum 2 days) post-op day in the laparoscopic group while it was 2.35 days (minimum 1 day and maximum 11 days) and 2.3 days (minimum 1 day and maximum 5 days) post-op day in an open group, respectively. there were no per-op complications in the laparoscopic approach as compared to 2 cases of minor ivc injury in the open approach. there were no conversions from laparoscopic to open. it is evident from the results that overall, patients undergoing laparoscopic nephrectomies had no intraoperative complications as compared to the open approach. two patients in the open group had a small tear in the inferior vena cava and in both cases, a repair with a 5/0 prolene was done and the patients fared well. another limitation of our study is that in the open radical nephrectomy group, the majority of patients had tumors of larger sizes, the majority being more than 6cm while in the laparoscopic radical nephrectomy group, there was no tumor above 9cm. one patient in the laparoscopic radical nephrectomy group developed an incisional hernia over a period of 6 months. this patient was a 65 years old lady who was multi-para and was having very thin/weak abdominal muscles the specimen was retrieved through a grid iron incision as compared to other cases where organ retrieval was done through a small subcostal incision by just enlarging a 10mm port site. one patient who died on the first post-op day in the open simple nephrectomy group was a 59 years old lady who had copd, crf and her possible cause of death was pe rather than a surgical complication. one patient in the open group developed renal failure and jaundice secondary to severe hypotension in a perioperative and post-operative period which was attributed to an acute cardiac event and this patient was managed successfully and recovered fully. patients in the laparoscopic group developed wound infections which were managed successfully with iv antibiotics. however, 2 patients in the open group developed wound infections that required repeated debridement and hence prolonged hospital stay, and their wound swabs revealed pseudomonas infections. all the patients in the laparoscopic group who developed fever post-operatively were managed with paracetamol as the maximum temperature recorded was 100 f. the transfusion rate in our review of open and laparoscopic nephrectomy was 55% and 10.5% respectively (p=0.001). in the laparoscopic group, 3 393 journal of rawalpindi medical college (jrmc); 2022; 26(3): 389-394 patients required a single pint transfusion, and 1 patient required 2 pints. while in the open group 9 patients required a single pint, 9 patients 2 pints, 3 patients 3 pints and 1 patient required 5 pints of blood transfusion. the transfusion rate for open cases was high but the file review showed that patients who received 2, 3, or more pints of blood received them preoperatively due to low hb, and 3 patients required even clot evacuation from the bladder secondary to hematuria. a study conducted in india by tapan agrawal et al17 revealed that out of 97 procedures 6 were converted to open surgeries due to vascular injuries, adhesions, and bowel injuries and 46% of patients develop complications while no mortality was in patients undergoing laparoscopic surgeries for renal pathology. a similar study conducted in south africa reveals that the mean duration of hospital stay and hdu admission in the laparoscopic group was 5 days, 12.1% as compared to 10 days and 50% in open nephrectomy. open surgeries were having 9.9% while laparoscopic nephrectomies were having no complications.18 a study conducted in rajavithi hospital thailand shows that the rate of complications was 31.0% in open and 13.2% in laparoscopic. average blood loss and length of hospital stay in open versus laparoscopic surgery were 871.59+1,125.62 ml vs. 290.00+262.00; p = 0.002) while in our study blood loss was 361.25ml and 59.86ml, and hospital stay were 8.91+3.89 days vs. 6.58+1.87 days; p = 0.001, while in our study were 2.8days and 4.5days respectively.19 our study has limitations that need to be addressed such as a retrospective, single-center study with small sample size and a shorter follow-up. a prospective, randomized controlled analysis with a longer followup may give a better understanding of the oncological outcomes of laparoscopic versus open radical nephrectomies especially. however, it is recommended that more and more surgeons need to be trained in laparoscopy as this approach has obvious advantages in terms of fewer peri-operative and post-operative complications, shorter hospital stay, less pain, early drain, and catheter removal, reduced blood loss and transfusion rates, and last but not the least, cosmetically more acceptable scars. conclusion after the analysis of our study, we can conclude that the laparoscopic approach for nephrectomy is far superior as compared to the open approach and it is recommended that laparoscopic simple and radical nephrectomy should be considered a gold standard treatment. it is further recommended to do awareness programs in our region to ensure that more and more surgeons and surgical trainees be trained in laparoscopic surgery in order to compete with the rest of the world where minimally invasive techniques are the standard of care. references 1. clayman rv, kavoussi lr, soper nj. laparoscopic nephrectomy. n eng j med 1991; 324: 1370-1371. doi.org/10.1016/j.juro.2016.10.074 2. binsaleh s, alomar m, madbouly k. pfannenstiel incision for intact specimen extraction in laparoscopic transperitoneal radical nephrectomy: a longitudinal prospective outcome study. clinics 2015;70(7):475-480. 3. sanli o, tefik t, ortac m, karadeniz m, oktar t, nane i, tunc m. laparoscopic nephrectomy in patients udergoing hemodialysis treatment. jsls 2010;14:534-540. doi: 10.4293/108680810x12924466008123 4. skrekas g, papalois ve, mitsis m, hakim ns. laparoscopic live donor nephrectomy: a step forward in kidney transplantation? jsls 2003;7:197-206. 5. jain s, saltzman, miller a, ortiz j, nofziger j. same-day discharge for laparoscopic donor nephrectomy. jsls 2017;21(2) e2017.00019. doi: 10.4293/jsls.2017.00019 6. mahesan n, choudhury sm, khan ms, murphy dg, dasgupta p. one hand is better than two: conversion from pure laparoscopic to the hand-assisted approach during difficult nephrectomy. ann r coll surg engl 32011;93:229-231. doi.org/10.1308/003588411x563970 7. silberestein j, parsons k. hand-assisted and total laparoscopic nephrectomy: a comparison. jsls 2009;13:36-43. 8. dirie ni, wang q, wang s. two-dimentional versus threedimentional laparoscopic systems in urology: a systematic review and meta-analysis. journal of endourology 2018;32(9):781-790. doi.org/10.1089/end.2018.0411 9. eskicorapci se, teber d, schulze m, ates m, stock c, rassweiler jj. lparoscopic radical nephrectomy: the new gold standard surgical treament for localized renal cell carcinoma. tsw urology 2007;2:99-110. doi.org/10.1100/tsw.2007.153 10. yang f, zhou q, li x, xing n. the methods and techneques of identifying renal pedicle vessels during retroperitoneal laparoscopic radical and partial nephrectomy. world journal of surgical oncology 2019;17:38. 11. lee h, lee cu, yoo jh, et al. comparison of oncological outcomes and perioperative complications between laparoscopic and open radical nephrectomies in patients with clinical t2 renal cell carcinoma(≥7cm). plos one 13(1):e0191786. doi.org/10.1371/journal.pone.0191786 12. rosoff js, raman jd, sosa re, del pizzo jj. laparoscopic radical nephrectomy for renal masses 7 centimeters or larger. jsls 2009;13:148-153. 13. xu h, ding q, jiang h. fewer complications after laparoscopic nephrectomy as compared to the open procedure with the modified clavien classification system-a retrospective analysis from southern china. world journal of surgical oncology. 2014;12:242. (http://www.wjso.com/content/12/1/242) 14. reifsnyder je, ramasamy r, shariat sf. laparoscopic and open partial nerphrectomy: complication comparasion using 394 journal of rawalpindi medical college (jrmc); 2022; 26(3): 389-394 the clavien system. jsls 2012;16:38-44. doi: 10.4293/108680812x13291597716942 15. ma l, yu y, ge g, li g. laparaoscopic nephrectomy outside gerota fascia and en bloc ligation of the renal hilum for management of inflammatory renal diseases. ibju 2018;44(2):280-287. doi.org/10.1590/s16775538.ibju.2017.0363 16. parker pa, swartz r, fellman b, urbauer d, li y, pisters ll, rosser cj, wood cg, matin sf. comprehensive assessment of quality of life and psychosocial adjustment in patients with renal tumours undergoing open, laparoscopic and nephron-sparing surgery. j urol 2012;187(3):. doi:10.1016/j.juro.2011.10.151. doi.org/10.1016/j.juro.2011.10.151 17. agrawal t, kumar r, singh p, saini a, seth a, dogra p. have we overcome the complications of laparoscopic nephrectomy? a prospective, cohort study using the modified clavien–dindo scale. indian journal of urology: iju: journal of the urological society of india. 2017 jul;33(3):216. doi: 10.4103/iju.iju_47_17 18. singh a, urry rj. laparoscopic versus open nephrectomy in resource-constrained developing world hospitals: a retrospective analysis. african journal of urology. 2020 dec;26(1):-8. 19. thaidumrong t, duangkae s. comparison of the outcomes of laparoscopic and open nephrectomy in rajavithi hospital. journal of the medical association of thailand. 2018 feb 1;101(2):103. 491 journal of rawalpindi medical college (jrmc); 2022; 26(3): 491-496 original article the frequency of stroke-acquired pneumonia in patients admitted to icu with cerebrovascular accident (cva) muhammad azeem-ur-rehman1, muhammad asim saddique2, muhammad bilal3, kashif rauf4, komal jabeen5, qudsia anjum qureshi6 1 medical specialist, khawaja arshad hospital, sargodha. 2 consultant cardiologist, niazi medical complex, sargodha. 3 medical officer, district head-quarter hospital, sargodha. 4 consultant, department of biochemistry, rawalpindi medical university, rawalpindi. 5 m.phil pharmacology, institute of physiology & pharmacology, university of agriculture, faisalabad. 6 assistant professor, rawalpindi institute of cardiology, rawalpindi. author’s contribution 1 conception of study 3 experimentation/study conduction 5 analysis/interpretation/discussion 2,5 manuscript writing 2,4 critical review corresponding author dr. muhammad asim saddique, consultant cardiologist, niazi medical complex, sargodha email: drasimsaddique@hotmail.com article processing received: 11/05/2022 accepted: 31/08/2022 cite this article: rehman, m.a., saddique, m.a., bilal, m., rauf, k., jabeen, k., qureshi, q.a. the frequency of stroke-acquired pneumonia in patients admitted to icu with cerebrovascular accident (cva). journal of rawalpindi medical college. 30 sep. 2022; 26(3): 491-496. doi: https://doi.org/10.37939/jrmc.v26i3.1947 conflict of interest: nil funding source: nil access online: abstract introduction: stroke is the most prevalent disorder. in our country, it can cause significant mortality and morbidity due to its associated complications such as stroke-associated pneumonia (sap). stroke can be fatal directly due to affecting the respiratory system and neurological damage. stroke-acquired pneumonia is defined as any respiratory tract infection acquired within 7 days of stroke. objective: to find out the actual frequency of stroke-acquired pneumonia in icu patients. study design: descriptive case series. setting: department of medicine, dhq teaching hospital, sargodha. duration: six months from 15th october 2018 to 15th april 2019. materials and methods: in this study, the cases of either gender or aged 30 to 70 years suffering from stroke within 12 hours were included. sap was labelled based on fever, cough, and non-homogenous opacities on chest x-ray. results: current study comprises about 160 cases of stroke and out of these 78 were (48.75%) females and 82 (51.25%) were males. the mean duration of stroke was 7.05±2.54 hours and the average age of the subjects was 54.24±7.15 years. they were 30 (18.75%) cases that had a history of smoking, 28 (17.50%) had htn, and 35 (21.88%) cases that had dm. stroke-acquired pneumonia (sap) was seen in 20 (12.50%) of the cases. sap was seen in 12 (15.38%) female cases as compared to 8 (9.75%) males with p= 0.34. sap was more seen in cases with dm where this was observed in 7 (20%) of the cases as compared to 13 (10.4%) with no dm with p= 0.15. sap was seen in 5 (17.85%) cases with htn and 4 (13.33%) cases with a history of smoking with p values of 0.35 and 1.0 respectively. sap was seen in 15 (14.42%) cases with a duration of stroke of 6-12 hours in contrast to 5 (8.92%) cases with a duration less than this with p= 0.45. conclusion: sap is not infrequent and is found in more than 1 out of every 10 cases and the cases of sap were found more in females and those who have a history of dm, htn, and a duration of stroke of 6 to 12 hours; though none of this variable was found statistically significant. keywords: sap, htn, dm, smoking. 492 journal of rawalpindi medical college (jrmc); 2022; 26(3): 491-496 introduction because of its consequences, acute ischemic stroke is associated with a poor clinical prognosis. by assessing the occurrence and adopting suitable therapeutic approaches, such complications can be avoided. pneumonia is among the most frequent respiratory complications of a stroke, affecting 4 to 9% of those who have it. the prevalence of this type of pneumonia seems to be much higher among the patients in the neurologic intensive care unit (21%) with acute ischemic stroke and the patient with tube feeding (44%).1,2 when compared with individuals lacking pneumonia, people with stroke-related pneumonia had a mortality rate and a worse protracted prognosis. clinical manifestation of pneumonia is high fever during the first 48 hours after facing the acute stroke and moreover, it is among the commonest complication up to a month after supra tentorial ischemic infarction. furthermore, evidence suggests that pneumonia and respiratory disease are by far the most common causes of re-hospitalization among stroke survivors in the first five years following the ischemic stroke. a total of 412 individuals with acute ischemic stroke were included in the investigation. in a prospective study, 412 patients with acute stroke were included. amongst this population age >65 years, dysarthria or aphasia, severe post-stroke disability, cognitive impairment, and an abnormal water swallow test were all deemed independent predisposing factors for stroke-related pneumonia. a total of 124 patients with acute stroke who have been treated in the medical icu were studied in another prospective study. mechanical ventilation, an abnormal chest radiograph upon admission to the hospital, and dysphagia were all the predisposing factors in this study. admitted patients with facial palsy and a low state of consciousness were both independent risk factors for pneumonia, necessitating nasogastric feeding.3,4 various field studies indicate that gastric acid inhibition via h2 receptor blockers or proton pump inhibitors has been associated with a higher risk of acquiring nosocomial pneumonia. in a report of 1676 hospitalized patients admitted with acute stroke, it was seen that these medications were ordered in 80% of the patients, and hospital-acquired pneumonia developed in 17% of this population. the occurrence of nosocomial pneumonia was considerably greater in the acid-suppressive drug group compared to the control group (21 vs 4 percent, adjusted odds ratio 2.3, 95 percent ci 1.2-4.6).5 almost 60% of stroke-related pneumonia is caused by aspiration of stomach contents. the pulmonary complications of improper admission of fluid, particulate foreign substances, or natural secretions into the lower airways are known as aspiration pneumonitis. condition of pneumonia appears upon "aspiration" of pathogenic microorganisms from the oropharynx or nasal passage. the most common causes of aspiration pneumonia following the acute stroke are mainly due to stroke-related dysfunction of sensory and motor mechanisms involved in deglutition, or a lower state of consciousness that compromises the expectoration and epiglottis closure.1 aspiration pneumonia tends to affect interdependent pulmonary sections. if the patient aspirates when recumbent, the far more common locations of involvement are the posterior sections of the upper lobes or apex segments of the lower lobes, and the lower lobes if the patient aspirates whilst upright or semi-upright. healthcare-associated pneumonia (hcap) is defined as pneumonia that develops in an outpatient clinical setting or within 48 hours of hospitalization in admitted patients who are at high risk of infection from multidrug-resistant bacteria. hospitalization for 2 or more days in an inpatient facility within ninety days of present ailment, exposure to antibiotics, chemo, or wound management during thirty days of existing ailment, hemodialysis, or clinic-acquired infections are all potential causes for mdr bacterial infection in hcap. nowadays the term nosocomial pneumonia is reinstating as ventilatorassociated pneumonia (vap) and hospital-acquired pneumonia (hap). nonetheless, the term nosocomial pneumonia to date has its way in the nomenclature and is used still in many parts of the world. hospitalacquired infections have been considered as a "tip of the hat towards the more aggressive management of the populace, typified via the use of advanced techniques and special equipment," a significant factor in gravely ill individuals in pulmonary care.11 when pneumonia emerges at least 48 hours after hospitalization, it is referred to as hospitalacquired pneumonia (hap). it is characterized by an increased risk of being exposed to multi-drug resistance microorganisms 6 along with gram-negative pathogens.12 the below are major predisposing factors for interaction with such pathogens in hap:  antibiotics within ninety days of the illness being caught in the hospital.  a five-day or longer stay in the hospital.  increased antibiotic resistance in the community or the vicinity of a hospital. 493 journal of rawalpindi medical college (jrmc); 2022; 26(3): 491-496  immuno-compromised status of the patient or chemotherapy  hcap predisposing factors that determine exposure to mdr pathogens. materials and methods study design: the design for this investigation was a descriptive case study. study area/ settings: department of medicine, dhq hospital, sargodha. duration of study: approximately 6 months. sample size: a total of 160 samples size were calculated with a 95% confidence level, 5% margin of error, and taking an expected percentage of sap i.e. 11.7% in patients of stroke.5 sampling technique: non-probability, consecutive sampling. inclusion criteria: patients within the 30 – 70 years age group of both genders (male, female) presenting within 12 hours of stroke and admitted to icu were included in this study. exclusion criteria: patients with co-morbidity with other conditions like hepatic problems (ast>40iu, ast>40iu), nephritic problems (serum creatinine >1.2gm/dl), asthma (on medical record), previous acs (on medical record) and patients with pneumonia before stroke (on history) within last 1 month of stroke were excluded. data collection procedure: after the acceptance from the institutional ethical review committee, patients meeting the inclusion criteria were chosen from the emergency of the medical department of dhq in sargodha. it was decided to gain explicit consent. on a pre-configured performa, personal information such as name, age, gender, stroke duration, and recorded history of high blood pressure, diabetes, and smoking was also acquired and recorded. patients were then brought to the icu and monitored for 3 consecutive days. data was gathered if the patient acquired strokeassociated pneumonia within 72 hours, as defined by the operational criteria. all of this data was entered into performa. data / statistical analysis: all the data was entered in spss version 21.0, which was then used to analyze it. the mean and sd of quantitative variables including age and stroke duration were calculated. gender, diabetes, hypertension, smoking, and the outcome variable, sap, were all computed as percentages and frequency. to see how age, gender, stroke duration, hypertension, diabetes, and smoking affected the outcome variable, data were divided by age, gender, stroke duration, hypertension, diabetes, and smoking. the chi-square test was used after stratifying, and a pvalue of 0.05 was found to be significant. results the current study comprises about 160 cases of stroke and out of these 78 were (48.75%) females and 82 (51.25%) males (figure 1). the mean duration of stroke was 7.05±2.54 hours and the average age of the subjects was 54.24±7.15 years. they were 30 (18.75%) cases that had a history of smoking, 28 (17.50%) had htn, and 35 (21.88%) cases that had dm. sap was seen in 20 (12.50%) of the cases. sap was seen in 12 (15.38%) female cases as compared to 8 (9.75%) males with p= 0.34. there was no significant difference in terms of sap with different age groups (p= 1.0).sap was highly found in cases with dm where this was detected in 7 (20%) of the cases as compared to 13 (10.4%) with no dm with p= 0.15. sap was found in 5 (17.85%) cases with htn and 4 (13.33%) cases with a history of smoking with p values of 0.35 and 1.0 respectively. sap was seen in 15 (14.42%) cases with a duration of stroke of 6-12 hours in contrast to 5 (8.92%) cases with a duration less than this with p= 0.45. table 1: risk factors stratification with stroke acquired pneumonia (sap) risk factors stratification stroke acquired pneumonia (sap) p-value yes no total age group 30-49y 5(11.11%) 40(88.89%) 45(100.0%) 1.0 50-70y 15(13.04%) 100(86.96%) 115(100.0%) total 20(12.5%) 140(87.50%) 160(100.0%) gender male 8(9.75%) 74(90.25%) 82(100.0%) 0.34 female 12(15.38%) 66(84.62%) 78(100.0%) total 20(12.50%) 140(87.50%) 160(100.0%) hypertension yes 5(17.85%) 23(82.15%) 28(100.0%) 0.35 no 15(11.36%) 117(88.64%) 132(100.0%) total 20(12.5%) 140(87.5%) 160(100.0%) 494 journal of rawalpindi medical college (jrmc); 2022; 26(3): 491-496 diabetes yes 7(20%) 28(80%) 35(100.0%) 0.15 no 13(10.4%) 112(89.6%) 125(100.0%) total 20(12.5%) 140(87.5%) 160(100.0%) smoking yes 4(13.33%) 26(87.67%) 30(100.0%) 0.35 no 16(12.3%) 114(87.7%) 130(100.0%) total 20(12.5%) 140(87.5%) 160(100.0%) duration of sap <6 hr 5(8.92%) 51(8.92%) 56(100%) 0.45 6-12 hr 15(14.42%) 89(85.59%) 104(100%) total 20(12.5%) 140(87.5%) 160(100%) table 2: age in study subjects (n=160) age (years) mean 54.24 std. deviation 7.15 minimum 34 maximum 70 figure 1: gender distribution in study subjects (n=160) discussion stroke is a primary cause of disability, with fatal consequences, and can affect a wide range of entities, all of which have a significant impact directly or indirectly on one's life and life quality.11-15 according to a latest survey in pakistan, 21.8 percent of people have had a stroke or a transient ischemic attack.16 in our country, numerous studies on stroke mortality have found that mortality rates vary from 7 to 20%.nearly 60% of the patients affected by stroke are at increased risk of severe complications, and a large number of patients (89%) are unable to do normal tasks unaided. likewise the western world where a large proportion of the population has predisposing factors such as cardiac disorder, obesity, diabetes, high bp and dyslipidemia 16-17 the possible causes for strokes are the same in our country. pneumonia, along with other clinical and neurological problems, is one of the leading causes of mortality after a stroke.17 stroke-related pneumonia is more common in those who have had an acute ischemic stroke and are being treated in a neurology intensive care unit, with 21% and 44% requiring nasogastric tube feeding, respectively. pneumonia is the most prevalent cause of pyrexia in the first 48 hours after an acute stroke, and it is also found in most cases with common health consequences within 30 days after a supra-tentorial ischemic infarction.19 in the present study, stroke-acquired pneumonia was seen in 20 (12.50%) out of the 160 cases admitted with stroke. these results were comparable to the findings of the studies done in the past; however, a wide variable prevalence of this is seen in the past. sap was seen in 12 (15.38%) female cases as compared to 8 (9.75%) males with p= 0.34 in the present study. according to various studies done in the past on stroke patients, the frequency of stroke-acquired pneumonia ranged from 3.9 to 44% of cases that were admitted to the stroke units.20 according to a study by dziewas r et al, pneumonia related to stroke was diagnosed in 44% of the patients with acute stroke admitted to the icu.21 according to another study by teh wh et al it was seen in 11.7% of the cases.22 in a study overall prevalence of the stroke associated pneumonia was seen in 18 (18%) out of 100 cases admitted with stroke and out of these cases that had this there was no significant difference in terms of gender and 51% of the cases were males and 49% females. they further described that the chance of sap was highest in cases that had higher age groups where 3/4th of the cases were aged more than 50 years. however, there was no significant difference in both the age groups of the present study with a p-value of 1.0.23 according to various studies, the variability of the frequency of strokes can be due to the difference in the local protocols and the site of admission of these cases. the cases that were admitted to icu had better chances of early ventilation to protect the airways as compared to those that were admitted to the medical floors. furthermore, other factors like the time of the 495 journal of rawalpindi medical college (jrmc); 2022; 26(3): 491-496 start of feeding and the mode of this i.e. continuous, intermittent, and bolus have also been shown to impact the likelihood of development of this. there are a few other factors as well that can result in its high probability and that can be the difference in the level of care, regarding head postures, aspiration rechecks, and the need for ionotropic supports; all of these have shown their association with a variable degree as a risk factor for the development of sap.24-28 sap was more seen in cases with dm and htn, where this was observed in 7 (20%) of the cases as compared to 13 (10.4%) with no dm with p= 0.15 and 5 (17.85%) cases with htn with a p-value of 0.35; non-significant in both the aspects. there was not much data regarding these particular variables in previous studies. however, they had shown that the cases with co-morbid conditions like heart failure, dm and those with the immune-compromised condition had a higher likelihood of sap.29-33 in one study it was seen that the cases that had already a history of fever due to any causes, led to more cases with sap in a study done by yan f et al.29 furthermore, these studies described that the subtypes of stroke have also an influence on the development of sap, and more cases had a hemorrhagic stroke. in a study done by adrees et al, they found that hemorrhagic stroke leads to a higher risk of sap and was seen in around 2/3rd of the cases and so was seen in the other studies and this can be explained by the factor that this leads to an earlier and more detrimental effect on a consciousness level and that’s why this had more risk of aspiration.30 along with all these parameters, the cases that needed invasive mechanical ventilation had a higher risk of sap and that can be explained by the possibility of an increased risk of ventilator-associated pneumonia. the same above-mentioned studies also supported this data.31-36 sap was observed in 15 (14.42%) cases with a duration of stroke of 6-12 hours in contrast to 5 (8.92%) cases with a duration less than this with p= 0.45. there was no such data regarding the duration of stroke and sap, but this can be attributed to the fact that the cases that were left unattended or referred from the clinics and smaller centers were more at risk of aspirations and to develop sap as compared to the cases that presented earlier to the intensive care units where airways were relatively better managed. conclusion stroke-related pneumonia is prevalent, occurring in higher than 1 out of each 10 cases. it is much more common among females, those with a history of diabetes, high blood pressure, and a stroke lasting 6 to 12 hours; however, none of these variables were shown to be statistically significant. limitation this study has a few limitations, such as not looking for the kinds of stroke, such as hemorrhagic and/or ischemic, as well as the preceding history of fever and food tendencies in such instances. however, there were numerous positive aspects to this study, as it highlighted a previously underappreciated element of stroke that has a significant impact on total morbidity and death in such cases. references 1. johnston kc, li jy, lyden pd, et al. medical and neurological complications of ischemic stroke: experience from the ranttas trial. ranttas investigators. stroke 1998; 29:447. 2. ingeman a, andersen g, hundborg hh, et al. in-hospital medical complications, length of stay, and mortality among stroke unit patients. stroke 2011; 42:3214. 3. kim br, lee j, sohn mk, et al. risk factors and functional impact of medical complications in stroke. ann rehabil med 2017; 41:753. 4. sellars c, bowie l, bagg j, et al. risk factors for chest infection in acute stroke: a prospective cohort study. stroke 2007; 38:2284. 5. herzig sj, doughty c, lahoti s, et al. acid-suppressive medication use in acute stroke and hospital-acquired pneumonia. ann neurol 2014; 76:712. 6. anand n, kollef mh. the alphabet soup of pneumonia: cap, hap, hcap, nhap, and vap. seminrespircrit care med. 2009 feb. 30(1):3-9. [medline]. 7. el solh aa. nursing home-acquired pneumonia. seminrespircrit care med. 2009 feb. 30(1):16-25. [medline]. 8. kuti jl, shore e, palter m, nicolau dp. tackling empirical antibiotic therapy for ventilator-associated pneumonia in your icu: guidance for implementing the guidelines. seminrespircrit care med. 2009 feb. 30(1):102-15. [medline]. 9. kalil ac, metersky ml, klompas m, muscedere j, sweeney da, palmer lb, et al. executive summary: management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of america and the american thoracic society. clin infect dis. 2016 sep 1. 63 (5):575-82. [medline]. 10. chalmers jd, rother c, salih w, ewig s. healthcareassociated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. clin infect dis. 2014 feb. 58 (3):330-9. [medline]. 11. kung hc, hoyert dl, xu jq, murphy sl, and the division of vital statistics. deaths: final data for 2005. national vital statistics reports. hyattsville, md: national center for health statistics april 2008: 56(10). http://www.cdc.gov. available at http://bit.ly/i3ath5. accessed: january 13, 2011. 12. cillóniz c, ewig s, polverino e, marcos ma, esquinas c, gabarrús a, et al. microbial aetiology of community-acquired pneumonia and its relation to severity. thorax. 2011 apr. 66(4):340-6. [medline]. 496 journal of rawalpindi medical college (jrmc); 2022; 26(3): 491-496 13. fang wf, yang ky, wu cl, yu cj, chen cw, tu cy, et al. application and comparison of scoring indices to predict outcomes in patients with healthcare-associated pneumonia. crit care. 2011 jan 19. 15(1):r32. [medline]. 14. lim ws, van der eerden mm, laing r, boersma wg, karalus n, town gi, et al. defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. thorax. 2003 may. 58(5):377-82. [medline]. 15. sligl wi, majumdar sr, marrie tj. triaging severe pneumonia: what is the "score" on prediction rules?. crit care med. 2009 dec. 37(12):3166-8. [medline]. 16. phua j, see kc, chan yh, widjaja ls, aung nw, ngerng wj, et al. validation and clinical implications of the idsa/ats minor criteria for severe community-acquired pneumonia. thorax. 2009 jul. 64(7):598-603. [medline]. 17. bloos f, marshall jc, dellinger rp, et al. multinational, observational study of procalcitonin in icu patients with pneumonia requiring mechanical ventilation: a multicenter observational study. crit care. 2011 mar 7. 15(2):r88. [medline]. 18. el-solh aa, alhajhusain a, aboujaoude p, drinka p. validity of severity scores in hospitalized patients with nursing homeacquired pneumonia. chest. 2010 dec. 138(6):1371-6. [medline]. 19. españa pp, capelastegui a, gorordo i, esteban c, oribe m, ortega m, et al. development and validation of a clinical prediction rule for severe community-acquired pneumonia. am j respircrit care med. 2006 dec 1. 174(11):1249-56. [medline]. 20. rello j, rodriguez a, lisboa t, gallego m, lujan m, wunderink r. piro score for community-acquired pneumonia: a new prediction rule for assessment of severity in intensive care unit patients with community-acquired pneumonia. crit care med. 2009 feb. 37(2):456-62. [medline]. 21. charles pg, wolfe r, whitby m, fine mj, fuller aj, stirling r, et al. smart-cop: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. clin infect dis. 2008 aug 1. 47(3):375-84. [medline]. 22. light rw. clinical practice. pleural effusion. n engl j med. 2002 jun 20. 346 (25):1971-7. [medline]. 23. bafadhel m, clark tw, reid c, medina mj, batham s, barer mr, et al. procalcitonin and c reactive protein in hospitalised adult patients with community acquired pneumonia, exacerbation of asthma and chronic obstructive pulmonary disease. chest. 2010 oct 28. [medline]. 24. ketai l, jordan k, marom em. imaging infection. clin chest med. 2008 mar. 29(1):77-105, vi. [medline]. 25. kamal ak, itrat a, murtaza m, khan m, rasheed a, ali a. the burden of stroke and transient ischemic attack in pakistan: a community-based prevalence study. bmc neurol2009;9:58 26. farooq mu, majid a, reeves mj, birbeck gl. the epidemiology of stroke in pakistan: past, present, and future. int j stroke 2009;4:381-9. 27. taj f, zahid r, syeda ue, murtaza m, ahmed s, kamal ak. risk factors of stroke in pakistan: a dedicated stroke clinic experience. can j neurolsci2010;37:252-7. 28. koennecke hc, belz w, berfelde d. factors influencing inhospital mortality and morbidity in patients treated on a stroke unit. neurology 2011;77:965-972. 29. ingeman a, andersen g, hundborg hh. in-hospital medical complications, length of stay, and mortality among stroke unit patients. stroke 2011;42:3214. 30. hannawi b, rao cpv, suarez ji, bershad em. strokeassociated pneumonia: major advances and obstacles. cerebrovasc dis. 2013;35(5):430-43. 31. teh wh, smith cj, barlas rs, wood ad, bettencourt-silva jh, clark ab, et al. impact of stroke-associated pneumonia on mortality, length of hospitalization, and functional outcome. actaneurol scand. 2018.12956. 32. attar h, beilman c, sila c. stroke associated pneumonia; the university hospital-cleveland medical center experience. neurology. 2017;88(16):301. 33. sari im, seortidewi l, yokota c, kikuno m, koga m, toyoda k. comparison of characteristics of stroke-associated pneumonia in stroke care units in indonesia and japan. j stroke cereberovasc dis. 2017;26(2):280-85. 34. adrees m, subhanullah, rasool s, ahmad n. frequency of stroke associated pneumonia in stroke patients. apmc 2017;11(2):154-157. 35. vermeij fh, scholte op reimer wj, de man p. strokeassociated infection is an independent risk factor for poor outcome after acute ischemic stroke: data from the netherlands stroke survey. cerebrovasc dis 2009;27:465–71. 36. roger vl, go as, lloyd-jones dm. heart disease and stroke statistics – 2012 update: a report from the american heart association. circulation 2012;125:e2–e220. 404 not found jrmc vol. 27 (issue 2) journal of rawalpindi medical college https://doi.org/10.37939/jrmc.v27i2.2182 (c) 2023 by rawalpindi medical university 343 page no. occurrence of severe cognitive impairment in elderly individuals with poor glycemic control vs elderly individuals with no dm or good glycemic control: a case-control study basma salman1, fatima jehangir2, aroosa jahan3, saira aslam4, nadra ansari5 abstract background: there is substantial corroboration that diabetes (both t1dm and t2dm) plays an essential role in predisposition to cognitive decline thus leading to dementia in both human and animal studies. (1,2,3). there is a lack of data from our community to support this. we aim to observe the occurrence of cognitive impairment in individuals aged 65 or above with poor glycemic control and compare it with similar age groups of individuals with no dm or good glycemic control. frailty independently contributes to cognitive decline. we also assessed the frailty index and incorporated it into our result interpretation. methods: we conducted a case-control study in the primary health care center of ziauddin university from 1st december 2021 to 30th june 2022. cases included 83 individuals 65yrs with hba1c =7 and above and controls included 91 individuals 65yrs and above with hba1c <7. both groups were assessed for cognitive decline using the mmse score and cfs score to determine their dependency status. results: moderately uncontrolled diabetes had the highest association with severe cognitive decline(50%) p-value 0.000 and those who could not manage to do iadls were severely dementia in our study( p-value 0.046). we also found dm to be associated with high frailty scores. severely uncontrolled dm was associated with cfs of 5, meaning those dependent on others for instrumental activities of daily living. those who managed well independently were associated with pre dm in our study. ( p-value 0.041) conclusion: severe cognitive decline has a high association with uncontrolled glycemic control. keywords: iadls (instrumental activities of daily living), cfs (chronic frailty scale), mci (mild cognitive impairment), mmse (mini-mental state examination), dm (diabetes mellitus) 1 resident, ziauddin university; 2 associate professor, ziaudding university; 3 consultant, ziaudding university; 4 resident, ziauddin university; 5 resident, ziaudding university correspondence: dr basma salman, resident, ziauddin university, karachi. email: drbasmasalman@gmail.com cite this article: salman, b., jehangir, f., jahan, a., aslam, s., & ansari, n. (2023). occurrence of severe cognitive impairment in elderly individuals with poor glycemic control vs elderly individuals with good glycemic control or no dm: a case control study”. journal of rawalpindi medical college, 27(2). https://doi.org/10.37939/jrmc.v27i2.2182 received january 16, 2023; accepted may 07, 2023; published online june 24, 2023 1. introduction diabetes is a complex metabolic syndrome characterized by elevated levels of blood glucose which leads to serious damage to the heart, brain, blood vessels, eyes, kidneys and nerves over time. according to the international diabetes federation, in 2022, 26.7% of adults in pakistan are affected by diabetes making the total number of cases approximately 33 million. the number continues to rise globally and has been a great source of economic and physical disease burden. it has been established from several studies that diabetes mellitus type 1 and type 2 play an essential role in contributing to cognitive decline which may lead to dementia over the years. (1,2,3). a review of the literature has suggested that diabetes-related cognitive decline is closely linked to changes within the cns that are secondary to chronic hyperglycemia. (4-7) however its mechanism is poorly understood but believed to be attributed to a multitude of factors including persistent glucose peaks, cerebral and hippocampal atrophy, increase amyloid metabolism and direct cerebral glucotoxicity. hypoglycemia has been associated with an increased risk of developing cognitive impairment. (4) cognitive impairment is a broad term used to describe the analytical integrity of one’s brain. however, it is mainly related to memory but is not limited to, and includes comprehension, problem-solving, reasoning as well as decision-making abilities. there are sufficient studies to support that the elderly with dm show an increase in the rate of cognitive decline. frailty is a complex state of physical vulnerability attributed to multiple physiological changes. there is transpiring data in the literature to link frailty with cognitive deterioration. in addition, diabetes impairs cognitive function pathophysiologically similar to jrmc vol. 27 (issue 2) journal of rawalpindi medical college 344 alzheimer’s dementia thus rendering elderly frail individuals more susceptible. (3) we decided to conduct our study on the prevalence of cognitive impairment in the elderly population because there is a dearth of data on it from pakistan. although there are multiple studies done throughout the world associating mild cognitive impairment with dm. unfortunately, we don’t have enough data to establish strong evidence in our population. we aim to establish the association of glycemic control with mci in the elderly as well as find out its association with the degree of fragility in elderly individuals either with poor or good glycemic control. 2. materials & methods a case-control study was conducted in the primary health care center of ziauddin university, from 1st december 2021 to 30th june 2022. all patients coming to primary care centres aged 65 and above voluntarily willing to participate were enrolled in the study either case (dm or poor glycemic control) or controls (no dm or good glycemic control) with 83 and 91 patients in each group respectively. after taking the informed and voluntary written consent to participate in the study, family physicians asked questions of the subjects and fill the pre-designed questionnaire. cognitive impairment was assessed using the mmse score. the chronic frailty score was used to assess the frailty index. it evaluates specific domains, including comorbidity, function, and cognition, to generate a frailty score ranging from 1 (very fit) to 9 (terminally ill). higher scores mean greater risk. inclusion criteria the inclusion criteria for cases included any individual aged 65 or more having type 2 dm with hba1c>7 available in the past 3 months. inclusion criteria for controls are individuals 65 and above with hba1c <7 done in the past 3 months of the interview. exclusion criteria the exclusion criteria were any recent major cardiac or neurological event in the last 6 months like cva/mi/ malignancy/mental illness/covid-19 requiring hospitalization that may interfere with the mental functioning of the participating individuals, unavailability of recent hba1c report and patient refusal to participate. tools : the cognitive impairment will be assessed using the mmse score. (18) case or control enrolment will be based on their last available hba1c within the last 3 months. a chronic frailty score (9 points) was used to assess the frailty index. limitations: as we are a resource-limited community we do not have the resources or means to obtain multiple hba1c or obtain reliable history with evidence. we enrolled case/control based on a single available hba1c test. it may not pertain to accurate estimation of individuals with controlled dm or no dm. this accounts for the limitation of our study. spss analysis: data entry was done by using spss version 20. mean and standard deviation was analyzed for numerical variables like age and bmi. frequency and percentage were computed for categorical variables such as frailty score, mmse score, hba1c, and the presence of other co-morbidities. paired sample t-test was computed for comparing mmse score and hba1c. an independent ttest was computed to see the association of gender with mmse score. the association of underlying cognitive impairment with variables was analyzed by crosstabulation and chi-square was computed. p-value <0.05 was considered significant. 3. results the mean age of the participants was 70.21+5.39 years. on paired sample t-test mean mmse score was 24.89+2.87, mean hba1c was 7.2+1.4 with a p-value of 0.000. the mean frailty scale was 3.14+0.669. on the independent t-test, the mean of males and females were 25.47+2.65 and 24.21+2.99 respectively showing mmse score of males was significantly ( p-value 0.004) higher as compared to females. figure one demonstrates the association of glycemic control with the severity of cognitive decline depicting that moderately uncontrolled diabetes has the highest association with severe cognitive decline (50%) with a p-value of 0.000. jrmc vol. 27 (issue 2) journal of rawalpindi medical college 345 table-1 age of patients as compared to mmse score and fragility scale. x+sd p-value age in years 70.21+5.39 mmse score 24.89+2.87 0.000 frailty scale 3.14+0.669 gender males 25.47+2.65 females24.21+2.99 0.004 figure 2 shows the association of frailty with glycemic control. it was seen that those who could not manage to do iadls were severely dementia in our study. (pvalue 0.046) figure 3 demonstrates the association of frailty with glycemic control. severely uncontrolled dm was associated with cfs of 5 meaning those who were dependent on others for instrumental activities of daily living and those who were managing well independently were associated with pre dm in our study. (p-value 0.041). figure-1 glycemic control association with cognitive decline figure-2 association of the severity of frailty with the severity of dementia figure-3 association of frailty with glycemic control 5. discussion in our study, we compared the mmse scores of elderly individuals with poor glycemic control to the individuals with good glycemic control or no dm to establish the association of diabetes and/or poor glycemic control with cognitive decline. it has been suggested in the past from various studies that diabetes (both type 1 and 2) impairs cognitive function similar to alzheimer’s mechanism.(19,20,21) it has also been postulated earlier that diabetes causes similar neurodegeneration as dementia. (3) hypoglycemia is presumed to have a direct relationship with cognitive impairment. (3) in our study, we found similar results with poor glycemic controls corresponding to increased cognitive impairment. thus our study supports that poor glycemic control is associated with mild to moderate degrees of cognitive decline. interestingly they were also associated with higher degrees of frailty. largescale studies in the literature have shown a strong correlation between dementia and diabetes. (8-10) in a recent meta-analysis of 17 studies published in the scandinavian journal of primary health care (2020) they found consistent evidence to support dm as an independent risk factor for low cognitive ability in elderly individuals. (11) moreover, our study also links low levels of education to mild to moderate cognitive impairment. jrmc vol. 27 (issue 2) journal of rawalpindi medical college 346 in 2015 research collaboration from mayo clinic and shanghai reported that diabetes-related cognitive impairment was independent of age, gender and comorbidities.(13,14,15) whereas our study shows slightly higher mmse scores in males as compared to females (p-value 0.004). it can be attributed to gender inequality in terms of education and career opportunities prevailing in our society, especially in lower socioeconomic communities. frailty is a better predictor of health and functional capacity in elderly diabetics. (12) it has been established from several studies that there’s an association of cognitive impairment with frailty especially in attention and specialized functions. (15) diabetes contributes to the physical decline of an individual affecting their robustness and energy. (17) in our study elderly individuals with high frailty scores showed significant cognitive impairment in both diabetic or poor glycemic control as well as good glycemic control or no dm groups establishing frailty as an independent risk of cognitive impairment. however, we reported in our study that the incidence of severe dementia was associated with high frailty indices. furthermore, similar to our study another study from europe has shown increased evidence of alzheimer’s and vascular dementia in diabetics particularly individuals with poor glycemic control. (3.5) diabetes increases the risk of vascular as well as alzheimer’s dementia regardless of the age of diabetes diagnosis. (7,21,23) there can be more complex mechanisms involved in the neuro-regulation of glucose metabolism and vascular stressors in the brain. we need further research in the area to understand and alter this mechanism. another longitudinal cohort study was conducted in the usa in 2007 in which about 900+ participants were studied for a year and individuals with dm were found to have more incidence of mci similar to our study. (24) in addition, it was also evident that individuals with dm had more cerebrovascular accidents and hence vascular dementia was also more prevalent in them. (25,26,27) correspondingly, cognitive impairment has also been linked to individuals with lower educational levels comparable to our study. (28) we incidentally found that more robust and fit elderly individuals who had mild cognitive impairment fell into the pre-diabetes criteria. further studies are needed to find other factors contributing to these results in our population to develop a strong causative association between diabetes and cognitive impairment. 5. conclusion overall our study establishes a strong association of cognitive impairment with poor glycemic control in elderly individuals in our community. additionally, individuals with high frailty scores correspond to an increase incidence of cognitive impairment in both dm and non-dm groups affirming that frailty is an independent risk factor for cognitive impairment. hence we can state that both frailty and poor glycemic control contribute to cognitive decline in the elderly population in our community. conflicts of interestnone financial support: none to report. potential competing interests: none to report contributions: b.s, f.j conception of study b.s, a.j, s.a, n.a experimentation/study conduction b.s, f.j analysis/interpretation/discussion b.s manuscript writing f.j, a.j, s.a, n.a critical review b.s facilitation and material analysis references [1] wong rh, scholey a, howe pr. assessing premorbid cognitive ability in adults with type 2 diabetes mellitus—a review with implications for future intervention studies. current diabetes reports. 2014 nov;14:1-2. https://doi.org/10.1007/s11892-014-0547-4 [2] grünblatt e, bartl j, riederer p. the link between iron, metabolic syndrome, and alzheimer’s disease. journal of neural transmission. 2011 mar;118:371-9. https://doi.org/10.1007/s00702-010-0426-3 [3] biessels gj, staekenborg s, brunner e, brayne c, scheltens p. risk of dementia in diabetes mellitus: a systematic review. the lancet neurology. 2006 jan 1;5(1):64-74. https://doi.org/10.1016/s1474-4422(05)70284-2 [4] lyoo ik, yoon sj, musen g, simonson dc, weinger k, bolo n, ryan cm, kim je, renshaw pf, jacobson am. altered prefrontal glutamate–glutamine–γ-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus. arch gen psychiatry. 2009;66(8):878-887. doi:10.1001/archgenpsychiatry.2009.86 [5] kellar d, craft s. brain insulin resistance in alzheimer's disease and related disorders: mechanisms and therapeutic approaches. the lancet neurology. 2020 sep 1;19(9):758-66. https://doi.org/10.1016/s1474-4422(20)30231-3 jrmc vol. 27 (issue 2) journal of rawalpindi medical college 347 [6] kodl ct, seaquist er. cognitive dysfunction and diabetes mellitus. endocrine reviews. 2008 jun 1;29(4):494-511. https://doi.org/10.1210/er.2007-0034 [7] strachan mw. rd lawrence lecture 2010^. the brain as a target organ in type 2 diabetes: exploring the links with cognitive impairment and dementia. diabetic medicine. 2011 feb;28(2):141-7. https://doi.org/10.1111/j.14645491.2010.03199.x [8] yoshitake t, kiyohara y, kato i, ohmura t, iwamoto h, nakayama k, et al. incidence and risk factors of vascular dementia and alzheimer's disease in a defined elderly japanese population: the hisayama study. neurology. 1995 jun 1;45(6):1161-8. doi: https://doi.org/10.1212/wnl.45.6.1161 [9] leibson cl, rocca wa, hanson va, cha r, kokmen e, o'brien pc, palumbo pj. risk of dementia among persons with diabetes mellitus: a population-based cohort study. american journal of epidemiology. 1997 feb 15;145(4):301-8. https://doi.org/10.1093/oxfordjournals.aje.a009106 [10] ott a, stolk rp, van harskamp f, pols ha, hofman a, breteler mm. diabetes mellitus and the risk of dementia: the rotterdam study. neurology. 1999 dec 1;53(9):1937doi: https://doi.org/10.1212/wnl.53.9.1937 [11] papunen s, mustakallio-könönen a, auvinen j, timonen m, keinänen-kiukaanniemi s, sebert s. the association between diabetes and cognitive changes during aging. scand.j.phc. 2020 jul 2;38(3):281-90. https://doi.org/10.1080/02813432.2020.1802140 [12] von haehling s, anker sd, doehner w, morley je, vellas b. frailty and heart disease. int.j.cardiol. 2013 oct 3;168(3):17457. https://doi.org/10.1016/j.ijcard.2013.07.068 [13] zhao q, roberts ro, ding d, cha r, guo q, meng h, et al. diabetes is associated with worse executive function in both eastern and western populations: shanghai aging study and mayo clinic study of aging. journal of alzheimer's disease. 2015 jan 1;47(1):167-76. doi: 10.3233/jad-150073 [14] ebady sa, arami ma, shafigh mh. investigation on the relationship between diabetes mellitus type 2 and cognitive impairment. diabetes res clin pract. 2008;82:305–309. https://doi.org/10.1016/j.diabres.2008.08.020 [15] saedi e, gheini mr, faiz f, arami ma. diabetes mellitus and cognitive impairments. world j diabetes. 2016 sep 15;7(17):412-22. doi: 10.4239/wjd.v7.i17.412. pmid: 27660698; [16] canevelli m, cesari m, van kan ga. frailty and cognitive decline: how do they relate? current opinion in clinical nutrition and metabolic care 18(1):p 43-50, january 2015. | doi: 10.1097/mco.0000000000000133 [17] assar, mariam ela,b; laosa, olgaa,b; rodríguez mañas, leocadioa,b,c. diabetes and frailty. current opinion in clinical nutrition and metabolic care 22(1):p 52-57, january 2019. | doi: 10.1097/mco.0000000000000535 [18] wild s, roglic g, green a, sicree r, king h. global prevalence of diabetes: estimates for the year 2000 and projections for 2030. diabetes care. 2004 may 1;27(5):1047-53. https://doi.org/10.2337/diacare.27.5.1047 [19] xue m, xu w, ou yn, cao xp, tan ms, tan l, yu jt. diabetes mellitus and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 144 prospective studies. ageing research reviews. 2019 nov 1;55:100944. https://doi.org/10.1016/j.arr.2019.100944 [20] sutherland gt, lim j, srikanth v, bruce dg. epidemiological approaches to understanding the link between type 2 diabetes and dementia. journal of alzheimer's disease. 2017 jan 1;59(2):393-403. doi: 10.3233/jad-161194 [21] ojo o, brooke j. evaluating the association between diabetes, cognitive decline and dementia. int. j. environ. res. public health 2015, jul;12(7):8281-94. https://doi.org/10.3390/ijerph120708281 [22] luchsinger ja. adiposity, hyperinsulinemia, diabetes and alzheimer's disease: an epidemiological perspective. eur. j. pharmacol. 2008 may 6;585(1):119-29. https://doi.org/10.1016/j.ejphar.2008.02.048 [23] kloppenborg rp, van den berg e, kappelle lj, biessels gj. diabetes and other vascular risk factors for dementia: which factor matters most? a systematic review. eur.j.pharmacol. 2008 may 6;585(1):97-108. https://doi.org/10.1016/j.ejphar.2008.02.049 [24] luchsinger ja, reitz c, patel b, tang mx, manly jj, mayeux r. relation of diabetes to mild cognitive impairment. arch neurol. 2007;64(4):570-575. doi:10.1001/archneur.64.4.570 [25] curb jd, rodriguez bl, abbott rd, petrovitch h, ross gw, masaki kh, et al. longitudinal association of vascular and alzheimer’s dementias, diabetes, and glucose tolerance. neurology. 1999 mar 1;52(5):971-.doi: https://doi.org/10.1212/wnl.52.5.971 [26] tatemichi tk, desmond dw, paik m, figueroa m, gropen ti, stern y,et al. clinical determinants of dememtia related to stroke. annals of neurology: off.j.ana and child neurol s. 1993 jun;33(6):568-75. https://doi.org/10.1002/ana.410330603 [27] c.a. luis, d.a. loewenstein, a. acevedo, w.w. barker, r. duara neurology aug 2003, 61 (4) 438-444; doi: 10.1212/01.wnl.0000080366.90234.7f [28] luchsinger ja, tang m, miller j, green r, mayeux r. relation of higher folate intake to lower risk of alzheimer disease in the elderly. arch neurol. 2007;64(1):86–92. doi:10.1001/archneur.64.1.86. 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 215-218 215 original article anti chlamydial antibodies in women with ectopic pregnancy hina bokhari 1, imtenan shahid 2, farhan rasheed 3, abbas hayat 4 1.department of pathology , services institute of medical sciences, lahore;2. social security hospital, multan road, lahore; 3. department of pathology, allama iqbal medical college, lahore;4. department of pathology, rawalpindi medical university, rawalpindi abstract background: to compare the frequency of chlamydia trachomatis infection in women with ectopic and with normal pregnancies. methods: in this case-control study diagnosed patients of ectopic pregnancy(ep)were included . the control group comprised of early normal intra uterine pregnancies (1st trimester). a total number of 88, comprising 44 cases and 44 controls were included in this study. sera from patients was drawn at the time of operation or within the subsequent 24 hours. anti-chlamydial igg was performed by elisa. results: sampled cases population (n=44) had mean age distribution 26.48 years while among controls, mean age was 25.32 years. presenting symptoms of cases showed pelvic pain (54.5%), bleeding (27.3%), vomiting (11.4%) and burning micturition (6.8%). during contraceptive practices , out of 88 patients, 5 cases and 20 controls gave history of safe sex practices. out of 63 patients, who did not give history of any contraceptive practice, anti-chlamydia igg was detected in 11 cases and 5 controls. regarding anti-chlamydia igg distribution among cases and controls, igg was detected in 11(25%) cases and in 5(11.3%) controls. conclusion: frequency of anti-chlamydial igg antibodies was much higher in women with ectopic pregnancy (25%) as compared to healthy controls(11.3%). key words: ectopic pregnancy, elisa, enzyme linked immunosorbant assay, anti-chlamydia igg introduction ectopic pregnancy is pregnancy production outside the uterine cavity, with more than 98% of the implant in the fallopian tube. tubal ectopic pregnancy is the most common reason for maternal mortality in the first three months of pregnancy especially in developing countries. the main risk factors for tubal ectopic pregnancy are damage to the tubes from surgery or injury, smoking, in vitro fertilization and chlamydia trachomatis infection. 1,2 the main risk for tubal ectopic pregnancy factors are damage to the tubes from surgery or injury, smoking and in vitro fertilization.3 another important postulate for underlying cause of ectopic tubal may be the idea of change in transport media and environment of fallopian tubes leading to retention of the fetus.4 chlamydia infection is the most common sexually transmitted bacterial infection in the world, and it is highest in adolescents and young adults.5 chlamydia trachomatis is an obligate intracellular gram negative pathogens and the majority of infections are asymptomatic, and thus continues to be diagnosed in substantial proportion of the infected individuals who may develop complications. untreated cases of chlamydial infection can also cause chronic pelvic pain in women. ectopic pregnancy (ep), infertility and pelvic inflammatory disease (pid) are also caused by chlamydial infections.6chlamydia trachomatis passed during childbirth may cause neonatal conjunctivitis and pneumonia.7,8 chlamydia infection also leads to the continuous transmission of infection to and fro in sexual partners and thus causing chronicity. pelvic inflammatory disease is usually the ultimate outcome.6 inflammation ascends from the cervix of the infected female to the peritoneal cavity.9-11 several case control studies and group analysis concluded that ectopic pregnancies are due to the sequelae of chlamydia trachomatis salpingitis.12 despite the strong epidemiological, serological and histological associations between upper genital chlamydia infection and subsequent ectopic pregnancy and fallopian infertility , the pathogenic mechanism leading to tubal damage still needs to be determined.10 the appearance of plasma cell salpingitis has a strong commitment to women with ectopic pregnancy with anti-chlamydial igg positive. histopathologic findings of tubal tissue of chlamydia trachomatis associated ectopic pregnancy shows plasma cell infiltration in lamina propria and submucosa.13 journal of rawalpindi medical college (jrmc); 2017;21(3): 215-218 216 persistent infection and re-infection with c. trachomatis is linked to a deterioration in the long pass complications.14 capacity to form elementry body(eb) and reticulate body (rb) during replication cycle improves survival of organisms in the genital tract. 15 the eb and c. trachomatis adheres to the epithelial cell surface and incorporated into phagosomes, which migrate to the distal region of golgi complex and prevent lysosome fusion to chlamydia infection and contact immediate destruction.16 the infectious particles stability in humans, suggest that persistent infection may remain undetected for many years. once the fallopian tube epithelial cells are infected, degeneration and damage of inflammation along the tube steps in fallopian tube .agglutination aggravates edema and inflammation of the endometrium trumpet. it leads to trumpet clubbing and pili partial or complete obstruction of the cavity. peritonitis caused by chlamydia trachomatis, which can affect the uterus, fallopian tubes causes fibrin exudation on the surface of the ovary. often these adhesions are associated with chronic pelvic pain. subsequent episodes of pid doubles the risk of ectopic pregnancy and infertility. 17-19 chlamydia antibodies testing has been incorporated on large scale for workup of infertility and has proven to be a non-invasive examination and effective way in terms of the cost.20 other modalities include hysterosalpingogram (hsg) and laparoscopy. hsg is not cost effective and laparoscopy is an invasive procedure. despite of the clinical significance of the test for chlamydia antibodies, it has its limits, because of false negative and false positive results of the tests.21 as a cause of false negative chlamydia antibody tests, it has been assumed that igg antibodies may be reduced with the passage of time after c. trachomatis infection, in light of the time period between initial infection in adolescence and fertility work -up in adulthood. patients and methods this was a case-control study conducted in pathology department, holy family hospital. this study was conducted in a period of six months from june 2014 to november 2014. a total number of 88, comprising 44 cases and 44 controls were included in this study. simple random sampling was done. control group comprised of early normal intra uterine pregnancies (1st trimester). the diagnosis of ectopic pregnancy was confirmed on ultrasound. women using an intrauterine contraceptive device (iucd) at the time of conception and women with prior tubal surgery including tubal ligation were excluded from the study. after taking informed consent both cases and controls were interviewed using a questionnaire for age, sociodemographic characteristics, medical and obstetric histories. the patients' blood was collected for the detection of anti-chlamydia igg.all sera aliquots were kept at –20°c till evaluation for anti-chlamydial igg . positive and negative controls served as internal controls for the reliability of the test procedure were analyzed with each test. results age distribution of sampled population (n=88)ranged from 19 to 38 years, with a mean age of 25.90 years ± 3.91. sampled population was divided into four age groups. age group ranging from 19 to 24 years had 12 (27.3%) cases and 20 (45.5%) controls. age group ranging from 25-29 years had frequency of cases 23 (52.3%) and of controls 15 (34.1%). using chi square test, p value was non-significant (p value=0.91) showing equal age distribution among cases and controls (table 1). table 1: age distribution of cases and controls group cases no(%) controls n0(%) 19-24 years 12 (27.3%) 20(45.5%) 25-29 years 23 (52.3%) 15(34.1%) 30-34 years 8 (18.2%) 7(15.9%) >35 years 1(2.3%) 2(4.5%) total 44 (100.0%) 44 (100.0%) using chi square test, p value = 0.91 (non-significant) table 2: presenting complaints in patients with positive anti-chlamydial antibodies presenting complaint no(%) pelvic pain 24(54.5) bleeding 12(27.3) burning micturition 3(6.80 vomiting 5911.4) table 3: parity status distribution of cases (n=44) and controls (n=44) parity cases no(%) controls no(%) primigravida 4 9.1 17 38.6 multigravida 40 90.9 27 61.4 total 44 100.0 44 100.0 using chi square test, p value = 0.001 (significant) frequency of illiterate cases was 27.2%. pelvic pain (54.5%) was the commonest complaint (table 2). in patients’ group multigravida ware commonest 40(90.9%) and among controls 27(61.4%) were multigravida (table 3).regarding anti-chlamydia igg distribution among cases and controls, igg was journal of rawalpindi medical college (jrmc); 2017;21(3): 215-218 217 detected in 11(25%) cases and in 5(11.3%) controls. the difference was statistically non-significant at present sample size. (table 4) table 4: anti-chlamydia igg status of cases and controls antichlamydi a igg case frequency (percentage) control frequency (percentage) present 11% 25% 5 11.3% absent 33% 75% 39 88.7% total 44% 100% 44 100% using pearson chi-square test p value = 0.097;odds ratio = 0.385 (95% confidence interval 0.121 to 1.220) table 5: cross tabulation between parity & presence of anti-chlamydia igg among cases & controls parity group total case control primigravida antichlamydia igg absent 4 16 20 present 0 1 1 total 4 17 21 multigravida antichlamydia igg absent 29 23 52 present 11 4 15 total 40 27 67 using pearson chi-square test p value = 0.1 (non-significant) table 6: absence of safe sex practice and antichlamydia igg among cases and controls practice of safe sex group total case control no antichlamydia igg absent 28 19 47 present 11 5 16 total 39 24 63 using pearson chi-square test p value = 0.514;odds ratio = 0.67 (95% confidence interval 0.2 to 2.24) on cross tabulation, between parity and antichlamydia igg among cases and controls, out of 21 primigravida among control group, anti-chlamydia igg was present only in 1. while out of 67 multigravida patients, 11 among cases and 4 among control group were positive for anti-chlamydia igg. when chi-square test was applied, p value came out 0.1 i.e. non-significant. (table 5). on cross tabulation, safe sex practices among cases and controls, out of 88 patients, 5 cases and 20 controls gave history of safe sex practices. when we cross tabulated absence of safe sex practices and anti-chlamydia igg among cases and controls, out of 63 eligible sampled population anti-chlamydia igg was detected in 11 cases and 5 controls (table 6) discussion chlamydia trachomatis is a silent infection and remains asymptomatic in majority. it is associated with ectopic pregnancy with a varying degree in different populations. this association is much related with sexual practices behaviour of the target population. in developing world, prevalence of chlamydia trachomatis is supposedly increasing secondary to change in lifestyles, family traditions and western style of living. in present prevalence of anti-chlamydia igg i.e. infection with chlamydia trachomatis is high in women with ectopic pregnancy as compared to healthy controls. the total frequency of chlamydia trachomatis is quite in excess as presented by other studies. in another pakistani study, infection rate was reported 4% in women presenting to obstetric department of a tertiary care hospital of khyber pukhtunkhwa.22 the reason behind this difference may be sampling technique implied in our and the discussed study. similarly an indian study has shown chlamydia trachomatis infection rate 17.6% in tribal women.23 in an observational study of saudi population of pregnant females residing in makah, seropositivity of chlamydia trachomatis came out about 8.7%. 24 among cases with ectopic pregnancy, anti-chlamydia igg was detected in 25% patients showing a high prevalence among cases showing an association with early miscarriage. in one of previously elaborated study, 7.6% women with chlamydia trachomatis infection were infertile/sub fertile.22 in another study, 59.1% of sampled population had more than once diagnosis of chlamydia trachomatis infection prior to presentation with ectopic pregnancy. this study concluded that number of infections with chlamydia trachomatis and its duration is associated with ectopic pregnancy.25 among healthy pregnant controls, the frequency of chlamydia trachomatis was found high i.e. 11.3%. this shows an increasing trend in toll of sexually transmitted diseases in our population. in a norwegian study on pakistani couples, 1% women had positive chlamydia trachomatis (anti-chlamydia igg detected) as compared to 12% men with antichlamydia igg.26 cases presented with different symptoms. its spectrum may help us stratify the patients with more need of screening and treatment. pelvic pain was journal of rawalpindi medical college (jrmc); 2017;21(3): 215-218 218 found in 24 (54.5%) patients, bleeding in 12(27.3%), vomiting in 5(11.4%) and burning micturition in 3(6.8%). so we may conclude that the pregnant females presenting to antenatal services with above nonspecific symptoms should be screened for antichlamydia igg. regarding parity distribution of cases and controls, primigravida had frequency of 4(9.1%) among cases and 17 (38.6%) among controls. while cases showed frequency multigravida about 40(90.9%) and 27(61.4%) among controls were multigravida. safe sex practices may play an important role in prevention as depicted by data of our study. safe sex practices among cases was low i.e. 1.1% while45.5% among controls. conclusions 1. frequency of chlamydia trachomitis as detected by positive anti-chlamydia igg infection in women with ectopic pregnancies is 25% and with normal pregnancies is 11%.although in present sample size the difference is statistically non-significant but there is a difference in frequencies of chlamydia trachomatis as detected by positive anti-chlamydia igg infection in cases and controls. references 1. varma r, gupta j. tubal ectopic pregnancy. bmj clinical evidence. 2012. 2. al-azemi m, refaat b, amer s, ola b.expression of inducible nitric oxide synthase in human fallopian tube during menstrual cycle and in ectopic pregnancy. fertility and sterility. 2010 ;94(3):833-40. 3. tay j i, moore j, walker j j.ectopic pregnancy. bmj 200;, 320, 916-19. 4. felemban a, sammour a, tulandi t. serum vascular endothelial growth factor as a marker for early ectopic pregnancy. human reproduction 2002;17(2):490-92. 5. gerbase ac, rowley jt, heymann dh, berkley sf. global prevalence and incidence estimates of selected curable stds. sexually transmitted infections. 1998 ; 1;74(1):s12-s15. 6. nadala ec, goh bt, magbanua jp, barber p. performance evaluation of a new rapid urine test for chlamydia in men: prospective cohort study. bmj 2009;29;339-41. 7. bjartling c, osser s, persson k. deoxyribonucleic acid of chlamydia trachomatis in fresh tissue from the fallopian tubes of patients with ectopic pregnancy. european journal of obstetrics & gynecology and reproductive biology 2007; 30;134(1):95-100. 8. brocklehurst p, rooney g. interventions for treating genital chlamydia trachomatis infection in pregnancy. the cochrane library. 1998. 9. bender n, herrmann b, andersen b, hocking js. chlamydia infection, pelvic inflammatory disease, ectopic pregnancy and infertility. sex transm infect. 2011. 10. bakken ij. chlamydia trachomatis and ectopic pregnancy: recent epidemiological findings. current opinion in infectious diseases. 2008 ;21(1):77-82. 11. daponte a, pournaras s, deligeoroglou e. serum interleukin-1β, interleukin-8 and anti-heat shock 60 chlamydia trachomatis antibodies as markers of ectopic pregnancy. journal of reproductive iimmunology. 2012 ;93(2):102-08. 12. egger m, low n, smith gd, lindblom b. screening for chlamydial infections and the risk of ectopic pregnancy. bmj 1998;316(7147):1776-80. 13. brunham rc, peeling r, maclean ik, kosseim ml. chlamydia trachomatis-associated ectopic pregnancy: serologic and histologic correlates. journal of infectious diseases 1992;165(6):1076-81. 14. den hartog je, morre sa, land ja. chlamydia trachomatisassociated tubal factor subfertility: immunogenetic aspects and serological screening. human reproduction update. 2006 ;12(6):719-30. 15. kawana k, matsumoto j, miura s, shen l. expression of cd1d and ligand-induced cytokine production are tissue specific in mucosal epithelia of the human lower reproductive tract. infection and immunity. 2008 ;76(7):3011-18. 16. linhares im and witkin ss. immunopathogenic consequences of chlamydia trachomatis 60 kda heat shock protein expression in the female reproductive tract. cell stress and chaperones. 2010 ;15(5):467-73. 17. khan r and anwar f. rana p,.ectopic pregnancy –a review. arch gynecol obstet. 2013;288:747-57. 18. gijsen ap, land ja, goossens vj, slobbe me. chlamydia antibody testing in screening for tubal factor subfertility: the significance of igg antibody decline over time. human reproduction. 2002 ;17(3):699-703. 19. henry-suchet j, askienazy-elbhar m, thibon m. posttherapeutic evolution of serum chlamydial antibody titers in women with acute salpingitis and tubal infertility. fertility and sterility. 1994 ;62(2):296-304. 20. mol bw, ankum wm, bossuyt pm, van der veen f. contraception and the risk of ectopic pregnancy: a metaanalysis. contraception. 1995 ;52(6):337-41. 21. piura b, sarov b, sarov i. persistence of antichlamydial antibodies after treatment of acute salpingitis with doxycycline. european journal of obstetrics & gynecology and reproductive biology. 1993;48(2):117 21. 22. qayum m and khalid-bin-saleem m. prevalence of chlamydia trachomatis among asymptomatic women. journal of ayub medical college abbottabad. 2013 ;25(12):28-30. 23. rao vg, anvikar a, savargaonkar d, bhat j. prevalence of sexually transmitted disease syndromes in tribal population of central india. journal of epidemiology & community health. 2009 ;63(10):805-06. 24. ghazi ho, daghestani mh, mohamed mf. seropositivity of chlamydia trachomatis among saudi pregnant women in makkah. journal of family & community medicine. 2006 ;13(2):61-64. 25. batteiger b. descriptive characteristics and chlamydia (ct) testing in a cohort of women with ectopic pregnancy. national std prevention conference, 2012. cdc. 26. bjerke se, holter e, vangen s, stray-pedersen b. sexually transmitted infections among pakistani pregnant women and their husbands in norway. international journal of women's health. 2010;2:303-06. summary journal of rawalpindi medical college (jrmc); 2023; 27(1): 225-230 225 original article effect of reperfusion on time domain parameters of heart rate variability sadia mubarak1, bushra riaz2, mehwish ashfaq3, sidra hamid4, amina rasul5, mamoona shafiq6 1 associate professor, islamabad medical and dental college. 2 associate professor, pak international medical college. 3 assistant professor, department of physiology, hitecinstitute of medical sciences (ims) taxila. 4 assistant professor physiology, rawalpindi medical university. 5 associate professor, watim medical college, rawalpindi. 6 professor of physiology, islam medical college, sialkot author’s contribution 4 conception of study 1,2,3,4,5,6 experimentation/study conduction 1,2,3,4,5,6 analysis/interpretation/discussion 3,5 manuscript writing 1,2,3,4,5,6 critical review 1,2 facilitation and material analysis corresponding author dr. sadia mubarak associate professor islamabad medical and dental college islamabad email: sadia.smcian@gmail.com article processing received: 20/08/2022 accepted: 15/02/2023 cite this article: mubarak, s., riaz, b., ashfaq, m., hamid, s., rasul, a., & shafiq, m. (2023). effect of reperfusion on time domain parameters of heart rate variability. journal of rawalpindi medical college, 27(1). doi: https://doi.org/10.37939/jrmc.v27i1.2246 conflict of interest: nil funding source: nil abstract objective: to compare the effect of reperfusion by measuring time domain parameters of heart rate variability before and after percutaneous transluminal coronary angioplasty. study design: quasi-experimental study design place and duration: department of clinical cardiac electrophysiology, armed forces institute of cardiology/national institute of heart diseases (afic/nihd), rawalpindi in 2018. patients and methods: 40 patients with coronary artery disease having a mean age of 55.20 ± 8.03 years were recruited by non-probability convenience sampling. dms 300-4a holter monitors were used to obtain 24 hours of ambulatory ecg recording before and within 24 hours after percutaneous transluminal coronary angioplasty. digital ecg data were transferred to the computer and edited with the help of dms cardio scan software. heart rate variability was analyzed in time domain measures. for time domain analysis normal heart rate, sdnn, sdnni, sdann, rmssd, and pnn50 were recorded from 12 lead digital ecg data. results: the results of our study demonstrated significantly decreased heart rate variability in coronary artery disease patients on comparison of pre and post-angioplasty values only sdnni was significantly reduced (pvalue = 0.035) whereas the reduction in sdnn and pnn50 was statistically insignificant (p-value > 0.05). on the contrary, sdann and rmssd displayed a slight rise after angioplasty, but it was not significant (p-value > 0.05). conclusion: reperfusion after percutaneous transluminal coronary angioplasty decreases heart rate variability within 24 hours after the procedure. whereas heart rate during the same period after angioplasty increases. this reflects autonomic balance shifts towards sympathetic predominance as indicated by reduced heart rate variability and a rise in heart rate. this makes the susceptible patients vulnerable to the development of ventricular arrhythmias, especially during 24 hours after angioplasty. therefore, patients with decreased heart rate variability are at risk of ventricular arrhythmogenesis so they may be kept under medical surveillance for at least 24 hours after percutaneous transluminal coronary angioplasty. keywords: ischemia, holter monitoring, coronary artery disease, heart rate variability journal of rawalpindi medical college (jrmc); 2023; 27(1): 225-230 226 introduction according to the world health organization, ischemic heart disease due to coronary artery occlusion is the chief cause of death globally.1 severe ischemia can alter electrical potentials which can quicken fatal ventricular arrhythmias which may lead to sudden cardiac arrest.2 mostly fatal arrhythmia in ischemic heart disease patients results due to a disparity of the autonomic nervous system with the sympathetic multitude.3 various noninvasive methods have been established to forecast these events in patients and diversify the high-risk patients of sudden cardiac arrest.4 these include signal-averaged electrocardiogram, heart rate variability, q-t dispersion, heart rate turbulence, and t-wave alternan.5 heart rate variability (hrv) is a biological phenomenon defined as the chronological difference of heartbeat-to-beat variation in normal sinus rhythm.6 hrv is represented as variations in heart rate around the mean value. heart rate variability is also known as rr length variability or cardiac cycle variability. heart rate variability is regulated by the autonomic nervous system through the antagonistic activity of sympathetic and parasympathetic branches which results in oscillation of heart rate. on surface electrocardiogram, this oscillation is represented as recurring fluctuations in rr intervals.7 heart rate variability can be used as a non-invasive marker of the autonomic nervous system. different factors like respiration, baroreflex sensitivity, and genetic and environmental factors can affect heart rate variability by altering autonomic regulation. 8 heart rate variability is measured by time and frequency domain methods. frequency domain parameters are vlf (very low frequency), lf (low frequency), hf (high frequency), and lf/hf ratio. whereas time domain indices are sdnn (standard deviation of all normal to normal intervals in 24 hours), sdann (standard deviation of the 5-minute mean of normal to normal intervals), rmssd (root mean squared successive differences between adjacent normal to normal intervals over the entire recording) and pnn50 (percentage of differences between successive normal to normal intervals over 24 hours that are greater than 50 milliseconds).9 the time domain parameters of hrv are actually arithmetical derivations demonstrating the dispersion of normal oscillation of heartbeat.10 to do statistical analysis of time domain analysis in ecg recordings, we need a total of 24 hours to be edited and their mathematical derivatives are developed through statistical formulations.11 heart rate variability has been found to be reduced in patients with ischemic heart disease.12 chronic myocardial ischemia is the basis of redistribution of autonomic nerve endings, increased catecholamines, hypersensitivity for sympathetic stimulation, accumulation of metabolites, and electrolyte imbalance leading to structural and functional alterations in ventricles.13 these changes can cause heterogeneity of impulse propagation in ischemic tissues and decreased ventricular refractoriness which results in the onset of lethal arrhythmias.14 the current study was designed to determine the effect of reperfusion achieved by percutaneous transluminal coronary angioplasty on time domain parameters of heart rate variability in coronary artery disease patients. we planned to investigate the changes in heart rate variability using 24 hours of holter monitoring before and within 24 hours after percutaneous transluminal coronary angioplasty. the results of the study would provide insight into the early effects of reperfusion on autonomic imbalance within 24 hours. this would certainly help in improving the health care facilities provided to the susceptible patients who are at risk of ventricular arrhythmogenesis. materials and methods the study was a cross-sectional comparative study that was carried out at the cardiac electrophysiology department of the armed forces institute of cardiology (afic) in collaboration with army medical college, rawalpindi. the study was started after the official approval of the ethical review board of army medical college, rawalpindi. written informed consent was taken from all the patients undergoing the study. 50 coronary artery disease patients of either sex was encompassed in our study. the patients were diagnosed on the basis of angiography and those included had more than 70% occlusion of the vessel’s lumen. the diabetic, hypertensive, bundle block, and structural heart disease patients were not included in the study. we used dms 300-4a holters from “diagnostic journal of rawalpindi medical college (jrmc); 2023; 27(1): 225-230 227 monitoring software (dms)” us limited. we obtained 12-lead ecg recording pre and post-angioplasty. after effective pre-angioplasty monitoring in 53 patients the post angioplasty data in 6 patients could not be done because there was unsuccessful catheterization of occluded vessels which hampered our results as there was no successful reperfusion of the cardiac muscle. we discarded data of 7 patients due to distortions in more than two leads of the recordings. final data was of 40 patients with successful angioplasty and interpretable pre and post ecg recordings. inferential statistics were used for the comparison of continuous variables as the time field indices of hrv like sdnn, sdnni, sdann, pnn50 and rmssd. the data were also explored for the presence of outliers. parametric ‘one sample t test’ and ‘paired samples t test’ were used to compare pre-angioplasty time domain heart rate variability with normal reference values and post-angioplasty values respectively. the alpha value was set at < 0.05 for significance at confidence level of 95%. results we analyzed the data of 40 patients with mean age in years of 55.2 ± 8. there were 39 male and one female patients with male to female ratio of 39:1. pre and post-angioplasty mean heart rates were 75.95 ±5.88 and 78.55 ± 7.62 beats per minute respectively. shapiro wilk test showed that heart rate data followed normal distribution (p-value > 0.05). therefore ‘parametric, paired samples t test’ was applied to compare pre and post angioplasty heart rates. the result showed that post-angioplasty heart rate was significantly higher when compared to pre-angioplasty heart rate (p-value = 0.044) as shown in table 1. pre-angioplasty, time domain indices of heart rate variability were compared with the post-angioplasty indices as illustrated in table 3. values of sdnn, sdnni and pnn50 showed reduction after angioplasty as compared to the values before the procedure. however, only sdnni was significantly reduced (p-value = 0.035) whereas the reduction in sdnn and pnn50 was statistically insignificant (pvalue > 0.05). on the contrary, sdann and rmssd displayed slight rise after angioplasty, but it was not significant (p-value > 0.05). table-1 comparison of pre and post-angioplasty mean heart rates (n=40) *p-value significant (< 0.05), sd = standard deviation table-2 comparison of pre and post-angioplasty time domain indices of heart rate variability (n=40) time domain variables values (mean ± sd) one sample t-test preangioplasty postangioplasty t-value pvalue sdnn (ms) 102.15 ± 23.66 99.83 ± 34.416 0.425 0.673 sdnni (ms) 45.83 ± 11.09 41.60 ± 11.67 2.18 0.035* sdann (ms) 90.45 ± 24.66 92.00 ± 37.72 -0.267 0.791 rmssd (ms) 24.98 ± 7.26 25.50 ± 9.632 -0.320 0.751 pnn50 (%) 6.88 ± 6.12 6.10 ± 7.01 0.671 0.506 *p-value significant (< 0.05) discussion patients with coronary artery disease have significantly decreased heart rate as compared to the normal values in healthy people. on comparison of pre and post-angioplasty heart rate variability in patients with coronary artery disease, it was found that values of almost all the post-angioplasty heart rate variability time domain indices were decreased, however only sdnni was significantly decreased. the disequilibrium of autonomic nerves in the form of boosted sympathetic and diminished vagal activity heart rate values (mean ± sd) paired samples t-test t-value p-value pre-angioplasty 75.95 ± 5.88 -2.08 0.044* postangioplasty 78.55 ± 7.62 journal of rawalpindi medical college (jrmc); 2023; 27(1): 225-230 228 causes reduction in heartrate variability in the coronary occlusion patients.15 there are various articles suggesting that increased release of norepinephrine and enhanced disturbance in vagal nerve endings causes alteration of normal autonomic balance in patients with chronic ischemia.16 ischemia due to constant occlusion also causes redistribution of autonomic nerve endings. 17 this enhancement in inhomogeneity of autonomic innervation augments sympathetic response and causes reduction in vagal inflection in the ischemic patients which leads to reduction in heart rate variability.18 ischemia related changes are the underlying cause of reduced heart rate variability in coronary artery disease patients 19. therefore, it follows that removal of ischemia after reperfusion should enhance heart rate variability by restoring the balance of autonomic nervous system. however, effects of reperfusion on heart rate variability are complex, multifaceted and depend upon time after reperfusion at which heart rate variability is recorded. the effects of reperfusion can be divided into early i.e. within 24 hours of angioplasty and late i.e. after 24 hours especially after 3 to 5 days. early after angioplasty reperfusion decreases heart rate variability whereas late after angioplasty it increases the variability.20 time after angioplasty at which heart rate variability is recorded is therefore, an important factor in determining the final status of heart rate variability. on comparison of pre and post-angioplasty heart rate variability, we found that heart rate variability was reduced after the angioplasty. reduced heart rate variability denotes sympathetic predominance over the vagal activity. we analysed the post-angioplasty heart rate variability ‘early’ that is within 24 hours after angioplasty when the patients were retained in post-catheterization ward. as the patients were kept in hospital for a day after angioplasty, the anxiety level of the patients must be raised as they had undergone an invasive procedure of percutaneous transluminal coronary angioplasty. anxiety and stress is the outcome of sympathetic stimulation which reciprocally suppresses parasympathetic activity. this state of autonomic imbalance with sympathetic preponderance leads to reduction in heart rate variability. according to studies done by verkuil et al and pieper et al, anxiety can decrease heart rate variability and increase heart rate due to increased sympathetic drive during stress 21, 22. the logic of increased sympathetic inflection in our patients after angioplasty is also supported by a significant increase in average heart rate after angioplasty. the mean heart rate before angioplasty was 75.95 beats per minute whereas after the angioplasty it was 78.55 beats per minute. the post-angioplasty heart rate was significantly higher as compared to the initial value before the procedure (p=0.044). increased heart rate in our study population, after the procedure, indicates heightened sympathetic response which led to reduced heart rate variability in these patients. a certain amount of time is required for reperfusion to increase heart rate variability by restoring normal autonomic balance. however, the immediate effect of reperfusion is to decrease heart rate variability by inducing the ‘reperfusional injury’. transluminal ballooning pressure and sheer effect of blood flow cause intravascular muscular filament strain which can lead to transient oedema and denervation of myocardial nerve endings. this reperfusional injury involves especially the subendocardial layer where the vagal nerve endings are in abundance.13 local damage to vagal nerve endings in re-perfused myocardium may be another reason for reduced heart rate variability.23 a subcellular paradigm of reperfusional injury was explored by jennings who conducted a study to examine the effects of reperfusion on mitochondria.24 according to her, the mitochondria of injured myocardial cells swell extensively on reflow of calcium rich plasma. swollen mitochondria absorb calcium and calcium accumulation occurs inside them in the form of hydroxyapatite making amorphous matrix densities (amds).25 after 24 hours normal myocardium and injured myocardial cells are indistinguishable. the only signs left after a day is presence of amorphous matrix densities in the ischemic region. she concluded that cellular injury after reperfusion of ischemic myocardium persisted for at least 24 hours. we conducted our study within 24 hours of reperfusion when the acute cellular injury was there which might have affected the heart rate variability.24 the cumulative effect of anxiety and reperfusional injury along with damage to vagal nerve endings and mitochondria appear to be the logical basis for reduced heart rate variability in our study. erdogan et al evaluated heart rate variability in 139 patients with coronary artery disease and compared pre and post-angioplasty values.26 they analysed heart rate variability in both time and frequency domains within 24 hours after angioplasty. they reported that heart rate variability was reduced after the procedure but none of the parameters showed statistically significant reduction. erdogan et al concluded that revascularization did not affect heart rate variability journal of rawalpindi medical college (jrmc); 2023; 27(1): 225-230 229 within 24 hours which supported the results of our study. in a follow up study conducted by sedziwy et al, heart rate variability was measured in time domain at three different occasions after the angioplasty.27 they recruited 65 patients with coronary artery disease and analysed heart rate variability after 14 days, 3 months, 6 months and finally one year of reperfusion. they reported that heart rate variability was significantly higher when recorded 14 days after the procedure as compared to the pre-angioplasty value. their results are opposite to those of our study where we found decreased heart rate variability after angioplasty. the opposing results seem to be due to the different timings of heart rate variability recording after the procedure. we recorded heart rate variability within 24 hours after angioplasty whereas sedziwy et al had their first recording after 14 days of the procedure. sedziwy et al further reported that heart rate variability kept increasing significantly till three months after the procedure. after three months heart rate variability did not show any significant increase when measured at 6 months and one year after the procedure. the results imply that more the time elapses after angioplasty the better would-be autonomic balance but up till about three months. by three months, maximum optimization of the autonomic nervous system takes place and there is no additional change after that time. effects of reperfusion on heart rate variability are diverse and complicated. multiple factors with opposing effects on heart rate variability come into play simultaneously after reperfusion is achieved by angioplasty. some of these factors are altered catecholamine release due to anxiety, damage to vagal nerve endings and mitochondria due to reperfusion injury, extent of ischemia and reperfusion and the effects of ballooning. balance between these opposing factors determines the final status of heart rate variability. time at which heart rate variability is recorded after angioplasty is an important factor determining the ultimate balance between these opposing factors. within 24 hours after angioplasty the factors reducing heart rate variability predominate. after about 3 to 5 days these factors fade away and the ones increasing heart rate variability take over reflecting restoration of normal autonomic balance with vagal predominance.28 the process of improving heart rate variability continues up till about three months after angioplasty with no significant change beyond that time. conclusion reperfusion after percutaneous transluminal coronary angioplasty decreases time domain parameters of heart rate variability when recorded within 24 hours after the procedure. whereas heart rate during the same period after angioplasty increases. autonomic balance shifts towards sympathetic predominance as indicated by reduced heart rate variability and rise in heart rate. this makes the susceptible patients vulnerable to development of ventricular arrhythmias especially during 24 hours after angioplasty. therefore, patients at risk of ventricular arrhythmogenesis may be kept under medical surveillance for at least 24 hours after percutaneous transluminal coronary angioplasty. references 1. nowbar an, gitto m, howard jp, francis dp, al-lamee r. mortality from ischemic heart disease: analysis of data from the world health organization and coronary artery disease risk factors from ncd risk factor collaboration. circulation: cardiovascular quality and outcomes. 2019;12(6):e005375. 2. lee s, li g, liu t, tse g. covid-19: electrophysiological mechanisms underlying sudden cardiac death during exercise with facemasks. medical hypotheses. 2020;144:110177. 3. olshansky b, ricci f, fedorowski a. importance of resting heart rate: heart rate and outcomes. trends in cardiovascular medicine. 2022. 4. ebrahimzadeh e, pooyan m, bijar a. a novel approach to predict sudden cardiac death (scd) using nonlinear and time-frequency analyses from hrv signals. plos one. 2014;9(2):e81896. 5. vorobiev a, vaykhanskaya t, melnikova o, krupenin v, polyakov v, frolov a. a digital electrocardiographic system for assessing myocardial electrical instability: principles and applications. современные технологии в медицине. 2020;12(6 (eng)):15-9. 6. schafer a, vagedes j. how accurate is pulse rate variability as an estimate of heart rate variability? a review on studies comparing photoplethysmographic technology with an electrocardiogram. int j cardiol. 2013;166(1):15-29. 7. quiroz-juarez ma, jimenez-ramirez o, vazquez-medina r, ryzhii e, ryzhii m, aragon jl. cardiac conduction model for generating 12 lead ecg signals with realistic heart rate dynamics. ieee transactions on nanobioscience. 2018;17(4):525-32. 8. li c, chang q, zhang j, chai w. effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension. medicine. 2018;97(18). 9. schuurmans aa, de looff p, nijhof ks, rosada c, scholte rh, popma a, et al. validity of the empatica e4 wristband to measure heart rate variability (hrv) parameters: a comparison to electrocardiography (ecg). journal of medical systems. 2020;44(11):1-11. 10. mubarak s, majeed mi, khan ma. time domain analysis of heart rate variability in patients with coronary artery journal of rawalpindi medical college (jrmc); 2023; 27(1): 225-230 230 disease. pakistan journal of physiology. 2014;10(12):21–4-–4. 11. pathak k. comparative analysis of heart rate variability signals 2018. 12. fujita h, acharya ur, sudarshan vk, ghista dn, sree sv, eugene lwj, et al. sudden cardiac death (scd) prediction based on nonlinear heart rate variability features and scd index. applied soft computing. 2016;43:510-9. 13. pourhanifeh mh, dehdashtian e, hosseinzadeh a, sezavar sh, mehrzadi s. clinical application of melatonin in the treatment of cardiovascular diseases: current evidence and new insights into the cardioprotective and cardiotherapeutic properties. cardiovascular drugs and therapy. 2020:1-25. 14. colli-franzone p, gionti v, pavarino l, scacchi s, storti c. role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry. mathematical biosciences. 2019;315:108228. 15. figueiredo tdg, de souza hcm, neves vr, do rêgo barros aev, dornelas de andrade adf, brandão dc. effects of physical exercise on the autonomic nervous system in patients with coronary artery disease: a systematic review. expert review of cardiovascular therapy. 2020;18(11):749-59. 16. vaseghi m, shivkumar k. the role of the autonomic nervous system in sudden cardiac death. prog cardiovasc dis. 2008;50(6):404-19. 17. cascio we. myocardial ischemia: what factors determine arrhythmogenesis? j cardiovasc electrophysiol. 2001;12(6):726-9. 18. gourley b. exploring the relationship between anxiety sensitivity and heart rate variability: eastern michigan university; 2019. 19. myerburg rj, junttila mj. sudden cardiac death caused by coronary heart disease. circulation. 2012;125(8):1043-52. 20. szwoch m, ambroch-dorniak k, sominka d, dorniak w, daniłowicz-szymanowicz l, krassowski w, et al. comparison the effects of recanalisation of chronic total occlusion of the right and left coronary arteries on the autonomic nervous system function. kardiologia polska. 2009;67(5):467-74. 21. verkuil b, brosschot jf, meerman ee, thayer jf. effects of momentary assessed stressful events and worry episodes on somatic health complaints. psychology & health. 2012;27(2):141-58. 22. pieper s, brosschot jf, van der leeden r, thayer jf. prolonged cardiac effects of momentary assessed stressful events and worry episodes. psychosomatic medicine. 2010;72(6):570-7. 23. pilz pm, lang m, hamza o, szabo pl, inci m, kramer am, et al. semi-minimal invasive method to induce myocardial infarction in rats and the assessment of cardiac function by an isolated working heart system. jove (journal of visualized experiments). 2020(160):e61033. 24. jennings rb. historical perspective on the pathology of myocardial ischemia/reperfusion injury. circulation research. 2013;113(4):428-38. 25. sarja h, anttila t, mustonen c, honkanen h-p, herajarvi j, haapanen h, et al., editors. diazoxide attenuates ischemic myocardial injury in a porcine model. heart surgery forum; 2017. 26. erdoğan e, akkaya m, bacaksız a, tasal a, kul s, turfan m, et al. short term effect of percutaneous recanalization of chronic total occlusions on qt dispersion and heart rate variability parameters. journal of the american college of cardiology. 2013;62(18_s2):c200-c. 27. sedziwy e, olszowska m, tracz w, pieniazek p. [heart rate variability in patients treated with percutaneous transluminal coronary angioplasty]. przegl lek. 2002;59(9):695-8. 28. lin i-m, fan s-y, lu h-c, lin t-h, chu c-s, kuo h-f, et al. randomized controlled trial of heart rate variability biofeedback in cardiac autonomic and hostility among patients with coronary artery disease. behaviour research and therapy. 2015;70:38-46 summary journal of rawalpindi medical college (jrmc); 2017;21(3): 222-225 222 original article impact of time taken on the surgical outcome of extradural hematoma in patients with road traffic accidents muhammad mujahid sharif 1 , adil aziz khan 2, rayif rashid kanth 1, ali tassadaq hussain minhas 2 1. department of neurosurgery, pakistan institute of medical sciences, islamabad; 2. department of neurosurgery, rawalpindi medical college abstract background: to determine the impact of time taken on the surgical outcome of extradural hematoma in patients with road traffic accidents. methods: sixty adult patients with history of road traffic accident with extradural hematoma on axial images of ct scan brain were included. all patients were allocated into three groups with 20 patients in each group. patients in group i were those in whom time from the occurrence of trauma to the surgical evacuation of hematoma was < 1 hour, 1 to 6 hours in group ii and > 6 hours in group iii. results: in group i, majority (90 %) showed favourable outcome. in group ii, 70 % showed favourable outcome. in group iii, 50 % showed favourable outcome. significant association was found between outcome and time of surgery (p<0.05). conclusions: frequency of favourable outcome after surgical evacuation was significantly higher in patients in whom surgery was performed within one hour after the trauma (p<0.05). key words: extradural hematoma, neurosurgical emergency, time of surgery. introduction accumulation of blood in the potential space between dura and bone is called extradural hematoma. extradural hematomas have three classical presentation. first, brief post-traumatic loss of consciousness. secons,a lucid interval for several hours. third,obtundation, contralateral hemiparesis, ipsilateral pupillary dilatation.1,2 the commonest mechanisms of injury are an accident involving a motorbike and a fall from height.3,4 extradural hematoma of the temporal region is the most common site of supra-tentorial extradural bleeding; other locations are considered atypical.5 traumatic extradural hematoma is a neurosurgical emergency and timely surgical intervention for significant extradural hematoma is the standard treatment.6 the most significant factors influencing outcome in our patients are glasgow coma score or consciousness level on admission, age, and associated intradural lesions and also time taken in evacuation of hematoma due to transfer of patient to neurosurgical unit.7,8 patients who present early after road traffic accidents and with good gcs (13-15) have favorable outcome in 87% and unfavorable outcome in 9%. time taken is defined as the time from the occurrence of trauma to the surgical evacuation of hematoma.9,10 mortality and long-term morbidity are low with early diagnosis and prompt treatment.11,12 clinical deterioration is quick, especially in posterior fossa to become fatal in most of patients with extradural hematoma so surgery can be life saving when performed in a timely manner.13-16it is generally perceived that patients with extradural hematoma present late either because of ignorance, negligence or lack of facilities in the vicinity.17,18 patients and methods this descriptive study was carried out in department of neurosurgery, pakistan institute of medical sciences, islamabad, for six months. it included sixty cases of extradural hematoma(sample size was calculated using who sample size calculator keeping level of significance 5%,anticipated population proportion(p1: 87%)1,absolute precision required:10%). favourable outcome was defined as ability to carry on normal activity and to work; no special care needed. unfavourable outcome was defined as inability to care for self; requires equivalent of institutional or hospital care. inclusion criteria was all the patients with age from 15-45 years,patients of either gender,size of hematoma more than 20 ml.(calculated by the scale on axial images of ct scan brain) and only those cases of edh with h/o road traffic accident regardless of gcs score.exclusion criteria was age under 15 years or more than 45 years, size less than 20 ml when patient is stable,spinal extradural hematoma(because only head injured patients are included in study),extradural hematoma journal of rawalpindi medical college (jrmc); 2017;21(3): 222-225 223 with evidence of diffuse axonal injury, subdural hematoma or brain contusions and those cases of edh with h/o fall or assault. patients were enrolled from neurosurgery department of pakistan institute of medical sciences islamabad. all patients were allocated into three groups with 20 patients in each group. patients in-group i were those in whom time from the occurrence of trauma to the surgical evacuation of hematoma was < 1 hour, 1 to 6 hours in group ii and > 6 hours in group iii. their gcs recorded. patients matched for gcs in each group into mild (gcs: 13-15) moderate (gcs:9-12) and severe(gcs:3-8) head injury on the basis of gcs score . final outcome assessed at 03 months of follow up for the favourable and unfavourable outcome. follow up was ensured through telephone contact. chi square test was used to compare the impact of time taken on surgical outcome in 03 groups. p value < 0.05 considered significant. results majority of the patients were young (table 1).patients matched for gcs in each group into mild (gcs: 13-15) moderate (gcs:9-12) and severe(gcs:3-8) head injury on the basis of gcs score. table 1: demographic profile of study population groups mean age (years) standard deviation (±years) group i (< 1 hour ) 32.4 13.37 group ii (1-6 hours ) 33.05 10.36 group iii (> 6 hours ) 34.6 13.98 favourable outcome was maximum in group i, where evacuation of haematoma contemplated very early (table 2). table 2: outcome of surgery outcome group i group ii group iii p-value favourable 18(90%) 14 (70%) 10 (50%) 0.022 (<0.05) unfavourable 2 (10 %) 6 (30 %) 10 (50%) total 20(100%) 20 (100%) 20 (100%) observed difference in percentages of favourable and unfavourable outcome in different groups are statistically independent, i.e. the observed difference in the column and row variables is not significant and is just a random phenomenon. the pvalue was found to be 0.022 (< 0.05) providing sufficient justification for rejecting the null hypothesis that the row variable is unrelated (that is, only randomly related) to the column variable and the observed difference between them is not statistically significant. frequency of favorable outcome was significantly higher in the group i (surgery within one hour). discussion traumatic extradural hematoma is a neurosurgical emergency and timely surgical intervention for significant extradural hematoma is the standard treatment.1-3 the most significant factors influencing outcome are glasgow coma score or consciousness level on admission, age, and associated intradural lesions and also time taken in evacuation of hematoma due to transfer of patient to neurosurgical unit.4-7 patients who present early after road traffic accidents and with good gcs (13-15) have favourable outcome. time taken is defined as the time from the occurrence of trauma to the surgical evacuation of hematoma.8-10 mortality and long-term morbidity are low with early diagnosis and prompt treatment.11,12 clinical deterioration is quick, especially in posterior fossa to become fatal in most of patients with extradural hematoma so surgery can be life saving when performed in a timely manner.13-15it is generally perceived that patients with extradural hematoma present late either because of ignorance, negligence or lack of facilities in the vicinity.16-18 the rationale of this study is to highlight the importance of time taken on the surgical outcome of extradural hematoma particularly in patients with history of road traffic accidents. outcome is usually found to be predominantly influenced by the preoperative state of consciousness, associated brain lesions, and, in comatose patients, the duration of the time interval between onset of coma and surgical decompression. 1 an interval under two figure 1:right parietal extradural hematoma with signific ant mass effect figure 2:. right frontal extradural hematoma journal of rawalpindi medical college (jrmc); 2017;21(3): 222-225 224 hours leads to 17% mortality and 67% of good recoveries (90% in our study) compared to 65% mortality and 13% of good recoveries after an interval of more than two hours. prasad gl et al studied the outcome by dividing the patients in two groups. in one group they did the surgery and in the second they managed the patients conservatively. in surgically treated group the outcome was favourable and there was no mortality. our study exhibits the same results.2 zhao x et al studied the importance of ct guided evacuation of the extradural hematoma thus emphasizing the importance of surgery in the favourable outcome. 3 balik v et al studied the surgical outcome of posterior fossa extradural hematoma. though rare in occurrence but surgery is helpful. 4 lu z et al managed the extradural hematoma in close proximity to transverse sinus,surgery helped in the favourable outcome. 5 wang w et al studied the minimally invasive puncture and aspiration performed in 59 cases of acute epidural hematoma with various hematoma volumes (13–145 ml. mortality rate was higher in aspiration as compared to surgical outcome. in a study by flaherty bf et al patients undergoing surgery were more likely to have an altered mental status (17 vs. 72%, p < 0.001), but there were no other significant clinical differences between the groups. 10 the mean initial edh thickness and volume were 8.0 mm and 8.6 ml in the observed group and 15.5 mm and 35 ml in the surgery group, respectively (p < 0.001 for both comparisons). mezue wc et al in their prospective analysis of 817 head injuries, 69 (8.4%) had edh, a mean of 9.9 patients per year. 17 causes were road traffic accidents (57%), assault (22%) and falls (9%). twenty-six (38%) patients presented within 24 hours of injury and only one patient presented within 4 hours. the average time lag before presentation was 94.2 hours. the most common location of hematoma was temporal (27.5%). forty (59%) patients had surgery while 14 (20%) were managed conservatively. ten patients (14.5%) died and of these 70% had gcs <8 and 60% had a seizure. they concluded that early appropriate treatment of edh results in good high quality survival (glasgow outcome score 4 or 5). low gcs should not be an absolute contraindication for surgery. according to khan mb et al 19 on univariate analysis, admitting gcs score, patient's age, the time from injury to admission and injury to surgery, anisocoric pupils at presentation and effacement of basal cisterns were significantly associated with the outcome of gos score. 19they concluded that lower gcs at presentation, younger age at trauma, increased time since trauma to surgery and admission, anisocoria and effacement of basal cisterns are statistically significant variables in surgically treated pediatric patients of edh that confer a poorer prognosis. a timely surgical intervention can result in excellent outcomes.according to sencer a et al pfedh in children can be treated in experienced centers with excellent outcome, and there is no need to avoid surgery when it is indicated.this study also highlights the importance of early surgery. 20according to han j et al, preoperative gcs score and thickness of hematoma on brain computed tomography are important determinants of prognosis, almost comparable results with our study. 24 different studies demonstrate that, in children and adolescents with moderate and stbi, lesions in multiple zones, total flair lesion volume, and lesion volumes within specific brain zones correlated with long-term functional outcome. 24,25 conclusion frequency of favourable outcome after surgical evacuation was significantly higher in patients in whom surgery was performed within one hour after the trauma (p<0.05). 2. time is not the only factor responsible for the favourable outcome, as is evident in patients who present early but with poor gcs. references 1. aurangzeb a, ahmed e, maqbool s. burr hole evacuation of extradural hematoma in trauma. a life saving and time saving procedure.turk neurosurg. 2016; 26(2):205-08. 2. prasad gl, gupta dk, sharma bs, mahapatra ak. traumatic pediatric posterior fossa extradural hematomas.india.pediatr neurosurg. 2015; 50(5):250-56. 3. zhao x, jiang h, liu g, wang t. efficacy analysis of 33 cases with epidural hematoma treated by brain puncture under ct surveillance..turk neurosurg. 2014;24(3):323-26. 4. balik v, letho h, hoza d. posterior fossa extradural hematomas. cen eurneurosrug. 2010;71:167-72. 5. lu z, zhu g, qiu y, cheng x. minimally-invasive aspiration and drainage for management of traumatic epidural hematoma straddling transverse sinus.neurol india. 2013 ;61(2):111-16 6. wang w. minimally invasive surgical treatment of acute epidural hematoma: case series.biomed res int. 2016; 2016:650-54. 7. noguchi m, inamasu j, kawai f. ultrasound-guided needle aspiration of epidural hematoma in a neonate after vacuumassisted delivery.childs nerv syst 2010;26(5):713-16. 8. talbott jf, gean a, yuh el, stiver si. calvarial fracture patterns on ct imaging predict risk of a delayed epidural hematoma following decompressive craniectomy for traumatic brain injury. american journal of neuroradiology. 2014;35(10):211-15 https://www.ncbi.nlm.nih.gov/pubmed/24848168 https://www.ncbi.nlm.nih.gov/pubmed/24848168 https://www.ncbi.nlm.nih.gov/pubmed/24848168 https://www.ncbi.nlm.nih.gov/pubmed/23644308 https://www.ncbi.nlm.nih.gov/pubmed/23644308 https://www.ncbi.nlm.nih.gov/pubmed/23644308 https://www.ncbi.nlm.nih.gov/pubmed/20076989 https://www.ncbi.nlm.nih.gov/pubmed/20076989 https://www.ncbi.nlm.nih.gov/pubmed/20076989 journal of rawalpindi medical college (jrmc); 2017;21(3): 222-225 225 9. shen j, pan jw, fan zx, zhou yq. surgery for contralateral acute epidural hematoma following acute subdural hematoma evacuation: five new cases and a short literature review..acta neurochir 2013 ; 155(2):335-41. 10. flaherty bf, loya j, alexander md, pandit r. utility of clinical and radiographic findings in the management of traumatic epidural hematoma. pediatric neurosurgery. 2013;49(4):208-14. 11. page c, gardner k, height s, rees dc. nontraumatic extradural hematoma in sickle cell anemia: a rare neurological complication not to be missed. american journal of hematology. 2014 ;89(2):225-27. 12. zakaria z, kaliaperumal c, kaar g, o'sullivan m. extradural haematoma--to evacuate or not? revisiting treatment guidelines.clin neurol neurosurg. 2013; 115(8):1201-05. 13. nelson ks, brearley am, haines sj. evidence-based assessment of well-established interventions: the parachute and the epidural hematoma. neurosurgery. 2014;75(5):552-59. 14. lapadula g, caporlingua f, paolini s. epidural hematoma with detachment of the dural sinuses. journal of neurosciences in rural practice. 2014 ;5(2):191 94. 15. jung sw and kim dw. our experience with surgically treated epidural hematomas in children. journal korean neurosurgical society. 2012;51:215-18 16. yusuf as, odebode to, adeniran jo, salaudeen ag, adeleke an. motorcyclists head injury in ilorin, nigeria. nigerian journal of basic and clinical sciences. 2014;11:80-84. 17. mezue wc, ndubuisi ca, chikani mc, achebe ds. traumatic extradural hematoma in enugu, nigeria. nigerian journal of surgery. 2012;18:80-84 18. aras y, sabanci pa, unal tc, aydoseli a, izgi n. epidemiologic study in hospitalized patients with head injuries. european journal of trauma and emergency surgery. 2016:1-7. 19. khan mb, riaz m, javed g, hashmi fa, sanaullah m. surgical management of traumatic extradural hematoma in children: experiences and analysis from 24 consecutively treated patients in a developing country. surgical neurology international. 2013;4:103-06. 20. sencer a, aras y, akcakaya mo, goker b, kırıs t, canbolat at. posterior fossa epidural hematomas in children: clinical experience with 40 cases: clinical article. journal of neurosurgery: pediatrics. 2012 ;9(2):139-43. 21. inoue h, nakagawa y, ikemura m, shinone k, okada k, nata m. a subacute epidural haematoma extending over the occipital region and posterior cranial fossa due to a laceration in the transverse sinus. international journal of legal medicine. 2012 ;126(3):467-71. 22. oluigbo co, wilkinson cc, stence nv, fenton lz. comparison of outcomes following decompressive craniectomy in children with accidental and nonaccidental blunt cranial trauma: clinical article. journal of neurosurgery: pediatrics. 2012 ;9(2):125-32. 23. su tm, lee th, lee tc, cheng ch. acute clinical deterioration of posterior fossa epidural hematoma. chang gung med j. 2012 ;35(3):271-80. 24. han j, cho tg, moon jg, lee hk, kim ch. traumatic epidural hematoma of the posterior cranial fossa. korean journal of neurotrauma. 2012 ; 8(2):99-103. 25. sigurta a, zanaboni c, canavesi k, citerio g, beretta l, stocchetti n. intensive care for pediatric traumatic brain injury. intensive care medicine. 2013 39(1):129-36. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 226-228 226 original article visual outcome of open globe injuries in paediatric patients ambreen gul1 and ali raza2 1 senior registrar holy family hospital and rawalpindi medical university;2 department of ophthalmology, sahiwal medical college, sahiwal. abstract background: to determine visual outcome of open globe injuries in children. methods: in this descriptive study children, between 4-16 years (n=80), who had open globe injury and who presented within one week of injury, were included . all patients underwent surgical repair surgery. corrected post-operative visual acuity at 4 weeks was recorded. effect modifiers like age, gender, mechanism of injury and time delay in presentation was controlled by stratification. for post stratification chi square was applied. p-value of ≤ 0.05 accepted as statistically significant. results: visual improvement was observed in 70% (n=56) of patients as per operational definition, which was significantly higher in patients who presented before 24 hours (p<0.05). no other significant association was found. conclusions: open globe injuries require emergency surgery as a standard of care. visual improvement was observed in 70% in this study which was significantly associated with earlier presentation (<24 hours). key words: open globe injury, visual outcome, visual acuity. introduction ocular trauma is a significant, preventable, worldwide public health problem, accounting almost 8-14% of total injuries suffered by children.1,2 approximately 1.6 million people are blind owing to ocular trauma and 2.3 million are bilaterally visually impaired.1 it has considerable impact on the patient’s future worth of life and patients are exposed to a major risk of amblyopia caused by prolonged period of light and formed visual deprivation. about two-thirds of those affected are males, due to their aggressive and hostile nature, predominantly children and young adults, due to their immature motor skills, curious and exploratory nature. 3,4 ocular injury occurs in three forms: open globe, closed globe and chemical injuries.1 patients with open globe injuries have a rupture or a laceration, with the latter being either a penetrating or perforating injury.1 open globe injuries are one of the frequent emergencies in ophthalmology and require immediate operation. they are caused by wooden sticks, including pencils, chopsticks or toothpicks, or by sharp objects like scissors or a knife. projectile toys, air guns and syringes cause serious permanent ocular damage. these injuries yield the worst visual outcome due to retinal detachment, cataract and postoperative inflammation, infectious endophthalmitis or scarring.1,2,5-8 delayed medical and surgical intervention in such trauma cases often leads to poor visual outcome9,10,11. they lead to development of a corneal opacity which is a significant cause of blindness the world over, more in developing countries.5 most of these patients are young males, who are active members of the society and need a better visual status in order to earn their livelihood or to pursue their professional educational demands.12 by identifying any underlying factors in the etiology of serious injuries; it may be possible to devise effectual methods for reducing the incidence of visually damaging trauma.13-15 previous studies have measured the visual outcome of open globe injuries.1,2,4 according to these studies visual prognosis of open globe injuries in children is worse than adults due to severe nature of injuries, amblyopia and infectious endophthalmitis due to delayed presentation.1,2,4 patients and methods in this descriptive study, performed from january 2016 to december 2016, a total of eighty patients ,of either gender aged between 4-16 years who had open globe injury, who presented within one week of injury, were included. patients having posterior segment trauma of retina or optic nerve, chemical injuries and patients with phthisis bulbi were excluded. every patient underwent complete ophthalmic examination including visual acuity by snellen chart, pupil, intraocular pressure by perkins tonometer and extraocular movements. detailed examination of journal of rawalpindi medical college (jrmc); 2017;21(3): 226-228 227 anterior segment by standard and handheld slit lamp where needed and posterior segment by indirect ophthalmoscope was done. if posterior segment was not visible, b-scan ultrasonography was done to rule out any posterior segment pathology. every patient underwent corneal/scleral tear repair surgery under general anaesthesia. corneal lacerations was repaired with 10/0 nylon suture and scleral lacerations with 6/0 vicryl. in case of vitreous /uveal tissue prolapse, reposition of uveal tissue along with vitrectomy was done. post-operative topical treatment was started after 24 hours which included topical dexamethasone 0.1% suspension (1 drop after every 1 hour), moxifloxacin eye drops (one drop after every 2 hours), 1% cyclopentolate eye drops (one drop after every 8 hours) in every patient to control confounding factors like infection, intraocular pressure and uveitis. treatment was continued for 4 weeks and steroids were tapered off accordingly. main outcome measure was final visual improvement. corrected postoperative visual acuity at 4 weeks was recorded by snellen chart and visual improvement was entered. chi square was applied and p-value of ≤ 0.05 accepted as statistically significant. results penetrating injury was commonest (table 1).out of total eighty (n=80) patients, 75% (n=60) were males with mean age 10.5 years ± 3.3 sd and 25% (n=20) were females with mean age 8.6 years ± 3.3 sd (table 2). table 1: mechanism of injury in study population mechanism of injury no percentage penetrating 66 82.5 perforating 2 2.5 blunt trauma(globe rupture) 7 8.8 penetrating with intra-ocular foreign body 5 6.3 table 2: time delay in injury to presentation in study population time delay (hours) no percentage < 24 56 70.0 > 24 24 30.0 baseline visual acuity was 6/60 in 75 (93.8%) patients and 6.2% (n=5) with no light perception or who didn’t cooperate (table 3). post treatment va was found to be 6/9 or better in 17.5% (n=14) patients, 6/12 to 6/36 (useful) in 52.5% (n=42) patients and 6/60 or worse in 30% (n=24) patients (table 3). in the overall study population visual improvement was observed in 70% (n=56) (table 4). table 3: baseline (presenting) visual acuity in study population presenting va no percentage 6/60 or worse (hm/pl) 75 93.8 nlp* or did not cooperate 5 6.3 *nlp=no light perception table 4 : post treatment visual acuity post treatment va no percentage 6/9 or better 14 17.5 6/12 to 6/36 or useful 42 52.5 6/60 or worse 24 30.0 table 5 : overall post treatment visual improvement visual improvement no percentage present 56 70.0 absent 24 30.0 discussion whenever there is suspicion or definite evidence of globe rupture or laceration, immediate ophthalmic consultation is indicated, with prompt transfer to another hospital if ophthalmology consultation is not readily available. rapid primary closure of an open globe injury by an ophthalmologist promotes the best visual outcome for the patient.16,17 many factors determine optimal timing for surgical repair. in general, closure within 24 hours of injury is ideal.18,19 kadappu s, et al found parameters which indicated a poor visual outcome including globe ruptures, zone 3 injuries, poor initial visual acuity, wound length >10 mm and lens trauma. 20,21 al-mahdi hs, et al in cases of serious ocular trauma ,found that initial visual acuity was more than 6/60 in 37.3% of patients with open globe injury. final visual acuity was more than 6/18 in 63% patients.22 they concluded that most eye injuries in children are preventable so this reflects the importance of health education, adult supervision and application of appropriate measures that is necessary for reducing the incidence and severity of trauma. yalcin tök o, et al found that penetrating injury was the most common type of injury. 23 in a univariate analysis, the factors contributing to a final va worse than 20/200 included being older than 50 years, injury in zone 2 or 3, blunt injury, rupture-type injury, poor initial va, and the presence of endophthalmitis, retinal detachment, relative afferent papillary defect, hyphema, vitreous prolapse, and uveal prolapse. in a journal of rawalpindi medical college (jrmc); 2017;21(3): 226-228 228 multiple logistic regression analysis in which all factors that may influence final va were analyzed together, poor initial va, retinal detachment, and vitreous prolapse were found to be statistically significant. they concluded that the most important factors influencing final va were initial va, retinal detachment, and vitreous prolapse, all of which are important with regard to informing the patient of the prognosis and determining the approach of treating physician. agrawal r, et al, found in patients with open globe injury,that 15.7% eyes had no light perception (nlp). after surgical repair, final visual acuity remained nlp in 66.7% eyes. final vision improved to light perception/ hand movement (lp/hm) in 7.4% eyes, 1/200 to 11.1% in 3 eyes and 20/50-20/200(14.8%) in 4 eyes. they concluded that presence of afferent papillary defect, wound extending posterior to rectus insertion and associated vitreoretinal trauma can adversely affect the outcome in severely traumatized eyes with nlp. timely intervention may restore useful vision in severely traumatized eyes. 24 in a study by ojabo co et al, of open globe injuries in children, 30.0% presented within the first 24 hours of the injury and 25.6% were blind on presentation.25 visual acuity at last follow up indicated that 39.7% patients were visually impaired and 39.7% were blind. in a study by onyekonwu gc, blunt ocular injury constituted 79.4% cases whereas penetrating injury were 14.7% cases. visual prognosis was poorer in penetrating injuries than in mild blunt injuries. 26 conclusion 1.visual improvement was observed in 70% in this study which was significantly associated with early presentation (<24 hours). 2.open globe injuries require emergency surgery as a standard of care. references 1. junejo sa, ahmed m, alam m. endophthalmitis in pediatric penetrating ocular injuries in hyderabad. j pak med assoc. 2010;60:532-35. 2. bukhari s, mahar ps, qidwai u, bhutto ia, memon as. ocular trauma in children. pak j ophthalmol. 2011;27:20813. 3. schimel am, miller d, flynn hw jr. endophthalmitis isolates and antibiotic susceptibilities: a 10-year review of cultureproven cases. am j ophthalmol. 2013;156:50-52. 4. el-sebaity dm, soliman w, soliman am, fathalla am. pediatric eye injuries in upper egypt. clin ophthalmol. 2011;5:1417-23. 5. adio ao, nwachukwu h, pattern of paediatric corneal laceration injuries in the university of port harcourt teaching hospital, river state, nigeria. bmc res notes. 2012;5:683-89. 6. zhang y, zhang mn, jiang ch, yao y, zhang k. endophthalmitis following open globe injury. br j ophthalmol. 2010;94:111-14. 7. zhang y, zhang m, jiang c. intraocular foreign bodies in china: clinical characteristics, prognostic factors, and visual outcomes in 1,421 eyes. am j ophthalmol. 2011;152:66-69. 8. andreoli cm, andreoli mt, kloek ce. low rate of endophthalmitis in a large series of open globe injuries. am j ophthalmol. 2009;147:601-04. 9. lesniak sp, bauza a, son jh. twelve-year review of pediatric traumatic open globe injuries in an urban u.s. population. j pediatr ophthalmol strabismus. 2012;49:73-75. 10. rüfer f, peters a, klettner a. influence of alcohol consumption on incidence and severity of open-globe eye injuries. graefes arch clin exp ophthalmol. 2011;249:1765-68. 11. ben simon gj, moisseiev j, rosen n, alhalel a. gunshot wound to the eye and orbit: a descriptive case series and literature review. j trauma. 2011;71:771-74. 12. chhablani j. fungal endophthalmitis. expert rev anti infect ther. 2011;9:1191-201. 13. ahmed y, schimel am, pathengay a, colyer mh, flynn hw jr. endophthalmitis following open-globe injuries. eye (lond). 2012;26:212-17. 14. shazly ta, al-hussaini ak. pediatric ocular injuries from airsoft toy guns. j pediatr ophthalmol strabismus. 2012;49:54-57. 15. faghihi h, hajizadeh f, esfahani mr, rasoulinejad sa, lashay a, mirshahi a, et al. post-traumatic endophthalmitis. retina. 2012;32:146-51. 16. andreoli mt, andreoli cm. geriatric traumatic open globe injuries. ophthalmology. 2011;118:156-59. 17. yuan wh, hsu hc, cheng hc. ct of globe rupture: analysis and frequency of findings. ajr am j roentgenol. 2014;202:1100-04. 18. qi y, zhang fy, peng gh, zhu y. characteristics and visual outcomes of patients hospitalized for ocular trauma. int j ophthalmol. 2015;8:162-68. 19. hernández dm, gómez vl. ocular trauma score comparison with open globe receiving early or late care attention. cir cir. 2015;83:9-14. 20. madhusudhan al, evelyn-tai lm, zamri n. open globe injury in hospital universiti sains malaysia: a 10-year review. int j ophthalmol. 2014;7:486-90. 21. kadappu s, silveira s, martin f. aetiology and outcome of open and closed globe eye injuries in children. clin experiment ophthalmol. 2013;41:427-34. 22. al-mahdi hs, bener a, hashim sp. clinical pattern of pediatric ocular trauma in fast developing country. int emerg nurs. 2011;19:186-91. 23. yalcin tök o, tok l, eraslan e, ozkaya d, ornek f. prognostic factors influencing final visual acuity in open globe injuries. j trauma. 2011;71:1794-800. 24. agrawal r, wei hs, teoh s. predictive factors for final outcome of severely traumatized eyes with no light perception. bmc ophthalmol. 2012;12:16-18. 25. ojabo co, malu kn, adeniyi os. open globe injuries in nigerian children: epidemiological characteristics, etiological factors, andvisual outcome. middle east afr j ophthalmol. 2015;22:69-73. 26. onyekonwu gc, chuka-okosat cm. pattern and visual outcome of eye injuries in children at abakaliki, nigeria. west afr j med. 2008;27:152-54. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 241-244 241 original article comparison of ephedrine versus lidocaine in reducing the frequency of pain on propofol injection during elective surgeries sumbal rana, jawad zaheer, ali arslan munir, huma fatima department of anaesthesia, holy family hospital and rawalpindi medical university abstract background: to compare the ephedrine with lidocaine for reducing frequency of pain on propofol injection during elective surgeries. methods: in this randomized controlled trial 80 patients were observed by taking 40 patients in each group, i.e. group a: ephedrine group and group b:lidocaine group. patients with asa–i (normal healthy patient), ii (mild systemic disease with no functional limitation) aging between 20 and 40 years and opting for elective surgical procedures were included. the pain intensity was classified in four levels from no pain to severe pain. the frequencies of pain intensity were recorded during the injection period before the loss of consciousness according to the verbal rating scale (vrs) explained to patients at the preoperative visit. chi square test was used to compare the frequency of pain in two groups, where p-value <0.05 was considered statistically significant. effect modifiers i.e. the age, gender and asa were controlled by stratification. the post stratification chi-square test was applied keeping the p-value <0.05 as significant. results: in group a, 35% complained of severe pain, 42.5% had moderate pain, 22.5% had mild pain and no patients reported absence of pain as per our operational definition. in group b 47.5% reported no pain during propofol injection, 40% complained of mild pain, 12.5% had moderate and no patients reported severe pain. the p-value is 0.00. conclusion: pretreatment with lidocaine resulted in significantly better pain control during propofol infusion than pretreatment with ephedrine. key words: propofol, procedural sedation, ephedrine, lidocaine introduction propofol (2,6-diisopropylphenol) is one of the most commonly used intravenous anaesthetic agent. it is preferred for its rapid onset, short duration of action, early recovery and minimal organ toxicity. it is commonly used for induction and maintenance of general anesthesia and sedation in intensive care units for its simplicity, stability and safety. two main side effects of propofol use are pain on injection and hypotension. incidence of pain on injection is 80-90% if injected in vein of dorsum of hand.1 exact mechanism of pain is not known but many are proposed. immediate pain results from action of phenol on vein and delayed pain by stimulation of nerve endings between intima and media by endothelium releasing kininogens.1 to date, many methods are proposed to eliminate its pain like adding lidocaine, injecting into larger veins like antecubital,changing temperature, diluting solution with 5% dextrose or intralipid2, varying speed of injection3, prior medication with metoclopramide, clonidine, ephedrine, magnesium sulphate, opioids, thiopentol, ketamine, paracetamol, flurbiprofen axetil, nitroglycerine and nitrous oxide, oxygen mixture4. new preparations like the one with sodium metabisulphite and one with 1% propofol in 16% polyoxyethylated castor oil also decrease pain. but none of these has resulted in reliable attenuation of pain, though lidocaine pretreatment is considered most effective so far.5 lidocaine is a local anesthetic agent. it reduces propofol injection pain by 30%.5its exact mechanism of action is not known but is thought to be decreased neuronal conduction in peripheral nerves by attenuating the neuronal membrane's permeability to sodium ions or due to alteration in propofol's ph by adding hcl to it.3,5 pain by lidocaine pretreatment with prior venous occlusion has failure rate of 24-37% and augments hypotension associated with propofol.5 ephedrine is a sympathomimetic, used for its effects to counter hypotension and bradycardia. it has both direct and indirect actions; direct by acting on alpha and beta receptors (more on beta) and indirect by journal of rawalpindi medical college (jrmc); 2017;21(3): 241-244 242 releasing norepinephrine from sympathetic nerve terminals. cheong et al suggested in 2002 that ephedrine by its indirect action can reduce effect on bradykinin responsible for propofol injection pain.6 incidence of this pain reduction is 65%.2 it is also a venodilator and increases contact between propofol in aqueous phase and free nerve endings. it is also buffered with hcl resulting in altered ph and decreased pain.4 agarwal et al. found that ephedrine pretreatment did not reduce pain so there are conflicting evidences about ephedrine’s role in reducing propofol injection pain. but as pain reduction by ephedrine is 65% as compared to lidocaine 30% with additional benefit of heamodynamic stability so aim of this study is to compare ephedrine with lidocaine for reducing pain on propofol injection during elective surgeries.4 patients and methods this randomized controlled trial was conducted at department of anaesthesia, holy family hospital, rawalpindi, from august 2014 to february 2015. a total of 80 patients were observed by taking 40 patients in each group. group a: ephedrine group. group b:lidocaine group. the sample size was calculated by using who sample size calculator following are the calculations: level of significance: 5% power of test: 80% anticipated population proportion a is 65%12 anticipated population proportion b is 30%10. patients with asa–i (normal healthy patient), ii (mild systemic disease with no functional limitation), age ranged 2040 years and elective surgical procedures were included while patients patients with difficulty in communication e.g. psychiatric illness, dementia, aphasia etc, with history of adverse response or allergy to propofol, lidocaine or ephedrine,neurologic disease and cardiovascular disease were excluded. cases in which vasopressor drugs are contraindicated e.g. thyrotoxicosis, diabetes mellitus, and hypertension of pregnancy and patients receiving monoamine oxidase inhibitors therapy were excluded. patients were allocated to two groups “a”or “b” using computer generated random numbers. in both groups heart rate, non-invasive blood pressure, oxygen saturation and electrocardiography was monitored. intravascular access in antecubital vein with one 18g cannula was established. intravenous fluids administered to each patient as per requirement of patient and procedure. all the patients were preoxygenated with 100% oxygen via face mask for 3 minutes. syringes of the pretreatment drugs, intravenous ephedrine 30 microgram/kg labeled as a and intravenous lidocaine 0.5 mg/kg labeled as b prepared. the coded syringes were identical and the drugs prepared by the personnel not involved in the study. drugs were handed over to the anesthetists for pretreatment who was unaware of the identity of the drug. so investigator who assess the patient response was also ignorant of the nature of the solution. all drugs were used within 15 minutes after preparation. patients were randomly assigned into two groups to receive either drug. one minute after the administration of the test solution, the 1% solution of propofol at 2 mg/kg was given through the iv catheter while the running of iv infusion temporarily ceased. after the injection of propofol the crystalloids were administered. patients were informed regarding the possible stinging sensation on administration of a drug at the start of the anesthesia and they were asked about their pain during the injection period before the loss of consciousness according to the verbal rating scale (vrs) explained to patients at the preoperative visit. furthermore, a blinded anesthesiologist evaluated the pain score during propofol injection. means and sd were calculated for continuous variables i.e. age, weight and height. frequency and percentage were calculated for categorical variables i.e. gender, asa and pain on injection. chi square test was used to compare the frequency of pain in two groups, where p-value <0.05 was considered statistically significant. effect modifiers i.e. the age, gender and asa were controlled by stratification. the post stratification chisquare test was applied keeping the p-value <0.05 as significant. results the patients included in the study were asa-i and asa-ii. in group a, 25 (62.5%) patients were asa i and 15 (37.5%) patients were asa ii. in group b, 22 (55%) patients were asa i while 18 (45%) patients were asa ii. in overall study population, 47 (58.75%) patients were asa i while 33 (41.25%) were asa ii. mean and standard deviation of their age, weight and height were calculated within each group as well as of the whole population (table 1).thirteen patients from group a complained of severe pain while no patient from group b complained of severe pain (table 2). the p-value was found to be 0.00 (<<0.05). poststratification chi-square tests were applied and pvalue was found to be 0.00 (<<0.05). the results showed significant difference in the observed outcomes with pretreatment with lidocaine resulting in significantly better pain control than ephedrine during propofol infusion regardless of considered journal of rawalpindi medical college (jrmc); 2017;21(3): 241-244 243 effect modifiers, i.e. age, gender, height and asa classification (table 3). table 1: demography of the study population group a group b male female total male female total no 17 23 40 20 20 40 age (years) 30.82 ± 7.03 30.35 ± 7.08 30.56 ± 6.98 33.95 ± 9.5 33.55 ± 6.13 33.75 ± 7.89 height (cm) 170.7 ± 13.7 152.6 ± 13.8 166.0 ± 14.2 163.7 ± 10.9 159.8 ± 14.4 161.6 ± 13.2 weigh t (kg) 62.74 ± 9.56 56.08 ± 8.33 58.85 ± 9.36 65.95 ± 10.34 56.0± 10.31 60.98 ± 11.37 table 2: group wise frequency of pain intensity group a group b no percentage no percentage no pain 2 5 19 47.5 mild pain 9 22.5 16 40 moderate pain 16 40 5 12.5 severe pain 13 32.5 0 0 table 3: pain frequency and percentages after treatment in both groups pain group a (ephedrine) group b (lidocaine) pvalue yes 2 (5%) 21 (52.5%) 0.000 (< 0.05) no 38 (96%) 19 (47.05%) discussion the practice of acute care medicine often requires the performance of procedures that can cause pain and anxiety. procedural sedation reduces the discomfort, apprehension, and potential unpleasant memories associated with such procedures and facilitates performance of the procedure. procedural sedation involves the use of short-acting analgesic and sedative medications to enable clinicians to perform procedures effectively, while monitoring the patient closely for potential adverse effects. propofol is an intravenous anaesthetic that is commonly used for sedation of the agitated adult intensive care unit (icu) patient. it is particularly useful when rapid sedation and rapid awakening is desirable (e.g., patients who require frequent neurological examinations) because it has a short duration of effect.7,8 propofol is a highly lipophilic phenol derivative that is insoluble in water. it is administered by continuous infusion in the icu and not by intermittent infusion because it is associated with doseand rate-dependent hypotension.9 other main side effect of propofol use is pain during infusion. incidence of pain on injection is 80-90% if injected in vein of dorsum of hand.1 although, under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides.10,12 the choice of drugs to be compared in this study, i.e. ephedrine and lidocaine followed from already existing studies, which show that ephedrine, by its indirect action, can reduce effect on bradykinin responsible for propofol injection pain.1,6 furthermore, it has been reported that the two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pre-treatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.10 dependence of pain intensity during injection of microemulsion propofol on the amount of dose of lidocaine has been investigated in literature and it is established that increasing lidocaine dosage, within a dose range, significantly reduces pain during injection of microemulsion propofol.3,13 chi-square test was applied and p-value was found to be 0.000 (<0.05) implicating significant difference in the observed outcomes with pretreatment with lidocaine resulting in significantly better pain control than ephedrine during propofol infusion. the data was stratified with respect to effect modifiers like age, gender and asa. the post stratification chi-square test was applied and p-value was found to be 0.000 (<0.05). hence the significance of pain control treatment difference was found to be invariant of effect modifiers. the present study shows ephedrine not to be the most effective approach for reduction of pain caused by propofol injection. this is analogical to available literature, where it is reported that the low dose ketamine or ephedrine pretreatment may prevent hypotension due to propofol induction but, despite the reduction in injection pain intensity after ketamine, both drugs were found to be ineffective in lowering the injection pain incidence.11,14 the study also found lidocaine to be effective measure in reducing the pain during propofol injection. similar results have been deduced in other studies too, where lidocaine is found journal of rawalpindi medical college (jrmc); 2017;21(3): 241-244 244 to be the most effective measure to reduce the pain caused by the propofol injection.10 it is also known that increasing the dosage of lidocaine results in higher reduction in pain.3,15 the natural intuition that may follow as a result of comparison of ephedrine and lidocaine is to consider their combination as a pain reducing measure. the idea has already been addressed in literature and shows that pretreatment with combination of smalldose ephedrine and lidocaine could reduce the incidence and intensity of propofol-induced pain and also result in more stable hemodynamic profile, but however, the combination of two drugs failed to work better in further reduction of pain.1 conclusion pretreatment with lidocaine results in significantly better pain control during propofol infusion than pretreatment with ephedrine. references 1. khezri mb, kayalha h. the effect of combined ephedrine and lidocaine pretreatment on ain and hemodynamic changes due to propofol injection. acta anaesthesiol taiwan. 2011;49:54-58. 2. han yk, jeong cw, lee hg. pain reduction on injection of microemulsion propofol via combination of remifentanil and lidocaine. korean j anesthesiol. 2010;58:435-39. 3. kim hs, cho kr, lee jh, kim yh, lim sh, lee km, et al. prevention of pain during injection of microemulsion propofol: application of lidocaine mixture and the optimal dose of lidocaine. korean j anesthesiol. 2010;59:310-13. 4. austin jd, parke tj. admixture of ephedrine to offset side effects of propofol: a randomized controlled trial. minerva anestesiol. 2009;21:44-49. 5. fujii y, itakura m. efficacy of the lidocaine/flurbiprofen axetil combination for reducing pain during injection of propofol. minerva medica. 2011;77:693-97 6. ishiyama t, kashimoto s, oguchi t, furuya a. clonidineephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence. j clin anesth. 2006:18:211-15. 7. carson ss, kress jp, rodgers je. a randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. crit care med. 2006;34:1326-29. 8. lonardo nw, mone mc, nirula r. propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients. am j respir crit care med. 2014;189:1383-7. 9. hug cc jr, mcleskey ch, nahrwold ml. hemodynamic effects of propofol: data from over 25,000 patients. anesth analg. 1993;77:21-24. 10. jalota l, kalira v, george e, shi yy, hornuss c. prevention of pain on injection of propofol: systematic review and metaanalysis. bmj. 2011;342:d1110-14. 11. ozkoçak i, altunkaya h, ozer y, ayoğlu h, demirel cb. comparison of ephedrine and ketamine in prevention of injection pain and hypotension due to propofol induction. eur j anaesthesiol. 2005;22:44-48. 12. vardy jm, dignon n, mukherjee n. audit of the safety and effectiveness of ketamine for procedural sedation in the emergency department. emerg med j. 2008;25:579 82. 13. sener s, eken c, schultz ch. ketamine with and without midazolam for emergency department sedation in adults: a randomized controlled trial. ann emerg med. 2011;57:10913. 14. wathen je, roback mg, mackenzie t, bothner jp. does midazolam alter the clinical effects of intravenous ketamine sedation in children? a double-blind, randomized, controlled, emergency department trial. ann emerg med. 2000;36:579-82. 15. thorp aw, brown l, green sm. ketamine-associated vomiting: is it dose-related? pediatr emerg care. 2009;25:15-18. 404 not found 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 233-236 233 original article harmonic scalpel hemorrhoidectomy vs milligan-morgan hemorrhoidectomy muhammad umer fayyaz, muhammad salman shafique, jahangir sarwar khan, raheel ahmad , sheikh haseeb ahmad, naqqash adnan department of surgery, holy family hospital & rawalpindi medical university, rawalpindi. abstract background: to compare harmonic scalpel hemorrhoidectomy (hsh) with classical milligan morgan hemorrhoidectomy (mmh) in terms of operation time and post-operative pain to establish effectiveness of this novel procedure. methods: a total of 62 patients planned for excision hemorrhoidecotmy were randomly selected into hsh and mmh groups. mean operation time was calculated during surgery and pain at time of first defecation was recorded on visual analog scale (vas). results: mean vas after surgery at time of first defecation was 4.32 (sd 0.909) in hsh group and 6.97 (sd 1.426) in mmh group (p value <0.000). mean operation time in hsh group was 18.13 (sd 3.956) minutes and that of mmh group was 22.90 (sd 4.901) minutes (p value <0.000). conclusion: harmonic scalpel hemorrhoidectomy is better than milligan morgan hemorrhoidectomy in terms of post-operative pain and operation time. key words: harmonic scalpel®, milligan morgan hemorrhoidectomy, visual analog scale, post hemorrhoidectomy pain. introduction hemorrhoids arise from congestion of anal cushions and characteristically lie in the 3, 7 and 11 o’ clock positions (with the patient in lithotomy position). symptoms may include bright red, painless bleeding, mucus discharge and prolapse. surgical excision of hemorrhoids still remains gold standard treatment for grade iii and iv. harmonic scalpel® hemorrhoidectomy (hsh) is one of them which seems to be safe, efficient and rapid technique. haemorrhoid is the most common anorectal disease.1,2 etiologic factors for hemorrhoidal disease include chronic constipation, diarrhea, prolonged straining, pregnancy, heredity, prolonged erect posture, increased intra-abdominal pressure with obstruction of venous return, aging, and internal sphincter abnormalities.3 the most common pathological finding is the abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, although exact pathophysiology of hemorrhoids is poorly understood. the most widely accepted theory for its pathophysiology is called ‘sliding anal canal lining’. it proposes that when the supporting tissues of the anal cushions disintegrate or deteriorate, it leads to development of hemorrhoids.4 haemorrhoids characteristically lie in the 3, 7 and 11 o’ clock positions (with the patient in lithotomy position).5 according to goligher’s classification they are classified into four grades based on their appearance and degree of prolapse.1 in first-degree hemorrhoids (grade i),anal cushions bleed but do not prolapse. in second-degree hemorrhoids (grade ii) the anal cushions prolapse through the anus on straining but reduce spontaneously.in third-degree hemorrhoids (grade iii) ,the anal cushions prolapse through the anus on straining or exertion and require manual replacement into the anal canal. in fourth degree hemorrhoids (grade iv), prolapse stay out at all times and is irreducible. grade iii, grade iv and those with grade ii who failed to respond to medical treatment are classically managed with excision of hemorrhoidal tissue called hemorrhoidectomy. milligan morgan hemorrhoidectomy is considered the gold standard procedure for hemorrhoidectomy.2 major complication associated with milligan morgan hemorrhoidectomy (mmh) is post-operative pain. other complications are post-operative hemorrhage, urinary retention, soiling, stenosis and incontinence.3 subsequent modifications to counter complications in this procedure are the use of diathermy and ligasure®. harmonic scalpel® (hs) is a new device introduced to surgery in last decade. it uses high frequency sound wave energy to cut and coagulate tissues at the same time at precise point of application. it denatures protein by using ultrasonic vibration to transfer mechanical energy sufficient to journal of rawalpindi medical college (jrmc); 2017;21(3): 233-236 234 break tertiary hydrogen bonds. the blade vibrates at 55.5 khz over a distance of 80 μm. in different studies, authors found that hs was found to seal arteries 3.8 mm in diameter on average and veins 9.9 mm in diameter on an average. when the effect is prolonged, secondary heat is produced that seals larger vessels. because ultrasound is the basis for harmonic scalpel® technology, no electrical energy is conducted to the patient.6 harmonic scalpel® hemorrhoidectomy (hsh) has emerged to be a safe, rapid modality, with reduced blood loss and post-operative pain. ramadan et al demonstrated decreased operation time (13.2 [1.7] min for hsh vs. 29.6 [5.4] min for mmh [p-value 0.0001]), and less post-operative pain (pain on vas as 4.3 [1.3] for hsh vs. 7.4 [1.6] pain score for mmh [p-value 0.0001]).7 multiple studies favor this technique.8-10 there are studies with variable results.11 the rationale for evaluating the use of the harmonic scalpel® for surgical hemorrhoidectomy lay in decreased lateral thermal damage with rapid coagulation of vascular cushions, resulting in reduced operating time and post-operative pain. no local data is available and locally this technique is not in practice. patients and methods this randomized controlled trial was conducted at surgical unit-i of holy family hospital rawalpindi from december 2013 to june 2014. 62 patients with hemorrhoids were included in this study, and divided into group 1 and group 2. group 1 included 31 patients, in whom harmonic scalpel® hemorrhoidectomy was used as treatment. group 2 – included 31 patients,in whom classical milligan morgan hemorrhoidectomy was used. all patients with grade iii, grade iv and grade ii hemorrhoids in whom conservative approaches failed were admitted through opd on an elective basis. both genders were aged 12 years and above, up to 80 years of age were included. exclusions were recurrent hemorrhoids, presence of additional anorectal pathology (fistula in ano, anal fissures etc.), patients with neurological deficit, and patients with chronic pain syndrome, already on narcotics. randomization was performed at the time of anesthesia by drawing sealed envelopes (lottery method) into group 1 and group 2. surgery was performed under general or spinal anesthesia at the discretion of the anesthetist.patients in group 1 underwent harmonic scalpel® hemorrhoidectomy. the power of the harmonic scalpel® was set at level 3. the internal and external components of each hemorrhoidal complex grasped and elevated by a tooth forceps and the hemorrhoid bundle carefully dissected off the internal anal sphincter using the harmonic scalpel® shears. control of the pedicle was achieved by coagulation using the same device. homeostasis was obtained using the harmonic scalpel® or electrocautery. patients in group 2 underwent classical milligan-morgan procedure for hemorrhoidectomy. this technique used scissors to excise the three anal cushions leaving a mucosal bridge between each wound. the cranial aspect of the cushions was ligated using an absorbable suture and the wounds were left open to heal by secondary intention. surgery was standardized in each case by same team of surgeons. mean operation time was documented, and post-operative pain was assessed. results twenty patients were females and 42 males. the study population was in age group of 24 to 70 years with mean age of 43.76±12.49 years. mean age in group a was 46.65±12.26 years while it was 41.87±12.64 years in group b. majority were in grade iii (table 1). the mean pain score on visual analog scale (vas) for patients undergoing harmonic scalpel® hemorrhoidectomy was 4.32±0.91 compared to 6.97±1.42 in those undergoing milligan morgan hemorrhoidectomy (p < 0.000) (table 2). the mean operation time for patients undergoing harmonic scalpel® hemorrhoidectomy was 18.13±3.95 minutes compared to 22.90±4.90 minutes in those undergoing milligan morgan hemorrhoidecotmy with statistically significant lesser operation time in hsh group (p < 0.000). (table 3) table 1: distribution of patients according to the grade of haemorrhoids treatment group grade of haemorrhoids i ii iii iv hsh 01 06 08 16 mmh 00 07 16 08 table 2: mean pain score on vas in both groups treatment group n mean pain score std. deviation std. error mean p value hsh 31 4.32 0.909 0.163 0.000 mmh 31 6.97 1.462 0.256 table 3: mean operation time in both groups treatment group n mean std. deviation std. error mean p value hsh 31 18.13 3.956 0.711 0.000 mmh 31 22.90 4.901 0.880 journal of rawalpindi medical college (jrmc); 2017;21(3): 233-236 235 discussion haemorrhoidectomy remains the most effective and definitive treatment of choice for grade iii and iv hemorrhoids.11 however, postoperative pain is the aftermath most dreaded by patients undergoing the procedure.12therefore, various new treatment modalities have recently been developed with the aim of overcoming postoperative pain. during the past 20– 30 years, the favourite operation has been the mmh because of its relatively simple technique and reliable outcomes.13 complication rate is relatively low in experienced hands and is simple to manage. the obvious disadvantage of mmh is the postoperative pain resulting from the surgical raw area in the sensitive peri-anal skin and the anoderm. much of this discomfort arises from the thermal injury induced by the electrocautery. hsh possesses the unique advantage of causing very little lateral thermal injury in the tissues. a decreased lateral thermal injury (<1.5 mm) at the surgical site is translated into decreased postoperative pain. dejan et al compared mean pain score between mmh and hsh on first, second and seventh day after surgery.9 they concluded that harmonic scalpel® hemorrhoidectomy, due to less thermal damage, statistically significantly reduced postoperative pain with better hemostasis, compared with milliganmorgan's method of treating hemorrhoidal disease. armstrong et al randomized fifty consecutive patients into two groups: harmonic scalpel® and electrocautery hemorrhoidectomy.14 pain was assessed using a visual analog scale preoperatively and on postoperative days . twenty-four-hour narcotic usage (hydrocodone, 10 mg) was recorded on postoperative days. pain in the harmonic scalpel® hemorrhoidectomy group was significantly less than in electrocautery patients on each postoperative day studied. analgesic requirements were also significantly less in the harmonic scalpel® group on days 1, 2, 7, and 14. there was no correlation between postoperative pain and grade of hemorrhoid. in another study,armstrong et al performed 500 consecutive cases of harmonic scalpel® hemorrhoidectomy. he concluded that it is a safe and effective surgical modality. although the incidence of postoperative hemorrhage compares very favorably with previous large studies, the surgical defects should be closed to minimize the risk, and postoperative toradol® administration should be limited to 24-hour to 48-hour usage.14 talha et al compared ligasure, hs and conventional hemorrhoidectomy. the median operative time was 8 min (range, 7–18) for the ligasure and harmonic scalpel® groups and 18 min (range, 15–21) for the diathermy group (p < 0.001). throughout the first post-operative week, the daily median pain score was lower in the ligasure and harmonic scalpel® groups than in the diathermy group (p <0.001). the median number of analgesic ampoules during the first 24 h postoperatively was lower in the ligasure and harmonic scalpel® groups (p < 0.001).15 ramadan et al compared 54 consecutive cases between harmonic scalpel® and milligan morgan hemorrhoidectomy, in his study duration of surgery was significantly higher in the mm group (p<0.0001). postoperative hospitalization was longer in the mm group (p<0.0001), and the pain degree was higher in mm group (p<0.0001). no significant difference was noted in the overall amount of analgesics used in the two groups at week 1, although it was significantly higher in the mm group 2 and 3 weeks after the operation.10 ozer et al compared hs and classical method using open and closed hemorrhoidectomy techniques. they randomized into open hs (n= 22), closed hs (n=22), milligan morgan (n=22), and ferguson (n=21) hemorrhoidectomy. patients were evaluated for operation time, postoperative pain, bleeding, and analgesic consumption. bleeding volume was significantly lower in groups i-ii (p<0.001). operation time was significantly shorter in group i (p<0.001). postoperative pain and pain at the time of first defecation, was significantly lower in groups i-iii (p<0.001) compared with the other 2 groups and lower during days 2-6 in group i compared to the group iii (p<0.004). visual analogue scale results were similar in groups ii and iv. analgesic consumption in groups i-iii was significantly lower than groups ii-iv (p<0.001). oral consumption of analgesic during 2nd& 5thpostoperative days was lower in group i than in group iii (p<0.007) and similar in closed hemorrhoidectomy group.16 in another study, tsunoda et al compared a novel technique of doppler-guided transanal hemorrhoidal dearterialization and mucopexy (thd surgery) with harmonic scalpel® hemorrhoidectomy. they observed that the pain scores were significantly lower in the thd patients on days 6 and 7 after the operation. the number of analgesic tablets consumed during the first postoperative week in the thd patients was significantly lower than that in the us patients. the blood loss was significantly greater in the thd patients. the hospital stay and length of time until the first defecation after surgery were both significantly shorter in the thd patients.1 journal of rawalpindi medical college (jrmc); 2017;21(3): 233-236 236 conclusion 1. harmonic scalpel® hemorrhoidectomy is a safe and quick procedure for grade iii and iv hemorrhoids with relatively less post-operative pain as compared to conventional milligan morgan procedure. 2.in comparison to recent and novel techniques like ligasure and doppler-guided transanal hemorrhoidal dearterialization, hs offers similar outcomes. references 1. lohsiriwat v. hemorrhoids: from basic pathophysiology to clinical management. world j gastroenterol. 2012; 18(17): 2009-17. 2. song sg, kim sh. optimal treatment of symptomatic hemorrhoids.j korean soccoloproctol. 2011 ; 27(6):277-81. 3. li yd, xu jh, lin jj, zhu wf.excisional hemorrhoidal surgery and its effect on anal continence.world j gastroenterol. 2012;18(30):4059-63. 4. haveran la, sturrock pr, sun my, mcdade j. simple harmonic scalpel hemorrhoidectomy utilizing local anesthesia combined with intravenous sedation: a safe and rapid alternative to conventional hemorrhoidectomy.int j colorectal dis. 2007 ;22(7):801-06. 5. zorcolo l, giordano p, zbar ap, wexner sd, seow-choen f. the italian society of colo-rectal surgery annual report 2010: an educational review.tech coloproctol. 2012 ; 16(1):9-19. 6. gibbons cp, bannister jj, read nw.role of constipation and anal hypertonia in the pathogenesis of haemorrhoids.br j surg. 1988 ; 75(7):656-60. 7. hulme-moir m, bartolo dc.hemorrhoids.gastroenterolclin north am. 2001 ; 30(1):183-97. 8. mosley jg, galland rb, saunders jh, spencer j.haemorrhoids--objective measurement of proctoscopic appearances.postgrad med j. 1980 ; 56(651):30-33. 9. ivanov d, babović s, selesi d, ivanov m.harmonic scalpel hemorrhoidectomy: a painless procedure?med pregl. 2007 ; 60(9-10):421-26. 10. ramadan e, vishne t, dreznik z.harmonic scalpel hemorrhoidectomy: preliminary results of a new alternative method.tech coloproctol. 2002 ; 6(2):89-92. 11. khan s, pawlak se, eggenberger jc, lee cs.surgical treatment of hemorrhoids: prospective, randomized trial comparing closed excisional hemorrhoidectomy and the harmonic scalpel technique of excisional hemorrhoidectomy.dis colon rectum. 2001 ; 44(6):845-49. 12. armstrong dn, frankum c, schertzer me.harmonic scalpel hemorrhoidectomy: five hundred consecutive cases.dis colon rectum. 2002 ; 45(3):354-59. 13. tsunoda a, sada h, sugimoto t, kano n, kawana m. randomized controlled trial of bipolar diathermy vsultrasonic scalpel for closed hemorrhoidectomy.world j gastrointest surg. 2011 27; 3(10): 147-52. 14. armstrong dn, ambroze wl, schertzer me, orangio gr.harmonic scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.dis colon rectum. 2001; 44(4):558-64. 15. talha a, bessa s, wahab ma. ligasure, harmonic scalpel versus conventional diathermy in excisional haemorrhoidectomy: a randomized controlled trial. anz j surg. 2014 ;87(4): 252–56. 16. ozer mt, yigit t, uzar ai, mentes o, harlak a. a comparison of different hemorrhoidectomy procedures.saudi med j. 2008; 29(9):1264-69. 17. tsunoda a, kiyasu y, fujii w, kano n.comparison of the early results of transanal hemorrhoidal dearterialization and hemorrhoidectomy using an ultrasonic scalpel.surg today. 2015 ; 45(2):175-80. 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 253-256 253 original article risk factors of infection in total knee arthroplasty junaid khan, riaz ahmed, tehreem zahid, rahman rasool akhtar. department of orthopedics, benazir bhutto hospital, holy family hospital and rawalpindi medical college, rawalpindi. abstract background: to determine risk factors of infection in total knee arthroplasty methods: in this descriptive study all patients undergoing primary total knee arthroplasty were included. patients were followed post-operatively at 2,4,8,12 and 24 weeks. signs of inflammation and inflammatory markers such as total leukocyte count (tlc), c-reactive protein (crp) and esr were measured. risk factors like age, body mass index (bmi), asa, co-morbid conditions were also noted. results: out of the 78 patients osteoarthritis (94.87%) was the pre-dominant cause of total knee replacement (tkr). 6.41% cases got infected. in majority of the infected cases (60%), staphylococcus aureus was the infective organism. diabetes mellitus (p=0.01) and obesity (p=0.02) had a significant relation to post-operative infection. conclusion: pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-tkr which will not only improve the mobility of patient but also its morbidity and mortality as well. key words: c-reactive protein (crp), erythrocyte sedimentation rate (esr), staphylococcus aureus, total knee arthroplasty (tka). introduction total knee arthroplasty (tka) is the mainstay of surgical treatment of patients with advanced osteoarthritis.1 it is the most efficient and cost-effective alternative to medication which lasts for the remainder of their life. 2 following tka, patients have a chance of developing post-operative pain, infection, deep venous thrombosis, etc.3 although care is taken to promote asepsis by prophylactic antibiotics, sterilization methods, improving surgical skill and limiting intra-operative time. 4 post-operative joint infection remains the most debilitating complication ensuing all joint arthroplasties.5the risk factors for infection are obesity (elevated bmi), diabetes, prior joint infection, immunocompromised patients (hepatitis b, hepatitis c, hiv), malnutrition, prolonged hospital stay and systemic infections. most of these risk factors are modifiable.6-10 the diagnosis of infection is made on the basis of history (toxic symptoms such as fever, swelling, joint pain extending beyond four weeks after arthroplasty),clinical examination of the affected limb and laboratory evaluation of inflammatory markers such as c-reactive protein (crp), esr, etc.11 the most commonly implicated organisms are staphylococcus species (52.9%), streptococcus (19.2%), e.coli (5.9%) and anaerobes (2.8%).12the worldwide incidence of postoperative infection in prosthetic joints is < 2% and is a significant morbidity in elderly patients presenting to the orthopaedic clinic. patients and methods this descriptive study was conducted in the department of orthopaedics, benazir bhutto hospital, rawalpindi for a duration of three years from january 2014 to january 2017. all patients undergoing primary total knee replacement were included in the study. exclusion criteria were all patients operated in another hospital and revision total knee replacement. all patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. to see the effect of tranexamic acid in minimizing blood loss during surgery and on postoperative infection, 30 patients were given two doses intravenously (15 mg/kg body weight mixed in 10 ml normal saline each), i.e. one 15 minutes prior to incision and other immediately post-operatively while in 23 patients tranexamic acid infiltrated intraarticularly (ia) after wound closure (2 grams mixed in 10 ml normal saline). in 25 patients tranexamic acid not used. stitches were removed at 2nd post-operative week. signs of inflammation such as fever, skin changes (erythema), raised temperature, swelling and discharge from the operative site were noted. inflammatory markers such as complete blood count (cbc), erythrocyte sedimentation rate (esr) and creactive protein (crp) levels were done pre and post operatively to monitor infection if any signs of inflammation were found. american society of anesthesiologists (asa) score was noted (table 1). descriptive statistics such as mean, standard deviation journal of rawalpindi medical college (jrmc); 2017;21(3): 253-256 254 and frequency of patients with post-operative infection were calculated. p value < 0.05 was significant table-1: american society of anaesthesiologists (asa) scoring system asa i patient is completely healthy fit ii patient has mild systemic disease iii patient has severe systemic disease that is not incapacitating iv patient has incapacitating disease that is a constant threat to life v a moribund patient who is not expected to live 24 hour with or without surgery results a total of 78 patients underwent primary unilateral total knee replacement (tkr) during the study period. of these, 30 (34.09%) were male and 48 (61.54%) female patients. 32 (41.02%) of these underwent unilateral tkr. mean age of patients was 68.32  8.54 years. average bmi 25.89 kg/m2.osteoarthritis was the pre-dominant cause of total knee replacement (table-2). among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. upon anaesthesia fitness pre-operatively, 91.02% patients had an american society of anaesthesiologist score (asa) between 0-2 while 07 (8.97%) between 35.average duration of surgery was 85.62± 4.11 minutes. table-2: indication for total knee replacement (tkr) indication for tkr no percentage osteoarthritis 74 94.87% rheumatoid arthritis 02 2.56% septic arthritis 01 1.28% psoriatic arthritis 01 1.28% table-3: factors related to surgery factor no mean  s.d average 24-hour volume of drain output (without tranexamic acid) 2 309.23±58.92 average 24-hour volume of drain output (with iv tranexamic acid) 30 265.79±34.40 average 24-hour volume of drain output (with ia tranexamic acid) 23 215.92±55.18 average duration of surgery 78 85.62±4.11 minutes mean volume of post-operative drain output was less in patients who were given tranexamic acid during surgery (table-3). among various factors involved in surgery, patients with diabetes mellitus (p = 0.01) and obesity (p = 0.02) showed a significant correlation with infection after total knee arthroplasty (table 4). out of the total 78 cases, 05 (6.41%) cases got infected. staphylococcus aureus was the pre-dominant (60%) organism in infected cases (table-5). all patients were given antibiotics according to sensitivity along with daily dressings. in 02 patients drainage of infective collection had to be done. table-4: risk factors associated with infection risk factors total no. of patient s no. of patients with infected wound p-value diabetes mellitus 26 03 0.01 ischemic heart disease 22 01 0.69 obesity 34 04 0.02 3 or more surgeons involved in surgery 37 02 0.89 foley’s catherization 19 01 0.99 american society of anaesthesiologists (asa) score 3 or more 07 01 0.81 use of tranexamic acid 53 03 0.54 table-5: frequency of organisms in infected cases infective organism number of patients percentage staphylococcus aureus 03 60% klebsiella pneumoniae 01 20% acinetobacter baumanii 01 20% discussion despite thorough sanitation and aseptic measures adopted by the surgeons and paramedical staff, intraarticular infection is the leading complication following arthroplasty which warrants extensive management, both medical and surgical.the overall risk factors that were significant in our study were the patients’ age, gender, bmi, co-morbid conditions, asa score and foley’s catheterization. the route of administration of txa and number of surgeons involved per surgery were the factors associated with the orthopaedic team. the patients who presented journal of rawalpindi medical college (jrmc); 2017;21(3): 253-256 255 for primary tka were predominantly female, within the age bracket of 65-75 years. these findings were consistent with results shown by woolheadet al and feldman et al. 14,16 the leading indication for tka was osteoarthritis, followed by rheumatoid arthritis, septic arthritis and other degenerative infections. this was also reported by nassif et al and beal et al17in their studies in 2015 and 2016 respectively. 15,17 diabetes was the predominant co-morbid condition in 34.2% of all cases and 11% of those cases got infected. ischemic heart disease and chronic lung disease were the second and third most common premorbidities. worldwide statistics corroborate the same results with diabetes mellitus and ihd fluctuating as the leading cause depending upon the prevalence and incidence of the co-morbidity in that particular area. elmallah et al, moon et al and bolognesi et al cited results similar to ours. 18-20 as reported by mi et al use of intra-articular tranexamic acid was associated with better postoperative outcome in our study, evidenced by monitoring drain output in all patients for at least 48 hours. 21 the overall rate of infection was 6.41% in our study whereas a study conducted on the same patterns and lines by babkin22 et al in 2007 showed rates of 5.6%. 22 the predominant organism was staphyloccocus aureus with 60% cultures being positive for the organism. 3 bongartz et al and cho et al observed similar rates of 65.2% and 52.9%.1,13the measures that need to be undertaken to limit infection after arthroplasty extend beyond the nursing staff and orthopaedic team, all factors must be taken account when devising a disinfection protocol.23 points of entry in the operating room must be limited, with only surgeons and staff relevant to the case being allowed entry. all machinery, surgical instruments, gowns, drapes and devices installed in the operating room (or) must be inspected and inspected for contamination, especially air conditioning.ventilation systems must be inspected and laminar air flow must be established with a 5 micrometre filter which should be cycled through the or about 25 times per hour to keep the bacterial count less than 180 colony forming units/m3. surgical techniques must be proper and hemostasis must be maintained at all times since a peri-operative hematoma leads to bacterial growth and wound infection. intra-operative time must be limited.24,25 diabetics and hypertensive patients must reach optimum control prior to surgery . wounds must be monitored in diabetics since they are prone to poor wound healing and sepsis.focal source of sepsis in or around the incision site must be disinfected properly before surgery. prophylactic antibiotics must be administered in all patients pre-operatively.26 since the pre-dominant organism causing infection was the patients’ own flora (staphylococcus aureus resides in the skin) antiseptic measures are a must for control of infection. conclusion despite pre-operative risk assessment and prevention, joint infection still remains the most feared complication after arthroplasty. it takes a toll on the patients’ mobility, morbidity and mortality. early recognition of infection and aggressive control can drastically improve outcomes. references 1. bongartz t, halligan cs, osmon dr, reinalda ms. incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid arthritis. arthritis & rheumatism. 2008;59:1713–20. 2. lavernia cj, guzman jf, gachupin-garcia a. cost effectiveness and quality of life in knee arthroplasty. clin orthop relat res. 1997;45:134–39. 3. poss r, thornhill ts, ewald fc, thomas wh, batte nj. factors influencing the incidence and outcome of infection following total joint arthroplasty. clin orthop relat res. 1984;18:117–26. 4. vaisbrud v, raveh d, schlesinger y. surveillance of antimicrobial prophylaxis for surgical procedures. infect control hosp epidemiol. 1999;20:610-13. 5. lidwell om. the control of infection after total joint replacement. j hosp infect. 1993;23:5-15. 6. simons mj, amin nh, scuderi gr. acute wound complications after total knee arthroplasty: prevention and management. j am acad orthop surg. 2017;25:547-55. 7. fehring tk, odum s, griffin wl, mason jb. early failures in total knee arthroplasty. clinorthoprelat res. 2001;39:31518 8. segawa h, tsukayama dt, kyle rf. infection after total knee arthroplasty. a retrospective study of the treatment of 81 infections. j bone joint surg. 2009;81:1434-45. 9. dowsey m and choong p. obese diabetic patients are at substantial risk for deep infection after primary tka. clinical orthopaedics and related research. 2008;467(6):1577-81. 10. jiranek w. modifiable risk factors in total joint arthroplasty. the journal of arthroplasty. 2016;31(8):161921. 11. vasso m, schiavone panni a. low-grade periprosthetic knee infection: diagnosis and management. journal of orthopaedics and traumatology 2015;16(1):1-7. 12. chun kc, kim km, chun ch. infection following total knee arthroplasty. knee surgery & related research. 2013;25(3):93-99. 13. cho ws, jeong yg, park jh, shin hk, kim ky. treatment of infected tkra. j korean orthop assoc. 2001;36:561–67. 14. woolhead g. outcomes of total knee replacement: a qualitative study. rheumatology. 2005;44(8):1032-37. 15. nassif j, pietrzak w. clinical outcomes in men and women following total knee arthroplasty with a high-flex knee: no journal of rawalpindi medical college (jrmc); 2017;21(3): 253-256 256 clinical effect of gender. the scientific world journal. 2015;15:1-6. 16. feldman c, dong y, katz j, donnell-fink l. association between socioeconomic status and pain, function and pain catastrophizing at presentation for total knee arthroplasty. bmc musculoskeletal disorders. 2015;16(1):38-42. 17. beal m, delagrammaticas d, fitz d. improving outcomes in total knee arthroplasty—do navigation or customized implants have a role? journal of orthopaedic surgery and research. 2016;11(1):71-77. 18. elmallah r, cherian j, robinson k, harwin s. the effect of comorbidities on outcomes following total knee arthroplasty. journal of knee surgery. 2015;28(05):411-16. 19. moon h, han c, yang i, cha b. factors affecting outcome after total knee arthroplasty in patients with diabetes mellitus. yonsei medical journal. 2008;49(1):129-34. 20. bolognesi m, marchant, jr. m, viens n, cook c. the impact of diabetes on perioperative patient outcomes after total hip and total knee arthroplasty. the journal of arthroplasty. 2008;23(2):322-23. 21. mi b, liu g, lv h, liu y, zha k, wu q et al. is combined use of intravenous and intraarticulartranexamic acid superior to intravenous or intraarticulartranexamic acid alone in total knee arthroplasty? a meta-analysis of randomized controlled trials. journal of orthopaedic surgery and research. 2017;12(1):122-29. 22. babkin y, raveh d, lifschitz m, itzchaki m, wiener-well y, kopuit p et al. incidence and risk factors for surgical infection after total knee replacement. scandinavian journal of infectious diseases. 2017;39(10):890-95. 23. rezapoor m, parvizi j. prevention of periprosthetic joint infection. the journal of arthroplasty. 2015;30(6):902 07. 24. cuckler j. minimizing the risk of tjr infection: a checklist. seminars in arthroplasty. 2015;26(2):44-46. 25. shohat n, parvizi j. prevention of periprosthetic joint infection: examining the recent guidelines. the journal of arthroplasty. 2017;24(2):18-27. 26. devon r. infection prevention society awards 2016. journal of infection prevention. 2017;18(1):43-46. 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 262-264 262 original article screening for chronic kidney disease in family members of dialysis patients. jais kumar 1,ghiasuddin butt 2 ,faran maqbool 3 1. department of nephrology, islamabad medical and dental college; 2. department of nephrology, pakistan institute of medical sciences islamabad; 3. department of medicine, district headquarter hospital rawalpindi and rawalpindi medical university abstract background: to study the prevalence of chronic kidney disease in family members of dialysis patients methods: in this cross-sectional observational study relatives of incident dialysis patient were enrolled. family members of patients of all ages with history of diabetes mellitus, hypertension, family history of chronic kidney disease, chronic pyelonephritis and autoimmune diseases were included. relatives already on renal replacement therapy, hepatitis b and c, hiv reactive patients and with chronic heart and liver failure, chronic infections and septicemia patients were excluded . results: out of these 200 participants, majority (72%) were male. minimum age of the study population was 18 years and maximum age was 66 years. mean age was 35.5 ± 9.93 years. frequency of risk factors in study population showed that out of 200 participants 15% had hypertension, 6% had diabetes, 2.5% had renal stone disease and 74% participants did not have any risk factor. blood pressure was normal in 83% participants. blood glucose was normal in 92.5%. conclusion: screening of the family members of esrd patients is important for the prevention of kidney disease in other family members. key words: family members,chronic kidney disease,dialysis patients introduction chronic kidney disease (ckd) is a worldwide public health problem.1 the declaration of world kidney day to be observed annually beginning in march 2006 sends a clear message to the public, government health officials, physicians, allied health professionals, patients, and families that ‘ckd is common, harmful, and treatable. 2 chronic kidney disease (ckd) is receiving increased public attention, with early prevalence estimates at 11% and more recent estimates showing that 13% of the us population has some evidence of kidney damage.3,4 more than 20 million americans aged 20 and older may have ckd, based on a decreased glomerular filtration rate (gfr), a measure of kidney function. although ckd is common, many americans with the key risk factors—diabetes and high blood pressure—do not know they are at risk. in addition, the rising rates of diabetes and obesity will continue to fuel its growth, as both conditions increase the risk of developing ckd and speed its progression. a recent national survey in china indicates that the prevalence of ckd in china is 10.8%.5 in addition to kidney failure, other serious complications— particularly cardiovascular disease (cvd)—are associated with ckd. other complications include anemia, malnutrition, bone disease, and depression the exact prevalence of chronic kidney disease in pakistan is not clear in the absence of regular national registry data and provided only by small observation series or reports from personal experience, and the quality of data is quite uneven. ckd is defined as presence of kidney damage or glomerular filtration rate less than 60ml/min/1.73msq for 3 or longer, irrespective of cause.6-8 ckd and esrd impose a tremendous public health burden, costing the u.s. health care system billions of dollars. in 2006, costs for medicare patients with ckd exceeded $49 billion, accounting for nearly one-quarter of general medicare costs (usrds, 2008). medicare spending for esrd reached $22.7 billion during the same year (usrds, 2008). by 2020, medicare esrd costs are expected to reach $55.6 billion (usrds, 2007). survival, mortality and causes of death in esrd patients despite advances in dialysis and transplantation, the prognosis of kidney failure remains bleak. the usrds reported more than 60000 deaths of patients with esrd, and an annual mortality rate of dialysis patients in excess of 20%. expected remaining lifetime of patients treated by dialysis were shorter than the age matched general population, varying (depending on race and gender) from 7.1 to 11.5 years for patients aged 40 to 44 years, journal of rawalpindi medical college (jrmc); 2017;21(3): 262-264 263 and from 2.7 to 3.9 years for patients aged 60 to 64 years. 9-11 therapeutic interventions at earlier stages of chronic kidney disease are effective in slowing the progression of chronic kidney disease the major therapeutic strategies that have been tested include strict blood glucose control in diabetes, strict blood pressure control, angiotensin-converting enzyme (ace) inhibitors and angiotensin-receptor blockers, and dietary protein restriction. patients with ckd have a large number of comorbid conditions. comorbidity is defined as conditions other than the primary disease (in this case, chronic kidney disease). screening and early detection of kidney disease has the aim not only to prevent kidney damage but also to prevent comorbidities associated with chronic kidney disease patients and methods this cross sectional observational study was conducted at nephrology department, pakistan institute of medical sciences from january 2014 to january 2015.all relatives of incident dialysis patients were taken for the study. documentation of existing standards of care for chronic diseases associated with renal disease was done and institution of disease management program that facilitate the systematic management of patient with chronic diseases that lead to end stage renal disease. randomized non-biased sampling of patients admitted or consulted the nephrology department of pakistan institute of medical sciences was done. patients of all ages with history of diabetes mellitus, hypertension, family history of chronic kidney disease, chronic pyelonephritis and autoimmune diseases were included. patients with renal replacement therapy, hepatitis b and c, hiv, those with chronic heart and liver failure and finally patients with chronic infections and septicaemic patients were excluded from study. results total 200 family members of the patients on maintenance dialysis for esrd were included after taking the consent and fulfilling the inclusion and exclusion criteria. out of these 200 participant majority (72%) were male . minimum age of the study population was 18 years and maximum age was 66 years. mean age is 35.5 ± 9.93 years. donors’ breakup revealed that 112 (56%) were sons, followed by 36(18%) daughters and 24(12%) brothers. hypertension (15%) was the commonest risk factor found (table 1). blood pressure was normal in 83%. blood glucose was found to be normal in 92.5% and increased in 7.5% participants (table 2). majority (85.5%) of the participants did not have any urinary protein, 21(10.5%) had 1+ protein, 6(3%) had 2+ protein, and 2 (1%) participants had 3+ urinary protein . similarly 178 (89%) participants did not have urinary glucose, 10(5%) had 1+ glucose, 7(3.5%) had 2+ glucose, 4(2%) had 3+ glucose and one (0.5%) had 4+ urinary glucose. lipid profile was normal in 73.5%. minimum hb was 8, maximum was 18, mean was 12.12 ±2.09 g/dl. (table 2). on ultrasound kidney sizes were normal in 79%. table 1:frequency of risk factors risk factors number percentage hypertension 30 15% diabetes mellitus(dm) 12 6% coronary artery disease 2 1% stone disease 5 2.5% hypertension+dm 3 1.5% no risk factor 148 74% table 2:descriptive statistics of the study population (n=200) variables range min max mean sd age 48 18 66 35.95 9.931 weight(kg) 67 42 109 72.67 15.34 blood glucose(mg /dl) 232 54 234 106.21 31.41 urine ph 3.0 5.0 8.0 6.007 .7933 rbc in urine 62 0 62 2.37 6.937 wbc in urine 43 0 43 1.88 4.440 serum creatinine (mg/dl) 6.68 .32 3.20 .8176 .4342 haemoglobin 97.0 8.0 18.0 12.12 2.090 serum phosphorus 2.18 3.00 5.18 3.7380 .3880 serum calcium 8.9 7 9.5 8.44 .3991 discussion chronic kidney disease (ckd) is increasingly recognized as a global public health problem. the declaration of world kidney day to be observed annually beginning in march 2006 sends a clear message to the public, government health officials, physicians, allied health professionals, patients, and families that ‘ckd is common, harmful, and treatable.12 the exact prevalence of chronic kidney disease in pakistan is not clear in the absence of regular national registry data and provided only by small observation series or reports from personal experience, and the quality of data is quite uneven. journal of rawalpindi medical college (jrmc); 2017;21(3): 262-264 264 ckd is defined as presence of kidney damage or glomerular filtration rate less than 60ml/min per 1.73 msq for 3 or more months, irrespective of cause.13 we included 200 relatives of the patients with esrd and on dialysis. though this number is not much large as compared to international screening analysis, it still gives us direction toward the future strategies. same cross-sectional survey of screening to identify ckd among family members of esrd patients was conducted at different community dialysis centers in georgia.14 family members of esrd patients were recruited for ckd screening. a medical history, measurements of bp, serum glucose, hemoglobin (hb), serum creatinine, and urinalysis were obtained at community screening sites. of 221 family members screened between 1999 and 2001 in georgia, 13.9% had an estimated creatinine clearance (ccr) _60 ml/min. proteinuria of 1+ or more was found on urinalysis in 9.9%. in our analysis proteinuria was significantly present and was 1+ in 10% of the patients. however in another screening survey, out of 84 participants, 26% of these had proteinuria.15-17a multicenter study in china shows presence of ckd is different between first-degree relatives and spouses of ckd patients.18 hypertension was present in 15% of our study population, where as it was present with much higher frequency in a cross-sectional survey in georgia where 58% of the study participants were hypertensive, some of which were getting treatment for hypertension and some unaware of their disease. 14 where as in other surveys, 21.9% of the family members of the esrd patients had hypertension, and these results were comparable with our study results. in present study, 7.5 % of the participants had impaired blood glucose and 92.5% of the participants had normal blood glucose. when we compare these results with international data, it was found that in georgia survey, 18.6% of the study population had increased blood glucose.8 where as in other survey 18.1 % of the participants had impaired blood glucose the study by iseki in the okinawa region of japan also demonstrated that proteinuria and high serum creatinine level are two valuable prognostic factors for end-stage renal disease. 18 out of 200 participants , 8% of the participants had increased serum creatinine. conclusion 1. screening of the family members of esrd patients is important for the prevention of kidney disease in other family members. 2. in present study 13 % of the patients had proteinuria, 15 % of the patients had increased blood pressure, 7.5 % of the participants had impaired blood glucose. references 1 kdigo. clinical practice guideline for the evaluation and management of chronic kidney disease. kidney int 2012; 63-72. 2 united states renal data system 2008 annual data report atlas of chronic kidney disease and end-stage renal disease in the united states. am j kidney dis 2009; 1(1):s1-s4. 3 levey as, eckardt ku, tsukamoto y. definition and classification of chronic kidney disease. kidney int 2005 ;67(6):2089-100. 4 peralta ca, shlipak mg, fan d, ordonez j . risks for endstage renal disease, cardiovascular events, and death in hispanic versus non-hispanic white adults with chronic kidney disease. j am soc nephrol 2006 ;17(10):2892-99. 5 zhang l, wang f, wang l. prevalence of chronic kidney disease in china: a cross-sectional survey. lancet 2012; 379 (9818): 815-22. 6 feehally, j. ethnicity and renal disease. kidney int 2005; 68:414-17. 7 tareen n, zadshir a, martins d, pan d, nicholas s. chronic kidney disease in african american and mexican american populations. kidney int suppl 2005 ;(97):s137-40. 8 rodriguez ra, hernandez gt, o'hare am, glidden dv. creatinine levels among mexican americans, puerto ricans, and cuban americans in the hispanic health and nutrition examination survey. kidney int 2004;66(6):2368-73. 9 scavini m, shah vo, stidley ca, tentori f, paine ss, harford am . kidney disease among the zuni indians: the zuni kidney project. kidney int suppl 2005 ;(97):s126-31. 10 choi hs, sung kc, lee kb. the prevalence and risk factors of microalbuminuria in normoglycemic, normotensive adults. clinnephrol. 2006 ;65(4):256-61. 11 viktorsdottir o, palsson r, andresdottir mb. prevalence of chronic kidney disease based on estimated glomerular filtration rate and proteinuria.nephrol dial transplant. 2005 ;20(9):1799-807. 12 hsu cc, hwang sj, wen cp, chang hy. high prevalence and low awareness of ckd in taiwan: a study on the relationship between serum creatinine. am j kidney dis. 2006 ;48(5):727-38. 13 hallan si, coresh j, astor bc, asberg a. international comparison of the relationship of chronic kidney disease prevalence and esrd risk. j am soc nephrol. 2006 ;17(8):2275-84. 14 levey as, andreoli sp, du bose t. chronic kidney disease: common harmful and treatable –world kidney day 2007. am j kidney dis 2007; 49: 175–79. 15 mital s, kher v, gulati s, agarwal lk, arora p. chronic renal failure in india. renal failure 1997;19(6):763-70. 16 satko sg and freedman bi. the importance of family history on the development of renal disease. curr opin nephrol hypertens 2004; 13:337-41. 17 iseki k. the okinawa screening program. j am soc nephrol 2003;14:s127-30. 18 kong x1, liu l, zuo l, yuan p, li z. association between family members of dialysis patients and chronic kidney disease: a multicenter study in china. bmc nephrol 2013; 18;14:19-22. 404 not found 165 journal of rawalpindi medical college (jrmc); 2022; 26(2): 165-168 short communication novel disease but responding to an old drug: role of prolonged corticosteroid use in prevention and treatment of post-covid interstitial lung disease (pc-ild) muhammad waseem1, maryam rafiq2 1,2 assistant professor, sahiwal medical college, sahiwal author’s contribution 1 conception of study 1 experimentation/study conduction 1 analysis/interpretation/discussion 1,2 manuscript writing 2 critical review corresponding author dr. maryam rafiq assistant professor of pathology, sahiwal medical college, sahiwal. email: mariamsheikh15@yahoo.com article processing received: 24/01/2022 accepted: 15/03/2022 cite this article: waseem, m., rafiq, m. novel disease but responding to an old drug: role of prolonged corticosteroid use in prevention and treatment of post-covid interstitial lung disease (pcild). journal of rawalpindi medical college. 30 jun. 2022; 26(2): 165-168. doi: https://doi.org/10.37939/jrmc.v26i2.1786 conflict of interest: nil funding source: nil access online: abstract coronavirus has affected more than 128 million humans worldwide with invasions in 129 countries across the globe. about 5-10 percent of these patients have pulmonary involvement in the form of covid pneumonia leading to ards. although there are no statistics at the moment, trends show that majority will get rid of acute covid respiratory involvement without any long-term pulmonary complications however several patients will face covid sequel in the form of post-covid fibrosis or post-covid interstitial lung disease. with more and more survivors of covid-19, long-term pulmonary complications of this infection especially post-covid ild are being recognized by treating physicians as having a great impact on patients’ functionality and quality of life. since there is no research-based internationally accepted strategy to prevent and treat post-covid ild, a strategy based upon observations of treating pulmonologists was devised in the covid management unit at sahiwal medical college sahiwal to prevent and treat post covid interstitial lung disease. keywords: anti-fibrotic, fibrosis, post-covid sequelae, post-covid fibrosis, post-covid ild. 166 journal of rawalpindi medical college (jrmc); 2022; 26(2): 165-168 introduction since its appearance in wuhan in december 2019, covid-19 has taken the world by storm. coronavirus has affected more than 128 million humans worldwide with invasions in 129 countries across the globe.1 initial research work about covid-19 involved infection control and management of covid-19 acute complications especially acute respiratory failure. covid pneumonia can lead to acute refractory respiratory failure.2 there is an urgent need to address the issue of post-covid fibrosis in severely affected covid pneumonia cases. many survivors of covid pneumonia are presenting with post-covid interstitial lung disease (pc-ild). which is a very fearsome complication leading to morbidity and reduced quality of life.1 due to lack of trials, there is no consensus about the management of post-covid-19 lung complications including lung fibrosis.3 sahiwal medical college sahiwal covid management center devised its strategy to cope with this complication including prevention and treatment for post-covidild. post-covid ild (pc-ild) interstitial lung diseases also known as diffuse parenchymal lung diseases are a heterogeneous group of diseases that involve lung parenchyma with hundreds of possible causes. a classification system broadly divides ilds into 2 groups: ilds with known etiology and ilds without known etiology. postcovid ild falls in the category of ilds with known etiology and a new entry in ild causes after 3 to 4 weeks of the onset of covid symptoms.4 its pathogenesis involves the pivotal role of angiotensinconverting enzymes, increased expression of tgf-beta, and myofibroblast activation.1 risk factors for the development of post-covid ild include age, disease severity markers (tachycardia, longer hospital stay, extent of disease at ct), acute respiratory distress syndrome (ards), and mechanical ventilation.2 the most common presentation of post-covid ild is exertional shortness of breath which is reported even several weeks after discharge from the covid facility. there are many patterns of post-covid ild in radiology that may show various stages of inflammation. the three most distinct patterns are ground-glass opacities, organizing pneumonia, and honeycombing out of which honey combing is found to be the most severe.2 ground glass opacities with or without consolidation, crazy paving pattern, interstitial thickening, and parenchymal bands. these findings are mainly bilateral with a predilection for the peripheries of the lower lobes.3 fortunately, most patients with post-covid ild tend to improve while a few remain in the static phase or deteriorating phase. various treatment options are being considered for post-covid ild including corticosteroids, pirfenidone, nintedanib, and long-term oxygen therapy and lung transplantation.1 figure 1: post-covid ild in a 45 years diabetic male figure 2: post-covid ild in a 56 years male observations at covid management center sahiwal medical college sahiwal several observations were made during the management of post-covid pneumonia cases in the covid management center at sahiwal medical college sahiwal. 1. the recovery trial led to the selective use of 10 days of dexamethasone (1.5cc od) for hospitalized covid pneumonia cases which 167 journal of rawalpindi medical college (jrmc); 2022; 26(2): 165-168 was certainly a practice-changing step (4). however, it was noted that many patients had difficulty in maintaining oxygen saturations immediately after withdrawal of corticosteroids and a considerable portion reported exertional shortness of breath several weeks after weaning. the majority of patients belonging to this group had hrct changes representing persistent ground-glass haze or organizing pneumonia. 2. these patients were given oral corticosteroids in a tapering dose after 10 days of injectable 1.5cc dexamethasone starting from 30mg daily and reducing the dose weekly in 3-4 weeks. patients with this regimen weaned from oxygen successfully and reported less shortness of breath however they developed more steroid-induced side effects most commonly proximal myopathy, steroidinduced diabetes, and gastrointestinal side effects which were managed by reassurance, and glucose-lowering agents, and proton pump inhibitors (ppis). the number of patients with residual fibrosis was very less with this tapering dose of oral corticosteroids. 3. patients with early administration of oral steroids with minimal symptoms like slight shortness of breath (mmrc-2), a mild drop of oxygen saturation (range from 92-94%), and signs of early disease on chest x-ray and less involvement on hrct were less likely to develop severe covid pneumonia and postcovid lung complications. there was reluctant use of steroids during the early days of covid-19. 4. based on the above observations following a treatment plan for prevention of post-covid fibrosis was developed for admitted cases of covid pneumonia which was not earlier developed(table 1) table: 1 strategy for prevention and treatment of post-covid ild (pc-ild) target population (admitted severe cases) severity of indoor admitted cases of covid pneumonia proven either by 1-oxygen saturation less than 94% 2-radiological evidence either by chest x-ray or hrct chest choice of corticosteroid for the first 10 days dexamethasone intravenous patients criteria for oral corticosteroids after stopping intravenous steroids 1-patients failing to maintain oxygen saturation after 10 days of dexamethasone 2-patients having exertional sob 3-patients who desaturate on exertion 4-patients with persistent radiological changes like ground glass haze and organizing pneumonia after 2 weeks 2 choice and dose of oral corticosteroid prednisolone 0.5mg/kg with tapering dose duration according to the clinical response (no sob) and radiological response (clearing of ggo or organizing pneumonia pattern). 2 weeks to 8 weeks. depends upon the treating physician. observed benefits the majority of patients were prevented from developing lung fibrosis which was assessed on chest x-ray. only a few patients developed residual functional or radiological abnormalities. exceptions patients with honey combing on hrct chest or septal thickening were not benefitted from prolonged oral corticosteroid use conclusion 1. oral corticosteroids followed by intravenous dexamethasone in a selected group of patients can be beneficial in preventing and treating post-covid ild. 2. there should be a low threshold considering post-covid ild in patients who are difficult to wean from oxygen, have exertional sob, or have persistent radiological abnormalities. 3. post-covid ild with features like honeycombing and septal thickening can be tried with the use of new anti-fibrotic agents like pirfenidone or nintedanib or their combination. 4. patients with early stage of covid pneumonia-like slight shortness of breath (mmrc-2), a mild drop of oxygen saturation (range from 92-94%), and signs of early disease on chest x-ray and less involvement on hrct can be started with oral steroids to prevent disease progression. 5. however, we found timely and prolonged use of steroids as the best possible and cheap 168 journal of rawalpindi medical college (jrmc); 2022; 26(2): 165-168 therapy for the prevention and control of pcild. references 1. myall kj, mukherjee b, castanheira am, lam jl, benedetti g, mak sm, et al. persistent post–covid-19 interstitial lung disease. an observational study of corticosteroid treatment. ann am thorac soc. 2021 may;18(5):799-806. doi: 10.1513/annalsats.202008-1002oc 2. ambardar sr, hightower sl, huprikar na, chung kk, singhal a, collen jf. post-covid-19 pulmonary fibrosis: novel sequelae of the current pandemic. j clin med. 2021 jan;10(11):2452. doi: 10.3390/jcm10112452 3. udwadia zf, koul pa, richeldi l. post-covid lung fibrosis: the tsunami that will follow the earthquake. lung india. 2021 mar 1;38(7):s41-s4.doi: 10.4103/lungindia.lungindia_818_20. 4. wells au, devaraj a, desai sr. interstitial lung disease after covid-19 infection: a catalog of uncertainties. radiology. 2021 apr;299(1):e216-e218. doi: 10.1148/radiol.2021204482. 5. yu m, liu y, xu d, zhang r, lan l, xu h. prediction of the development of pulmonary fibrosis using serial thin-section ct and clinical features in patients discharged after treatment for covid-19 pneumonia. korean j radiol. 2020 jun;21(6):746755. doi: 10.3348/kjr.2020.0215. 6. wise j, coombes r. covid-19: the inside story of the recovery trial. bmj. 2020 jul 8;370. doi: https://doi.org/10.1136/bmj.m2670 summary journal of rawalpindi medical college (jrmc); 2017;21(3): 265-268 265 original article predictors of tuberculosis treatment default in pulmonary and extrapulmonary tuberculosis khalid mehmood1, inaam qadir javed hashmi2, javed akhtar rathore3, muhammad luqman satti4, khadeeja tul kubra hashmi 2, shizza khalid5., abdur rahman hashmi 6 1.department of community medicine, mohi-ud-din islamic medical college, mirpur, azad jammu & kashmir;2.department of pathology,mohi-ud-din islamic medical colege, mirpur, azad jammu & kashmir;3. department of medicine, ajk medical college muzaffarabad; 4.department of microbiology, armed forces institute of pathology, rawalpindi;5.yusra medical & dental college,islamabad;6. central park medical college (cpmc), lahore abstract background : to detect the predictors of treatment defaults in pulmonary tuberculosis (ptb) and extra pulmonary tuberculosis (eptb). methods: in this cross sectional study 140 adults, with diagnosis of pulmonary tuberculosis (ptb) and extra pulmonary tuberculosis ( eptb), with treatment defaults, were included . the study protocol incorporated demographic, clinical characteristics of patients, structured questionnaire, physical examinations, radiological, laboratory investigations and relevant predictors for tb treatment defaults. the statistical analysis was performed using spss 20. results: mean age of study group was 42.3±20.3. majority (67.1%) were male. ninety four (67.1%) had ptb and 46 (32.9%) had eptb. factors identified to be associated with tb treatment default were male gender ,distance from the health post, displacement, financial constraints, no body at home to bring medicine or take patients to hospital, routes closed in winters, subjective improvement of symptoms and travelling /shifting to other place. conclusions: treatment default is seen in pulmonary and extra pulmonary tuberculosis. due to lack of uniform diagnostic and therapeutic strategy in eptb treatment, most physicians treat on clinical symptoms for a prolonged duration of 12 to 24 months. key words: tuberculosis (tb), multidrug resistance (mdr), pulmonary tuberculosis (ptb), extrapulmonary tuberculosis (eptb), treatment default. introduction world health organization (who) declared tb a globally prevalent and leading cause of death in almost all countries of the world.1-3 about 0.5 million mdr-tb cases were reported worldwide. poverty, emergence of hiv and mdr-tb are the important factors to re-emergence of tuberculosis in developing countries. in 2007 there were an estimated 181/100,000 new cases and 223/100,000 prevalent cases in our country. who ranked pakistan as fifth amongst tb high burden 22 countries of the world, and is also estimated fourth one in the highest prevalence of mdr-tb, globally. 4 although ptb is the most common presentation of tb cases but eptb is not altogether rare. eptb involves any part of the body other than lungs. mycobacterium tuberculosis (mtb) may spread through blood, lymphatics, and lie dormant for years in any organ.5-6 as eptb presents non specifically, therefore diagnosis becomes difficult with extraordinary delay. who estimated that 34,000 (15%) of newly reported cases in 2007 were eptb category in pakistan.7-8 eptb is also a common problem all over the world. in 2011, 14% of all cases of tb in brazil reported belonged to eptb. patients co-infected with human immunodeficiency virus (hiv) also reported in this category. eptb is favored by aids epidemic infection. such and other conditions that suppress immune function have not been studied in our country. 9-10 patients and methods all adults with clinical diagnosis of tb, based on history, clinical examination and laboratory investigations were admitted to hospital. the data was obtained on standardized forms and entered in spss 20. tb defaulters were patients who interrupted treatment for two consecutive months or more as defined by who.11-12 variables studied were age, gender, treatment performed, type of treatment, clinical form, sputum smear microscopy, diabetes mellitus and other co-morbidities. the association of potential risk factors with defaulting was initially journal of rawalpindi medical college (jrmc); 2017;21(3): 265-268 266 studied. the ethical committee approved the study. ptb was defined as tb affecting the lung parenchyma. eptb was defined as tb affecting organs and tissues outside of the lungs (e.g. skin, bones and joints, meninges, etc.). miliary tb was also classified as eptb. pearson’s chi-square test was used to compare the rates of ptb and eptb. variables with a p value < 0.05 were included results total 140 tb patients were enrolled in the study. from the total study population 67.1% (94/140) were males and 32.9% (46/140) were females. the mean age of the study population was 42.3± 20.3 (mean± sd) (table 1). the statistical analysis of gender showed a statistical significant risk of default in male with eptb as compared to females with ptb. table 1: risk factors for ptb and eptb in tb treatment default cases main reasons for default total ptb p-value eptb p value n (%) 140 (%) 94 (67.1%) .004** 46 (32.9%) .022** age (mean ± sd) 42.3 ± 20.3 .669 .011 male 94 (67.1) 69 (49.2) .125 25 (17.9) .001 female 46 (32.9) 25 (17.9) .001* 21 (15.0) .323 distance 18 (12.9) 14 (10) .001* 4 (12.9) .007* displacement 12 (8.6) 4 (2.9) .001* 8 (5.7) .024* financial constraint 8 (5.7) 4 (2.9) .558* 4 (2.9) .001* nobody at home to bring medicine or take patient to hospital 13 (9.3) 11 (7.97) .399* 2 (1.4) .001* route closed in winters 21 (15) 15 (10.7) .001 6 (4’3) .001 side effect for drugs 28 (20) 20 (14.3) .001 8 (5.7) .001 improvement 39 (27.9) 25 (17.8) .525 14 (10) .003* went abroad 1 (.7) 1 (.7) .002 type of tb first time 140 (100) 87 (62.1) .001 53 (37.9) 001 contact of relation 99 (70.71) 58 (41.4) .720 41 (29.2) .998 duration of treatment default (weeks), mean ± sd) 8.44 ± 4.52 .398 .992 duration of treatment default (months), mean ± sd) 9.01 ± 7.6 .005 110 associated condition 55 (39.3) 29 (20.7) .001 26 (18.6) .070 default relative tb 20 (14.2) 10 (7.1) .635 10 (7.1) .992 reporting back 85(60.7) 55(39.3) 001 30(21.4) . 001 default numbers (each type treatment defaults during study) 118 (84.2) 118 (84.2) .224 118 (84.2) .257 condition of arrival (sick, bed bound & moribund) 104 (74.2) 57 (40.7) .011 47 (33.5) .039 mortality 14 (10) 5 (3.6) .001 9 (6.4) .001 the age has the statistical significant association with eptb treatment default in adults. there was statistically significant association between treatment defaults receiving treatment for first time with ptb & eptb (p=0.001).tb treatment default had been observed in both ptb and eptb patients. out of these pulmonary tb cases were 94 (67.1%) including pulmonary parenchymal tb (58.6%), pleural effusion (2.11%), pneumothorax (0.7%) and extensive ptb (5.69%). amongst 46 (32.9%) eptb, abdominal tb 8 (5.8%), tb lymph-adenopathy 14 (10%), tbm 14 (10%) skin tb 2 (2.1%), disseminated tb 2 (1.4%) and bone tb 1 (.7%) , miliary tb 3 (2.2%) and breast tb 1 (0.7) cases were reported. the plum-ordinal analysis revealed that clinical tb forms ptb (p=004**) eptb (p=0.002**) to its tb treatment defaults was of high significance .there was significant association between improvement to treatment and tb treatment default as well as co-infection of tb in diabetes mellitus and corticosteroid therapy. duration of treatment in weeks, number of defaults and treatments default in relative had no significant association with treatment default in contrary to treatment default in months (p=0.05). discussion both ptb & eptb are common in tb treatment defaults. high tb treatment default rate is most significant factor for the development of multi drug resistance (mdr-tb), high morbidity and mortality in ptb and eptb. the thick population in city, distant periphery, traveling from far away, poverty and road closed during winter makes difficult for treatment follow-up. in addition, special diagnostic difficulty in eptb further complicates the situation. the factors leading to treatment default should be considered before making effective strategies for tb control programs. tb patient groups having dot's coverage were higher in city than in the remote district. in south east asia gender as well as non-compliance are risk factors for treatment default13. we observed that the adult’s population, gender, non-compliance and poor socio economic class were at risk of abandoning treatment. tb/ hiv coinfection and alcoholism has been identified as risk factor for treatment default worldwide.1,14 alcoholism and anti tuberculosis drugs have been associated with increase in the risk of liver damage.14-15 diabetes mellitus (dm) being the disease of old had no increased risk of treatment default.16 the double burden of tb and dm is a significant public health problem in low and middle income countries.17 the poor quality of tb service, large population, suboptimal implementation of public health facilities, inadequate knowledge, insufficient explanation of disease to the patients were also important risk factors for low adherence to treatment. the statistically similarity of the results with and without dots in asia, raises questions about quality anti tb programs. the uniform strategy should be investigated to deal with issues like relationship journal of rawalpindi medical college (jrmc); 2017;21(3): 265-268 267 between patient and health professional, positive attitude of the patient and service provider. the easy accessibility of patients to healthcare units can improve treatment adherence. others significant factors associated with treatment default are poor education, the occurrence of default in the previous treatment, tb/ hiv coinfection, alcoholism and other comorbidities. patients with these conditions should be considered as target populations, for individualized attention and priority by health professionals, with main emphasis on contemplating dots. the limitation of the our study was non evaluation of tb/ hiv coinfection, alcoholism, negative attitudes of health professionals and patient, sub-optimal implementation of public health facilities and other comorbidities and under reporting of eptb. we found that the most frequent sites of eptb were meninges, lymph nodes followed by the abdomen, skin and bone involvement. the lymph node was the most common site of extrapulmonary involvement in usa in the past. tb pleurisy occurs frequently in association with ptb. evidence suggests that pleural tb represents an early manifestation of primary infection by mtb and may serve as a sentinel event in recent transmission studies.18 the proportion of eptb as tb clinical forms seems to be higher in countries with a low incidence of tb, such as in australia, japan, and usa. the reasons for these differences are unknown but could be related to different epidemiological patterns of persons with tb as a consequence of recent infection. conversely in countries with a high incidence of tb, eptb usually represents a smaller fraction of all cases. in 2011 eptb was 19% in india, 4% in indonesia and 18% in pakistan. eptb was 12.6% in our study which is similar to high tb burden countries19.the higher ratio females in ptb cases compared with eptb cases was statistically significant in our study. western investigators have reported that eptb is more prevalent as racial distribution in asian as compared to the caucasians and ethnicity has relevancy in other region.19-27 clinical parameters in our study have significant relevance with earlier reports22. eptb prevalent and occurred in 26.2% of hiv-infected patients.23 mycobacterial cultures are not usually performed during evaluation of tb suspects and are indicated only in specific instances, such as in cases of suspected eptb or drug resistant tb and in vulnerable populations. dots is strongly recommended to enhance treatment completion and cure of the patient. eptb is also hazardous health problem due to its high mortality and morbidity rates in world24-26. eptb is less contagious, less frequent, and difficult to diagnose than ptb, hence less well addressed in pakistan and in azad kashmir. conclusions 1. both ptb & eptb are an important clinical problem in tb treatment defaults in our country. 2. high tb treatment default rate is most significant factor for the development of mdr-tb and high morbidity and mortality in tb treatment defaults. 3. improved diagnostic and therapeutic modalities in ptb & eptb in tb treatment defaults and supervised treatment programes are essential prerequisites for optimizing care and better treatment outcomes. 4. easy accessibility of patients to health care facilities and direct observational treatment (dot) can improve treatment adherence references 1. world health organization: highlights of activities from 1989 to 1998. world health forum 1988; 9: 441-56. 2. world health organization. global tuberculosis control: surveillance, planning, financing. who report 2008. ho/ htm/ tb/ 2008. 393. 3. geneva, switzerland: who, 2008. 6. yang z. identification of risk factors for extrapulmonary tuberculosis. clin infect dis 2004; 38: 199-205. 4. world health organization. global tuberculosis report. geneva, 2016. 5. jaggaraajamma k, sudha g, chandrasekaran v. noncompliance among patients treated under revised national tuberculosis control programme.indian j tuberc.2007; 54: 130-35. 6. kliiman k, altraja a. predictors and mortality associated with treatment default in pulmonary tuberculosis. int j tuberc lung dis 2010; 14: 454–63. 7. eastern mediterranean regional office (world health organization) . cairo: stop tb: tb situation in region country profile pakistan; 2008 . 8. butt t, kazmi sy, ahmad rn, mahmood a. antibiotic susceptibility pattern of mycobacterial isolates from extrapulmonary tuberculosis cases. j pak med assoc 2003; 53: 328-32. 9. peto hm, pratt rh, harrington ta, lobue pa. epidemiology of extrapulmonary tuberculosis in united states, 1993–2006. clin infect dis. 2009;14:1350–57. 10. forssbohm m, zwahlen m, loddenkemper r. demographic characteristics of patients with extrapulmonary tuberculosis in germany. eur respir j. 2008;14:99–105. 11. world health organization. global tuberculosis report 2012. paris; . 12. buu tn, lonnroth k, quy ht. initial defaulting in national tuberculosis programme in vietnam.ult. int j tuberc lung dis2003; 7: 735-41. journal of rawalpindi medical college (jrmc); 2017;21(3): 265-268 268 13. balasubramanian r, garg r, santha t, gopipg. gender disparities in tuberculosis: report from rural dots programme. int j tuberc lung dis 2004; 8: 323-32. 14. kassim s, sassam-morokro m, akhan a, abouya ly. two-year follow-up of persons with hiv-1 and hiv-2associated pulmonary tuberculosis treated with shortcourse in west africa. aids 1995; 9: 1185–91. 15. mitchison da . how drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. int j tuberc lung dis 1998; 2: 10–15 16. singla r, khan n, al-sharif n, ai-sayegh mo. influence of diabetes on manifestations and treatment outcome of pulmonary tb patients. int j tuberc lung dis 2010;10: 74–79. 17. dooely ke and chaisson re. tuberculosis and diabetes mellitus: convergence of two epidemics. lancet infect dis. 2009; 9 (12): 737–46. 18. ong a, creasman j, hopewell pc, gonzalez lc. a molecular epidemiological assessment of extrapulmonary tuberculosis in san francisco. clin infect dis.2004;14:25–31. 19. world health organization. tuberculosis countries profiles. [ http://www.who.int/tb/country/en/] 20. hoa nb, wei c, sokun c, lauritsen jm, rieder hl. characteristics of tuberculosis patients at intake in cambodia, two provinces in china, and vietnam. bmc public health. 2011;14:1471–74 21. golden mp, vikram hr. extrapulmonary tuberculosis: an overview. am fam physician.2005;14:1761–68. 22. sankar mm, singh j, angelin diana sc. molecular characterization of mycobacterium tuberculosis isolates from north indian patients with extrapulmonary tuberculosis.tuberculosis 2012;14:75–83 23. ilgazli a, boyaci h, basyigit i, yildiz f. extrapulmonary tuberculosis: clinical and epidemiologic spectrum of 636 cases. arch med res 2004; 35: 435-41. 24. naing c, mak jw, maung m, wong sf. meta-analysis: the association between hiv infection and extrapulmonary tuberculosis. lung. 2013;14:27–34. 25. golden mp, vikram hr. extrapulmonary tuberculosis: an overview. am fam physician.2005;14:1761– 68. 26. yone ew, kengne ap, moifo b. prevalence and determinants of extrapulmonary involvement in patients with pulmonary tuberculosis . scand j infect dis. 2013;14:104–11 27. broekmans j, caines k, paluzzi je. investing in strategies to reverse the global incidence of tb. london: un millenium project, united nations development programme; 2005. http://www.who.int/tb/country/en/ 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 272-275 272 original article relationship of anthropometric indices of obesity with arterial stiffness and blood pressure muhammad sajid mehmood1, kamil asghar imam 2, shahida parveen3 1 .dept. of physiology, poonch medical college, rawalakot, ajk; 2. department of physiology; army medical college, rawalpindi; 3. department of physiology, fazaia medical college, islamabad. abstract background: to determine the comparison and relationship of anthropometric indices with blood pressure and arterial stiffness index (asi) in normotensive, prehypertensive and hypertensive male adults. methods: in this randomized case control study ninety male subjects between 35-55 years of age were selected with each group comprising of thirty normotensive, pre-hypertensive and hypertensive subjects. according to the world health organization (who) guidelines their height, weight, hip (hc) and waist circumferences (wc) were measured. waist hip ratio (whr), body mass index (bmi), conicity index (ci) and waist stature ratio (wsr) were calculated. blood pressure (bp) was measured by mercury sphygmomanometer with auscultatory method. photoplethysmography was done by placing velcro scrap on volar surface of middle finger and digital volume pulse (dvp) was recorded with iworx-214 physiological interface system and asi was calculated. statistically, difference amongst the three groups was determined by applying one way anova. difference between the groups was analyzed by post hoc tukey’s test. pearson’s correlation coefficient was calculated to study the relationship. p-value<0.05 was considered significant. results: there was statistically significant difference in wc (0.003), whr (0.0001) and asi (0.0001) between the three groups but not bmi (0.223). amongst the anthropometric measurements, wc and whr were positively correlated to the systolic and diastolic blood pressure. conclusions: central obesity is better predictor of arterial stiffening and hypertension than bmi. key words: prehypertension, hypertension, arterial stiffness index, central obesity,waist circumference,body mass index introduction there is progressive increase in blood pressure (bp) with upsurge in obesity which is result of industrialization, urbanization, sedentary life styles and behavioral adaptations. the prevalence of obesity is rising not only in affluent societies but also in developing countries irrespective of age, race and ethnicity. 1 childhood obesity is associated as risk factor for cardiovascular diseases.2 the anthropometric indices like waist circumference (wc), body mass index (bmi), waist-hip ratio (whr), conicity index (ci) and waist-stature ratio (wsr) have been proposed as markers of obesity in various studies. yet, it is not clear which of these markers has the strongest link with bp in our population. body mass index is the major determinant of overall obesity while central or visceral obesity is more closely linked with bp and cardiovascular diseases (cvd) as evident from literature survey.3, 4 bmi is usually near similar among the groups while waist to hip ratio (whr) and waist circumference (wc) were significantly different among normotensive, prehypertensive and hypertensive groups. the measures of central obesity i.e. whr and wc are distinctly correlated with blood pressure and asi than bmi which represents the index of overall obesity. according to gus et al.(2009) waist to hip ratio and waist-stature ratio are better predictors of incidence of hypertension when compared with bmi especially in male gender.men’s hypertension is primarily dependent onvisceral obesity in contrast to women’s hypertension which correlates predominantly with overall adiposity.5 it has been proposed that physical compression of the kidneys by visceral fat deposits and the activation of renin-angiotensin system might be important factors in elevation of blood pressure with increasing body weight.6 it is proposed that the visceral fat cell volume has positive correlation with arterial stiffness, central fat mass and cardiovascular risk.7 the visceral fat and journal of rawalpindi medical college (jrmc); 2017;21(3): 272-275 273 abdominal obesity are closely associated with large artery stiffness. these findings highlight the importance of anthropometric indices of obesity as risk factors for arterial stiffening in middle-aged adults.8 arterial stiffness is a cause rather than a consequence of hypertension and precedes the development of hypertension in animal model. 9 it is argued that arterial stiffness index (asi) is a useful non-invasive tool for the cvd risk stratification because of its capability to detect early target organ injury. 10 different techniques have been employed to measure the asi in various studies ranging from simple to intricate ones. the stiffness index score determined by photoplethesmography is comparable to the arterial stiffness calculated by pulse-wave velocity which is unanimously agreed gold standard marker. 11,12 asi has been documented to be more sensitive non-invasive tool for assessing the patients at risk of cvd in comparison to total cholesterol,plasma glucose and waist to hip ratio in deceptively healthy population.13 obese individuals are at higher risk of arterial stiffness irrespective of their metabolic conditions. 14 arterial stiffness is considered to be one of the earliest detectable measures of vascular damage.15 it is increased in obese/overweight subjects without obvious cardiovascular diseases. 16,17 obesity is a major modifiable risk factor for coronary artery disease (cad). 15 the role that systemic arterial stiffness plays in pathogenesis of hypertension and cardiovascular disease has generated great interest in defining basic mechanisms that stiffen the vascular wall, increase blood pressure and contribute to target organ damage with a hope that clarification of these mechanisms will allow for development of more effective treatments.18 subjects and methods this case control study was carried out in dept. of physiology army medical college, from jan 2014 to dec 2014. total ninety male subjects between 35-55 years of age were selected by non-probability, convenience sampling with each group comprising thirty subjects. normotensive subjects were defined as those with a diastolic blood pressure < 80 mmhg and systolic blood pressure <120 mmhg. prehypertensive subjects were defined as those with a diastolic blood pressure between 80-89 mmhg and systolic blood pressure between 120-139 mmhg. hypertensive subjects were those with diastolic blood pressure >90 mmhg and systolic blood pressure >140 mmhg.the subjects were placed into various groups according to jnc-vii report.19 more than one thousand subjects were interviewed and those having fever, any allergic disease, or taking any kind of medications for at least last two weeks were excluded. those who had chronic inflammatory disease, diabetes or any prolonged illness were also excluded. the study was started after approval from post graduate board of studies army medical college and ethical review committee, centre for research in experimental and applied medicine (cream). after written informed consent bp was measured by mercury sphygmomanometer. blood sugar was checked (in order to exclude diabetes mellitus). weight nearest to 0.1 kgwas measured using pointer spring balance without shoes and single light clothing. height nearest to 0.5 cm was recorded. wc was measured horizontally halfway between iliac crest and lower border of rib cage using plastic measuring tape. hip circumference (hc) was measured at the broadest part of buttocks. both hc and wc were quantified nearest to 0.1 cm. waist to hip ratio was calculated.bmi was calculated by dividing weight in kilograms by height in meters square. waist-stature ratio was calculated by dividing wc by height. conicity index was calculated by the formulae [ci=wc (m)/ ]. photoplethysmography was done by placing velcro scrap on volar surface of middle finger and digital volume pulse (dvp) was recorded via iworx-214 physiological interface system and asi was calculated. labscribe® software was used to analyze recorded data. by placing cursor on two peaks of dvp, reflection time was calculated. asi was calculated by the formulae [asi = height (meters)/ reflection time (seconds)].one way anova was applied followed by post-hoc tukey’s test to compare the means of anthropometric indices of obesity, bp variables and asi in normotensive, prehypertensive and hypertensive subjects. pearson’s correlation coefficient was determined to study the correlation between various variables. p-value<0.05 was considered statistically significant. results the mean arterial pressure was 37 sd 5; systolic bp 110 sd 6 and diastolic blood pressure was 73 sd 6 in group i, 44 sd 4; 130 sd4 in group ii and 59 sd 8; 164 sd 12 in group iii (p-value 0.0001). whr was 0.95 sd 6 meters; waist circumference 0.90 sd 0.08 in normotensive group. in pre-hypertensive group the values were 0.95 sd 0.09 meters and 0.98 sd 0.08 in hypertensive group (p-value 0.0001). waist hip ratio 0.94 sd 0.56 in group i, 0.99 sd 0.08 in group ii and 1.03 sd 0.09 in group iii (p-value 0.0001); waist-stature ratio 0.54 sd 0.05 in normotensive group. journal of rawalpindi medical college (jrmc); 2017;21(3): 272-275 274 table-1: comparison of anthropometric indices and arterial stiffness index amongst the groups variables group 1 normotensive mean ± sd (n=30) group 2 prehypertensive mean ± sd (n=30) group 3 hypertensive mean ± sd (n=30) p-value (sig.) age 40 ± 4 43 ± 5 47 ± 5 0.0001 map 37 ± 5 44 ± 4 59 ± 8 0.0001 sbp 110 ± 6 130 ± 4 164 ± 12 0.0001 dbp 73 ± 6 86 ± 2 105 ± 11 0.0001 whr 0.94 ± 0.56 0.999 ± 0.08 1.03 ±.09 0.0001 wc 0.90 ± 0.08 0.95 ± 0.09 0.98 ± 0.08 0.003 wsr 0.54 ± 0.05 0.54 ± 0.11 0.57 ± 0.05 0.102 ci 1.28 ± 0.07 1.32 ± 0.08 1.32 ± 0.08 0.051 bmi 25 ± 3 26 ± 3 27 ± 3 0.223 asi 6.7 ± 0.5 7.8 ± 0.6 12.2 ± 2.6 0.0001 all values are expressed as mean plus/minus standard deviation;[map: mean arterial pressure; sbp: systolic blood pressure; dbp: diastolic blood pressure; whr: waist to hip ratio; wc: waist circumference; wsr: waist stature ratio; ci: conicity index; bmi: body mass index; asi: arterial stiffness index] table-2: comparison of anthropometric indices and arterial stiffness index between the groups variables normotensive vs prehypertensive normotensive vs hypertensive prehypertensive vs hypertensive age 0.048 0.0001 0.001 map 0.0001 0.0001 0.0001 sbp 0.0001 0.0001 0.0001 dbp 0.0001 0.0001 0.0001 whr 0.011 0.0001 0.371 wc 0.057 0.003 0.523 asi 0.014 0.0001 0.0001 map: mean arterial; sbp: systolic blood pressure; dbp: diastolic blood pressure; pressure; whr: waist to hip ratio; wc: waist circumference; asi: arterial stiffness index in pre-hypertensive group the values were same and 0.57 sd 0.05 in hypertensive group (p-value 0.0001). the bmi was 25 sd 3, in group i, 26 sd 3 in group ii and 25 sd 3 in group iii (p-value 0.223). the asi was 6.7 sd 0.5 in group i, 7.8 sd 0.6 in group ii and 12.2 sd 2.6 in group iii (p-value 0.0001) (table 1).the difference between the groups,evaluated by post hoc tukey’s test, showed that waist circumference was significantly different between normotensive and hypertensive group (0.003). asi was significantly different between group i and ii (0.014). it was also significantly different between normotensive and hypertensive group (0.0001). asi was also significantly different between group ii and iii (0.0001) (table 2).relationship between variables, studied by pearson’s correlation coefficient,revealed statistically significant relationship between bp, waist circumference and waist-hip ratio (table 3). table-3: relationship of anthropometric indices with arterial stiffness index and blood pressure variables variables bmi wc whr ci wsr asi r p 0.107 0.316 0.218 0.038 0.269 0.010 0.136 0.201 0.098 0.357 sbp r p 0.177 0.095 0.323 0.002 0.372 0.0001 0.192 0.070 0.167 0.116 dbp r p 0.181 0.088 0.346 0.001 0.362 0.0001 0.250 0.017 0.186 0.080 map r p 0.182 0.086 0.341 0.001 0.372 0.0001 0.228 0.031 0.180 0.089 pp r p 0.135 0.204 0.323 0.002 0.209 0.003 0.070 0.051 0.167 0.116 asi: arterial stiffness index; sbp:systolic blood pressure; dbp:diastolic blood pressure; map: mean arterial pressure; wsr: waist stature ratio; ci: conicity index; whr: waist to hip ratio; wc: waist circumference; bmi: body mass index discussion in present study it was revealed that the markers of central obesity (whr>wc>wsr>ci>bmi) are better related with arterial stiffness index and bp than bmi. these findings were similar to the study by gus et al.(2009), recio-rodriguez jiet al. (2012) and lee et al. (2015) that the anthropometric measures of central obesity were better predictors of the incidence of hypertension than the measures of generalized obesity like bmi in male gender especially (table 4).20-22 our results supported the findings of study by zhou et al.(2003)that in male gender hypertension is associated with central obesity and overall adiposity correlates mainly with women’s hypertension. 5 the study by mark et al. revealed that the frequency of elevated blood pressure was positively associated with visceral adipose tissue .23 significant compression of renal mass by visceral adipose tissue and stimulation of reninangiotensin system have been proposed to be important factors in causing hypertension with growing body weight.6 the visceral fat deposits have been proposed to release various factors which may contribute in causing hypertension by increasing sympathetic activity. 24 the bmi was statistically similar in three groups in our research project which was similar to the findings of another study conducted in population of peshawar, pakistan. it was detected in that study that large percentage of male gender in the normal bmi category had raised blood pressure than normal. 25 the studies bymufunda et al. (2006) and sakurai et al. (2006) also support our observation that bmi was not significantly related with blood pressure especially in journal of rawalpindi medical college (jrmc); 2017;21(3): 272-275 275 male subjects. 26, 27 ononamadu, c. j. et al. (2017)study revealed that bmi and either wc or waist height ratio have same prediction value in determining risk of hypertension. 28 table-4: correlation orders of anthropometric indices with systolic and diastolic blood pressure in various studies studies diastolic blood pressure systolic blood pressure present study (n=90) whr> wc > ci > wsr >bmi (0.000)(0.001)(0.01)( 0.06)(0.09) whr> wc > wsr > ci >bmi (0.000)(0.002)(0.04 )(0.07)(0.09) yalcin et al.29 (n=267) bmi>wc>wsr>w hr>ci wsr>bmi>wc> whr>ci ghosh & bandyopadhy ay.30 (n=180) bm>wc>wsr>w hr>ci wsr>bmi>wc> whr>ci zhou z et al.4 (n=29079) bmi>wc>wsr>w hr>ci bmi>wc>wsr> whr>ci ghosh jr, bandyopadhy ay ar. 31 (n=179) wc > ci > wsr >bmi (0.01) (0.01) (0.05) (0.53) wc > ci > wsr >bmi (0.01) ( 0.01) (0.62) (0.70) bmi:body mass index; whr: waist to hip ratio; wc: waist circumference; ci: conicity index; wsr: waist stature ratio conclusion central obesity (determined bywhr and wc) is better predictor of arterial stiffness and raised blood pressure in middle aged pakistani men. references 1. lobstein t, jackson-leach r. child overweight and obesity in the usa: prevalence rates according to iotf definitions. int j pediatr obes. 2007;2(1):62-64. 2. cote at, phillips aa, harris kc, sandor gg. obesity and arterial stiffness in childrensignificance. arteriosclerosis, thrombosis, and vascular biology. 2015;35(4):1038-44. 3. jensen md, ryan dh. new obesity guidelines: promise and potential. jama. 2014;311(1):23-24. 4. zhou z, hu d, chen j. association between obesity indices and blood pressure or hypertension: which index is the best? public health nutrition. 2009;12(8):1061-71. 5. zhao lc, wu yf, zhou bf, li y, yang j.mean level of blood pressure and rate of hypertension among people with different levels of body mass index and waist circumference. zhonghua liu xing bing xue za zhi 2003;24(6):471-75. 6. hall je, kuo jj, da silva aa, de paula rb. obesity-associated hypertension and kidney disease. current opinion in nephrology and hypertension. 2003;12(2):195-200. 7. arner p, backdahl j, hemmingsson p. regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects. int j obes 2015;39(2):222-27. 8. strasser b, arvandi m, pasha ep, haley ap. abdominal obesity is associated with arterial stiffness in middle-aged adults. nutr metab cardiovasc dis. 2015;25(5):495-502. 9. weisbrod rm, shiang t, al sayah l. arterial stiffening precedes systolic hypertension in diet-induced obesity. hypertension. 2013;62(6):1105-10. 10. pusuroglu h, akgul o, erturk m. analysis of leukocyte & leukocyte subtypes among isolated systolic hypertensive, systodiastolic hypertensive and nonhypertensive patients.kardiologia polska. 2014;14/02/15. 11. rasouli m, kiasari am, bagheri b. total and differential leukocytes counts, but not hscrp, esr, and five fractioned serum proteins have significant potency to predict stable coronary artery disease. clinica chimica acta. 2007;377(1–2):127 32. 12. millasseau sc, kelly rp, ritter jm, chowienczyk pj. determination of age-related increases in large artery stiffness by digital pulse contour analysis. clin sci 2002;103(4):371-77. 13. lee hy and oh bh. aging and arterial stiffness. circulation journal : official journal of the japanese circulation society. 2010;74(11):2257-62. 14. yang f, wang g, wang z, sun m, cao m. visceral adiposity index may be a surrogate marker for the assessment of the effects of obesity on arterial stiffness. plos one. 2014;9(8):e104365. 15. melanson kj, mcinnis kj, rippe jm, blackburn g. obesity and cardiovascular disease risk: research update. cardiol rev. 2001;9(4):202-07. 16. li p, wang l, liu c. overweightness, obesity and arterial stiffness in healthy subjects: a systematic review and metaanalysis of literature studies. postgrad med. 2017;129(2):22430. 17. drapeau v, lemieux i, richard d, bergeron j. waist circumference is useless to assess the prevalence of metabolic abnormalities in severely obese women. obes surg. 2007;17(7):905-09. 18. mitchell gf. arterial stiffness and hypertension. hypertension. 2014;64(1):13-18. 19. chobanian av, bakris gl, black hr, cushman wc. seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. hypertension. 2003;42(6):1206-52. 20. gus m, cichelero ft, moreira cm, escobar gf. waist circumference cut-off values to predict the incidence of hypertension: an estimation from a brazilian population-based cohort nutrition, metabolism and cardiovascular diseases. 2009;19(1):15-19. 21. recio-rodriguez ji, gomez-marcos ma, patino-alonso mc. abdominal obesity vs general obesity for identifying arterial stiffness, subclinical atherosclerosis and wave reflection in healthy, diabetics and hypertensive. bmc cardiovasc disord. 2012;12:3-7. 22. lee jw, lim nk, baek th, park sh. anthropometric indices as predictors of hypertension among men and women aged 40-69 years. bmc public health. 2015;15:140-45. 23. mark al, correia m, morgan da, shaffer ra obesity-induced hypertension new concepts from the emerging biology of obesity. hypertension. 1999;33(1):537-41. 24. seals dr and bell c. chronic sympathetic activation: consequence and cause of age-associated obesity? diabetes. 2004;53(2):276-84. 25. humayun ass, alam s. relationship of body mass index and dyslipidemia in different age groups . j ayub med coll abbottabad. 2009;21(2):114-17 26. mufunda j, mebrahtu g, usman a, nyarango p. prevalence of hypertension and its relationship with obesity. journal of human hypertension. 2006;20(1):59-65. 27. sakurai m, miura k, takamura t, ota t. gender differences in the association between anthropometric indices of obesity and blood pressure in japanese. hypertension research 2006;29(2):75-80. 28. ononamadu cj, ezekwesili cn, onyeukwu of. analysis of anthropometric indices of obesity as correlates and potential predictors of risk for hypertension and prehypertension. cardiovasc j afr. 2017;28(2):92-99. 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 281-285 281 original article use of chorionic villous sampling for prenatal diagnosis of beta thalassaemia: attitudes and practices of parents sundas ali1, asfa zawar1, samina tufail amanat 2, shahzad ali jiskani 1, aliena sohail 1, humaira rizwan 1, sara jamal 2 department of pathology , pakistan institute of medical sciences, islamabad;2. department of pathology, pakistan atomic energy commission hospital, islamabad abstract background: to assess the attitudes and practices of parents of beta-thalassaemia major children regarding chorionic villous sampling (cvs), as prenatal diagnosis in subsequent pregnancies. methods: in this cross-sectional study a predesigned questionnaire was used to evaluate the socio-demographic profile and attitudes of parents of 210 registered thalassaemic children, regarding cvs.only those parents who had one or more pregnancies after the index case were included in the study. results were entered and analyzed on spss version 20. results: after the index case, 36.2% parents underwent cvs in all subsequent pregnancies . the common reasons not to utilize this facility were lack of knowledge (47.7%), careless attitude (41.7%), family pressure (4.4%) and financial issues (1.5%). religious reason was not found in any of the cases. majority of the families (54.3%) belonged to lower middle class financial status. there was a significant association between cvs practice and educational level of the mother and genetic counselling at the time of diagnosis of index case. in future pregnancies, 52.8% parents had no planning, while 15.7% showed interest in undergoing cvs in next pregnancies. conclusion: despite the availability of cvs in the country, very few families had opted for it; the major reasons being lack of knowledge, careless attitude and family pressure. as against the common thought, religious reason was not a significant factor. key words: prenatal diagnosis, chorionic villous sampling, beta-thalassaemia major. introduction beta-thalassemia major (btm) is an autosomal recessive, inherited disorder of haemoglobin synthesis, caused by reduced or absent synthesis of beta globin chains, resulting in life-threatening anaemia and requiring regular blood transfusion for survival. it is common in the mediterranean, indian subcontinent, and middle east regions. approximately, 5000-9000 children with β-thalassemia are born annually in pakistan with an estimated carrier rate of 5-7%.1 both the parents of an affected child are carriers, having a single copy of mutated beta globin gene. at each conception, the child has 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being normal.2 high fertility and birth rate, low educational status, trends of consanguineous marriages and lack of awareness are some of the reasons that have made this disease highly prevalent in pakistan.3 the mainstay to control this preventable disease is by population screening, appropriately timed genetic counselling, prenatal diagnosis and option of terminating affected pregnancies.1 the preferred method for prenatal diagnosis is detection of betachain mutation by polymerase chain reaction (pcr) of fetal dna obtained by chorionic villous sampling (cvs). this technique can prevent the birth of an affected child in developing countries in which beta-thalassaemia is very much prevalent. this facility initially reported in 1994, is now available at many centers in the country and offered to all couples at risk for a child with btm. cvs is performed at 10-12 weeks of gestation by trans-abdominal route, and after seeking appropriate level of training and performance of initial procedures under supervision, it is a simple, easy to apply, useful, and fairly safe technique. in comparison to estimated total cost of the long-term treatment of beta -thalassaemia, cost required for cvs and laboratory diagnosis of betathalassaemia mutation is minimal. in cases where fetus is detected to be homozygous for beta -thalassaemia mutation, termination is done soon after the diagnosis, usually from 13-16th weeks of gestation which is usually uneventful and without any untoward complications.4 subjects and methods this was a cross-sectional descriptive study, which was based on a pre-designed structured questionnaire. it was conducted in the thalassaemia center, children journal of rawalpindi medical college (jrmc); 2017;21(3): 281-285 282 hospital, pakistan institute of medical sciences (p.i.m.s) islamabad, pakistan from january to march 2017. parents of 210 registered patients of btm, who had history of at least one pregnancy after the index case, were included in the study. parents having children with any other haemoglobinopathy, betathalassaemia intermedia and those having only a single child were excluded from the study. a carefully designed questionnaire was used to collect data from either of the parents available with the child at the time of interview, regarding socio-demographic status, number of thalassaemic children, family history and previous knowledge of thalassaemia,provision of genetic counseling at the time of diagnosis of first thalassaemic child, parents’ future pregnancy plan and approximate treatment related expenses. they were also inquired if they had opted for cvs or not; and if not, reasons for not opting. all data was entered and analyzed using spss version 20 and a p-value of <0.05 was considered statistically significant. results (54.3%) belonged to lower middle class (table 1). majority can not bear the expenses more than 10,000 per month (table 2). the total number of children in the families under study ranged from 2 – 10, with majority parents (31.9%) having 3 children. out of those, number of children suffering from btm ranged from 1-4. most of the families (63.3%) had 1 thalassaemic child, followed by 2 in 66 (31.4%) of the families. only 22 (10.5%) parents had previous knowledge about the mode of inheritance of thalassaemia, regardless of the family history. none of the parents had received pre-marital screening and no parent reported any complication following cvs. the 2 major reasons among parents not practicing cvs testing in 1 or more pregnancies, were lack of proper knowledge about cvs in 64(47.7%) and careless attitude in 56 (41.7%) (table 3). majority (52.8%) had no planning, 66(31.4%) were practicing family planning methods and 33(15.7%) desired 1 or more children in future after undergoing cvs prenatally. there was significant association between the trend of opting for cvs among the parents and educational level of the mother (p=0.008). similarly, if the parents were offered good genetic counseling at the time of diagnosis of first thalassaemic child, there was a higher trend of practicing cvs in the subsequent pregnancies (p <0.05). however, neither the educational level of the father nor the financial status of the family had any significant association with the cvs practice. table i : socio-demographic profile of families n % residence province-wise distribution (n=210) punjab federal capital kpk ajk fata sindh 106 54 32 16 01 01 50.4 25.7 15.2 7.6 0.4 0.4 educational status (n=210) mothers: fathers: uneducated under-primary primary under-matric matric inter graduate masters 72 09 27 24 46 16 10 06 34.3 4.3 12.9 11.4 21.9 7.6 4.8 2.9 uneducated under-primary primary under-matric matric inter graduate masters 40 12 21 30 65 18 15 09 19.0 5.7 10.0 14.3 31.0 8.6 7.1 4.3 financial status (with average monthly income) n=210 poor (<5000 rs.) lower middle (500015,000 rs.) middle (15,000-50,000 rs.) upper middle (>50,000 rs.) 38 114 55 03 18.1 54.3 26.2 1.4 table 2: treatment related expenses per month (pkr) no. of families no (%) <1000 rs 76 36.1% 1000-5000 rs 89 42.3% 5000-10,000 rs 27 12.8% >10,000 rs 18 8.5% discussion about 3% of the world’s population carries the genes for beta thalassaemia; the carrier rate in pakistan ranges between 5-8%. around 5000 children are diagnosed annually with btm in pakistan; consanguinity being one of the major factors leading to its high prevalence in the country.5in a family having a patient of btm (extended family) the prevalence of carrier is more than 30%.6 as in many other developing countries in asia, β thalassaemia increases the burden for healthcare services in pakistan and with limited available national resources, it is very difficult to provide safe journal of rawalpindi medical college (jrmc); 2017;21(3): 281-285 283 table 3. knowledge, attitudes and practices among parents regarding prenatal diagnosis by cvs. no % genetic counseling offered(n=210) yes no 140 70 66.6 33.3 cvs undergone after the index case (n=210): never in some pregnancies in all pregnancies 97 37 76 46.2 17.6 36.2 reasons for not opting for cvs (n=134) lack of proper knowledge careless attitude family pressure financial reason health concerns non-availability of one parent transportation problem late diagnosis of index case 64 56 06 02 02 02 01 01 47.7 41.7 4.4 1.5 1.5 1.5 0.7 0.7 termination of pregnancy sought after diagnosis of thalassemia major on cvs (n=32) yes no 27 05 84.3 15.7 blood transfusion and iron chelation therapy to each and every patient. 7 multidisciplinary approach is needed to treat this disease but it is difficult due to shortage of resources and poor coordination among the existing facilities.8 bone marrow transplantation, the only curative option, is extremely expensive and unaffordable for most pakistani patients. therefore, prevention is the most effective and the least expensive option available, to deal with β-thalassemia in our country. 7 different strategies to prevent thalassemia include parental awareness, population screening, genetic counseling, and prenatal diagnosis. creating awareness and educating parents is a cost-effective tool in preventing and improving the quality of life of patients with thalassemia. 8,9 the developed countries are more focused at preventing the disease by detection of thalassemia carriers and marriage counseling.10,11 in cyprus, the incidence of btm cases dropped by 96% through preventive programs. 12 the provision of cvs sampling in the first trimester of pregnancy makes it more acceptable. it is preferable to do cvs before 120 days (17 weeks) of pregnancy. in one study, almost all prenatal diagnoses were carried out in the first trimester with >95% of women opting for termination of pregnancy in case of btm fetus. 13 in case of homozygous fetus, termination is physically and emotionally more feasible and acceptable in the earlier stages of pregnancy. the results of one study showed that the performance of cvs test was reliable; especially considering the validity and predictive value in the diagnosis of thalassaemia major. thus, couples with thalassemia trait can safely undergo this test to prevent the birth of the children with major thalassaemia.14 in pakistan, punjab thalassaemia prevention programme (ptpp) has been started by the government of punjab to provide free prenatal diagnostic service (collection of chorionic villous sample and mutation analysis) which is catering whole of the province through its field officers, especially covering the districts of rawalpindi, mianwali, jhelum, gujrat, chakwal, khoshab, sargodha and attock. people from khyber pukhtoon khwa , gilgit baltistan and azad jammu and kashmir are also taking advantage through this initiative .15 in our study, most of the patients, 106 (50.4%) were residents of punjab province, followed by 54 (25.7%) from federal capital islamabad and 32 (15.2%) from kpk. the thalassemia center at pims islamabad has more than 1500 patients of thalassaemia registered and caters for the transfusion services of many of the patients from these parts of the country. regarding the educational level of the parents, majority of the mothers, 72(34.3%) were uneducated and majority of the fathers, 65(31%) had received formal education up to matric level. this is comparable to other studies done in the same context in different settings in pakistan. ali s. et al. 10,16,17 positive family history for thalassemia was found in 26% cases. despite a high rate of consanguineous marriages in our country, the prevalence of positive family history is low in present study. most of the families, 114 (54.3%) belonged to lower-middle class with an average income of rs. 5000-15,000/month. the maximum number of parents that is 89 (42.3%) spent between rs. 1000-5000/month on the treatment of their one or more thalassaemic children. the expenditures included money spent on travelling, food, stay and medicines. majority of the patients were supported by the bait-ul-maal pakistan as well as by hospital zakat funds. in a study conducted in india, they found that the average annual cost of treatment was $137.9±47.8, the expenditure included amount spent for blood transfusion and related expenses, iron chelation therapy (if prescribed), folate and calcium supplementation therapy, investigations (viz. serum ferritin level, hb estimation), splenectomy (if done in journal of rawalpindi medical college (jrmc); 2017;21(3): 281-285 284 last 1 yr), vaccination for hepatitis b and others like treatment costs for adverse effects of transfusion.18 a study from iran showed that proper genetic counseling teams consisting of a doctor and a professional with a bsc. degree in health studies were established in designated accessible urban health posts in every city.19a formal genetic counseling session should include explanation of the nature and prognosis of the disorder and available treatment options, estimation and communication of genetic risk for parents and providing options for avoiding them including technique of prenatal diagnosis and associated problems and supporting the individual or couple in making the decision that is right for them.20 in present study a significant association between genetic counselling and undergoing cvs testing (p <0.05). in the present study, only 76 (36.2%) parents had undergone cvs in all subsequent pregnancies, while the majority 97 (46.2%) had never opted for cvs testing. another study showed that after the index case, 72% families did not undergo prenatal diagnosis of thalassemia by cvs.21 common reasons in our study were lack of awareness about prenatal testing (47.7%) and careless attitude by the parents (41.7%). despite the fact that majority of the families belonged to lower middle class, financial reasons were found in only 1.5% of the cases. this might be because cvs is done free of cost now at few government-based centers. in spite of the common notion in our country that termination of pregnancy is not religiously permitted, our study showed no significant relationship between not undergoing cvs and religious reasons. in one study comparable to ours, cvs was not advised in 48% families and there were 24% families in which it was advised but they did not opt for it. 21 in another study 37.5% knew about prenatal diagnosis but did not use it.22 termination of pregnancy (top) was done in 84% of families after the diagnosis of thalassemia on cvs. in the rest, reasons for not opting top were delay in collecting report and reaching hospital in time especially in those patients who belong to far flung areas where there is no local specialized center for prenatal diagnosis. in a study conducted in saudi arabia, the attitude towards abortion was greatly affected by religious values. 23another study in egypt showed that the change in attitude towards termination of pregnancy was related to good counseling of the religious aspects towards prenatal diagnosis and termination of pregnancy.[24]in comparison, a study done to assess attitudes towards prenatal diagnosis and termination of pregnancy for thalassemia in pregnant pakistani women in the north of england showed influence by various other factors, similar to our findings. 25 it can therefore be concluded that religion should not be taken as a proxy for their attitudes either for or against termination of pregnancy. conclusion 1.beta-thalassemia major poses a major burden of disease in our country, and prevention is the only way to reduce its incidence. 2. prenatal diagnosis by chorionic villous sampling is a safe procedure to detect cases, but nonutilization of this facility is evident, due to lack of awareness. religious reasons were not found in any of our cases. 3.specialized genetic counseling sessions at the time of diagnosis of thalassaemia child regarding family screening and prenatal diagnosis emphasizing on its long term benefits should be carried out. references 1. ansari sh, shamsi ts, ashraf m, bohray m, farzana t. molecular epidemiology of β-thalassemia in pakistan: far reaching implications. int j mol epidemiol genet. 2011;2(4):403-08. 2. galanello r, origa r. beta-thalassemia. orphanet j rare dis. 2010;5(11):1-15. 3. majeed t, akhter ma, nayyar u, riaz ms, mannan j. frequency of beta-thalassemia trait in families of thalassemia major patients, lahore. j ayub med coll abbottabad. 2013;25(3-4):58-60. 4. tasleem s, tasleem h, siddiqui ma, adil mm. prenatal diagnosis of beta-thalassemia by chorionic villous sampling. j pak med assoc. 2007;57(11):528-31 5. asif n and hassan k. prevention of beta thalassemia in pakistan. j islam med dent coll.2014;3(2):46-47 6. amanat s, ikram n, baqai hz. pattern of haemoglobin disorders. j rawalpindi med coll. 2012;16(1):15-18 7. nosheen a, inamullah m, ahmad h, qayum i, siddiqui n. premarital genetic screening for beta thalassemia carrier status of indexed families using hba2 electrophoresis. j pak med assoc. 2015;65(10):1047-49 8. ansari sh, shamsi ts, ahmed fn, perveen k, ahmed g. effectiveness and feasibility of transabdominal chorionic villous sampling procedure for prenatal diagnosis of βthalassaemia in a muslim majority community of pakistan. pak j med sci 2012;28(4):575-79 9. goyal jp, hpapani pt, gagiya h. awareness among parents of children with thalassemia major from western india. int j med sci public heal. 2015;4(10):1356-59. 10. arif f, fayyaz j, hamid a. awareness among parents of children with thalassemia major. j pak med assoc. 2008;58(11):621-24. 11. cao a, rosatelli c, galanello r, monni g, olla g. the prevention of thalassemia in sardinia. clin genet. 1989;36:277-85. 12. buki mk, qayum i, siddiqui n. prevalence and preventive measures for thalassemia in hazara region of nwfp pakistan. j pak med assoc.1998;10:28-31 13. anwar t, ikram n, zafar t. prenatal diagnosis of β thalassaemia. j rawalpindi med coll.2014;18(1):16-19 journal of rawalpindi medical college (jrmc); 2017;21(3): 281-285 285 14. ghahramani f, ali m y, mmahnbonbi m. negative predictive value of the chorionic villous sampling in the diagnosis of thalassaemia in a genetic laboratory. arch iran med 2014; 17(7): 483-85 . 15. ikram n, bashir s, khan s, chaudhry r. role of prenatal diagnosis in thalassaemia prevention. j rawalpindi med coll. 2017;21(2): 109-12 16. ali s, safiullah, malik f. awareness of parents regarding beta thalassemia major disease. khyber med univ j.2015;7(2):72-75. 17. naseem s, ahmed s, vahidy f. impediments to prenatal diagnosis for beta-thalassemia: experiences from pakistan. prenat diagn.2008;28:1116-18. 18. mallik s,chatterjee c, mandal pk, sardar jc, ghosh p. expenditure to treat thalassaemia: an experience at a tertiary care hospital in india. iran j public health. 2010; 39(1): 78–84. 19. samavat a, modell b. iranian national thalassemia screening programme. bmj br med j 2004;329:1134 17. 20. amin sk. prevention of thalassaemia by genetic counseling. akmmc j. 2011; 2(2): 26-28 21. khan m, asif n, yaqoob n, anwar t, hassan k. prenatal diagnosis of thalassemia: practices among parents of thalassemia major patients. j islam med dent coll.2012;2:77-80. 22. ahmed s, saleem m, sultana n, raashid y, amin w. prenatal diagnosis of beta-thalassemia in pakistan: experience in a muslim country. prenat diagn [internet].2000;20:378-83. 23. alkuraya fs, kilani ra. attitude of saudi families affected with hemoglobinopathies towards prenatal screening and abortion and the influence of religious ruling (fatwa). prenat diagn. 2001;21(6):448-51 24. el-beshlawy a, el-shekha a, momtaz m, said f, hamdy m. prenatal diagnosis for thalassemia in egypt: what changed parents’ attitude? prenat diagn. 2012;32(8):777-82 25. ahmed s, green jm, hewison j. attitudes towards prenatal diagnosis and termination of pregnancy for thalassemia in pregnant pakistani women in the north of england. prenat diagn.2006;26(3):248-57. https://www.ncbi.nlm.nih.gov/pubmed/22693141 404 not found 404 not found 253 journal of rawalpindi medical college (jrmc); 2022; 26(2): 253-256 original article conventional cold steel and modern technique bizact ligasure for tonsillectomy: a comparative analysis muhammad saleem1, ashar alamgir2, syeda jamila ali3, hafiz sajjad hyder4, sarwat bibi5, sumara tabassum6 1,5,6 associate professor, aziz fatimah medical & dental college, faisalabad. 2 assistant professor, district headquarter hospital, rawalpindi. 3 senior registrar, general hospital ghulam muhammadabad, faisalabad. 4 senior registrar, faisalabad medical university, faisalabad. author’s contribution 1 conception of study 1,5 experimentation/study conduction 2,5 analysis/interpretation/discussion 2,4,6 manuscript writing 3,6 critical review 1 facilitation and material analysis corresponding author dr. muhammad saleem, associate professor of ent, aziz fatimah medical & dental college, faisalabad email: drsaleementspt@gmail.com article processing received: 05/11/2021 accepted: 17/02/2022 cite this article: saleem, m., alamgir, a., ali, s.j., hyder, h.s., bibi, s., tabassum, s. conventional cold steel and modern technique bizact ligasure for tonsillectomy: a comparative analysis. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 253256. doi: https://doi.org/10.37939/jrmc.v26i2.1834 conflict of interest: nil funding source: nil access online: abstract objective: the definitive treatment of tonsilitis is surgical resection of inflamed tonsils. various surgical techniques have been implicated to refine preoperative and post-operative care of the patients. one such innovation is the use of bizact ligasure for tonsillectomy. the study compares the conventional cold steel method and the modern technique bizact ligasure for tonsillectomy. materials & methods: a comparative study was designed using a non-probability purposive sampling technique at aziz fatimah hospital, faisalabad. one hundred participants were enrolled and divided into two groups (50 each). one group underwent bizact ligasure tonsillectomy and participants of the other group were treated with the conventional cold steel method. per-operative (blood loss, operative time) and post-operative variables (pain) were assessed using an independent t-test. results: the blood loss calculated in group a patients who underwent bizact ligasure tonsillectomy was 0.39 0.15 and in group b, 15.9 2.65. the mean operative time assessed in groups a and b was calculated as 4.26 0.66 and 32.38 5.56 respectively. both of these variables were recorded as highly significant as the p value = 0.000. the pain was assessed using the (visual analogue scale) vas pain scale. the post-operative pain variable was also recorded as a highly significant variable. conclusion: bizact ligasure tonsillectomy procedure is a more effective and safe procedure than the conventional cold steel method as this significantly reduces the blood loss during surgeries, operative time and minimizes postoperative pain. keywords: bizact ligature, cold steel, tonsillectomy. 254 journal of rawalpindi medical college (jrmc); 2022; 26(2): 253-256 introduction the inflammation of the tonsils is known as tonsillitis. tonsillitis is common among every age group and either gender. surgical resection remains the only best option for treating recurrent inflamed tonsils. tonsillectomy comprises a major bulk of operations undergoing in otorhinolaryngology throughout the world.1 tonsillectomy dates back 3000 years, referred to in indian medicine. however, much literature evidence is the testaments for the radical change surgical procedure to remove chronically inflamed tonsils.2 from the past few decades, surgical approaches and procedures have taken a dynamic shift minimizing the risk of primary hemorrhage, postoperative complications, pain, and hemorrhage. the paramount to improving these parameters has led the surgeons to devise modern surgical techniques that minimize the risks involved and are cost-effective.3 tonsillectomy carries a significant risk of morbidity and complications. the surgeons and investigators are now more inclined toward modern techniques than the old conventional cold steel method due to the advent of various new techniques that pose a lesser risk of morbidity and complications. over the past few years, various techniques have been developed to achieve the ideal aim of rapid, bloodless surgical procedures and uneventful recoveries, such as bipolar electrocautery, thermal welding, cold steel method, and ultrasonic dissector coagulator.4 one of the latest interventions devised for tonsillectomy is the use of the bizact ligasure device. the bizact ligasure device provides a 12 cm shaft for safe access and handling. the shape of the instrument is designed to keep a picture of the tonsillar bed in mind. this ergonomic device provides intuitive controls to seal and divide the tissue and vessels up to 3mm in diameter. literature evidence advocates the efficacy and minimal surgical risks of bizact ligasure.5 our study aims to evaluate the intra-operative variables such as surgical time, blood loss, and postoperative variables such as pain using the visual analogue pain scale and compare it with the conventional cold steel method. ethical considerations: the institutional ethical committee approved the study of aziz fatimah medical and dental college, faisalabad, under ethical certificate number iec/34-20. materials and methods a comparative study was conducted in aziz fatimah trust hospital, faisalabad, at the department of otorhinolaryngology from march 3, 2020, to june 26, 2021. a non-probability purposive sampling technique was implied, and after taking informed consent from the patients between the ages of 6 to 55 years of either gender presented with inflamed tonsils undergoing tonsillectomy were included in the study. patients with uncontrolled diabetes, hypertension, anemia, acute infection, and undergoing emergency tonsillectomies were excluded from the study. the sample size was calculated by taking a reference from the study conducted by ali, et al conducted at faisalabad medical university, faisalabad.4 one hundred patients were enrolled and divided randomly into two groups using random numbers in two equal groups of 50 labeled as a and b. group a comprised 50 patients operated by the bizact ligasure method, and group b underwent the conventional cold steel method. patients of either group were enrolled in groups randomly. patients were admitted for tonsillectomy one day before the surgery. a complete preoperative investigation package including, bleeding profile, complete blood count, x-ray chest, and electrocardiography (ecg) in patients above forty years was done on all patients before surgery. oral intake was stopped 8 hours before the surgery and all the participants were given a broad-spectrum antibiotic, ceftriaxone 1 gram twice before the surgery. operative time and blood loss were measured in minutes and milliliters, respectively. blood loss was estimated using the calorimetric method. cotton and ribbon gauze of the same size and weight were used during each surgery. the suction bottle and rubber tube were cleaned and emptied with a measured amount of saline and were used for intermittent suctioning to avoid blockage. in group a, patients undergoing bizact ligasure tonsillectomy noted immediate coagulation, while in group b hemostasis was achieved by ligature and local pressure. the pain assessment was done using the visual analog score (1= no pain, 4-6= moderate pain, 10= worst pain). before the surgical procedure, a visual analog pain scale was demonstrated to the patient. the post-operative antibiotic cover was given to avoid any sort of secondary bacterial infection. 255 journal of rawalpindi medical college (jrmc); 2022; 26(2): 253-256 the first pain assessment was taken immediately after 6 hours of the surgery and the patients were instructed to maintain a follow-up by visiting the hospital on the 3rd and 7th day after surgery. the data collected was analyzed in spss 20 using an independent t-test. age and gender distribution between the two groups were represented in percentages and frequencies. the comparison of peroperative variables such as blood loss and operation time was analyzed and represented in the form of and p-value. the pain was assessed using the vas pain scale and the data analyzed was represented in. the pvalue of 0.005 was considered significant and 0.000 was highly significant. results our study comprised 100 patients ranging from 6 years to 55 years. table 1 depicts the percentage and means & standard deviation among the two groups. age and gender distribution in group a depicts 34 (68%) participants between the age range of 6-21 years, 12 (24%), and 4 (8%) between 22-38 years and 39-55 years respectively. group b comprised 37 participants in the range of 6-21 years. mean and standard deviation was calculated between two groups stated as two different identities. table 1: age and gender distribution between group a and b the two groups evaluated per-operative variables such as blood loss (ml) and surgery time (minutes). group a recorded a blood loss of 0.39 ± 0.15, while group b recorded a response of 15.9 ± 2.65 and a pvalue=0.000. the mean operative time recorded for group a was 4.26 ± 0.66 and group b 32.38 ± 5.56. the analyzed p-value was 0.000. table 2: comparison of per-operative variables in group a and group b variables group a (n=50) group b (n=50) p-value mean ± sd blood loss (ml) 0.39 ± 0.15 15.9 ± 2.65 0.000 operative time (minutes) 4.26 ± 0.66 32.38 ± 5.56 0.000 table 3 depicts the postoperative pain assessment by two different surgical approaches for tonsillectomy. pain assessment was carried out using the visual analog score on days 1, 3, and 7. table 3: comparison of pain assessment on days 1, 3, and 7 using visual analogue pain scale pain as vas group a (n=50) group b (n=50) p-value mean ± sd pain on day 1 6.32 ± 0.89 7.86 ± 1.03 0.015 pain on day 3 5.20 ± 1.06 5.76 ± 1.45 0.000 pain on day 7 4.34 ± 1.22 3.80 ± 0.83 0.000 discussion one of the most commonly performed surgical operations in the otorhinolaryngology department across the globe is tonsillectomy. with an extensive history of surgical approaches and major bulk surgeons have changed the course of surgical approach devising new strategies and procedures to minimize the risks of morbidity and mortality.6 the surgeons have evolved various advances in the technology and instrumentation for tonsillectomy and homeostasis. the surgeon's perception concerning less operative time, minimum per-operative and postoperative bleeding, and increased recovery time towards a specific surgical technique influences his choice to advocate and treat the patients via that procedure.7 the present study focuses to compare the efficacy of bizact ligasure tonsillectomy with the conventional cold steel method. bizact ligasure is a bipolar currentcarrying device that seals the vessels simultaneously. the device measures the tissue impedance and supplies the controlled energy.8 in our study, the patients were divided into two groups. group a underwent bizact ligasure age group (years) group a (n=50) group b (n=50) no. of patients percent age no. of patients percent age 6-21 34 68% 37 74% 22-38 12 24% 7 14% 39-55 4 8% 6 12% total 50 100% 50 100% gender male 24 48% 21 42% female 26 52% 29 58% total 50 100% 50 100% 256 journal of rawalpindi medical college (jrmc); 2022; 26(2): 253-256 tonsillectomy while group b with conventional cold steel method. intra-operative parameters were compared in both groups. in group a, blood loss and operative time were measured at 0.39 ± 0.15ml and 4.26 ± 0.66 minutes respectively as compared to the blood loss of 15.9 ± 2.65ml and operative time of 32.38 ± 5.56 minutes in group b patients. both the parameters were found to be highly significant statistically with a p-value of 0.000. similar results were found in the study conducted by adeel niaz et al. and muhammad ali et al. in allied hospital faisalabad and combined military hospital kharian and lahore.4,9 another study by lucy huang et al. states the efficacy of bizact ligasure with a blood loss average of 2.7 ml and operative time of approximately 4 minutes similar to our study. moreover, the study also focuses on the parental perception of the child’s quality of life.10 literature evidence by giri krishnan et al. also reported a mean surgical time of 5 minutes and a blood loss of fewer than 1 ml observed in the majority of the cases.11 all these results indicate the intraoperative efficacy of using these modern techniques such as bizact ligasure as compared to the conventional cold steel method. one of the most important post-operative parameters is the assessment of pain during the recovery phase. the majority of patients seeking medical care after tonsillectomy were due to pain. in the present study, the pain was assessed using the visual analog score for the pain scale. according to our study, the assessment of pain on day 1 in group a patients was 6.32 0.89, 7.86 1.03 in group b patients, and p-value= 0.015. significant statistical difference was found on day 3 and day 7 having a p-value=0.000. muhammad ali et al. also document significant values of the pain assessed using the vas scale.4 similar results were stated by the systematic review conducted by robert et al. the main reason for this difference in pain score is that more thermal damage was caused during the bipolar diathermy dissection procedure.12 a study carried out by pang et al. reported a minimum blood loss of 10 ml during bipolar electrothermy advocating the efficacy of the surgical intervention. conclusion tonsillectomies done by bizact ligasure were effective and rapid surgical procedures with an added advantage of less operative time, and minimum blood loss during the surgery as compared to the cold steel dissection method. post-operative pain was also recorded as a significant variable for bizact ligasure. references 1. bohr c, shermetaro c. tonsillectomy and adenoidectomy. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021 jan–. pmid: 30725627. 2. verma, r., verma, r. r., & verma, r. r. (2017). tonsillectomy-comparative study of various techniques and changing trend. indian journal of otolaryngology and head and neck surgery: official publication of the association of otolaryngologists of india, 69(4), 549–558. doi: https://doi.org/10.1007/s12070-017-1190-6 3. besser g, grasl s, meyer el, schnoell j, bartosik tj, brkic ff, heiduschka g. a novel electrosurgical divider: performance in a self-controlled tonsillectomy study. eur arch otorhinolaryngology. 2021. doi:10.1007/s00405-021-07008-9. epub ahead of print. pmid: 34338876. 4. mofatteh, m. r., salehi, f., hosseini, m., hassanzadehtaheri, m., meghdadi, s., & hassanzadeh-taheri, m. (2019). postoperative outcomes in cold dissection versus bipolar electrocautery tonsillectomy: a randomized double-blind controlled study. indian journal of otolaryngology and head and neck surgery: official publication of the association of otolaryngologists of india, 71(suppl 1), 182–187. doi: https://doi.org/10.1007/s12070-017-1204-4 5. bizact™ tonsillectomy device [instructions for use]. boulder, co: medtronic; 2017. [internet, accessed on september 22, 2021] 6. cullen ka, hall mj, golosinskiy a. ambulatory surgery in the united states. natl health stat report. 2008. 28;(11):1-25. pmid: 19294964. 7. krishna p, lapage mj, hughes lf, lin sy. current practice patterns in tonsillectomy and perioperative care. international journal of pediatric otorhinolaryngology. 2004 jun;68(6):77984. doi: 10.1016/j.ijporl.2004.01.010. pmid: 15126019. 8. çelikoyar, m. m. (2020). tonsillectomy with bizact: impressions from four cases. praxis of otorhinolaryngology, 8(1), 51–55. doi: https://doi.org/10.5606/kbbu.2020.52714 9. niaz, a., saeed, m., & hyder, h. (2020). comparison of bipolar diathermy tonsillectomy versus cold steel dissection tonsillectomy. annals of punjab medical college, 14(2), 102105. doi: https://doi.org/10.29054/apmc/2020.802 10. huang, l., stepan, l., woods, c. m., huynh, j., & ooi, e. h. (2018). surgery and medicine. 3. doi: https://doi.org/10.29011/2575-9760.c1.006 11. krishnan g, stepan l, du c, padhye v, bassiouni a, dharmawardana n, ooi eh, krishnan s. tonsillectomy using the bizact: a pilot study in 186 children and adults. clinical otolaryngology. 2019. 44(3):392-396. doi: 10.1111/coa.13273. epub 2019 feb 4. pmid: 30576062. 12. leinbach rf, markwell sj, colliver ja, lin sy. hot versus cold tonsillectomy: a systematic review of the literature. otolaryngol head neck surgery. 2003 oct;129(4):360-4. doi: 10.1016/s0194-5998(03)00729-0. pmid: 14574289. 13. pang yt, el-hakim h, rothera mp. bipolar diathermy tonsillectomy. clinical otolaryngology allied science. 1994 aug;19(4):355-7. doi: 10.1111/j.1365-2273.1994.tb01247.x. pmid: 7994897. 404 not found 552 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 review article a viewpoint on clinical approach towards assessment of chronic shoulder pain muhammad shahid khan1, denny tijauw tjoen lie2, andrew tan hwee chye3, wael azzam4 1 assistant professor, department of orthopaedics, isra university, hyderabad, pakistan. 2 associate professor, department of orthopaedics, singapore general hospital, singapore. 3 associate professor & hod, department of orthopaedics, singapore general hospital, singapore. 4 assistant professor, department of orthopaedic surgery, faculty of medicine, tanta university, tanta, egypt. author’s contribution 2,3 conception of study 2,3 experimentation/study conduction 2,3 analysis/interpretation/discussion 1,4 manuscript writing 1,2,3,4 critical review corresponding author dr. muhammad shahid khan, assistant professor, department of orthopaedics, isra university, hyderabad, pakistan. email: khan.shahid1945@gmail.com article processing received: 16/10/2021 accepted: 03/12/2021 cite this article: khan, m.s., lie, d.t.t., chye, a.t.h., azzam, w. a viewpoint on clinical approach towards assessment of chronic shoulder pain. journal of rawalpindi medical college. 31 dec. 2021; 25(4): 552-559. doi: https://doi.org/10.37939/jrmc.v25i4.1814 conflict of interest: nil funding source: nil access online: abstract introduction: the shoulder joint offers a wide range of motion and therefore pathologies leading to restriction of its movements affect the routinely performed activities. symptoms of the shoulder pathologies are often overlapping and usually are not specific to a certain pathology. lack of consensus for the diagnostic criteria for different shoulder pathologies may lead to difficulty in selecting appropriate treatment options by the physician. this viewpoint proposes that with a targeted history, related clinical examination, and appropriate investigations, still a diagnostic algorithm can be made to conclude a diagnosis. material and methods: landmark studies on history and examination of shoulder joints were searched and identified. the databases utilized for finding the articles were google scholar and pubmed. conclusion: symptoms of different shoulder pathologies are quite overlapping. however, with a comprehensive history, a diagnostic approach can be made by carefully digging out the proportion of a symptom in a patient’s existing problem. based on this dominant clinical finding, a differential diagnosis can be made which can then be further fine-tuned with the help of clinical examination including special provocative tests and appropriate investigations, if needed. as initial conservative management is common in most shoulder pathologies it can be started in a primary care facility with referral to a higher level of care if the patient is non-responsive. keywords: shoulder pain, differential diagnosis, orthopedic special tests. 553 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 introduction the shoulder joint is very versatile with regard to its mobility and therefore decrease in its arc of motion may lead to deleterious effects on the functional ability of the arm with regard to the performance of activities of daily living. shoulder pain accounts for around 16 percent of all musculoskeletal complaints and it is the third most common cause of bone and joints consultation in primary care.1 shoulder problems can be divided into six major diagnostic categories including rotator cuff tendinosis, rotator cuff tears, adhesive capsulitis, glenohumeral osteoarthritis, glenohumeral instability, and acromioclavicular joint pathology. symptomatology of the shoulder can be broadly divided into pain, weakness, stiffness, and instability. however, each of these symptoms is not specifically related to a separate pathology, instead, a symptom can be present in different pathologies. with a comprehensive history, still, a diagnostic algorithm can be made by carefully digging out the proportion of a symptom (table 1) in different pathologies. based on the dominant clinical finding, a differential diagnosis can be made (table 2) which can then be further fine-tuned with the help of clinical examination including special provocative tests2,3,4 (table 3) and appropriate investigations. this article is targeted at undergraduate and postgraduate medical students. with the help of landmark studies on the assessment of chronic painful shoulder, the manuscript describes different points in history and clinical examination and helps the reader to come up with a diagnosis. materials and methods landmark studies on the history and examination of shoulder joints were searched and identified. the databases utilized for finding the articles were google scholar and pubmed. table 1: major shoulder pathologies and their characteristic symptoms2-8 shoulder pathologies main shoulder symptoms rotator cuff tendinosis pain weakn ess stiffn ess instability +++ + + rotator cuff tear  small to mediu m  massiv e ++ + + +++ +/ + (pseu do) +/ frozen shoulder + +++ glenohumeral osteoarthritis ++ ++ acromioclavicu lar joint osteoarthritis ++ glenohumeral instability +/+++ table 2: integrated approach towards differential diagnosis based on dominant clinical findings2-8 dominant clinical finding differential diagnosis stiffness  classical frozen shoulder pain  tendinosis  impingement syndromes  early capsulitis  partial rotator cuff tear weakness  large to massive rotator cuff tear instability  shoulder instability disorders results figure 1: radio-graphing anterioposterior view of the shoulder 554 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 figure 2: radio-graphing y-scapular view of the shoulder figure 3: mri image showing supraspinatous tear figure 4: mri image showing supraspinatous tendinosis table 3: provocative tests for different shoulder pathologies pathology & test name sensitivity & specificity how to perform anterior glenohumeral instability anterior apprehension2 surprise test2 sens 65.6 spec 95.4 sens 81.8 spec 86.1 the test is considered positive if the patient complains of pain or apprehension when the patient’s elbow is flexed to 90° along with 90-degree shoulder abduction and rotating the shoulder externally followed by application of an anterior force from the posterior aspect of the shoulder. with the patient in a supine position, an anterior force is applied to the shoulder with the patient’s arm in 90 degrees of abduction, 90 degrees of elbow flexion with maximum external rotation of the shoulder. release of anterior force to the shoulder with resultant pain or apprehension indicates a 555 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 bony apprehension2 olecranon manubrium percussion2 sens 94 spec 84 sens 84 spec 99 positive test. while standing behind the patient, the examiner grasps the patient’s supraclavicular region with one hand and the forearm with the other hand. while flexing the patient’s elbow to 90 degrees, abduct and externally rotate the shoulder to 45 degrees. a positive test is indicated by pain or apprehension in this position. the patient is asked to cross both arms with elbows flexed to 90 degrees. percuss the olecranon while listening to the sound over the patient’s manubrium with the help of a stethoscope. repeat the procedure with percussion on the opposite olecranon. a positive test is indicated by a difference in the quality of sound on the affected versus unaffected side. rotator cuff tendinosis supraspinatous pathology empty can or jobe’s test2 painful arc2 supscapularis pathology modified belly press test2 lift off test2 napoleon test3 bear hug3 sens 81 spec 89 sens 53 spec 76 sens 86 spec 91 sens 6-69 spec 23-84 sens 41 spec 80 sens 75 spec 56 patient’s arms are abducted to 90 degrees and forward flexed 30 degrees with their elbow extended and thumbs facing downward. the examiner applies downward force over the forearm while the patient is asked to resist this. a positive test is indicated by the weakness of the affected shoulder in comparison to the opposite side a positive test is characterized by complaints of pain between 60 and 120 degrees of abduction and reduction in pain once past 120 degrees of abduction patient is asked to keep the hand flat on the abdomen and the elbow close to the body. while keeping the hand on the abdomen, the patient is instructed to bring the elbow forward and straighten the wrist. flexion angle of the wrist or belly-press angle is measured by a goniometer. an angle difference of at least 10 degrees from the normal side is considered a positive test. the patient, in the standing position, is asked to place the hand behind their back with the dorsum of the hand touching the back. the patient is instructed to raise the hand away from the back by increasing internal rotation of the humerus and extension at the shoulder. a positive test is indicated by the inability to move the dorsum of the hand away from the back. the patient is asked to place the hand on the belly. the test is graded as:  negative (or normal) if the patient can push the hand against the belly with the wrist straight  positive, if the wrist was flexed to 90° to push against the belly  intermediate, if the wrist is flexed from 30° to 60° to do the belly press. the patient is asked to place the palm (with fingers extended) of the involved arm on the opposite shoulder while keeping the elbow anterior to the body. 556 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 infraspinatous and teres minor pathology resisted external rotation test4 sens 76 spec 57 the patient is then instructed to hold that position (resisted internal rotation) while the examiner tries to pull the patient’s hand away from the shoulder with an external rotation force. a positive test is indicated by the inability to maintain the hand position against the shoulder. the patient’s arms are kept by his or her side in neutral flexion and abduction. the patient is instructed to rotate the shoulders externally up to 45 to 60 degrees. the examiner applies force over the dorsum of the hands thereby trying to rotate the shoulders internally while the patient is asked to resist. a positive test is indicated by pain and weakness. impingement syndrome hawkin’s kennedy test2 neer test2 sens 80 spec 56 sens 72 spec 60 the patient's arm is forward flexed to 90 degrees followed by elbow flexion to 90 degrees as well then the shoulder is internally rotated. this leads to greater tuberosity impingement under the coracoacromial ligament. a positive test is indicated by pain. while stabilizing the scapula, the examiner raises the affected arm is forces forward elevation, resulting in the greater tuberosity impingement against the acromion. a positive test is indicated by pain. acromioclavicular joint pathology cross-body adduction test2 sens 57 spec 96 while standing behind the patient, the examiner grasp the patient’s arm and passively flex the patient’s shoulder to 90 degrees followed by maximally adducting the patient’s shoulder thereby bringing it across the patient’s body towards the opposite shoulder. a positive test is indicated during the adduction motion of localized pain over the acromioclavicular joint. glenohumeral osteoarthritis shoulder shrug test2 sens 91 spec 57 the patient is instructed to abduct both arms to 90° in the plane of the body and to maintain this position for short time. a positive test is indicated by elevation of the whole scapula to lift the arm to 90°. adhesive capsulitis /frozen shoulder shoulder shrug test2 sens 95 spec 50 as described above labral pathologies crank test2 (also known as compression rotation test / o’brian’s test) sens 34 spec 75 the patient is asked to flex the shoulder to 90° then do 10° of horizontal adduction followed by maximum internal rotation of the shoulder while keeping the elbow in full extension. the patient is instructed to resist a downward force applied by the examiner. the same maneuver is repeated while keeping the shoulder and forearm in a neutral position. a positive test is characterized by pain or clicking in the shoulder with initial position and 557 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 speeds test2 sens 20 spec 78 reduced or no symptoms with the second position. patient is instructed to forward flex the shoulder to 90 degrees while keeping the elbow extended and the forearm supinated. the patient is then asked to maintain this position while the examiner applies the resistance to the forearm. a positive is indicated by pain localized to the bicipital groove. bicep tendinopathy speed test2 yergason’s test2 sens 49-71 spec 60-85 sens 14-75 spec 78-89 as above the patient is instructed to flex the elbow to 90 degrees and keep the forearm pronated. the patient is then asked to actively supinate the forearm while the examiner attempts to resist this by applying an internal rotation force to a patient’s wrist. a positive is indicated by pain localized to the bicipital groove. discussion i. history as in other pathologies, a detailed history is of utmost importance and this includes the patient’s age, pain characteristics, profession, sports involvement, history of trauma, and comorbid conditions. a patient’s age may give us a clue regarding possible pathology. shoulder instability and mild rotator cuff problems are common in age less than 40 years while adhesive capsulitis, moderate to severe cuff pathologies, and shoulder joint osteoarthritis are more likely after the age of 40. pain characteristics including onset, location, duration, progression, radiation, aggravating and relieving factors are determined. pain localized to the lateral shoulder area is usually due to rotator cuff problems while acromioclavicular osteoarthritis usually presents with pain mainly over the anterior shoulder or over the ac joint itself. pain over the anterior aspect of the shoulder with radiation distally over the anterior aspect of the arm along bicep muscle may indicate bicep tendinopathy. symptoms progression may point to specific shoulder pathology like adhesive capsulitus which typically show a progressive pattern of three distinct stages of pain (freezing), stiffness (frozen), and recovery (thawing).5 professional history or sports involvement requiring overhead activities favors the likelihood of rotator cuff pathology whereas history of trauma, contact sports, or weight lifting points more towards acromioclavicular or glenohumeral osteoarthritis. history of previous shoulder surgery is important as it may lead to secondary adhesive capsulitis or early glenohumeral osteoarthritis. inflammatory arthritis, diabetes, and thyroid disorders may affect the shoulder as well so systemic inquiry regarding these problems is important.6,7 night pain and sleep disturbance are common in patients with rotator cuff tears.8 ii. physical examination the physical examination can be divided into inspection, palpation, range of motion followed by special provocative tests to further narrow down the differential diagnosis. after adequate exposure, the shoulder is inspected for scar marks, atrophy of muscles, deformity, and symmetry of both shoulders. palpate and try to localize the tenderness which could be over the acromioclavicular joint, bicipital groove, and lateral aspect of the shoulder. range of motion (rom) is assessed in all directions including flexion, extension, abduction, internal rotation, and external rotation. passive range of motion need not be performed if the patient can perform a full active range of motion. adhesive capsulitis is characterized by loss of both active and passive range of motion. in rotator cuff pathology, active rom is affected more and passive rom is relatively preserved. typically in rotator cuff disease, abduction is painful between 60 to 100 degrees which is known as a painful arc sign.9 iii. provocative tests keeping in mind the differential diagnosis based on history and clinical examination, provocative tests are performed. these tests are meant to reproduce the symptoms by performing some specific maneuvers. combinations of these tests provide better accuracy in contrast to performing any single test to come up with 558 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 a diagnosis.2 relevant provocative tests with regard to a suspected pathology are described in table 3. iv. diagnostic imaging to further narrow down the differential diagnosis, relevant investigations are done to come up with a definitive diagnosis. radiographs (figure 1-2) are usually considered firstline investigations for chronic shoulder pain. with a background history of trauma, radiographs may show evidence of bony injuries. they may show findings of osteoarthritis of the glenohumeral and acromioclavicular joints. secondary signs of massive rotator cuff tear may be seen which include superior migration of the humeral head and sclerosis of the undersurface of the acromion. rotator cuff tendinosis and tears can be detected by ultrasonography. in contrast to mri, it is a dynamic assessment that is relatively less expensive, has better patient tolerance but is highly operator dependent.10 it has a reported sensitivity of 67% for partial-thickness rotator cuff tear and 97% for full-thickness rotator cuff tear. its specificity for partial-thickness rotator cuff tear is 94% and for full-thickness, rotator cuff tear is 96%.10 although expensive, the use of magnetic resonance imaging (mri) is increasingly becoming the noninvasive diagnostic modality of choice for detecting soft tissue problems around the shoulder including rotator cuff (figure 3 and 4), bicep long head, and labral pathologies. it is the preferred test for diagnosing rotator cuff disorders.10 reported sensitivity of mri is 44% for partial-thickness rotator cuff tear and 89% for full-thickness rotator cuff tear with the specificity of 90% for partial-thickness rotator cuff tear and 93% for full-thickness rotator cuff tear.10 the ct scan is usually reserved to detect bony pathologies or bone stock of the shoulder, including glenohumeral instability with associated bone loss of the humeral head or the glenoid, osteoarthritis with significant erosion, occult fractures, and neoplasms. v. management typical impingement syndromes and partial-thickness rotator cuff tear are initially managed with conservative treatment of at least six months. management consists of education regarding daily activity modification, physiotherapy, antiinflammatory medications, and if needed subacromial corticosteroid injection. failure to respond to this regimen needs a referral for a surgical opinion.11 rotator cuff tears involving less than 50% of the tendon thickness are usually treated arthroscopically by debridement, subacromial decompression, and acromioplasty. repair of the rotator cuff tear is done if the tear involves more than 50% of the tendon thickness. this can be done arthroscopically or through a mini-open approach. full-thickness rotator cuff tears which are clinically symptomatic, especially in the young age group, should be surgically repaired as early as possible because later repair may be more difficult to perform.12 massive irreparable rotator cuff tears, especially in the elderly, can be treated by debridement, subacromial decompression, and biceps tenotomy with good pain relief. management of degenerative conditions such as glenohumeral arthritis or rotator cuff tear arthropathy is generally initiated with conservative management including anti-inflammatory medications and physical therapy. failure to respond to conservative management is an indication for shoulder joint replacement surgery. non-operative management is not, however, mandatory if severe arthritic changes are present on radiographs, as the chances of longterm symptom relief are negligible.13 for adhesive capsulitis, there is no consensus in the literature regarding which treatment modality; like non-operative, operative, or combined; is superior to others. there is a general consensus about nonoperative management as the initial treatment of choice for adhesive capsulitis, which includes physical therapy, anti-inflammatory medications, and corticosteroid injections. operative treatment is indicated if a conservative treatment trial of 6 months fails to provide symptom relief.14 acrmioclavicular osteoarthritis usually responds to activity modification, anti-inflammatory medications, and if needed local steroid injection.15 failure to respond to conservative measures warrants operative treatment and resection of the distal one cm of the clavicle is often effective in relieving pain symptoms.16,17 in the literature, there is little support for nonoperative treatment for patients with glenohumeral joint instability, so early surgical referral is recommended in this group of patients.15 conclusion symptoms of different shoulder pathologies are quite overlapping. however, with a comprehensive history, a diagnostic approach can be made by carefully digging out the proportion of a symptom in a patient’s existing problem. based on this dominant clinical finding, a differential diagnosis can be made which 559 journal of rawalpindi medical college (jrmc); 2021; 25(4): 552-559 can then be further fine-tuned with the help of clinical examination including special provocative tests and appropriate investigations, if needed. as initial conservative management is common in most shoulder pathologies it can be started in a primary care facility with referral to a higher level of care if the patient is non-responsive. references 1. urwin m, symmons d, allison t, et al. estimating the burden of musculoskeletal disorders in the community: the comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation. annals of the rheumatic diseases. 1998 nov 1;57(11):649-55. doi: 10.1136/ard.57.11.649 2. hegedus ej, goode ap, cook ce, et al. which physical examination tests provide clinicians with the most value when examining the shoulder? update of a systematic review with meta-analysis of individual tests. br j sports med. 2012 nov 1;46(14):964-78. doi: 10.1136/bjsports-2012-091066 3. schiefer m, ching-san júnior ya, silva sm, et al. clinical diagnosis of subscapularis tendon tear using the bear hug semiological maneuver. revista brasileira de ortopedia (english edition). 2012 sep 1;47(5):588-92 doi: 10.1016/s2255-4971(15)30008-2. ecollection sep-oct 2012. 4. beaudreuil j, nizard r, thomas t, et al. contribution of clinical tests to the diagnosis of rotator cuff disease: a systematic literature review. joint bone spine. 2009 jan 1;76(1):15-9. doi: 10.1016/j.jbspin.2008.04.015. epub 2008 dec 6. 5. reeves b. the natural history of the frozen shoulder syndrome. scandinavian journal of rheumatology. 1975 jan 1;4(4):193-6. doi: 10.3109/03009747509165255 6. cakir m, samanci n, balci n, et al. musculoskeletal manifestations in patients with thyroid disease. clinical endocrinology. 2003 aug;59(2):162-7. doi: 10.1046/j.1365-2265.2003.01786.x 7. smith ll, burnet sp, mcneil jd. musculoskeletal manifestations of diabetes mellitus. british journal of sports medicine. 2003 feb 1;37(1):30-5. doi: 10.1136/bjsm.37.1.30. 8. austin l, pepe m, tucker b, et al. sleep disturbance associated with rotator cuff tear: correction with arthroscopic rotator cuff repair. the american journal of sports medicine. 2015 jun;43(6):1455-9. doi: 10.1177/0363546515572769. epub 2015 mar 16. 9. burbank km, stevenson jh, czarnecki gr, et al. chronic shoulder pain: part i. evaluation and diagnosis. american family physician. 2008 feb 15;77(4). doi 2008 feb 15;77(4):453-60. 10. dinnes j, loveman e, mcintyre l, et al. the effectiveness of diagnostic tests for the assessment of shoulder pain due to soft tissue disorders: a systematic review. health technol assess. 2003;7(29):iii, 1-166. doi: 10.3310/hta7290. 11. gartsman gm. (iii) partial thickness rotator cuff tears— evaluation and treatment. current orthopaedics. 2000 may 1;14(3):167-72. doi: 10.1054/ cuor.2000.0103 12. safran o, schroeder j, bloom r, et al. natural history of nonoperatively treated symptomatic rotator cuff tears in patients 60 years old or younger. the american journal of sports medicine. 2011 apr;39(4):710-4. doi: 10.1177/0363546510393944. epub 2011 feb 10. 13. michael codsi, chris r. howe. shoulder conditions diagnosis and treatment guideline. physical medicine and rehabilitation clinics. 2015; 26(3):467-206. doi: https://doi.org/10.1016/j.pmr.2015.04.007 14. yip m, francis am, roberts t, et al. treatment of adhesive capsulitis of the shoulder: a critical analysis review. jbjs reviews. 2018 jun 1;6(6):e5. doi: 10.2106/jbjs.rvw.17.00165. 15. hossain s, jacobs lg, hashmi r. the long-term effectiveness of steroid injections in primary acromioclavicular joint arthritis: a five-year prospective study. journal of shoulder and elbow surgery. 2008 jul 1;17(4):535-8. doi: 10.1016/j.jse.2007.12.001 16. montellese p, dancy t. the acromioclavicular joint. primary care: clinics in office practice. 2004 dec 1;31(4):857-66. doi: 10.1016/j.pop.2004.07.011. 17. rabalais rd, mccarty e. surgical treatment of symptomatic acromioclavicular joint problems: a systematic review. clinical orthopaedics and related research®. 2007 feb 1;455:30-7. doi: 10.1097/blo.0b013e31802f5450. 404 not found 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 248-252 248 original article treatment of molluscum contagiosum with 10% potassium hydroxide solution atiya rahman 1, aisha akhtar 1, saadia tabassum 2,rana shakil ahmad 3 1. department of dermatology, combined military hospital lahore & cmh lahore medical college; 2. department of dermatology, aga khan university hospital, karachi;3.clinical research executive abstract background: to determine the efficacy and safety of topical 10% potassium hydroxide solution in the treatment of molluscum contagiosum (mc) . methods: an open, prospective, non-randomized study of one year duration was conducted using 10% koh solution to treat mc. twenty eight patients completed the study. a total of seven appointments were planned; one baseline and six follow-up visits. 10% koh was applied to molluscum lesions daily till the lesions resolved or till 3 months had elapsed. results: twenty eight patients, among which 22 were children, completed the study. the mean age of patients was 10.6 years. the total lesion count in the patients varied from 5 – 94, with the mean lesion count of 22.14 sd +_ 18.32. there was complete resolution of lesions in 20 (71.4%) of patients , 4 (14.3) had a near complete, 2 (7.1%) had partial and 2 (7.1%) patients had no improvement. 82% patients tolerated the treatment well with no side effects. conclusion:10% koh solution is an effective and well tolerated treatment for mc. it is less painful and cost-effective as compared to many wellestablished therapeutic modalities. it has the advantage of ease of application at home making it an acceptable and feasible option for the treatment of mc. key words: molluscum contagiosum, potassium hydroxide, efficacy. introduction molluscum contagiosum (mc) is among the most common viral skin infections. common treatment options include destructive therapy, topical therapy and immunotherapy. destructive therapy is poorly tolerated because of pain on application. in addition, these therapies are expensive and have inconvenience of application in hospital setting. mc is among the most common viral skin infections , occurring in approx 2-8% of children.1,2 it is caused by a member of the poxvirus family, the genus molluscipox virus. the virus is transmitted by close physical contact, autoinoculation, and fomites.mc presents as asymptomatic, discrete, smooth, flesh-coloured, domeshaped papules with central umbilication.1 the lesions can be numerous and recurrent. the infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection.3treatment options include destructive therapy, topical therapy, immunotherapy and oral therapy.1 destructive treatment modalities include curettage, cryotherapy, expression or pricking with a sterile needle, electrodesiccation, photodynamic therapy, and laser ablation.4,5among topical therapies different chemical agents, like cantharidin,6 povidoneiodine,7 potassium hydroxide,8 tretinoin,9 and imiquimod10 have been used with variable success. immune modulating agents include interferon alpha, imiquimod and cimetidine.1 destructive therapy is poorly tolerated in children because of pain on application. in addition, these therapies are expensive and have inconvenience of application in hospital setting. patients and methods an open, prospective, non-randomized study of one year duration was conducted at dermatology department of combined military hospital, lahore using 10% koh solution to treat mc. sample size of 28 cases was estimated using 95% confidence interval and 14% deviation acceptance with a percentage of complete response in 85% in the previous studies. a total of seven appointments were planned; one baseline and six follow-up visits. during the baseline visit thorough history and dermatological examination was carried out. cases were studied for number of lesions, their site, any eczematous change, presence of pain or pruritus. first application of 10% koh solution was performed with the patient or parent closely observing the procedure and was advised to apply the drug in a similar way at home journal of rawalpindi medical college (jrmc); 2017;21(3): 248-252 249 twice daily. six follow-up visits were planned at the end of week 1, 2, 4, 6, 8 and 12. the medication was to be applied till the lesions resolved or till 3 months had elapsed. koh applied on the skin initiates an inflammatory response leading to lesion clearance. the number of lesions, their site, crusting , erythema , erosions , pain , pruritus , improvement of lesion were documented. the clinical response to treatment was assessed using the methods devised by marsalet al and capriotti et al. 11,12 the patients were divided into 4 groups on the basis of improvement of mc lesions. group 4= complete cure; group 3= near complete response (with less than 5 mc lesions all over the body) ;group 2= partial response (less than 60% of the lesions since the baseline visit and more/equal than 5 lesions);group 1= poor response (>60% of the lesions since baseline visit). patients whose lesions cleared up before 3 months were documented and were discharged from the study having attained “complete cure”. at the end of 3 months final assessment was made . results twenty eight patients, 22 children and 6 adults completed the study. age of patients ranged from 2 years to 36 years and the mean age was 10.6 years ± 8.96. eleven (39.3%) patients were female and 17 (60.7%) were male. the duration of mc lesions varied from 2 – 39 weeks, with a mean duration of 8.6 weeks (table 1). twelve (42.9%) of the patients gave positive family history in a first degree relative. the total lesion count in the patients varied from 5 – 94, with the mean lesion count of 22.14 sd +_ 18.32. 32.2% patients had been treated previously with other therapeutic modality (17.9% with cryotherapy and 14.3% with phenolization) but had unsatisfactory response. successful 10% koh solution application to mc initiates an inflammatory response consisting of erythema, crusting, erosion and usually associated with a mild stinging or pruritus(figure 1). there was complete resolution of lesions in 20 (71.4%) of patients , 4 (14.3%) had a near complete, 2 (7.1%) had partial and 2 (7.1%) patients had no improvement (table 2). complete cure was seen in majority of patients in age group2 to 20 years (table 3;figure 14).duration of disease could prolong the response time for the patients as it has strong effect on treatment and improvement in patients with a significant value (table 4). there was no significant effect noted for other demographical factors like age, gender and site of disease. an equal distribution was observed on evaluation on different sites, but most commonly the lesions were present on multiple sites; 16(57%) of cases ( table 1:distribution of the characteristics in study population (n=28) mean percentages age 10.60±8.96 gender male 11(39.3%) female 17(60.7%) family history yes 12(42.9%) no 16(57.1%) duration of disease 8.57±9.36 site of disease head & neck 5(17.9%) trunk 3(10.7%) upper limb 1(3.6%) lower limb 2(7.1%) genitalia 1(3.6%) multiple sites 16(57.1%) table 2:percentage improvement in the disease grades of the patients response no percentage 1. poor response 2 7.1 2. partial response 2 7.1 3. near complete response 4 14.4 4. complete cure 20 71.4 table 3: impact of demographical variables on the study outcome improvement grades total p-value group 1: poor response group 2:partial response group 3: near complete response group 4: complete cure gender female 0 0 1 10 11 0.273 .0% .0% 25.0% 50.0% 39.3% male 2 2 3 10 17 100.0% 100.0% 75.0% 50.0% 60.7% age group 2-20 year 1 2 2 17 22 0.267 50.0% 100.0% 50.0% 85.0% 78.6% >20 year 1 0 2 3 6 50.0% .0% 50.0% 15.0% 21.4% table 5).majority of the patients (82%) tolerated the treatment well with no side effects. 2 (7.1%) developed contact dermatitis after application of koh; 3 (10.7%) patients developed secondary bacterial infection requiring oral antibiotic therapy. four patients developed transient post-inflammatory hypopigmentation once the lesions cleared; this resolved within a month of stopping koh application.the hypopigmentation settled after the completion of study duration with no further treatment. journal of rawalpindi medical college (jrmc); 2017;21(3): 248-252 250 table 4:stratification of the improvement with respect to family history and duration of disease improvement grades total pvalue group 1: poor response group 2: partial response group 3: near complete response group 4: complet e cure family history yes 1 1 1 9 12 0.887 50.0% 50.0% 25.0% 45.0% 42.9% no 1 1 3 11 16 50.0% 50.0% 55.0% 75.0% 57.1% duration of disease 2-12 year 1 0 3 19 23 0.000 50.0% .0% 75.0% 95.0% 82.1% 13-23 year 0 2 0 0 2 .0% 100.0% .0% .0% 7.1% >23 year 1 0 1 1 3 50.0% .0% 25.0% 5.0% 10.7% table 5: improvement according to body site improvement grades total site of lesion group 1 poor response group 2. partial response group 3. near complete response group4. complet e cure p-value head & neck 0 0 0 5 5 0.667 .0% .0% .0% 25.0% 17.9% trunk 0 0 0 3 3 .0% .0% .0% 15.0% 10.7% upper limb 0 0 0 1 1 .0% .0% .0% 5.0% 3.6% lower 0 1 0 1 2 .0% 50.0% .0% 5.0% 7.1% genitalia 0 0 0 1 1 .0% .0% .0% 5.0% 3.6% multiple sites 2 1 4 9 16 100.0% 50.0% 100.0% 45.0% 57.1% discussion mc is a common viral infection that frequently affects children of school going age. it is thought that using community bathing facilities/swimming pools or siblings using the same washing sponges or towels spreads the infection.11in healthy patients, cutaneous mc is a self-limiting disease that often spontaneously resolves in 6 to 9 months, usually without scarring. quality of life is a factor to consider when deciding whether or not to treat a paediatric patient as he or she may suffer chastisement from peers at school if the lesions are visible. not treating paediatric infections also carries the risk of the disease spreading to others, and this consideration may favour the option of treatment over benign neglect.13 conditions like atopic dermatitis may cause widespread development of mc, making it imperative to treat the lesions promptly. destructive treatment options like curettage, expression or pricking with a sterile needle, electrodessication and laser ablation are not welltolerated by children because of pain and are expensive. among drugs that are applied topically imiquimod has been found to be of limited efficacy. in a study spanned over more than 10 yrs in usa it was found that it has been prescribed in only 7% of the patients of mc.10 koh has been used in varying strengths; 2.5%, 5%, 10% and 20%. the rationale for using the lower strengths is to minimize its side effects, especially reducing irritant effects on face. the exact mechanism by which koh clears mc lesions is not clear. it appears that topical application of koh digests keratin and induces inflammation; this in turn stimulates innate and cell-mediated immune response that inhibits mc-induced immunosuppression and eliminates the infection of mc. considering the same mechanism of action koh has been successfully used in warts.14-16 short et al, conducted a double blind, randomized, placebo-controlled study comparing 10% koh solution with a placebo.17 the end point of their study was the complete clearance of the lesions. they recruited 20 patients (10 in each group), age ranging from 2 – 12 years. they excluded patients with facial lesions. 2 (20%) of the patients complained of severe stinging sensation and developed severe inflammatory response and 2 (20%) reported transient post inflammatory hyperpigmentation. 70% of their patients’ lesions were cleared with 10% koh. only 20% of the patients in the placebo group cleared the lesions at the end of the study. in our study the majority of the patients (82%) tolerated the drug well. fig 1:signs of inflammation after application of 10% koh solution fig 2: 6 year old boy, baseline fig 3 same patient, after 2 weeks of treatment fig 4:same patient, at 8 weeks of treatment, mostly resolved lesions, 2 healed crusted lesions at the base of the neck and post inflammatory hypopigmentation at few sites journal of rawalpindi medical college (jrmc); 2017;21(3): 248-252 251 7% developed contact dermatitis at the site of application but it was easily managed by the use of low potency topical steroids. in a similar study handjani et al8 compared 10% koh with cryotherapy, whose efficacy for treating mc is well established. the two groups had 15 patients each. age varied from 1 – 24 years. 86.6% in the koh group had complete clearance as compared to 93.3% in the cryotherapy group (p>0.05). post inflammatory hyperpigmentation was noticed more commonly with cryotherapy. a study on 2 different concentrations of koh (2.5% and 5%) was conducted.18 out of the 29 patients recruited in the study 25 completed it; 13 in 2.5% group and 12 in 5% group. 11 (44%) of the patients had lesional clearance at the end of the study. 8 of these patients were in the 5% treatment group and 3 were in the 2.5% koh group. this difference was statistically significant (p < 0.047). there were no statistical differences between the two groups with respect to side-effects (p = 0.682). we have used higher percentage 10% koh solution and achieved better efficacy. we would suggest against using concentration of koh lesser than 10%.al sudanyet al19have compared 10% koh with 25% podophyllin solution. they found 64% of their patients were cleared of mc lesions at the end of the study. however, the study duration was 4 weeks. we present the case that had their patients continued the medication the percentage of patients cleared of mc could have increased. in pakistan, qureshi et al have used 10% koh to treat their mc patients. 20 they have compared its efficacy with cryotherapy. the mean age of their patients was 20.53 years. a later incidence peak in young adults is attributable to sexual transmission with lesions more common in genital area.21 80% of their patients achieved clinical clearance of the lesions. they did not find statistically significant difference in the clearance of the lesions amongst the patients receiving two different treatment modalities, indicating 10% koh has the same efficacy as cryotherapy. the patients in our study were predominantly children, unlike their study based mainly on adults. therefore, our study sheds light on how 10% koh solution treats children, the age group mainly affected by mc. side effects like severe stinging sensation and hypopigmentation has been reported with 10% koh use.22in our study 82% of the patients tolerated the topical medicament well. only a few patients developed contact dermatitis, secondary infection and hypopigmentation at the site which resolved with the passage of time. in contrast, destructive therapies like cryotherapy and electrodessication are associated with much higher chances of burning, pain and pigmentary changes which can last for a long time.23-25in our setup where patients come from far flung areas, it is difficult for them to have regular follow up for hospital based treatment. a treatment modality which is economical, acceptable, efficacious and easily tolerated is the need of the hour. conclusion 1.10% koh solution is an effective treatment for mc. 2. it has the advantage of ease of application at home making it a good and feasible option in the treatment of mc. references 1. forbat e, al-niaimi f, ali fr. molluscum contagiosum: review and update on management. pediatrdermatol. 2017 ;34(5):504-15. 2. scheinfeld n. treatment of molluscum contagiosum: a brief review and discussion of a case successfully treated with adapelene. dermatol online j. 2007 ;13(3):15-18. 3. van der wouden jc, van der sande r, kruithof ej. interventions for cutaneous molluscum contagiosum. cochrane database syst rev. 2017 17; 5: 4767-70. 4. sterling j. treatment of warts and molluscum: what does the evidence show? curropinpediatr. 2016 ;28(4):490-99. 5. shahriari m, makkar h, finch j. laser therapy in dermatology: kids are not just little people. clindermatol. 2015 ;33(6):681-86. 6. moye v, cathcart s, burkhart cn. beetle juice: a guide for the use of cantharidin in the treatment of molluscum contagiosum. dermatolther. 2013 nov-;26(6):445-51. 7. capriotti k, stewart k, pelletier j. molluscum contagiosum treated with dilute povidone-iodine.j clin aesthet dermatol. 2017 ;10(3):41-45. 8. handjani f, behazin e, sadati ms. comparison of 10% potassium hydroxide solution versus cryotherapy in the treatment of molluscum contagiosum: an open randomized clinical trial. j dermatolog treat. 2014 ;25(3):249-50. 9. rajouria ea, amatya a, karn d. comparative study of 5 % potassium hydroxide solution versus 0.05% tretinoin cream for molluscum contagiosum in children. kathmandu univ med j (kumj). 2011 oct-dec;9(36):291-4. 10. farhangian me, huang ke, feldman sr. treatment of molluscum contagiosum with imiquimod in the united states.pediatrdermatol. 2016;33(2):227-28. 11. marsal mjr, cruz i, teixido c, diez o. efficacy and tolerance of the topical application of potassium hydroxide (10% and 15%) in the treatment of molluscumcontagiosum: randomized clinical trial: research protocol bmc infectious diseases 2011, 11:278-81 12. capriotti k, stewart k, pelletier j. molluscum contagiosum treated with dilute povidone-iodine. journal of clinical and aesthetic dermatology. 2017; 10 (3): 41 45. 13. olsen jr, gallacher j, finlay ay, piguet v, francis na. time to resolution and effect on quality of life of molluscum contagiosum in children in the uk: a prospective community cohort study.lancet infect dis. 201515(2):190-95 14. de abreu camargo cl, walter beldawjr, fagundes lj.a prospective, open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of https://www.ncbi.nlm.nih.gov/pubmed/28884917 http://www.ncbi.nlm.nih.gov/pubmed?term=%22scheinfeld%20n%22%5bauthor%5d javascript:al_get(this,%20'jour',%20'dermatol%20online%20j.'); https://www.ncbi.nlm.nih.gov/pubmed/?term=sterling%20j%5bauthor%5d&cauthor=true&cauthor_uid=27269886 https://www.ncbi.nlm.nih.gov/pubmed/27269886 journal of rawalpindi medical college (jrmc); 2017;21(3): 248-252 252 genital warts in men. an bras dermatol. 2014;89(2):23640. 15. loureiro wr, cacao fm, belda w jr, fagundes lj, romiti r. treatment of genital warts in men with potassium hydroxide. br j dermatol. 2008;158:180-82. 16. allen al, siegfried ec. management of warts and molluscum in adolescents. adolesc med.2001; 12: 229-42. 17. short ka, fuller c, higgins em. double-blind, randomized, placebo-controlled trial of the use of topical 10% potassium hydroxide solution in the treatment of molluscum contagiosum. pediatric dermatology. 2006, 23 (3): 279–81 18. uçmak d, akkurt mz, kacar sd, sula b, arica m. comparative study of 5% and 2.5% potassium hydroxide solution for molluscum contagiosum in children. cutanocultoxicol. 2014 ;33(1):54-59. 19. nameer k. al-sudany a,dler r. abdulkareem. a comparative study of topical 10% koh solution and topical 25% podophyllin solution as home-based treatments of molluscum contagiosum. journal of dermatology & dermatologic surgery. 2016; 20: 107–14. 20. qureshi a, zeb m, jalal-ud-din m, sheikh zi. comparison of efficacy of 10% potassium hydroxide solution versus cryotherapy in treatment of molluscum contagiosum. j ayub med coll abbottabad. 2016 ;28(2):382-85. 21. hanson, d., diven, d.g.,. molluscum contagiosum. dermatol online j 2003; 9 (2) 2-5. 22. can b, topaloglu f, kavala m, turkoglu z, zindanci i. treatment of pediatric molluscum contagiosum with 10% potassium hydroxide solution. j dermatolog treat. 2014 ;25(3):246-48. 23. hughes cm, damon ik, reynolds mg (2013) understanding us healthcare providers’ practices and experiences with molluscum contagiosum. plosone 8(10): e76948. 24. whetmore sj. cryosurgery for common skin lesions. treatment in family physicians' offices.canadian family physician. 1999; 45: 964-74. 25. al-mutairi n, al-doukhi a, al-farag s, al-haddad a. comparative study on the efficacy, safety, and acceptability of imiquimod 5% cream versus cryotherapy for molluscum contagiosum in children. pediatr dermatol. 2010 ;27(4):38894. https://www.ncbi.nlm.nih.gov/pubmed/?term=al-doukhi%20a%5bauthor%5d&cauthor=true&cauthor_uid=19804497 https://www.ncbi.nlm.nih.gov/pubmed/?term=al-farag%20s%5bauthor%5d&cauthor=true&cauthor_uid=19804497 https://www.ncbi.nlm.nih.gov/pubmed/?term=al-haddad%20a%5bauthor%5d&cauthor=true&cauthor_uid=19804497 https://www.ncbi.nlm.nih.gov/pubmed/19804497 summary journal of rawalpindi medical college (jrmc); 2017;21(3): 211-214 211 original article effect of intraumbilical oxytocin on duration of third stage of labour tabinda khalid 1, nisar ahmed malik 2, zainab sarfraz 3 1. department of gynae/obs, cantonment general hospital rawalpindi; 2. cantonment general hospital rawalpindi; 3. medical student, rawal medical and dental college abstract background:to determine the efficacy of intraumbilical oxytocin in reducing duration of third stage of labor, compared to routine active management of third stage of labor(amtsl). methods: in this randomized controlled trial one hundred parturient women were divided in two groups consisting of 50 each. active management of third stage was done in both the groups. the study group in addition to active management, received oxytocin 10 international units( iu) diluted in 10ml normal saline through the umbilical vein and control group received equal volume of normal saline as placebo .the mean time taken for the completion of third stage was calculated for both groups in terms of minutes. the mean time “t” between the two groups was compared using independent samplet test. p value<0.05 was taken significant. results: the mean duration of third stage of labor was 4.38±0.88 minutes in the study group, compared to 5.12±1.32 minutes in the control group which was significant statistically p=0.001. there was no incidence of retained placenta and none of placenta remain undelivered beyond 15 minutes in both groups. conclusion: intraumbilical oxytocin when given along with active management significantly reduces the mean duration of third stage of labour, compared to active management alone. key words: oxytocin, third stage of labour, intraumbilical uterotonics. introduction actively managed third stage is known to reduce the incidence of retained placenta and life threatening blood loss. recently studies to evaluate the efficacy of uterotonics like oxytocin or misoprostol administered through the umbilical vein using pipingas technique in reducing the duration of third stage of labour, incidence of retained placenta, and associated blood loss, show controversial results.third stage of labour is an important event occurring during normal vaginal delivery. third stage of labour commences with the delivery of the baby till delivery of placenta and membranes. the uterus contracts and retracts even after delivery of the baby, which facilitates the separation of placenta, and occludes the blood flow to the placental site by compression due to criss cross arrangement of smooth musculature. hence a prolonged third stage and retained placenta can lead to major obstetric haemorrhage. an attempt to prevent such catastrophies has lead to development of third stage of labour. if managed expectantly third stage of labour can last up to one hour. but when actively managed it lasts from 5 to 15 minutes. risk of postpartum haemorrhage (pph) increases significantly when duration of third stage is 20 minutes or more.1 amtsl, includes the use of uterotonics (oxytocin), early clamping of umbilical cord and controlled cord traction(cct) for delivery of placenta using the brandt andrews method and uterine massage .amtsl can saves the woman from life threatening blood loss around 1000ml.2 postpartum haemoglobin was higher, and duration of third stage was shorter (p=0.001) in actively managed group.3 controlled cord traction decreases the risk of manual removal of placenta and pph.4,5 use of oxytocin in amtsl and cct reduce risk of pph by 66%. 6 about 83.3% maternal deaths in pakistan are caused by serious postpartum bleeding7. most women are anaemic due to malnutrition, repeated child births and a general trend in low socio economic group to seek traditional attendants, who have no knowledge about timely use of uterotonics and their importance.amtsl,with oxytocin as uterotonic is a good strategy for preventing pph in low resource countries. however due to it’s heat instability and requirement of a trained person,misopprostol can be used.8 natural oxytocin is a peptide hormone released from posterior pituitary. synthetic preparations have wide spread use. oxytocin is the preferred uterotonic in amtsl when compared to,ergometrine,due its serious journal of rawalpindi medical college (jrmc); 2017;21(3): 211-214 212 cardiovascular side effects9.another study found oxytocin more effective in preventing uterine atony,than misoprostol.10 recent trials have compared the efficacy of different uterotonics injected through the umbilical vein using piping as technique. our local study using intraumbilical oxytocin showed significant reduction in duration of the third stage of labour. this study used combination of oxytocin and ergometrine as active management. the mean time duration was 2.59±0.52 minutes in study group, and 7.56 minutes±3.9 in control group, which was statistically significant (p=0.001, 95% c1 4.80-5.46).11 accoding to recent guidelines on pph, ergometerine + oxytocin versus oxytocin 5 and 10 international units(iu), alone have similar efficacy in prevention of postpartum hemorrhage. the prophylactic of ergometrine needs to be weighed against its adverse effects. ergometrine itself causes strong uterine contractions and facilitates delivery of placenta, hence appears to be a confounding factor. therefore in our study diluted oxytocin 10 iu was used both for intravenous and intraumbilical routes .the procedure is simple, inexpensive and without serious maternal or fetal side effects. patients and methods one hundred parturient women were included in this study conducted at pakistan railways hospital between dec 2012,till may 2013 . fifty patients were assigned randomly to each group after fulfilling the inclusion criteria. low risk, singleton, term ( 37-40 completed weeks of gestation) women, with cephalic presentation of the baby in spontaneous labour, were enrolled. all high risk cases, i.e pre eclampsia hypertension, multiple pregnancies, preterm or post dates, previous cesarean section, diabetes and fetal macrosomia, severe anaemia, other medical disorders, and contraindication for vaginal delivery were excluded. all patients were booked (least six antenatal visits) parity of the patients ranged from 0-5 and age from 21-35years.a time duration of greater than 15 minutes was considered a prolonged third stage. study was conducted by making two equal groups 50 each. allocation to either group was random using lottery method. patients with non reassuring cardiotocograph( ctg )or poor progress of labour were excluded.when cervical dilatation was 7-8cm, labour room staff was alerted to prepare delivery trolley and intraumbilical injections. oxytocin solution (10 iu+ normal saline 10ml) labelled as syringe a, or equal volume of placebo labelled as syringe b .active management of third stage was done in both the groups, which included intravenous oxytocin (10 iu) slowly at the delivery of anterior shoulder of the baby. umbilical cord was clamped as soon as baby was delivered. intraumbilical injection was given after delivery of the baby, through syringe about 2cm away from introitus, over 20 to 30 seconds and solution was milked towards cord insertion. in this way the study group a, in addition to active management, received oxytocin solution through the umbilical vein, and control group b received active management and equal volume of placebo. delivery of placenta was facilitated by brandt andrew method of controlled cord traction both groups, when signs of placental separation were observed. the time taken for the completion of third stage was calculated in terms of minutes. the mean time “t” between the two groups was compared using independent samplet test. a p value<0.05 was taken significant. results parity ranged from 0 to 5. majority were multiparous with only 21 primigravidas (table 1). mean parity being 2.9±1.54 in study group and 2.62±1.25 in control group (table 2). age ranged from 21 to 35years, with 60 women between 21-29years.mean age in study and contol groups were 26.56±0.84,26.66±0.82 respectively (table 3). the mean duration of third stage of labor was 4.38±0.88 minutes in the study group ,compared to 5.12±1.32 minutes in the control group which was significant statistically p=0.001 (table 4). table 1. parity of patients and their percentage parity frequency percent primigravida 21 21.0 1 26 26.0 2 27 27.0 3 14 14.0 4 6 6.0 5 6 6.0 total 100 100.0 there was no incidence of retained placenta 0% and none of the placenta remain undelivered beyond 15 minutes (our specified time limit) in either of the groups. table 2. duration of third stage of labour intraumbilic al oxytocin vs control no mean + sd std.err or mean mean duration of 3rd stage of labour (a)study 50 4.38+0.884 0.12451 (b)control 50 5.126+1.32 0.18713 p-value = 0.001 hence third stage was not considered prolonged in both groups (15 ≥min), although it was shorter with journal of rawalpindi medical college (jrmc); 2017;21(3): 211-214 213 the addition of intraumbilical oxytocin when given along with the active management of third stage of labor. table 3. age of patients and their percentage age of patients in years frequency percent 21-24yrs 29 29.0 25-29yrs 31 31.0 30-35yrs 40 40.0 total 100 100.0 table 4. age, duration of third stage, parity a study, b control parity of patients age in yrs time in minutes a mean n std.deviation 2.9000 50 1.5419 26.56 50 0.8429 4.3880 50 0.8804 b mean n std deviation 2.6200 50 1.2599 26.66 50 0.8171 5.1262 50 1.3232 total mean n std 2.7600 100 1.4079 26.61 100 0.8274 4.7571 100 1.17808 discussion according to a study rate of amtsl was 57% in irani population.oxytocin was used by 94% ,71% applied early clamping of umbilical cord and 65% used controlled cord traction.12 another study showed adequately performed amtsl was only 48% in vaginal delieveries.13there are variations in relation to choice of uterotonic, optimal dosing and time of administration.a study comparing intraumbilical oxytocin,intravenous carbetocin and sublingual misoprostol found that carbetocin was more effective(16.6±3.76 min) than intraumbilical oxytocin (18.28±3.34 min) and misoprostol.(23.00±3.38min).14 habek d et al compared oxytocin, prostaglandins and ergot via umbilical route. the success rates in reducing duration of third stage were, 76.9%, 85.7%and 64.2% respectively.15while some studies showed that misoprostol was more effective than oxytocin solution when given through umbilical route.16 gungorduk et al found significant reduction in mean time of third stage in oxytocin group as compared to placebo(4.5±1.6min compared to 7.9±3.4 min p<0.001).17 studies found the intraumbilical intervention effective and safe.18,19 according to a randomized controlled trial a significant reduction in the rate of manual removal of placenta, uterine atony and need for additional uterotonics observed in the intraumbilical oxytocin group compared to controls.20.contrary to this, a systemic review found no role of oxytocin once a diagnosis a retained placenta was made. 21 the strength of present study includes its design. in present study 10 iu oxytocin was used to avoid any harmful effect. active management of third stage was done in both groups .in order to minimize the bias we provided the doctors conducting deliveries with equal volume of normal saline as placebo. one of the limitations of our study is that all term pregnancies (≥37-40 weeks of gestation) were included, while the risk of retained placenta and delayed third stage is more commonly associated with preterm deliveries. secondly the age limit in our study was up to 35 years. once again older maternal age is correlated with prolonged third stage and risk of pph.we excluded the high risk cases e.g previous scar,multiple pregnancies, prolonged second stage and instrumental deliveries , medical disorders such as preeclampsia, severe anaemia, diabetes etc. so any benefit to high risk group has not be studied. since there was no incidence of retained placenta ,and none of placenta delivered beyond 15 minutes so active management of third stage still proved to be effective, and at present is the gold standard. use of intraumbilical route is an additional intervention ,which may be attempted by a skilled person if placental separation has not occurred till 15 minutes, before attempting manual removal of placenta and in patients who are at very high risk of retained placenta and prolong third stage. this will not only reduce the third stage duration, but saves the patient from anaesthesia hazards , risks of manual removal of placenta, blood transfusions, and cost of prolonged hospital stay. conclusion 1.in a dedicated maternity unit , active management with timely use of uterotonic in optimal dose and route of administration can significantly reduce span of third stage . 2.prophylactic use of intraumbilical oxytocin alongwith active management can cause a significant reduction in the mean duration of third stage of labor. however use of intraumbilical route is an additional intervention ,which may be attempted by a skilled person if placental separation has not occurred till 15 minutes, before attempting manual removal of placenta and in patients who are at very high risk of retained placenta and prolong third stage. this will not only reduce the third stage duration, but saves the patient from anaesthesia hazards , risks of manual removal of placenta, blood transfusions, and cost of prolonged hospital stay. journal of rawalpindi medical college (jrmc); 2017;21(3): 211-214 214 references 1. frolova al,stout mj,tuuli mg,lopez jd. duration of third stage of labor and risk of postpartum hemorrhage.obstet gynecol 2016;127(5):951-56. 2. begley cm,gyte gm,devane d,mc guire w. active versus expectant mangement for women in the third stage of labor.cochrane data base syst rev 2015 ;(3):7412-15. 3. yildirim d,ozyurek se,ekiz a.comparison of active vs expectant management of the third stage of labor in women with low risk of postpartum hemorrhage. ginekol pol.2016;87(5):399-404. 4. hofmeyr gj,mshweshwe nt,gulmezoglu am. controlled cord traction for third stage of labor.cochrane database syst rev 2015;1:8020-24. 5. du y,ye m,zheng f.active management of third stage of labor with and without controlled cord traction: a systemic review and meta analysis of randomized controlled trials. acta obstet gynecolscand.2014 ;93(7):626-33. 6. sheldon wr,durocher j,winiikoff b,blum j.how effective are the components of active management of third stage of labor? bmc pregnancy childbirth 2013 ;13:46 49. 7. rozina m, haleema h. near miss obstetrical events and maternal deaths. j coll physicians surg pak 2009; 19(12):781-85 8. prata n,bell s,weidert k.prevention of postpartum hemorrhage in low resource settings: current perspectives. int j womens health 2013 ;5:737-52. 9. sharma m,kaur p,kaur k,kaur a .a comparative study of oxytocin/misoprostol,methylergometrine for active management of the third stage of labor.j obstet gynecol india 2014 ;64(3):175-79. 10. evensen a,anderson jm,fontaine p. postpartum hemorrhage:prevention and treatment .am fam physican 2017 1;95(7):442-49. 11. tehseen f, anwar a, arfat y. intraumbilical vein injection of oxytocin in active management of third stage of labor. coll physicians surg pak.2008 ; 18(9):551-54. 12. afshari p,medforth j,aarabi m,abodi p,soltani h.management of third stage of labor following vaginal birth in iran:a survey of current policies.midwifery 2014;30(1):65-71. 13. prick bw,vos aa,hop wc,bremer ha .the current state of active third stage management to prevent postpartum hemorrhage:a cross sectional study.acta obstet gynecol scand 2013:92(11):1277-83. 14. maher ma,sayyed tm,elkhouly ni. different routes and forms of uterotonics for treatment of retained placenta: a randomized clinical trial. j mater fetal neonatal med 2017 :30(18):2179-84. 15. habek d, franicevic d. intraumbilical injection of uterotonics for retained placenta. int j gynecol obstet. 2007 ;99(2):105-09. 16. harara r, hanafy s, zidan ms, alberry m. intraumbilical injections of three different uterotonics in the management of retained placenta.j obstet gynaecol res.2011 ; 37(9):1203-07. 17. gungorduk k, asicioglu o, besimoglu b, gungorduk oc.using intraumbilical vein injection of oxytocin in routine practice with active management of third stage of labor: a randomized controlled trial.obstet gynecol.2010 ;116(3):619-24. 18. nankali a,kashavarzi f,fakheri t,zare s. effect of intraumbilical vein oxytocin on third stage of labor.taiwan j obstet gynecol.2013 ;52(1):57-60. 19. puri m,taneja p,gami n,rehan hs. effect of different doses of intaumbilical oxytocin on the third stage of labor.int j gyneacol obstet 2012 ;118(3):210-12. 20. lim ps, singh s, lee a, muhammad yassin ma. umbilical vein oxytocin in the management of retained placenta: an alternative to manual removal of placenta? arch gynecol obstet.2011;284(5):1073-79. 21. duffy jm,mylan s,showell m,wilson mj,khan ks. pharmacologic intervention for retained placenta:a systemic review and meta analysis. obstet gynecol 2015 ;125(3):711-18. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 219-221 219 original article association between placenta previa and preeclampsia ammara dawood, sadia hanif, madiha khalid department of gynaecology and obstetrics sir ganga ram hospital lahore abstract background: to determine association between placenta previa and pre-eclampsia in pregnant women presenting to a tertiary care hospital. methods: in this prospective study 187 pregnant women with placenta previa and 187 pregnant, total 374, women without placenta previa were enrolled. ultrasonography examination was performed on all patients to ascertain the attachment of placenta on uterine wall. all patients were followed every fourth week till 38th weeks. pre-eclampsia was labelled if mean of three readings of blood pressure was more than 139/89 in a pregnant woman with history of normal blood pressure before pregnancy and proteinuria on urine laboratory examination. results: mean age was 27.23 ± 3.633 and ranged from 21 to 43 years. primipara were 45.7% and 54.3% were multipara. eight patients (2.1%) were having pre-eclampsia. all patients belonged to non placenta previa group. relative risk came out 1.045 ranging from1.014 to 1.077 at 95% confidence interval. there was no effect of age and parity on the association. conclusion: there is a protective association between placenta previa and pre-eclampsia in pregnant women. key words: placenta previa, pre-eclampsia, pregnancy induced hypertension, parity introduction hypertension complicates up to 10% of all pregnancies and is associated with increased risk of adverse fetal, neonatal and maternal outcomes, including preterm birth, intrauterine growth restriction, perinatal death, acute renal or hepatic failure, antepartum hemorrhage, postpartum hemorrhage and maternal death.1, 2 pregnancy hypertension has its onset from 20 weeks of gestation and ranges from hypertension alone through proteinuria and multi-organ dysfunction to seizures.3 between 2011 and 2013, pregnancy-induced hypertension caused 7.4% of maternal deaths in the united states.4 pre-eclampsia may be superimposed on pre-existing chronic hypertension. although preeclampsia represents the severe end of the spectrum, women with any form of pregnancy hypertension are at increased risk of adverse outcomes.5, 6 in a study pih have demonstrated an increased risk for intrauterine growth retardation.7 placenta previa is associated with major pregnancy complications and is thought to be becoming more common.8 it is also associated with pih.9 some studies reported the protective effects, other studies did show any associations, slightly increase in the incidence and significantly elevated incidence of spectrum of hypertension ranging from pih to eclampsia in women with placenta previa.9, 10 placenta previa was a significant protective factor of pre-eclampsia showing negative association.6, 9 in another japanese study, preeclampsia was observed in 0 and 4.1% of women with and without placenta previa, respectively.11, 12 but the impact of these changes is largely unknown.5 validation of the above mentioned results in our local population i.e. reduced frequency of pre-eclampsia in patients with placenta previa may help us make certain management decisions. evidence based counselling will be possible for patients with previous abortions and miscarriages secondary to pre-eclampsia as there would be no risk if they have placenta previa. patients and methods this prospective cohort study was conducted in department of gynaecology, sir ganga ram hospital, lahore from october 2014 toapril 2015.using 95% confidence interval and 80% power of study, taking frequency of pre-eclampsia 0% and 4.1% (7) in groups with and without placenta previa respectively, estimated sample size is 374 i.e. 187 in each group. pregnant women of age 18-45 years at gestational age <24weeks (determined by last menstrual period) were included. one group women were with placenta previa determined by ultrasonography while second group women were without placenta previa. females with history of chronic hypertension, diabetes (hba1c level > 7%), severe anaemia (haemoglobin level, < 8 g per deciliter)measured by chemical analyzer, history of in vitro fertilization and history of antiphospholipid syndrome or systemic lupus erythematosus were excluded.placenta previa was determined by ultrasonography before 24 week journal of rawalpindi medical college (jrmc); 2017;21(3): 219-221 220 gestation and defined as placental anchorage within 3 cm of internal os. one hundred and eighty seven pregnant women with placenta previa and 187 pregnant women without placenta previa according to selection criterion were enrolled. ultrasonography examination was performed on all patients to ascertain the attachment of placenta on uterine wall. all patients were followed every fourth week till 38th weeks. preeclampsia was labelled if mean of three readings of blood pressure was more than 139/89 in a pregnant woman with history of normal blood pressure before pregnancy and proteinuria on urine laboratory examination. risk ratio was calculated to determine the association between pre-eclampsia and placenta previa. p value <0.05 was considered significant. results the mean age of patients was 27.23 ± 3.633 ranged from 21 to 43 years of age. there were 144 patients (38.5%) <25 years of age whereas 230 patients (61.5%) were more than 25 years in age (table 1). about 171 patients (45.7%) were primipara and 203 patients (54.3%) were multipara. out of 374 patients only 8 patients (2.1%) were having pre-eclampsia. the frequency of pre-eclampsia was significantly higher among case group as compared to control group (p=0.004) (table 2). relative risk came out 1.045 (95% confidence level; 1.014 to 1.077)(table 2) table 1: baseline characteristics of patients age 27.23±3.63 age<25years 144(38.5%) age≥25years 230(61.5%) primiparity 171(45.7%) multiparity 203(54.3%) table 2: association of preeclampsia and placenta previa preeclampsia total yes no placenta previa yes 8(100%) 179(48.9%) 187 no 0 187(51.1%) 187 total 8 366 374 relative risk = 1.045 (95%ci;1.014, 1.077) discussion iimportant health problems among adolescents in the developing countries are increased incidence of preterm labour and delivery, hypertensive disease, anaemia, more severe forms of malaria, obstructed labour, poor maternal nutrition and poor breastfeeding, low birth weight and increased neonatal mortality and morbidity.13-15pih has its onset from 20 weeks of gestation and ranges from hypertension alone (gestational hypertension) through proteinuria and multi-organ dysfunction (pre-eclampsia) to seizures (eclampsia).3pre-eclampsia may be superimposed on pre-existing chronic hypertension. although pre-eclampsia represents the severe end of the spectrum, women with any form of pregnancy hypertension are at increased risk of adverse outcomes.5 awareness of risk factors of pre-eclampsia can help to monitor patients, ensure earlier diagnosis and predict which patients are more likely to develop pre-eclampsia.16 placenta praevia is an obstetric complication in which the placenta is inserted partially or wholly in the lower uterine segment. it is a leading cause of antepartum haemorrhage (vaginal bleeding).18 caesarean delivery is more likely in women with preeclampsia. it is to be remembered that delivery is the long-term cure, but most women get worse after delivery and most maternal deaths occur postpartum.19, 20recently, it has been shown that placenta previa is associated with low frequencies of pre-eclampsia and low maternal blood pressure.21 however, there is scant literature on the association between placenta previa and pre-eclampsia. while some studies reported the protective effects, other studies did show any associations, slightly increase in the incidence and significantly elevated incidence preeclampsia in placenta previa.11, 22maternal risks with placenta previa include life threatening hemorrhage, anesthetic and surgical complications due to emergency cesarean delivery with sub optimal preparation for surgery. postpartum hemorrhage, cesarean hysterectomy, postpartum sepsis, air embolism and abnormal degree of placental adherence can often occur.23, 24 in present study cohort, out of 374 patients only 8 patients (2.1%)developed pre-eclampsia. when we cross tabulated group with preeclampsia the results were significant (p value=0.004). all of the patients of pre-eclampsia were in category of no placenta previa.relative risk came out 1.045 ranging from 1.014 to 1.077 at 95%confidence interval. so we may reject the null hypothesis and may conclude that there is an association between placenta previa and preeclampsia in pregnant women. it also implies that placenta previa has a protective role as concerned with pregnancy induced hypertension. there should be a focus on mechanisms involving the placement and anchorage of placenta during early weeks of gestation. results of present study matches with previous studies. it was reported that placenta previa was a significant protective factor of pre-eclampsia(ord 0.3, journal of rawalpindi medical college (jrmc); 2017;21(3): 219-221 221 95% ci: 0.1–0.7) showing negative association.9 in another japanese study, pre-eclampsia was observed in 0 and 4.1% of women with and without placenta previa, respectively (p = 0.004).11 about 144 patients (38.5%) in our study population were < 25years of age whereas 230 patients (61.5%) were > 25 years in age. it implies that there is still room to control or delay age of conception in our population by effective techniques of population control. 171 patients (45.7%) were primipara and 203 patients (54.3%)were multipara. in a sudani study, there were 3.2% women with preeclampsia out of 54,339 deliveries. the placenta previa occurred in 0% and 3.3%, p < 0.001 in pre-eclamptic and control women, respectively, thus it became a protective factor in this case.22 the results from one study clearly show a decreased frequency of pregnancy-induced hypertension among those pregnancies with placenta previa. it was noticed that the pathophysiologic mechanisms for this finding may be due to altered placental perfusion seen among women diagnosed with placenta previa.25 on age stratification, after cross tabulation between preeclampsia and placenta previa, 2 pre-eclampsia patients were more than 25 years in age whereas 6 were having age less than 25 years but results were non-significant for both age groups (p=0.112 &0.037). these results imply that there is no role of advancing age on association between placenta previa and preeclampsia in pregnant women. when we performed parity stratification after cross tabulation between preeclampsia and placenta previa, 5 patients of preeclampsia were in group multipara and 3 were in group primipara. results for both groups were nonsignificant (p=0.059 & 0.121). these result suggest that there is no role of parity on association between placenta previa and pre-eclampsia in pregnant women. conclusion frequency of developing the pre-eclampsia is significantly different in groups with and without placenta previa (0% vs. 4.1%) (p value < 0.05). relative risk came out 1.045ranging from 1.014 to 1.077 at 95% confidence interval. references 1. steegers ea, von dadelszen p, duvekot jj, pijnenborg r. preeclampsia. lancet 2010;376(9741):631-44. 2. redman cw, jacobson sl, russell r. hypertension in pregnancy. de swiet's medical disorders in obstetric practice, fifth edition 2010:153-81. 3. duley l, editor. the global impact of pre-eclampsia and eclampsia. seminars in perinatology; 2009: elsevier. 4. centers for disease control and prevention. reproductive health: pregnancy mortality surveillance system. 2017 5. roberts cl, ford jb, algert cs, antonsen s. population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study. bmj open 2011:101-05. 6. gagnon r, morin l, bly s, butt k, cargill ym. guidelines for the management of vasa previa. international journal of gynecology & obstetrics 2010;108(1):85-89. 7. muhammad t, khattak aa, shafiq-ur-rehman km. maternal factors associated with intrauterine growth restriction. j ayub med coll abbottabad 2010;22(4):64-69. 8. fitzpatrick ke, sellers s, spark p, kurinczuk j. incidence and risk factors for placenta accreta/increta/percreta in the uk: a national case-control study. plos one 2012;7(12):e52893. 9. adam i, haggaz ad, mirhagni oa, elhassan em. placenta previa and pre-eclampsia: analyses of 1645 cases at medani maternity hospital, sudan. frontiers physiol 2013;4:32-35. 10. silver rm. abnormal placentation: placenta previa, vasa previa, and placenta accreta. obstetrics & gynecology 2015;126(3):654-68. 11. hasegawa j, sekizawa a, farina a, nakamura m. location of the placenta or the umbilical cord insertion site in the lowest uterine segment is associated with low maternal blood pressure. bjog 2011;118(12):1464-69. 12. allahdin s, voigt s, htwe t. management of placenta praevia and accreta. journal of obstetrics and gynaecology 2011;31(1):1-6. 13. adeyinka da, oladimeji o, adekanbi ti, adeyinka fe. outcome of adolescent pregnancies in southwestern nigeria: a case–control study. the journal of maternal-fetal & neonatal medicine 2010;23(8):785-89. 14. vest ar, cho ls. hypertension in pregnancy. current atherosclerosis reports 2014;16(3):395-98. 15. obstetricians aco, gynecologists. acog practice bulletin no. 125: chronic hypertension in pregnancy. obstetrics and gynecology 2012;119(2 pt 1):396-99. 16. kashanian m, baradaran hr, bahasadri s, alimohammadi r. risk factors for pre-eclampsia: a study in tehran, iran. archives of iranian medicine 2011;14(6):412-15. 17. arulkumaran s. best practice in labour and delivery. cambridge: cambridge university press; 2016: 142– 46. 18. faiz a, ananth c. etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. the journal of maternal-fetal & neonatal medicine 2003;13(3):175-90. 19. walker jj. severe pre-eclampsia and eclampsia. best practice & research clinical obstetrics & gynaecology 2000;14(1):57-71. 20. tareen r, tareen m, mobin-ur-rehman, shiestra b. maternal outcomes of pregnancy induced hypertension. pjmhs online 2012;6(3):598-600. 21. kiondo p, wamuyu‐maina g, bimenya gs, tumwesigye nm. risk factors for pre‐eclampsia in mulago hospital, kampala, uganda. tropical medicine & international health 2012;17(4):480-87. 22. adam i, haggaz ad, mirghani oa. placenta previa and preeclampsia: analyses of 1645 cases at medani maternity hospital, sudan. frontiers in physiology 2013;4: 112-15 23. dynin m, lane dr. bleeding in late pregnancy. emergency department management of obstetric complications: springer 2017;53-62. 24. kausar s, zahoor b, ali r. morbidity with placenta previa. apmc 2012;6(2):18689. 25. ananth cv, bowes wa, savitz da. relationship between pregnancy-induced hypertension and placenta previa: a population-based study. american journal of obstetrics and gynecology 1997;177(5):997-1002. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 257-261 257 original article effectiveness of grade 1 and 2 joint mobilizations with non steroidal anti inflammatory drugs (nsaids) in comparison with nsaids alone in pain management of knee osteoarthritis salman akram, murtaza gondal, sumera mushtaq, uzma rafiq, furqan ahmad, mohammad arshad. foundation university medical college & hospital, rawalpindi abstract background: to analyze the effectiveness of grade 1 and 2 joint mobilizations with nsaids in comparison with nsaids alone in pain management of knee osteoarthritis. methods: in this randomized controlled trial patients with knee osteoarthritis (n=50) were divided into two groups, 25 patients in each group. control group received diclofenac salt 50mg in twice daily dose along with quadriceps and knee joint exercises, while experimental group received knee joint mobilizations grade 1 and 2 in addition to the diclofenac salt 50mg twice daily dose and quadriceps and knee joint exercises. main outcome was moderate, good or excellent control of pain with the intervention. among secondary parameters were the effect on pain intensity, quality of life, and functionality.grades of mobilizations used are defined as per kaltenborn. results: at the end of six weeks the knee pain with activities improved in the experimental group (mean7.44) compared to control group (mean 11.28) and pain with physical function also showed improvement in experimental (mean 25.84) as compared to control (mean 36.28). the stiffness also showed better mean values in the experimental (mean 2.08) to control (mean 3.12). visual analog scale readings also showed improvement in experimental group (mean 5.12) compared to control (mean 6.84). conclusions: grade 1 and 2 manual knee joint mobilizations in combination with diclofenac salt are more effective than diclofenac salt alone. emphasis of this therapy should be given to reduce knee joint pain, stiffness and improvement in physical function on various activities. key words: osteoarthritis , non steroidal anti inflammatory drugs (nsaid’s), manual knee joint mobilizations, pain introduction physiotherapists often utilize joint mobilization to reduce pain in knee osteoarthritis and to improve function. however, there is insufficient experimental data confirming its efficacy. this research was targeted to prove the effectiveness of joint mobilizations in management of pain in knee osteoarthritis (oa). the knee is the most complex and largest joint in our body. it’s also the most susceptible joint to injuries and arthritis because it bears colossal weight and pressure loads while providing flexible movements. when we walk, our knees support 1.5 times our body weight; climbing stairs is about 3-4 times our body weight and squatting about 8 times. osteoarthritis (oa) is the most common form of arthritis and is a leading cause of disability. about 75% of people over age seventy exhibit radiographically detectable changes consistent with osteoarthritis of knees. osteoarthritis is characterized by cartilage destruction and narrowing in the joint space. as the cartilage breaks down, pieces may break off into the synovial fluid in the joint space. this will lead to further irritation and inflammation. some believe that a tendency to the disorder coupled with other factors like age, obesity, previous injury or surgery on the joint, excessive physical activities and diet contribute to the onset of the disease. however, relatively little is known of the roots of the pain and disability of osteoarthritis. osteoarthritis is the commonest cause of pain among the middle age and elderly, which creates a damaging profile on the patient health, the people lose their ability to ambulate and also progressively lose their cardiopulmonary endurance owing to reduced journal of rawalpindi medical college (jrmc); 2017;21(3): 257-261 258 walking and decreased aerobic activity due to painful knee joint. now a days research is focused on a manual therapy procedure by kaltenborn which uses joint mobilizations in grade 1 and 2 to reduce pain in the knee joint in combination with nsaids. diclofenac sodium is a nsaid with analgesic and antipyretic properties . it is widely used in treatment of mild to moderate pain particularly when inflammation is also present as in cases of rheumatoid arthritis, osteoarthritis, musculoskeletal injuries and some postoperative conditions. its pharmacological effects are believed to be due to jamming the conversion of arachidonic acid to prostaglandins by inhibiting cyclooxygenase enzymes. the action of one single dose is much longer (6 to 8 hours) than the very short half-life that the drug indicates. this could be partly because it remains for over 11 hours in synovial fluids.there is some evidence that diclofenac blocks the lipoxygenase pathways thus eliminating or reducing formation of the leukotrienes . there is also speculation that diclofenac may inhibit phospholipase a2 as part of its mechanism of action. these additional actions may explain the high potency of diclofenac – it is the most potent nsaid on a broad basis. the primary aim of this study was to estimate the proportion of subjects who achieve adequate pain control (moderate, good, or excellent) with combination therapy of knee joint oscillations grade 1 and 2 alongwith 42 days of a drug therapy (diclofenac salt 50mg twice daily dose) and quadriceps exercises and compared with individuals on only drug therapy with quadriceps exercises. patients and methods this study was conducted in outpatient department of medicine and physiotherapy in fauji foundation hospital rawalpindi in six weeks time. a total of 50 patients are included in the study after careful monitoring of exclusion and inclusion criteria and taking the informed consent. patients were kept in two groups, the experimental group of 25 patients which are given diclofenac salt 50mg twice daily dose along with joint grade 1, 2 oscillations and general exercise plan for home. the second control group comprising 25 patients was only given 50 mg twice daily diclofenac salt with postural correction tips and general exercise plan for home. male and female patients between ages 35 to 65 years diagnosed with symptomatic oa of the target knee joint as evidenced by knee pain for at least 3 months (for at least 20 days of each month) and osteophytes confirmed by an x-ray taken within the last two years. it was also ensured with the help of physician that patients must meet the criteria of diagnosis of osteoarthritis of knee according to american college of rheumatology and must be on pain medication (diclofenac sodium 50mg bd dose).pregnant females, breast feeding mothers and subjects who have received treatment with a strong opioid (e.g. morphine, methadone, long-acting oxycodone etc.) in last 4 weeks preceding study entry were excluded from study. subjects for whom a treatment was planned within the study period that could alter the degree or nature of pain (e.g. arthroscopic techniques, osteotomy, joint replacement surgery, etc),subjects with a significant psychiatric disorder (including major depression), subjects receiving anti-psychotic medication and subjects who have taken sedatives, hypnotics, phenothiazines, anticonvulsants, tranquilizers or muscle relaxants within two weeks preceding study entry were excluded from the study. a section of “womac questionarre”was used to assess pain status and functional outcome. the patients were instructed to take treatment in the experimental group twice per week and follow up recording of variables was taken on 7, 14, 28, 42 days. the weight was recorded on 1st, 3rd and 4th visit. likewise the patients in the control group were handled with the same protocol except they were not offered the manual therapy treatment and only general exercises and pain medication was used as treatment.the primary objective of this study was to determine the proportion of subjects, who experienced “moderate”, good, or “excellent” pain control and joint stiffness during 45 days of treatment with diclofenac salt and joint oscillations by using a section of womac osteoarthritis index questionnaire. subjects will rate their pain, stiffness and physical function at baseline and each visit by means of the womac questionnaire (western ontario and mcmaster university osteoarthritis index). a oneweek recall period was applied to all questions. visual analog scale(vas) was used as a measure of pain to have an idea of pain intensity. patients were asked to assume 0 as no pain and 10 means extreme pain you cannot tolerate or may even die of that pain and to rate their pain accordingly.vas taken at the beginning and then at each follow up visit. results in the control group the maximum score for pain with physical function on the questionnaire (n=25, mean=43.56, sd =6.752) was 52 maximum and minimum 28 out of 64 after the therapy on the initial visit while it was observed to be minimum 13 and maximum 50 on the final visit with (mean 36.28, sd http://en.wikipedia.org/wiki/lipoxygenase http://en.wikipedia.org/wiki/leukotriene journal of rawalpindi medical college (jrmc); 2017;21(3): 257-261 259 8.629). on the other arm in experimental group in which the initial visit showed a reading of minimum 12 and maximum 52(mean 43.64 sd 10.681) which declined to become minimum 06 and maximum 40 showing improvement in symptoms(mean25.84 sd 8.479) (table 1). the second variable of joint stiffness was scored as minimum 01 and maximum 06 out of a total of 08 in the control(n=25, mean 4.68, sd 1.626) on the initial visit while on the final visit was minimum 01 and maximum 05 ( mean 3.12, sd .971). as compared with this in the experimental group this variable on the first visit was recorded as 01 and 06 (mean 3.28, sd 1.792) while on the final visit was recorded as 00 and 04(mean 2.08, sd 1.115) (table 2). the third variable was visual analog scale (vas) and the recordings on the first visit in the control were 06 and 08 out of a total of 10 (mean 7.48, sd0.586) while on the final visit it showed a reading of 05 and 08 (mean 6.84, sd0.987). while on the other arm of experimental group the vas recorded on initial visit was 04 and 08(mean6.76, sd 1.091) which improved to be a minimum of 03 and a maximum of 07 (mean5.12, sd1.201) on the final visit showing a lot of improvement (table 3). table 1: improvement in pain control in control and experimental group visit pain with physical function in control pain with physical function in experimental initial visit 43.56/64 43.64/64 final visit 36.28/64 25.84/64 table 2: improvement in joint stiffness in control and experimental group. visit pain with physical function in control pain with physical function in experimental initial visit 4.68/8 3.28/8 final visit 3.12/8 2.08/8 table 3: improvement in visual analog scale (vas) in control and experimental group. visit pain with physical function in control pain with physical function in experimental initial visit 7.48/10 6.76/10 final visit 6.84/10 5.12/10 tabulated values of mean and their standard deviation of each dependent variable , along with standard mean error, the values are each of the initial and final visits, t test is used to estimate level of significance α = 0.05, before the estimation of level of significance levene’s test for equality of variances to determine the significance of mean calculated values (table 4) table 4: group statistics groups n mean std. deviati -on std. error mean pvalue stiffness control 25 3.12 .971 .194 <0.001 experimental 25 2.08 1.115 .223 <0.00 1 pain with physical function -ns control 25 36.28 8.629 1.726 <0.00 1 experi mental 25 25.84 8.479 1.696 <0.001 visual analog scale control 25 6.84 .987 .197 <0.001 experi mental 25 5.12 1.201 .240 <0.001 discussion knee joint mobilizations are an acceptable mean of improving pain in patients with osteoarthritis. many researches all over the world support its effectiveness on shoulder and hip joint but data on knee joint is still lacking in literature. christine clar described these methods and the same principal was used in this research and a research hypothesis was formulated that the technique brings some relief of pain, the data from patients was rigorously examined and it supported the research hypothesis.10 the patients selected for the study were of low socioeconomic group of the society, who lack the facilities for prevention and maintenance of disease. an important feature in this population in contrast to america and europe where commodes are mainly used. use of ground toilet seat(indian seat) leads to further damage to the knee joint, which seemed a very important factor of less pain management in study population; if alternative ways are available pain scale could have been much lower. given the design of our study in which random selection of study participants was done and the testers were blinded to group to be assessed and given the lack of improvement, it is unlikely that the journal of rawalpindi medical college (jrmc); 2017;21(3): 257-261 260 desirable outcomes were caused by the passage of time or by some tester bias and it is also unlikely that other causes unrelated to the intervention were responsible for the observed improvements. the dropout rate was higher in the treatment group (21%) than in the placebo group (12%). if the treatment itself had led to negative outcomes, causing the patients to withdraw, this differential dropout rate might significantly affect the interpretation of our results. however, the reasons given for withdrawal were unrelated to treatment. previously reported dropout rates in similar trials of exercise for osteoarthritis of the knee are 9.8%, 15%, 17%, 20%, 25%, 26% and 52% in various studies. patients with higher initial womac scores may be less likely to complete a regimen of physical therapy. as initial womac scores were substantially higher in patients from both the treatment and the placebo groups who did not complete the study than in those who completed the study, we do not believe that aspects of the therapeutic regimen were responsible for the failure to complete all visits during the treatment phase. the benefits of treatment were achieved in four clinic visits. most previous studies have demonstrated the benefits of exercise in 36 to 48 clinical visits. our study required 24 telephone contacts in addition to 4 clinical visits. previous reports of average improvement with exercise have ranged from 8% to 27% decreases in pain and 10% to 39% improvements in function . the total improvement in womac score in our study averaged 56%; average subscale improvements were 60% for pain, 54% for stiffness, and 54% for functional ability. most important, these changes can be compared with those in control patients who experienced no meaningful change. changes of 20% to 25% are generally considered to be clinically important. the greater overall improvement compared with results of previous studies may be due to the manually applied treatment, which allowed the therapist to focus treatment on the specific structures that produced pain and limited function for each patient. the comprehensive exercise program may also have addressed more of the impairments found in patients with osteoarthritis of the knee. the design of our study precludes determination of which aspect of the treatment program produced the changes in performance. the effects of the manual therapy procedures cannot be separated from either the clinical or home exercise programs. a recent randomized clinical trial found that a combination of manual therapy and clinical exercise provided greater improvements in strength, pain, and function than did clinical exercise alone for impingement syndrome of the shoulder, another chronic inflammatory joint condition. the exercise program was simple, but it adequately addressed the lower limb physical findings that are common in patients with osteoarthritis of the knee. to prevent increasing inflammation, pain, and boredom with the program, patients did not perform multiple exercises with the same therapeutic effect or exercise more than once each day. ettinger stressed the importance of targeting the clinical treatment and appropriately dosing the exercise to improve joint motion, muscular strength, and cardiovascular fitness for patients with osteoarthritis of the knee. 21 patients frequently reported 20% to 40% relief of symptoms after only two to three clinical treatments of manual therapy and exercise. this rapid reduction of symptoms implies that the structures responsible for at least part of the pain are not the most fixed or unchangeable aspects of the pathology of osteoarthritis. periarticular connective and muscular tissue could be implicated as symptom sources. perhaps the repeated challenge to the end range of movement, as occurs with closed-chain strengthening exercises, manually applied passive movement, and active range-of-movement exercises, provides a strong stimulus to connective tissue, resulting in pain relief. the effects of the physical therapy intervention beyond 1 year are unknown. continued relief over a longer period may depend in part on patient compliance with the home exercise program. longerterm follow-up may answer some of these questions. many patients with osteoarthritis typically receive very little physical therapy before undergoing total joint replacement. because short-term physical therapy can decrease pain and stiffness and increase functional capacity in patients with osteoarthritis of the knee, it represents a cost-effective way to improve patient function. physical therapy may also delay or defer the need for total joint replacement . we observed fewer knee replacement surgeries in the treatment group. as military health system beneficiaries, all patients had equal access to orthopedic surgery. the surgeons were aware that a study was under way to examine the effectiveness of a physical therapy intervention, but they were unaware of patients’ group assignments. the surgeons were also unaware that the number of patients receiving surgery in the two groups would be compared. patients were asked at 1 year if they were seeking knee surgery; no patient who had not undergone surgery was seeking it. journal of rawalpindi medical college (jrmc); 2017;21(3): 257-261 261 conclusion 1. combination of manual physical therapy and supervised exercise is more effective than no treatment in improving walking distance and decreasing pain, dysfunction, and stiffness in patients with osteoarthritis of the knee. such treatment may defer or decrease the need for surgical intervention. 2. benefit of manual therapy augment the patient recovery ,but still awareness about the manual therapy in pakistan is not at the desired level. 3. training facilities and workshops on the use of such interventions can play a pivotal role in the improvement of public awareness. references 1. carolyn j, rana sh, kim l. physiotherapy management of knee osteoarthritis. international journal of rheumatic diseases 2015; 14: 145-51 2. walsh ne, hurley mv. evidence based guidelinesand current practice for physiotherapy management ofknee osteoarthritis. musculoskeletal care 2014: 7: 45–56. 3. threlkeld, ja, currier, dp: osteoarthritis: effects on synovial joint tissues. physther 1998:68:346-54 4. mazieres b, thevenon a, coudeyre e, chevalier x. adherence to and results of, physical therapy programs in patients with hip or knee osteoarthritis: french clinical practice guidelines. joint bone spine 2008:75: 589-96. 5. jessep sa, walsh ne, ratcliffe j. longtermclinical benefits and costs of an integrated rehabilitationprogramme compared with outpatient physiotherapyfor chronic knee pain. physiotherapy 2016:5: 85-92. 6. simon ls: arthritis: new agents herald more effective symptom management. geriatrics 2014:54(6):37-9 7. felson dt, lawrence rc, hockberg mc. osteoarthritis: new insights in treatment approaches. ann intern med 2012:133(9):726-29 8. wolfe mm, lichetenstein dr, singh g. gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs used in osteoarthritis knee. n engl j med 2014; 340:1888-99. 9. deyle gd, henderson ne, matekel rl. effectiveness of manual physical therapy and exercise in osteoarthritis of the knee. ann intern med. 2010;122(2):163–71 10. christine c, tsertsvadze a, court r, hundt gl. clinical effectiveness of manual therapy for the management of musculoskeletal and non-musculoskeletal conditions. chiropractic & manual therapies 2014,22:12-19 11. sweeney a, doody c: manual therapy for the cervical spine and reported adverse effects: a survey of irish manipulative physiotherapists. manual ther 2015,15:82-88 12. nguyen us, zhang y, zhu y, niu j, zhang b.increasing prevalence of knee pain and symptomatic knee osteoarthritis. ann intern med 2011;155(11):725-32 13. ettinger wh, burns r, messier sp, applegate w. comparison of aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis.jama. 1997;277:25-31. 14. jansen mj, viechtbauer w, lenssen af, hendriks ej. strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilization each reduce pain and disability in people with knee osteoarthritis: a systematic review. j physiother. 2011;57(1):11–20 15. deyle gd, allison sc, matekel rl, ryder mg. physical therapy treatment effectiveness for osteoarthritis of the knee: a randomized comparison of supervised clinical exercise and manual therapy procedures versus a home exercise program. phys ther. 2015;35(11):1201-15 16. ottawa panel evidence-based clinical practice guidelines for therapeutic exercises and manual therapy in the management of osteoarthritis. physther. 2005;85(9):907–71 17. brantingham jw, bonnefin d, perle sm, cassa tk. manipulative therapy for lower extremity conditions. j manipulative physiol ther 2012, 35:127–36 18. mangione kk, axen k, haas f. mechanical unweighting effects on treadmillexercise and pain in elderly people with osteoarthritis of the knee. phys ther. 2014;44:282-8 19. zhang w, nuki g, moskowitz rw, abramson s. oarsi recommendations for the management of hip and knee osteoarthritis: part iii: changes in evidence following systematic cumulative update of research published through january 2009. osteoarthrcartil. 2010;18(4):476– 99. 20. lawrence rc, felson dt, helmick cg, arnold lm, choi h, deyo ra, et al. estimates of the prevalence of arthritis and other rheumatic conditions in the united states. part ii. arthritis rheum. 2008;58(1):26–35 21. ettinger wh , afable rf. physical disability from knee osteoarthritis: therole of exercise as an intervention. med sci sports exerc. 1994;26:1435-40. 22. fisher nm, gresham ge, abrams m, hicks j.quantitative effects of physical therapy on muscular and functional performancein subjects with osteoarthritis of the knees. arch phys med rehabil1993;74:840-47. 23. pribicevic m, pollard h, bonello r, de lk: a systematic review of manipulative therapy for the treatment of shoulder pain. j manipulative physiolther 2010,33:679-89 24. bronfort g, haas m, evans r, leininger b, triano j: effectiveness of manual therapies: the uk evidence report. chiropr osteopathy 2010,18:3 25. tichenor cj, mccord p, baker pk, kulig k.orthopaedicmanual physical therapy document describing advanced clinical practice.american academy of orthopaedic manual physical therapists.j manipulative physio ther 2013,21:179-89 377 journal of rawalpindi medical college (jrmc); 2022; 26(3): 377-381 original article reticulocyte count and platelet count as predictors of morphological remission/hemopoitic recovery in acute lymphoblastic leukemia (all) after induction chemotherapy huma riaz1, hamzullah khan2, shahtaj khan3, sadaf chiragh4 1 assistant professor hematology, mti hayatabad medical complex, peshawar 2 professor hematology, nowshera medical college, nowshera. 3 professor hematology, mti hayatabad medical complex, peshawar 4 associate professor oncology, mti hayatabad medical complex, peshawar author’s contribution 1,2 conception of study 1,2,3,4 experimentation/study conduction 1,2 analysis/interpretation/discussion 1,2 manuscript writing 3,4 critical review 3,4 facilitation and material analysis corresponding author dr. hamzullah khan, professor hematology, nowshera medical college, nowshera email: hamzakmc@gmail.com article processing received: 05/10/2021 accepted: 02/09/2022 cite this article: riaz, h., khan, h., khan, s., chiragh, s. reticulocyte count and platelet count as predictors of morphological remission/hemopoitic recovery in acute lymphoblastic leukemia (all) after induction chemotherapy. journal of rawalpindi medical college. 30 sep. 2022; 26(3): 377-381. doi: https://doi.org/10.37939/jrmc.v26i3.1790 conflict of interest: nil funding source: nil access online: abstract objectives: to determine the predictive values of reticulocyte and platelet count for remission in cases of acute lymphoblastic leukemia after induction therapy. materials and methods: this cross-sectional observational study was conducted in the department of hematology, mti hayatabad medical complex, peshawar. all cases of all referred to the department for remission after taking induction therapy, irrespective of age and gender were included. relevant information was collected on a predesigned proforma prepared in accordance with the objectives of the study. results: a total of 84 cases referred for remission were included, 56(66.7%) were males and 28 (33.3%) were females. 50(59.5%) cases were in the age range of 5-18 years. the mean with a standard deviation of the age of patients was 15+ 4 years. 75(89.3%) of the cases were classified into all-1) by fab classification. 50(59.5%) of the referred cases had achieved morphological remission by bone marrow aspiration. there was a statistically significant rise in platelet count of the remission vs non-remission cases (p-0.001). again there was a statistically significant difference in the retic count of the cases with remission (p-0.05). we observed a statically significant downhill moderate correlation of retic count with remission (in terms of blast count of bm aspiration) (p-0.04, r:0.32). platelet count also had an inverse significant correlation with remission ( p-0.01, r:-0.37). the diagnostic roles of the peripheral platelet count and retic yielded an area under curves of (0.768 and 0.648 respectively) to predict remission. we observed that the retic count and platelet count have been shown to have strong predictive values for remission in all with interaction values of (r= 0.28**, δr²=0.02, p=0.08). similarly, an increase in platelet also has a strong predictive value for remission in all cases with interaction values of (r= 0.41**, δr²=0.16, p=0.001) conclusion: in all cases of post-induction therapy, the peripheral blood reading for an increase in retic and platelet count predicts remission with 95% confidence. these values if strictly observed can reduce the frequency of invasive procedures like bone marrow aspiration. keywords: all, remission, reticulocyte count, platelet count. 378 journal of rawalpindi medical college (jrmc); 2022; 26(3): 377-381 introduction acute lymphoblastic leukemia (all) is a malignant hematological disorder due to abnormal proliferation of lymphoid progenitors (lymphoblasts in the bone marrow, peripheral blood, and also in extra medullary sites. all occur predominantly in pediatric ages (80%). its prognosis is good in early ages while poor when occurs in adults. in the united states, its incidence is 1.6/million.1 globally the remission rate of up to 90% is reported for all in pediatric ages.2 acute lymphoblastic leukemia (all) prevalence and incidence studies are rarely reported in pakistan. similarly, less is reported to highlight the response of all to chemotherapy in our population. a local study covering sindh province reported 70% remission in pediatric age.3 regarding remission, literature has reported the clinical significance of hematological markers (reticulocyte count, anc, and platelet) to predict remission in cases of all. a regular increase in trends of using these markers has dramatically decreased the frequencies of invasive procedures like bone marrow aspiration and trephine.4. furthermore immature reticulocyte count as a fraction of new parameters added in advanced hematology analyzers can predict the hemopoitic remission before other tests become positive after induction therapy in cases of all. a study reported that 52% of patients showed retic fraction improvement in follow-up cases much before than improvement in anc in cases of all to document hemopoitic recovery.5 a study from turkey also concluded that immature reticulocyte fraction detects remission in all in pediatric age earlier than anc.6 platelet recovery or time to platelet recovery (tpr) has been reported to predict disease-free survival (dfs) and also the overall survival rate (osr) in all. similarly, tpr can also be used as a prognostic factor in leukemia.7 we could not find literature from pakistan documenting the predictive roles of these hematological parameters in remission cases of all, therefore present study was designed to determine the predictive values of reticulocyte, anc, and platelet count in remission of acute lymphoblastic leukemia after induction therapy to avoid expensive (pcr, immuno-histochemistry) and invasive (bone marrow aspiration and trephine) procedures. materials and methods this was an observational study conducted in the department of hematology / pathology hayatabad medical complex, peshawar from january 2020 to march 2021. using open-epi software for sample size calculation, a sample size of 84 was selected to represent the true population based on the anticipated proportion of 70% remission in all cases, keeping a 95% confidence level and 6% absolute precision due to feasibility issues.3 a total of 84 diagnosed patients of acute lymphoblastic leukemia (all) undergoing induction of remission were included. the diagnosis in all these patients was based on cytological including giemsa stained peripheral blood smear, bone marrow aspirate smears, and trephine biopsy, immune-phenotypic and cytogenetic criteria. patients of all ages and both gender were included. patients with complications and patients in whom standard treatment protocol could not be observed due to any limitation were excluded from our study. all the patients were subjected to a detailed history and clinical examination. on day 07th of the end of the 4th cycle of induction chemotherapy. 3 ml venous blood was collected into a vacuotainer containing k3 edta (tripotassium ethylene diamine tetra acetic acid) and platelet counts were performed within 02 hours of sample collection by five parts sysmex automated haematology analyzer (xe-3000). a supravital stain of unfixed red blood cells was done with new methylene blue by mixing 100 ul of the patient's blood with 100ul methylene blue, after incubation for 20 minutes at a temperature of 37 ˚ c, the mixture was remixed and wedge blood smear was performed to obtain reticulocyte count, after which the procedure of bone marrow aspiration and trephine biopsy was performed. all the haematological procedures as well as reporting were performed by experienced hematologists. data was entered in the spss version 25 for analysis. the normality of data distribution was determined by shapiro wilk test. the quantitative variables (age, platelet count, retic count) were presented with mean + sd. the categorical variables were presented with frequency and percentages. an independent t-test was used to determine the difference between quantitative variables in remission vs non-remission cases. the pearson correlation test was used to determine the quantitative correlation between continuous variables. for the diagnostic role of the peripheral platelet count and retic, receiver operating curve (roc) was used in spss to determine the area under the curve (auc) to determine the relationship of clinical sensitivity of different hematological 379 journal of rawalpindi medical college (jrmc); 2022; 26(3): 377-381 indicators (retic and platelet count) and to predict remission. results a total of 84 cases referred for remission were included, 56(66.7%) were males, and 28 (33.3%) were females. out of the total, 50(59.5%) cases were in the age range of 5-18 years. the mean with a standard deviation of the age of patients was 15+4 years. 75(89.3%) of the cases were classified into all-1) by fab classification. 50(59.5%) of the referred cases had achieved morphological remission by bone marrow aspiration. (table 1) we observed a statistically significant rise in platelet count of the remission vs non-remission cases (p0.001). again there was a statistically significant difference in the retic count of the cases with remission (p-0.05) using the student t-test as a test of significance. the difference in absolute neutrophil count in both categories was not statistically significant. (table 2) we observed a statically significant downhill moderate correlation (pearson correlation test) of retic count with remission (in terms of blast count of bone marrow aspiration) (p-0.04, r:-0.32). platelet count also had an inverse significant correlation with remission (p-0.01, r:-0.37). (table 3) the diagnostic roles of the peripheral platelet count and retic yielded an area under curves of (0.768 and 0.648 respectively) to predict remission. (figure 1) table 1: descriptive statistic of patients a. gender wise distribution of patients frequency percent male 56 66.7 female 28 33.3 total 84 100 b. age wise distribution of patients frequency percent <5 years 10 11.9 5.1-18 years 50 59.5 18-39 years 21 25 >39years 3 3.6 total 84 100 c. morphological diagnosis frequency percent all-1 75 89.3 all-2 6 7.1 all3 3 3.6 total 84 100 d. remission status of patients frequency percent yes 50 59.5 no 34 40.5 total 84 100 table 2: the impact of platelet and reticulocyte count on remission in acute lymphoblastic leukemia (all) hematological indices remission status n mean+sd p-value platelet count yes 50 332.1+136 0.001 no 34 207.9+135 reticulocyte count yes 50 1.7+1.4 0.049 no 34 1.4+1.2 anc yes 50 5255+37 0.067 no 34 3286+58 table 3: correlations of reticulocyte count and platelet count with the number of blast cells in remission cases after induction therapy morphological remission reticulocyte count reticulocyte count rs -.312** p 0.004 n 84 platelet count rs -.367** .327** p 0.001 0.002 n 84 84 ** correlation is significant at the 0.01 level 380 journal of rawalpindi medical college (jrmc); 2022; 26(3): 377-381 figure 1: discussion survival in cases of acute lymphoblastic leukemia mainly depends on complete remission. complete remission can be defined based on certain variables in different procedures/investigations to be more accurately defined remission. however, we hypothesized that a reticulocyte count of more than 2.5% and a platelet count of more than 250000/cmm3 is essential to label a case as remission before going into the invasive procedures. in the present study, the mean age of patients was 15+4 years with male gender predominance (66.7%). 89.3% of the cases were classified into all-1 by fab classification. the correlation strength of retic count and platelet count with remission was (p-0.04, r:-0.32), (p-0.01, r:-0.37) respectively. a study on the bio-clinical and demographic (age & gender) characteristics of a large cohort of 5000 all patients concluded that the peak incidence of all was reported at 1-5 years of age followed by another spike in age 6-10 years, with a progressive decrease in cohort 11-30 years, and disappear in the 50-60 years cohort. furthermore, they reported a lower incidence in the female gender which supports our findings.8 rauf et al6 also reported the mean age of children with all as 12+5 years in their study conducted in the department of hematology, armed force institute of pathology rawalpindi which matches the age of occurrence of all with our population. the rate of morphological remission was 59.5% in the present study which is lower than as reported by vallacha a et al7 from karachi (70%). another study from malysia5 reported 63% remission which is in concordance with our findings. in european countries, a remission rate of up to 90-95% is reported in pediatric age.9 regarding the clinical significance of the hematological parameter in remission, a statistically significant rise in platelet count and retic count was observed in cases with remission vs no remission (p-0.001) and (p-0.05) respectively. while no such difference in absolute neutrophil count in both the categories was noted in groups. a study published in “leukemia” journal reported an increase in reticulocyte count in all patients who achieved remission /recovery after chemotherapy (atco) (p<0.001) that matches our findings.10 reticulocyte count is used by many clinical centers to assess hemopoitic recovery in all cases. microscopically quantification is done by hematologists and flowcytometry or advanced hematology analyzers can give you accurate immature reticulocyte fractions (irf). according to a study performed by rawalpindi afip to show remission success in all, they reported 78% sensitivity for irf 381 journal of rawalpindi medical college (jrmc); 2022; 26(3): 377-381 to predict remission which is higher than the present study.11 replication analysis has also confirmed the prognostic value of platelet count on treatment day 33 and has a strong inverse correlation with the number of blast cells after induction therapy (p<0.001) 12 which is consistent with our findings. we did not measure and analysed the platelet indices to see the correlation of the individual platelet indices with remission, a study from bangladesh reported that platelet count and platelet-crit (pct) were significantly higher in the post-therapy remission cases versus non-remission cases (p<0.05) 13 still in term of platelet count it correlates with our findings. total leukocyte count (tlc) and anc are easily ascertainable hematological parameters that reflect the plasma levels of chemotherapy to achieve remission in all. however, we could not appreciate the difference in absolute neutrophil count in remission cases versus no remission groups and our findings are in concordance with the study of lucas k et al.14 however they have reported an inverse relationship of post-induction therapy with tlc and anc. a study reported mean tlc in relapsed and non-relapsed groups respectively (p = 0.03) and the same was for mean anc (x 10(3)/mm3) were 3.0 +/0.9 and 2.5 +/ 0.6 in both groups (p = 0.05).13 authors have reported anc with 96% sensitivity even to predict the hemopoitic recovery in all.15 on the roc curve, the platelet count and retic yielded an area under curves of (0.768 and 0.648 respectively) to predict remission. another study from china reported using the receiver operating curve (roc) and regression analysis with findings that platelet count can have a predictive value for the prognosis of patients with acute leukemia.16 conclusion the higher reticulocyte and platelet count in cases of post-induction therapy can predict remission in acute lymphoblastic leukemia (all). there is a statistically significant inverse correlation of reticulocyte and platelet count with the number of lymphoblasts in all after induction therapy. the diagnostic values of reticulocyte and platelet count on the roc curve as acceptable to be used in clinical setup to reduce the frequency of invasive procedures like (bone marrow aspiration and trephine biopsy) and expensive procedures (immune histochemistry and pcr). references 1. terwilliger t, abdul-hay m. acute lymphoblastic leukemia: a comprehensive review and 2017 update. blood cancer j. 2017 jun 30;7(6):e577. doi: 10.1038/bcj.2017.53. pmid: 28665419; pmcid: pmc5520400. 2. riley s, jonathon m, ezra b, goel r, tidwell a. reticulocytes and reticulocyte enumeration. journal of clinical laboratory analysis 2001;15:267294 3. vallacha a, haider g, raja w, kumar d. remission rate of acute lymphoblastic leukemia (all) in adolescents and young adults (aya). j coll physicians surg pak. 2018 ;28(2):118-21. 4. bhatnagar s, chandra j, narayan s. hematological changes and predictors of bone marrow recovery in patients with neutropenic episodes in acute lymphoblastic leukemia. j trop pediatr. 2002; 48(4):200-3. doi: 10.1093/tropej/48.4.200. pmid: 12200979. 5. raja-sabudin rz, othman a, ahmed-mohamed ka, ithnin a, alauddin h, alias h, abdul-latif z, das s, abdul-wahid fs, hussin nh. immature reticulocyte fraction is an early predictor of bone marrow recovery post-chemotherapy in patients with acute leukemia. saudi med j. 2014;35(4):346-9. 6. rauf se, khan sa, ali n, afridi nk, haroon m, arslan a. immature reticulocyte fraction and absolute neutrophil count as predictor of hemopoietic recovery in patients with acute lymphoblastic leukemia on remission induction chemotherapy. turk j haematol. 2016;33(2):131-4. doi: 10.4274/tjh.2014.0379. 7. faderl s, thall pf, kantarjian hm, estrov z. time to platelet recovery predicts outcome of patients with de novo acute lymphoblastic leukaemia who have achieved a complete remission. br j haematol. 2002 ;117(4):869-74. doi: 10.1046/j.1365-2141.2002.03506.x. 8. foa r. acute lymphoblastic leukemia: age and biology. pediatr rep. 2011 jun 22;3 suppl 2(suppl 2):e2. doi: 10.4081/pr.2011.s2.e2. 9. redaelli a, laskin bl, stephens jm, botteman mf, pashos cl. a systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (all). eur j cancer care (engl). 2005 mar;14(1):53-62. doi: 10.1111/j.1365-2354.2005.00513.x. 10. kajiguchi, t, yamamoto, k, sawa, m. increased erythropoietin level and reticulocyte count during arsenic trioxide therapy. leukemia 2005;19:1–3 https://doi.org/10.1038/sj.leu.2403635 11. rehman h, zafar l, rehan m, khalique s, imran, imran t. post chemotherapy bone marrow recovery in acute leukaemiascomparison of immature reticulocyte fraction with absolute neutrophil count. jour rawalpind med coll, 2015; 19(2):117-119 12. zeidler l, zimmermann m, moricke a, meissner b, bartels d, tschan c, schrauder a, cario g, et al. low platelet counts after induction therapy for childhood acute lymphoblastic leukemia are strongly associated with poor early response to treatment as measured by minimal residual disease and are prognostic for treatment outcome. haematologica. 2012; 97(3):402-9. 13. khan m, morshed aa, ahmed tu, khan hh, ahmed au, roy s, et al. platelet indices as markers for remission in all during induction of remission: an experience of 52 cases. bangladesh j child health 2020; vol 44 (1) : 34-39 14. lucas k, gula mj, blatt j.relapse in acute lymphoblastic leukemia as a function of white blood cell and absolute neutrophil counts during maintenance chemotherapy. pediatr hematol oncol, 1992;9(2):91-7 15. buttarello m, bulian p, farina g, petris mg, temporin v. five fully automated methods for performing immature reticulocyte fraction. am j clinpathol 2002;117:871-79 16. zhang q, dai k, bi l, jiang s, han y, yu k, zhang s. pretreatment platelet count predicts survival outcome of patients with de novo non-m3 acute myeloid leukemia. peerj. 2017 dec 21;5:e4139. doi: 10.7717/peerj.4139. jrmc vol. 27 (issue 2) journal of rawalpindi medical college https://doi.org/10.37939/jrmc.v27i2.1963 (c) 2023 by rawalpindi medical university 378 page no. prevalence of parafunctional habits and temporomandibular disorder symptoms in young individuals reporting to watim dental hospital aleshba saba khan1, aleeza sana2, zarah sufian3, ammarah afreen4, asma shakoor5, eruj shuja6 abstract objective: this study aims to identify the prevalence of parafunctional habits and common symptoms of temporomandibular disorders in young individuals reporting to the watim dental college materials and methods: this cross-sectional study was carried out by a survey and clinical examination over a period of six months from september 2021 to february 2022. data from 103 patients, who fulfilled the inclusion criteria, were collected using a structured questionnaire and clinical examination regarding their parafunctional habits and temporomandibular joint symptoms. informed consent was filled out by all the participants. data were analyzed using spss version 23. a descriptive analysis was calculated for both quantitative and qualitative variables. results: the prevalence of oral parafunctional habits among the study sample was quantified on a binary scale (yes/no) where nail-biting was observed to be highly prevalent (38%), followed by mouth breathing (27%). the most frequently reported temporomandibular joint symptom was noise (clicking or crepitation) which was 66%. difficulty in mouth opening was the least common (20%) of all the symptoms noted. conclusion: it may be concluded from our study that amongst parafunctional habits nail biting is the most common habit amongst young individuals and amongst the temporomandibular joint disorder clicking and crepitation is the most common symptom persistent with the condition. keywords: clicking, nail-biting, parafunctional habits, temporomandibular joint symptoms 1 assistant professor prosthodontics, shahida islam dental college, lodhran; 2 demonstrators, science of dental materials, school of dentistry, islamabad; 3 assistant professor and hod prosthodontics, watim dental college, rawalpindi; 4 assistant professor, operative dentistry, watim dental college rawalpindi; 5 associate professor, community and preventive dentistry, cmh lahore; 6 assistant professor, watim mental and dental college; correspondence: dr aleshba saba khan, assistant professor of prosthodontics, shahida islam dental college, lodhran. email: aleshbasaba@hotmail.com cite this article: khan, a. s., sana, a., sufian, z., afreen, a., shakoor, a., & shuja, e. (2023). prevalence of parafunctional habits and temporomandibular disorder symptoms in young individuals reporting to watim dental hospital . journal of rawalpindi medical college, 27(2). https://doi.org/10.37939/jrmc.v27i2.1963 received july 3, 2022; accepted may 13, 2023; published online june 24, 2023 1. introduction the temporomandibular joint is a bilateral, synovial, hinge joint between the mandible and skull that helps in complex movements of the jaw while mastication, speech, and drinking.1 it works as a functional unit in coordination with the muscle of mastication, some ligaments as well as teeth.2 any alterations in this functional unit beyond its adaptive capacity can have an impact on the adequate functioning of the joint, resulting in temporomandibular disorders.1 temporomandibular disorders, which have multifactorial aetiology, according to the american academy of orofacial pain (aaop) are defined as a collection of dysfunctional, painful conditions in the temporomandibular joint and associated structures.1, 3 the cause of these disorders can be attributed to psychological stress, tooth loss or malalignment, bruxism, clenching, parafunctional habits, poor posture for long durations, destructive changes within or around the joints, injuries, genetic factors or tumorous growths.1, 3, 4 the signs and symptoms can vary depending upon the severity of the condition and can present as pain, noise, the issue with adequate mouth opening, headache, tooth wear or jaw getting stuck.1, 3oral parafunctional habits, which present as abnormal or excessive use of teeth or masticatory muscles, are among the main causes leading to temporomandibular disorders.5,6these habits include clenching, bruxism, nail-biting, lip or cheek biting, and gum chewing, keeping pencil or anything in mouth habitually.1, 6 temporomandibular disorders are mostly observed to be reported in individuals in the age range of 20 to 40 years and three times more commonly in females.1,5diagnosis of tmd and finding its cause is a challenging task.1 there are no universally accepted criteria established yet to figure out the accurate diagnosis.1,7 a questionnaire was formulated in 1994 based on fonseca's anamnestic index which was first made for brazilian people and had been used multiple times since then as it provides a cost-efficient and simple tool for assessing signs and symptoms of tmds.1 a study conducted on university students showed the prevalence of tmds to be 63% among jrmc vol. 27 (issue 2) journal of rawalpindi medical college 379 which 43.1% showed mild symptoms, 18.4% had moderate and only 1.3% showed severe symptoms.1 temporomandibular disorders are one of the reasons for seeking dental care other than dental pain. this study aims to identify the prevalence of parafunctional habits and common symptoms of temporomandibular disorders in young individuals reporting to watim dental college. much research has not been carried out regarding the issue in pakistan hence this study will prove to be a contributing factor to bring this to light. early diagnosis will help in controlling or limiting the issue so avoid the severity of signs and symptoms and thus help in better management. 2. materials & methods this cross-sectional study was carried out by a survey and clinical examination over a period of six months from september 2021 to february 2022. written informed consent was signed by all patients before joining the study. the purpose of the study was explained at the beginning of the questionnaire. patients attending dental outpatient department with different oral health issues were examined by assigned doctors. the patients were seated upright during the examination. a mouth mirror and explorer were used for examination. no radiographs were taken. patients after examination were asked different questions using a pre-existing questionnaire by fonseca for classifying tmj.8,9 the criteria for inclusion included men and women ranging from 15-35 years of signs of bruxism and other parafunctional habits. bruxism was evaluated by clinically observing signs of tooth wear, cracks, scalloped tongue, linea alba, muscle hypertrophy or patient reporting pain. mouth breathing was assessed by asking questions given in the questionnaire as well as oral examination showing dry mouth, high arched palate and adenoid faces. exclusion requirements included patients above 35 years of age and patients with neurological disorders or severe chronic diseases. a sample size of 103 subjects was selected using a 1.1 who calculator and a nonprobability, consecutive sampling technique. the sample was estimated using a 90%confidence level, and a 5% margin of error. the questionnaire was divided into three components. the first component (section i) gathered information about demographic data, and the second component (section ii) consisted of questions about participant’s dental history, questions such as teeth sensitivity, caries, dental trauma, pain history, and gum disease in them and the third component (section iii) consisted of questions about parafunctional habits, locking of the jaw, experienced clicking sounds while eating or talking, difficulty in opening the mouth, difficulty while yawning/chewing and question regarding a complaint of aesthetics. the questionnaire also contained other questions about parafunctional activities such as nail/lips biting chewing, bruxism, tongue thrusting, left baby/feeder bottle at a later age, and finger and thumb sucking. data were analyzed using the software statistical package for the social sciences (spss version 23). descriptive statistics were computed for the variables in terms of frequency and percentages. 3. results 103 individuals were selected for the study. out of 103, 61(59%) were females and 42 (41%) were males. the mean age of the participants was 24.11±4.76 and the age range was 15-35 years. the prevalence of oral parafunctional habits among the study sample was quantified on a binary scale (yes/no) where nail-biting was observed to be highly prevalent (38%), followed by mouth breathing (27%), tongue thrusting (23%), lip biting and clenching was seen in 17% of the participants and thumb sucking was prevalent in only 11% of the participants (figure 1). the prevalence of the temporomandibular joint disorder among the study sample was quantified as difficulty in mouth opening (yes/no/rarely), pain in the temporomandibular joint (yes/no/rarely), tmj noise either clicking or crepitation(yes/no/rarely), sudden stocking of the jaw (yes/no/rarely). the most frequently reported symptom was noise (clicking or crepitation) from tmj which was 66%. difficulty in mouth opening jrmc vol. 27 (issue 2) journal of rawalpindi medical college 380 was the least common (20%) of all the symptoms noted. 5. discussion the cross-sectional research was conducted at watim dental college, rawalpindi to assess the prevalence of parafunctional habits and temporomandibular disorder symptoms in patients reporting to the outpatient department of the institute. the most commonly seen habit was nail-biting, followed by mouth breathing, tongue thrusting, clenching and lip biting and lastly thumb sucking with the least prevalence. this is in partial accordance with a study by aloumi et al10 who reported nail biting and mouth breathing to be among the top two common factors and in partial contrast to the present study as aloumi et al reported teeth clenching to be the least common parafunctional habit (6%) whereas in this study thumb sucking was the least common habit (11%).10 the present study was in total accordance with alawsi et al who reported that mouth breathing and nail biting are the most commonly seen habits.11 present study contradicts dy by murshid et al who reported clenching to be the most common parafunctional habit whereas clenching was seen to be the second least common habit. 12 this study also is in contrast to findings by atsu et al who reported bruxism and lip biting to be more common than nail biting.13 the variation in the prevalence of multiple parafunctional habits might be due to disparity in sociodemographic factors, age and difference in the region of the target population.10mouth breathing was the second most common habit in the present study as well as in results reported by aloumi et al.10 this may be due to the high prevalence of deviated nasal septum or adenoids in the general population.14,15 the results of the present research show that the most prevalent temporomandibular joint disorder symptom observed is noise from tmj (66%) followed by pain, and difficulty in mouth opening and the least common symptom seen was jaw getting stuck (24%). these results are in total accordance with the results of the study by atsu et al and chazopoulos et al who reported tmj noises to be the most common, pain to be 2nd most common followed by difficulty in jaw opening.13,16the results of our study are also similar to findings by al warren et al who reported tmj noises as most commonly observed followed by pain.17 in another research by al khotani et al, tmj pain was seen to be most commonly reported.18the results of this study are in contrast with the present study which found tmj noise to be 66% and tmj pain to be 23%, that is almost half of tmj noises. the reason for this difference may be because the study by al khotani et al did not consider tmj noises in the evaluation of the patient at all thus pain turned out to be the most common, which is the second most common observation in the present study.18 the prevalence of tmds is slightly greater in females as compared to males. this is by a study published by beaumont et al in australian dental journal. according to that study the tmds persisted for a longer time in females as compared to males. 19 however their study shows that oral habits might be an independent factor when compared with tmd in the same individuals.19 sergio et al in their study found gum chewing to be the most prevalent habit for causing temporomandibular joint disorders. however, the prevalence of tmd was less in young individuals than in the older population.20 hong mh et al study conducted in korea suggests that multiple factors such as oral health status, mental health status, and temporomandibular joint symptoms are positively correlated.21 limitations and future gap: the study was carried out using a convenience sampling technique and participants were assessed based on a questionnaire. detailed evaluation of all the causes i.e. hormonal changes, diet, routine, sociodemographic factors, etc. was not done. the etiologic factors leading to parafunctional habits and tmds must be assessed. in future, similar studies can be done while keeping in consideration the other factors as well as clinical examination can be compared to radiographic evaluation for a more definitive diagnosis of the signs and symptoms. this will help in the provision of a more targeted management strategy. 5. conclusion it may be concluded from our study that amongst parafunctional habits nail biting is the most common habit amongst young individuals and amongst the temporomandibular joint disorder clicking and crepitation is the most common symptom persistent with the condition. conflicts of interestnone financial support: none to report. potential competing interests: none to report jrmc vol. 27 (issue 2) journal of rawalpindi medical college 381 contributions: a.s.k, a.sconception of study a.s.k, a.s, z.s, a.a experimentation/study conduction a.s.k, a.s, z.s, a.a , a.s, e.sanalysis/interpretation/discussion a.s.k, z.s, a.s manuscript writing z.s, a.a, a.s, e.s critical review a.s, a.a, a.s, a.a, e.s facilitation and material analysis references [1] khan mw, zaigham am. prevalence and severity of temporomandibular disorders in medical/dental undergraduate students. j pak dent assoc 2021;30(2):94-98, doi.org/10.25301/jpda.302.94 [2] domenyuk d, dmitrienko s, domenyuk s, harutyunyan y. structural arrangement of the temporomandibular joint given the constitutional anatomy. archiveuromedica. 2020;10(1):126. doi: 10.35630/2199-885x/2020/10/37 [3] paulino mr, moreira vg, lemos ga, silva pl, bonan pr, batista au. prevalence of signs and symptoms of temporomandibular disorders in college preparatory students: associations with emotional factors, parafunctional habits, and impact on quality of life. ciência&saúdecoletiva. 2018;23:17386. doi.org/10.1590/1413-81232018231.18952015 [4] acharya s, pradhan a, chaulagain r, shah a. temporomandibular joint disorders and its relationship with parafunctional habits among undergraduate medical and dental students. journal of college of medical sciences-nepal. 2018 sep 30;14(3):154-9. doi.org/10.3126/jcmsn.v14i3.20289 [5] ekici ö. association of malocclusion, parafunctional habits and quality of life in patients with temporomandibular joint disorder. turkiyeklinikleri. dishekimligibilimleridergisi. 2021;27(4):551-8. doi: 10.5336/dentalsci.2020-79483 [6] fale h, hnamte l, deolia s, pasad s, kohale s, sen s. association between parafunctional habit and sign and symptoms of temporomandibular dysfunction. journal of dental research and review. 2018 jan 1;5(1):17. doi: 10.4103/jdrr.jdrr_1_18 [7] habib sr, al rifaiy mq, awan kh, alsaif a, alshalan a, altokais y. prevalence and severity of temporomandibular disorders among university students in riyadh. saudi dent j. 2015;27:125-30. doi.org/10.1016/j.sdentj.2014.11.009 [8] melou c, leroux l ,meary f, bertaud v, lemaire a, dominique cl. relationship between occlusal factors, oral parafunctions and temporomandibular disorders: a case control study. intl j dent oral health. 2019:5(44); 1-5. doi: http://dx.doi.org/10.16966/2378-7090.295 [9] feteih r. m.signs and symptoms of temporomandibular disorders and oral parafunctions in urban saudi arabian adolescents: a research report. head & face medicine.2006:2(25); 1-7. https://doi.org/10.1186/1746-160x2-25 [10] aloumi a, alqahtani a, darwish a. oral parafunctional habits among preschool children in riyadh, saudi arabia. saudi journal of oral sciences. 2018 jan 1;5(1):22. doi: 10.4103/sjos.sjoralsci_46_17 [11] alawsi hr, hassan ba, al-talabani sz. prevalence of parafunctional habits among preschool children and its correlation to parental education status. polytechnic journal. 2021 aug 26;11(1):42-5. doi.org/10.25156/ptj.v11n1y2021.pp42-45 [12] murshid za, abdulaziz aa, amin he, al nowaiser am. assessment of parafunctional oral habits among a sample of saudi dental patients. journal of king abdulaziz universitymedical sciences. 2007 oct 1;14(4):35-47. [13] atsü ss, güner s, palulu n, bulut ac, kürkçüoğlu i. oral parafunctions, personality traits, anxiety and their association with signs and symptoms of temporomandibular disorders in the adolescents. african health sciences. 2019 apr 23;19(1):180110. doi: 10.4314/ahs.v19i1.57 [14] valcheva z, arnautska h, ivanova g, atanasova i, gogushev k. influence of adenotomy/adenoidectomy on the respiration and occlusion in mouth-breathing children. journal of the union of scientists-varna. medicine and ecology series. 2020 dec 1;25(1):67-71. [15] šidlauskienė m, lopatienė k, šidlauskas m, šidlauskas a. mouth breathing habit correction. interdisciplinary literature review. in95th european orthodontic society congress (eos 2019): 17-22 june 2019, nice france: abstracts: houston and scientific poster/european orthodontic society 2019. https://hdl.handle.net/20.500.12512/23285 [16] chatzopoulos gs, sanchez m, cisneros a, wolff lf. prevalence of temporomandibular symptoms and parafunctional habits in a university dental clinic and association with gender, age, and missing teeth. cranio®. 2019 may 4;37(3):159-67. doi.org/10.1080/08869634.2017.1399649 [17] alwarawreh am, altamimi zh, khraisat hm, kretschmer w. prevalence of temporomandibular disorder symptoms among orthognathic patients in southern germany: retrospective study. international journal of dentistry. 2018 oct 18;vol 2018. doi.org/10.1155/2018/4706487 [18] al-khotani a, naimi-akbar a, albadawi e, ernberg m, hedenberg-magnusson b, christidis n. prevalence of diagnosed temporomandibular disorders among saudi arabian children and adolescents. the journal of headache and pain. 2016 dec;17(1):1-1. doi 10.1186/s10194-016-0642-9 [19] beaumont s, garg k, gokhale a, heaphy n. temporomandibular disorder: a practical guide for dental practitioners in diagnosis and management. australian dental journal. 2020 sep;65(3):172-80. doi.org/10.1111/adj.12785 [20] sergio paduano md, rosaria bucci dd, roberto rongo dd, silva r, michelotti a. prevalence of temporomandibular disorders and oral parafunctions in adolescents from public schools in southern italy. cranio®. 2018 dec 14. doi.org/10.1080/08869634.2018.1556893 [21] hong mh. effects of mental health levels and oral habits on temporomandibular joint symptom in some adolescents. journal of the korea academia-industrial cooperation society. 2020;21(2):381-7. doi.org/10.5762/kais.2020.21.2.381 jrmc vol. 27 (issue 2) journal of rawalpindi medical college https://doi.org/10.37939/jrmc.v27i2.2210 (c) 2023 by rawalpindi medical university 352 page no. comparison of the effectiveness of daily versus weekly oral iron supplementation in preventing anemia during pregnancy maliha sadaf1, khansa iqbal2, saira ahmed3, mehak sehar4, nabeela waheed5 abstract objectives: to compa re mea n ha emoglobin a nd hema tocrit in non-pregna nt fema les ta king da ily ora l iron vs. weekly iron supplements in the third trimester of pregna ncy. results: there wa s no sta tistica lly significa nt difference between the two groups in terms of ha emoglobin level before ta king iron thera py. mea n post-trea tment ha emoglobin wa s 13.2±0.9a /d1 in group a a nd 12.9±0.95 g/dl in group b (0.18), mea n cha nge of ha emoglobin wa s 1.07±0.34 011 g/dl in group a a nd 0.63±0.56 g/dl in group b (0.000), mea n post-trea tment hema tocrit wa s 35.857±0.87 % in group a a nd 32.857±0.9l % in group b (p 0.000) mea n cha nge of hema tocrit wa s 2.942±0.59 % in group a a nd 1.000±0.00% in group b (p 0.000). conclusion: weekly iron supplementa tion in non-a na emic pregna nt women is a s effective a s da ily iron supplementa tion in terms of improvement in ha emoglobin level. keywords: pregna ncy, iron supplements, da ily, weekly, hemoglobin, hema tocrit 1,2 assistant professor, holy family hospital, rawalpindi medical university; 3 senior registrar, holy family hospital , rawalpindi medical university; 4 ex post graduate trainee , holy family hospital, rawalpindi medical university; 5 ex professor holy family hospital , rawalpindi medical university correspondence: dr. maliha sadaf, assistant professor, holy family hospital, rawalpindi medical university . email: drmaliha1978@gmail.com cite this article: sadaf, m., iqbal, k., ahmed, s., sehar, m., & waheed, n. (2023). comparison of the effectiveness of daily versus weekly oral iron supplementation in preventing anemia during pregnancy . journal of rawalpindi medical college, 27(2). https://doi.org/10.37939/jrmc.v27i2.2210 . received january 18, 2023; accepted may 03, 2023; published online june 24, 2023 1. introduction anaemia is a global health problem for pregnant women as 32.4 million (38.2%) pregnant women worldwide have anemia1. anaemia in pregnancy is a major risk factor for maternal and perinatal mortality and low birth weight babies2. about 50% of the cases of anaemia are due to iron deficiency 3. anaemia in pregnancy is defined as haemoglobin (hb) concentration less than 11 g/dl, and hb concentrations reduce by approximately 0.5 g/l during the second trimester of pregnancy.4 an imbalance of iron regulation can result in significant maternal and perinatal morbidity and mortality. any interruption in iron regulation can result in either iron deficiency or iron overload and iron deficiency is more common among the two. 5 daily oral iron and folic acid intake are recommended as part of antenatal care6. but daily iron intake is associated with multiple side effects which can affect patient compliance. therefore, weekly oral iron therapy can be used as a substitute for a daily iron regimen. intestinal mucosal cells are blocked by large amounts of iron with daily iron therapy which may decrease the iron absorption from the intestines.7 weekly iron therapy may expose the intestinal cells to iron less frequently which can improve iron absorption. once weekly 120 mg of elemental iron and 2.8 mg folic acid is recommended for non-anemic pregnant women to prevent anemia 8 which is an alternative regimen to a daily iron dosage by who. many studies carried out previously show that there is no difference in the efficacy of daily compared to weekly oral iron therapy in non-anaemic pregnant females for prevention of anaemia. a randomized controlled trial conducted in sri lanka showed thgroup(nausea significant difference between the groups in mean haemoglobin and hematocrit levels, pre supplementation mean haemoglobin was 11.9 in the daily and 11.8 in the weekly group ('p' 0.239), after therapy haemoglobin in daily group 11.8 and in weekly group 11.7 ('p' 0.731), mean hematocrit was 34.8 in daily and 34.4 in the weekly group (`p' 0.360) in the pre supplementation and post supplementation hematocrit was 35.2 in daily group and 35.2 in weekly group ('p' 0.913) respectively, while significantly greater side effects occurred in the daily compared to weekly group( nausea 39% in daily and 17% in weekly group ('p'<0.001))9. a prospective randomized longitudinal study in india showed that weekly iron supplementation is an effective option in non-anaemic pregnant women for prophylaxis of anemia9. a study in iran showed that levels of haemoglobin and hematocrit and other indices do not differ significantly (`p'>0.05) in daily or intermittent oral iron therapy group 10. oral iron jrmc vol. 27 (issue 2) journal of rawalpindi medical college 353 intake once or twice a week can be used as a substitute for daily iron in pregnant women.11 this study aims to compare the effectiveness of weekly and daily oral iron supplementation in pregnancy. 2. materials & methods this study was designed as a randomized controlled clinical trial during the period from november 2019 to may 2020. the study was conducted at holy family hospital, rawalpindi in the outpatient antenatal clinics. seventy (70) pregnant women were randomly assigned through a computer-generated randomization sheet to receive oral iron supplementation either daily or weekly. inclusion and exclusion criteria: all pregnant females of reproductive age (15 -40 years) with singleton pregnancies, at a gestational age of 14 to 22 weeks with a haemoglobin level of 11g/dl and above were included in the study. while females are intolerant to oral iron supplements, haematological disorders or chronic illness (for example, thalassemia, chronic renal diseases), serum ferritin less than 30µg/l were excluded from the study. permission from the institute’s ethical forum was obtained. the women were equally divided into two groups. group a of 35 received a 200 mg ferrous sulphate tablet (65 mg elemental iron) daily while group b of 35 women received 400 mg ferrous sulphate (130 mg elemental iron) weekly. every patient fulfilling the selection criteria was allocated a study id number in chronological order, ssps generated a study group corresponding to that id number was the study group of that patient. data was collected in the form of questionnaires after asking the patients. for serum haemoglobin and hematocrit levels, a 5 ml venous sample was taken and tests were carried out from the hospital laboratory. haemoglobin and hematocrit levels are checked before starting iron supplementation and repeated three weeks after starting oral iron therapy. all women are advised to take 100 mg of mebendazole twice daily for 3 days for deworming before selection. all the information on patients was collected in the form of a structured questionnaire. statistical analysis: data were analyzed using spss version 20 on a computer. descriptive statistics were calculated for both qualitative and quantitative variables. for qualitative variables i.e. parity, frequency and percentages were calculated. for quantitative variables for example mean serum hemoglobin and mean hematocrit, standard deviation was calculated. independent sample ‘t-test was applied at a 5% level of significance to compare mean levels of serum haemoglobin and serum hematocrit. ‘p-value <0.05 was considered statistically significant. to control any potential effect, modifiers for example parity, age, and stratified analysis was done. post-stratification independent sample t-test was applied. 3. results the age range in this study was from 15 to 40 years with mean baseline haemoglobin of 12.14±0.91 g/dl in group a while 12.23±0.97 g/dl in group b, mean posttreatment haemoglobin was 13.21±0.93 g/dl in group a and 12.86±0.95 g/dl in group b, mean change of haemoglobin was 1.07±0.34 g/dl in group a and 0.63±0.56 g/dl in group b, mean baseline hematocrit was 32.91±0.91 % in group a while 32.86±0.91 % in group b, mean post-treatment hematocrit was 35.86±0.87 % in group a and 32.86±0.91 % in group b, mean change of hematocrit was 2.94±0.59 % in group a and 1.000±0.00 % in group b as shown in table-1. table-1 comparison between both groups as regards demographic data and characteristics demographics mean±sd group a (n=35) mean±sd group b (n=35) p value baseline haemoglobin (g/dl) 12.14±0.91 12.23±0.97 0.705 post-treatment haemoglobin (g/dl) 13.21±0.93 12.86±0.95 0.118 change of haemoglobin (g/dl) 1.07±0.34 0.63±0.56 0.000 baseline hematocrit (%) 32.91±0.91 32.86±0.91 0.795 post-treatment hematocrit (%) 35.86±0.87 33.86±0.91 0.000 mean change of hematocrit (%) 2.94±0.59 1.00±0.00 0.000 while comparing the variables, mean baseline haemoglobin was 12.142±0.91 g/dl in group a while 12.228±0.97 g/dl in group b (p 0.705), mean posttreatment haemoglobin was 13.214±0.93 g/dl in group a and 12.857±0.95 g/dl in group b (0.118), mean change of haemoglobin was 1.071±0.34 g/dl in group a and 0.628±0.56 g/dl in group b (0.000), mean baseline hematocrit was 32.914±0.91 % in group a while jrmc vol. 27 (issue 2) journal of rawalpindi medical college 354 32.857±0.91 % in group b (p 0.795), mean posttreatment hematocrit was 35.857±0.87 % in group a and 32.857±0.91 % in group b (p 0.000), mean change of hematocrit was 2.942±0.59 % in group a and 1.000±0.00 % in group b (p 0.000) as shown in table 1. stratification of baseline haemoglobin, posttreatment haemoglobin, change of haemoglobin, baseline hematocrit, post-treatment hematocrit and mean change of hematocrit of both groups concerning age and parity are shown in table-2, 3, 4 and 5. table-2 stratification of hemoglobin in both groups concerning parity parity group baseline haemoglobin (g/dl) p-value posttreatment haemoglobin p value mean change of haemoglobin (g/dl) p value 0-3 a (n=26) 12.192±0.98 1.000 13.211±1.02 1.0 1.019±0.29 1.0 b (n=27) 12.033±0.93 12.703±0.89 0.666±0.62 >3 a (n=9) 12.000±.70 <0.001 13.222±0.66 0.458 1.222±0.44 1.0 b (n=8) 12.876±0.83 13.375±1.02 0.500±0.26 table-3 stratification of hemoglobin concerning age in both groups age (years) group baseline haemoglobin (g/dl) p-value posttreatment haemoglobin p value mean change of haemoglobin (g/dl) p value 15-30 a 12.190±1.03 1.000 13.214±1.04 1.0 1.023±0.29 1.0 b 12.000±.95 12.673±0.89 0.673±0.66 31-40 a 12.071±.73 0.003 13.214±0.77 1.0 1.142±0.41 1.0 b 12.666±0.88 13.208±0.98 0.541±0.25 table-4 stratification of hematocrit concerning parity in both groups parity group baseline hematocrit (%) p-value posttreatment hematocrit (%) p value mean change of hematocrit (%) p value 0-3 a 33.000±0.89 1.000 35.923±0.89 1.0 2.923±0.48 1.0 b 32.925±0.91 33.925±0.91 1.000±0.0 >3 a 32.666±1.00 1.00 35.666±0.86 1.0 3.000±0.86 1.0 b 32.625±0.91 33.625±0.91 1.000±0.0 table-5 stratification of hematocrit concerning age in both groups. age (years ) group baseline hematocrit (%) p-value posttreatment hematocrit (%) p value mean change of hematocrit (%) p value 15-30 a 33.047±0.86 1.000 35.952±0.86 1.0 2.904±0.53 1.0 b 32.782±0.90 33.782±0.90 1.000±0.0 31-40 a 32.714±0.99 0.221 35.714±0.91 1.0 3.000±0.67 1.0 b 33.000±0.95 34.000±0.95 1.000±0.0 5. discussion this study aimed to compare the haemoglobin levels in non-anaemic pregnant women receiving weekly versus daily iron supplementation. two groups were matched and no statistically significant difference could be detected between both groups as regard maternal age, parity (demographic data); haemoglobin level and hematocrit before starting iron supplementation and after treatment which can be attributed to proper randomization. concerning the improvement of iron status at near term in pregnancy, our study showed that supervised weekly iron supplementation did not differ in outcome from daily supplementation. though in our study the haemoglobin rise was more significant in the daily group, it increased to a significant level in the weekly group too and was maintained at a safe level. in a study by mumtaz et al12, the haemoglobin rose to a significant level in the weekly group (p=0.0037). the serum iron values increased to a significant level in both groups but the increase in the daily group was significantly more than in the weekly group. in the jrmc vol. 27 (issue 2) journal of rawalpindi medical college 355 study by khangura et al.13, post-treatment haemoglobin and hematocrit levels increased both in the daily and intermittent supplementation groups but this rise in haemoglobin and hematocrit was more in the daily as compared to the intermittent supplementation group. they concluded that intermittent iron therapy is equally effective as daily iron therapy and is associated with less nausea. these findings are similar to our study. in another study by chu lam et al14, conducted on pregnant women with mild anaemia, the increase in haemoglobin and hematocrit levels was almost the same in the daily iron group as compared to the alternate day iron group af ter 6 weeks of iron supplementation. this study concluded that daily and intermittent iron supplementation has no difference in the treatment of iron deficiency anaemia in pregnancy. these findings are also consistent with our study. yaznil mr and colleagues also found in their study that there is no significant difference in mean haemoglobin and hematocrit between daily and weekly groups before and after iron supplementation.15 weekly iron supplementation as a prophylaxis in non-anaemic pregnant women is as good as daily supplementation as regards the increase in haemoglobin level, in addition, it was associated with significantly fewer side effects and much better compliance 16, 17, 18, 19. 5. conclusion according to the results of this study, iron supplementation every week as a preventative measure in non-anaemic or mildly anaemic patients is just as effective as daily supplementation in terms of improvement in haemoglobin and hematocrit levels. weekly iron supplementation is also associated with fewer side effects and better patient compliance. conflicts of interestnone financial support: none to report. potential competing interests: none to report contributions: m.s, n.w conception of study m.s experimentation/study conduction m.s, k.i, s.a analysis/interpretation/discussion m.s, s.a manuscript writing k.i, n.w critical review m.s facilitation and material analysis references [1] world health organization (who), (2015): hemoglobin concentrations for the diagnosis of anaemia and assessment of severity. vitamin and mineral nutrition information system . cochrane database syst rev., 10.1002/14651858.cd009997.pub2. [2] boschi-pinto c, young m, black re. the child health epidemiology reference group reviews of the effectiveness of interventions to reduce maternal, neonatal and child mortality. int j epidemiol. 2010;39 suppl 1(suppl 1):i3‐i6. [3] stevens ga, finucane mm, de-regil lm, paciorek cj, flaxman sr, branca f, peña-rosas jp, bhutta za, ezzati m, nutrition impact model study group. global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and nonpregnant women for 1995–2011: a systematic analysis of population-representative data. the lancet global health. 2013 jul 1;1(1):e16-25. [4] benoist bd, mclean e, egll i, cogswell m. worldwide prevalence of anaemia 1993-2005: who global database on anaemia. worldwide prevalence of anaemia 1993-2005: who global database on anaemia 2008. [5] world health organization. guideline: daily iron and folic acid supplementation in pregnant women. world health organization; 2012. [6] frazer dm, anderson gj. the orchestration of body iron intake: how and where do enterocytes receive their cues?.blood cells mol dis.2003;30(3):288‐297. [7] guideline: intermittent iron and folic acid supplementation in nonanaemic pregnant women. geneva: world health organization; 2012. available from: https://www.ncbi.nlm.nih.gov/books/nbk299510/. [8] goonewardene imr, senadheera di. randomized control trial comparing effectiveness of weekly versus daily antenatal oral iron supplementation in preventing anemia during pregnancy. j obstet gynaecol res. 2018;44(3):417‐424. [9] sipra b, shanti s, kimmi a. effect of weekly iron supplementation on iron indices in pregnant women. int j med res health sci. 2015;4(4):857-860. [10] sadighian f, haydehsamiei h, alaoddolehei h, kalantari n. efficacy of daily versus intermittent administration of iron supplementation in anemia or blood indices during pregnancy. caspian j intern med. 2013;4(1):569‐573. [11] world health organization(who), (2011): the global prevalence of anemia in 2011. geneva: world health organization. cochrane database syst rev.,110.1002/14651858.cd009997.pub2. [12] mumtaz z, shahab s, butt n, rab ma, demuynck a. daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in pakistan in a randomized double-blind clinical trial. the journal of nutrition. 2000 nov 1;130(11):2697702. [13] khangura rk, torti s, tesfay l, hammer e, bakaysa s, campbell w. daily vs. intermittent iron therapy in moderate iron deficient pregnant patients: a randomized non-inferiority trial. ajog. february 2021; 224(2), supplement, s28. doi: https://doi.org/10/1016/j.ajog.2020.12.114 [14] chu lam mt, khandakar b, heon i, overbey j, brustman l, rosenn b. daily vs. alternate day iron for pregnant women jrmc vol. 27 (issue 2) journal of rawalpindi medical college 356 with iron deficiency anemia: randomized controlled trial. ajog. february 2021; 2024(2), supplement, s107. doi: https://doi.org/10/1016/j.ajog.2020.12.179 [15] yaznil mr, lubis mp, lumbanraja sn, barus mng, sarirah m. comparison of maternal outcomes of daily and weekly iron tablet supplementation in pregnant women in coastal region, medan, indonesia. open access maced j med sci. september 2020; 8(b):1088-91 doi.org/10.3889/oamjms.2020.5056 [16] abdelgawad m, mansour d, mohammed m. daily versus weekly oral iron supplementation in pregnant women: a randomized controlled clinical trial. evidence based women's health journal 2021;2(2):120-126. doi:10.21608/ebwhj.2019.17526.1031 [17] demuth ir, martin a, weissenborn a. iron supplementation during pregnancy a cross-sectional study undertaken in four germanstates. bmc pregnancy childbirth. 2018;18(1):491. [18] bouzari z, basirat z, zeinal zadeh m, cherati sy, ardebil md, mohammadnetaj m, barat s. daily versus intermittent iron supplementation in pregnant women. bmc res notes. 2011 oct 25;4:444. [19] kumar s, dubey n, khare r. study of serum transferrin and serum ferritin during pregnancy and their correlation with pregnancy outcome. int j med sci public health. 2017;6:11822 doi.org/10.5455/ijmsph.2017.04072016570 summary journal of rawalpindi medical college (jrmc); 2017;21(3): 245-247 245 original article efficacy of oral zinc sulphate in the treatment of recalcitrant common warts nadia waqas 1, shazia amir khan 2, aqsa naheed 2, zafar iqbal sheikh 3 1.department of dermatology benazir bhutto hospital and rawalpindi medical university;2.department of dermatology, yusra medical and dental college islamabad;3. department of dermatology, military hospital, rawalpindi. abstract background: to determine the efficacy of oral zinc sulphate in treatment of recalcitrant common warts. methods: in this randomized control trial 90 patients with recalcitrant warts were randomly allocated to two groups by lottery method named group a (oral zinc sulphate) and group b (placebo). group a patients were given oral zinc sulphate in a dose of 10mg/kg to a maximum dose of 600mg/day for two months. group b received glucose tablets as placebo results: out of 45 patients in oral zinc sulphate group, 28 (62.22%) patients had complete eradication or at least 75% reduction in number of warts noted at presentation. on the other hand in the placebo group only 2 (4.44%) patients had > 75% reduction in number of warts.in oral zinc sulphate group it was noted that only 6 (13.3%) patients had less than 50% reduction in no. of warts. 11 (24.4%) had 50-75% efficacy and majority 28 (62.2%) patients had > 75 % reduction in number of warts. in contrast, in the placebo group 33 patients (73.3%) had less than 50% reduction, followed by 10 (22.2%) patients having 5075% reduction and only 2 (4.4%) patients had > 75% reduction in no. of warts conclusion: warts are common viral infection of skin caused by human papilloma virus. despite various treatment options available at times warts become recalcitrant. oral zinc sulphate is an effective treatment option for recalcitrant multiple viral warts. being oral therapy it is easy to take with less frequent follow up visits required. key words: zinc sulphate, common warts, placebo. introduction warts are common, benign and usually self limiting lesions caused by human papilloma viruses (hpv).1 hpv can cause disease at any site in stratified squameous epithelium either keratinized (skin) or non keratinized (mucosa). warts are broadly classified as cutaneous, oral, genital and laryngeal warts. among cutaneous warts are common warts, plane warts, plantar warts, periungual and filliform warts.2not all warts need treatment as many give little inconvenience and will resolve spontaneously.3,4,5 different treatment options are available for warts which include duct tape occlusion, topical salicylic acid, glutaraldehyde, podophyllin and podophyllotoxin, 5-fluororacil, cryotherapy, electrocautery and curettage, imiquimod, photodynamic therapy, lasers and many others.6,7 among the systemic treatments documented are cimetidine, levamisol and zinc sulphate.8of the available treatment options none is uniformly effective or virucidal9. their safety and efficacy have not been assessed in double blind controlled clinical trials. cryotherapy, electrocautery and topical salicyclic acid are most commonly used treatment options but none without side effects. electrocautery carries a risk of scarring, cryotherapy causes pain and salicylic acid is irritant on facial skin and may cause contact dermatitis. 5,10 hpv infection does not induce inflammatory cytokines and therefore options aimed at modulating immune system and facilitating production of cytokines have been proposed11. one immunomodulatory approach involves prescribing oral zinc, a micronutrient that is necessary for normal functioning of cells.12 mun jh, et all showed complete resolution of warts in 50% of patients with no serious side effects.11 sadighha a in 2009 conducted a study showing a remarkable clearance rate of 76.9% in zinc sulphate treated patients versus 7.8% in placebo group.13 raza n demonstrated that serum zinc levels were low in patients with persistent, progressive and recurrent viral warts. according to their study zinc levels were low in 56% of patients compared to 32% of control with a significant p value of 0.003.14. oral zinc sulphate is not being used locally for the treatment of recurrent viral warts. it is speculated that being an oral therapy it would be more convenient for patients, requiring lesser clinic visits as are required journal of rawalpindi medical college (jrmc); 2017;21(3): 245-247 246 for other available treatment options. patients and methods this comparative study was conducted in dermatology department of pakistan institution of medical sciences(pims) islamabad, from june 2016 to dec 2016. sample size (n) 90 patients ,45 in each group. patients of either gender between 18 and 65 years of age having single or multiple common warts on extragenital skin that are resistant to salicylic acid , electrocautery and cryotherapy used for at least six months(recalcitrant) were included. immunocompromised patients and those having co morbidities like hypertension, diabetes or any other known chronic illness were not included in the study. pregnant and lactating women were also not included. number and site of warts were noted. patients were randomly allocated to group a and group b by lottery method. oral zinc sulphate in a dose of 10 mg/kg body weight upto a maximum of 600 mg/kg per day were given to group a for a period of two months. group b received glucose tablets as placebo.patients were reviewed after 4 weeks. final outcome was seen at 8th week. confounding factors like age, gender and duration of warts were controlled by stratification. comparison of efficacy in two groups was calculated by chi-square test. p value of < 0.05 was considered as significant. results majority (54.4%) of the patients were from the age interval of 20 – 30 years (table 1).mean age of group a was 22.02±5.864 years having minimum age of 18 and maximum of 49 years. the mean age of placebo group was 22.96 years ±6.582 years having range of 18 to 44 years . according to gender distribution of the patients there were 23 (51.1%) males in group a (experimental group) and 21 (46.7%) in placebo group having almost equal distribution (table 2). there was no main difference in average number of warts on presentation before treatment. the mean number of warts in oral zinc sulphate group was 6.98±1.803 with a range of 2 to 13 warts and in placebo group it was 6.73±1.405 ranging from 3 to 10. after 4 weeks of treatment total number of warts reduced to 4.24±1.209 warts on average with a range of 1 to 7 warts in group a and in group b the number of warts reduced to 5.49±1.272 warts on average ranging from 2 to 8 warts after 8 weeks of treatment the average number of warts reduced very significantly in oral zinc sulphate group to 1.73±1.452 warts with a range of 0 to 6 warts and in placebo group the average number of warts were noted to 4.29±1.160 warts with a range of 2 to 7 warts . the efficacy of the treatment was defined as at least 75% reduction in number of warts and it was noted that in oral zinc sulphate group majority of the patients had > 75% reduction in number of warts i.e. 28 (62.22%) . in the placebo group majority of the patients 33 (73.3%) had less than 50% reduction (table 3).the cross tabulation with respect to gender shows that there was no significant (p-value > 0.05) association between gender and efficacy of drug . table 1: age distribution (n=90) categorized age frequency percent cumulative percent < 20 34 37.8 37.8 20 – 30 49 54.4 92.2 30 – 40 3 3.3 95.6 > 40 4 4.4 100.0 table 2: distribution of gender in both groups group gender frequency percent cumulative percent group a (oral zinc sulphate) male 23 51.1 51.1 female 22 48.9 100.0 total 45 100.0 group b (placebo) male 21 46.7 46.7 female 24 53.3 100.0 total 45 100.0 table 3: distribution of efficacy percentage in both groups group efficacy percentage frequency percent cumulati ve percent group a (oral zinc sulphate) < 50% 6 13.3 13.3 50 75 % 11 24.4 37.8 > 75 % 28 62.2 100.0 total 45 100.0 group b (placebo) < 50% 33 73.3 73.3 50 75 % 10 22.2 95.6 > 75 % 2 4.4 100.0 total 45 100.0 discussion warts are benign epithelial proliferations caused by human papillomavirus (hpv). more than 200 types of journal of rawalpindi medical college (jrmc); 2017;21(3): 245-247 247 hpv have been recognized.15 common warts are the commonest type of warts in children and adults.1 hpv is efficient at evading recognition. the virus can globally downregulate keratinocyte innate immune sensors and suppress the type i interferon response, which is critical for the control of viral infection. there is no viremia and no virus-induced cell death; hence, there is no inflammation or danger signal to the immune system.17therefore, methods aim at modulating and enabling the immune system to detect and defend against this virus, can be a therapeutic option. one such option is oral zinc sulphate. zinc is required for multiple cellular tasks, and especially the immune system depends on a sufficient availability of this essential trace element.18 thymulin which is a thymus specific hormone binds to highly specific binding receptors on t cells, induces several t cell markers and promotes t cell functions including allogenic cytotoxicity, suppressor function and il-2 production. levels of thymulin are significantly decreased in minor zinc deficiency. infᵞ is a major component of th1 response and it upregulates mhc i antigen expression. inf ᵞ is decreased in zinc deficiency.19 there are several other mechanisms by which zinc acts in boosting the immune system and enabling to counteract various bacterial and viral infections.19 al gurairi et al first conducted a randomized placebo controlled trial. he administered oral zinc sulphate in a dose of 10mg/kg body weight for two months in patients with recalcitrant warts and showed a clearance rate of 87% versus no response in placebo group.20,21 two placebo controlled rcts showed remarkable cr rates: 76.9%and 78.1% in the zinc sulphate treated group compared with 7.8%and 13% in the placebo group after 2 months of treatment.13,22another randomized double-blind prospective study comparing the efficacy of oral zinc sulfate and cimetidine revealed a 62.5% cr in the zinc-treated group versus 0% in the cimetidine group.23mun jh, et all showed complete resolution of warts in 50% of patients treated with oral zinc sulphate with no serious side effects.11 conclusion oral zinc sulphate is an effective treatment option for recalcitrant multiple viral warts. being oral therapy it is easy to take with less frequent follow up visits required. references 1. bernard hu, burk rd, chen z. classification of papilloma viruses (pvs) based on 189 pv types and proposal of taxonomic amendments. virology. 2010; 401:70-79 2. lowg dr, androphy ej. warts. in: fitzpatric tb, editors. dermatology in general medicine. 7th ed. new york: mcgraw-hill book company; 2008:1915–23 3. keogh-brown mr, fordham rj, thomas ks, bachmann mo. to freeze or not to freeze: a cost-effectiveness analysis of wart treatment. br j dermatol. 2007; 156:687-92 4. gibbs s, harvey i. topical treatments for cutaneous warts. cochrane database syst rev. 2006; (3):cd001781. 5. sterling jc. virus infections. in: rooks tb, tony b, stephen b, neil c, editors. textbook of dermatology. 8th ed. vol. 2. italy: blackwell publishing company; 2010:33.39–33.51 6. dall’soglio f, d’amico v, nasca mr, micali g. treatment of cutaneous warts: an evidence-based review. am j clin dermatol. 2012; 13:73-96 7. richard c, reichman . human papilloma virus infections. in: braunwald e, isselbacher kj, petersdorf rg, wilson jd, editors. harrison's principle of medicine.16th ed. vol. 169. new york: mcgraw-hill company; 2005:1056–58. 8. simonart t, de maertelaer v. systemic treatments for cutaneous warts: a systemic review. j dermatolog treat. 2012; 23:72-77 9. kim sy, jung sk, lee sg, yi sm. new alternative combination therapy for recalcitrant common warts: the efficacy of imiquimod 5% cream and duct tape combination therapy. ann dermatol. 2013; 25:261-63 10. rivera a, tyring sk. therapy of cutaneous human papillomavirus infections. dermatol ther. 2004; 17:441-48 11. mun jh, kim sh, jung ds, ko hc, kim bs. oral zinc sulfate for viral warts: an open label study. j dermatol. 2011; 38:541-45 12. prasad as. zinc in human health: effect of zinc on immune cells. mol med. 2008; 14:353-57 13. sadighha a. oral zinc sulphate in recalcitrant multiple viral warts: a pilot study. j eur acad dermatol venereol. 2009; 23:715-17 14. raza n, khan da. zinc deficiency in patients with persistant viral warts. j coll physicians surg pak. 2010; 20:83-86 15. cubie ha. diseases associated with human papillomavirus infection. virology. 2013; 445:21-34 16. al-mutairi n, alkhalaf m. mucocutaneous warts in children: clinical presentations, risk factors, and response to treatment. acta dermatovenerol alp panonica adriat. 2012; 21:69-72 17. stanley ma. epithelial cell responses to infection with human papillomavirus. clin microbiol rev. 2012; 25:21522 18. overbeck s, rink l, haase h. modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. arch immunol ther exp (warsz). 2008; 56:15–30 19. prasad as. zinc in human health: effect of zinc on immune cells. mol med. 2008; 14:353-57 20. al-gurairi ft, al-waiz m, sharquie ke. oral zinc sulphate in the treatment of recalcitrant viral warts: randomized placebo-controlled clinical trial. br j dermatol. 2002; 146:423–31 21. gibbs s. zinc sulphate for viral warts. br j dermatol. 2003; 148:1082–83 22. yaghoobi r, sadighha a, baktash d. evaluation of oral zinc sulfate effect on recalcitrant multiple viral warts: a randomized placebo-controlled clinical trial. j am acad dermatol. 2009; 60:706–08. 23. stefani m, bottino g, fontenelle e, azulay dr. [efficacy comparison between cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts. an bras dermatol. 2009; 84:23-27 http://www.ncbi.nlm.nih.gov/pubmed?term=bernard%20hu%5bauthor%5d&cauthor=true&cauthor_uid=20206957 http://www.ncbi.nlm.nih.gov/pubmed?term=burk%20rd%5bauthor%5d&cauthor=true&cauthor_uid=20206957 http://www.ncbi.nlm.nih.gov/pubmed?term=chen%20z%5bauthor%5d&cauthor=true&cauthor_uid=20206957 http://www.ncbi.nlm.nih.gov/pubmed/?term=.+.+classification+of+papillomaviruses+(pvs)+based+on+189+pv+types+and+proposal+of http://www.ncbi.nlm.nih.gov/pubmed?term=keogh-brown%20mr%5bauthor%5d&cauthor=true&cauthor_uid=17326748 http://www.ncbi.nlm.nih.gov/pubmed?term=fordham%20rj%5bauthor%5d&cauthor=true&cauthor_uid=17326748 http://www.ncbi.nlm.nih.gov/pubmed?term=thomas%20ks%5bauthor%5d&cauthor=true&cauthor_uid=17326748 http://www.ncbi.nlm.nih.gov/pubmed?term=bachmann%20mo%5bauthor%5d&cauthor=true&cauthor_uid=17326748 http://www.ncbi.nlm.nih.gov/pubmed/17326748 http://www.ncbi.nlm.nih.gov/pubmed?term=kim%20sy%5bauthor%5d&cauthor=true&cauthor_uid=23717030 http://www.ncbi.nlm.nih.gov/pubmed?term=jung%20sk%5bauthor%5d&cauthor=true&cauthor_uid=23717030 http://www.ncbi.nlm.nih.gov/pubmed?term=lee%20sg%5bauthor%5d&cauthor=true&cauthor_uid=23717030 http://www.ncbi.nlm.nih.gov/pubmed?term=yi%20sm%5bauthor%5d&cauthor=true&cauthor_uid=23717030 http://www.ncbi.nlm.nih.gov/pubmed?term=rivera%20a%5bauthor%5d&cauthor=true&cauthor_uid=15571494 http://www.ncbi.nlm.nih.gov/pubmed?term=tyring%20sk%5bauthor%5d&cauthor=true&cauthor_uid=15571494 http://www.ncbi.nlm.nih.gov/pubmed/?term=dermatologic+therapy+of+cutaneous+humantherapy%2c+vol.+17%2c+2004%2c+441%e2%80%93448 http://www.ncbi.nlm.nih.gov/pubmed/23599126 http://www.ncbi.nlm.nih.gov/pubmed/23599126 http://www.ncbi.nlm.nih.gov/pubmed/23599126 http://www.ncbi.nlm.nih.gov/pubmed/22491770 http://www.ncbi.nlm.nih.gov/pubmed/22491770 http://www.ncbi.nlm.nih.gov/pubmed?term=stefani%20m%5bauthor%5d&cauthor=true&cauthor_uid=19377755 http://www.ncbi.nlm.nih.gov/pubmed?term=bottino%20g%5bauthor%5d&cauthor=true&cauthor_uid=19377755 http://www.ncbi.nlm.nih.gov/pubmed?term=fontenelle%20e%5bauthor%5d&cauthor=true&cauthor_uid=19377755 http://www.ncbi.nlm.nih.gov/pubmed?term=azulay%20dr%5bauthor%5d&cauthor=true&cauthor_uid=19377755 http://www.ncbi.nlm.nih.gov/pubmed/19377755 http://www.ncbi.nlm.nih.gov/pubmed/19377755 summary journal of rawalpindi medical college (jrmc); 2017;21(3): 229-232 229 original article clinical spectrum of advanced neuroblastoma alia ahmad, , nayla asghar, najaf masood, najamuddin, fauzia shafi khan, zunaira rathore, ahsan waheed rathore department of paediatric haematology/oncology department, the children’s hospital & the institute of child health lahore pakistan abstract background: to analyze the spectrum of neuroblastoma and burden of high risk malignancy on the public sector tertiary center. methods: in this descriptive study, 70 patients with neuroblastoma were enrolled. data regarding their age, sex, type (infantile <547 days or 18 months or more than 18 months), staging and clinical features, bone and bone marrow involvement, course of therapy and outcome was analyzed . the staging was done on the basis of bilateral bone marrow biopsy and imaging ct scans, mri neck chest and abdomen and bone scans. patients were treated with conventional vincristine, cyclophosphamide, doxorubicin, etoposide and carboplatin for 6-8 courses 2-3 weeks apart depending upon the age whether 18 months or older group. evaluation was done after 2-4 courses to see the response and options for surgery by doing imaging in the form of mri or ct scans. results: total 70 patients with age ranging from< 1 year to 15 years (median age of 3 yrs) were included. m: f ratio was 1.8:1. non-infantile type (70%), stage iv (79%) and adrenal mass (47%) were the commonest presentations. bone and bone marrow involvement was seen in 53% and 70% , respectively. thirty out of seventy (43%) successfully completed the chemotherapy, 12/70(17%) abandoned treatment, 17/70 (24%) expired due to progressive disease and infections, 7/70(10%) were put on palliative treatment at presentation 4/70(6%) relapsed and given palliation therapy. conclusion: in resource limited settings, neuroblastoma stage iv is a challenging malignancy to deal with. there is intense need of increased capacity building to diagnose them early and implementation of effective infection control measures with better survival options in these patients. key words: neuroblastoma, low income countries introduction neuroblastoma is the most common extracranial solid tumor in childhood in high income countries , where it accounts for 10% of pediatric cancers. 1 in lowand middleincome countries (lmic) with populationbased registries, it accounts for only 1–3% of cancers, and in most lmic its true incidence is unknown. 2-4 neuroblastoma is the most common extracranial solid tumour in childhood, accounting for 50% of neoplasms diagnosed in the first year of life. 5 neuroblastoma is the most common neonatal solid tumour (47%) followed by germ cell tumours 28.8% in france in a study done from 2000-2009 with overall survival of 84% and most common site is abdomen 86% followed by chest and neck. 6 neuroblastoma, the second most common childhood solid tumour, accounts for 8% of all childhood (0–14 years) cancers in the united kingdom. however, survival remains poor for children diagnosed with high-risk disease (50% of all neuroblastoma).7 this disease has a heterogeneous course, ranging from spontaneous regression to inexorable progression and death, depending on the biologic features of the tumor. identification of risk groups on the basis of clinical and molecular prognostic variables has allowed tailoring of therapy to improve outcomes and minimize the risk of deleterious consequences of therapy.8 neuroblastoma is notable for its broad range of clinical behaviors. tailored treatment approaches, based on the presence or absence of specific clinical and biologic factors, have been used for decades, and successive institutional and cooperative group risk based clinical trials have led to substantial improvement in outcome for patients classified as low or intermediate risk. 9 outcomes for the vast majority of patients with low-stage (international neuroblastoma staging system [inss] stages 1 and 2) neuroblastoma are excellent. local recurrences can typically be managed with surgery and/or radiation therapy. metastatic recurrences are rare and often treated successfully with chemotherapy. treatment of journal of rawalpindi medical college (jrmc); 2017;21(3): 229-232 230 patients with localized neuroblastoma with unfavourable biologic features is controversial. among patients with low-stage, mycn-amplified neuroblastoma, outcomes of patients with hyperdiploid tumors were statistically, significantly better than those with diploid tumors.10 advanced neuroblastoma is a systemic disease that spreads to the whole body, including the bone marrow, liver, lymph nodes, and bones. morphologic or radiologic methods only detect metastases larger than a certain size. this indicates that high-risk neuroblastoma should be considered as a systemic disease and that an increase of chemotherapy intensity is a premise for the improvement of treatment outcome. high dose chemotherapy (hdc), with stem cell salvage following intensive induction chemotherapy has been widely accepted as being required for neuroblastoma treatment in high-risk groups, and treatment results have improved. however, the 5-year event-free survival (efs) rate is 30–40% and remains unsatisfactory despite various intensive efforts. 9, 11in low income countries like pakistan advanced neuroblastoma, with dismal outcome, at presentation is more common. patients and methods in this descriptive study, performed in the department of paediatric haematology/ oncology of the children’s hospital lahore from june 2015 to december 2016, patients with neuroblastoma were enrolled. data regarding their age, sex, type (infantile <547 days or 18 months or more than 18 months), staging and clinical features, bone and bone marrow involvement, course of therapy and outcome was analyzed. criteria of entry were children with diagnosis of neuroblastoma based on physical examination, basic laboratory, radiographic and pathologic evaluation along with immunohistochemistry (ihc) in all cases. the staging was done on the basis of bilateral bone marrow biopsy and imaging ct scans, mri neck chest and abdomen and bone scans. patients were treated with conventional vincristine, cyclophosphamide, doxorubicin, etoposide and carboplatin for 6-8 courses 2-3 weeks apart depending upon the age whether 18 months or older group. evaluation was done after 2-4 courses to see the response and options for surgery by doing imaging in the form of mri or ct scans. no facility was available in our center for myeloablative chemotherapy with autologous hematopoietic stem cell rescue and immunotherapy for minimal residual disease to decrease relapse in high risk disease. results total 70 patients with age ranging from< 1 year to 15 years (median age of 3 yrs) were included. five patients were more than 10 years (7%). m: f ratio was 1.8:1. forty nine cases were of non-infantile type(>18 months old) and 21 (30%) with infantile type (>18months).fifteen (22%) had stage iii at presentation while 55 (78%) was of stage iv. no one presented at stage i or ii. thirty three (47%) had mainly adrenal mass as the main presenting complaint, 5 (7%) as paraplegia, 4 (6%) as nasal polyp, neck and mediastinal involvement , 2 (3%) as bony masses and proptosis, 26 (37%)with multiple presentations. fifty two (74%) had to travel more than 100 km to reach the primary treatment center. thirty seven (53%) had bone involvement at presentation and 49(70%) had bone marrow involvement. thirty (43%) had successfully completed the chemotherapy followed by surgical resection and radiotherapy if required for residual tumour, 12 (17%) abandoned treatment, 17 (24%) expired due to progressive disease and infections, 7(10%) were put on palliative therapy at presentation 4 (6%) were put on palliation after relapse (table 1 &2). table 1: staging and outcome stage treatment complete treatment abandoned expired palliation on arrival palliation after relapse iii 7 0 6 0 2 15 iv 23 12 11 7 2 55 total 30 12 17 7 4 70 p-value-0.05 table 2: staging and clinical spectrum stage adrenal mass multiple presentat ions nonadrenal masses total pvalue=0 .019 stage iii 9 1 5 15 stage iv 24 25 6 55 total 33 26 11 70 % 47% 37% 16% figure 1: round blue cell tumour figure 2: advanced stage neuroblastoma at presentation journal of rawalpindi medical college (jrmc); 2017;21(3): 229-232 231 discussion this is the most common extra-cranial solid tumour in west, however it is 4th most common solid tumour after lymphomas and wilms tumor in our center. neuroblastoma is uncommon in africa with burkitt’s lymphoma being the commonest, but when seen usually presents as high-risk disease with a poor prognosis with overall survival of 4%. this aggressive biology of the tumor is frequently augmented by delayed presentation. current treatment depends upon technologies and skills that are scarce in developing countries and the cost involved is generally beyond the means of healthcare providers who are faced with a myriad more pressing healthcare issues. 12 it is more common in males almost twice than females in our study as compared to seer pediatric monograph illustrated that the overall incidence among males was 6.5% higher compared with that of females.13 seventy percent presented at older age group > 18 months in our study as compared to data analyzed in over 8800 children with neuroblastoma from 1999-2002 and 17% having stage iii, 43% presented at >18 months age with age < 18 months having prognostic value with better 5-year overall survival of 95% than 76% in older age group having inss stage iii cohort (p-value=<0.001).14 nb incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents >10 years. there is increasing evidence that neuroblastoma in older children and adolescents has unique biology and an indolent disease course, but ultimately dismal survival. 15 in present study there was no patient with localized disease and stage iv in more than two third of cases as compared to another study done in morocco they had more than a third of cases of localized neuroblastoma (inss stage i ii) in 61.1% of cases, tumors were widespread at the diagnosis, whereas 38.9% did not extend beyond the primary site. similar is the case in hic for the proportion of lowstage neuroblastoma as shown by data from inrg international neuroblastoma risk group (30%) had low-stage (international neuroblastoma staging system inss stages 1 and 2) neuroblastoma (2660/8800 cases) from 1990 to 2002.10, 16 present study showed that two thirds of these neuroblastoma patients had bone marrow involvement and more than half had bony metastases at their first presentation indicating their advanced stages due to late diagnoses . high risk neuroblastoma requires modern high-risk treatment regimens include five to six cycles of induction chemotherapy and surgery, consolidation therapy with high-dose therapy (hdt) with autologous hematopoietic stem-cell rescue and irradiation, and post consolidation therapy to treat minimal residual disease. as these regimens are not available in our center therefore these patients are inadequately treated or put on palliation as demonstrated by siop-podc working group in their study. due to the lack of transplant expertise, reduced access to blood products and pharesis, and difficulty supporting patients through the period of myelosuppression, few centers in lmic have attempted curative treatment of high-risk neuroblastoma, and have commonly prescribed palliative care. furthermore, the cost of isotretinoin and lack of access to monoclonal anti-gd2 antibody impede effective mrd treatment in some lmic. 17 neuroblastoma is one of the most difficult childhood cancers to cure with uk and ireland 5-year survival of 64.7% for cases diagnosed. the greatest improvements were in eastern europe, where 5-year survival increased from 65.2% in 1999-2001, to 70.2% in 200507. 18 in low income countries only a limited proportion of all children with cancer receive curative and/or palliative therapy. 19, 20 majority of these children in our study presented with adrenal masses along with other presentations and less than 5% had mediastinal disease as a main clinical spectrum and 7% had spinal masses presenting as paraplegia. as compared to another study done on children younger than age 21 years diagnosed with nb or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the international neuroblastoma risk group inrg database. patients with adrenal tumours had higher risk of events and more frequent poor prognostic clinical and biological factors (stage iv disease, mycn amplification, elevated serum ferritin and ldh and chromosomal aberrations) than in non-adrenal tumours (p-value=0.001). 21 figure 3: infantile neuroblastoma figure 4: bony metastases and right proptosis at presentation. journal of rawalpindi medical college (jrmc); 2017;21(3): 229-232 232 conclusion in resource limited settings, neuroblastoma stage iv is a challenging malignancy to deal with. there is intense need of increased capacity building to diagnose them early and treat in earliest possible staging for better results. references 1. gurney jg, davis s, severson rk, fang jy. trends in cancer incidence among children in the us. cancer 1996; 78: 532– 41 2. parkin dm, stiller ca, draper gj, bieber ca. the international incidence of childhood cancer. int j cancer1988; 42: 511–20. 3. stiller ca, parkin dm. international variations in the incidence of neuroblastoma. int j cancer. 1992; 52: 538–43 4. magrath i, steliarova-foucher e, epelman s. paediatric cancer in low-income and middle-income countries. lancet oncol 2013; 14: 104 –16. 5. brodeur gm, maris jm. neuroblastoma.in: pizzo pa, poplack dg, eds. principles and practice of pediatric oncology. 4th ed. philadelphia: lippincott williams & wilkins, 2002:895938.) 6. cohn sl, pearson ad, london wb. the international neuroblastoma risk group (inrg) classification system: an inrg task force report. j clin oncol 2009; 27:289 97. 7. desandes e, guissou s, ducassou s. neonatal solid tumors: incidence and survival in france. pediatr blood cancer 2016; 63: 1375-80 8. baker dl . outcome after reduced chemotherapy for intermediate-risk neuroblastoma engl j med 363; 14nejm.org: 2010 1313-23. 9. pinto nr, applebaum ma, volchenboum sl. advances in risk classification and treatment strategies for neuroblastoma. jco 2015; 33: 3008-22 10. bagatell r, beck-popovic m, london wb. significance of mycn amplification in international neuroblastoma staging system stage 1 and 2 neuroblastoma: a report from the international neuroblastoma risk group database 2009; 27:365-70 11. hashii y, kusafuka t, ohta h. a case series of children with high-risk metastatic neuroblastoma treated with a novel treatment strategy consisting of postponed primary surgery until the end of systemic chemotherapy. pediatric hematology and oncology 2009; 25:5: 439-450 12. hadley gp, heerden jv. high-risk neuroblastoma in a subsaharan african country: telling it like it is. trop doct. 2017; 10:1177-80 13. goodman mt, gurney jg, smith ma. sympathetic nervous system tumors. in: cancer incidence and survival among children and adolescents: united states seer program 1975– 1995national cancer institute seer program 1999; 99:4649. 14. meany hj, london wb, ambrose pf. significance of clinical and biologic features in stage 3 neuroblastoma: a report from the international neuroblastoma risk group project pediatr blood cancer 2014; 61: 1932-39 15. mosse yp, deyell rj, berthold f. neuroblastoma in older children, adolescents and young adults: a report from the international neuroblastoma risk group project. 16. imane tabyaoui i ,tahiri-jouti n, serhier z. high incidence of mycn amplification in a moroccan series of neuroblastic tumors. diagn mol pathol 2013; 22:112–18. 17. parikh ns, howard sc, chantada g. clinical practice guidelines siop-podc adapted risk stratification and treatment guidelines: recommendations for neuroblastoma in lowand middle-income settings. pediatr blood cancer 2015; 62: 1305–16 18. gatta g, botta l, rossi s. childhood cancer survival in europe 1999-2007: results of eurocare-5--a populationbased study. lancet oncology 2014; 15(1):35-47 19. magrath i, steliarova-foucher e, epelman s. paediatric cancer in low-income and middle-income countries. lancet oncology 2013; 14, 3: 104–16. 20. 2balkin e m, thompson d, and colson ke. physician perspectives on palliative care for children with neuroblastoma: an international context. pediatr blood cancer 2016; 63: 872–879 21. vo kt, mattay kk, london wb.. clinical, biologic, and prognostic differences on the basis of primary tumor site in neuroblastoma: a report from the international neuroblastoma risk group project. journal of clinical oncology 2014;10:1621-25 321 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 original article perception of doctors towards relationship with pharmaceutical industry mumtaz ahmad1, neelam zaka2, inayat ur rahman3, sehrish mumtaz4, mobina ahsan dodhy5, lubna meraj6 1 professor, azad jammu kashmir medical college, muzaffarabad, ajk. 2 assistant professor, shifa tameer-e-millat university, islamabad. 3 professor, northwest school of medicine, peshawar. 4 registrar medicine, azad jammu kashmir medical college, muzaffarabad, ajk. 5 head of department pathology, holy family hospital, rawalpindi. 6 associate professor, district headquarter hospital, rawalpindi. author’s contribution 1 conception of study 3 experimentation/study conduction 2 analysis/interpretation/discussion 4 manuscript writing 5 critical review 6 facilitation and material analysis corresponding author dr. inayat ur rehman, professor of biochemistry, northwest school of medicine (nwsm), peshawar email: drinayat@gmail.com article processing received: 10/02/2022 accepted: 06/06/2022 cite this article: ahmad, m., zaka, n., rahman, i., mumtaz, s., dodhy, m.a., meraj, l. perception of doctors towards relationship with pharmaceutical industry. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 321-329. doi: https://doi.org/10.37939/jrmc.v26i2.1906 conflict of interest: nil funding source: nil access online: abstract introduction: doctors and pharmaceutical companies are the major components of the health care system. their interdependency on such a large scale calls for a better relationship between two stakeholders of the health care system. most of the time this relationship has a bad impact on the reputation of the prestigious medical profession, as well as, affects the health of the poor patient causing the malafied relationship. materials & methods: in order to see how the relationship works in the hospitals of azad kashmir, the study was conducted on the doctors of abbas institute of medical sciences, muzaffarabad. a mixed type of study was conducted from january through june 2017. in this study, 100 doctors were selected for data collection in the questionnaire method. while three different focus groups involving doctors from different specialties were made. results: out of 100 doctors, 36 doctors agreed that the doctors in aims are aware of such guidelines, 92 doctors agreed that there is a need for national guidelines to monitor the doctor and pharmaceutical company’s relationship, and 67 responded that doctor's prescription is influenced by the gifts given by pharmaceutical companies, 52 doctors agreed that pharmaceutical companies should be banned from giving gifts to physicians, 88 responded that the information provided by those representatives is only superficial and they don’t know the core information like side effects and mode of action of the drugs, 15 thought that yes it is ethical to accept the gifts from the pharmaceutical companies but only to the extent of samples of medicines. out of 100, 89 doctors responded in favour of the incorporation of bioethics in the curriculum of the medical education conclusion: pharmaceutical companies have hijacked our whole health system to some extent and are polluted because of these pharmaceutical company’s representatives. there is a need to ascertain the fact that if this phenomenon is not controlled, in near future we will have to face very severe consequences and our patients will be at the mercy of pharmaceutical companies rather than the doctor. keywords: pharmaceutical companies, doctor-pharma regulations, abbas institute of medical sciences (aims) 322 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 introduction doctors and the pharmaceutical industry are the two main components of the healthcare system which have been contributing valuable services to the medical profession. medical sciences and pharmaceuticals are interdependent on each other. many ethical issues may erupt during interactions between physicians and the pharmaceutical industry, mainly due to conflict of interest. these moral issues might be the suitability of doctors taking gifts and other advantages from the medicine industry that can definitely affect the decision of physicians about the treatment. this state is so astonishing that arnold relman a professor from harvard, and ex-editor of the new england journal of medicine said, “the field of physicians is being bought by the medicine industry, not only in terms of usage of medicine but also in times of research and teaching”.1 unethical drug practices are a common phenomenon around the world, but it is more severe in developing countries. most physicians don’t consider it an unethical practice to accept drug samples and other gifts from medical representatives (mrs).2 medical representatives visit a doctor's clinic to promote their companies products. they offer drug samples, gifts, and sponsorships for conferences. these are the various ways that drug companies try to influence the doctor's prescription in various ways.3 different studies showed that 80-95% of doctors are regularly visited by drug company representatives.4 majority of doctors receive gifts from drug companies. most doctors deny their influence in writing prescriptions by these gifts.5 according to another study,6 some doctors admit that drug samples and entertainments offered by pharmaceutical companies influence the prescribing behavior of medications. pharmaceutical companies interact with doctors to take gifts frequently and it is quite common practice.7 therefore, it is the most important moral issue in the medical profession so many researchers give their analytical views about it.5,8 even though the behavior of the doctor must not be influenced by the prd (physiciandrug representative) proved by many researchers.9 these changes result in the development of mistrust between the physician and patient giving little importance to the prescribed prescription.10 main advantages of humanizing this type of ethical relationship will not only serve the patients but will also bring positive change in the behavior of doctors as well as in the health care institutions. mal-practicing in this type of relationship goes on increasing day by day.11,12 one more important factor was given due consideration to doctors' behavior and their interaction with the medicine industries, therefore, this factor is also a source of information for the doctors.13 in the light of the above facts there is a dire need of making policies, rules, and regulations that will monitor the relationship between doctors and the medicine industry. various measures should be taken to undermine the various aspects of moral issues to correct the unconstructive attitude that arises from a change in the perception and knowledge of doctors who are not able to manage the relationship.15 but the changes that take place are absurd, changes influence the practice of the doctor that including the changes in the prescription writing and knowledge.13,14 a physician might act as an advisor for the pharmaceutical industry. this might be in a relationship with a specific product. all the process undergoes like a business deal. if a physician works as an advisor to the pharmaceutical industry, this type of agreement shall be publicly announced. it should be recognized and reported to the concerned authorities who handle the marketing of specific drugs.15 some physicians insist on a different type of reward from pharmaceutical industries for prescribing medicine. they never recommend drugs to companies that do not agree to give a handsome amount of money to the physicians as a reward. immoral drug prescription is in vogue around the globe but it is more prevalent in developing nations. despite all those guidelines, some doctors are prescribing medicines just for the promotion of drug companies. the condition is worst in pakistan. pharmaceutical companies usually spend huge money on sales promotions through medical representatives. however, studies examining the attitude of physicians towards the pharmaceutical industry are lacking in pakistan. so, more studies are required to highlight the ethical issues and explore explanations for the influence of the practice setting on the physician-industry relationship. this study will assess the opinions of doctors on accepting items of various values from pharmaceutical representatives, whether accepting such items is ethical, and whether they thought accepting such items would influence their prescribing practices. this study will also analyze how the relationships between physicians and drug companies are likely to change in the future. objective: to assess the perception of doctors towards the relationship with the pharmaceutical industry. materials and methods a mixed study (qualitative and quantitative) was carried out from january through june 2017 at abbas 323 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 institute of medical sciences. all ranks of doctors employed in abbas institute of medical sciences were enrolled in the study after informed consent. data were collected using the questionnaire method and focus group discussion method. for the questionnaire method, a self-designed and self-administered questionnaire was distributed among the doctors, and a questionnaire was mailed to the participants who were not available for live sessions, and data was collected accordingly. for focus group discussions, three focus groups were constituted and there were 24 doctors from the hospital who took part in the 3 focus groups, each having 8 members. one group comprised of consultants/professors, the second was of postgraduate (pg) trainees and house job officers, and the third of medical officers. every group was having doctors from different specialties. data analysis of the data from the questionnaire was carried out through spss and the results were shown in the form of charts and graphs for easy interpretation while in the case of focus group discussions, all the discussions were audio-tapped, and then verbatim transcription was done. after that, each transcript was read carefully and then content analysis of the data was done. data were coded and themes were extracted and finally, three themes were finalized. results in our study questionnaire was distributed among 100 doctors at abbas institute of medical sciences. for some doctors who were out of reach, questionnaires were mailed to them while for others data was obtained in live sessions. before evaluating the questions pertaining to the pharmaceutical companies, different demographic characteristics like gender, experience, and specialty of the doctors were assessed. in our study 56 doctors were male while 44 were female, eight doctors were having experience with less than one year, 33 were having experience from one to five years, 31 were having experience from 6-10 years and 28 were having experience with more than ten years. our study included doctors from different specialties like 16 doctors were from medicine, 15 were from surgery, 13 from obstetrics, 7 from cardiology, 15 from emergency, 4 from the eye, 6 from ent, and 24 from different other specialties. a summary of the demographic characteristics of the doctors is depicted in the tables below. figure 1: demographic characteristics of the doctors after the demographic characteristics of the doctors, responses given by the doctors to different questions from the questionnaire were analysed below: table 1: responses of doctors to different questions: summary of results questions agree disagree doctors in our institution aware of guidelines regarding acceptance of gifts from the drug industry 36 64 any need for national guidelines for the monitoring of the doctorpharmaceutical relationship 92 8 decisions of doctors regarding the use of certain medications are influenced after getting the gifts from pharmaceutical companies 67 33 pharmaceutical companies should be banned from giving gifts to physicians 52 48 pharmaceutical sales representatives provide accurate information about their products? 12 88 ethical to accept gifts and other kinds of benefits from pharmaceutical companies 15 85 incorporation of bioethics in the curriculum of medical colleges resolve the ethical issues in interactions between physicians and pharmaceutical industry 89 11 table 1 shows the overall responses of the doctors to the questionnaire. when asked about the awareness of the doctors regarding guidelines for accepting gifts from pharmaceutical companies, 36 doctors agreed that the doctors in aims are aware of such guidelines 324 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 while 64 thought that the doctors are unaware of those guidelines. out of 100 doctors, 92 doctors agreed that there is a need for national guidelines to monitor the doctor and pharmaceutical company’s relationship while 8 responded that the prevalent guidelines should be strengthened and implemented in their true sense so that the relationship between doctors and different pharmaceutical companies can be monitored. for the question that whether the prescription of doctors is influenced by getting different gifts from pharmaceutical companies, 67 responded that yes this might be the case while 33 were of the view that doctors have their own prescription and are not influenced by the gifts of pharmaceuticals companies. in response to the question that whether pharmaceutical companies should be banned from giving any sort of gifts to doctors, 52 doctors agreed with the question while 48 had the view that they shouldn’t be banned from giving gifts to doctors. another very important question was about the information provided by the pharmaceutical company’s representatives and out of 100, only 12 were of the view that the information provided by those representatives is most of the time accurate while 88 responded that the information provided by those representatives is only superficial and they don’t know the core information like side effects and mode of action of the drugs. next question was that is it ethical to accept gifts from pharmaceutical companies and out of 100, 15 thought that yes, it is ethical to accept gifts from pharmaceutical companies but only to the extent of samples of medicines while 85 responded against the acceptance of any sort of gifts from the pharmaceutical companies. the last question was about the incorporation of bioethics in the curriculum and out of 100, 89 doctors responded in favor of the incorporation of bioethics in the curriculum of medical education while 11 thought that doctors had enough information and they can decide on their own whether something is ethical or not. after these results, each question was analyzed and depicted in the form of different graphs. focus group discussions: there are 24 doctors from the hospital who took part in the 3 focus groups, each having 8 members. one group comprised of consultants/professors, the second was of pg trainees and house job officers, and the third consisted of medical officers. every group was having doctors from different specialties. doctors clarified that the sole objective of the work was to know about the perceptions of the doctors in relation to interactions with the pharmaceutical industry for the purpose of research. the consent of doctors was also taken for audio-taping of the event. after the audio-tapping, verbatim transcription of the whole discussion was done. each transcript was read carefully and then open codes were assigned to them manually. overlapped data was analyzed to facilitate the modification of emergent findings. after that final themes were selected based on their significance and comprehensiveness. three themes that were finalized after detailed deliberation were; 1. doctor-pharma regulations 2. accepting the gifts from pharmaceutical companies and the influence of these interactions on physicians’ drug prescribing behaviors 3. changing the prescribing behaviors of doctors theme 1: doctor-pharma regulations almost all doctors of the three fg talked about the rudimentary or non-existing regulations on the doctors-pharma relationship in the country. due to this reason, pharmaceutical companies and doctors freely make contracts as there is not legally binding. one doctor said that regulation and accountability in pakistan are only found in papers and not in practice. most doctors supported his statement. several doctors highlighted that a few organizations, such as pmdc, drug regulatory authority of pakistan, and the karachi bioethics group have made some guidelines, but most of the doctors are not aware of these guidelines, therefore are not in the practice. doctors generally agreed that the regulatory authority has “failed to regulate” and is “not controlling the situation” (fg 1). one reason mentioned for weak regulatory processes may be the devolution of powers from the federal government to the provinces as a result of the 18th constitutional amendment, 2010), which led to the decentralization of powers (fg3). it was realized that in the absence of government regulation, poor patients are left at the mercy of pharmaceutical companies and unethical practices, costing patients unnecessary and wasteful expenditure as well as posing a great threat to the well-being and life of patients. many physicians expressed that in pakistan, their interactions with pharmaceutical companies were mostly self-regulated by a physician of choice (fg 2). the physicians from almost all levels were interviewed and the results that were observed the interaction of physicians with the pharmaceutical industry is led by their own choice and is largely governed by their own moral sense as well as their principles. in fact, among the whole community one pg trainee confessed that “the policies and codes of 325 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 conduct are always on the general level but on a personal level the thing that affects the most is your own interest, choices and your own likings and disliking” (fg3). the majority of doctors suggested that “the first step is to make and implement the regulations and control the quackery across the country. theme 2: accepting the gifts from pharmaceutical companies and the influence of these interactions on physicians’ drug prescribing behaviors the majority of doctors defended that the medical reps could not change the prescribing behaviors of doctors. one doctor said that physicians’ prescriptions cannot be influenced by small gifts from pharmaceutical representatives because, as doctors, they are the ones who make their own decisions about the medicines required for treating the patients. another physician explained that pharmaceutical representatives just present their products, they could not compel for writing their products. commenting on funding received from pharmaceutical companies, one senior consultant told the group that pharmaceutical companies spare almost 20% of the price for doctors. we take the gifts or funds for cme within this percentage. if we will not take the benefit of this, it will benefit the company, not the patients. he also added that doctors all over the world accept gifts and honorariums, not just in pakistan. some doctors said they “would never prescribe those drugs which were substandard” (fg 2). prescribing behaviors of doctors might be influenced by the costeffectiveness of gifts. as one medical officer explained, “i am not ought to be influenced by the minor gifts that pharmaceutical companies offer, however, big deals are more likely to be considerable” (fg 2). senior consultants admitted that although the pharmaceutical companies sponsor conferences and symposia, this does not influence their drug prescribing behaviors, as the “being senior, the more you realize this as a professional relationship” (fg 3). very few doctors realized that the concept of “give and take” between the doctors and pharmaceutical companies is not ethical and it affects patients badly (fg 1). some doctors agreed that there are “physicians who are involved in this blame game don’t even realize what they are doing wrong” and will have negative publicity in the future. (fg1). theme 3: how the prescribing behaviors of doctors can be changed? different groups suggested different views to change the prescribing behavior of doctors. most doctors urged the importance of bioethics education in medical college. one physician said that “20 years ago medical students didn’t even know the word bioethics” in pakistan, now people are talking about the incorporation of this field into the curriculum (fg3). they were of the view that current medical professionals are involved in unethical practice because they were not taught medical ethics in their courses. the doctors suggested that bioethics should be mandatory at the grassroots level when students “get interaction with the pharmaceutical companies from 3rd year onward” (fg1). one consultant said that ethical teachings should be reinforced throughout the career in the medical profession and there should be refresher courses on “moral and cultural values” (fg2). a few doctors suggested that enforcement of law, regulation and accountability could be helpful to change the prescribing behavior of doctors, but most of the doctors were not in favor. discussion doctors and the pharmaceutical industry are the two main components of the healthcare system which have been contributing valuable services to the medical profession. medical sciences and pharmaceuticals are interdependent on each other. many ethical issues may erupt during interactions between physicians and the pharmaceutical industry, mainly due to conflict of interest. unethical drug practices are a common phenomenon around the world, but it is more severe in developing countries. most physicians don’t consider it unethical to accept drug samples and other gifts from medical representatives. an immature attitude toward working among various sectors of health care units may be the root cause of disagreement between doctors, and it will in turn distress the main principle of these institutions. the medical institutions and clinics are highly saturated by the effect of the drug industries this impact are highly influential in all other health-related areas and the doctors are the main concern. this business is observed to have aptitude in developing focused associations with doctors by giving them the required things for the sake of clinical consideration related to cpd exercises in the form of advantages and privileges for persuasive doctors. furthermore, the shortfall of administrative guidelines in the medical care area, and the weak implementations of the policies exist highly entertaining. these policies gap make space for industries to direct their terms with doctors and the doctors feel no difficulty or hurdle to 326 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 accept their proposals without the fear of any action against them. in addition to this, the educational institutions have likewise surrendered their space to the business, since it is a willing wellspring of financing with enormous assets. the additional efforts needed to assemble support from these institutions are considered excessively impressive, so the industry has many more options to avail. however, during the research study, the most alarming situation is observed that some people in the medical profession have the guts to discourage the influence of the pharmaceutical industry in the healthcare sector. the situation that is prevailing in pakistan is now considered a part of the norm and culture so the people who discourage these behaviors feel difficulty in challenging this so-called culture. our current study was a mixed study (qualitative and quantitative) which was carried out at abbas institute of medical sciences, an affiliated hospital of ajk medical college muzaffarabad. data were collected using the questionnaire method and focus group discussion method. in our study questionnaire was distributed among 100 doctors at abbas institute of medical sciences. for some doctors who were out of reach, questionnaires were mailed to them while for others data was obtained in live sessions. first of all, the demographic attributes of the doctors were studied. in our study 56 doctors were male while 44 were female, eight doctors were having experience with less than one year, 33 were having experience from one to five years, 31 were having experience from 6-10 years and 28 were having experience with more than ten years. our study included doctors from different specialties like 16 doctors were from medicine, 15 were from surgery, 13 from obstetrics, 7 from cardiology, 15 from emergency, 4 from the eye, 6 from ent, and 24 from different other specialties. after the demographic characteristics of the doctors, responses given by the doctors to different questions from the questionnaire were analyzed. every question from the questionnaire was analyzed on two different grounds i.e. gender of the doctors and experience of the doctors as these two factors can have an effect on the questions asked in the questionnaire. when asked about the awareness of the doctors regarding guidelines for accepting gifts from pharmaceutical companies, 36 doctors (gender: male = 21 and female = 15) (experience: less than one year = 2, 1-5 years = 9, 6-10 years = 12 and more than 10 years = 13) agreed that the doctors in aims are aware of such guidelines while 64 doctors (gender: male = 35 and female = 29) (experience: less than one year = 6, 1-5 years = 24, 6-10 years = 19 and more than 10 years = 15) thought that the doctors are unaware of those guidelines. these results stated that doctors are aware of the fact that there are certain guidelines regarding the acceptance of gifts from pharma companies but these regulations are very frail that most of the doctors are not willing to follow those guidelines. in our study also 36% of the doctors knew that there are certain guidelines for acceptance of gifts from pharmaceutical companies but they were unwilling to follow those guidelines as these guidelines were not strictly adhered to in our country.16 out of 100 doctors, 92 doctors (gender: male = 53 and female = 39) (experience: less than one year = 4, 1-5 years = 31, 6-10 years = 30, and more than 10 years = 27) agreed that there is need of national guidelines to monitor the doctor and pharmaceutical company’s relationship while 8 (gender: male = 3 and female = 5) (experience: less than one year = 4, 1-5 years = 2, 610 years = 1 and more than 10 years = 1) responded that the prevalent guidelines should be strengthened and implemented in their true sense so that the relation of doctor and different pharmaceutical companies can be monitored. these results showed concurrence with the study whose results were that in developing countries health authorities don’t have dependable rules and they don’t have their own research models and depend on the research models of the western countries, so pakistan being a developing country showed similar problem as identified in our study. so there is a need to have our own research model based on which we should have our own guidelines that are implementable in our country.17 for the question that whether the prescription of doctors is influenced by getting different gifts from the pharmaceutical companies, 67 (gender: male = 36 and female = 31) (experience: less than one year = 5, 1-5 years = 19, 6-10 years = 22 and more than 10 years = 21) responded that yes this might be the case while 33 (gender: male = 19 and female = 14) (experience: less than one year = 3, 1-5 years = 14, 6-10 years = 9 and more than 10 years = 7) were of the view that doctors have their own prescription and is not influenced by the gifts of pharmaceutical companies. our results were exactly in correspondence with the study that carried out the meta-analysis of 19 studies and found out that 15 out of 19 studies showed the relationship between accepting gifts from pharmaceutical companies and the rate of prescription of drugs by that company.18 in response to the question that whether pharmaceutical companies should be banned from 327 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 giving any sort of gifts to doctors, 52 (gender: male = 27 and female = 25) (experience: less than one year = 4, 1-5 years = 14, 6-10 years = 15 and more than 10 years = 19) doctors agreed to the question while 48 (gender: male = 29 and female = 19) (experience: less than one year = 4, 1-5 years = 19, 6-10 years = 16 and more than 10 years = 9) had the view that they shouldn’t be banned from giving gifts to the doctors. another very important question was about the information provided by the pharmaceutical company's representatives and out of 100, only 12 (gender: male = 7 and female = 5) (experience: less than one year = 3, 1-5 years = 4, 6-10 years = 2 and more than 10 years = 3) were of the view that the information provided by those representatives is most of the time accurate while 88 (gender: male = 49 and female = 39) (experience: less than one year = 5, 1-5 years = 29, 6-10 years = 29 and more than 10 years = 25) responded that the information provided by those representatives is only superficial and they don’t know the core information like side effects and mode of action of the drugs. our results showed an almost similar percentage of respondents who responded that the pharma representatives don’t have accurate information about the medicines. so, these representatives don’t have the exact information about the probable side effects of the drugs and the mode of action of the drug and it is inappropriate to rely on their information while prescribing a certain drug.19 next question was that is it ethical to accept gifts from pharmaceutical companies and out of 100, 15 (gender: male = 8 and female = 7) (experience: less than one year = 5, 1-5 years = 4, 6-10 years = 4 and more than 10 years = 2) thought that yes it is ethical to accept the gifts from the pharmaceutical companies but only to the extent of samples of medicines while 85 (gender: male = 48 and female = 37) (experience: less than one year = 3, 1-5 years = 29, 6-10 years = 27 and more than 10 years = 26) responded against the acceptance of any sort of gifts from the pharmaceutical companies. results of our study were 15% who considered it ethical to accept gifts which shows in their study that out of total doctors participated in the study 25 % thought that it is suitable to accept gifts from pharmaceutical companies.20 the last question was about the incorporation of bioethics in the curriculum and out of 100, 89 (gender: male = 49 and female = 40) (experience: less than one year = 4, 1-5 years = 30, 6-10 years = 29 and more than 10 years = 26) doctors responded in favor of incorporation of bioethics in the curriculum of the medical education while 11 (gender: male = 7 and female = 4) (experience: less than one year = 4, 1-5 years = 3, 6-10 years = 2 and more than 10 years = 2) thought that doctors had enough information and they can decide on their own whether something is ethical or not. a study on the inclusion of bioethics in the curriculum involved students from both private and public medical colleges and as per the results of that study, 57% of students from private medical colleges had some information about bioethics, and 43% of students from public medical colleges had information about bioethics and these results strongly recommend the addition of bioethics in the curriculum and our study 89% doctors did support the incorporation of bioethics in the curriculum of medical colleges.21 in the case of focus group discussion, 24 doctors from the hospital took part in the 3 focus groups, each having 8 members. one group comprised of consultants/professors, the second was of pg trainees and house job officers, and the third consisted of medical officers. every group was having doctors from different specialties. doctors clarified that the sole objective of the work was to know about the perceptions of the doctors in relation to interactions with the pharmaceutical industry for the purpose of research. the consent of doctors was also taken for audio-taping of the event. after the audio-tapping, verbatim transcription of the whole discussion was done. each transcript was read carefully and then open codes were assigned to them manually. overlapped data was analyzed to facilitate the modification of emergent findings. after that final themes were extracted from the data. three themes were; doctor-pharma regulations, accepting the gifts from pharmaceutical companies and the influence of this interaction on physicians’ drug prescribing behaviors, and changing the prescribing behaviors of doctors. as far as theme-1 is concerned, fg-i inferred that although there pmc, drug regulatory authority of pakistan, and karachi bioethics group but these organizations have failed to make the doctors adherent to the guidelines or regulations set for their relationship with pharmaceutical companies. fg-ii stated that every physician had some interaction with the pharmaceutical companies and that is totally selfregulated and is not governed by any regulation or guideline. fg-iii was of the view that every doctor builds some relationship with the pharmaceutical companies keeping in view his/her own interest or benefit. after listening to the discussion of all the fgs, it can be concluded that in order to make a transparent and privileged relationship of doctors with pharma 328 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 companies there is a dire need that the regulations and guidelines for these types of relationships must be reconsidered and should be made strict to the level that every doctor is bound to abide by the rules and regulations set by a certain regulatory body. the second theme was “accepting gifts from pharmaceutical companies and the influence of this interaction on physician’s drug prescribing behavior”. in this theme, there were different responses from the doctors of all the focus groups. from fg-i very few doctors realized the fact that it is not ethical to have such a relationship with pharmaceutical companies and they also don’t think in doing so and prescribing the wrong medicine will have a worse impact on the patient. fg-ii doctors were happier with the bigger gifts and said that smaller incentives will not affect their prescription of medicine, however, they can consider only if the gift is of higher or better value. and the fg-iii doctors were of the view that the relationship with pharmaceutical companies is just a professional relationship and they will not even think to harm their reputation which they have earned after so many years of hard work just to please pharmaceutical companies in return for gifts. so this theme had different answers from all the focus groups and there should be a stringent policy of monitoring health professionals who have malafide relationships with pharmaceutical companies. third and the final theme was changing the prescribing behavior of doctors. the crux of the discussion of all the focus groups was to incorporate bioethics in the curriculum of mbbs so that when in practice they have to face these pharmaceutical companies, they should be equipped with enough knowledge of ethics and regulations regarding these types of relationships with the pharmaceutical companies. this will enable them to value their patients and their own hard work of lots years rather than depending on the pharmaceutical company’s representatives. conclusion pharmaceutical companies have hijacked our whole health system to some extent. they have representatives who are trained in a way to convince the doctors to give benefits to the companies and they also give huge remunerations to the doctors in the form of gifts like drug samples, lunches, foreign visits, clinic or home decorations, and accessories, etc. recommendations: there are no boundaries marked for the doctors in acceptance of gifts from pharmaceutical companies. the regulations to monitor the relationship of doctors with the pharmaceutical companies are so frail that they are unable to stop this catastrophic situation. similarly, it was also found that the understandings of ethical codes and considerations are so meager. there is a dire need to incorporate certain bioethics and the regulations regarding these types of relationships with pharmaceutical companies in the curriculum of medical education so that our future doctors will be able to tackle the inappropriate policies of these pharmaceutical companies. monitoring of mal-practioner is important and need of the day. references 1. moynihan r. who pays for pizza? redefining the relationships between doctors and drug companies. bmj, 2003;326:1189-1192. doi: 10.1136/bmj.326.7400.1189. 2. imran asif, shehzad amin. the impact of doctor–pharma relationships on prescribing practice. journal of basic & applied sciences, 2012, 8, 174-180 doi: http://dx.doi.org/10.6000/1927‐5129.2012.08.01.20 3. shahuingole, radha yegnanarayan. international journal of pharma sciences and research (ijpsr), vol.2(2), 2011, 49-57 4. lexchin j. what information do physicians receive from pharmaceutical representatives? can fam physician, 1997; 43: 941-5. 5. wazana a. physicians and the pharmaceutical industry, is a gift ever just a gift? jama, 2000; 283: 373-80. doi: 10.1001/jama.283.3.373 6. greenberg rd. conflicts of interest: can a physician serve two masters? clin dermatol, 2012;30:160–73. https://doi.org/10.1016/j.clindermatol.2011.06.003 7. robbins nm. ethical issues pertaining to conflicts of interest between neurologists and the pharmaceutical and medical device industries. semin neurol.2018; 38:589–98. doi: https://doi.org/10.1055/s-0038-1668081 8. fadlallah r, alkhaled l, brax h, nasser m, rajabbik mh, nass h, et al. extent of physician-pharmaceutical industry interactions in lowand middle-income countries: systematic review. eur j public health.2018;28:224–30. doi: https://doi.org/10.1093/eurpub/ckx204 9. green mj, masters r, james b, simmons b, lehman e. do gifts from the pharmaceutical industry affect trust in physicians? fam med.2012; 44:325–31. 10. lexchin j. interactions between physicians and the pharmaceutical industry: what does the literature say? cmaj.1993;149:1401–7. 11. mohammed saud almasri et al, ethical considerations in doctors & pharmaceutical industries relationship: a narrative review. 2020;4(1):244–252. doi: 10.24911/ijmdc.511572794591 12. wilkes ms, bell ra, kravitz rl. direct-to-consumer prescription drug advertising: trends, impact, and implications. health aff (millwood). 2000; 19:110–28. doi: 10.1377/hlthaff.19.2.110 13. saito s, mukohara k, bito s. japanese practicing physicians' relationships with pharmaceutical representatives: a national survey. plos one. 2010;5: 12193. doi: https://doi.org/10.1371/journal.pone.0012193 329 journal of rawalpindi medical college (jrmc); 2022; 26(2): 321-329 14. mckinney wp, schiedermayer dl, lurie n, simpson de, goodman jl, rich ec. attitudes of internal medicine faculty and residents toward professional interaction with pharmaceutical sales representatives. jama.1990;264:1693–7. doi: 10.1001/jama.1990.03450130065028 15. imran asif and shehzad amin. the impact of doctor– pharma relationships on prescribing practice. journal of basic & applied sciences, 2012, 8, 174-180. doi: http://dx.doi.org/10.6000/1927‐5129.2012.08.01.20 16. marisa d. a. amir j. sualeha s. and nikolina a. the ethics of pharma–physician relations in pakistan: “when in rome”, ethics & behavior, 2019: 29:6, 473-489. doi: 10.1080/10508422.2018.1481751 17. ia raja and chaudary mr. “islam and medical ethics.” actaneurochir 74(1999), 29-34. doi: 10.1007/978-3-21133303-7_3 18. hneine b, racha f, lara ak, hala n, and elie aa. association between physicians’ interaction with pharmaceutical companies and their clinical practices: a systematic review and metaanalysis. plos one; 2017; doi: https://doi.org/10.1371/journal.pone.0175493 19. mustafa a. alssageer & stefan r. kowalski (2012) doctors’ opinions of information provided by libyan pharmaceutical company representatives, libyan journal of medicine, 7:1. doi: https://doi.org/10.3402/ljm.v7i0.19708 20. deborah k. salomeh k. and joseph s. r. physician attitudes toward industry a view across the specialties. arch surg. 2010;145(6):570-577. doi: 10.1001/archsurg.2010.75 21. tabinda a, aiesha i, faisal s and fahad s. knowledge and perception about bioethics: a comparative study of private and government medical college students of karachi pakistan. journal of family medicine and primary care., 2021; 10(3); 1161-1166. doi: 10.4103/jfmpc.jfmpc_103_21 480 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 original article sub-categorization of pediatric small round blue cell tumors using immunohistochemistry muhammad mudassar1, shireen hamid2, muhammad sarwar zia3, sadia hameed4, muhammad usman5, muhammad asif aleem6 1 associate professor, pathology department, independent medical college, faisalabad. 2 assistant professor, pathology department, independent medical college, faisalabad. 3 associate professor, anatomy department, gujranwala medical college, gujranwala. 4 professor (ex) umdc, faisalabad & consultant pathologist, meezan private lab, faisalabad. 5 house officer, jinnah hospital, lahore. 6 associate professor, pediatrics department, continental medical college, lahore. author’s contribution 1 conception of study 1,3 experimentation/study conduction 2,5,6 analysis/interpretation/discussion 1,2 manuscript writing 3,4,6 critical review 4 facilitation and material analysis corresponding author dr. muhammad mudassar, associate professor, pathology department, independent medical college, faisalabad email: drmudassarmajeed@gmail.com article processing received: 26/03/2022 accepted: 09/09/2022 cite this article: mudassar, m., hamid, s., zia, m.s., hameed, s., usman, m., aleem, m.a. subcategorization of pediatric small round blue cell tumors using immunohistochemistry. journal of rawalpindi medical college. 30 sep. 2022; 26(3): 480486. doi: https://doi.org/10.37939/jrmc.v26i3.1921 conflict of interest: nil funding source: nil access online: abstract introduction: the category of small round blue cell tumors includes neoplasms that are undifferentiated and contain similar-looking growth of small round blue cells having bigger nuclear size as compared to the cytoplasm (high n/c). it includes non-hodgkins lymphoma, synovial sarcoma, ewings sarcoma/ primitive neuroectodermal tumor, rhabdomyosarcoma, hepatoblastoma, retinoblastoma, neuroblastoma, neuroendocrine carcinoma, nasopharyngeal carcinoma, desmoplastic small round cell tumor, dysgerminoma, and wilm's tumor. immunohistochemistry can be very helpful in the accurate diagnosis of this diverse group of tumors. objective: the objective of the study is to sub-categorize pediatric malignant small round blue cell tumors using immunohistochemistry. study design: descriptive cross-sectional study setting: meezan private lab, faisalabad, pakistan duration of study: 4 years, from january 2017 to december 2020. sample size: 46 cases. sampling technique: non-probability purposive sampling materials and methods: 46 cases, which fulfilled the inclusion and exclusion criteria were selected for the study. all these cases were subjected to immunohistochemistry. the ihc technique used was based on the peroxidase anti-peroxidase (pap) method. based on site and morphological clues, initially leukocyte common antigen (lca), myogenin, cytokeratin (ck), desmin, chromogranin, neuron specific enolase (nse), s-100, smooth muscle actin (sma), and cd99 were used. further immune stains panels were used afterward, as and when needed like cd20, cd3, cd30, bcl2, cd117, ki-67, tdt, synaptophysin, sma, cd56, melan a, hmb45, and wt1. results: among all the malignant small round cell tumors, rhabdomyosarcoma was the highest in frequency i.e. 8 (17.4%), followed by ewing’s sarcoma/pnet 7(15.2%). both diffuse large b cell lymphoma and neuroblastoma were 5 each in number (10.9%). non-hodgkins lymphoma as a whole was 13 (28.2%), including 5 cases (10.9%) of diffuse large b cell lymphoma, 4 cases (8.7%) of t lymphoblastic lymphoma, 3 cases (6.5%) of burkitt’s lymphoma, and only 1 case (2.2%) of nk/t cell lymphoma. conclusion: immunohistochemistry is an essential tool for accurate sub-categorization of pediatric small round blue cell tumors. keywords: malignant small round blue cell tumor, msrbct, pediatric round blue cell tumor, immuno-histochemistry. 481 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 introduction round blue cell tumor (rbct) is a diagnosis that can be a lifesaver for the working pathologist since it gives a clue to the malignant nature of the neoplasm, but practically speaking, it becomes a dilemma for the treating physician. most of the time, it leads to a series of investigations and consultations, which not only increases the burden on medical resources but also delays the proper management of the patients.1 on routine hematoxylin and eosin (h & e) staining, many tumors can look alike in their morphology. so much so, that even with expert eyes, it becomes nearly impossible to give a definite diagnosis in all cases. one such scenario is small round blue cell tumors. these are neoplasms that are highly undifferentiated and contain similar-looking growth of small round cells. individual cells depict increased basophilic staining and a high n/c ratio.2 they are further characterized by sheets of primitive-looking cells lacking a clue of the cell of origin at routine h & e.3 following tumors are included in the differential diagnosis (d/d) of malignant small round blue cell tumors (msrbct). non-hodgkin lymphoma, retinoblastoma, lymphoblastic lymphoma, hepatoblastoma, ewing sarcoma/primitive neuroectodermal tumor, neuroblastoma, synovial sarcoma, wilm's tumor, neuroendocrine carcinoma, osteosarcoma, desmoplastic small round cell tumor, nasopharyngeal carcinoma, dysgerminoma, mesenchymal chondrosarcoma, dendritic cell tumor, malignant melanoma (small cell variant) and rhabdomyosarcoma.2,4,5 this list can be more gigantic if we consider site-related blue cell tumors.6–8 these tumors are more usually diagnosed in the pediatric age group, nevertheless, they are seen in adults also.9,10 accurate sub-categorization and the final diagnosis are highly important because the treatment of each tumor can be unique. for example, chemotherapy is the mainstay of treatment in sarcomas and lymphoma. anti-cd20 therapy is the mainstay option in cd20positive lymphoma. melanomas are treated by surgery and interferon therapy. chemotherapy is the treatment of choice in extra-gonadal germ cell tumors and neuroendocrine tumors. moreover, desmoplastic small round cell tumors are treated with a totally different approach.4,11–13 therefore, many diagnostic modalities are in practice for precise diagnosis of this entity, including immunohistochemistry (ihc)10, electron microscopy, fish (fluorescence in situ hybridization)3, cytogenetic studies and molecular techniques14 like reverse transcriptase polymerase chain reaction.5,15 cytogenetic techniques are best for confirmatory diagnosis but they are too costly for poor folks.16 so immunohistochemistry remains the mainstay in these setups. pakistan is also a resource-poor country, where access to sophisticated diagnostic modalities is limited to a few setups, which are inaccessible to the common public. faisalabad is the third largest city in pakistan, but it sophisticated laboratory setups, and most of the malignant challenging cases are sent to referral labs located in lahore or karachi. our rationale is to use immunohistochemistry at the local level to subcategorize this diverse group as a minimum requirement and thereby facilitate prompt management and treatment. objective: the objective of the study is to sub-categorize pediatric small round blue cell tumors using immunohistochemistry. materials and methods study design: descriptive cross-sectional study. setting: meezan private lab, faisalabad, pakistan. duration of study: 4 years, from january 2017 to december 2020. sample size: 46 cases of pediatric malignant small round blue cell tumor. sampling technique: non-probability purposive sampling inclusion criteria:  all cases up to age 15, are diagnosed as malignant small round blue cell tumor on routine hematoxylin and eosin staining. exclusion criteria:  autolyzed tissue  immuno-histochemistry could not be done, because of technical or logistics issues. data collection procedure after ethical approval, 46 cases, which fulfilled the inclusion and exclusion criteria were selected for the study. all these cases were subjected to immunohistochemistry. the ihc technique used was based on the peroxidase anti-peroxidase (pap) method. the protocol used is as follows: 1. cut tissue sections 2.0 – 4.0 microns thick and spread wrinkle-free on the slide. 2. put the slides on a hot plate 60°-65° for 45 to 50 min. 3. for deparaffinisation, gave 3-changes of xylene 5 min each. 482 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 4. rehydrated the tissue with graded isopropanol (100%, 80%, 70%, 50%) 5 min each. 5. put distilled water for 3 to 5 min two changes. 6. then put in antigen retrieval solution (target retrieval solution) in kortil coplin jar: dilution 1:50. ph was 9.0 for cd5, cd10, cd3, cd30, cd99 and 2.5 ph for myogenin, ki-67, wt1. all remaining had ph 6. 7. put in the water bath at 99.5° for 45 mins 1 hour. 8. took out from water bath and put at room temperature. 9. then washed in wash buffer solution for 10 min, two changes. dilution 1:20 (ph 7.6) 10. poured peroxidase blocking reagent on slide covering the tissue area and put in humidity chamber for 10 min. 11. washed again in wash buffer for 10 min, two changes. 12. poured 50 ul of primary antibody on tissue area and put in humidity chamber for 45 min to 1 hour (as per literature). 13. again washed in wash buffer for 10 min, two changes. 14. poured 50 ul of the secondary antibody (hrp) on the tissue area and put in a humidity chamber for 45 min to 1 hour. 15. washed again in wash buffer for 10 min, two changes. 16. added dabe chromogin 50 ul on tissue area for 3-5 min (dabe chromogin 50 ul and substrate 1 ml). 17. washed in distilled water for 3 to 5 min. 18. counter-stained with hematoxylin by 3-5 dips. 19. washed in tap water for 3 to 5 min. 20. put the slides rack in proponol for 3 cycles of 5 min, 3 min, and 5 min respectively. 21. air dried and given 3 cycles of xylene 5 min, 3 min, and 5 min respectively. 22. mounting with dpx (disrtenedibutyl-pthalate xylene) and then observed the slide. based on site and morphological clues, initially leukocyte common antigen (lca), myogenin, cytokeratin (ck), desmin, chromogranin, neuronspecific enolase (nse), s-100, smooth muscle actine (sma) and cd99 were used. further immune stains panels were used afterward, as and when needed like cd20, cd3, cd30, bcl2, cd117, ki-67, tdt, synaptophysin, sma, cd56, melan a, hmb45, and wt1. the results were analyzed independently by 2 histopathologists. staining intensity was graded as negative, or weak, moderate to strong positive. the extent of positive ihc reaction was scored as focal (< 10%), patchy (10-50%), or diffuse (>50%)17, and the final diagnosis was rendered. data analysis: all the collected information was entered and analyzed using spss version 24. the qualitative variables like gender, site, and diagnosis were presented by calculating frequency and percentage. results out of 46 cases of msrbct, rhabdomyosarcoma was the highest in frequency i.e. 8 (17.4%), followed by ewing’s sarcoma/pnet 7 (15.2%). both diffuse large b cell lymphoma and neuroblastoma were 5 each in number (10.9%). non-hodgkins lymphoma as a whole, was 13 (28.2%), including 5 cases (10.9%) of diffuse large b cell lymphoma, 4 cases (8.7%) of t lymphoblastic lymphoma, 3 cases (6.5%) of burkitt’s lymphoma, and only 1 case (2.2%) of nk/t cell lymphoma. (table 1) table 1: frequency of subcategories of malignant small round blue cell tumors tumors frequency percent diffuse large b cell lymphoma 5 10.9 t lymphoblatic lymphoma 4 8.7 burkitt's lymphoma 3 6.5 nk/t cell lymphoma 1 2.2 nasopharyngeal carcinoma 1 2.2 ewing's sarcoma/pnet 7 15.2 rhabdomyosarcoma 8 17.4 synovial sarcoma 4 8.7 malignant melanoma 1 2.2 neuroblastoma 5 10.9 germ cell tumor 3 6.5 rhabdoid tumor 1 2.2 desmoplatic small round cell tumor 1 2.2 round blue cell tumor, unclassified 2 4.3 total 46 100.0 common pediatric age group for msrbct is below 5 years of age i.e. 22 (47.9%) and least commonly from 13 to 15 years of age i.e. 10 (21.7%). (table 2) 483 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 table 2: frequency of different categories of malignant small round blue cell tumors (msrct) in different age groups differential diagnosis of round blue cell tumor age groups total 1 month to 5 years ˃5 to 12 years ˃ 12 to 15 years diffuse large b cell lymphoma 1 4 0 5 t lymphoblatic lymphoma 1 1 2 4 burkitt's lymphoma 3 0 0 3 nk/t cell lymphoma 0 1 0 1 nasopharyngeal carcinoma 0 0 1 1 ewing's sarcoma/pnet 2 3 2 7 rhabdomyosarcoma 6 1 1 8 synovial sarcoma 0 1 3 4 malignant melanoma 0 1 0 1 neuroblastoma 4 0 1 5 germ cell tumor 2 1 0 3 rhabdoid tumor 1 0 0 1 desmoplatic small round cell tumor 1 0 0 1 round blue cell tumor, unclassified 1 1 0 2 total 22 (47.9%) 14 (30.4%) 10 (21.7%) 46 (100%) if we consider the site of origin, then 24% of cases were biopsied from the cervical lymph node, followed by abdominal mass (11%) and retroperitoneum (9%). (table 3) table 3: frequency of individual categories and their site of origin tumors frequency site of origin diffuse large b cell lymphoma 5 cervical lymph node (1), intestine (1), abdominal mass (2), retroperitoneum (1), t lymphoblatic lymphoma 4 cervical lymph node (2), nasopharynx (2), burkitt's lymphoma 3 liver mass (1), nasopharynx (1), intestine (1) nk/t cell lymphoma 1 abdominal mass (1) nasopharyngeal carcinoma 1 cervical lymph node (1) ewing's sarcoma/pnet 7 cervical lymph node (2), bone (1), chest mass (2), pelvic mass (1), wrist joint (1) rhabdomyosarcoma 8 cervical lymph node (3), inguinal lymph node (1), liver mass (1), testis (1), urinary bladder mass (1), eyelid (1) synovial sarcoma 4 pelvic mass (1), thigh mass (3) malignant melanoma 1 scalp mass (1) neuroblastoma 5 cervical lymph node (2), retroperitoneum (3), germ cell tumor 3 testis (1), abdominal mass (1), ovarian mass (1) rhabdoid tumor 1 kidney mass (1) desmoplatic small round cell tumor 1 abdominal mass (1) round blue cell tumor, unclassified 2 left ankle (1), pelvic mass (1) total 46 it was noticed in the present study, that some tumors were only seen in males like dlbcl, burkitt’s, and desmoplastic small round cell tumors, while some were only seen in females like nk/t cell lymphoma and malignant melanoma. higher percentages of rhabdomyosarcoma, ewings, and neuroblastoma were present in males and germ cell tumors were frequent in females. (figure 1) 484 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 figure 1: gender distribution among malignant small round blue cell tumors in our study, one case from the ankle and 2nd case from the pelvic area remained undiagnosed with available panels of immunostains discussion numerous studies have mentioned the benefits of ihc for confirmatory diagnosis of pediatric small round blue cell tumors.2,5,17–23 moreover, thomas et al. reported that “immunohistochemistry changed the diagnosis of 24% of the cases”.9 in our article, we used established panels of antibodies that have been used by other studies in the literature.2,4,10,16,21 however, some research papers, used novel antibodies like pax719, nkx2.217, bcor24, etv425, etc for differential diagnosis, claiming that they are better and specific. nevertheless, financial limitations did not allow us to use these novel antibodies. in the current study, lymphomas were most frequent, when they were grouped together i.e. 13(28.2%) out of 46 cases. it included 5 cases (10.9%) of diffuse large b cell lymphoma, 4 cases (8.7%) of t lymphoblastic lymphoma, 3 cases (6.5%) of burkitt’s lymphoma, and 1 case (2.2%) t/nk cell lymphoma (refer to table 1). this fact was also reported by thomas et al9 and patel et al.10 nevertheless, the exact frequency was different in all articles. this might be due to racial and geographical differences. contrary to it, round cell tumors of the sinonasal location showed more carcinomas than lymphomas5, but this is a locationbased difference since other studies also highlighted this particular aspect.6,26 based on this fact, it can be narrated that ihc panels for msrbct, should include lymphoma panels like lca (cd45), cd30, cd20, cd3, cd5, tdt, cyclin d1, and ki-67, etc. other specific markers like cd10, bcl2, and alk can be added to the above panel, if and when needed. if we consider individual tumors, then rhabdomyosarcoma is the highest tumor in our study 8/46(17.4%). out of a total of 21 soft tissue tumors in the current study, 8 are rhabdomyosarcoma with a percentage of 38%. it is consistent with other studies, which mentioned that it has an incidence of 40 % and is the most frequent pediatric soft tissue malignancy.2,27 site of biopsy for rhabdomyosarcoma was variable i.e. cervical region3, and 1 case each from the inguinal region, urinary bladder, liver, testis, and eyelid. and this particular aspect has been reported by other studies also.2,27–29 ewing’s/pnet is 3rd in the list comprising of 7 cases (15.2%), biopsied mostly from the cervical area, followed by the extra-skeletal site of the chest. thigh and shoulder, as the extra-skeletal site was also mentioned by patel et al.4 shi wei et al. reported that “ewing’s/pnet is 2nd most common bone malignancy in children and young adults with 68% incidence and 20% could be extra skeletal”.3 the reason for putting ewing’s and pnet in one group is 485 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 that they depict the same morphology and cytogenetic alteration. it has been noticed that although ewing’s sarcoma of bone is mostly undifferentiated, pnet shows some degree of neuro-ectodermal differentiation.30 synovial sarcoma is 4(8.7%) in number and biopsy is taken from pelvic mass1 and thigh mass.3 many other studies also mentioned the site of origin of synovial sarcoma, near the joints like the thigh and knee.2,17,31 neuroblastoma is 5 out of 46 in the current study with 10.9%. sharma et al reported it as the “3rd most malignant extracranial solid tumor of childhood, arising from primitive neural crest cells”.2 in our research, 3/5 of neuroblastoma cases were taken from retroperitoneum, which is also highlighted by machado i et.al.17 in our study, there was only 1 (2.2%) case of desmoplastic small round cell tumor (dsrct), arising from the abdominal tissue. bulbul et al. also exclaimed that “dsrct has a predilection for abdominal and pelvic cavity”.13 it was noticed that some tumors were only seen in males like dlbcl, burkitt’s, and desmoplastic small round cell tumor, while some were only seen in females like nk/t cell lymphoma and malignant melanoma. higher percentages of rhabdomyosarcoma, ewings, and neuroblastoma were present in males and germ cell tumors were common in females (figure 1). likewise, thompson et al and shi wei et.al. quoted slight male predominance of ewing’s/pnet and neuroblastoma.3,5 however, the less number of cases limits the ability to clearly define gender differences in the current study. regarding age group, since these msrbcts are more commonly seen in children and younger age groups, so we also found that 22 (47.9%) patients were within 5 years of age at the time of diagnosis. this particular aspect has been shown by many studies.9,16 two cases (4.3%), ankle and pelvic area respectively, could not be classified even after the use of all available antibodies. this aspect concurs with patel et al10, in which the percentage of unclassified cases was 3.75%. the cause in our study was unequivocal ihc results and the unavailability of novel antibodies. to solve this matter, wider ihc panels and sophisticated techniques like em, cytogenetic and molecular techniques should be used for further categorization. limitation of study limited resources and a lack of cytogenetics studies hindered the proper sub-categorization of some of our cases. moreover, newer ihc antibodies, which are more promising and specific, as reported in a few studies were not used because of economic issues. we suggest future research should be performed, to solve above stated deficiencies. conclusion for true and accurate sub-categorization of pediatric small round blue cell tumors, immunohistochemistry is an essential diagnostic tool, which should be used in all cases. acknowledgements the authors are grateful to the laboratory staff of fatima memorial medical college lab for performing immunohistochemistry. we also wholeheartedly thank the pathologist and lab staff of meezan lab, faisalabad for their logistics support and never-ending cooperation. references 1. gazula s, rani vl, jonathan g, kumar nn. extraskeletal ewing’s sarcoma masquerading as infantile benign neck mass. j indian assoc pediatr surg. 2019;24(3):209. 2. sharma s, kamala r, nair d, ragavendra tr, mhatre s, sabharwal r, et al. round cell tumors: classification and immunohistochemistry. indian j med paediatr oncol [internet]. 2017 [cited 2019 jan 14];38(3):349. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5686981/ 3. wei s, siegal gp. round cell tumors of bone : an update on. adv anat pathol [internet]. 2014 [cited 2019 jan 14];21(5):359–72. available from: https://journals.lww.com/anatomicpathology/abstract/2014/09000/ro und_cell_tumors_of_bone__an_update_on_recent.5.aspx 4. patel a, patel m, bhagat v, naik k. role of immunohistochemistry in the differential diagnosis of malignant small round cell tumor: a study of 38 cases. int j res med sci [internet]. 2015 [cited 2019 jun 17];3(12):3833–9. available from: https://pdfs.semanticscholar.org/8791/92784eb4f7236ee61e6f685807e bf5dab9f8.pdf 5. thompson ldr. small round blue cell tumors of the sinonasal tract: a differential diagnosis approach. mod pathol [internet]. 2017 [cited 2019 jun 17];30(s1):s1–26. available from: https://www.nature.com/articles/modpathol2016119 6. rooper lm, bishop ja. sinonasal small round blue cell tumors. surg pathol clin [internet]. 2016 [cited 2019 jan 14];10(1):103–23. available from: https://www.sciencedirect.com/science/article/pii/s187591811630092 7 7. narayanan g, rajan v, preethi tr. primitive neuroectodermal tumors of the kidney. baylor univ med cent proc [internet]. 2017 apr 11 [cited 2019 jun 17];30(2):205–8. available from: https://www.tandfonline.com/doi/full/10.1080/08998280.2017.11929 588 8. tsukamoto y, futani h, yoshiya s, watanabe t, kihara t, matsuo s, et al. primary undifferentiated small round cell sarcoma of the deep abdominal wall with a novel variant of t(10;19) cic-dux4 gene fusion. pathol res pract [internet]. 2017 [cited 2019 jun 17];213(10):1315–21. available from: https://www.sciencedirect.com/science/article/pii/s034403381730255 8 9. thomas j, aa o-e. immunocytochemistry in the diagnosis of small blue cell tumours of childhood. west afr j med [internet]. 2006 [cited 486 journal of rawalpindi medical college (jrmc); 2022; 26(3): 480-486 2019 jun 17];25(3):199–204. available from: https://www.ajol.info/index.php/wajm/article/view/28278 10. patel mm, dhandha zb, italiya sl, shah mb, kaptan kr, mansuri bm, et al. role of immunohistochemistry in differential diagnosis of round cell tumor. indian j res. 2013;3(5):217–20. 11. frezza am, benson c, judson ir, litiere s, marreaud s, sleijfer s, et al. pazopanib in advanced desmoplastic small round cell tumours: a multiinstitutional experience. clin sarcoma res [internet]. 2014 dec 29 [cited 2019 jan 14];4(1):7. available from: http://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/204 5-3329-4-7 12. menegaz ba, cuglievan b, benson j, camacho p, lamhamedi‐cherradi s, leung ch, et al. clinical activity of pazopanib in patients with advanced desmoplastic small round cell tumor. oncologist [internet]. 2018 [cited 2019 jun 17];23(3):360–6. available from: http://theoncologist.alphamedpress.org/content/23/3/360.short 13. bulbul a, fahy bn, xiu j, rashad s, mustafa a, husain h, et al. desmoplastic small round blue cell tumor: a review of treatment and potential therapeutic genomic alterations. sarcoma [internet]. 2017 [cited 2019 jun 17];2017:1–12. available from: https://www.hindawi.com/journals/sarcoma/2017/1278268/abs/ 14. koelsche c, hartmann w, schrimpf d, stichel d, jabar s, ranft a, et al. array-based dna-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information. mod pathol [internet]. 2018 [cited 2019 jun 17];31(8):1246–56. available from: https://europepmc.org/abstract/med/29572501 15. owosho aa, estilo cl, huryn jm, zhang l, fletcher cdm, antonescu cr. head and neck round cell sarcomas: a comparative clinicopathologic analysis of 2 molecular subsets: ewing and cicrearranged sarcomas. head neck pathol [internet]. 2017 dec 23 [cited 2019 jun 17];11(4):450–9. available from: http://link.springer.com/10.1007/s12105-017-0808-z 16. qiaoxin li, wenli cui, gulinaer abulajiang, yuqing ma, xia liu, wei zhang, et al. application of immunohistochemistry in the diagnosis of small round blue-cell tumors of soft tissue. clin lab [internet]. 2013 [cited 2019 jan 14];59(01+02/2013). available from: https://www.clinlab-publications.com/article/1564 17. machado i, yoshida a, morales mgn, abrahão-machado lf, navarro s, cruz j, et al. review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, “undifferentiated small round cell tumors”. a clinicopathologic, immunophenotypic and molecular analysis. ann diagn pathol [internet]. 2018 jun [cited 2019 jun 18];34:1–12. available from: http://www.ncbi.nlm.nih.gov/pubmed/29661713 18. magro g, brancato f, musumeci g, alaggio r, parenti r, salvatorelli l. cyclin d1 is a useful marker for soft tissue ewing’s sarcoma/peripheral primitive neuroectodermal tumor in children and adolescents: a comparative immunohistochemical study with rhabdomyosarcoma. acta histochem [internet]. 2015 [cited 2019 jan 14];117(4–5):460–7. available from: https://www.sciencedirect.com/science/article/pii/s006512811500034 3 19. charville gw, varma s, forgó e, dumont sn, zambrano e, trent jc, et al. pax7 expression in rhabdomyosarcoma, related soft tissue tumors, and small round blue cell neoplasms. am j surg pathol [internet]. 2016 [cited 2019 jan 14];40(10):1305–15. available from: https://www.ingentaconnect.com/content/wk/ajsp/2016/00000040/0 0000010/art00002 20. mccuiston a, bishop ja. usefulness of nkx2.2 immunohistochemistry for distinguishing ewing sarcoma from other sinonasal small round blue cell tumors. head neck pathol [internet]. 2018 mar 14 [cited 2019 jun 17];12(1):89–94. available from: http://link.springer.com/10.1007/s12105-017-0830-1 21. yamada y, kuda m, kohashi k, yamamoto h, takemoto j, ishii t, et al. histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with cic-dux4 and bcor-ccnb3 fusion genes. virchows arch [internet]. 2017 apr 14 [cited 2019 jun 17];470(4):373–80. available from: https://link.springer.com/article/10.1007/s00428-017-2072-8 22. hung yp, lee jp, bellizzi am, hornick jl. phox2b reliably distinguishes neuroblastoma among small round blue cell tumours. histopathology [internet]. 2017 nov [cited 2019 jun 17];71(5):786–94. available from: http://doi.wiley.com/10.1111/his.13288 23. magro g, salvatorelli l, alaggio r, d’agata v, nicoletti f, di cataldo a, et al. diagnostic utility of cyclin d1 in the diagnosis of small round blue cell tumors in children and adolescents. hum pathol [internet]. 2017 [cited 2019 jan 14];60:58–65. available from: https://www.sciencedirect.com/science/article/pii/s004681771630264 7 24. kao yc, sung ys, zhang l, jungbluth aa, huang sc, argani p, et al. bcor overexpression is a highly sensitive marker in round cell sarcomas with bcor genetic abnormalities. am j surg pathol [internet]. 2016 [cited 2019 jan 14];40(12):1670–8. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5106294/ 25. le guellec s, velasco v, pérot g, watson s, tirode f, coindre jm. etv4 is a useful marker for the diagnosis of cic-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions. mod pathol [internet]. 2016 [cited 2019 jan 14];29(12):1523–31. available from: https://www.nature.com/articles/modpathol2016155 26. thompson ldr, franchi a. new tumor entities in the 4th edition of the world health organization classification of head and neck tumors: nasal cavity, paranasal sinuses and skull base. virchows arch [internet]. 2018 mar 25 [cited 2019 jun 17];472(3):315–30. available from: https://link.springer.com/article/10.1007/s00428-017-2116-0 27. hibbitts e, chi y, hawkins ds, barr fg, bradley ja, dasgupta r, et al. refinement of risk stratification for childhood rhabdomyosarcoma using foxo1 fusion status in addition to established clinical outcome predictors: a report from the children’s oncology group. cancer med [internet]. 2019 oct 27 [cited 2020 apr 21];8(14):6437–48. available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.2504 28. córdoba rovira sm, inarejos clemente ej. rabdomiosarcoma infantil. radiologia [internet]. 2016 nov 1 [cited 2020 apr 21];58(6):481–90. available from: https://linkinghub.elsevier.com/retrieve/pii/s0033833816301400 29. bhaskar bhuvan l, radhakrishnan v, raja a, ganesarajah s, sagar t. outcomes in rhabdomyosarcoma: experience from a tertiary cancer center in india. cancer res stat treat. 2019;2(1):4. 30. machado i, navarro l, pellin a, navarro s, agaimy a, tardío jc, et al. defining ewing and ewing-like small round cell tumors (srct): the need for molecular techniques in their categorization and differential diagnosis. a study of 200 cases. ann diagn pathol [internet]. 2016 [cited 2019 jan 14];22:25–32. available from: https://www.sciencedirect.com/science/article/pii/s109291341630029 6 31. scheer m, blank b, bauer s, vokuhl c, stegmaier s, feuchtgruber s, et al. synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups: a report of the cooperative weichteilsarkom studiengruppe (cws). j cancer res clin oncol. 2020 apr 1;146(4):953–60. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 237-240 237 original article haemodynamics during percutaneous nephrolithotomy in spinal anaesthesia with two doses of hyperbaric bupivacaine (0.75%) muhammad ali, muhammad shafiq, aleena hassan department of anaesthesia, benazir bhutto hospital and rawalpindi medical university, rawalpindi abstract background: to compare variation in haemodynamics during percutaneous nephrolithotomy in spinal anaesthesia with two doses of hyperbaric bupivacaine (0.75%). methods: in this randomized comparative study 60 patients, undergoing percutaneous nephrolithotomy, were included. it was done to compare the variation in haemodynamic parameters after spinal anaesthesia using two different doses of local anaesthetic before and after keeping patients in prone position. patients were divided into two groups: group a(n=30) (22.5 mg hyperbaric bupivacaine 0.75%) and group b (n=30)(30 mg hyperbaric bupivacaine 0.75%). spinal block was performed in sitting position. hemodynamic measurements were carried out at different time points while patients were in supine and prone position. results: decrease in heart rate was significant in group b than in group a after 10 minutes of spinal block while in supine position (p<0.001) and the drop in heart rate was significant statistically in group b when patients were turned to prone position (p<0.001).systolic and diastolic blood pressures decreased in group b at 5 and 10 minutes in supine position which further decreased following prone positioning and the decrease was highly significant statistically(p=<0.001). conclusion: 22.5 mg of injection hyperbaric bupivacaine is haemodynamically safer as compared to 30 mg of the same drug during spinal anaesthesia in percutaneous nephrolithotomy. key words: haemodynamics, spinal anaesthesia, percutaneous nephrolithotomy introduction monitoring haemodynamics during surgeries is one of the most important tasks that anaesthesiologists have to do in the operating theatres. perioperative anaesthesia has made many different and difficult surgeries possible with significantly reduced morbidity and mortality. among those, one of the procedures in the treatment of nephrolithiasis is percutaneous nephrolithotomy (pcnl). pcnl is the treatment of choice for large renal stones, staghorn calculi, and stones that are multiple or resistant to shock wave lithotripsy.1,2 anaesthesia for pcnl can be general or regional.3 regional anaesthesia has many advantages over general anaesthesia in the abdomen and extremities including avoidance of anaphylaxis that may be caused by the latter due to the use of multiple drugs.4,5 complications of general anaesthesia such as pulmonary (atelectasis), vascular, and neurologic disorders (brachial nerve injury or spinal cord injury), or airway related complications especially during change of the position are more likely than of spinal anesthesia.6,7surgery performed in prone position poses anaesthetic challenges in two ways: prone positioning either following general or regional anaesthesia brings about hemodynamic alterations due to reduction in cardiac index and control of airway may not be easy in prone position as compared to supine position. meticulous and careful delivery of anaesthesia and vigilant monitoring during intraoperative period avoids this difficulty. surgeries are successfully carried out keeping patients prone following careful deliberation of spinal anaesthesia. this obviates the need of endotracheal intubation and avoids multiple drugs used in general anaesthesia. patients are able to maintain their airway on their own as they remain awake and conversant during the procedure. the exact volume of local anaesthetic for spinal anaesthesia to patients going to be kept in prone position has not yet been clearly described.8 shrestha br, et al investigated to find out the level of sensory block in supine and prone position in two groups of patients undergoing pcnl in spinal anaesthesia with two different volumes of hyperbaric journal of rawalpindi medical college (jrmc); 2017;21(3): 237-240 238 bupivacaine. 8 they concluded that three ml of hyperbaric bupivacaine for spinal anaesthesia is good enough for the surgery in prone position with relatively more hemodynamic safety as compared to the four ml of the same drug. patients and methods this prospective randomized comparative study was conducted by the department of anaesthesia at benazir bhutto hospital, rawalpindi, from august 2016 till january 2017.the inclusion criteria was all the adult patients undergoing percutaneous nephrolithotomy, asa i and ii, patients having body weight of 45-80 kg and with a minimum height of height of 150 cm. patients with history of coagulopathy, ingestion of antiplatelet drugs and infection on their back at the site of lumbar puncture, patients with deformed spine, who refused for spinal anaesthesia or cases with ineffective or partial spinal block not reaching the desired sensory level of t5-6 and needing general anaesthesia afterwards, were excluded. randomization was done through random number list already generated using spss software version 22 equally but randomly allocating 60 patients either group a for bupivacaine dose 22.5 mg or group b for bupivacaine 30 mg. thirty patients in group a received 22.5 mg of hyperbaric bupivacaine (0.75%) for spinal anaesthesia , while 30 patients of group b received 30 mg of the same drug. spinal anaesthesia was given in sitting position with full aseptic precautions using 25 g whitacre spinal needle at l3-4 intervertebral space. patients were kept in supine position for some time. haemodynamic parameters were recorded at different time intervals of 5 and 10 minute following spinal block while they were supine and first 10 minute of prone positioning. to facilitate venous drainage and have abdomen free, two bolster rolls were kept at two different sitesone at the xiphisternum and other one at iliac crest level. heart rate less than 50/minute and mean arterial pressure (map) drop more than 30% of the baseline value were managed with anticholinergics and crystalloid/vasopressor (phenylephrine) respectively. results there were 42 male patients in the study while 18 patients were female (table 1). mean age in group a was 37.93±5.27. in group b mean age was 40.46±6.22 (table 2). the decrease in heart rate was significant in group b than in group a after 10 minutes of spinal block while in supine position (p<0.001) and the drop in heart rate was significant statistically in group b when patients were turned to prone position (p<0.001). more of anticholinergics were used to increase the heart rate in group b (table 3). the systolic blood pressure decreased in group b at 5 and 10 minutes in supine position which further decreased following prone positioning and the decrease was highly significant statistically(p=<0.001) (table 4). the diastolic blood pressure in group b followed a similar trend as that of systolic blood pressure with a decrease at 5 and 10 minutes supine and a further decrease following prone positioning and it was also highly significant statistically(p<0.001). more of vasopressors were used to increase the blood pressure in group b (table 5). table igender distribution in two groups male female group a 21 9 group b 21 9 table 2age distribution mean±sd parameter group a group b mean differr-ence pvalue significance age(ye ars) 37.93± 5.27 40.46± 6.22 2.53 .095 not significant table 3. heart rate per minute in two groups group baseline value at 5 min supine at 10 min supine at 10 min prone a 87±5.69 79±9.22 76±9.53 73±9.40 b 85±5.73 75±5.44 67±4.37 62±9.41 p-value 0.236 0.051 <0.001 <0.001 table 4.systolic blood pressure in mmhg in two groups group baseline value at 5 min supine at 10 min supine at 10 min prone a 132±7.36 118±9.38 110±9.35 98±6.35 b 133±6.75 109±8.75 97±7.26 88±5.50 p-value 0.549 <0.001 <0.001 <0.001 table 5. diastolic blood pressure in mmhg in two groups group baseline value at 5 min supine at 10 min supine at 10 min prone a 85±4.10 77±6.13 70±5.88 63±4.68 b 85±4.06 71±4.28 64±3.97 56±4.31 pvalue 0.777 <0.001 <0.001 <0.001 journal of rawalpindi medical college (jrmc); 2017;21(3): 237-240 239 discussion this study reveals that more number of patients receiving 30 mg local anaesthetic in spinal block demonstrated a significant decrease in heart rate, systolic and diastolic pressures as compared to the group receiving 22.5 mg of the drug. median age of patients in two groups was not different statistically. age difference may contribute in local anaesthetic distribution according to cameron ae et al 9 who stated that the greater the age the more cephalad the spread of the level of anaesthesia. 9gender distribution in two study groups was similar in this study, having male patients predominant in each group. sex of a patient has no direct effect on distribution of local anaesthetic solution in cerebrospinal fluid if all other factors involved in determining the distribution are kept constant.10 the technique, site and speed of injection, size and direction of bevel of spinal needle were kept constant for all patients in both groups in the study. these factors could have effect on the local anaesthetic spread in cerebrospinal fluid.11the local anaesthetic administered to intrathecal space gets fixed to its receptors ranging from 10 to 25 minutes after giving fixed maximum possible sensory height before regression of the block commences in due course of time.12 to perform pcnl the sensory height attained with 22.5 mg of hyperbaric bupivacaine was more than sufficient for the patients going to be positioned prone after 10 min of supine position with acceptable haemodynamic changes than with 30 mg of the same agent for spinal anaesthesia which could produce higher sensory and thereby autonomic blockade leading to clinically significant bradycardia and hypotension. the significant haemodynamic changes are further accentuated by the decreased cardiac index of prone position.13 there has been a finding that the physiologic impact of prone position on cardiorespiratory function is minor so long as the abdomen is not compressed.14 in our study there was more consumption of crystalloids, anticholinergics and vasopressors in patients of group b to correct the resulting decreased heart rate and blood pressure. this is in accordance with the study done by shrestha br et al.8spinal anaesthesia is relatively easy to perform, has many advantages over general anaesthesia and allows the surgery to take place in the best possible conditions.1517 there are certain possible risks of spinal anaesthesia for prone position surgery like potential for higher blocks, limited access to airway if patients are not fully awake, uncomfortable position for surgeries of long periods, need of repositioning if critical events occur and inconvenient if spinal anaesthesia does not work. questions arise what in case of cardiac arrest. the patient can be turned supine on to the trolley. literatures state that chest compressions in the prone position are possible and may generate higher systolic pressure and improve ventilation. 18,19 furthermore it is possible to defibrillate patients in the prone position with lateral pad positions.20 in this study none of the patients required repositioning or faced complications or failure of spinal blocks. nevertheless spinal anaesthesia allows early ambulation and enhanced recovery after surgery with adequate postoperative pain relief.21,22,23 studies are being conducted to explore other modalities of regional anaesthesia like combined spinal-epidural anaesthesia or epidural anaesthesia alone in pcnl.24,25 efficient and safe local anaesthetic doses in all these modalities need further studies. conclusion 22.5 mg of injection hyperbaric bupivacaine is hemodynamically safer as compared to 30 mg of the same drug during spinal anaesthesia in percutaneous nephrolithotomy. references 1. mehrabi s, shirazi k. results and complications of spinal anesthesia in percutaneous nephrolithotomy. urol j. 2010;7(1):22-25. 2. keoghane sr, cetti rj, rogers ae, walmsley bh. blood transfusion, embolisation and nephrectomy after percutaneous nephrolithotomy (pcnl). bju international. 2013 apr 1;111(4):628-32. 3. gonen m, basaran b. tubeless percutaneous nephrolithotomy: spinal versus general anesthesia. urol. j. 2014 ;11(1):121115. 4. movasseghi g, hassani v, mohaghegh mr, safaeian r. comparison between spinal and general anesthesia in percutaneous nephrolithotomy. anesth pain med. 2014 ;4(1): 112-15 5. cicek t, gonulalan u, dogan r, kosan m, istanbulluoglu o. spinal anesthesia is an efficient and safe anesthetic method for percutaneous nephrolithotomy. urology. 2014 ;83(1):50-55. 6. kuzgunbay b, turunc t, akin s, ergenoglu p. percutaneous nephrolithotomy under general versus com¬bined spinalepidural anesthesia. j endourol. 2009;23(11):1835–38. 7. karacalar s, bilen cy, sarihasan b. spinal-epidural anesthesia versus general anesthesia in the management of percu¬taneous nephrolithotripsy. j endourol. 2009;23(10):1591–97. 8. shrestha br, khadgi s, shrestha s. two different volume of local anaesthetic in subarachnoid block for minipercutaneous nephrolithotomy in prone position. journal of kathmandu medical college. 2012 dec ;(1):1015. journal of rawalpindi medical college (jrmc); 2017;21(3): 237-240 240 9. cameron ae, arnold rw, ghoris mw, lamieson v. spinal analgesia using bupivacaine 0.5% plain: variation in the extent of the block with patient age. anesthesia. 1981;36:318-22. 10. brown dt, wildsmith jaw, covino bg, scott db. effect of baricity on spinal anesthesia with amethocaine. br j anesth. 1980;52:589-95. 11. kitahara t, kuri s, yoshida j. the spread of drugs used for spinal anesthesia. anesthesiology. 1956;17:205 08. 12. david cw. spinal anesthesia. anesthesiology. 2001;94:888– 906. 13. hatada t, kusunoki m, sakiyama t. hemodynamics in the prone jack-knife position during surgery. am j surg. 1991;162:55-58 14. archer dp and ravussin p. perioperative effects of the prone position: anesthesiologic aspects. ann fr anesth reanim. 1998;17:172-76. 15. c. pu, j. wang, y. tang. “the efficacy and safety of percutaneous nephrolithotomy under general versus regional anesthesia: a systematic review and meta-analysis,” urolithiasis 2015; 43( 5): 455–66. 16. kim ss, lee jw, yu jh, sung lh.percutaneous nephrolithotomy: comparison of theefficacies and feasibilities of regional and general anesthesia.korean journal of urology 2013; 54(12):846–50. 17. cicek t, gonulalan u, dogan r.spinal anesthesia is an efficient and safe anesthetic method for percutaneous nephrolithotomy. urology 2014; 83(1): 50–55. 18. mazer sp, weisfeldt m, bai d, cardinale c, arora r, ma c. reverse cpr: a pilot study of cpr in the prone position. resuscitation. 2003 ;57(3):279-85. 19. wei j, tung d, sue sh, wu sv. cardiopulmonary resuscitation in prone position: a simplifi ed method for outpatients. j chin med assoc. 2006 ;69(5):202-06. 20. walsh sj, bedi a, miranda c. successful defibrillation in the prone position. br j anesth. 2009 ;21(6):408-13. 21. tyson md and chang ss .enhanced recovery pathway versus standard care after cystectomy: a meta-analysis of theeffect on perioperative outcomes. european urology 2016; 70( 6): 995–1003. 22. persson b, carringer m, andr´en o,andersson so.initial experiences with the enhance recovery after surgery (eras) protocol in open radical cystectomy.scandinavian journal of urology 2015; 49(4):302-07. 23. lojanapiwat b, chureemas t, kittirattarakarn p.efficacy of peritubal analgesic infiltration in postoperativ pain following percutaneous nephrolithotomy a prospective randomized controlled study. international brazilian journal of urology 2015; 41( 5): 945–52. 24. rawal n, zimdert av,holmstr¨om b.combined spinalepidural technique. regional anesthesia andpain medicine 1997; 22(5):406–23. 25. tangpaitoon t, nisoog c,lojanapiwat b.efficacy and safety of percutaneous nephrolithotomy (pcnl): a prospective and randomized study comparing regional epidural anesthesia with general anesthesia. international brazilian journal ofurology 2012; 38( 4):504–11. 404 not found 408 journal of rawalpindi medical college (jrmc); 2022; 26(3): 408-413 original article factors leading to an unexpected early control of covid-19 in pakistan sarwat jahan1, abdus salam2, farrukh ansar3, manzoor khan4, syed irfan ullah5, sonia javed6 1 assistant professor pharmacology, northwest school of medicine, hayatabad, peshawar. 2 lecturer pharmacology, northwest school of medicine, hayatabad, peshawar. 3 final year student, northwest school of medicine, hayatabad, peshawar. 4 resident cardiology, mti khyber teaching hospital peshawar. 5 research associate, centre of disaster management, peshawar university, peshawar. 6 post-graduate trainee obs & gynae, hayatabad medical complex, hayatabad, peshawar author’s contribution 1 conception of study 1,2,4,5 experimentation/study conduction 1.2,3,4,5 analysis/interpretation/discussion 1,2,3,4,5,6 manuscript writing 1 critical review corresponding author dr. sarwat jahan, assistant professor pharmacology, northwest school of medicine, hayatabad, peshawar email: sarwatt.jahan@gmail.com article processing received: 03/11/2021 accepted: 05/09/2022 cite this article: jahan, s., salam, a., ansar, f., khan, m., ullah, s.i., javed, s. factors leading to an unexpected early control of covid-19 in pakistan. journal of rawalpindi medical college. 30 sep. 2022; 26(3): 408-413. doi: https://doi.org/10.37939/jrmc.v26i3.1826 conflict of interest: nil funding source: nil access online: abstract introduction: different types of planning and strategies have been formulated following the rise of covid-19 in an attempt to limit the spread and minimize both crises but the situation is still getting worse even in the developed states. unexpectedly the rate of rising covid-19 declined after june 2020 in pakistan and the slope decreased to 8,884 active cases out of 313,984 confirmed cases till september 2020. in addition to this unexpected decline, a number of covid-19 related deaths. the fall in the covid-19 was unforeseen in this area and it led to curiosity regarding the factors that were responsible for this scenario. this study aimed to identify the factor (s) that may be responsible for the early control of covid-19 in pakistan. materials and methods: a country-based research project was carried out at the northwest school of medicine for a period of 6 months. a sample group of 877 individuals of both genders, age range from 15 to 80 years, belonging to various occupations, educational and socioeconomic backgrounds were included. a questionnaire on probably responsible factors for early control and shared with the participants. the factors included the strategies in knowledge, attitudes & practices, which were assessed to identify the preventive factor that was specific to this population. results: although the population was well prepared for the pandemic and followed most of the preventive measures like the rest of the world, however, the most prominent factor identified was the lack of stress and optimistic attitude that may have been responsible for early control. conclusion: the optimistic attitude and low-stress levels not only decreased the disease spread but also reduced its morbidity level. keywords: covid-19, unexpected control, morbidity, factors. 409 journal of rawalpindi medical college (jrmc); 2022; 26(3): 408-413 introduction corona-virus was an inciting panic for a number of reasons including, its new origin and hence no previously developed immunity or any available vaccine.1 therefore the virus behavior was uncertain. the origin dates back to december 2019.2 the coronavirus disease was labeled as a pandemic by january 30th, 2020 by who.3 the disease started spreading unchecked and till may 2021, globally there were 154,676,421 confirmed cases, including 3,233,394 deaths, reported to w.h.o.4 w.h.o published a number of guidelines that were strictly applied.5 however, the disease frequency kept rising exponentially, in some regions more than others.6 meticulous research was initiated for the development of a treatment and vaccines.7,8 the virus reached pakistan by march 2020.9 sops were strictly applied at the earliest and precautions were made mandatory but that did not stop the disease spread and the number of cases started increasing very rapidly, reaching a peak by june 2020 with a total of 108,273 active cases out of 213,470 confirmed cases. however, unexpectedly the rate of rising declined afterward in pakistan and the slope decreased to 8,884 active cases out of 313,984 confirmed cases till september 2020. in addition to this unexpected decline, the number of covid-19 related deaths has been comparatively a lot less, adding up to a total of 6,507 deaths by september 2020 while 298,593 infected people recovered. this fall in covid-19 was unforeseen in this area and it led to curiosity regarding the factors that were responsible for this scenario. this study was directed at identifying the knowledge, practices, and attitude of the pakistani population towards covid-19 and also other general factors which could be responsible for effective control of the pandemic. materials and methods country-based research was carried out in the northwest school of medicine for a period of 6 months from 1st march to 1st september 2020. the survey involved volunteers from all provinces who interviewed people in their vicinity before and after the start of the covid-19 outbreak. the study population was also searched and contacted via social media i.e. whatsapp groups, facebook, instagram, and twitter. the sample size was calculated to be 664 by openepi keeping, population size (for finite population correction factor or fpc)(n): 22000000 0 hypothesized % frequency of outcome factor in the population (p): 50%+/-5 confidence limits as % of 100(absolute +/%)(d): 1% design effect (for cluster surveysdeff): however, the number of consenting participants above the sample size was also included in the study making a total of 877 individuals of both genders, with ages ranging from 15 to 80 years and belonging to various occupations, educational and socioeconomic backgrounds. all the consenting participants were included in the study. participants who could not be followed up later because of any issue were excluded. the questionnaire was developed from an extensive literature review and probably responsible factors for early control.10,11 there were 12 questions for knowledge, 3 each for attitude and practices that explored the factors under these three headings. except for the practice question, every question had 3 multiple choices (true, false, i don’t know). each correct question was given one point, and then all points were added to calculate the final score. based on the final score, the most prominent factors were narrowed down and identified. spss version 23 was used for data entry and analysis. frequencies and percentages of the prevalence of various factors were measured. an independent t-test was utilized to calculate and compare mean scores. results among 877 participants, 455 (51.9%) were male and 422 (48.1%) were female. the minimum reported age was 15 while the maximum age was 80 years. the majority of the participants were in the age group of 21-30 years (64.2%). almost half of the respondents 422(48%) had a bachelor's degree. (table 1) table 1: demographical data of the study population (n=877) baseline characteristic number of participants (n=877) percentage (%) gender male female 455 422 51.9 48.1 age group less than 20 years 21 to 30 years 80 563 9.1 64.2 410 journal of rawalpindi medical college (jrmc); 2022; 26(3): 408-413 31 to 40 years 41 to 50 years more than 50 years 146 55 33 16.6 6.3 3.8 marital status married unmarried 313 564 35.7 64.3 educational status middle school and below matric/o-level fa/fsc/a-level bachelor's degree master's degree and above 9 13 116 422 317 1 1.5 13.2 48.1 36.1 occupation healthcare providers non-healthcare providers 215 662 24.5 75.5 number of family members less than 4 between 4 to 7 more than 7 75 549 253 8.6 62.6 28.8 family monthly income (pkr) less than 20,000 between 20,000 to 50,000 between 50,000 to 100,000 between 100,000 to 200,000 more than 200,000 111 250 266 154 96 12.7 28.5 30.3 17.6 10.9 residence khyber pakhtunkhwa punjab sindh balochistan gilgit baltistan tribal areas azad jammu kashmir islamabad 333 117 188 73 25 11 86 44 38 13.3 21.4 8.3 2.9 1.3 9.8 5 the majority of the participants had relatively good knowledge (85%), of the importance of social distancing (96%), and quarantine (95%). the overall attitude of participants was optimistic, 88% of them agreed that pakistan can win the battle against the coronavirus. figure 1: distribution of participants according to positive and negative knowledge, attitude, and practices of covid-19 *positive kaps were defined based on the number of questions answered correctly in the questionnaire, with >50% correct answered labelled as positive a total of 87% of the people were regularly using masks and 96% were practicing frequent hand washing. the mean knowledge score (maximum 12) was 9.24 ±1.76; while mean attitude and practices scores (maximum 3) were 1.68±0.58 and 2.68±0.56 respectively. (table 2) (table 3) table 2: factors contributing to the early control of covid-19 questions true (%) false (%) i don’t know (%) knowledge questions (k) k1. the main clinical symptoms of coronavirus disease 2019 (covid-19) are fever, fatigue, dry cough, and muscle pain. 85.6 10.2 4.2 k2. unlike common cold symptoms like stuffy nose, runny nose, and sneezing are less common in persons infected with the coronavirus. 23.7 48.1 28.2 k3. there is currently no effective cure for coronavirus disease, but early symptomatic and supportive treatment can help most patients recover from the infection. 87.8 2.2 10 k4. not all persons with coronavirus will develop severe symptoms. only those who are elderly, have chronic illnesses, and are obese are more likely to become severe cases. 68.5 17.6 13.9 411 journal of rawalpindi medical college (jrmc); 2022; 26(3): 408-413 k5. eating or touching wild animals would result in infection by the coronavirus. 26.6 45 28.4 k6. individuals infected with coronavirus cannot spread the virus to others when fever is not present. 5.8 78.3 15.8 k7. coronavirus spreads via respiratory droplets of the infected individuals. 84.9 4.8 10.3 k8. general public can wear simple medical masks to prevent infection by the coronavirus 76.2 16.5 7.3 k9. it is not necessary for children and young adults to take measures to prevent infection by the coronavirus 11.5 83.6 4.9 k10. to prevent infection by corona virus, individuals should avoid going to crowded places such as train/bus stations, bazaar and avoid taking public transportation. 96.4 0.6 3.1 k11. isolation and treatment of people who are infected with the coronavirus are effective ways to reduce the spread of the virus. 95.8 1.3 30 k12. people who have had close contact with the coronavirus infected individual should be immediately isolated in a proper place. in general, the observation period is 14 days. 95 1.5 3.5 attitude questions (a) a1. do you agree that coronavirus will be successfully controlled? 1.4 9.8 88.8 a2. do you have confidence that pakistan can win the battle against the coronavirus? 76.7 10.3 13 a3. people can shake hands or hug each other because it has no association with the spread of corona virus. 4.6 90 5.4 practice questions (p) p1. in recent days, have you gone to any crowded places? 15.2 84.8 p2. in recent days, have you worn a mask when leaving home? 87.8 12.2 p3. do you use hand sanitizer or wash your hands with soap for 20 seconds after coming home from outside or before touching your face? 96.4 3.6 table 3: comparison of demographic characteristics with mean knowledge, attitude and practices score demographics knowledge score attitude score practice score mean sd p mean sd p mean sd p gender male female .001 .001 .012 8.96 1.95 1.62 0.57 2.64 0.59 9.55 1.48 1.74 0.49 2.73 0.52 age group less than 20 years 8.57 2.41 .001 1.58 0.58 .101 2.58 0.68 .292 21 to 30 years 9.40 1.65 1.70 0.52 2.68 0.56 31 to 40 years 9.12 1.70 1.69 0.49 2.76 0.48 41 to 50 years 9.03 1.53 1.67 0.57 2.69 0.57 more than 50 years 9.12 1.99 1.48 0.71 2.66 0.59 marital status married 9.23 1.81 .773 1.66 0.55 .720 2.71 0.54 .341 unmarried 9.24 1.70 1.68 0.53 2.67 0.57 educational status middle school and below 7.88 2.42 .001 1.77 0.44 .149 2.88 0.33 .806 matric/o-level 7.69 3.14 1.69 0.63 2.61 0.65 fa/fsc/a-level 8.95 1.76 1.57 0.57 2.68 0.59 bachelor's degree 9.33 1.73 1.71 0.50 2.69 0.55 master's and above 9.34 1.67 1.66 0.56 2.67 0.57 occupation healthcare providers 9.77 1.2 .001 1.72 0.50 .789 2.70 0.50 .390 non-healthcare providers 8.77 1.7 1.68 0.54 2.68 0.56 number of family members less than 4 9.33 1.64 .860 1.65 0.58 .777 2.84 0.43 .031 between 4 to 7 9.25 1.67 1.69 0.53 2.69 0.54 more than 7 9.20 1.98 1.66 0.54 2.64 0.62 412 journal of rawalpindi medical college (jrmc); 2022; 26(3): 408-413 family monthly income (pkr) less than 20,000 8.63 2.10 .001 1.71 0.52 .181 2.63 0.68 .337 20,000 to 50,000 8.94 1.91 1.68 0.55 2.66 0.56 50,000 to 100,000 9.36 1.60 1.65 0.55 2.74 0.52 100,000 to 200,000 9.76 1.35 1.75 0.47 2.66 0.56 more than 200,000 9.57 1.62 1.59 0.59 2.72 0.53 about 44.8% of respondents chose social media. the second major source of knowledge was electronic media (18%) while 17% of the people gained knowledge from healthcare professionals. almost 90% of the participants had a perception that the government is strictly dealing with this pandemic and that preventive strategies are adequate (table 4). table 4: information sources regarding covid-19 question yes no yes, but not much have you searched literature regarding the covid-19 pandemic? 90.3 3.8 5.9 have you made preparations before the onset of the pandemic/lockdown in your country? 89.3 6.3 4.4 did you spread awareness to your family and friends about the covid-19 disease? 88.9 5.8 5.2 do you strictly follow the government rules regarding covid-19? 91 4.3 4.7 do you make sure the rules regarding covid-19 are being followed in your surrounding? 88.1 2.3 9.6 are masks and sanitizers easily available in your locality? 89.3 4 6.7 if you get a chance will you do any volunteer work for the eradication of covid-19? 81.2 9.5 9.4 discussion on wednesday, march 11, world health organization held a media briefing to declare the covid-19 outbreak a global pandemic.12 very the preventive protocols were formulated to tackle the virus including activation of emergency mechanisms, isolation, and quarantine, tests were made available, social distancing was followed, use of masks, sanitizers, and public hygiene was made mandatory and a majority of the world went into the lockdown state, closing all the business as well as educational institutes for an undefined period of time with hopes to confine the spread of the disease.13 however, even under strict policies and preventive measures, the virus could not be constrained in a large part of the world. the infected cases and death rate kept getting higher, while the research on treatment and vaccine was still in trials.14 under the given circumstances where even the developed world was suffering to keep a check on the virus, it was highly unexpected for a developing country with limited resources like pakistan to be able to control the pandemic. however, to everyone’s surprise in september 2020, the rate of rising of covid-19 started to fall. the death rate has been comparatively quite low in this area too, the recovery rate has been very high and disease morbidity has been reportedly low. our findings have shown that the majority of the study population had sufficient knowledge regarding covid-19. approximately 77% of the people scored excellent points on our knowledge scale. a comparative study from malaysia depicts that 80% of their population had a significant level of covid-19 knowledge.11 another investigation from china asserted that people were knowledgeable about the basics of covid-19.10 the good knowledge of participants may be attributed to the reason that the majority of the respondents had (84%) had a bachelor, master's, or a higher degree. an educated person has relatively better access to electronic, print, and social media that can enhance their knowledge. besides 90% of our participants revealed that they searched various databases to learn more about covid-19. a similar trend was shown in various other studies as in nigeria 90% of the respondents had a bachelor's degree.15 studies from malaysia and saudi arabia showed the same trend which was directly proportional to the good knowledge of participants.11,16 in the present study, results have demonstrated that the practice of people towards covid-19 prevention was brilliant. as 96% of the participants were frequently using sanitizers and soap hand washing while 87% of them were using face masks when going outside. besides, 84% of the respondents avoided crowded places. the same results were retrieved from a chinese study 413 journal of rawalpindi medical college (jrmc); 2022; 26(3): 408-413 where 98% of the people were using facemasks and 96% of them avoided crowded places.10 attitudes towards the disease have been known to affect the disease outcomes for a long hence giving rise to placebo and nocebo effects.17 our study also focused on the reaction and attitude of the population towards the uprising pandemic and followed the stress level after the disease was full-blown. around 88.8% of the population in the study had a very positive attitude and were ready but stress-free. these individuals were noted to have no symptoms, minimal symptoms, and complete recoveries even when they got infected. studies conducted based on stress levels related to covid-19 have shown a greater rise and severity of the disease in populations with high-stress levels.18 an american study showed a high level of stress among the participants. in addition journal of anxiety disorders states higher stress-related covid-19 infection acquisition as well as severity.19 conclusion the study identified a number of factors that were probably responsible for the unexpected early control of covid-19. most of the population was well versed and well aware of the disease and its prevention protocols and had started following the regulations strictly. government awareness programs and support further helped reduce the expected morbidity index. however, all these factors are also observed all over the world, yet the disease is going out of hand. we identified that the main reason for different disease statistics in this region was related directly to the positive optimistic attitude and mental steadiness and belief that the pandemic could be defeated. references 1. ahn dg, shin hj, kim mh, lee s, kim hs, myoung j, kim bt, kim sj. current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (covid-19). doi.org/10.4014/jmb.2003.03011 2. wang c, horby pw, hayden fg, et al. a novel coronavirus outbreak of global health concern. the lancet 2020; 395: 470– 473. doi.org/10.1016/s0140-6736(20)30185-9 3. covid-19 public health emergency of international concern (pheic) global research and innovation forum, https://www.who.int/publications/m/item/covid-19-publichealth-emergency-of-international-concern-(pheic)-globalresearch-and-innovation-forum. 4. covid-19 live update: 154,676,421 cases and 3,233,394 deaths from the coronavirus worldometer, https://www.worldometers.info/coronavirus. 5. corley da, peek rm. covid-19: guidance for what clinicians and scientists should do and when. gastroenterology. 2021 may 1;160(6):1922-3. doi.org/10.1053/j.gastro.2021.04.011 6. noorimotlagh z, jaafarzadeh n, martínez ss, et al. a systematic review of possible airborne transmission of the covid-19 virus (sars-cov-2) in the indoor air environment. environ res 2021; 193: 110612. doi.org/10.1016/j.envres.2020.110612 7. afzal a. molecular diagnostic technologies for covid-19: limitations and challenges. j adv res. 2020; 26: 149–159. doi.org/10.1016/j.jare.2020.08.002 8. kaur sp, gupta v. covid-19 vaccine: a comprehensive status report. virus research 2020; 288: 198114. doi.org/10.1016/j.virusres.2020.198114 9. abid k, bari ya, younas m, et al. progress of covid-19 epidemic in pakistan. asia-pacific j public heal. 2020; 32: 154– 156. doi.org/10.1177/1010539520927259 10. zhong bl, luo w, li hm, 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 crosssectional survey. int j biol sci. 2020; 16: 1745–1752. doi.org/10.7150/ijbs.45221 11. azlan aa, hamzah mr, sern tj, ayub sh, mohamad e. public knowledge, attitudes and practices towards covid-19: a cross-sectional study in malaysia. plos one. 2020 may 21;15(5):e0233668. doi.org/10.1371/journal.pone.0233668 12. world health organization. coronavirus disease ( covid19) : situation report, 166. 13. maipas s, panayiotides ig, tsiodras s, kavantzas n. covid19 pandemic and environmental health: effects and the immediate need for a concise risk analysis. environmental health insights. 2021 feb;15:11. doi.org/10.1177/1178630221996352 14. han s. clinical vaccine development. clin exp vaccine res 2015; 4: 46. doi.org/10.7774/cevr.2015.4.1.46 15. reuben rc, danladi m, saleh da, ejembi pe. knowledge, attitudes and practices towards covid-19: an epidemiological survey in north-central nigeria. journal of community health. 2021 jun;46(3):457-70. doi.org/ 10.1007/s10900-020-008811 16. al-hanawi mk, angawi k, alshareef n, qattan a, helmy hz, abudawood y, alqurashi m, kattan wm, kadasah na, chirwa gc, alsharqi o. knowledge, attitude and practice toward covid19 among the public in the kingdom of saudi arabia: a crosssectional study. frontiers in public health. 2020 may 27;8:217. doi.org/ 10.3389/fpubh.2020.00217/full 17. colloca l, barsky aj. placebo and nocebo effects. nejm. 2020 feb 6;382(6):554-61. doi.org/10.1056/nejmra1907805 18. park cl, russell bs, fendrich m, finkelstein-fox l, hutchison m, becker j. americans’ covid-19 stress, coping, and adherence to cdc guidelines. j gen intern med. 2020 aug;35(8):2296-303. doi.org/10.1007/s11606-020-05898-9 19. asmundson gj, paluszek mm, landry ca, rachor gs, mckay d, taylor s. do pre-existing anxiety-related and mood disorders differentially impact covid-19 stress responses and coping. j anxiety disord. 2020 aug 1;74:102271. doi.org/10.1016/j.janxdis.2020.102271 404 not found summary journal of rawalpindi medical college (jrmc); 2011;15(1):13-15 13 management of penetrating chest injuries muhammad ateeq*, shazia jahan*. azhar sajjad**, faisal .g. bhopal* * department of surgery, district head quarters teaching hospital, rawalpindi ** pakistan atomic energy commission hospital, islamabad abstract background: to determine the pattern of penetrating thoracic injury, including the causes, the role of surgery and intervention outcomes in general surgical unit. methods: in this descriptive study patients of all age groups and either sex with isolated penetrating chest trauma or poly trauma were included. results: out of total 926 patients, studied during ten years period, 694 cases (74.94%) were medico legal. haemopneumothorax was the most commonly observed consequence of penetrating chest injury. (n=539). tube thoracostomy was performed in 855 (92.33%) cases.acute respiratory distress syndrome(ards) was the commonest complication(5.07%). overall mortality rate was 08.96%. conclusion: timely rescue of patients, from site of accident, to the adequate health facility ensures better outcome key words: chest injury, tube thoracostomy, introduction road traffic accidents and the increasing violence are common causes of increasing chest injuries.blunt trauma is not usually associated with military or civilian violence, while penetrating chest trauma often is. 1 according to united states national trauma data bank 25% deaths occurring due to trauma in united states are due to chest injuries.2 many patients with chest injuries die after reaching hospital and many of those patients can be saved with prompt adequate management.3 the operative competence of a general surgeon in this anatomical region of the body can not be compared with a cardiothoracic surgeon, however most of the cases of chest trauma are adequately and successfully being managed by general surgeons.4 in spite of high mortality associated with chest injuries most of the chest injuries can be managed by simple interventions like tube thoracostomy. critical condition of the patients with chest trauma can become challenging for general surgeons on certain occasions. 4 firearm injuries and stab wounds of the chest are the major cause of chest injuries. road traffic accidents are second common cause of chest injuries. pre hospital deaths due to chest injuries are mostly due to great vessel injuries, cardiac injuries and tension pneumothorax. 5 chest trauma management is difficult, but the results are usually rewarding. all patients who reach hospital alive should survive by appropriate management. the selection of patients for operation or observation can be made by clinical examination and appropriate investigations. the indications of surgical intervention include significant pneumothorax, hemothorax, hemopnemothorax, diaphragmatic injuries, extensive pulmonary laceration, and great vessel injuries. the most frequent complication of chest trauma is atelectasis. other potentially fatal complications range from exsanguinations to adult respiratory distress syndrome. the general outlook of penetrating chest injuries is improving as better treatment and prevention of complications have greatly reduced morbidity. although hospital mortality has fallen by a factor of ten since the mid 19th century, the total mortality caused by penetrating chest injuries has undergone less change. 6 patients and methods this descriptive study was conducted in surgical unit, district headquarters (teaching) hospital rawalpindi from june 2000 to june 2010. this hospital is a main referral centre for trauma cases including all medico legal cases from the rawalpindi division. a total of 926 consecutive patients with penetrating thoracic injuries presenting in emergency department were included and evaluated. patients of all age groups who presented with penetrating chest trauma either isolated or associated with poly trauma were included. patients with blunt chest injuries were excluded from the study. on arrival to emergency department of hospital all patients were evaluated and resuscitated according to atls guideline of trauma care. 7 emergency tube thoracostomy was performed in life threatening chest injuries.secondary survey was performed once the patient had been stabilized. journal of rawalpindi medical college (jrmc); 2011;15(1):13-15 14 associated injuries were managed on their merit. haemoglobin levels, blood grouping and chest x rays were the main investigations done in emergency room. ventilator support was provided where indicated. ct scan chest, bronchoscopy, pulmonary function test were performed in the surgical ward / icu where indicated. results a total number of 926 patients with penetrating chest trauma due to different causes were admitted in surgical unit during the study period. out of 926 patients 439 patients (47.40%) sustained multiple injuries in addition to chest injury. majority of patients were male 74.94% (n= 694) where as 232 were females (25.05%). most of the patients were of young age group, mean age 37 years, and 43 patients were of paediatric age group. 694 (74.94%) patients out of total 926 were medico legal cases. table 1:mode of injury mode of injury number (%) gunshot injuries 536(57.88) stab wounds 216(23.32) road traffic accidents 143(15.44) fall 31(03.4) table 2:nature of injuries nature of injuries number (%) haemopneumothorax 539(58.20) haemothorax 382(41.25) pneumothorax 205(21.81) rib fracture 87(15.18) flail segment chest 45(04.85) tension pneumothorax 17(02.96) cardiac tamponade 04(0.69) poly trauma 439(47.40) table 3:surgical intervention intervention number of patients(%) chest intubations 855(92.33%) thoracotomy emergency elective 103(12.04%) 73 30 conservative 13(01.40) gunshot injuries were the most common mode of injury (57.88%)(table 1). haemopneumothorax was the most frequent consequence of chest injury (58.20%)(table 2) out of total 926 patients of penetrating chest injuries 47.40% patients sustained multiple injuries in addition to chest injury. combined thoracoabdominal injuries were seen in 20.84% patients, who underwent exploratory laparotomy. tube thoracostomy was done in 92.33% cases, out of which 12.04% patients underwent thoracostomy ( table iii). massive haemothorax was the most common indication of emergency thoracotomy in70.83%.(table4) table 4:thoracotomy indications indication number(%) massive haemothorax 73(70.83) empyema 24(30.30) bronchopleural fistula 06(05.82) adult respiratory distress syndrome (ards) was the most common cause of morbidity in our series(08.96%). total mortality was 8.96%, out of which 19 patients died due to non chest injury related complications (table 5). table 5:complications complication number(%) ards 47(05.07) empyema thoracis 39(04.01) mortality 83(08.96) discussion management of polytrauma patients is a task which surgeons in public sector hospitals are often faced with. a study conducted in uk showed that most general surgeons should retain the ability to manage trauma. they consider that the best services for severely injured patients would be to manage their injuries at a hospital with specialist trauma services either through direct referral from site of incident or transfer from an acute receiving hospital after the initial resuscitation and stabilization. 8 penetrating chest trauma is a challenging surgical problem worldwide. present study presents data of a tertiary care hospital of the city, which is a main referral centre of the medico legal cases of rawalpindi division. after the provision of government ambulance transport services, rescue 1122, the trauma patients are being more efficiently and quickly transferred to tertiary care hospitals, but this service is not yet available in all metropolis. even journal of rawalpindi medical college (jrmc); 2011;15(1):13-15 15 in developed world, 10% of accidents victims die before reaching a hospital. 9 at district head quarter’s (teaching) hospital (dhq) rawalpindi, where thoracic surgery unit is not available, general surgical team is responsible for providing surgical management to chest trauma victims. studies show that chest trauma is common in second to fifth decade of age and in males. it has been observed that incidence of penetrating chest trauma is rising with time because of gunshot injuries, due to increasing violence and availability of weapons in the society. 10 haemothorax is the most commonly observed consequence of penetrating chest injury. successful management of haemothorax, in these cases, by thoracostomy is well established. simple rib fracture without haemothorax / pneumothorax were found in 44% cases in study by farooqi et al and 76% cases by hanif. 1,9 in present study the frequency of rib fracture was 9.39% , which is low due to the fact that we have included only patients with penetrating chest injuries, whereas as others have included patients with both penetrating and blunt chest injuries in their studies. in our set up still thoracostomy is performed more frequently, while in developed world video assisted thoracoscopic surgery is in vogue. 11-13 overall mortality rate was 08.96%, (83 patients) out of which 19 patients had poly trauma. our mortality rate is comparable with other studies. the reported mortality rate in a nigerian study was 7.7%. 11 conclusion to reduce pre hospital stay facility of public ambulance transport system like rescue 1122 should be extended to the peripheral areas. references 1. farooq u, raza w,zia n,hanif m, khan mm. classification and management of chest trauma. j coll physicians surg pak 2006; 16(2):101-03. 2. american college of surgeons. national trauma data bank.chicago: ann surg 2004; 240:96-104. 3. locicerco j, mattox kl. epidemiology of chest trauma. surg clin north am 1989; 69:15-16. 4. marya sks, singla sl. management of chest injuries by a general surgeon. ind j surg 1987; 49:235-38. 5. brooks a, butcher w,walsh m,lambert a,brownej.the experience and training of british general surgeons in trauma surgery for abdomen, thorax and major vessels. ann r coll surg engl 2002; 84:409-13. 6. richardson jd. indications for thoracotomy in thoracic trauma. curr surg 1985; 42:361-63. 7. american college of surgeons. advanced trauma life support (atls) student manual. 6th ed. chicago, il: american college of surgeons, 1997. 8. better care for the severely injured. joint report of the royal college of surgeons of england and british orthopaedic association; london: 2000. 9. hanif f, mirza sm, chaudhry am. re-appraisal of thoracic trauma. pak j surg 2000; 16:25-28. 10. khan mlz, haider j, alam sn, jawaid m, malik ka. chest trauma management: good outcomes possible in a general surgical unit. pak j med sci 2009; 25(2):217-21. 11. thomas mo, .ogunleye eo. penetrating chest trauma in nigeria. asian cardiovasc thorac ann 2005; 13:103-06. 12. segers p, van schil p, jorens o, van den brande f. thoracic trauma: an analysis of 187 patients. acta chir belg 2001; 101:277-82. muhammad ateeq*, shazia jahan*. azhar sajjad**, faisal .g. bhopal* * department of surgery, district head quarters teaching hospital, rawalpindi ** pakistan atomic energy commission hospital, islamabad abstract introduction results discussion conclusion references 208 journal of rawalpindi medical college (jrmc); 2022; 26(2): 208-213 original article comparison of frequency of diagnosis, induction of labour and caesarean section in patients with isolated oligohydramnios diagnosed by amniotic fluid index versus single deepest vertical pocket saleema rehman1, humera rizwan2, ayesha akram3, sharmeen kausar4, samina irshad5 1 post-graduate trainee, holy family hospital, rawalpindi. 2,4 senior registrar, holy family hospital, rawalpindi. 3 assistant professor, gynae/obs, hitec-ims, taxila. 5 associate professor, gynae/obs, fauji foundation hospital, rawalpindi. author’s contribution 1 conception of study 1,2,4 experimentation/study conduction 2,3,4 analysis/interpretation/discussion 3,5 manuscript writing 5 critical review 3 facilitation and material analysis corresponding author dr. ayesha akram, assistant professor of gynae/obs, hitec-ims, taxila email: ayeshaakram582@gmail.com article processing received: 02/09/2021 accepted: 16/03/2022 cite this article: rehman, s., rizwan, h., akram, a., kausar, s., irshad, s. comparison of frequency of diagnosis, induction of labour and caesarean section in patients with isolated oligohydramnios diagnosed by amniotic fluid index versus single deepest vertical pocket. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 208-213. doi: https://doi.org/10.37939/jrmc.v26i2.1765 conflict of interest: nil funding source: nil access online: abstract objective: to compare the frequency of diagnosis, induction of labour, and caesarean section in patients with isolated oligohydramnios diagnosed by amniotic fluid index versus single deepest vertical pocket. study design: randomized controlled trial place and duration of study: department of obstetrics and gynecology, holy family hospital, rawalpindi from march 2020 to august 2020. materials & methods: a total of 110 (55 in each group), 18 to 35 years of age of parity <5 were included. group a females were evaluated by using afi and group b females were evaluated by using sdvp. patients were managed according to standard protocol practiced in the department. caesarean section was performed in case of fetal distress, in presence of meconium-stained liquor, or in case of failure to the progress of labour. results: in my study, oligohydramnios was recorded in 19/55 (34.50%) in group a (amniotic fluid index) versus 11/55 (20.0%) in group b (single deepest vertical pocket) (p-value = 0.086). similarly induction of labour was recorded in 19/55 (34.50%) in group a (amniotic fluid index) versus 11/55 (20.0%) in group b (single deepest vertical pocket) (p-value = 0.086) and caesarean section was recorded in 16/55 (29.09%) in group a (amniotic fluid index) versus 07/55 (12.73%) in group b (single deepest vertical pocket) (p-value = 0.035). conclusion: this study concluded that the frequency of diagnosis, induction of labour, and caesarean section in patients with isolated oligohydramnios diagnosed by the amniotic fluid index is higher as compared to single deepest vertical pocket. keywords: oligohydramnios, amniotic fluid index, single deepest vertical pocket. 209 journal of rawalpindi medical college (jrmc); 2022; 26(2): 208-213 introduction amniotic fluid volume is a fundamental part of the evaluation of fetal wellbeing. amniotic fluid is vital for proper fetal growth and development.1 in many highrisk conditions a reduction in amniotic fluid volume (oligohydramnios) is noted that is linked with poor perinatal outcome.2 after diagnosing oligohydramnios at term, a plan of delivery is made either by inducing the patient or by performing a caesarean section.3 amniotic fluid volume is calculated by using ultrasound, the techniques that are most commonly employed are the assessment of the amniotic fluid index (afi) or the single deepest vertical pocket (sdvp) technique.4 oligohydramnios is associated with higher rates of adverse fetal and neonatal outcomes that include a 5fold increase in stillbirths and a 3-fold rise in neonatal deaths.5 oligohydramnios is diagnosed if the afi measures less than or equal to 5cm. when using the sdvp technique, it is diagnosed when the sdvp is less than 2 cm.6 it is an intimidating condition to fetal health for which treatment options are under evaluation and at present not much treatment is available. it is associated with congenital anomalies, increased pregnancy complications, and perinatal mortality. the reported incidence is to be 0.5 to 5%.7 pregnant women with oligohydramnios have more chances of compression of the umbilical cord, passage of meconium by fetus, and decelerations on fetal heart trace with a two-fold increased risk for cesarean delivery and fivefold increased risk for < 7 apgar score.8 in a study conducted, the rate of caesarean delivery in the afi group was higher as compared to the sdvp group with a p-value=0.017 making it statically significant. 90% of patients were diagnosed with oligohydramnios in the afi group and 46% in the sdvp group.9 but another study reported that the frequency of caesarean delivery was almost equal i.e. 24.7% in afi and 27.3% in sdvp (p=0.53).10 the purpose of this study is to create indigenous data comparing both the techniques used for estimation of amniotic fluid volume i.e. afi and sdvp in their frequency of diagnosis of oligohydramnios. this study may help to avoid unnecessary interventions like induction of labour and caesarean section, especially in low-risk pregnancies. materials and methods it was a randomized controlled trial. the study was carried out in the department of obstetrics and gynecology, holy family hospital, rawalpindi over a period of six months from 01-03-2020 to 31-08-2020. the sample was drawn by consecutive nonprobability sampling. pregnant women of age 18-35 years, parity <5, presenting at >37 weeks gestation were included in the study. pregnancy with the noncephalic presentation, multiple fetuses, structural or chromosomal fetal malformation, intrauterine growth restriction, intrauterine fetal death, placenta previa, or placental abruption (on ultrasound) were excluded. also, pregnant women with premature rupture of the membranes, previous caesarean section presenting in active labour, chronic or gestational hypertension (bp≥140/90mmhg), diabetes (ogtt>186mg/dl), thyroid disorder (tsh>5miu) and asthma were excluded. after taking approval from the hospital ethical committee, 110 females fulfilling the selection criteria were enrolled in the study from opd of the department of obstetrics/ gynecology, holy family hospital, rawalpindi. written informed consent was taken. demographic detail including name, age, bmi, parity, and gestational age was noted. then females were divided into two groups. group a females were evaluated by using afi and group b females were evaluated by using sdvp. the patient’s scan was done by the senior obstetrician. in the afi technique, the amniotic cavity was divided into four quadrants and the deepest vertical pocket was measured in each quadrant, the measurements were then added to give an estimated total amniotic fluid volume. a value <5cm was taken as oligohydramnios. in the sdvp group, the image of the deepest cord-free pool pocket was frozen and measured along its maximum length in centimeters. value <2cm was taken as significant. if a patient is not in labour already then induction of labour was done in both groups meeting respective diagnostic criteria by methods according to the department protocol. patients were managed according to standard protocol practiced in the department. caesarean section was performed in case of fetal distress, in presence of meconium-stained liquor, or in case of failure to the progress of labour. the information was recorded on the preformed proforma. all the data was entered and analyzed through spss version 22. all the quantitative variables; like maternal age, bmi, and gestational age standard deviation were 210 journal of rawalpindi medical college (jrmc); 2022; 26(2): 208-213 calculated. all the qualitative variables; like parity, diagnosis, induction of labour, and caesarean section frequency and percentages were calculated. to compare the frequency of diagnosis, induction of labour, and caesarean section in both study groups “chi-square test” was applied. p value ≤ 0.05 was considered significant. data was stratified for age, bmi, parity, and gestational age. post-stratification, both groups were compared for cesarean section by using the chi-square test. p value ≤ 0.05 was considered significant. results during the six months study period, a total of one hundred and ten patients (fifty-five in each group) who met the inclusion criteria were included. 18 to 35 years was the range of age in this study with a mean age of 24.90 ± 4.41 years. the mean parity was 1.51 ± 1.52. the mean bmi was 24.89 ± 3.29kg/m2. the mean gestational age in group a and group b are shown in table 1. table 1: distribution of patients according to gestational age ga (weeks) group a (n=55) group b (n=55) total (n=110) no. of patient s %age no. of patient s %age no. of patient s %age 37-39 08 14.5 4 27 49.1 0 35 31.8 2 >39 47 85.4 6 28 50.9 0 75 68.1 8 mean ± sd 39.20 ± 1.01 39.10 ± 1.21 39.20 ± 1.21 in my study, oligohydramnios was diagnosed in 19/55 (34.50%) in group a (amniotic fluid index) versus 11/55 (20.0%) in group b (single deepest vertical pocket) (p-value = 0.086), similarly, induction of labour was recorded in 19/55 (34.50%) in group a (amniotic fluid index) versus 11/55 (20.0%) in group b (single deepest vertical pocket) (p-value = 0.086) and caesarean section was recorded in 16/55 (29.09%) in group a (amniotic fluid index) versus 07/55 (12.73%) in group b (single deepest vertical pocket) (p-value = 0.035) as shown in table 3. table 2: comparison of the frequency of diagnosis, induction of labour, and caesarean section in patients with isolated oligohydramnios diagnosed by amniotic fluid index versus single deepest vertical pocket (n=110) outcome group a (n=55) group b (n=55) p value no. %age no. %age oligohydramnios yes 19 34.54 11 20.00 0.086 no 36 65.46 44 80.00 induction of labour yes 19 34.54 11 20.00 0.086 no 36 65.46 44 80.00 cesarean section yes 16 29.09 07 12.73 0.035 no 39 70.91 48 87.27 out of diagnosed oligohydramnios patients in each group, the rate of caesarean section came out to be 84.2% (16/19) in the afi group and 63.6% (7/11) in the sdvp group. stratification of oligohydramnios with reference to patients’ age, bmi, parity, and gestational age is shown in table 3. table 3: stratification of oligohydramnios with respect to age, gestational age, parity and bmi effect modifiers group a (n=55) group b (n=55) p-value oligohydramnios oligohydramnios yes no yes no age (years) 18-25 11 23 07 22 0.471 26-35 08 13 04 22 0.075 ga (weeks) 37-39 04 04 02 25 0.004 >39 15 32 09 19 0.983 parity ≤2 15 24 07 24 0.155 >2 04 12 04 20 0.518 bmi (kg/m 2 ) ≤25 12 30 06 20 0.617 >25 07 06 05 24 0.015 stratification of induction of labour with reference to patients’ age, bmi, parity, and gestational age is shown in table 4. 211 journal of rawalpindi medical college (jrmc); 2022; 26(2): 208-213 table 4: stratification of induction of labour with respect to age, gestational age, parity and bmi effect modifiers group a (n=55) group b (n=55) p-value induction of labour induction of labour yes no yes no age (years) 18-25 11 23 07 22 0.471 26-35 08 13 04 22 0.075 ga (weeks) 37-39 04 04 02 25 0.004 >39 15 32 09 19 0.983 parity ≤2 15 24 07 24 0.155 >2 04 12 04 20 0.518 bmi (kg/m 2 ) ≤25 12 30 06 20 0.617 >25 07 06 05 24 0.015 stratification of caesarean section with reference to patients’ age, bmi, parity, and gestational age is shown in table 5. table 5: stratification of cesarean section with respect to age, gestational age, parity and bmi effect modifiers group a (n=55) group b (n=55) p-value cesarean section cesarean section yes no yes no age (years) 18-25 10 24 05 24 0.258 26-35 06 15 02 24 0.058 ga (weeks) 37-39 04 04 02 25 0.004 >39 12 35 05 23 0.442 parity ≤2 14 25 06 25 0.128 >2 02 14 01 23 0.326 bmi (kg/m 2 ) ≤25 09 33 03 23 0.298 >25 07 06 04 25 0.006 discussion amniotic fluid volume is a useful gauge and predictor of fetal well-being. a rise in the risk of abnormalities in fetal heart rate traces, meconium staining of amniotic fluid, and rate of caesarean sections for fetal distress is linked with oligohydramnios.11 at present, there is no consensus about the effectiveness of different ultrasonographic techniques used for amniotic fluid estimation in predicting adverse perinatal outcomes.12 we have conducted this study to draw a comparison regarding diagnostic frequency also rate of induction of labour and caesarean section in patients with isolated oligohydramnios as detected by calculating amniotic fluid index versus single deepest vertical pocket. in my study, oligohydramnios was detected in 34.50% in group a versus 20% in group b with a significant pvalue=0.086. similarly, induction of labour was recorded in 34.50% in group a versus 20% in group b with a significant p-value=0.086 and caesarean section was recorded in 29% in group a versus 12.73% in group b with a significant p-value=0.035. out of diagnosed oligohydramnios patients in each group, the rate of caesarean section came out to be 84.2% in the afi group and 63.6% in the sdvp group. one cochrane review was done including five randomized controlled trials, involving 3226 pregnant women between the years 1997 to 2004. the goal was to determine which of the two techniques (afi /mvp measurement) for assessing amniotic fluid volume is more precise in reducing the risk of poor pregnancy outcomes. this review concluded that there is no constant standard for measuring amniotic fluid volume. so more research is needed.12 the frequency of oligohydramnios diagnosed by the afi method was 8% while it was 1% using the sdp method as studied by maggan ef et al13 rosati et al14 stated the incidence of oligohydramnios was 4.47% and 3.75% when afi and sdvp method used respectively. the selection criteria may be a reason for the difference between our study and other studies. the difference in frequency of oligohydramnios is noted when different methods are employed i.e. between sdvp and afi methods, resulting in unnecessary 212 journal of rawalpindi medical college (jrmc); 2022; 26(2): 208-213 interventions which on one hand may not lead to any improved neonatal outcome but on the other hand do lead to a rise in maternal and perinatal morbidity. afi is used commonly in the estimation of amniotic fluid volume and its categorization despite the fact that sdvp seems to be better practice for calculating amniotic fluid volume.15 in one study, moore16 diagnosed 9.6% of women with oligohydramnios using the afi measurement while this incidence was 4% with the sdvp technique. afi had identified more pregnancies with oligohydramnios than the sdvp technique in this study. following trials reached differing conclusions when a comparison between the two methods was made in predicting pregnancy outcomes. some reported afi as being the better test,17 some stated sdvp as the better option18 and in other studies, neither test was superior to the other when it comes to the identification of perinatal complications.19 nabhan af in their study stated that the afi method for measuring amniotic fluid volume nearly doubles the risk of induction of labour.20 in a study by noor n et al, a total of 140 pregnant women were included and divided into two groups based upon the estimation of amniotic fluid volume either by afi method or by measuring mvp. in group ia, 59 women (65.56%) out of 90 women went into spontaneous labour while 31(34.44%) had induction of labour. in group ib, based on oligohydramnios that is diagnosed based on decreased afi but normal mvp, 50(100%) women had undergone induction of labour. therefore they concluded that afi measurement gives rise to the rate of diagnosis of oligohydramnios and induction of labour.21 rossi and prefumo did a meta-analysis and it was found that obstetric interventions occurred more frequently in the isolated oligohydramnios than normal amniotic fluid (af) group (io: 89/679, 13% vs. normal af: 166/3354, 5%; or: 2.30; 95% ci: 1.005.29).22 therefore, presently selection of techniques is based on local protocols and clinical predilection. therefore, we can infer from the present study that the frequency of diagnosis, inducing labour, and performing caesarean section in patients with isolated oligohydramnios detected by afi (amniotic fluid index) method is higher as compared to the single deepest vertical pocket which is being supported by other studies. conclusion this study concluded that the frequency of diagnosis, induction of labour, and caesarean section in patients with isolated oligohydramnios diagnosed by an amniotic fluid index is higher as compared to a single deepest vertical pocket. so, we recommend that the single deepest vertical pocket sdvp method is a superior choice as compared to the afi method for estimation of amniotic fluid volume as its use avoids unnecessary interventions, especially in low-risk pregnancies. it is therefore related to improved maternal and fetal outcomes. references 1. figueroa et al. oligohydramnios: a prospective study of fetal, neonatal and maternal outcomes in low-middle income countries. reproductive health bmc 2020; 17:19 doi.org/10.1186/s12978-020-0854-y 2. kehl s, schelkle a, thomas a, puhl a, meqdad k, tuschy b, et al. single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (safe trial): a multicenter, openlabel, randomized controlled trial: a multicenter, open-label, randomized controlled trial. obstet gynecol surv [internet]. 2016;71(10):578–80. doi: 10.1002/uog.14924 3. roberts d, vause s, martin w, green p, walkinshaw s, bricker l, et al. amnioinfusion in very early preterm prelabor rupture of membranes (amiprom): pregnancy, neonatal and maternal outcomes in a randomized controlled pilot study: outcomes of the amiprom pilot study. ultrasound obstet gynecol [internet]. 2014;43(5):490–9. doi.org/10.1002/uog.13258 4. luntsi g, burabe fa, ogenyi pa, zira jd, chigozie ni, nkubli fb, et al. sonographic estimation of amniotic fluid volume using the amniotic fluid index and the single deepest pocket in a resource-limited setting. j med ultrasound [internet]. 2019;27(2):63–8. doi.org/10.4103/jmu.jmu_26_18 5. siraj a, baqai s, naseer s, raja a. the effect of oligohydramnios on perinatal outcome. pak armed forces med j. 2016;66(3):333–6. 6. kumari g. a comparative study of intravenous hydration and amnioinfusion for iugr associated with oligohydramnios in pregnant women and fetomaternal outcome. international journal of reproduction, contraception, obstetrics and gynecology. 2021 feb 24;10(3):955. doi: https://dx.doi.org/10.18203/2320-1770.ijrcog20210715 7. rosati p, guariglia l, cavaliere af. a comparison between amniotic fluid index and the single deepest vertical pocket technique in predicting adverse outcome in prolonged pregnancy. j prenat med 2015; 9(1/2):12-5. doi:10.11138/jpm/2015.9.1.012. 8. shah r, sharma p. comparison of amniotic fluid index and single deepest vertical pool method for predicting fetal outcome. j coll med sci-nepal [internet]. 2017;13(4):401–5. doi.org/10.3126/jcmsn.v13i4.16893 9. mukhopadhyay b, ahmad sn, agarwal s, kabra sl. evaluation of feto-maternal outcome using afi and sdvp for amniotic fluid assessment; which is a better method? int j reprod contracept obstet gynecol. 2017;6(7):3109. doi.org/10.18203/2320-1770.ijrcog20172943 10. uche eb, chijioke o, chukwuemeka oe, robinson oc. incidence of oligohydramnios-amniotic fluid index (afi) versus single deepest vertical pocket (sdp). asian j med health. 2018;10(3):2456–8414. doi: 10.9734/ajmah/2018/28069 11. kahkhaie kr, keikha f, keikhaie kr. perinatal outcome after diagnosis of oligohydramnious at term. iranian red crescent med j. 2014;16. doi: 10.5812/ircmj.11772 213 journal of rawalpindi medical college (jrmc); 2022; 26(2): 208-213 12. coombe-patterson j. amniotic fluid assessment: amniotic fluid index versus maximal vertical pocket. j diagn med sonography. 2017;33(4):280–3. doi.org/10.1177/8756479316687269 13. magann ef, sanderson m, martin jn, chauhan s. the amniotic fluid index, single deepest pocket, and two-diameter pocket in normal human pregnancy. am j obstet gynecol [internet]. 2000;182(6):1581–8 doi.org/10.1067/mob.2000.107325 14. rosati p, guariglia l, cavaliere af, ciliberti p, buongiorno s, ciardulli a, et al. a comparison between amniotic fluid index and the single deepest vertical pocket technique in predicting adverse outcome in prolonged pregnancy. j prenat med [internet]. 2015;9(1–2):12–5. doi.org/10.11138/jpm/2015.9.1.012 15. peixoto ab, da cunha caldas tmr, giannecchini cv, rolo lc, martins wp, araujo júnior e. reference values for the single deepest vertical pocket to assess the amniotic fluid volume in the second and third trimesters of pregnancy. j perinat med [internet]. 2016;44(6):723–7. doi.org/10.1515/jpm-2015-0265 16. moore tr. superiority of the four-quadrant sum over the single deepest pocket technique in ultrasonographic identification of abnormal amniotic fluid volumes. am j obstet gynecol. 1990;163(3):762-7.doi.org/10.1016/0002-9378(90)91064-j 17. myles td, santolaya-forgas j. normal ultrasonic evaluation of amniotic fluid volume in low-risk patients at term. j reprod med. 2002;47:621–4. pmid: 12611088 18. youssef aa, abdulla sa, sayed eh, salem ht, abdelalim am, devoe ld. superiority of amniotic fluid index over amniotic fluid pocket measurement for predicting bad fetal outcome. south med j [internet]. 1993;86(4):426–9. dx.doi.org/10.1097/00007611199304000-00011 19. verrotti c, bedocchi l, piantelli g, et al. amniotic fluid index versus largest vertical pocket in the prediction of perinatal outcome in post term pregnancies. acta biomed. 2004;75(suppl 1):67–70 pmid: 15301295 20. nabhan af, abdelmoula ya. amniotic fluid index versus single deepest vertical pocket as a screening test for preventing adverse pregnancy outcome. cochrane database syst rev [internet]. 2008;(3):cd006593. doi.org/10.1002/14651858.cd006593.pub2 21. noor n, raza sa, parveen s, khalid m, ali sm. amniotic fluid index versus maximum vertical pocket measurement in predicting perinatal outcome at 40 weeks or beyond. int j reprod contracept obstet gynecol. 2018;7(12):4887. doi.org/10.18203/2320-1770.ijrcog20184934 22. rossi ac, prefumo f. perinatal outcomes of isolated oligohydramnios at term and post-term pregnancy: a systematic review of literature with meta-analysis. eur j obstet gynecol reprod biol. 2013;169(2):149–54. doi.org/10.1016/j.ejogrb.2013.03.011 404 not found 404 not found 395 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 original article comparison of neonatal respiratory morbidity in neonates delivered at term by elective caesarean section with and without antenatal corticosteroid shabnam tahir1, faiza iqbal2, saima jabeen3, asma nawaz4, zunaira arshad5, shazia rasul6 1 associate professor, shalamar hospital, lahore. 2 senior registrar, shalamar hospital, lahore. 3 professor, shalamar hospital, lahore. 4 post-graduate trainee, shalamar hospital, lahore. 5 consultant, thq hospital, chichawatni. author’s contribution 1 conception of study 3 experimentation/study conduction 2 analysis/interpretation/discussion 1 manuscript writing 4 critical review 5 facilitation and material analysis corresponding author dr. faiza iqbal, senior registrar, shalamar hospital, lahore email: faizaiqalshehzadi@gmail.com article processing received: 04/12/2021 accepted: 14/09/2022 cite this article: tahir, s., iqbal, f., jabeen, s., nawaz, a., arshad, z., rasul, s. comparison of neonatal respiratory morbidity in neonates delivered at term by elective caesarean section with and without antenatal corticosteroid. journal of rawalpindi medical college. 30 sep. 2022; 26(3): 395-401. doi: https://doi.org/10.37939/jrmc.v26i3.1820 conflict of interest: nil funding source: nil access online: abstract introduction: performing elective caesarean section prior to 39 completed weeks, it can lead to breathing problems in neonates as compare to those, who are born through caesarean section without antenatal corticosteroid. who recommends the administration of intramuscular corticosteroids either dexamethasone or betamethason (total 24mg in divided doses) in the antenatal period, when there is a risk of preterm birth. the advantages and disadvantages of a similar regimen given after 37 weeks of pregnancy prior to elective caesarean section (lscs) to prevent respiratory morbidity in a newborn is yet a topic of discussion. in pakistan still, many clinicians are doing caesarean section at 37 or 38 weeks without antenatal corticosteroids. the rationale is to emphasize the use of steroids before caesarean at 39 weeks. objective: to compare neonatal respiratory distress in neonates delivered between 37 --38+6 weeks of gestation by elective caesarean section with and without antenatal corticosteroid. study design: randomized controlled trial. setting: department of gynae & obstetrics, unit 2, shalamar hospital, lahore. duration: six months from 12th september 2018 to 12th march 2019. materials and methods: the study included women who were, planned for elective lscs at 37-38+6 weeks, divided into two groups .the sample size was 140 (70 in each group), recruited by non-probability consécutive sampling. inclusion criteria were singleton pregnancy, at 37 to 38+6 weeks for elective lscs due to indications like primi breech, previous caesarian scar/scars, and maternal wish. all eligible participants were allocated to one of the following groups. group (a) received an injection of dexamethasone 48 to 72 hours before elective lscs. group (b), did not receive an injection of dexamethasone. the outcome to be measured in this study were the apgar score at 1& 5 minutes, the incidence of transient tachpnea of the neonate (ttn) and respiratory distress syndrome (rds) in newborns, and the need for mechanical ventilation among neonates from two different groups. the data was collected and analyzed by spss version 20. descriptive statistic were applied to calculate the mean and sd for age, gestation age & bmi. student t-test was used to compare the continuous outcome measures. neonatal respiratory morbidity was compared in two groups by using the chi-square test at the level of significance of 0.05. results: mean age in group-a was 28.12± 5.6 and in group-b was 28.97± 6.3 years. there was no statistically significant difference in these groups in terms of body mass index, gestational age at the time of delivery, age of mother, birth weight, apgar score at 1 and 5 min, and indications for cesarean section. neonatal respiratory morbidity was higher in group-b as compared to group-a (30% vs.12.9%) p-value-0.013. conclusion: antenatal dexamethasone administration significantly reduces the respiratory morbidity among neonates delivered at 37 to 38+6 by elective cesarean section. but further studies are required to assess the beneficial role of dexamethasone in the reduction of neonatal respiratory morbidity with a large sample size. keywords: neonatal respiratory morbidity, transient tachypnea of newborn, elective caesarean section, antenatal corticosteroids. 396 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 introduction cesarean section is one of the most commonly performed procedures in obstetrics which is performed whenever there is a risk to the life of the mother or fetus during vaginal delivery.1 however, there is an alarming rise in the caesarean section rate in the last 20 years and it’s a matter of great concern to health experts globally. this rapid spurt in the rate of abdominal delivery in recent years deserves paramount concern.2 cesarean section rate should not be higher than 10%–15%0 3 according to world health organization (who) recommendation. the rising trend toward elective caesarean section is due to various indications like increasing maternal age at first pregnancy4, primigravida with breech presentation, maternal request and downswing in a trial of previous one caesarean section, etc. safety of the procedure has been increased due to the availability of spinal anesthesia, antibiotic prophylaxis, and better control of hemorrhage with uterotonics leading to decreased risk of caesareans-related complications like hemorrhage, infection, and thromboembolic events. the result is that obstetricians as well as a patient have evolved a reduced threshold for selecting elective caesarean section as an easy mode of delivery. although increased safety of the procedure has reduced maternal risks, the adverse effects on the baby due to elective caesarean delivery before the onset of labour is yet a matter of paramount concern and needs to be addressed. change in trend has been seen currently in women especially primigravida’s with high heads and post-dated pregnancies, requesting for elective caesarean section to avoid prolonged hours of induction of labor, and uncertain labor outcome5 which has emerged as another indication of c-section i.e. c-section on maternal wish. trial of labor after caesarean delivery has also decreased significantly in many countries, due to fright of the risk of scar rupture of previous cesarean leading to increased maternal and perinatal mortality as compared to a planned caesarean section.6,7,8 both the obstetrician, as well as pregnant women, feel more comfortable with the planned caesarean section as compared to taking risks associated with vaginal birth after c-section. the largest randomized controlled trial, the term breech trial, compared the effect of the mode of breech deliveries on neonatal outcomes. its results were published in the year 2000, showing a significant decrease in neonatal mortality & morbidity in elective cesarean compared to vaginal breech delivery. publication of national guidelines after this trial changed management practices regarding the mode of breech delivery.9,10 cesarean rate increased by 28% within 3 months after the publication of the term breech trial in the netherlands. similarly, an increasing rate of caesarean deliveries has been documented in pakistan. the studies conducted in various regions of pakistan have shown trends toward rising rates of abdominal deliveries.11,12 one of the known complications of elective c-section conducted between 37-38+6 weeks of gestation is neonatal respiratory morbidity which includes a range of conditions, varying from its milder form, transient tachypnea (ttn) of the neonate to its severe form i.e. respiratory distress syndrome (rds). ttn is a selfresolving state caused by a delay in the absorption of fluid from the lung's alveoli after delivery. it usually presents with an increased respiratory rate of > 60 breaths per minute, grunting, and mild signs of respiratory distress usually lasting up to 48 to 72 hours. on the other hand, rds is a severe form of respiratory distress, due to a deficiency of surfactant which is the main contributor to elastic properties of pulmonary tissue, leading to a collapse of lung alveoli. during fetal life, lung epithelium secrets a fluid in alveoli. along with the passage of time as gestational age advances the production of this fluid decreases and gradually lung epithelium becomes more absorptive in nature rather than secretary due to the increase in the number and function of sodium channels. the factors responsible for this change in sodium channels are not well known, but it is well documented that with increasing gestational age and stress of labor, glucocorticoids are released leading to the maturation of type ii pneumocytes, which produce surfactants. it results in a significant reduction of fluid volume in alveoli close to term and before delivery, with additional removal of fluid during labor. elective caesarean bypasses this physiological process assisted by nature, thereby increasing the likelihood of neonatal respiratory morbidity.11 this underlying physiology provides strong justification and philosophy for the administration of corticosteroids in the antenatal period to women who are planned to be delivered by elective cesarean section.12 exogenous corticosteroids are readily transported across the placenta to the fetus. the exact mechanisms of their action are not fully known. however, it is believed that antenatal corticosteroids when given intramuscularly improve respiratory outcomes in several ways i.e. by thinning of the alveolar septae, enhancing differentiation of type ii pneumocytes, decreasing surface tension within alveoli, increasing 397 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 pulmonary circulation by endothelial nitric oxide synthase, improving pulmonary adaptation at birth due to increased number of epithelial sodium channels, which clears fluid from the alveolar lumen to the interstitium and preventing v/q mismatch. thereby reducing overall neonatal respiratory morbidity because the retained fluid in the alveoli leads to ineffective gas exchange through the respiratory membrane leading to respiratory distress, and tachypnea by stimulating the respiratory center in the medulla oblongata in the brain stem. an increase in respiratory rate continues until the fluid is absorbed generally takes 48 to 72 hours after delivery. rcog (royal college of obstetrics & gynecology) recommends that the most appropriate time to perform elective lscs is around 39 weeks of gestation.13,14 if an elective caesarean is desired to perform before 39 weeks of gestation, dexamethasone injections 48 to 72 hours before caesarean section should be given to decrease the risk of nrm.13,14 there are a limited number of studies conducted in pakistan regarding this issue and yet most elective cesarean sections are being performed before 39 weeks without antenatal corticosteroids which increases the risk of respiratory morbidity in neonates. we carried out this study in our setup to compare neonatal respiratory morbidity in neonates delivered by elective cesarean between 37-38+6 weeks after administering dexamethasone as compared to neonates of those mothers who did not receive prophylactic dexamethasone before elective cesarean. materials and methods this study was conducted at a tertiary care level hospital in lahore. it included those women who were delivered by elective lower segment caesarean section at 37-38+6 weeks. the sample size was 140 (70 in each group) recruited by non-probability consécutive sampling technique. inclusion criteria were pregnant women with a singleton pregnancy, gestational age≥37 weeks with an indication for elective lscs like previous caesarian scar/scars, primi breech, and maternal wish. only those women included in the study who were sure of their last menstrual date, their previous menstrual cycle was regular and they had their early dating scan for confirmation of dates by measuring crown-rump length. informed written consent was obtained for participation. we excluded women with obstetric complications including preeclampsia, diabetes mellitus, ante-partum hemorrhage, fetal anomaly, twin pregnancy, and intrauterine growth restriction. all eligible participants were allocated to one of the following groups. group a, received an injection of 12 mg dexamethasone, intramuscular two doses 12 hours apart, 48 to 72 hours before elective cs. group b did not receive dexamethasone. all patients underwent caesarean section under spinal anesthesia by senior residents/consultants. all deliveries were attended by senior pediatric residents; details of the resuscitation were recorded. apgar scores at 1 and 5 minutes were recorded. neonatal respiratory morbidity was compared between the two groups. all neonates were assessed for signs of transient tachypnea of newborn, which is a period of rapid breathing 4060 times/min, and rds which is diagnosed based on the presence of at least 2 of the following criteria: tachypnea, central cyanosis in room air, expiratory grunting, subcostal, intercostals recessions, and nasal flaring. all neonates admitted to nicu had chest x-rays to exclusion of other associated pathologies and to confirm /rule out a diagnosis of rds. the primary outcomes of this study were to see the incidence of ttn and rds. the secondary outcomes included admission to nicu and the need for mechanical ventilation within 24 hours after birth. data was entered and analyzed by spss version 20. descriptive statistics were applied to calculate the mean and sd for age, gestation age, and bmi. frequencies and percentages were calculated for outcome variables like parity, gravidity, and neonatal respiratory morbidity in both groups. the demographic data were compared between groups. student t-test was used to compare the continuous outcome measures. neonate respiratory morbidity in both groups was compared by using the chi-square test at the level of significance of 0.05. results the total number of patients in the study was equally divided into two groups. the mean age of women in group-a was 28.12±5.62 and in group b was28.97±6.36 years. there was no statistically significant difference in both groups in terms of parity, body mass index, indications for c-section, and gestational age at the time of planned delivery. birth weights of babies in both groups a & b were 2.47+0.23 vs 2.48+0.18 kilogram respectively. neonatal respiratory morbidity was significantly higher in group b as compared to group a, 30% vs 12.9%. 398 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 table 1: the demographic characteristics of the study participants variables group a (n=70) group b (n=70) p-value age (years )+sd 28.12+5.62 29.97+6.36 >0.05. parity  primigravida (72)  multigravida (68) 31(44.3%) 39(55.7%) 41(58.6%) 29(41.4%) >0.05. bmi (kg/m2)+sd normal overweight obese 23(32.9%) 23(32.9%) 24(34.3%) 24(34.3%) 28(40%) 21(30% >0.05. gestational age at the time of delivery (weeks),+sd 37.38+0.49 37.57+0.49 >0.05. indication of cs n (%) 1. caesarean sections, on maternal request. 2. breech presentation. 3. previous scar/scars 15(21.4%) 10(14.2%) 45(64.2%) 13(18.5%) 09(12.8%) 48(68.5%) >0.05. group-a: study group (dexamethasone), group-b: controls group (without dexamethasone) table 2: comparison of neonatal respiratory morbidity in two groups variables group( a) group( b) p-value birth weight. mean+sd(range) 2.47+0.23 2.48+0.18 >0.05. apgar score, mean+sd at 1-minute at 5-minute 8.97 ± (0.21) 9.99 ± (0.10) 8.99 ± (0.14) 10.00 ± (0.06) >0.05. neonatal respiratory morbidity, n (%) 9(12.9%) rds (0) ttn (9) 21(30%) ( mild rds) (2) ttn (28) 0.013 need for mechanical ventilation 0% 0% ------ group-a: study group (dexamethasone), group-b: controls group table 3 neonatal respiratory morbidity in relation to gestational age gestational age respiratory morbidity group-a (n=70) group-b (n=70) p-value 38-38+6 yes 5(11.6%) 8(26.7%) 0.021 no 38(88.4%) 22(73.3%) 37-37 +6 yes 4(14.8%) 13(32.5%) 0.011 no 23(85.2%) 27(67.5%) group-a: study group (dexamethasone), group-b: controls group discussion the risk of neonatal respiratory morbidity including transient tachpnea of newborns, hyaline membrane disease, and persistent fetal circulation syndrome is higher for elective cesarean delivery compared with vaginal delivery earlier than 39 to 40 weeks of gestation.15,16,17 several studies have been conducted to evaluate the correlation of gestation age at the time of birth with neonatal respiratory morbidity and all these strongly support an inverse relationship between them, among infants born by elective caesarean birth.18,19 southfield et al reported in their research that planned caesarean section before 40 weeks gestation increases neonatal admissions due to breathing problems.2 respiratory morbidity was 1.7 times higher in those neonates who were delivered between 37 and 37+6 weeks of gestation as compared to those who had a delivery at 38-38+6 weeks; when the same group was compared with those newborns who were delivered at 39-39+6 weeks26 risk of respiratory morbidity increased up to 2.4 times higher. therefore, many guidelines 399 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 recommend that planned caesarean section should not be routinely carried out before 39 weeks of gestation.21,22 our study was designed to compare neonatal respiratory morbidity in patients delivered between 37 to 38+6 by planned caesarean section with or without injection of dexamethasone given intramuscularly to mothers 48 to 72 hours before delivery. results of this study showed that neonatal respiratory morbidity was significantly higher in women who were not given dexamethasone i.e. group-a (12.9%) vs group-b (30%), p-value=0.013. the results of our study are consistent with the findings of mohammed n. saleem who reported in his study that the incidence of neonatal respiratory morbidity was quite higher in the women, who had elective c-sections without prophylactic dexamethasone administration compared to the study group who received dexamethasone 48 to 72 hours before planned delivery through abdominal route (4.7% versus 0.8%, respectively; p=0.001).23 a cochrane systemic review in 2009, on the prophylactic administration of corticosteroids before elective csection at term deduced that although it reduced the number of neonatal admissions in nicu significantly but as far as incidence of respiratory distress syndrome and transient tachypnea of the newborn is concerned there was no statically significant difference in two groups who were delivered with or without prophylactic dexamethasone. (rr=0.15). the study concluded that more studies should be conducted before the routine recommendation of antenatal corticosteroid therapy for elective c-sections.24 however, results of a meta-analysis have been published in 2018 in which the same researcher strongly supported the use of prophylactic antenatal corticosteroid to decrease the risk of respiratory distress syndrome significantly in patients who are delivered by elective c-section at term between 37 to 39 weeks.24 stutchfeld and coworkers performed a randomized trial which convinced that two doses of dexamethasone given within 48 to 72 hours before planned caesarean significantly decreases the risk of respiratory distress by converting the alveolar lining epithelium of lungs to be absorptive in nature rather than secretory in function.25 .peter stutchfield, rhiannon whitaker on behalf of, the large, antenatal steroids for term elective caesarean section research (astecs) in 2005, a non blinded randomized trial has proven that incidence of respiratory distress at 3739 weeks of gestation is remarkably decreased with two doses of antenatal steroids, ttn decreases from 4% to 2.1% and rds from 1% to 0.2%. this trial also showed that infants who received this therapy had lower rates of nicu admission and were less likely to require resuscitation/ventilation at birth. results of our study also favored this trial as newborns delivered at 38 to 38+6 weeks of gestation had better neonatal respiratory outcomes as compared to those who delivered between 37 to 37+6 weeks of gestation, with 26.7% vs 32.5% neonatal respiratory morbidity respectively. another non-blinded randomized trial by ahmed et al measured the effectiveness of two doses of dexamethasone administered before elective delivery by c-section to a group of pregnant women at 37 weeks or beyond.26 ttn was reduced in the dexamethasone group compared to the nonintervention group (7% vs. 19.6%).27 although there was no neonatal mortality in our control group, however, increased number of neonatal admissions caused increased anxiety to the parents and increased costs due to prolonged hospital stays and compromised mother & neonate bonding. regarding the harmful effects of corticosteroids, studies have suggested that more than one course of antenatal steroids has harmful effects in terms of low birth weight and reduced neonatal head circumference size.28 however there are a number of studies that have proven that a single course of antenatal corticosteroids is not related to an increased risk of maternal or fetal infection and has no adverse neurological effects.29-32 besides the mode of delivery, gestational age at the time of delivery also affects the risk of neonatal respiratory problems as well as compromises mother-infant bonding due to staying in the neonatal nursery. in 2013, the american college of obstetricians and gynecologists (acog) suggested that early-term should be defined as delivery occurring between 37 to 39 weeks gestation. they noted that neonatal outcomes, in particular respiratory morbidity, were different depending on the time of delivery hence the need to redefine the traditional definition of term deliveries occurring between 37 and 41 weeks gestation.33 however deferring planned caesarean section to 39 weeks or beyond has its own demerits because of the risk of labour to start or rupture of membranes prior to the date of planned caesarean section with increased risk of umbilical cord prolapse in footling/flexed breech, thus requiring caesarean section in an emergency with significantly increased risk of intrapartum complications like dense adhesions due to previous surgeries, hemorrhage, bladder injury, gut injury all leading to increased 400 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 maternal morbidity and increase workload for duty staff and blood transfusion services due to increasing in numbers of emergency lscs. this increased maternal hazard associated with emergency needs to be weighed against the expected improved neonatal outcomes of performing elective lscs near term. to balance the risk it is recommended that in women without additional risks, a planned caessarean section should be performed around 39 weeks of pregnancy. in those scenarios where delivery is anticipated before 39 weeks of pregnancy, the administration of corticosteroids has advantages in reducing neonatal respiratory morbidity. dexamethasone has an advantage over betamethasone in terms of lower cost and wider availability. however repeated courses of antenatal corticosteroids are yet not recommended until further studies prove increased benefit versus the potential risk of hazard to the mother and fetus.9 conclusion results of this study showed that antenatal dexamethasone administration significantly reduces respiratory morbidity among neonates delivered at 37 to 38+6 by elective cesarean section. obstetricians should weigh and balance the risks of elective cesarean delivery before 39 weeks gestation in terms of increased neonatal morbidity against the risks of caesarean section performed in an emergency. ideally, elective caesarean should be performed around 39 completed weeks of gestation, but when early required to perform, an injection of dexamethasone should be administered 12 mg intramuscular 12 hours apart two doses 48 to 72 hours before elective delivery to decrease respiratory morbidity in newborns. but further studies are required to assess the beneficial role of dexamethasone in the reduction of neonatal respiratory morbidity with a large sample size references 1. khan r, blum ls, sultana m, bilkis s, koblinsky m. an examination of women experiencing obstetric complications requiring emergency care: perceptions and sociocultural consequences of caesarean sections in bangladesh. j health popul nutr. 2012 jun;30(2):159-71. doi: 10.3329/jhpn.v30i2.11309. pmid: 22838158; pmcid: pmc3397327. 2. sethi p, vijaylaxmi s, shailaja g, bodhare t, devi s. a study of primary caesarean section in multigravidae. perspectives in medical research. 2014;2:3-7. doi: http://dx.doi.org/10.18203/2320-1770.ijrcog20175843 3. chalmers b.who appropriate technology for birth revisited. bjog: br j obstet gynaecol.1992; 99:709–710. 4. kenny lc, lavender t, mcnamee r, o'neill sm, mills t, khashan as. advanced maternal age and adverse pregnancy outcome: evidence from a large contemporary cohort. plos one. 2013;8(2):e56583. doi: 10.1371/journal.pone.0056583. epub 2013 feb 20. pmid: 23437176; pmcid: pmc3577849. 5. kottmel a, hoesli i, traub r, urech c, huang d, leeners b, tschudin s. maternal request: a reason for rising rates of cesarean section? arch gynecol obstet. 2012 jul;286(1):93-8. doi: 10.1007/s00404-012-2273-y. epub 2012 mar 10. pmid: 22407124.4.-fong a, king e, pan d, ogunyemi d. declining vbac rates despite improved delivery outcomes compared to repeat cesarean delivery. obstetric gynecol. 2016; 127:144 6. fong a, king e, pan d, ogunyemi d. declining vbac rates despite improved delivery outcomes compared to repeat cesarean delivery. obstetric gynecol. 2016; 127:144 7. uddin sf, simon ae. rates and success rates of trial of labor after cesarean delivery in the united states, 1990-2009. matern child health j. 2013 sep;17(7):1309-14. doi: 10.1007/s10995012-1132-6. pmid: 22991012. 8. fitzpatrick ke, kurinczuk jj, alfirevic z. uterine rupture by intended mode of delivery in the uk: a national case-control study. plos med. 2012; 9(3). 9. betrán ap, merialdi m, lauer ja, bing-shun w, thomas j, van look p, wagner m. rates of caesarean section: analysis of global, regional and national estimates. paediatr perinat epidemiol. 2007 mar;21(2):98-113. doi: 10.1111/j.13653016.2007.00786.x. 10. term breech deliveries in the netherlands: did the increased cesarean rate affect neonatal outcome? a population‐based cohort study first published: 11 august 2014 11. mumtaz s, bahk j, khang yh (2017) rising trends and inequalities in cesarean section rates in pakistan: evidence from pakistan demographic and health surveys, 1990-2013. plos one 12(10): e0186563. doi: https://doi.org/10.1371/journal.pone.0186563 12. ali y, khan mw, mumtaz u, salman a, muhammad n, sabir m. identification of factors influencing the rise of cesarean sections rates in pakistan, using mcdm. int j health care qual assur. 2018 oct 8;31(8):1058-1069. doi: 10.1108/ijhcqa-042018-0087. pmid: 13. madar j, richmond s, hey e. surfactant-deficient respiratory distress after elective delivery at 'term'. acta paediatr. 1999 nov;88(11):1244-8. doi: 10.1080/080352599750030365. pmid: 10591427. 14. royal college of obstetricians and gynecologists’ scientific advisory committee. rcog guidelines no 7: antenatal corticosteroids to prevent respiratory distress syndrome. 2nd ed. london: rcog press; 2004. 15. jain l, eaton dc. physiology of fetal lung fluid clearance and the effect of labor. semin perinatol. 2006 feb;30(1):34-43. doi: 10.1053/j.semperi.2006.01.006. pmid: 16549212. 16. hansen ak, wisborg k, uldbjerg n, henriksen tb. elective caesarean section and respiratory morbidity in the term and near-term neonate. acta obstet gynecol scand. 2007;86(4):38994. doi: 10.1080/00016340601159256. pmid: 17486457. 17. kolas t, saugstad od, daltveit ak, nilsen st, øian p. planned cesarean versus planned vaginal delivery at term: comparison of newborn infant outcomes. am j obstet gynecol. 2006 dec;195(6):1538-43. doi: 10.1016/j.ajog.2006.05.005. epub 2006 jul 17. pmid: 16846577. 18. gouyon jb, ribakovsky c, ferdynus c, quantin c, sagot p, gouyon b. severe respiratory disorders in term neonates. paediatr perinat epidemiol 2007; 22: 19. hansen ak, wisborg k, uldbjerg n.risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study. bmj 2008; 336: 857. 401 journal of rawalpindi medical college (jrmc); 2022; 26(3): 395-401 20. stutchfield p, whitaker r, russell i. antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. 21. morrison jj, rennie jm, milton pj. neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. br j obstet gynaecol. 1995 feb;102(2):101-6. doi: 10.1111/j.1471-0528.1995.tb09060.x. pmid: 7756199. 22. yee w, amin h, wood s. elective cesarean delivery, neonatal intensive care unit admission, and neonatal respiratory distress. obstetrics & gynecology. 2008;111(4):8823-8.15. 23. salem mn, abbas am, ashry m. dexamethasone for the prevention of neonatal respiratory morbidity before elective cesarean section at term. proceedings in obstetrics and gynecology. 2016;6(3):1-10. doi: https://doi.org/10.17077/2154-4751.1321 24. sotiriadis a, makrydimas g, papatheodorou s, ioannidis jp. corticosteroids for preventing neonatal respiratory morbidity after elective caesarean section at term. cochrane database syst rev. 2009 oct 7;(4):cd006614. doi: 10.1002/14651858.cd006614.pub2. update in: cochrane database syst rev. 2018 aug 03;8:cd006614. pmid: 19821379. 25. 25-stutchfield p, whitaker r, russell i. antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. bmj. 2005;331(7518):662. 26. ahmed mr, sayed ahmed wa, mohammed ty. antenatal steroids at 37 weeks, does it reduce neonatal respiratory morbidity? a randomized trial. the journal of maternal-fetal & neonatal medicine. 2015;28(12):1486-90. 27. national institute of health and clinical excellence: clinical guideline caesarean section 2011. 28. royal college of obstetricians and gynecologists’ scientific advisory committee. rcog guidelines no 7: antenatal corticosteroids to prevent respiratory distress syndrome. 2nd ed. london: rcog press; 2004. 29. crowley p. prophylactic corticosteroids for preterm birth. cochrane database systematic review. 2000 ;(2) 30. doyle lw, ford gw, davis nm, callanan c. antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. clin sci (lond) 2000; 98: 137-42. 31. walfisch a, hallak m, mazor m. multiple courses of antenatal steroids: risks and benefits. obstet gynecol 2001; 98: 491-7. 32. bloom sl, sheffield js, mcintire dd, leveno kj. antenatal dexamethasone and decreased birth weight. obstet gynecol 2001; 97: 485-90. 33. saccone g, berghella v. antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. bmj. 2016;355:i5044. summary journal of rawalpindi medical college (jrmc); 2018;22(3): 287-290 287 original article knowledge among general population of rawalpindi, about crimean-congo haemorrhagic fever (cchf) tariq masood khan1, nadeem ikram 2 1. department of administration , holy family hospital, rawalpindi;2. department of pathology, rawalpindi medical college abstract background: to find out the awareness about crimean-congo hemorrhagic fever (cchf) among residents of rawalpindi methods: in this descriptive cross sectional survey, participants from general population of rawalpindi were included. the sample size for the study consisted of 300 individuals. the data was collected using a self structured pre tested questionnaire and was analyzed using spss 21. results: majority of the participants in the study were males (79%). regarding their educational status 55.7% were illiterate and almost 63% had heard previously regarding it and claimed to be having information regarding cchf. their sources of information were variable but the majority (25.3 %) got it through sources like friends, colleagues, warning posters, brochures etc. according to the people who were aware, 19.7% viewed its transmission from infected person and almost same number stated it to be transmitted by animal source, almost 13.3% labeled it as airborne, while 11% thought its transmission through ticks. conclusion: cchf is a life threatening disease and has more chances to become prevalent in pakistan . a meticulous multidisciplinary effort is required to manage the situation. due to poor infrastructure, lack of education and limited access to health-related and livestock-related facilities, preventive measures are rare. the general population of rural and urban areas should have awareness about the signs and symptoms, mode of spread and seriousness of the disease. key words: knowledge, crimean-congo hemorrhagic fever, general population. introduction crimean-congo hemorrhagic fever (cchf) is a disease which is due to arbo virus. arbo virus belongs to genus nairovirus and family bunyaviridae. the incubation period of arbo virus is small. sudden fever, shivering, disequilibrium, lumbago, headache and painful involuntary contraction of abdominal muscles are the main symptoms of cchf. further symptoms of this disease can be diarrhorrea, nausea, vomiting, circulatory, cardiac & neuropsychiatric changes. in advanced stages of cchf, haemorrhages occur which may vary from minor petechiae to a large ecchymosis.1 attained human contamination cases have been reported from different countries.2 except for homo sapiens, virus has been sequestered from ticks or mammals in central african republic, nigeria madagascar, afghanistan, hungary, ethiopia, senegal and greece and nosocomial contaminations outburst in pakistan, iran and dubai in late nineteenseventy’s,while in around 2000, outdoor situation was created in kosovo due to vulnerability of battle at a large scale, in albaniain roughly around 2001, and pakistan from 2001 to around 2002.3 in various regions of pakistan, cchf patients were inspected. in 1960’s, cchfv strain was isolated in chaanga maanga forest in lahore, while in 1976, the first case of cchf was diagnosed in general hospital, rawalpindi. in 1994, a case was reported in quetta.4 experiments were then conducted to inspect the ways of cchfv transmission by blood and body fluids of infected people. in december 2005, a cchfv victim was inspected in combined military hospital of abbottabad city located in north of hazara division, pakistan. in 2000, cchfv was revealed in peshawar. in 2002, a 25 years old woman was diagnosed with cchfv fever in kashmir. 5 according to who report, from january 1 to 9 june 2013 almost twenty six cchfv cases were diagnosed with mortality rate of 37.5%, however sixty nine cases were identified in 2015-16 from different regions of pakistan. 6 since 2011-2013, one hundred and eighty three cases were confirmed with 50% fatality rate. survey revealed about 62% cases were observed in area killa abdullah, killa saifullah, and quetta with some incidences in rawalpindi, multan, dera ismail khan, chakwal, and bannu. 77 cases of suspected cchf had been reported in the country with the inclusion of 15 deaths from journal of rawalpindi medical college (jrmc); 2018;22(3): 287-290 288 january to september 2013. out of these,48 reported cases were confirmed by laboratory tests. 2-7 from all the provinces of pakistan including islamabad, cchf has been reported during the recent year. investigations explored that the cause of cchf in most cases was contact with animal skin and animals.8 subjects and methods it was an observational descriptive study carried out in rawalpindi for 3 months. the data was collected from the general public of rawalpindi including the patients and their attendants visiting the major hospitals and public sites. the sample size for the study was calculated to be 300 using convenient sampling. the data was collected using a self structured questionnaire. only those individuals were included in the study who were capable to respond the questionnaire. results majority (55.7%) were illiterate. sixty three percent had information about congo fever. twenty-nine percent thought it any other type of fever, 20.7% thought that it is a bacterial infection and 13.3% considered that it is a viral fever. 37% individuals had just heard its name. 17.7% people had got the information about congo fever through tv and 5.3% through print media (table 1). there were 19.7% individuals who thought that contact with an infected patient is the main cause of congo fever. 19% (57) thought it is through contact with infected animals, 13.3% (40) considered it air borne, while 11% (33) people thought that ticks are responsible for the transmission of cchfv (table 2). 36.3% (109) thought that fever is the only symptoms in the patients with congo fever, 19% (57) thought that muscular pain is also a symptom along with fever in patients, while 7.7% (23) thought that bleeding also occurred along with fever in this disease. seventy six (25.3%) people preferred wearing a mask as a safety precaution, 7.3% (22) thought that by avoiding the contact with an infected person, they can save themselves while 67.3% (202) people didn’t have any safety measures in their mind. 18.7% (56) people thought that during the days of eid ul adha, congo fever spreads more widely than other days, 13.7% people thought that congo fever is common all over the year, 11% (33) people considered its occurrence only in spring season while 56.7% had no idea about it. according to 37.7% free treatment should be provided by the government for this disease, 22% had opinion that people should have more awareness about this disease. table 1. mode of information about congo fever source of information about congo fever? no percent no idea 111 37 tv 53 17.7 print media 46 15.3 radio 14 4.7 other sources 76 25.3 table 2. awareness about transmission of congo fever how the disease is transmitted? no percent infected animals 57 19 ticks 33 11 air borne 40 13.3 close contact with patient 59 19.7 don’t know 111 37 discussion a large number of wild and domestic animals can be infected by crimean-congo hemorrhagic fever virus. the bite of contagious ticks infect the animals with cchf. among animals, seroprevalence of cchfv has been discovered to be between 13% and 36%.9 the workers related to farm animals, farming, abattoir and veterinary practice were more prone to be infected by cchfv. the rural farmers of the northern senegal and south africa reported the seroprevalence of cchfv to be 13.1%. in 1976, the first case of cchf was diagnosed in pakistan and further 14 cases were reported during 1976 to 2010. the number of outbreaks which are previously reported in pakistan was thirteen. the recent reported cases be regarded as fourteenth outbreak of cchf in pakistan and the second breakout in rawalpindi. 43 deaths have been reported because of cchf since january 1976. cchf is diagnosed occasionally, but still it is well known disease among the medical staff in pakistan and they are afraid of this disease.10 nowadays, the reported cases of cchf has been increased. in karachi and rawalpindi, many reported cases of cchf were diagnosed from which seven deaths were recorded between january and june 2016.11 despite that, in the fatima jinnah general and chest hospital (fjch) quetta, 84 suspected patients of cchf have been reported. out of these , 22 patients were diagnosed with cchf of which ten patients died.12 it was disclosed from the clinical data that in journal of rawalpindi medical college (jrmc); 2018;22(3): 287-290 289 the rural areas of balochistan and afghanistan, where cattle herding is common, occasional cchf cases have been reported .13,14 in european, asian and african countries, hyalomma tick species is thought as the main culprit for the transmission of cchfv. it has been revealed from the findings that the areas of earth where land farming was common and climate was hot, there were more chances of occurring cchf infections. more cases of cchf are reported from the areas where land farmers come into more contact with livestock .15 it was revealed from a study that cchfv has been interchanged randomly between different countries and reported the free movement of asia-1genotype between iran and pakistan.16 in the same way, nearly all cases of cchf were either due to exposure with livestock or as the result of tickbite in turkey during 2005. inspite of the fact that it has not been possible to make serological surveys in pakistan.,many reported cases of cchf in karachi were due to contact with goats and sheeps brought from baluchistan to sindh.17 as cchf is a disease with high mortality rate and its transmission is mostly hospital acquired, so rapid confirmatory laboratory tests are necessary to control the disease and minimize its prevalence in pakistan.18 in pakistan, ticks are responsible for cchf virus transmission. despite of awareness about cchf and preventive measures among medical staff, hospital acquired outbreaks of cchf still continue in pakistan.19 in a study about the awareness of cchf, 78% people had knowledge about this disease. about 60% people thought it just a viral disease. in a study in which the source of information about cchf have been investigated, 35% people got information from tv , 23% patients from tutors and 50% people got information from the newspapers, articles and internet. 52% people thought it as communicable and life-threatening disease while 37% people did not have any idea about it. 23.3% people had knowledge about the role of tick in the virus transmission.20 majority (82%) considered the fever, bleeding from the body, muscular pain and headache as most important signs and symptoms of cchf. when asked about people at high risk, 26% people thought the shepherds at a high risk from cchf, 29% people considered the health workers at a high risk while others thought the workers in slaughter houses and milkman at a high risk from cchf.21 31% people thought that insecticides used in animal food against ticks was best preventive measure from cchf. conclusion 1.cchf is a serious disease and a meticulous multidisciplinary effort is required to manage the situation before the disease becomes more prevalent in pakistan. due to poor infrastructure, lack of education and limited access to health-related and livestockrelated facilities, preventive measures are rare. 2.general population of rural and urban areas should have awareness about the signs and symptoms, mode of spread and seriousness of the disease. protective and preventive measures should be provided to cattle husbandry. references 1. alam mm, khurshid a, sharif s, shaukat s, rana ms. genetic analysis and epidemiology of crimean congo hemorrhagic fever viruses in baluchistan province of pakistan. bmc infectious diseases. 2013;13(1):201-05. 2. altaf a, luby s, jamil a, najam a, aamir z, khan j. outbreak of crimean‐congo haemorrhagic fever in quetta, pakistan: contact tracing and risk assessment. tropical medicine & international health. 1998;3(11):878-82. 3. aradaib ie, erickson br, mustafa me, khristova ml, saeed ns. nosocomial outbreak of crimean-congo hemorrhagic fever, sudan. emerging infectious diseases. 2010;16(5):83740. 4. athar mn, baqai hz, ahmad m, khalid ma, bashir n. crimean-congo hemorrhagic fever outbreak in rawalpindi, pakistan, february 2002. the american journal of tropical medicine and hygiene. 2003;69(3):284-87. 5. burney m, ghafoor a, saleen m, webb p, casals j. nosocomial outbrak of viral hemorrhagic fever caused by crimean hemorrhagic fever-congo virus in pakistan, january 1976. the american journal of tropical medicine and hygiene. 1980;29(5):941-47. 6. deyde vm, khristova ml, rollin pe, ksiazek tg, nichol st. crimean-congo hemorrhagic fever virus genomics and global diversity. journal of virology. 2006;80(17):8834-42. 7. saeed ad, faizullah k, zafar t, arshad a. crimean congo hemorrhagic fever (cchf) outbreak in karachi. pakistan j med sci. 2002;41(1):36-38. 8. chinikar s, ghiasi sm, hewson r, moradi m, haeri a. crimean-congo hemorrhagic fever in iran and neighboring countries. journal of clinical virology. 2010;47(2):110-14. 9. mckenzie js, dahal r, kakkar m, debnath n, rahman m. one health research and training and government support for one health in south asia. infection ecology & epidemiology. 2016;6(1):33842-45. 10. wölfel r, paweska jt, petersen n, grobbelaar aa, leman pa. virus detection and monitoring of viral load in crimeancongo hemorrhagic fever virus patients. emerging infectious diseases. 2007;13(7):1097-99. 11. ölschläger s, gabriel m, schmidt-chanasit j, meyer m. complete sequence and phylogenetic characterisation of crimean–congo hemorrhagic fever virus from afghanistan. journal of clinical virology. 2011;50(1):90-92. 12. onguru p, dagdas s, bodur h, yilmaz m, akinci e, eren s. coagulopathy parameters in patients with crimean‐congo hemorrhagic fever and its relation with mortality. journal of clinical laboratory analysis. 2010;24(3):163-66. 13. ozkurt z, kiki i, erol s, erdem f, yılmaz n. crimean–congo hemorrhagic fever in eastern turkey: clinical features, risk journal of rawalpindi medical college (jrmc); 2018;22(3): 287-290 290 factors and efficacy of ribavirin therapy. journal of infection. 2006;52(3):207-15. 14. papa a, bino s, llagami a, brahimaj b, papadimitriou e. crimean-congo hemorrhagic fever in albania, 2001. european journal of clinical microbiology and infectious diseases. 2002;21(8):603-06. 15. smego jr ra, sarwari ar, siddiqui ar. crimean-congo hemorrhagic fever: prevention and control limitations in a resource-poor country. clinical infectious diseases. 2004;38(12):1731-35. 16. tonbak s, aktas m, altay k, azkur ak, kalkan a. crimeancongo hemorrhagic fever virus: genetic analysis and tick survey in turkey. journal of clinical microbiology. 2006;44(11):4120-24. 17. suleiman mneh, muscat-baron j, harries j, satti ago. congo/crimean haemorrhagic fever in dubai: an outbreak at the rashid hospital. the lancet. 1980;316(8201):939 41. 18. rodriguez ll, maupin go, ksiazek tg, rollin pe. molecular investigation of a multisource outbreak of crimeancongo hemorrhagic fever in the united arab emirates. the american journal of tropical medicine and hygiene. 1997;57(5):512-18. 19. yilmaz g, koksal i, topbas m, yilmaz h. the effectiveness of routine laboratory findings in determining disease severity in patients with crimean-congo hemorrhagic fever: severity prediction criteria. journal of clinical virology. 2010;47(4):361-65. 20. mild m, simon m, albert j, mirazimi a. towards an understanding of the migration of crimean–congo hemorrhagic fever virus. journal of general virology. 2010;91(1):199-207. 21. naveed s, rehman n, rehman s, malick s, yousuf s. knowledge and attitude about crimean congo hemorrhagic fever (cchf) amongst local residents of karachi, pakistn. j app pharm2014;21(30):78-81. summary journal of rawalpindi medical college (jrmc); 2017;21(3): 293-297 293 original article antibacterial potentials of human urine at acidic ph 5 mehveen iqbal1, aqeel ahmad1, ghulam fatima2, ejaz ahmed3, shakeel a. khan1, saira yahya1, faiz muhammad1and sabiha mirza4 1.department of microbiology, university of karachi; ,2 .civil hospital karachi; 3.united medical and dental college; 4.zubaida medical centre and fatima jinnah dental college, karachi abstract background: to identify factors determining susceptibility of individuals to urinary tract infections (utis). methods: in this descriptive study , 55 hospitalized patients' urine samples were analyzed. presence of red blood cells , pus cells, epithelial cells, casts and crystals were observed and counted under per high power field (hpf) by microscopy. while ph, specific gravity, protein, leukocytes, nitrites, glucose, ketones, urobilinogen, blood and bilirubin, were analyzed using dipstick method. all the samples were streaked on cled agar for isolation of bacteria; and sda for yeast. results: twenty urine samples were found culture positive, of which 15 were from females and 5 from males. cultures were isolated and identified as e. coli (11), enterococcus (4), klebsiella (3), pseudomonas (1) and yeast (1). interestingly, organisms were mainly isolated from urine samples having ph >5.5. in all the culture positive samples, pus cells were >20-40 /hpf. no patient with culture negative had urine ph 6.5 or above in the present study. conclusion: the probability of bacteriuria (uti) and pyuria (increase pus cells in urine) increases with rise in urine ph. persons with urine ph5 are generally protected from utis. thus mechanism/s needs to be elucidated. key words: urinary tract infections, ph, uropathogens, escherichia coli introduction infectious diseases are thought to be serious concerns for the entire world as infections are accountable for the death of large number of people since centuries. urinary tract infection is present both in community and hospital patients.1 females are more affected in comparison to males. structural abnormalities are considered as recognized predisposing factor of uti. 2 diagnosis and appropriate treatment of uti is of paramount importance in any developing countries with only 0.6% of gnp and the per capita income of only us$ 2. this makes the treatment of uti beyond the reach of any patient in a developing country particularly when 40% of population is below the poverty line. health-care should be the responsibility of the state but 0.6% of gnp cannot look after any patient properly and adequately. the importance of uti is being highlighted because the long standing / chronic uti can lead to permanent damage of the kidneys requiring renal replacement therapy (rrt) in the form of intermittent urinary dialysis/ continuous ambulatory peritoneal dialysis (capd) and transplantation. both modality of treatment cost pak. rs.300,000/to 500,000/per anum. any attempt to reduce the burden of patients requiring the above mentioned expensive treatment should be understood by researcher. 3,4 escherichia coli is predominate organism causing uti in both community and hospital environment . it has been observed that extremes of ages i.e. children and old age are more vulnerable to uti. 5,6ideally the urine should be cultured to find out the causative organisms so that effective treatment can be advised, however, the procedure is time consuming and expensive in pakistan particularly in rural areas where most of the family physician prescribed treatment of uti on the basis of symptoms of the patient where facilities of culture is not available. keeping the cost and relevance of diagnosis, this study was designed for simple, inexpensive diagnostic test for diagnosis of uti which is relevant to affordability of patient. in a normal healthy individual, rate of formation of urine is 800-2000 ml/day. however, various factors determine urinary output including water intake, weather conditions, etc. urine has up to 95% of water and rest is organic (urea,creatinine, uric acid) and inorganic (sodium, potassium, calcium, chloride, sulphate, magnesium, ammonium, chloride, sulphate and phosphates) substances. a very unique property of urinary tract is sterility, in spite of its close proximity to gastrointestinal system and parts of large intestine.7despite of constant exposure to microbes, nature has provided multiple barriers and different journal of rawalpindi medical college (jrmc); 2017;21(3): 293-297 294 systems to combat invading offenders.8 collectively all the barriers and mechanisms provided for defence of human body are termed as immune system. this system comprises of two arms; innate and adaptive. innate immunity is inborn, rapid and nonspecific. in contrast adaptive immune response is specific, delayed and required pathogen for activation. components of innate immunity include physical agents (skin, hairs, mucous membranes, ph etc.) and chemical barriers and immune cells (body secretions, phagocytic cell, enzymes, natural killer cells, etc.). the barricade apparatus of urinary tract, cells of epithelium and lining of the tract, along with continuous flushing contribute immensely towards pathogens.9 in addition, expression of certain receptors by host allows the immune system to sense and identify the intruder.10 after recognition, several arms and ammunition are employed by the immune organization to expel the foreign invader. similarly chemokine, cytokines and antimicrobial peptides, iron sequestering protein, and several others are constantly providing protection by innate and adaptive immunity.7 the adaptive immunity is delivered by lymphocytes; b lymphocytes for humoral immunity and t lymphocytes for cell-mediated immunity.11acidic ph of the urine also contributes toward controlling microbes. present study was designed to identify the ph at which most microbes are controlled. patients and methods this descriptive study includes school going children, young adults and grownups , suffering from acute or chronic urinary tract infection, catheterized or uncatheterized hospitalized patients were included. infants, toddlers, menstruating women and those suffered from tumours of urinary and genital tract of either sex were excluded. urine of 55 hospitalized patients was obtained from civil hospital karachi during january to december 2015. samples were analyzed within 6 hours of collection. microscopy was performed after centrifugation of urine samples for the presence of rbcs, pus cells, epithelial cells, casts and crystals. while ph, specific gravity, protein, leukocytes, nitrites, glucose, ketones, urobilinogen, blood and bilirubin were analyzed. all the samples were streaked on cysteine lactose electrolyte deficient (cled) (oxoid) agar by standard calibrated technique and incubated at 37°c for 24-48 h for isolation of bacteria; and saborauds dextrose agar (sda) (oxoid) for yeast. bacterial isolates were identified on the basis of cultural characteristic and gram staining. the isolates were further confirmed by biochemical tests using the standard methods for yeast direct microscopy and germ-tube formation test was performed.12-17antibacterial activity was determined by well diffusion method. briefly, escherichia coli atcc 25922 was grown overnight in muller hinton broth (oxoid) and its turbidity was adjusted to mcfarland 0.5 standard. 0.5 ml of adjusted culture was seeded to 20 ml melted macconkeys agar and poured into sterile petri plate. after solidification of agar, 8 mm wells were punched with a sterile borer. 0.1 ml of urine samples of different ph (57) were added in respective wells. similarly, antibiotics discs were added in respective wells and 0.1 ml of pbs or citrate buffer or urine was poured in each well, and plates were then transferred to 37oc incubator. zones of inhibition were measured in mm. dr and co-efficient correlation of pearson and statistical significance of variables were studied. results in all the culture positive samples, pus cells were found to be >20-40 /hpf. no other significant finding was observed (figure-1).while the analysis of ph, specific gravity, protein, leukocytes, nitrites, glucose, ketones, urobilinogen, blood and bilirubin revealed no significant difference between culture positive and culture negative samples. it is noteworthy to mention that cultures were isolated from urine samples at ph >5.5 (figure-1).the urine dr data were subjected to correlation analysis to estimate the pearson’s correlation coefficient (r) and statistical significance (pvalues) among variables using statistical package ibm spss statistics 20. pearson’s correlation indicates a predictive linear relationship (positive or negative). a strong positive correlation was observed between urine ph and bacteriuria (r = 0.551, p < 0.001).the probability of bacteriuria increases with the rise in urine ph and pus cells. nevertheless, there is strong relationship between pus cell count and bacteriuria with culture negative urine (p 3.644e-08).on testing the correlation between urine ph and pus cells, a statistically significant (p < 0.001) positive correlation of 0.659was observed. the urine parameters such as pus cells and bacteriuria were appraised under acidicph>5.5 (figure1).twenty urine (36%) samples were culture positive . majority (75%) were females.. escherichia coli was the commonest bacteria (55%) in urine samples (table-1). urine samples with ph 5 didn’t show any growth. organisms were mainly isolated from urine samples having ph >5.5 (figure2).growth was not detected in 63.64% urine samples of journal of rawalpindi medical college (jrmc); 2017;21(3): 293-297 295 hospitalized patients with utis (table-2). the reason for the negative culture could be prior antibiotic therapy or may have some physiological problems/ some lateral injuries or recovery from infection.). (p 0.0955) (p 0.000535) (p 0.01912) (p 0.000056) (p 0.009829 ) figure-1: relationship between bacteriuria (urine culture positive) and pus cells with urine table-1: distribution of organisms in culture positive urine samples organisms isolated percentage male% female% escherichia coli 55 18.18 81.82 klebsiella 15 33.33 66.66 enterococcus 20 25 75 pseudomonas 5 100 0 yeast 5 100 0 table-2: ph and growth of microorganisms in urine of hospitalized utis patients ph culture positive culture negative 5.0 0 19 5.5 05 11 6.0 10 05 6.5 04 0 7.5 01 0 total 20(36.36%) 35(63.64%) all culture negative urine samples having ph 5 to 6 are probably from the patients moving toward recovery from infections. no patient with culture negative had urine ph 6.5 or above. antibacterial activity of human urine ph5 was observed against e. coli atcc25922, but no activity was seen in urine ph5 obtained from old peoples aged 69 and 83 (table-3). little antibacterial activity was observed at ph5.no activity was detected in urine samples tested having ph6 or above. furthermore, ampicillin and norfloxacin activity was found slightly higher with the urine sample ph5 against e. coli atcc 25922 (table-4) 0 5 10 15 5 5.5 6 6.5 7 number of cases p h organisms isolated at different urine ph culture positive figure 2: relationship between urinary ph and organisms isolated table-3: effect of urine samples on escherichia coli atcc 25922 urine sample with zone of inhibitio n in mm s .no urine sample with zone of inhibition in mm ph 5 10 9 ph 5.5 nil ph 5 11 10 ph 6 nil ph 5 11 11 ph 6 nil ph 5 12 12 ph 6.5 nil ph 5 (age 69years) nil 13 ph 7 nil ph 5 (age 83years) nil 14 ph 7 nil ph 5.5 7 15 ph 7.5 nil ph 5.5 6 16 citrate buffer ph5 nil table-4: effect of antibiotics on microorganisms in the presence of urine ph5 zone of inhibition in mm treatment escherichia coli atcc 25922 pbs alone ph 7 nil nil citrate buffer ph5 nil nil urine ph5 10 11 pbs+ampicillin 26 26 citrate buffer+ampicillin 24 26 urine+ampicillin 28 28 pbs+norfloxacin 28 28 citrate buffer+ norfloxacin 30 30 urine+ norfloxacin 32 34 journal of rawalpindi medical college (jrmc); 2017;21(3): 293-297 296 0 25 50 20 5 54.3 31.4 14.3 0 0 0 10 20 30 40 50 60 ph 5 ph 5.5 ph 6 ph 6.5 ph 7.5 % o f c a s e s relationship of urine ph and culture culture + culture figure-3: culture negativity increases in urine of hospitalized utis patients with relation to ph of urine. discussion prevalence of urinary tract infection is unfortunately ignored and improperly treated both in community and hospital settings. this is leading to increase morbidity and mortality18. in the current study, it is observed that urinary ph, like stomach ph, is an important barrier for many pathogenic invaders in urinary tract.in a healthy person the urine ph ranges from 4.5 to 8. a number of factors contribute to determine the urine ph such as acid-base balance by kidneys, diet, water intake etc. vegetables, legumes and citrus fruit increase ph and cause alkalinity, while non-vegetarian diet contributes to acidic urine. urine sterility is maintained by the multiple barriers and factors of immune system to combat invading organisms.8 ph is an important barrier of innate immune system and this study reflects antimicrobial potential of urinary ph in the control of infectious diseases. in early 19th century bactericidal potential of dog urine was demonstrated against gram negative bacteria.19 another study suggested a role of ketogenic urine with bactericidal activity.20,21 reduction in growth of microorganisms due to accumulation of metabolic acid is also observed.22 antibacterial activity is also noted in young adults' urine ph5; and little higher activity of antibiotics was observed when tested with urine. however, urine samples ph5 from old peoples above age 69 did not show any activity. carlsson and his colleagues (2001 & 2003) established a link between nitrites and acidification of urine.23, 24 nitrate, a metabolic product, excreted in urine acts as bactericidal for nitrate-reducing bacteria at low ph. recently, shields-cutler et al. (2015), pointed out an antibacterial protein,siderocalin, produced naturally in response to infection.25 this protein binds iron and deprives bacteria from iron, required for bacterial growth,but this protein works better at neutral ph. however, body also produces aryl metabolites that control activity of siderocalin. similarly urine also contains small metabolites called aromatics, which vary depending on a person’s diet.urine samples that have more aromatic compounds restrict bacterial growth.sarah et al. (2015)demonstrated that urine contains substances, like mannosides, that inhibit uropathogenice. coli type-1 pilus mediated colonization and invasion of the bladder epithelium.26 in the present study a strikingly important observation that all the urine samples having ph 5 do not have detectable microbes, forcedus to believe that urine at ph 5 control infections owing to its acidic nature or presence of certain factor or components which are either produced in response to infection or become active at ph 5 or low. in view of above experience a hypothesis that urine at ph 5 or below possesses strong antimicrobial potentials is developed. recovery from uti could be high if urine is acidic. however, the mechanism needs to be elucidated. pyuria, is a prime index of bacteriuria requiring antibiotic therapy.27,28 in the present study all culture positive urine samples were found to have high count of pus cells(pyuria). this shows that after the pathogen overcome first-line of defence mechanism the other line is present to fight against intruders. in a latest study conducted in usa, cunha et al., (2016)demonstrated the importance of renal insufficiency and urine ph. 29 during this study, uti hospitalized patients with decreased renal function and acid / alkaline urinary ph were treated with ertapenem (antibiotic) and the time of bacteriuria eradication to negative urine cultures estimated. the study revealed that ertapenem eliminates bacteriuria efficiently in <3 days in patients with acidic urinary ph compared to patients with urine ph towards alkaline side. the results further strengthen and firmly affirm the proposed hypothesis that there is a very strong correlation between ph and antimicrobial potential of urine. glen et al., (1996)described minor difference in the efficacy of ampicillin in microbiological media and human urine against bacteria30. similar results were recorded in present study. on the other hand, hohl and felber,(1988) indicated that urine ph influence the activity of quinolones, such as urine ph 5 markedly reduces the activity of norfloxacin compared to ph 6 and 7.31 similarly, anandkumaret al.(2003)demonstrated that the activity of norfloxacin decreases four folds at ph 5.0 and 2000 mg/dl sugar concentration under in vitro condition.32nevertheless, in severe diabetic individuals, norfloxacin may not be a drug of choice. http://www.ijmm.org/article.asp?issn=0255-0857;year=2003;volume=21;issue=1;spage=37;epage=42;aulast=anandkumar#ref12 journal of rawalpindi medical college (jrmc); 2017;21(3): 293-297 297 ph of urine can be used as important diagnostic tool for utis in patients with clinical manifestations together with other specific tests; and for selecting appropriate therapy. acidification of urine both via diet modification and by other means can reduce the treatment period and hence prompt recovery. furthermore, utis patients with acidic urine generally respond better to therapy. this procedure can reduce the cost of treatment in uti patients with a reduction in therapy duration and doses. conclusion acidic urine ph5 play a pivotal role in controlling utis. the probability of bacteriuria (uti) increases with rise in urine ph; and severity of uti is proportional to the number of pus cells present in the urine. references 1. nielubowicz gr,mobley hl.host-pathogen interactions in urinary tract infection. nat rev urol 2010; 7(8):430-41. 2. alós ji. etiology of urinary tract infections in the community. antimicrobial susceptibility of the main pathogens. enferm infecc microbiol clin2005; 23(40):3-8. 3. james ht, jeffrey g, arash h, sarah ld,valerie hl, puneet c.uropathogens and host characteristics. j clin microbiol 2008; 46(12): 3980–86. 4. ronald a. the etiology of urinary tract infection: traditional and emerging pathogens. am. j. med2002; 113(1a):14s19s 5. gauthier m, chevalier i, sterescu a.treatment of urinary tract infections among febrile children with intravenous antibiotic therapy. pediatrics 2004; 114(4):469-76. 6. caljouw ma, den elzen wp, cools hj. predictive factors of urinary tract infections among the oldest old in the general population. bmc med 2011; 16; 9:57-60. 7. weichhart t, haidinger m, hörl wh. current concepts of molecular defence mechanisms operative during urinary tract infection. eur j clin invest 2008; 38 (2):29-38. 8. schubert s. urinary tract immunology. urologea 2010; 49(5):606-11. 9. kaye d. host defense mechanisms in the urinary tract. urolclin north am 1975; 2(3):407-22. 10. lautaro d and jean-pierre g. bacterial manipulation of innate immunity to promote infectionnature reviews microbiology 2010; 117-28 11. song j and abraham sn.innate and adaptive immune responses in the urinary tract.eur j clin invest 2008;38 (2):21-28. 12. thomson rb and miller jm. specimen collection, transport, and processing: bacteriology. in: manual of clinical microbiology (eds. p.r. murray, e. j. baron, j.h. jorgensen, m.a. pfaller, and r. h. yolken), 8th ed. american society for microbiology, washington, d.c 2003 13. foxman b, barlow r, arcy hd, gillespie b, sobel jd. urinary tract infection: self-reported incidence and associated costs. annals of epidemiology 2000;10(8):509–15. 14. foxman b, brown p. epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs. infectious disease clinics of north america 2003;17(2):227–41. 15. andreua a, alós ji, gobernado m, marco f. etiology and antimicrobial susceptibility among uropathogens causing community-acquired lower urinary tract infections. enfermedades infecciosas microbiología clínica 2005; 23(1): 4–9. 16. gow na. germ tube growth of candida albicans. curr top med mycol. 1997; 8(1-2):43-55. 17. williams dw, lewis mao. isolation and identification of candida from the oral cavity. oral diseases 2000;6(1):3– 11. 18. curtis nj. urinary tract infections and resistant bacteria: highlights of a symposium at the combined meeting of the 25th international congress of chemotherapy (icc) and the 17th european congress of clinical microbiology. rev urol 2007; 9(2): 78–80. 19. davis eg, hain rf. urinary antisepsis. the antiseptic properties of normal dog urine. j. urol 1918;2:309-12. 20. clark al. escherichia colibacilluria under ketogenic treatment. proc. staff meetings mayo clinic 1931; 6: 60508. 21. helmholz hf. the ketogenic diet in the treatment of pyuria of children with anomalies of the urinary tract. proc. staff meetings mayo clinic 1931; 6: 609-12. 22. philip m, daniel mk, robert em. restricted ph ranges and reduced yields for bacterial growth under pressure . microbial ecology 1974; 1(1): 176-89. 23. carlsson s, govoni m, wiklund np.in vitro evaluation of a new treatment for urinary tract infections caused by nitratereducing bacteria. antimicrob agents chemother2003; 47(12): 3713–18. 24. carlsson s, wiklund np, engstrand l.effects of ph, nitrite, and ascorbic acid on non-enzymatic nitric oxide generation and bacterial growth in urine. nitric oxide. 2001; 5(6):58086 25. shields-cutler rr, crowley jr, hung cs, stapleton ae. human urinary composition controls antibacterial activity of siderocalin. j biolchem 2015; 290 (26):15949-60. 26. sarah eg, michael eh, james j, swaine lc.human urine decreases function and expression of type 1 pili in uropathogenic escherichia coli. m bio 2015; 6(4):117-20 27. stamm we, running k, mckevitt m, counts gw, turck m,holmes kk. treatment of the acute urethral syndrome. n engl j med 1981; 304:956–58 28. hoberman a, wald er, reynolds ea, penchansky l. is urine culture necessary to rule out urinary tract infection in young febrile children?pediatr infect dis j 1996; 15(4):304 09. 29. cunha ba, giuga j, gerson s. predictors of ertapenem therapeutic efficacy in the treatment of urinary tract infections in hospitalized adult.eur. j. clin. microbiol. infect. dis 2016; 35:673-79. 30. glen rd, james ak, daryl jh, george gz. antibiotic activity in microbiological media versus human urine.. antimicrobial agents and chemotherapy1996; 40:237-40. 31. hohl p and felber am. effect of method, medium, ph and inoculum on the in-vitro antibacterial activities of fleroxacin and norfloxacin. j antimicrob chemother 1988;22(d):7180. 32. anandkumar h, dayanand a, vinodkumar cs.in vitro activity of norfloxacin against uropathogens and drug efficacy in simulated bladder model under diabetic conditions. indian j. med. microbiol 2003; 21(1):37-42. http://www.ncbi.nlm.nih.gov/pubmed/?term=nielubowicz%20gr%5bauthor%5d&cauthor=true&cauthor_uid=20647992 http://www.ncbi.nlm.nih.gov/pubmed/?term=mobley%20hl%5bauthor%5d&cauthor=true&cauthor_uid=20647992 http://www.ncbi.nlm.nih.gov/pubmed/?term=tabibian%20jh%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=gornbein%20j%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=heidari%20a%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=dien%20sl%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=lau%20vh%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=chahal%20p%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=chahal%20p%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=gauthier%20m%5bauthor%5d&cauthor=true&cauthor_uid=15466073 http://www.ncbi.nlm.nih.gov/pubmed/?term=chevalier%20i%5bauthor%5d&cauthor=true&cauthor_uid=15466073 http://www.ncbi.nlm.nih.gov/pubmed/?term=sterescu%20a%5bauthor%5d&cauthor=true&cauthor_uid=15466073 http://www.ncbi.nlm.nih.gov/pubmed/?term=caljouw%20ma%5bauthor%5d&cauthor=true&cauthor_uid=21575195 http://www.ncbi.nlm.nih.gov/pubmed/?term=den%20elzen%20wp%5bauthor%5d&cauthor=true&cauthor_uid=21575195 http://www.ncbi.nlm.nih.gov/pubmed/?term=cools%20hj%5bauthor%5d&cauthor=true&cauthor_uid=21575195 http://www.ncbi.nlm.nih.gov/pubmed/?term=weichhart%20t%5bauthor%5d&cauthor=true&cauthor_uid=18826479 http://www.ncbi.nlm.nih.gov/pubmed/?term=haidinger%20m%5bauthor%5d&cauthor=true&cauthor_uid=18826479 http://www.ncbi.nlm.nih.gov/pubmed/?term=h%c3%b6rl%20wh%5bauthor%5d&cauthor=true&cauthor_uid=18826479 http://www.ncbi.nlm.nih.gov/pubmed/?term=schubert%20s%5bauthor%5d&cauthor=true&cauthor_uid=20414764 http://www.ncbi.nlm.nih.gov/pubmed/?term=kaye%20d%5bauthor%5d&cauthor=true&cauthor_uid=242105 http://www.ncbi.nlm.nih.gov/pubmed/?term=abraham%20sn%5bauthor%5d&cauthor=true&cauthor_uid=18826478 http://www.ncbi.nlm.nih.gov/pubmed/?term=gow%20na%5bauthor%5d&cauthor=true&cauthor_uid=9504066 http://www.ncbi.nlm.nih.gov/pubmed/9504066 http://www.ncbi.nlm.nih.gov/pubmed/9504066 http://www.ncbi.nlm.nih.gov/pubmed/?term=nickel%20jc%5bauth%5d http://link.springer.com/journal/248 http://www.ncbi.nlm.nih.gov/pubmed/?term=carlsson%20s%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=govoni%20m%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=wiklund%20np%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=carlsson%20s%5bauthor%5d&cauthor=true&cauthor_uid=11730365 http://www.ncbi.nlm.nih.gov/pubmed/?term=wiklund%20np%5bauthor%5d&cauthor=true&cauthor_uid=11730365 http://www.ncbi.nlm.nih.gov/pubmed/?term=engstrand%20l%5bauthor%5d&cauthor=true&cauthor_uid=11730365 http://www.ncbi.nlm.nih.gov/pubmed/11730365 http://www.ncbi.nlm.nih.gov/pubmed/?term=shields-cutler%20rr%5bauthor%5d&cauthor=true&cauthor_uid=25861985 http://www.ncbi.nlm.nih.gov/pubmed/?term=crowley%20jr%5bauthor%5d&cauthor=true&cauthor_uid=25861985 http://www.ncbi.nlm.nih.gov/pubmed/?term=hung%20cs%5bauthor%5d&cauthor=true&cauthor_uid=25861985 http://www.ncbi.nlm.nih.gov/pubmed/?term=stapleton%20ae%5bauthor%5d&cauthor=true&cauthor_uid=25861985 http://www.ncbi.nlm.nih.gov/pubmed/?term=hibbing%20me%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=janetka%20j%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=chen%20sl%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=stamm%20we%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://www.ncbi.nlm.nih.gov/pubmed/?term=running%20k%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://www.ncbi.nlm.nih.gov/pubmed/?term=mckevitt%20m%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://www.ncbi.nlm.nih.gov/pubmed/?term=counts%20gw%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://www.ncbi.nlm.nih.gov/pubmed/?term=turck%20m%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://www.ncbi.nlm.nih.gov/pubmed/?term=turck%20m%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://www.ncbi.nlm.nih.gov/pubmed/?term=holmes%20kk%5bauthor%5d&cauthor=true&cauthor_uid=7010167 http://jac.oxfordjournals.org/search?author1=a.m.+felber&sortspec=date&submit=submit summary journal of rawalpindi medical college (jrmc); 2010;14(1):31-32 31 congenital heart diseases in neonates rehan farooqui* , umme farha haroon** ,allauddin niazi***, nosheen rehan****,.tayaba khawar butt , manal niazi . *department of paediatrics , frontier medical college , abbottabad **department of neonatology, children hospital , lahore *** department of paediatrics , islamabad medical and dental college , islamabad ****department of radiology, frontier medical college, abbottabad abstract background: to determine the frequency of congenital heart diseases in neonates methods: in this descriptive study, echocardiography was performed in all 459 suspected cases of congenital heart diseases. results: in 162 confirmed cases, the frequency of congenital heart disease was 2.86%. male outnumbered female (100vs 62). acyanotic lesions were more common than cyanotic lesions (127vs 35). ventricular septal defect was the most common acyanotic lesion while transposition of greater arteries was the most common cyanotic lesion conclusion: congenital heart diseases, being one of the commonest problem in newborns, requires early diagnosis, so that the affected child can get maximum medical support and benefit key words: neonates, congenital heart disease (chd), acyanotic, cyanotic lesion introduction the incidence of congenital heart diseases (chd) in different studies varies from about 4/1,000 to 50/1,000 live births.1 it accounts for nearly 25% of all congenital malformations.2 by definition chd is a gross structural abnormality of the heart or intrathoracic great vessels that is actually or potentially of functional significance.3 presentation can vary from asymptomatic accidental findings to severe cardiac decompensation and death. early recognition has great implications on prognosis. patients and methods this descriptive study was done in department of neonatology children hospital lahore over a period of 11 months (jan 2007-nov2007). .all admitted neonates with the clinical suspicion of congenital heart disease, who presented with cyanosis, tachypnea or tachycardia, audible heart murmur, low oxygen saturation on pulse oximeter or x ray evidence of cardiomegaly and hemodynamically stable were included in this study. they were sent to cardiology out patient department for echocardiography. neonates with other congenital anomalies, syndromes or hemodynamically unstable were excluded. results out of total 5650 admissions , 459 had clinical suspicion of chd. age ranged from 1 to 28 days. a total of 162 neonates were confirmed to have chd on echocardiography. the frequency of chd was 2.86% . out of 162 neonates, 127 had acyanotic lesions and 35 had cyanotic lesions (table 1).male babies outnumbered female babies (100 versus 62).fifty two (32.09%) cases were diagnosed within 7 days of birth, followed by 39 (24.07%) cases diagnosed within 814 days after birth.(fig 1).in acyanotic lesions ventricular septal defect(vsd) was diagnosed in 58 neonates followed by patent ductus arteriosis (pda)in 49 neonates (table 2). in cyanotic lesions, tga was the commonest ( 21 neonates) followed by tetralogy of fallot (7 neonates) ( table 3) . table 1: frequency and gender distribution lesion no. of patients % m f acyanotic 127 78.39% 77 50 cyanotic 35 21.60% 23 12 total 162 100% 100 62 journal of rawalpindi medical college (jrmc); 2010;14(1):31-32 32 52 39 33 38 0 10 20 30 40 50 60 1-7 days 8-14 141 days 15-21 days 21-28 days no of patients fig 1: age distribution table 2: frequency of acyanotic lesions: acyanotic lesion no of patients % ventricular septal defect (vsd) 58 45.66% patent ductus arteriosus (pda) 49 38.58% atrial septal defect (asd) 8 6.29% combined atrio ventricular septal defect (cavsd) 7 5.51% pulmonary atresia (pa) 3 2.36% coarctation of aorta (co a) 2 1.57% total 127 100% table 3: frequency of cyanotic lesions cyanotic lesions no. of patients % transposition of greater arteries (tga) 21 60.00% tetralogy of fallot (tof) 7 20.00% tricuspid atresia 4 11.42% pulmonary atresia 1 2.85% truncus arteriosus 1 2.85% total anomalous pulmonary venous circulation(tapvc) 1 2.85% total 35 100% discussion each year there are about 1.5 million new cases worldwide. 4 in pakistan, approximately forty thousand child are born each year with a congenital heart disease .it is the most common congenital condition diagnosed in newborns. in pakistan only a few centers are taking care of children , especially neonates , with congenital heart diseases. children hospital lahore is a unique centre in this regard . approximately , fifty percent surgeries in this cohort were done here at an age of less than one year. 5 in present study male outnumbered females. the result is similar as shown by amir but stephen et al showed equal distribution. 6,7 acyanotic lesions are more common than cyanotic lesions.similar inference was drawn by jackson and rahim.8,9 among acyanotic lesions,vsd was the most common lesion found on echo. similar results were shown by rehan and faud.10.11 pda was found second most common lesion. similar result were shown by faud but differs from various studies. 11-13 it can be ascribed to the inclusion of only neonates while majority of studies included children upto 14-15 years of age. in those studies asd was the second most common lesion. regarding cyanotic lesions tga was the most common lesion followed by tof.this differs with other studies in which tof was the most common cyanotic lesion 10 14. as mentioned for acyanotic lesions, in cyantoic lesions too, the difference can be because of inclusion in the study of only neonates, while majority of studies included children upto 14-15 years of age and usually tetralogy of fallot presents after few months of life. in conclusion, neonatology and children cardiology is a technology intense issue requirng highly trained staff . there is a dire need to establish centers and to train medical staff at all levels. early detection of chd is of utmost importance for its proper management. references 1. hoffman jie. incidence of congenital heart disease. i. postnatal incidence. pediatr cardiol. 1995;16:103–113 2. abruawi e.the burden of congenital heart disease in libya.libyan j med 2006;06:902. 3. mitchell sc, korones sb, berendes hw. congenital heart disease in 56,109 births. incidence and natural history. circulation. 1971;43:323-32. 4. moller jh,taubert ka,allen hd .cardiovascular health and disease in children: current status. a special writing group from the task force on children and youth, american heart association. circulation. 1994 feb;89(2):923-30. 5. express news . point blank with mubashir , 10th june , 2010. 6. khaled a.pattern of congenital. heart disease at prince hashim hospital jordan.middle east journal of family medicine. 2008; (6):66 7. stephen ss, sigfusson, jt syresson g. congenital heart defects in iceland1990-1999 laeknabladid 2002 apr:88(4)281-7 8. jackson m, walsh kp, peart i, arnold r. epidemiology of congenital heart disease in merseyside – 1979 to 1988. cardiol young 1996: 6:272-280. 9. fazal r,mohammad y,amin j.pattern of chd in children at tertiary care centre in peshawar.pjms 2003; 19 (1)19-22 10. rehan a, zahid a, fauzia b.a prevelance study of chd in nwfp pakistan .pjms 2002;18(2)95-8 11. faud a. pattern of congenital heart disease in the southwestern region of saudi arabia. ann saudi med 1998;18(5):393-395. 12. kwon tc,kimjs,leesl, kimms.incidence of chd in neonates by colour doppler echo.j korean ped1998;41(3)363-68 journal of rawalpindi medical college (jrmc); 2010;14(1):31-32 33 13. shamima s, azizul h, iqbal b, ayub a pattern and clinical profile of congenital heart disease in a teaching hospital .taj 2008; 21(2): 58-62 14. mumtaz h,naseer a, farhat m,saqib l.congenital heart disease in children hospital at pims.j pak inst med sci 1995;6(1,2) :334-8 rehan farooqui* , umme farha haroon** ,allauddin niazi***, nosheen rehan****,.tayaba khawar butt , manal niazi . *department of paediatrics , frontier medical college , abbottabad **department of neonatology, children hospital , lahore *** department of paediatrics , islamabad medical and dental college , islamabad ****department of radiology, frontier medica... abstract introduction patients and methods results discussion references summary journal of rawalpindi medical college (jrmc); 2017;21(3): 290-292 290 original article bacteriological spectrum and sensitivity pattern in culture proven urinary tract infection in children mulazim hussain 1, bilal ahmad 2, nasira bhatti 1, shagufta husain 1 1.the children hospital, pakistan institute of medical sciences (pims),islamabad;2.department of paediatrics , railway hospital and islamic international medical college, rawalpindi abstract background: to determine the different types of organisms causing urinary tract infections in children and their sensitivity to antibiotics. methods: this cross sectional study was conducted at children hospital, pims islamabad and consisted of 117 patients of either gender between age of 03 months to 12 years. results: mean age of children enrolled in our study was 4.4 (± 2.6) years. out of 117 patients, 63 (54 %) were girls. the most common isolate was e. coli (57.3%) percent, followed by klebsiella (18.8 %), staphylococcus aureus (13.7 %), pseudomonas (5.1 %) and proteus (3.4 %) children. all isolates were sensitive to ciprofloxacin, of loxacin, amikacin, cefixime and imepenem. only 38.5% e coli and 37.5% klebsiella were sensitive to ampicillin, and 14.3% e coli and 9.1% klebsiella were sensitive to trimethoprim-sulphamethoxazole. conclusion: the most common isolate was e. coli, followed by klebsiella, staphylococcus aureus, pseudomonas and proteus. most antibiotics tested for the e. coli, klebsiella, staphylococcus, pseudomonas and proteus are effective except cotrimoxazole, ampicillin, and gentamicin which show high resistance. key words: urinary tract infections, bacteriological spectrum, sensitivity pattern. introduction urinary tract infections (utis) are responsible for considerable morbidity and when associated with urinary obstruction or renal papillary damage. early treatment of uti with an effective antibiotic is essential for prevention from long-term consequences. selection of appropriate antibiotic needs knowledge of possible pathogens and their sensitivity pattern .girls are more susceptible because their urethra is shorter and closer to the anus. this makes it easier for the bacteria to get access to urethra and then to bladder. 1,2 up to 11.3% of girls and 3.6% of boys will have had a uti by the age of 16 years, and recurrence of infection is also common.3 the incidence of uti varies in early infancy and childhood, being more common in boys in first three months of life with reported male to female incidence of 5:1.in later childhood the reported male to female ratio was 1:10.4 imaging studies to detect anatomic abnormalities of the urinary tract should be obtained in infants and young children following a first-time diagnosis of acute pyelonephritis. the purpose of these studies is to identify those at increased risk for kidney damage and recurrent infections, namely those with obstructive malformations, renal abnormalities, or severe vur. the risk of uti is increased by incomplete bladder emptying secondary to anatomic obstruction or a neurogenic bladder and by voiding dysfunction.5 untreated and recurrent utis can cause serious complications in children including renal scarring, hypertension and end-stage renal disease.1 early and effective treatment with carefully selected antibacterial agent can prevent most of these complications. success of the treatment is based on and guided by results of urine culture.6 the choice of empiric antibiotic therapy depends on the knowledge of the expected causative organisms and their susceptibility pattern. growing resistance to multiple antibiotics has been reported world over which poses an important challenge for clinicians.7,8 patients and methods this cross sectional study was carried out over a period of six months from april 1, 2009 to september 30, 2009, at inpatient department of children hospital, pakistan institute of medical sciences, islamabad.in children who were admitted with clinical suspicion of urinary tract infection (fever, dysurea, pain abdomen, vomiting, unusual crying, poor weight gain, mal odorous urine etc.), a urine sample was carefully collected. in case of infants a sterile, adhesive urine collection bag was applied after disinfecting the skin of genitals, whereas in toilet trained children a mid stream sample was obtained. when it was not possible journal of rawalpindi medical college (jrmc); 2017;21(3): 290-292 291 to collect the urine by non-invasive methods a catheterized sample was collected. a routine urinalysis including microscopy and culture and sensitivity were done on all specimens. a colony count of >100,000 per cmm of a single organism or >10,000 per cmm in symptomatic children was considered as a positive culture. antibiotic sensitivity was tested to different antibiotics. results out of 117 children 54% were girls. age of children ranged between 3 months and 12 years with a mean of 4.4 (± 2.6) years. table 1 .patient characteristics number percentage age categories (years) < 1 5 4.3% 1 to 5 77 65.8% > 5 35 29.9% gender male 54 46.1% female 63 53.9% table 2.microorganisms isolated on urine culture number percentage e-coli 67 57.2% klebsiella 22 18.8% staph. aureus 16 13.6% pseudomonas 6 5.1% proteus 4 3.4% others 2 1.7% (table 1). e. coli (57.2%) was the commonest isolate(table 2).all organisms (100%) were sensitive to amikacin, norfloxacin , ofloxacin , ciprofloxacin and imepenem. only 38.5 % e coli and 37.5 % klebsiella were sensitive to ampicillin where as 14.3% esch. coli and 9.1 % klebsiella were sensitive to trimethoprimsulphamethaxazole.100% esch coli and 75% klebsiella were sensitive to cefixime.94.7% esch coli and 83.3% klebsiella were sensitive to ceftriaxone. however sensitivity of ceftriaxone to staphylococcus and pseudomonas was 100%(table 3). discussion urinary tract infections (utis) are one of the most frequent infections in children and a significant cause of morbidity, occurring in about 5 percent of febrile infants and 2 percent of febrile children of less than 5 years of age particularly when associated with structural abnormalities of urinary tract. 9 the most common organism isolated in our study was esch. coli (57.3%) .this finding is similar to most of the studies conducted around the world where e coli was isolated from 42.3 % to 81.7 %. 10-14 information obtained through these studies indicates that irrespective of hospital setting, community or country e coli remains the most common uropathogen. klebsiella (18.8%) was the second most common organism isolated in our study. this finding is similar to the observations in other studies where klebsiella was isolated in 16.7 % to 25 %, although, rare isolation of klebsiella (5.5%) has also been reported in bangladesh.15-17 interestingly staphylococcus aureus was a common isolate in our study(13.7%).this is in contrast to most of the early findings where staph aureus was an uncommon isolate although occasionally it has been reported in many studies.11,17 pseudomonas auroginosa and proteus mirabilus were rare isolates like all other studies we could access.18,19 the results of sensitivity to different antibiotics show that all organisms isolated in our study had low to poor sensitivity to the common antibiotics used in community i,e, ampicillin and trimethoprim sulphamethaoxazole. increasing antibiotic resistance among urinary tract isolates to ampicillin, trimethoprim sulphamethoxazole, and first generation cephalosporins has earlier been reported by many observers.20 on the other hand sensitivity to flouroquinolones and aminoglycosides is almost 100 %. gupta and coinvestigators reported in their study that resistance to table 3: sensitivity pattern amp ctx cef norfl amk gen ofl pip imi ceft cip ecoli 38.5% 14.3% 100% 100% 100% 86.7% 100% 89.5% 100% 94.7% 100% kleb 37.5% 9.1% 75% 100% 100% 88.9% 100% 90.9% 100% 83.3% 100% staph 66.7% ---100% 100% 100% 100% -100% 100% pseud ---100% 100% 66.7% -66.7% 100% 100% 100% amp: ampicillin, cef: cefixime, ctx: trimethoprim sulphamethoxazole, norfl: norfloxacin, amk: amikacin, gen: gentamicin, ofl: ofloxacin,: pipemidic acid, imi:imipenem, ceft: ceftriaxone, cip: ciprofloxacin, kleb: klebsiella, staph: staphlococcus aureus, pseud: pseudomonas journal of rawalpindi medical college (jrmc); 2017;21(3): 290-292 290 fluoroquinolones was absent among gram-negative pathogens and christiaen et al reported that only one percent of the pathogens were resistant to fluoroquinolones.21,22 this low resistance of pathogens might be attributed to the fact that quinolones are relatively new antibiotics and have not been extensively used in children. although sensitivity to gentamycin is around 90 % it is 100 % to amikacin. this is possibly due to less frequent use of amikacin in community and widespread use of gentamycin. sensitivity to imepenem is also 100 % which is comparable to the findings of m.i.majumder et al. from bangladesh who have reported 98% sensitivity of uropathogens to meropenem. 23 cefixime is a 3rd generation oral cephalosporin which has good palatability and tolerance in children due to its taste and convenient dosage regimen. this was effective against all e coli isolates though it was only 75 % effective against klebsiella. these findings are comparable with study of dreshaj sh,which showed 88% effectiveness of cefixime in uncomplicated utis.24) conclusion e coli and klebsiella are common bacterial urinary pathogens in children. cefixime, quinolones and aminoglycosides maintain good sensitivity to common pathogens. resistance to antibiotics frequently used in community is increasing. references 1. al-harthi aa, al-fifi sh. antibiotic resistance pattern and empirical therapy for urinary tract infections in children. saudi med j. 2008;29:854-58. 2. hooton tm, stamm we. diagnosis and treatment of uncomplicated urinary tract infection. infect dis clin north am. 1997;11:551-81. 3. lacromb j. urinary tract infection in children. bmj clin evid. 2010; 2010: 0306. 4. elder js. urinary tract infection. behrman re, kliegman rm, jenson hb, editors. nelson textbook of pediatrics. 20th ed. philadephia: wb saunders company; 2015. 2556–61. 5. hellerstien s. urinary tract infections in children: pathophysiology, risk medscapewww.medscape.com/viewarticle/447232_3 6. chang sl, shortliffe ld. pediatric urinary tract infections. in: hrair o, merobian g, cynthia p, eds. pediatric clinic of north america. philadelphia: w. b saunders 2006:379-400. 7. zorc jj, kiddoo da, shaw kn. diagnosis and management of pediatric urinary tract infections. clin microbiol rev. 2005;18:417-22. 8. bahram f, farhad h, mohammad e, marzieh a. detection of vancomycin resistant enterococci (vre) isolated from urinary tract infections (uti) . daru.2006;14:1415. 9. .hoberman a, chao hp, keller dm. prevalence of urinary tract infection in febrile infants. j pediatr 1993;123:17–23 10. akram m, shahid m, khan au. etiology and antibiotic resistance patterns of community-acquired urinary tract infections . ann clin microbiol antimicrob. 2007;6:4. 11. badhan r, singh d v,badhan l r. evaluation of bacteriological profile and antibiotic sensitivity patterns in children with urinary tract infection. ind j urology;2016 ;32(1):50-56 12. mashouf ry, babalhavaeji h, yousef j. urinary tract infections: bacteriology and antibiotic resistance patterns. indian pediatr 2009;46:617-20. 13. lehrasab w, aziz t, ahmed n, ahmed i.causative organisms of urinary tract infection and their sensitivity pattern in children. ann pak inst med sci 2016;12(4):181-85 14. ipek io, bozaykut a, arman dc, sezer rg. antimicrobial resistance patterns of uropathogens among children in istanbul, turkey. southeast asian j trop med public health. 2011;42(2):355-62. 15. kaur n, sharma s, malhotra s, madan p. urinary tract infection: aetiology and antimicrobial resistance pattern in infants.india j clin diagn res. 2014 ; 8(10): 117-20 16. aiyegoro o.a. igbinosa o.o.ogunmwonyi i. n. african journal of microbiology research.2007;july;pp 013-019 17. haque r. prevalence and susceptibility of uropathogens:a recent report from teaching hospital in bangladesh. bmc.res notes.2015 :5;8:416-19. 18. lawhale ma, naikwade r. recent pattern of drug sensitivity of most commonly isolated uropathogens from central india int j res med sci. 2017 ;5(8):3631-36 19. pobiega m .urinary tract infection caused by pseudomonas aeruginosa among children in poland. journal of paediatric urology 2015;05:034-37 20. lutter sa, currie ml, mitz lb, greenbaum la. antibiotic resistance patterns in children hospitalized for urinary tract infections. arch pediatr adolesc med. 2005;159:924-28. 21. gupta k, hooton tm, webbe cl, stamm we. the prevalence of antimicrobial resistance among uropathogens causing actor uncomplicated cystitis in young women. int j antimicrob agents. 1999;11:305-08. 22. christiaens th, heytens s, verichraegen g, demeyers d. which bacteria are found among belgian women with uncomplicated urinary tract infectionsand what is their sensitivity pattern . act clin belg. 1998;53:184-88. 23. majumder mi . bacteriology and antibiotics sensitivity patterns of uti in tertiary hospital in bangladesh. mymensingh med.j 2014 ;23(1):99-104 24. dreshaj sh. clinical role of cefixime in community acquired infections. prilozi2011,32(2):143-55). https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2907613/ https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2907613/ https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahukewj5tb-5sihxahwhpbqkhy4sbpsqfggtmae&url=http%3a%2f%2fwww.medscape.com%2fviewarticle%2f447232_3&usg=aovvaw162zv632-cms7hhlf81c5z https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahukewj5tb-5sihxahwhpbqkhy4sbpsqfggtmae&url=http%3a%2f%2fwww.medscape.com%2fviewarticle%2f447232_3&usg=aovvaw162zv632-cms7hhlf81c5z https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahukewj5tb-5sihxahwhpbqkhy4sbpsqfggtmae&url=http%3a%2f%2fwww.medscape.com%2fviewarticle%2f447232_3&usg=aovvaw162zv632-cms7hhlf81c5z summary journal of rawalpindi medical college (jrmc); 2010;14(1):46-48 46 unintentional poisoning: experience at a medical unit muhammad khurram*, najia mahmood*, nadeem ikram** *department of medicine, rawalpindi medical college and allied hospitals, rawalpindi. ** department of pathology, rawalpindi medical college, rawalpindi abstract background: to note types of acute unintentional poisoning in patients presenting to medical emergency of rawalpindi medical college, rawalpindi. methods: this cross sectional observational study; was conducted in a medical unit of rawalpindi medical college from january to december 2006. adult, unintentional poisoning (when a subject poisoned him/herself without an intention to be harmed) cases presenting to medical emergency were included. each patient was managed in standard way. type of poisoning, and outcome (death or discharge) of each patient were noted. results: twenty-eight patients were managed during the study period. majority (60.7%) of patients were female. mean patient age was 25.68±11.39 years. snake bite (25%), various medicines like benzodiazepines and analgesics/nsaids (21.4%), organophosphate (17.9%), and corrosive intake (17.9%) were most frequently noted types of unintentional poisoning. poisoning related mortality was 7.1%. conclusion: snake bite and various medicines like benzodiazepines and analgesics/nsaids are commonest types of unintentional poisoning. key words: poisoning, snake bite, medicines, benzodiazepines, analgesics/nsaids. introduction poisoning is worldwide problem occurring in all regions and countries. it affects people of all ages, gender and income groups. it is an important cause of morbidity and mortality. about 2 million poison exposures reported to all poison centers in united states in the year 2004.1 majority of fatal poisoning occurs in developing countries . causes and frequency of poisoning vary at different places. 2 based on intentions, poisoning can be divided into deliberate self poisoning, unintentional poisoning, and homicidal poisoning. deliberate self poisoning is commonest of these types and has been receiving considerable attention locally and internationally compared to other types of poisoning. 3,4 detailed knowledge of nature and magnitude of poisoning in a particular area are important for early diagnosis, and prompt treatment. it is also helpful for devising appropriate preventive measures. patients and methods this cross sectional, observational study was conducted at the medical emergency of one of the medical units of rawalpindi medical college, rawalpindi for one year (january to december 2006). study protocol was approved by departmental committee. adult unintentional poisoning cases presenting during study period were included. poisoning was defined as ingestion of a poison or excessive dose of a medicine. unintentional poisoning was diagnosed when a subject poisoned him/herself without wanting to cause harm to his/her body. informed consent was obtained from patients or their attendants. each patient was managed in standard way i.e., general measures including; hemodynamic stabilization, correction of dehydration, acidosis, hypoglycaemia etc and specific measures like; gastric lavage, administration of activated charcoal or anti snake venom wherever appropriate. after initial management and re-evaluation, unstable patients were admitted to medical unit or intensive care unit according to clinical scenario for further management. details regarding age, gender, occupation, educational level, urban or rural address, socio-economic class, and marital status were also collected. a specifically designed proforma was used to record data. continuous data was expressed as mean ± sd. categorical data was expressed as number of patients with a specified class of clinical variable. results a total of 28 patients were managed with diagnosis of unintentional poisoning during study period. majority (60.7%) of patients were female. mean journal of rawalpindi medical college (jrmc); 2010;14(1):46-48 47 patient age was 25.68±11.39 years. most of the patients were married and belonged to urban area. majority of patients (42.37%) had household related occupation. snake bite, various medicines, organophosphate, and corrosive intake were most frequently noted types of unintentional poisoning(table 1). two patients ( 7.1%) expired while the rest were discharged healthy. patients who expired included one male and one female. organophosphate intake and snake bite were cause of death in each respectively. table: 1 types of poisoning poisoning type n and (%) snake bite 7 (25%) medicines* 6 (21.4%) corrosives 5 (17.9%) organophosphates 5 (17.9%) unknown 3 (10.7%) bhang 1 (3.6%) mixed 1 (3.6%) *medicinesbenzodiazepines (7.1%, n=2), analgesics and non steroidal anti inflammatory drugsnsaids (7.1%, n=2), sedative/hypnotics (3.6%, n=1), oral hypoglycaemic agents (3.6%, n=1). discussion snake bite was commonest type of poisoning noted in this study. snake bite poisoning is a frequently noted public health problem in countries like pakistan. it is responsible for about 1,000 deaths per year in pakistan. 5 in various pakistani studies 0.54% snake bite related mortality has been noted.6,7 present study revealed a comparatively high percentage (14.28%). in developed countries analgesics, tranquilizers, and antidepressants are common types of poisoning.8 studies from our neighbourhood countries india, china, and srilanka have shown that organophosphate pesticides poisoning is widespread. 2,9,10,11 .over-the-counter availability of benzodiazepines and nsaids/analgesics is responsible for accidental intake and poisoning noted in our study. similarly organophosphate poisoning is also common in pakistan as these are freely available because of agricultural based economy and lack of effective regulatory measures.12, 13 corrosive are chemicals which dissolve or erode the tissue in which these come in contact.14 bleach, toilet cleaner, detergents, sulphuric acid, and hydrochloric acid are included in this category. this kind of poisoning has been frequently noted in pakistan.13 corrosive (mainly bleach and toilet cleaner) intake was also common in our patients. this kind of poisoning is different from others as short-term sequelae (morbidity and death) are less compared to long-term (stricture etc). 15 in western countries poisoning related mortality is low, about 0.5%. 10,16,17 overall fatality in asian acute poisoning patients is more than 10%. 11 mortality in our study was comparatively less (7.14%) and relates with pakistani studies. 18-20 two limitations of this study are worth mentioning i.e., 1) number of patients, 2) study patients were mainly from urban area. number of patients is less because the study represents one of the five medical units of rawalpindi medical college, rawalpindi. additionally we did not include other types of poisoning like deliberate self-poisoning which constitutes major bulk of poisoning patients.3 characteristics of acute poisoning patients may be different in rural area which is under represented in the study. this study may thus represent trend in the area. references 1. watson wa, litovitz tl, rogers gc, klein-schwartz w, reid n, youniss j, et al. 2004 annual report of the american association of poison control centers toxic exposures surveillance system. american journal of emergency medicine 2005; 23(5):589-66. 2. konradsen f, hoek w, cole dc, hutcinson g, daisley h, singh s, et al. reducing acute poisoning in developing countriesoptions for restricting the availability of pesticides. toxicology 2003; 192: 249-61. 3. singh b, unnikrishnan b. a profile of acute poisoning at mangalore (south india). j clin forens medi 2006; 13:112-16. 4. khurram m, mahmood n. deliberate self-poisoning: experience at a medical unit. j pak med assoc 2008: 58(8): 456-58. 5. kasturiratne a, wickremasinghe ar, de silva n, gunawardena nk, pathmeswaran a,. (2008) the global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. plos med 5(11): e218. doi:10.1371/journal.pmed. 0050218 6. hayat as, khan ah, shaikh tz, ghouri ra, shaikh n. study of snake bite cases at liaquat university hospital hyderabad/jamshoro. j ayub med coll abottabad 2008; 20(3): 125-27. 7. suleman m, shahab s, rab m.snake bite in the thar desert. j pak med assoc 1998; 48(10): 306-08. 8. greene sl, dargan pi, jones al. acute poisoning: understanding 90% of cases in a nutshell. postgrad med j 2005; 81; 204-16. journal of rawalpindi medical college (jrmc); 2010;14(1):46-48 48 9. dash sk, raju as, mohanty mk, patnaik kk, mohanty s. sociodemographic profile of poisoning cases. jiafm 2005; 27 (3): 133-38. 10. srivastava a, peshin ss, kaleekal t, gupta sk. an epidemiological study of poisoning cases reported to the national poisons information centre, all india institute of medical sciences, new delhi. hum exp toxicol 2005; 24(6): 279-85. 11. konradsen f. acute pesticide poisoninga global public health problem. danish med bulletin 2007; 54: 8-9. 12. jamil h. acute poisoninga review of 1900 cases. j pak med assoc 1990; 40(6): 131-33. 13. turabi f. poisoning cases in and around karachi and their management along with medicolegal aspects [dissertation]. [karachi]: university of karachi; 2004. 379p 14. rao rb, hoffman rs. caustics and batteries. in: goldfrank lr, flomenbaum ne, lewin na, howland ma, hoffman rs, nelson ls, eds. goldfrank's toxicologic emergencies. 7th ed. new york, ny: mcgraw-hill; 2002: 1323-45. 15. eddleston m. patterns and problems of deliberate self poisoning in the developing world. q j med 2001; 94: 715-13. 16. gunnell d, eddleston m. suicide by intentional ingestion of pesticides: a continuing tragedy in developing countries. international journal of epidemiology 2003; 32: 902-09. 17. gunnell d, ho dd, murray v. medical management of deliberate drug overdosea neglected area for suicide prevention? emerg med j 2004; 21(1): 35-38. 18. naheed t, akbar n, akbar n, munir r. acute poisoning in the city of punjab how can we help these souls? j fatima jinnah med coll lahore 2007; 1(3-4): 56-58. 19. suleman mi, jibran r, rai m. the analysis of organophosphorpus poisoning cases treated at bahawal victoria hospital, bahawalpur in 2000-2003. pak j med sci 2006; 22(3): 244-49. 20. farooqi an, tariq s, asad f, abid f, tariq o. epidemiological profile of suicidal poisoning at abbasi shaheed hospital. ann abbasi shaheed hosp karachi med dent coll 2004; 9(1): 502-05 muhammad khurram*, najia mahmood*, nadeem ikram** *department of medicine, rawalpindi medical college and allied hospitals, rawalpindi. ** department of pathology, rawalpindi medical college, rawalpindi abstract introduction patients and methods results discussion references summary journal of rawalpindi medical college (jrmc); 2017;21(3): 269-271 269 original article breast self examination practice and awareness about breast cancer rizwana anjum 1, sobia nawaz 2 , somayyah bibi 1 department of gynaecology and obstetrics, lady aitchison hospital, lahore; 2. department of gynae/obs, dhq hospital rawalpindi abstract background: to assess females’ awareness about breast cancer and self-reported practice of breast self-examination. methods: in this population-based cross sectional study data was collected via a structured questionnaire containing questions on demographic status, family history of breast cancer, subjective knowledge about breast cancer covering its symptoms, the screening methods and practice of breast self-examination (bse). results: a total of 1500 women were interviewed. the mean age of respondents was 36 + 16.1 years. majority (76.1%) were married. in 90.9% there was no family history of carcinoma breast. familiarity about breast cancer was found in 15.1%. only a few (3.2%) knew about breast cancer screening programs and most indicated that electronic media (television 8.3% and radio 4.9%) were their source of information. only 1.9% of women said that they were conducting occasional breast self-examination. the main reason for women not doing breast selfexamination was due to the fact that they did not know how to do it (97.5%). conclusion: women’s knowledge about breast cancer warning signs and effective screening methods i.e. breast self examination, and mammography were insufficient. key words: breast cancer ,breast self examination ,screening programs, awareness. introduction carcinoma of the breast is the commonest malignancy in females all over the world and second leading cause of death due to cancer among females. 1 global statistics show the annual incidence of breast cancer is increasing and this is occurring more rapidly in countries with a low incidence rate of breast cancer.2 it has been reported that each year over 1.15 million women worldwide are diagnosed with breast cancer and 502,000 die from the disease.3 in pakistan it is more common at a young age contrary to the west where it is more common after 60 years. approximately one in every nine pakistani women is likely to suffer from breast cancer. this is one of the highest incidence rates in asia.4,5 all women regardless of their racial or ethnic origin or heritage are at risk of developing breast cancer. key factors among those that affect breast carcinoma development, are the genetics, environmental factors ,reproductive experience, the effect of endogenous and exogenous hormones in females, the change in immune status, host vulnerability, and the biologic determinants of breast carcinoma.6,7 breast cancer related mortality and the patients' prognostic outcome can be significantly improved by timely detection of this disease.7 mammography, clinical breast examination and breast self-examination (bse) are recommended screening methods for its early detection.8.9 mammography requires logistic and professional manpower before its use and this imaging technique is very expensive , therefore, is not affordable for most part of the population.10 unlike mammography , bse is simple, inexpensive, low in technology and teaching is possible to both health professionals and women.11 the simplest technique of bse is to check oneself monthly. trained medical practitioners and nurses at health centers teach the women, how to use bse.12 bse still needs its complete acceptance. 10,11 for early detection of breast cancer, american cancer society recommends that bse can be used as an option.13 bse makes women more "breast aware”, so that she can easily notice any changes in their breasts as early as possible. 14 the rationale behind extending bse practice as a screening test is the fact that breast cancer is often discovered by women themselves without any other symptoms.15 for breast cancer screening, none of the above modalities could be considered as the best method for early detection and mortality reduction. these approaches have their own potential benefits and harms.15 thus, at present journal of rawalpindi medical college (jrmc); 2017;21(3): 269-271 270 the emphasis is to raise breast cancer awareness among women to overcome ever-increasing burden of the disease. subjects and methods this descriptive and cross-sectional study was carried out in outpatient department of lady aitcheson hospital lahore and district headquarter hospital rawalpindi , from july 2015 to december 2015. the study population consisted of female of aged 20 to 70years (n = 1500). data were collected via a structured questionnaire derived from the literature. an informed consent was obtained before conducting the interviews. the questionnaire consisted of 10 items on knowledge about breast cancer covering its symptoms, screening methods, knowledge of bse and family history of breast cancer. knowledge of bse was assessed with three questions including knowledge about frequency of bse, knowledge about appropriate time for bse and knowledge of bse procedure. depending on the frequency of bse, the participants were categorized as regular (who performed bse every month), occasional (those who performed bse infrequently) and none (those who never had bse) . results the mean age of the respondents was 36 + 16.1 years and most were married (76.1%) (table 1).the positive family history of breast cancer reported by 9.1% of women. when the respondents were asked about breast cancer in pakistan, 15.1% said that "they have heard about the disease" .the respondents' knowledge of breast cancer symptoms was also studied. only 13.8 %( 207) had knowledge of few breast cancer symptoms (table 2). table 1.demographic characteristics of the study sample (n=1500) age groups (years) number (%) 20-29 836 (54.3%) 30-39 471 (30.6%) 40-49 119 (7.7%) 50-59 53 (3.4%) >60 21 (1.4%) marital status single 358(23.2%) married 1142(74.2%) family history of breast cancer yes 136(9.1%) no 1364(90.9%) only 3.2% of the respondents knew about breast cancer screening methods:1.9% knew about breast self-examination and about 1.3% about mammography. the remaining 96.7% claimed that they know nothing about breast cancer screening methods.when the respondents were asked about breast self-examination, 1.9% reported that they practice breast self-examination occasionally'.no one said that 'they do regular breast self-examination'. when it was investigated to find out women's reasons for not doing breast self-examination, 97.5% claimed that 'they do not know how to do it'. table 2: respondents' knowledge of breast cancer and self-reported practice of breast selfexamination (n = 1500) variable yes number(%) no number (%) have you heard about breast cancer in pakistan? 227(15.1%) 1273(84.9%) do you know about breast cancer symptoms 207(13.8%) 1293(86.2%) do you know method of bse* 38(2.5%) 1462(97.5%) do you know the importance of bse 47(3.1%) 1453(96.9%) do you know the timing of bse 009(%) 1500(100%) any of your friend/relatives affected by breast carcinoma 136(9.1%) 1364(90.9%) do you have the knowledge about the treatment of breast carcinoma 125(8.3%) 1375(91.7%) *bse=breast self examination discussion educated health habits can have profound, long-term implications on health. one of these habits is bse.5 a number of studies from the developing countries reported lower rates of bse practices. a study from saudi arabia found that only 30.3% of the women were aware of breast self-examination and 18.7% reported they practiced bse within the previous year.8 a nigerian study demonstrated that women did not had sufficient knowledge about breast cancer and only 34.9% claimed to ever-practiced bse. 11 while a study of bse behavior among chinese immigrant women living in san francisco indicated that 80.9% reported having heard of bse and 53.9% of the women had performed bse during the past year. comparing the figures with that of developed countries clearly journal of rawalpindi medical college (jrmc); 2017;21(3): 269-271 271 suggests that there are obvious differences. in united states, about 75% of the women conduct bse and its adequate quality was rated in 27%. also higher duration, frequency and quality of bse were predictors of further diagnostic investigations . an australian study reported that about 31% of women examined their breasts thoroughly . in present study only 13.8% of women said that painless lump is a common symptom of breast cancer. the remaining 86.2% indicated that they know nothing about breast cancer symptoms. only 1.9% and 1.3% had respectively heard about breast self-examination and mammography. this is consistent with other studies from developing countries and women from minority ethnic groups.11,16 a study from u.k showed that 70% of women were aware of breast cancer symptom.18 a british study reported a significant lack of the prerequisite knowledge and confidence to detect a breast change among older women aged 63 to 73 years. 17,18 though, these variations may be due to cultural differences, the role of some other underlying factors on breast health awareness in women should not be ignored.19 a turkish study indicated that theoretical educations about breast cancer awareness and bse training were quite helpful even in illiterate and loweducated women.19 studies indicated that media continued to be an important source of information about breast cancer and bse and highlighted the cooperation between public health educators and the media in dissemination of breast cancer information and bse practices . 11use of mass media is quite helpful in raising awareness about cancer.18 in most developing countries, mass media are governed by the 'states'. these programmes often receive less attention in public media because of some religious and cultural reasons.19 a low proportion of women indicated that they had received any information from their doctors. primary health care providers can play vital role in transmitting accurate knowledge about breast cancer . this study revealed that there is no significant difference between personal and family history of breast cancer and performing bse as compared to women without personal and family history of breast problems. this is contrary to other studies that have shown women with a family history of breast cancer do excessive bse.18,19 conclusion 1. awareness of females about breast cancer warning symptoms and screening methods i.e. breast selfexamination and mammography is insufficient. 2. screening and awareness programs should be planned and implemented in collaboration with governments.media should be used to increase awareness among general population. references 1. miller ab. conundrums in screening for cancer. mini review. int j cancer2010;126:1039-46. 2. moss s. over-diagnosis in randomised controlled trials of breast cancer screening. breast cancer res2005;7:230-34. 3. welch hg. over-diagnosis and mammography screening. bmj2009;339:182-83. 4. nelson hd, tyne k, naik a. screening for breast cancer: an update for the u.s. preventive services task force. ann intern med 2009;151(10):727–37. 5. defrank jt and brewer n. a model of the influence of falsepositive mammography screening results on subsequent screening. health psychol rev 2010;4(2):112–27. 6. berg wa, blume jd, cormack jb. combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. jama 2008;299(18):2151–63. 7. us preventive services task force. screening for breast cancer: u.s. preventive services task force recommendation statement. ann intern med. 2009;151(10):716-26. 8. national health service (nhs) breast cancer screening programme. what does the nhs breast screening programme do? nhs breast cancer screening programme website. http://www.cancerscreening.nhs.uk/breastscreen/screenin g-programme.html. accessed january 21, 2014. 9. norwegian breast cancer screening programme. cancer registry of norway website. cancer-prevention/breastcancer-screening-programme/.2012. 10. american cancer society. press release:american cancer society responds to changes to uspstf mammography guidelines. american cancer society website. http://pressroom.cancer.org/2009. 11. miller ab, wall c, baines cj, sun p. twenty five year followup for breast cancer incidence and mortality of the canadian national breast screening study. bmj 2014;348:366-66 12. welch hg, passow hj.quantifying benefits and harms of screening mammography. jama intern med 2014;174:44854 13. independent uk panel on breast cancer screeningthe benefits and harms of breast cancer screening: an independent review. lancet 2012;380:1778-86 14. colditz ga, bohlke k. priorities for the primary prevention of breast cancer. ca cancer j clin 2014;64:186-94 15. dewar ja, thompson sg, wilcox m. the benefits and harms of breast cancer screening: an independent review. br j cancer. 2013;108(11):2205-40. 16. carter jl, coletti rj, harris rp. quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. bmj. 2015;350:7773-76. 17. independent uk panel on breast cancer screening.the benefits and harms of breast cancer screening: an independent review. lancet 2012;380:1778–86. 18. gøtzsche pc, jørgensen kj, zahl p-h. why mammography screening has not lived up to expectations from the randomised trials. cancer causes control2012;23:15-21. 19. anderson wf, katki ha, rosenberg ps. incidence of breast cancer in the united states: current and future trends. j natl cancer inst. 2011;103:1397-1402. 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(3): 276-280 276 original article cytological pattern of salivary gland lesions abdul rauf 1 and ammara ejaz 2 1.department of pathology, nawaz sharif medical college, gujrat;2.department of pathology, benazir bhutto hospital and rawalpindi medical university abstract background: to study the cytological pattern of salivary glands swellings on fine needle aspiration cytology (fnac). methods: patients who underwent fine needle aspiration cytology (fnac) for their salivary gland swellings, were included. data was analyzed from various angles including site, diagnostic categories, diagnostic entities, age and gender. results: parotid gland (74.3%) was the most frequently affected site, followed by submandibular gland (23.6%). the cases were divided into four main reporting groups i.e. unsatisfactory, inconclusive/ lesion of undetermined significance, non neoplastic and neoplastic constituting 0.7%, 3.6%, 22.9% and 72.9% of all the lesions respectively. non neoplastic lesions included non specific sialadenitis, cystic lesions without any evidence of neoplasia and sialadenosis comprising 43.8%, 37.5% and 18.8% of these lesions respectively. neoplastic lesions were divided into three categories namely benign, malignant and indeterminate. benign tumors constituted 79 (56.4%), malignant neoplasms consisted of 8 (5.7%) and indeterminate category contained 15 (10.7%) of all cases. mean age was 43 years and mf ratio was 1:1.7. pleomorphic adenoma was the most frequent diagnosis among all cases, in all neoplasms as well as in benign neoplasms. conclusion: parotid was the commonest site of involvement. pleomorphic adenoma and mucoepidermoid carcinoma were the most common lesions in benign and malignant neoplastic categories respectively. key words: salivary glands,parotid gland, submandibular glands, pleomorphic adenoma, mucoepidermoid carcinoma. introduction fnac is an established pathological tool for preoperative evaluation of salivary swellings.1 rather it is a first line investigation for most of the palpable head and neck masses.2 the salivary glands contain small proportion of pathological lesion in the human body. these consisted of 0.30% (100/34135) of cases in one study.3-7 salivary gland cytology is a challenging task due to less common occurrence of pathological lesions, histological diversity, overlapping features, rare entities, lack of uniform system of reporting and inherent limitations of cytological study like lack of architecture. 1,2,8 one of the most difficult problem in salivary cytology is to differentiate a benign entity from malignant.2 several workers have performed cytohistological comparison in their studies to determine its accuracy, sensitivity, specificity, positive predictive value and negative predictive values. most of these workers have reported good efficacy of fnac e.g. a study from italy has reported an overall accuracy of 92%. even in experienced hands there is a proportion of cases in each study in which the diagnosis remains uncertain and there are false positive as well as false negative cases. 4,5,6,9 most frequent error is a false negative diagnosis.10 in spite of its inherent limitations and complex nature of salivary lesions, fnac is a very useful investigation because it is safe, rapid, economical, least traumatic and contributes significant diagnostic information for better planning and management of cases.1,2,5 currently, no uniform reporting or risk stratification system is in use for cytological study of salivary glands lesions/ tumors. however, some workers have proposed these systems.1,11 patients and methods this is a study of all the patients which were referred with their salivary glands swellings and underwent fnac in aziz bhatti shaheed hospital, gujrat, affiliated with nawaz sharif medical college, from january 2012 to june 2016. most of the lesions were sampled with 23 gauge needle and 5ml disposable syringe. 22 or 21 gauge needles and 10 ml syringe were used in some cases. the smears were prepared, stained and examined. histopathological specimens/ reports of most cases were not available therefore no cytohistopathological correlation could be done. results a total of 140 patients underwent fnac during the period of study. these were divided into four main reporting categories (table 1). most of the lesions fell journal of rawalpindi medical college (jrmc); 2017;21(3): 276-280 277 into neoplastic category comprising 72.9% of the cases. most commonly affected site was parotid having 74.2% of the cases. pleomorphic adenoma (pa) was the commonest lesion (figure 1,2). there were 71 cases of pa that constituted 50.7% of all the 140 cases. mean age for all cases was 43 years, peak incidence was found in fifth decade (22.86%). the age ranged from 5 years to 80 years. more cases were seen in females than males. there were 89 females as compared to 51 males with a male to female ratio of 1:1.7. a total of 137 cases were found in parotid and submandibular glands. most of these i.e. 70 cases were found on right side, 63 on left side and four were bilateral. among the four bilateral cases, 2 were bilateral sialadenitis in parotids, 1 was bilateral sialadenitis in submandibular glands and 1 case was of bilateral cysts in parotid glands. there were three types of non neoplastic lesions in the study (table 2). most of these were located in parotid (62.5%). non specific sialadenitis was the commonest lesion with 43.8% of non neoplastic cases (fig 3-4). mean age of non neoplastic lesions was 43.6 years and m:f ratio was 1:2.2. table 1: overall and site wise frequency of diagnostic groups main groups total parotid submandibular palate no % no % no % no % unsatisfactory/ inadequate 1 0.7 1 0.7 inconclusive/ lesion of undetermined significance 5 3.6 3 2.1 1 0.7 1 0.7 non neoplastic 32 22.9 20 14.3 12 8.6 neoplastic 102 72.9 81 57.9 19 13.6 2 1.4 total 140 100.0 104 74.2 33 23.5 3 2.1 table 2: lesion and site wise frequency of non neoplastic lesions (n=32). lesion total parotid submandibular palate no % no % no % no % sialadenitis 14 43.8 7 21.9 7 21.9 0 0.0 cysts 12 37.5 10 31.3 2 6.3 0 0.0 sialadenosis 6 18.8 3 9.4 3 9.4 0 0.0 total 32 100.0 20 62.5 12 37.5 0 0.0 table 3: site and frequency of salivary gland neoplasms (n=102) sub groups lesion total parotid submandibular palate no % no % no % no % benign pa 71 69.6 61 59.8 10 9.8 wt 5 4.9 5 4.9 myoepithelioma 1 1.0 1 1.0 unspecified 2 2.0 1 1.0 1 1.0 group total 79 77.5 67 65.7 11 10.8 1 1.0 malignant mucoepidermoid carcinoma 5 4.9 5 4.9 adenoid cystic carcinoma 1 1.0 1 1.0 squamous cell carcinoma 1 1.0 1 1.0 carcinoma 1 1.0 1 1.0 group total 8 7.8 6 5.9 2 2.0 indeterminate probably benign 5 4.9 2 2.0 3 2.9 probably malignant 8 7.8 4 3.9 3 2.9 1 1.0 oncocytic neoplasm 2 2.0 2 2.0 group total 15 14.7 8 7.8 6 5.9 1 1.0 total 102 100.0 81 79.4 19 18.6 2 2.0 journal of rawalpindi medical college (jrmc); 2017;21(3): 276-280 278 neoplastic lesions in the study were reported in three subcategories namely benign, indeterminate and malignant (table 3). most of these neoplastic lesions were benign (77.5 %, 79/102). parotid contained most of the lesions i.e. 79.4%. pa was the commonest lesion comprising 69.6% of neoplastic cases (71/102). warthin tumor (wt) was the second most common benign tumor. there were five cases of wt, all of which were found in parotid. mucoepidermoid carcinoma (mec) was the most common lesion in malignant category. all the five cases of this entity were seen in parotid glands. mean age was 41.7 years for all neoplasms. most of the pas presented in third and fourth decade (39 out of 71) while most of the wts presented in fifth decade (3 out of 5). mean age was 39.2 years for pas and 55 years for wts. the mean age for mec was 34 years. the m:f ratio was 1:1.76 for all, 1:2.6 for benign-neoplastic and 1:1 for malignant cases. highest m:f ratio was observed for wt at 4:1. discussion the frequency of neoplastic cases in the present study was 72.9%. the frequency ranged between 56% to 80% in other studies..3,4,6,12,13 the lowest frequency of 50% was noted in only one study in which the frequency of both neoplastic and non neoplastic lesions was same i.e. 50% each.8 parotid is the most commonly involved site in almost all studies with frequency of parotid involvement varying from 48.2 to 77.3%. 5,6,7,8,14,15 parotid was followed by submandibular glands with 23.6% of cases, the frequency comparable to 21.6% (19/88) reported in the study of fernandes.15 the palate contained 2% of cases in present study, a finding similar to a study from lahore.14 pa was the commonest lesion in our study as it was also commonest lesion in all studies.4,5,6,15 soni et al and fernandes et al have reported relatively lower frequencies of 43% and 45% rspectively.3,15 mean age for all cases was 43 years in present study and it was closest to mean age of 45 years in the study of tessy.16 ashraf et al have reported a lower mean age of 33.39 years.14 a study from thailand has reported a higher mean age of 53 years.5 more cases were seen in females than males in present study with a male to female ratio of 1:1.7. the findings in m:f ratio are interesting. in two out of three studies from pakistan, lesions are more common in females. in the study of ashraf et al from lahore it is 1:1.5, in the study of iqbal et al from karachi it is 1:1.5 (84 females vs 56 males) and in the study of naz et al from karachi it is 1:1. 4,6,14 a study from thailand reported a mf ratio of 1:1.2. 5 on the other hand the lesions are more common in males in studies from india i.e. a mf ratio of 1.6:1, 1.1:1, 1.3:1 and 1.36:1 in the studies of fernandes et al, jain et al and sarvaiya et al and tessy et al respectively.7,13,15,16 the benign category of neoplasms contained most lesions in our study (77.5% of neoplasms). benign category is the largest category of neoplasms in other studies but with relatively lower fequencies i.e. 60.3% in the study of tayal et al, 69.3% in the study of soni et al, 58% in the study of iqbal et al, 60.9% in the study of naz et al and 72.5 in that of jain et al.3,4,6,7,8 in a few studies the minor salivary glands are 2nd most frequent site after parotid.17,19 a possible explanation of this fact may be the availability of oral and maxillofacial surgery facilities in the institutions reporting a higher frequency of minor salivary gland tumors(sgts). the study of niazi et al was conducted in lahore where a well established department of maxillofacial surgery is present.17 the frequency of minor salivary gland lesions was at 2% in our study but there is wide variation in literature. this frequency varies from lower to higher as follows: al sarraj et al:0% (0/314), jain et al:2.5%, sarvaiya et al:10.2%, tayal et al:12.3%, vasconcelos et al:14.6% and niazi et al:22.78%.7,8,13,17-19 wt was the second commonest among benign tumors in present study with a frequency of 6.3%. it is 2nd commonest benign tumour in several studies.4,19,20 naz et al have reported this frequency at 7%.4 all five cases fig 1: pleomorphic adenoma. epithelial and myoepithelial cells in mucinous background fig 2: pleomorphic adenoma-epithelial and myoepithelial cell groups fig 3: chronic sialadenitis salivary gland acini with background of inflammatory cells fig 4: chronic sialadenitis journal of rawalpindi medical college (jrmc); 2017;21(3): 276-280 279 in our study were found in parotid, a finding similar to the study of niazi et al.17 mec was the commonest malignant tumor with 4.9 % (5 cases) of all neoplasms. it is been found commonest malignant tumour in most other studies.3,6,17,18 in the present study, the indeterminate category contained 14.7% (15/102) of neoplastic cases. it is not possible with cytological studies to categorize all the neoplasms into benign and malignant categories only. this category may contain significant number of cases in cytological studies.1 mean age was 41.7 years for all neoplasms. sarraj et al and niazi et al have reported very closer mean ages of 42 years and 44 years respectively.5,17 mean age for benign neoplasms was 40 years. jain et al has reported an almost similar age of 37.4 years.7 mean age was 42 years for malignant cases in present study. other authors have reported variable mean ages for malignant cases like jain et al, who has reported a lower age of 33 years while soni et al and sarvaiya et al have observed higher ages of 50.4 and 48.2 years respectively. 3,7,13 in present study, most of the pas presented in third and fourth decade (39 out of 71) while most of the wts presented in fifth decade (3 out of 5). soni et al has reported similar findings that pa was commonly seen in 3rd to 5th decade while wts were seen in the higher age group.3 among malignant lesions, mec occurred in younger patients in present study i.e. the youngest patient being 17 years of age. niazi et al and vasconcelos et al have reported similar findings of mec in younger patients.17,19 the m:f ratio was 1:1.76 for all neoplasms in present study. it correlates with mf ratio reported by vasconcelos et al ( 1:1.06) and laishram et al (1:1.08) but contrasts with that of sarvaiya et al (1.04:1). 12,13,19 there were 22.9% non-neoplastic lesions in the present study. our finding is closer to that of iqbal et al at 20% and fernandes et al at 19% while naz et al and tayal et al mentioned higher frequencies at 39.6% and 50% respectively.4,6,8,15 non neoplastic cases in our study comprised of three types i.e. sialadenitis, cysts and sialadenosis, a finding same as that of jain et al and fernanades et al.7,15 sialadenitis (non specific) was the most common lesion in non neoplastic category in our study. it is the most common lesion in several other studies.3,6,7 some studies have reported significant cases of granulomatous sialadenitis (caseating granulomatous sialadenitis, tuberculous sialadenitis).4,6,8 our study did not contain any such case like the studies of fernandes et al, jain et al, sarvaiya et al and soni et al.3,7,13,15 one of the reasons may be that such cases may have been reported as granulomatous lymphadenitis due to lack of salivary cells in the smears. there may be other epidemiological factors as well. benign cystic lesions were second commonest non neoplastic lesion in present study, a finding similar to that of iqbal et al and naz et al.4,6 mean age was 43.6 years for nonneoplastic lesions in present study. other authors have reported lower ages i.e. commonest age group is 20 to 29 years in study of tayal et al and jain et al has reported the occurrence of these cases in younger patients at lower mean age of 20.5 years.7,8 another study has observed that nonneoplastic lesions were common in the 3rd to 4th decade of life.3 the m:f ratio was 1:2.2 for non neoplastic lesions in our study. indian studies have reported opposite m:f ratios in favor of males by sarvaiya et al at 2:1 and 4.32:1 by tayal et al.8,13 different epidemiological factors may be responsible for this contrast. conclusion parotid was the commonest site of involvement. pleomorphic adenoma and muco-epidermoid carcinoma were the most common lesions in benign and malignant neoplastic categories respectively. references 1. wang h, fundakowski c, khurana js, jhala n, fine-needle aspiration biopsy of salivary gland lesions. arch pathol lab med 2015;139:1491-97. 2. inancli hm, kanmaz ma, ural a, dilek gb. fine needle aspiration biopsy: in the diagnosis of salivary gland neoplasms compared with histopathology. indian j otolaryngol head neck surg. 2013 ; 65(1): 121–25. 3. soni d, mathur k, yadav a, kumar v. histopathological spectrum of salivary gland lesions. int j med res prof. 2016; 2(2); 209-15. 4. naz s, hashmi aa, khurshid a, faridi n. diagnostic role of fine needle aspiration cytology in evaluation of salivary gland swelling.bmc research notes 2015, 8:101-04 5. nguansangiam s, jesdapatarakul s, dhanarak n. accuracy of fine needle aspiration cytology of salivary gland lesions. asian pacific journal of cancer prevention. 2012; 13(4): 1583–88. 6. iqbal sm, memon im, hussain si. diagnostic role of fnac with histopathological correlation of salivary gland swellings. pak j surg 2013; 29(4):248-51 7. jain r, gupta r, kudesia m,singh s. fine needle aspiration cytology in diagnosis of salivary gland lesions. cyto journal 2013;10:05-09. 8. tayal u, bajpai m, jain a, dhupia js. fnac of salivary gland lesion study of 126 cases at a tertiary care center of national capital region india. journal of medical and dental science research 2014, 1(2): 04-06 9. pastore a, borinl m, malaguttp n, di laoral a. preoperative assessment of salivary gland neoplasms with fine needle aspiration cytology and echography. international journal of immunopathology and pharmacology 2013; 26(4):965-71 10. barnes l, eveson jw, reichart p, sidransky d. tumors of the salivary glands. in: world health organization classification journal of rawalpindi medical college (jrmc); 2017;21(3): 276-280 280 of tumors. pathology and genetics of head and neck tumors.lyon: iarc; 2005; vol9: 209-81. 11. griffith cc, pai rk, schneider f. salivary gland tumour fineneedle aspiration cytology:proposal for a risk stratification classification. am j clin pathol 2015; 143 (6): 839-853. 12. laishram rs, kumar ka, pukhrambam gd. pattern of salivary gland tumors in manipur, india: a 10 year study. south asian journal of cancer. 2013;2(4):250-53. 13. sarvaiya an, gajjar hk, panjvani si. histopathological study of salivary gland lesions. international journal of scientific research 2014; 3(1): 367-69. 14. ashraf a, shaikh as, kamal f, sarfraz r, bukhari mh. diagnostic reliability of fnac for salivary gland swellings: a comparative study. diagn cytopathol. 2010;38:499– 504. 15. fernandes h, d’souza crs, khosla c, george l, katte nh. role of fnac in the preoperative diagnosis of salivary gland lesions. j clin diagn res. 2014 sep; 8(9): fc01–fc03. published online 2014 sep 20. doi: 10.7860/jcdr/2014/6735.4809 16. tessy pj, jayalekshmy ps, cicy pj. fine needle aspiration cytology of salivary gland lesions with histopathological correlation int j of healthcare and biomedical research 2015;3(4):91-99 17. niazi s, arshad m, iqbal a, jaffery a, bokhari mh, the morphological spectrum of salivary gland tumours at kemu and mayo hospital, lahore.biomedica 2013; 29:1-11. 18. al sarraj y, nair sc, al siraj a, al-shayeb m, characteristics of salivary gland tumours in the united arab emirates. ecancer 2015, 9:583 19. vasconcelos ac, nor f, meurer l, salvadori g. clinicopathological analysis of salivary gland tumors over a 15-year period. braz. oral rres 2016;30(1):1807-10 20. jo hj, ahn hj, jung s, yoon hk. diagnostic difficulties in fine needle aspiration of benign salivary glandular lesions. korean j pathol. 2012; 46(6): 569–575. 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(2): 122-126 122 original article inferior alveolar nerve injury caused by coronectomy or conventional method in third molar extractions fouzia aslam1, zahoor ahmad rana2,muhammad umar farooq2,nida qasim2 1. department of oral and maxillofacial surgery, rawal institute of health sciences, islamabad; 2. department of oral and maxillofacial surgery, pakistan institute of medical sciences, islamabad abstract background: to compare the frequency of injury to the inferior alveolar nerve as a result of coronectomy and removal of mandibular third molars having nerve approximation. methods: in this comparative study 110 patients with inferior alveolar nerve approximation were selected and randomly allocated into group-a and group-b. group-a patients underwent coronectomy and group-b patients underwent traditional removal. inferior alveolar nerve damage was assessed one week post operatively, then further assessed after 01, 03 and 06 months. results: out of total 110 patients included in the study, 9 (8.2%) patients were having nerve damage. in traditional removal group, 9 (16.4%) patients were found to have nerve damage. seven patients with nerve injury recovered within 06 months whereas 2 patients had permanent nerve damage. in coronectomy group none of the patients had nerve damage. conclusion: coronectomy is an effective procedure in significantly reducing the incidence of inferior alveolar nerve injury when compared with traditional removal of wisdom teeth. key words: coronectomy, inferior alveolar nerve, molar extraction introduction mandibular third molars are the most frequently impacted teeth. complete surgical removal is the traditional method of treatment of the most impacted mandibular third molars. one of the serious complication associated with traditional removal of these teeth is injury to the inferior alveolar nerve resulting in dysaesthesia.risk factor associated with inferior alveolar nerve injury is approximation of the inferior alveolar nerve (ian), to the apex of the root which can be predicted by certain radiographic features. current trend is that whenever nerve approximation exists, option of coronectomy is considered which reduces ian injury.injury to inferior alveolar nerve(ian) is a well recognized serious complication of mandibular third molar extraction.1incidence of temporary injury to inferior alveolar nerve(ian) after third molar extraction range from 0.41% to 8% and permanent injury upto 3.6% of cases.2risk factors for ian injury include advanced age, gender of the patient, amount of bone cutting required in operation according to the difficulty index and an important risk factor is the proximity of the third molar to the nerve canal.1 the intimate relationship of inferior alveolar nerve to the apex of the root can be predicted by radiographs such as peri-apical and panoramic tomographic views. this offers the opportunity to alter the extraction technique to minimize risk to the nerve. it is common practice for the broken root fragments of vital teeth to be left in place and most heal uneventfully. this has led to evolution of concept of coronectomy which is deliberate retention of the roots adjacent to the nerve.3coronectomy was proposed as a clinical procedure more than 30 years ago. 3 studies have provided evidence that coronectomy decreases the risk of ian damage when compared to the traditional extraction. coronectomy prevents nerve damage as it avoids the nerve canal by ensuring retention of the roots which are close to the canal.4renton et al.2reported 0 % ian injury in coronectomy patients and 19% ian injury in those having traditional extractions. the incidence of inferior alveolar nerve injury according to different authors varies from 0.81% to 22% of cases5,6,7,8,9coronectomy is an alternative procedure to complete extraction when a tooth is deemed ‘high risk’ but vital and in a patient who is not medically compromised (diabetic, long term steroids, chemotherapy, hiv); or potential poor healing [previous irradiation]).10 inferior alveolar nerve injury can cause paresthesia to complete numbness or pain in the zone of the mental area, the lower lip, mucous membranes, and the gingiva as far posteriorly as the second premolar.11 furthermore this commonly journal of rawalpindi medical college (jrmc); 2017;21(2): 122-126 123 interferes with speech, kissing,eating, make-up application, drinking and shaving.12 patients and methods the study was carried out in the department of oral and maxillofacial surgery, pakistan institute of medical sciences(pims),islamabad. approval from the hospital ethical committee was sought before the start of the study. patients were selected from the out patient department of oral & maxillofacial surgery, pims, islamabad. routine baselines were carried out for fitness purpose. informed consent of the patients were taken on consent form after explaining the procedure. patients who were judged to be at high risk of injury to the inferior alveolar nerve i.e. proximity of mandibular third molar to nerve canal, based on radiographic features in routine pre-operative dental radiograph including peri-apical and panoramic views were included in the study. these features included darkening of the roots, deflection of roots, narrowing of the roots, bifid root apex, narrowing of the canal, diversion of canal, interruption of lamina dura. patients who were predisposed to local infection in diabetes, immuno-compromised patients including hiv and chemotherapy, previous radiotherapy to the head and neck, osteosclerosis or osteopetrosis, patients having carious and non-vital third molars, patients having previous or existing defects of the inferior alveolar nerve and neuromuscular disorders were excluded from the study. random allocation of patients into group a and group b was done by table of random numbers generated by microsoft excel .opg and periapical x-rays were also advised.groupa patients underwent coronectomy and group-b patients underwent traditional removal. all patients were advised pre-operative chlorhexidine mouthwash rinse.patients were draped under aseptic condition.la was given on the involved side. full thickness mucoperiosteal flap was raised. flap elevation and reflection was done. buccal bone osteotomy was done till full crown exposure, then both procedures were performed. full tooth extraction was done in traditional manner. coronectomy was performed by doing transection of the tooth with fissure bur using controlled force. the crown was totally transected so that it could be removed with tissue forceps alone and did not need to be fractured off the roots. this minimizes the possibility of mobilizing the roots. the pulp was left in place after crown has been levered off (figures 1 -3). the socket was then irrigated with saline and mucoperiosteal flap was replaced with vicryl suture. inferior alveolar nerve function was assessed after 01 week by the presence of subjective sensory changes and objective neurosensory testing by light touch test,pain threshold test and two-point discrimination test. inferior alveolar nerve damage was diagnosed if both subjective and objective measurements were different from non-affected side or preoperative baselines.these patients were further followed up after 01, 03 and 06 months to determine the duration of nerve injury whether temporary or permanent. fig 1: pre-operative radiograph of patient showing mandibular right sided third molar with ian approximation fig 2: coronectomy done fig 3: post-operative opg showing retained roots of rt mandibular third molar results total of 110 (n=55 in each group) subjects of mandibular third molar with ian approximation were included in this study. mean age (yrs.) of the study subjects was 28.66 + 6.154 with ranges from 17 to 50 years (table 1). males constituted 55.5 % (n = 61) of the study subjects, whereas female subjects were 44.5% (n=49).(table. 2).nerve damage was observed postoperatively at 01 week, then further assessed after 01, 03 and 06 months. out of total 110 study subjects, 9 (8.2%) patients were having nerve damage and all were from traditional removal group. seven subjects with nerve injury recovered within 06 months whereas 2 subjects had permanent nerve damage. in journal of rawalpindi medical college (jrmc); 2017;21(2): 122-126 124 coronectomy group none of the subjects had nerve damage.in traditional removal group 06(9.8%) males and 03(6.1%) females had ian damage.in coronectomy group no nerve damage was present both in males and females, however coronectomies in 2 female subjects failed as the roots were mobilized and were removed as a whole, but no nerve damage was present (table 2 & 3). p value calculated using chi-square test was 0.002. table 1: age characteristics of patients age n min max mean std. deviation 110 17 50 28.66 + 6.154 table 2: frequency of nerve damage nerve damage temporary nerve damage no nerve damage permanen t nerve damage p value groups coronectomy 0 55 0 0.002 traditio-nal removal 7(6.4 %) 46 2(1.8%) total 7 101 2 table : 3 gender distribution gender total male female groups coronectomy 27 28 55 traditional removal 34 21 55 total 61 49 110 discussion coronectomy was proposed as a clinical procedure more than 30 years ago but has not been commonly performed, largely owing to the lack of well-designed evidence-based trials to support its use. the first published description of this technique was by ecuyer and debien in 1984.their technique was further elaborated in a letter in 1995.13no clinical trial demonstrating effectiveness of coronectomy in reducing ian injury versus traditional removal in mandibular third molars(mtm) having ian approximation has been reported from this part of the world, despite very encouraging results from studies conducted in different parts of the world. the predominant age in the present study was second and third decade of life. no significant co-relation between patient’s age and ian injury is seen in this study. however removal of impacted teeth in adult patients was found to be more difficult. the influence of the patient’s age on the incidence of injury to the inferior alveolar nerve is discussed controversially. several investigators demonstrated a correlation between these factors,14 whereas others did not.15according to bruce et al.16older patients had higher rates of ian injury. 14 ian damage was more common in males 06(9.8%) than females 03(6.1%) according to the current study. some papers dealing with nerve injuries following variant surgical procedures, including third molar surgery, observed a distinct female over representation.17several other studies showed that sensory deficit was evenly distributed among male and female patients.14the reason for increase ian damage in males in the current study is due to increased male population in the study and more dense bone in males as compared to females. nerve damage was the primary outcome variable which was observed postoperatively at 01 week. the results of this study are in line with those reported in the randomized controlled clinical trial of renton et al.2who compared the incidence of injury to the inferior alveolar nerve as a result of coronectomy and removal of mandibular third molars. in the study by renton et al, out of total 128 patients, 102 teeth were extracted, while coronectomy was performed for 94 teeth.2among all cases, no nerve damage was found in the coronectomy group. however, nerve damage was observed in 19(19%)subjects in the extraction group. leung et al.18 showed 09(5%) patients in the control group presented with ian injury, compared with 01 (0.06%) in the coronectomy group. hantano et al.19reported that in the extraction group 6 patients (5%) suffered idni, of which 3 patients were diagnosed with permanent injury, where as in the coronectomy group 01 patient (1%) complained of altered sensation post-operatively which resolved within one month. in retrospective analysis of o’riordan1303 cases had transient ian injury, 01 patient developed permanent ian injury, which was thought to be as a result of perforation of the canal due to operator error rather than the coronectomy technique itself. though the volume of evidence remains small it shows clear drift that coronectomy can reduce ian injury in high risk mtms. in this study, we observed a low rate of coronectomy failure (3.6%) and found no ian damage associated with failed coronectomies. both the patients with failed coronectomies were females and had conical roots. our findings of risk factors associated with failed coronectomies (female patients with conical roots), co-relate with that of renton’s findings. renton et al.2 reported a 38% failure rate of coronectomy, in journal of rawalpindi medical college (jrmc); 2017;21(2): 122-126 125 which subsequent root removal was needed. the author was of view that women below the age of30 years with conically shaped roots of the third molars were more likely to sustain mobilization of the roots during coronectomy. another reason for high failure rate in renton et al.2 study maybe due to the reason that the roots were only sectioned halfway before an attempt was made to remove the crown. 2 this appeared to mobilize the roots in many cases and did result in an 8% incidence of temporary ian involvement with no permanent injuries in the failed coronectomy group. in pogrel’ssecond report,20 18/450 were failed coronectomies,whereby the roots were mobilized during the procedure when the crown was elevated. these roots were removed at the same time, and paraesthesia developed in 02 patients, which was resolved. however in our opinion, low failure rate of coronectomies in our study may be due to full sectioning of crown with fissure bur, using controlled force. sectioning through the crown was partial by renton2, leung & cheung21and o’riordan.22 2,21,22 complete section of the crown from the roots was undertaken by pogreland dolanmaz23.this may explain why there were relatively few root mobilizations in the fully sectioned groups. the follow-up duration of our study for coronectomy patients was not as long as in other studies.however, this would not affect the assessment of the primary outcome of the study, which was to compare the postoperative ian deficit of coronectomy and total removal of wisdom teeth. coronal migration of the roots has been reported as the most commonly reported long-term consequence of coronectomy2,24,25 conclusion 1. coronectomy is an effective procedure insignificantly reducing the incidence of ian injury when compared with traditional removal of wisdom teeth and is the best treatment alternative for third molars with roots in close proximity to the ian. 2. the risk of the injury to ian during mtm surgery can be significantly reduced through appropriate patient assessment, planning of the surgery, proper patient counseling and considering the alternative techniques like coronectomy when indicated. 3. longer follow-up of the patients undergoing coronectomy is required for the assessment of other factors like root migration away from ian and need for reoperation for removal of retained roots. 4. assessment of high risk third molars using cone beam computed tomography (cbct) is also a feasible option ,due to ease of availability of cbct. cbct reaffirms the relationship that would support the planned coronectomy and help in decreasing inferior alveolar nerve injury references 1. savi a, manfredi m, pizzi s, vescovi p, ferrari s. inferior alveolar nerve injury related to surgery for an erupted third molar. oral surg oral med oral pathol oral radiol endod 2007; 103(2): 7-9. 2. renton t, hankins m, sproate c, mcgurk m.a randomisedcontrod clinical trial to compare the incidence of injury to the inferior alveolar nerve as a result of coronectomy and removal of mandibular third molars. br j oral maxillofac surg 2005; 43(4): 7-12. 3. patel v, moore s, sproat c. coronectomy oral surgery's answer to modern day conservative dentistry.br dent j 2010 ; 209(3): 111-14. 4. figueiredo r, valmaseda-castellón e, berini-aytés l, gayescoda c.delayed-onset infections after lower third molar extraction: a case-control study.j oral maxillofac surg 2007 ; 65(1): 97-102. 5. kim jw, cha ih, kim sj, kim mr. which risk factors are associated with neurosensory deficits of inferior alveolar nerve after mandibular third molar extraction?. j oral maxillofac surg 2012 ; 70(11):2508-14. 6. renton t, yilmaz z, gaballah k. evaluation of trigeminal nerve injuries in relation to third molar surgery in a prospective patient cohort. recommendations for prevention.int j oral maxillofac surg 2012 ; 41(12):150918. 7. leung yy, cheung lk. correlation of radiographic signs, inferior dental nerve exposure, and deficit in third molar surgery. j oral maxillofac surg 2011 ; 69(7):1873-79. 8. smith wp. the relative risk of neurosensory deficit following removal of mandibular third molar teeth: the influence of radiography and surgical technique. oral surg oral med oral pathol oral radiol 2013; 115(1):18-24. 9. umar g, obisesan o, bryant c, rood jp. elimination of permanent injuries to the inferior alveolar nerve following surgical intervention of the “high risk” third molar. br j oral maxillofac surg 2013 ; 51(4):353-57. 10. renton t. notes on coronectomy.br dent j 2012 apr 13 ;212(7):323-26. 11. roy ts, sarkar ak, panicker hk.variation in the origin of the inferior alveolar nerve. clinanat 2002 ;15(2):143-47. 12. ziccardi vb, assael la.mechanisms of trigeminal nerve injuries. atlas oral maxillofac surg clin north am 2001 ;9(2):1-11. 13. o’riordan bc. uneasy lies the head that wears the crown. br j oral maxillofacsurg 1997; 35:209-12. 14. pogrel ma, mcdonald ar, kaban lb. gore-tex tubing as a conduit for repair of lingual and inferior alveolar nerve continuity defects: a preliminary report. j oral maxillofac surg 1998;56(3):319–21. 15. kipp dp, goldstein bh, weiss ww. dysaesthesia after mandibular third molar surgery: a retrospective study and http://www.ncbi.nlm.nih.gov/pubmed/20706244 http://www.ncbi.nlm.nih.gov/pubmed/20706244 http://www.ncbi.nlm.nih.gov/pubmed?term=%22figueiredo%20r%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22valmaseda-castell%c3%b3n%20e%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22berini-ayt%c3%a9s%20l%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22gay-escoda%20c%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22gay-escoda%20c%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed/17174771 journal of rawalpindi medical college (jrmc); 2017;21(2): 122-126 126 analysis of 1377 surgical procedures. j am dent assoc 1980;100(2): 185–92. 16. bruce ra, frederickson gs, small gs. age of patients and morbidity associated with mandibular third molar surgery. jam dent assoc 1980;10:240-45. 17. venta i, lindqvist c, ylippavalniemi p. malpractice claims for permanent nerve injuries related to third molar removals. actaodontolscand 1998;56(4): 193–96. 18. leung yy, cheung lk. safety of coronectomy versus excision of wisdom teeth: a randomized controlled trial.oralsurg oral med oral pathol oral radiol endodontol 2009;108:821–27. 19. hatano y, kurita k, kuroiwa y, yuasa h, ariji e. clinical evaluations of coronectomy (intentional partial odontectomy) for mandibular third molars using dental computed tomography: a case-control study. j oral maxillofacsurg 2009;67:1806–14. 20. pogrel ma. an update on coronectomy. j oral maxillofac surg 2009;67:1782–83. 21. leung yy, cheung lk. safety of coronectomy versus excision of wisdom teeth: a randomized controlled trial. oral surg oral med oral pathol oral radiol endodontol 2009;108:821–27. 22. o’riordan bc. coronectomy (intentional partial odontectomy of lower third molars). oral surg oral med oral pathol oral radiol endod 2004;98:274 80. 23. dolanmaz d, yildirim g, isik k, kucuk k, ozturk a.a preferable technique for protecting the inferior alveolar nerve: coronectomy. j oral maxillofac surg 2009;67:1234– 38. 24. gady j, fletcher mc. coronectomy: indications, outcomes, and description of technique. atlas oral maxillofac surg clin north am 2013 ;21(2):221-26. 25. patel v, gleeson cf, kwok j, sproat c. coronectomy practice. paper 2: complications and long term management. br j oral maxillofac surg 2013 ;51(4):34752. ----------------------------------------------------------- authorship: 1conception , synthesis and planning of the research; 3,4active participation in methodology, interpretation and discussion . . . . for electronic submission of articles email of journal: journalrmc@gmail.com to view volumes of journal of rawalpindi medical college and to search by authors names , contents , keywords-visit website of the journal: www.journalrmc.com mailto:journalrmc@gmail.com summary journal of rawalpindi medical college (jrmc); 2010;14(1):2-6 2 clinicohaematological spectrum of females with inherited bleeding disorders nadeem ikram* , tahira zafar**, arshad ali sabir***, khalid hassan**** , samina amanat ***** * department of pathology, rawalpindi medical college ** department of pathology, islamabad medical and dental college, islamabad *** department of community medicine , rawalpindi medical college. **** department of pathology , pakistan institute of medical sciences , islamabad ***** department of pathology, pakistan atomic energy commission hospital, islamabad abstract background: inherited bleeding disorders in females are under-diagnosed, eventually leading to multiple problems. this situation is further worsened by the inadequate information , non – availability of diagnostic facilities and low awareness on the clinical side methods: in this non – interventional descriptive study , females with inherited bleeding disorders were assessed. clinical presentations, demographic data and management received was recorded. complete blood counts, prothrombin time, activated partial thromboplastin time, thrombin time and platelet function studies were performed, where required.. results: in all the patients with inherited bleeding disorders , females constituted 16.85%. von willebrand disease was the commonest (50.84%) out of all inherited bleeding disorders in females. in rest of the females autosomal recessive coagulation defects and platelet function defects constituted 25.42% and 23.72%, respectively. majority of the females (83.04%) were below 17 years of age. menorrhagia (46.87%) was the commonest clinical episode. spontaneous bleed was seen in 95% episodes. majority of the episodes (94.14%) were soft tissue bleeding episodes and joint bleeds were minimal (5.68%). tranexamic acid was the most commonly used therapeutic agent . surgical intervention was employed in 18 episodes. conclusion: females with inherited bleeding disorders have severely impaired quality of life , fail to get proper management and go through unwanted surgeries ( d&c; hysterectomies). introduction very little information is available regarding gynaecological and obstetric problems in females with inherited bleeding disorders 1 estimates suggest that 10 to 20% of women with menorrhagia have an underlying inherited bleeding disorder2,3. menorrhagia is the most common manifestation seen in women with inherited bleeding disorders, but it is not the only abnormality. females in their child bearing years are more likely to manifest an inherited bleeding disorder than premenarcheal or postmenopausal females. during pregnancy there is greater risk of miscarriage and bleeding complications. at the time of child birth, women with bleeding disorders appear to be more likely to experience postpartum haemorrhage, particularly delayed or secondary postpartum haemorrhage. vaginal or vulvar haematomas, extremely rare in women without bleeding disorder, are not uncommon. women with bleeding disorders are more likely to undergo a hysterectomy and more likely to have this operation at a younger age. most of the times hysterectomies in these patients are performed in ignorance, rather than an option. these women appear to be at an increased risk of developing haemorrhagic ovarian cysts and possibly endometriosis. as they grow older, they may be more likely to manifest conditions, which present with bleeding such as fibroids, endometrial hyperplasia and polyps. while women with bleeding disorders are at risk for the same obstetrical and gynaecological problems that affect all women, they appear to be disproportionately affected by conditions that manifest with bleeding.4 with this background, an overview of common inherited bleeding disorders, in females, focusing on their clinical manifestations, complications, diagnosis, treatment options and hindrances in their management can be considered as a likely objective to explore. patients and methods in this non – interventional descriptive study, females with inherited bleeding disorders presenting to haemophilia patients welfare society, rawalpindi/islamabad chapter and district head quarters hospital rawalpindi were analyzed. demographic data, presenting episodes, diagnostic journal of rawalpindi medical college (jrmc); 2010;14(1):2-6 3 evaluation and treatment received were recorded .diagnosis was established on the basis of prothrombin time (pt), activated partial thromboplastin time (aptt) , thrombin time (tt), bleeding time (bt), clotting time (ct), factor level estimation ,platelet count , platelet aggregation studies and examination of peripheral smear. mixing studies were performed by using aged serum (24 hours old serum kept at 37 0 c) and adsorbed plasma (normal plasma adsorbed by barium sulphate). factor levels were estimated by using commercially available deficient plasmas. platelet aggregation studies were performed by collecting 10 ml of blood in sodium citrate. platelet rich plasma (prp) was prepared by centrifuging the samples at 250 xg and 1500 xg respectively for ten minutes. the aggregation pattern was studied against different agonists ( adp, epinephrine, ristocetin, collagen) results von willebrand disease was the commonest ,followed by glanzmann’s thrombasthenia (table1). age group from 6 to 15 years constituted the main patient’s group (table 2) menorrhagia was the most frequent presentation (46.87%) . majority of the episodes were soft tissue bleeds. joint bleeds were seen in 6.8% episodes. one patient died because of post partum bleed.(table 3). three patients presented with an acute abdomen due to haemorrhagic ovarian cyst. table 1: distribution of females with inherited bleeding disorders total number of patients with inherited bleeding disorders = 350 female patients with inherited bleeding disorders = 59/350( 16.85%) disease number of patients(%) von willebrand disease 30/59 (50.84%) glanzman’s thrombasthenia 9/59 ( 15.25%) factor v deficiency 7/59 (11.86%) factor x deficiency 4/59 ( 6.77%) factor xiii deficiency 3/59 ( 5.08%) bernard soulier syndrome 5/59 ( 8.47%) factor xi deficiency 1/59 ( 1.69%) table 2: inherited bleeding disorders in females: age distribution age number of patients (%) less than 5 years 10/59 ( 16.94%) 6 – 15 years 39/ 59 (66.10%) 16 – 25 years 5 / 59 (8.47%) 26 – 35 years 2 / 59 ( 3.38%) 36 – 45 years 2 / 59 (3.38%) 46 – 55 years 1 / 59 ( 1.69%) table 3: inherited bleeding disorders in females: bleeding episodes menorrhagia 165/352 ( 46.87%) epistaxis 61/352 ( 17.32%) gum bleed 42/352 ( 11.93%) dental bleed 35/352 (9.94%) bruising 21/352 ( 5.96%) joint bleed 20/352 (5.68%) umbilical cord bleed 4/352 ( 1.13%) haemorrhagic ovarian cysts 4/352 ( 1.13%) cns bleed 2/352 ( 0.56%) postpartum bleed 1/352(0.28%) table 4: platelet agggregation studies von willebrand disease glanzmann’s thrombasthenia bernard soulier syndrome platelet count normal normal decreased platelet size normal normal large aggregation with adp normal absent normal aggregation with collagen normal absent normal aggregation with ristocetin absent normal absent journal of rawalpindi medical college (jrmc); 2010;14(1):2-6 4 aggregation with epinephrine normal absent normal fig1 : platelet aggregation studies in females with inherited bleeding disorders table5: inherited bleeding disorders in females: treatment received* treatment number of episodes tranexamic acid 84 / 105 fresh frozen plasma 40 / 105 cryoprecipitate 10 / 105 platelet’s concentrates 32 / 105 kaote 5 / 105 ddavp 21 /105 hormonal therapy 39 /105 recombinant factor vii 2 /105 dilatation and curettage 10 / 105 laparotomies 5/105 hysterectomies 3 /105 in laboratory evaluation prolonged bleeding time and aptt and normal pt , along with aggregation with all agonists, except ristocetin , established the diagnosis of vwd. bernard soulier syndrome and vwd gave similar results on platelet aggregation studies, but in vwd patient’s plasma plus control plasma gave normal aggregation with ristocetin and in bernard soulier syndrome there was thrombocytopenia with giant platelets on peripheral smear (table 4 ; fig 1). tranexamic acid was the most commonly used therapeutic agent . surgical intervention was employed in 18 episodes (table 5) discussion despite their high prevalence, these disorders often remain undiagnosed, and particularly so unless significant iron deficiency anaemia, post operative bleeding and/ or transfusion occurs. failure to recognize or even consider a diagnosis of a bleeding disorder either by patient or providers, limitation of available diagnostic tests ,which are complex to perform and interpret and the lack of available therapeutic agents to treat these disorders are a few of the mentionable obstacles 2. the commonest inherited bleeding in females is von willebrand disease (vwd), followed by platelet function defects and some autosomal recessive coagulation factor deficiencies. rarely female carriers of haemophilia can also have gynaecologic complications 1. world wide vwd is considered as the most common inherited bleeding disorder 5 . data on its epidemiology and impact in developing countries are limited. the biologic heterogeneity and variable presentation of vwd make diagnosis difficult. although there is no accurate data of the prevalence of vwd in developing countries, available data suggests that the proportion of diagnosed cases is lower than the expected number, often accounting for only 6% to 13% of patients with hereditary bleeding disorders . the number is expected to be much higher in our set up due to high rate of consanguinity . the prevalence of different types of vwd is also not known which is essential for a proper management of these cases 6,7 . in an indian study majority of the patients of vwd were type 3 (59.5%), with severe clinical manifestations . the high prevalence of type 3 and low prevalence of type 1 , which is in contrast to western reports , can be ascribed to the consanguineous marriages , low awareness of the disease and also the under diagnosis of mild cases in this part of world 8 . the diagnosis of vwd is difficult because the intensity of symptoms is highly variable . at one end are type 3 patients who present in childhood with severe bleeding tendency and seek medical advice earlier and on the other end the patients with milder disease have very vague symptoms which they only tell when they are specifically asked . in between are the majority of patients who have unusual bleeding tendency but diagnosis is missed or delayed in laboratory diagnosis of these problems time of testing in women’s cycle is an important confounding factor. fluctuating estrogen levels can glanzman’s thrombastheniavon willebrand diseasenormal control restocetine restocetine patient+control ristocetine restocetine epinephrine epinephrine epinephrine a.d.p. a.d.p. a.d.p. collagen collagen collagen journal of rawalpindi medical college (jrmc); 2010;14(1):2-6 5 interfere in the estimation . most of these women remain undiagnosed , diagnosed after a long delay or go through repeated laboratory evaluations before getting a proper diagnosis. it is recommended that blood testing, in these women, should be done during the first four days of menstrual period when their factor levels are lowest 9 . with the exception of haemophilia a and b , deficiencies of all the other plasma clotting proteins such as afibrinogenemia, hypofibrinogenemia, deficiencies of factor v and combined factor v and viii , vii, x, xi, and xiii are inherited in an autosomal, mostly recessive, manner. due to rarity of these deficiencies , which are expressed clinically only in homozygous or compound heterozygous , the type and severity of symptoms , the underlying molecular defects and the actual management of bleeding episodes are not well established as for haemophilia . in countries where consanguineous marriages are frequent recessive inherited coagulation deficiencies are more frequent. all these are associated with menorrhagia , recurrent abortions, haemorrhagic ovarian cysts , post partum haemorrhage and many other complications related with female reproductive system 10 . as many as 10 to 20% of women with menorrhagia have an underlying bleeding disorder and in females with inherited bleeding disorders it is the commonest manifestation (table 3) 11. approximately 80% of women with inherited bleeding disorders suffer from menorrhagia . menorrhagia in females with inherited bleeding disorders typically present at menarche , in contrast to other causes of menorrhagia 12 . in our data majority of patients were under 18 years of age (table 2) .it leads to under representation of menorrhagia in our data as compared to international data. then in this part of the world majority of the cases of vwd are of type 3, with severe bleeding manifestations , while world wide type –1 is the commonest . it reflects under diagnosis of cases of vwd with mild menorrhagia . but it must be appreciated that over the time this percentage will increase, reflecting an upcoming disease load 5 . in the present series the cases of haemorrhagic ovarian cysts underwent laparotomies. surgeries in these cases might have been prevented if they had been diagnosed earlier and therapeutic/conservative management considered 13. these cysts are due to excessive bleeding into the corpus luteum at the time of ovulation. rupture of these cysts may result in haemoperitonium and secondary increased production of fibrin in the peritoneal cavity can be a major cause of increased formation of pelvic adhesions, external occlusion of the fallopian tubes, and destruction of the ovarian tissue. it can lead to reduced fertility in these patients 14,15 . post partum haemorrhage(pph) is a catastrophic emergency in these females 16 .in present series one female with glanzmann’s thrombasthenia succumbed fatally to this complication . women with risk factors for post partum haemorrhage can be identified in antenatal period. pregnancy usually causes a rise in all of the plasma clotting factors except factor ix. so, often there is no bleeding problem during pregnancy . however following child birth, factor levels may fall rapidly and lead to post partum bleeding. every labour suite should have appropriate pph protocols, a multidisciplinary approach involving senior obstetrician, intensive care, haematologist and blood bank services are the corner stone in the management of pph 17 . pregnancy in this group of women has been found to be associated with bleeding in early pregnancy , repeated miscarriages , abruption placenta , intrauterine demise and increased incidence of both primary and secondary postpartum haemorrhage .it is difficult to describe pregnancy and labour complications in individual manner 18 . many women with inherited bleeding disorders are on birth control pills or other hormonal therapies .this affects a women’s ability to conceive. the long term impact of such prolonged hormonal therapy on conception is unknown. some women with inherited bleeding disorders report excessive bleeding with intercourse , which may also cause difficulty in conception . the impact of inherited bleeding disorders on the implantation of fertilized embryo, into uterus, is not fully understood 1 . different treatment modalities are used in these females , depending upon the type of lesion and the nature of episode. commonly employed agents are oral contraceptive pills(ocp), tranexamic acid, desmopressin , and factor replacement. desmopressin is contraindicated in vwd type 2b. and not useful in type 3. ocp are recommended as the first line treatment , especially in adolescent menorrhagia , and have been found to effective in majority of women 19 . tranexamic acid is the most frequently used therapeutic agent in different bleeding episodes (table 5) in a dose of 1 gm every six hour, for 3 – 4 days, during menstruation. it has been found effective in 54% of cases , when given over 2-3 menstrual cycles 18 . commonly, non steroidal anti inflammatory medicines journal of rawalpindi medical college (jrmc); 2010;14(1):2-6 6 are prescribed for control of menorrhagia , but their use in inherited bleeding disorders is usually contraindicated . recently recombinant factor vii (rf vii a) was launched, as a universal haemostatic agent, for varied haemorrhagic manifestations. the rfviia acts via tissue factor pathway. limitations to its use are its short half life (2 hours) and high cost. it is contraindicated in disseminated intravascular coagulation 20 . conclusions 1. bleeding manifestations severely affect quality of life of the women with inherited bleeding disorders, leading to a limitation in the performance of day to day chores, change in career, loss of faith on medical profession after being told for years their problems are not real, constant fatigue due to iron deficiency, painful menstruation or coitus, feeling of embarrassment, undue endometrial biopsies and hysterectomies. a proper management approach is usually rewarded with an overall change in the patient’s personality. 2. failure to investigate the women with inherited bleeding disorders limit the potential benefits of different therapies like, desmopressin (ddavp), tranexamic acid, ffp and cryoprecipitate 3. the milder forms or carrier states of these disorders may remain asymptomatic. so, the diagnosis of inherited bleeding disorder in a female should provide clear prognostic and therapeutic indications that are distinct from the burdens associated with an unjustified genetic disease stigma, anxiety that may be caused by overestimates of a patient’s bleeding risk and inappropriate resource expenditures. therefore, at least for the mild from, it remains unclear whether the benefits of a diagnosis outweigh its disadvantages. 4. there is inadequate information, non availability of diagnostic and management facilities and low level of awareness on the clinical side, about inherited bleeding disorders in females. hence it is required to raise understanding about the intricacies of these disorders. references 1. paper r. gynaecological complications in women with bleeding disorders. treatment of haemophilia, 2004; 6(5): 1 – 8 2. james ah, ragni mw, picozzi vj. bleeding disorders in premenopausal women :(another) public health crisis for haematology. haematology 2006. american society of hematology education programme book, 2006; 474 – 485 3. demers c, derz kc, david m . gynaecological and obstetric management of women with inherited bleeding disorders .int j gynaecol obstet, 2006; 95(1): 75 87 4. james ah. more than menorrhagia : a review of the obstetric and gynaecological manifestations of bleeding disorders . haemophilia, 2005;1(4): 295 – 307. 5. federci ab. diagnosis of inherited von willebrand disease: a clinical perspective. semin thromb hemostasis,2006; 32(6): 555 565 6. srivastava a. von willebrand disease in the developing world. semin hematol, 2005; 42(1): 36 – 41 7. trasi sa, pathare av, shetty sd, ghosh k, salvi v, mohanty d . the spectrum of bleeding disorders in women with menorrhagia : a report from western india . ann hematol, 2005: 84(5):339 – 342 8. trasi s, shetty s, ghosh k, mohanty d. prevalence and spectrum of von willebrand disease from western india . indian j med res, 2005;121(15): 628 630 9. clement p. women’s experience with undiagnosed bleeding disorders. parent empowerment news letter,2004;5:6-11 10. vijapurkar l, mota s, shetty s , ghosh k. menorrhagia and reproductive health in rare bleeding disorders: a study from the indian subcontinent . haemophilia,2009; 15: 199 – 202 11. edlund m , bloomback m, von schoultz b, anderson d. on the value of menorrhagia as a predictor for coagulation disorders . am j haematol, 1996;5(1): 40 – 48 12. ragni mv. bleeding disorders in premenopausal women – the view of the hematologist . hematology 2006american society of hematology education programme book . 477 – 482 13. radakovic b and grgic o. von willebrand disease and recurrent hemoperitoneum due to the rupture of haemorrhagic ovarian cysts. hemophilia , 2009; 15: 607 – 609 14. meschengieser ss, alberto mf, salvin j, beronejo e, lazzori ma. recurrent haemoperitonium in mild von willebrand disease . blood coagul fibrinolysis, 207 – 209 15. radakovic b & grgic o. von willebrand disease and recurrent hematoperitonium due to rupture of haemorrhagic ovarian cysts. haemophilia, 2009; 15: 607 – 09 16. kadir ra, lee ca, sabin ca, pollard d, economiodes dl. pregnancy in women with von willebrand disease or factor xi deficiency. br j obstet gynarcol, 1998; 105(3):314 – 21 17. hossain n. postpartum haemorrhage . in haematologic disorders in gynaecology and obstetrics. sahmsi t, hossain n,eds,2010. najam printers, karachi,pakistan.p43. 18. kulkarni aa, lee ca, kadir ra. pregnancy in women with congenital factor vii defiicnecy. haemophilia 2006; 12(4): 413 – 6 19. lee ca, chi c, pavord sr, maggs ph, pollard d, wood a, et al the obstetric and gynaecological management of women with inherited bleeding disorders review with guidelines produced by a taskforce of uk haemophilia centre doctors organization . haemophilia, 2006;12(4): 301 – 36 20. monoroe dm, hoffman m, allen ga, roberts hr. the factor vii – platelet interplay:effectiveness of recombinant factor vii-a in the treatment of bleeding in severe thrombocytopenia . emin thromb hemost, 2000;26: 373 – 377. nadeem ikram* , tahira zafar**, arshad ali sabir***, khalid hassan**** , samina amanat ***** * department of pathology, rawalpindi medical college ** department of pathology, islamabad medical and dental college, islamabad *** department of community medicine , rawalpindi medical college. **** department of pathology , pakistan institute of medical sciences , islamabad ***** department of pathology, pakistan atomic energy commission hospital, islamabad abstract introduction patients and methods results discussion conclusions references summary journal of rawalpindi medical college (jrmc); 2017;21(3): 286-289 244 original article carrier status of methicillin-resistant staphylococcus aureus (mrsa) amna tariq1, shireenrafiq2, azad ali azad1, sophia khan2, nauzhat nauman2 1.department of prosthodontics armed forces institute of dentistry;2.department of pathology holy family hospital and rawalpindi medical college rawalpindi. abstract background: to investigate nasal carriage of methicillin-resistant staphylococcus aureus (mrsa) among dental healthcare workers (hcws) , as the carriers could be the potential risk factor for the transmission of nosocomial infection when exposed to hospital setting during clinical posting. methods: one hundred hcws including postgraduate trainees, house physicians, staff nurses and technicians participated in the study. nasal specimens were obtained by using cotton swabs moistened in sterile saline. the nasal specimens collected were processed as per (clsi, 2008). specimens were inoculated on blood agar to look for β-hemolysis of staphylococcus aureus. nutrient agar was used for the direct colony identification of staphylococcus aureus. mannitol salt agar (msa) and dnase were used as selective media for the isolation of staphylococcus aureus and incubated at 35˚c for 48 hrs.resistance to methicillin was detected with cefoxitin(30 μg) through disk diffusion test and interpreted according to (clsi, 2009). a diameter of ≥22 mm was considered as susceptible and ≤21 mm as resistant as per (clsi, 2010). results: out of 100 nasal swabs collected, 71 nasal swabs were from the dental surgeons and 29 were from the nursing staff, 35 (35%) showed a growth of staphylococcus aureus. among those who were positive for staphylococcus aureus 62.85%were positive for mrsa. overall 22 (22%) out of a 100 individuals came out to be positive for mrsa. conclusion: health care workers (hcws) were the potential colonizers of methicillin resistant staphylococcus aureus and may serve as reservoirs or disseminators of mrsa. key words: dental health care workers, nasal carriage, staphylococcus aureus, mrsa, introduction staphylococcus aureus remains as one of the most important nosocomial pathogen. both methicillinsensitive staphylococcus aureus (mssa) and methicillin-resistant staphylococcus aureus(mrsa) have been implicated in a variety of endemic and epidemic nosocomial infections worldwide. 1staphylococcus aureus has been recognized as an epidemiologically important pathogen. despite rigorous antibiotic therapy, staphylococcal infections occur frequently in hospitalized patients resulting in severe consequences.2 asymptomatic carriage of staphylococcus aureus has been shown to have a higher prevalence in healthy individuals, especially in healthcare workers (hcws).3,4,5 several studies conducted worldwide have reported the rate of nasal carriage of staphylococcus aureus strains among hospital personnel varying from 16.8% to 90%.2,5,6 evidence suggests an increase in the carriage of mrsa among hospital personnel as the exposure to hospital environment increases the potential risk of being colonized by different hospital borne pathogens including staphylococcus aureus. the main inhabiting ecological carrier site for staphylococcus aureus is the anterior nares.7,8 transmission of infection among dental healthcare settings is different from most other healthcare settings. the environment of the dental office is highly contaminated by airborne and blood borne microbial aerosol and spatter produced by intraoral devices, such as air-water syringes, turbines, and ultrasonic scalers.4,5 mrsa occurrence in the dental environment is less frequently reported 1. in most studies, mrsa carriage in dental healthcare workers has not been above the level of the normal adult population.8,9 in the greater houston metropolitan area 4.2% of dentists and 1.5% of dental hygienists were positive for mrsa 8,10 whereas only 1.5% of the non-institutionalized us citizens were colonized with mrsa.8,11 other studies showed that 21% of dental students were nasal carriers for mrsa.8,12nasal carriage of mrsa among the dental staff could pose a risk for transmission of mrsa to the patients or co-workers. mrsa infection is typically preceded by the colonization of the anterior nares and skin by staphylococcus aureus. other sites for potential colonization of staphylococcus aureus journal of rawalpindi medical college (jrmc); 2017;21(3): 286-289 245 includes the urine of patients with indwelling urinary catheters, implantation sites of invasive devices and the postoperative wounds.13,14 subjects and methods this is a prospective study conducted atarmed forces institute of dentistry (afid) rawalpindi and holy family hospital (hfh) rawalpindi. pakistan. this study was conducted over a 3-month period in the year 2014 from the months of october to december. after the approval to perform the study was obtained, oral consent from the subjects for the participation in the study. one hundred hcws including postgraduate trainees, house physicians, staff nurses and technicians participated in the study. hcws having history of upper respiratory tract infection or having taken any antibiotic during the last one week were excluded from the study. all study participants underwent swabbing of the anterior 1.5 cm of the nasal vestibule. nasal specimens were obtained by using cotton swabs, moistened in sterile saline. the swabs were inserted into both anterior nares and rotated five times. the nasal specimens collected were processed as per (clsi, 2008).15 specimens were inoculated on blood agar to look for β-hemolysis of staphylococcus aureus. nutrient agar was used for the direct colony identification of staphylococcus aureus. mannitol salt agar (msa) and dnase were used as selective media for the isolation of staphylococcus aureus and incubated at 35˚c for 48 hrs. all isolates were identified routinely by grams stain, catalase test, coagulase test, mannitol salt agar (msa) test and the dnase test. the identification of organisms was based on their cellular, cultural and biochemical characteristics. resistance to methicillin was detected with cefoxitin(30 μg) through disk diffusion test (bauer et al., 1966)16 and interpreted according to (clsi, 2010). a diameter of ≥22 mm was considered as susceptible and ≤21 mm as resistant as per (clsi, 2010).17 results a total of 100 nasal swabs were collected.71 nasal swabs were collected from the dental surgeons and 29 were collected from the nursing staff (table 2).out of 71 dental surgeons 24 (33.80%) were post graduate (pg) trainees and 47 (66.19%) were house officers. out of the 100 samples, 35 (35%) showed a growth of staphylococcus aureus. among those who were positive for staphylococcus aureus, 62.85%were positive for mrsa. overall 22 (22%) out of a 100 individuals came out to be positive for mrsa.from the total population of 100 individuals, 88% showed a growth of either staphylococcus aureus or staphylococcus spp. of these, 39.77% of the individuals were detected with staphylococcus aureus and 60.22 % of the individuals were detected with staphylococcus spp. of a total of 62 clinical dentists that showed positive results for staphylococcus. aureus or staphylococcus spp., 21(33.87%) showed a growth of staphylococcus aureus(table 1). table1: distribution of staph. aureus, staph. spp. and mrsa total sample total mrsa positive no growth staphylo coccus aureus + staph spp. staphylo coccus aureus staphylo coccus spp. n=100 n=88 n=35 n=53 n=22 n=12 total dental surgeons 71 71/100 (71%) 62 62/71 (87.32%) 21 21/62 (33.87%) 41 41/62 (66.12%) 13 13/21 (61.90% ) 09 09/71 (12.6%) pg trainees 24 24/71( 33.80%) 22 22/62(35 .48%) 06 06/21 (28.57%) 16 16/41 (39.02%) 05 05/13 (38.4%) 02 02/9 (2.22%) house officers 47 47/71 (66.19%) 40 40/62 (64.51%) 15 15/21 (71.42%) 25 25/41 (60.90%) 08 08/13 (61.5%) 07 07/9 (7.77%) nursing staff 29 29/100 (29.00%) 26 26/29 (89.65%) 14 14/26 (53.80%) 12 12/26 (46.1%) 09 09/14 (64.2%) 03 03/29 (10.34%) out of which 13 (59.09%) were methicillin resistant staphylococcus aureus (mrsa).of the 29 swabs collected from the dental nursing staff, 26 (89.65%) showed positive results for staphylococcus aureus or staphylococcus spp. of these individuals,14 (53.8%) strains of staphylococcus aureus were isolated, out of which 9 (64.2%) strains were methicillin resistant staphylococcus aureus (mrsa). from the specimens taken from the nursing staff, 3 (10.34%) of the individuals showed no growth. out of total mrsa isolated (n=22), 64.2% were from nursing staff and 59.09 % were from clinical dentists. discussion mrsa outbreaks in hospitals can be traced to the medical personnel as being a major source of infection. 18 the main reservoir for staphylococcus aureus is the anterior nares.5 colonization of mrsa in anterior nares servers as a reservoir from which mrsa can be introduced into the body when the host defenses are breached.19 it is important to accurately detect mrsa in patients not only for choosing an appropriate journal of rawalpindi medical college (jrmc); 2017;21(3): 286-289 246 antibiotic therapy, but also for the rapid control of the mrsa epidemic. in this study we have assessed the prevalence of colonization of mrsa among dental health care workers and the possibility of its spread in dental hospital. results of bacteriological study of nasal swabs from participating hcws in this study revealed staphylococcus aureus strains be present in 35% of the hcws (dental surgeons and dental nursing staff). among staphylococcus aureus isolates n=22 (62.85%) were mrsa positive strains. the overall mrsa carriage rate in dentists was n=13 (64.90 %) out of n=21 positive isolates of staphylococcus aureus and in the dental nursing staff was n=9 (64.2%) out of n=14 positive isolates of staphylococcus aureus. this proves that staphylococcus aureus remain one of the most commonly encountered nosocomial pathogen. human carriers are predominantly colonized by staphylococcus aureus in the nares and contamination of hands.20in the hospitals, mrsa holds immense clinical significance21. the results of this study regarding the carrier rate of mrsa among dentists and dental nursing staff coincide with the results reported by opal et al. (1990), who found high rates (56%) of staphylococcus aureus colonization among nurses, 65% of which were mrsa positive22. high rates of nasal carriage of staphylococcus aureus have been reported by badawi et al.(2001), and kamp et al.(2003)but their studies showed much lower rates of mrsa carriage (26% and 5%; 33.8% and 0.7% respectively.23, 24 higher nasal carriage rates (33% and 48%) for staphylococcus aureus in the hcws have been reported in two pakistani studies.25, 26 the population sample for this study is also from pakistan and shows a n=35 (39.77%) out of n=88 positive isolates for nasal carriage of staphylococcus aureus, similar to the rate reported in the other two pakistani studies. prevalence of the nasal carriage of staphylococcus aureus in other countries ranged between 16.8-56.1%.2the difference in the nasal carriage rates of staphylococcus aureus, can be due to the differences in geographical distribution of the population, differences in the quality and size of samples and the difference in the culturemethods utilized to detect staphylococcus aureus.this study showed 62.85% (n=22/n=35) of the total population detected with staph. aureus to be mrsa positive. varying rates for mrsa carriage have been reported by the hcws in pakistan (14%) and india (39.7%). 26, 27 a high nasal carriage rateof mrsa observed in this study can be attributed to several factors including a high prevalence of mrsa among patients which increases the potential exposure of acquiring mrsa among thehcws.24 a study done by jain k et al. (2014) in central india, states that a higher prevalence of mrsa among patients leads to a higher prevalence of mrsa nasal carriage among the health care workers that have a direct patient contact.28 suboptimal infection control practices in the hospitals have a strong influence on the possibility of transmission of mrsa between patients and hospital staff.29 these suboptimal infection control practices include: failure to perform active surveillance cultures to identify the colonized patient’s timely, hcws non-compliance with hand hygiene and non-compliance with the use of protective barrier equipment’s. in our study, nursing staff showed a comparatively higher carriage rate of mrsa as compared to the dental surgeons. this can be explained by the fact that hcws including the dental nursing staff having direct patient contact have a higher mrsa carriage rate than those who have lesser contact.30 study done by lakshmi s. kakhandki et al. (2012) states higher carriage rate in nursing staff than clinical doctors which is in accordance to our study.31 conclusion health care workers are potential colonizers of methicillin resistant staphylococcus aureus and may serve as reservoirs or disseminators of mrsa. references 1. akhtar n. staphylococcal nasal carriage of health care workers j coll of physicians and surgeons pakistan,2010; 20 (7): 439-43 2. kluytmans j, van belkum a, verbrugh h. nasal carriage of staphylococcus aureus: epidemiology, underlying mechanism and associated risks. clin microbiol rev 1997; 10 : 505–20 3. kogekar s p, jain k, kumari p, chavan n, peshattiwar p. high levels of mrsa colonization in health care workers: alarm to implement health care policy. world j clin pharmacol microbiol toxicol 2015; 1(2) 21-25. 4. uhlemann ac, knox j, miller m, hafer c. the environment as an unrecognizedreservoir for community-associated methicillin resistant staphylococcus aureususa300: a casecontrol study.plos one 2011;6:e22407 . 5. lin yc, lauderdale tl, lin hm, chen pc, cheng mf. an outbreak of methicillin-resistant staphylococcus aureus infection in patients of a pediatric intensive care unit and high carriage rate among healthcare workers. j microbiol immunol infect 2007; 40:325–34. 6. ghasemian r,najafi n,shojaifar s.nasal carriage and antibiotic resistance of staphylococcus aureus isolates. mazandaran univ med sci 2003; 44: 79–86. 7. al-anazi a. prevalence of methicillin-resistant staphylococcus aureus in a teaching hospital in riyadh,saudi arabia. biomed res 2009;20:7-11. 8. srivastava n, goyal a,goyal s,kumar r, gupta br. comparative study on prevalence of nasal carriage of mrsa and mssa in medical students with clinical posting and without ccinical posting: is introduction of hospital infection control policy in medical curiculum need of hour. journal of rawalpindi medical college (jrmc); 2017;21(3): 286-289 247 iosr journal of dental and medical sciences 2015; 14( 4) 77-79. 9. mosavi m. positive staphylococcus-coagulase carriers in qazvin hospital staff j qazvin univ med sci health serv 1996;1: 29–37 10. mansuri sh, khaleghi m. nose and throat carrier rate of s. aureus in the staff of four university hospitals in kerman and comparison with the control and patients groupj tehran fac med 1997;1:36–41 11. rahbar m,karamiyar m,gra-agaji r. nasal carriage of methicillin-resistant staphylococcus aureus among healthcare worker of an iranian hospitalinfect control hospepidemiol 2003; 24:236–37 12. mosavi m. positive staphylococcus-coagulase carriers in qazvin hospital staffj qazvin univ med sci health serv 1996;1 : 29–37 13. ghasemian r, najafi n, shojaifar a. nasal carriage and antibiotic resistance of staphylococcus aureus isolates .mazandaran univ med sci 2003;79–86 14. alghaithy aa, bilal ne, gedebou m,weily ah. nasal carriage and antibiotic resistance of staphylococcus aureus isolates from hospital and non-hospital personnel in abha, saudi arabiatrans r soc trop med hyg 2000;, 94 : 504–07. 15. clinical laboratory standards institute. performance standards for antimicrobial susceptibility testing. approved standard. clinical and laboratory standard institute: wayne pa-usa 2008. 16. bauer aw, kirby wmm, sherris jc, turck m. antibiotic susceptibility testing by a standardized single diskmethod. american journal of clinical pathology 1966; 45: 493-96. 17. clinical and laboratory standards institute, 2010. performance standards for antimicrobial susceptibilitytesting: 20th informational supplement (june 2010 update). wayne, pa. 18. locksley rm, cohen ml, quinn tc. multiple antibiotic resistant staphylococus aureus: introduction, transmission and evolution of noscocomial infection. ann int med 1982;. 97:317-24 19. von eiff c, becker k, machka k, stammer h, peters g. nasal carriage as a source of staphylococcus aureus bacteremia. n engl j med 2001; 344:11–16. 20. blok h e, troelstra a, hopmans t e. role of hcws in outbreaks of mrsa: a 10 years evaluation from a dutch university hospital. infect control hospital epidemiology 2003;24: 679-85. 21. warren d k, nitin a, kollef m h.occurrence of cocolonization with vre and mrsa in a medical icu. infect control hosp. epidemiol 2004;; 25: 99104. 22. opal s m, mayer k h,musser j m.frequent acquisition of strains of methicillin resistant staph.aureus by health care workers in an endemic hospital environment. infect. control hosp. epidemiol 1990; 11: 479-85. 23. badawi h, omar m,helmi h. evaluation of screening method for detection and typing of mrsastrains involved in noscomial spread. egypt j. med. microbiol 2001; 10(4): 679-89. 24. kampf g, adena s,weist k.inducibility and potential role of meca gene positive oxacillin susceptible staphylococcus aureus from coloniged health care warkers as a source for no socomial infections. j. hosp. infect 2003;54: 124-29. 25. naheed a, saima s, mobina d, hayat a.nasal carriage of staphylococcus aureus in health care workers. j rawal med coll 2002; 6:74-76. 26. kalsoom f, zermina r, akhtar n, abdul sattar, khan ja. nasal carriage of staphylococci inhealthcare workers: antimicrobial susceptibility profile. pak j pharm sci 2008; 21:290-94. 27. . rajaduraipandi k, mani kr, panneerselvam k. prevalence andantimicrobial susceptibility pattern of methicillin resistant staphylococcus aureus: a multicentre study. indian jmed microbiol 2006;24:34-38. 28. jain k, chavan ns, jain sm.14.bacteriological profile of post-surgical wound infectionalongwith specialreference to mrsa in central india, indore. int j intgmed sci 2014; 1(1):9-13. 29. boyce j. m., havill n. l, ligi c. e. do infection control measures work for mrsa? infect control hosp epidemiology 2004; 25: 395-401. 30. john jf jr, grieshop tj, atkins lm, platt cg. widespread colonization of personnel at a veterans affairsmedical center by methicillin-resistant coagulase-negative staphylococcus. clin infect dis 1993;17:380 88. 31. lakshmi s and kakhandki bv. study of nasal carriage of mrsa among the clinical staff and healthcare workers of a teaching hospital of karnataka, india. al ameen j med sci 2012; 5 (4): 367-70. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 20-22 20 original article birth asphyxia clinical experience and immediate outcomes arshad rafique , muhammad akram , rizwan asad khan, muhammad fakhar-ul-zaman department of paediatrics, central park medical college, lahore abstract background: to find out immediate outcome of neonates with birth asphyxia and its association with risk factors. methods: this cross sectional study included all consecutive babies admitted with diagnosis of birth asphyxia . babies with congenital heart disease, congenital malformations and prematurity were excluded. biodata and clinical parameters including place of delivery,dai handling,time of arrival in hospital,mode of delivery, grades of hypoxic ischemic encephalopathy, outcome in terms of discharge and death were recorded. results: sixty one patients were included in the study. majority (80.3%) were male..mothers having regular antenatal checkup were 65.5%. eleven (18%) babies were home delivered and 50(82%) in hospital setup. in 16.4% babies there was history of dai handling. 60.7% babies were delivered by svd and 39.3 % by csection. majority (83.6 %) presented within 6 hours. hypoxic ischemic encephalopathy stage i, ii and iii was seen in 39.3%, 49% and11.5% respectively. forty eight (78.7%) babies were discharged and 13(21.3%) died. no evidence of association was found between outcome at discharge and time of arrival at hospital (p value=0.33)and dai handling (p value= 0.114). significant association was found between outcome at discharge and place of delivery (p value=0 .031) and outcome at discharge and hypoxic ischemic encephalopathy stage (p value=0.000). conclusion: asphyxiated newborns have significant short term mortality in association with home deliveries and hypoxic ischemic encephalopathy stage iii. key words: birth asphyxia,hypoxic ischemic encephalopathy, apgar score introduction birth asphyxia is an important and leading cause of mortality and morbidity in neonates.1-3 although a lot of research work has been done in this regard, yet there is no universal consensus definition of birth asphyxia. who defines it as “failure to initiate and sustain breathing at birth.4 gasping and ineffective breathing at 1 minute after birth is also taken as birth asphyxia.5 according to american academy of pediatrics and a task force on cerebral palsy birth asphyxia needs the presence of profound metabolic or mixed acidemia (ph < 7) in an umbilical artery blood sample( if obtained),persistence of an apgar score of 0-3 for longer than 5 minutes,neonatal neurologic sequelae (e.g, seizures, coma, hypotonia) and multiple organ involvement (e.g, kidney, lungs, liver, heart, intestines) . 6 about 99% of neonatal mortality occurs in low and middle-income countries.7 in pakistan neonatal mortality rate is 49/1000 live births accounting for 7% of the global neonatal deaths.8its incidence in the developed countries is low(0.5-1/1000 live births) owing to better perinatal and antenatal care.9sarnat and sarnat staging system is a useful tool to assess the severity of hypoxia and to classify the degree of hypoxic ischemic encephalopathy (hie).10many local, regional and international studies have addressed antenatal, intrapartum and postpartum risk factors and their association with neonatal morbidity and mortality.11,12,13to decrease the grave consequences of this problem all inculcate preventive measures and advocate early interventions. patients and methods this descriptive, cross sectional study was conducted from november 2015 to april 2016 at bhatti international teaching (trust) hospital, kasur to find out immediate outcome of neonates with diagnosis of birth asphyxia and its association with risk factors. children included in the study were full term newborns (gestational age 37-42 weeks) with the diagnosis of hie. data collection tools consisted of a self-designed questionnaire including maternal and neonatal information. clinical examination of all the admitted babies for the study was performed and documented at admission, 12 hours, 24 hours, 48 hours, 72 hours and at the time of discharge. newborns were labelled as hie if they have history of delayed initiation of respiration or need for journal of rawalpindi medical college (jrmc); 2017;21(1): 20-22 21 resuscitation and had evidence of cardiorespiratory and neurological depression (defined as apgar score < 7 at 5 minutes after birth) . severity of hypoxia and hie was graded by using sarnat and sarnat staging system at 24 hours of age into stage i, ii, or iii. the early outcome was recorded at time of discharge as clinical improvement or death. patients with congenital neuromuscular, cardiovascular and pulmonary disorders, dimorphism, extreme prematurity and those who left against medical advice were not included in this study. analysis of relationship between different variables was measured with p-value applying chi-square test.p-value of < 0.05 was considered significant. results were given in graphs and tables. results out of 61, majority (80.3%) were male. their weights ranged from 2 to 3.8kg. mothers having regular antenatal checkup were 40 (65.5%) while 21(34.4%) mothers were with no antenatal checkup. a total of 11(18%) babies were home delivered and 50(82%) in hospital setup. in only 10(16.4%) babies there was history of dai handling. 60.7% babies were delivered by svd and 39.3 % by csection. as far as hospital arrival is concerned, 51(83.6 %) patients presented within 6 hour and 10(16.4%) patients came later than 6 hours. hypoxic ischemic encephalopathy stage i, ii and iii was seen in 24(39.3%), 30(49%) and 7(11.5%) respectively (table 1). artificial ventilation was required in 10(16.4%) babies. forty eight (78.7%) babies were discharged and 13(21.3%)died. no association was found between outcome at discharge and time of arrival at hospital (p value=0 .33)(table 2) and dai handling (p value= 0.114)(table 3). table 1: stages of hypoxic ischemic encephalopathy stage no (%) stage i 24(39.30) stage ii 30(49.20) stage iii 7(11.5) table 2.time of arrival and outcome at discharge value df asymptomatic significance (2-sided) p value exact sig (2sided) exact sig. (1 sided) pearson chi square fisher’s exact test .913 1 .339 .674 .314 table 3.dai handling and outcome at discharge value df asymptomatic significance (2-sided) p value exact sig. (2sided) exact sig. (1 sided) pearson chi square fisher’s exact test 2.491 1 .114 .198 .126 table 4.delivery place and outcome at discharge value df asymptomatic significance (2-sided) p value exact sig. (2sided) exact sig. (1 sided) pearson chi square fisher’s exact test 4.665 1 .031 .046 .046 table 5. hypoxic ischemic encephalopathy and outcome at discharge value df asymptomatic significance (2-sided) p value pearson chi square lineae by linear association 32.377 25.203 2 1 .000 .000 significant association was found between outcome at discharge and place of delivery (p value=0 .031)(table 4). also significant association was found between outcome at discharge and hypoxic ischemic encephalopathy stage (p value=0.000) (table 4). hypoxic ischemic encephalopathy and outcome at discharge also had significant association (table 5) discussion a total of 61 patients were included in the study. their weights were from 2 to 3.8and range 1.8 kg. in saeed et al 69.7% were between 2.1 to 3 kg,13 whereas in another study majority of the babies were between 1.5 and 2.5 kg.12 the difference is due to inclusion criteria of the patients for studies. in our study, male patients were in majority 49(80.3%) which is in correspondence to the other studies with figure of 60%, 64% and 80%.12,14,15the association of antenatal checkup and outcome is insignificant(p-value 0.31). the incidence of birth asphyxia was significantly higher in babies of un-booked mothers in other studies.16,17 the sample journal of rawalpindi medical college (jrmc); 2017;21(1): 20-22 22 size of our study was small so the association found statistically insignificant. a total of 50 (82%) newborn were hospital delivered. a comparable figure of 90.5% hospital delivered babies were reported in the study from services hospital.15in our study statistically significant association was found between outcome at discharge and place of delivery (p value= 0.031) and also in other study place of delivery was associated with mortality significantly.13in our study no evidence of association was found between outcome at discharge and dai handling (p value=0.114). babies with hie were more likely to be delivered by unskilled birth attendants.18failure to have significant association in our study may be attributed to small number of patients in the study.in our study, 60.7% babies were delivered by svd and 39.3 % by lscs. it is comparable with the figure from liaquat university of medical health sciences (lumhs).14but in the study from services hospital 64.1% delivered by lscs.15 this may be due to the fact that hospital is receiving all the difficult referred patients that is depicted by the datum. as far as hospital arrival is concerned, 51(83.6 %) patients presented within 6 hour and 10(16.4%) patients came later than 6 hours. in another study, 54.3% approached within 6 hours.14according to other studies mean age of the asphyxiated patients was 13.8 hours and in an indian study 71.6% babies arrived within 24 hours.19 in our study, no association was found between outcome at discharge and time of arrival at hospital (p value= 0.33) in expired babies. however, late presentation is associated with poor outcome in many studies.12,13,16the observation may be due to fact that in our study most of hie stage iii babies presented within 6 hours. hypoxic ischemic encephalopathy stage i, ii and iii was seen in 24(39.3%), 30(49%) and 7(11.5%), respectively in this study. these figures are comparable with study done by vidyasagar.20 forty eight (78.7) babies were discharged and 13(21.3%) died. this figure is comparable with other study15.a significant association was found between hypoxic ischemic encephalopathy stage and outcome at discharge (p value.000) that is in accordance with the other studies.15,21 conclusion 1. asphyxiated newborns have significant short term mortality in association with home deliveries and hypoxic ischemic encephalopathy stage iii. 2. it is required to encourage and facilitate hospital deliveries. references 1. waqar t and haque kn. birth asphyxia: brief review of pathogenesis and prognostic guidelines. pak paed j 2012; 36(2): 61-79. 2. lawn je, lee acc, kinney m . two million intrapartum related stillbirths and neonatal deaths: where, why and what can be done. int j gynaecol obstet. 2009; 107, supplement 1: s5-s19. 3. aneela z, azhar jm, saleem rm. causes/pattern of admissions and deaths at a tertiary care hospital in suburban area of lahore. pjmhs 2016; 10(1): 49-53. 4. spector jm, daga s. preventing those so-called stillbirths. bull world health organ. 2008; 86(4): 315-6. 5. report of the national neonatal perinatal database. new delhi. national neonatology forum india; 2000. 6. american college of obstetricians and gynecologists. task force on neonatal encephalopathy and cerebral palsy.american college of obstetricians and gynecologists; 2003. 7. oestergaard mz, inoue m, yoshida s. neonatal mortality levels for 193 countries in 2009 with trends since 1990: a systematic analysis of progress, projections, and priorities. plos med 2011; 8(8): e1001080. 8. sikander r and memon a. maternal and perinatal outcome following emergency caesarean section: med channel 2005;11:68-70. 9. bhutta za, ali n, hyder aa. perinatal and newborn care in pakistan : seeing the unseen. in bhutta za, ed. maternal and child health in pakistan: challenges and opportunities. karachi, pakistan: oxford university press, 2004. 10. sarnat hb and sarnat ms. neonatal encephalopathy following fetal distress. a cinical and electroencephalographic study. arch neurol 1976; 33: 696-705 11. siva ssb, chaithanya cn, madhu gn. clinical profile and outcome of perinatal asphyxia in a tertiary care centre. curr pediatr res 2015; 19 (1 & 2): 9-12 . 12. afzal mf, anjum a, sultan ma. risk factor analysis in asphyxiated newborns and their outcome in relation to stage of hypoxic ischemic encephalopathy. pak paed j 2007; 31(2): 6368. 13. saeed t, zulfiqar r, afzal ma, raja tm. outcome of asphyxiated newborns in relation to the time of referral to a tertiary care hospital. jrmc; 2012;16(1): 34-36. 14. shazia s, salma s, seema b. to compare the outcome (early) of neonates with birth asphyxia in-relation to place of delivery and age at time of admission. j pak med assoc 2012; 62(12): 127781. 15. rana mn, kazi my, nasir a. outcome of babies admitted with hypoxic ischemic encephalopathy. ann king edward med college 2006;12(2):243-44. 16. rajlaxmi m, ahanthem s s, manika a. utilization of antenatal care and its influence on fetal-maternal outcome: a tertiary care experience. int j reprodcontraceptobstet gynecol. 2013; 2(4): 600-606 17. chigbu b, onwere s, kamanu ci, aluka c, okoro o. pregnancy outcome in booked and unbooked mothers in south eastern nigeria. east afr med j. 2009;86(6):267-71. 18. tayyaba kb, rehan f, amanullah mk. risk factors for hypoxic ischemic encephalopathy in children. jcpsp 2008; 18(7):42832. 19. sehgal a, roy ms, dubey nk. factors contributing to outcome in newborns delivered out of hospital and referred to a teaching institution. indian pediatr 2001; 38: 1289-94. 20. vidyasagar. a global view of advancing neonatal health and survival. j perinatal 2002;22(7):513-15 21. bruckmann ek and velaphi s. intrapartum asphyxia and hypoxic ischemic encephalopathy in a public hospital. s afr med j 2015; 105(4):298-303. http://www.scopemed.org/?jid=89 http://www.scopemed.org/?jid=89&iid=2013-2-4.000 https://www.ncbi.nlm.nih.gov/pubmed/?term=chigbu%20b%5bauthor%5d&cauthor=true&cauthor_uid=20358788 https://www.ncbi.nlm.nih.gov/pubmed/?term=onwere%20s%5bauthor%5d&cauthor=true&cauthor_uid=20358788 https://www.ncbi.nlm.nih.gov/pubmed/?term=kamanu%20ci%5bauthor%5d&cauthor=true&cauthor_uid=20358788 https://www.ncbi.nlm.nih.gov/pubmed/?term=aluka%20c%5bauthor%5d&cauthor=true&cauthor_uid=20358788 https://www.ncbi.nlm.nih.gov/pubmed/?term=okoro%20o%5bauthor%5d&cauthor=true&cauthor_uid=20358788 https://www.ncbi.nlm.nih.gov/pubmed/20358788 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 13-15 13 original article association of hepcidin with hepatitis c induced diabetes mellitus hina arif 1, umbreen ahmed 1, shahid ahmed 2, komal nadeem1 1.department of physiology, army medical college, rawalpindi;2.department of medicine, military hospital, rawalpindi abstract background: to compare serum hepcidin levels of patients with hepatitis c induced diabetes mellitus with healthy controls methods: sixty individuals were included in the study. thirty were diagnosed cases of chronic hepatitis c who developed diabetes mellitus during the course of hcv infection. thirty age and gender matched healthy controls were included. individuals with acute hepatitis c, familial diabetes mellitus, iron deficiency anemia, recent history of blood transfusion, iron or erythropoietin supplementation and inflammatory diseases like rheumatoid arthritis, renal, cardiac, pulmonary diseases and on interferon therapy were excluded from the study. blood samples were collected from all the individuals and serum hepcidin levels were measured by elisa. results: significant decrease in serum hepcidin levels was found in patients with the chronic hepatitis c and diabetes mellitus having mean value of 2.7±1.03ng/ml as compared with controls having mean value of 28.5±5.3ng/ml. the difference among the two groups was significant at p-value of <0.001. conclusion: serum hepcidin levels in patients with chronic hepatitis c with diabetes mellitus are significantly less as compared to healthy controls. key words: hepcidin, hepatitis c induced diabetes mellitus introduction hepatitis c virus (hcv) is notorious for causing acute and chronic liver disease worldwide.1 it is an rna virus that belongs to family flaviviradae. according to an estimate in 85% of the cases, acute hcv infection becomes chronic and 10% of the population in pakistan is chronically infected with hepatitis c virus.2 hcv infection becomes chronic when its rna persists in blood for more than 6 months and is frequently associated with extra-hepatic manifestations such as diabetes, arthralgias and thyroiditis. about one third of the chronically infected population develops diabetes.3 the important feature of pathogenesis of hcv induced diabetes is the development of insulin resistance. 4 numerous mechanisms have been proposed to explain this insulin resistance including upregulation of inflammatory cytokines, hypophosphorylation of insulin receptor substrate-1 and 2, upregulation of gluconeogenic and lipogenic genes, accumulation of lipids and targeting lipid storage organelles. 2 the infection by hepatitis c virus is characterized by hepatocyte injury and iron overload has been identified as one of the factors behind it. 5 hepcidin, a biologically active hepatic peptide, is known as the major regulator of body iron metabolism.6 it is synthesized primarily by hepatocytes. however, kidney tissue, pancreatic beta cells, macrophages and adipocytes have also been reported as the other sites of hepcidin production.7 regulation of iron homeostasis is mainly carried out by binding iron efflux channels called ferroportin [8] which are responsible for iron export from enterocytes and macrophages.7 hepcidin binds these iron exporting channels and cause their internalization and degradation thus decreasing iron export into blood.8 the expression of hepcidin is regulated at transcription level by bone morphogenetic protein (bmp). other cofactors involved in iron dependent regulation of hepcidin expression are haemochromatosis protein hfe, tfr2 (tf receptor2), hjv (haemojuvelin), tmprss6.8 its transport in blood is in free form as well as bound to α-macroglobulin and the excretion is by kidney. 9 conditions involving oxidative stress, hypoxia, erythropoietin or vitamin d therapy have been reported to decrease serum hepcidin levels whereas conditions involving inflammation, infection or iron supplementation increase serum hepcidin levels.5, 9-12 excess iron resulting from altered levels of hepcidin activates inflammatory cells and hepatic stellate cells and catalyzes the production of reactive oxygen species (ros) and inflammatory cytokines which then evoke fibrosis. 8,13 chronic hcv infection causes iron accumulation by hepcidin suppression which has been proposed as major mechanism responsible for causing glucose intolerance by influencing insulin signaling. 14 the accumulated iron causes increased glucose production by hepatocytes, increased fatty acid journal of rawalpindi medical college (jrmc); 2017;21(1): 13-15 14 oxidation and decreased glucose oxidation in skeletal muscles and adipocytes and altered levels of adipokines in adipocytes.15 furthermore, it causes oxidative stress, a factor independently responsible for causing insulin resistance. the resultant hyperinsulinemia then causes rapid iron uptake by liver since insulin redistributes transferrin receptors from an intracellular compartment to cell membrane and further exacerbates iron overload.16 patients and methods in this descriptive study thirty adults of either gender with blood sugar fasting (bsf) <110mg/dl (for group i), diagnosed patients with hcv infection for >6months and diabetes mellitus (for group ii) were included via non-probability purposive sampling. after recording detailed history of every individual followed by general physical examination, individuals with acute hepatitis c, familial diabetes, interferon therapy, iron deficiency anemia, recent history of blood transfusion, iron or erythropoietin supplementation and inflammatory diseases like rheumatoid arthritis, renal, cardiac, pulmonary and hepatic diseases (other than hcv infection) were dropped . blood sampling was then done after a 12 hour overnight fast for the measurement of serum glucose, serum insulin and serum hepcidin levels. 5ml of blood was collected by venipuncture under aseptic measures from each individual and was transferred to gel separator tubes. it was allowed to clot and the clotted sample was then centrifuged at 2000-3000rpm for 20 minutes. the separated serum was then pippetted out into the polypropylene tubes for storage at -20oc until analysis .serum glucose levels were estimated at the time of sampling while serum hepcidin levels were measured by enzyme linked immunosorbent assay (glory sciences, human hepcidin elisa kit). . means and standard deviations were calculated for quantitative variables like age, fasting blood sugar levels (bsf) and serum hepcidin levels whereas percentage and frequency were calculated for categorical variables. serum hepcidin in the two groups were compared by independent t-test and correlation between the bsf and serum hepcidin levels was found by pearson’s correlation and p-value of <0.05 was considered statistically significant. results in present study, sixty individuals were included. group 1 (n=30) involved healthy controls of mean age of 63.1± 12.3 years while the group 2 (n=30) included patients with hepatitis as well as diabetes mellitus, having mean age of 67.3±10.6 years. there was no significant difference between the ages of the two groups. in group 1, 21 were male while 9 were female. on the other hand group 2 included 22 male and 8 female. there was no significant difference between the gender representations in the two groups (table 1).the mean values of bsf in mmol/l in the two groups were compared via independent samples t-test as well and were found to be significantly different in the two groups at p-value of <0.001. the bsf values were noted to be significantly higher in group 2 (12.1± 3.1mmol/l) as compared to group 1 (5±1.3mmol/l) (table 2). the significantly negative correlation of bsf with serum hepcidin revealed about 77% association between the two parameters and showed that glucose levels in blood are significantly increased with the decreasing hepcidin levels in patients with chc induced diabetes.mean values of serum hepcidin were found to be significantly different in the two groups at p-value of 0.000. table 1: comparison of ages and male to female of the healthy controls and cases parameters group 1 (healthy controls) group 2 (cases with hcv and dm) age 63.1±12.3 years 67.3±10.6years n 30 30 male: female 21 : 9 22 : 8 table 2: comparison of serum hepcidin levels and bsf (mmol/l) between the two groups parameters group 1 (healthy controls) group 2 (cases with hcv and dm) p-value blood sugar fasting (mmol/l) 5±1.3 12.1± 3.1 0.000* serum hepcidin (ng/ml) 28.5± 5.3 2.7± 1.03 0.000* *p-value is significant (<0.001) the mean values of group 2 (2.7±1.03ng/ml) were found to be significantly lower as compared to the values observed in group 1 (28.5± 5.3ng/ml) (table 2). levels of serum hepcidin showed significant negative correlation with bsf levels at r-value of -0.769 and pvalue of 0.000. the above mentioned observations not only confirm the suppressing action of chc on serum hepcidin levels but also validate the negative association of hepcidin with rising bsf seen in hcv induced diabetes. discussion in present study decreased serum hepcidin levels were found in patients with hepatitis c induced diabetes mellitus as compared with the healthy controls. it shows that suppression of hepcidin is associated with the development of diabetes mellitus journal of rawalpindi medical college (jrmc); 2017;21(1): 13-15 15 in chronic hepatitis c. the probable mechanism behind the development of this extrahepatic manifestation is the role of hepcidin in the regulation of iron metabolism. thus, suppression of hepcidin results in decreased internalization and degradation of iron transporting channels, ferroportin. the ensuing increased and uninhibited transport of iron then causes iron overload. this iron accrual causes decreased glucose oxidation and increased lipid breakdown in adipocytes, results in increased fatty acid oxidation and decreased glucose oxidation in muscles and in hepatocytes causing increased glucose production ,thus causing insulin resistance and hyperglycemia and forming a picture identical to diabetes mellitus.15 accumulated iron stimulates inflammatory cells and hepatic stellate cells which then play role in mounting reactive oxygen species and progression of hepatic fibrosis, independently infamous as a risk factor for the development of insulin resistance.16 the results of our study are comparable to girelli et al. who measured serum hepcidin in 81 untreated chronic hepatitis c patients and 57 healthy controls and found a significant decrease in chc patients 33.7 versus 90.9 ng/ml respectively (p-value <0.001).17 similarly tsochatzis et al. found a decrease in serum hepcidin levels in chc patients as compared to healthy individuals. they included 96 chronic cases of hepatitis c and 30 controls and found significantly decreased serum hepcidin levels by elisa, 14.6±7.3 versus 34.3±17.3 ng/ml at the p-value of <0.001. 18 the values in our study are although generally lower which could be due to difference in the kit used yet, the difference between the serum hepcidin levels of controls and cases is nearer to that reported by tsochatzis et al. (20.3ng/ml) that is 25.1ng/ml. the difference reported by girelli et al. is much larger which may be explained by the large difference between the ages of controls and cases (35 versus 42.2 years). the association of hepcidin with standard endocrine type 2 diabetes mellitus has been reported by wang et al. in spraguedawley rats. he showed a 40% decrease in hepatic hepcidin expression in rats with streptozotocin induced type 2 diabetes mellitus. 19 gan et al. reported lowering of risk of diabetes mellitus in individuals with hepcidin suppressing mutations of tmprss 6 (transmembrane protease serine 6).20. conclusion 1.aberrations in glucose metabolism have been frequently linked with altered body iron regulation and in present study similar association is found between hepatitis c induced diabetes mellitus and hepcidin, the major iron regulating hormone. 2.suppressed levels of hepcidin,in hepatitis c patients, explains the iron accrual and resulting alteration in glucose metabolism thus providing a substance that can help in assessment of disease progression and stratification for the risk of development of diabetes mellitus in patients with chronic hepatitis c. references 1. afdhal nh. the natural history of hepatitis c. semin liver dis, 2004;24( 2): 3-8. 2. parvaiz f, manzoor s, tariq h, javed f.hepatitis c virus infection: molecular pathways to insulin resistance. virol j, 2011; 8: 474-77. 3. safi sz shah s,yan go, qvist r. insulin resistance provides the connection between hepatitis c virus and diabetes. hepat mon, 2015; 15(1):2394-97. 4. lecube, a. hernández c, genescà j. proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis c patients. diabetes care, 2006;29(5):1096-1101. 5. miura k, taura k, kodama y,schanabi y. hepatitis c virusinduced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity. hepatology, 2008; 48(5): 1420-29. 6. liu, h trinh tl, dong h, keith hr, nelson d. iron regulator hepcidin exhibits antiviral activity against hepatitis c virus. 2012. plos one 7. aregbesola, a.,voutelian s,vitranan jk.serum hepcidin concentrations and type 2 diabetes. world journal of diabetes, 2015;6(7): 978-81. 8. wang j. and pantopoulos k. regulation of cellular iron metabolism. biochem j, 2011; 434(3): 365-81. 9. huang ml, austin cj,sari ma. hepcidin reduces ferroportin-1 expression and enhances its activity at reducing iron levels. j biol chem, 2013;288(35): 25450-65. 10. ganz t. hepcidin and iron regulation, 10 years later. blood, 2011;117(17):4425-33. 11. bacchetta, j., zaritsky jj, sea jl, chun rf. suppression of ironregulatory hepcidin by vitamin d. j am soc nephrol, 2014; 25(3):564-72. 12. sany d and elsawy ae, elshahawyy.hepcidin and regulation of iron homeostasis in maintenance hemodialysis patients. saudi j kidney dis transpl, 2014; 25(5): 967-73. 13. fallahi p, ferri c, ferrari sm, corrado a, sansonno d, antonelli . cytokines and hcv-related disorders. clin dev immunol, 2012; 2012; 468107-10. 14. corradini e. and pietrangelo a. iron and steatohepatitis. journal of gastroenterology and hepatology, 2012;27(s2):42-46. 15. basuli, d., stevens rg, torti fm, tort sv.. epidemiological associations between iron and cardiovascular disease and diabetes. front pharmacol, 2014;5: 117-20. 16. el-zayadi ar and anis m. hepatitis c virus induced insulin resistance impairs response to anti viral therapy. world j gastroenterol, 2012;18(3): 212-24. 17. girelli, d., et al., reduced serum hepcidin levels in patients with chronic hepatitis c. j hepatol, 2009. 51(5): p. 845-52. 18. tsochatzis, e., papatheodoridis gv, koliaraki v. hepcidin levels are related to severity of liver histological lesions in chronic hepatitis c. j viral hepat, 2010;17(11): 800-06. 19. wang h, li h, jiang x, shi w, shen z. hepcidin is directly regulated by insulin and plays an important role in iron overload . diabetes, 2014;63(5): 1506-8. 20. gan, w., guan y, wu q, an p.association of tmprss6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a chinese han population. the american journal of clinical nutrition, 2012;95(3): 626-32. https://www.ncbi.nlm.nih.gov/pubmed/?term=hern%c3%a1ndez%20c%5bauthor%5d&cauthor=true&cauthor_uid=16644643 https://www.ncbi.nlm.nih.gov/pubmed/?term=genesc%c3%a0%20j%5bauthor%5d&cauthor=true&cauthor_uid=16644643 https://scholar.google.com.pk/citations?user=noyhyx4aaaaj&hl=en&oi=sra https://www.ncbi.nlm.nih.gov/pubmed/?term=zaritsky%20jj%5bauthor%5d&cauthor=true&cauthor_uid=24204002 https://www.ncbi.nlm.nih.gov/pubmed/?term=sea%20jl%5bauthor%5d&cauthor=true&cauthor_uid=24204002 https://www.ncbi.nlm.nih.gov/pubmed/?term=chun%20rf%5bauthor%5d&cauthor=true&cauthor_uid=24204002 https://www.ncbi.nlm.nih.gov/pubmed/?term=ferri%20c%5bauthor%5d&cauthor=true&cauthor_uid=22611419 https://www.ncbi.nlm.nih.gov/pubmed/?term=ferrari%20sm%5bauthor%5d&cauthor=true&cauthor_uid=22611419 https://www.ncbi.nlm.nih.gov/pubmed/?term=corrado%20a%5bauthor%5d&cauthor=true&cauthor_uid=22611419 https://www.ncbi.nlm.nih.gov/pubmed/?term=sansonno%20d%5bauthor%5d&cauthor=true&cauthor_uid=22611419 https://www.ncbi.nlm.nih.gov/pubmed/?term=antonelli%20a%5bauthor%5d&cauthor=true&cauthor_uid=22611419 https://scholar.google.com.pk/citations?user=p32aq9saaaaj&hl=en&oi=sra https://www.ncbi.nlm.nih.gov/pubmed/?term=papatheodoridis%20gv%5bauthor%5d&cauthor=true&cauthor_uid=20002304 https://www.ncbi.nlm.nih.gov/pubmed/?term=koliaraki%20v%5bauthor%5d&cauthor=true&cauthor_uid=20002304 https://www.ncbi.nlm.nih.gov/pubmed/?term=li%20h%5bauthor%5d&cauthor=true&cauthor_uid=24379355 https://www.ncbi.nlm.nih.gov/pubmed/?term=jiang%20x%5bauthor%5d&cauthor=true&cauthor_uid=24379355 https://www.ncbi.nlm.nih.gov/pubmed/?term=shi%20w%5bauthor%5d&cauthor=true&cauthor_uid=24379355 https://www.ncbi.nlm.nih.gov/pubmed/?term=shen%20z%5bauthor%5d&cauthor=true&cauthor_uid=24379355 microsoft word 5_pattern of bone marrow infiltration in non-hodgkin’s lymphomas journal of rawalpindi medical college (jrmc); 2008;12(2):66-71 66 pattern of bone marrow infiltration in non-hodgkin’s lymphomas jamila and khalid hassan department of pathology, pakistan institute of medical sciences, islamabad abstract background: non-hodgkin’s lymphomas have a predilection for bone marrow involvement, and bone marrow biopsy is performed in an attempt to evaluate stage iv disease. this study was conducted to evaluate the pattern of bone marrow infiltration and morphology of atypical cells in freshly diagnosed patients of nonhodgkin’s lymphomas (nhl). methods: this prospective, descriptive study was conducted in the department of pathology, pakistan institute of medical sciences (pims) islamabad from january 2003 to december 2004. a total of 50 cases of nonhodgkin’s lymphoma diagnosed on tissue biopsy, and found to have bone marrow infiltration were randomly selected. the h & e stained trephine sections were examined for evidence of infiltration and pattern of infiltration, viz. focal random, focal para-trabecular, diffuse interstitial and diffuse infiltration. results: in 52% patients, the infiltration was diffuse; of these patients, 34% showed a complete replacement of normal marrow cellular elements by lymphoma cells, and 18% manifested diffuse interstitial infiltration. an additional 10% cases manifested diffuse as well as diffuse interstitial infiltration. in 30% of patients diffuse or diffuse interstitial infiltration was accompanied with focal random or focal paratrabecular infiltration. conclusion: diffuse bone marrow infiltration is much more common in our set-up probably because of a relatively late presentation by patients of non-hodgkin’s lymphoma key words: non-hodgkin’s lymphoma; nhl; bone marrow infiltration introduction non-hodgkin’s lymphomas (nhls) are characterized by neoplastic transformation of lymphoid cells, and have a high potential for spread to various tissues throughout the body especially bone marrow, liver, spleen, lungs, and brain etc. bone marrow biopsy is an essential part of diagnostic workup in nhl, and the patients presenting in stage iv disease with infiltration of bone marrow and/or other tissues manifest poor prognosis and response to treatment.1,2 it has been observed that patients in developing countries generally present at a relatively advanced stage in comparison with western patients.3-5 in patients with bone marrow involvement, the marrow smears and trephine sections are collectively interpreted for cytology, pattern of bone marrow infiltration, and sometimes immunophenotyping.6 on marrow smears, the infiltrating cells can be recognized as atypical cells, and their number is usually determined on 500-cell myelogram as percentage. trephine imprints are also very useful, especially if aspiration has manifested a blood/dry tap. trephine biopsy permits an assessment of pattern and extent of infiltration, which is of both diagnostic and prognostic relevance.7 sometimes, trephine biopsy may demonstrate lymphoma when no abnormal cells have been detected in blood and bone marrow smears. four distinct patterns of infiltration by nhl are usually recognized1: interstitial pattern, in which lymphoid cells are loosely dispersed amidst haematopoietic and fat cells. ii) diffuse (packed marrow) pattern, in which lymphoid cells are densely packed within the marrow spaces; lymphoid nodules are not discernable. iii) nodular pattern, in which multiple, partly confluent nodular aggregates of lymphoid cells are recognized. the nodules vary in size from 0.53 mm in diameter and are usually located in the central intertrabecular areas. iv) para-trabecular pattern, in which the striking morphological feature is streaming of lymphoid infiltrate in apposition to osseous trabeculae. correspondence: prof khalid hassan department of pathology pakistan institute of medical sciences, islamabad email: kh_pims@yahoo.com journal of rawalpindi medical college (jrmc); 2008;12(2):66-71 67 the objective of the present study was to evaluate the pattern of bone marrow infiltration and morphology of atypical cells in freshly diagnosed patients of nhl. patients and methods this prospective, descriptive study was conducted in the department of pathology, pakistan institute of medical sciences (pims) islamabad from january 2003 to december 2004. a total of 50 cases of non-hodgkin’s lymphoma diagnosed on tissue biopsy, and found to have bone marrow infiltration were randomly selected. the patients who had already received cytotoxic therapy and those who were not found to have bone marrow infiltration were excluded from the study. the wright-stained bone marrow smears were examined for cellularity, number and maturation of normal cells and the number and morphology of atypical lymphoid (lymphoma) cells. the following features of atypical cells were noted: size; nuclear chromatin; nuclear cleavage; cell and nuclear outline and nucleoli the h & e stained trephine sections were examined for evidence of infiltration and pattern of infiltration, viz. focal random, focal para-trabecular, diffuse interstitial and diffuse infiltration. results bone marrow smears: bone marrow smears showed atypical lymphoid cells in 46 (92%) patients. as shown in table 1, the cell size was variable; about half of the patients showed large and about a quarter mixed small and large cells; 20 of patients manifested predominantly small-sized cells. table 1 also gives the nuclear morphological details. nuclear chromatin was coarsely stippled in majority of cases. nuclear cleavage was a prominent feature in 28% of patients. nucleoli were conspicuous in 20% and inconspicuous in 50% of cases bone marrow trephine biopsy: the marrow fragments were hypercellular in 45 cases; in 5 of them hypocellular pockets were also observed. in 4 cases, marrow fragments were moderately cellular and in 1 hypocellular. pattern of infiltration (table 2): in 26 (52%) patients, the infiltration was diffuse without any areas of focal infiltration. of these patients, 17 (34%) showed a diffuse infiltration thereby replacing the normal bone marrow cellular elements in the area of infiltration with complete effacement of normal architecture. table 1: features of cells on bone marrow smears features no (%) size small large mixed small / large medium to large size cells. 10 (20) 23 (46) 12(24) 01 (02) cell /nuclear outline regular cell/nuclear outline irregular cell/nuclear outline regular cell/irregular nuclear outline 33 (66) 14 (28) 03 (06) nuclear chromatin fine stippled coarsely stippled vesicular 19 (38) 28 (56) 03 (06) nuclear cleavage present 14 (28) nucleoli conspicous inconspicuous 10 (20) 30 (50) table 2: pattern of infiltration (trephine biopsy) thus, the fat spaces were completely encroached upon. two additional patients manifesting similar diffuse infiltration presented in leukemic phase at the time of first diagnosis. in the remaining 9 cases (18%), the infiltrating atypical cells were admixed with the normal bone marrow cellular elements. fat spaces were found to be preserved to a variable extent. these type no (%) diffuse diffuse interstitial focal random/diffuse interstitial diffuse/ diffuse interstitial focal paratrabecular/interstitial focal paratrabecular/diffuse focal random / diffuse diffuse in leukemic phase follicular/diffuse interstitial focal random/ paratrabecular focal random 9 (18) 17 (34) 6 (12) 5 (10) 4 (08) 2 (04) 2 (04) 2 (04) 1 (02) 1 (02) 1 (02) journal of rawalpindi medical college (jrmc); 2008;12(2):66-71 68 patients were diagnosed as having diffuse interstitial infiltration. table 3: cell morphology on trephine biopsy cell morphology no (%) small non-cleaved small cleaved large non-cleaved large cleaved mixed small and large noncleaved mixed cells in leukemic phase small cleaved in leukemic phase 25 (50) 4 (08) 6 (12) 7 (14) 5 (10) 2 (04) 1 (02) in an additional 5 (10%) cases, areas manifesting diffuse as well as diffuse interstitial infiltration concomitantly were observed. table 4: pattern of bone marrow infiltration as compared to previous studies author (year) interstitial diff use paratrabecular focal nodular mixed zhongura et al (2006) 11.6% 44.9% 0.0% 29.36% 0.0% lim et al (2000) 0.0% 71.4% 0.0% 0.0% 0.0% chen et al (2000) 23.0% 22.0% 0.0% 7.0% 18.0% hassan* et al (1995) 0.0% 77.5% 10% 12.5% 0.0% lee et al (1994) 56% 31% .0% 0.0% 0.0% malik* et al (1992) 0.0% 46.3% 19.5% 12.5% 0.0% bartl r et al (1982) 26% 25% 8.0% 41% 0.0% amongst the remaining 17 cases, in 15 (30%) diffuse or diffuse interstitial infiltration was concomitantly associated with focal random or focal para-trabecular infiltration, or follicular pattern as detailed in table 2. in one patient (2%) areas of focal random as well as focal para-trabecular infiltration were observed, without an evidence of diffuse or diffuse infiltration. in one patient, only focal random infiltrates were observed atypical cells: as shown in table 3, half of the patients showed small non-cleaved cells. large cleaved, large non-cleaved and mixed small / large non-cleaved cells were observed in 7 (14%), 6 (12%) and 5 (10%) cases each. four (8%) patients exhibited small cleaved cells. amongst the patients in leukemic phase, mixed cells were observed in 2 (4%) and small cleaved cells in 1 (2%) patient, respectively (figs 1-6). fibrosis of a variable degree was observed in 33 cases. it was mild in 19 (38%), moderate in 8 (16%) and marked in 6 (12%) cases, respectively. fibrosis was not observed on routine h & e stained section in the remaining 17(34%) cases and marked. an evidence of scattered areas of necrosis was observed in histological trephine section in 3 patients discussion the non-hodgkin’s lymphomas (nhls) have a propensity to disseminate widely, and especially to bone marrow, liver and spleen. literature searched from within the country has shown two published studies regarding bone marrow infiltration by nonhodgkin’s lymphoma. in the first study, the lymphoma tissue in marrow presented as diffuse infiltrate in 46.3% cases, focal aggregates in 12.5%, and paratrabecular distribution in 19.5%of all types of lymphoma.8 in the second study the diffuse infiltrate was reported in 77.5% cases, focal random (non-paratrabecular) in 12.5 % and paratrabecular distribution in 10% of all types of lymphoma.9 the pattern of bone marrow infiltration by nhl cells in the present study, when compared with the two above mentioned series, shows almost similar findings. in the present study, the commonest pattern of bone marrow infiltration was that of diffuse type (66%), followed by focal (34%); amongst the latter, focal random or non paratrabecular pattern was observed in 20% cases, and focal paratrabecular in 14% cases. the percentage of diffuse infiltration in our series was lower than that in the study presented by hassan et al, but higher than series published by malik s et al8,9 the frequency of focal paratrabecular pattern in the present series was lower than the series published by malik s et al.8 however, in both the previous local series, the percentage of focal random journal of rawalpindi medical college (jrmc); 2008;12(2):66-71 69 and non paratrabecular infiltration were similar i.e., 12.5%. (table4) figure 1 : small non-cleaved cells in bone marrow smear figure 2 : small cleaved cells on bone marrow smear figure 3 : large sized lymphoma cells on bone marrow smear figure 4 : focal random infiltration on trephine section figure 5 : focal paratrabecular marrow infiltration by nhl on trephine section figure 6 : diffuse infiltration on trephine journal of rawalpindi medical college (jrmc); 2008;12(2):66-71 70 section the western studies have shown patterns of bone marrow infiltration varying from mainly focal random or focal paratrabecular in some to mainly diffuse in others. 8.10,11 we found high rate of diffuse infiltration in our patients (66%) as also observed in previous two local studies, and this probably reflects that most of our patients present rather late for examination or are diagnosed rather late when disease has already advanced to stage iv. in a study by lai et al, bone marrow involvement by nhl was the most frequently found in follicular small cleaved cell (57%), diffuse mixed small and large cell (56%), and lymphoblastic (56%) lymphomas. a paratrabecular pattern of marrow involvement tended to occur more frequently in low or intermediate grade lymphomas. high grade lymphomas tended to show an interstitial or diffuse pattern of marrow involvement. the results of marrow aspiration and biopsy were complementary to each other.12 in their study, in 43% of cases with marrow lymphoma there was peripheral blood involvement at the time of diagnosis. blood involvement was most frequently found in lymphoblastic lymphoma (70%). in general, the degree of blood involvement was related to the extent of marrow involvement. patients with marrow involvement often presented with ‘b’ symptoms and hepatomegaly. abnormalities in at least one of the blood counts were quite common (93%). patients with marrow involvement showed a significantly higher frequency of hepatomegaly and abnormal blood counts, as compared to those with negative marrows.12 in another study by chen et al, a total of 70 patients with nhl (male 52, female 18; median age: 49 years) were studied. the extent of bone marrow involvement was minimal in 15 cases, moderate in 16 cases and severe in 39 cases. the bone marrow involvement was of interstitial type in 23 cases, nodular type in 7 cases, mixed type in 18 cases and diffuse type in 22 cases. the frequency of splenomegaly in nodular type nhl was significantly higher than that in any other type. nodular type nhl occurred mainly in b-cell lymphoma.13 staples wg et al noted that in their study focal involvement of the bone marrow by nhl was frequent. they also stated that nonhodgkin’s lymphoma and hodgkin’s disease can occur primarily in the bone marrow.14 in a previous study the most frequent patterns of marrow involvement in nhl were interstitial and diffuse (56% and 31%, respectively).15 the paratrabecular pattern was relatively uncommon (4%). most lymphomas (42%) extensively involved marrow space thereby infiltrating greater than 76% of total marrow space. it was further stressed that bone marrow trephine biopsy was the best method for evaluation of bone marrow infiltration, especially when compared to bone marrow smear and clot sections. study revealed that most common histologic type of marrow lymphoma was diffuse large cell type with frequent interstitial and diffuse pattern and extensive involvement of marrow space.15 all types of nonhodgkin’s lymphomas do not invade the bone marrow with an equal frequency.16 the pattern of marrow involvement also differs to some extent in various nhl subtypes, for example paratrabecular infiltration is strongly associated with follicular lymphoma. a bone marrow biopsy performed in patients with low grade lymphoma sometime shows unexpected high grade transformation, which necessitates a different therapeutic approach.17 the cells infiltrating the marrow usually show a higher degree of concordance with corresponding lymph node histology. however, occasionally the cell morphology at the site of bone marrow infiltration is found to be different fro the primary site of lymphoma.118 conlan et al have reported a high incidence of morphologic discordance (40%) between lymph node and bone marrow (1990). we observed this type of discordance in four patients.19 in a similar study, adewuji b et al have reported that low grade lymphoma manifested predominantly diffuse pattern of marrow involvement and high grade lymphomas had nearly equal proportion with diffuse and focal patterns.20 a mixed pattern of infiltration was most common, followed by paratrabecular, nodular diffuse and interstitial patterns. they also found discordance between the bone marrow morphology and other tissue sites in 24.9% of cases. juneja sk et al published a study of 260 patients with nhl who underwent bilateral bone marrow biopsy. they observed a strong correlation between follicular lymphoma and paratrabecular pattern, which was observed in 40 of 45 positive cases. discordant histology was seen in 6 of 20 positive cases of dlcl and 2 of 37 positive cases of follicular small cleaved cell lymphomas.16 references journal of rawalpindi medical college (jrmc); 2008;12(2):66-71 71 1. bartl r,frisch b,burkhardt t, kettner g,mahl g,fateh a et al. assessment of bone marrow histology in malignant lymphoma(non-hodgkin’s) : correlation with clinical factor for diagnosis, prognosis, classification and staging br.j. haematol. 1982 ;51 :511-30. 2. knauf wu, guckel f, dohner h, semmler w, trumper l, ho ad. detection of bone marrow infiltration by nonhodgkin’s lymphoma. comparison of histological findings , analysis of gene rearrangements, and examination by magnetic resonance imaging. klin wochenschr. 1991; 69 (8):345-50. 3. gad-el-mawla n, hamza mr, abdel-hadi s. prolonged disease free survival in pediatrics non-hodgkin’s lymphoma using fosfamide containing combination chemotherapy. hematol oncol 1991;9:281-86. 4. ladjadj y, philip t, lenoir em.abdominal type burkitt lymphoma in algeria. br,j.cancer 1984 ;49 :503-12. 5. ibrahim em, satti mb,al idrissi my.non-hogkin’s lymphoma in saudi arabia. prognostic factor and an analysis of outcome of combination chemotherapy only for both localized and advanced disease.eur.j.cancer clin.oncol.1988 ;24 :391-401. 6. bain, bj bone marrow aspiration. j clin pathol 2001 ;54 : 657-63. 7. durosinmi ma, mabayoje vo, akinola no. a review of histology of bone marrow trephine in malignant lymphomas: niger j med. 2003;12 (4):198-201. 8. malik s, ahmad s , saleem m. bone marrow involvement in non-hodgkin’s lymphoma. a study of 41 untreated cases.pak armed forces med j 1992 ;42:90-92. 9. hassan k, ikram n,bukhari kp shah sh. the pattern of bone marrow infiltration in non-hodgkin’s lymphoma. j pak med assoc 1995 ;45(7) :173-76. 10. mckenna rw, bloomfield cd brunning rd. nodular lymphoma: bone marrow and blood menifestation. cancer 1975 ;36 :428-40. 11. foucar k, mckenna r, frizzera g, brunning rd.incidence and pattern of bone marrow and blood involvement by lymphoma in relationship to the lukes collins classification. blood 1979 ;54 :1417-22. 12. lai hs, tien hf, hsieh hc, chen yc, su ij, wang ch, bone marrow involvement in non-hodgkin’s lymphoma. taiwan yi xue za zhi , 1989 88(2): 114-21 13. chen h, qian l, shen l. clinicopathological studies on bone marrow involvement of non-hodgkin lymphoma. zhonghua zhong liu za zhi. 2000;22(6): 51315. 14. staples wg, getaz ep. bone marrow involvement in malignant lymphoma without peripheral lymphadenopathy. s. afr med j 1977; 52 (2): 60-63. 15. lee wi, lee jh, kim is, lee kn, kim sh. bone marrow involvement by nonhodgkin’s lymphoma. j korean med sci. 1994; 9(5): 402-08. 16. stein.rs, ultman je, byrne ge. bone marrow involvement in non-hodgkin’s lymphoma.implications for staging and therapy. cancer 1976; 37:629-36. 17. juneja sk, wolf mm, cooper ia. value of bilateral bone marrow biopsy specimens in nhl.j clin pathol. 1990;43 (8):630-32. 18. haddadin wj. malignant lymphoma in jordan: a retrospective analysis of 347 cases according to who classification. ann saudi med. 2005; 25 (5) :398403. 19. conlan mg, bast m, armitage jo, weisenburger dd. bone marrow involvement by non-hodgkin’s lymphoma :the clinical significance of morphologic discordance between lymph node and bone marrow. j clin oncol.1990; 8(7):1163-72. 20. adewuji b, coutts a, levy l, klein s and muronda c. bone marrow involvement in non-hodgkin’s lymphoma in zimbabwe. east afr med j 1994; 71(2); 773-75. summary journal of rawalpindi medical college (jrmc); 2017;21(2): 117-121 117 original article effect of spectacle centration on stereoacuity ayesha arshad 1, aamir ali choudhry 2, syed jawwad hussain 3, ijaz latif 1, ahmed kalasra 1 department of ophthalmology , bahawal victoria hospital, bahawalpur; 2. department of ophthalmology, madinah teaching hospital, faisalabad;3. department of food science and technology, university of faisalabad. abstract background: to determine the percentage of decentered spectacles ,the possible relationship of decentration of spectacles on stereoacuity,the difference between interpupillary distance (ipd) and optical centration distance (ocd), the relationship between decentration of spectacles and asthenopic symptoms, magnitude of prismatic effect and the direction of base of prism in decentered spectacles. methods:a hospital based cross-sectional study conducted on the 100 students, with the age range of 18 to 26 years.horizontal decentartion of spectacles was assessed by taking the difference between the interpupillary distance and the optical centration distance. vertical decentration was assessed by difference between the optical centre of the spectacles and the centre of the pupils. direction of decentration determines the prism base direction and stereoacuity was assessed by titmus fly test. results: all individuals were using decentered spectacles in both horizontal and vertical direction. decentration was highest (33%) in the range of 0 – 1.49 (mm) horizontally in both eyes. vertical decentration in the range of 3 – 5 (mm) was highest, 39% in right eye and 48% in the left eye of the individuals. 56% of the individuals have horizontal prismatic effect in their spectacles in right and left eye within the range of 0 – 0.49 prism diopters. vertical prismatic effect was within range of 0 – 0.99 prism diopters in maximum number of individuals. majority (76%) had base-in prisms induced in their spectacles in both right and left eyes. vertically induced prism was in the base-up direction in 87% and 90% of the individuals in their right and left eyes respectively and 8% and 7% base-down prisms in their right and left eyes respectively. difference between ipd (inter-pupillary distance) and ocd (optical centration distance) of individuals was quite significant with p-value 0.000. the mean difference between ipd and ocd was -3.57000. mean ipd was less than the mean ocd. horizontal prismatic effect in right eye caused decline in the stereo-acuity with p-value 0.019. highest number of individuals (42) had reduction of stereo-acuity within the range of 20 – 100 minutes of arc having horizontal prismatic effect in the range of 0 – 1.49 in their right eyes. conclusions: due to improper dispensing of the spectacles, prismatic effect is induced in the spectacles that shifts the image position formed on the retina and results in the reduction of the stereoacuity of the individuals. key words: interpupillary distance, optical centration distance, stereoacuity, spectacles introduction stereopsis is the ability to perceive depth due to horizontal retinal image disparity in binocular vision.1,2 decentration of ophthalmic lenses is one of the most important factor that effects the stereopsis and binocular vision. fusion is one of the component of binocular vision which is affected due to the decentration of ophthalmic lenses and it results in the alteration of fusional convergence as a result, causes the asthenopic symptoms like headaches, ocular fatigue, diplopia and blurry vision.3, 4one of the most common reasons in the spectacle non-tolerance is the decentration of the spectacles.5 when the centre of one or both of the ophthalmic lenses does not coincide with the centre of one or both of the pupils then these sort of spectacles are called decentered spectacles and they will cause the affect of unnecessary prisms in the spectacles.6 prismatic effect is induced due to the decentration of the ophthalmic lenses and causes the distortion of stereopsis.3interpupillary distance (ipd) is a centre to centre distance between the pupils. this measurement is very important for the optical industry to properly dispense the spectacles as it determines the depth perception by stereoscopically separating the two images perceived by the brain to produce the three dimensional view.7the spectacles should consist of optical centration distance equivalent to the interpupillary distance of a person , with correct ophthalmic prescription for ideal functioning of the spectacles.8 induced prism is defined as the unnecessary prismatic effect when the centre of the ophthalmic lenses does not coincide with the visual axis that passes from the journal of rawalpindi medical college (jrmc); 2017;21(2): 117-121 118 centre of one or both of the pupils.9the spectacles should consist of optical centration distance equivalent to the interpupillary distance of a person , with correct ophthalmic prescription for ideal functioning of the spectacles.8ray of light bends towards the base of the prism when it passes through the prism, same as, the ophthalmic lenses also act as a prism when the ray of light passes through the points other then the optical centre of the ophthalmic lenses. the more the light ray passes from the points away from the optical center, the more strongly the light rays bends from their parallel position.10 ophthalmic lenses act as a set of varying power prisms. each point away from the optical centre bends the light ray by different amount. the prismatic effect is calculated from the prentice rule (p = cf ). p denotes the prismatic effect in prism diopters, c is the distance of the point from the optical centre, or decentration, measured in centimeters, f denotes the power of the ophthalmic lenses in diopters.11 some of the amount of induced prism can be tolerated by the persons without any ocular discomfort, but it depends on the type of the lenses if it is multifocal, bifocal or monofocal lenses, prescription of ophthalmic lenses and type of the induced prisms if it is vertical or horizontal prism.12atchison et al (2001) investigated the effect of small prescription errors on spatial visual performance and spectacle lens acceptability.13 comas et al (2007) reported that difference of 0.25 d refraction between the two eyes resulted in the retinal images of two different sizes that effects the binocularity and caused asthenopic symptoms. most of the patients could only tolerate 5% of the retinal image difference between the two eyes.14 according to ansi standards a person can adapt upto 1/3 of the vertical prism or vertical decentration upto 1 mm and 2/3 prism diopters horizontal prismatic effect or horizontal decentration of 2.5 mm without any asthenopic symptoms.15induced vertical disparity decreases the local and global stereopsis. local stereopsis threshold is reduced by 10 seconds of arc or less on average with 1.0δ of induced vertical prism in front of either eye. however, global stereopsis threshold was reduced by over 100 seconds of arc by the same 1.0δ of induced vertical prism.16hence opticians should be advised to take into account for the proper centralization of the spectacles so that the image of the observed objects will fall on the ideal position in the visual pathway so that the proper fusion of the image and hence stereopsis is maintained. patients and methods a hospital-based cross sectional study was conducted from april 2016 to may 2016, through convenient sampling to include 100 students of the university of faisalabad, of age group 18 to 26 years, to assess the decentration in their spectacles and its effect on the stereoacuity. this was conducted at the department of ophthalmology at madinah teaching hospital, faisalabad, pakistan. inclusion criteria was subjects using monofocal spectacles, subjects visual acuity 6/6 bilaterally with spectacles,age ranged from 18 to 26 years and orthophoric subjects with spectacles. subjects using bifocals or multifocals, subjects being treated for any ocular pathologies and subjects with significant phorias/tropias were excluded. objective tests for the diagnosis of centration of spectacles was assessed by marking the centre of the spectacles by the marker in focimeter. interpupillary distance was measured by the ipd ruler. measurement was taken from the centre of pupillary reflex of one eye to the centre of pupillary reflex of the other eye. horizontal decentration was assessed by the difference between the interpupillary distance (ipd) assessed by the ipd ruler and the optical centration distance (ocd) assessed by the measurement taken from centre to centre points on the ophthalmic lenses marked by the focimeter. vertical decentration was assessed by the cm ruler. points were marked on the spectacles where the centre of the pupil was visible. centimeter ruler was used to measure the difference between the points marked for the centre of pupil on the spectacles and the points marked by the focimeter that represents the centre of the ophthalmic lenses. stereoacuity was measured by the titmus fly test (tft). visual acuity was measured from the snellens chart. prismatic effect was calculated from the prentice formula. (p=cf) results horizontal decentration in right eye and left eye was highest in the range of 0 – 1.49mm in 33% of the individuals(table 1). vertical decentration in right and left eye was 3 – 5mm in maximum individuals (39% and 48% respectively) (table 2). horizontal prismatic effect was 0 – 0.49 in 56% of individuals in right and left eye (table 3). vertical prismatic effect was 0 – 0.99 in 47% individuals in right eyes and 51% in their left eyes (table 4). 76% of the individuals had prisms in base-in direction in the right and left eye of their spectacles and 17% and 18% had base-out prisms in their right and left eye of the spectacles respectively. 87% and 90% of the individuals had base-up prism in their right eye and left eye of their spectacles journal of rawalpindi medical college (jrmc); 2017;21(2): 117-121 119 respectively(table 5). average of spherical powers of right eye and left eye was -2.5833 and -2.5788 respectively. average of cylindrical powers of right eye and left eye was -0.9667 and -0.9464 respectively (table 6). association between horizontal prismatic effect in right eye and stereoacuity was statistically significant with pvalue 0.019 (table 7). table 1: percentage distribution of horizontal decentration in right and left eye in spectacles range of horizontal decentration right eye frequency range of horizontal decentration left eye frequency 0-1.49 33 0-1.49 33 1.5-2.99 30 1.5-2.99 30 3-4.49 22 3-4.49 22 4.5-5.99 13 4.5-5.99 13 6-7.5 2 6-7.5 2 table 2: percentage distribution of vertical decentration in right and left eye in spectacles range of vertical decentration right eye frequency range of vertical decentration left eye frequency 0-2 18 0-2 25 3-5 39 3-5 48 6-8 27 6-8 20 9-11 15 9-11 7 12-14 1 table 3: percentage distribution of horizontal prismatic effect in right and left eyes horizontal prismatic effect right eye frequency horizontal prismatic effect left eye frequency 0-0.49 56 0-0.49 56 0.5-0.99 21 0.5-0.99 22 1-1.49 13 1-1.49 13 1.5-1.99 5 1.5-1.99 6 2-2.49 3 2.5-3 3 2.5-3 2 76% of the individuals had stereo-acuity in the range of 20-100 minutes of arc, 13% had 101-200 and 11% were in the range of 301 or above (table 8). mean value of interpupillary distance (64) was less than the mean of optical centration distance (67) (table 9). correlation between interpupillary distance (ipd) and optical centration distance (ocd) was statistically significant with p-value 0.000 ( figure 1) table 4: percentage distribution of vertical prismatic effect in right and left eyes vertical prismatic effect right eye frequency vertical prismatic effect left eye frequency 0-0.99 47 0-0.99 51 1-1.99 34 1-1.99 35 2-2.99 10 2-2.99 9 3-3.99 6 3-4 5 4-5 3 table 5: percentage distribution of horizontal prism base direction in right and left eye in spectacles base direction right eye left eye base in 76 76 base out 17 18 base up base down 87 8 90 7 table 6: average spherical and cylindrical powers in right and left eye in the spectacles right eye left eye spherical power -2.5833 -2.5788 cylindrical power -.9667 -.9464 table 7: association between horizontal prismatic effect in right eye in spectacles and stereoacuity horizontal prismatic effect right eye stereoacuity 20-100 101-200 301 or above 0-0.49 42 8 6 0.5-0.99 17 1 3 1-1.49 11 2 0 1.5-1.99 4 1 0 2-2.49 2 1 0 2.5-3 0 0 2 table 8: average of stereoacuity in different range groups stero-acuity range frequency 20-100 76 101-200 13 301 or above 11 journal of rawalpindi medical college (jrmc); 2017;21(2): 117-121 120 table 9: comparison between ipd and ocd mean std. deviation interpupillary distance 64.0200 3.36044 optical centration distance 67.5900 4.25950 figure 1: correlation between ipd and ocd discussion in present study , it was observed that 100% of the individuals were using decentered spectacles in both horizontal and vertical direction. according to vr moodley, 45% of the individuals were wearing incorrectly dispensed spectacles. 100% of the individuals were wearing decentered spectacles among these 51% individuals were in horizontal ansi tolerance and 3.12% were wearing vertically decentered spectacles within ansi tolerance. 47% of the individuals had vertically induced prismatic effect in their spectacles. 50% of the individuals reported asthenopic symptoms. no correlation was reported between the induced prismatic effect and the asthenopic symptoms. 50% had base out prisms in their spectacles. 45% of the individuals were symptomatic, 12% had asthenopic symptoms, 5% were experiencing headache. individuals wearing spectacles with base out prisms experience more symptoms as compared to others. 17 decentration was highest (33%) in the range of 0 – 1.49 (mm) horizontally in both eyes. vertical decentration in the range of 3 – 5 (mm) was highest, 39% in right eye and 48% in the left eye of the individuals. 56% of the individuals had horizontal prismatic effect in their spectacles in right and left eye within the range of 0 – 0.49. vertical prismatic effect was within range of 0 – 0.99 in maximum number of individuals, 47% and 51% in the right eye and left eye respectively. 76% had base-in prisms induced in their spectacles in both right and left eyes. 17% had base-out prism in their right eyes and 18% in their left eyes. vertically induced prism was in the base-up direction in 87% and 90% of the individuals in their right and left eyes respectively and 8% and 7% base-down prisms in right and left eyes respectively. osuobeni & al-zughaibi also reported that 100% of the individuals were wearing decentered spectacles among which 84% had horizontal decentration and 99% were wearing vertically decentered spectacles. most of the individuals had base-in prisms in their spectacles in horizontal direction. in vertically induced prisms, base-down prism was commonly observed in the vertically decentered spectacles. optical centration distance was greater than the inter-pupillary distance. average horizontally induced prismatic effect was 0.35 in right eye and -0.33 in left eye with base-in prismatic effect. average vertically induced prismatic effect was 1.08 in right eye and 1.09 in left eye with base-up prismatic effect in the spectacles. 5% of the individuals were reported to be symptomatic and 95% didn’t complain about their spectacles.18 this is because adaptation to prisms occurs with-in 5 minutes after the prisms are introduced in front of the eyes. 19-23disparity effects on local and global stereopsis, induced vertical disparity reduces the local and global stereopsis. there was a significant difference in the mean stereopsis before and after inducing the vertical disparity with prism of 0.5 or 1 prism diopter (p <0.05).24according to catherine, dispensing related non-tolerance of spectacles in individuals was 22%.25by applying paired t test the difference between ipd and ocd of individuals was quite significant with p-value 0.000. the mean difference between ipd and ocd was -3.57000. mean ipd was less than the mean ocd. chi – square test result shows that the horizontal prismatic effect in right eye caused decline in the stereo-acuity with pvalue 0.019. highest number of individuals (42) had reduction of stereo-acuity within range of 20 – 100 minutes of arc having horizontal prismatic effect in the range of 0 – 1.49 in their right eyes. references 1. wheatstone c. contributions to the physiology of visionpart the first. on some remarkable, and hitherto unobserved, phenomena of binocular vision. phil trans roy soclond 1838; 128:371-94. 2. bishop p o. binocular vision. in: moses r.a. ed. adler's physiology of the eye, clinical application. cv mosby 1987; 8:619-89. journal of rawalpindi medical college (jrmc); 2017;21(2): 117-121 121 3. brooks c w. essentials for ophthalmic lens work. chicago. professional press 1983. 4. jalie m. the principles of ophthalmic lenses. london. the association of british dispensing opticians 1988. 5. farrell j. dispensing causes of non-tolerance. optician 2005; 229:22–26. 6. khurana a k. theory and practice of optics and refraction. elsevier, india 2008; 2:190-91 7. quant j r, woo g c. normal values of eye position in the chinese population of hong kong. optom vis sci 1992; 69:152–58. 8. brooks c w, borish i m. system for ophthalmic dispensing. new york. professional press 1979; 27-65. 9. millodot m. dictionary of optometry and visual science. butterworth-heinemann. 2009; 7. 10. safir a. refraction and clinical optics. hagerstown. harper & row 1980; 257-58. 11. anderson a l. accurate clinical means of measuring intervisual axis distance. arch ophthalmol 1954; 52:349-52. 12. du toit r, ramke j, brian g. tolerance to prism induced by readymade spectacles: setting and using standard. am j optom 2007; 84: 1053-59. 13. atchison d a, schmid k l, edwards k p, muller s m, robotham j. the effect of under and over refractive correction on visual performance and spectacle lens acceptance. ophthalmic physiol. opt 2001; 21:255–61. 14. comas m, castells x, acosta e r, tuni j. impact of differences between eyes on binocular measures of vision in patients with cataracts. eye 2007; 21:702–07. 15. fernández-ruiz j, díaz r. prism adaptation and aftereffect: specifying the properties of a procedural memory system. learn mem 1999; 6:47-53. 16. fricke t r, siderov j. stereopsis, stereotests and their relation to vision screening and clinical practice. clin exp optoin 1997; 80:165-72. 17. moodley v r, kadwa f, nxumalo b, penceliah s, ramkalam b, zama b. induced prismatic effects due to poorly fitting spectacle frames. s afr optom 2011; 70:168-74. 18. osuobeni e p, al-zughaibi, mohammed a. induced prismatic effect in spectacle prescriptions sampled in saudi arabia. optometry & vision science1993; 70:16066. 19. henson d b, north r. adaptation to prism induced heterophoria. am j opto physiol opt 1980; 57:129-37. 20. sethi b. heterophoria : a vergence adaptive position. ophthal physiol opt 1986; 6:151-16. 21. pickwell l d and kurtz b h. lateral short-term prism adaptation in clinical evaluation. ophthal physiol opt 1986; 6:67-73. 22. dowley d. heterophoria. optom vis sci 1990; 67:45660. 23. dowley d. the orthophorization of heterophoria. ophthal physiol opt 1987; 7:169-74. 24. moghaddam h m, eperjesi f, kundart j, sabbaghi h. induced vertical disparity effects on local and global stereopsis. pacific university oregon 201325. 25. catherine e, freeman, bruce j w. evans.investigation of the causes of non-tolerance to optometric prescriptions for spectacles. ophthal physiol opt 2010; 30:1–11. ----------------------------------------------------------------------- authorship: 1,3conception , synthesis and planning of the research;2 drafting the article and revising it critically for important intellectual content; and final approval of the version to be published summary journal of rawalpindi medical college (jrmc); 2017;21(4): 339-343 339 original article comparison of decompressive craniectomy and multi-dural stabs with decompressive craniectomy and open-dural flap method, in the treatment of acute subdural hematomas adil aziz khan, soban sarwar gondal, muhammad mujahid sharif, muhammad ali tassaduq department of neurosurgery, dhq hospital and rawalpindi medical university, rawalpindi abstract background: to compare the functional outcome between decompressive craniectomy and multi-dural stabs, with decompressive craniectomy and opendural flap, in the removal of acute subdural hematomas . methods : in this randomized controlled trial, 64 patients, with acute sub-dural hematomas were included. patients were divided into two groups on the basis of lottery method. all patients gave informed written consent. in group a, all patients were operated upon by multi-dural stab technique and in group b, patients were operated upon by open-dural flap technique. the objective degree of recovery in the patients treated by both craniectomy techniques was assessed by glasgow outcome score (gos), having maximum of 5 and minimum of 1 score. favourable outcome was at points 4-5 and unfavourable at 1-3 points, at 2 weeks. gos attached as annexure a. favourable outcome was assessed at 2 weeks according to gos. results : the mean age in group-a and group-b was 59.09 ± 9.39 years and 59.56 ± 9.98 years. males constituted the main in both groups. mean gos in group a and in group b, was 3.06 ± 1.24 and 2.69 ± 0.82 respectively. statistically mean gos was same in this study groups, p-value 0.159, > 0.05. there were 37.5% patients in group a and 9.4% patients in group b who had favourable results, while in group a and group b, 62.5% and 90.60% patients had unfavourable results. favourable results were statistically more in group a as compared to group b, p-value =0.008. conclusion: treatment of acute subdural hematoma by decompressive craniectomy with multi dural stabs technique has more favourable results (using gos) than decompressive craniectomy with open-dural flap technique. key words: acute subdural hematoma, glasgow outcome score, craniectomy, dural stab incision. introduction acute sub dural hematomas are notorious for being associated with massive brain swelling, intraoperatively. the hematomas that are extracerebral, hyperdense, crecentic collections between the parenchyma and the dura are known as subdural hematomas.1 they are regarded as acute when diagnosed within 14 days of traumatic brain injury.2-4 56% of acute sdh (subdural hematomas) in the younger group were caused by mvas (motor vehicle accidents) and only 12% were caused by falls whereas in elderly 56% were due to falls.5,6 intracranial injuries occur in more than 50% of patients with acute sdh and have significant prognostic implications.7,8 extra-cranial injuries like facial fractures, limb fractures, thoracic and abdominal trauma occurs in 18-51%.9,10 radiological assessment includes measuring the exact thickness of the sdh by taking the ct scan brain images with a wide window to distinguish the hyper dense clot from the bone.11,12 conservative treatment should be considered in those patients who are fully conscious, the hematoma is a single lesion, the midline shift is not greater than 3 mm and the lesion is less than 10 mm at the thickest point, however, if more than 10mm thick it should be surgically evacuated.13-15 surgical option for acute sdh are decompressive craniectomy and craniotomy.16,17 if an acute sdh is composed of solid clots a large craniotomy cantered over the hematoma is recommended.18-20 if hematoma is fronto-temporal, a craniectomy cantered over a temporal burr hole may be performed the dura is opened and clots are removed.21,22 removal of acute subdural, extradural hematomas and contused infarcted brain is successful method especially after severe traumatic brain injury by open dural flaps. 23,24,25 journal of rawalpindi medical college (jrmc); 2017;21(4): 339-343 340 patients and methods a randomized controlled trial (rct) was done at department of neurosurgery, rmc & allied hospitals. data was collected over 6 months, from january 2014 to june 2014. the sample size was 64 and was collected by non-probability consecutive sampling. patients with acute sdh on non-contrast ct scan brain,those with significant midline shift more than 5mm and volume of hematoma more than 25 ml, on non-contrast ct scan brain were included. patients whose guardian and attendants did not give consent to participate in the study, bilateral acute subdural hematoma, chronic subdural hematomas, diagnosed on ct scan brain, were excluded from the study. after taking permission from the hospital ethical committee all the patients fulfilling the criteria were enrolled in the study. written informed consent was taken from the relatives. all patients fulfilling the inclusion criteria were admitted through the out patients and emergency department of neurosurgery at rmc & allied hospitals. patients were divided into two groups on the basis of lottery method. in both groups, decompressive craniectomy was performed but in group a, all patients was operated upon by multidural 3 stab technique and in group b, patients was operated upon by open-dural flap technique. in both groups surgery was performed under general anesthesia and bone flap raised. in group a multiple linear dural incisions of about 5-8 mms long, in horizontal lines, parallel to vessels and 2-2.5 cm apart from each other,was made but in group b dural flap was opened and raised. in both groups hematoma was evacuated and remaining clots removed by irrigating with warm saline through a silastic catheter. in both groups bone was not put back rather placed in abdominal fat, to be replaced at a later time (4 weeks to 3 months). wound was closed in layers in both the groups. the patients were assessed at 2 weeks according to gos. frequencies and percentages were calculated for qualitative data i.e., gender, gos, favourable and un-favourable outcome. pie chart were made for qualitative data, mean and standard deviation was calculated for quantitative data i.e., age. chi square test was applied to compare the difference between two groups in terms of favorable outcome. a p-value ≤ 0.05 was considered statistically significant results the mean age in group-a and group-b was 59.09 ± 9.39 years and 59.56 ± 9.98 years (table 1) . males constituted the main (table 2).the mean glasgow outcome score (gos) was as follows: 2.87 ± 1.06 with table – 1: comparison of age (years) age (years) group-a group-b n 32 32 mean 59.09 59.56 std. deviation 9.39 9.98 minimum 38.00 43.00 maximum 76.00 80.00 p-value 0.847 group-a = multi dural stab incisions and group-b = open dural flap table – 2: comparison of gender study groups total group-a group-b sex male 23 25 48 71.9% 78.1% 75.0% female 9 7 16 28.1% 21.9% 25.0% total 32 32 64 100.0% 100.0% 100.0% p-value 0.564 group-a = multi dural stab incision and group-b = open dural flap table – 3: descriptive statistics of glasgow outcome score (gos) total n 64 mean 2.87 std. deviation 1.06 minimum 1.00 maximum 5.00 table – 4: comparison of glasgow outcome score (gos) in both study groups group-a group-b n 32 32 mean 3.06 2.69 std. deviation 1.24 0.82 minimum 1.00 1.00 maximum 5.00 5.00 journal of rawalpindi medical college (jrmc); 2017;21(4): 339-343 341 group-a group-b n 32 32 mean 3.06 2.69 std. deviation 1.24 0.82 minimum 1.00 1.00 p-value 0.159 group-a = multi dural stab incisions, group-b = open dural flap minimum and maximum gos score 1 and 6(table 3&4).there were 12 (37.5%) patients in group a and 3 (9.4%) patients in group b who had favourable results, while in group a and group b, 20(62.5%) and 29(90.60%) patients had unfavourable results(table-5) table – 5: comparison of final results in both study groups study groups total group-a group-b results favourable 12 3 15 37.5% 9.4% 23.4% unfavourable 20 29 49 62.5% 90.6% 76.6% total 32 32 64 100.0% 100.0% 100.0% p-value 0.008 group-a = multi dural stab incisions and group-b = open dural flap discussion men are four times likely to be affected than women with an acute sdh.1-3acute sdh often occur in the 5th and 6th decade of life.4-7 the nature and reasons of brain edema after traumatic brain are poorly understood.8 research has highlighted that secondary insult to brain is also considered an important cause of brain swelling, in addition to primary parenchymal injury.9,10 even after operative decompression, the outcome of subdural hematoma remains poor in most of the cases due to compression of the microcirculation which in part may be due to the constrictive effects of the dural flaps .11,12 nevertheless, there is documentary evidence to recommend that it may be secondary to ischemia produced by the compressive hematoma as well. 13,14 the increased death rate of acute subdural hematoma patients is explainable by the principle of monrokellie doctorine and its frequent association with primary brain damage consisting of contusion and brain swelling.15,16 the concept of utilizing wide decompressive craniectomy in severe traumatic brain injury, is due to the fact that intracranial volume is fixed, because of rigid and inelastic nature of skull . 1719 acute subdural hematomas usually accumulate after traumatic brain injury and become symptomatic within 24-72 hours of injury.20,21 if the lesion is more than 10mm thick and midline shift is more than 5mm on ct scan brain, it is evacuated surgically.22,23 conventional surgery could not avoid pouting and laceration of the brain and cortical vasculature. this headed in unfavorable results. 1 conversely, patients who belonged to the multi-dural stab group had favorable outcomes. multi-dural stabs allow evacuation of acute subdural hematoma (sdh), by oozing of blood clots and fluid, as well as simultaneously preventing the pouting and laceration of the brain. in contrast to the, open-dural flap method, there was no control on the pouting and subsequent laceration of brain, which became the reason of secondary brain injury and resulted in much more morbidity and mortality. when researchers measured the effect of fast and late surgical evacuation on brain edema formation and its physiological effects in a rat model of acute subdural hematoma, in combination with hypoxemia or diffuse brain injury, they found that rapid evacuation was not in favor of a better clinical outcome. 11 as an established fact, decompressive craniectomy, is performed in patients in whom gcs is worsening or those with a low gcs on presentation.11 at skims ,60.50% (72/119) of multi-dural stabs and 58.49% (62/106) of open-dural flaps were having a low admission gcs of 3-6 and none of all patients (225) had a gcs above 8 , the results were still better, when multi-dural stabs method was performed. 11 the final results in terms of favorable and unfavorable results were calculated as per gos, there were 37.5% patients in group a and 9.4% patients in group b who had favourable results, while in group a and group b, 62.5% and 90.60% patients, respectively, had unfavourable results. similar findings are also reported in another study i.e. favourable outcomes were observed in 42.02% of multi-dural stab group versus 15.09% in open dural flap group. an earlier study on severe traumatic brain injury, showed a mortality of 52.5%. however at skims, the survival rate was 77.31%, with only 22.69% mortality in patients with multi-dural stabs.8 in a study by barthélemy ej et al, after one year follow up mortality rate was 58 (40.8%) and 8 (5.6%) patients were persistent vegetative state. 2 the final outcome journal of rawalpindi medical college (jrmc); 2017;21(4): 339-343 342 was found to be unfavorable in 77 (54.2%) patients. these are the results of decompressive craniotomy while in our study in group a and group b, 20(62.5%) and 29(90.60%) respectively patients had unfavorable results. in present study there were 12 (37.5%) patients in group a and 3 (9.4%) patients in group b who had favorable results signifying the importance of multiple dural slits technique. phan k et al conducted a literature search using major online databases and a manual search of references on the topic of craniotomy and craniectomy for evacuation of subdural hematoma . the outcome variables were analyzed which included residual sdh, revision rate, and clinical outcome. 4six comparison studies, with a total number of 2006 craniotomy and 451 craniectomy patients, fulfilled the inclusion criteria. patients who underwent craniectomy scored significantly lower on the glasgow coma scale at the time of initial presentation. postoperatively, the rate of residual sdh was significantly lower in the craniectomy group than the craniotomy group (p = 0.004), with no difference in the revision rate. the odds of a poor outcome at follow-up was found to be lower in the craniotomy group (50.1% vs. 60.1%, respectively; p = 0.004). similarly, mortality rates was lower in the craniotomy group than the craniectomy group (p = 0.004). hutchinson pj et al performed a study on patients with traumatic brain injury and refractory elevated intracranial pressure (>25 mm hg), who underwent decompressive craniectomy. 7 the primary outcome was the rating on the extended glasgow outcome scale (gos-e) (an 8-point scale, ranging from death to "upper good recovery" (no injury-related problems) at 6 months. the primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. if the model was rejected, that would indicate a significant difference in the gos-e distribution, and results would be reported descriptively. the gos-e distribution differed between the two groups (p<0.001). the proportionalodds assumption was rejected, and therefore results are reported descriptively. at 6 months, the gos-e distributions showed 26.9% deaths among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group. at 12 months, the gos-e distributions revealed deaths 30.4% among 194 surgical patients versus 52.0% among 179 medical patients. surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm hg after randomization (median, 5.0 vs. 17.0 hours; p<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, p=0.03).so this study also shows the importance of decompressive craniectomy in reducing the mortality rate among head injury patients. kurland db et al showed in their study that decompressive craniectomy is an effective means of controlling elevated icp and is life saving, which accounts for the dramatic rise in the use of this procedure . 9 this study is in agreement in present study which suggests that decompressive craniotomy, when combined with multiple dural slits, then it is helpful in increasing the favourable outcome of head injuries.optimal selection of surgical modality is unclear and decision may vary with surgeon's experience. 21 in selective cases of few unfavorable clinical findings, co may also be an effective surgical option for asdh. although dc remains to be standard of surgical modality for patients with poor clinical status, co can be an alternative considering the possible complications of dc. conclusion treatment of acute subdural hematoma by decompressive craniectomy with multi dural stabs technique has more favorable results (using gos) than decompressive craniectomy with open-dural flap technique. references 1. bhat ar, kirmani ar, wani ma. decompressive craniectomy with multi-dural stabs–a combined (skims) technique to evacuate acute subdural hematoma with underlying severe traumatic brain edema. asian journal of neurosurgery 2013;8(1):15-19. 2. barthélemy ej, melis m, gordon e, ullman js, germano im. decompressive craniectomy for severe traumatic brain injury: a systematic review. world neurosurgery 2016;88:411-20. 3. khan b, khan afridi ea, khan b, khan sa. decompressive craniectomy for acute subdural haematoma with expansile duraplasty versus dural-slits. j ayub med coll abbottabad 2016 ; 28(2):285-88. 4. ghosh ak, piek j, balan c, alliez b, cushing h, guerra wk. different methods and technical considerations of decompressive craniectomy in the treatment of traumatic brain injury. indian journal of neurosurgery 2017;6(01):36-40. 5. fountain dm, kolias ag, lecky fe, bouamra o, lawrence t. survival trends after surgery for acute subdural hematoma in adults. annals of surgery 2017;265(3):590-95. 6. melo jr, di rocco f, bourgeois m, puget se c. surgical options for treatment of traumatic subdural hematomas in children younger than 2 years of age. journal of neurosurgery: pediatrics 2014;13(4):456-61. 7. hutchinson pj, kolias ag, timofeev is, corteen ea. trial of decompressive craniectomy for traumatic intracranial hypertension. new england journal of medicine 2016;375(12):1119-30. journal of rawalpindi medical college (jrmc); 2017;21(4): 339-343 343 8. kolias ag, kirkpatrick pj, hutchinson pj. decompressive craniectomy: past, present and future. nature reviews neurology 2013 ;9(7):405-15. 9. kurland db, khaladj-ghom a, stokum ja, carusillo b. complications associated with decompressive craniectomy. neurocritical care 2015 ;23(2):292-304. 10. rumalla k, bijlani p, reddy ay, mittal mk. decompressive craniectomy reduces inpatient mortality in subdural hematoma. annals of neurology 2015 1;78:69-72. 11. kramer ah, deis n, ruddell s, couillard p, zygun da. decompressive craniectomy in patients with traumatic brain injury: are the usual indications congruent with those evaluated in clinical trials?. neurocritical care 2016;25(1):10-19. 12. phan k, moore jm, griessenauer c, dmytriw aa. craniotomy versus decompressive craniectomy for acute subdural hematoma: systematic review and meta-analysis. world neurosurgery 2017 ;101:677-85. 13. karibe h, hayashi t, hirano t, kameyama m, nakagawa a. surgical management of traumatic acute subdural hematoma in adults: a review. neurologia medicochirurgica. 2014;54(11):887-94. 14. chaturvedi j, botta r, prabhuraj ar, shukla d, bhat di, devi bi. complications of cranioplasty after decompressive craniectomy for traumatic brain injury. br j neurosurg 2016;30:264–68. 15. shiomi n t,echigo h, oka m, nozawa m, okada s. emergency decompressive craniotomy in the emergency room was effective in severe acute subdural hematoma treatment. neurological surgery 2017; 45( 2): 155-58. 16. barret r, rousseau j, mypinder s, donald e. craniotomy versus craniectomy for acute traumatic subdural hematoma in the united states: a national retrospective cohort analysis. world neurosurgery 2016; 88: 25-31. 17. edoardo p, caspani ml,iaccarino c, pastorello g, salsi p,viaroli e.intracranial pressure monitoring after primary decompressive craniectomy in traumatic brain injury: a clinical study.acta neurochirurgica 2107; 159( 4): 615-22. 18. honeybul s, janzen c, kruger k, ho km. decompressive craniectomy for severe traumatic brain injury: is life worth living? clinical article. journal of neurosurgery 2013;119(6):1566-75. 19. sam z, soon s, lin ck, iao ks, yang lh.intracranial pressure monitoring alone: not an absolutely reliable tool after decompressive craniectomy for traumatic acute subdural hematoma.journal of medical sciences 2016;36(6): 217-21. 20. piedra mp, nemecek an, ragel bt. timing of cranioplasty after decompressive craniectomy for trauma. surgical neurology international 2014;5::25-29 21. kwon r, sub y, yang kh,lee yh.craniotomy or decompressive craniectomy for acute subdural hematomas: surgical selection and clinical outcome.korean journal of neurotrauma 2016;2,( 1): 22-27. 22. essen v, thomas a, godard cw, ruiter d.neurosurgical treatment variation of traumatic brain injury: evaluation of acute subdural hematoma management. journal of neurotrauma 2017; 34 (4): 881-89. 23. bonadio le1, mello rg1, haas lj, boer ht.decompressive craniectomy (dc)-comparative study of 30-day mortality in surgeries of severe brain trauma with subdural hematoma, with and without dc. brazilian neurosurgery 2017;36(01): 21-25. 24. grindlinger ga, skavdahl dh, ecker rd, sanborn mr. decompressive craniectomy for severe traumatic brain injury: clinical study, literature review and meta-analysis. springerplus. 2016;5(1):1605. 25. kolias a g,adams h,timofeev i,czosnkya m.decompressive craniectomy following traumatic brain injury: developing the evidence base. british journal of neurosurgery 2016;30(2): 246-50. summary journal of rawalpindi medical college (jrmc); 2017;21(1): 29-32 29 original article association of etiological and pathological features of brain abscess with outcome mushtaq ahmad mian1, saleem abbasi2, fazal amin khan 1, muhammad usman 3 1. department of neurosurgery , rehman medical institute, peshawar; 2. children hospital, pims, islamabad; 3 department of neurosurgery, gaju khan medical college, swabi abstract background: to study the etiological and pathological factors of brain abscess and to relate with the final outcome. methods: in this observational study patients with brain abscess were observed in detail with the clinical profile, etiology, microbiology and their final outcome after one year.chi-square test was applied to associate etiological and pathological factors with management outcome. results: the majority of patients were in their 2nd and 3rd decade of life with two third proportion comprising of males. the most frequent etiological factor was chronic suppurative otitis media (csom) ( 55%),followed by head injury (12% ) and congenital heart disease (10%). microbiological data revealed 16% streptococci, 10% staph. aureus, 7% staph. epidermidis and 5% proteus as major pathogens in the study patients. head injury and csom were found associated with death and morbidity in this study. conclusion: brain abscess has multi dimensional causes. csom and head injury were found associated with death and severe morbidity as hemiparesis and fits. ct findings and microbiological data were not associated with outcome. key words: brain abscess, head injury, chronic suppurative otitis media introduction brain abscess is a very serious life threatening infection of the brain parenchyma.1 it was very lethal in the preantibiotic era, however, despite the advent of modern imaging facilities, neurosurgical techniques and new antibiotics, brain abscess remains a potentially fatal central nervous system (cns) infection.2,3 the common causes of brain abscess are direct trauma to the brain or spread of infection from contiguous nonneuronal tissue and hematogenous seeding.4 currently the mortality rate from brain abscess is approximately 10%. 5 however, if the abscess ruptures into the ventricular system, the mortality rate may be 80%.5 morbidity in survivors is generally due to residual neurologic defects, increased incidence of seizures due to scar tissue foci, or neuropsychiatric changes.6 the etiological factors of this brain abscess are suppurative process in middle ear, mastoid and paranasal sinuses.7 hematogenous spread can occur through primary foci that include pulmonary infections, endocarditis, dental abscess, skin pustules. post traumatic brain abscess can result from penetrating injuries, compound depressed fractures and after craniotomy.7many predisposing factors have been identified, these include congenital heart disease with a right-to-left shunt, infections of the middle ear, mastoid, paranasal sinuses, orbit, face, scalp, penetrating skull injury, comminuted skull fracture or intracranial surgery including insertion of ventriculoperitoneal shunts, dermal sinuses and abnormal immune functions.6,7 causative agents vary from time to time according to geographic distribution, age and underlying medical condition of the patients, and the way the infection was contracted. a wide variety of organisms can cause brain abscess, depending on the portal of entry, and up to one third may be polymicrobial.8 the prognosis of brain abscess depends on a number of factors but with the availability of effective antibiotics, ct scan and improved surgical techniques, the outcome of brain abscess has dramatically improved but still needs further verification1,2. patients and methods this cross sectional study was conducted at the department of neurosurgery, pakistan institute of medical sciences, shaheed zulfiqar ali bhutto medical university, islamabad. a total of 43 patients presenting with brain abscess were enrolled in the study in three years time period from january 2008 to january 2011. a written informed consent was taken from all patients before participation in the study. the study information was gathered on a structured proforma specifically designed for the study. in this study all patients operated in neurosurgery journal of rawalpindi medical college (jrmc); 2017;21(1): 29-32 30 department of pims between january 2008 and 2011 who were diagnosed to have brain abscess were included in the study. these were both males and female patients and of all age groups including children and adults. patients who were treated medically were excluded from the study. the information of patient’s baseline characteristics and clinical signs and symptoms was recorded. the other details during hospitalization, the information regarding management i.e. laboratory work-up, treatment strategy and outcome was also recorded. condition of the patients was assessed and recorded at each follow-up till one year. the study parameters were associated with the management outcome at the time of discharge of patients. descriptive analysis was done to calculate the proportions, percentages for categorical variables. means and standard deviations were calculated for continuous numerical variables. chi-square test was applied to see the association between etiological and pathological study parameters with the outcome of patients. results in this study the mean + sd age of patients was 26.7 + 15.5 years ranging from 1-68 years. most of the patients 16 (37.2%) and 11 (25.5%) were in their 2nd and 3rd decade of life respectively. male gender was preponderant 28 (65.1%) (table 1). analysis was done by making two categories; one patients who recovered after management and second category comprised of those who died or had disability. the most prevalent cause of brain abscess in this study was csom and head injury. left csom was found related to death or disability compared to recovery (50.0% vs 17.9%), however, it was not found statistically significant. similarly, head injury was also found proportion wise related to death and disability (25.0% vs 10.2%). meningitis was also found proportion wise associated with death and/or disability in the study (25.0% vs 2.5%). since the two categories were not equal in numbers and very few but only 4 cases had table 1: baseline characteristics of study patients(n=43) age categories (years) number %age 1 to 10 4 9.3% 11 to 20 16 37.2% 21 to 30 11 25.5% 31 to 40 5 11.6% 41 to 50 1 2.3% 51 or above 6 13.9% sex male female 28 15 65.1% 34.9% table 2: association of etiological factors with management outcome (n=43) recovery (n=39) death and/or disability (n=4) p-value right csom 12 (30.7%) 0 (0.0%) 0.56 left csom 7 (17.9%) 2 (50.0%) 0.18 head injury 4 (10.2%) 1 (25.0%) 0.40 congenital heart disease 4 (10.2%) 0 (0.0%) 1.0 b/l csom 3 (7.6%) 0 (0.0%) 1.0 meningitis 1 (2.5%) 1 (25.0%) 0.17 pulmonary metastasis 1 (2.5%) 0 (0.0%) 1.0 sinusitis 1 (2.5%) 0 (0.0%) 1.0 others 6 (15.3%) 0 (0.0%) 1.0 table 3: association of investigative parameters with management outcome (n=43) recovery (n=39) death and/or disability (n=4) pval ue ct findings temporal 19 (48.7%) 1 (25.0%) 0.61 cerebellar 6 (15.3%) 1 (25.0%) 0.52 frontal 4 (10.2%) 1 (25.0%) 0.40 fronto-parietal 4 (10.2%) 0 (0.0%) 1.0 parietal 4 (10.2%) 0 (0.0%) 1.0 parieto-occipital 2 (5.1%) 0 (0.0%) 1.0 temporo-parietal 0 (0.0%) 1 (25.0%) 0.09 culture results no growth 23 (58.9%) 2 (50.0%) 1.0 streptococcus pneumonia 6 (15.3%) 1 (25.0%) 0.52 staph. aureus 4 (10.2%) 0 (0.0%) 1.0 staph. epidermidis 3 (7.7%) 0 (0.0%) 1.0 proteus spp 2 (5.1%) 0 (0.0%) 1.0 pseudomonas 1 (2.5%) 0 (0.0%) 1.0 acenobacter 0 (0.0%) 1 (25.0%) 0.09 death/disability, the statistical significance was not proven. (table 2). the investigative parameters of the study i.e. ct findings and microbiology findings were associated with the two defined outcome categories. it was found out that frontal and temporoparietal brain abscess was proportion wise related to death or disability in the study (25.0% vs 10.2%) and (25.0% vs 0%) respectively, however, no significant journal of rawalpindi medical college (jrmc); 2017;21(1): 29-32 31 associated could be proven statistically. moreover, temporal and cerebellar brain abscess was equally distributed among the two management categories. on microbiology, most of the study cases had no growth, however, strep. pneumoniae was found proportion wise related to death and/or disability in the study (25.0% vs 15.6%). similarly, acinobacter was also found almost significantly associated with death and/or disability (25.0% vs 0%). (table 3) .on the 6 month follow-up, 37 (86.0%) patients had good recovery whereas 3 (6.9%) had moderate disability while 1 (2.4%) patient had an episode of fits. on the follow-up after 1 year, 40 (93.0%) had good recovery (gos-5) and 1 (2.4%) patient had moderate disability (gos-4). discussion in present study the most prevalent causative factors of brain abscess were csom, head injury, congenital heart disease and meningitis. ct imaging showed that temporal, cerebellar and frontal abscess were the regions of brain affected. it was found out that left csom, head injury and meningitis were prevalently related to poor management outcome i.e. death or disability in the present study. previous studies have also found a comparable trend of contiguous, haematogenous and neurosurgical or trauma being the main source of brain abscess and the primary driver of poor outcome.9,10 a recent retrospective analysis by helweg-larsen j et al reported that contiguous and haematogenous abscesses were seen in majority of their study cases followed by surgical or traumatic.11 they found out that brain abscess caused by meningitis was more likely to have adverse outcome after management. lakshmi v et al witnessed that otogenic abscesses were the main source in their study followed by post traumatic abscess.6 moreover, they found that csom continues to be the most frequent predisposing condition in all age groups. there is other evidence as well documenting csom as a major source of brain abscess12,13. direct extension may also occur through osteomyelitis in the posterior wall of the frontal sinus, sphenoid, and ethmoid sinuses and this path of intracranial extension is quite often associated with subacute and chronic otitic infection and mastoiditis than with sinusitis. otogenic abscess occurs almost exclusively in the temporal lobe and cerebellum, while abscess associated with sinus infection is predominantly frontal14. this was validated by our results as well, where we witnessed csom being the single most source of abscess and its poor outcome. in this study as per ct scan temporal, frontal and cerebellar abscess were the most frequent, however, they have no association with death and/or disability. however, proportion wise temporoparietal abscess was found related to death or disability. a study by lakshmi v et al reported that trend of frontal, temporal, parietal and cerebellar brain abscess is on a rise.6 another study by muzumdar d et al also witnessed that temporal, parietal and occipital brain abscesses were predominant in their analysis.15 microbiological findings were normal in majority of cases, however, strep. pneumonia and acenobacter were found related to death or disability in this study. helweg-larsen j et al witnessed that streptococcus species and staphylococci infections have role in poor outcome of brain abscess.11 moreover, previous literature validated our findings that otogenic abscesses are often associated with streptococcus milleri and streptococcus pneumonia organisms.16,17 because brain abscess is a serious life threatening and quality of life affecting infection, it must be diagnosed early and treated aggressively. the outcome of brain abscess has improved over the past years, due to tremendous improvements in cranial imaging techniques, availability of antimicrobial treatment regimens, and the introduction of minimally invasive neurosurgical procedures. mortality has declined from 40% in the 1960s to 15% noted in the past decade. at current, 70% of patients with brain abscess achieve good outcome, with no or minimal neurologic sequelae. though data on functional and neuropsychological evaluation after brain abscess are lacking and makes the ground for further detailed research on this topic.18 microbiological and radiological procedures are the accurate and key diagnostic tools for brain abscess provided timely presentation and initiation of treatment. treatment requires a combination of antimicrobials, surgical intervention and eradication of primary infected foci. a high index of clinical suspicion with early intervention would definitely have a better outcome.19 conclusion 1. main source of brain abscess is csom followed by head injury, congenital heart disease and meningitis which were related to poor outcome. 2. frontal, parietal and cerebellar sites were common for brain abscess. frontoparietal site found closely related to death and disability. 3. strep. pneumonia and acenobacter pathogens were found related to death or disability. the etiological factors, microbiology and radiological journal of rawalpindi medical college (jrmc); 2017;21(1): 29-32 32 evidence derives the management outcome of brain abscess. references 1. ko sj, park kj, park dh, kang sh, park jy. risk factors associated with poor outcomes in patients with brain abscesses. j korean neurosurg soc 2014; 56: 34-41 2. sudhaharan s, chavali p, vemu l. anaerobic brain abscess. iran j microbiol. 2016; 8: 120-24. 3. sarmast ah, showkat hi, bhat ar. analysis and management of brain abscess; a ten year hospital based study. turk neurosurg 2012;22:682-89. 4. lakshmi k, santhanam r, chitralekha s. brain abscess as a complication of chronic thromboembolic pulmonary hypertension. j clin diagn res 2013; 7: 2027–29 5. muzumdar d, jhawar s, goel a. brain abscess: an overview. int j surg 2011; 9: 136-44 6. lakshmi v, umabala p, anuradha k, padmaja k. microbiological spectrum of brain abscess.pathol res int 2011; 2011:112-15 7. park sy, park kh, cho yh, choi sh. brain abscess caused by enterococcus avium. infection & chemotherapy 2013; 45:335–8. 8. romero oap, mara cristina pm, daniel d, diogo l, ernesto vj. brain abscess due to staphylococcus aureus of cryptogenic source in an hiv-1 infected patient in use of antiretroviral therapy. rev inst med trop 2016; 58:34-37. 9. mustafa m, iftikhar m, latif mi, munaidy rk. brain abscess: pathogenesis, diagnosis and management strategies. int j res applied, natural soc sci 2014; 2: 299 308 10. manzar n, manzar b, kumar r, bari me. the study of etiologic and demographic characteristics of intracranial brain abscess: a consecutive case series study from pakistan. world neurosurg 2011;76:195-200 11. helweg-larsen j, astradsson a, richhall h, erdal, j. pyogenic brain abscess, a 15 year survey. bmc infectious diseases 2012; 12: 332-35 12. menon s, bharadwaj r, chowdhary a,kaundinya dv.current epidemiology of intracranial abscesses: a prospective 5 year study. j med microbiol 2008; 57: 1259– 68 13. prasad kn, mishra am, gupta d, husain n, husain m. analysis of microbial etiology and mortality in patients with brain abscess. j infection 2006; 53: 221–27 14. faraji-rad m and samini f. clinical features and outcome of 83 adult patients with brain abscess. arch iran med 2007;10:379-82 15. muzumdar d, jhawar s, goel a. brain abscess: an overview. international journal of surgery 2011; 9: 136–44 16. kao pt, tseng hk, liu cp, su sc, lee cm. brain abscess: clinical analysis of 53 cases. j microbiol immunol infect. 2003;36(2):129-36. 17. nathoo n, nadvi ss, narotam pk. brain abscess: management and outcome analysis of a computed tomography era experience with 973 patients. world neurosurg. 2011; 75(5-6):716-26 18. patel k and clifford db. bacterial brain abscess. neurohospitalist 2014; 4: 196–204 19. qureshi hu, siddiqui aa, habib aa, mozaffar t, sarwari ar. predictors of mortality in brain abscess. j pak med assoc 2002; 52:111-14 for electronic submission of articles email of journal: journalrmc@gmail.com to view volumes of journal of rawalpindi medical college and to search by authors names , contents , keywords-visit website of the journal: www.journalrmc.com https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4906718/ https://www.ncbi.nlm.nih.gov/pubmed/?term=k%20l%5bauthor%5d&cauthor=true&cauthor_uid=24179934 https://www.ncbi.nlm.nih.gov/pubmed/?term=r%20s%5bauthor%5d&cauthor=true&cauthor_uid=24179934 https://www.ncbi.nlm.nih.gov/pubmed/?term=s%20c%5bauthor%5d&cauthor=true&cauthor_uid=24179934 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3809673/ http://www.sciencedirect.com/science/journal/17439191 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4212419/ mailto:journalrmc@gmail.com summary journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 141 original article validity of e-flow colour doppler indices in differentiating benign and malignant ovarian tumours sumera mushtaq, nuwayrah jawaid, ishtiaq hussain. department of radiology, foundation university medical college & hospital, rawalpindi abstract background: to determine the validity of pulsatility and resistive index of trans-abdominal doppler ultrasound(e-flow) in distinguishing between benign and malignant adnexal masses keeping histopathology as gold standard. methods: in this cross sectional study patients scheduled for elective surgery due to adenaxal masses were included. all patients were sonographically evaluated for pulsatility and resistance indices aided with colour e-flow doppler before the elective surgery of lesions. the performing radiologist had no information on the patients, to differentiate between benign and malignant adnexal masses based on doppler indices. the final diagnoses were based on pathological and operative findings, keeping histopathology as gold standard. results: two hundred and twenty-nine patients were recruited out of which 18 were excluded, since the masses were finally not proven to be adnexal. of the remaining 211 cases available for analysis, 163 were benign and 48 were malignant. the sensitivity and specificity of the pulsatility index for distinction were 89.57% and 85.42% and values for the resistance index were 89.57% and 89.58% respectively. conclusions: pulsatility and resistance indices with trans-abdominal doppler ultrasound (e-flow) have high accuracy in differentiating between benign and malignant adnexal masses. key words: adnexal mass, pulsatility index,resistance index,doppler ultrasound,ovarian tumours. introduction to differentiate between benign and malignant adnexal masses is of great value as therapeutic approach is markedly different between the two entities. 1 benign lesions like benign ovarian masses or functional changes need more conservative approach like either close observation or laparoscopic surgery, whereas malignant tumours require urgent laparotomy and in most of cases patient is being referred for further chemotherapy or radiotherapy by involving oncologists.2 several attempts have been made to distinguish between the conditions in the past but with the availability of high-resolution ultrasound machines, colour doppler ultrasound is a possible technique for differentiation of benign from malignant adnexal masses as well as for early diagnosis of ovarian carcinoma for several years. 3,4 some reports also showed the superiority of this technique in screening ovarian cancer while there are some other reports favouring its ability in differentiating benign from malignant tumours preoperatively. 5,6however, colour doppler application in such previous reports was often needed via transvaginal approach and this might be inconvenient to some patients. 7 currently, high-resolution colour doppler with extended flow (eflow) has been developed, resulting in higher sensitivity in detection of blood flow in minute vessels even during trans abdominal examination. 8,9therefore, the purpose of the present study was to determine the sensitivity and specificity of pulsatility index (pi) and resistance index (ri), derived from trans-abdominal colour doppler e-flow, in differentiating benign from malignant ovarian tumours. patients and methods this cross-sectional validation study was done at department of gynecology and radiology at fauji foundation hospital rawalpindi from january 2014 to december 2014.two hundred and eleven patients of ovarian masses were included in the study with nonprobability purposive sampling. all patients referred by gynecologist with suspected ovarian mass for diagnostic workup and who are going to be operated from indoor and outdoor department were included in the study. patients with disseminated disease and with severe co-morbid conditions and declared inoperable, patients with known diagnoses of ovarian malignancy which was scheduled for a second look operation and patients with past history of major pelvic surgery for non-ovarian pathological fibrosis or vascular changes journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 142 were excluded from study.doppler ultrasonography was performed using a curvilinear probe of aloka ssd 5500 in dimly lit room with comfortable temperature (22-24c) in supine position and resistive and pulsatility indices were calculated. both pulsatility index (pi) and resistance index (ri) were calculated. the value of each artery was calculated from a curve fitted to the average waveform over three cardiac cycles. the formulas used for pi and ri were pi = (sd)/ mean and ri = (s-d)/s respectively, when s is the peak doppler frequency shift and d is the minimum. signals from various areas within the tumour were determined but the lowest pi and ri were considered for data analysis. the area distribution of visualized vessels in the adnexal masses was also categorized and recorded as center of the mass, in the septum, in the papillae, at tumour wall or peri-tumor areas the final diagnosis as gold standard was based on either pathological findings or intraoperative findings in case of no pathological specimen. all of adnexal masses were divided into 2 groups as benign and malignant adnexal masses. the sensitivity and specificity of various cut-off levels of pi and ri were calculated and all data were analyzed using spss software version 16.0. resistive index (ri) is calculated as ri = [peak systolic velocity end diastolic velocity]/peak systolic velocity. value should be less than 4 for malignant mass.pulsatility index (pi) is defined as the difference between the maximum flow and the minimum flow divided by the mean and value should be less than 1 for malignant lesion. lesions were categorized as simple cyst (anechoic with a thin wall and acoustic enhancement, with or without a single thin septations), dermoid cyst(fluid layer or echogenic mural nodule with shadowing), or an endometrioma (cyst with diffuse low-level echoes with one or two thin septations and a thin wall).atypical features such as a thick wall or multiple irregular septations, lesions having nodules or solid elements.histopathological features of malignant tumours include nuclear atypia and degree of mitoses (> 12 per 10 high-power fields) p53, brca1/2 genes and other genetic mutations, solid and cystic areas, extensive haemorrhage and necrosis and degree of micro-invasion. results between january 2014 to december 2014, 229 patients initially diagnosed as ovarian tumours were recruited to undergo e-flow colour trans-abdominal, doppler ultrasound examinations. out of these eighteen patients were excluded because of pathological diagnoses of non-ovarian tumour including subserous myoma, hydrosalpinx and patients who lost follow up due to domestic reasons etc. the remaining 211 patients were analyzed. mean age (yrs) of 211 female patients was 45.29+10.51 with ranges from 20 to 80 years.histopathological examinations revealed 163 patients (77.25%) having benign tumours and 48 patients (22.75%) having malignant tumours.out of 211 patients, there were 151 patients who you were found benign (ri < 0.5) by doppler ultrasound, in which 146 patients were benign and 05 patients were found malignant histopathologically. similarly, out of 211 patients, there were 60 patients who you were found malignant (ri > 0.5) by doppler ultrasound, in which 17 patients were benign and 43 patients were found malignant histopathologically. so the sensitivity, specificity, ppv and npv of doppler ultrasound measurements (resistive index) was 89.57%, 89.58%, 96.69%, 71.67% respectively (table 1). out of 211 patients, there were 153 patients who were found benign (pi < 1) by doppler ultrasound, in which 146patients were benign and 07 patients were found malignant histopathologically. similarly, out of 211 patients, there were 58 patients who were found malignant (pi > 1) by doppler ultrasound, in which 17 patients were benign and 41 patients were found malignant histopathologically. sensitivity, specificity, ppv and npv of doppler ultrasound measurements (pulsatility index) was 89.57%, 85.42%, 95.42% and70.69% respectively(table 2). table 1:doppler usg (resistive index) with histopathology histopathology total benign malignant doppler measurements (resistive index) benign 146 5 151 malignant 17 43 60 total 163 48 211 table 2:doppler usg (pulsatility index) with histopathology histopathology total benign malignant doppler measurements (pulsatility index) benign 146 7 153 malignant 17 41 58 total 163 48 211 discussion ovarian pathology is 5th most common malignancy and is characterized by few early nonspecific symptoms and signs.10,11 the cure rate for disease at journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 143 early stage is 80-90 % and five-year relative survival rate for stage i is 95%. 12ultrasound abdomen is considered the best initial imaging technique while ct and mri also play a role in the minority of cases where ultrasound is inconclusive. the sonographic examination includes trans-abdominal and transvaginal scans combined with colour and pulsed doppler images. 13 the trans-abdominal scans, in comparison with transvaginal approach, also provide assessment of ascites, adenopathy, hydronephrosis, and liver metastases. on trans-vaginal studies, the field of view is much smaller compared to the field of view on trans-abdominal scans and it is also difficult to assess a mass high in pelvis. 14 many centers are now using colour doppler in early assessment of ovarian mass. combination of both morphology and doppler is more accurate than either used alone but there is no agreement as to which doppler index is best and at which level the threshold should be set to distinguish between high and low impedance flow. 15 considering the above mentioned limitations of transabdominal and endo-vaginal ultrasound we used to see the validity of e-flow colour doppler indices (pulsatility and resistive index) for detection of malignancy in ovarian tumours which were referred to radiology department for evaluation. differentiation of benign from malignant tumours is very important due to vast difference in mode of treatment and it might be achieved by several methods such as clinical signs and symptoms, serum ca 125 levels, and ultrasound.16,17 conventional ultrasound parameters for the differentiation of malignant from benign tumours are based merely on morphological features. the introduction of colour doppler ultrasound, especially high-resolution colour e-flow doppler with higher sensitivity in detection of blood flow in minute vessels, might allow a step forward from morphological to functional evaluation of the masses. the theoretical background comes from the observation that the new tumour vessels that grew as a result of angiogenesis differ from the normal vessels with respect to cellular composition, basement membrane structure and permeability. as a result, the haemodynamics of these vessels is changed. 18 considering angiogenesis as a neoplastic marker for malignancy, colour doppler ultrasound allows a better insight in the biological behaviour of the tumour and early diagnosis of cancer could become possible by detecting neo-vascularization in the tumour.19 in previous studies, some authors suggested the existence of clear cut-off points of pi and ri of benign and malignant tumours; kurjak et al reported only one false positive and two false negative results in a screening program involving 624 benign ovarian tumours and 56 malignant tumours by using a cut-off value of ri 0.4. 20 sengoku et al reported sensitivity and specificity of 81.3% and 91.7% respectively when the cutoff value of pi 1.5 was used. 21 in the present study 54% of benign and 100% of malignant including borderline tumours had detectable arterial blood flow in the tumours using a colour doppler unit. this information may enable us to conclude that tumour without detectable blood flow is very unlikely to be malignant. our cut-off pi value of 1.00, giving the sensitivity and specificity of 89.57% and 85.42%, respectively, was different from the study of sengoku et al but was consistent with the data reported by weiner et al.22 the scanning approach (trans-vaginal or trans-abdominal) and frequency of the probes might partially explain inconsistent results reported previously by different authors (zanetta et al). 23 unlike previous reports in which they firstly used trans-abdominal probe and then trans-vaginal probe is performed if trans-abdominal examination was unable to visualize, our study with e-flow colour doppler we could identify the tumour in all cases. this may be the advantage of new high-resolution ultrasound technology permitting us avoiding the inconvenience of trans-vaginal approach. all authors agree that recognition of angiogenesis as a reference point for malignant changes within the ovary has proved to be a highly sensitive parameter.24 neovascularization is an obligate event in malignant change. this recognition enables to observe the earliest stages in ovarian oncongenesis. the signs of neo-vascularization tumours, considered benign by conventional ultrasound, can be missed by insufficient evaluation of the vascularity, whereas the tumours with suspicion of malignancy would be examined more thoroughly until the expected lowest pi and ri were found.25 it is important to examine all arterial signals to find out the lowest ones in each case to reduce the bias described. the present study pertinently cater for it. conclusion 1. trans-abdominal e-flow colour doppler indices are a useful tool in preoperative diagnosis of ovarian tumours. 2.it is a objective sonological evaluation of the lesions and morphological features particularly those pointing to malignancy allows early detection and differentiation of benign and malignant tumours. thus, it can help in timely referral of malignant cases to specialist care resulting in better outcome. journal of rawalpindi medical college (jrmc); 2017;21(2): 141-144 144 references 1. yazbek j, raju sk, ben-nagi j, holland tk. effect of quality of doppler ultrasonography on management of patients with suspected ovarian cancer. lancet oncol 2015; 8:131–37. 2. chan jk, cheung mk, husain a, teng nn, west d.patterns and progress in ovarian cancer over 14 years. obstetgynecol2012, 108:521-28. 3. hamper um, sheth s, abbas fm, rosenshein nb. transvaginal color doppler sonography of adnexal masses: differences in blood flow impedance in benign and malignant lesions. ajr am j roentgenol 1993;160:1225-28 4. yazbek j, helmy s, ben-nagi j, holland t. value of preoperative ultrasound examination in the selection of women with adnexal masses for laparoscopic surgery. ultrasound obstet gynecol 2013; 30: 883-88. 5. stein sm, laifer-narin s, thomsom rd. value of gray-scale, color doppler, and spectral doppler sonography in differentiation of benign and malignant adnexal masses. american journal of roentgenology 2015; 184(2):281-86. 6. enakpene ca, omigbodun ao, goecke tw. preoperative evaluation and triage of women with suspicious adnexal masses using risk of malignancy index. j obstet gynaecol res 2009; 35:131–18. 7. fleischer ac, lyshchik a, jones hw jr. contrast enhanced transvaginal sonography of benign versus malignant ovarian masses: preliminary findings. j ultrasound med 2008; 27:1011–18. 8. marchesini ac, magrio fa, berezowski at. critical analysis of doppler velocimetry in the differential diagnosis of malignant and benign ovarian masses.j womenshealth . 2013;17(1):97-102. 9. madan r, narula mk, chitra r, bajaj p. e-flow color doppler imaging evaluation of adnexal masses. indian j radiol imaging 2014; 14:365-72. 10. murta ef and nomelini rs.early diagnosis and predictors of malignancy of adnexal masses.curr opin obstet gynecol 2014; 8: 14-19. 11. zafar af, fazil a, asifa a, karim a, akmaln. clinical manifestations of benign ovarian tumors. ann ke med coll. 2015; 11:258-59. 12. fields mm and chevlen e. ovarian cancer screening: a look at the evidence. clin j oncol nurs. 2014;10:77-81 13. timmerman d, valentin l, bourne th. measurements to describe the sonographic features of adnexal tumors: a consensus opinion from the international ovarian tumor analysis (iota) group. ultrasound obstet gynecol 2015;16:500-04. 14. vuento sh, pirhonen jp, mäkinen ji.comparison of tranvaginal ultrasonography with color doppler ultrasound in assessment of asymptomatic postmenopausal women with suspected ovarian tumours. cancer 2016; 92:114– 17. 15. ahmed kk, shaukat a, khosa hl, rashid n. the role of ultrasound in diagnosis of gynaecologic / pelvic tumors. ann ke med coll 2011; 7: 319-23 16. hogdall e: cancer antigen 125 and prognosis. curr opin obstet gynecol 2008, 20:4-8 17. umemoto m, shiota m, shimono t, hoshiai h. preoperative diagnosis of ovarian tumors, focusing on solid area based on diagnostic imaging. j obstet gynaecol res 2016; 32: 195201 18. chan jk, cheung mk, husain a.patterns and progress in ovarian cancerover 14 years.obstet gynecol2016, 108:52128 19. dock w, grabenwoger f, metz v, eibenberger k, farres mt. tumor vascularization: assessment with duplex sonography. radiology 2011; 181:241-44. 20. kurjak a, zalud i, alfirevicz. evaluation of adnexal masses with transvaginal color ultrasound. j ultrasound med.2012; 10, 295-97. 21. sengoku k, satoh t, saitoh s, abe m, ishikawa m. evaluation of transvaginal color doppler sonography, transvaginal sonography and ca 125 for prediction of ovarian malignancy. int j gynaecol obstet, 2004; 46, 3943. 22. weiner z, thaler i, beck d. differentiating malignant from benign ovarian tumors with transvaginal color flow imaging. obstet gynecol 2002;79, 159-62. 23. zanetta g, vergani p, lissoni a. color doppler ultrasound in the preoperative assessment of adnexal masses. acta obstet gynecol scand2014; 73, 637-41. 24. levine d, asch e, mehta ts, broder j.assessment of factors that affect the quality of performance and interpretation of sonography of adnexal masses. j ultrasound med 2008;27:721–28. 25. brown dl, doubilet pm, miller fh.benign and malignant ovarian masses: selection of the most discriminating grayscale and doppler sonographic features. radiology 1998; 208:103–110. http://www.ncbi.nlm.nih.gov/pubmed?term=%22marchesini%20ac%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22magrio%20fa%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed?term=%22berezowski%20at%22%5bauthor%5d http://www.ncbi.nlm.nih.gov/pubmed/18240986 https://www.ncbi.nlm.nih.gov/pubmed/?term=brown%20dl%5bauthor%5d&cauthor=true&cauthor_uid=9646799 https://www.ncbi.nlm.nih.gov/pubmed/?term=doubilet%20pm%5bauthor%5d&cauthor=true&cauthor_uid=9646799 https://www.ncbi.nlm.nih.gov/pubmed/?term=miller%20fh%5bauthor%5d&cauthor=true&cauthor_uid=9646799 summary journal of rawalpindi medical college (jrmc); 2018;22(1): 14-17 14 original article screening for peripheral arterial disease in patients with coronary artery disease using ankle-brachial index hajira sarwar 1, inamullah shah 1, sajida shah 2, eitezaz ahmad bashir 1 1.department of surgery, fauji foundation hospital, rawalpindi ;2.department of radiology, shifa international hospital, islamabad abstract background : to screen for presence of peripheral arterial disease (pad) in coronary artery disease (cad) patients using anklebrachial index (abi). methods: in this descriptive cross-sectional study patients (n=310) above the age of 40 years of both genders, admitted with diagnosis of coronary arterial disease were included. smokers and patients with hyperlipidemias, diabetes mellitus, or ankle brachial index (abi) >1.5 were excluded. patients with abi of less than 0.9 in one or both lower limbs were diagnosed to have pad. results : out of 310 patients, 26.77% (n= 83) had abi < 0.9. majority of these patients (85.1%) were asymptomatic. abi was able to detect pad in all these patients. there was no statistical difference in prevalence between genders. conclusion: arterial brachial index is able to dectect peripheral arterial disease in patients with coronary artery disease . key words:peripheral artery disease, coronary artery disease, ankle-brachial index. introduction peripheral arterial disease (pad) is atherosclerosis of arteries beyond aortic bifurcation.1 atherosclerosis can affect multiple vascular beds simultaneously. so peripheral arterial disease often co-exists with symptoms of systemic atherosclerosis elsewhere, including cerebrovascular disease and coronary artery disease (cad). 2 patients with pad are 3-6 times more likely to develop myocardial infarction (mi) and stroke than patients without pad.3 overall mortality rate after the diagnosis of pad has been shown to be as much as 30% at 5 years and 70% at 15 years and it is mainly attributed to the coexistence of cad. 3 the evidence that pad represents an independent indicator for cardiovascular morbidity has triggered a renewed clinical interest in pad and its epidemiology.4 the process of development of atheromatous plaque is similar in all genders, ethnicities and in all geographical locations. however, the rate of growth of plaque is more rapid in patients with certain risk factors. these include diabetes mellitus, hypertension, obesity,tobacco smoking, and a genetic predisposition to the disease.5 frequency of coexisting cad with peripheral arterial disease accounts from 28% to 94%.6 race, ethnicity and geographical location have a bearing on the coexistence of peripheral disease with cad,[6]it is necessary to be aware of the extent of this association in pakistani patients. 6 it has been reported that some patients, particularly those more than 70 years old, may not present with typical symptoms of pad.7 patients undergoing conservative or surgical treatment for cad may also be suffering from asymptomatic pad. admission in hospital of patients with cad is an opportunity to screen other vascular beds for atherosclerosis. it is important to know the status of peripheral arteries in patients with cad for another reason. these patients are prone to arrhythmias that can lead to embolism to the lower limbs. differentiating an acute ischemic event in the limb, which is reversible with prompt treatment, becomes easier when the status of peripheral pulses in the limb is already known.8 calculating the ankle-brachial index (abi) is a costeffective,non-invasive and objective method of detecting the presence and severity of peripheral arterial disease.9 abi ratio less than 0.9 is an indication of presence of pad with 95% sensitivity and 100% specificity.1 an abi value 0.9 -1.2 is considered normal, 0.4 0.9 indicates mild to moderate disease in the limb and a value lesser than 0.4 indicates severe peripheral arterial disease or critical limb ischemia, implying a threat to viability of affected limb.therefore, abi has been shown to be an effective screening tool to diagnose pad in asymptomatic patients and to estimate severity of the disease in symptomatic ones.1 patients and methods this descriptive cross-sectional study was conducted in the surgery department and coronary care unit of fauji foundation hospital, rawalpindi from october 2014 to march 2017. consecutive patients (n=310) were selected for the study after obtaining their journal of rawalpindi medical college (jrmc); 2018;22(1): 14-17 15 informed consent. sample size was calculated using who sample size calculator. anticipated population proportion was 0.28, with a confidence interval of 95%. patients above 40 years of age, of either gender, admitted in coronary care unit with diagnosis of cad, were included in the study.diagnosis of cad was confirmed if there was evidence of myocardial ischemia or infarction on ecg, coronary angiogram or myocardial perfusion scan (thallium201 scan). patients having ankle brachial index value of more than 1.5 were excluded as this is usually related to noncompressible vessels in legs. patients with history of diabetes mellitus, smoking and hyperlipidemia were also excluded as these are independent risk factors for pad.10 each patient was then evaluated for peripheral vascular disease. variables included were history of intermittent claudication or rest pain, and physical examination findings of chronic ischemia, arterial pulses and abi value. abi was obtained by dividing systolic blood pressure (sbp) in lower limb by the sbp in upper limb. if sbp was unequal in both upper limbs, the higher reading was used and limbs evaluated by performing a ct angiogram. diagnosis of pad was made when abi was less than 0.9 in one or both lower limbs.the sbp in the arm was recorded with a standard sphygmomanometer and stethoscope while that in ankle was recorded using a portable doppler ultrasound sensor.all recordings were made with the patient at rest and lying down in bed. all patients with abi <0.9 were evaluated for pad using ct angiogram. descriptive statistics were calculated for qualitative variables. frequency of pad in patients with cad was analyzed as percentage, and comparison of pad in males and females was done using chi-square test with a statistical significance of 0.05 or less. results a total of 310 patients with cad were included in the study with their ages ranging between 44 and 90 years. mean age of patients was 60.38 8.8 years. median age was 59 years. 46.5% (n=144) patients were male while 53.5% (n=166)patients were female.the ankle brachial index values ranged from 0.5 to 1.2 (table 1). out of these, 83 were found to have abi of less than 0.9(table2).ct angiogram confirmed presence of peripheral vascular disease of varying degree in all these patients. out of all patients with pad, 37 were male and 46 were female(table 3). chi square test was applied to compare prevalence of pad in males and females and it was found to be not significant statistically (p = .394).patients diagnosed with cad presented with angina, myocardial infarction or congestive cardiac failure (table 4). most of the patients diagnosed to have coexistent pad had asymptomatic disease. only 18 patients were symptomatic (table 5). table 1: ankle-brachial index abi value number percentage .5 3 1.0 .6 17 6.5 .7 29 15.8 .7 1 16.1 .8 33 26.8 .9 96 57.7 1.0 99 89.7 1.1 24 97.4 1.2 8 100.0 total 310 table2: frequency of abi <0.9 abi value number percentage abi <0.9 83 26.8 abi 0.9 or more 227 73.2 total 310 100.0 table 3: gender comparison (p = .394) gender of patient abi value total <0.9 0.9 or more male 37 107 144 female 46 120 166 total 83 227 310 table4:frequency of various presentations of cad presentation of cad percent of total angina 33.8% (n = 105) myocardial infarction 28.8% (n = 89) congestive cardiac failure 37.4% (n = 116) table5:symptomatic vs asymptomatic pad patients patients with pad n = 83 symptomatic 14.9% (n = 18) asymptomatic 85.1% (n = 71) discussion awareness regarding association of pad with cad is grossly deficient amongst all levels of health care professionals.11 this accounts for inability to diagnose the condition at a stage when limb salvage is possible. there is a general perception amongst pakistani physicians that peripheral arterial disease is relatively uncommon in pakistan. another misconception is that journal of rawalpindi medical college (jrmc); 2018;22(1): 14-17 16 diagnosis of pad requires resorting to expertise of a vascular surgeon and expensive investigations like angiography. therefore, patients even with coronary disease are not investigated for pad unless they have symptoms suggesting it.principal finding of this study was that by using measurement of ankle-brachial index, it is possible to diagnose all patients harbouring latent pad. this conforms to previous studies done in different ethnic populations.1,12 in patients admitted with cad in a tertiary care hospital at rawalpindi, 26.77% were suffering from overt or asymptomatic peripheral arterial disease in one or both lower limbs. this finding is similar to kriessmann et al, who reported a prevalence of 28%. 13 a similar study by siddiqi et al, conducted at karachi reported a frequency of pad of 17.7% in patients with cad. 14 prevalence in our study would be even higher if we account for the fact that diabetics, smokers and patients with hyperlipidemia were excluded in our study. the different sampled population may be the reason for this finding. population in this study was mostly from northern pakistan, including northern punjab, khyber pakhtunkhwa and gilgit/ baltistan. patients with symptomatic pad were found to be 14.9%. symptoms included intermittent claudication, rest pain or both, unilaterally or bilaterally. hennion et al reported that only 10% patients with pad were symptomatic whereas siddiqi et al reported 12% patients who had symptoms. 14,15 it is pertinent to note that diabetics, who were not included in our study but included by siddiqi et al, are well known to have an asymptomatic pad. a ratio of 85.1%, even after excluding diabetic patients, indicates that most patients with pad are asymptomatic. this makes it imperative to look for the disease in patients who are prone to this disorder including diabetics and those who are suffering from other atherosclerotic manifestations like cad. detecting and managing pad in time can avoid preventable limb loss in these patients. there was no statistically significant difference based on gender,in prevalence of pad in patients who presented with cad, in our study (p= .394). this finding is different from the higher frequency in males as reported by siddiqi et al.14 practice guidelines of 2005 by american heart association (aha) describe male gender as a risk factorfor pad.16 however, many recent studies report similar or higher prevalence of pad in women.17-20 sigvant et al reported a prevalence of 16.5% and 19.2% in men and women respectively in a population based study.17 the difference was analyzed to be statistically insignificant. this is similar to the findings in our study. the present study is of a singular kind in pakistan for three reasons. firstly, it confirms that abi is a sensitive measure of presence of pad in pakistani population. secondly, no such study has previously attempted to assess the population for presence of pad in cad patients in northern pakistan. finally, in our study, confounding variables like smoking, hyperlipidemias and diabetes mellitus were excluded unlike the previous studies elsewhere.21,22 this was important to establish a direct association between coronary and peripheral arterial disease as smoking and diabetes mellitus are known risk factors for both.23,24 our study could have been further strengthened by inclusion of patients from other hospitals in the region and by a larger sample size. 25 conclusion 1.it is important to realize by primary healthcare professionals, cardiologists as well as surgeons that patients with cad may also be suffering from overt or latent peripheral arterial disease and vice versa. 2.pad can easily be ruled out by measuring abi. keeping this in mind while treating either condition, we can prevent and preempt undue morbidity and mortality. references 1. sarangi s, srikant b, rao dv, joshi l, usha g. correlation between peripheral arterial disease and coronary artery disease using ankle brachial index—a study in indian population. indian heart j. 2012; 64(1):2-6. 2. diehm. c, allenberg jr, pittrrow d, mahn m, tepohl g. mortality and morbidity in older adults with asymptomatic versus symptomatic peripheral arterial disease. circulation 2009; 120:2053-61. 3. bartholomew jr, olin jw. pathophysiology of peripheral arterial disease and risk factors for its development. cleve clin j med 2006; 73 (suppl 4): s8-14. 4. cassar k. peripheral arterial disease.bmj clin evid 2011;11:211.pmcid: pmc3275103. 5. zhang yj, wu sl, li hy, zhao qh, ning ch. comparison of arterial stiffness in non-hypertensive and hypertensive population of various age groups. zhonghuaxinxue guan bing zazhi. 2018 jan 24;46(1):56-63. 6. hur dj, kizilgul m, aung ww, rousillon kc, keeley ec. frequency of coronary artery disease in patients undergoing peripheral artery disease surgery. am j cardiol. 2012; 110(5): 736–40. 7. de winter cf, van den berge ap, schoufour jd, oppewal a. a 3-year follow-up study on cardiovascular disease and mortality in older people with intellectual disabilities.res devdisabil. 2016;53-54:115-26. 8. gabel j, jabo b, patel s, kiang s, bianchi c, chiriano j. analysis of patients undergoing major lower extremity amputation in the vascular quality initiative. ann vasc surg. 2018;46:75-82. journal of rawalpindi medical college (jrmc); 2018;22(1): 14-17 17 9. lilly sm, jacobs dr, kronmal r. arterial compliance across the spectrum of ankle-brachial index: the multiethnic study of atherosclerosis.atherosclerosis 2014;233(2): 691-96. 10. peach g, griffin m, jones kg, thompson mm, hinchliffe rj.diagnosis and management of peripheral arterial disease.bmj. 2012;345:e5208. 11. cronin ct, mccartan dp, mcmonagle m, cross ks.peripheral artery disease: a marked lack of awareness in ireland.eur j vasc endovasc surg. 2015;49(5):556-62. 12. meyer d, bureau jm, vu tri d. ankle brachial index: motivations, training, and practices among 165 general practitioners in île-de-france. j mal vasc. 2014 ;39(1):1825. 13. kriessmann a, seidlmann w, neiss a, sebening h.frequency of peripheral arterial occlusive disease in patients with coronary heart disease with and without infarction. dtsch med wochenschr. 1979 ;104(45):1604-07. 14. siddiqi ro, paracha mi, hammad m. frequency of peripheral arterial disease in patients presenting with acute coronary syndrome at a tertiary care centre in karachi. j pak med assoc. 2010;60(3):171-74. 15. hennion dr, siano ka.diagnosis and treatment of peripheral arterial disease.am fam physician. 2013;88(5):306-10. 16. hirsch at, haskal zj, hertzer nr, bakal cw. acc/aha 2005 practice guidelines for the management of patients with peripheral arterial disease. circulation. 2006;113:e463-e654 17. sigvant b, wiberg-hedman k, bergqvist d, rolandsson o, andersson b. a population-based study of peripheral arterial disease prevalence with special focus on critical limb ischemia and sex differences. j vasc surg. 2007; 45: 1185– 91. 18. moussa id, jaff mr, mehran r, gray w, dangas g. prevalence and prediction of previously unrecognized peripheral arterial disease in patients with coronary artery disease: the peripheral arterial disease in interventional patients study. catheter cardiovasc interv. 2009; 73: 719– 24. 19. he y, jiang y, wang j, fan l, li x, hu fb. prevalence of peripheral arterial disease and its association with smoking in a population-based study in beijing, china. j vasc surg. 2006; 44: 333–38 20. ato d, sawayama t. factors associated with high brachialankle pulse wave velocity in non-hypertensive and appropriately treated hypertensive patients with atherosclerotic risk factors. vasc health risk manag 2017; 13:383-92. 21. ambrosetti m, temporelli pl, faggiano p, febo o, diaco tl. lower extremities peripheral arterial disease among patients admitted to cardiac rehabilitation: the thinkpad registry.int j cardiol. 2014 feb 1;171(2):192 98. 22. pereira c, miname mh, makdisse mr, watanabe c, pesaro ae.peripheral arterial disease in heterozygous familial hypercholesterolemia.atherosclerosis.2015;242(1):174 78. 23. lu l, mackay df, pell jp.meta-analysis of the association between cigarette smoking and peripheral arterial disease.heart. 2014;100(5):414-23. 24. eshcol j, jebarani s, anjana rm, mohan v, pradeepa r. peripheral arterial disease in patients with type 2 diabetes. j diabetes complications 2014;28(6):913-17. 25. teodorescu vj, vavra ak, kibbe mr. peripheral arterial disease in women. j vasc surg. 2013;57(4 suppl):18s 26s. summary journal of rawalpindi medical college (jrmc); 2017;21(2): 153-156 153 original article low dose perioperative lidocaine infusion for postoperative pain in open cholecystectomy ahsan raza shahzad, muhammad shafiq, muhammad ali department of anaesthesia, benazir bhutto hospital and rawalpindi medical university abstract background : to compare low dose peri-operative lidocaine infusion and placebo for post-operative mean pain score and mean analgesic requirement in open cholecystectomy. methods: in this prospective randomized comparative study 120 patients, undergoing open cholecystectomy in general anaesthesia, were included. patients were randomly allocated to either lidocaine infusion (l) or saline group (s) using systematic randomized sampling with 60 patients in each group. patients in the lidocaine infusion group were given bolus injection of lidocaine 30 minutes before the skin incision followed by a continuous intraveonous via infusion pump whereas the patients in the saline group received 0.9% normal saline in equal volume and in the same manner. the infusion was continued throughout the surgery and was terminated 60 min after the skin closure. results: out of the 120 patients 34 (28.3%) were male while 86 (71.7%) were female. mean age was 41.32±11.512 years. both mean vas pain score and mean analgesic requirement were found to be significantly lower in the lidocaine group (p-values 0.04 and 0.29 respectively), as compared to controls. conclusion: peri-operative low dose systemic lidocaine appears to reduce pain in the immediate post-operative period. . key words: lidocaine, post-operative pain, open cholecystectomy. introduction post-operative pain has unpleasant nature and physiological consequences. search for safe and effective modalities for post-operative pain relief has been of great interest for perioperative physicians. optimal post-operative pain relief not only increases patient’s comfort but also intensifies his satisfaction towards surgery. provision of effective analgesia in post-operative periods also facilitates early mobilization and rehabilitation of patients. optimal post-operative pain control is associated with less post-operative cognitive impairment, enhanced quality of life and less risk of chronic post-surgical pain. effective post-operative pain relief leads to shortened hospital stay, reduces hospital costs and increased patient’s satisfaction.nsaids are commonly used for post-operative pain relief, they are easy to use but only ketorolac is available in injectable form. these drugs have potential deleterious effects on gastric and renal functions.opioids are the most commonly used drugs for post-operative pain relief. they provide excellent pain relief but they can cause delay in recovery time, nausea and vomiting and respiratory depression.regional techniques may also be used for effective post-operative pain control. 1,2 lidocaine , is amino amide type local anesthetic and class 1b antiarrhythmic drug. it has rapid onset of action and intermediate duration of action. its use in chronic neuropathic pain is well established.3 now peri-operative use of lidocaine for post-operative pain relief is a topic of interest.4 peri operative systemic lidocaine has beneficial post-operative analgesic effects.5 it also reduces post-operative analgesic requirement.3, 6,7 baral bk et al and colleagues conducted a study in 60 patients undergoing upper abdominal surgery. thirty patients received 2%lidocaine infusion and 30 patients received normal saline according to randomization. post-operative analgesic requirement were significantly reduced (142.50±37.80mg vs185.00±41.31mg p<0.001) in lidocaine group as compared to control group.6 one study shows that post-operative pain intensity is less in lidocaine group (visual analogue scale score 3.1±2.04 vs 4.5±2.9; p = 0.043).8 another study showed that there is no significant beneficial effect of peri-operative lidocaine infusion on post-operative pain relief vas (3.5 ± 1.7) in control group vs. (3.4 ±1.6) in lidocaine group. perioperative lidocaine administration has no influence on postoperative analgesic consumption.9 postoperative pain is a major issue after every surgical procedure and is a burden on hospitals because different modalities are used for postoperative pain relief.lidocaine infusion is not used for postoperative journal of rawalpindi medical college (jrmc); 2017;21(2): 153-156 154 pain relief locally and no local study is available on lidocaine for postoperative pain relief although it is an effective modality to control postoperative pain while there are international studies showing controversy in its effectiveness as an analgesic. patients and methods this prospective randomized comparative study was conducted by the department of anaesthesia at benazir bhutto hospital, rawalpindi, for 6 months from march, 2014 to august, 2014. patients of elective cholecystectomy,patients of age 1860 years and patients of asa i and asa ii physical status were included . patients with emergency surgery, with known hepatic or renal dysfunction, with cardiac dysrhythmias /atrioventricular block, having and anticipated duration of surgery more than 3 hours and with a known hypersensitivity/allergy to the study medication were excluded. patients were randomly allocated to either lidocaine infusion (l) or saline group (s) using systematic randomized sampling. patients in the lidocaine infusion group were given bolus injection of lidocaine (1.5 mg/kg slowly over 10 min) 30 minutes before the skin incision followed by a continuous iv infusion at the rate of 1.5 mg/kg/h via infusion pump whereas the patients in the saline group received 0.9% normal saline in equal volume and in the same manner. the infusion was continued throughout the surgery and was terminated 60 min after the skin closure. patients were pre-medicated with inj midazolam 1mg iv 2 hours prior to surgery. in all the patients, anesthesia was induced with inj.propofol 2.0 mg/kg, nalbuphine 0.1 mg/kg, followed by atracurium 0.5 mg/kg intravenously to facilitate the laryngoscopy and orotracheal intubation. after tracheal intubation, anesthesia was maintained with sevoflurane and 50%oxygen+50%n2o with intermittent intravenous boluses of atracurium 10 mg after every 20 min. after completion of surgery, inhalational anesthetics were stopped and the residual neuromuscular blockade was antagonized with the mixture of inj. neostigmine 0.05mg/kg and atropine 0.02mg/kg iv. infusion was continued for further 1 hour.severity of pain was monitored at 0 min, 30 min and 60 min in the immediate post-operative period. the severity of pain was assessed by asking the patient to indicate on the 10 cm line at the point that corresponded to the level of pain intensity they felt. the distance in centimeter from no pain end of visual analogue scale (vas) to the patient’s mark was used as a numerical index of the severity of pain.any patient complaining of pain immediately after extubation was considered to have a pain vas more than 4 and was managed accordingly. a patient with vas score of more than four was treated with inj. diclofenac sodium 75 mg im. if the patient’s vas remained more than four even after 30 minutes of inj. diclofenac sodium then inj. tramadol 100mg iv was given as rescue analgesic. further and subsequent doses of diclofenac were allowed after an interval of 6 hours without exceeding a total dose of 225mg in 24 hours.after one hour of observation, the patient was shifted to the surgical ward from the pacu where the severity of pain was again measured at 8, 16 and 24 hours post-op. the number of cumulative doses of injection diclofenac and tramadol given during study period were recorded. if any signs of systemic toxicity or hypersensitivity reaction of the drugs were encountered, they were treated accordingly and patient was excluded from the study. results one hundred and twenty patients were randomized into two groups by the lottery method. sixty patients were allocated to the lidocaine group while 60 patients were allocated to the control group. mean age of the patients in the study was 41.32±11.512 years. mean vas scale pain score was 3.5±1.604 and the mean analgesia requirement was 78.75±62.9 mg.there were 34 male patients while 86 patients were female. in the control group the mean age of the patients was 41.43±11.238 years, mean vas pain score was 3.8±1.802 and mean analgesia requirement was 91.25±64.903 mg (table 1). table 1 comparison of mean vas pain scores between patients belonging to lidocaine group and control group (n=120) mean vas pain score p-value lidocaine group 3.2±1.325 0.04 control group 3.8±1.802 table 2 comparison of mean analgesia requirement between patients belonging to lidocaine group and control group (n=120) mean analgesia requirement in mg p-value lidocaine group 66.25±58.734 0.029 control group 91.25±64.903 there were 18 male patients (30%) and 42 female patients (70%) in this group.mean vas pain score was journal of rawalpindi medical college (jrmc); 2017;21(2): 153-156 155 3.2±1.325 and mean analgesia requirement was 66.25±58.734 mg. the mean vas pain score and the mean analgesia requirement were compared between the two groups using independent sample t-test (table 2). discussion the mean age in our study was 41.32±11.512 years while female patients were 86 (71.7%) in number. this is in line with the so called famous 5 f’s of cholelithiasis which include female and forty. 10 the presentation of patients in our study demonstrates that the international epidemiological data presented on cholelithiasis also holds true in our region, which shows the same epidemiology as the rest of the world.the mean vas pain score of patients treated with lidocaine infusion peri-operatively in our study was found to be 3.2±1.325, which is significantly less as compared to the mean score of patients treated with placebo, 3.8±1.802. this finding can be compared with the results of mckay et al. whose study also showed a significant difference between the two groups7. these findings can also be correlated to some other studies which have shown similar results.3, 5, 11 the mean dose of analgesic required by the patients in the lidocaine group, 66.25±58.734, was also significantly lower than the mean dose required by patients in the placebo group, 91.25±64.903. this also validates the results of mckay et al. and baral bk et al.7, 8 these results can also be compared with other studies which demonstrated the efficacy of lidocaine infusion peri-operatively in reducing post-op pain.2, 3,12, 13 the results of our study are in contrast to the study done by wuethrich py et al. whose study did not show any benefit of lidocaine infusion. this may be due to the difference in the outcome variable, the small sample size of wuethrich py et al. and the nature of the procedure. as compared to 120 patients in our study wuethrich py et al. had only 64 patients with the outcome variable of length of hospital stay. the patients in the study done by wuethrich py et al. underwent laparoscopic renal surgery conferring the benefit of laparoscopy in the form of reduced post-op pain and early ambulation.9 there is a growing body of data suggesting the role of lidocaine in pain management in the immediate postoperative period but data also suggests that although lidocaine reduces post-operative pain and analgesic requirement, it does not affect the length of hospital stay and discharge timing of the patient.8, 9intravenous lidocaine should not be used in patients with arrhythmias, heart failure, coronary artery disease, adams-strokes or heart block and may be used with caution in patients with liver failure, sinusoidal bradycardia and incomplete branch block.14-17 most common side-effects are in general mild and relate to central nervous system. patients may present with: sleepiness, dizziness, metal taste, headache, blurred vision, paresthesia, dysarthria, euphoria and nausea.18-20 higher doses rapidly administered may cause tinnitus, shivering and agitation.21,22 cardiovascular changes are in general minimal with usual doses.23,24 a meta-analysis on the use of intravenous lidocaine in abdominal surgeries reports that with regard to infusion dose beginning and duration there is still not a consensus.25 conclusion lidocaine reduces mean vas pain score and mean analgesic requirement in patients undergoing open cholecystectomy. references 1. rawal n. epidural technique for postoperative pain: gold standard no more? regional anesthesia and pain medicine. 2012;37(3):310-17. 2. grimsby gm, conley sp, trentman tl, castle ep. a doubleblind randomized controlled trial of continuous intravenous ketorolac vs placebo for adjuvant pain control after renal surgery. mayo clinic proceedings; 2012: 3. grigoras a, lee p, sattar f, shorten g. perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. clin j pain. 2012;28(7):567-72. 4. choi sj, kim mh, jeong hy, lee jj. effect of intraoperative lidocaine on anesthetic consumption, and bowel function, pain intensity, analgesic consumption and hospital stay after breast surgery. korean j anesthesiol. 2012;62(5):429-34. 5. vigneault l, turgeon af, côté d, lauzier f. perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis o frandomized controlled trials. can j anaesth. 2011; 58(1):22-37. 6. de oliveira jr gs, fitzgerald p, streicher lf, marcus r-j, mccarthy rj. systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. anesthesia & analgesia. 2012;115(2):262-67. 7. baral bk, bhattarai bk, rahman tr, singh sn, regmi r. perioperative intravenous lidocaine infusion on postoperative pain relief in patients undergoing upper abdominal surgery. nepal med coll j. 2010;12(4):215-20. 8. mckay a, gottschalk a, ploppa a, durieux me. systemic lidocaine decreased the perioperative opioid analgesic requirements but failed to reduce discharge time after ambulatory surgery. anesth analg. 2009;109(6):1805-08. 9. wuethrich py, romero j, burkhard fc. no benefit from perioperative intravenous lidocaine in laparoscopic renal surgery. european journal of anaesthesiology (eja). 2012;29(11):537-43. 10. schirmer bd, winters kl, edlich rf. cholelithiasis and cholecystitis. j long term eff med implants. 2005;15(3):329-38. 11. mccarthy gc, megalla sa, habib as. impact of intravenous lidocaine infusion on postoperative analgesia and recovery journal of rawalpindi medical college (jrmc); 2017;21(2): 153-156 156 from surgery: a systematic review of randomized controlled trials. drugs. 2010;70(9):1149-63. 12. kranke p, jokinen j, pace nl, schnabel a, hollmann mw. continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. cochrane database syst rev. 2015;7:cd009642. 13. kim kt, cho dc, sung jk, kim yb. intraoperative systemic infusion of lidocaine reduces postoperative pain after lumbar surgery: a double-blinded, randomized, placebocontrolled clinical trial. spine j. 2014;14(8):1559-66. 14. moldovan m, alvarez s, romer rosberg m, krarup c. axonal voltage-gated ion channels as pharmacological targets for pain. eur j pharmacol. 2013;708(1-3):105-12. 15. detoledo jc. lidocaine and seizures. ther drug monit. 2000;22(3):320-22. 16. kindler ch, yost cs. two-pore domain potassium channels: new sites of local anesthetic action and toxicity. reg anesth pain med. 2005;30(3):260-74. 17. clarke c, mcconachie i, banner r. lidocaine infusion as a rescue analgesic in the perioperative setting. pain res manag. 2008;13(5):421-23. 18. catterall wa, mackie k. local anesthetics. in: brunton ll, lazo js, parker kl, (editors). goodman and gilman’s the pharmacological basis of therapeutics. 11th ed.new york: mcgraw-hill; 2006. 369-85. 19. olschewski a, schnoebel-ehehalt r, li y, tang b, bräu me. mexiletine and lidocaine suppress the excitability of dorsal horn neurons. anesth analg.2009;109(1):258-64. 20. lui kc and chow yf, safe use of local anaesthetics: prevention and management of systemic toxicity. hong kong med j. 2010;16(6):470-75. 21. lauretti gr. mechanisms of analgesia of intravenous lidocaine. rev bras anestesiol. 2008;58(3):280-86. 22. light ar, trevino dl, perl er. morphological features of functionally defined neuron in the marginal zone and substantia gelatinosa of the spinal dorsal horn. j com neurol. 1979;186(2):151-71. 23. kindler ch and yost cs. two-pore domain potassium channels: new sites of local anesthetic action and toxicity. reg anesth pain med. 2005;30(3):260-74. 24. sheets mf and hanck da. molecular action of lidocaine on the voltage sensors of sodium channels. j gen physiol. 2003;121(2):163-75. 25. mccarthy gc, megalla sa, habib as. impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery: a systematic review of randomized controlled trials. drugs. 2010;70(9):1149-63. ------------------------------------------------------------------ authorship: 1-3 designed the study, data analysis and manuscript writing summary journal of rawalpindi medical college (jrmc); 2017;21(2):131-135 131 original article association of maternal hypertension with intrauterine growth retardation isfandyar khan 1, israr liaquat 2, qaisar shahzad humayyon 2 1. department of paediatrics, benazir bhutto hospital rawalpindi and rawalpindi medical university; 2. department of paediatrics, holy family hospital and rawalpindi medical university. abstract background: to find out the association of intrauterine growth retardation (iugr) with maternal hypertension. methods: in this case control study 124 cases and 249 controls (thus giving the case to control ratio of 1:2.) were enrolled. all were born full term and delivered in obstetrics department . after taking verbal consent for the study the mothers were interviewed for the presence or absence of hypertension during pregnancy and their antenatal records checked (if available). to rule out the confounders, a study proforma was used to record maternal hypertension, maternal height, weight, bmi, age, anemia, socioeconomic status, preeclampsia, eclampsia, number of children, age of last born, gender, mode and date of delivery. cases and controls were identified and assigned an identification number. all the study cases were seen by the pediatrician on the first day of life, weighed properly, their length and head circumference noted and plotted on centile charts in accordance with their gender to note the presence or absence of intra uterine growth restriction (iugr). a p-value of 0.05 or less was used to see the significance of the association. results: mothers of small for gestational age (sga) babies were more than two times likely to have hypertension. both low maternal bmi and anemia in mother were significantly associated with iugr in both univariate and multivariate analysis. socioeconomic condition was also showing significant association with iugr. other factors like gravidity, maternal age, parity were not showing any association with iugr. conclusion: maternal anemia and low bmi are showing strong association with iugr while maternal hypertension is not showing a strong association. key words: maternal hypertension, intrauterine growth retardation, small for gestational age introduction the term intrauterine growth retardation (iugr) or small for gestational age (sga) is generally used for fetuses weighing less than the tenth percentile for gestational age or less than two standard deviations below the mean for gestational age.1 the factors responsible for iugr are fetal, placental, environmental and maternal. iugr affects 23.8% of new borns around the world and 75% of these affected infants are born in asia. in pakistan incidence of iugr is around 25%.2,3 among the maternal factors, hypertension is one of the main factors related with iugr.4 both chronic hypertension and pih are associated with low birth weight.5 even if the pregnant women with chronic hypertension do not develop pre eclampsia, hypertension in the presence of proteinuria will lead to restricted fetal growth.6 the term maternal hypertension is used when a blood pressure of 140/90mmhg or increase in systolic pressure of at least 30mmhg or an increase of at least 15mmhg diastolic pressure over the baseline first trimester readings is observed. the hypertension in pregnancy may be seen, as preeclampsia (hypertension with proteinuria), eclampsia (preeclampsia with seizure activity) and pregnancy induced hypertension (hypertension without proteinuria).hypertension has its role in fetal growth restriction throughout the pregnancy. usually from conception till 24 weeks of gestation, it is the chronic hypertension responsible for iugr. from 24 weeks onwards, it is the pregnancy induced hypertension ( pih) that leads to iugr.7 pih is one factor that is related to parity also. chronic hypertension is associated with increased fetal risk.8 studying the pathophysiology of iugr reveals that maternal disorders like preeclampsia, eclampsia, chronic reno vascular disease and chronic hypertension lead to iugr by causing uteroplacental insufficiency. due to decreased oxygenation of tissues, the organ growth and muscular maturation is impaired. preeclampsia can cause placental infarction journal of rawalpindi medical college (jrmc); 2017;21(2):131-135 132 that disturbs the provision of nutrients and leads to iugr and poor placental flow and hence poor oxygenation of tissues cause restricted fetal growth.9 preeclampsia occurring in the later part of pregnancy can lead to asymmetric form of iugr because more of the blood is directed towards the vital organs like brain and the head is comparatively spared. as a result of chronic hypoxia due to placental insufficiency polycythemia occurs in the fetus. when scanning is being done to detect iugr hypertension in the mother is one of the corroborative signs needed to support the diagnosis.10 the control of hypertension by various drugs like methyldopa, labetalol, calcium channel blockers like nifedipine and ace inhibitors has a role in the outcome of pregnancy. regular antenatal checkups are an important part of management regarding the detection of hypertension. the treatment of extreme preeclamptic hypertension includes the use of drugs like hydralazine, labetalol, nitroglycerine or sodium nitroprusside. magnesium sulphate is also used for the treatment or prevention of preeclampsia.11 complications of iugr and sga are many and include higher risk of perinatal mortality and sudden infant death syndrome. at any gestational age, the morbidity and mortality are increased among term infants whose birth weights are at or below 3rd percentile for gestational age. sga babies are prone to perinatal asphyxia and hypoglycemia in the first twenty four hours after birth.12 patients and methods study was conducted in paediatric department (neonatal intensive care unit) and in obstetrics and gynecology department of holy family hospital rawalpindi from june 2006 to feb 07. the sampling technique was convenience sampling. total 124 cases and 249 controls (thus giving the case to control ratio of 1:2.) were enrolled in this study, that are born full term and delivered in obstetrics department of holy family hospital, rawalpindi. admitted newborns were seen in the neonatal intensive care unit while those being kept with the mother after delivery were seen in the obstetrics and gynecology department. after taking verbal consent for the study the mothers were interviewed for the presence or absence of hypertension during pregnancy and their antenatal records checked (if available). to rule out the confounders, a study proforma was used to record maternal hypertension (as defined earlier) maternal height, weight, bmi, age, anemia, socioeconomic status, preeclamsia, eclampsia, number of children, age of last born, gender, mode and date of delivery.cases and controls were identified and assigned an identification number. all the study cases were seen by the pediatrician on the first day of life, weighed properly, their length and head circumference noted and plotted on centile charts in accordance with their gender to note the presence or absence of iugr. results majority were in age group 20 to 30 years (table 1). primigravida were 49 (39.2%) in case group and 100 (40%) in control group (table 2). out of the cases, 52 (42.6%) were delivered by svd and 70 (57.4%) were delivered by lscs. the number of controls delivered by svd were 95 (38.2%) and 154 (61.8%) of the controls were delivered by lscs. out of the cases, 69 (55.2%) were males and 56 (44.8%) were females. out of the controls, 157 (62.8%) were males and 93 (37.2%) were females. the univariate analysis obtained showed association of iugr with different maternal factors. majority (61.6 %) of the cases and 211(84.4%) of the controls did not have maternal hypertension (or 1).48 (38.4%) of the cases and 39 (15.6%) of the controls were having maternal hypertension (or 2.2; p-value .004). only 2 (1.6%) of the cases and 6 (2.4%) of the controls were having teenage mothers (or 1.01) while 123 (98.4%) of the cases and 244 (97.6%) of the controls did not have teen age mothers (or 1;p-value .989). seventy three (58.4%) of the cases and 204 (81.6%) of the controls were having mothers with normal weight (or 1). 52 (41.6%) of the cases and 46(18%) of the controls were having thin mothers (or 2.9;p-value <.001). thirty seven (29.6%) of the cases and 203 (81.2%) of controls were not having anemia in mothers (or 1) while 88 (70.4%) of cases and 47 (18.8%) of the controls were having anemia in mothers (or3.2;p-value <.001). 66 (52.8%) of the cases and 219 (87.6%) of the controls had mothers with normal (25+) bmi (or 1) while 59 (47.2%) of the cases and 31 (12.4%) of the controls had thin mothers with a bmi of < 25(or 3.7;p-value <.001) (table 3). in the univariate analysis, the weight of the newborn in our dataset ranged from 1.2kg to 3.8kg.a binary dependent variable termed as intrauterine growth retardation(iugr) was created where newborns having birth weight <2.2kg were iugr. univariate logistic regression analysis was done with biological characteristics of the mother which were considered as possible risk factors for iugr. independent variables were converted into dichomotous variables for ease of analysis and clarity. in the univariate analysis cases compared to controls were more than two times likely to have their mothers having hypertension(or journal of rawalpindi medical college (jrmc); 2017;21(2):131-135 133 2.2,95%ci 1.3-3.6), and almost three times likely that their mothers would be underweight (or 2.9,95% ci 1.7-4.8),over three times likely to have their mothers anemic (or 3.2,95% ci 2.3-4.3)table 6. cases compared to controls showed that the mothers of the cases were four times likely to have a low bmi (or 3.7, 95%ci 2.26.2). table 1: maternal age maternal age case control 17to 19years 2 (1.6%) 6 (2.4%) 20 to 30 years 107(85.6%) 219(87.2%) 31 to 35 years 13 (10.4%) 23 (9.2%) 36 years and above 3 (2.4%) 3 (1.2%) table 2: number of children born characteristic cases controls p-value (chi-sq) primigravida 49 100 0.777 2-4 children 54 113 5-12 children 22 37 total 125 250 table 3: univariate analyses showing association of iugr with maternal factors variable cases (number) controls (number) odds ratio (or) pvalue (95% ci) hypertension no 77 221 1 0.004 (1.3-3.6) yes 48 39 2.2 mothers’ weight normal (1-80 kg) 73 204 1 <0.001 (1.74.8) thin (upto 60 kg) 52 46 3.2 anaemia no 37 203 1 <0.001 (2.34.3) yes 88 47 3.2 mothers’ bmi normal (25+) 66 219 1 <0.001 (2.26.2) thin (<25) 59 31 3.7 hypertension however has shown a weak and non significant association and therefore has been discarded. a multivariate regression analysis model was developed by including those variables whose significance level was 0.02 or below. many interactions were tried and variables were added to the model to look for confounding factors. hypertension was not a significant factor and therefore was removed from the model. the risk factors associated with iugr in the final model shows that cases compared to controls were greater than five times likely to have their mothers having anemia ( adjusted or 5.17, p-value <.001, 95%ci 2.98-8.96), and their mothers would more than twice likely to be thin having bmi <20 (adjusted or 2.67, p-value .001, 95%ci 1.49-4.77) (table 4). table 4: multivariate logistic regression model showing association of independent variables to iugr independent variable adjusted or p-value 95% ci maternal anaemia no 1 0.001 2.98-8.96 yes 5.17 mothers’ bmi normal 1 0.001 1.49-4.77 thin 2.67 discussion the present study (a casecontrol study) shows that intrauterine growth retardation is poorly related to maternal hypertension. the other factors having a significant relation to intrauterine growth retardation were maternal anemia, maternal body mass index, maternal age and family income.12-14intrauterine growth retardation was seen more in newborns with gestational age in the range of 37 to 38 weeks gestation as compared to those delivered at 39 to 41 weeks of gestation. the results of the study differ from various studies conducted in various parts of the world which showed that maternal hypertension during pregnancy was associated with intrauterine growth retardation. 4,5,10 in present study maternal hypertension was poorly associated with intrauterine growth retardation. in the univariate analysis of our study, it was found that cases compared to controls were more than two times likely to have their mothers having hypertension. the calculated p-value for this maternal factor was .004. in our study maternal hypertension was found in 38.4% of the cases and 15.6% of the controls. the results of our study are also different from the study conducted in our country by muhammad t et-al which showed preeclampsia and eclampsia as possible causes for low birth weight of the fetus.15 the study by mohammad t also stated that low birth weight of the newborn was associated with both primiparity and grand multi parity. in our study, out of the cases 39.2% had journal of rawalpindi medical college (jrmc); 2017;21(2):131-135 134 primigravida mothers, those with 2 to 4 children were 43.2% and 17.6% of the cases had mothers with 5 to 12 children while among the controls, 40% were born to primigravida mothers, 45.2% were having mothers with 2 to 4 children and 14.8% were those whose mothers had 5 to 12 children. the p-value calculated for this characteristic was 0.777. as shown by the figures mentioned, our results did not show any significant difference in the two groups (cases and controls) regarding this demographic characteristic i.e. parity of the mother . our study has shown results different from those shown in a study by ayaz et al in abbottabad, their study showed that young age of the mother, maternal hypertension, and close birth spacing was the risk factors for low birth weight of the newborn.16 our results are different from this study because no significant association of growth retardation of the newborns was found with young age of the mother. regarding the maternal age, in our study the univariate logistic regression analysis revealed that out of all the cases only 1.6% had mothers in the teenage group (17 to 19 years). the results of our study are also different from a study conducted abroad which showed that maternal age at delivery was significantly associated with poor pregnancy outcomes like low birth weight.17 in our study no such association of maternal age with low birth weight of the newborns was seen. the results of our study correspond to the study carried out by khan mn et al which showed that maternal body mass index (bmi) was related to the birth weight of the newborn. 18 in this study it was recommended that pre pregnancy weight gain should be attained to reduce the incidence of low birth weight in newborns. in our study 47.2% of the cases were having mothers with bmi less than 25 while out of all the controls 12.4% were having mothers with a bmi of less than 25.52.8% of the cases were having a maternal bmi of 25 and above and 87.6% of the controls were having maternal bmi in the same range . body mass index is calculated by dividing the weight in kilograms by surface area of the body in meter squares. if we ignore the racial factors and consider malnutrition as the main factor in the causation of decreased weight then our results also correspond to the study done by rehman et al where maternal malnutrition, anemia was considered a factor of unique importance for intrauterine growth retardation.19 the univariate logistic regression analysis revealed that the mothers of the cases were almost four times likely to have a low bmi (or 3.7, 95% ci 2.2-6.2) the final multivariate model for detecting association of independent variables to intrauterine growth retardation showed that the mothers of cases would be more than twice likely to be thin having bmi less than 20 (adjusted or 2.67, p-value .001, 95% ci 1.49-4.77). intrauterine growth retardation was a perinatal outcome related to maternal anemia. 20 our study also corresponds to a study done in zimbabwe where it was shown that iron supplementation during pregnancy was associated with higher birth weights of newborns independent of other pregnancy care factors, nutritional status of the mother, smoke exposure and a number of demographic and socioeconomic factors.21,22 our study has shown strong correlation of intrauterine growth retardation with maternal anemia. 88% of the cases had mothers with anemia while 18.8% of the controls were having mothers with anemia. the univariate logistic regression analysis revealed that the cases are over three times likely that their mothers would be anemic ( or 3.2,95% ci 2.3-4.3). the results of our study are also corresponding with those of a study conducted by moin a et al and imdad a et al showing a significant correlation of birth weight of the newborn, maternal body weight and hemoglobin level. 23,24 the final multivariate analysis of our results revealed that cases compared to controls were greater than five times likely to have their mothers having anemia . the results of our study resemble the study carried out by fikree ff et al , which was a prospective study for determinants of low birth weight of the babies. 25 their study showed that 46% of the low birth weight babies belonged to the low socioeconomic group. in our study when the various demographic characteristics of the cases and controls were compared it was found that the difference between cases and controls was significant (pvalue<.001). 88% of the cases were having a family income in the range of 3001 to 10000 while 51.6% of the controls were having family income in this range. 28% of the cases were having a family income in the range of 10001 to 20000 and 46.4% of the controls were having family income in the same range.according to the results of the study, maternal anemia, low body mass index of mother and low socioeconomic conditions play a major role in causation of growth retardation of the neonates. maternal factors like cigarette smoking, alcohol intake and drug abuse ,playing a definite role in the incidence of low birth weight of the newborn in the west, are not significant in our set up. journal of rawalpindi medical college (jrmc); 2017;21(2):131-135 135 conclusions 1. the maternal factors having a significant role in causation of intrauterine growth retardation are low body mass index of mother, anemia in the mother and poor socioeconomic conditions. 2. intrauterine growth retardation is not related to parity or young age of the mother. 3. hypertension is not strongly associated with intrauterine growth retardation. 4. efforts should be made to ensure proper weight gain by the mother during pregnancy. this can be done by education of the mother through sessions related to nutrition during pregnancy, proper follow up and regular antenatal checkups. 5. anaemia in the mother should be detected early through regular antenatal check ups and iron supplementation should be done in pregnant mothers. nutritional programmes should be arranged in all centers to provide proper food and other micro nutrients to the mothers. correction of anemia in the teenage before marriage can improve the situation. 6. early antenatal diagnosis of intrauterine growth retardation through ultrasonic examination is necessary to reduce the fetal morbidity and mortality. 7. high quality obstetric and pediatric units should be established by the government to provide low cost and accessible services to the low income groups. 8. references 1. unterscheider j, daly s, geary mp, kennelly mm, mcauliffe fm,. definition and management of fetal growth restriction: a survey of contemporary attitudes. eur j obstet gynecol reprod biol. 2014 ;174:41-45. 2. rasyid h and bakri s.intra-uterine growth retardation and development of hypertension. acta med indones. 2016 ;48(4):320-24. 3. sadovsky ad, matijasevich a, santos is, barros fc, miranda ae, silveira mf. lbw and iugr temporal trend in 4 population-based birth cohorts: the role of economic inequality. bmc pediatr 2016 ; 29;16:115-18. 4. sehested lt and pedersen p.prognosis and risk factors for intrauterine growth retardation. dan med j 2014 ;61(4):4826-29. 5. haşmaşanu mg, bolboaca sd, drugan tc, matyas m, zaharie gc. parental factors associated with intrauterine growth restriction. srp arh celok lek 2015;143(1112):701-06. 6. bertagnolli m, luu tm, lewandowski aj, leeson p. preterm birth and hypertension: is there a link? curr hypertens rep 2016;18(4):28-31. 7. fauvel jp. hypertension during pregnancy: epidemiology, definition.presse med 2016 ;45(7-8 pt 1):618-21. 8. veerbeek jh, nikkels pg, torrance hl, gravesteijn j, post uiterweer ed. placental pathology in early intrauterine growth restriction associated with maternal hypertension. placenta 2014;35(9):696-701. 9. shamshirsaz aa, paidas m, krikun g.preeclampsia, hypoxia, thrombosis, and inflammation. j pregnancy. 2012;374047. 10. sharma d, shastri s, sharma p.intrauterine growth restriction: antenatal and postnatal aspects.clin med insights pediatr 2016;10:67-83. 11. molvi sn, mir s, rana vs, jabeen f, malik ar role of antihypertensive therapy in mild to moderate pregnancyinduced hypertension: a prospective randomized study comparing labetalol with alpha methyldopa. arch gynecol obstet 2012;285(6):1553-62. 12. deshmukh vl, jadhav m, yelikar k impact of high bmi on pregnancy: maternal and foetal outcome. j obstet gynaecol india 2016;66(suppl 1):192-27. 13. demirci o, yılmaz e, tosun ö, kumru p, arınkan a. effect of young maternal age on obstetric and perinatal outcomes: results from the tertiary center in turkey. balkan med j 2016;33(3):344-49. 14. vidal ac, benjamin neelon se, liu y, tuli am, fuemmeler bf.maternal stress, preterm birth, and dna methylation at imprint regulatory sequences in humans. genet epigenet 2014;6:37-44. 15. muhammad t, khattak aa, shafiq-ur-rehman, khan ma. maternal factors associated with intrauterine growth restriction. j ayub med coll abbottabad 2010;22(4):64-69. 16. ayaz a, muhammad t, hussain sa, habibs neonatal outcome in pre-eclamptic patients. j ayub med coll abbottabad 2009 ;21(2):53-55. 17. muhihi a,, sudfeld cr, smith er, noor ra, mshamu s. risk factors for small-for-gestational-age and preterm births among 19,269 tanzanian newborns. bmc pregnancy childbirth 2016;17(16):110-14. 18. khan mn, rahman mm ,shariff aa, rahman mm, rahman ms. maternal undernutrition and excessive body weight and risk of birth and health outcomes. arch public health 2017: 3(75):12-15. 19. rahman mm, abe sk, rahman ms, kanda m, narita s.maternal anemia and risk of adverse birth and health outcomes in lowand middle-income countries: systematic review and meta-analysis.am j clin nutr 2016;103(2):495504. 20. lone fw, qureshi rn, emmanuel f. maternal anaemia and its impact on perinatal outcome in a tertiary care hospital in pakistan. east mediterr health j 2004;10(6):801-07. 21. fall ch, fisher dj, osmond c, margetts bm; maternal micronutrient supplementation study group. multiple micronutrient supplementation during pregnancy in food nutr bull 2009;30(4 suppl):533-46. 22. mishra v, thapa s, retherford rd, dai x. effect of iron supplementation during pregnancy on birthweight: evidence from zimbabwe.food nutr bull 2005;26(4):33847. 23. moin a and lassi zs. can routine screening and iron supplementation for iron deficiency anemia in nonsymptomatic pregnant women improve maternal and infant health outcomes? j family med prim care 2015;4(3):333-34. 24. imdad a and bhutta za. routine iron/folate supplementation during pregnancy: effect on maternal anaemia and birth outcomes paediatr perinat epidemiol 2012 ;26(1):168-77. 25. fikree ff, berendes hw, midhet f, d'souza rm. risk factors for intrauterine growth retardation: results of a community-based study from karachi. j pak med assoc 1994;44(2):30-34. https://www.ncbi.nlm.nih.gov/pubmed/?term=unterscheider%20j%5bauthor%5d&cauthor=true&cauthor_uid=24360357 https://www.ncbi.nlm.nih.gov/pubmed/?term=daly%20s%5bauthor%5d&cauthor=true&cauthor_uid=24360357 https://www.ncbi.nlm.nih.gov/pubmed/?term=geary%20mp%5bauthor%5d&cauthor=true&cauthor_uid=24360357 https://www.ncbi.nlm.nih.gov/pubmed/?term=kennelly%20mm%5bauthor%5d&cauthor=true&cauthor_uid=24360357 https://www.ncbi.nlm.nih.gov/pubmed/?term=mcauliffe%20fm%5bauthor%5d&cauthor=true&cauthor_uid=24360357 https://www.ncbi.nlm.nih.gov/pubmed/?term=mcauliffe%20fm%5bauthor%5d&cauthor=true&cauthor_uid=24360357 https://www.ncbi.nlm.nih.gov/pubmed/24360357 https://www.ncbi.nlm.nih.gov/pubmed/24360357 https://www.ncbi.nlm.nih.gov/pubmed/?term=rasyid%20h%5bauthor%5d&cauthor=true&cauthor_uid=28143994 https://www.ncbi.nlm.nih.gov/pubmed/?term=bakri%20s%5bauthor%5d&cauthor=true&cauthor_uid=28143994 https://www.ncbi.nlm.nih.gov/pubmed/28143994 https://www.ncbi.nlm.nih.gov/pubmed/?term=sadovsky%20ad%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=matijasevich%20a%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=santos%20is%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=barros%20fc%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=miranda%20ae%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=miranda%20ae%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=silveira%20mf%5bauthor%5d&cauthor=true&cauthor_uid=27473678 https://www.ncbi.nlm.nih.gov/pubmed/27473678 https://www.ncbi.nlm.nih.gov/pubmed/?term=sehested%20lt%5bauthor%5d&cauthor=true&cauthor_uid=24814595 https://www.ncbi.nlm.nih.gov/pubmed/?term=pedersen%20p%5bauthor%5d&cauthor=true&cauthor_uid=24814595 https://www.ncbi.nlm.nih.gov/pubmed/24814595 https://www.ncbi.nlm.nih.gov/pubmed/?term=ha%c5%9fma%c5%9fanu%20mg%5bauthor%5d&cauthor=true&cauthor_uid=26946765 https://www.ncbi.nlm.nih.gov/pubmed/?term=bolboaca%20sd%5bauthor%5d&cauthor=true&cauthor_uid=26946765 https://www.ncbi.nlm.nih.gov/pubmed/?term=drugan%20tc%5bauthor%5d&cauthor=true&cauthor_uid=26946765 https://www.ncbi.nlm.nih.gov/pubmed/?term=matyas%20m%5bauthor%5d&cauthor=true&cauthor_uid=26946765 https://www.ncbi.nlm.nih.gov/pubmed/?term=zaharie%20gc%5bauthor%5d&cauthor=true&cauthor_uid=26946765 https://www.ncbi.nlm.nih.gov/pubmed/26946765 https://www.ncbi.nlm.nih.gov/pubmed/?term=bertagnolli%20m%5bauthor%5d&cauthor=true&cauthor_uid=26951245 https://www.ncbi.nlm.nih.gov/pubmed/?term=luu%20tm%5bauthor%5d&cauthor=true&cauthor_uid=26951245 https://www.ncbi.nlm.nih.gov/pubmed/?term=lewandowski%20aj%5bauthor%5d&cauthor=true&cauthor_uid=26951245 https://www.ncbi.nlm.nih.gov/pubmed/?term=leeson%20p%5bauthor%5d&cauthor=true&cauthor_uid=26951245 https://www.ncbi.nlm.nih.gov/pubmed/26951245 https://www.ncbi.nlm.nih.gov/pubmed/?term=fauvel%20jp%5bauthor%5d&cauthor=true&cauthor_uid=27476778 https://www.ncbi.nlm.nih.gov/pubmed/27476778 https://www.ncbi.nlm.nih.gov/pubmed/?term=veerbeek%20jh%5bauthor%5d&cauthor=true&cauthor_uid=25052232 https://www.ncbi.nlm.nih.gov/pubmed/?term=nikkels%20pg%5bauthor%5d&cauthor=true&cauthor_uid=25052232 https://www.ncbi.nlm.nih.gov/pubmed/?term=torrance%20hl%5bauthor%5d&cauthor=true&cauthor_uid=25052232 https://www.ncbi.nlm.nih.gov/pubmed/?term=gravesteijn%20j%5bauthor%5d&cauthor=true&cauthor_uid=25052232 https://www.ncbi.nlm.nih.gov/pubmed/?term=post%20uiterweer%20ed%5bauthor%5d&cauthor=true&cauthor_uid=25052232 https://www.ncbi.nlm.nih.gov/pubmed/?term=post%20uiterweer%20ed%5bauthor%5d&cauthor=true&cauthor_uid=25052232 https://www.ncbi.nlm.nih.gov/pubmed/25052232 https://www.ncbi.nlm.nih.gov/pubmed/?term=shamshirsaz%20aa%5bauthor%5d&cauthor=true&cauthor_uid=22175023 https://www.ncbi.nlm.nih.gov/pubmed/?term=paidas%20m%5bauthor%5d&cauthor=true&cauthor_uid=22175023 https://www.ncbi.nlm.nih.gov/pubmed/?term=krikun%20g%5bauthor%5d&cauthor=true&cauthor_uid=22175023 https://www.ncbi.nlm.nih.gov/pubmed/22175023 https://www.ncbi.nlm.nih.gov/pubmed/?term=sharma%20d%5bauthor%5d&cauthor=true&cauthor_uid=27441006 https://www.ncbi.nlm.nih.gov/pubmed/?term=shastri%20s%5bauthor%5d&cauthor=true&cauthor_uid=27441006 https://www.ncbi.nlm.nih.gov/pubmed/?term=sharma%20p%5bauthor%5d&cauthor=true&cauthor_uid=27441006 https://www.ncbi.nlm.nih.gov/pubmed/27441006 https://www.ncbi.nlm.nih.gov/pubmed/27441006 https://www.ncbi.nlm.nih.gov/pubmed/?term=molvi%20sn%5bauthor%5d&cauthor=true&cauthor_uid=22249781 https://www.ncbi.nlm.nih.gov/pubmed/?term=mir%20s%5bauthor%5d&cauthor=true&cauthor_uid=22249781 https://www.ncbi.nlm.nih.gov/pubmed/?term=rana%20vs%5bauthor%5d&cauthor=true&cauthor_uid=22249781 https://www.ncbi.nlm.nih.gov/pubmed/?term=jabeen%20f%5bauthor%5d&cauthor=true&cauthor_uid=22249781 https://www.ncbi.nlm.nih.gov/pubmed/?term=malik%20ar%5bauthor%5d&cauthor=true&cauthor_uid=22249781 https://www.ncbi.nlm.nih.gov/pubmed/22249781 https://www.ncbi.nlm.nih.gov/pubmed/22249781 https://www.ncbi.nlm.nih.gov/pubmed/?term=deshmukh%20vl%5bauthor%5d&cauthor=true&cauthor_uid=27651602 https://www.ncbi.nlm.nih.gov/pubmed/?term=jadhav%20m%5bauthor%5d&cauthor=true&cauthor_uid=27651602 https://www.ncbi.nlm.nih.gov/pubmed/?term=yelikar%20k%5bauthor%5d&cauthor=true&cauthor_uid=27651602 https://www.ncbi.nlm.nih.gov/pubmed/27651602 https://www.ncbi.nlm.nih.gov/pubmed/27651602 https://www.ncbi.nlm.nih.gov/pubmed/?term=demirci%20o%5bauthor%5d&cauthor=true&cauthor_uid=27308080 https://www.ncbi.nlm.nih.gov/pubmed/?term=y%c4%b1lmaz%20e%5bauthor%5d&cauthor=true&cauthor_uid=27308080 https://www.ncbi.nlm.nih.gov/pubmed/?term=tosun%20%c3%96%5bauthor%5d&cauthor=true&cauthor_uid=27308080 https://www.ncbi.nlm.nih.gov/pubmed/?term=kumru%20p%5bauthor%5d&cauthor=true&cauthor_uid=27308080 https://www.ncbi.nlm.nih.gov/pubmed/?term=ar%c4%b1nkan%20a%5bauthor%5d&cauthor=true&cauthor_uid=27308080 https://www.ncbi.nlm.nih.gov/pubmed/27308080 https://www.ncbi.nlm.nih.gov/pubmed/?term=vidal%20ac%5bauthor%5d&cauthor=true&cauthor_uid=25512713 https://www.ncbi.nlm.nih.gov/pubmed/?term=benjamin%20neelon%20se%5bauthor%5d&cauthor=true&cauthor_uid=25512713 https://www.ncbi.nlm.nih.gov/pubmed/?term=liu%20y%5bauthor%5d&cauthor=true&cauthor_uid=25512713 https://www.ncbi.nlm.nih.gov/pubmed/?term=tuli%20am%5bauthor%5d&cauthor=true&cauthor_uid=25512713 https://www.ncbi.nlm.nih.gov/pubmed/?term=fuemmeler%20bf%5bauthor%5d&cauthor=true&cauthor_uid=25512713 https://www.ncbi.nlm.nih.gov/pubmed/?term=fuemmeler%20bf%5bauthor%5d&cauthor=true&cauthor_uid=25512713 https://www.ncbi.nlm.nih.gov/pubmed/25512713 https://www.ncbi.nlm.nih.gov/pubmed/?term=muhammad%20t%5bauthor%5d&cauthor=true&cauthor_uid=22455264 https://www.ncbi.nlm.nih.gov/pubmed/?term=khattak%20aa%5bauthor%5d&cauthor=true&cauthor_uid=22455264 https://www.ncbi.nlm.nih.gov/pubmed/?term=shafiq-ur-rehman%5bauthor%5d&cauthor=true&cauthor_uid=22455264 https://www.ncbi.nlm.nih.gov/pubmed/?term=khan%20ma%5bauthor%5d&cauthor=true&cauthor_uid=22455264 https://www.ncbi.nlm.nih.gov/pubmed/?term=iugr+and+pih+in+pakistn https://www.ncbi.nlm.nih.gov/pubmed/?term=ayaz%20a%5bauthor%5d&cauthor=true&cauthor_uid=20524469 https://www.ncbi.nlm.nih.gov/pubmed/?term=muhammad%20t%5bauthor%5d&cauthor=true&cauthor_uid=20524469 https://www.ncbi.nlm.nih.gov/pubmed/?term=hussain%20sa%5bauthor%5d&cauthor=true&cauthor_uid=20524469 https://www.ncbi.nlm.nih.gov/pubmed/20524469 https://www.ncbi.nlm.nih.gov/pubmed/20524469 https://www.ncbi.nlm.nih.gov/pubmed/?term=muhihi%20a%5bauthor%5d&cauthor=true&cauthor_uid=27183837 https://www.ncbi.nlm.nih.gov/pubmed/?term=sudfeld%20cr%5bauthor%5d&cauthor=true&cauthor_uid=27183837 https://www.ncbi.nlm.nih.gov/pubmed/?term=smith%20er%5bauthor%5d&cauthor=true&cauthor_uid=27183837 https://www.ncbi.nlm.nih.gov/pubmed/?term=noor%20ra%5bauthor%5d&cauthor=true&cauthor_uid=27183837 https://www.ncbi.nlm.nih.gov/pubmed/?term=mshamu%20s%5bauthor%5d&cauthor=true&cauthor_uid=27183837 https://www.ncbi.nlm.nih.gov/pubmed/27183837 https://www.ncbi.nlm.nih.gov/pubmed/27183837 https://www.ncbi.nlm.nih.gov/pubmed/?term=khan%20mn%5bauthor%5d&cauthor=true&cauthor_uid=28174626 https://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20mm%5bauthor%5d&cauthor=true&cauthor_uid=28174626 https://www.ncbi.nlm.nih.gov/pubmed/?term=shariff%20aa%5bauthor%5d&cauthor=true&cauthor_uid=28174626 https://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20mm%5bauthor%5d&cauthor=true&cauthor_uid=28174626 https://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20ms%5bauthor%5d&cauthor=true&cauthor_uid=28174626 https://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20ms%5bauthor%5d&cauthor=true&cauthor_uid=28174626 https://www.ncbi.nlm.nih.gov/pubmed/28174626 https://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20mm%5bauthor%5d&cauthor=true&cauthor_uid=26739036 https://www.ncbi.nlm.nih.gov/pubmed/?term=abe%20sk%5bauthor%5d&cauthor=true&cauthor_uid=26739036 https://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20ms%5bauthor%5d&cauthor=true&cauthor_uid=26739036 https://www.ncbi.nlm.nih.gov/pubmed/?term=kanda%20m%5bauthor%5d&cauthor=true&cauthor_uid=26739036 https://www.ncbi.nlm.nih.gov/pubmed/?term=narita%20s%5bauthor%5d&cauthor=true&cauthor_uid=26739036 https://www.ncbi.nlm.nih.gov/pubmed/?term=narita%20s%5bauthor%5d&cauthor=true&cauthor_uid=26739036 https://www.ncbi.nlm.nih.gov/pubmed/26739036 https://www.ncbi.nlm.nih.gov/pubmed/?term=lone%20fw%5bauthor%5d&cauthor=true&cauthor_uid=16335767 https://www.ncbi.nlm.nih.gov/pubmed/?term=qureshi%20rn%5bauthor%5d&cauthor=true&cauthor_uid=16335767 https://www.ncbi.nlm.nih.gov/pubmed/?term=emmanuel%20f%5bauthor%5d&cauthor=true&cauthor_uid=16335767 https://www.ncbi.nlm.nih.gov/pubmed/16335767 https://www.ncbi.nlm.nih.gov/pubmed/?term=fall%20ch%5bauthor%5d&cauthor=true&cauthor_uid=20120795 https://www.ncbi.nlm.nih.gov/pubmed/?term=fisher%20dj%5bauthor%5d&cauthor=true&cauthor_uid=20120795 https://www.ncbi.nlm.nih.gov/pubmed/?term=osmond%20c%5bauthor%5d&cauthor=true&cauthor_uid=20120795 https://www.ncbi.nlm.nih.gov/pubmed/?term=margetts%20bm%5bauthor%5d&cauthor=true&cauthor_uid=20120795 https://www.ncbi.nlm.nih.gov/pubmed/?term=maternal%20micronutrient%20supplementation%20study%20group%5bcorporate%20author%5d https://www.ncbi.nlm.nih.gov/pubmed/?term=maternal%20micronutrient%20supplementation%20study%20group%5bcorporate%20author%5d https://www.ncbi.nlm.nih.gov/pubmed/?term=mishra%20v%5bauthor%5d&cauthor=true&cauthor_uid=16465980 https://www.ncbi.nlm.nih.gov/pubmed/?term=thapa%20s%5bauthor%5d&cauthor=true&cauthor_uid=16465980 https://www.ncbi.nlm.nih.gov/pubmed/?term=retherford%20rd%5bauthor%5d&cauthor=true&cauthor_uid=16465980 https://www.ncbi.nlm.nih.gov/pubmed/?term=dai%20x%5bauthor%5d&cauthor=true&cauthor_uid=16465980 https://www.ncbi.nlm.nih.gov/pubmed/16465980 https://www.ncbi.nlm.nih.gov/pubmed/?term=moin%20a%5bauthor%5d&cauthor=true&cauthor_uid=26288769 https://www.ncbi.nlm.nih.gov/pubmed/26288769 https://www.ncbi.nlm.nih.gov/pubmed/?term=imdad%20a%5bauthor%5d&cauthor=true&cauthor_uid=22742609 https://www.ncbi.nlm.nih.gov/pubmed/?term=bhutta%20za%5bauthor%5d&cauthor=true&cauthor_uid=22742609 https://www.ncbi.nlm.nih.gov/pubmed/22742609 https://www.ncbi.nlm.nih.gov/pubmed/?term=fikree%20ff%5bauthor%5d&cauthor=true&cauthor_uid=8040989 https://www.ncbi.nlm.nih.gov/pubmed/?term=berendes%20hw%5bauthor%5d&cauthor=true&cauthor_uid=8040989 https://www.ncbi.nlm.nih.gov/pubmed/?term=midhet%20f%5bauthor%5d&cauthor=true&cauthor_uid=8040989 https://www.ncbi.nlm.nih.gov/pubmed/?term=d%27souza%20rm%5bauthor%5d&cauthor=true&cauthor_uid=8040989 https://www.ncbi.nlm.nih.gov/pubmed/8040989 summary journal of rawalpindi medical college (jrmc); 2018;22(2): 152-155 152 original article effect of lower third molar status on fracture of mandibular angle and condyle muhammad adil asim1,ayesha maqsood1, fouzia aslam1, anosha mujtaba 2 department of oral and maxillofacial surgery, rawal institute of health sciences, islamabad;2. department of oral and maxillofacial surgery, pakistan institute of medical sciences, islamabad abstract background:to determine the correlation between impacted m3 and mandibular angle and condylar fractures considering the hypothesis that the presence of m3s increases the risk of mandibular angle and simultaneously decreases the risk of condylar fracture and vice versa.. methods: in this cohort study seventy-five patients having ninety-two hemi-mandibles with fracture of condylar process or angle were included. status of third molar on the fractured side of mandible was determined. based on status of mandibular third molars patients were broadly classified into two groups i.e. erupted and impacted. results:among the total 92 hemi-mandibles that were fractured, 56.5% had angle fractures while 43.5% had condylar fractures. out of total 48 hemimandibles with impacted third molars, mandibular angle was fractured in 72.92%. while among 44 hemi-mandibles having erupted third molars, 61.36% had condylar fractures. conclusion: mandibular angle fractures more readily as the result of facial trauma in the presence of an impacted m3,especially with class b depth and class 2 ramus position. absence of an impacted mandibular third molar increases the risk of condylar fractures while concomitantly decreasing the risk of mandibular angle fracture. key words: mandibular impacted third molar, condyle fracture, angle fracture. introduction the most common bone to fracture because of facial trauma is the mandible. the presence of an impacted mandibular third molar (m3) weakens the mandibular angle region thus predisposing it to fracture more commonly when compared with mandibular condyle which tend to fracture more in the absence of impacted m3.the facial bone commonly fractured as a result of trauma is the mandible, although it has been perceived to be a strong and inflexible bone of the facial skeleton.1in literature the frequency of mandibular fractures is quite variable, alternating from 24.3% to 68.6%, of all maxillofacial fractures.2,3 this disparity may be due to variety of reasons such as the age of the patient and the etiology of trauma and socio economic status as well. the pattern of fracture of the mandible is again dependent upon a variety of factors. primary reason is the force and direction of the injury but it is also dependent upon the type and amount of bone, and presence of certain anatomical structures. one such anatomical structure is the presence of impacted third molars (m3) which has been suggested as a strong contributing factor for mandibular angle fracture.4,5 as the presence of an impacted third molar affects the amount and quality of bone at the angle of mandible, a 2-3 fold increased risk for fracture of mandibular angle has been found in the presence of impacted m3s. 6,7concurrently, it has been observed that the absence of an impacted m3 while decreasing the risk of mandibular angle fracture however increases the risk of mandibular condylar fracture.8 the calculation of this relative risk of mandibular condyle and angle fracture is significant because the treatment of condylar fracture is more challenging and associated with more surgical morbidity.9 the aim of this study was dual, firstly to determine whether the presence of impacted m3s affects the frequency of mandibular condylar and angle fracture and secondly to determine if this risk of fracture is also dependent on m3s position in the mandible. this position in the mandible was determined according to pell and gregory classification. it has been suggested theoretically that the impacted m3s decrease the bony volume in the angle region, so we wanted to investigate would it increase the risk of angle fracture while simultaneously decreasing the risk of condylar fracture and whether the degree of tooth impaction would be directly related to the risk of fracture. patients and methods this cohort study was carried out in department of oral & maxillofacial surgery at rawal institute of health sciences islamabad from jan 2016 to dec 2017. after taking verbal consent, all patients who reported with mandibular condyle or angle fractures as a result journal of rawalpindi medical college (jrmc); 2018;22(2): 152-155 153 of trauma were enrolled in the study. exclusion criteria were patients younger than 18 years of age, patients with comminuted fractures, gunshot or blast injuries, and patients having pathological fractures. the demographic data and information regarding the type of fracture and status of mandibular third molar was noted on a performa. clinical and radiographic examination (orthopantomogram and pa mandible), was performed to diagnose the type of mandibular fracture. mandibular angle fracture was defined, according to kelly and harrigan,while condylar fracture was defined as a fracture above the base of sigmoid notch on the condylar process of mandible.10 by radiographic examination the status of third molar on the fractured side of mandible was determined according to pell and gregory classification.11 the third molars were classified for angulation according to sciller’s classification.12 cases presenting with impacted third molars onthe fractured side of mandible were divided into two groups i.e. impacted third molar “present” and “absent” group. in impacted third molar “absent” group,the hemimandible with fully erupted m3s, missing m3s or m3s having pell and gregory 1a classification were included. while all other m3s were regarded as impacted and were included in the impacted third molar “present” group. chi square test was applied to determine the relationship between status of mandibular third molar and type of fracture. p value < 0.05 was considered significant. results the study comprised of seventy-five patients having ninety-two hemi-mandibles with fracture of mandibular angle or condyle. majority (84%) were male while 13 (16%) were female having mean age 28.23±12.37 years (age range 18 to 75 years). in present study 35 (46.7%) patients had unilateral mandibular angle factures while unilateral condylar fracture was present in 23 (30.7%) patients. bilateral condylar and angle fractures were present in 12 (16%) patients whereas just 5 (6.7%) patients reported with bilateral condylar fractures and none of the patients had bilateral angle fractures. road traffic accident (rta) was the most common cause of fractures (n=56, 76.7%) followed by fall (n=10, 13.3%),assault (n=6, 8%), sports injury (n=2, 2.7%)and animal injury (n=1, 1.3%).among the total 92 hemi-mandibles that were fractured, 52 (56.5%) had angle fractures while other 40 (43.5%) had condylar fractures. status of mandibular third molar was analyzed (table 1), third molars were categorized into impacted third molars “present” and “absent” groups according to the already mentioned criteria. it was found that in 52.17% hemi-mandibles third molars were considered impacted while in 47.83% cases teeth were either fully erupted or missing. it was further analyzed that out of total 48 hemi-mandibles with impacted third molars mandibular angle was fractured in 72.92% cases. while among 44 hemi-mandibles in impacted m3s “absent group”, 27 (61.36%) had condylar fractures. chi square test was applied to analyze the association of mandibular third molars with angle and condyle fractures and p value was found to be 0.001(table 2). table 1 :third molar status status of third molars frequency percentage pell and gregory class class 1 46 50 class 2 37 40.2 class 3 6 6.5 absent 3 3.3 pell and gregory position position a 44 47.8 position b 38 41.3 position c 7 7.6 absent 3 3.3 angulation mesioangular 32 34.8 horizontal 22 23.9 vertical 26 28.3 distoangular 9 9.8 absent 3 3.3 when the association of mandibular fracture (condyle and angle) to the occlusal position of third molar was assessed, it was found that 28 (73.68%) hemimandibles having third molars at position b had angle fractures while just 10 (26.32%) hemi-mandibles had condylar fractures. the chi square test was applied, and p value of 0.047 was calculated (table 03).lastly upon evaluating the association of mandibular fracture (condyle and angle) with third molar ramal position, it was interestingly noted that at class 2 position 27(72.97%) hemi-mandibles had angle fractures while only 10 (27.03%) hemi-mandibles had condyle fractures. chi square test was applied and p value of 0.059 was found which is considered non-significant (table 4). journal of rawalpindi medical college (jrmc); 2018;22(2): 152-155 154 table 2 : relationship between impacted third molars and mandibular angle and condyle fracture impacte d third molar condyle fracture p-value angle fracture p-value present absent 0.001 present absent 0.001 present (n=48) 13 (27.08%) 35 (72.92%) 35 (72.92%) 13 (27.08%) absent (n= 44) 27 (61.36%) 17 (38.64%) 17 (38.64%) 27 (61.36%) total 40 52 52 40 table 3: correlation of position of third molars to mandibular angle and condyle fracture position of third molars condyle fracture p value angle fracture pvalue present absent present absent position a 24(54.55%) 20(45.45%) 0.047 20(45.45%) 24(54.55%) 0.047 position b 10(26.32%) 28(73.68%) 28(73.68%) 10(26.32%) position c absent 4(57.14%) 2(66.67%) 3(42.86%) 1(33.33%) 3(42.86%) 1(33.33%) 4(57.14%) 2(66.67%) total 40 52 52 40 table 4: relationship between ramal classification of third molars and mandibular angle and condyle fracture ramal classification of third molars condyle fracture p value angle fracture p value present absent present absent class 1 24(52.17%) 22(47.83%) 0.059 20(45.45%) 24(54.55%) 0.059 class 2 10(27.03%) 27(72.97%) 27(72.97%) 10(27.03%) class 3 absent 4(66.67%) 2(66.67%) 2(33.33%) 1(33.33%) 2(33.33%) 1(33.33%) 4(66.67%) 2(66.67%) total 40 52 52 40 discussion mandible is a rigid and strong facial bone but still it is to be commonly fractured as a result of trauma. it is the quantity and quality of bone at different sites of mandible which directly affects the incidence of mandibular fractures. our hypothesis is based on the theory that presence of impacted third molars directly affects quantity of bone at the mandibular angle region, thus predisposing it to fracture as suggested by other researchers as well.13 in present study it was found that in 52.17% hemimandibles with impacted third molars,mandibular angle was fractured in 72.92%. as noted in our study that more mandibular angles were fractured in the presence of impacted m3,this was supported by various other studies as well.14,15moreover this risk is not only dependent on the presence of an impacted m3 but position of impacted m3 also has a significant effect, as shown in a study by fuselier et.al. and duan et.al.16,17 in our study we also observed that 73.68% patients having class b impacted m3s, 72.9 % patients having class 2 ramus position of m3 reported with angle fractures. we know that fractures of mandibular angle present with an area of strain at the superior alveolar border and an area of compression at the lower border of mandible.18the impacted m3s with class ii and class b position thus interrupt the continuity of the supper border of mandible. this results in a characteristic weakness in the mandibular angle, thereby predisposing it to fracture more easily. this explain why the highest risk of angle fractures was observed for class ii and class b positions of m3 when compared with the impacted m3 having class iii and class c position, where the impactions are deep and do not interrupt the continuity of the upper border of mandible. another common fracture site in the mandible is the condylar process which due to its anatomy and location can be considered another weak area in the mandible. it has been hypothesized that the presence of impacted third molars while increasing the risk for angle fracture simultaneouslyreduces the incidence of condylar fractures.19,20a study reports that mandibles in the absence of an impacted m3, show a 1.8 fold increased risk of condylar fracture.21 our study also supported this because we found out that in the patients with absence of impacted third molars there was a higher incidence of condylar fracture .these findings were supported in some other studies as well which when determining the effect of the third molar on condylar fractures, demonstrated that in the presence of an impacted m3 , the tension forces increase slightly in the angle region predisposing it to fracture more easily as compared to the condylar process. in the absence of an impacted m3,these forces are transmitted to the mandibular condyle thus predisposing it to fracture.19,20 not much research is done about the association of m3 position with the risk of condylar factures, but the few studies which have been conducted show that the relativerisk of fracture is more in mandibular sides with m3 in class i and class a position.21,24,25, although these investigators found a statistically significant relationship, which our study could not validate because we did not find any significant risk. the proponents of the debate of prophylactic removal of impacted m3 suggest that its early removal in young individuals can decrease the surgical morbidity associated with of m3 in later age. they suggest its removal especially in those young athletes who are journal of rawalpindi medical college (jrmc); 2018;22(2): 152-155 155 involved in competitive contact sports, recommending that this removal of m3 would further decrease the risk of mandibular angle fracture.15,26 but from our results we can conclude that while decreasing the risk of angle fracture it will predispose the mandible to condylar fractures, surgical management of which is comparatively more challenging.27therefore we recommend that suggestion of prophylactic extraction of impacted m3s should be carefully reconsidered because its long term effects may not be beneficial. conclusion presence of an impacted mandibular third molar predisposes the mandibular angle to fracture, particularly at pell and gregory class b depth and class 2 ramus position of impacted third molar whereas it reduces the risk of concomitant condylar fractures. references 1. yaltrik m, tanyel cr, katiboglu b. a comparative study of the clinical aspects and relationship between fractures of mandibular angle and the presence of a lower third molar. turk j med sci 2002;32:391–95. 2. gassner r, tuli t, hächl o, rudisch a, ulmer h. craniomaxillofacial trauma: a 10 year review of 9,543 cases with 21,067 injuries. j craniomaxillofac surg. 2003;31:51–61. 3. tanaka n, tomitsuka k, shionoya k, andou h, kimijima y, tashiro t, et al. aetiology of maxillofacial fracture. br j oral maxillofac surg. 1994;32:19–23. 4. meisami t, sojat a, sandor gk, lawrence hp, clokie cm: impacted third molars and risk of angle fracture. int j oral maxillofac surg 2002;31:140-44. 5. syed adnan ali shah, adnan aslam, muhammad yunus. third molars and angle fractures. pak oral dental j jan mar 2015;35(1):24-29. 6. ma’aita j, alwrikat a. is the mandibular third molar a risk factor for mandibular angle fracture? oral surg oral med oral pathol oral radiol endod 2000; 89: 143-46. 7. lee jt1, dodson tb. the effect of mandibular third molar presence and position on the risk of an angle fracture. j oral maxillofac surg 2000; 58: 394-98. 8. zhu sj, choi bh, kim hj, park ws, huh jy, jung jh. relationship between the presence of unerupted mandibular third molars and fractures of the mandibular condyle. int j oral maxillofac surg 2005 ;34:382-85. 9. xu s, huang j-j, xiong y, tan y-h, how is third molar status associated with the occurrence of mandibular angle and condyle fractures? journal of oral and maxillofacial surgery, 2017;03:021-25. 10. harrigan w. a survey of facial fractures related to teeth and edentulous regions. j oral surg 1975;33:146-49. 11. pell g, gregory g. impacted mandibular third molars, classification and modified technique for removal. dental digest 1933;39:330-34. 12. sciller wr: positional changes in mesioangular impacted third molars during a year. j am dent assoc 1975;99: 460e464. 13. meisami t, sojat a, sandor gkb, lawrence hp, clokie cml. impacted third molars and risk of angle fracture. int j oral maxillofac surg 2002;31(2) :140-44. 14. safdar n, meechan jg: relationship between fractures of mandibular angle and the presence and state of eruption of lower third molar. oral surg oral med oral pathol oral radiol endod 1995;79: 680-84. 15. tevepaugh db, dodson tb: are mandibular third molars a factor for angle fractures? a retrospective cohort study. j oral maxillofac surg 1995;53: 646-49. 16. fuselier jc, ellis iii ee, dodson tb. do mandibular third molars alter the risk of angle fracture? j oral maxillofac surg 2002: 60: 514–18. 17. d. h. duan, y. zhang: does the presence of mandibular third molars increase the risk of angle fracture and simultaneously decrease the risk of condylar fracture?. int. j.oral maxillofac surg 2008; 37: 25–28. 18. tams j, van loon jp, rozema fr, otten e. a threedimensional study of loads across the fracture for different fracture sites of the mandible. br j oral maxillofac surg 1996: 34: 400–05. 19. zhu sj, choi bh, kim hj, park ws, huh jy, jung jh. relationship between the presence of unerupted mandibular third molars and fractures of the mandibular condyle. int j oral maxillofac surg 2005; 34: 382-85. 20. gaddipati r. impacted mandibular third molars and their influence on mandibular angle and condyle fractures a retrospective study, j cranio maxillo fac surg 2014;42:1102-05. 21. naghipur s, shah a, elgazzar rf, does the presence or position of lower third molars alter the risk of mandibular angle or condylar fractures? j oral maxillofac surg 2014;72:1766-69. 22. antic s, saveljic i, nikolic d, jovicic g, filipovic n. does third molar and mandibular condyle fractures the presence of an unerupted lower third molar influence the risk of mandibular angle and condylar fractures? int j oral maxillo-fac surg 2016; 45:588–92. 23. antic s, vukicevic am, milasinovic m, saveljic i, jovicic g, filipovic n. impact of the lower third molar presence and position on the fragility of mandibular angle and condyle: a three-di-mensional finite element study. j cranio-maxillofac surg 2015; 43:870–78. 24. choi bj, park s, lee dw, ohe jy, kwon yd. effect of lower third molars on the incidence of mandibular angle and condylar fractures. j craniofac surg 2011;22:1521-24. 25. duan dh, zhang y. does the presence of mandibular third molars increase the risk of angle fracture and simultaneously decrease the risk of condylar fracture? int j oral maxillofac surg 2010; 37:25-29. 26. schwimmer a, stern r, kritchman d. impacted third molars: a contributing factor in mandibular fractures in contact sports. am j sports med 1983;11:262-65. 27. ellis e. complications of mandibular condyle fracture. int j oral maxillofac surg 1998; 27:255-58. http://www.pakmedinet.com/31442 http://www.pakmedinet.com/podj https://www.ncbi.nlm.nih.gov/pubmed/?term=lee%20jt%5bauthor%5d&cauthor=true&cauthor_uid=10759119 https://www.ncbi.nlm.nih.gov/pubmed/?term=dodson%20tb%5bauthor%5d&cauthor=true&cauthor_uid=10759119 summary journal of rawalpindi medical college (jrmc); 2017;21(4): 366-370 366 original article diagnostic accuracy of ultrasound in detection of synovial hypertrophy in patients with osteoarthritis sidra manzoor 1, rabia waseem butt 1, sidra nadeem 2, fazeela farid 3, manal niazi 4 1. department of radiology, hitec institute of medical sciences. taxila cantt;2. department of radiology, holy family hospital rawalpindi;3.department of radiology, city lab rawalpindi;4. department of radiology, islamabad medical & dental college abstract objective: to determine the diagnostic accuracy of ultrasound in the detection of synovial hypertrophy in patients with osteoarthritis by using mri as the gold standard. methods: in this descriptive study, 150 patients with complaint of joint pain and stiffness, were included. ultrasound was carried out. subsequently, mri scan of affected joint was performed. results: by taking the synovial thickness of more than 2.3mm as discriminatory level for synovial proliferation, the overall sensitivity of ultrasound was 94.23%, and specificity was 87.23%. the positive predictive values of the ultrasound in patients with synovial hypertrophy was 95.14% and negative predictive value was calculated to be 92.67%. the diagnostic accuracy of the test was 89.12%. conclusion: duplex doppler ultrasound can detect synovial hypertrophy with sensitivity of approximately 94.23 %. key words: osteoarthritis, synovial proliferation, ultrasound, diagnostic accuracy introduction osteoarthritis (oa)is a common arthritis and is one of the leading causes of disability in older population.1 it affects approximately 34% of the united states population over age 65.2 it is a chronic, progressive, debilitating disease characterized by degenerative changes in the bones, cartilage, menisci, ligaments, and synovial tissue of joints.3 although oa is classified as non-inflammatory arthritis, mechanical stress and chronic inflammatory process in the joint micro-environment may lead to synovial inflammation and proliferation. as disease progresses, the proliferating synovial tissue may resemble the pannus tissue characteristic of rheumatoid arthritis.4 the presence of inflammatory synovium at baseline may be predictive of structural progression of cartilage damage.5 oa is currently diagnosed based on clinical and radiographic findings.6 radiography however is not very sensitive to identify early structural change as it takes several years to detect progression of radiographic oa.7 magnetic resonance imaging (mri) and ultrasound (us) serve as additional tools to determine the extent of joint involvement. synovitis can be demonstrated by us, appearing as hypoechogenic hypertrophy of synovial tissue in gray scale (b mode).8,9 mri demonstrates synovitis in early oa in joints when synovitis is not clinically detected.4 synovial thickening seen on mri has been confirmed as histological synovitis using arthroscopic sampling of the areas of mri detected synovial thickening.10 on mri, synovitis is defined as thickened area of synovium that shows greater than normal enhancement on post gadolinium t1-weighted images.11 in early oa, mostly hyperplastic oa synoviopathy is found.12 both us and mri are sensitive for the detection of synovitis, and both are superior to radiography.13 ultrasound has the advantage over mri in that it is economical, convenient and easier to use, is dynamic and has no contraindications to its use.14 ultrasound is more patient friendly, has the ability to scan several joints in different body regions in one session and can directly correlate clinical and imaging findings.15 there is a wide range of difference in cut-off value for synovial thickness taken for diagnosis of synovial hypertrophy. in a study, carried out carried out in egypt, the sensitivity and specificity of ultrasound was found 82.5% and 95% respectively in detecting synovial thickness of knee joint.16 quantitative measurement of synovial thickness using gadoliniumenhanced mri is the gold standard for assessment of synovitis on mri.4 mri can visualize all tissues in the joint involved in oa , i.e., cartilage, menisci, bone and soft tissue.6 the mean sensitivity and specificity of low field mri for detection of synovitis is 90% and 96% respectively.17 journal of rawalpindi medical college (jrmc); 2017;21(4): 366-370 367 patients and methods after taking approval from institutional review board and ethics committee, the descriptive study was conducted at the armed forces institute of radiology and imaging (afiri), rawalpindi, from october 2015 to april 2016. by using who sample size calculator taking sensitivity 82.5% and specificity 95%, prevalence is 27.6% , desired precision for sensitivity 10%, for specificity 5% and confidence interval of 95% , a minimum of 160 patients were required as the sample size. 14-18 during the study period, 150 patients referred by the orthopedics and rheumatology department with osteoarthritis who were diagnosed on the basis of clinical examination and were advised mri scan . patients of either gender, between 50 to 80 years of age, who gave informed consent for the study and had morning stiffness and joint pain less than 30 min were included. those excluded were patients with renal problems and deranged rfts resulting in need for haemodialysis, patients with infectious or traumatic arthritis, mentally retarded persons. affected joint was examined in real time in axial and sagittal planes prior to mri scan. joints were scanned in longitudinal and transverse planes with the joint supported in 30° flexion for ventral and lateral scans and in extension for dorsal scans. the supra-patellar pouch was scanned widely (including the lateral and medial recesses). synovial thickness was measured and thickness of more than 2.3mm was taken as indicator of synovial hypertropy. preand postgadolinium sequences of a single knee were evaluated. mri was taken as positive if thickened area of synovial compartment was seen that appeared hyper-intense on t2ws and stir sequences and showed greater than normal enhancement on gadolinium-enhanced t1-weighted images. mri diagnosis was then compared with the findings of the ultrasound scan reports. mean, median, mode and mean standard deviation for numerical data like age and frequency percentages for categorical data like true positive and true negative was calculated. a 2 x 2 table was constructed to determine sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. true positive were defined as synovial hypertrophy diagnosed both on ultrasound and on mri. true negative were the cases negative for synovial hypertrophy both on ultrasound and on mri. synovial hypertrophy diagnosed on ultrasound but not found on mri was taken as false positive, while the cases who do not have synovial hypertrophy on ultrasound but are positive on mri were defined as false negative.sensitivity was equal to: true positive/true positive + false negative x 100; while specificity was equal to: true negative/false positive + true negative x 100. true positive / true positive + false positive x 100, and npv as, true negative / false negative + true negative x 100. the diagnostic accuracy was calculated by the formula: true positive + true negative / true positive + false positive + false negative + true negative x 100. results age distribution of the patients (n=150) shows that majority (74,67%) were between 50-65 years of age (table 1). gender distribution shows that 58.67% were females. (table 2). frequency of synovial proliferation in patients with osteoarthritis(on gold standard) was recorded in 30.67%(figure 1-3;table 3).diagnostic accuracy of ultrasound in the detection of synovial proliferation in patients with osteoarthritis by using mri as the gold standard was calculated as 89.12%, 94.23%, 87.23%, 95.14% and 92.67% for sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate. (table 4).effect modifiers like gender and age was controlled by stratification. post stratification chi –square test was applied. p value < and equal to 0.05, as significant, was documented . (table no. 5 -8) table 1. age distribution (n=150) age(in years) no. of patients % 50-65 112 74.67 65-80 38 25.33 total 150 100 mean+sd 62.12+7.68 mode= 53.00;median=62.00 table 2. gender distribution (n=150) gender no. of patients % male 62 41.33 female 88 58.67 total 150 100 table 3. frequency of synovial proliferation in patients with osteoarthritis(on gold standard) synovial proliferation no. of patients % yes 46 30.67 no 104 69.33 journal of rawalpindi medical college (jrmc); 2017;21(4): 366-370 368 total 150 100 table 4. diagnostic accuracy of ultrasound in the detection of synovial proliferation by using mri as the gold standard ultrasound findings synovial proliferation total synovial hypertrophy present (positive) synovial hypertrophy present (negative) positive true positive(a) 41 (27.33%) false positive (b) 6 (4%) a + b 47(31.33%) negative false negative(c) 5 (3.33%) true negative (d) 98 (65.33%) c + d 103 (68.67%) total a + c 46 (30.67%) b + d 104 (69.33%) 150 (100%) sensitivity = a / (a + c) x 100 =89.12%;specificity= d / (d + b) x 100 = 94.23%;positive predictive value = a / (a + b) x 100 =87.23%;negative predictive value = d / (d + c) x 100 =95.14%;accuracy rate = a + d / (a + d + b + c) x 100 = 92.67% table 5. stratification for age ( 50-65 years) ultrasound findings synovial proliferation p value synovial hypertrophy (positive) synovial hypertrophy present (negative) positive true positive(a) 31 false positive (b) 5 negative false negative(c) 2 true negative (d) 74 total a + c 33 b + d 79 sensitivity= a / (a + c) x 100 =93.93%;specificity = d / (d + b) x 100 = 93.67%;positive predictive value = a / (a + b) x 100 =86.11%;negative predictive value = d / (d + c) x 100 =97.36%;accuracy rate = a + d / (a + d + b + c) x 100 =93.75% table 6. stratification for age (66-80 years) ultrasound findings synovial proliferation p-value synovial hypertrophy present (positive) synovial hypertrophy present (negative) positive true positive(a)10 false positive (b) 1 negative false negative(c) 3 true negative (d) 24 total a + c 13 b + d25 sensitivity= a / (a + c) x 100 =76.92%;specificity = d / (d + b) x 100 =96%;positive predictive value = a / (a + b) x 100 =90.91%;negative predictive value = d / (d + c) x 100 =88.89%;accuracy rate = a + d / (a + d + b + c) x 100 = 89.47% table 7. stratification for gender ( male) ultrasound findings synovial proliferation p value synovial hypertrophy present (positive) synovial hypertrophy present (negative) positive true positive(a) 20 false positive (b) 2 0.000 negative false negative(c) 4 true negative (d) 36 total a + c 24 b + d 38 sensitivity= a / (a + c) x 100 =83.33%;specificity = d / (d + b) x 100 = 94.73%;positive predictive value = a / (a + b) x 100 =90.90%;negative predictive value = d / (d + c) x 100 =90%;accuracy rate = a + d / (a + d + b + c) x 100 =90.32% table 8. stratification for gender (female) ultrasound findings synovial proliferation p value synovial hypertrophy present (positive) synovial hypertrophy present (negative) positive true positive(a) 21 false positive (b) 4 0.000 negative false negative(c) 1 true negative (d) 62 total a + c 22 b + d 66 sensitivity= a / (a + c) x 100 =95.45%;specificity= d / (d + b) x 100 = 93.93%;positive predictive value = a / (a + b) x 100 =84%;negative predictive value = d / (d + c) x 100 =98.41%;accuracy rate = a + d / (a + d + b + c) x 100 = 94.32% figure 1: ultrasound image of thickened vascularized synovium longitudinal figure 2 :suprapatellar recess with thickened synovium longitudinal journal of rawalpindi medical college (jrmc); 2017;21(4): 366-370 369 figure 3: gadolinium enhanced sagittal t1 weight mri of a patient with osteoarthritis showing joint effusion and enhanced synovium indicating synovitis discussion ultrasound can be used to detect synovial proliferation with greater sensitivity than clinical examination. ultrasound has also been utilized to define the presence of synovitis in oa patients, and at least one report indicates that contrast-enhanced us may be as sensitive as contrast-enhanced mri in detecting synovitis.19 on average the synovitis of oa is low-grade in comparison to the high-grade synovitis of ra, but still distinguishable from normal sm.20 it has been demonstrated that synovitis can be accurately quantified without using contrast21 but recent studies have incorporated the use of contrastenhanced mr imaging techniques to distinguish synovial thickening from effusion.22 for example, in a recent study by roemer et al23 the authors used both contrast-enhanced and non-enhanced images to examine a group of subjects with knee oa, and noted that synovitis was present in over 95% of the knee joints with an effusion, but also in 70% of knee joints in patients without an effusion.23 loeuille and colleagues noted that areas of synovial thickening identified on mr images correlated well with individual histologic changes, including inflammatory cell infiltration and lining hyperplasia.24 70 75 80 85 90 95 100 this study algergawy s et al karim z et al sensitivity specificity figure 4: comparison of the current study with others we compared our results with a study carried out at benha university, al qalyubiyah, egypt in 2011 where the sensitivity and specificity of ultrasound was 82.5% and 95% respectively in detecting synovial thickness of knee joint by taking synovial thickness of 2.3mm as a cut off.16 karim z and others assessed the validity and reproducibility of ultrasonography (us) as a means of detecting synovitis in the knee, by comparing us findings with findings of arthroscopy and clinical examination (figure 4). 25 they demonstrated that with the use of arthroscopy as the gold standard, us had a higher sensitivity (98% versus 85%), specificity (88% versus 25%), accuracy (97% versus 77%), positive predictive value (98% versus 88%), and negative predictive value (88% versus 20%) compared with clinical examination. they concluded that ultrasonography is a valid and reproducible technique for detecting synovitis in the knee, and is more accurate than clinical examination. it may be valuable as a tool in studies investigating pain, diagnosis, and treatment response in knee arthritis. value of ultrasound, focusing on major applications of ultrasound in rheumatologic diseases shows concluded that ultrasound is emerging as a tool in the management of rheumatology patients through its gradual incorporation into routine clinical use in many countries and rheumatology centers. evidence for the reliability, validity as well as clinical value of ultrasound is increasing with continuing studies of this modality. future development in technology together with consensus of international and national educational programs may spur the wider application of ultrasound for various rheumatologic diseases, enabling it to become a powerful imaging tool for rheumatologists. 15,26,27 conclusion diagnostic accuracy of ultrasound is higher for the detection of synovial proliferation in patients with osteoarthiritis by using mri as the gold standard. references 1. hunter d j. guermazi a. imaging techniques in osteoarthritis. pm&r. 2012; 4(5):68-74. 2. lawrence rc, felson dt, helmick cg, arnold lm.esimates of the prevalence of arthritis and other rheumatic conditions in the united states. part ii. arthritis rheum. 2008;58:26–35. 3. braun h j, gold g e. diagnosis of osteoarthritis: imaging. bone. 2011; 11: 019-22. 4. attur m, krasnokutsky s, abramson s b. targeting the synovial tissue for treating osteoarthritis: where is the evidence? best practice & research clinical rheumatology. 2010; 24: 71–79. javascript:void(0); javascript:void(0); journal of rawalpindi medical college (jrmc); 2017;21(4): 366-370 370 5. ayral x, pickering eh, woodworth tg. synovitis: a potential predictive factor of structural progression of medial tibio-femoral knee osteoarthritis. osteoarthritis cartilage 2005;13:361–67. 6. menashe l, hirko k, losina e, kloppenburg m. the diagnostic performance of mri in osteoarthritis. osteoarthritis cartilage. 2012 ; 20: 13–21. 7. ijaz khan h, chou l, aitken d, mcbride a, ding c. correlation between changes in global knee structures assessed on mri and radiographic osteoarthritis changes over 10 years in a mid-life cohort. arthritis care & research 2016; 68(7):958–64. 8. zufferey p, tamborrini g, gabay c, krebs a. recommendations for the use of ultrasound in rheumatoid arthritis: literature review and sonar score experience. swiss med wkly. 2013; 143:w13861. 9. jain m,jonathan samuels j, m.d. musculoskeletal ultrasound as a diagnostic and prognostic tool in rheumatoid arthritis. bulletin of the nyu hospital for joint diseases. 2011; 69(3):215-19. 10. fernandez-madrid f, karvonen rl, teitge ra.synovial thickening detected by mr imaging in osteoarthritis of the knee confirmed by biopsy as synovitis. magn reson imaging. 1995;13:177–83. 11. rowbotham el,grainger ej. rheumatoid arthritis:ultrasound versus mri. american journal of roentgenology. 2011; 197:54146. 12. oehler s, neureiter d, meyer-scholten c. subtyping of osteoarthritic synoviopathy. clin exp rheumatol 2002;20:633-40. 13. kim cw, kim m j, park sb, han sh, a case of rheumatoid arthiritis with unilateral knee synovial hypertrophy in h emiplegia. ann rehabil med. 2012;36: 144-47. 14. abraham a m, goff i , pearce m s, francis r m. reliability and validity of ultrasound imaging of features of knee osteoarthritis in the community. bmc musculoskeletal disorders 2011, 12:70-78. 15. kang t, horton l, emery p, wakefield j. value of ultrasound in rheumatologic diseases. j korean med sci. 2013; 28: 497-507. 16. algergawy s, haliem t, al-shaer o. clinical, laboratory, and ultrasound assessment of the knee in juvenile rheumatoid arthritis. arthritis and musculoskeletal disorders. 2011; 4: 21–27. 17. ejbjerg b j, narvestad e, jacobsen s, thomsen h s. optimised, low cost, low field dedicated extremity mri is highly specific and sensitive for synovitis and bone erosions in rheumatoid arthritis wrist and finger joints: comparison with conventional high field mri and radiography. ann rheum dis. 2005; 64:1280 –87. 18. ganvir s.d, zambare b r. prevalence and identification of risk factors for knee osteoarthritis among elderly men and women. sch. j. app. med. sci. 2013; 1(6):700-03. 19. song ih, althoff ce, hermann kg, scheel ak. contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with mri. ann rheum dis. 2009;68:75–83. 20. slansky e, li j, haupl t, morawietz l. quantitative determination of diagnostic accuracy of the synovitis score and its components. histopathology. 2010;57:436–43. 21. pelletier jp, martel-pelletier j, abramson sb. osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. arthritis rheum 2001;44:1237–47. 22. guermazi a, roemer fw, hayashi d, crema md. assessment of synovitis with contrast-enhanced mri using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the most study. ann rheum dis. 2011;70:805–11. 23. roemer fw, kassim javaid m, guermazi a. anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced mri. osteoarthritis cartilage. 2010;18:1269–74. 24. loeuille d, chary-valckenaere i, champigneulle j.macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity. arthritis rheum. 2005;52:3492– 501. 25. karim z, wakefield rj, quinn m, conaghan pg. validation and reproducibility of ultrasonography in the detection of synovitis in the knee: a comparison with arthroscopy and clinical examination. arthritis & rheumatism 2004;50:387 94. 26. jones g, ding c, scott f, glisson m, cicuttini f. early radiographic osteoarthritis is associated with substantial changes in cartilage volume and tibial bone surface area in both males and females. osteoarthritis cartilage 2004;12:169– 74. 27. wildi lm, martel-pelletier j, abram f, moser t. assessment of cartilage changes over time in knee osteoarthritis diseasemodifying osteoarthritis drug trials using semiquantitative and quantitative methods: pros and cons. arthritis care res 2013;65:686–94. summary journal of rawalpindi medical college (jrmc); 2017;21(2): 165-168 165 original article catheter related infections in medical intensive care units malik shehryar 1, zuhair ali rizvi 2, muhammad osama 3, muhammad tauseef dildar 4, muhammad umar5 1. coronary care unit holy family hospital and rawalpindi medical university ; 2. medical student 4th year rawalpindi medical university; 3. medical icu, holy family hospital and rawalpindi medical college; 4. combined military hospital, sialkot; 5. department of medicine holy family hospital and rawalpindi medical university abstract background: to determine the frequency of different isolates from samples taken from catheter tips of tracheal suction catheters, endotracheal tubes and central venous pressure line catheters among the patients of medical intensive care units methods: in this descriptive cross sectional study a total of 200 patients were checked for bacterial or fungal growth. included samples were 140 from suction catheters, 51 from endotracheal tubes and 9 from cvp catheters cultured for bacterial or fungal growth. different organisms were identified on the basis of colony morphology, colony staining and biochemical reactions. results: out of 200 patients, majority (72.5%) patients were found to be positive for bacterial or fungal growth. out of which 89(62.2%) were male and 54(37.8%) were females. one hundred and one (69.7%), 38(26.2%), 6(4.1%) growth cultures were obtained from samples of tracheal suction catheter tips, ett tips and cvp catheter tips respectively. microorganisms isolated were acinetobacter species 62(42.8%), klebsiella species 43(29.7%), pseudomonas species 19(13.1%), e.coli 8(5.5%), mrsa 5(3.4%), candida albicans 4(2.8%), proteus 2(1.4%) and staphylococcus aureus 2(1.4%). conclusion: acinetobacter, klebsiella and pseudomonas were the most frequent infectious agents isolated from catheter tips in settings of medical intensive care units. key words: catheter related infections, intensive care units, acinetobacter, klebsiella, pseudomonas,e.coli, mrsa, candida albicans introduction in 1929, forssmann introduced one of the first techniques for central venous catheterization and shared the 1956 nobel prize for medicine along with 2 other colleagues for pioneering work in this field.1since then, various catheter insertion techniques and indications for placement have evolved and currently about more than 450 million catheter devices are used every year in the world. in intensive care units (icu), multiple invasive devices are installed into patients. tracheal suction catheters, endotracheal tubes (ett) and central venous pressure(cvp) catheters are most commonly used. they provide secure access to the central circulation for infusion therapy, nutritional support, hemodynamic monitoring, plasmapheresis, apheresis and hemodialysis. 1-4 the issue in catheter insertion which has gained increasing attention in recent years is the associated infection with catheter placement. catheter-related infections occurring in the intensive care unit are common, costly and potentially lethal. patients with catheters are at risk of developing local as well as systemic infectious complications like local insertionsite infection, catheter related blood stream infections (crbsi), septic thrombophlebitis, endocarditis and other metastatic infections. crbsis are considered among the first and most “preventable” classes of nosocomial infections especially in icu. the most serious complications in these catheter related infections are bacteremia, sepsis and death. the definitive diagnosis of catheter infection can be made by using a combination of clinical signs and symptoms together with the quantitative culture techniques.2-5 the organisms most commonly encountered in catheter related infections in icu in initial days are gram positive organisms while in later stages gram negative organisms are more prevalent with acinetobacter, klebsiella and pseudomonas as the most notoriously known for causing hospital acquired pneumonias, ventilator associated pneumonias, septicemias and many other infections.6patients with prolonged hospital stays, critical conditions, open wounds, especially those on ventilators and patients with multiple invasive devices are most likely to have a greater risk of reinfections by these organisms leading to multiple drug resistant strains.7 air, person to person contact and contaminated hands and surfaces are common modes of transmission of these organisms. journal of rawalpindi medical college (jrmc); 2017;21(2): 165-168 166 maintenance of proper sterilization techniques, sterilization of taps, disinfectant bottles and other materials, hand washing of visitors, paramedics, nurses and doctors along with continuous subglottic suctioning can reduce the chances of patients acquiring nosocomial infections by these organisms and can also decrease the cost of health care management. patients and methods this descriptive cross sectional study was conducted in medical intensive care unit of holy family hospital (hfh) from july-dec 2016 after ethical approval from institutional research forum of rawalpindi medical college. a total of 200 (126 male and 74 female) patients were checked for bacterial or fungal growth. majority (70%) samples from tracheal suction catheters, 51(25.4%) from endotracheal tubes and 9(4.5%) from cvp line catheters.inclusion criteria included all those patients admitted in medical icu for minimum of two weeks and having tracheal suction catheters, ett tube or cvp line passed after admission in micu. patients having admission duration less than two weeks in medical icu and suction catheters, ett tube or cvp line installed before admission to medical icu of hfh were excluded from our study. the samples included initial 2-3cm of catheter tips which were then cultured for bacterial or fungal growth. different organisms were identified on the basis of colony morphology, colony staining and biochemical reactions. the data was analyzed using spss v 22 and descriptive statistics were applied. results majority (145/200;73%) of samples taken from catheters of patients of medical icu showed positive growth for different microorganisms. one hundred and one out of one hundred and forty (72.1%), 38/51 (74.5%) and 6/9 (66.6%) samples taken from tracheal suction catheter tips, ett tips and cvp catheter tips showed positive results for growth cultures. acinetobacter, klebsiella and pseudomonas were the most common microorganisms to be isolated. (table 1 &2).all the organisms were almost equally distributed in both genders except for acinetobacter and klebsiella. acinetobacter was found to be more common in females (35.1% ) as compared to males (28.6%) while klebsiella was found to be more common in males (27.0%) as compared to females (12.2%) (table 2).mean age for isolation of acinetobacter, klebsiella and pseudomonas from catheter tips of patients of medical icu was 40.9, 39.7 and 32.3 years respectively. acinetobacter and klebsiella table 1. organisms cultured organisms isolated %prevalence acinetobacter 31.0% no growth 27.5% klebsiella 21.5% pseudomonas 9.5% e.coli 4.0% mrsa* 2.5% candida 2.0% staphyloccus 1.0% proteus 1.0% *mrsa=methicillin resistant satph aureus table 2 : percentage of organisms at culture sites organism culture site cvp ett suction catheter count %age count %age count %age acinetobacter 4 44.4% 14 27.5% 44 31.4% candida 0 0.0% 1 2.0% 3 2.1% e.coli 0 0.0% 2 3.9% 6 4.3% klebsiella 2 22.2% 6 11.8% 35 25.0% mrsa* 0 0.0% 1 2.0% 4 2.9% n0 growth 3 33.3% 13 25.5% 39 27.9% proteus 0 0.0% 2 3.9% 0 0.0% pseudomonas 0 0.0% 10 19.6% 9 6.4% staphylococcus (methicillin sensitive) 0 0.0% 2 3.9% 0 0.0% table 3. gender wise distribution of organisms organism gender female male count column n % count column n % acinetobacter 26 35.1% 36 28.6% candida 2 2.7% 2 1.6% e.coli 4 5.4% 4 3.2% klebsiella 9 12.2% 34 27.0% mrsa 5 6.8% 0 0.0% no growth 20 27.0% 35 27.8% proteus 0 0.0% 2 1.6% pseudomonas 8 10.8% 11 8.7% staphylococcus 0 0.0% 2 1.6% journal of rawalpindi medical college (jrmc); 2017;21(2): 165-168 167 were found to be more common in two age groups i.e, young (20-40yrs old) and elderly (60-onwards). such pattern wasn’t observed in pseudomonas and other microorganisms).the period prevalence rates were calculated for acinetobacter, klebsiella and pseudomonas. 3 out of every 10, 2 out of every 10 and 1 out of every 10 patients was found to be culture positive for acinetobacter, klebsiella and pseudomonas respectively. discussion in the early 20th century various people started thinking of invasive devices for better hemodynamic monitoring and patient outcome. in 1929, forssmann introduced one of the first techniques for central venous catheterization and shared the 1956 nobel prize for medicine along with 2 other colleagues for pioneering work in this field.1 since then a lot of work has been done on it and multiple invasive techniques have been invented. later on attention was diverted to the infection associated with these devices leading to huge increase in amount of money spent on patient care. in the growth cultures obtained from tracheal suction catheter tips, it was seen that gram negative bacteria were more common than gram positive bacteria. among gram negative bacteria, the most common isolates were obtained of acinetobacter, klebsiella and pseudomonas which is in accordance with the study conducted to determine the etiological profile in patients with ventilator associated pneumonias in india. 2 early-onset vap, which occurs between 48 to 72 hours after intubation, is usually the result of aspiration and is often due to s aureus, haemophilus influenzae, or streptococcus pneumoniae.while lateonset ventilator associated pneumonia has been attributed to antibiotic-resistant organisms, like pseudomonas aeruginosa, mrsa, acinetobacter species, and enterobacter species. 3 the mean duration of intubation before sampling in our study was 7 days which might be responsible for the diversity of organisms found.it has been stated that the rapid colonization of endotracheal (within 12–36 hours after intubation) is by gram-positive bacteria from the mouth. 4-5 cardenosa cendrero et al found an 89% prevalence of tracheal colonization. in their study, it was observed that within 24 hours of mechanical ventilation, only gram positive bacteria were found while later during the course of intubation only gram-negative bacteria, antibiotic-resistant organisms, and yeast were found which is in accordance with our study. since all our samples were taken during later course of intubation hence gram negative microorganisms were more commonly found.6 in a study conducted to determine the antimicrobial susceptibility of various bacteria, it was stated that recurrent infections with same strains of bacteria at same site have led to development of resistance against rare antibiotics like colistin and tigecycline.7 new endotracheal tubes have been introduced to provide continuous aspiration of subglottic secretions and have been effective in reducing the occurrence of vap8-10 merrer et al conducted a randomized controlled trial so that patients were randomly assigned to undergo insertion of central venous catheter at either subclavian vein or femoral vein. various microorganisms were recovered from colonized central venous catheter or catheter related clinical sepsis with or without blood stream infections and the results were compared between subclavian and femoral group. staphylococcus and enterobacteriaceae were the most common microorganisms to be isolated from both sites followed by entertococcus and pseudomonas from femoral site. in our study central venous catheters inserted only at subclavian vein or internal jugular vein were included and pseudomonas could not be isolated which is in accordance with the study done by merrer et al.11 in our study, acinetobacter and klebsiella were the most common gram negative bacterias to be isolated from the central venous catheters which in accordance with the study done by parameswaran et al on intravascular catheter related infections.12 it has been stated that central venous catheterization longer than five to seven days was associated with a higher risk of catheter-related infection13-16it has been suggested that the order for punction, to minimize cvc-related infection risk, should be subclavian (first order), jugular (second order) and femoral (third order).15-16. deshpande et al. reported that there was no statistically significant difference in the incidence of infection and colonization at the subclavian, internal jugular and femoral sites.23 cobb found that 21% of the catheters studied were positive on semiquantitative culture (sqc), of which 16% were associated with local catheter associated infection (cai) and 5% with bloodstream infection.24 charalambous et al. found that 34% of the catheters studied were positive on sqc.25 according to fortun et al., the rate of incidence of tip colonization was 2.9 per 1000 catheter-days and of bacteremia was 1.2 per 1000 catheter-days.23 journal of rawalpindi medical college (jrmc); 2017;21(2): 165-168 168 a cohort and quasi-experimental multicenter study study was conducted to compare the effectiveness of alcoholic chlorhexidine with povidine idonine for cutaneous antispectic use in prevention of central venous catheter related infections, it was observed that povidone iodine was more effective than 2% chlorhexidine (p=0.037).18 it has also been stated that the disinfectants like chloroxylenol (dettol) and chlorhexidine gluconate(savlon) can be used as alternatives to phenol and sodium hypochloride solution.19abelehorn et al found that in patients receiving mechanical ventilation for more than 4 days, oropharyngeal decontamination reduced the rate of colonization and infection significantly.20 conclusion 1.acinetobacter, klebsiella and pseudomonas are the most frequent infectious agents isolated from catheter with course of intubation longer than 7 days in settings like medical intensive care units. 2. the antimicrobial sensitivity patterns of common isolates can be used to provide guidelines for the intensivist in critical care medicine to start appropriate empirical antibiotic therapy depending upon the clinical scenario. this can be cost-effective and can prevent indiscriminate use of antibiotics. 4.the importance of strict asepsis and ideal catheter care has to be reinforced to minimize these infections. references 1. kollef mh. the prevention of ventilator-associated pneumonia. n engl j med. 1999;340:627–33. 2. barie ps. importance, morbidity, and mortality of pneumonia in the surgical intensive care unit. am j surg. 2000;179(2 suppl 1):2–7. 3. feldman c, kassel m, cantrell j. the presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation.eurrespir j. 1999;13:546–51. 4. cardenosa ja, sole-violan j, bordes benitez a. role of different routes of tracheal colonization in the development of pneumonia in patients receiving mechanical ventilation. chest. 1999;116:462–70. 5. baveja s, anuradha de, taklikar s, sonavane a, wanjari k. multidrug resistant bacteria in a tertiary care hospital journal of evolution of medical and dental sciences 2012;1(6):944-51 6. schorr a and o’malley p. continuous subglottic suctioning for the prevention of ventilator-associated pneumonia: potential economic implications. chest.2001;119:228–35. 7. valles j, artigas a, rello j. continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. ann intern med.1995;122:179–86. 8. kollef mh, skubas nj, sundt tm. a randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients. chest.1999;116:1339–46. 9. merrer j, de jonghe b, golliot f, lefrant jy. complications of femoral and subclavian venous catheterization in critically ill patients. jama 2001;286: 700-07 10. parameswaran r , jatan b, sherchan , muralidhar varma d. intravascular catheter-related infections in an indian tertiary care hospital j infect dev ctries 2011; 5(6):452-58 11. richet h, hubert b, nitemberg g, andremont a. vascular catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients. j clin microbiol 1990; 28: 2520-25. 12. heard so, wagle m, vijayakumar e, mclean s, brueggemann a. influence of triple-lumen central venous catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia. arch intern med 1998;158:81-87. 13. moro ml, vigano ef, cozzilepri a .risk factors for central venous catheter-related infections in surgical and intensive care units. the central venous catheter related infections study group. infect control hosp epidemiol 1994; 15: 253264 14. gil rt, kruse ja, thill-baharozian mc, carlosn rw. triple vs single-lumen central venous catheters. a prospective study in a critically ill population. arch intern med 1989;149:1139-43. 15. parameswaran r , jatan b. sherchan , muralidhar varma d. intravascular catheter-related infections in an indian tertiary care hospital j infect dev ctries 2011; 5(6):452-58 16. pages j, hazera p, mégarbane b, du cheyron d, thuong m, dutheil jj.venous sites for catheterization .intensive care med 2016;42(9):1418-26. 17. abele-horn m, duaber a, bauernfeind a. decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (sod). intensive care med 1997;23:187–195. 18. lemaster ch, agrawal at, hou p, schuur jd. systematic review of emergency department central venous and arterial catheter infection. int j emerg med. 2010;3:409–23. 19. koh db, gowardman jr, rickard cm, robertson ik. prospective study of peripheral arterial catheter infection and comparison with concurrently sited central venous catheters. crit care med. 2014;36:397–402. 20. 20. lucet jc, bouadma l, zahar jr, schwebel c, geffroy a, pease sl. infectious risk associated with arterial catheters compared with central venous catheters. crit care med. 2013;38:1030–35. 21. fortún j, perez-molina ja, asensio a, calderón c. semi quantitative culture of subcutaneous segment for conservative diagnosis of intravascular catheter related infection. jpen j parenter enteral nutr 2015;24:210–14. 22. deshpande ks, hatem c, ulrich hl, currie bp. the incidence of infectious complications of central venous catheters at the subclavian, internal jugular and femoral sites in an intensive care unit population. crit care med. 2014;33:13–20. 23. cobb dk, high kp, sawyer rg, sable ca, adams rb, lindley da, et al. a controlled trial of scheduled replacement of central venous and pulmonary-artery catheters. n engl j med. 1992;327:1062–68. 24. charalambous c, swoboda sm, dick j, perl t. risk factors and clinical impact of central line infections in the surgical intensive care unit. arch surg. 1998;133:1241–46. 25. juste rn, hannan m, glendenning a, azadin b, soni n. central venous blood culture: a useful test for catheter colonisation? intensive care med. 2000;26:1373–75. authorship: 1conception , synthesis & planning of the research;2,3 active participation in methodology; 4 critical revision of the article and final approval of the version to be published summary journal of rawalpindi medical college (jrmc); 2018;22(1): 22-26 22 original article visual outcome of intravitreal bevacizumab in treatment of diabetic retinopathy kanwal zareen abbasi 1, warda ali 1, qamar farooq 1, ali raza 1, ana rizvi 2 1.department of ophthalmology benazir bhutto hospital and rawalpindi medical university; 2. department of radiology, krl hospital, islamabad. abstract background :to evaluate the efficacy of monthly intravitreal bevacizumab injections (1.25 mg/.05 ml) in improving or stabilizing visual acuity measured by snellen’s visual acuity charts for diabetic retinopathy. methods: this was a prospective quasi experimental study of 59 diabetic patients having diabetic retinopathy with indication of intravitreal anti vegf,bevacizumab. patients diagnosed of having fresh vitreous haemorrhage and diabetic macular edema were included. maximum three intravitreal bevacizumab injections were given, each with a dose of 1.25mg in 0.05ml(at 0month, 1 month, 2 months) with final follow up at the period of 3 months. the criteria for improvement was a gain of at least one line on snellen’s visual acuity chart, compared to the baseline while stabilization was considered if the visual acuity was unchanged relative to the baseline. results: a total of 59 patients, 25 (49.1%) males and 34 (50.84%) females , having age range 40-65 years,were given intravitreal injection. twenty six eyes (44.06%) with diabetic macular edema showed improvement while visual acuity was stabilized in 4 eyes (6.7%). in patient with vitreous hemorrhage, 27 eyes (45.76%) showed improvement while stabilization of visual acuity was noted in 2 eyes (3.3%). no patient with worsening of visual acuity was noted. conclusion: intravitreal bevacizumab is very effective in improving the visual outcome in diabetic patients having macular edema and vitreous hemorrhage. key words: visual outcome, intravitreal, bevacizumab, diabetic retinopathy introduction as the prevalence of diabetes is increasing in the world, diabetic retinopathy (dr) is becoming a most important public health problem and threat to sight in the working-age population.1, 2 it is also a major cause of blindness in developing countries. according to the diabetic association of pakistan – world health organization (dap-who) survey (1994-1998), overall prevalence of diabetes in pakistani population is 11.47%.1in diabetic retinopathy there are abnormal retinal blood vessels which can be either due to the proliferation of new vessels (proliferative retinopathy) or due to functionally incompetent and leaky vessels. the vascular endothelial growth factor (vegf) has been suggested as a main factor, firstly in proliferation of new weak vessels which can rupture causing vitreous hemorrhage and resulting in decrease visual acuity, and secondly it causes the breakdown of the blood-retinal barrier causing increased vascular permeability which results in retinal edema by disturbing the endothelial tight junction proteins. this retinal edema in macular area is called diabetic macular edema and when it fulfills a certain clinical criteria, it is known as clinically significant macular edema.2, 3 most of the adults became blind due to proliferative diabetic retinopathy (pdr) and principally treated by pars plana vitrectomy and argon laser but the bleeding from fibrovascular membrane (fvm) is still a risk to be considered. a humanized vascular endothelial growth factor (vegf) antibody known as bevacizumab (avastin genetech inc, south san francisco, california, usa) previously used for metastatic colorectal carcinoma but recent reports have showed its effectiveness in the treatment of neovascular disorder in the eye like proliferative diabetic retinopathy and in diabetic macular edema.4 though the normal human retina contains vegf, its levels are considerably raised in eyes with diabetic macular edema(dme) and proliferative diabetic retinopathy( pdr). therefore, intravitreal anti-vegf treatments have been recommended as an adjunctive treatment for dme.3 the drug acts by decreasing the size and number of new vessels and also helps in resolving the vitreous hemorrhage . currently, some journal of rawalpindi medical college (jrmc); 2018;22(1): 22-26 23 anti-vegf drugs, including pegaptanib, ranibizumab, bevacizumab, and aflibercept, are available.5 bevacizumab (avastin, genentech inc., san francisco, ca) is a complete full-length humanized antibody, it binds to and competitively inhibits all isoforms of the vegf-a family. while bevacizumab is presently fda approved for the treatment of metastatic colorectal cancer, metastatic breast cancer, and non-small cell lung cancer , it is widely used off-label for treatment of ocular diseases like retinal vein occlusion, neovascular age-related macular degeneration, dme, proliferative diabetic retinopathy, rubeosis irides, and retinopathy of prematurity5. although intravitreal use of bevacizumab is an offlabel option, its use has increased exponentially in the past few years primarily due to its efficacy and cost effectiveness.5 the purpose of this study was to evaluate the efficacy of monthly intravitreal bevacizumab injections (1.25 mg/.05 ml) in improving or stabilizing visual outcomes (best corrected visual acuity (bcva)), as measured by snellen’s visual acuity charts, for diabetic retinopathy. patients and methods this prospective study which was conducted at benazir bhutto hospital, rawalpindi from july to june 2015.a total number of 59 eyes of 59 patients were selected on the basis of non-probability, purposive sampling. inclusion criteria was diabetic patients with vitreous hemorrhage (associated with proliferative diabetic retinopathy) with absence of tractional retinal detachment on b-scan ultrasonography,diabetic macular edema with any stage of non proliferative diabetic retinopathy and diabetic macular edema with proloferative diabetic retinopathy but without vitreous hemorrhage. diabetic patients who had received prior treatments with other modalities like laser photocoagulation, intravitreal ranibizumab, intravitreal or posterior subtenon triamcinolone, patients with anterior segment diseases, diseases affecting the vision like corneal opacity, uveitis, glaucoma, visually significant cataract, etc. due to which exact role of bevacizumab, regarding visual outcome, cannot be assessed .patients with other associated posterior segment diseases affecting the vision like age related macular degeneration, central retinal vein occlusion, central retinal artery occlusion, retinal detachment (rhegmatogenous, tractional, serous, all type of), opic nerve disease, etc and patients who developed any complications of intravitreal bevacizumab which can affect the visual acuity , were excluded. pre-operatively visual acuity was measured using snellen’s acuity chart, complete anterior segment and posterior segment examination was done using slit lamp, +90d lens, indirect ophthalmoscopy. intraocular pressure (iop) was measured using goldman applanation tonometer. fundus fluorescein angiography and b-scan ultrasound examinations were done where necessary. the risks and benefits of treatment were discussed and informed consent was taken .all the patients included in the study received intravitreal bevacizumab with a dose of 1.25mg in 0.05ml and given by the same surgeon. topical anesthetic proparacaine was given before injection and repeated as necessary. all the injections were given with strict sterile technique (cleaning conjunctival sac with diluted povidone iodine) under full aseptic conditions in operation theatre. injection was given 4mm, 3.5mm, 3mm posterior to the limbus in phakic, psuedophakic and aphakic eyes respectively through the infero-temporal pars plana with a 30-gauge needle . the injection site was compressed for several seconds to avoid reflux of avastin when the needle was removed. patients were advised to use antibiotic and steroid combination eye drops for 07 days after the intravitreal injection. follow up was scheduled after 1 week, 4 weeks and every month till the end of follow up at 3 months. follow up visits included checking visual acuity by snellen’s chart and complete ocular examination. at each visit complications like endophthalmitis, vitreous hemorrhage (not present pre-injection , in case of macular edema), traumatic cataract, uveitis, retinal detachment which can affect the visual acuity, were evaluated . the primary end point of the treatment was a change in best corrected visual acuity from baseline over 03 months. the maximum number of injections given was three for each eye and they were given four weeks apart.the criteria for improvement was a gain of at least one line on snellen’s visual acuity chart , compared to the baseline while stabilization was considered if the visual acuity on the snellen’s chart was unchanged relative to the baseline. results out of 59 diabetic patients, 42.4% were males and 57.6% were females. the age range was from 45 to 67 years with a mean of 53.02 ± 9.79. (table 1). all patients completed 1 month of follow-up after the last injection. the glycosylated hemoglobin (hba1c) was 6.0 ± 1.3 at baseline. pre-injection, there were 16 (27%) eyes with best corrected visual acuity (bcva) better than or equal to 6/15, 27 eyes (45%) with va between 6/24 and 6/60 and 16 (27%) with va below 6/60. at journal of rawalpindi medical college (jrmc); 2018;22(1): 22-26 24 the end of 1 month of follow up after 3rd injection, 37 (62.7%) eyes had bcva better than or equal to 6/15; 18 (30.50%) between 6/24 and 6/60 and in 4 (6.7%) eyes the vision was worse than 6/60. two (10%) eyes had bcva better than or equal to 6/18. so, the final assessment was 1 month after the 3rd injection.a total number of 59 patients, 25 males and 34 females with an age range of 40-65 years, mean age 53.02 (± sd 9.79) were subjected to intravitreal injection of bevacizumab (table 1 ). out of the total 59 eyes, 30 (50.84%) had diabetic macular edema and 29 (49.16%) with diabetic vitreous hemorrhage (dvh) (table 2). table 1: patient’s characteristics age range 40-65 males 25 (42.4%) females 34 (57.6%) no. of patients 59 duration of study 1 year average follow up 3 months table 2: frequency of dme and vitreous hemorrhage total number of eyes 59 dme 30 (50.84%) vitreous hemorrhage 29 (49.16%) table 3: baseline visual acuity (preinjection) baseline visual acuity dme(no. of eyes) dvh(no. of eyes) 6/300 10 5 6/150 1 6/60 1 6/30 8 5 6/24 7 6 6/15 3 11 6/12 2 twenty six eyes (44.06%) with diabetic macular edema showed improvement while visual acuity was stabilized in 4 eyes (6.7%). in patients with diabetic vitreous hemorrhage associated with proliferative diabetic retinopathy (pdr) with vitreous hemorrhage, 45.76%eyes showed improvement while stabilization of visual acuity was noted in 2 eyes (3.3%). no patient with worsening of visual acuity was noted. a significant outcome in visual acuity was noted (table 3-5; figure 1). the wilcoxon test was used for comparison of preoperative and postoperative bcva (table 6). for all statistical tests a p value of <0.05 was considered statistically significant and in our study it is <0.05 which is statistically significant. snellen visual acuity was converted to log mar for data analysis.no systemic side effects of the given treatment were observed.however amongst the local side effects, subconjunctival hemorrhage was the most frequent; occured in 20 eyes (19.6%). complications like endophthalmitis, retinal detachment or traumatic cataracts were not seen in any case. table 4: visual outcomes of ivb: post injection improvement at 3 months post injection visual acuity dme(no. of eyes) dvh(no. of eyes) 6/6 2 6/7.5 3 11 6/12 2 3 6/15 8 8 6/24 2 2 6/30 3 3 6/60 8 6/300 4 table 5: pre and post injection visual acuities ( taking all diseases in account) visual acuity preinjection, no. of eyes post injection, no. of eyes 6/6 – 6/15 16 37 6/24 – 6/60 27 18 < 6/60 16 4 figure 1. mean visual acuity before and after injection table 6: wilcoxon test: journal of rawalpindi medical college (jrmc); 2018;22(1): 22-26 25 mean visual acuity before injection mean visual acuity after injection p-value 0.921 0.562 0.001 discussion common causes of visual loss in patients of diabetic retinopathy are macular edema, vitreous haemorrhage and tractional retinal detachment. in patients of diabetic retinopathy, angiogenic mediators such as insulin like growth factor-1, erythropoietin, fibroblast growth factor and endothelial growth factor (vegf) are released as a result of retinal ischemia and lead to the formation of new vessels in the retina. vitreous hemorrhage occurs as a result of these neovascular growths and by precluding the retinal view, prevents panretinal photocoagulation, the gold standard treatment in proliferative diabetic retinopathy. the clinical use of anti-angiogenic agents has developed new opportunities for the treatment of retinal vascular disorders. considering the antiangiogenic therapy, it accelerates the resolution of hemorrhage and facilitates prp. so, it’s a good choice for patients with vitreous hemorrhage.6 diabetic macular edema is the main cause of decreased central vision in patients with diabetic retinopathy. it can be diffuse or localized. clinically significant macular edema includes retinal thickening within 500 µm of the center of the fovea, hard exudates within 500 µm of the center with associated retinal thickening (which may be outside the 500 µm) and at least one disc diameter of retinal thickening, any part of which is within one disc diameter of the center of the fovea. 7 diagnosis of macular edema is clinical but we also confirmed our diagnosis by fundus fluorescein angiography, the available investigation in our department. anti-angiogenic agents have been proved to be effective in resolving this macular edema. the agent which we used was bevacizumab. bevacizumab was first approved by the us food and drug administration (fda), for the treatment of carcinomas8. bevacizumab is used as an off-label treatment intravitrealy for ocular diseases with high levels of vegf, such as choroidal neovascularization (cnv), proliferative diabetic retinopathy, diabetic maculopathy and retinal vein occlusion.8 vegf, was first documented in 1989 by napoleon ferrara.8vegf inhibition induces several effects on endothelial cells including inhibition of proliferation.8 bevacizumab has been used on “off-label” basis since 2005. it is used as first line treatment in macular degeneration because of its cost effectiveness as compared to other drugs like lucentis and macugen (fda approved antivegf).9,10 the most common indications of bevacizumab shown in one paper by lihteh wu et al were diabetic retinopathy and cnv of several etiologies.11 similarly in our study, the main indications were diabetic retinopathy, with diabetic macular edema (50.84%) and pdr with vitreous hemorrhage(49.1%). in diseases like diabetic retinopathy, diabetic maculopathy, and retinal vein occlusions, increased levels of vegf were found in vitreous. regardless of a large antibody, bevacizumab confirmed full penetration of retina12. no evidence of a noxious effect was observed in patients treated with 1.25mg of bevacizumab measured by full field and multifocal erg.13 in a prospective study of patients with proliferative diabetic retinopathy treated with intravitreal injections of bevacizumab, a rapid regression of actively leaking neovascularization, as well as significant improvement in mean visual acuity from 20/160 to 20/125 at three months follow up, was found.14 in our prospective study, out of 59 patients with diabetic macular edema and pdr, 53 patients showed significant improvement (89.8%), however, 6 patients (10.2%), shows no change in bcva , and there was no patient with worsening of visual acuity. it is comparable to a local study by jahangir t, et al which also showed significant improvement in visual acuity in patients with diabetic macular edema after intravitreal avastin.15 in a study by tareen ifh, the mean bcva at base line was 0.42±0.14 log mar units. 16 this improved to 0.34±0.13, 0.25±0.12, 0.17±0.12 and 0.16±0.14 log mar units at 1 month after 1st, 2nd 3rd injections and at final visit at 6 months respectively, a difference that was statistically significant (p>0.0001) from base line. the mean 1mm central macular thickness measurement was 452.9 ± 143.1 µm at base line, improving to 279.8 ± 65.2 µm (p<0.0001) on final visit.in a study of bahoo mla , overall improvement rate was 11 (15.7%) with signifcant improvement from 1.028 log mar at baseline to 0.99 at 12 weeks. 17in a study of bokhari sa,mean central macular thickness (cmt) reduced from 502µm to 384µm. 18in a study of shaikh ff, mean central macular thickness was 520.40±139.1 µm at baseline, which decreased to 385.90±98.30 µm (p<0.0001) at one month and to 427.40±112.6 µm (p=<0.0001) at three months.19 conclusion 1.anti-vegf therapy is the mainstay for the treatment of many retinal diseases. journal of rawalpindi medical college (jrmc); 2018;22(1): 22-26 26 2.treatment with bevacizumab is beneficial in improving and stabilizing visual acuity in diabetic retinopathy. references 1. khan a, mahar ps, hanfi an, qidwai u. ocular complications after intravitreal bevacizumab injection in eyes with choroidal and retinal neovascularization. pak j ophthalmol 2010;26( 4): 291-95 2. khaled ag, shala by. ocular complications after intravitreal bevacizumab (avastin) in patients with diabetic retinopathy. journal of american science 2012;8(12):111014. 3. shima c, sakaguchi h, gomi f, kamei m, ikuno y.complications in patients after intravitreal injection of bevacizumab. acta ophthalmol 2008;86(4):372-76. 4. sigfourd dk, reddy s, mollineaux c, schaal s. global reported endophthalmitis risk following intravitreal injections of anti-vegf: a literature review and analysis. clin ophthalmol.2015; 9: 773–81. 5. falavarjani kg, nguyen qd. adverse events and complications associated with intravitreal injection of antivegf agents: a review of literature. eye 2013; 27(7): 787– 94. 6. alagoz c, yildirim y, kocamaz m, baz o, cicek u. the efficacy of intravitreal bevacizumab in vitreous hemorrhage of diabetic subjects. turk j ophthalmol. 2016 ; 46(5) : 221 25. 7. chun dw, heier js, topping tm. a pilot study of multiple intravitreal injections of ranibizumab in patients with center involving clinically significant macular edema. ophthalmology 2006;113:1706-12. 8. afaq a, shahid e, sharif-ul-hassan k. effectiveness of intravitreal bevasizumab in various ocular diseases. pak j ophthalmol 2013;29(2):578-81 9. ferrara n, hillan kj, gerber hp, novothy w. discovery and development of bevacizumab, an anti-vegf antibody for treating cancer. nat rev drug disc. 2004; 3: 391-400. 10. lihteh wu, maría a, castellanos m,quiroz-mercado h. 12 month safety of intravitreal injection of bevacizumab, results of panamerican collaborative retina study group (pacores). graefes arch clin exp ophthalmol 2008; 246: 81-87 11. hames d. assessing tumor angiogenesis using macromolecular mr imaging contrast media. j magn reson imaging. 1994; 7; 68-74. 12. shahar j, avery rl, hellwell g. electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (avastin). retina 2006; 26: 262-69. 13. maturi rk, bleau ia, wilson dl. electro physiologic findings after intravitreal bevacizumab (avastin) treatment. retina 2006; 26: 270-74. 14. jorge r, costa ra, callucci d. intravitreal bevacizumab for persistent new vessels in diabetic retinopathy (ibeppe study). retina 2006; 26; 1006-13. 15. jahangir t, jahangir s, tayyab h, hamza u. visual outcome after intravitreal avastin (bevacizumab) for persistent diabetic macular edema. pak j ophthalmol 2011; 27; 4;187-90 16. tareen i, aziz-ur-rahman, mahar ps, memon ms. primary effects of intravitreal bevacizumab in patients with diabetic macular edema. pak j med sci. 2013 ; 29(4): 1018–22 . 17. bahoo mla, karamat b, mirza ka, frooq mu. effect of intravitreal bevacizumab injection on visual acuity in patients with diabetic retinopathy. pak j med sci 2011;27(5):1063-66. 18. bokhari sa, kamil z, rizwi f. to compare the effect of intravitreal bevacizumab on the resolution of macular edema secondary to diabetic retinopathy and branch retinal vein occlusion. pak j ophthalmol 2012; 28 ( 2): 117-20 19. shaikh ff, arain a. effect of intravitreal bevacizumab in diabetic macular edema. pak j med sci 2011; 27( 3): 101822 http://www.ncbi.nlm.nih.gov/pubmed/?term=reddy%20s%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=mollineaux%20c%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=schaal%20s%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=ghasemi%20falavarjani%20k%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=nguyen%20qd%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=tareen%20iu%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=rahman%20a%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=mahar%20p%5bauth%5d http://www.ncbi.nlm.nih.gov/pubmed/?term=memon%20ms%5bauth%5d summary journal of rawalpindi medical college (jrmc); 2018;22(2): 164-167 164 original article evaluation of levonorgestrel subdermal implant as long term reversible contraceptive taqdees iftikhar, jehan ara, humaira arshad, nadra sultana department of gynae/obs, rawal institute of health sciences, islamabad abstract background: to study the reasons of acceptability, efficacy,short term and long term side effects of levonorgestrel subdermal implant as long term reversible contraceptive. methods: in this descriptive study women (n=13)were counselled regarding levonorgestrel sdi. levonorgestrel sdi was inserted sub-dermally in the upper arm under local anaesthesia. information was collected regarding study specific variables. follow up was performed at 1 and 6 months and 12,24 and 36 months. results: maximum number of patients wanting levonorgestrel subdermal implants were between 3035 years. majority of women opting for this procedure had 3-4 live issues. majority (44%) of the women choose this method based on personal information. most common side effect was heavy and irregular vaginal bleeding 18.7% after 6 months, and 17.3% after 12 months. patients advised medical treatment for heavy menstrual bleeding did not respond well(cyclical progestogens and tranexamic acid). fifteen percent of users got sdi removed by end of 12 months, mainly due to above side effects. the 3year cumulative pregnancy rate was zero. conclusion: levonorgestrel sdi can be an acceptable, convenient and effective long term reversible contraceptive method. menstrual disturbances and feeling of weight gain are the major reported side effects, leading to discontinuation of the method. key words: long term reversible contraception, levonorgestrel, irregular vaginal bleeding. introduction pakistan is a developing country with high maternal mortality and perinatal mortality and significant maternal and child morbidity. this situation can only be improved if pregnancies are planned and unwanted pregnancies are avoided through promotion of appropriate methods of contraception in young women. rapid population growth high rates of unintended pregnancies and hazards of unsafe abortions are problems faced by developing countries like pakistan.maternal mortality and morbidity is higher in patients without contraception use. 1. most of the women (75.8 %),in reproductive age, require and seek family planning services . 2 in 2011 peripert et al proposed that long acting reversible contraceptives (larc) have high efficacy and in order to reduce the number of unwanted pregnancies clinicians should offer long term reversible contraceptives as first line options 3 recent advances in contraception have developed methods which are safe, reversible and more easily available. 4. levonorgestrel subdermal implants (sci) were introduced nearly 28 years back and are marketed in more than 25 countries. currently they are available in pakistan with trade name of jedelle and sino ll.levonorgestrel sdi are two flexible rods containing 150 mg of levonorgestrel which is released slowly over 3-4 years causing anovulation, endometrial thinning and thickened cervical mucous. 5 these implants provide contraception for 3-5 years. 1 they are inserted by minor surgical procedure where two match stick size, soft rods are placed sub-dermally in the upper arm under local anaesthesia.4 levonorgestrel sdi can be removed any time before the specified period on clients wish. this method has many advantages e.g. is free from hassle of daily pill taking and there is no need of monthly clinical visits as in case of injectable contraceptives. sci becomes active in nearly 48 hours after insertion and does not interfere with coital activity. they are suitable for patients suffering from medical disorders like mild hypertension and diabetes and safer regarding thromboembolic effects. but they offer no protection against sexually transmitted diseases.6 common side effects include irregular menses, breast tenderness, headache, dyspepsia and feeling of weight gain. insertion of the implants is done as an outdoor surgical procedure. under aseptic measures and local anaesthesia two flexible rods containing levonorgestrel are inserted under the skin of upper arm with the help of a trocar. small aseptic dressing is applied to cover the wound. for removal, a small incision is made at the lower edge of the inserted rods journal of rawalpindi medical college (jrmc); 2018;22(2): 164-167 165 which then are removed with the help of small artery forceps. 7 subjects and methods this prospective observational study was performed at contraception clinic, department of gynae/obs, rawal institute of health sciences, islamabad,from july 2014 to december 2017. women, 20 to 45 years old (n=130), opting for the study were told about its purpose,method of insertion and plan of follow up. follow up was performed at 1, 6, 12, 24, and 36 months interval. insertion was performed in the minor operating theatre. after evaluation patient was advised to come on 4th to 5th day of menses. the inner side of upper arm was cleaned and draped, under local anaesthesia two rods of levonorgestrel subdermal implant (jedelle – trocar, reference 81075175 bayer pharma ag.berlin germany) were placed under the skin 8 cm above the elbow (figure 1 &2).women with bmi >= 30 kg/m2,with severe liver disease, with high risk for thromboembolism and who were within first 6 weeks postpartum, were excluded . clients were counselled regarding possible side effects and care of insertion site. follow up was performed in the contraceptive clinic or on telephone at specified intervals. women were informed that they can come to the clinic any time they need help or treatment. figure 1&2. subcutaneous levonorgestrel subdermal implant placed under the skin 8 cm above the elbow results mean age of implant users was 32 years, with maximum number between 31-35 years. women having 1-4 children were equally interested in the method. majority (38%) had 3-4 children. weight of women ranged from 60-65 kg (table 1). more than half (58.6 %) of the clients were previously using a contraceptive method, but wanted a new, safe and convenient method (table 2).fifty four (42%) adopted levonrgestrel on doctor or health care providers advice (table 3). the most common short term side effect was dyspepsia and loss of appetite (7.7 %), and feeling of weight gain (7.7%) . the most common long term side effect was heavy menstrual bleeding mostly reported at 6 to 12 months by 14% and 13.3%respectively (table 4). this was also the major cause for removal of sdi. cumulative pregnancy rate over 3 years was zero (table 4). table 1: sociodemographic characteristics (n = 130) age / years no percentage 20 25 22 17 % 26 30 38 29% 31 35 52 40% 36 40 14 11% 41 45 4 03 % number of live children 1-2 48 37% 3-4 50 38% 5-6 22 17% >6 12 09% last child born /years <1 56 43% 1-2 30 23% 3-4 24 18% >5 10 7.6% not known 10 7.6% table 2: previous contraception used by levonorgestrel sdi users method no percentage contraceptive pills 16 12% contraceptive injections 18 13% condoms 10 08% withdrawal method iucd 32 24% none 54 41% table 3: reason for accepting levonorgestrel sdi (n=130) reason no percentage doctor’s/ health-care provider’s advice 54 42% personal decision (information through social media, literature, etc.) 57 44% good experience by relative / friend 19 14% the method continuation at end of 24 months was 79%. at 36 months it was 73% (figure 3). the main reason for discontinuation was menstrual problems, 18 users were unable to tolerate this side effect. the second-most common reason for discontinuation was journal of rawalpindi medical college (jrmc); 2018;22(2): 164-167 166 gastric problems (dyspepsia and loss of appetite) weight gain resulting in device removal in 3 cases each (table 5) table 4: frequency of side effects over 3 years side effect 1 month 6 months 12 months 24 months 36 months (n= 130) (n= 129) (n= 120) (n= 101) (n=: 94) no(%) no(%) no(%) no(%) no(%) no complaint 92(70.8) 88(68.2) 55(45.8) 70(69.3) 78(83.0 ) p/v spotting 4(3.1) 2(1.6) 4(3.3) 2(2.0) 1(1.1) irregular menses 0(0.0) 4(3.1) 10(8.3) 4(4.0) 4(4.3) heavy menstrual bleeding 10(7.7) 18(14.0) 16(13.3) 8(7.9) 2(2.1) amenorrho ea 1(0.8) 2(1.6) 4(3.3) 0(0.0) 0(0.0) vaginal discharge 2(1.5) 0(0.0) 0(0.0) 0(0.0) 0(0.0) change of appetite / dyspepsia 10(7.7) 4(3.1) 2(1.7) 4(4.0) 0(0.0) weight gain 10(7.7) 2(1.6) 12(10.0) 4(4.0) 4(4.3) reported pregnancy 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0 0.0 lost 1(0.8) 3(2.3) 3(2.5) 4(4.0) 0(0.0) removed 0(0.0) 6(4.7) 14(11.7) 5(5.0) 5(5.3) figure 3: method continuation over study period table 5: reason for discontinuation levonorgestrel sdi (n= 30) reason frequency percentage planning next pregnancy 05 16% menstrual problems 18 60% medical reasons 01 3.3% weight gain 03 10% gastric problems 03 10% social reasons -- reported pregnancy -- discussion unwanted and unintended pregnancies are major cause of maternal morbidity and mortality in terms of induced abortions, social problems and uncontrolled medical diseases like severe anaemia, diabetes and hypertension.this grave problem can only be solved if these women are advised appropriate and effective contraceptive method.pakistan being a developing country needs larc (long acting reversible contraceptives) to be included in public welfare programs. levonorgestrel sdi are on wholist of essential medicine as most effective and safe medicine needed for health care system . 8this method is highly effective birth control method with one year failure rate of 0.05.9,10 this is consistent with our study where no pregnancy was reported during implant use. also it was acceptable by women of all parities. in pakistan use of levonorgestrel sdi is nearly 1% according to statistics provided by marie stopes society, pakistan.11we wanted to determine the reason of acceptability of levonorgestrel sdi, in our study. majority (42%) users opted for the method on doctors’ advice, hence health care providers play important role in helping women’s decision making. similar results were shown by a study carried at family planning centre of liaquat university hospital.12 but majority of women 44% who opted for the method, made their own choice based on media and social information.these findings were inconsistent with an international study carried out in greece, germany and turkey stating that women’s decision regarding family planning method is influenced more by family members and health care provider.13we found out that if media campaigns, information leaflets and lectures are designed keeping in view cultural, religious and economic factors. they are highly effective in promoting the use and continuity . different side effects were reported by levonorgestrel sdi users. in usa even lawsuits were filed against the manufacturer and the doctors who prescribed the method. 14in our study the most intolerable side effects reported were irregular menstrual bleeding, weight gain. less common effects were headache, nausea,dyspepsia and feeling of weight gain. implanon, a sdi consisting a single match stick size rod containing etonogestrel, now it has been replaced by naxplanon .15implanon users also reported side effects e.g. irregular menstrual bleeding, breast tenderness, loss of libido, headache and mood changes.16 severity of this side effect was not emphasized in previous studies by azmat sk, bahamondes l, and ali m. 11,17,18 we found out that journal of rawalpindi medical college (jrmc); 2018;22(2): 164-167 167 most common side effect was irregular menstrual bleeding but its frequency was higher than reported by previous studies 18.7%). 17,18 in most women it was not so heavy so as to cause medical problems like anaemia but had serious religious and social impact, this is consistent with a multicentre study carried by population welfare department sind. 11 the affected women were unable to perform prayer regularly or maintain fast.they were unable to have desired sexual relationship due to irregular vaginal bleeding which caused marital discord. demographic features, religious beliefs and husband and wife communications greatly influence the choice and continuation of family planning method. 19 we also experienced that most women who were willing for medical treatment with tranexamic acid and cyclical progestogens did not respond well to this treatment and ultimately got the implant removed. conclusion 1. levonorgestrel sdi is a convenient, effective and acceptable long term reversible contraceptive method for our population. 2. services provided by trained health care provider with good clinical judgment increases acceptability of the method. 3. menstrual disturbances is major side effect and its incidence is higher than reported in previous studies. intolerance to irregular and heavy menses was the most common reason which compelled users to discontinue this method. 4. regular follow up is important because early recognition of users’ problems, timely education and treatment improves long term adherence of the method. references 1. javed n, mehmood t, almas h. experiences of women and assessment of efficacy and side effects of sub-dermal implants. pakistan journal of medical research. 2016; 55(4): 99-102 2. shamin n, inayatullah a, rehan n. use of norplant in pakistan. journal of pakistan medical association. 1994 : 3-7 3. peipert jf, zhao q, allsworth je, petrosky e. continuation and satisfaction of reversible contraception. obstetrics & gynecology. 2011 ; 117(5):1105-13. 4. (ccp) jhbsophfcp, (who/rhr) whodorhar. family planning: a global handbook for providers (2011 update); 2011. 5. training on implants – green star trainers' manual 2014. 2014th ed 6. guttmatcher institute fact sheet 2015. [online]. available from: https://www.guttmatcher.org/factsheet/unintended-pregnancy-and-induced-abortionpakistan 7. united nations population fund. [online].; 2014. available from: http://www.unfpa.org/webdav/site/global/shared/factshe ets/srh/en-srh%20fact%20sheet-lifeanddeath.pdf 8. who model list of essential medicines (19th list). [online].; 2015. available from: http://www.who.int/medicines/publications/essentialmedi cines/eml_2015_final_amended_nov2015.pdf?ua=1 9. shoupe d, jr drm. the handbook of contraception: a guide for practical management. 2nd ed.: humana press; 2015 10. centers for disease control and prevention. [online].; 2016. availablefrom: https://www.cdc.gov/reproductivehealth/unintendedpregn ancy/pdf/contraceptive_methods_508.pdf 11. azmat sk, hameed w, lendvay a, shaikh bt, siddiqui ma. rationale, design, and cohort enrolment of a prospective observational study of the clinical performance of the new contraceptive implant (femplant) in pakistan. international journal of women's health. 2014 ; 6: 573-83. 12. memon a, hamid s, kumar r. client satisfaction and decision making amongst females visiting family planning clinics.journal of ayub medical college abbotabad pakistan. 2017; 29(4):626-29 13. blumenthal pd, edelman a. attitudes towards contraception in three different populations. clinical and experimental obstetrics & gynecology. 2008; 35(1): 22-26 14. johnson e, smyth c, jones c. cbc news. [online].; 2003. available from: https://web.archive.org/web/20030418181912/http://w ww.cbc.ca/consumers/market/files/health/medical_device s/lawsuits.html 15. . cameron s. methods of contraception implant. in bickerstaff h, kenny lc, editors. gynaecology by ten teachers. 20th ed.: crc ; 77 16. health24. [online].; 2016. available from: https://www.health24.com/lifestyle/woman/menstruatio n/woman-goes-through-hell-with-implanon-birth-controlimplant-20160422 17. bahamondes l, brache v, meirik o, ali m, habib n, landoulsi s. a 3-year multicentre randomized controlled trial of etonogestreland levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls. human reproduction. 2015 ; 30(11): 2527-38 18. ali m, akin a, bahamondes l, brache v, habib n, landoulsi s. extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant. human reproduction. 2016 ; 31(11): 2491-98. 19. mahmood n, ringheim k. factors affecting contraceptive use in pakistan. the pakistan development review. 1996; 35(1):1-22 https://www.guttmatcher.org/fact-sheet/unintended-pregnancy-and-induced-abortion-pakistan https://www.guttmatcher.org/fact-sheet/unintended-pregnancy-and-induced-abortion-pakistan https://www.guttmatcher.org/fact-sheet/unintended-pregnancy-and-induced-abortion-pakistan http://www.unfpa.org/webdav/site/global/shared/factsheets/srh/en-srh%20fact%20sheet-lifeanddeath.pdf http://www.unfpa.org/webdav/site/global/shared/factsheets/srh/en-srh%20fact%20sheet-lifeanddeath.pdf http://www.who.int/medicines/publications/essentialmedicines/eml_2015_final_amended_nov2015.pdf?ua=1 http://www.who.int/medicines/publications/essentialmedicines/eml_2015_final_amended_nov2015.pdf?ua=1 https://www.cdc.gov/reproductivehealth/unintendedpregnancy/pdf/contraceptive_methods_508.pdf https://www.cdc.gov/reproductivehealth/unintendedpregnancy/pdf/contraceptive_methods_508.pdf https://www.ncbi.nlm.nih.gov/pubmed/?term=blumenthal%20pd%5bauthor%5d&cauthor=true&cauthor_uid=18757668 https://www.ncbi.nlm.nih.gov/pubmed/?term=edelman%20a%5bauthor%5d&cauthor=true&cauthor_uid=18757668 https://web.archive.org/web/20030418181912/http:/www.cbc.ca/consumers/market/files/health/medical_devices/lawsuits.html https://web.archive.org/web/20030418181912/http:/www.cbc.ca/consumers/market/files/health/medical_devices/lawsuits.html https://web.archive.org/web/20030418181912/http:/www.cbc.ca/consumers/market/files/health/medical_devices/lawsuits.html https://www.health24.com/lifestyle/woman/menstruation/woman-goes-through-hell-with-implanon-birth-control-implant-20160422 https://www.health24.com/lifestyle/woman/menstruation/woman-goes-through-hell-with-implanon-birth-control-implant-20160422 https://www.health24.com/lifestyle/woman/menstruation/woman-goes-through-hell-with-implanon-birth-control-implant-20160422 404 not found 404 not found summary journal of rawalpindi medical college (jrmc); 2010;14(1):33-35 33 rota virus gastroenteritis in children upto five years of age ayesha afzal*, parveen akhtar tariq**, shehla choudhry** * social security hospital, islamabad **department of paediatrics, fauji foundation hospital, rawalpindi background: to estimate the proportion and peak age of rotavirus diarrhoea among children of age two months to five years methods: in this descriptive study five hundred patients with acute watery diarrhoea (awd) were screened for rotavirus. stool sample of about 5 ml was taken & tested in the laboratory for group a rotavirus antigen by enzyme immunoassays (eia). results: mean age of patients with awd was 12.5 months . out of 500 patients 147 ( 29.4%) were positive for group a rotavirus. majority of positive patients 116/147 (78.9%) were in the age group 2 months to 12 months. conclusions: as there are many types of rotavirus i.e. a, b, c, d, and e so overall burden for all serotypes will be much higher. rotavirus vaccine is an effective preventive measure available against rotavirus diarrhea. key words: acute watery diarrhoea; awd ; rotavirus introduction rotaviruses are most common cause of acute watery diarrhea in children worldwide. it is estimated that rotavirus causes 125-million diarrheal cases/year. rotavirus diarrhea deaths account for 20-40 deaths/year in developed countries and 440,000 deaths/year in developing countries. about 1/3 of these deaths occur in indian subcontinent.1 rotavirus diarrhea is more common during winter season in temperate climate. peak age of rotavirus diarrhea in children is 3 months to 2 years.2 rotavirus infection is transmitted through feco-oral route. after incubation period of 48 hours, patient develops fever and vomiting followed by profuse watery diarrhea lasting for 5 to 7 days.2 many studies are being done worldwide to estimate the incidence and prevalent strains of rotavirus gastroenteritis which will help in decision making for implementation of immunization against rotavirus. in india, there is marked diversity of rotavirus strains reported by studies performed in 18 indian cities. rotaviruses were detected in 23.4% of patients presenting to hospital with diarrhea.3 in australia, most prevalent serotype is g1 strain.4 a study conducted in america from 2002 to 2005, has shown diversity of group a rotavirus strains, most common g genotype detected was g9. changes in the g genotype frequency were observed from year to year.5 it is estimated that in asia 171,000 children will die of rotavirus diarrhea, 1.9 million will be hospitalized and 13.5 million will require outpatient visit by the time asian cohort reaches 5 years of age and medical cost will approximate $191million.rotavirus vaccine could be cost-effective and valuable in preventing rotavirus diarrhea associated morbidity and mortality.6 china is 2nd highest in mortality due to rotavirus and the only country licensed for rotavirus vaccination.7 clinically rotavirus diarrhea mimics any other cause of acute watery diarrhea and is treated with standard management protocol, i.e., oral rehydration therapy and continued feeding. antiinfective agent nitazoxanide has reduced the duration of severe rotavirus diarrhea in a study of hospitalized children in egypt. 8 use of probiotics for treatment of rotavirus diarrhea has shown improvement in mild cases but no role in dehydrating disease.9 hence the only costeffective option is prevention of rotavirus diarrhea through rotavirus vaccination. 10 currently two new live, oral, attenuated pentavalent and monovalent vaccines against rotavirus diarrhea have been licensed by the european medicines agency and the us food and drug administration, respectively, in 2006.11 pentavalent human-bovine reassortant rotavirus vaccine (hbrv) directed against rotavirus is being tried. hbrv vaccine has shown 68.8%-76.6%efficacy against any rotavirus diarrhea and 100% efficacy against severe rotavirus diarrhea.12 the pentavalent vaccine protects against rota virus diarrhea when administered as 3 dose series at 2,4, and 6 months of age. the 1st dose should be administered between 6 and 12 weeks of age, with all three doses completed by 32 wk of age. clinical trials in europe, latin america, and the us have demonstrated that these vaccines are safe and highly efficacious for preventing rotavirusassociated severe gastroenteritis.13 in pakistan, very little research is conducted journal of rawalpindi medical college (jrmc); 2010;14(1):33-35 34 regarding frequency of rotavirus diarrhea. this study was done to estimate burden and peak age of rotavirus diarrhea, so as to justify the recommendation and use of rotavirus vaccination at particular age as a preventive measure/tool. patients and methods it was a descriptive case series study conducted in the department of paediatrics, rawalpindi general hospital in 1 year duration from 6th november 2006 to 5 th november 2007. admitted patients of age two months to five years with non-bloody acute watery diarrhea were screened for rotavirus. stool sample of about 5 ml was taken in screw top container within 48 hours of admission and kept in refrigerator before being tested in the hospital laboratory for rotavirus antigen by enzyme immunoassays (eia).eia test was performed by centrifuging the stool sample with reagent (dako ideia rotavirus eia detection kit) at 20-30 c for 20 min. results were interpreted by 2 methods visual and photometric determination and by comparing them with standard positive and negative controls. limitations of test were that it detected only group a rotaviruses & test could be false negative in case of improper sampling e.g. stool sample taken after 3-5 days or not refrigerated. in order to determine the peak age prevalence of rotavirus diarrhea, patients were divided into age groups i-e ,group 1 =2months – 12 months ; group 2 =13months – 24 months ;group 3 =25months –36 months ; group 4 =37months48months;group 5 = 49months – 60months data was analyzed using spss version 10.mean +s.d was estimated for quantitative variable i.e age. simple frequency tables were used for qualitative variables. proportion was calculated for disease burden and peak age was measured using mode in frequency distribution of age. results of the 500 pts with awd of age 2months60months enrolled in study , 260 (52%) were male and 240 (48%) were female. mean age of all pts with awd was 12.5 months with sd of 11.7. out of 500 patients screened for rotavirus 147 pts ( 29.4%) were positive for group a rotavirus and 355 pts( 70.6 % ) were negative (fig.1), out of 147 patients (29.4%) positive for rota virus 116 pts (78.9%) fell into age group 1 (2m to12m) so peak age was found to be 2months 12months(table.1). mean age of rotavirus positive pts was 10.4 months with sd of 7.8. ro ta vi ru s id en tif ie d in s to ol positive negative percent 806040200 71 29 fig 1: rota virus positive cases in stool table 1: rota virus awd: case distribution according to age age groups frequency percentage group 1 (2 to 12 months) 116 78.9 group 2 13-24months 23 15.6 group 3 25-36months 6 4.1 group 4 37-48months 2 1.4 group 5 49-60months 0 0 total 147 100 discussion in asia 171,000 children die of rotavirus. china is 2nd highest in mortality due to rotavirus. in bangladesh between 5,756 and 13,430 children died each year in between 2001 and 2004 from severe rotavirus gastroenteritis.14 in pakistan very little research is being conducted regarding prevalence of rotavirus diarrhea. preventive measures like good hygienic measures and improved sanitation have no specific role in prevention, so vaccination is the only preventive tool. in present study burden of only group a rotavirus estimated was 29.4%. similar studies from different countries have shown different results. in journal of rawalpindi medical college (jrmc); 2010;14(1):33-35 35 indonesia rotavirus prevalence was about 45.5%.15 in india rotavirus positivity rates of group a rotavirus in hospitalized patients were 20%. 16 in another study from italy, rotavirus was observed in 29.5% of children with awd17 & in france general prevalence of rotavirus diarrhea was 27.9%. 17 in present study peak age of rotavirus diarrhea was 2 months to 12 months. a study conducted in isfahan, iran has shown that 84.2% of cases with rotavirus gastroenteritis were less than 2 years of age with peak age between 6-12 months.18 in another study conducted in yangon, myanmar showed rotavirus diarrhea most frequently occurred in children 6-17 months of age, and it was more commonly identified in boys (62%)19 ,whereas in present study rotavirus was more commonly identified in girls(52%).a study from denmark has shown that rotavirus diarrhea admissions peaked twice during early childhood i-e between 7-12 months of age and 79% of admissions had occurred before the age of 2 years ; proportion by sex were 56% boys and 44% girls.20 i in conclusion further studies are needed to find out overall burden of disease from all serotypes of rotavirus. as vaccination is the only cost-effective preventive strategy for rotavirus diarrhea so the role of vaccination against rota virus must be highlighted references 1. glass ri, bresee js, turcios r rotavirus vaccines: targeting the developing world. j infect dis. 2005; 192: s160-6. 2. bass m. rotavirus & other agents of viral gastroenteritis. in: behrmanre, kliegmanrm, jensonhb. nelson textbook of paediatrics.17th ed. philadelphia: judith fletcher; 2004:1081t. 3. kang g, kelkar sd, chitamber sd ray p, naik t. epidemiological profile of rotaviral infection in india: challenges for the 21st century. j infect dis 2005; 192: s 120-6. 4. kirkwood cd, cannan d, bogdanovic-sakran n, bishop rf, barnes gl.australian rotavirus surveillance program: annual report, 2006-07.commun dis intell. 2007 dec;31(4):375-9 5. parra gi, espínola ee, amarilla aa, stupka j, martinez m, zunini m . diversity of group a rotavirus strains circulating in paraguay from 2002 to 2005: detection of an atypical g1 in south america j clin virol. 2007 oct;40(2):135-41. epub 2007 aug 27. 6. podewils lj, antil l, hummeiman e, bresse j. projected cost effectiveness of rota virus vaccination for children in asia. j infect dis 2005; 192: s133-45. 7. fang zy, wang b, kilgore pf, bnresee js: sentinel hospital surveillance for rotavirus diarrhea in the people’s republic of china. j infect dis 2005; 192: s94-9. 8. lanta cf,franco m:nitazoxanide for rotavirus diarrhea. lancet 2006;368:100-101. 9. pant n, marcotte h, brüssow h, svensson l, hammarström l. effective prophylaxis against rotavirus diarrhea using a combination of lactobacillus rhamnosus gg and antibodies. bmc microbiol. 2007 sep 27;7:86 10. gill h, pasad j.probiotics,immunomodulation,and health benefits.advexp med biol.2008;606:423-54. 11. ruiz-palacios g, pérez-schael i, velázquez, f. safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. new england journal of medicine. 2006;354(1):11–22. 12. heaton pm, goveia mg, miller jm, offit p, clark hf. development of pentavalent rotavirus vaccine against prevalent serotypes of rotavirus gastroenteritis. j infect dis 2005; 192: s17-21. 13. vesikari, t, matson d, dennehy p.. safety and efficacy of a pentavalent human–bovine (wc3) reassortant rotavirus vaccine. new england journal of medicine. 2006;354(1):23–33. 14. national institute of population research and training, bangladesh demographic and health survey 2004.dhaka, national institute of population research and training, 2005.339 p. 15. putnam sd, sedyaningsih er, listiyaningsih e, pulungsih sp, komalarini s , soenarto y,et al. group a rotavirusassociated diarrhea in children seeking treatment in indonesia. j clin virol. 2007 dec;40(4):289-94. epub 2007 oct 30. 16. ramani s, kang g. burden of disease & molecular epidemiology of group a rotavirus infections in india. indian j med res. 2007 may;125(5): 619-32. 17. akoua-koffi c, akran v, peenze i, adjogoua v, de beer mc, steele ad, epidemiological and virological aspects rotavirus diarrhoea in abidjan, côte d'ivoire (1997-2000) bull soc pathol exot. 2007 oct;100(4):246-9. 18. kazemi a, tabatabaie f, reza m, ghazvini a.the role of rotavirus in acute pediatric diarrhea in isfahan, iran.pak j med sci. 2006 september;22(3) :282-285 19. moe k, hummelman eg,lwin t, htwe tt.hospital-based surveillance for rotavirus diarrhea in children in yangon, myanmar. j infect dis. 2005 sep 1;192: s111-3. 20. fischer tk, nielsen nm, wohlfahrt j..incidence and cost of rotavirus hospitalizations in denmark.,2007 (13):252254. http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22parra%20gi%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22esp%c3%adnola%20ee%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22amarilla%20aa%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus 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http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22adjogoua%20v%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22de%20beer%20mc%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22steele%20ad%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus javascript:al_get(this,%20'jour',%20'bull%20soc%20pathol%20exot.'); http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22moe%20k%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22hummelman%20eg%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22lwin%20t%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22htwe%20tt%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus javascript:al_get(this,%20'jour',%20'j%20infect%20dis.'); ayesha afzal*, parveen akhtar tariq**, shehla choudhry** * social security hospital, islamabad **department of paediatrics, fauji foundation hospital, rawalpindi introduction patients and methods results discussion references 404 not found 404 not found 404 not found summary journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 2 original article cardiovascular risk profile and prevalence of microalbuminuria in patients with type 2 diabetes mellitus: the campaign disease registry results ebrahim m. a1, khan a 2, zahir m 2, hassan z 2 1. zubaida medical centre , karachi ;2.sanofi-aventis pakistan abstract background: to assess the cardiovascular risk profile of patients with type 2 diabetes mellitus (t2dm), the prevalence of microalbuminuria, and the prescription pattern in management of overall cardiovascular/renal risk in out patient practice. methods: in this cross sectional study consecutive adult patients with t2dm signed the informed consent and were interviewed by the investigator to establish the cardiovascular risk profile. presence of microalbuminuria (20–200mg/l) was diagnosed using micral-test® strips. analysis was done by descriptive statistics, and multivariate logistic regression was performed to identify the independent risk-factors for the development of microalbuminuria. results: of the 1763 patients enrolled, data was analyzed on 1596 patients. major cardiovascular riskfactors included hypertension (55.4%), sedentary lifestyle (49.8%), and metabolic syndrome (30.5%). microalbuminuria was prevalent in 55.6% (95% ci 53.1-58.0) patients. on multivariate analysis, significant association was observed with total cholesterol (p = 0.029, or: 2.26, 95% ci: 1.09 – 4.71) and diastolic bp (p = 0.015, or: 2.67, 95% ci: 1.21 – 5.91). the most commonly prescribed antihypertensive drugs were angiotensin-converting enzyme inhibitors (41.7%), calcium channel blockers (13.2%) and beta blockers (10%), while most commonly prescribed antidiabetic drugs were sulfonylureas (61.9%), biguanides (56.1%) and thiazolidinediones (17.4%). conclusions: patients with t2dm are at increased cardiovascular risk specifically with uncontrolled diastolic blood pressure and high total cholesterol levels. there is also a high prevalence of microalbuminuria in patient with t2dm. key words: type 2 diabetes mellitus, cardiovascular risk, microalbuminuria. introduction diabetes mellitus (dm) is the commonest endocrine disorder .1,2 patients with type 2 diabetes mellitus (t2dm) often experience a long asymptomatic period of hyperglycemia leading to numerous complications at the time of diagnosis.3 diabetic nephropathy (dn), a common consequence of long-standing t2dm, has become the most common cause of end-stage renal disease.4,5 about one third of patients with t2dm develop progressive deterioration of renal function.6,7microalbuminuria (mau) is defined as “a urinary albumin excretion rate of 30 to 300 mg in 24 hour urine collection or of 20 to 200 mg/min in a timed overnight urine collection” and is most often the primary manifestation of nephropathy in patients with dm.8-13 mau significantly impacts the risk of related vascular events like cardiac abnormalities, cerebrovascular disease, and, possibly, peripheral arterial disease (pad). 14-18,20,21 the implicit associations between the troika of mau, cv disease and progressive renal impairment are being unraveled.the hypothesis that “the kidney is a window of the vasculature” suggests that albumin leakage into the urine is a manifestation of widespread vascular damage, it is unclear whether mau is a cause or a consequence of vascular disease. in light of these observations, endothelial function and chronic inflammation have been advanced as factors underlying the association.22, 23 the risk factors associated with mau are poor glycemic control, insulin resistance , uncontrolled hypertension, smoking and central obesity.13,24 in patients with t2dm, the risk of mau is impacted by factors including age, gender, body mass index (bmi), duration of diabetes, and dyslipidemia [24]. apart from old age and weight gain, hypertension and diabetes are reported as the two important physiological risk factors for mau.25 arterial hypertension is known to significantly increase the risk of cardio-renal disease when present along with t2dm.26 conversely, a higher rate of prevalence of journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 3 hypertension is seen in patients with t2dm and elevated urinary albumin excretion.27 cv damage like left ventricular hypertrophy, carotid artery thickening, and other end-organ damage are common presentations in hypertensive patients with mau.28-30 in addition to the periodic measurement of albuminuria in all patients with t2dm and hypertension, preventive steps against albuminuria to prevent future renal and cv adverse events are warranted.9,31,32 treatment targeting urinary albumin levels demonstrably reduce the risk for cv events as well as kidney disease progression.31,14 mau can be reversed and the future development of overt dn, and consequently, cv risk can be significantly reduced.15,3336 there is a lack of standardized nationwide data from pakistan to define the prevalence of mau and understand its association with adverse cv risk factors in patients with t2dm. in view of this, the cardiovascular risk profile and microalbuminuria prevalence in type 2 diabetes mellitus patients in the out patient setting in pakistan (campaign) study was conducted. patients and methods present study was a national, multicenter, observational, cross-sectional, and epidemiological study conducted between april 2009 and july 2009. this study aimed to recruit 1800 patients from 100 centers across 13 cities of pakistan. the study was conducted in the ambulatory care setting, at individual outpatient clinics. exclusion criteria included presence of type 1 diabetes, no diabetes, presence of primary renal pathology, concomitant urinary tract infection (diagnosed either on patient’s history or available investigations or both), menstruation, pregnancy and refusal of consent. of the 100 investigators who participated in the study, 70 were physicians and 30 were specialists such as medical internists, diabetologists, and cardiologists. this study entailed a single visit. the patients were recruited within a period of one month from the date of ‘first patient in’ in the given center. patients had to undergo a micral-test® (by roche diagnostics) on the day of the consultation at the investigator’s clinic. the test was performed using test strips for the immunological, semi-quantitative in vitro determination of urinary albumin from morning urine sample. a value of 20-200 mg/l of albumin was judged as pathological. our objective was to identify the proportion of t2dm suffering from microalbuminuria (micral test strips) in outpatient practice and not clinical (macroalbuminuria (> 200 mg/l)). patients with > 200 mg/l were not specifically identified on 24 hours urinary/albumin test as the patient was diagnosed on micral test. information on lipid profile including total cholesterol, high density lipoprotein (hdl), low density lipoprotein, very low density lipoprotein, triglycerides and other investigations such as serum creatinine, fasting blood glucose, random blood glucose, and abnormal glucose metabolism (hba1c) was recorded pakistan has a diabetic population of 5.2 million.37 in the dap-who study , non-insulin dependent diabetes was reported as 98.0%. 38 this makes the population with non-insulin dependent diabetes mellitus equivalent to 5,096,000 patients with t2dm. as there were no local statistics available on cv risk profile (primary objective of this study), the best estimate was assumed to be 50.0%. estimates show the prevalence of mau as 34.0% in a study conducted in karachi, pakistan [39]. in order to capture the lower estimated prevalence between mau and cv risk profile, 34% was plugged in as the expected frequency of mau in the universal population of patients with t2dm with an assumption of a worst acceptable prevalence of 37%. aiming for 99% confidence level and 3% precision, a sample size of 1,654 was required. accounting for incomplete forms, ineligible patients etc., a sample size of 1800 patients was proposed. estimations were done at country level. analysis population included only those who met inclusion and exclusion criteria and on whom all responses were documented and micral-test® was performed. cv risk variables were assessed as categorical and continuous variables depending on variable type. continuous variables were reported as means with standard deviations. no comparisons were envisaged as this was a descriptive exploratory study. bivariate analysis was performed to identify the associations between mau and cv risk factors. factors that showed a significant association with mau in bivariate analysis were entered into a logistic regression to identify the independent risk factors for the development of mau. in both the analyses, a p value <0.05 was considered significant. results of 1763 patients enrolled , 1596 (90.5%) patients were evaluable in this study. remaining patients (167) were excluded because they did not meet the inclusion criteria. the mean age of the patients was 52.7 (±10.4) years and 83.5% of patients were between 4th to 6th decades of life. an equal gender distribution was observed among patients (49.9% men vs. 51.1% women). the mean duration of t2dm was 6.8 (±5.5) journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 4 years with a mean age at diagnosis of 43.8 (±12.6) years. about 65% of the patients had a bmi ≥25 kg/m2. mean waist circumference was 99.4 (±13.2) cm. mean height and mean weight was 161.6 (±10.9) cm and 73.7 (±13.6) kg respectively. uncontrolled hypertension was observed in 58.0% of patients at the time of visit(table 1). patients with a known case of hypertension were 55.4% (884/1596 ) in which 19.1% (169/884) had a controlled bp. patients with a history of antihypertensive intake was 50.3% (802/ 1596) in which 20.7% (166/802) had a controlled bp. micral-test was performed on a random urine sample in 81% patients and on an early morning sample in 17% patients. more than half of the patients (55.6%; 95% ci: 54.2% 59.1%) with t2dm in outpatient practice were detected to have urinary albumin excretion of 20-200 mg/l on the test. only 10.7% had a similar test done prior to this study. the major cv risk factors based on patients’ history included hypertension in 55.4% patients, sedentary lifestyle in 49.8% patients and metabolic syndrome in 30.5% patients. bivariate analysis was performed to study the correlation between cv risk factors and mau . compared to proportion of patients with negative micral-test results the analysis indicated a significant association between positive mau and systolic bp ≥130 mm hg (p <0.01), diastolic bp ≥85 mm hg (p <0.01), fasting blood glucose >140 mg/dl (p = 0.008), total cholesterol ≥200 mg/dl (p = 0.003), triglycerides >200 mg/dl (p = 0.02), hba1c >7 (p = 0.004), sedentary lifestyle (p = 0.02), family history of premature cv disease in first degree relative before 50 years of age (p = 0.002), hypertension (p <0.01), diabetic nephropathy (p <0.01), congestive heart failure (p <0.01), metabolic syndrome (p <0.01), cad (p <0.01), pad (p <0.01) and mean duration of diabetes (p <0.01). out of 1596 patients enrolled in the study, hba1c was available for 553 patients. of the 553 patients, 412 patients had hba1c > 7%. i.e 26% of all patients had an elevated hba1c. of the 412 patients, 253 (61.4%) mau positive patients had an hba1c >7 (table 2). significant association was observed with total cholesterol (p = 0.029, or: 2.26, 95% ci: 1.09 – 4.71) and diastolic bp (p = 0.015, or: 2.67, 95% ci: 1.21 – 5.91). patients with mau were 2.26 times more likely to have high total cholesterol levels and 2.67 times more likely to have high diastolic bp. high cholesterol and dbp does contribute to the model with higher average for the mau positive after controlling other factors constant. table 1.demographic and clinical characteristics of patients (n = 1596) parameters values* mean age (years) 52.7 ± 10.4 mean age at diagnosis (years) 43.8 ± 12.6 mean duration of diabetes (years) 6.8 ± 5.5 mean weight (kg) 73.7 ± 13.6 mean height (cm) 161.6 ± 10.9 proportion of males 49.9 mean bmi 28.3 ± 5.6 proportion overweight (25 – 29.9 kg/m2) 36.0 proportion obese (≥ 30.0 kg/m2) 29.0 mean waist circumference (cm) 99.4 ± 13.2 proportion (%) of males with wc ≥ 90 cm 34.9 female ≥ 80 cm 39.6 mean systolic blood pressure (mm hg) 135.6 ± 19.8 mean diastolic blood pressure(mm hg) 85.9 ± 11.1 sbp ≥ 130 mm hg / dbp ≥ 80(mm hg) 925 (58.0) hba1c (%) 8.5 ± 4.3 *all values are mean ± sd except values expressed for gender, overweight, obesity, waist circumference for male and female, and sbp ≥ 130 / dbp ≥ 80, which are in n (%) ;bmi, body mass index; wc, waist circumference; sbp, systolic blood pressure; dbp, diastolic blood pressure; hba1c, glycosylated haemoglobin. the most common antihypertensive drug classes prescribed to the patients with t2dm were angiotensin-converting enzyme (ace) inhibitors (41.7%).similarly, the most common oral antidiabetic drug pioglitazone (16.6%) being the most prescribed drugs in each category, respectively (table 3). journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 5 table 2. bivariate analysis of risk factors and microalbuminuria (n = 1596) risk factors +mau, n (%) -mau, n (%) p-value bp systolic mmhg <130 214 (41.1) 307 (58.9) <0.01 ≥ 130 632 (64.6) 346 (35.4) bp diastolic mmhg < 85 335 (47.1) 376 (52.9) <0.01 ≥ 85 511 (64.8) 277 (35.2) fbg mg/dl ≤ 140 260 (53.8) 223 (46.2) .008 >140 243 (62.8) 144 (37.2) total cholesterol mg/dl < 200 178 (51.1) 170 (48.9) .003 ≥ 200 137 (64.0) 77 (36.0) triglycerides mg/dl < 200 134 (51.1) 128 (48.9) 0.02 ≥ 200 106 (62.7) 63 (37.3) hba1c (%) ≤ 7 67 (47.5) 74 (52.5) 0.004 >7 253 (61.4) 159 (38.6) gender male 437 (54.8) 360 (45.2) 0.14 female 462 (58.5) 328 (41.5) sedentary lifestyle yes 479 (60.3) 316 (39.7) 0.02 no 316 (53.1) 279 (46.9) unknown 53 (54.1) 45 (45.9) family history of premature cvd in 1st degree relative < 50 years of age yes 233 (62.3) 141 (37.7) 0.002 no 462 (53.5) 402 (46.5) unknown 125 (64.1) 70 (35.9) hypertension yes 578 (65.4) 306 (34.6) <0.01 no 259 (43.7) 334 (56.3) unknown 24 (68.6) 11 (31.4) diabetic nephropathy yes 286 (80.8) 68 (19.2) <0.01 no 476 (47.1) 534 (52.9) unknown 89 (68.5) 41 (31.5) congestive heart failure yes 76 (69.7) 33 (30.3) <0.01 no 705 (55.0) 577 (45.0) unknown 65 (67.7) 31 (32.3) metabolic syndrome yes 304 (62.4) 183 (37.6) <0.01 no 477 (53.8) 409 (46.2) unknown 59 (62.8) 35 (37.2) coronary artery disease yes 115 (65.7) 60 (34.3) <0.01 no 646 (54.4) 541 (45.6) unknown 94 (67.6) 45 (32.4) peripheral artery disease yes 102 (69.9) 44 (30.1) <0.01 no 664 (54.4) 557 (45.6) unknown 83 (65.9) 43 (34.1) history of stroke yes 28 (56.0) 22 (44.0) 0.53 no 786 (56.7) 600 (43.3) unknown 39 (63.9) 22 (36.1) history of mi yes 44 (61.1) 28 (38.9) 0.08 no 760 (56.2) 593(43.8) unknown 47 (69.1) 21 (30.9) duration of diabetes (years) <1 yrs 48 (46.2) 56 (39.9) <0.01 1-5 yrs 352 (50.3) 348 (49.7) 6-8 yrs 165 (63.7) 94 (36.3) 9-11 yrs 159 (65.7) 83 (34.3) >11 157 (61.1) 100 (38.9) mau, microalbuminuria; bp, blood pressure; fbg, fasting blood glucose; hba1c, glycosylated haemoglobin; cvd, cardiovascular disease; mi, myocardial infarction table 3.distribution of patients based on prescription pattern (n = 1596) prescribed drugs n (%) class of antihypertensive drugs ace inhibitors 666 (41.7) calcium channel blockers 211 (13.2) beta blockers 162 (10.2) angiotensin receptor blockers 145 (9.1) diuretics 120 (7.5) nitrates 26 (1.6) others 113 (7.1) class of antidiabetic drugs sulfonylureas 988 (61.9) biguanides 896 (56.1) thiazolidinediones 278 (17.4) insulin 167 (10.5) alpha glucosidase inhibitors 47 (2.9) ace, angiotensin-converting enzyme monotherapy was given to 36.6% and 39.3% of patients using antidiabetic and antihypertensive drugs, respectively; while remaining proportion of patients from both the classes were given treatment using combination of 2 drugs in 56.1% and 13.7%, 3 drugs in 8.6% and 3.6% and 4 drugs in 0.9% and 1.1%, respectively. discussion in this large prospective epidemiological study a high burden was found , of mau ,in patients with t2dm in outpatient setting in pakistan. major cv risk factors observed among the patients were hypertension, journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 6 sedentary lifestyle and metabolic syndrome. more than half of the patients (55.6%) with t2dm in outpatient practice were detected to have urinary albumin excretion of 20-200mg/l on the micral test. a value of 20-200 mg/l of albumin was judged as pathological. the well-established risk factors that showed high significance included fasting blood glucose, total cholesterol, poor glycemic control, family history, hypertension, metabolic syndrome, microvascular complications and duration of diabetes. the study also offers interesting hypothesis about the possible independent role of diastolic bp and total cholesterol levels as independent correlates of mau. the prevalence of mau in the study population was 55.6% (95% ci 53.1 – 58.0). it could also reflect a rapid rise in cases where kidneys are impacted because of uncontrolled and poor glycemic control. 40-42 the association of mau with hypertension has long been established and is known to be accompanied by left ventricular diastolic dysfunction and left ventricular hypertrophy.43-45 mau was found to be significantly associated with hypertension in the current study, in accordance with previous findings.46 similar findings were observed in previous studies that reported systolic bp and diastolic bp to be associated with mau.43-48 multivariate logistic regression also reported diastolic bp to be significantly associated with mau in the current study. a higher incidence of silent myocardial infarction has been reported in t2dm patients with mau compared to normoalbuminuria. 49 while the trends of association between specific cv events and mau vary between these studies, they are in agreement about the overall relationship between cv risks with mau. high triglyceride levels, a significant cv risk factor, could initiate endothelial damage and eventually induce renal disease in patients with t2dm. 50 high triglyceride levels were significantly associated with presence of mau which confirms data from a study in pakistan where 93.7% patients with mau had triglyceride>150 mg/dl. 11 according to world health organization and other studies , mau is one of the most important components of metabolic syndrome. 51,52 a significant correlation was observed between increased hba1c and mau in our study population corroborating results from other studies [40,53]. euglycaemia exerts a stronger influence on mau than macroalbuminuria, implying that early glycaemic control must be considered to avoid the onset of nephropathy rather than initiating diabetes management post-onset.54 in the current study effects of life style on cv risk in t2dm patients with mau was assessed. so far, only few studies indicate smoking as a risk factor for albuminuria among patients with t2dm.55 a statistically non-significant difference was seen in the smoking status of patients in mau positive and negative groups, though more patients in the mau positive group were past or current smokers. in present study, ace inhibitors were the most commonly prescribed antihypertensive drugs, followed by calcium channel blockers, beta blockers, angiotensin-receptor blockers (arbs), and diuretics. recent guidelines advocate the use of ace inhibitors as the first choice for diabetic hypertension and arb+ace inhibitors for dn.56-58 addition of beta blockers to ace inhibitors improves endothelial function and reduces urinary albumin excretion in t2dm patients with mau.59 in patients with congestive heart failure, arbs are recommended as a first-line drug by american diabetes association for their superiority over calcium channel blockers in reducing heart failure.60,61 the prophylactic use of beta blockers is recommended for high risk patients, in view of its post-myocardial infarction protective effect on cv mortality. ace inhibitor or arbs result in significant cv and/or renal morbidity reductions in patients with albuminuria, with or without good glycaemic control.62 the prescription pattern of antihypertensive drugs in the present study was found to be consistent with the evidence-based guidelines. in this study, sulphonylureas were most commonly prescribed antidiabetic drugs followed by biguanides and thiazolidinediones. a similar pattern of prescription was observed in studies from asia.63,64 the prescription pattern of different classes of drugs in patients with t2dm in pakistan was found to be rational and, to a great extent, compliant with evidence-based guidelines. conclusion 1. prevalence of mau in pakistani patients with t2dm is high. these patients are also at an increased cv risk, specifically with uncontrolled diastolic bp and high total cholesterol levels. 2. early screening strategies for dn, with better glycemic, hypertension and cholesterol control will aid in averting/reducing adverse cardiovascular consequences in these patients. acknowledgements the authors would like to thank the following physicians from pakistan, who participated as investigators in this study: from hyderabad muhammad adam chania, nadeem anwar, jawaid sakrani, m m haroon, mubeen uddin, and merajuddin journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 7 nizam; from mirpurkas lal mohammad khan; from nawabshah asif raza brohi; from quetta ghulam dastagir, ejaz ahmad, wali muhammad, naseeb ullah shah, irshad ahmad khoso, wasim ahmad; from karachi jabir hussain, ayesha nasir, amir kamal, javid qureshi, abid minhas, riasat ali khan, shaukat ali,veromal lohano, rashid jameel, shakir hussain, m. javaid, m. majid khan,ahmed madni,shafqat mirza, muhammad khalid farooq, abdul rasheed, m ashfaq, ahmed pervaiz, abdul razzaq memon, and farooq akbani; from sukkur munir azam, abbas shaikh, imdad shaikh, pawan kumar, rachpal, raj kumar, and farhan baloch; from multan m. amin, m. amjad aziz, m hussain malik, mansoor jaffri, saeed ahmed, faiz athar, safdar khan, hafiz qamar munir, faisal masood qureshi, and muhammad abid; lahore muhammad sohail, mazhar-ul-islam, javaid iqbal, muhammad abu zafar, muhammad ijaz, najma pervaiz, nauman bashir kurd, bashir ahmed qamar, tariq hamid, muhammad asghar siddique, manzoor-ul-haq, tahir rasool, sabahat javaid butt, muhammad ali awan, zulfiqar ahmed, ashfaq rana, nusair a malik, zafar iqbal bhatti, qamar rafiq, and sohail rasheed waraich; from faisalabad zahid yasin hashmi, amir shaukat, noman khursheed, zahid masood, khalid mustafa, khalid mehmood yahya, and hafeez; from gujranwalla ajmal bhatti, qaiser mehmood, haji maqsood mehmood, fatah uddin, ahsan malik, and armaghan riaz; from peshawar khalid mahmood, amer azhar, a.h. amir, and ohd. shafiq orakzai; from islamabad/pindi sultan haider, tanvir ahmed, syed sohail asif, mustafa ali khan, shehzad tahir, tariq mehmood, syed ahmed sohail, m yaqoob mirza, afzaal qureshi, and asim zulfiqar; from rahim yar khan m. pervaiz. the authors thank jeevan scientific technology limited, hyderabad, india, and anahita gouri from sanofi (india) for editorial assistance and iqbal mujtaba, biostatistician from sanofi (pakistan) for data management and analysis. references 1. http://www.idf.org/diabetesatlas/5e/the-global-burden (accessed on: 02 april, 2013) 2. http://www.idf.org/diabetesatlas/5e/update2012 3. satchell sc, tooke je. what is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? diabetologia, 2008;51:714–25. 4. brenner bm, cooper me, de zeeuw d. renaal study investigators. effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. n engl j med,2001;345:861-69. 5. gross jl, de azevedo mj, silveiro sp, canani lh. diabetic nephropathy: diagnosis, prevention, and treatment. diabetes care, 2005;28:164-76. 6. remuzzi g, schieppati a, ruggenenti p. clinical practice. nephropathy in patients with type 2 diabetes. n engl j med , 2002;346:1145-51. 7. haffner sm, lehto s, ronnemaat. mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. n engl j med ,1998;339:229–34 8. sarafidis pa, riehle j, bogojevic z, basta e. a comparative evaluation of various methods for microalbuminuria screening. am j nephrol ,2008;28:324-29. 9. parving hh, lewis jb, ravid m, demand investigators. prevalence and risk factors for microalbuminuria in a referred cohort of type ii diabetic patients: a global perspective. kidney int, 2006;69:2057-63. 10. al-maskari f, el-sadig m, obineche e. prevalence and determinants of microalbuminuria among diabetic patients in the united arab emirates. bmc nephrol, 2008;9:1-5. 11. ahmadani my, fawwad a, basit a. microalbuminuria prevalence study in hypertensive patients with type 2 diabetes in pakistan. j ayub med coll abbottabad ,2008;20:117-20. 12. naz s, sadaruddin a, khannum a, osmani r. frequency of microalbuminuria in diabetic patients of islamabad and rawalpindi. pak j med res ,2007;46:70–74. 13. ahmed s and ahmad sa. gender difference and relationship of insulin resistance with microalbuminuria type-2 diabetes. j coll physicians surg pak,2010;20:26-32. 14. asselbergs fw, diercks gf, hillege hl. prevention of renal and vascular endstage disease intervention trial (prevend it) investigators. effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. circulation,2004;110:2809-16. 15. dinneen sf and gerstein hc. the association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. arch intern med,1997;157:1413–18. 16. arnlov j, evans jc, meigs jb. low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals. circulation, 2005;112:969-75. 17. hillege hl, fidler v, diercks gf, van gilst wh. prevention of renal and vascular end stage sisease (prevend) study group. urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. circulation, 2002;106:1777–82. 18. verhave jc, gansevoort rt, hillege hl, bakker sj. prevend study group. an elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. kidney int suppl ,2004:s18–21. 19. adler ai, stevens rj, manley se, bilous rw. ukpds group. development and progression of nephropathy in type 2 diabetes: the united kingdom prospective diabetes study (ukpds 64). kidney int ,2003;63:225-32. 20. gerstein hc, mann jf, yi q, zinman b, dinneen sf.albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. jama ,2001;286:421–26. 21. brantsma ah, bakker sj, hillege hl. prevend study group: urinary albumin excretion and its relation with c-reactive protein and the metabolic syndrome in the prediction of type 2 diabetes. diabetes care,2005;28:2525–30. 22. stehouwer cd, henry rm, dekker jm. microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction—the hoorn study. kidney int suppl, 2004;92:s42–44. 23. stehouwer cd and smulders ym. microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. j am soc nephrol ,2006;17:2106–11. 24. mongkolsomlit s, patumanond j, tawichasril c. metaregression of risk factors for microalbuminuria in type 2 diabetes. southeast asian j trop med public health,2012;43:455-66. 25. diabetes and high blood pressure. available at http://www.patient.co.uk/health/diabetes-and-highblood-pressure. 26. garcía-donaire ja, ruilope lm. reducing both microalbuminuria and cardiovascular events: how easy is it to reach this target? medicographia, 2012;34:48-56. 27. stamler j, vaccaro o, neaton jd. diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the multiple risk factor intervention trial. diabetes care ,1993;16:434-44 http://www.idf.org/diabetesatlas/5e/the-global-burden http://www.idf.org/diabetesatlas/5e/update2012 http://www.patient.co.uk/health/diabetes-and-high-blood-pressure. http://www.patient.co.uk/health/diabetes-and-high-blood-pressure. journal of rawalpindi medical college (jrmc); 2017;21(1): 2-8 8 28. montalescot g and collet jp. preserving cardiac function in the hypertensive patient: why renal parameters hold the key. eur heart j,2005;26:2616-22. 29. naidoo dp. the link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. cardiovasc j s afr,2002;13:194-99. 30. american diabetes association: standards of medical care in diabetes. diabetes care,2005: 28( 1):s4–s36. 31. parving hh, lehnert h, brochner-mortensen j. irbesartan in patients with type 2 diabetes and microalbuminuria study group. the effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. n engl j med ,2001;345:870–78. 32. basi s, fesler p, mimran a, lewis jb. microalbuminuria in type 2 diabetes and hypertension: a marker, treatment target, or innocent bystander? diabetes care,2008;31( 2):s194-201. 33. miettinen h, haffner sm, lehto s. proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects. stroke ,1996;27:2033-39. 34. williams jr. revising the declaration of helsinki. world med j, 2008; 54: 120-22 35. international edpidemiological association. good epidemiology practice (gep). available from url: http://ieaweb.org/good-epidemiological-practice-gep/. 36. the seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. bethesda, md. department of health and human services; 2004. nih publication no. 04-5230. 37. wild s, roglic g, green a, sicree r. global prevalence of diabetes: estimates for the year 2000 and projections for 2030. diabetes care ,2004;27(5):1047-53. 38. ahmad z, 2005, incidence of diabetes and estimating the effects of different risk factors in diabetes in pakistan. ph.d thesis, g.c. university, lahore. 39. ahmedani my, hydrie mz, iqbal a. prevalence of microalbuminuria in type 2 diabetic patients in karachi: pakistan: a multi-center study. j pak med assoc, 2005;55:382-86. 40. kassab a, ajmi t, issaoui m, chaeib l. homocysteine enhances ldl fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes. ann clin biochem, 2008;45:476–80. 41. buch ac, dharmadhikari m, panicker nk. microalbuminuria: an early detector of diabetic and hypertensive nephropathy. international journal of basic and applied medical sciences ,2012;2:218-25. 42. fischbacher cm, bhopal r, rutter mk. microalbuminuria is more frequent in south asian than in european origin populations. diabet med ,2003;20:31-36 43. grandi am, santillo r, bertolini a. microalbuminuria as a marker of preclinical diastolic dysfunction in never-treated essential hypertensives. am j hypertens, 2001;14:644-48. 44. wachtell k, palmieri v, olsen mh. urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy. the life study. losartan intervention for endpoint reduction. am heart j ,2002;143:319-26. 45. knight el, holly m, curhan gc. high-normal blood pressure and microalbuminuria. am j kidney dis ,2003;41:588-95. 46. herrera-pombo jl, aguilar-diosdado m, hawkins f. is increasing urinary albumin a better marker for microvascular than for macrovascular complications of type 2 diabetes mellitus? nephron clin pract ,2005;101:116-21. 47. tapp rj, shaw je, zimmet pz, balkau b. albuminuria is evident in the early stages of diabetes onset: results from the australian diabetes, obesity, and lifestyle study (ausdiab). am j kidney dis ,2004;44:792-98. 48. varghese a, deepa r, rema m, mohan v. prevalence of microalbuminuria in type 2 diabetes mellitus at a diabetes center in southern india. postgrad med j ,2001;77:399-402. 49. hussein af and strak sk. silent myocardial ischemia and microalbuminuria in asymptomatic type-2 diabetic patients. pak j med sci, 2006;22:116-21 50. colhoun hm, lee et, bennett ph, lu m, keen h. risk factors for renal failure: the who mulinational study of vascular disease in diabetes. diabetologia, 2006;44:s46-53. 51. definition, diagnosis and classification of diabetes mellitus and its complications. report of a who consultation,who, geneva ,1999;1-60. 52. atkins rc, polkinghorne kr, briganti em, shaw je. prevalence of albuminuria in australia: the ausdiab kidney study. kidney int suppl ,2004:s22-24. 53. sheikh sa, baig ja, iqbal t, kazmi t, baig m. prevalence of microalbuminuria with relation to glycemic control in type2 diabetic patients in karachi. j ayub med coll abbottabad,2009;21:83-86. 54. taleb n, salti h, al-mokaddam m. prevalence and determinants of albuminuria in a cohort of diabetic patients in lebanon. ann saudi med, 2008;28:420-25. 55. sawicki pt, didjurgeit u, mühlhauser i, bender r. smoking is associated with progression of diabetic nephropathy. diabetes care, 1994;17:126-31. 56. chobanian av, bakris gl, black hr. national heart, lung, and blood institute joint national committee on prevention, detection, evaluation, and treatment of high blood pressure 7 report. jama,2003;289:2560-72. 57. mancia g, de backer g, dominiczak a, cifkova r, fagard r. 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the european society of hypertension (esh) and of the european society of cardiology (esc). eur heart j, 2007;28:1462-536. 58. mcalister fa, zhang j, tonelli m, klarenbach s, manns bj.alberta kidney disease network. the safety of combining angiotensin-converting-enzyme inhibitors with angiotensinreceptor blockers in elderly patients: a population-based longitudinal analysis. cmaj ,2011;183:655-57. 59. jawa a, nachimuthu s, pendergrass m. beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in subjects with diabetes and hypertension. j diabetes complications, 2008;22:303-08. 60. laffel lm, mcgill jb, gans dj. the beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive iddm patients with microalbuminuria. am j med ,1995;99:497-504. 61. bakris gl, williams m, dworkin l, elliott wj. preserving renal function in adults with hypertension and diabetes: a consensus approach. am j kidney dis, 2000;36:646 61. 62. weir mr. microalbuminuria and cardiovascular disease. clin j am soc nephrol, 2007;2:581-90. 63. chiang cw, chiu hf, chen cy, wu hl, yang cy. trends in the use of oral antidiabetic drugs by outpatients in taiwan: 1997-2003. j clin pharm ther,2006;31:73-82. 64. yuen yh, chang s, chong ck, lee sc. drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs. j clin pharm ther 1998;23:287-94. http://ieaweb.org/good-epidemiological-practice-gep/ 169 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 original article comparison of efficacy of halstead and vazirani akinosi block technique in achieving mandibular anesthesia eruj shuja1, sadia daaniyal2, osama mushtaq3, naseer ahmed4, ammarah afreen5, zarah afreen6 1,5,6 assistant professor, oral & maxillofacial surgery, watim dental college, rawalpindi. 2,3 senior registrar, oral & maxillofacial surgery, watim dental college, rawalpindi. 4 medical officer, oral & maxillofacial surgery, shifa international hospital, islamabad. author’s contribution 1 conception of study 1 experimentation/study conduction 1,2 analysis/interpretation/discussion 2 manuscript writing 4,5 critical review 3,6 facilitation and material analysis corresponding author dr. eruj shuja, assistant professor, oral & maxillofacial surgery, watim dental college, rawalpindi email: erujshuja@hotmail.com article processing received: 16/04/2021 accepted: 02/03/2022 cite this article: shuja, e., daaniyal, s., mushtaq, o., ahmed, n., afreen, a., afreen, z. comparison of efficacy of halstead and vazirani akinosi block technique in achieving mandibular anesthesia. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 169-173. doi: https://doi.org/10.37939/jrmc.v26i2.1627 conflict of interest: nil funding source: nil access online: abstract objective: to compare the efficacy of halstead and vazirani akinosi block techniques in achieving mandibular anesthesia during exodontia among subjects reporting to watim teaching hospital. study design: randomized controlled trial. place and duration of study: this study was conducted in the department of maxillofacial surgery, watim dental hospital, rawalpindi from july 2019 to january 2020. materials and methods: this is a randomized control trial of 60 patients. duration of onset of anesthesia, pain during injection, the incidence of aspiration, success, and failure of halstead and vazirani akinosi techniques and their mean doses were analyzed and compared by using spss version 17. comparison of categorical variables was done by chi-square test. comparison of non-categorical variables was done by independent sample t-test. a p-value of less than or equal to 0.005 was considered significant. results: 28(93.3%) experienced moderate while 2(6.7%) experienced severe pain in the halstead group, while 30(100%) experienced mild pain in the vazirani akinosi group. halstead technique was successful in 22(73.3%) while unsuccessful in 8(26.7%) patients. vazirani akinosi technique was successful in 29(96.7%) and unsuccessful in 1(3.3%) patients. conclusion: it may be concluded from analysis in the present study that the vazirani akinosi technique was statistically superior in all parameters such as duration of onset, pain during injection, aspiration, and success rate as compared to the conventional halstead block technique. keywords: extraction tooth, local anesthesia, nerve block, vazirani-akinosi technique. 170 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 introduction the main objective of an oral surgeon during performing any kind of surgical procedure is adequate anesthesia.1 there are different techniques available for achieving mandibular anesthesia including the halstead technique, vazirani akinosi, and gow gates mandibular block techniques.2 painful stimulus is reversibly blocked by the use of a local anesthetic agent such as lignocaine which acts on preventing the generation of action potential on a nerve.3 2% lignocaine with 1:100,000 epinephrine is the drug of choice for exodontia and minor local anesthetic procedures.1 the inferior alveolar nerve is the primary sensory nerve supply of the mandible, innervating mandibular teeth and their surrounding soft tissue, tongue, and floor of the mouth.1 maxillary anesthesia is easily achieved as compared to mandibular anesthesia owing to the fact that maxillary bone is less compact as compared to the mandibular bone so the infiltration technique that is the deposition of local anesthetic near the root apices provides adequate anesthesia with less expertise and within a shorter duration of time.3 halstead block is the most common technique used in providing adequate analgesia during minor surgical procedures however previous studies have revealed that the failure rate for it is around 20-25%.2 various reasons for failure to achieve mandibular anesthesia with the halstead technique are patient apprehension, anatomical variation, technical failure, infected tissue at the injection site, and accessory innervations.4 vazirani akinosi technique also known as the closed mouth block is mainly indicated in cases of trismus.5 it aims to anesthetize the inferior alveolar nerve at a higher level as compared to the halstead technique.2 anatomic variability and accessory innervations account for failure in achieving adequate anesthesia in the case of open mouth technique however vazirani akinosi technique has proved to overcome these shortcomings as it requires less expertise in identifying the anatomic landmarks and by bathing nerves at a deeper level.5 the rationale of the study is to compare the efficacy of the two block techniques in terms of duration of onset of anesthesia, pain during injection, the incidence of aspiration, and anesthetic success. materials and methods this is a randomized control trial of 60 patients, 30 patients in each group. the sample size was calculated using the who calculator. this study was conducted at the department of maxillofacial surgery watim dental hospital rawalpindi. the duration of the study was 7 months from july 2019 to january 2020. ethical clearance was obtained from the institution prior to the commencement of the study. a written consent form was obtained by all the participants for inclusion in the study. a single operator was used for administering both techniques. patients were randomly divided into two groups by lottery method. group a (halstead technique) and group b (vazirani akinosi technique). inclusion criteria comprise d of healthy patients both males and females with no known medical history that reported to the oral and maxillofacial surgery department for extraction of mandibular teeth. exclusion criteria comprised patients that had a medical history of cardiac disease, diabetes mellitus, renal condition, smokers, allergy to local anesthesia, established infection, and pregnant females. both groups received 2% lignocaine with 1:100,000 epinephrine. an aspirating syringe of 40 mm with a 27 mm gauge was used with a total amount of 1.5 ml solution. the anesthetic solution was injected slowly within the duration of 60 seconds into an inferior alveolar nerve. for group a i.e. the conventional inferior alveolar block technique the patient was instructed to open his/her mouth, the external oblique ridge was palpated and the coronoid notch was identified. the target area for injection was the medial side of the ramus lateral to the pterygomandibular raphe. the syringe was positioned at the level of opposite premolars after initial aspiration. 1.5ml solution was deposited after the 2/3rd needle had penetrated the soft tissue and bone contact was positive. a needle was then retracted and local anesthesia for deposited for the lingual nerve. for group b i.e. vazirani akinosi block technique patient was put in a supine position and instructed to close his/her mouth in maximum intercuspation. the maxillary mucobuccalfold opposite to the 2nd molar was penetrated and almost whole of the length of the needle was inserted within the soft tissue after aspiration 1.5 ml of solution was deposited. subjective assessment for the onset of anesthesia was made by the patient, describing onset by the achievement of lower lip numbness and numbness of ipsilateral half of the tongue. objective assessment for anesthetic success was made by periodontal probing in the gingival sulcus in the area of anesthetized tissues. 171 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 the time for onset of anesthesia was noted using a stopwatch. pain during the administration of individual techniques was measured by vas scale from 0 to 10mm and was divided into three groups mild (0-4) moderate (5-7) and severe (8-10). aspiration of blood was noted as positive or negative by use of a self-aspirating syringe at the time of initial administration of the block technique. failure of anesthetic technique was labeled when the patient did not report numbness of the lower lip and tongue along with pain on probing after 10 minutes of administration of the respective block. in such instances, supplemental injections were given to achieve the desired result. duration of onset of anesthesia, pain during injection, the incidence of aspiration, success, and failure of technique, and mean dose were analyzed and compared by using spss version 17. percentages and frequencies along with mean± s.d were calculated for various variables. comparison of categoric variables was done by chi-square test. comparison of noncategoric variables was done by independent sample ttest. a p-value of less than or equal to 0.05 was considered significant. results a total of 60 patients 27 (45%) males and 33 (55%) females, mean age 36.90±12.67 years were included in our study. in group a, alstead block technique, 16 patients were female while 14 were males. in group b, vazirani akinosi block technique 16 patients were female while 14 were males. the mean duration of onset of anesthesia in the halstead technique is 172.67±41.55 seconds which is much earlier compared to the vazirani akinosi technique i.e. 198.56+18.18 seconds (table 1). the independent sample t-test showed a p-value ˂ 0.001. a comparison of the intensity of pain during injection in the halstead technique and vazirani akinosi showed that 28(93.3%) experienced moderate while 2(6.7%) experienced severe pain in the halstead group, while 30(100%) experienced mild pain in vazirani akinosi group chi-square test showed significant difference p-value ˂ 0.001. (table 2) aspiration during administration was compared between the groups. it was positive in 6(20%) and negative in 24(80%) patients in the halstead technique and positive in 1(3.3%) and negative in 29(96.7%) in the vazirani akinosi technique. this was statistically significant on chi-square test p-value˂ 0.004. (table3) a comparison of the rate of success in achieving anesthesia was noted for each group. halstead technique was successful in 22(73.3%) while unsuccessful in 8(26.7%) patients. vazirani akinosi technique was successful in 29(96.7%) and unsuccessful in 1(3.3%) patients. this was statistically significant on the chi-square test with a p-value ˂ 0.001(table 4). the total dose of local anesthesia used was calculated in ml. a mean dose of 2.28±0.80 was observed in the halstead group which was higher as compared to the mean dose of1.86±0.32 for the vazirani akinosi group. the independent sample t-test shows statistical significance with a p-value ˂ 0.001. table 1: statistics for duration of onset of anesthesia local anesthesia technique mean duration ±sd (seconds) p-value halstead technique 172.67±41.55s <0.001 vazirani akinosi technique 198.56±18.18s table 2: statistics for pain during the administration of local anesthesia local anesthetic technique mild pain moderate pain severe pain p-value halstead technique 0% 93.3% 6.7% <0.001 vazirani akinosi technique 100% 0% 0% table 3: statistics for aspiration during the administration of local anesthesia local anesthesia technique positive aspiration (%) negative aspiration (%) p-value halstead technique 20% 80% <0.004 vazirani akinosi technique 3.3% 96.7% table 4: statistics for rate of success in achieving anesthesia local anesthesia technique successful (%) unsuccessful (%) pvalue halstead technique 73.3% 26.7% <0.001 vazirani akinosi technique 96.7% 3.3% 172 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 discussion this study was done to compare the efficacy of the halstead block and vazirani akinosi block technique. the first parameter that was measured is the onset of anesthesia. according to our research, the onset of the duration of anesthesia in the halstead technique is 172.6 seconds and 198.6 seconds for the vazirani akinosi technique which are consistent with the results of debojyoti roy et.al1, kiran bs et al2 study also supports the results of our study. however jendisk et al4 show contradictory results with respect to the onset of anesthesia which was 78.36 seconds for the halstead technique and 104.24 seconds for the vazirani akinosi technique. this discrepancy in results could be attributed to a decrease in the concentration of adrenaline i.e. 1:1200,000 used in their study. the intensity of pain during anesthesia injection administration was compared between the two selected techniques. 28(93.3%) experienced moderate while 2(6.7%) experienced severe pain in the halstead group, while 30(100%) experienced mild pain in the vazirani akinosi group. nakkeeran kp et al8 favor our study with a mean pain score of 3.05 for the halstead technique and 1.93 for the va technique this was statistically significant with a p-value less than 0.001. mild pain experienced during the vazirani akinosi technique could be attributed to the fact that during injection no bony landmark is contacted with the needle and also the buccal soft tissue in the maxillary region is less sensitive and less resistant to penetration with less musculofascial bands in the concerned region.9 sangeethakarunakaran et al10 show that both the inferior alveolar nerve group and vasirani akinosi group experienced mild pain on injection. differences in pain perception might be due to subjective understanding of pain. in another study by costa fa et al11 pain perception by subjects was reported as being mild for both the techniques. misra s et al12 in their study revealed mild pain was experienced by the va group and moderate pain by the ian group which is consistent with our study. this is due to anatomical divergence of medial pterygoid muscle from the ramus thus providing greater pterygomandibular space and preventing the risk of penetration of medial pterygoid muscle.12 a comparison of aspiration in our study between the two study groups revealed positive aspiration in 20% of the ian group and 3.3% in the va group, the difference was statistically significant. jendisk et al4 reported positive aspiration in 15% of the ian group and 3% in the va group which is supporting the current study. mohajerani h at el13 study results is also consistent with our results showing 15% aspiration in the ian group and 5% in the va group this is statistically significant p-0.04. this study revealed that the halstead technique was successful in 22(73.3%) while unsuccessful in 8(26.7%) patients. vazirani akinosi technique was successful in 29(96.7%)and unsuccessful in 1(3.3%)patients. saatchi m et al14 checked the efficacy of ian block with a success rate of 44%. haas et al8 showed an increased success rate in vazirani akinosi as compared to the conventional block technique. aggarwal v et al15 in their study the success rate of conventional ian block was 36% and of va was 41% this contradiction of results with our study may be due to assessment of pain associated with irreversible pulpitis as compared to our study in which participants experienced pain during extraction of teeth. alhindi m et al16 favour our result as well. the mean dose used in the ian block was more as compared to the vazirani-akinosi block.17,18 there were a few limitations in this research such as the detailed complications and their incidences associated with anesthesia administration were not recorded. individual nerves and their responses were also not calibrated. thus this study can be improved with a larger sample size and taking into account above mentioned factors. conclusion it may be concluded from our analysis that the vazirani akinosi technique was statistically superior to the conventional block technique in parameters such as duration of onset, pain during injection, aspiration, and success rate as compared to the conventional halstead block technique. we found that vazirani akinosi is an underestimated inferior alveolar nerve block as it provides better outcomes. references 1. roy d, talukdar b. comparison between conventional inferior alveolar nerve block with vazirani-akinosi technique and gow-gates technique of the mandibular nerve block.ijrr vol 6,issue 8,august 2019. 2. kiran bs, kashyap vm, uppada uk, tiwari p, mishra a, sachdeva a. comparison of efficacy of halstead, vaziraniakinosi and gow gates techniques for mandibular anesthesia. journal of maxillofacial and oral surgery. 2018 dec;17(4):570-5. 3. maqsood a, asim ma, aslam f, khalid r, khalid o. comparison of efficacy of gow-gates mandibular nerve block and inferior alveolar nerve block for the extraction of mandibular 173 journal of rawalpindi medical college (jrmc); 2022; 26(2): 169-173 molars. annals of abbasi shaheed hospital and karachi medical & dental college. 2018 dec 31;23(4):177-83. 4. jendi sk, thomas bg. vazirani–akinosi nerve block technique: an asset of oral and maxillofacial surgeon. journal of maxillofacial and oral surgery. 2019 dec;18(4):628-33. 5. nagendrababu v, ahmed hm, pulikkotil sj, veettil sk, dharmarajan l, setzer fc. anesthetic efficacy of gow-gates, vazirani-akinosi, and mental incisive nerve blocks for treatment of symptomatic irreversible pulpitis: a systematic review and meta-analysis with trial sequential analysis. journal of endodontics. 2019 oct 1;45(10):1175-83. 6. haas da. alternative mandibular nerve block techniques: a review of the gow-gates and akinosi-vazirani closed-mouth mandibular nerve block techniques. the journal of the american dental association. 2011 sep 1;142:8s-12s. 7. ghoddusi j, zarrabi mh, daneshvar f, naghavi n. efficacy of ianb and gow-gates techniques in mandibular molars with symptomatic irreversible pulpitis: a prospective randomized double blind clinical study. iranian endodontic journal. 2018;13(2):143. 8. nakkeeran kp, ravi p, doss gt, raja kk. is the vaziraniakinosi nerve block a better technique than the conventional inferior alveolar nerve block for beginners?. journal of oral and maxillofacial surgery. 2019 mar 1;77(3):489-92. 9. haghighat a, jafari z, hasheminia d, samandari mh, safarian v, davoudi a. comparison of success rate and onset time of two different anesthesia techniques. medicina oral, patologia oral y cirugiabucal. 2015 jul;20(4):e459 10. sangeethakarunakaran bd, alankruthagangasani bd, priyanka unnam bd. evaluation of efficacy and pain in open mouth versus closed mouth ianb technique for third molar extraction. saudi j oral dent res, july, 2020; 5(7): 317-320. 11. costa fa, souza lm, groppo f. comparison of pain intensity during inferior alveolar nerve block. revista dor. 2013 sep;14(3):165-8 12. mishra s, tripathy r, sabhlok s, panda pk, patnaik s. comparative analysis between direct conventional mandibular nerve block and vazirani-akinosi closed mouth mandibular nerve block technique. int j adv res technol. 2012 nov;1(6):112-7. 13. mohajerani h, pakravan ah, bamdadian t, bidari p. anesthetic efficacy of inferior alveolar nerve block: conventional versus akinositechnique.journal of dental school 2014;32(4):210-215. 14. saatchi m, shafiee m, khademi a, memarzadeh b. anesthetic efficacy of gow-gates nerve block, inferior alveolar nerve block, and their combination in mandibular molars with symptomatic irreversible pulpitis: a prospective, randomized clinical trial. journal of endodontics. 2018 mar 1;44(3):384-8. 15. aggarwal v, singla m, kabi d. comparative evaluation of anesthetic efficacy of gow-gates mandibular conduction anesthesia, vazirani-akinosi technique, buccal-plus-lingual infiltrations, and conventional inferior alveolar nerve anesthesia in patients with irreversible pulpitis. oral surgery, oral medicine, oral pathology, oral radiology, and endodontology. 2010 feb 1;109(2):303-8. 16. alhindi m, rashed b, alotaibi n. failure rate of inferior alveolar nerve block among dental students and interns. saudi medical journal. 2016 jan;37(1):84. 17. shah fa, jan iu, ahsan a, afridi ru, zain m, haider s. comparison of anesthetic efficacy of inferior alveolar nerve block and vazirani-akinosi techniques in patients with irreversible pulpitis. pakistan oral & dental journal. 2019 sep 30;39(3):301. 18. lee cr, yang hj. alternative techniques for failure of conventional inferior alveolar nerve block. journal of dental anesthesia and pain medicine. 2019 jun;19(3):125. 19. sakdejayont w, chewpreecha p, boonsiriseth k, shrestha b, wongsirichat n. does the efficacy of direct inferior alveolar nerve block depend on patient position?.m dent j volume 36,2016 may-august. 20. devarakonda bv, issar y, goyal r, vadapalli k. difficult airway ‘made easy’ with vazirani-akinosi (closed mouth) technique of mandibular nerve block. medical journal, armed forces india. 2019 apr;75(2):225. summary journal of rawalpindi medical college (jrmc); 2008;12(2):75-77 75 nitrous oxide in oxygen and air in oxygen for perioperative analgesia : a comparative study jawad zahir, muhammad shafiq, muhammad salman maqbool, muhammad nadeem khan department of anaesthesiology, holy family hospital and rawalpindi medical college rawalpindi. abstract background: to determine that additional dose of nalbuphine is required while using medical air instead of nitrous oxide in oxygen to maintain anaesthesia so that inadequate intra-operative analgesia could be avoided. methods: this quasi experimental study was carried out in the department of anaesthesia, holy family hospital, rawalpindi, from october 2007 to march 2008. one hundred patients were selected by non probability convenient sampling. patients between 20 to 40 years of age were included, belonging to asa class-i and ii. they were divided into two groups (a and b) scheduled for different elective surgical procedures under general anaesthesia. group a comprised of fifty patients who received medical air in oxygen. group b comprised of fifty patients who received nitrous oxide in oxygen. the conduct of anaesthesia was kept same in both the groups. patients heart rate, mean arterial pressure, pulse oximetry, ecg were monitored and requirement of additional dose of nalbuphine in both the groups was noted. intraoperative tachycardia and hypertension indicated additional dose of nalbuphine. average value of heart rate and blood pressure of each case was determined and the data compared and analyzed by spss-10. results: forty patients in group a did not require intraoperative additional nalbuphine while the remaining ten patients required it. forty eight patients in group b did not require additional intra-operative nalbuphine and only two patients required it. conclusion: the use of nitrous oxide significantly reduces the intra-operative narcotic analgesia requirement. key words: nitrous oxide, nalbuphine, analgesia introduction nitrous oxide is still commonly used in combination with volatile agents to maintain anaesthesia1.it is said to be a good analgesic but a weak anaesthetic.2nitrous oxide alone is insufficient to produce an adequate depth of anaesthesia.3however, there is a growing concern regarding its toxic effects and cost.4 concerns regarding its safety have led to continued interest in alternatives.5 consequently, medical air is being used more frequently in combination with oxygen during anaesthesia because it is readily available, economical and non toxic.6 inadequate analgesia however, remains a high concern for the patients during surgery.7 numerous techniques and number of analgesics have been used for this purpose with variable results.8 it is difficult to judge or measure intra-operative pain as anaesthetist has to rely on different clinical signs e.g. tachycardia, raised blood pressure and sweating which are effected by other factors such as surgical stimulation, type of surgery and surgical incision.9,10 many studies have been conducted to compare medical air with nitrous oxide in oxygen for general anaesthesia but none shows marked difference with respect to analgesia.11 a lot of work has been done in the past in the management of intra operative pain. the use of air in oxygen for general anaesthesia is devoid of serious side effects like diffusion hypoxia and expansion of air embolism as caused by nitrous oxide.10 we are presenting a randomized, single blind standardized trial, conducted in the department of anaesthesiology, holy family hospital, rawalpindi. the purpose of the study was to compare medical air with nitrous oxide in oxygen during anaesthesia so that inadequate intra-operative analgesia could be avoided. patients and methods this quasi experimental study was conducted in the department of anaesthesiology, holy family hospital, rawalpindi from october 2007 to march 2008. patients between the ages 20 to 40 years, having physical status asa grade i or ii, under going elective surgical procedures and planned for general anaesthesia were included in the study. cases with pneumothorax, acute intestinal obstruction, air journal of rawalpindi medical college (jrmc); 2008;12(2):75-77 76 embolism, tympanic membrane grafting and surgery of closed spaces were excluded. patients aged less than 20 years or more than 40 years were also excluded. patients were divided into two groups. group a and group b. each comprised of fifty patients. group a received medical air in oxygen and group b received nitrous oxide in oxygen. regarding group description and sampling technique, the technique devised was non probability convenience sampling. patients were divided into two groups on the basis of even and odd numbers i.e., from number 1to100, all the odd numbers were taken as group a and all the even numbers were taken as group b. the procedures were carried out after routine pre-anaesthesia evaluation and obtaining written informed consent from the patients. on arrival in operation theatre venous access was secured and basic monitoring parameters including pulse oximetry , non-invasive blood pressure, mean arterial pressure, heart rate and ecg were started. group b patients received nitrous oxide in oxygen. conduct of anaesthesia in both groups included injection nalbuphine, 5mg, thiopentone sodium 5mg/kg, atracurium 0.5mg/kg, followed by endotracheal intubation, intermittent positive pressure ventilation and isoflurane 1% . tachycardia and hypertension were taken as indicators for the requirement of nalbuphine 0.1mg/kg in the maintenance phase. additional nalbuphine was given when heart rate increased more than 20 beats/min or mean arterial pressure increased more than 20 mm of hg from the base line. average value of each indicater was determined and the data compared and analyzed by spss-10. results it was observed that 80% i.e. forty patients of group a did not require additional nalbuphine while 20% i.e. 10 patients required it. table 1: nalbuphine cross tabulation count nalbuphine total no yes group a 40 10 50 b 48 2 50 total 88 12 100 however forty-eight patients (96%) of group b did not require nalbuphine and only 2(4%) required it. group statistics, independent sample tests, case processing and cross tabulation of the two groups are summarized in tables 1and 2. table 2: statistical analysis statistical analysis value df asymp. sig. (2sided) exact sig. (2-sided) exact sig. (1-sided) pearson chisquare 6.061 (b) 1 .014 continuity correction(a) 4.640 1 .031 likelihood ratio 6.550 1 .010 fisher's exact test .028 .014 linear-bylinear association 6.000 1 .014 n of valid cases 100 (a) computed only for a 2x2 table (b) 0 cells (.0%) have expected count less than 5. the minimum expected count is 6.00. discussion inadequate analgesia remains a high concern for the patients during surgery. numerous methods, techniques and number of analgesics have so far been used for this purpose with variable results. intra operative pain remains under-treated due to fear of side effects of commonly used drugs like narcotic analgesics. apart from untoward effects of nitrous oxide like diffusion hypoxia and bone marrow depression, it is also expensive as compared to medical air. on the other hand it has good analgesic properties, weak anesthetic, concentrating and second gas effect (carrier gas).12 it also reduces the minimum alveolar concentration of inhalational agents13. having these properties, it is considered superior to medical air during maintenance of anaesthesia.14 intra-operative pain may lead to catecholamine release which may result into life threatening arrhythmias in susceptible individuals.15 journal of rawalpindi medical college (jrmc); 2008;12(2):75-77 77 although nitrous oxide has toxic effects but its benefits are more than its risks. however its risks are minimized or ameliorated by modifications in the modern anaesthetic machines.16. the study showed that 20% i.e. ten patients of group a in which medical air in oxygen was used required additional nalbuphine whereas only 4% i.e. two patients of group b(in which nitrous oxide in oxygen was used) required nalbuphine. thus nitrous oxide plays an important role to prevent intraoperative pain during anaesthesia . conclusion there is a significant difference regarding additional dose of nalbuphine between the groups in which air instead of nitrous oxide in oxygen was used for the maintenance of anaesthesia. thus nitrous oxide in oxygen is proved to be superior to medical air in oxygen for maintenance of anaesthesia with the volatile agent as less or no analgesia is required compared with the latter. it is recommended that nitrous oxide in oxygen should be used instead of medical air in oxygen for maintenance of anaesthesia to avoid inadequate analgesia or excessive use of opioids. references 1. morgan e, maged sm, michael jm,. inhalation anesthetics. clin anesthesiol 2006;04:164—65 2. aitkenhead ar, smith g, rowbotham dj. anesthetic gases. textbook of anesthesia 2007;05:32—33.. 3. aitkenhead ar, smith g, rowbotham dj. anesthetic gases. textbook of anesthesia 2007;05:28—29.. 4. reinstrup p, ryding e, algotsson l effects of nitrous oxide on human regional cerebral blood flow and isolated pial arteries. anesthesiology 1994;81:396–402. 5. field lm, dorrance de, krzeminska ek, barsoum lz. effect of nitrous oxide on cerebral blood flow in normal humans. anaesth 1993;70:154–59. 6. strebel s, kaufmann m, anselmi l, schaefer hg. nitrous oxide is a potent cerebrovasodilator in humans when added to isoflurane. acta anaesthesiol scand 1995; 39:653–58. 7. smielewski p, czosnyka m, kirkpatrick p. assessment of cerebral autoregulation using carotid artery compression. stroke 1996; 27:2197–03. 8. mahajan rp, cavill g, simpson ej, hope dt. transient hyperaemic response: a quantitative assessment. in: klingelhofer j, bartels e, ringelstein eb, eds. new trends in cerebral hemodynamics and neurosonology. amsterdam:elsevier science bv, 1997:618–23. 9. mahajan rp, cavill g, simpson ej. reliability of the transient hyperemic response test in detecting the changes in cerebral autoregulation induced by the graded variations in end-tidal carbon dioxide. anesth analg 1998; 87:843– 49. 10. smielewski p, czosnyka m, iyer v. computerised transient hyperaemic response test : a method for the assessment of cerebral autoregulation. ultrasound med biol 1995;21:599–611. 11. smielewski p, czosnyka m, kirkpatrick p, pickard jd. evaluation of the transient hyperemic response test in head-injured patients. j neurosurg 1997; 86:773– 78. 12. cavill g, simpson ej, hope dt, mahajan rp. quantitative assessment of cerebral autoregulation using transcranial doppler ultrasonography [abstract]. br j anaesth 1996; 76:198. 13. cavill g, simpson ej, mahajan rp. factors affecting the assessment of cerebral autoregulation using the transient hyperaemic response test. br j anaesth 1998; 81:317–21. 14. omae t, ibayashi s, kusuda k. effects of high atmospheric pressure and oxygen on middle cerebral blood flow velocity in humans measured by transcranial doppler. stroke 1998;29:94–97. 15. paulson ob, strangaard s, edvinsson l. cerebral autoregulation. cerebrovasc brain metab rev 1990; 2:161–92. 16. reasoner dk, warner ds, todd mm, mcallister a. effects of nitrous oxide on cerebral metabolic rate in rats anaesthetized with isoflurane. br j anaesth 1990; 65:210– 15. jawad zahir, muhammad shafiq, muhammad salman maqbool, muhammad nadeem khan department of anaesthesiology, holy family hospital and rawalpindi medical college rawalpindi. abstract introduction patients and methods results (a) computed only for a 2x2 table (b) 0 cells (.0%) have expected count less than 5. the minimum expected count is 6.00. discussion conclusion references summary journal of rawalpindi medical college (jrmc); 2010;14(1):15-18 15 body mass index, physical activity, high normal fasting plasma glucose levels and the risk of diabetes mellitus type 2 nasreen qazi, madiha shah, shaheen shah, manzoor unar, gulshan ara jalbani, mahboob ahmed wagan liaqat university of medical and health sciences, jamshoro. abstract background: to find out the relationship between obesity, sedentary lifestyle and fasting plasma glucose (fpg)levels in apparently healthy individuals belonging to the paramedical staff of the liaqat university of medical and health sciences, jamshoro. methods: 50 healthy individuals were included in the study. fpg levels were measured at baseline and after three years. body mass index was calculated as weight in kilograms divided by the square of the height in meters, and the subjects were defined as obese if their bmi was 30 or greater. a specially designed questionnaire nice guidelinephi2 physical activity: implementation advice 2006 was filled at baseline & at the end of the study. patients with known dm were excluded from the study. results: at baseline the mean fpg level was 88 ± 5.62 mg/dl which increased to 98.4 ± 4.22 mg/dl in a three year period. 41% of subjects had fpg of ≥100 when followed up after 3 years. there were two incident cases of dm type 2. the study revealed that in men with fpg of 100 mg/dl or higher there was a progressively greater risk for type 2 diabetes as the fpg values rose, compared with men who had an fpg of less than 86 mg/dl, p <0.001. a similar large risk was detected in men with a bmi of 30 or more, compared with a bmi less than 25 .it was also observed that most of the subjects were among the moderately inactive group. conclusion: persons with normal blood sugar at a given examination, who are over weight and living a sedentary life style; can develop diabetes in coming years as compared to people with less bmi and lower normal fasting plasma glucose levels. key words: diabetes mellitus type 2, fasting plasma glucose levels, body mass index. introduction diabetes mellitus type 2 is one of the fastest growing public health problems in the world. the prevalence of diabetes for all age groups worldwide was estimated to be 2.8% in 2000 and to rise to 4.4% in 2030.1 the total number of individuals with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030.1cardiovascular disease accounts for more than 70% of total mortality among patients with dm type 2.2 both genetic and environmental factors have been implicated in the etiology of dm type 2.3 lifestyle factors, the main determinants of the disease, are physical inactivity and obesity.4 results from prospective studies and clinical trials have shown that moderate or high levels of physical activity or physical fitness, as well as changes in lifestyle (dietary modification and enhanced physical activity) can prevent type 2 dm. 5-11 recent clinical trials in china, finland, and the united states have demonstrated that lifestyle intervention (dietary modification and enhanced physical activity) reduced the risk of progressing from impaired glucose tolerance to type ii diabetes.12-14 insulin resistance develops in response to decreased insulin secretion and plays a part in the development pathogenesis of dm type 2. insulin resistance is a decrease in the endogenous sensitivity to insulin action. endogenous insulin secretion suppresses hepatic glucose biosynthesis, increases glucose uptake and glycogen synthesis in target cells, and reduces the lipolysis of adiposities. increased insulin resistance hinders normal insulin activity, leading to hyperinsulinemia and, eventually, dm type 2. in fact, decreased insulin secretion and increased insulin resistance precede the development of clinical hyperglycemia.15 epidemiologic evidence has shown that physical activity and body fat loss are of medical benefit, not just for preventing diabetes but also for cardiovascular health and quality of life.16 regular physical activity is a crucial component of a healthy lifestyle. healthcare professionals and policy makers should aggressively promote physical activity and weight control.17 it is well known that increasing physical activity and losing weight can prevent 40 to 80 percent of adult onset diabetes in those with http://www.nice.org.uk/page.aspx?o=320519 http://www.nice.org.uk/page.aspx?o=320519 http://www.nice.org.uk/page.aspx?o=320519 journal of rawalpindi medical college (jrmc); 2010;14(1):15-18 16 elevated blood sugar levels. in a finnish study physical activity and weight has been weighed in promoting or protecting from diabetes in those with normal blood sugar and those with high blood sugars, but not high enough to be called diabetes.18 subjects and methods after taking informed consent, 50 men aged between 30 to 57 years were included in the study. at the end two patients were dropped, one because of long leave and the other due to retirement from the job. the study period was three years (march 2006 through march 2009). we obtained blood measurements for fasting plasma glucose levels, bmi and physical lifestyle information from apparently normal individuals of paramedical staff, belonging to liaqat university of medical and health sciences, jamshoro. fpg levels were measured at baseline and at the end of the study. body mass index (bmi) was calculated as weight in kilograms divided by the square of the height in meters. bmi was calculated at start of the study and after three years and the subjects were defined as obese if their bmi was 30 or greater. a specially designed questionnaire nice guideline phi2 physical activity: implementation advice 2006 was filled at start and end of the study. nice (national institute for health and clinical excellence) has developed tools to help organizations implement the nice public health intervention guidance on physical activity. nice recommends that primary care practitioners should take the opportunity, whenever possible, to identify inactive adults and advise them to aim for 30 minutes of moderate activity on 5 days of the week (or more). 19 inclusion criteria: apparently healthy males with no history of dm, hypertension or renal problem. exclusion criteria: patients were excluded from the study if they had confirmed type 1 or type 2 diabetes at the time of enrolment. results the men included in the study belonged to the lower socio-economic class, with the mean age of 42±7.23. at baseline the mean fasting glucose level was 88 ± 5.62 mg/dl which increased to 98.4 ± 4.22 mg/dl in a three year period. 41% 0f subjects had fbs of ≥100 as they were followed up after three years. (table 1) bmi when calculated, it was noted that 38 (76%) subjects were having bmi between 25-29 at start of the study and 12 (24%) were having bmi of ≥ 30 but when they were followed after three years 28(58.3%) were having bmi of 25-29 and 20(41%) were found to be obese i.e. having bmi of 30 or more (table 1, figure 1). the general practice physical questionnaire was filled twice at baseline. it showed that 22 (44%) men were among the moderately inactive group, 16(32%) in moderately active group, and 12(24%) in active group, while at three years 24(50%) in moderately inactive, 18(37.5%) in moderately active group, 6(12.5%) in active group. (table 1, figure 3). table 1: characteristics of patients at baseline and at three years characteristic baseline n=50 after 3years n=48 age (years) mean age range 42 (±7.23) 30-57 44(±6.84) 33-58 fasting plasma glucose level(mg/dl) mean range 88 ± 5.62 77-97 98.4 ± 4.22 84 -130 body mass index(bmi) 25-29 ≥ 30 38(76%) 12(24%) 28(58.3%) 20(41%) family history of dm* 08 08 physical activity (%) ** moderately inactive moderately active active inactive 22 (44%) 16(32%) 12(24%) 00 24(50%) 18(37.5%) 06(12.5%) 00 plus–minus values are mean sd. *a family history of diabetes indicates the presence of type 2 diabetes in a first degree relative. ** physical activity denotes engagement in physical activity for a minimum of 20 min at least three times per week. 36 12 2 1513 20 0 5 10 15 20 25 30 35 40 45 50 baseline after 3 years 80-89 90-99 >100 http://www.nice.org.uk/page.aspx?o=320519 journal of rawalpindi medical college (jrmc); 2010;14(1):15-18 17 figure 1: fasting plasma glucose levels at baseline and after 3 years during follow-up (from 2006 through 2009), there were two incident cases of dm type 2, the study revealed that in men with fpg of 100 mg/dl or higher there was a progressively greater risk for dm type 2 as the fpg values rose, as compared with men who had an fpg of less than 86 mg/dl p value <0.001. a similarly large risk was detected in men with a bmi of 30 or more compared with a bmi less than 25-29. 38 12 28 20 0 5 10 15 20 25 30 35 40 45 50 baseline after 3 years 25-29 >30 figure 2: bmi at baseline and after 3 years figure 3: grouping of patients according to general practice physical activity questionnaire discussion it is often seen that sedentary life style and obesity go together, but the problem is that more people are adopting such lifestyle. this study highlights those persons whose fasting plasma glucose levels were within normal range but at upper limit of the normal range. the definition of a normal fasting plasma glucose level has recently been revised by the expert committee on the diagnosis and classification of diabetes mellitus of the american diabetes association. an impaired fasting plasma glucose level is now considered to include the range of 100 to 109 mg per deciliter (5.55 to 6.05 mmol per liter).20 obese persons who do not have diabetes consistently exhibit an enhanced rate of glucose production. this enhanced rate may emanate from elevated levels of free fatty acids that directly accelerate the rate of hepatic gluconeogenesis, combined with desensitization of the hepatic regulatory loop involving hypothalamic sensing of fatty acids.21-22 obesity-associated altered secretion of adipocytokines from adipocytes, macrophages in fat tissue, or both has been suggested as the mechanism involved in mediating such dysregulations between fatty tissue and the liver.23-25 our study is in accordance with the study conducted by tirosh et al, according to which a high normal fpg level is independent risk factor for dm type 2 along with bmi and physical activity.26 conclusions 1. a sedentary lifestyle, and being obese can lead to dm type 2 in coming years of individuals who are at risk. 2. changes in lifestyle are effective in preventing both diabetes and obesity in high-risk adults with impaired glucose tolerance. 3.high normal fpg value alone may not be a detector of type 2 diabetes, so along with fpg, bmi, physical activity and eating habits questionnaires might serve as better screening methods. references 1. wild s, roglic g, green a, sicree r, king h. global prevalence of diabetes: estimates for the year 2000 and projections for 2030. diabetes care 2004; 27:1047–1053. 2. laakso m. hyperglycemia and cardiovascular disease in type 2 diabetes. diabetes 1999;48:937–942. 3. neel jv. diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? am j hum genet 1962; 14:353–362. 4. wing rr, goldstein mg, acton kj, behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity. diabetes care 2001; 24:117–123. 5. hu fb, leitzmann mf, stampfer mj, colditz ga, willett wc, rimm eb. physical activity and television watching in relation to risk for type 2 diabetes mellitus in men. arch intern med 2001;161:1542–1548. 6. hu g, qiao q, silventoinen k. occupational, commuting, and leisure-time physical activity in relation to risk for type 2 diabetes in middle-aged finnish men and women. diabetologia 2003; 46:322–329. 22 16 12 0 24 18 6 00 5 10 15 20 25 30 35 40 45 50 at baseline after 3 years moderately inactive moderately active active inactive journal of rawalpindi medical college (jrmc); 2010;14(1):15-18 18 7. kriska am, saremi a, hanson rl. physical activity, obesity, and the incidence of type 2 diabetes in high-risk population. am j epidemiol 2003; 158: 669–675. 8. sawada ss, lee im, muto t, matuszaki k, blair sn. cardiorespiratory fitness and the incidence of type 2 diabetes: prospective study of japanese men. diabetes care 2003; 26:2918–2922. 9. hu g, lindstrom j, valle tt. physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. arch intern med 2004; 164:892–896. 10. tuomilehto j, lindstrom j, eriksson jg. prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. n engl j med 2001;344:1343–1350. 11. knowler wc, barrett-connor e, fowler se. reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. n engl j med 2002; 346:393–403. 12. gang hu, timo al, nael c physical activity in prevention of type ii diabetes. cardiovascular medicine 2004; 394-405. 13. lindstrom j, eriksson jg, silvio. high normal plasma glucoce levels predict type ii diabetes. diabetes 2005; 11: 321-326. 14. laaksonen de, lindström j, lakka ta. physical activity in the prevention of type 2 diabetes: the finnish diabetes prevention study. diabetes 2005; 54:158–165. 15. rhee sy, kwon km, park bj, chon s. differences in insulin sensivity and secretory capacity based on ogtt in subjects with impaired glucose regulation. the korean j int med 2007; 22: 270-274. 16. genuth s, alberti kg, bennett p. follow-up report on the diagnosis of diabetes mellitus. diabetes care 2003; 26:3160-3167. 17. silvio e. inzucchi, m. high-normal plasma glucose levels predict type ii diabetes. clinical insight in diabetes 2005; 8: 124-128. 18. chan jm, rimm eb,colditz ga . obesity, fat distribution and weight gain as risk factors for clinical diabetes in men. diabetescare 1994 ;17 :961-969. 19. nice guideline phi2 physical activity: implementation advice 2006 20. gastaldelli a, miyazaki y, pettiti m. separate contribution of diabetes, total fat mass, and fat topography to glucose production, gluconeogenesis, and glycogenolysis. j clin endocrinol metab 2004; 89:3914-3921. 21. lam tk, pocai a, gutierrez-juarez r. hypotshalamic sensing of circulating fatty acids is required for glucose homeostasis. nat med 2005; 11:320-327. 22. wellen ke, hotamisligil gs. obesity-induced inflammatory changes in adipose tissue. j clin invest 2003; 112:17851788. 23. muse ed, obici s, bhanot s. role of resistin in diet-induced hepatic insulin resistance. j clin invest 2004; 114:232239. 24. banerjee rr, rangwala sm, shapiro js. regulation of fasted blood glucose by resistin. science 2004; 303:1195-1198. 25. bajaj m, suraamornkul s, hardies lj, pratipanawatr t, defronzo ra. plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type ii diabetic patients. int j obes relat metab disord 2004; 28:783-789. 26. tirosh a, iris s, dorit t. normal fasting plasma glucose levels and type ii diabetes mellitus in young men.n eng j med 2005;353:1454-62. http://www.nice.org.uk/page.aspx?o=320519 body mass index, physical activity, high normal fasting plasma glucose levels and the risk of diabetes mellitus type 2 nasreen qazi, madiha shah, shaheen shah, manzoor unar, gulshan ara jalbani, mahboob ahmed wagan liaqat university of medical and health sciences, jamshoro. abstract introduction subjects and methods results discussion references microsoft word 2_outcome of 2000 cases of phacoemulsification journal of rawalpindi medical college (jrmc); 2007; 11(1): 5-9 5 outcome of 2000 cases of phacoemulsification badr-ud-din athar naeem, rabia bashir, shahzad iftikhar, khawaja naeem akhtar, abrar raja, rasheed hussain jaffri, mustafa kamal akbar department of ophthalmology, foundation university medical college, rawalpindi. abstract background: to evaluate the outcome of phacoemulsification cases performed at fauji foundation hospital, rawalpindi. methods: this study was conducted in the department of ophthalmology, fauji foundation hospital, rawalpindi, from october 2004 to march 2007. it comprised 2000 cases of phacoemulsification with intraocular lens (iol) implantation which were performed at fauji foundation hospital in two and a half years. variables analysed included patient’s age and sex, pre-existing conditions limiting final visual acuity (va), and type of anesthesia used. outcome measures included intra operative and postoperative complications and final visual acuity. results: of the 2000 cases, there were 72% female and 28% male patients. 62% of patients were given periocular whereas 38% were operated in topical anesthesia. 15.35% of patients suffered intra operative complications. intra operative complications were: radial tear in 5% cases, posterior capsular (pc) rent without vitreous loss in 3.45% and pc rent with vitreous loss in 4.85% of patients, iris damage in 0.83%, zonular dehiscence in 0.6% of cases, and nuclear fragment drop in 0.3% of patients. of total patients, 91% of patients kept their appointment for 8 weeks follow up. postoperatively corrected visual acuity after elimination of factors reducing best corrected visual acuity (bcva) was 6/9 or better in 89% of cases. postoperative complications were seen in 20.83% of patients, which included mild to moderate striate keratitis in 11.98%, mild to moderate anterior uveitis in 4.01%, raised intra ocular pressure (iop) in 0.73%, wound leakage in 0.3%, ophthalmoplegia in 0.05% and endophthalmitis in 0.10% of cases. posterior capsular opacification (pco) was seen in 3.65% of patients in 8 weeks of followup. post operative astigmatism was from 0 – 4.5 d. conclusion: phacoemulsification is much safer, predictable, relatively atraumatic procedure and it provides early rehabilitation. it is associated with more patient as well as surgeon satisfaction. introduction phacoemulsification was introduced in 1966 by charles kelman1. it took a very long time to be accepted as a procedure of choice by majority of surgeons. the main reason for this delay was probably a long and difficult learning curve and high cost of procedure2. with the description of capsulorrhexis by neuhann and gimbel3, advent of much improved microsurgical techniques, good supervision and readily available guiding material like books, cds and videos and with the availability of new and better viscoelastic agents, the technique has now become the procedure of choice for the surgeons all over the world4. phacoemulsification permits removal of cataract through 3 – 5.25 mm self sealing incision thus eliminating many complications associated with the wound. it also allows faster visual rehabilitation. it is associated with decreased post operative inflammation, lesser astigmatism and early refractive stability5. the purpose of this study was to evaluate the outcome of phacoemulsification in the setting of this hospital, and to find the ways of reducing complications. patients and methods this study was conducted in the department of ophthalmology, fauji foundation hospital, rawalpindi from october 2004 to march 2007. a total of 2000 cases of phacoemulsification were included. 91% (n=1820) of total patients kept their 8 weeks follow up. 72% (n=1440) of patients were females and there were 28% (n=560) male patients. preoperative examination included visual acuity (va), slit lamp examination, tonometry and fundus examination. preoperatively, the associated ocular problems which could decrease the final visual acuity were noted such as band keratopathy, corneal journal of rawalpindi medical college (jrmc); 2007; 11(1): 5-9 6 opacities, pseudoexfoliation, diabetic retinopathy, fig. 1: intra operative complications of phacoemulsification 100 97 69 23 12 6 0 10 20 30 40 50 60 70 80 90 100 radial tear pc rent with vitreous loss pc rent without vitreous loss iris damage zonular dehiscence nuclear fragment drop fig. 2: pre operative visual acuity 4% 32% 48% 16% pr hm cf 6/60 6/36 fig. 3: post operative visual acuity 89% 7% 4% 6/9 or better 6/12 6/18 less than 6/18 early age related macular degeneration and squint. previous refractive history was taken. all patients were admitted one day prior to surgery and were screened and treated for hypertension, diabetes and chest problems. before surgery, the pupils were dilated with 1% tropicamide eye drops, one drop every 10 minutes and 10% phenylephrine eye drops journal of rawalpindi medical college (jrmc); 2007; 11(1): 5-9 7 fig. 4: post operative complications 218 73 13 6 1 2 66 0 50 100 150 200 250 corneal oedema uveitis raised iop wound leakage ophthalmoplegia endophthalmitis pco once or twice. nsaids like diclofenac sodium were also used in some patients. 62% (n=1240) of patients who received peribulbar anesthesia were injected with 4-5 ml of local anesthetic (equal quantities of 0.5% bupivicaine and 2% xylocaine) in the peribulbar space. whereas 38% (n=760) patients were given topical anesthesia in the form of 0.5% proparacaine eye drops in conjunctival sac, one drop every 5 minutes starting half an hour before surgery. two types of tunnel incisions were employed. in 88% (n=1760) of patients clear corneal incision, and in 12% (n=240) of patients scleral tunnel incision was given. anterior chamber (ac) was entered with 3.25 mm keratome. two 11.5 mm side port incisions were made on the nasal and temporal sides. after filling the ac with viscoelastic, capsulorrhexis was done with a 29 guage bent tip needle through the side port on the right side of main corneal incision. hydrodissection and hydrodelineation was performed with 23 gauge cannula attached to a syringe filled with ringer lactate solution. endocapsular phacoemulsification and aspiration was carried out. residual cortical matter was removed by irrigation and aspiration cannula. ac and capsular bag was filled with viscoelastic substance. incision was enlarged with 5.25 mm keratome to implant 5.25 or 5.50 mm optic diameter pmma intraocular lens (iol) in 89% (n=1780) of patients. in 11% (n=220) of patients hydrophilic acrylic foldable iols were implanted through 3.25 mm incision. the wound was left unsutured. only in 0.65% (13) patients a single or a kratz suture had to be applied. in majority of cases stromal hydration was enough to seal the incision in doubtful cases. subconjunctival injection of 4 mg dexamethasone and 20 mg gentacin was given in all cases. oral antibiotics were given for five days and topical steroid antibiotic combination was given for 4-6 weeks. the postoperative visits were scheduled at second, fourth and eighth week. at each visit slit lamp examination was done, unaided and pin hole vision was recorded. refraction was done at 2nd and 8th week, which was found to be more or less the same. final refraction was given at 8th week. results the patients varied in age from 46-83 years. out of these 2000 patients 8.7% had systemic hypertension, 11.2% had diabetes mellitus, and 2% had established but controlled glaucoma. of the total of 2000 cases of phacoemulsification. 15.35% (n=307) patients suffered intra operative complications. radial tear was seen in 5% (n=100) (table 1 & fig. 1). these cases ended up uneventful without extension of the tear or any further complication and in all these cases in the bag iol implantation was ensured. pc rent without vitreous loss occurred in 3.45% (n=69) and pc rent with vitreous loss occurred in 4.85% (n=97), which was managed by anterior vitrectomy and iol implantation on the anterior capsule. most of these rents occurred as a result of an attempt to chase nuclear fragment, or as an extension of radial tear. iris damage was seen in 1.15% (n=23) cases which was due to pupil constriction during surgery. 0.6% (n=12) cases were complicated by zonular dehiscence (mostly in the cases of pseudoexfoliation, hypermature cataract or during attempts to break the hard nucleus), 7 of these patients were managed by putting in a capsular tension ring and the remaining 5 patients having less than 90o of dehiscence ended safely with in the bag iol implantation. nuclear fragment drop occurred in 0.3% (n=6) patients. 0.5% (n=10) patients had to be converted to extracapsular cataract extraction (ecce) because of difficulty in phacoemulsification due to very hard cataract and due to fear of extension of radial tear. eight weeks follow up was 91% (n=1820). preoperative va of patients varied from light projection (pr) to 6/36. postoperative va at 8 weeks was 6/12 or better in 80.5% (n=1465) of patients. when pre existing conditions limiting final bcva (best corrected visual acuity) were eliminated 89% (n=1611) of patients achieved bcva of 6/9 or better. refraction done at 2nd week and 8th weeks was more or less the journal of rawalpindi medical college (jrmc); 2007; 11(1): 5-9 8 same (figs. 2 & 3). table 1: intra operative complications of phacoemusification (n=2000) intra operative complications no. of patients percentage radial tear 100 5.00% pc rent with vitreous loss 97 4.85% pc rent without vitreous loss 69 3.45% iris damage 23 1.15% zonular dehiscence 12 0.60% nuclear fragment drop 6 0.30% total 307 15.35 postoperative astigmatism in patients with 5.25 5.50 mm incision was between 0.50 to 4.50 d whereas, in patients with 3.25 mm incision the astigmatism was from 0 to 1.75 d. in majority of patients, astigmatism was less than 2.00 d with surprises in 4 cases where astigmatism was upto 4.50 d (table 2). table 2: post operative astigmatism (n=1820) astigmatism no. of patients percentage 0 – 0.5 d 400 21.98% 0.62 – 1.0 d 437 24.01% 1.12 – 1.5 d 765 42.03% 1.62 – 2.25 d 214 11.76% 2..50 – 4.50 d 4 0.22% 20.83% (n=379) of patients had postoperative complications (table 3 & fig. 4). corneal oedema was the commonest complication with the incidence of 11.98% (218). in most of the cases it was mild to moderate and resolved in one week. only in 0.15% (n=3) it ended up in pseudophakic bullous keratopathy. 4.01% (n=73) patients had mild to journal of rawalpindi medical college (jrmc); 2007; 11(1): 5-9 9 moderate anterior uveitis, out of which 5 patients developed pupillary membrane which settled with medical treatment, one patient needed nd:yag laser later on for removal of membrane. postoperative rise of iop was seen in 0.73% (n=13) which settled well with medicines. wound leak was seen in 0.31 % (n=6), all of them responded well to patching, no one needed suturing. one patient 0.05% (n=1) had ophthalmoplegia on 1st post operative day which settled in one day without any treatment. posterior capsular opacification (pco) was seen in 3.65% (n=66) in first 8 weeks of follow up. 2% (n=40) cases of pco causing gross visual impairment were treated with nd:yag laser posterior capsulotomy later on. endophthalmitis occurred in 0.10% (n=2) patients. both were diabetics and unfortunately the eyes could not be saved. table 3: post operative complications of phacoemulsification (n=1820) post operative complications no. of patients percentage corneal oedema 218 11.98% uveitis 73 4.01% raised iop 13 0.73% wound leakage 6 0.31% ophthalmoplegia 1 0.05% endophthalmitis 2 0.10% pco 66 3.65% total 379 20.83% discussion our study had a predominantly large number of females, 72% (n=1440) compared to males, 28% (n=560). the reason for this gender difference is that our hospital is entitled for the families of ex-service men. phacoemulsification is much superior to planned extra capsular cataract extraction (ecce) for many reasons. operation time is less. there is small incision which results in shorter stay in hospital and early physical and visual recovery. post operative astigmatism is also less. tunnel incision provides a secure wound with rapid healing. ac is maintained throughout the procedure which allows better cortical cleanup and decreased incidence of pc rent. even in case of pc rupture, vitreous disturbance is less because of closed chamber. there is decreased post operative reaction in phacoemulsification than in planned ecce. no surgery is without the risk of complications. those like corneal oedema, iris trauma, sphincter damage, pc rent, vitreous loss, loss of nuclear fragments in vitreous and zonular dehiscence are more common in learning phase. with experience, good patient selection and precautions the incidence of complications decreases. radial tear formation and its extension is quite a common intra operative problem. this was seen in 5% of our cases. this can be minimized by keeping ac deep and tight with viscoelastic especially during later half of capsulorrhexis. a relatively common complication of cataract surgery especially during learning curve is pc rupture with or without vitreous loss. our series had 3.45% of patients with pc rents without vitreous loss and 4.85% with vitreous loss. commonly the rupture occurred as a result of direct damage to the capsule during phaco and secondly due to extension of radial tear. this can be avoided by keeping the capsulorrhexis directly under observation and doing the phaco in central 5-6 mm zone initially in the bag and then in iris plane with fully dilated pupil. another reason for pc rupture is temptation to chase nuclear pieces. nuclear fragments should be engaged by using high vacuum. it is important to be careful while sculpting the nucleus in the peripheral part as the nucleus is thickest in the centre and becomes thinner in periphery. cruz et al6 reported the incidence of pc rupture in 9.9% of 181 eyes, whereas hasmani et al reported 8% of cases to be complicated by pc rupture7. we managed our cases by doing anterior vitrectomy and putting in 6.5 mm pmma iol over anterior capsule. another serious complication which haunts phaco surgeons is dislocation of nucleus or nuclear fragments into the vitreous. this happened in 6 of our patients and was managed by giving systemic and topical steroids with pressure lowering medicines. two of our patients with nucleus drop were referred journal of rawalpindi medical college (jrmc); 2007; 11(1): 5-9 10 to vitreoretinal surgeon. tommica et al8 and gilliland and colleagues recommended early vitrectomy as it allows early restoration of vision, rapid resolution of uveitis and glaucoma9. in this study our patients achieved visual acuity of 6/12 or better in 80.50 % of cases. when conditions decreasing bcva were eliminated the corrected vision was 6/9 or better in 89% of patients. hussain et al showed that 70% of their patients achieved va of 6/12 or better10. whereas in another series of 150 patients by hashmani et al 89.3% of patients achieved va of 6/12 or better7. seward and colleagues did a study on 400 cases and the bcva came out to be 6/9 or better in 83.6% of cases11. our results are comparable and perhaps a little better than others probably because these studies were carried out during learning phase of phacoemulsification. astigmatic changes in our cases range between 0 4.50 d, which is comparable to other studies12. astigmatism is less with 3.25 mm incision for foldable iols. because of high cost, most of our patients could not afford foldable iols. most common post operative complication was corneal oedema. this was also noted by prince et al in their study13. to avoid this complication viscoelastic should be used more freely and frequently. phaco should be avoided in ac to prevent damage to endothelium, and wound burn. larger fragments of hard nucleus should not be allowed to touch the endothelium, so it is better to chop the nucleus into smaller pieces within the capsular bag and aspirate them with high vacuum. to prevent iris damage, it is important to have a fully dilated pupil. careful tunnel construction can also prevent iris prolapse during the procedure and wound leakage after surgery. during learning phase one should avoid surgery in deep sunken eyes, brunescent cataract and eyes with shallow ac (hypermetropic). the surgeon must avoid surgery with cloudy cornea in the beginning. avoid phacoemulsification in semi dilated pupil. it is extremely important not to do any procedure blindly during any part the surgery. lastly, in order to avoid problems it is important to understand all the features of the phaco unit completely. it would be better to write down all important points told by the technical staff regarding phaco machine, and paste it close to the unit in the theatre. conclusion our study reinforces this impression that phacoemulsification is much superior to planned ecce. it is safer, more predictable and almost atraumatic procedure in experienced hands. it provides more patient as well as surgeon satisfaction. references 1. kelman cd. history of phacoemulsification. in: emery jm, little jh. phacoemulsification and aspiration of cataracts. st louis. cv mosby and company 1979:5-7. 2. boyd bf. highlights of ophthalmology. 1995; 23: 2. 3. boyd bf. highlights of ophthalmology. 1995; 23: 13-18. 4. holmberg as, philipson bt. sodium hyaluronate in cataract surgery. report on the use of healon in extracapsular cataract surgery using phacoemulsification. ophthalmology. 1984; 91: 53-59. 5. obstbaum sa. phacoemulsification: the favoured surgical technique,(editorial: comment). j cataract refract surg 1991; 17: 267. 6. cruz oa, wallace gw, gay ca, motoba ay, koch dd. visual results and complications of phacoemulsification with intraocular lens implantation performed by ophthalmology residents. ophthalmology 1992; 99: 448-52. 7. hashmani s, haider i, khan ma. phacoemulsification, results and complications during the learning curve. pak j ophthalmol 1997; 13(2): 32-36. 8. tommilla p, immonen i. dislocated nuclear fragments after cataract surgery. eye 1995: 437-41. 9. gilliland gd, hutton wi, fuller dg. retained intravitreal lens fragments after cataract surgery. ophthalmology 1992; 99: 1268-69. 10. hussain m, durrani j, nisar a. phacoemulsification: a review of 210 cases. pak j ophthalmol 1996; 12: 38-43. 11. seward hc, dalton r, davis a. phacoemulsification during the learning curve: risk / benefit analysis. eye 1993; 7: 164-68. 12. khan aa, azher an, chohan am. review of 100 cases of phacoemulsification. pak j ophthalmol 1997; 13(2): 37-40. 13. prince rb, tax rl, miller dh. conversion to small incision phacoemulsification; experience with the first 50 eyes. j cataract refract surg 1993; 19: 246-50. summary journal of rawalpindi medical college (jrmc); 2017;21(1):16-19 16 original article ameliorative effects of two forms of pomegranate on glomerular transvertical diameter in steroidinduced kidney damage in mice humaira ali 1 ,bushra riaz 2 , aamna khalil 2 ,khadija qamar 2 ,fatima shoaib 2 1. department of anatomy, hit medical college, taxilla; 2.department of anatomy, army medical college, rawalpindi abstract background: to observe the effects of pomegranate juice (pj) and pomegranate peel extract (ppe) on glomerular transvertical diameter in steroid induced mice kidney damage. methods: in this experimental study forty healthy adult mice (balb/c strain), average weighing 25-30 gms were divided into four groups, having ten mice each. control group a received only standard laboratory diet without alteration.experimental groups b, c and d were injected nd (nandrolone decanoate) (1 mg/100 gm body weight), intramuscularly (i/m), in the hind limb once a week for 8 weeks. experimental group c was also given pj (3ml/kg body weight) by oral gavage tube daily for 8 weeks and experimental group d was given ppe (200mg/kg body weight) through oral gavage tube,daily for 8 weeks.after the experimental period, the animals were sacrificed and both kidneys of all mice were obtained. kidneys were processed, embedded and stained for histological study by using hematoxylin and eosin (h&e) and periodic acid schiff (pas) stains. the results were compiled and compared. results: after nd administration, glomerular diameter was significantly reduced in experimental group b when compared to control group a.protective effects were seen when comparison of experimental group b was done with pj and ppe administered experimental groups c and d, respectively. when results of experimental groups c and d were compared with each other no statistical significance was present. conclusion: both forms of pomegranate has ameliorative effects on glomerular transvertical diameter in steroid induced mice kidney disease. key words: pomegranate, nandrolone decanoate, glomerulus, kidney. introduction about 25 centuries back, the father of medicine, hippocrates stated, “let food be thy medicine and let medicine be thy food’’. globally,in reference to this statement, , various researches have shown the protective and curative benefits of many fruits, vegetables, pulses, spices and herbs which now plays an important role in health management.1 pomegranate is commonly known as “anar”.current scientific name of pomegranate,“punicagranatum” is derived from the name pomum (apple) and granatus (seeded), or granular apple.2 pomegranate is a great natural source of phenolic compounds such as gallotannins, anthocyanins, free ellagic acid, ellagic acid glycosides, ellagitannins, punicalagin and punicalin which contribute to its antioxidant, anticancer, anthelminthic and antimicrobial potentials as per research.3-5 anabolic androgenic steroids (aas’s) are synthetically produced drugs correlated to the hormone testosterone, formed in the interstitial leydig cells of the testes. aas’s are used therapeutically to supplement two different situations; firstly it is administered as androgen replacement therapy because of androgen deficit due to hypothalamic, pituitary or testicular genomic disorders in order to achieve optimum testosterone levels. secondly, aas’s are given as pharmacological androgen therapy (pat) in non-androgen-deficient patients having prolonged and devastating diseases to improve the quality of life.6 besides having beneficial therapeutic effects, aas’s have been recognized to produce undesirable effects towards patient’s health, such as cardiovascular system failure, prostate gland diseases, lipid metabolic disorders, insulin sensitivity,cholestatic jaundice,testicular atrophy, gynecomastia and compromised spermatogenesis.7 stanozolol, oxandrolone, oxymetolon, nandrolonedecanoate and testosteonespionat are commonly abused aas’s.8 these drugs are capable of growing muscle mass and boosting physical strength, so they are often misused and self-administered by bodybuilders and young athletes to enhance their stamina and performance. 8data of renal disorders is intermittently evolving from clinical reports among aas’s users.9 journal of rawalpindi medical college (jrmc); 2017;21(1):16-19 17 material and methods this experimental trial was conducted at anatomy department, army medical college, rawalpindi in association with national institute of health (nih), islamabad.forty healthy male and female balb/c mice weighing 25-30 gms were equally divided into four groups, having ten animals each.they were kept in nih under controlled conditions of temperature and light. group a served as control and was given standard laboratory micepellets for 8 weeks. groups b, c and d served as experimental groups. mice in these three experimental groups were injected nd (at the dose of 1 mg/100 gm body weight), as single i/m injection in the hind limb once a week for 8 weeks.10 after preparation, pj was stored at-20°c after diluting with distilled water to volume of 1:3 and mice in experimental group c was also given pj (at the dose of 3ml/kg body weight) by oral gavage tube daily for 8 weeks, and mice in experimental group d was given ppe (at the dose of 200mg/kg body weight) by oral gavage tube daily for 8 weeks. 11-14this extract was dissolved in plain water and was given to each mouse by oral gavage tube.at the end of experimental period, the animals were sacrificed. both kidneys of each specimen were washed in saline and observed for size, color or cystic appearance. texture was appreciated by palpation. the coronal section of each of the right kidney was taken and each left kidney was cut transversely at the level of hilum. tissues were fixed in 10% formalin solution, dehydrated by passing through graded alcohol, embedded in paraffin waxto form blocks. blocks were mounted on rotary microtome to obtain sections having thickness of 5μm. h&eand pas stains were used for histological study. transvertical diameter of glomeruli was measured by using ocular micrometer which was calibrated by a stage micrometer (figure-1). three glomeruli were randomly chosen in three different fields in one slide per specimen at 40x magnification. both transverse and vertical diameters of same glomerulus were measured and then mean of both diameters was calculated, the result was the transvertical diameter of the glomerulus. three readings were taken and then mean of the three readings was taken as the observed diameter of the glomeruli for the particular specimen. the data was entered and analyzed by using spss version 21.anova test was applied for intergroup comparison of quantitative variables followed by post hoc tukey’s test that was taken as mean and standard deviations (mean ± sd). p-value of <0.05 was taken as significant. results mean glomerular transvertical diameter ± sd of right and left kidneys of control group a were 50.997±1.591µm which was statistically significant when compared with nd administered experimental group b (p-value=0.000) and nonsignificant when compared with pj administered experimental group c and ppe administered experimental group d (pvalue=0.159 and 0.083) respectively (table-1) . mean glomerular transvertical diameter ± sd in right and left kidneys of experimental groups b was 37.365±1.249 showing renal damage caused by nd. in experimental groups c and d mean glomerular transvertical diameter ± sd were 48.323±23.917 and 47.927±3.414 respectively, (table-2) showing remarkable improvement in both pomegranate administered groups. on intergroup comparison, statistical significance was found when experimental group b was compared with experimental groups c and d (p-value=0.000). when experimental group c was compared with control group a and experimental group d (p-value=0.159 and 0.989) respectively,no statistical difference was present (table-1). no remarkable difference was present when experimental groups c and d were compared with each other (0.989) showing that both forms of pomegranate has nearly equal protective effects on steroid induced renal damage (figure-2). table1: statistical difference for glomerular transvertical diameter on intergroup comparison of control group a and experimental groups b, c and d groups group a vs. group b group a vs group c group a vs group d group b vs group c group b vs group d group c vs group d p-value 0.00* 0.159 0.083 0.00* 0.001 0.989 table-2: mean values of glomerular transvertical diameter of control group a and experimental groups b, c and d glomerular transvertical diameter (µm) group a group b group c group d mean value±sd 50.99± 1.591 37.36±1.2 49 48.32±3.9 17 47.92±3.4 14 journal of rawalpindi medical college (jrmc); 2017;21(1):16-19 18 figure-1: comparison of mean values of glomerular transvertical diameter between the control group a and experimental groups b, c and d figure-2: photomicrograph showing micrometry of glomerulus in animal no. 5 of control group a, h & e 400x discussion anabolic androgens and other appearance and performance enhancing substances are abused worldwide. nephrotoxicity and hepatotoxicity are often associated to oxidative stress, as these are major organs involved in metabolism, detoxification and excretion of drugs.15 elevated creatinine and decreased gfr (glomerular filtration rate) may occur as a result of rhabdomyolysis in highly muscular androgen users engaged in heavy resistance training.16 numerous studies recommend that anabolic androgens exert a direct toxic effect on podocytes leading to their depletion, glomerular cell damage and accumulation of mesangial matrix.17 high doses of aass enhanced androgen receptor expression on glomerular and mesangial cells, increased mrna levels of the pro-fibrotic cytokine, thus providing a potent pro-apoptotic stimulus to podocytes and promote fsgs (focal segmental glomerulosclerosis), the direct nephrotoxic effect of anabolic steroids.18,19 it is reported that bodybuilders abusing high doses of aas’s are diagnosed with end-stage renal disease. renal biopsy of these patients revealed glomerulosclerosis with discrete obstructive lesions of pre-glomerular vessels and chronic diffuse tubulointerstitial damage.20 fragmentations of glomeruli along with few atrophied elements are also observed.21,22 these pathological alterations cause an abnormal production of cytokines and growth factors. consequently, they enhance the synthesis of extracellular matrix proteins and their deposition in the glomerulus that eventually lead to mesangial expansion, glomerular basement thickening and glomerular shrinkage.23,24 these modifications increase hydrogen peroxide production in the mesangial cells and lipid peroxidation of the glomerulus.25 a cellular damage and lipid peroxidation products lead to oxidative stress.26 oxidative stress occurs whenever there is an imbalance between pro-oxidant compounds and antioxidant defences leading to modifications of dna, lipids and proteins .these structural alterations in biomolecules can modify cellular functions and processes, and play a substantial role in causing a variety of common diseases and degenerative conditions.27marked improvement in glomerular diameter was seen in pomegranate administered experimental groups c and d. mean diameters were increased and no statistical difference was seen when compared with mean diameters of control group a. reno-protective effects of pomegranate involve the activation of nitric oxide-dependent and peroxisome proliferator-activated receptor (ppar-γ) signaling pathway.28 in another study improvement in renal pathology was observed in adenine-treated rats coadministered with pomegranate juice or pomegranate peel extract and this was also attributed to the activation of ppar-γ and increased no (nitric oxide) production.29 another research also documented protective role of no in renal failure, including glycerol-induced renal failure in animal model.30 studies have shown that pomegranate is very effective scavenger of toxic hydroxyl radicals and is a potent antioxidant. it enhances the antioxidant enzyme activity like of superoxide dismutase, glutathione peroxidase and catalase in conditions of increased oxidative stress and regulate mrna levels in the cells for these enzymes this antioxidant ability was attributed to large amount of phenolics, flavonoids and proathocyanidins contained both in peel as well as pulp extract.31-33both forms of pomegranate appeared to have markedly high potential to be used as a health supplement rich in natural antioxidants in various chronic and debilitating diseases. conclusion 1. nandrolone decanoate treated group showed significant reduction in glomerular transvertical diameter indicating renal damage. improvement was seen in pomegranate administered experimental groups c and d. journal of rawalpindi medical college (jrmc); 2017;21(1):16-19 19 2. pomegranate in both forms has nearly equal ameliorative effects on steroid induced renal damage. references 1. cristofori v, caruso d, latini g, dell’agli m . fruit quality of italian pomegranate (punicagranatum l.) autochthonous varieties. european food research and technology, 2011; 232(3):397-403. 2. asrey r, singh rb, shukla hs. effect of sodicity levels on growth and leaf mineral composition of pomergranate (punicagranatum l.). annals of agricultural research, 2002; 23: 398-401. 3. saad h, charrier-el bouhtoury, f., pizzi a, rode k, charrier b. characterization of pomegranate peels tannin extractives. industrial crops and products, 2012; 40: 239-46. 4. bhandari pr. pomegranate (punicagranatum l), ancient seeds for modern cure? review of potential therapeutic applications. international journal of nutrition, pharmacology, neurological diseases, 2012;2(3):171-76. 5. arun n and singh dp. punicagranatum: a review on pharmacological and therapeutic properties. international journal of pharmaceutical sciences and research, 2012; 3(5):1240-43. 6. pope jr hg and kanayama g. treatment of anabolicandrogenic steroid related disorders. textbook of addiction treatment: international perspective,2015; 621-36. 7. mutalip ssm, surindar singh gk, mohd shah a, mohamad m, mani v. histological changes in testes of rats treated with testosterone, nandrolone, and stanozolol. iranian journal of reproductive medicine, 2013;11(8):653-58. 8. hijazi mm, azmi ma, hussain a. androgenic anabolic steroidal-based effects on the morphology of testicular structures of albino rats. pakistan journal of zoology, 2012;44(6):1529-37. 9. daher ef, júnior, gbs, queiroz al, ramos lm.acute kidney injury due to anabolic steroid and vitamin supplement abuse. international urology and nephrology, 2009;41(3):717-23. 10. frankenfeld sp, de oliveira lp, ignacio dl. nandrolone decanoate inhibits gluconeogenesis and decreases fasting glucose in wistar male rats. journal of endocrinology, 2014;220(2):143-53. 11. faria a, monteiro r, mateus n, azevedo i. effect of pomegranate (punicagranatum) juice intake on hepatic oxidative stress. european journal of nutrition,2007; 46(5):271-78. 12. moneim aea, dkhil ma, al-quraishy s. studies on the effect of pomegranate juice and peel on liver and kidney in adult male rats. j med plants res,2011; 5(20):5083-88. 13. el-habibi em. renoprotective effects of punicagranatum (pomegranate) against adenine-induced chronic renal failure in male rats. life sci j, 2013;10(4):2059-69. 14. parmar hs and kar a. medicinal values of fruit peels from citrus sinensis, punicagranatum, and musa paradisiaca with respect to alterations in tissue lipid peroxidation and serum concentration of glucose, insulin, and thyroid hormones. journal of medicinal food, 2008;11(2):376-81. 15. mcwilliam lj. drug-induced renal disease. current diagnostic pathology, 20007;13(1):.25-31. 16. brenu e, mcnaughton l,marshall-gradisnik s. is there a potential immune dysfunction with anabolic androgenic steroid use?: a review. mini reviews in medicinal chemistry,2011; 11(5):438-45. 17. rodrigues-diez r, lavoz c, carvajal g, rayego-mateo s. gremlin is a downstream profibrotic mediator of transforming growth factor-beta in cultured renal cells. nephron experimental nephrology, 2013;122(1-2):62-74. 18. elliot sj, berho m, korach k. gender-specific effects of endogenous testosterone: female α-estrogen receptordeficient c57bl/6j mice develop glomerulosclerosis. kidney international, 2007;72(4):464-72. 19. droguett a, krall p, burgos me, valderrama g, carpio d, ardiles l. tubular overexpression of gremlin induces renal damage susceptibility in mice. plos one, 2014;9(7),101879. 20. herlitz lc, markowitz gs, farris ab, schwimmer ja, stokes mb.development of focal segmental glomerulosclerosis after anabolic steroid abuse. journal of the american society of nephrology, 2010;21(1):163-72. 21. ha h. and kim kh. pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase c. diabetes research and clinical practice, 199; 45(2):147-51. 22. alexandra gb, fuhrman b, moscovici yb. consumption of pomegranate decreases serum oxidative stress and reduces disease activity in patients with active rheumatoid arthritis. israel medical association journal, 2011; 13 (80):474-79. 23. hartung r, gerth j, fünfstück r, gröne hj. end‐stage renal disease in a bodybuilder: a multifactorial process or simply doping?. nephrology dialysis transplantation, 2001 16(1):163-65. 24. d'errico s, di battista b, di paolo m, fiore c, pomara c. renal heat shock proteins over-expression due to anabolic androgenic steroids abuse. mini reviews in medicinal chemistry, 2011 11(5):446-50. 25. ruiz-munoz lm, vidal-vanaclocha f,lampreabe i. enalaprilat inhibits hydrogen peroxide production by murine mesangial cells exposed to high glucose concentrations. nephrology dialysis transplantation,1997; 12(3):456-64. 26. torres-bugarin o, covarrubias-bugarín r, zamora-perez al. anabolic androgenic steroids induce micronuclei in buccal mucosa cells of body builders. british journal of sports medicine, 2007;41(9):592-96. 27. berning jm, adams kj,stamford ba. anabolic steroid usage in athletics: facts, fiction, and public relations. the journal of strength & conditioning research, 2004;18(4):908-17. 28. singh ap, singh aj,and singh n. pharmacological investigations of punicagranatum in glycerol-induced acute renal failure in rats. indian journal of pharmacology, 2011; 43(5):551-54. 29. miguel mg, neves ma, antunes m pomegranate (punicagranatum l.): a medicinal plant with myriad biological properties-a short review. j med plants res,2010; 4:2836-47. 30. valdivielso jm, lopez-novoa jm, eleno n.role of glomerular nitric oxide in glycerol-induced acute renal failure. canadian journal of physiology and pharmacology,2000; 78(6):476-82. 31. aboonabi a, rahmat a, othmanf. effect of pomegranate on histopathology of liver and kidney on generated oxidative stress diabetic induced rats. journal of cytology & histology 2015; 6:294:2157-59 32. ahmed at, belal sk,salem age. protective effect of pomegranate peel extract against diabetic-induced renal histopathological changes in albino rats. iosr-jdms,2014; 13(10):94-105. 33. riezzo i, turillazzi e, bello s, cantatore s. chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and tnf-α mediated apoptosis in the kidneys of cd1 treated mice. toxicology and applied pharmacology, 2014;280(1):97-106. summary journal of rawalpindi medical college (jrmc); 2017;21(4): 354-357 354 original article vascular surprises in calot’s triangle during laproscopic choleystectomy tariq nawaz, maryam barkat, muhammad atif, qasim ali. department of surgery, holy family hospital and rawalpindi medical university abstract background: to identify the vascular anomalies,variations of calot’s triangle during laparoscopic cholecystectomy methods: in this prospective observational study one thousand patients with a diagnosis of cholithiasis were included. exclusion criteria were patients younger than 12 years and older than 80 year. calot’s triangle dissection was done meticulously.cystic artery and hepatic artery anomalies and variations were observed and analyzed on spss 21. results: the age varied from 12 to 80 years. on the basis of distributional variation the cystic artery was single in 90% cases, branched in 7% cases and absent in 3% cases. on positional variations the cystic artery was superomedial to the cystic duct in 85% cases, anterior in 7% cases, and posterior in 3% cases and low lying in 5% of the cases. on the basis of length variation results showed that 80% cases had a normal cystic artery .a short cystic artery was found in 5% cases and a long cystic artery was present in 5%. other arterial variations are of hepatic artery i.emoynihan’s hump (3%) and right hepatic artery present in calots triangle in 5% conclusions: for the safety of laparoscopic cholecystectomy one should be well aware of the anatomical variations of the cystic and hepatic artery. key words: cholelithiasis, cholecystitis, laparoscopic cholecystectomy. introduction cholithiasis is very common in western countries and their frequency varies from 20-30%. it is increasing every year and the reason is because of increased intake of junk food.1cholithiasis is common in pakistan as well and the standard procedure for it is cholecystectomy. 2 laparoscopic cholecystectomy is very popular among minimal invasive surgery and replacing the conventional surgery. 3its advantages are truly based not only on the skill but also the good knowledge of anatomy and variations of calot’s triangle. with the advent of laparoscopic cholecystectomy, though there are a lot of benefits but initially surgeons had faced a lot of complications.4 surgeon were not really well aware about the anatomical variations of the calot’s triangle. there was injudicious use of vessel sealing devices and third excessive skeletonization of the triangle .vigilant steps should be carried out during dissection of cystic duct and artery in open as well in laparoscopic cholecystectomy to prevent complications. 5 in 1891 ccalot described the calot’s triangle and it is very important landmark during laparoscopic cholecystectomy. this triangle is formed below by cystic duct, above by inferior border of liver and medially by common hepatic duct and cystic artery and lymph node lie within it. patients and methods it was an observational study in which the vascular anomalies were assessed .it was conducted at the surgical unit ll of holy family hospital, rawalpindi from january, 2012 to december, 2016. a total of 1000 patients were included who underwent laparoscopic cholecystectomy. the length of the cystic artery was measured by cautery tip which is 1cm in length. surgeon evaluated the dissection of calot’s triangle easy and difficult. dissection of gall bladder done by hook, ligasure or harmonic. informed consent was taken from all patients. on a pre-designated patient proforma data were collected. the cystic artery distributional (single, double, branched), positional and length variations were noted. cystic artery variations in the form of number and position and length in term of frequency, difficult dissection and hepatic artery anomalies and variations were carried out with the help of descriptive statistics. results out of 1000 patients majority were between 12-80 years (mean 48±13). only 200(20 %)patients were male and females were 800 (98%). per operatively in 80% were of cholthiasis, acute cholecystitis were seen in 6% patients while 6% patients had an empyema gall journal of rawalpindi medical college (jrmc); 2017;21(4): 354-357 355 bladder and 8% had a mucocele of the gall bladder. calot’s triangle dissection was assessed easy in 80%.anatomical variations are elaborated as positional, distributional and length variations of cystic and hepatic artery. in 90% cases, there was a single cystic artery (table 1;figure;1).in 3% cases, cystic artery was absent and gallbladder was receiving blood supply from liver bed. (table 1). according to cystic artery length, it was divided into three groups i.e. short ,normal (1-3 cm) and long .the results showed that 800 (80%) patients had a normal cystic artery.(figure;4) .a short cystic artery was found in 15%(figure;3) and a long cystic artery(figure;2) was present in 5% ( table 2). positional variations of the cystic artery was seen in the calot’s triangle. in 85% cases the cystic artery was superiomedial to the cystic duct.(figure;8). the most common variation was a cystic artery anterior to the cystic duct in 7% cases.(figure;5) a cystic artery posterior to the cystic duct was found in 3% (figure;6) and low-lying 5%(figure;7)(table 3). caterpillar hepatic artery seen in 3% (figure 10) and in 6% right hepatic artery was taking a sharp turn in front of the cystic duct and lies within calot’s triangle. (figure 9;table 4). ten patients (1%) out of 1000 suffered from intra-operative bleeding which required conversion to open operation. 5 patients have hemorrhage because of branched cystic artery which was controlled by applying the clip. 5 patients had uncontrollable bleeding because of damage to right hepatic artery which was assumed by surgeon cystic artery figure 1. branched cystic artery and cystic duct already clipped at common bile duct site figure:10 moynihan’s hump on medial side and cystic artery is originating from it.maryland is pointing towards cystic artery figure:2 long cystic artery seen above the cystic duct figure:3 short cystic artery seen above the cysitc duct figure 4. normal cystic artery seen above the cystic duct figure 5. anterior cystic artery which is clipped figure 6. posterior cystic artery which is twisted around cystic duct figure:7 low lying cystic artery infront of clipper prong figure8.superiomedial cystic artery lying above the cystic duct figure:9 right hepatic artery in calot’s triangle colour page journal of rawalpindi medical college (jrmc); 2017;21(4): 354-357 356 table1. distributional variations of cystic artery single cystic artery 90% branched cystic artery 7% absent cystic artery 3% table:2 length variations of cystic artery normal length cystic artery 80% short length cystic artery 15% long length cystic artery 5% table:3 positional variations of cystic artery. superiomedial cystic artery 85% anterior cystic artery 7% posterior cystic artery 3% low lying cystic artery 5% table:4 hepatic artery variations and anomalies. caterpillar hepatic artery 3% right hepatic artery within calot’s triangle 6% discussion minimal invasive surgery is replacing the conventional surgery.7 in order to prevent complications, it is very important to know the details of anatomy and the variations of cystic artery and duct.9 in present study the age range was 12-80 years which is the same as that of western population. 1cholithiasis occurs mainly in obese patients as described in classical textbooks, even in pakistan the cholilthiasis is more common in obese people. 10in our study 98% of patients were female and only 4 (2%) male. international data suggests that gallstone disease is 3 to 4 times more common in females than males. 11 per operatively 80% were of cholelthiasis, acute cholecystitis were seen in 60(6%) patients while 60 (6%) patients had an empyema gall bladder and 80 (8%) patients had a mucocele of the gall bladder. in his study, m.taimur noticed similar results i.e. biliary colic in 88% cases. acute cholecystitis was seen in 7%, mucocele in 3% and empyema in 2% cases 12.minimal invasive surgery is beneficial in acute cholecystitis.13 we found that in 85% of the cases cystic artery lies within the calot’s triangle. this normal path of cystic artery was also seen by badshah and colleagues which is 66.6% . in the study by hugh and colleagues, the normal path was in 76%.17 we also assessed the positional variation of cystic artery i.e it lies anterior to the cystic duct in 70 (7%) cases and it was consistent with haythem a and colleagues which reported that cystic artery lies anterior to cystic duct in 16% of cases.18 this anomaly is dangerous because during skeletonization of the cystic duct, the anterior lying artery may be damaged or excessive bleeding can start. another positional variation we noted that cystic artery lies posterior to the cystic duct and it was seen in 6% of cases.4th positional variation of cystic duct seen was that cystic artery is low lying and it was seen in 5% of the cases and it was consistent with the study of badshah and colleagues in which 4% cases had low lying cystic artery. in our study, the cystic artery was absent in 3% cases while there was a single cystic artery in 90% cases. badshah and colleagues reported a single cystic artery in 66.6% of their patients.18 in 7% cases a branched cystic artery was found. singh et al and adnan al et al noticed a branched cystic artery in 6% of their cases. 4,19 we have also noticed that in 800 (80%) cases, the cystic artery was of normal length. a short cystic artery was seen in 5% cases while a long cystic artery in 50 (5%) cases. de silva reported a mean length of cystic artery to be 2.3cm seen in his study and m.taimur and colleagues had the same the result. 9 when the cystic artery is not found in the usual common position, then a variant anatomy should be kept in mind to avoid troublesome bleeding during the procedure. in 6 (3%) cases, the right hepatic artery was taking a sharp turn in front of the cystic duct and the cystic artery was arising as a short twig from the right hepatic artery. most of the time young surgeon assume it cystic artery and try to clip it .uncontrolled bleeding can start which sometime end in disaster because of panic to control, sometimes damage the other surrounding structures. another anomaly i.e moynihan’s hump is reported in 1% of cases by ayyaz et al and 4% by adnan al et al.19,26 ten out of 1000 suffered from intra-operative hemorrhage which required conversion to open technique and bleeding control by pressure and ligature. khan in his study noticed a conversion rate of 6.4%.24the morbidity encountered in our study is comparable to local and international data and is in the acceptable range. there was no mortality in this series. more emphasis is however needed to properly train young surgeons in the field of laparoscopic surgery. 25 conclusions journal of rawalpindi medical college (jrmc); 2017;21(4): 354-357 357 1.in order to avoid the iatrogenic injuries, it is very important that surgeon must be well versed about the anatomy and their variations and how to deal with this situation. 2.it is required to emphasize on basic principle of calots triangle that critical angle and dissection above the sulcus of rouviere’s.when nature has created any anatomical variations, it should always be respected. references 1. jessri m, rashidkhani b. dietary patterns and risk of gallbladder disease: a hospital-based case-control study in adult women. journal of health, population, and nutrition. 2015;33(1):39-49. 2. channa na, khan fd, bhanger mi, leghari mh. surgical incidence of cholelithiasis in hyderabad and adjoining areas of pakistan. pakistan j med sci 2004; 20:13-17. 3. hamzam,jaffara,hassana.vascular and gallbladder variations in laparoscopic cholecystectomy.medical journal of babylon 2014;5:1-5. 4. singh k,singhr,kaurm.clinical reappraisal of vasculobiliary anatomy relevant to laparoscopic cholecystectomy.jminimaccesss surg.2017;13(4):273-79. 5. azeem m, abbas sm, wirk nm, durrani k. bile duct injuries during laparoscopic cholecystectomytwo years experience at sheikh zaid hospital, mechanism of injury, prevention and management. ann king edward med coll 2001; 7: 23841. 6. larobina m, nottle pd. extrahepatic biliary anatomy at laparoscopic cholecystectomy: is aberrant anatomy important? anz j surg.2005; 75:392-95. 7. soomro ah, ram k, shaikh ms, abro as, balouch id, abro a. experience of first 100 cases of laparoscopic surgery. j surg pakistan 2002; 7:47-49. 8. mühe e. long-term follow-up after laparoscopic cholecystectomy. endoscopy 1992; 24:754-58. 9. de silva m, fernendo d. anatomy of the calot’s triangle and its relevance to laparoscopic cholecystectomy. ceylon med j 2001; 46: 33-35. 10. russell rcg, williams ns, bullstrode cjk. bailey and love short practice of surgery. 24th ed. arnold 2004; 1104 07. 11. kim sb, kim kh, kim tn. sex differences in prevalence and risk factors of asymptomatic cholelithiasis in korean health screening examinee: a retrospective analysis of a multicenter study. canena. jmt, ed. medicine. 2017;96(13):e6477. 12. taimur m, hasan a, ullah s, masood r,imran m.vascular variations in the calot?s triangle seen on laparoscopic cholecystectomy.pafmj 2011;61:4-7. 13. hosseini sn, mousavinasab sn, rahmanpoorh.outcome of laparoscopic cholecystectomy in acute and chronic cholecystitis. j coll physicians surg pak 2007; 17:406-09. 14. kwon ah, inui h, imamura a, uetsuji s, kamiyama y. preoperative assessment for laparoscopic cholecystectomy: feasibility of using spiral computed tomography. ann surg. 1998; 227:351-56. 15. maudar kk. evaluation of surgical options in difficult gall bladder stone disease.j indian med assoc. 1996; 94:138-40. 16. badshah m, soames r , nawab j, abbas f. the anatomical relationship of cystic artery to calot’s triangle. j med sci 2016; 24: (4) 199-201. 17. hugh tb, kelly md, li b. laparoscopic anatomy of the cystic artery. am j surg. 1992; 163:593-95. 18. haythem a. al-sayigh.the incidence of cystic artery variation during laparoscopic surgery.medical journal of babylon 2010; 7: 4 -7 . 19. helli aa, al taee m, khafaji ma.laparoscopic surgical anatomy of calot`s triangle.karbala j. med. 2011; 4:1-2. 20. nagral s. anatomy relevant to cholecystectomy. j min access surg 2005; 1:53-58. 21. flisinski p, szpinda m, flisinski m. the cystic artery in human fetuses.folia morphol (warsz).2004; 63:47-50. 22. saidi h, karanja tm, ogengo ja. variant anatomy of the cystic artery in adult kenyans.clinanat 2007; 20:943-46. 23. ding ym, wang b, wang wx, wang p, yan js. new classification of the anatomic variations of cystic artery during laparoscopic cholecystectomy world j gastroenterol 2007; 13: 5629-34. 24. khan s, oonwala zg. an audit of laparoscopic cholecystectomy. pak j surg 2007; 23:100-03. 25. kamath kb.an anatomical study of moynihan’s hump of right hepaticartery and its surgical importance.j anatomical society of india 2016,65:65-67. 26. .ayyaz m, fatima t, ahmed g. arterial anatomy in calot’s triangle as viewed through the laparoscope. ann k e med coll.2001; 7:183-85. summary journal of rawalpindi medical college (jrmc); 2018;22(2): 161-163 161 original article comparison of immediate induction (within 6 hours) versus late induction (after 24 hours) in terms of mean prom to delivery interval in females presenting with term prom kanwal firdos , maliha sadaf , farzana kazmi department of gynae / obs, district headquarters teaching hospital, rawalpindi and rawalpindi medical university abstract background: to compare the immediate induction (within 06 hours) versus late induction (after 24 hours) in terms of mean pre-labour rupture of membranes (prom) to delivery interval in females presenting with term prom. methods ; in this randomized controlled trial, 100 patients were enrolled per inclusion and exclusion criteria and randomly assigned to two groups. for group a, induction of labor was immediately started with prostaglandin e2 vaginal tablet, whereas for group b it was done 24 hours later. the prom to delivery time for both groups was noted down, whether delivered vaginally or by caesarean section. the spss version 17 was used to analyse the collected data. quantitative variables like age, gestational age, parity and prom to delivery interval were assessed by calculating mean and sd. comparison of prom to delivery interval between the two groups was done by using independent t test. pvalue <0.05 was considered significant. results :the mean age of the patients included in the study was 28.40 ± 4.04 years. the means for gestational age and parity were 38.64 ± 1.15 weeks and 1.09 ± 1.00 respectively. the mean of prom to delivery interval for group a (immediate induction) was 13.36 ± 3.16 hours. the mean for patients in group b (late induction) was 33.60 ± 4.06 hours (pvalue=0.00) conclusion :the mean time to delivery after prom is shorter with immediate induction (within 6 hours) as compared to delayed induction (after 24 hours). key words:immediate induction,late induction,prom introduction pre-labour or premature rupture of membranes (prom) is defined as the spontaneous leakage of amniotic fluid before the labour starts.1 this definition is subcategorized into preterm prom (when the gestational age is less than 37 weeks) and term prom (when the gestational age is 37 weeks or greater). this diagnosis excludes women who have rupture of the fetal membranes (amniorrhexis) following the onset of spontaneous labour. the incidence of prom is about 15% of all pregnancies and the term prom constitutes 90% of it. 2,3 while the incidence of prom is 2.7 – 7% in china and 5 – 15 % in america. 4 preterm prom cases have the involvement of intrinsic or extrinsic factors (in the form of inflammatory mediators) leading towards the weakening of fetal membranes.2 in women with prom at term, these risk factors are usually absent, and amniorrhexis occurs without premonitory signs or symptoms.5 amniorrhexis most likely occurs as a result of proteolytic enzymes, causing weakening of fetal membranes in the cases of term prom. proteolytic enzymes involved in weakening of the fetal membranes may originate from bacteria present in the lower genital tract, maternal inflammatory cells, or seminal secretions.6 spontaneous labour starts within 24 hours in 90% of patients having rupture of membranes at term.7 the duration of rom is directly proportional to the risk of intrauterine infection which is the most serious complication for the mother and the neonate. risk of chorioamnionitis is reduced with induction of labour, as compared to expectant management, without increase in the rate of caesarean section. 6,8,9 groups having early induction show reduced prom to delivery interval compared with groups having expectant or delayed management. early induction shortens prom–delivery interval, reduces the risk of maternal and neonatal infection resulting in shorter hospital stay without increase in caesarean section rate. 10 as rupture of membranes is in itself an indication for the presence of infection, it is not recommended to wait for long before active intervention.11 journal of rawalpindi medical college (jrmc); 2018;22(2): 161-163 162 patients and methods this randomized controlled trial was conducted at department of obstetrics and gynaecology, district headquarters teaching hospital rawalpindi from december, 2013 to may, 2014. one hundred patients (50 in each group) were enrolled in the study. patients having singleton pregnancy with cephalic presentation, gestational age between 37 to 41 completed weeks, admitted to labour room within 6 hours of spontaneous prom and cervical dilation <3 cm and having no evidence of uterine contractions were included in the study. exclusion criteria was patients having preterm rupture of membranes (before 37 completed weeks), showing sign & symptoms of chorioamnionitis, meconioum staining of liquor, multiple pregnancies and patients in active labour.after taking informed consent from the pregnant women enrolled in the study, rupture of membranes was confirmed by history and clinical examination (speculum examination). the patients were randomized into two groups after assessment of maternal and fetal status and finding it satisfactory. in the first group (group a) induction of labour was started immediately i.e. within 06 hours of prom with prostaglandin e2 vaginal tablet and the 2nd group (group b) was induced 24 hours after prom with prostaglandin e2 tablet. in both the groups vaginal tablet was repeated if required after 6 hours of the induction. intermittent fetal heart monitoring with ctg was done and colour of liqour was also noted. induction was considered to be failed if labour did not commence after repeating 2 doses of 3mg pge2 tablet. prom to delivery interval was noted in both groups, whether delivered vaginally or by caesarean section. any maternal and fetal complications faced were also recorded and managed accordingly. independent sample t test was used to compare the prom to delivery interval between the two groups. p value <0.05 was considered significant. results the mean age of participants was 28.40± 4.04 years. the mean age of patients stratified in group a was 28.28±4.13 years compared to patients in group b 28.52±3.98 years. there was no statistical difference between the two groups (p-value=0.77) (table 1). the mean gestational age was 38.64 ±1.15 weeks. the mean gestational age of participants in group a was 38.60 ±1.21weeks compared to patients in group b was 38.68±1.10 weeks. the p-value was 0.73. (table 1). the mean parity of all patients in the study was 1.09 ±1.00. the mean parity for patients in group a was 1.08± 1.03 versus the patients in group b1.10± 0.97. p-value again was not significant for both groups (p-value=0.93). (table 1).the mean for prom to delivery interval for all patients was 23.48 ±10.80 hours. the mean for patients in group a was 13.36 ±3.16 hours. the mean for patients in group b was 33.60 ± 4.06 hours. the difference was statistically highly significant (pvalue=0.00). (table 2) table 1: baseline characteristics. gory all patients =100) group a (n=50) group b (n=50) p-value mean std mean std mean std age 28.40 ±4.04 28.28 ±4.13 28.52 ±3.98 0.77 gestational age 38.64 ±1.15 38.60 ±1.21 38.68 ±1.10 0.73 parity 1.09 ±1.00 1.08 ±1.03 1.10 ±0.97 0.93 std= standard deviation. table 2: prom to delivery interval in hours group mean standard deviation p-value group a (n=50) 13.36 ± 3.16 0.00 group b (n=50) 33.60 ± 4.06 0.00 discussion aetiology of prom and pprom is multi-factorial, but the most important causative factor is localized or systemic infection.12,13 prolonged prom refers to prom greater than 24 hours and is associated with increased risk of ascending infection so induction of labour is recommended as it decreases the risk of infection. 14-16 in the management of prom in term pregnancy to induce labour immediately, for the possible risk of infection or to wait expectantly for the onset of spontaneous labour are the issues, which make the decision difficult. during the last decade, the new recommendations regarding management of patients with term prom have evolved due to introduction of new antibiotics and improved treatment of maternal and neonatal infection. in majority of the reports, where immediate induction with misoprostol was done, the latency period were significantly shorter, hence the duration of labour and hospitalization period were reduced. however, expectant management was another approach used where in, the operative intervention rate was lesser, without rise in the perinatal and maternal morbidity. the cases of term prom are benefited by active management due to reduction in latent period between prom and delivery. the studies also suggests that there is no significant increase in journal of rawalpindi medical college (jrmc); 2018;22(2): 161-163 163 incidence of caesarean section due to induction of labour.17 in the present study early induction group shows significant reduction in prom to delivery interval. different studies inferred that mean period from rupture of membranes to delivery interval was significantly shorter in the induction group as compared to the expectant group.18,19 in our study the mean time interval for prom to delivery was shorter in group a (immediate induction) (13.36 hrs) than group b (delayed induction/ expectant group) (33.60hrs).the difference between the two groups was highly significant. the present study shows consistent results with the study done by krupa et al.20 the results of the present study are also compatible with the study done by rath et al.21 studies have shown that oxytocin and prostaglandins (e1 & e2) are beneficial for cervical ripening and stimulation of labor in prom.22 some studies also compared oxytocin alone with transcervical foley / oxytocin for stimulation of labour in patients with prom. results show that the use of foley bulb in addition to oxytocin does not shorten the time to delivery as compared to oxytocin alone, but may increase the incidence of intra-amniotic infection. 23-25 the findings of the current study are contrary to another study conducted in 2011 which concluded that expectant management and delayed induction is better than active intervention and immediate induction in cases of term prom. the spontaneous labor and vaginal delivery occur in most of the women without increase in the caesarean section rate and infectious morbidity for mother and fetus.10 conclusion the mean time to delivery after prom is shorter with immediate induction (within 6 hours) as compared to late induction (after 24 hours). references 1. chandra i, sun li. third trimester pre-term and term premature rupture of membranes: is there any difference in maternal characteristics and pregnancy outcomes? journal of the chinese medical association 2017; 80 (10): 657-61. 2. naeye rl: factors that predispose to premature rupture of the fetal membranes. obstet gynecol 1982;60:93-97. 3. gunn gc, mishell dr, morton dg: premature rupture of the fetal membranes: a review. am j obstet gynecol 1970;106:46983. 4. xia h, li x, li x, liang h, xu h. the clinical management & outcome of term premature rupture of membranes in east china. int j clin exp med 2015; 8: 6212-17. 5. ekwo ee, gosselink ca, moawad a: unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy. obstet gynecol 1992; 80:166-72. 6. pasquier jc, bujold e. a systematic review of intentional delivery in women with preterm prelabor rupture ofmembranes. j matern fetal neonatal med. jul 2007; 20(7):567-68. 7. beckmann, charles. obstetrics & gynaecology, 7 e. philadelphia: wolters kluwer health / lippincott williams & wilkins. 2014 chapter 17: premature rupture of membranes, 169 – 73. 8. hartling l, chari r, friesen c, vandermeer b. a systematic review of intentional delivery in women with preterm prelabor rupture of membranes. j matern fetal neonatal med. mar 2006; 19(3):177-87. 9. middleton p, shepherd e, flenady v. planned early birth vs expectant management (waiting) for pre-labor rupture of membranes at term (37 weeks or more). cochrane database syst rev 2017; 1: cd 005302. 10. poornima b, reddy d.b.d. premature rupture of membranes at term: immediate induction with pge2 gel compared with delayed induction with oxytocin. j obstet gynaecol india 2011; 61: 516–18. 11. ismail aq, lahiri s. management of prelabour rupture of membranes (prom) at term. j perinat med 2013; 4: 1-3. 12. nadeau hc, subramaniam a, andrews ww. infection & preterm birth. semin fetal neonatal med 2016; 21 (2): 100-05. 13. lamont rf. advances in the prevention of infection related preterm birth. front immunol 2015; 6: 566-69. 14. caughey ab, robinson jn, norwitz er. contemporary diagnosis and management of preterm premature rupture of membranes. rev obstet gynecol 2008; 1(1): 11 – 22. 15. acog practice bulletin no. 80. premature rupture of membranes. obstet gynecol 2007; 109: 1007 – 19. 16. acog practice bulletin no. 188. pre-labor rupture of membranes. obstet gynecol 2018; 131 (1): 187 – 89. 17. ayaz a, saeed s, farooq mu . pre-labour rupture of membranes at term in patients with an unfavorable cervix: active verses conservative management. taiwan j obstet gynecol 2008;47:192-96. 18. bangal vb, gulati p, shinde kk, borawake sk. induction of labour versus expectant management for premature rupture of membranes at term. int j biomed res 2012; 3:164-70. 19. agnes jmb, lavanya s. two years comparative study on immediate versus delayed induction in term premature rupture of membranes. int j reprod contracept obstet gynecol 2018;7: 94-98. 20. graca krupa f, jose cecatti jg, castro surita fg. misoprostol versus expectant management in premature rupture of membranes at term. bjog: an international journal of obstetrics and gynaecology 2005; 112:1284-90. 21. rath dm, manas k. induction of labor with oral misoprostol in women with prelabour rupture of membranes at term. j obstet gynecol india 2007;57(6): 505-08. 22. dare mr, middleton p, crowther ca. planned early birth versus expectant management for pre labour rupture of membranes at term (37 weeks or more). cochrane database syst rev 2006; 1: cd005302. 23. amorosa jmh, stone j, factor sh. a randomized trial of foley bulb for labour induction in premature rupture of membranes in nulliparas (flip). am j obstet gynecol 2017; 217: 363 69. 24. cabrera ib, quinones jn, durie d. use of intracervical ballons and chorioamnionits in term premature rupture of membranes. j matern fetal neonatal med 2016; 29: 967-70. 25. mackeen ad, durie de, lin m. foley plus oxytocin compared with oxytocin for induction after membrane rupture: a randomized controlled trial. obstet gynecol 2018; 134: 4-7. summary journal of rawalpindi medical college (jrmc); 2018;22(1): 47-49 47 original article incidental parasitic infestations in surgically removed appendices and its association with inflammation muhammad arham 1, muhammad arish 1, jahangir sarwar khan 2 1.medical student , rawalpindi medical university ; 2.department of surgery, holy family hospital and rawalpindi medical university, rawalpindi abstract background:. to determine the frequency and type of parasitic infestations in surgically removed appendices based on histopathological findings and to assess its association with inflammation. methods: in this cross-sectional study 471 appendices removed were included and their histopathologic examination reports were observed. in cases with parasitic infestations, information regarding gender, age and presence of inflammation was gathered. fisher’s exact test at 5% level of significance was applied to compare presence of inflammatory infiltrates in appendices with and without parasites. results: of the 471 appendectomies performed, 15 (3.18%) specimens were found to contain parasites, all of which were enterobius vermicularis (pinworm). in those 15 cases, age of patients ranged from 9 to 45 years with a mean age of 19.07 ± 9.04 years. out of those 15 patients, 11 (73.3%) were females and 4 (26.7%) were males (male to female ratio was 1:2.75). only 2 out of 15 cases (13.3%) with parasitic infestation had inflammation, whereas in 456 of the remaining non-parasitic appendices, 324 (71.1%) were positive for inflammation. this difference was statistically significant with a p value < 0.05. conclusion: frequency of parasitic infestations in surgically removed appendices is low. very few appendices with parasitic infestation are associated with inflammation as compared to appendices without parasites. key words: parasitic infestations, appendices, enterobius vermicularis introduction parasitic infestation of the appendix can cause appendiceal colic similar to the right lower quadrant pain of usual acute appendicitis the vermiform appendix, mostly considered to be a vestigial organ, is a blind ending pouch extending from the posteromedial wall of the cecum.1 appendicitis is defined as the inflammation of the mucosa of the vermiform appendix.2 acute appendicitis is the most common cause of an ‘acute abdomen’ and one of the most common reasons for emergency gastrointestinal surgery.3-6 it is generally seen in patients aged 10-30 years and is the most common cause of emergency abdominal surgery in children.7 the lifetime risk of acute appendicitis for men and women is 8.6% and 6.7%, respectively.8 the inflammation usually results from obstruction of the appendiceal lumen which can be attributed to lymphoid hyperplasia within the appendix or mechanical obstruction by a fecolith or a stricture.6 due to this obstruction, the mucus secreted by the appendiceal glands and the inflammatory exudate continues to accumulate within the lumen. the intraluminal pressure gradually increases and becomes sufficient to obstruct the lymphatic drainage and later on the venous blood flow, leading to ischemia of the appendix wall. this is followed by bacterial invasion through the muscularis propria and submucosa, producing acute appendicitis.2 interestingly, the initial insult of appendiceal obstruction can be caused byparasites in its lumen and lead to the right lower quadrant pain of usual acute appendicitis, which may or may not be associated with inflammation.9-12physical signs and symptoms of such patients are similar to the cases of classic acute appendicitis. however, in the absence of any inflammatory reaction, such an infestation is considered to be a component of false acute appendicitis.10enterobius vermicularis, schistosoma species, taenia species and ascaris lumbricoides are most commonly associated with appendicitis.7,13however, it is still not clear that whether the parasites found in the appendix are actually involved in the pathogenesis of appendicitis or are just an incidental finding.14,15 patients and methods this cross-sectional study was conducted in pathology department of benazir bhutto hospital, rawalpindi. all 471 appendices that were removed either by journal of rawalpindi medical college (jrmc); 2018;22(1): 47-49 48 laparoscopic or open appendectomy were included in the study. in cases with parasitic infestations, further information regarding gender and age of patients was gathered. presence or absence of inflammatory reaction in those appendices with parasites was noted. similarly, the number of appendices with inflammation but without parasites was also determined. fisher’s exact test at 5% level of significance was then applied to compare the presence of inflammatory infiltrates in appendices with and without parasites. results a total of 471 appendectomies (laparoscopic and open) were performed at benazir bhutto hospital, rawalpindi in 2016. of the 471 appendectomies performed,15(3.18%) specimens were found to contain parasites. figure 1: pinworm infestation within the lumen of appendix without acute inflammation table 1: pattern of inflammation in appendices with and without pinworms appendices with pinworms appendices without pinworms inflammation present 2 324 inflammation absent 13 132 the parasite in all those 15 cases was enterobius vermicularis, also known as pinworm (figure 1). in those 15 cases, age of patients ranged from 9 to 45 years with a mean age of 19.07 ± 9.04 years. out of those 15 patients, 11 (73.3%) were females and 4 (26.7%) were males. male to female ratio was 1: 2.75. only 2 out of 15 cases (13.3%)with parasitic infestation showed evidence of inflammation. on the other hand, out of 456 appendices without parasites, 324 (71.1%) were positive for inflammation (table1). this difference was statistically significant with a p value <0.05. discussion gastrointestinal infection due to enterobius vermicularis occurs worldwide and is considered to be the most common helminth infection,especially in children younger than 12 years.16,17 e. vermicularis is transmitted by fecal-oral route. theeggs enter the gastrointestinal tract and then hatch into larvae which differentiate into adult worms. this cycle takes approximately 6 weeks.18the infection is usually asymptomatic but the patient complains of perianal pruritus, lethargy, generalized weakness or abdominal colic.19 due to its low pathogenicity, e. vermicularis infestation is not considered to be a serious disease, but it has been associated with colitis, perianal abscess or granulomas, significant morbidity in females with ectopic infections, chronic pelvic pain, pelvic inflammatory disease and acute appendicitis.17however, the role of e. vermicularis in clinical appendicitis has been controversial since its discovery in the appendiceal lumen in 1898.20 according to this study finding parasites in surgically removed appendices is a rare occurrence, as only 3.18% of the specimens were found to contain the parasite, e. vermicularis. globally, the reported incidence of e. vermicularis in patients with symptoms of appendicitis ranges from 0.2% to 41.8%.15 a study done in the uk concluded that 13 (2.61%) of the 498 patients that underwent an appendectomy were diagnosed with the parasite enterobius vermicularis.17 on the other hand, parasitic infestation was identified in 12 (1.8%) out of 660 appendectomies performed , showed a much lower incidence. 21 out of those 12 appendices with parasitic infestation, 9 had enterobius vermicularis, whereas the remaining 3 had taenia.21 another study done solely on children revealed a pinworm infection rate of 3.14% in appendices removed in midwestern regional hospital, limerick, ireland.22 the role of e. vermicularis as a cause of acute appendicitis has been controversial.14 some studies confirm the findings of inflammation in appendices found to have pinworms. majority of the studies report a lower incidence of inflammatory changes in patients with appendiceal pinworms.23 the reported rates of inflammation in specimens from appendices infested with e. vermicularis range from 13% to 37%.15in our study, 2 out of 15 cases (13.3%) showed evidence of inflammation. in greece, a retrospective study showed similar results that only 1 out of 7 appendices with pinworms was positive for inflammation.24 however, it is unclear that whether journal of rawalpindi medical college (jrmc); 2018;22(1): 47-49 49 the inflammatory infiltrates are present because of the parasite or if the pinworms are incidental findings in appendices where inflammation is already present.15 parasites obstructing the lumen of the appendix can result in symptoms mimicking acute appendicitis,25 but histopathological examination may not reveal findings of acute inflammation,11,26as shown by our study results. as already mentioned, pinworm infestation without inflammatory reaction is considered to be a component of false acute appendicitis and the removal of a pathologically normal appendix is termed as negative appendectomy.27it is still a matter of debate among surgeons who perform laparoscopic appendectomy that whether an appendix appearing normal macroscopically with no other alternate pathology, should be removed. if the appendix is not acutely inflamed, appendectomy should be done carefully as there is a possibility of e. vermicularis infection and hence a risk of peritoneal contamination.17 when suspected, these patients should be clinically observed and re-evaluated before considering appendectomy.10,17pinworm is most commonly diagnosed with the scotch tape test which involves pressing the strip of cellophane tape over the anal area and examining under the microscope for eggs.16,28 for pinworm infection the drug of choice is either albendazole, mebendazole or pyrantel pamoate.16 conclusion 1.frequency of parasitic infestations in surgically removed appendices is low. 2.very few appendices with parasitic infestation are associated with inflammation as compared to appendices without parasites. references 1. sinnatamby c, last r. last's anatomy. edinburgh: churchill livingstone/elsevier; 2011. 2. williams n, bulstrode c, o'connell p. bailey & love's short practice of surgery 26e. hoboken: crc press; 2013. 3. khan gm, grillo ia, abu-eshy sa, khan ar, mubarak j. pathology of the appendix. j natl med assoc2000; 92: 533-35. 4. zakaria om, zakaria hm, daoud my. parasitic infestation in pediatric and adolescent appendicitis: a local experience. oman med j 2013; 28: 92-96. 5. ahmadi mh, seifmanesh m. taeniasis caused appendicitis without local tenderness: a rare case. hospıtalchronıcles2011; 6: 207-09. 6. yabanoğlu h, aytaç hö, türk e. parasitic infections of the appendix as a cause of appendectomy in adult patients. turkiyeparazitolderg2014; 38: 12-16. 7. thanikachalam mp, kasemsuk y, mak jw. study of parasitic infections in the luminal contents and tissue sections of appendix specimens. trop biomed 2008; 25: 166-72. 8. flum d, koepsell t. the clinical and economic correlates of misdiagnosed appendicitis. archives of surgery. 2002;137(7):799804. 9. yildirim s, nursal t, tarim a, kayaselcuk f. a rare cause of acute appendicitis: parasitic infection. scandinavian journal of infectious diseases. 2005;37(10):757-59. 10. aydin ö. incidental parasitic infestations in surgically removed appendices: a retrospective analysis. diagnostic pathology. 2007;2(1):16-19. 11. çallı g, özbilgin m, yapar n, sarıoğlu s, özkoç s. acute appendicitis and coinfection with enterobiasis and taeniasis: a case report. turkiyeparazitolderg2014; 38: 58-60. 12. nordstrand iaj, jayasekera lk. enterobius vermicularis and clinical appendicitis: worms in the vermiform appendix. aust n z j surg 2004; 74:1024e5. 13. akbulut s, tas m, sogutcu n. unusual histopathological findings in appendectomy specimens: a retrospective analysis and literature review. world j gastroenterol 2011; 17: 1961-70. 14. surmont i, liu l. enteritis, eosinophilia, and enterobius vermicularis. the lancet. 1995;346(8983):1167-70. 15. dahlstrom j, macarthur e. enterobius vermicularis: a possible cause of symptoms resembling appendicitis. pathology. 1993;25:5-8. 16. levinson w. review of medical microbiology and immunology 14e. new york: mcgraw-hill education; 2016. 17. ariyarathenam a, nachimuthu s, tang t. enterobius vermicularis infestation of the appendix and management at the time of laparoscopic appendicectomy. international journal of surgery. 2010;8(6):466-69. 18. markell e, voge m, john d. enterobius vermicularis in medical parasitology. philadelphia: wb saunders company. 1992;:268-70. 19. chaudhary r, shukla a. pin worm causing acute appendicitis: case report. surgery: current research. 2016;06(03): 265-66 20. wiebe bm: appendicitis and enterobious vermicularis. scand j gastroenterol; 1991; 26: 336-38. 21. altun e, avci v, azatçam m. parasitic infestation in appendicitis. a retrospective analysis of 660 patients and brief literature review. saudi medical journal. 2017;38(3):314-18. 22. akhigbe t, smith f, adeyemo a,adeyanju t, condon e, waldron d. pinworm and appendicitis in children. the internet journal of surgery 2013;30( 3): 176–83 23. panidis s, paramythiotis d, panagiotou d, batsis g, salonikidis s. acute appendicitis secondary to enterobius vermicularis infection in a middle-aged man: a case report. journal of medical case reports. 2011;5(1): 24. gialamas e, papavramidis t, michalopoulos n, karayannopoulou g. enterobius vermicularis: a rare cause of appendicitis. turkish journal of parasitology. 2012;36(1):37-40. 25. karatepe o, adas g, tukenmez m, battal m. parasitic infestation as cause of acute appendicitis. g chir2009; 30: 426-28. 26. ilhan e, senlikci a, kızanoglu h. do intestinal parasitic infestations in patients with clinically acute appendicitis increase the rate of negative laparotomy? analysis of 3863 cases from turkey. prz gastroenterol 2013; 8: 366-69. 27. balthazar e, rofsky n, zucker r. appendicitis: the impact of computed tomography imaging on negative appendectomy and perforation rates. the american journal of gastroenterology. 1998;93(5):768-71. 28. pinworm test: medlineplus medical encyclopedia .medlineplus.gov. 2018. summary journal of rawalpindi medical college (jrmc); 2017;21(4): 362-365 362 original article steroid injection as an effective treatment for lateral epicondylitis saad riaz, imtiaz ahmed shakir, nadeem kashmiri, shehzad anjum, nayyar qayyum department of orthopaedics, dhq teaching hospital and rawalpindi medical college, rawalpindi abstract background: to determine efficacy of local steroid infiltration in patients with lateral epicondylitis. methods: in this case control study 70 patients with lateral epicondylitis with no previous history of trauma, surgery around elbow joint or previous history of steroid injection were included. patients were given local steroid injection after preparing the area with an antiseptic solution. the most tender point was localized and 40 mg methyl-prednisolone solution mixed with one ml of 2% xylocaine solution was infiltrated. patients were followed up at six weeks for the evaluation of global improvement in symptoms using likert-type scale. results:the mean age of the sample was 43 years. 42 patients were in the age group of 41-50 years. majority (81.4%) patients were females. most of the patients (81.4%) scored 1 and 2 on linkert type scale, showing global improvement. nine patients improved with the second dose of steroid injection making cumulative efficacy to 94%. conclusion: local steroid infiltration is an effective method of relieving pain and improving function in patients with tennis elbow. key words;tennis elbow, lateral epicondylitis, steroid injection, likert type scale introduction tennis elbow or lateral epicondylitis is a common condition characterized by pain around the lateral aspect of the elbow joint. it is associated with a combination of forceful and repetitive activities of the upper extremity and extreme non-neutral postures of the hands and arms. nonsurgical treatment is the mainstay of management. frst described as a clinical entity by runge in 1873, lateral elbow pain or tennis elbow is also known by many other names like lateral epicondylalgia and lateral elbow tendinosis. 1 this is an idiopathic or a work related condition. it is a common condition characterized by pain around the lateral aspect of the elbow joint. most of the time the pain is provoked by resisted use of either the extensor or flexor muscles of the wrist but in most cases pain persists at rest. the prevalence of the condition is 1.3% with equal incidence between males and females.2for women, the incidence increases to 10% between the ages of 42 – 46. individuals between the ages 45-54 are most commonly affected.3 some studies suggested that there is no difference in incidence between men and women or association between the lateral epicondylitis and the dominant arm. contradictory to this, goguin jp showed that it seems more common in women. still, more evidences exist which show that dominant arm is affected in most cases and the condition is bilateral in a few. 4 contradictory findings have been reported on the associations between individual and work-related physical factors and epicondylitis. there is evidence of an association of epicondylitis with forceful work tasks, a combination of forceful and repetitive activities of the upper extremity, and extreme nonneutral postures of the hands and arms.5 there is still insufficient evidence to support a relation between this disorder and exposure to repetitive work alone.6 smoking,obesity, repetitive movements, and forceful activities independently of each other showed significant associations with lateral epicondylitis.7 none of the treatment options has been universally accepted as a treatment of choice as yet. nonsurgical treatment includesa myriad of options including rest or “wait and see”, systemic and topical non-steroidal anti-inflammatorydrugs, physical therapy, cortisone, blood and botulinum toxin injections, supportive forearm bracing and local modalities like extracorporeal shock wave therapy (eswt), iontophoresis, phonophoresis and hyaluronic acid injections. 7 amongst these treatment options the three most commonly employed treatments are local steroid injections, physiotherapy, and the combination of both above methods. remaining treatment options are supported by only a few published studies and there is still no consensus on their use in patients and also the cost of most of these treatments is high.surgery is mainly reserved for the resistant cases and surgical options include open, percutaneous and arthroscopic journal of rawalpindi medical college (jrmc); 2017;21(4): 362-365 363 procedures. multiple procedures are described which include boyd mcleod procedure, nirschl procedure, knife and fork day case surgery, open release of common extensor origin, fractional lengthening of forearm extensors, open and percutaneous tenotomy and excision, release and repair of common extensor origin and extensor carpi radialis brevis debridement. 8-16 patients and methods study was conducted from january 2015 to february 2017 at district headquarter hospital rawalpindi. all patients aged 20 to 60 years of either gender presenting with lateral epicondylitis with no previous history of trauma, surgery around elbow joint or previous history of steroid injection were included in the study. patients with lateral elbow pain having tenderness and painful resisted extension of wrist were diagnosed as having lateral epicondylitis. all patients fulfilling the criteria were selected from outpatients clinics. detailed history and informed consent was taken from all patients.a liket-type scale was used to assess global improvement in each subject in the study. the likert-type scale used in the study consists of six point scale in which point 1 represents completely recovered, point 2 represents much improved, point 3 represents slight improvement, point 4 represents no improvement, point 5 represents slightly worse and point 6 represents much worse. point 1 which is completely recovered and point 2 which is much improved were considered success. patients were given local steroid injection after preparing the area with an antiseptic solution. the most tender point was localized and 40 mg methylprednisolone solution mixed with one ml of 2% xylocaine solution was infiltrated. patients were followed up at six weeks for the evaluation of global improvement in symptoms using likert-type scale. results the sample study consisted of 70 patients. the mean age was 43 years, with the youngest patient being 35 years of age and oldest 56 years. patients were divided into different age groups after calculating mean (table 1). majority (81.4%) patients were female(table 2). sixty two (88.5%) patients had right sided tennis elbow and 8 (11.42%) patients had left sided tennis elbow. after six weeks 57 patients 81.4% scored 1 and 2 on likert type scale and reported the steroid injection treatment to be effective. 13 patients (18.6%) did not respond to the steroid injection and out of them 11 patients scored 4 and 2 patients scored 5, with slight worsening of symptoms, on likert type scale (table 3). 13 patients who did not respond to the treatment were offered another session of steroid injection. females responded better(table 4).nine patients who had repeat dose of steroid injection improved with the second dose. four patients who refused second dose were given medical treatment and physiotherapy. skin depigmentation was noticed in 8 patients for which observation was advised. six patients complained of initial increase in symptoms after steroid infiltration which was followed by complete relief of symptoms in 1-2 days. table 1:age distribution of patients (n=70) age group no (%) 31-40 14(20) 41-50 42(60) 51-60 14(20) table 2:sex distribution of patients gender no(%) female 57(81.4) male 13(18.6) table 3:frequency and percentage of efficacy efficacy no(%) yes 57(81.4) no 13(18.6) table 4:comparison of efficacy in male and female gender efficacy gender total female male yes 48 9 57 no 9 4 13 total 57 13 70 discussion the natural history of tennis elbow is that of a benign self-limiting condition which improves with or without treatment within 12 months , this statement being true in between 70% and 80% of patient. 17,18 whilst there is wide consensus on these two facts, a year is a long time for a patient to wait not only in terms of pain and disability, but also loss of economic productivity. what patients often require is a safe minimally invasive procedure that will enable them to return to their daily activities as soon as possible. most of the patients in our study were in their fifth decade of life. this supports the theory of degenerative nature of the tear in ecrb. females are found to be more commonly affected than males and this may be attributed to their social lifestyles which may include repetitive forceful activities of upper journal of rawalpindi medical college (jrmc); 2017;21(4): 362-365 364 limbs especially while washing clothes and in cooking. on the other hand males are found to be more resistant to the treatment. this is probably due to the fact that corticosteroid injection produces rapid pain relief and this is followed by immediate resumption of heavy activities leading to recurrence of symptoms. it was noticed that dominant hand is affected more than the non-dominant hand because most of the forceful activities are performed with the dominant hand. the overall efficacy was 81.4% with single injection of steroids. this is close to the results already published in other studies but we have noticed improvement in results after repeating the same dose of steroid injection in patients who did not respond to the initial session. this is probably due to improper localization of the tender point and improper infiltration of the drug at first instance. after careful re-injection, all nine patients improved and this increased the cumulative efficacy from 81.4% to 94%. many treatments have been proposed leading to a number of trials, but reviews including several recent meta-analyses have led to no conclusions as to which is the best. this is due to low statistical strength, low internal validity and insufficient study data reporting. schmidt et al 2003 reviewed literature on physical therapy prior to 1999 and found no evidence of effect, with the exception of ultrasound, where a minor effect was shown. 19 bissetet al 2006 published a metaanalysis of 28 randomized studies published before 2003 of different physical therapies for lateral epicondylitis.15 most studies had a small number of subjects, and only eight had long term follow-up of effect of therapy. extra corporeal shock wave therapy was found to have no effect, and manipulation and exercise were found to have only a short-term effect. a meta-analysis by smidtet al 2002 on the effect of corticosteroid injections found evidence of short-term pain relief, but no effect beyond the initial 6 weeks. 20 there was however some uncertainty due to few and small studies. the cochrane library has several reviews of treatment for lateral epicondylitis: acupuncture, deep transverse friction massage, nsaids, orthosis, extra corporeal shock wave therapy and surgery. these reviews all conclude that there is insufficient evidence to draw firm conclusions as to which methods of treatment are effective. however, there are indications that topical nsaids and manipulation and exercise have a short term effect. as to nsaids taken orally, there is probably a short term effect, although it is impossible to either recommend use or not. there has been contradicting evidence as to the efficacy of eswt. some studies noted that patients who received eswt had improved symptoms. 21–22 other studies, however, have demonstrated a lack of effectiveness with eswt.23–24 for extracorporeal shockwave therapy, there is evidence to conclude that this treatment has no effect. ultrasound has a possible short-term effect based on one meta-analysis19. brace treatment is favored by some studies but brace alone does not relieve the symptoms of tennis elbow as effectively as steroid injection and also the course of treatment and duration of symptoms is more protracted. tens requires training of specialized equipment required for this purpose and is also associated with certain side effects. in fact, there is scant support for any long-term treatment in the literature. two studies compared corticosteroid injection with naproxen orally and placebo medication. both concluded that corticosteroid injection is safe and effective for pain relief during the first 6 weeks, and the effect of this treatment is better than physiotherapy, wait-and-see and naproxen orally within the same time-frame. 25,26 a more recent study comparing physiotherapy and corticosteroid injection concluded that the significant short term benefits can be obtained with corticosteroid injections.15 our results also support these studies showing relief of symptoms in patients receiving corticosteroid injections. several studies have acknowledged the perceived benefits of iontophoresis as a potential method of delivering steroid to the patients; however, its efficacy over that of placebo has been called into question. in view of this, and due to comparative ease of availability and delivery, traditional approach of local targeted delivery of corticosteroid by means of injection therapy is preferable in our setting. conclusion 1.there is an efficacy of local steroids injections in patients with lateral epicondylitis in first six weeks. 2.steroid injections should be carefully injected after proper localization of the tender area and should be followed by advice regarding graduated resumption of usual activities to avoid recurrence of symptoms. references 1. runge f. zurgenese und behandlung des schreiberkrampfes. berlklinwochenschr 1873; 10: 2458-61. 2. shiri r, viikari-juntura e, varonen h, heliövaara m. prevalence and determinents of lateral and medial epicondylitis: a population study. american journal of epidemiology 2006; 164: 1065-74. journal of rawalpindi medical college (jrmc); 2017;21(4): 362-365 365 3. descatha a, leclerc a, chastang jf. medial epicondylitis in occupational settings: prevalence, incidence and associated risk factors. j occup environ med 2003; 45:993–1001. 4. gouging jp, rush. lateral epicondylitiswhat is it really? current orthop 2003; 17:386-89. 5. piligian g, herbert r, hearns m. evaluation and management of chronic work-related musculoskeletal disorders of the distal upper extremity. am j ind med 2000; 37:75–93. 6. haahr jp, andersen jh. physical and psychosocial risk factors for lateral epicondylitis: a population based casereference study. occup environ med 2013; 60:322–29. 7. calfee rp, patel a, dasilva mf, akelman e. management of lateral epicondylitis: current concepts. j am acad orthop surg2008; 16: 19-29. 8. dunn jh, kim jj, davis l, nirschl rp. tento 14-year follow-up of the nirschl surgical technique for lateral epicondylitis. am j sports med. 2012; 36(2):261-66. 9. dwyer aj, govindaswamy r, elbouni t, chambler af. are "knife and fork" good enough for day case surgery of resistant tennis elbow? int orthop. 2010; 34(1):57-61. 10. thomas s, broome g. patient satisfaction after open release of common extensor origin in treating resistant tennis elbow. acta orthop belg. 2007; 73(4):443-45. 11. wang aw, erak s. fractional lengthening of forearm extensors for resistant lateral epicondylitis. anz j surg. 2007; 77(11):981-84. 12. khan ms, kamran h, khan sa, ahmed m, khan a. outcome of modified open surgery in tennis elbow. j ayub med coll 2007; 19: 50-53. 13. radwan ya, elsobhi g, badawy ws, reda a. resistant tennis elbow: shock-wave therapy versus percutaneous tenotomy. int orthop. 2008; 32(5):671-77. 14. rosenberg n, henderson i. surgical treatment of resistant lateral epicondylitis. follow-up study of 19 patients after excision, release and repair of proximal common extensor tendon origin. arch orthop trauma surg. 2002; 122(910):514-17. 15. bisset l, beller e, jull g, brooks p, darnell r, vicenzino b. mobilisation with movement and exercise, corticosteroid injection, or wait and see for tennis elbow: randomized trial. br med j 2006; 333 (7575): 939-42. 16. tonks jh, pai s. k, murali sr. steroid injection therapy is the best conservative treatment for lateral epicondylitis: a prospective randomised controlled trial.int j clinpract 2007; 61: 240-46. 17. cyriax jh. the pathology and treatment of tennis elbow. j bone joint surg 1936; 18(20):921– 40. 18. boyer mi, hastings ii h. lateral tennis elbow: ''is there any science out there?''. j should elbow surg 1999; 8(27): 48191-94. 19. smidt n, assendelft wj, arola h, malmivaara a, greens s. effectiveness of physiotherapy for lateral epicondylitis: a systematic review. ann med 2011; 35 (37): 51-62. 20. smidt n, assendelft wj, windt da van der, hay em, buchbinder r. corticosteroid injections for lateral epicondylitis: a systematic review.pain 2002; 96 (68):23-40. 21. ko jy, chen hs, chen lm. treatment of lateral epicondylitis of the elbow with shock waves. clin orthop 2001; 387 (31):60– 67. 22. hammer ds, supp s, ensslin s, kohn d, seil r. extracorporeal shock wave therapy in patients with tennis elbow and painful heel. arch orthop trauma surg 2000; 120 (32):304– 07. 23. crowther ma, bannister gc, huma h, rooker gd. a prospective randomised study to compare extracorporeal shock-wave therapy and injection of steroid for the treatment of tennis elbow. j bone joint surg 2002; 84933):678 –79. 24. haake m, konig ir, decker t, riedel c, buch m. extracorporeal shock wave therapy in the treatment of lateral epicondylitis. a randomized multicenter trial. j bone joint surg 2014; 84 (34):1982– 91. 25. smidt n, windt da van der, assendelft wj, deville wl, korthals-de bos ib. corticosteroid injections, physiotherapy, or a wait-and-see policy for lateral epicondylitis: a randomized controlled trial.lancet 2002, 359 (69):657-62. 26. hay em, paterson sm, lewis m, hosie g, croft p: pragmatic randomized controlled trial of local corticosteroid injection and naproxen for treatment of lateral epicondylitis of elbow in primary care.bmj 1999; 319 (70):964-68. summary journal of rawalpindi medical college (jrmc); 2017;21(4): 344-348 344 original article significance of clinical and laboratory variables in early detection and prognosis of malignant lymphoma aiyesha humaira , syed samiullah department of basic sciences, college of sciences and health professions, king saud bin abdulaziz university , kingdom of saudi arabia abstract background: to study clinical, laboratory and radiological variables including bone marrow assessment in patients with malignant lymphomas. methods: in this cross sectional study cases of malignant lymphoma were included. clinical variables included age, gender, lymphadenopathy and hepatosplenomegaly. laboratory variables included blood complete counts and bone marrow aspiration and bone trephine biopsy.immunohistochemistry was performed to identify the specific lineage and developmental stages of lymphoma.serum ldh, bun, creatinine, and sgpt were also performed . statistical analysis were performed by student t-test and pearson chi square test results: hepatosplenomegaly, haemoglobin, ct scan chest abdomen and immunohistochemistry were found significant factors in patients diagnosed to have lymphoma with bone marrow involvement. variables such as wbc, bun, creatinine, ldh and sgpt had no significant correlation. conclusion: the variables in the study are in favour of the previous studies. whereas regarding serum ldh levels the results were found insignificant which are not in favor of previous studies . key words: malignant lymphoma, immunohistochemistry, lhh, introduction the variables like age, gender, bone marrow involvement, visceromegaly, lymphadenopathy and certain biochemical and radiological variables provides important information regarding, prognosis and planning of optimal therapeutic strategies in patients suffering from malignant lymphoma. over the last two decades there has been a continuous enhancement in the measures which are helpful in the laboratory to evaluate malignant lymphoma. this has proved critical in providing the consistent and accurate information that is needed for clinical decision making in these patients. the laboratory evaluation of patients with malignant lymphoma remains centred on 4 primary aspects:(1) recognition and diagnosis of disease; (2) appropriate classification (3) providing information regarding disease stage; and (4) providing prognostic indications that predict the risk of death from disease.1-3 the early detection of lymphoma allows for more treatment options. the best way to diagnose lymphoma is to pay attention to possible symptoms. the most common symptom is the painless enlargement of one or more lymph nodes. the most frequent site is the side of the neck, in the groin or in the armpit. the accompanying features include fever unexplained weight loss and night sweats 4.bone marrow examination is routinely carried out during the evaluation of patients in malignant lymphoma. bone marrow involvement indicates stage iv disease and is indicative of poor prognosis. accurate staging is essential for the physician to plan an effective treatment strategy. bone marrow infiltrations of prime importance not only in staging the disease but also in deciding the treatment protocols 5. bone marrow involvement is one of the most important prognostic factors in patients with lymphoma, thus in patients with high grade lymphoma or intermediate grade lymphoma is associated with significantly shorter survival. therefore, bone marrow biopsy is now included as a part of the essential evaluation for the initial staging in patients with malignant lymphoma 6 anaemia is prevalent among patients with cancer at initial presentation. patients with non–hodgkin’s lymphoma have usually anaemia at diagnosis.7bone marrow biopsies are commonly performed for the initial diagnosis or staging of malignant lymphoma, and the frequency of bone marrow involvement in staging marrows for lymphoma is quite variable in the literature.8,9the lymphomas has a unique feature that journal of rawalpindi medical college (jrmc); 2017;21(4): 344-348 345 is these are considered as clonal proliferation of lymphocytes arrested at different stages of cell differentiation, thereby recapitulating stages of normal lymphocyte differentiation. immunohistochemistry (ihc) with various antibodies identifies the specific lineage and developmental stage of the lymphoma. a panel of markers is decided based on morphologic differential diagnosis (no single marker is specific) which includes leukocyte common antigen (lca), bcell markers (cd20 and cd79a), t-cell markers (cd3 and cd5) 10 immunophenotyping and molecular genetic studies are useful, yet the importance of morphology can not be undermined.11,12 patients and methods in this cross sectional study, conducted in the clinical laboratory of aga khan university hospital karachi. following were the variables related to the clinical presentation such as the age, gender, lymphadenopathy and hepato splenomegaly. as far as the laboratory data is concerned the results of the following at the time of presentation were considered.cbc performed on stks coulter and peripheral films were stained by leishman stain. bone marrow & bone trephine were performed with salah and jamshadi needles and leishman stain was applied on bone marrow aspirate and haematoxylin stain on bone trephine and slides were reviewed by consultant haematologist & histopathologist. in immunohistochemistry, ihd markers,cd3 stains t cells from the stage of late thymocytes,positive in t cell neoplasms and some natural killer cell neoplasms.cd15 which stains cell membranes and golgi bodies of reed sternberg cells in hodgkin’s lymphoma, large cells in some t cells and b cell lymphoma.cd30 which is characteristically positive in hodgkin’s lymphoma.ldh, bun, creatinine and sgpt were performed on synchron cx-7 & cx-9 pro. observations were recorded and subjected to the student’s t test and pearson chi-square test for statistical analysis. the results were taken as significant considering the p-value found equal to or less than 0.05. results age was found insignificant with the involvement of bone marrow in our sample (p value>0.05). in 33 cases out of 58 the mean haemoglobin level was found 9.6 mg/dl with involvement of bone marrow and more than 11.7 mg/dl in 22(40%) cases (p value>0.001*, significant)(table 1).the ratio of involvement of bone marrow in females was found less, i.e. 25% as compared to non-involvement of bone marrow in 75% cases. (p value=0.05*,significant) (table 2; figure 1 &2).in males it was 54% in which bone marrow was involved and in 46% cases bone marrow was not involved. (p value>0.50),11 (91.7%) cases presented with hepatosplenomegaly with involvement of bone marrow by lymphoma, only 01(8.3%) case had enlargement of liver and spleen without bone marrow involvement,(p value<0.004*),ref table 2..enlarged lymph nodes present in 13(72.2%) cases with bone marrow involvement and 5(27.8%) cases presented with enlarged lymph nodes without bm involvement,(p value=0.05*).regarding ct scan chest 08 (100%)cases shows signs of moderate to large lymph nodes enlargement similarly 07 (87.5%) cases in abdomen the lymph nodes involved in cases in which bone marrow were involved (p value=0.00* and p value< 0.05* respectively) (table 2). the results of serum ldh, serum creatinine, bun and sgpt were found insignificant. table 1 clinical & laboratory investigation with and without involvement of bone marrow in lymphoma variables bone marrow involved by lymphomas mean(n) bone marrow not involved mean(n) pvalue p-vlaue sig* / non sig age 42.8 years(24) 43.4 years (24) 0.879 >0.05 haemoglo bin ( mg/dl ) <9.6 (33) >11.7 (22) <o.oo 1 <o.oo1* white cells count (per cubic mm of blood) 8.7 (33) 8.5 (23) 0.773 >0.05 platelets (per cubic mm of blood) 227 (33) 226 (23) 0.828 >0.05 serum ldh 723 (28) 501 (6) 0.073 >0.05 bun 24 (16) 15.7 (4) 0.572 >0.05 serum creatinine 1.1 (17) 0.8 (4) 0.108 >0.05 sgpt 100 (14) 28.3 (3) 0.59 >0.05 p value significant, <0.05* as per data available regarding immunohistochemistry which was done for the subtyping, prognostication and potential for targeted therapy were found positive in 26(100%) cases (p value=0.00*) whereas immunohistochemistry was found negative in 2 cases(13.3%) in patients having journal of rawalpindi medical college (jrmc); 2017;21(4): 344-348 346 involvement of bone marrow with lymphomas(p value=0.005*) (table 3). table 2 clinical and radiological parameters with and without involvement of bone marrow in lymphoma. variab les bone marrow involved by lymphoma no (%) bone marrow not involved no (%) p-value p-value sig* / non sig sex m=54% f= 25% m=46% f=75% 0.75 0.053 >0.50 0.05* lymph node yes 13 (72.2) 5 (27.8) 0.059 0.05* no 12 (46.2) 14 (53.8) 0.695 >0.50 hepatosplenomegaly yes 11 (91.7) 1 (8.3) <0.004 <0.004* no 17 (53.1) 15 (46.9) 0.724 >0.50 ct scan chest yes 8 (100) o no 6 (33.3) 12 (66.7) 0.157 0.20 ct abdomen yes 7 (87.5) 1 (12.5) 0.034 <0.05* no 6 (38.9) 11 (61.1) 0.346 >0.10 pvalue significant, <0.05* table 3.immunohistochemistry in lymphoma (n=41 cases) variable bone marrow involved by lymphoma no(%) bone marrow not involved by lymphoma no(%) p-value p-value sig* / non sig positive 26 (100) 0 0.000 0.000* negative 2 (13.3) 13 (86.7) 0.005 0.005* p value significant, <0.05* figure 1. lymph node involvement in follicular non – hodgkin’s lymphoma figure 2;bone trephine showing involvement with diffuse large b cell lymphoma figure 3:bone trephine showing involvement with hodgkin’s lymphoma discussion in the present study haemoglobin, hepatosplenomegaly, ct scan chest & abdomen and immunohistochemistry were found significant factors in patients having lymphoma with bone marrow involvement. cancer patients treated with chemotherapy often suffer from anaemia, which is a major contributing factor to fatigue leading to compromised quality of life.13,14 in addition, the presence of anaemia is associated with shorter survival of patients with malignancies.15 journal of rawalpindi medical college (jrmc); 2017;21(4): 344-348 347 in our study the results obtained regarding the level of haemoglobin in patients of malignant lymphoma with bone marrow involvement is in favour of the study conducted by jacobi n in which the author signifies the role of haemoglobin as a prognostic factor at initial diagnosis. 16 it was found statistically significant in univariate log-rank comparisons of kaplan-meier survival curves used to build a multi-variate proportional hazard regression model of overall survival. median overall survival for these patients were 10.3 years. overall survival differed only with high (>12 g/dl) versus low (<12 g/dl) hemoglobin (p=0.001).our study signifies the role of immunohistochemistry in patients having lymphoma .this was again in favour of the study conducted by paydas s. 17 regarding the role of biopsy, in the literature we found a study conducted by quereux g et al studied retrospectively 62 cases of cutaneous b-cell lymphomas in which bone marrow biopsy was performed and it was demonstrated that it is not indispensable to perform a routine bone marrow biopsy for a primary cutaneous b-cell lymphoma with cutaneous lesions and with negative ct scan and blood laboratory evaluations. 18another study conducted by simon e, richardson et.al stated that conventional bone marrow biopsy staging in hodgkin’s lymphoma is extremely insensitive. ffluoro-2-deoxyglucose positron emission tomography/computed tomography (fdg-pet/ct) can rule out bone marrow involvement in hodgkin’s lymphoma. the bone marrow biopsy should be targeted to a minority of patients with fdg-pet/ct + bone/marrow uptake and only when management would be altered by the result.19although the 1989 cotswold modification limited the routine use of invasive procedures in favour of improved imaging diagnostics. routine bone marrow biopsy was restricted to patients with ct-assessed advanced stage disease or disease at initial stage with adverse factors and in case a finding would alter the management. 20 regarding the results related to the white blood cell count, our study is not in favour of the study conducted by the porrata lf et al in which the author assessed the prognostic significance of absolute lymphocyte count at the time of first relapse in diffuse large b-cell lymphoma. 21 alc-r was found an independent prognostic factor for overall survival [rr = 0.4, p < 0.01] and progression-free survival [rr = 0.5, p < 0.005]. alc-r predicts survival suggesting that host immunity is an important variable predicting survival in first relapsed dlbcl. again a large population based study is required for absolute lymphocyte count to reach the conclusion. the results obtained in our study regarding serum ldh level are not in favour of the 25-year study in japan conducted by katsumata n et al in which the author stated the importance of age and serum ldh as significant predictors of survival in japanese patients with follicular lymphoma. 22 in addition the levels of serum ldh are again not in favor of the study conducted by hung chang et.al in which they reported eleven out of twelve had elevated levels of lactate dehydrogenase however a study on large population is required to address the occurrence of serum ldh in such cases. 23 conclusion 1.hepatosplenomegaly, haemoglobin, ct scan chest & abdomen and immuno histochemistry were significant factors in patients diagnosed to have lymphoma with bone marrow involvement. 2.variables such as wbc, bun, creatinine, ldh and sgpt had no significant correlation. references 1. harris nl, jaffe es, stein h, banks pm, chan jk. a revised european-american classification of lymphoid neoplasms: a proposal from the international study group. blood 84:1994:1361-65 2. shipp ma: prognostic factors in aggressive nonhodgkin's lymphoma: who has "high-risk" disease? blood 83: 1994:1165 -70 3. shipp ma: can we improve upon the international index? ann oncol: 1997:8:43-46 4. juneja sk, wolf mm, cooper ia: value of bilateral bone marrow biopsy in non-hodgkin's lymphoma. j clin pathol : 1990 :43:630-35 5. s muzahir1, m mian, i munir m. clinical utility of 18f fdg-pet/ct in the detection of bone marrow disease in hodgkin's lymphoma, british journal of radiology, 2014;85 ( 1016): 1121-24 6. hori hnm,obara k. primary isolated bone marrow diffuse large b-cell lymphoma with the initial presentation as severe thrombocytopenia, successfully treated with chemotherapy: a case report and review of the literature. journal of cancer therapeutics & research.2012; 1:28-31 7. moullet i, salles g, ketterer n. frequency and significance of anemia in non-hodgkin’s lymphoma patients. ann oncol 1998; 9:1109–15. 8. lambertenghi-deliliers g, annaloro c, soligo d. incidence and histologic features of bone marrow involvement in malignant lymphomas. ann hematol. 1992; 65:61-65. 9. mckenna rw, hernandez ja. bone marrow in malignant lymphoma. hematol oncol clin north am. 1988; 2:617-35 http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22quereux%20g%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22porrata%20lf%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.birpublications.org/author/muzahir%2c+s http://www.birpublications.org/author/mian%2c+m http://www.birpublications.org/author/munir%2c+i http://www.birpublications.org/toc/bjr/85/1016 journal of rawalpindi medical college (jrmc); 2017;21(4): 344-348 348 10. rao is.role of immunohistochemistry in lymphoma.indian j med paediatr oncol. 2010 ; 31(4): 145–47. 11. crotty pl, smith br, tallini g. morphologic, immunophenotypic, and molecular evaluation of bone marrow involvement in non-hodgkin's lymphoma. diagn mol pathol. 1998; 7:90-95. 12. kang yh, park cj, seo ej. polymerase chain reactionbased diagnosis of bone marrow involvement in 170 cases of non-hodgkin lymphoma. cancer. 2002; 94:3073-82 13. groopman je, itri lm. chemotherapy-induced anaemia in adults: incidence and treatment. j nat’l cancer ins 1999; 91:1616–34. 14. causes of fatigue in cancer patients—general information about fatigue.cancer.gov for nci-usa – updated may 7, 2015 15. caro jj, salas m, ward a, goss g. anemia as an independent prognostic factor for survival in patients with cancer. cancer 2001; 91:2214–21. 16. jacobi n, rogers tb, peterson ba,prognostic factors in follicular lymphoma: a single institution study.. oncology reports 2008 ; 20(1):185-93. 17. paydas s, seydaoglu g, ergin m, erdogan s, yavuz s. the prognostic significance of vegf-c and vegf-a in non-hodgkin lymphomas. leuk lymphoma. 2009; 50(3):311-14. 18. quereux g, frot as, brocard a, leux c, renaut jj, dreno b routine bone marrow biopsy in the initial evaluation of primary cutaneous b-cell lymphoma does not appear justified. eur j dermatol 2009;19(3):216-20. 19. simon e. richardson, jagoda sudak. routine bone marrow biopsy is not necessary in the staging of patients with classical hodgkin lymphoma in the 18ffluoro-2-deoxyglucose positron emission tomography era, journal leukemia & lymphoma 2012;53(3):38185. 20. el-galaly tc, amore f, mylam kj . routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography–staged treatment-naive patients with hodgkin lymphoma, journal of clinical oncology,2012; 30:4508-14. 21. porrata lf, ristow k, habermann tm, witzig te, inwards dj. absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large b-cell lymphoma. am j hematol 2009 ; 84(2):93-97. 22. katsumata n, matsuno y, nakayama h, takenaka t, kobayashi y. prognostic factors and a predictive model of follicular lymphoma: a 25-year study at a single institution in japan. jpn j cl oncol 1996 ; 26(6):44554 23. chang h, hung ys, lin tl. primary bone marrow diffuse large b cell lymphoma: a case series and review. annals of hematology, 2011;90(7):791– 96 https://www.ncbi.nlm.nih.gov/pubmed/?term=rao%20is%5bauthor%5d&cauthor=true&cauthor_uid=21584221 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3089924/ http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22jacobi%20n%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22rogers%20tb%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22peterson%20ba%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22paydas%20s%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22seydaoglu%20g%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22ergin%20m%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22erdogan%20s%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22yavuz%20s%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/pubmed/19347719?ordinalpos=1&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/pubmed/19347719?ordinalpos=1&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22quereux%20g%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22frot%20as%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22brocard%20a%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22leux%20c%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22renaut%20jj%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22dreno%20b%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus javascript:al_get(this,%20'jour',%20'eur%20j%20dermatol.'); http://www.tandfonline.com/author/richardson%2c+simon+e http://www.tandfonline.com/author/sudak%2c+jagoda http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22porrata%20lf%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22ristow%20k%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22habermann%20tm%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22witzig%20te%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22inwards%20dj%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus javascript:al_get(this,%20'jour',%20'am%20j%20hematol.'); http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22katsumata%20n%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22matsuno%20y%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22nakayama%20h%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22takenaka%20t%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22kobayashi%20y%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus summary journal of rawalpindi medical college (jrmc); 2017;21(2): 157-160 157 original article prevalence of menstrual dysfunction and its comparative correlation with anaemia rakhshanda toheed 1, talha bin ayub 2, hafiza sidra ali 3, faiza ali 4 1.department of gynae/obs, avicenna medical college, lahore ;2. department of medicine, ittifaq hospital lahore;3 lady aitchison hospital lahore;4. medical student, king edward medical university, lahore. abstract background: to find out prevalence and pattern of menstrual abnormalities and its contribution to anaemia in teen age students and compare it with other causes of anaemia in them. methods: in this observational cross sectional study,317 students were included after taking their consent. all girls included in the study; were students ranging from school to medical college, and aged 10-19 years . details of menarche and menstrual cycle, history of passage of worms in stools, thyroid disease, liver disorder and bleeding clotting disorders were noted . results: out of 317 cases 159(50.6%) were anemic. sixty percent of adolescents belonged to relatively better socio-economic group, 90% were unmarried, 87.4% non-vegetarian, body mass index (bmi) >25 was present in 53/317 cases, <19 in 29/317. all these variables had no significant relationship with anemia statistically (p-value >0.05).mean age of menarche was 12.95 years in anaemic adolescents and 12.83 in those without anaemia.out of 317 menstrual cycle was normal in 60.9%, scanty menstruation in 0.3%, irregular normal flow 6.6%, while 15.8 % had irregular heavy menses, 3.5%: heavy regular menses. heavy menstrual bleeding both regular & irregular was highly associated with anaemia (p-value <0.001).dysmenorrhea was present in 57.9% anaemic teens (p-value <0.001).worm infestation was present in 10.1% cases (p-value <0.001) indicating highly significant association with anaemia. p-value for bleeding/clotting disorders was 0.014 showing significant link with anemia. conclusion:menstrual dysfunction is the main contributor to anaemia in female adolescents other factors being worm infestation and bleeding/clotting disorders. it needs urgent attention of parents and healthcare providers to correct anaemia according to cause and improve their quality of life and ensure healthy mothers in future. key words: menstrual dysfunction, anaemia, menorrhagia introduction adolescence (10-19 years of age) is critical period of life characterized by significant changes like increasingly pulsatile secretion of gonadotrophins, change in body contour and development of brain (prefrontal cortex, improved connectivity of various networks). these changes (adrenarche, thelarche, menarche, growth spurt) are more marked in early phase(10-14 years) and further consolidated in its late part(15-19 years) marking a paradigm shift in the pattern and style of life. 1-3 normally menarche is expected within 2-3 years of the larches, cycle length varies from 21-45 days, duration of menstrual period 2-7 days, and 3-6 pads/day are consumed. menstrual cycles become predominantly ovulatory within 8-12 years of menarche. 4 pattern of menstruation may not be regular, menstrual blood loss may be excessive adding to stress, and causing compromised quality of life. hesitation to share these issues with parents and health care providers aggravates implications of irregular, heavy and prolonged menstruation. irregularity of newly initiated menstrual cycle, a common occurrence in adolescents, is largely attributed to immaturity of hypothalamic pituitary ovarian axis. 5 anovulation is the most frequent physiological cause of heavy and prolonged periods. other causes are stress, eating disorders, thyroid dysfunction, diabetes mellitus, bleeding disorders etc. 6 menorrhagia and polymenorrhagia is a risk factor for development of anemia in adolescents in addition to other causes like worm infestation, poor socio-economic status, dietary habits etc. assessment of menstruation serves as a benchmark indicator of reproductive health in teen agers. 7 studies from developing countries show prevalence of excessive menstrual bleeding in <1-18% adolescents.8anaemia affects 30% women worldwide.9very high percentage of anaemia was seen in pakistani adolescent girls in one study. 10anemia was found highly prevalent in adolescents in rural areas of maharashtra india.11 journal of rawalpindi medical college (jrmc); 2017;21(2): 157-160 158 globally largest generation of adolescents is approaching adulthood in human history. 2, 7pakistan has a great population (9619874 girls in 10-14 years group, and 8211804 girls in 15-19 years group) of adolescent girls approaching adulthood without proper care of their health especially the newly acquired menstrual function. 12 the anemic adolescent girls enter into adulthood with poor general health and little resistance to infections and low threshold to develop serious morbidity as a result of even mildly excessive blood loss in labor.13 in a study on prevalence of anaemia in primigravida, 78% of them were found anaemic indicating that root causes lie in pre-marital period (childhood and adolescence) and this is the motivation for this study.14 patients and methods this observational cross sectional study was conducted in king edward medical university. three hundred and seventeen students, aged 10-19 years ,were included after taking their consent. convenient sampling method was used; duration of study was 6 months from july 2014-jan. 2015. details of menarche and menstrual cycle were noted .menarche was defined as the time of onset of first menstrual period. normal age range for menarche is 12-15 years. menorrhagia was defined as heavy and/or prolonged cyclical bleeding.oligomenorrhoea was defined as scanty bleeding. infrequent menstruation was bleeding every 3-4 months. dysmenorrhoea the painful menstruation. anaemia was defined as hemoglobin level less than 12 grams/deciliter.severe anaemia: <7gm./dl, moderately severe anaemia: 7-9gm./dl, mild anaemia: >9-11.9 gm./dl.weight and height were measured to calculate body mass index in kg/m*2 results out of 317 cases 159(50.6%) were anaemic. sixty percent of adolescents belonged to relatively better socio-economic group, 90% were unmarried, 87.4% non-vegetarian, body mass index(bmi) >25 was present in 53/317 cases, <19 in 29/317. all these variables had no significant relationship with anaemia statistically(p-value >0.05). mean age of menarche was 12.95 years in anaemic adolescents and 12.83 in those without anaemia (table 1).no statistically significant association of anaemia with age of menarche was found in this study. out of 317 adolescents, menstrual cycle was normal in 66.9%, scanty menstruation in 0.3%, irregular normal flow 6.6%, while 15.8 % had irregular heavy menses, 3.5%: heavy regular menses. heavy menstrual bleeding both regular & irregular was highly associated with anaemia (p-value table 1:mean age, bmi and age at menarche in anaemic and non-anaemic cases anemia no. of cases mean s.d minim um maxim um pvalue age (years) absent 158 17.39 1.48 13.00 19.00 <0.001 ** present 159 16.67 1.85 12.00 19.00 total 317 17.03 1.71 12.00 19.00 bmi absent 158 22.42 3.03 16.45 32.00 0.947 present 159 22.39 3.26 13.70 35.60 total 317 22.41 3.14 13.70 35.60 menarche absent 158 12.83 0.59 11.00 14.00 0.131 present 159 12.95 0.81 11.00 16.00 total 317 12.89 0.71 11.00 16.00 bmi= body mass index, s.d = standard deviation;** highly significant association table 2: menstrual dysfunction and anaemia factors responsible no percentage income <10000 32 10.1 10000-15000 93 29.3 20000 and above 192 60.6 total 317 100.0 menstruation scanty 2 .6 normal 212 66.9 heavy 11 3.5 irregular heavy 50 15.8 irregular normal flow 21 6.6 irregular scanty 21 6.6 diet veg 40 12.6 non-veg 277 87.4 marital unmarried 285 89.9 married 32 10.1 dysmenorrhea 142 44.8 heavy bleeding 18 5.7 hypothyroidism 7 2.2 liver dysfunction 3 0.9 bleeding clotting disorder 6 1.9 worm infestation 73 10.1 <0.001).dysmenorrhea was present in 57.9% anaemic teens (p-value <0.001). statistically significant journal of rawalpindi medical college (jrmc); 2017;21(2): 157-160 159 association of anemia with dysmenorrhea associated both with heavy menstrual bleeding as well as those with normal or scanty bleeding was found. worm infestation: worm infestation was present in 10.1% cases (p-value <0.001) indicating highly significant association with anemia (table 2).while p-value for bleeding/clotting disorders was 0.014 showing significant link with anaemia (table 3). anaemia was seen in 52% of women with dysmenorrheal (table 4) table 3.comparative association of anaemia with different variables anaemia p-value absent present income <10000 15(9.5%) 17(10.7%) 0.936 10000-15000 47(29.7%) 46(28.9%) 20000 and above 96(60.8%) 96(60.4%) marital status married 142(89.9%) 143(89.9%) 0.985 unmarried 16(10.1%) 16(10.1%) body mass index <19 14(8.9%) 15(9.4%) 0.595 normal 121(76.6%) 114(71.7%) >25 23(14.6%) 30(18.9%) menstruation scanty 2(0.6%) 0(.0%) <0.001** normal 122(77.2%) 90(56.6%) heavy 1(.6%) 10(6.3%) irregular heavy 7(4.4%) 43(27.0%) irregular normal flow 10(6.3%) 11(6.9%) irregular scanty 16(10.1%) 5(3.1%) diet veg 18(11.4%) 22(13.8%) 0.512 non-veg 140(88.6%) 137(86.2%) dysmenorrhea 50(31.6%) 92(57.9%) <0.001* hypothyroidism 5(3.2%) 2(1.3%) 0.248 liver dysfunction 1(0.6%) 2(1.3%) 0.566 bleeding clotting disorder 0(0%) 6(3.8%) 0.014* worm 20(12.7%) 53(33.3%) <0.001** ** highly significant association, *significant association table 4 :correlation of dysmenorrhea with anaemia dysmenorrhoea anemia p -value total absent present no dysmenorrhoea 108 67 175 dysmenorrhea present 45 52 .000 97 dysmenorrhea with menorrhagia 05 40 .000 45 158 159 317 discussion prevalence of anaemia in present study was 50.6% having highly significant association with abnormally heavy menstrual bleeding and dysmenorrhea in addition to worm infestation and bleeding from gums and nose. prevalence of anaemia was 68.8%, 21%, 90% and 52.2%in adolescent girls in different studies. 15-18 menstrual function is an important landmark measure of normal adolescence. pattern of menstruation in adolescents of our study revealed normal cycle in 66.9% participants. regular/ irregular scanty menstruation (7.2%), irregular cycle with normal flow(6.6%), and heavy regular/ irregular heavy cycles were present in(19.3%).heavy regular and irregular cycles are important contributory factors to adolescence anaemia especially in developing countries with gender bias and low socio-economic status among other contributory factors. in a singaporean study oligomenorrhoea was present in 15.3% while polymenorrhoea in 2.0% adolescents and dysmenorrhea was reported in 83.2% girls . 5 in a study from hyderabad 76% adolescents had normal menstrual cycle, 17% had heavy cycles, and 7% had scanty menstruation while 60% girls were anaemic. 19 prevalence of heavy cycles in this study is comparable to that in our study. 57.9% anaemic adolescents in our study reported dysmenorrhea. association was significant in those having heavy cycles and those not having heavy menstrual bleeding. dysmenorrhea was experienced in 75 to 89% adolescents, in different studies. 20-23 it appears that in addition to its association with heavy, prolonged cycles, its impact on attitude and quality of life can not be ruled out. 24 worm infestation was reported in 10% of adolescents in our study, which is expectable in the context of lack of clean water supplies for a large segment of our population. worm infestation is highest among school children according to unicef, and hence this problem continues in to adolescence if these children are not dewormed in time. 25other factors like bmi, age of menarche, liver dysfunction, thyroid disorders, vegetarian or nonvegetarian dietary habits, were not found associated with anaemia. in a nutritional survey, prevalence of anaemia in children under 5 years of age was 33.3%.26 in girls, approaching puberty, menstrual dysfunction irrespective of the underlying cause plays leading role in producing or worsening of pre-existing anaemia. so that these young women enter in to marital life in substandard health and account for high prevalence of journal of rawalpindi medical college (jrmc); 2017;21(2): 157-160 160 anemia in primigravida in our population and hence exposed to high maternal morbidity and mortality. 14 conclusion menstrual dysfunction is the main contributor to anemia in female adolescents other factors being worm infestation and bleeding/clotting disorders. references 1. who: young people’s health-a challenge for society: 1986; report of a who study group on young people and “ health for all by the year 2000” meeting; available at: www.who.int/iris/handle/10665/41720 2. patton g c, sawyer s m, santelli j s. our future: a lancet commission on adolescent health and well being. lancet 2016; 387: 2423-78. 3. srivastava n, veroda p, venugopal a.menstrual cycle pattern among adolescent school girls in chhattisgarh. the international journal of indian psychology 2016; 3(3): 9297. 4. american academy of pediatrics, committee on adolescence, american college of obstetricians & gynecologists and committee on adolescent health care. menstruation in girls & adolescents using the menstrual cycle as a vital sign. pediatrics 2006; 118(5): 2245. 5. agarwal n, venkat a, annapoorna p.questionnaire study on menstrual disorders in adolescent girls in singapore. journal of pediatric and adolescent gynecology 2009;22(6): 36571. 6. gray sh and emans sj. abnormal vaginal bleeding in adolescents.pediatr rev. 2007;28,175-82 7. fatusi s, hindin ao,michelle r."adolescents and youth in developing countries: health and development issues in context. journal of adolescence 2010;33(4): 499-508. 8. harlow sd, oona mr, campbell t. epidemiology of menstrual disorders in developing countries: a systematic review. bjog 2004;111(1): 6-16. 9. balarajan y,ramakrishinan u, uzaltin u, shankar e, anuraj h.anaemia in low-income and middle-income countries. the lancet 2012;378(9809): 2123-135 10. aabroo talpur, aftab ahmad khand, zulfiqar ali leghari. "prevalence of anemia in adolescent girls." pak j physiol 2012;8: 1-4. 11. ahankari s, myles as, fogarty pr,dixit aw, tata jv.prevalence of iron-deficiency anaemia and risk factors in 1010 adolescent girls from rural maharashtra, india: a cross-sectional survey. public health 2016; 142:159-66. 12. pds -2007|pakistan bureau of statistics. available at: www.pbs.gov.pk/content/pakistan-demographic-survey2007 13. gibbs cm, wendt a,peters s,hogue c.“impact of early age at first childbirth on maternal & infant health. pediatr perinat epidemiol 2012; 26(01): 259-84. 14. toheed r, ayub t, ali hs, mumtaz s, hanif a. prevalence of anemia and its main determinants among primigravidae in antenatal population of a tertiary care hospital.pak j of med &health sciences 2015; 9(3): 907-10. 15. akramipour h, rezaei r, rahimi m.prevalence of iron deficiency anemia among adolescent schoolgirls from kermanshah, western iran. hematology 2008;13(6): 35255. 16. kulkarni, durge mv, kusturwar pm.prevalence of anemia among adolescent girls in an urban slum. national journal of community medicine 2012;3(1): 108-11. 17. raj m, chopra a , sood ak.to find out prevalence of anaemia among adolescent girls in rural area of district jabalpur (mp). indian journal of public health research & development 2015;6(4): 256-60. 18. shah n, gupta bk, piyush s."anemia in adolescent girls: a preliminary report from semi-urban nepal. indian pediatrics 2002;39(12): 1126-30. 19. dar s, syed k, yousafzai z.relationship of menstrual irregularities to bmi and nutritional status in adolescent girls. pakistan journal of medical sciences 2014;30(1): 14144. 20. hillen p, grabavac tj, johnston sl,straton p,keogh j, john mf. primary dysmenorrhea in young western australian women: prevalence, impact, and knowledge of treatment. journal of adolescent health 1999;25(1): 40-45. 21. agarwal ak andagarwal a.a study of dysmenorrhoea during menstruation in adolescent girls. indian j community med 2010; 35(1):159-64. 22. houstan z, abraham am, huang a,angelo zd, lawrence j. knowledge, attitudes, and consequences of menstrual health in urban adolescent females. journal of pediatric and adolescent gynecology 2006;19(4): 271-75. 23. cakir, mungan m,karakas i, girisken t, okten t.menstrual pattern and common menstrual disorders among university students in turkey. pediatrics international 200749(6): 938-42. 24. unsal s, tozun au, arslan m, calik g.prevalence of dysmenorrhea and its effect on quality of life among a group of female university students. upsala journal of medical sciences 2010;115(2): 138-45 25. luong t. de-worming school children and hygiene intervention. international journal of environmental health research 2003;13(sup1): s153-s159. 26. habib ma, black k, soofi sb, hussain i, bhatti z, bhutta za. (2016). “ prevalence & predictors of iron deficiency anemia in children under five years of age in pakistan, a secondary analysis of national nutrition survey data 20112012.” plos one 11(5): e155051.doi: ------------------------------------------------------------ authorship: 1,2 conception , synthesis, planning of the research and manuscript writing ; 3,4 active participation in methodology , interpretation and discussion; 4 data analysis http://www.pbs.gov.pk/content/pakistan-demographic-survey-2007 http://www.pbs.gov.pk/content/pakistan-demographic-survey-2007 summary journal of rawalpindi medical college (jrmc); 2018;22(2): 144-147 144 original article an audit of rigid bronchoscopy mahboob yazdani khan department of ent, dhq hospital and rawalpindi medical university abstract background: to determine the utility of rigid bronchoscopy in terms of age, sex and seasonal variations. methods: in this descriptive study all patients undergoing rigid bronchoscopy were included. the data was analyzed on the basis of age, sex, indication, nature of foreign body and seasonal variations. the patients were divided as per indication of bronchoscopy in individual cases. as regard nature of foreign body, patients were divided into those having metallic and non-metallic foreign bodies. special stress was paid to evaluate incidence of rigid bronchoscopies in relation 2 main seasons of this part of the world i.e winter and summer. the outcome of seasonal variations in incidence and results of bronchoscopies was analyzed. results: age ranged from 1 year to 60 years. the male to female ratio was equivalent as 10 patients in each group. there were 12 children and 8 adults. the most common indication of bronchoscopy was foreign body(65%). . out of 13 cases of bronchoscopy for foreign body bronchus 84.6% were children. there were 11 cases of bronchoscopy (55%) in winter season and 45% in summer. peanut (90.9%) was the commonest foreign body encountered in paediatric age group. there were no complications of bronchoscopy except 2 cases with failure to remove foreign body in first sitting but successfully removed in second sitting. conclusion: foreign body bronchus is the most common indication of rigid endoscopy and majority of the patients are children under the age of 12. the most common foreign body bronchus is peanut especially in winter season. key words: rigid bronchoscopy, foreign body nose, seasonal variation. introduction rigid bronchoscopy is a procedure that is used to examine the trachea and main proximal bronchi.it was first used by german ent surgeon gustavo kalians in 1897.later american otolaryngologist chevalier jackson improved rigid bronchoscopes in a significant manner. in the past rigid bronchoscopy was the sole procedure available for the needful but later on in 1960 shgitolikida from japan invented fiber optic or flexible bronchoscopy which emerged as alternate to rigid one. rigid or inflexible bronchoscopy is usually performed under general anaesthesia. inflexible bronchoscopy is usually performed under local anesthesia .fiberoptic bronchoscopy has improved a lot in the recent years. it is used for the diagnostic as well as therapeutic purposes. it can be used with local anesthesia to examine the airway, suction clearance of tracheobronchial tree. it is flexible, easy to use with less chances of injury. as of late, cognizant sedation has come up as the alternate ,but general anaesthesia still remains a standard system..1 rigid bronchoscopy is an old procedure used for various indications in of trachea-bronchial ailments. it is usually performed under general anaesthesia in all age groups.it is a very useful procedure but is also associated with major complications like cardiopulmonary arrest, injury to tracheo-bronchial tree, bronchial perforation, mediastinitis and pneumonitis. 2with the advent of fibrotic bronchoscopy, it has replaced the rigid bronchoscopy especially for diagnostic purposes. fiber optic bronchoscopy is a safe procedure in infants /children serving as an important diagnostic/therapeutic tool in the disorders of respiratory in this age group3 fibrotic bronchoscopy has got its own demerits with known limitations in extraction of foreign bodies and proper biopsies. standards of rigid bronchoscopy have also improved with the advent of fibrotic lights, ventilating rigid bronchoscopes and installation of telescopes and microscopes with the rigid bronchoscopes,enhancing rigid bronchoscopy utility in various indications of bronchoscopy .rigid bronchoscopy in experienced hands under general anesthesia is safe /effective diagnostic and therapeutic procedure2fiber optic bronchoscopy is a latest method in little babies and kids. the rigid-bronchoscope is otherwise called an open-tube bronchoscope, straight bronchoscope, or ventilating bronchoscope. it is an unbending, straight, empty metal tube that is accessible in a few sizes.the outer diameter of a rigid bronchoscope ranges from 2 -14 mm, thickness of bronchoscope wall ranges from 2 3 mm, with length from a very short tube in children to a long /extralong tube in adult.. most unbending bronchoscopes journal of rawalpindi medical college (jrmc); 2018;22(2): 144-147 145 are a similar width from the proximal to the distal end,some have a sloped or decreased tip to lift the epiglottis amid intubation. varieties in the tip configuration likewise encourage the enlargement of airway strictures. most inflexible bronchoscopes are round when envisioned in cross-segment, with outer side ports that allow the presentation of suction catheters, laser filaments, and ventilation. rigid bronchoscopes have also been modernized with fiber optic lights, inbuilt forceps with computerized monitors and telescopes.the indications of rigid bronchoscopy are diagnostic and therapeutic. rigid bronchoscopy is the most effective procedure for the removal of foreign bodies in tracheobronchial tree4. the most common indication of rigid bronchoscopy is confirmation and extraction of foreign body bronchus in suspected cases of foreign body bronchus. although some research workers challenge this but to date it has not lost its worth in this regard. patients and methods the data of patients undergoing rigid bronchoscopy at bbh rawalpindi was continuously collected on the case to case basis for one year from march 2011 to march 2012. those below 12 years of age were included in "paediatric group" and those from 12 and above were included in "adult group". special stress was paid to evaluate incidence of rigid bronchoscopies in relation to main seasons of this part of the world i.e winter and summer. total number of bronchoscopies in both seasons were collected and analyzed with regards to age, sex, indications of procedure,type of foreign boy and outcome of bronchoscopies in both the seasons. results out of twenty patients 10 were male and 10 were female. the age of patients ranged from 1-60 years. out of 20 patients 60%were in the paediatric group and 40% were in the adult group. the average time of procedure was 10-15 minutes. the indication of bronchoscopy in all the paediatric cases (100%) was foreign body bronchus. in paediatric group 10 patients ( 83.3%) were below five years of age and 2 above 5 (16.7%) . in majority of the cases the foreign body was in the right bronchus 60% (table 1). the nature of foreign body in 7 children out of 12 (58.3%) was peanut, chickpea in 2 (16.6%), 1 each child (8.33%) was having rubber, pulse seed and a rare foreign body nail. in winter season 7 children (58.33%) underwent rigid bronchoscopy while 5 (42.67%) children in summer. there were 4 females (57.14%) and 3 males (42.86%). there were 5 patients (45.45%) under 5 years of age and 6 (54.5%) were above 5 years of age . there were 2 females (40%) and 3 males (60%) among those under 5 years of age. in the 4 patients (80%) under 5 years the nature of foreign body was peanut and in one case 20% a nail. the nature of foreign body in children above 5 was variable from peanut to chickpea and pulse seed. in summer season there were 3 (60%) females and 2 (40%) males. all the children (100%) in summer season were below 5 years of age and nature of foreign body was variable from rubber to metallic foreign bodies (table 2). table 1:bronchoscopydemographic profile variable no(%) total number of patients 20 sex male 10 female 10 age group paediatric 60% adult 40% average time of procedure 10-15 minutes incident of foreign body right bronchus 60% left bronchus 40% in adult group there were 8 patients (40%) of the total. males to female ratio was same as 4(50%) in each group . the age range was 14 years to 58 years.3 patients(37.5%) were below 30 years of age and 4 patients(50%) were 40 and above while one person(12.3%) was 36 years old. foreign body bronchus was the indication in 37.5%, while carcinoma bronchus, carcinoma postcricoid region and carcinoma hypopharynx were indications of bronchoscopy in other 3 patients(37.5%) and hoarseness of voice and post tracheostomy in rest of two patients making 12.5% in each. the age range of those who underwent bronchoscopy for foreign body was 14-27 years while those undergoing for carcinoma was from 40-58 years.in the group who underwent bronchoscopy for foreign body bronchus 2(66.6%) were lodged in right bronchus and 1(33.4%) was in left bronchus. the nature of foreign body in all (100%) cases was metallic one (table 3). the seasonal variation showed 4 cases 50% in summer and 50% in winter in all adult cases while in those for foreign body 2 cases(66.6%) in winter and one (33.4%) in summer . there were no complications of bronchoscopy except in 2 cases extraction of foreign body was not successful in first attempt but second attempt proved fruitful journal of rawalpindi medical college (jrmc); 2018;22(2): 144-147 146 table2:bronchoscopy – indications, age profile and seasonal variation – paediatric group (n=12) characteristic no(%) sex male 5 female 7 age <5 years 10(83.3%) >5 years 2(16.7) indications for bronchoscopy foreign body 100% type of foreign body peanut 58.5% chickpea 16.6% rubber 8.3% nail 8.3% pulses 8.3% seasonal variation winter 58.3% summer 41.7% table3:bronchoscopy – indications, age profile and seasonal variation – adult group (n=08) characteristic no(%) sex male 4 female 4 age (range=14-58 years) < 40 years 3(37.5%) >40 years 5(62.5%) indications of bronchoscopy foreign body 36.5% carcinoma 37.5% others 25% nature of foreign body metal pieces 100% seasonal variation summer 50% winter 50% discussion the results of this study indicate that rigid bronchoscopy is still an effective procedure in terms of diagnosis and therapeutics. different entanglements, associated with rigid bronchoscope, include laryngeal edema or bronchospasm requiring tracheostomy or re intubation, pneumothorax, pneumo-mediastinum, heart failure, tracheal or bronchial injury and hypoxic cerebral damage5. hypoxemia is the most usually watched occasion amid inflexible bronchoscopy. the hazard factors related with intraoperative or with postoperative hypoxemia in unbending bronchoscopy incorporate age, kind of foreign body , term of methodology, pneumonia previously or after system, ventilation mode and span of rising up out of anesthesia.6 a lot of complications are mentioned in the literature but with a cautious approach it is still a safe procedure with low morbidity and mortality. rigid ventilation bronchoscopy is safer and effective procedure to remove the mucous plugs and restore pulmonary function7. therapeutic rigid bronchoscopy has become a critical component in the treatment of lung cancer patients with chronic airway obstruction who are not surgical candidates.8 the inflexible bronchoscopy is the foremost strategy utilized for extraction of foreign body yet its utilization as a demonstrative instrument suggests a specific rate of negative examinations, presenting the patient to the danger of methodology and anesthesia related entanglements. 9 it is mentioned that ct scan or digital subtraction fluoroscopy must be done to rule out foreign body bronchus but in our setups these facilities are not readily available or they are not affordable, so we have to embark on rigid bronchoscopy. present study indicates that rigid bronchoscopy can be employed for a wide range of age group successfully. as no complications were encountered in this wide range so it can be said that rigid bronchoscopy can smoothly and safely undertaken in all age groups. in this series average time of procedure under anaesthesia was 10-15 minutes. the prolongation of anesthesia beyond 30 minutes was associated with complications.10 in majority (60%) foreign body was encountered in right bronchus. right bronchus is the commonest site to be lodged with a foreign body 1112.it is due to anatomical reasons as right bronchus is almost an in line continuation of trachea while left bronchus is lies at an angle. foreign body aspiration represents an emergency event that requires immediate medical intervention. 13 foreign body aspiration is a dreadful scenario for the parents and a red alert for the clinician as well as the patients are usually underage children with limited cardio-respiratory reserves and can choke any time. efficient diagnostics and extraction are imperative for the aspirated foreign body preventing life-threatening complications.14 in this study 83.3 % percent patients undergoing rigid bronchoscopy for foreign body were below 5 years of age. so in this scenario an anaesthetist well versed with the procedure is required.the nature of foreign bodies in majority of children (74%) were eatables organic in nature. peanut was most common among the vegetable foreign bodies amounting to 58.3%.15 studies showed watermelon seed as most common organic foreign body (39.7%) in turkey. betel-nuts (57,84%) and plastic whistles (12,43%) were commonest offending agents, followed by peanuts (11.35%), gram seeds (5.41%), peas (4.33%).16 the foreign bodies were mostly of vegetative origin like peanuts, beans, grams , while others were plastic objects and beads etc17. this difference among our studies is most probably due to prevalence of particular organic matter popularly consumed in different cultures. journal of rawalpindi medical college (jrmc); 2018;22(2): 144-147 147 in this study majority of children (58.33%) underwent rigid bronchoscopy in winter season and in all of these cases 100% foreign body was peanut. the reason for this specification was that potohar region is known for the cultivation of peanuts crop and in winter season there is increased in the rate of consumption of peanuts due to high caloric values. the negligence on the part of parents and other family members and lack of public education leads to instillation of peanuts in the mouths of young who inhale them rather to swallow. this is a public hazard and needs proper awareness through media and organizations. high index of clinical suspicion is mandatory for early diagnosis and management to prevent fatal outcome and long term morbidity.18 there were no complications of rigid bronchoscopy in present series. safe and suitable general anaesthesia by an experienced anaesthesiologist is required for complete removal of tracheobronchial foreign body.19 conclusion 1.rigid bronchoscopy is a safe and effective procedure 2. foreign body extraction is the commonest indication of rigid bronchoscopy,which is more common in paediatric age group. references 1. chadha m, kulshrestha m, biyani a. anaesthesia for bronchoscopy. indian j anaesth. 2015;59(9):565–73. 2. said m, ahmad n. experience with removal of foreign bodies with rigid broncoscope. j postgrad med inst. 2006 ;20(2):178–81. 3. nussbaum e. flexible fiberoptic bronchoscopy and laryngoscopy in infants and children.the laryngoscope. 1983 ;93(8):1073–75. 4. ahmad khan i, javed m, zada b. foreign body tracheobronchial tree in children managed by rigid bronchoscopy. ann pak inst med sci 2006;2(3):112-15 5. fidkowski cw, zheng h, firth pg. anaesthetic considerations of tracheobronchial foreign bodies in children. anesth analg. 2010 ;1: 112-15 6. chen l, zhang x, li s, liu y, zhang t. risk factors for hypoxemia in children younger than 5 years old undergoing rigid bronchoscopy.anesthanalg. 2009 ;109(4):1079–84. 7. wu k-h, lin c-f, huang c-j, chen c-c. rigid ventilation bronchoscopy under general anaesthesia for treatment of pediatric pulmonary atelectasis. int surg. 2006 ;91(5):291– 94. 8. jung b, murgu s, colt h. rigid bronchoscopy for malignant central airway obstruction from small cell lung cancer complicated by svc syndrome. ann thorac cardiovasc surg 2011;17(1):53–57. 9. cavel o, bergeron m, garel l,arcand p. questioning the legitimacy of rigid bronchoscopy as a tool for establishing the diagnosis of a bronchial foreign body. int j pediatr otorhinolaryngol. 2012 ;76(2):194–201. 10. maddali mm, mathew m, chandwani j. outcomes after rigid bronchoscopy in children with foreign body aspiration. j cardiothoracvascanesth. 2011 ;25(6):1005– 08. 11. farooqi t, hussain m. foreign body aspiration in children: an experience at nishtar hospital multan. pak j paed surg dec 1999;1-2:32-35. 12. asif m, shah sa, khan f, ghani r. foreign body inhalationsite of impaction and efficacy of rigid bronchoscopy. j ayub med coll abbottabad. 2007;19(2):46–48. 13. montero-cantú ca, garduño-chávez b, elizondo-ríos a. rigid bronchoscopy and foreign body. obsolete procedure?. cir cir. 2006 ;74(1):51–53. 14. mrvić sa, milosavljević mz, stojković d. foreign body extraction through the rigid bronchoscopy. vojnosanit pregl mil-med pharm rev. 2011 ;68(10):878–80. 15. aydoğan lb, tuncer u, soylu l, kiroğlu m. rigid bronchoscopy for the suspicion of foreign body in the airway.int j pediatr otorhinolaryngol. 2006;70(5):823–28. 16. khemani am, hussain i, memon gn. laryngotracheobronchial foreign bodies an experience at nawabshah. med channel. 2004;10:35–37. 17. samad r, nawaz g, zakirullah. role of clinical assessment and plain chest radiograph in the management of suspected tracheobronchial foreign body.jpma 2008;13(3):901-05 18. tariq p. foreign body aspiration in children--a persistent problem. jpma j pak med assoc. 1999 ;49(2):33– 36. 19. gilani sm, ghani r, nabi g. anesthetic management of tracheobronchial foreign bodies in children. j ayub med coll abottabad 1999;11(1):34-46 http://www.pakmedinet.com/jamc http://www.pakmedinet.com/jamc summary journal of rawalpindi medical college (jrmc); 2017;21(2): 136-140 136 original article activity of indoleamine 2, 3 dioxygenase (ido) in type 2 diabetes mellitus patients in pakistan syed harris hussain 1, syed muarraf hussain 2, nadeem ikram 3, yasmin badshah 4, kashif asghar 5 1. department of biomedical engineering , umm,heidelberg university, germany;2. department of physiology, sahiwal medical college, sahiwal; 3. department of pathology , rawalpindi medical university; 4. national university of sciences and technology (nust), islamabad; 5. shaukat khanum memorial cancer hospital & research centre (skmch&rc) abstract background: to assess the activity of indoleamine 2, 3 dioxygenase (ido) in type 2 diabetes mellitus patients in pakistan methods: in this prospective study, activity and expression of ido , was assessed in sera of diabetics and healthy controls (n=28). colorimetric assay was performed to analyze ido activity in samples. results: a significant difference was observed between the means of control and diabetic patients with a p-value of 0.0001. conclusion: ido concentrations were significantly higher in the serum of samples of diabetes mellitus patients as compared to control . key words: diabetes mellitus, indoleamine 2, 3 dioxygenase, kynurenine pathway introduction indoleamine 2, 3 dioxygenase, an intracellular enzyme, regulates the degradation of l-tryptophan through kynurenine pathway. upon induction of ifn-γ, dendritic cells (dcs), macrophages, fibroblasts and endothelial cells specify ido protein. specific immune systems are modulated by ido in the course of various inflammatory and autoimmune diseases. diabetics with over expression of ido are susceptible to various bacterial, viral and fungal infections. diabetes mellitus is a worldwide issue, responsible for effecting approximately 381 million individuals. according to who, 7 million people are affected by diabetes in pakistan in 2012. diabetes characterized by hyperglycemia, is a group of metabolic diseases resulting from irregularity in secretion or action of insulin or both. long-term damage, irregular function and organ failure specifically the kidneys, nerves, eyes, heart and blood vessels are involved in chronic hyperglycemia of diabetes. 1 diabetics are found to be more susceptible to certain bacterial, viral and fungal infections and have enhanced prevalence of cardiovascular, atherosclerotic, cerebrovascular disease and peripheral arterial. 2 there are two classes of diabetes mellitus i.e. type 1 and type 2 of which type 2 constitutes 90% of the cases. according to the world health organization (who), in 2015, approximately 422 million individuals were affected with diabetes. prevalence is rapidly increasing and this number is determined to almost double by 2030. according to world health organization (who), in pakistan, seven million people are affected with diabetes mellitus, both types. currently, diabetes mellitus is incurable, but depending on the type of diabetes suffered by the individual it can be managed. the goal for the treatment of diabetes is controlling blood glucose levels, in turn to prevent disease complications. indoleamine 2, 3 dioxygenase (ido), heme containing enzyme, regulate catalytic degradation of tryptophan.3 ido is involved in the modulation and downregulation of immune system by tryptophan degradation.4 tryptophan, an essential amino acid (aa) and is vital for all living organisms and required in various metabolic pathways. degradation of tryptophan results in the production of kynurenines leading to the suppression of cell proliferation. immunomodulatory effects are produced in the biological systems 5. ido is involved in progression of several inflammatory reactions occurring in major diseases ranging from cancer, autoimmunity, infection and allergic reactions.4 immunology of ido is complex in nature. according to current knowledge, activity of ido directly affects t-cells. apoptosis is induced by ido either through depletion of tryptophan or through tryptophan metabolites. the first mechanism discovered for ido activity was tryptophan depletion. induction of ido is predominantly triggered by macrophages and dendritic cells. during inflammation, ido is significantly upregulated by interferon gamma (ifnγ), which in turn is extremely fundamental for the development of t-cell and initiation of inflammatory response against infections and diseases. enzymatic activity of ido is indicated by the rate of tryptophan degradation and the ratio of kynurenine to tryptophan (kyn/trp) can be used as an indicator for https://w2.umm.de/ journal of rawalpindi medical college (jrmc); 2017;21(2): 136-140 137 degradation of tryptophan as well as in the activation of immune system. 6 many inhibitors of ido are being studied but 1methyl tryptophan (1mt) has been considered as a potent inhibitor of enzymatic activity of ido.3 1mt has favorable pharmacokinetic characteristics such as oral availability, low protein binding and low clearance.7 ido is involved in the progression of numerous pathological conditions ranging from various cancers, infections, allergies and autoimmune diseases. ido and its differential response have been studied in several systems. current study focuses on the assessment of activity of indoleamine 2, 3 dioxygenase in diabetes mellitus type 2. according to a who survey in 2014, global prevalence of prevalence of diabetes was estimated to be 9% among adults aged 18 and above years. in pakistan, approximately 7 million individuals are affected by diabetes. ido has never been studied previously in relation to diabetes mellitus type 2. patients and methods total 89 blood samples were collected from which 61 were diabetic samples while 28 were control samples. serum was extracted from blood samples through centrifugation at 14000 rpm for 5-7 minutes. extracted samples were stored at -80 degree c. for colorimetric assay of kynurenine two solutions namely solution a and solution b were prepared . solution a was 30% trichloro-acetic acid (tca) solution in glacial acetic acid while solution b was 20% ehlrich reagent (pdimethylbenzaldehyde) in glacial acetic acid. the function of tca is to precipitate proteins in sample and ehlrich reagent imparts color which binds to ido. 200μl of serum sample was added from diabetic patient as well as from healthy control in an eppendorf tube. they were labelled on the basis of their well number.100μl of solution a was addedin the samples. this process was repeated for all the samples separately. the mixture was then centrifuged at 14000 rpm for 3 minutes. after centrifugation two separate layers are established. 125μl of supernatant was added from each 96 eppendorf tube to a separate well of 96-well plate. after all the wells were filled and 125μl of solution b was added which resulted in an immediate change of colour. this change in colour was assessed through dynex technologies microplate reader by measuring the absorbance of light at 490nm. ido activity corroborated in diabetic samples as well as control samples through kynurenine concentration absorbance procured from microplate reader. different concentrations of kynurenine were checked for absorbance at 490nm and a standard curve was established in 96-well plate by conducting colorimetric assay (figure 1). figure 1: kynurenine standard curve results enzymatic activity of ido, due to the incongruity between ido expression and activity. six diabetics had hypertension (table 1). a significant difference was observed between the means of control and diabetic patients with a p-value of 0.0001 (table 2). unpaired t-test was applied and it revealed significant up regulation in ido expression with a p-value of 0.0095. table 1: diabetics and controlsdemographic and clinical profile characteristics diabetic samples (n=61) control samples (n=28) age 58 (43-84) 33 (21-40) sex (m/f) 25/36 14/14 hypertension (y/n) 6/55 0/28 cardiac complications 6/55 0/28 viral infections (y/n) 0/61 0/28 table 2: ido activity in diabetics and controls ido activity in samples patients diabetic samples (n=61) control samples (n=28) p-value kynurenine conc. absorbance average 0.2521 0.0545 0.0001 discussion according to the world health organization (who), in 2015, approximately 422 million individuals were affected with diabetes. prevalence is rapidly increasing and this number is determined to almost double by 2030. according to world health organization (who), in pakistan, seven million people are affected journal of rawalpindi medical college (jrmc); 2017;21(2): 136-140 138 with diabetes mellitus, both types. being an underdeveloped country, pakistan allots minimal quota for the health budget, 24 dollars per person cost of diabetes in pakistan. ido is involved in the up regulation of ifn-γ in diabetic patients and up regulates production through human islets cells. 8 in this study, we established a correlation between up regulation of ido and diabetes mellitus. we evaluated the enzymatic activity of ido in serum of diabetes mellitus patients. a marked higher expression and activity of ido was observed in diabetes mellitus patients as compared to healthy controls. indoleamine 2, 3 dioxygenase (ido), heme containing enzyme, regulate catalytic degradation of tryptophan, an essential amino acid 3. it has vital role in metabolism of tryptophan and performs cleavage in indole ring of a double bond at 2, 3 positions, consequently is also the rate limiting step of this catabolic pathway 3. ido is expressed in varying amounts by numerous tissues along with antigen presenting cells (apcs). it is intracellular in nature, extracellular form has not been reported yet. activity and expression of ido has been evident in trophoblast cells at fetal-maternal interface. 9 lately, a new enzyme has been reported having similar activity to ido 10. the enzyme is cited as indoleamine 2, 3 dioxygenase-2 (also proto indoleamine 2, 3-dioxygenase or indoleamine 2, 3dioxygenase like protein) because of its structural and functional analogy with ido. ido is a monogenic protein and has 15 kb gene, constituted of 10 exons, present in chromosome 8 at the syntenic region in mice as well as humans. ido is reported to be well conserved. 11ido gene transcription is strictly regulated and is prevalent in a limited number of cells. only specific set inflammatory and genetic promoters can upregulate ido transcription. various proinflammatory promoters are strong inducers of ido like type ii interferons (ifn-γ) in turn type i interferons (ifn-α and ifn-β) are less potent inducers.12 ido protein is specifically expressed by macrophages, endothelial cells, fibroblasts and dendritic cells (dcs) upon the induction by ifn-γ. 9 stat-1 and irf1 along with ifn-γ are involved in the ido induction 13. ifn-γ is strongly associated with inflammation and ido induction; consequently various others potent inducers are also present to induce ido expression along with ifn-γ. tumor necrosis factors (tnf) and lipopolysaccharide (lps) are potent inducers.14 absence of ifn-γ is unaffected in the induction of ido through lps, although lps requires tnf to support its responsiveness 15 which reiterates metabolic pathways of ido induction independent of ifn-γ present. complex transcription and expression is enhanced by certain cell specific cytokines. tryptophan, an essential amino acid (aa) and is vital for all living organisms and required in various metabolic pathways. animals are unable to produce tryptophan by themselves and hence are dependent on primary producers for the flow of tryptophan. from the digestive system, tryptophan is taken to the liver where it is utilized in various ways:biosynthesis of serotonin, protein synthesis and kynurenine degradation pathway .various biological mechanisms are affected; kynurenine pathway metabolizes most of the tryptophan. it is imperative in the production of serotonin. degradation of tryptophan results in the production of kynurenines leading to the suppression of cell proliferation. 5 in tryptophan catabolism, two important enzymes are involved , e.g., indoleamine 2, 3-doioxygenase (ido) and tryptophan 2, 3dioxygenase (tdo).tryptophan and certain metabolic steroids activate the enzyme.16 ifn-γ is the potent inducer of ido and is expressed in several tissues. 17 activated t-cells secrete ifn-γ as well as other leukocytes having the ability for the induction of reactive nitrogen species (rns) and reactive oxygen species (ros) in macrophages and neutrophils. 18,19 inexplicable role of ifn-γ during an immune response is well documented during vigorous and sustained catabolism of tryptophan. 20 although the biological significance of ifn-γ mediated degradation of tryptophan is not completely comprehended, researchers believe that it is linked in prevention of tryptophan supply to intracellular parasites, cancer cells and pathogens.21 in recent years, these roles have gained attention. immunology of ido is complex in nature. in specific cases, ido can proliferate the pathogen growth or be beneficial to any disease inflicting factor thus in turn damaging the host. in tissues, generation of immunosuppressive microenvironment is a matter of extensive research. according to current knowledge, activity of ido directly affects t-cells. apoptosis is induced by ido either through depletion of tryptophan or through tryptophan metabolites. the first mechanism discovered for ido activity was tryptophan depletion. on the other hand, antimicrobial effects of ido are reversed by the addition of tryptophan. inhibition of t-cells was observed to be reversed through numerous studies conducted by different researchers. 22 t-cells are detrimentally effected by metabolites journal of rawalpindi medical college (jrmc); 2017;21(2): 136-140 139 produced by the degradation of tryptophan through ido i.e. 3-hydroxyanthranilic acid and quinolinic acid even if externally added. it is hypothesized that the metabolites bind to the receptors and either block or be directly toxic to the cells. t-cell affinity determined by molecular pathways to metabolites of ido is yet to be studied. however, specific pathways such as activation of gcn2 kinase pathway by amino acid withdrawal and inhibition of mtor (mammalian target of rapamycin) pathway are known. through advancement in knowledge of biological effects of ido and computer mediated drug design strategies, study and synthesis of inhibitors of ido has got attention from numerous researchers. competitive and non-competitive ido inhibitors have been studied along with competitive inhibitors constituted from tryptophan derivatives and noncompetitive inhibitors derived from βarboline. 23 1-methyl tryptophan (1mt) is the most widely studied inhibitor of ido. 1mt has favourable pharmacokinetic characteristics such as oral availability, low protein binding and low clearance 24. methyl-thiohydantoin-l-tryptophan (mth-trp) was found be much potent inhibitor than 1mt during screening for ido inhibitors of competitive nature. 25 in different pathological conditions, ido has numerous roles in human beings. enhanced activity of ido has been reported in various tumors in their microenvironment 26 resulting in t-cell suppression. poor prognosis of cancer is associated with ido and elevated levels of kynurenine have been reported in patient samples. 27,28 conclusion 1. enzymatic activity of ido measured through colorimetric assay indicates that ido might be involved in progressing the symptoms and susceptibility to infections in diabetes mellitus patients. 2.blocking ido or inhibiting its production can provide new strategies as an advent intervention therapy for diabetes mellitus references 1. bartoli m, lamoke f, baban b. preventing hyperglycemia and tissue injury in diabetes: the dynamic role of 2, 3 indoleamine dioxygenase (ido) in diabetes and its complications. in new strategies to advance pre/diabetes care: integrative approach by pppm 2013; 265-282. 2. cooper-dehoff r m, gong y, handberg e m, bavry a a. tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. jama 2010;304(1): 61-68. 3. grohmann u, fallarino f, puccetti p. tolerance, dcs and tryptophan: much ado about ido. trends in immunology 2003; 24(5): 242-48. 4. mellor a l and munn d h. tryptophan catabolism and tcell tolerance: immunosuppression by starvation?. immunology today 1999; 20(10): 469-73. 5. mackenzie c r, gonzález r g, kniep e, roch s. cytokine mediated regulation of interferon-gamma-induced ido activation. in tryptophan, serotonin, and melatonin 1999; 533-39. 6. schröcksnadel k, wirleitner b, winkler c, fuchs d. monitoring tryptophan metabolism in chronic immune activation. clinicachimicaacta 2006;364(1): 82-90. 7. uyttenhove c, pilotte l, théate i, stroobant v, colau d. evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3dioxygenase. nature medicine 2003; 9(10): 1269-74. 8. sarkar s a, wong r, hackl s i, moua o, gill r g, wiseman a. induction of indoleamine 2, 3-dioxygenase by interferonγ in human islets. diabetes 2007; 56(1): 72-79. 9. taylor m w feng g s.relationship between interferongamma, indoleamine 2, 3-dioxygenase, and tryptophan catabolism. the faseb journal 1991;5(11): 2516-22. 10. ball h j, yuasa h j, austin c j, weiser s, hunt n h. indoleamine 2, 3-dioxygenase-2; a new enzyme in the kynurenine pathway.the international journal of biochemistry & cell biology 2009; 41(3), 467-71. 11. suzuki, t., yokouchi, k., kawamichi, h., yamamoto, y., uda, k., and yuasa, h. j. comparison of the sequences of turbo and sulculusindoleamine dioxygenase-like myoglobin genes. gene,2003; 308: 89-94. 12. dai w and gupta s l. regulation of indoleamine 2, 3dioxygenase gene expression in human fibroblasts by interferon-gamma. upstream control region discriminates between interferon-gamma and interferon-alpha. journal of biological chemistry 1990; 265(32): 19871-77. 13. chon s y, hassanain h h, gupta s l. cooperative role of interferon regulatory factor 1 and p91 (stat1) response elements in interferon-γ-inducible expression of human indoleamine 2, 3-dioxygenase gene. journal of biological chemistry 1996; 271(29), 17247-52. 14. babcock t a and carlin j m. transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor α in interferon-treated epithelial cells. cytokine 2000; 12(6): 588-94. 15. fujigaki s, saito k, sekikawa k, tone s, takikawa o, fujii h. lipopolysaccharide induction of indoleamine 2, 3‐dioxygenase is mediated dominantly by an ifn‐γ‐independent mechanism.european journal of immunology 2001; 31(8): 2313-18. 16. salter m and pogson c i. the role of tryptophan 2, 3dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. effects of glucocorticoids and experimental diabetes. biochemical journal 1985;229(2), 499-504. 17. yoshida r, imanishi j, oku t, kishida t, hayaishi o. induction of pulmonary indoleamine 2, 3-dioxygenase by interferon. proceedings of the national academy of sciences 1981; 78(1), 129-32. 18. nathan c f, murray h w, wiebe m e, rubin b y. identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. the journal of experimental medicine 1983; 158(3), 670-89. journal of rawalpindi medical college (jrmc); 2017;21(2): 136-140 140 19. tennenberg s d, fey d e, lieser m j. oxidative priming of neutrophils by interferon-gamma. journal of leukocyte biology 1993; 53(3), 301-08. 20. werner-felmayer g, werner e r, fuchs d, hausen a. characteristics of interferon induced tryptophan metabolism in human cells in vitro. biochimicaet biophysica acta (bba)-molecular cell research 1989; 1012(2), 140-47. 21. hayaishi o. utilization of superoxide anion by indoleamine oxygenase-catalyzed tryptophan and indoleamine oxidation. in recent advances in tryptophan research 1996; 285-89. 22. munn d h, shafizadeh e, attwood j t, bondarev i, pashine a, mellor a l.inhibition of t cell proliferation by macrophage tryptophan catabolism. the journal of experimental medicine 1999; 189(9), 1363-72. 23. pucchio t d, danese s, cristofaro r d, rutella s. inhibitors of indoleamine 2, 3-dioxygenase: a review of novel patented lead compounds. expert opinion on therapeutic patents 2010; 20(2), 229-50. 24. uyttenhove c, pilotte l, théate i, stroobant v, colau d,parmentier n. evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase. nature medicine 2003; 9(10), 1269-74. 25. muller l m, gorter k j, hak e, goudzwaard w l. increased risk of common infections in patients with type 1 and type 2 diabetes mellitus.clinical infectious diseases 2005; 41(3), 281-88 26. oyama t, ran s, ishida t, nadaf s, kerr l, carbone d p. vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-κb activation in hemopoietic progenitor cells. the journal of immunology 1998; 160(3), 1224-32. 27. okamoto a, nikaido t, ochiai k, takakura s, saito m. indoleamine 2, 3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. clinical cancer research 2005; 11(16), 6030039. 28. rose d p. tryptophan metabolism in carcinoma of the breast. the lancet 1967; 289(7484), 239-41. ----------------------------------------------------------- authorship:1-3 conception , synthesis, planning of the research, methodology and writing of manuscript ; 4,5 literature review, manuscript writing and data analysis summary journal of rawalpindi medical college (jrmc); 2017;21(2): 148-152 148 original article pattern of bimalleolar ankle fractures nadeem kashmiri, imtiaz ahmed shakir, tehreem zahid, nayyar qayyum. department of orthopedics, district head quarter hospital and rawalpindi medical university, rawalpindi. abstract background:. to determine the pattern and outcome of bimalleolar ankle fractures . methods: in this prospective observational study of 72 patients with bimalleolar ankle fractures were included and were followed up for 12 weeks. the american orthopaedic foot and ankle score (aofas) and visual analog pain scale (vas) were used to assess short term outcomes as at 12 weeks. the main outcome measures were pain, functional capacity and alignment. results: the patients’ age ranged from 19 to 63 mean 36.4 ±10.4 years. the male to female ratio was 3:2. falls caused 50% of the fractures, motor vehicle accidents 36.1% and motor cycle accidents 13.9%. closed fractures accounted for 63.9% of the cases. the most common fractures based on the weber classification were b and c which occurred in 33 (45.8%) and 31 (43.1%) patients, respectively. at 3 months, the mean aofas was 78.2. the vas between 1 and 3 was 43.1%. twenty eight patients (38.8%) had no pain. there was no difference in aofas and vas between operative and non operative, open or closed weber b fracture outcomes. the weber c fractures managed operatively had a significantly lower aofas, 63 compared to nonoperative cases who scored 84.3. medial clear space greater than 4mm was associated with a poor outcome. conclusion: patients mostly were young. delay in definitive treatment of up to a week post-fracture does not seem to adversely affect the outcome. the main determinant of good outcome was the medial clear space that was less than 4mm. key words: bimalleolar fractures, visual analog pain scale (vas), american orthopaedic foot and ankle score (aofas), weber classification, outcome. introduction ankle fractures account for 10% of all fractures. their incidence is projected to triple over the next 15 years. bimalleolar fractures constitute 25% of all ankle fractures where on an average basis 12 patients with bimalleolar fractures are treated at district head quarter hospital (dhq), rawalpindi every month. bimalleolar fractures may be managed either operatively or non-operatively. the ankle joint is a synovial mortise and tenon joint variety, functionally uniaxial. the lower end of the tibia and its medial malleolus, together with the lateral malleolus of the fibula and the distal tibio-fibular syndesmosis, form a mortise for the body of the talus. ankle stability is conferred mainly by the medial and lateral ligament complexes, the distal tibiofibular ligaments, the tendons crossing the joint, the bony contours and the capsular attachments.1-2 a bimalleolar fracture is a fracture of the distal tibia and fibula in which the medial malleolus of the distal tibia and the lateral malleolus of the distal fibula are fractured.2-4bimalleolar ankle fractures disrupt the medial and lateral stabilizing structures of the ankle joint. these fractures are commonly caused by indirect rotational, translational and axial forces. these result in subluxation or dislocation of the talus out of the ankle mortise, usually associated with a fracture complex.5 the standard ankle radiographs include the anteroposterior (ap), mortise and lateral views.6 the number and incidence of low-trauma ankle fractures in above 60 years of age rose substantially in a 30 year old period: the total number of fractures increased from 369 in 1970 to 1545 in 2000(a 319% increase), and the crude incidence increased from 57 to 150(a 163% increase). it is estimated that there will be a threefold increase in these fractures by the year 2030.2most ankle fractures are isolated malleolar fractures, accounting for two-thirds of fractures, with bimalleolar fractures occurring in 25% of patients and trimalleolar fractures in the remaining 5% to 10%.3 patients and methods a prospective observational study of patients with bimalleolar ankle fractures was done at the orthopaedics department of district head quarter hospital (dhq), rawalpindi. it was conducted between january and december 2015. inclusion criteria were all patients diagnosed to have isolated bimalleolar fractures on radiography and treated at district head quarter hospital (dhq), rawalpindi within 3 weeks of injury. weber a, b and c injuries journal of rawalpindi medical college (jrmc); 2017;21(2): 148-152 149 were included (figure 1) excluded were patients with bilateral ankle injuries, pre-existing ipsilateral or contralateral ankle pathology, pathological fracture (e.g. a stress fracture), refracture of a previous ankle fracture, diabetes mellitus, neuropathic vascular disorders that may impair healing, unimalleolar and trimalleolar fractures, concurrent foot deformities, inability to attend clinic for follow-up or inability to follow the postoperative regime, refusal to give consent. patients with isolated ankle injuries were identified and radiographs taken (at least the anteroposterior and lateral views) (figure 2). figure 1: weber classification figure 2: bimalleolar fracture and its open reduction internal fixation (orif) those with bimalleolar fractures were recruited into the study and followed up. patients’ bio data on age and sex were recorded on a pre-formed questionnaire. fractures were classified as either weber a, b or c (figure-1). the patients were then followed-up and the modality of treatment documented, as they came for review in the fracture clinic. assessment was done at 2, 6 and 12 weeks. the assessment at 2 weeks was for maintenance of reduction and surgical site infection (for orif group), at 6 weeks for clinical and radiological union, and at 12 weeks the visual analog pain scale (vas) and american orthopaedic foot and ankle score (aofas) were administered and documented. results the mean age of the adults presenting to district head quarter hospital (dhq)with bimalleolar fractures was 36.4 years (sd ±10.4) with an age range between 19 and 63 years (table 1). the modal age group was between 19 and 29 years with this group accounting for 24 (33.8%) patients followed by patients aged between 30 and 39, n = 22 (31%). these 2 groups account for 64.8% of the patients. most (42, 58.3%) bimalleolar fractures occurred in male patients. there were 30 (41.7%) female patients with bimalleolar fractures resulting in a male-to-female ratio of approximately 3:2. the right limb was involved in 62% of the patients. closed fractures comprised 63.9% (n=46). the most common fractures were weber b and c which occurred in 45.8% and 43.1% respectively. most of the tibial fractures were transverse 58 (84.1%) while the fibular fractures were commonly of the oblique type, 50%. table 1: bimalleolar ankle fracturesage distribution (n=72) age (years) no(%) 19-29 24(33.8) 30-39 22(31.0) 40 – 60 26(35.2) table 2: presentation of bimalleolar fractures by site and fracture type frequency (n) percentage (%) fractured limb right 44 62 left 27 38 injury type open 26 36.1 closed 46 63.9 weber classification of fracture a 8 11.1 b 33 45.8 c 31 43.1 tibial fracture transverse 58 84.1 oblique 9 13 comminuted 2 2.9 fibular fracture transverse 21 29.2 oblique 36 50 comminuted 15 20.8 journal of rawalpindi medical college (jrmc); 2017;21(2): 148-152 150 fall accounted for the most number of bimalleolar fractures (50%).among the weber a fractures, 1 was open, 7 closed, weber b; 12 open and 21 closed, weber c; 13 open and 18 closed. of the 35 operatively managed fractures, 1 was weber a, 18 weber b and 16 weber c (table 2). indications for operative management were; open fractures, displaced fractures (lateral displacement of more than 2mm) and dislocations. superficial surgical site infection was found in 2 (5.7%) patients who were managed operatively (table 3). table 3: treatment and reassessment of patients with bimalleolar fracture frequency percent treatment operative 35 49 non-operative 37 51 surgical site infection (operative at 2 weeks) yes 2 5.7 no 33 94.3 clinical or radiologic union (at 6 weeks) yes 70 97.2 no 2 2.8 radiographs taken at 2 weeks showed a medial clear space greater than 4mm in 6(8.3%) patients. three had been managed operatively. one was weber b and the other 5 weber c. there were no patients reporting severe pain (vas score ≥7).most patients reported mild levels of pain represented by scores between 1 and 3 (43.1%). twenty eight patients (38.8%) scored pain at 0 and the remaining 18.1% of patients reported moderate pain (vas scores 4-6). there were no significant differences in the patients reported level of pain on vas and type of treatment (p = 0.759), time since treatment (p = 0.535), type of injury (p = 0.405) or weber classification of fracture (p = 0.478). most 56 (84.8%) patients with medial clear space of 0-4 mm reported vas < 3 compared to 50% of patients with medial clear space > 4 mm who similarly reported vas < 3 (p = 0.034). the mean aofas score for patients with bimalleolar fractures at dhq was 78.2 (sd ± 20.7), range 17 to 100. the mean aofas for weber a, b and c were 96.6, 80.3 and 72.9 respectively (table 4). there were significant differences in mean aofas score for patients on the operative compared to non-operative treatment (p = 0.001) and patients with open compared to closed injury (p = 0.002). the aofas score was significantly related with patient level of education (p = 0.03) but not with age (p = 0.790) or sex (p = 0.111) (table 5). table 4: mean aofas scores according to type of injury and treatment mean sd anova f p value type of treatment operative 69.6 20.6 12.28 0.001 non-operative 85.6 17.5 time to treatment <48 hrs 77.0 20.7 0.12 0.891 <7 days 81.7 15.6 >7 days 77.7 21.8 type of injury open 68.3 21.1 10.65 0.002 closed 83.8 18.4 weber classification of fracture a 90.6 12.9 2.77 0.070 b 80.3 21.2 c 72.9 20.5 table 5: comparison of clinical aofas and vas pain scores and clinical outcomes according to weber classification clinical / radiologic union, n (%) median vas mean aofas p* 6 weeks 12 weeks 12 weeks injury type open (n = 26) weber a (n = 1) 1 (100%) weber b (n = 12) 12 (100%) 2 68.3 weber c (n = 13) 13 (100%) 3 66.3 0.821 closed (n = 42) weber a (n =7) 6 (86%) 1 90 weber b (n = 21) 21 (100%) 0 87.1 weber c (n = 18) 17 (94%) 2 77.6 0.121 medial clear space space <4 (n = 66) 64 (97%) 2 80.2 space >4 (n = 6) 6 (100%) 3.5 57.2 0.008 treatment operative (n = 35) weber a (n = 1) 1 (100%) weber b (n = 18) 18 (100%) 2 74.1 weber c (n = 16) 16 (100%) 3 63 0.117 non operative (n = 37) weber a (n = 7) 6 (86%) 1 90 weber b (n = 15) 15 (100%) 0 87.7 weber c (n = 15) 14 (93%) 1 83.4 0.523 * comparison of weber b versus c journal of rawalpindi medical college (jrmc); 2017;21(2): 148-152 151 anova analysis showed that patients with secondary level education on average had an aofas score that was15.5 points higher compared to those with primary education (p = 0.03) corresponding to less pain in patients with primary compared to secondary education. the scores for secondary and tertiary levels did not differ (p = 0.435). there was no significant difference between open and closed, or operative and non operative weber b fractures. operatively managed weber c fractures had a significantly lower score than conservatively managed fractures at 63 and 84.3 respectively. the aofas score did not show any significant clinical or radiologic union, physiotherapy (p = 0.052), medial clear space (p > 0.99), surgical site infection or time of surgery. discussion majority of the patients were young patients under 40 years with a slight male predominance. fifty percent of the fractures were caused by rtas while the other 50% was by falls. african studies showed a predominance of rtas as the main cause of the fractures majority of them being men as opposed to caucasian studies where the majority were caused by falls and were predominantly women. 7-14 it was consistent with a nigerian study that had rtas causing 46.3% of the ankle fractures and a south african study that had falls causing 53% of the injuries. road traffic injuries are common in 3rd world countries due to, social inequality, vulnerable road pedestrians, cyclists, bus and minibus passengers.11,13,14 open fractures were 26 (36%), this was higher than the caucasian studies where open bimalleolar fractures were lower than 5%.15 this may be related to the aetiology of the fractures where in the caucasian population most ankle fractures were caused by falls which are low energy as opposed to the pakistani population where the fractures were due to high energy trauma. weber b fractures were the most common (45.8%) which was comparable to other results by hughes, reuwer and schweiberer.16,17forty nine percent of the patients were managed operatively. these were patients who had displaced weber b and c injuries and also open fractures. there was no significant difference in the aofas score between the operative and non operative weber b fractures. however the operative weber c bimalleolar fractures had a significant lower aofas score than the non operative weber c fractures. the low operative aofas score may be as a result of the severity of the injury or syndesmotic injury, rather than the operative treatment. operatively managed fractures were likely to be severe ankle injuries that were displaced and comminuted. sixty one percent had the definitive treatment done after a week. the causes of delayed treatment were; late presentation to the hospital due financial or infrastructure constraints, septic openfractures, blistering, swelling and theatre space unavailability. there was no significant difference between early and late treatment of bimalleolar fractures. these findings were similar to those of breederveld who found no difference in outcome on patients who had delayed treatment up to 8 days.24 konvath also found no difference in outcome between early (mean 1.5 days from injury to surgery) and late (mean of 13.6 days from injury to surgery) treatments of bimalleolar fractures. 23 the longest duration was 11 days due to lack of theatre space. early surgery is recommended to reduce the hospital stay and cost to the patient, however if there is swelling or blistering treatment should be delayed until it subsides.20,21 there was mild to moderate pain in 61.2% of the patients. previous studies report pain at 23%-60% at one year.18,19 the pain incidence was higher in this study because it has a short duration of follow up. it is expected to reduce with time. patients with a medial clear space >4mm had a poorer vas than the well reduced fractures which was similar to the clement et al study.22 the functional capacity was reduced by a high medial clear space, operative management and physiotherapy. previous studies show either a better outcome with operative treatment or similar outcome between operative and non-operative treatment.22-26 makwana’s study showed a better functional capacity in the non operative group although there was no difference between the two groups overall outcome.23,27most of the above studies were on the elderly majority of whom had low energy trauma. majority of the patients in this study were young, the patients who underwent surgery were likely to have had high energy injuries with displacement and syndesmotic injuries. the open fractures were managed operatively which were associated with a lower aofas score. only 23.6% of patients had physiotherapy, yet these patients had reduced functional capacity. these are likely to be those who had severe injuries and therefore functional impairment was anticipated and therefore needed physiotherapy. majority of the patients had a basic and secondary level of education; these are likely to be journal of rawalpindi medical college (jrmc); 2017;21(2): 148-152 152 low income earners, who walk for long distances. this may explain why the functional outcome was good despite not having physiotherapy. conclusion 1.patients presenting were mostly young. 2.delay in definitive treatment of up to a week postfracture does not seem to adversely affect outcomes despite poorly supervised physiotherapy. 3.the main determinant of good outcome was the medial clear space, if it was less than 4mm. references 1. http://www.medilexicon.com/medicaldictionary.php. accessed on 15th august 2015. 2. kannus p, palvanen m, niemi s. increasing number and incidence of low-trauma ankle fractures in elderly people: finnish statistics during 1970 – 2000 and projections for the future. bone 2002;31(3): 430-33 3. hong cc, roy sp, nashi n, tan kj. functional outcome and limitation of sporting activities after bimalleolar and trimalleolar ankle fractures. foot ankle int. 2013; 34(6): 805-10. 4. standring s. gray’s anatomy. the anatomical basis of clinical practice. 40 baltimore: churchill livingstone elsevier publication 2008. 5. canale st, beaty jh: campbell's operative orthopaedics, 11th ed. philadelphia, pennsylvania: mosby publication 2007. 6. davidovitch ri, egol ka. ankle fractures. in: bucholz rw, court-brown cm, heckmanjd(eds) rockwood and green’ s fractures in adults, 7th edition. philadelphia: lippincott williams& wilkins publication 2010. 1977-78. 7. twagirayezu e, j.m.v dushimiyimana, a. bonane. open fractures i rwanda: the kigali experience. east and central african journal of surgery. 2008; 13(1): 77-84. 8. kuubiere cb, alhassan a, majeed sf. management of complex ankle fracture: a ghanaian experience. j med biomed sciences. 2012; 1(4): 1-6. 9. lin cc, moseley am, herbert rd, refshauge km. pain and dorsiflexion range of motion predict shortand mediumterm activity limitation in people receiving physiotherapy intervention after ankle fracture: an observational study. aus j physio. 2009; 55: 31-37. 10. van staa t.p, dennison e.m, leufkens h.g.m, cooper c. epidemiology of fractures in england and wales bone 2001 29, (6): 517–22. 11. jensen sl, andresen bk, mencke s. epidemiology of ankle fractures. a prospective population-based study of 212 cases in aalborg denmark. actaorthopaedicascandinavica. 1998; 69(1): 48-50. 12. thur ck, edgren g, jansson ka. epidemiology of adult ankle fractures in sweden between 1987 and 2004. a populationbased study of 91,410 swedish inpatients. actaorthop. 2012; 83(3):276-81. 13. www.bestpractice.bmj.com/bestpractice/monograph/385/basics/epidemiology.html. accessed on 10thjune 2015. 14. ameratunga s, hijar m, norton r. road-traffic injuries: confronting disparities to address a global-health problem. lancet. 2006; 367: 1533–40. 15. hunt kj, hurwit d. use of patient-reported outcome measures in foot and ankle research. j bone joint surg. 2013; 95(16): 1-9. 16. wronka k.s, salama h, ramesh b. management of displaced ankle fractures in elderly patientsis it worth perfomingosteosynthesis of osteoporotic bone. ortopediatraumatologiarehabilitacja. 2011; 3(6); 293-98. 17. dietrich a, lill h, engel t, josten c. conservative functional treatment of ankle fractures. arch orthop trauma surg. 2002; 122(3): 165-68. 18. makwana nk, bhowal b, harper wm, hui aw. conservative versus operative treatment for displaced ankle fractures in patients over 55 years of age. bone joint surg [br]. 2001; 83b: 525-29 19. ifesanya o.a, alonge o.t. operative stabilization of open long bone fracture: a tropical tertiary hospital experience nigeria medical journal. 2012; 53: 16-20. 20. breederveld rs, van straaten j, patka p. immediate or delayed operative treatment of fractures of the ankle. injury. 1988; 19(3):436-39. 21. rowley d.i, norris s.h, duckworth t. a prospective trial comparing operative and manipulative treatment of ankle fractures 2009; 68(1): 4-8. 22. clare mp. a rational approach to ankle fractures. foot ankle clin n am. 2008; 13: 593–610. 23. hancock mj, herbert rd, stewart m. prediction of outcome after ankle fracture. j orthop sports physther. 2005; 35(12): 786-92. 24. clements jr, motley ta, garrett a, carpenter bb. nonoperative treatment of bimalleolar equivalent ankle fractures. j foot ankle surg. 2008; 47(1): 40-45. 25. christopher bibbo. complications of ankle fractures in diabetic patients. ocna. 2001; 32(1): 113-16. 26. chaudhary sb, liporace fa, gandhi a, donley bg, pinzur ms, lin ss. complications of ankle fracture in patients with diabetes. j am acadorthop surg. 2008; 16(3): 159-70. 27. wukich dk, kline aj. the management of ankle fractures in patients with diabetes. j bone joint surg am. 2008;90(7): 1570-78. 195 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 original article hypomagnesaemia in acute exacerbation chronic obstructive airway disease; association with anthonisen’s levels of exacerbation javaira aziz1, muhammad amir2, abrar akbar3, sadia aziz4, nadia shams5, lubna meraj6 3 assistant professor, holy family hospital, rawalpindi. 4 national university of medical sciences, rawalpindi. rawalpindi. 5 professor of medicine, rawal institute of health sciences, rawalpindi. 6 associate professor, district headquarter hospital, rawalpindi. author’s contribution 1,4 conception of study 1 experimentation/study conduction 3 analysis/interpretation/discussion 2,6 manuscript writing 3 critical review 5,6 facilitation and material analysis corresponding author dr. nadia shams professor of medicine rawal institute of health sciences rawalpindi email: nadiashams@gmail.com article processing received: 23/08/2021 accepted: 24/01/2022 cite this article: aziz, j., amir, m., akbar, a., aziz, s., meraj, l. hypomagnesaemia in acute exacerbation chronic obstructive airway disease; association with anthonisen’s levels of exacerbation. journal of rawalpindi medical college. 30 jun. 2022; 26(2): 195201. doi: https://doi.org/10.37939/jrmc.v26i2.1758 conflict of interest: nil funding source: nil access online: abstract introduction: copd claims significant morbidity and mortality all globally. hypomagnesaemia has been observed in copd patients with acute exacerbations. this study aims at identifying hypomagnesemia as a predictor of copd exacerbations. this may minimize the exacerbations and hence the need for admission. materials and methods: the descriptive cross-sectional study was conducted at dhq hospital rawalpindi from 16 july 2016 to 15 jan 2017 after the ethical approval and informed consent. the indoor adult (> 18 years) diagnosed cases of copd exacerbation were included by consecutive sampling. patients with malignancy, pregnancy, and receiving magnesium supplements were excluded. demographic details were documented and after complete clinical evaluation, serum magnesium levels were assessed. serum magnesium < 1.80 mg/dl labeled hypomagnesaemia. data were analyzed by spss with a significant p< 0.05. results: amongst 176 patients; there were 93(52.8%) male patients and 83(47.2%) female copd patients. the mean age was 56+7 years. the mean duration of copd was 6.56 + 5.24 years (2-10 years). the mean height in the study was 181 +12 cm and the mean weight was 56.06 + 7.08 kg. the mean serum magnesium level was 1.5 + .49mg/dl. low serum magnesium (<1.8 mg/dl) was observed in 103(58.5%), and gender wasn’t associated with hypomagnesemia (p=0.294). hypomagnesaemia in accordance to types of anthonisen’s criteria was observed in 19(44.2%) with type i, 37(57.8%) with type ii, and 47(68.1%) with type iii copd exacerbation. hypomagnesaemia had a significant association with anthinosen’s levels of exacerbation (p=0.043). the mean age in patients with hypomagnesemia was 56.61+6.78 vs. 55.30+7.47 in patients without hypomagnesemia (p=0.228). conclusion: the study concludes that mean serum magnesium was significantly lower in acute exacerbation of copd (58.5%), particularly in type ii and iii. the serum magnesium should be performed in all copd exacerbations irrespective of gender and age. replacement of magnesium may be helpful in alleviating symptoms and reducing the frequency of exacerbations. keywords: copd, acute exacerbation, serum magnesium levels, hypomagnesaemia. 196 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 introduction chronic obstructive pulmonary disease (copd) is globally observed in developing as well as developed countries. the actual prevalence is much higher because copd is under-recognized so far, copd worldwide prevalence is from 4-10%. the numbers are still on the rise and by the year 2021, it is expected to be the third most common cause of mortality. approx. 70% of hospital admissions are estimated to be related to copd acute exacerbation. however, it is not clear from available data whether magnesium can be therapeutically used to minimize the exacerbations of copd. available data shows that hypomagnesemia is observed in patients with acute exacerbations as compared to copd patients in the usual state of stable health.1 chronic obstructive pulmonary disease (copd) has two phenotypes i.e., emphysema and chronic bronchitis, they represent nearly 98% of the deaths. an italian study showed one out of four people ranges from 65–84 years suffered from a respiratory problem like copd or asthma, which coexist in a significant proportion. between 2006 and 2010, copd/emphysema remained the most common cause of mortality, i.e., 78.6% and 84.8% deaths in women and men, respectively, followed by chronic bronchitis.3 approx. 70% of the health expenditure is attributed to indoor admissions because of acute copd exacerbations.1 copd bears significant importance in view of its impacts on health facilities. limited studies have been conducted addressing the factors associated with indoor admission due to acute exacerbations. earlier studies showed certain factors associated with multiple admissions include age, the fev1 (i.e., the forced expiratory volume in one second), the duration of disease, certain psycho-social factors, physical endurance and quality of life, and past medical history and presence of hypercapnia. most of these abovementioned factors are non-modifiable and hence limited intervention is possible. there is ambiguity in the role of hypomagnesemia in acute exacerbations of copd. studies have demonstrated that the patients with copd exacerbations had low serum magnesium levels as compared to copd patients who were in the usual state of health and were stable otherwise. hypomagnesaemia has been found to be associated with the severity of respiratory disorders. this indicates that magnesium has a relevant role in decompensation of the respiratory illness.1 the exacerbation of copd-related admissions leads to poor quality of life, a decline in respiratory reserve, and a financial burden on the patient and healthcare system.2 treatment of these episodes includes rapidly reversing airway obstruction by decreasing bronchoconstriction and inflammation. guidelines and recommendations build stepwise approaches to management, with the mainstay of therapeutic interventions involving bronchodilators and sometimes including systemic corticosteroids, oxygen, antibiotics, and other treatments, depending on the severity of exacerbation. future therapies are evolving that target inflammatory processes and may improve efficacy and potential disease-modifying effects. magnesium (mg2) plays a vital character in the functioning of vital organs including the heart, neurological system, and skeletal muscles. in addition, magnesium has been found to have a role to reduce inflammation. the recommended intake of mg2 advised by the food and nutrition board of the usa is 420 mg for males and 320 mg for females per day. however, a significant number of people are mg2 deficient and may comprise up to 60% of critically ill patients. mg2 deficiency is measured ranges between 0.7-1.05 mmol/l in a healthy person. the study established that patients with hypomagnesemia were 3 times as likely to be hospitalized as compared to patients with normal serum magnesium concentrations. the use of magnesium sulphate has been proven to be of benefit in several pulmonary and extrapulmonary conditions. these include acute exacerbation of asthma, preeclampsia, cardiac arrhythmias (e.g., torsade de pointes, atrial fibrillation), cardiac arrest, and advanced life support. magnesium can be administered via various routes including intravenous, nebulization, or inhalation. the interesting explanation of the role of magnesium is that it may act during the “therapeutic gap” that exists between the short-acting and intermediate-acting medications i.e., bro nebulized bronchodilators and corticosteroids. a wide range of doses can be given from 1.2g to 6g depending upon various conditions. the magnesium can’t be given in judicious amounts via nebulization to avoid administering a hypertonic nebulized solution. also, the β2-agonists are preferred and immediately required in acute exacerbation of asthma and copd and preferred at initial presentation.6 there is limited data available addressing the reasons, contributing factors, and associated conditions of exacerbation and admission in copd cases. certain factors can be identified and relevant interventions 197 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 may help in preventing frequent exacerbations. current research may help us establish hypomagnesemia as a predictor of copd exacerbation. this may help us determine intervention measures other than the conventional therapies for copd hence improving the quality of life, morbidity, and mortality of copd cases. materials and methods the descriptive cross-sectional study was conducted at medicine department, dhq hospital rawalpindi from 16 july 2016 to 15 jan 2017(6 months). the study approval from the institutional research forum and ethics committee of rmc was taken followed by permission from hospital authorities. the sample size was calculated using the who sample size calculator formula keeping a 95% confidence level, 7% absolute precision, and 34% expected hypomagnesemia in patients with acute exacerbation from the reference study; the minimally required sample size was calculated to be 176.6 this study aims to determine the frequency of hypomagnesaemia in patients of acute exacerbation of copd. operational definitions: 1. hypomagnesaemia: normal range for serum magnesium levels: 1.8-2.4 mg/dl (0.74-0. 99mmol/l)1, hypomagnesaemia: serum magnesium below 1.80mg/dl/ 2. acute exacerbation of copd is defined as an acute worsening of respiratory symptoms which includes increased dyspnea, increased cough, or change in amount and purulence of sputum that is beyond the normal day-to-day variations of symptoms.2 3. anthonisen’s criteria1: type iall three symptoms (increased sputum volume, purulence, and increased dyspnea) type iiany two symptoms present type iii: one symptom plus one of the following: upper respiratory tract infection in last 5 days, increased cough, increased wheeze, fever without obvious source, 20% increase in respiratory rate, heart rate above baseline. inclusion criteria: patients fulfilling the criteria of exacerbation of copd were selected by nonprobability consecutive sampling technique and informed written consent was obtained. confirmed cases of copd, presenting with acute exacerbation according to anthonisen’s criteria, age > 18 years of both genders. exclusion criteria: patients with the following associated conditions which can be a separate risk factor for electrolyte imbalance were excluded. gastrointestinal disease (malabsorption syndrome, peptic ulcer disease, pancreatitis, severe diarrhea), pregnancy or lactation, endocrine disease (diabetes mellitus, hypothyroidism, hyperthyroidism), renal failure, drugs (thiazide diuretics, loop diuretics), malignancy, alcoholism. baseline characteristics of patients like age, gender, weight, height, and body mass index (bmi), were noted down on the special proforma for the study. the patients were clinically evaluated and laboratory/ radiological investigations were performed as per recommendation in each case. the blood samples were drawn, i.e., 4cc of serum was assessed for serum magnesium levels in the uniform lab and verified by a pathologist. serum magnesium levels below 1.80 mg/dl were labeled as hypomagnesemia. all the collected data were entered and analyzed using the statistical package of social sciences (version 22). quantitative data (i.e., age, weight, height, duration of copd, and serum magnesium levels were presented as mean and standard deviation. qualitative data (i.e., gender, type of copd, the status of hypomagnesemia) was presented as frequency and percentages. the independent sample’s t-test was applied to study the association of hypomagnesemia with various variables. p-value < 0.05 considered statistically significant. results a total of 176 patients were included having a mean age of 56 + 7 years with a range from 49 to 63. there were 93(52.8%) male and 83(47.2%) female cases with copd exacerbation. the mean duration of copd was 6.56 + 5.24 years (2-10 years). the mean height in the study was 181 +12 cm with a range from 169-193 cm. mean weight was 56.06 + 7.084 kg. out of 176 patients 73 (41.5%) patients had serum magnesium levels > 1.8 mg/dl (42 males and 31 females), while 103 patients (58.5%) had serum magnesium levels < 1.8 mg/dl (51 males and 52 females) (table 3). serum magnesium levels in accordance with types of anthonisen’s criteria are as follows. serum magnesium levels were > 1.8mg/dl in 24 and < 1.8mg/ dl 19 in patients with type i criteria. similarly, levels were >1.8mmg/dl in 27 and < 1.8mg/dl in 37 type ii patients. levels were > 1.8mg/dl in 22 and < 1.8 mg/dl in 47 patients with type iii (table 4). there was a significant association between low serum magnesium levels and 198 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 anthonisen’s criteria types (p=0.04). however, there wasn’t any association between hypomagnesemia and gender (p=0.294). the mean serum magnesium level was 1.83 + 0.26mg/dl amongst 176 cases of copd exacerbation. with respect to anthonisen’s types, mean magnesium level was 1.904 + 0.278 mg/dl in type i, 1.839 + 0.272 mg/dl in type ii and 1.792 + 0.238 mg/dl in type iii exacerbation cases (table 3). similarly, effect modifier like age stratification and duration of copd was also compared. the patient's age ranges from 55.81+8.61 years in type i, 54.95+7.02 years in type ii, and 57.3±5.91 years in type iii. the serum magnesium levels weren’t associated with age stratification (p= 0.72). table 1: descriptive statistics of age, weight(kg), height (cm), duration of copd, serum magnesium levels (n=176) s. no descriptive statistics mean +std. deviation range 1 age (years) 56.06 + 7.08 40-74 2 height (cm) 181.312 + 12.62 169-193 3 weight (kg) 56.0682 + 7.084 41-94 4 duration of copd (years) 6.56 + 5.24 2-10 5 serum magnesium levels(mg/dl) 1.5852 + 0.494 1.5-2.4 table 2: presenting hypomagnesaemia in relation to gender, age, and anthonisen’s criteria in patients with acute exacerbation of copd (n=176) (test of significance *chi-square test, **student t-test; significant p<0.05) table 3: the quantitative serum magnesium levels with respect to anthonisen’s type i, ii & iii anthonisen’s types n (%) n=176 mean serum magnesium standard deviation  type i 43 (24.4%) 1.904 0.278  type ii 64 (36.4%) 1.839 0.272  type iii 69 (39.2%) 1.792 0.238 among all cases 176 (100%) 1.836 0.263 figure 1: pie chart showing percentages of anthonisen’s criteria based types of copd exacerbation in admitted cases (n=176) variable among all n=176 s. magnesium< 1.8mg/dl n=103 s. magnesium >1.8mg/dl n=73 p-value gender  male  female 93(52.8%) 83(47.2%) 51(54.8%) 52(62.7%) 42(45.2%) 31(37.3%) **0.294 age (years) (mean+sd) 56.06+7.08 (40-74) 56.61+6.78 (42-74) 55.30+7.47 (40-72) **0.228 anthonisen’s criteria  type i  type ii  type iii 43(24.4%) 19(44.2%) 24(55.8%) *0.043 64(36.4%) 37(57.8%) 27(42.2%) 69(39.2%) 47(68.1%) 22(31.9%) 199 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 discussion the current study identifies a significant association of hypomagnesemia with copd exacerbation. more than half of the cases with copd exacerbation (i.e., 58.5%) had low serum magnesium levels. magnesium levels are considered a risk factor for copd exacerbation as well as have potential therapeutic benefits as well. this concept isn’t new while considering its role in respiratory diseases as magnesium has been used in the management of asthma exacerbations as well as status asthmaticus for almost a century.7 the possible explanation is the role of magnesium in muscle tone hence preventing fatigue and exhaustion during exacerbations. additionally, magnesium has a relaxation effect on the bronchial smooth muscles. certain mechanisms like the calcium channel blocking property of magnesium, the inhibition of cholinergic neuromuscular junction, and desensitization of neuromuscular junction to acetylcholine are considered as a mode of action of magnesium. additionally, magnesium has some disease-modifying properties like stabilization of the mast cells and tlymphocytes and activation of nitric oxide and prostacyclin.8 the pulmonary function and lung reserve vary according to the severity of exacerbations in view of relative airflow obstruction. the poor quality of life in copd cases is associated with a higher admission rate and a need for assistance. multiple copd exacerbations are managed at home also, by the patient himself and his family, or by local healthcare facilities. exacerbations have a pivotal role in the progression of the natural history of copd. the rapid decline in lung function is seen in patients having frequent episodes of exacerbations. also, these patients are found to have a poor quality of life, limited physical endurance, and increased inflammation and damage to the lungs. this also provokes high rates of infections including community-acquired, opportunistic infections, or hospital-acquired infections. the mean age of patients in our study was fifty-six years, the youngest case being forty-nine years and the eldest being sixty-three years old. in comparison, the study conducted by robert et al10 had a wide range of age groups i.e., from 27 to 102 years. robert et al found only 2% of cases below 50 years of age, 9% between 50-59 years of age, and the rest 89% above 60 years of age. we had the eldest case being 63 years old. this could be because of comparatively lower life expectancy in our county as compared to the west. however, we observed that type iii exacerbations had a higher mean age i.e., 57 years as compared to type i and ii exacerbations with mean ages of 55 and 54 years. regarding gender, we had an almost equal number of male and female cases, i.e., 53% males and 47% females. copd has been perceived as a disease in older men for ages. research shows that there is a male predominance in copd cases, i.e., 9% in men and 6% in women.11 this could be linked to the increased prevalence of smoking in men. however, recent data shows the rising prevalence of copd and associated mortality in females.12 certain mechanisms are implemented in this including increased susceptibility to tobacco smoking in women, hormonal differences, response to therapy, and exposure to domestic pollutants and smoke.13 these could be the reasons for a higher number of females presenting with exacerbations in this study. most of our cases presented as anthonisen’s type iii (39%) cases, followed by type ii (36%) and type iii (24%). ejiofer et al14 conducted research on 46 cases with alpha one antitrypsin-associated copd. he concluded that the maximum number of patients presented treated for copd exacerbations presented with type iii (43.6% cases) as compared to type ii and i. hence, a higher number of patients with dyspnea as a predominant symptom received treatment as compared to patients with changes in sputum volume (16.6%) or purulence (6.2%). we also had a higher number of cases presenting with type iii exacerbations which agrees with data of a study by ejiofer et al. hypomagnesemia was observed in more than half cases (58.5%). with respect to anthonisen’s types. more type ii and iii cases had hypomagnesemia, however more of the type i cases had normal magnesium levels. the reason for depletion of magnesium levels in stages ii and iii are characterized by chronic respiratory insufficiency and hypoxemia as well. a recent study conducted by tamizh et al15 upon 100 copd cases admitted from 2018-2020 with aecopd found significant improvement in serum magnesium levels from admission to discharge and recovery. the mean serum magnesium levels at admission were 1.287 vs. 2.009 mg/dl at discharge. we found mean serum magnesium of 1.836 mg/dl upon admission. the authors recommend further studies with follow-up of serum magnesium levels after recovery. the current guidelines recommend that copd has to be managed as a stepwise approach. the various 200 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 therapeutic options include oxygen inhalation, nebulization with β2 agonists and anticholinergic drugs, corticosteroids, antibiotics, and mechanical or non-invasive ventilation in severe cases. the bronchodilators act within minutes and provide instant relief, whereas the corticosteroids have extended action over several hours with delayed onset and longer half-life. this difference is considered the “therapeutic gap” that creates a potential space for magnesium sulphate (mgso4) as an additional treatment option. the mgso4 can be administered via intravenous and nebulized forms. the nebulized route is superior, the reason being the potential advantage of a rapid onset of action and decreased chances of systemic side effects. on the other hand, certain disadvantages include lesser bioavailability of drug delivered as compared to the intravenous route. also, it depends on the respiratory effort of the patient to inhale the drug. the intravenous route provides direct access to the venous system, thus allowing high drug concentrations in circulation. disadvantages include the requirement for intravenous access via cannula or infusion pump followed by administration of magnesium in specific dilution as an intravenous infusion at a particular rate.10 the significant hypomagnesemia in our patients with aecopd supports the possible role of magnesium diagnostically as a predictor of severity as well as therapeutically. each new exacerbation of copd adds to the risk of complications and death. the facts and figures predict that by the next two decades, the expiry rates due to copd exacerbations will rise by > 160%. smoking has been considered a major risk factor for copd, however current data shows that approx. 30% of copd cases had no smoking history during their lifetime. such patients might have other exposure like passive smoking, indoor air pollution, fumes or smoke from wood burning, and biomass fuels like animal dung or crop residues.16 our study has an appropriate sample size of 176 cases with aecopd. there is still limited data addressing non-conventional therapeutic options of aecopd and the current study may be considered thoughtprovoking in this context. we were unable to evaluate active and passive smoking in our cases i.e., considered to be a limitation of our study. also, the authors recommend further interventional regional studies to assess the impact of magnesium replacement in aecopd in terms of recovery, mortality reduction, and quality of life. conclusion the study concludes that the mean serum magnesium level is significantly lower in cases of copd with acute exacerbation, i.e., more than half of the cases in this study. the types of anthonisens criteria, in particular, type ii and ii have a significant association with hypomagnesemia. magnesium levels should be performed in all copd exacerbations irrespective of gender and age. we may conclude that screening and replacement of magnesium may help alleviate symptoms and reduce the frequency of exacerbations in patients with copd. references 1. s. p. bhatt, p. khandelwal, s. nanda, j. c. stoltzfus, and g. t. fioravanti, “serum magnesium is an independent predictor of frequent readmissions due to acute exacerbation of chronic obstructive pulmonary disease,” respiratory medicine, vol. 102, no. 7, pp. 999–1003, 2008 2. yamada m, ichinose m. cutting edge of copd therapy: current pharmacological therapy and future direction. copd research and practice. 2015 oct 2;1(1):5. 3. pesce, giancarlo. “mortality rates for chronic lower respiratory diseases in italy from 1979 to 2010: an age–period– cohort analysis.” erj open research 2.1 (2016): 00093–2015. pmc. web. 2 apr. 2017. 4. skrepnek gh, skrepnek sv. an assessment of therapeutic regimens in the treatment of acute exacerbations in chronic obstructive pulmonary disease and asthma. am j manag care. 2004 jul 1;10(s5). 5. de baaij jhf, hoenderop jgj, bindels rjm. magnesium in man: implications for health and disease. physiol rev 2015; 95: 1–46. 6. lum g. hypomagnesemia in acute and chronic care patient populations. american journal of clinical pathology. 1992 jun 1;97(6):827-30 7. kew km, kirtchuk l, michell ci. intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. cochrane database of systematic reviews. 2014(5). 8. shah ba, naik ma, rajab s, muddasar s, dhobi gn, khan aa, banday ka, baba s. serum magnesium levels in exacerbation of copd: a single centre prospective study from kashmir, india. jms skims. 2010 jun 21;13(1):15-9. 9. donaldson gc, law m, kowlessar b, singh r, brill se, allinson jp, wedzicha ja. impact of prolonged exacerbation recovery in chronic obstructive pulmonary disease. american journal of respiratory and critical care medicine. 2015 oct 15;192(8):943-50. 10. robert a. stone, derek lowe, jonathan m. potter, rhona j. buckingham, c. michael roberts, nancy j. pursey, managing patients with copd exacerbation: does age matter?, age and ageing, volume 41, issue 4, july 2012, pages 461–468, https://doi.org/10.1093/ageing/afs039 11. ntritsos g, franek j, belbasis l, et al. gender-specific estimates of copd prevalence: a systematic review and metaanalysis. int j chron obstruct pulmon dis. 2018;13:1507-1514. published 2018 may 10. doi:10.2147/copd.s146390 201 journal of rawalpindi medical college (jrmc); 2022; 26(2): 195-201 12. aryal s, diaz-guzman e, mannino dm. influence of sex on chronic obstructive pulmonary disease risk and treatment outcomes. int j chron obstruct pulmon dis. 2014; 9():1145-54. 13. buist as, vollmer wm, sullivan sd, weiss kb, lee ta, et al. the burden of obstructive lung disease initiative (bold): rationale and design. copd. 2005 jun; 2(2):277-83. 14. ejiofor si, stolk j, fernandez p, stockley ra. patterns and characterization of copd exacerbations using real-time data collection. int j chron obstruct pulmon dis. 2017;12:427434.https://doi.org/10.2147/copd.s126158 15. selvan t, rao r, priyasamy. a study of serum magnesium levels in acute exacerbation of chronic pulmonary disease on admission and at the time of discharge. j med sci clinical reseacrh. 2020: 8(11); https://dx.doi.org/10.18535/jmscr/v8i11.64. 16. kalagouda mahishale v, angadi n, metgudmath v, lolly m, eti a, khan s. the prevalence of chronic obstructive pulmonary disease and the determinants of underdiagnosis in women exposed to biomass fuel in india-a cross section study. chonnam medical journal. 2016 ;52(2):117-22 summary journal of rawalpindi medical college (jrmc); 2017;21(1): 23-28 23 original article risk factors of subependymal hemorrhage-intraventricular haemorrhage in preterm infants gulbin shahid 1,mahmood jamal 2, yasir bin nisar 3 1.department of paediatric medicine, children’s hospital, pakistan institute of medical sciences, islamabad ;2. department of paediatrics,islamabad medical and dental college, islamabad; 3. public health division , who, geneva. abstract background: to determine the frequency and peak time of occurrence of subependymal hemorrhage intraventricular hemorrhage (seh-ivh) in preterm infants and to identify the predisposing risk factors. methods: in this descriptive study consecutive live born babies (n=135), between the gestational ages of 28-34 weeks, were enrolled. information regarding weight, gestational age, mode of delivery and presence of risk factors were recorded. each newborn underwent cranial ultrasound on designated days and was followed up till the fourth week of life unless expired. results: the frequency of seh-ivh was found to be 20.8%. the most vulnerable group in terms of gestational age and weight were infants < 32 wks and weighing < 1.5 kg respectively. the peak age of occurrence of seh-ivh was first three days of life. risk factors found to be associated with seh-ivh were rds with ventilation, exchange transfusion and thrombocytopenia. conclusion: the incidence of seh-ivh in infants between 28-34 wks gestation is significantly high. the crucial period is the first three days of life and respiratory distress syndrome (rds) with ventilation, exchange transfusion and thrombocytopenia carry the highest risk of hemorrhage. there is a need to emphasize on the prevention of prematurity and optimum perinatal management to minimize the risk of hemorrhage. key words: subependymal hemorrhageintraventricular hemorrhage, premature infants. introduction subependymal haemorrhage intraventricular hemorrhage is one of several complications associated with prematurity and carries significant morbidity and mortality. it is principally a problem of very low birth weight infants i.e. infants weighing less than 1.5kg and also those delivered before 32-34wks of gestation.1-4 with improved obstetric and perinatal management, the incidence of seh-ivh has shown a significant decline. 5-10 tertiary centres currently report an incidence between 20-25% in infants born before 34 wks of gestation with figures rising with decreasing weight and gestational age.2,4,11-25the incidence of ivh in premature infants between 500g-749g is still very high and is approximately 45% . 26 upto 90% of ivh cases evolve in the first 72 hours of postnatal life; 30% in the first 6 hours, 40-60% in the first 24 hours and 60-80% within 48 hours27-30 hemorrhage on or after the fourth day of life occurs in 10% of all preterm infants with ivh.1intraventricular hemorrhage has been extensively documented in preterm newborns with respiratory distress syndrome requiring mechanical ventilation.10,18,31-33 other well recognized risk factors for ivh include asphyxia, hypercarbia, rapid volume expansion, routine care taking maneuvers, patent ductus arteriosus, high concentration of inspired oxygen, pneumothorax, seizures,anemia, low blood glucose, platelet and coagulation defects.1,18,31-42 better understanding of the pathogenesis of ivh has led to several therapeutic interventions aimed at counteracting the known risk factors. many such interventions like use of antenatal steroids and careful ventilator management have demonstrated a significant reduction in the incidence of ivh.43-49in developing countries incidence has been reported to be between 28%-75%.50-54 more recent data also shows a very wide range between 9%-64.4%.27, 55-62 patients and methods this non-interventional, descriptive, analytic study was carried out in the department of neonatology, children’s hospital, pakistan institute of medical sciences (p.i.m.s), islamabad from september 2002 to january 2003. during the study period, all consecutive live births delivered at the mch centre with gestational ages between 28-34 weeks were enrolled. weight was measured without clothes and grouped under four categories, namely 0.75kg-1kg, 1.1kg-1.5kg, 1.6kg-2.0kg, and >2.0kg. gestational age was estimated by dates i.e. last menstrual period or antenatal ultrasound if performed. in the absence of aforementioned information, dubowitz scoring was used for estimating the gestational age.63 groups assigned for gestational age were 28 wks, 29-30 wks, journal of rawalpindi medical college (jrmc); 2017;21(1): 23-28 24 31-32 wks and 33-34 wks. babies with gestational age <28 weeks, with weight <750gms and with lethal malformations were excluded from this study. cranial ultrasonography of selected patients was performed. images were obtained through the anterior fontanelle in both coronal and right and left parasagittal planes. every enrolled infant was followed up for 28 days or till death if earlier. thirteen babies, without ivh on the first two visits,failed to report for 3rd cranial ultrasonography on the designated days. they were reported as well on telephone by parents. these infants underwent cranial ultrasound examination at least three times, (0-3, 7-10, 21-28 days). admitted babies, however, had daily ultrasounds till they were discharged or expired. in addition to this, ultrasound was also done whenever clinical indications like abrupt fall in hematocrit, shock, bulging fontanel,i.e., change in the level of consciousness or change in the respiratory support without any other explanation, appeared at any time during admission. ivh was classified into four grades (gd. i-iv) according to the system of grading reported by papile; gd i-isolated seh, gd ii-rupture into ventricle but no ventricular dilatation, gd iii-rupture into ventricle with ventricular dilatation andgd iv-ivh with parenchymal extension.64 risk factors were defined according to standard recommendations and protocols used in the neonatal unit.sample size was calculated by using statcalc of software epiinfo version 6.0 by using descriptive study, random, non-cluster sampling technique. by keeping the population size as 400 (estimated annual deliveries in mch at the time with gestation of 28-34 weeks) and expected frequencies as 25% and worst expected being 20%, with confidence level of 95%, a sample size of 135 was calculated.univariate and multivariate analysis was carried out for risk factors to determine their effect on seh-ivh and odds ratio with 95% confidence interval were calculated by keeping p-value of < 0.05 as significant. results of these 135 babies with gestational age of 28-34 weeks, 60% were male and 40% were females. the mean gestational age was 31.42.05 weeks. the mean birth weight of study population was 1.590.42 kg.two third of babies were delivered by svd whereas about 1/3rd (30%) were delivered through csection (table 1).of the total 135 babies, 28 babies were found to have seh-ivh on ultrasonography during their neonatal period. eight babies each had grade i and grade ii bleed while 5 babies had grade iii and seven had grade iv bleed. three fourth (21) of the babies developed seh-ivh during the 1st three days of life. of these, again, the majority i.e. 12 out of 21 babies had seh-ivh within 1st 24 hours of life. almost all seh-ivh occurred within the 1st week of life with the exception of one, where the bleeding occurred on 14th day of life (table 2;figure 1).two of the studied risk factors i.e. birth asphyxia and hypoglycemia were not found to be associated with seh-ivh, while all others including rds, mechanical ventilation, hypoxia, pda, high fio2, exchange transfusion, anemia and thrombocytopenia were found to be significantly associated with seh-ivh (table 3). thrombocytopenia carried the highest odds ratio, however, rds with ventilation, exchange transfusion and thrombocytopenia retained their significance independently in multivariate logistic regression (stepwise) model (table 4). table 1: comparison of demographic factors of premature infants with and without sehivh (n = 135) variables seh-ivh (n = 28) no sehivh (n = 107) or (95%ci) , p-value sex male female 19 (67.9%) 9 (32.1%) 63 (58.1%) 44 (41.1%) 1.47(0.57-3.91) 0.51 gestational age median mean + sd 28 wks 29 to 30 wks 31 to 32 wks 33 to 34 wks 31.0 30.0 + 2.0 2 (2.1%) 11 (39.3%) 9 (32.1%) 6 (21.5%) 32.0 31.6 + 2.0 5 (4.7%) 27 (25.2%) 28 (26.2%) 47 (43.9%) 1.57(0.21-9.95) 0.96 1.92 (0.73–5.00) 0.21 1.34 (0.49-3.58) 0.69 0.35 (0.12-1.00) 0.05 weight (kg) median mean + sd 0.75 to 1.0 kg 1.1 to 1.5 kg 1.6 to 2.0 kg more than 2.0 kg 1.26 1.45+0.40 1 (3.6%) 17 (60.6%) 5 (17.9%) 5 (17.9%) 1.64 1.63 + 0.40 8 (7.5%) 42 (39.3%) 38 (35.5%) 19 (17.7%) 0.46(0.02-3.91) 0.75 2.39 (0.95-6.12) 0.06 0.39 (0.12-1.22) 0.11 1.01 (0.29-3.28) 0.79 mode of delivery svd c-section forceps 18 (64.3%) 9 (32.1%) 1 (3.6%) 73 (68.2%) 32 (29.9%) 2 (1.9%) 0.84 (.32-2.20) 0.86 1.11 (0.41-2.94) 0.99 1.94 (0.00-28.9) 0.86 journal of rawalpindi medical college (jrmc); 2017;21(1): 23-28 25 0 10 20 30 1 to 3 days 4 to 7 days more than a week 21(75.0%) 6 (21.4%) 1 (3.6%) f r e q u e n c y age of premature infant fig 1: relationship of age with seh-ivh of these, the babies on assisted ventilation with rds carried the highest risk of seh-ivh closely followed by babies undergoing exchange transfusion and thrombocytopenia. other risk factors like hypoxia, high concentration of o2, pda, and anemia lost their significance in multivariate logistic regression analysis.out of these 28 infants, 20(71.4%) expired and only 8(28.3%) were either discharged or remained admitted beyond 28 days of life. of this mortality group, majority (12) had grade iii and grade iv bleed while only three babies with grade i seh-ivh expired during their stay in the hospital. table 2: frequency of seh-ivh on days of life(n = 28) age in days number percentage first day 12 42.8% second day 5 17.8% third day 4 14.3% fourth day 1 3.6% fifth day 4 14.3% sixth day 1 3.6% fourteenth day 1 3.6% discussion the most common form of brain injury in the premature infant is subependymal hemorrhageintraventricular hemorrhage.most tertiary care centres from the united states, australia and other developed countries currently report an incidence between 2025% in infants born before 34 wks of gestation.2, 4, 11-18 data from the developing countries shows a wide range of incidence of ivh in premature infants.generally the incidence is very high primarily because of lack of optimum obstetric and perinatal care.53 table 3: predisposing factors associated with seh-ivh in premature infants (n = 135) variable sehivh (n = 28) n0 sehivh (n = 107) x2 df or (95% ci), p-value birth asphyxia 5 (17.9%) 6 (5.6%) 2.96 1 3.66(0.8715.2), 0.08 rds 12(42.9%) 19 (17.8%) 6.55 1 3.47(1.299.37) 0.01 mechanical ventilation 18(64.3%) 15 (14.0%) 27.7 1 11.04(3.9132.0) <0.00001 hypoxia 14(50.0% 18 (16.8%) 11.74 1 4.94(1.8413.39) <0.00001 pda 3 (10.7%) 1 (0.9%) 4.37 1 12.72(1.10331.79) 0.03 high concentra tion of inspired o2 12(42.9%) 12 (11.2%) 13.11 1 5.94(2.0617.34) <0.00001 exchange transfusion 15(53.6%) 21 (19.6%) 11.40 1 4.73(1.7912.57) <0.00001 anemia 6 (21.4%) 6 (5.6%) 5.04 1 4.59(1.1718.18) 0.02 hypoglycemia 6(21.4)%) 8 (7.5%) 3.27 1 3.38(0.9212.23) 0.07 thrombocytope nia 11(39.3%) 3 (2.8%) 27.97 1 22.43(5.93114.5) <0.00001 table 4: risk factors for seh-ivh in premature infants by using multivariate logistic regression risk factors or (95% ci) p-value rds with ventilation 8.21 (2.30 – 28.33) < 0.00001 exchange transfusion 7.79 (2.00 – 29.09) 0.003 thrombocytopenia 5.09 (1.70 – 14.98) 0.002 the most vulnerable group in present study were infants between 28-32 weeks gestation. this inverse relationship between gestational age and seh-ivh is expected and in accordance with other studies. dolfin et al reported a significant difference between the incidence of seh-ivh in infants whose gestational age was less than or equal to 29 weeks compared to infants between 30-34 weeks gestation. among infants less journal of rawalpindi medical college (jrmc); 2017;21(1): 23-28 26 than or equal to 29 weeks gestational age 56% had seh-ivh while only 8% had bleed in the gestational group of 32-34 weeks.66 it was seen in the present study that babies between 1.6-2.0 kg had an incidence of ivh of only 12% increasing to 30% in infants between 1.1-1.5 kg. this increasing trend in the frequency with decreasing weight was expected and in accordance with other studies. however, the prevalence of seh-ivh for infants between 750 gms to 1.0 kg was rather low (11%) in our study because very few babies fell in this group (7% of study population). it was observed that babies > 2 kg did not follow the inverse relationship between weight and frequency and showed a relatively higher incidence (21%). this can be explained by the fact that these babies had other risk factors in addition to being premature. the most vulnerable group prone to seh-ivh are infants weighing 1.5 kg or less and the incidence increases with decreasing birth weight.26,51,67 studies revealed that more than 95% of the bleeds occurred during the first week of life. 60,66,69,70 factors found to be significantly associated with sehivh by univariate analysis were respiratory distress syndrome, artificial ventilation, hypoxia, high concentration of inspired oxygen, patent ductus arteriosus, exchange transfusion, anemia and thrombocytopenia. two of the study risk factors i.e. birth asphyxia and hypoglycemia were not found to be associated with seh-ivh. on multivariate logistic model, only three factors retained their significance independently. these factors included rds requiring artificial ventilation, exchange transfusion and thrombocytopenia. of these, the babies on assisted ventilation with rds carried the highest risk of sehivh closely followed by babies undergoing exchange transfusion and thrombocytopenia. other risk factors like noxious stimulation during routine care giving maneuvers, tracheal suctioning, rapid infusion of colloid, infusion of hyperosmolar solutions like sodium bicarbonate and coagulation disturbances.70-75 the pathogenesis of seh-ivh is complex and multifactorial and influenced by intravascular, vascular and extravascular factors. the optimum mode of delivery for preterm infants at risk for seh-ivh is controversial. no consistent advantage has been documented with operative delivery compared with the vaginal route.76, 77 severe forms of seh-ivh i.e. grade iii and grade iv, carry a high mortality and morbidity. in the present study 71.4% of infants with seh-ivh died whereas only 28.6 were either still admitted or discharged. none of the infants with grade iii and grade iv bleeds survived whereas the mortality for grades i & ii was 37.5% and 62.5%respectively. this mortality is very high compared to that reported by murphy.78 in his study he categorized the mortality of different grades according to the weight of the preterm infants. mortality of infants <750gms was12%, 24%, 32% and 45% for grades i-iv respectively whereas for infants between751-1500gms (weight more comparable to our study) it was o%,2%,8%and 22%. this difference can be explained by better neonatal facilities available in the developed countries. conclusions 1. almost 1/5th of the babies between 28-34 weeks gestation developed bleed, a significantly high prevalence. this incidence increased with a decrease in gestational age and weight. 2. rds with ventilation, exchange transfusion and thrombocytopenia were found to be major risk factors. 3. the peak time of occurrence of bleed was first three days of life with, first 24 hours being the most crucial. 4. resource availability appears to influence aggressiveness of intervention and survival. within our constraints, a number of interventions are possible to tackle the issue. 5. antenatal steroids, careful management of premature deliveries, appropriate post-partum resuscitation, prevention of hypoxia and hypoglycemia, avoidance of hypertonic solutions like sodium bicarbonate, adequate control of seizures and gentle handling of small preterm babies are some of the factors easily applicable in all places caring for such infants. references 1. volpe jj. germinal matrix-intraventricular hemorrhage. in: volpe jj, editor. neurology of the newborn, pa: saunders elsevier; 2008:517-88. 2. kuban kck. intracranial hemorrhage. in: cloherty jp, stark ar. manual of neonatal care. 4th ed. philadelphia: lippincott raven, 1998:505-14. 3. volpe jj. brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. seminars in pediatric neurology, 1998;(5:3):135-51. 4. bolisetty s, legge n, bajuk b, lui k. preterm infant outcomes in new south wales and the australian capital territory. journal of paediatrics and child health. 2015 51(7):713-21. 5. ahmann pa, lazzara a, dykes fd, brann aw. intraventricular hemorrhage in the high‐risk preterm infant: incidence and outcome. annals of neurology. 1980 ;7(2):118-24. 6. papile la, burstein j, burstein r. evolution of subependymal and intraventricular hemorrhage: a study of infants with low birth weight. journal of pediatrics, 1978;92(4):529-34. journal of rawalpindi medical college (jrmc); 2017;21(1): 23-28 27 7. holt pj and allan wc. the natural-history of ventricular dilatation in neonatal intraventricular hemorrhage and its therapeutic implications.ann neurol 1981;10:293-96. 8. levene mi, wigglesworth js, dubowitz vi. cerebral structure and intraventricular hemorrhage in the neonate: a real-time ultrasound study. archives of disease in childhood. 1981 ;56(6):416-24. 9. philip ag, allan wc, tito am, wheeler lr. intraventricular hemorrhage in preterm infants: declining incidence in the 1980s. pediatrics. 1989 ;84(5):797-801. 10. roland eh and hill a. intraventricular hemorrhage and posthemorrhagic hydrocephalus. current and potential future interventions. clinics in perinatology, 1997;24(3):589-605. 11. davis jm, parad rb, michele t. pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human cuzn superoxide dismutase. pediatrics. 2003;111(3):469-76. 12. horbar jd, badger gj, carpenter jh, fanaroff aa. trends in mortality and morbidity for very low birth weight infants, 1991–1999. pediatrics. 2002;110(1):143-51. 13. cust ae, darlow ba, donoghue da. outcomes for high risk new zealand newborn infants : a population based, national study. archives of disease in childhood,2003 ;88(1):15-22. 14. larroque b, marret s, ancel py. white matter damage and intraventricular hemorrhage in preterm infants. journal of pediatrics. 2003 ;143(4):477-83. 15. hamrick se, miller sp, leonard c. trends in severe brain injury and neurodevelopmental outcome in premature newborn infants. journal of pediatrics, 2004;145(5):593-99. 16. jain nj, kruse lk, demissie k. impact of mode of delivery on neonatal complications. journal of maternal-fetal & neonatal medicine. 2009;22(6):491-500. 17. mccrea hj and ment lr. the diagnosis, management, and postnatal prevention of intraventricular hemorrhage in the preterms. clinics in perinatology. 2008;35(4):777-92. 18. ballabh p. intraventricular hemorrhage in premature infants: mechanism of disease. pediatric research, 2010 ;67(1):1-8. 19. wilcox aj and skjaerven r. birth weight and perinatal mortality: the effect of gestational age. american journal of public health. 1992 ;82(3):378-82. 20. horbar jd, mcauliffe tl, adler sm.variability in 28-day outcomes for very low birth weight infants. pediatrics. 1988 ;82(4):554-59. 21. horbar jd, badger gj, lewit em. oxford network. hospital and patient characteristics associated with variation in 28day mortality rates for very low birth weight infants. pediatrics. 1997 ;99(2):149-56. 22. fanaroff aa, wright ll, stevenson dk. very-low-birthweight outcomes of the national institute of child health and human development neonatal research network. american journal of obstetrics and gynecology.1995;173(5):1423-31. 23. lee sk, mcmillan dd, ohlsson a, pendray m, synnes a. variations in practice and outcomes in the canadian nicu network: 1996–1997. pediatrics , 2000;106(5):1070-79. 24. darlow ba, cust ae, donoghue da. improved outcomes for very low birthweight infants: evidence from new zealand national population based data. archives of disease in childhood-fetal and neonatal edition. 2003 88(1):23-28. 25. de vries ls, van haastert il, rademaker kj. ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. the journal of pediatrics, 2004 ;144(6):815-20 26. wilson-costello d, friedman h, minich n, fanaroff aa. improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. pediatrics. 2005;115(4):997-1003. 27. adegoke sa, olugbemiga ao, bankole kp. intraventricular hemorrhage in newborns weighing< 1500 g. annals of tropical medicine and public health. 2014 ;7(1):48-51. 28. kuperman aa, kenet g, papadakis e, brenner b. intraventricular hemorrhage in preterm infants: coagulation perspectives. seminars in thrombosis and hemostasis, 2011 ; 37(7): 730-36. 29. beverley dw, chance gw, inwood mj, schaus m, o'keefe b. intraventricular haemorrhage and haemostasis defects. archives of disease in childhood, 1984 ;59(5):444-48. 30. qureshi ai, adil mm, shafizadeh n. a 2-fold higher rate of intraventricular hemorrhage–related mortality in african american neonates and infants: clinical article. journal of neurosurgery: pediatrics. 2013;12(1):49-53. 31. haroon a, maheen h, salat ms, dileep d. risk factors for intraventricular haemorrhage in preterm infants. jpma. 2014;64(1146):112-15. 32. köksal n, baytan b, bayram y, nacarküçük e. risk factors for intraventricular haemorrhage in very low birth weight infants. indian journal of pediatrics, 2002 ;69(7):561-64. 33. aly h, hammad ta, essers j.is mechanical ventilation associated with intraventricular hemorrhage in preterm infants?. brain and development. 2012 ;34(3):201-05. 34. lee jy, kim hs, jung e, kim es, shim gh, lee hj. risk factors for periventricular-intraventricular hemorrhage in premature infants. journal of korean medical science. 2010 ;25(3):418-24. 35. lu hy, zhang q, wang qx, lu jy. contribution of histologic chorioamnionitis and fetal inflammatory response syndrome to increased risk of brain injury in infants with preterm premature rupture of membranes. pediatric neurology. 2016 ;61:94-98. 36. bilićčače i, milardović a, babićbožović i, kolak m. risk factors of intraventricular hemorrhage in preterm infants in the neonatal intensive care unit, university department of obstetrics and gynecology, university hospital center rijeka. medicina fluminensis. 2017;52(4.):515-26. 37. kim kr, jung sw, kim dw. risk factors associated with germinal matrix-intraventricular hemorrhage in preterm neonates. journal of korean neurosurgical society. 2014 ;56(4):334-37. 38. lupton ba, hill a, whitfield mf, carter c. reduced platelet count as a risk factor for intraventricular hemorrhage. american journal of diseases of children. 1988 ;142(11):1222-24. 39. antoniuk s and da silva rv. periventricular and intraventricular hemorrhage in the premature infants. revista de neurologia. 1999 ;31(3):238-43. 40. kenny jd, garcia-prats ja, hilliard jl. hypercarbia at birth: a possible role in the pathogenesis of lntraventricular hemorrhage. pediatrics. 1978 ;62(4):465-67. 41. disalvo d. the correlation between placental pathology and intraventricular hemorrhage in the preterm infant. the developmental epidemiology network investigators. pediatric research, 1998 ;43(1):15-19. 42. volpe jj. intraventricular hemorrhage in the premature infant—current concepts. part i. annals of neurology. 1989 ;25(1):3-11. 43. wei jc, catalano r, profit j, gould jb. impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants. journal of perinatology 2016; 36 (5): 35256 44. liggins gc, howie rn. a controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory journal of rawalpindi medical college (jrmc); 2017;21(1): 23-28 28 distress syndrome in premature infants. pediatrics. 1972 ;50(4):515-25. 45. roberts d, dalziel s. antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth (review). cochrane database syst rev. 2006;19:cd004454. 46. shalak l and perlman jm. hemorrhagic-ischemic cerebral injury in the preterm infant: current concepts. clinics in perinatology, 2002 29(4):745-63. 47. wells jt and ment lr. prevention of intraventricular hemorrhage in preterm infants. early human development. 1995 ;42(3):209-33. 48. schmid mb, reister f, mayer b, hopfner rj. prospective risk factor monitoring reduces intracranial hemorrhage rates in preterm infants. dtscharztebl int. 2013 ;110(29-30):48996. 49. .ment lr, oh w, ehrenkranz ra, philip ag, duncan cc. antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants. american journal of obstetrics and gynecology, 1995;172(3):795-800. 50. chaudhari s, kinare as, kumar r, pandit an. ultrasonography of the brain in preterm infants and its correlation with neurodevelopmental outcome. indian pediatrics, 1995 ;32(7):735-42. 51. soni jp, gupta bd, soni m, gupta m, dabi dr, nemal kr. ultrasonic diagnosis of intracranial hemorrhage in high risk neonates. indian pediatrics, 1995 ;32:453-56. 52. sandler dl, cooper pa, bolton kd, bental ry. periventricular-intraventricular haemorrhage in low-birthweight infants at baragwanath hospital. south african medical journal, 1994;84(1):26-29. 53. rehman m and khan grhi. prevalence of periventricular/intraventricular haemorrhage in premature infants. pakistan pediatr j 1998;22(4):145-47. 54. yakoob m. characteristics of very preterm infants delivered at a tertiary care center in pakistan. mymensingh med j. 2014 ;23(3)129-32. 55. debbarma r, de a, debbarma s. incidence of intracranial haemorrhage in low-birth weight infants and its outcome. international journal of research in medical sciences. 2016;4(10):4279-85. 56. mulindwa mj, sinyangwe s, chomba e.prevalence of intraventricular haemorrhage and associated risk factors in preterm neonates.medical journal of zambia. 2012;39(1):16-21. 57. afjeh sa, sabzehei mk, fallahi m. outcome of very low birth weight infants over 3 years report from an iranian center. iranian journal of pediatrics. 2013;23(5):579. 58. sajjadian n, fakhrai h, jahadi r. incidence of intraventricular hemorrhage and post hemorrhagic hydrocephalus in preterm infants. acta medicairanica, 2010(4):260-62. 59. marba s, caldas jp, vinagre le. incidence of periventricular/intraventricular hemorrhage in very low birth weight infants. jornal de pediatria,2011;87(6):505-11. 60. ajmal f, shaukat f, hussein w. intraventricular haemorrhageamongst preterm babiespreventive role of dexamethasone. proceeding s.z.p.g.m.i. 2010;24(2):61 65. 61. sabir s, ahmed z, ahmed i, razzaq a. frequency of intraventricular hemorrhage in premature infants. pakistan armed forces medical journal. 2011(4): 61: 157–182. 62. rashid j, shahid m, anwar s, sharaf d, bhatti t. frequency of intraventricular haemorrhage in preterm neonates. pak j med health sci, 2010;4(4):57578. 63. dubowitz lm, dubowitz v, goldberg c. clinical assessment of gestational age in the newborn infant. the journal of pediatrics. 1970 ;77(1):1-5. 64. avery me. resuscitation. in: avery me, taeusch hw. schaffer’s diseases of the newborn 5th ed. philadelphia: wb saunders 1984:105. 65. kumar a, bhat bv. epidemiology of respiratory distress of newborns. the indian journal of pediatrics. 1996 ;63(1):938. 66. dolfin t, skidmore mb, fong kw, hoskins em. incidence, severity, and timing of subependymal and intraventricular hemorrhages in preterm infants. pediatrics. 1983 ;71(4):541-6. 67. perlman jm, rollins n, burns d. relationship between periventricular intraparenchymalechodensities and germinal matrix-intraventricular hemorrhage in the very low birth weight neonate. pediatrics. 1993 ;91(2):474-80. 68. patridge jc, babcock ds, steichen jj. optimal timing for diagnostic cranial ultrasound in low-birthweight infants: detection of intracranial hemorrhage and intraventricular dilatation. j pediatr, 1983;102:281-87. 69. paneth n, pinto-martin j, gardiner j. incidence and timing of germinal matrix/intraventricular hemorrhage in low birth weight infants. american journal of epidemiology,1993 ;137(11):1167-76. 70. van de bor m, van bel f, lineman r. perinatal factors and periventricular-intraventricular hemorrhage in preterm infants. american journal of diseases of children. 1986;140(11):1125-30. 71. perlman jm, mcmenamin jb, volpe jj. fluctuating cerebral blood-flow velocity in respiratory-distress syndrome: relation to the development of intraventricular hemorrhage. new england journal of medicine. 1983 ;309(4):204-9. 72. goldberg rn, chung d, goldman sl, bancalari e. the association of rapid volume expansion and intraventricular hemorrhage in the preterm infant. the journal of pediatrics. 1980 ;96(6):1060-63. 73. andrew m, castle v, saigal s, carter c, kelton jg. clinical impact of neonatal thrombocytopenia. the journal of pediatrics, 19871;110(3):457-64. 74. bonifacio l, petrova a, nanjundaswamy s, mehta r. thrombocytopenia related neonatal outcome in preterms. the indian journal of pediatrics. 2007 ;74(3):269-74. 75. yulandari i, rundjan l, kadim m, amalia p. the relationship between thrombocytopenia and intraventricular hemorrhage in neonates with gestational age< 35 weeks. paediatrica indonesiana, 2016 ;56(4):242-50. 76. anderson gd, bada hs, shaver dc, harvey cj. the effect of caesarean section on intraventricular hemorrhage in the preterm infant. american journal of obstetrics and gynecology. 1992 ;166(4):1091-101 77. strauss a, kirz d, modanlou hd. perinatal events and intraventricular/subependymal hemorrhage in the very low-birth weight infant. american journal of obstetrics and gynecology. 1985;151(8):1022-27. 78. murphy bp, inder te, rooks v. posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. archives of disease in childhood-fetal and neonatal edition. 2002 ;87(1):37-41. summary journal of rawalpindi medical college (jrmc); 2018;22(1): 8-13 8 original article prevalence of essential hypertension and assessment of cardiovascular risk of pakistani adults in outpatient setting m a ebrahim 1, zeeshan hassan 2 1. zubaida medical centre, karachi; 2. sanofiaventis, karachi abstract background :to assess the prevalence of essential hypertension and evaluate cardiovascular risk in patients in pakistan. methods:this cross-sectional, non-interventional study was conducted at multiple centres throughout pakistan. data was collected from patients of either gender, ≥18 years of age, seeking routine medical consultation. diagnosis and staging of hypertension was carried out using guidelines laid by seventh report of joint national committee (jnc 7). genderwise framingham scores were calculated based on non-laboratory and laboratory parameters. results: out of 2336 patients evaluated, prevalence of hypertension and prehypertension was 51.5% and 31.4% , respectively. a total of 501 patients had coprevalent diabetes and hypertension. ten-year framingham scores calculated using non-laboratory parameters showed 56% (947/1693) patients aged ≥30 years were at medium-to-high risk for cardiovascular disease (cvd). while framingham scores based on laboratory or non-laboratory parameters were not significantly different for men, in women the nonlaboratory based score was higher. angiotensinconverting enzyme inhibitors and calcium channel blockers were antihypertensive agents of choice. conclusions: since prevalence of prehypertension and hypertension in pakistani adults continues to be on rise and substantial proportion of study population is at medium-to-high risk of developing cvd within the next 10 years, regular bp monitoring and risk scoring is mandated for identification of at-risk population and optimal management of cvd. key words:hypertension, physicians, primary care. introduction hypertension is an independent risk factor for coronary heart disease, heart failure, cerebrovascular disease, and chronic renal failure and a leading cause of cardiovascular (cv) morbidity and mortality. 1,2 over 2/3rd of patients with hypertension are from developing countries and this is attributed to modern lifestyles and increasing life spans. the global burden of hypertension is predicted to cross 1.5 billion by 2025.3-5 hypertension is widely prevalent in pakistan and the number of cases has doubled from 17% in 1980 to 35% in 2008. 6 results from pakistan national health survey in the late nineties showed that incidence of hypertension in adults >45 years of age (33%) was twice that in the general population (≥15 years and older; 18%). 7 in addition, approximately 1/4th of middle-aged adults in pakistan have coronary artery disease and 17% population carries at least two associated risk factors. 8,9 since hypertension is a progressive disease, early detection and blood pressure control are the keys to reduction in cv risk. clinical evidence demonstrates that screening for high blood pressure has benefits in reduction of cv events.10 guidelines laid down by the 7th report of the joint national committee on detection, evaluation, and treatment of high blood pressure (jnc 7) recommends screening individuals ≥18 years of age for hypertension, and evaluating those with hypertension for associated cv risk factors. 2 in recent years, rapid and significant changes in lifestyle practices in pakistan have a direct bearing on cv risk. consequently, there is an urgent need to determine the burden of hypertension as well as the associated cv risk in pakistani adults. risk prediction models are a useful tool in clinical practice to identify, communicate with, and treat highrisk individuals before disease complications set in. numerous risk factors interact and contribute to the pathology of cv disease. epidemiological and clinical evidence suggest that translating risk factors into scores can predict an individual’s cv risk with a certain amount of accuracy.risk prediction algorithms such as framingham risk score (frs), systematic coronary risk evaluation (score), and world health journal of rawalpindi medical college (jrmc); 2018;22(1): 8-13 9 organisation/international society of hypertension(who/ish) score are widely used to identify and manage patients at high cv risk. 1,11,12 the framingham model employs either laboratory parameters (such as serum lipid levels) or nonlaboratory parameters (such as body mass index and anthropometrics) for calculation of risk score. a comparative study published in the lancet in 2008 showed that scoring with non-laboratory parameters not only identifies patients at risk, but also offers the advantages of feasibility and cost-effectiveness.13 laboratory investigations in pakistan are generally expensive to conduct and can be an economic strain to a majority of the population, especially those in the low-income strata. hence, a risk scoring model that combines predictability with practicality and can be used in primary care physicians’ (pcp) clinic would be quite useful in cv risk estimation in pakistan. focusing on these issues, the primary goal of our study was to assess prevalence of hypertension in general population visiting pcps for medical consultation. in addition, we also sought to compare non-laboratory based parameters over standard laboratory parameters in predicting cv risk in adults ≥30 years of age, to stratify our hypertensive patients as per jnc 7 guidelines and to assess the antihypertensive therapy prescribed to them. patients and methods this was a national, cross-sectional, multicenter hypertension registry conducted between november to october 2014 at 140 sites in 12 cities in pakistan. study investigators were community-based pcps from these cities and were randomly selected from the physician database of sanofi-aventis pakistan ltd. the study was conducted in compliance with all international and applicable guidelines, national laws and regulations of pakistan. the study was conducted in the ambulatory care setting, at individual outpatient clinics.adults ≥18 years of age, who were seeking medical consultation with their pcp, irrespective of their hypertension status were included. patients with a past history of myocardial infarction or objectively confirmed angina pectoris, suspected/known secondary hypertension, or were pregnant, were excluded. each investigator recruited 20 consecutive patients. data collected by the investigator at the time of enrolment included patient demographics and anthropometrics, lifestyle choices, cv risk factors and medical history, and two consequent blood pressure recordings taken at the site at a 5-minute interval. patients ≥30 years of age were directed to a predetermined laboratory for estimation of serum cholesterol and high-density lipoprotein (hdl). laboratory tests were conducted by aga khan university hospital clinical laboratory.prevalence estimation and staging of hypertension were done using jnc 7 guidelines. hypertension was characterized as systolic blood pressure (sbp) ≥140 mmhg or diastolic blood pressure (dbp) ≥90 mmhg for patients without diabetes, and sbp ≥130 mmhg or dbp ≥80 mmhg for patients with diabetes. for each patient ≥30 years,framingham risk scores were calculated (models a and b, suppl. fig. 1 and 2) based on their laboratory and non-laboratory parameters. scores for each patient were multiplied by a factor of 1.4 as recommended by the national institute for health and care excellence (nice) in order to make them applicable to the south asian phenotype. 14 based on an estimated prevalence of hypertension of 18% with a 1.5% margin of error, 95% confidence level and anticipating 10% data unworthiness (due to incomplete information, missing forms, etc.) a sample size of 2800 patients was required. this sample size also allowed us to meaningfully evaluate cv risk with both framingham models with a 95% confidence limit and 1.5% margin of error. differences between scores generated by model a and b were probed for statistical validity by paired t-test. patients’ scores were also categorized for risk as low (<10%), medium (10%-20%), or high (>20%) and differences in proportion within each category were compared using chi-square testthe statistical analyses were performed using spss version 18 (spss inc., chicago, usa) results the study population comprised 56% males and had an average age of 40.813.1 years (table 1). the proportion of patients ≥30 years in the cohort was 72.5% (1693/2336. bmi at 28.25.1 kg/m2 was marginally higher in this subpopulation, as was the proportion of patients with bmi ≥25 kg/m2. in patients ≥30 years, the proportion of women with bmi ≥25 kg/m2 was greater than men (78.0% vs. 67.8%). this trend was replicated in the case of prevalence of diabetes i.e29.4% (497/1693) patients ≥30 years had diabetes and a larger proportion of women presented with diabetes (32.1% versus 26.9% in men). the proportion of smokers in patients ≥30 years was 21.3% (n=363). average cholesterol and fasting hdl levels in these patients were 192.945.0mg/dl and 44.612.8 mg/dl, respectively. journal of rawalpindi medical college (jrmc); 2018;22(1): 8-13 10 as per jnc 7 guidelines, 51.5%(n=1202, 95% ci. 48.6% 54.4%)of patients in our study had hypertension. average sbp and dbp in the overall cohort was 137.521.1 mmhg and 87.611.3 mmhg respectively, and both were marginally higher in patients ≥30 years sbp: 141.920.7 mmhg; dbp: 89.710.7mmhg. the study population had 31.4%patients with prehypertension, 29.9% patients with stage 1 hypertension, and 26.0% patients with stage 2 hypertension. staging of hypertension in diabetes versus non-diabetes showed that a substantially higher proportion of patients with diabetes were either in prehypertensive stage or had hypertension when compared to patients without diabetes (96.3% versus 84.7%; table 2). the incidence of diabetes in hypertensive patients was 47.1% (501/1202) in comparison to 3.0% (34/1134) in normotensive patients. the prevalence of hypertension in nondiabetic patients was 30% (c.i. 28.2 – 31.9) while the prevalence of hypertension in patients with diabeteswas 21.4% (c.i. 19.8 – 23.2). (table 2).mean framingham score in women calculated using nonlaboratory parameters (model a;18.19.1) was significantly higher than that estimated using laboratory parameters model b; mean score: 14.87.4; paired mean difference: 3.174.27; p<0.01; (table 3). in men, mean scores were 16.38.3 with model a and 16.985 with model b with a paired mean difference of -0.683.4 (p<0.01). the use of individual framingham scores for risk stratification showed disparate results in women (table 3). model b indicated 62.7% (n=502) and 8.9% (n=71) women in the low-risk and the highrisk category, respectively. in comparison, model a calculated 45.6% (n=366) and 25.3% (n=203) women in lowand high-risk categories, respectively (p<0.01). in contrast, both model a and b showed a similar proportion of men in either of the risk categories. at the time of enrolment, 84% (1014/1202) of patients with hypertension were prescribed antihypertensive medications (table 4). the most widely prescribed class of agents was angiotensinogen-converting enzyme (ace) inhibitors (in 41% [493/1202] patients). of the 734 patients in the pre-hypertensive stage, 251 (34.2%) were prescribed antihypertensive agents. of 139 patients with co-prevalent prehypertension and diabetes, 57% (n=80) were prescribed antihypertensive agents. the agents of choice in patients with coprevalent diabetes and hypertension were ace inhibitors and beta blockers. table 1. patient characteristics characteristics total study population (n=2336) patients ≥30 years of age (n=1693) n (%) mean (sd) n (%) mean (sd) age, in years 40.8 (±13.1) 46.6 (±10.4) gender male 1307 (56.0) 892 (52.7) female 1029 (44.0) 801 (47.3) height, in cms 163.5 (±10.6) 162.7 (±10.5) weight, in kg 72.9 (±13.5) 74.1 (±13.0) bmi, in kg/m2 27.4 (±5.3) 28.2 (±5.1) patient with bmi ≥25 kg/m2 1530 (65.5) 1231 (72.7) blood pressure, in mmhg sbp 137.5 (±21.1) 141.9 (±20.7) dbp 87.6 (±11.3) 89.7 (±10.7) hip circumference, in cms 101.0 (±14.6) 103.6 (±14.4) waist hip ratio (whr), overall 0.93 (±0.10) 0.94 (±0.10) whr males 0.95 (±0.09) 0.95 (±0.09) whr females 0.91 (± 0.10) 0.92 (± 0.10) truncal obesity males with whr ≥0.90 957 (41.0) 701 (41.4) females with whr ≥0.80 928 (39.7) 743 (43.9) pre-existent diabetes 535 (22.9) 497 (29.4) smoking 513 (22.0) 363 (21.4) total cholesterol ;192.9 (45.0) <160 329 (19.4) 160-199 620 (36.6) 200-239 422 (24.9) 240-279 134 (7.9) ≥280 62 (3.7) fasting hdl;44.6 (12.8) ≥60 139 (8.2) 50-59 255 (15.1) 45-49 251 (14.8) 35-44 670 (39.6) <35 252 (14.9) sd – standard deviation; bmi – body mass index; sbp – systolic blood pressure; dbp – diastolic blood pressure; hdl – high density lipoprotein; sd – standard deviation journal of rawalpindi medical college (jrmc); 2018;22(1): 8-13 11 table 2. prevalence and staging of hypertension as per jnc 7 guidelines prevalence (n = 2336) bp cut-off ranges prevalence n % (95% ci) non-diabetic patients sbp≥140 or dbp≥90 701 30.0 (28.2 – 31.9) diabetic patients sbp≥130 or dbp≥80 501 21.4 (19.8 – 23.2) staging n (%) total study population (n = 2336) normal* 295 (12.6) prehypertension† 734 (31.4) stage 1 hypertension‡ 699 (29.9) stage 2 hypertension∫ 608 (26.0) non-diabetic patients ≥18 yrs (n = 1801) normal* 275 (15.3) prehypertension† 595 (33.0) stage 1 hypertension‡ 505 (28.0) stage 2 hypertension∫ 426 (23.7) diabetic patients ≥18 yrs (n = 535) normal* 20 (3.7) prehypertension† 139 (26.0) stage 1 hypertension‡ 194 (36.3) stage 2 hypertension∫ 182 (34.0) *normal:sbp <120 mmhg and dbp <80 mmhg;† prehypertension:sbp 120– 139 mmhg or dbp 80–89 mmhg;‡ stage 1 hypertension: sbp 140–159 mmhg or dbp 90–99 mmhg;∫ stage 2 hypertension: sbp ≥160 mmhg or ≥100 mmhg;jnc 7 – seventh report of the joint national committee in prevention, detection, evaluation and treatment of high blood pressure;bp – blood pressure;sbp – systolic blood pressure; dbp – diastolic blood pressure; ci – confidence interval table 3. gender-based framingham scores (a) and risk stratification (b) using non-laboratory & laboratory predictors in patients aged ≥30 years (n=1693) (a) framingham scores nonlaboratory predictors (model a) laboratory predictors (model b) paired mean difference (±sd) p-value females, n = 801 mean total score (sd) 18.1 (± 9.1) 14.8 (± 7.4) 3.17 (± 4.27) <0.01 range -4 to 45 -6 to 39 males, n = 892 mean total score (sd) 16.3 (± 8.3) 16.9 (± 8.5) -0.68 (± 3.4) <0.01 range -3 to 39 0 to 41 (b) risk stratification risk category score n(%) nonlaboratory predictors (model a) laboratory predictors (model b) p-value female, n = 801 low: < 10% ≤ -2 to 12 366 (45.6) 502 (62.7) <0.01 medium: 10%-20% 13 to 17 232 (28.9) 228 (28.4) 0.59 high: >20% 18 to ≥21 203 (25.3) 71 (8.9) <0.01 male, n = 892 low: < 10% ≤ -3 to 10 380 (42.6) 367 (41.1) 0.53 medium: 10%-20% 11 to 14 213 (23.9) 222 (24.9) 0.62 high: >20% 15 to ≥18 299 (33.5) 303 (34.0) 0.84 sd – standard deviation table 4. therapeutic management according to stage of hypertension treatment prescribed hypertensives without diabetes hypertensives with diabetes n (%) n (%) prehyper tension n=734 stage 1 n=699 stage 2 n=608 prehyp ertensi on n=139 stage 1 n=194 stage 2 n=182 angiotensin converting enzyme inhibitors 67 (9.1) 269 (38.5) 277 (45.6) 30 (21.6) 79 (40.7) 81 (44.5) calcium channel blockers 53 (7.2) 154 (22.0) 191 (31.4) 22 (15.8) 32 (16.5) 44 (24.2) angiotensin receptor blockers 45 (6.1) 140 (20.0) 141 (23.2) 21 (15.1) 44 (22.7) 48 (26.4) beta blockers 36 (4.9) 113 (16.2) 139 (22.9) 16 (11.5) 54 (27.8) 61 (33.5) diuretics 12 (1.6) 68 (9.7) 108 (17.8) 4 (2.9) 29 (14.9) 40 (22.0) fixed dose combination 32 (4.4) 60 (8.6) 73 (12.0) 13 (9.4) 24 (12.4) 28 (15.4) others 6 (0.8) 21 (3.0) 36 (5.9) 2 (1.4) 7 (3.6) 12 (6.6) discussion in this nationwide estimate of the burden of essential hypertension in pakistani adults, we discovered that prevalence of hypertension in outpatient settings is substantially higher than in previous population-based surveys, and every second patient ≥18 years of age visiting a primary care physician (pcp) is likely to have high blood pressure. after staging patients’ blood pressureas per jnc 7, we determined that only 12.6% of our study population was normotensive and this proportion further decreased to 3.7% in patients with diabetes. furthermore, analysis of framingham scores revealed that >50% of the study population was at a medium-to-high risk of developing cv events within the next 10 years. the rising prevalence of hypertension in pakistan has been attributed to a plethora of factors like genetic predisposition, urbanization, dietary habits, concomitant rise in prevalence of obesity and diabetes, sedentary lifestyles, and lack of health awareness.15,16 our estimated prevalence of 51.4% is substantially higher than figures reported from previous studies in pakistan, south asia, the united states, and europe. however, we must consider that since our study was conducted in clinical settings,the study cohort could have a higher proportion of hypertensive patients than the general population. 4,6,7,17 prehypertension is defined as sbp of 120-139 mmhg or dbp of 80-89 mmhg per the jnc 7 guidelines and is a precursor stage to hypertension. 2 approximately 1/3rd of pre-hypertensive patients are estimated to progress to hypertensive stage within 4 years.18prehypertension, by itself, is also associated with adverse cv outcomes and progression of journal of rawalpindi medical college (jrmc); 2018;22(1): 8-13 12 diabetes. 19,20 hence, it becomes imperative to also monitor the prevalence of prehypertension and suggest appropriate intervention as per guidelines. various elaborate global studies such as the nhanes or a meta-analysis by guo, et al estimate the global burden of prehypertension to be 31%-36%. 21,22 our study population had 31.4% patients in the prehypertensive stage, which corroborates with the global estimate. additionally, the prevalence of prehypertension in our study is comparable to those estimated from other regional studies in asia – india, korea, japan, china, and iran.23-26 the united kingdom prospective diabetes study determined that hypertension is comorbid in approximately 70% of patients with diabetes, and is twice as prevalent in patients with diabetes. 28 a sizeable proportion of newly diagnosed diabetes patients have also been shown to have pre-existent hypertension. in our study, approximately 1/5th of the patients (n=501, 21.4%; ci: 19.8 – 23.2) had coprevalent diabetes and hypertension, and 701 (30.0%, ci: 28.2 – 31.9) patients had hypertension exclusively. the prevalence of diabetes in hypertensive patients was 41.7% . these findings are consistent with the belief that hypertension can worsen diabetic complications and strongly corroborate the association of hypertension and diabetes in cv pathology. despite proven usefulness of aforementioned risk prediction models, issues that have most likely hindered their routine use in clinical practice at a pcp level in pakistan are awareness of these models among the physicians’ community and the need for expensive and time-consuming laboratory tests to implement these. there is limited data on the applicability of these models in a population that is as heterogeneous in terms of ethnicity, lifestyle, socioeconomic status, and genetics, as in pakistan. a recent study that compared these models (frs, score, and who/ish) in malaysian population suggests use of frs for identifying individuals at high risk. 29 in our study, non-laboratory framingham scores indicated a higher risk profile in females in comparison with laboratorybased scores, with a paired difference of 3.174.27 between the average scores (p<0.01). in contrast, risk profiles were similar for males when either model was used. however, almost a quarter of pakistani women and approximately one-third of pakistani men over the age of 30 years are at a high risk of developing cardiovascular disease within the next 10 years. thus, our results demonstrate utility of non-laboratory based framingham risk scoring for identification of high cv risk individuals in pakistan and validate similar findings from other studies. 13,30-32 the pakistan hypertension league has drafted guidelines for therapeutic management of hypertension in pakistan and these are largely based on those laid by the national institute for health and care excellence (united kingdom). these recommend the use of ace inhibitors, arbs or ccbs as first line of treatment depending on the patients’ age (ace inhibitors or arbs for patients < 55 years and ccbs for patients > 55 years) and ethnicity and are in stark contrast with the jnc 7 guidelines which advocate use of thiazide diuretics for lowering bp. in our study we observed an adherence to the pakistani guidelines, since ace inhibitors were the drugs of choice across the hypertensive fraction of the study cohort. interestingly, despite 31.4% of the study cohort being pre-hypertensive, we discerned that only 1/3rd of them were prescribed antihypertensive medications. in prehypertensive patients with diabetes, only 57% were prescribed medical intervention. this is indeed alarming since jnc 7 guidelines specify prehypertension with diabetes to be a compelling indication that warrants the use of bp-lowering agents to ameliorate disease progression. 2 conclusion 1. prevalence of hypertension in clinical settings in pakistan is undesirably high and these patients are at a significant risk of developing cardiovascular disease. 2.this major health issue needs to be addressed by a concerted effort from the medical community and governmental authorities. 3 current national guidelines need to be harmonized with latest evidence-based guidelines to increase disease awareness and optimize treatments. acknowledgments the authors would like to thank the following physicians from pakistan, who participated as investigators in this study: from faisalabad bilal aziz, ijazanwer, tariq hameed, riaz ahmed awan, mubarak ali anjum, khalid ismail, muhammad arif, naeem akhtar khan; from karachi javaid qureshi, anwar adam, shahid akhter, m zahid shah, iqbal edhi, naseem akhter,m furqan ahmed, khan abdul bari, shiraz talibi, shaukat ali, tariq ali adnan, sajid mahmood, m javaid,ayesha nasir,khalid azeem, arshad ali shah, rashid jamil pirzada, m rathore, aqeel ahmed, noor asghar nadeem,muhammad anwer, abid hussain,shafqatmirza,shirin shahabuddin,m aqeelrai, faooq ismail suriya,arshad ali shah,khwajayawar abbas,naresh kumar shardha,majeed anwar, m a ebrahim, salma azam, ghazanfer ali shah, junaid zafar; from hyderabad -jamshed ahmed khanzada, manoj kumar, umar shehzad rathore, zoubia,abdul raheem noonari,tarique shiekh,lajpat lakhani,saleem raza,suresh kumar rathi,ghulam raza soomro,tnazir ahmed baloch,ali journal of rawalpindi medical college (jrmc); 2018;22(1): 8-13 13 goharabro,fakhruddin shaikh; from gujranwala maqsood mahmood,amanullah,muhammad jameel,arshad javaid,amjad iqbal; from lahore najmapervaiz,tariq mahmood,tariq shakoor,naveed ahmed,zill-e-huma,ambreen mudassir,syed iqbal hussain, imran k awan,fayyaz m baig,touqeer ahmed, dr mubasshir farooq, malik sajjad,m irfan, m ijaz, omer shahid, ashfaq rana,qaiser raza, arshad mahmood,bilal ahmed,sohail,waseem aslam; from sukkur yousufullah khan, muhammad anis memon,zaheeruddin sheikh,saleem sheikh,ayaz a bhatti,bhajan lal, atima ram, abdul qadir, aijaz ali abro; from peshawar ashfaq ali, asfandyar, shaukat a khan, adnan khan, asif izhar, muhammad abbas,ejaz anwar; from islamabad asadriazkichlew, tasneem elahi,syed nasir ali,nadeem islam shiekh, adalat khan, manzoor ahmed, ehsan ulhaq, nauman ahmed khan, humayyun haq,major hina babur; from rawalpindi arshad khan, mirza m yaqub, imtiaz ali chaudry, rafaqat ali, farooq sheikh, nazeer ahmed, muhammad irfan; from multan tauqeer ahmed, muneer ahmed rauf, haroonansar,saleem salimi,munir ahmed rashid,zahid mahmood, ilyas mahmood, nadeem qureshi.the authors wish to thank mr. satyendrashenoy of describe scientific writing & communication and dr. alina gomes and ms. anahitagouri of sanofi, india for providing drafting and editorial services for this manuscript. mr. iqbal mujtaba from sanofi (pakistan) for assistance regarding data management and statistical analysis;funding disclosure:the study was funded by sanofi pakistan limited references 1. d'agostino rb, sr., vasan rs, pencina mj, wolf pa. general cardiovascular risk profile for use in primary care: the framingham heart study. circulation. 2008;117(6):743-53. 2. chobanian av, bakris gl, black hr, cushman wc. seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. hypertension. 2003;42(6):1206-52. 3. kearney pm, whelton m, reynolds k, muntner p. global burden of hypertension: analysis of worldwide data. lancet. 2005;365(9455):217-23. 4. kearney pm, whelton m, reynolds k, whelton pk. worldwide prevalence of hypertension: a systematic review. journal of hypertension. 2004;22(1):11-19. 5. rodriguez bl, labarthe dr, huang b, lopez-gomez j. rise of blood pressure with age. new evidence of population differences. hypertension. 1994;24(6):779-85. 6. danaei g, finucane mm, lin jk, singh gm. national, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5.4 million participants. lancet. 2011;377(9765):568-77. 7. nanan d, white f. the national health survey of pakistan: review and discussion of report findings pertaining to selected risk factors for cardiovascular disease. procor digest. 1999;99:6-11. 8. jafar th. women in pakistan have a greater burden of clinical cardiovascular risk factors than men. international journal of cardiology. 2006;106(3):348-54. 9. jafar th, jafary fh, jessani s, chaturvedi n. heart disease epidemic in pakistan: women and men at equal risk. american heart journal. 2005;150(2):221-26. 10. siu al, force uspst. screening for high blood pressure in adults: u.s. preventive services task force recommendation statement. annals of internal medicine. 2015;163(10):778-86. 11. conroy rm, pyorala k, fitzgerald ap, sans s. estimation of ten-year risk of fatal cardiovascular disease in europe: the score project. european heart journal. 2003;24(11):987-1003. 12. world h, organization,. prevention of cardiovascular disease: guidelines for assessment and management of cardiovascular risk: world health organization; 2007 [cited 2016 april 19]. 13. gaziano ta, young cr, fitzmaurice g, atwood s. laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the nhanes i follow-up study cohort. lancet. 2008;371(9616):923-31. 14. bhopal r, fischbacher c, vartiainen e. predicted and observed cardiovascular disease in south asians: application of finrisk, framingham and score models to newcastle heart project data. journal of public health. 2005;27(1):93-100. 15. aziz ku. evolution of systemic hypertension in pakistani population. journal of the college of physicians and surgeons--pakistan : jcpsp. 2015;25(4):286-91. 16. dennis b, aziz k, she l, faruqui am. high rates of obesity and cardiovascular disease risk factors in lower middle class community in pakistan: the metroville health study. journal of the pakistan medical association. 2006;56(6):267-72. 17. neupane d, mclachlan cs, sharma r, gyawali b. prevalence of hypertension in member countries of south asian association for regional cooperation (saarc): systematic review and meta-analysis. medicine. 2014;93(13):e74. 18. vasan rs, larson mg, leip ep, kannel wb. assessment of frequency of progression to hypertension in non-hypertensive participants in the framingham heart study: a cohort study. lancet. 2001;358(9294):1682-86. 19. lewington s, clarke r, qizilbash n, peto r. prospective studies c. agespecific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. lancet. 2002;360(9349):1903-13. 20. mullican dr, lorenzo c, haffner sm. is prehypertension a risk factor for the development of type 2 diabetes? diabetes care. 2009;32(10):1870-72. 21. wang y, wang qj. the prevalence of prehypertension and hypertension among us adults according to the new joint national committee guidelines: new challenges of the old problem. archives of internal medicine. 2004;164(19):2126-34. 22. guo x, zou l, zhang x, li j. prehypertension: a meta-analysis of the epidemiology, risk factors, and predictors of progression. texas heart institute journal / from the texas heart institute of st luke's episcopal hospital, texas children's hospital. 2011;38(6):643-52. 23. singh rb, fedacko j, pella d, macejova z. prevalence and risk factors for prehypertension and hypertension in five indian cities. acta cardiologica. 2011;66(1):29-37. 24. choi km, park hs, han jh, lee js, lee j. prevalence of prehypertension and hypertension in a korean population: korean national health and nutrition survey 2001. journal of hypertension. 2006;24(8):1515-21. 25. ishikawa y, ishikawa j, ishikawa s. prevalence and determinants of prehypertension in a japanese general population: the jichi medical school cohort study. hypertension research. journal of the japanese society of hypertension. 2008;31(7):1323-30. 26. yang j, lu f, zhang c, liu z. prevalence of prehypertension and hypertension in a chinese rural area from 1991 to 2007. hypertension research : official journal of the japanese society of hypertension. 2010;33(4):331-37. 27. khosravi a, emamian mh, shariati m, hashemi h. the prevalence of pre-hypertension and hypertension in an iranian urban population. high blood pressure & cardiovascular prevention : the official journal of the italian society of hypertension. 2014;21(2):127-35. 28. tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: ukpds 38. uk prospective diabetes study group. bmj. 1998;317(7160):703-13. 29. selvarajah s, kaur g, haniff j, cheong kc. comparison of the framingham risk score, score and who/ish cardiovascular risk prediction models in an asian population. international journal of cardiology. 2014;176(1):211-18. 30. faeh d, braun j, bopp m. body mass index vs cholesterol in cardiovascular disease risk prediction models. archives of internal medicine. 2012;172(22):1766-68. 31. green bb, anderson ml, cook aj, catz s. using body mass index data in the electronic health record to calculate cardiovascular risk. american journal of preventive medicine. 2012;42(4):342-47. 32. sepanlou sg, malekzadeh r, poustchi h. the clinical performance of an office-based risk scoring system for fatal cardiovascular diseases in north-east of iran. plos one. 2015;10(5):e0126779. summary journal of rawalpindi medical college (jrmc); 2016;21(1): 9-12 9 original article relationship between serum lactate dehydrogenase levels and dengue severity shahida perveen1,hina firdous2, muhammad ali khalid1, naseer ahmed3, haider zaigham baqai 1 department of medicine, benazir bhutto hospital, rawalpindi.;2.cardiac surgery division, university of verona medical school, verona, italy;3.section of pharmacology, university of verona medical school, verona, italy. abstract background: to determine relationship between the levels of serum lactate dehydrogenase (ldh)on admission and prognosis of dengue fever. methods: patients (n=62) admitted with the diagnosis of dengue fever were included. on admission, serum ldh levels were measured in all patients and to find relationship we monitored all patients upto discharge. monitoring was done for vitals, different blood parameters and duration of hospitalization. results: forty one (66.1%) were males and 33.9% (n=21) were females with mean age 31.73±13years.during hospital stay, 61.3% patients had dengue fever (df)while 39.7% patients developed dengue hemorrhagic fever (dhf).ldh levels were higher in patients with dhf(mean 618.38u/l±219)as compared to the patients with dengue fever (mean 316.45u/l±104).mann whitney u test showed the difference was statistically significant (p<0.001). conclusion: patients with early increase in serum ldh showed more complications as compared to low serum ldh level. high ldh can be used to predict outcome in dengue patients. keywords: lactate dehydrogenase, dengue fever (df), dengue hemorrhagic fever (dhf), dengue shock syndrome (dss) introduction dengue is a vector borne disease epidemic with high morbidity and mortality. this disease is caused by dengue virus having 4 serotypes denv-1 to 4.1 it is mainly transmitted to humans by bite of female aedes aegypti and aedes albopictus mosquito but it can also be transmitted through blood transfusion, trans placental route, organ transplantation and needle stick or sharps injuries. 2-6 it is the most prevalent epidemic nowadays, across the world and especially in the asia. it affects about 50-100 million people per year as per who statistics. 7 in pakistan, first dengue epidemic was reported in 1994. 8 during 2011 dengue outbreak in pakistan there were more than 20,000 cases and 300 deaths reported. 9 dengue has varied clinical manifestations ranging from mild flu like symptoms, fever, arthralgia, myalgia, mild gi symptoms to potentially fatal complications of vascular leakage. it can be detected in asymptomatic case or may present as undifferentiated fever, dengue fever (df), dengue hemorrhagic fever (dhf), dengue shock syndrome (dss) and expanded dengue syndrome (eds). 10 while df is a mild, selflimiting disease dhf and dss may be fatal if not diagnosed and treated timely and appropriately. dengue passes through three clinical stages; febrile phase which may last for 2 to 10 days after which patient may enter recovery phase characterized by resolution of fever and other associated symptoms, or patient may progress into critical phase marked by resolution of fever and appearance of fluid leakage(10). most of the complications of dengue occur around the period of defervescence. 11 dengue causes micro vascular inflammation throughout the body, as evidenced by the increased markers of inflammation e.g. cytokines, chemokines, vegf and other angiogenic factors. 12-18 injury to vascular endothelial cells results from a complex interaction between the circulating proteins of dengue virus and host immune response. activation of cellular and humoral immune response increasesvascular permeability, which may be manifested by ascites, pleural effusion or shock. 19 lactate dehydrogenase (ldh) is an intracellular enzyme abundantly found in body tissues e.g. muscles, liver, placenta, rbcs, reticuloendothelial system. its serum levels increase after cell injury.it has been evaluated as prognostic marker of various inflammatory states e.g. sepsis, infections,mi, malignancies and cardio-pulmonary compromise. it is thought to be a marker of vascular permeability in immune mediated lung injury. 20-24 serum ldh levels are increased in df. various studies show that ldh levels are higher in dhf and dss patients. 25-28 an early increase in ldh (three times the normal value) journal of rawalpindi medical college (jrmc); 2016;21(1): 9-12 10 was an independent predictor of dhf. 29dengue has very high rate of admission in tertiary care hospitals. severe dengue requires aggressive monitoring, thus posing a burden on health system. so, the search for the prognostic factors, may help to reduce the rate of hospitalizations, as well as disease mortality and morbidity. this study evaluated the relation of at admission serum ldh levels with severity of df. patients and methods this cross sectional comparative study was carried out from 5thseptember 2016 to 27th november 2016 in the dengue inpatient department of benazir bhutto hospital (bbh),rawalpindi. we included the patients aged 18 to 80 years, admitted consecutively with probable df and having positive ns1 antigen and/or dengue igm. patients with negative dengue serology, taking anti-platelet medications, having platelet disorder, hemolytic anemia or co morbidities (like ihd, hepatitis due to non-dengue cause, pancreatitis, chronic renal or liver disease) and infections other than dengue were excluded. patients were managed as per standard guidelines of dengue expert advisory group(deag) and were categorized as df and dhf(30)as described below.df was defined as fever of 2-7 days with at least two of the followingheadache, retro-orbital pain, arthralgia/bone pain, myalgia,rash,leucopenia (tlc of less than 5*109), thrombocytopenia (platelets less than 150,000/ul) without any evidence of plasma leakage.dhf was defined as fever with bleeding, thrombocytopenia(platelets less than100,000/ul) and plasma leakage as indicated by one of the following >20% increase in haematocrit from baseline, >20% decrease in haematocrit after iv fluids or imaging evidence of plasma leakage e.g. ascites, pleural effusion, gb wall thickness or pericholecystic fluid. serum ldh levels of less than 200 units/ liters were considered normal. patients were divided into two groups depending upon their disease outcome. group 1 included the patients who had df. whereas, group 2 consisted of the patients who progressed to dhf. a structured performa was developed and used for data collection. data was analyzed using spss 24 version. ldh levels were compared between the two groups by mann whitney u test, and chi square test was applied wherever appropriate. results sixty-two patients were included in the study. male were predominant (table 1). male to female ratio was 1.94:1 in study population, 1.5:1 in group 1 and 3:1 in group 2. mean ldh level of the study population was 433.32±216 u/l. ldh levels were quantitatively higher in group 2 as compared to group (table 2). patients were further stratified according to their ldh levels into three categories and compared between the two groups (table 3). table 1demographic profile of the patients. total n=62 group 1 61.3%(n=38) group 2 38.7%(n=24) pvalue mean age (years) 31.7 ±13.40 32.47±14.67 30.54±11.30 0.822 male no (%) 41(66.1) 23(60.53) 18(75) 0.041 duration of fever* (mean± sd) 5.21±1.92 5.21±1.92 5.21±1.97 0.997 duration of hospital stay* (mean ± sd) 3.53±1.43 3.6±1.41 3.3±1.46 0.390 *in days. table 2comparison of mean serum ldh levels between the two groups d i s e a s e g r o u p ldh levels on admission ( u / l ) p value group 1 (mean ± sd) 3 1 6 . 4 5 ± 1 0 4 < 0 . 0 0 1 group 2 (mean ± sd) 6 1 8 . 3 8 ± 2 1 9 table 3: group wise comparison of ldh categories. ldh levels u/l d i s e a s e g r o u p p v a l u e group 1 g r o u p 2 l e s s t h a n 2 0 0 15.8%(n=6) 0 % < 0 . 0 0 1 2 0 0 t o 6 0 0 73.8%(n=31) 26.2%(n=11) more than 600 7.1%(n=1) 92.9%(n=13) discussion many studies show that serum ldh levels are raised in df but there are very limited studies evaluating it as a prognostic marker in this disease. no study has been found in pakistan regarding the prognostic role of ldh in dengue. in this study, it was notedthat ldh levels are elevated to more than 200 u/l inall of the dhf patients and majority of df patients. ldh levels at admission were significantly higher in patients who progress to dhf (618.38 ±219u/l)as compared to those withsimple df (316.45 ±104u/l), p<0.001. these results are similarto those reported by sirikutt et al and villar-centeno et al although mean levels in this study are lower in each group than reported in abovementioned studies, while liao b et al reported slightly lower levels in both df and dhf, 213.68 u/l journal of rawalpindi medical college (jrmc); 2016;21(1): 9-12 11 and 448.17 u/l respectively. 25,26,29,30 patients in group 2 had 3-fold increase in ldh levels. it was noted that although some patient with simple df had normal values of serum ldh, whereas, none of the patients in group 2 was found to have normal ldh levels. in majority of group 2 patients (92%) ldh levels were more than 600 units/liter, as reported by ravishankar et al. 31 in our study, majority of the patients were males (65.3% in group 1 and 75% in group 2), matching those reported in who surveillance data and study done by agarwal et al, the reason for this gender difference is not clearly understood but may be due to the greater exposure of males to mosquitoes due to theiroutdoor occupational activities. 32-34 we found that males are more likely to develop severe form of the disease as reflected by the differences in gender ratios between the two groups, literature has controversial results about this relation, results of vicente cr et al(35) favor our finding. 35 whereas,villar-centeno andrasul ch et al found no gender differences between those developing dhf as compared to those who did not. 29,36 mean age of our patients was 31.7 ±13.4 years which was slightly higher than that mentioned by villarcenteno(29). patients in dhf group were relatively younger than df group but the difference was not statistically significant(p-value 0.82) whereas, previous study reported higher age in patients with severe dengue.35 in our study mean duration of illness at the time of presentation was 5.21 days, while duration of hospitalization was 3.53 days, there was no difference between the two groups regarding these parameters with p values of 0.997 and 0.390 respectively. similar results are reported in previous studies. 29 but this was a small study with a relatively small sample size, carried out on relatively healthy adults without any major co morbidities. single sample for ldh levels was on average sought on 5th day of fever. critical phase in dengue usually extends from 3 to 7 days, seeking ldh levels at this time may have maximum impact. moreover, this study only included patients admitted in a tertiary care hospital, which mostly represent most severe form of disease. so, further larger prospective studies including the populations missing in this study at earlier stages of disease, are required to test this association. conclusion 1. serum ldh levels were found elevated in dhf patients. this correlation may be used as a predictor for severity in df. elevated levels of ldh on day 5 in dengue fever point towards the diagnosis of dhf. a cut off value of more than 600 u/l was seen in majority of these patients. 2. biomarker, like ldh, can lead to the establishment of predictors of dengue severity that is very important to control disease and reduction in morbidity and mortality caused by this disease. references 1. sundulagunta sr, sodalagunta mb, sepehrar m, bangalore raja sk, nataraju a, kumbhat m, et al. dengue shock syndrome. oxf med case reports. 2016;2016(11):211-14. 2. cdc. dengue epidemiology: transmission of the dengue virus,2014. 3. pozzetto b, memmi m, garraud o. is transfusiontransmitted dengue fever a potential public health threat? world journal of virology. 2015;4(2):113-23. 4. pouliot sh, xiong x, harville e, paz-soldan v. maternal dengue and pregnancy outcomes. obstetrical & gynecological survey. 2010;65(2):107-18. 5. tan fl, loh dl, prabhakaran k, tambyah pa. dengue haemorrhagic fever after living donor renal transplantation. nephrol dial transplant. 2005;20(2):447-48. 6. chen lh and wilson me. nosocomial dengue by mucocutaneous transmission. emerging infectious diseases. 2005;11(5):775-78. 7. who. dengue control: what is dengue [updated 2017]. availablefrom: http://www.who.int/denguecontrol/disease/en/. 8. jahan f. dengue fever (df) in pakistan. asia pac fem med. 2011;10(1):1-5. 9. khanani mr, arif a, shaikh r. dengue in pakistan: journey from a disease free to a hyper endemic nation. editorial board. 2011;5:81-84. 10. searo. comprehensive guidelines for prevention and control of dengue and dengue hemorrhagic fever 2011 [updated 2017]. available from: http://www.searo.who.int/entity/vector_borne_tropical_di seases/documents/searotps60/en/. 11. srikiatkhachorn a and green s. markers of dengue disease severity. current topics in microbiology and immunology. 2010;338:67-82. 12. aloia al, abraham am, bonder cs, pitson sm. dengue virus-induced inflammation of the endothelium and the potential roles of sphingosine kinase-1 and micrornas. mediators of inflammation. 2015;2015:13-15. 13. her z, kam yw, gan vc, lee b, thein tl. severity of plasma leakage is associated with high levels of interferon gammainducible protein 10, hepatocyte growth factor, matrix metalloproteinase 2 (mmp-2), and mmp-9 during dengue virus infection. the journal of infectious diseases. 2017;215(1):42-51. 14. suwanmanee s and natthanej l. immunopathogenesis of dengue virus-induced redundant cell death: apoptosis and pyroptosis. viral immunol. 2017;13(1):13-9. 15. rattanamahaphoom j, leaungwutiwong p, limkittikul k, kosoltanapiwat n. activation of dengue virus-specific t cells modulates vascular endothelial growth factor receptor 2 expression. asian pacific journal of allergy and immunology. 2016. 16. figueroa cl, gelvez m, niederbacher j. regulators of endothelial integrity as severity predictors in dengue. biomedica : revista del instituto nacional de salud. 2016;36(0):148-55. http://www.searo.who.int/entity/vector_borne_tropical_diseases/documents/searotps60/en/ http://www.searo.who.int/entity/vector_borne_tropical_diseases/documents/searotps60/en/ journal of rawalpindi medical college (jrmc); 2016;21(1): 9-12 12 17. mathew and rothman al. understanding the contribution of cellular immunity to dengue disease pathogenesis. immunological reviews. 2008;225:300-13. 18. inyoo s, suttitheptumrong a, pattanakitsakul sn. synergistic effect of tnf-alpha and dengue virus infection on adhesion molecule reorganization in human endothelial cells. japanese journal of infectious diseases, 2017;70(2):186-91. 19. leong as, wong kt, leong ty, tan ph, wannakrairot p. the pathology of dengue hemorrhagic fever. seminars in diagnostic pathology. 2007;24(4):227-36. 20. zein jg, lee gl, tawk m, dabaja m. prognostic significance of elevated serum lactate dehydrogenase (ldh) in patients with severe sepsis. chest. 2004;126(4):873-76. 21. erez a, shental o, tchebiner jz, laufer-perl m, wasserman a. diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients. the israel medical association journal, 2014;16(7):439-43. 22. danese e and montagnana m. an historical approach to the diagnostic biomarkers of acute coronary syndrome. annals of translational medicine. 2016;4(10):194-96. 23. inomata m, hayashi r, tokui k, taka c. lactate dehydrogenase and body mass index are prognostic factors in patients with recurrent small cell lung cancer receiving amrubicin. tumori. 2016;102(6):606-09. 24. hagadorn je, bloor cm, yang ms. elevated plasma activity of lactate dehydrogenase isoenzyme-3 (ldh(3)) in experimentally induced immunologic lung injury. the american journal of pathology. 1971;64(3):575-84. 25. sirikut p and kalayanarooj s. serum lactate and lactate dehydrogenase as parameters for the prediction of dengue severity. j med assoc thai. 2014;97(6):220-31. 26. liao b, tang y, hu f, zhou w, yao x. serum levels of soluble vascular cell adhesion molecules may correlate with the severity of dengue virus-1 infection in adults. emerg microbes infect. 2015;4:e24-27. 27. ahmad mm. clinical profile of dengue fever infection in king abdul aziz university hospital saudi arabia. j infect dev ctries. 2010;4(8):503-10. 28. zhao l, huang x, hong w, qiu s, wang j. slow resolution of inflammation in severe adult dengue patients. bmc infectious diseases. 2016;16(1):291-95. 29. villar-centeno la, díaz-quijano fa, martínez-vega ra. biochemical alterations as markers of dengue hemorrhagic fever. am j trop med hyg. 2008;78(3):370-74. 30. masood f, butt tk, ali m. dengue expert advisory group (deag), dengue gcp guidelines 2012. 31. ravishankar k, vinoth pn, venkatramanan p. biochemical and radiological markers as predictors of dengue severity in children admitted in a tertiary care hospital. int j contemp pediatr. 2015;2(4):311-16. 32. anker m, arima y. male-female differences in the number of reported incident dengue fever cases in six asian countries. western pacific surveillance and response journal. 2011;2(2):17-23. 33. prasith n, keosavanh o, phengxay m, stone s, lewis hc. assessment of gender distribution in dengue surveillance data, the lao people’s democratic republic. western pacific surveillance and response journal, 2013;4(2):17-24. 34. agarwal r, kapoor s, nagar r, misra a. a clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at lucknow, india. the southeast asian journal of tropical medicine and public health. 1999;30(4):735-40. 35. vicente cr, cerutti junior c, froschl g, romano cm, cabidelle as, herbinger kh. influence of demographics on clinical outcome of dengue: a cross-sectional study of 6703 confirmed cases in vitoria, espirito santo state, brazil. epidemiology and infection. 2017;145(1):46-53. 36. rasul ch, ahasan ha, rasid ak, khan mr. epidemiological factors of dengue hemorrhagic fever in bangladesh. indian pediatrics. 2002;39(4):369-72. for electronic submission of articles email of journal: journalrmc@gmail.com to view volumes of journal of rawalpindi medical college and to search by authors names , contents , keywords-visit website of the journal: www.journalrmc.com mailto:journalrmc@gmail.com